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10,700 | 29,313,369 | Conclusion In heart failure patients , we identified several baseline characteristics in favour of an improved LVEF , in response to evidence based therapy .
Patients with improved LVEF had significantly lower risks of mortality and appropriate shocks compared with patients with persistently reduced LVEF | Aims We assessed the clinical characteristics and prognosis of chronic heart failure patients with improved ejection fraction ( HFIEF ) compared with persistently reduced ejection fraction ( HFpREF ) after evidence -based therapy . | BACKGROUND Heart failure patients with primary prevention implantable cardioverter-defibrillators ( ICD ) may experience an improvement in left ventricular ejection fraction ( LVEF ) over time . However , it is unclear how LVEF improvement affects subsequent risk for mortality and sudden cardiac death . OBJECTIVES This study sought to assess changes in LVEF after ICD implantation and the implication of these changes on subsequent mortality and ICD shocks . METHODS We conducted a prospect i ve cohort study of 538 patients with repeated LVEF assessment s after ICD implantation for primary prevention of sudden cardiac death . The primary endpoint was appropriate ICD shock defined as a shock for ventricular tachyarrhythmias . The secondary endpoint was all-cause mortality . RESULTS Over a mean follow-up of 4.9 years , LVEF decreased in 13.0 % , improved in 40.0 % , and was unchanged in 47.0 % of the patients . In the multivariate Cox models comparing patients with an improved LVEF with those with an unchanged LVEF , the hazard ratios were 0.33 ( 95 % confidence interval : 0.18 to 0.59 ) for mortality and 0.29 ( 95 % confidence interval : 0.11 to 0.78 ) for appropriate shock . During follow-up , 25 % of patients showed an improvement in LVEF to > 35 % and their risk of appropriate shock decreased but was not eliminated . CONCLUSIONS Among primary prevention ICD patients , 40.0 % had an improved LVEF during follow-up and 25 % had LVEF improved to > 35 % . Changes in LVEF were inversely associated with all-cause mortality and appropriate shocks for ventricular tachyarrhythmias . In patients whose follow-up LVEF improved to > 35 % , the risk of an appropriate shock remained but was markedly decreased Background —Heart failure with recovered or improved ejection fraction ( HFiEF ) has been proposed as a new category of HF . Whether HFiEF is clinical ly distinct from HF with persistently reduced ejection fraction remains to be vali date d. Methods and Results —Of the 5010 subjects enrolled in the Valsartan Heart Failure Trial ( Val-HeFT ) , 3519 had a baseline left ventricular EF of < 35 % and a follow-up echocardiographic assessment of EF at 12 months . Of these , 321 ( 9.1 % ) patients who had a 12-month EF of > 40 % constituted the subgroup with HFiEF . EF improved from 28.7±5.6 % to 46.5±5.6 % in the subgroup with HFiEF and remained reduced ( 25.2±6.2 % and 27.5±7.1 % ) in the subgroup with HF with reduced ejection fraction . The group with HFiEF had a less severe hemodynamic , biomarker , and neurohormonal profile , and it was treated with a more intense HF medication regimen . Subjects who had higher blood pressure and those treated with a & bgr;-blocker or r and omized to valsartan had greater odds of being in the HFiEF group , whereas those with an ischemic pathogenesis , a more dilated left ventricle , and a detectable hs-troponin had lower odds of an improvement in EF . Recovery of the EF to > 40 % was associated with a better survival compared with persistently reduced EF . Conclusions —Our data support HFiEF as a stratum of HF with reduced ejection fraction with a more favorable outcome , which occurs in a minority of patients with HF with reduced ejection fraction who have a lower prevalence of ischemic heart disease , a less severe hemodynamic , biomarker , and neurohormonal profile , and who are treated with a more intense HF medication regimen . Clinical Trial Registration —URL : http://www . clinical trials.gov . Unique identifier : NCT00336336 Objectives The beneficial effects of cardiac resynchronization therapy ( CRT ) are thought to result from favorable left ventricular ( LV ) reverse remodeling , however CRT is only successful in about 70 % of patients . Whether response to CRT is associated with a decrease in ventricular arrhythmias ( VA ) is still discussed controversially . Therefore , we investigated the incidence of VA in CRT responders in comparison with non-responders . Methods In this nonr and omized , two-center , observational study patients with moderate-to-severe heart failure , LV ejection fraction ( LVEF ) ≤35 % , and QRS duration > 120 ms undergoing CRT were included . After 6 months patients were classified as CRT responders or non-responders . Incidence of VA was compared between both groups by Kaplan-Meier analysis and Cox regression analysis . ROC analysis was performed to determine the aptitude of LVEF cut-off values to predict VA . Results In total 126 consecutive patients ( 64±11years ; 67%male ) were included , 74 were classified as responders and 52 as non-responders . While the mean LVEF at baseline was comparable in both groups ( 25±7 % vs. 24±8 % ; P = 0.4583 ) only the responder group showed an improvement of LVEF ( 36±6 % vs. 24±7 ; p<0.0001 ) under CRT . In total in 56 patients VA were observed during a mean follow-up of 28±14 months , with CRT responders experiencing fewer VA than non-responders ( 35 % vs. 58 % , p<0.0061 ) . Secondary preventive CRT implantation was associated with a higher likelihood of VA . As determined by ROC analysis an increase of LVEF by > 7 % was found to be a predictor of a significantly lower incidence of VA ( AUC = 0.606 ) . Conclusions Improvement of left ventricular function under cardiac resynchronization therapy goes along with a reduced incidence of ventricular arrhythmia Background — We hypothesized that patients with heart failure ( HF ) who recover left ventricular function ( HF-Recovered ) have a distinct clinical phenotype , biology , and prognosis compared with patients with HF with reduced ejection fraction ( HF-REF ) and those with HF with preserved ejection fraction ( HF-PEF ) . Methods and Results — The Penn Heart Failure Study ( PHFS ) is a prospect i ve cohort of 1821 chronic HF patients recruited from tertiary HF clinics . Participants were divided into 3 categories based on echocardiograms : HF-REF if EF was < 50 % , HF-PEF if EF was consistently ≥50 % , and HF-Recovered if EF on enrollment in PHFS was ≥50 % but prior EF was < 50 % . A significant portion of HF-Recovered patients had an abnormal biomarker profile at baseline , including 44 % with detectable troponin I , although in comparison , median levels of brain natriuretic factor , soluble fms-like tyrosine kinase receptor-1 , troponin I , and creatinine were greater in HF-REF and HF-PEF patients . In unadjusted Cox models over a maximum follow-up of 8.9 years , the hazard ratio for death , transplantation , or ventricular assist device placement in HF-REF patients was 4.1 ( 95 % confidence interval , 2.4–6.8 ; P<0.001 ) and in HF-PEF patients was 2.3 ( 95 % confidence interval , 1.2–4.5 ; P=0.013 ) compared with HF-Recovered patients . The unadjusted hazard ratio for cardiac hospitalization in HF-REF patients was 2.0 ( 95 % confidence interval , 1.5–2.7 ; P<0.001 ) and in HF-PEF patients was 1.3 ( 95 % confidence interval , 0.90–2.0 ; P=0.15 ) compared with HF-Recovered patients . Results were similar in adjusted models . Conclusions — HF-Recovered is associated with a better biomarker profile and event-free survival than HF-REF and HF-PEF . However , these patients still have abnormalities in biomarkers and experience a significant number of HF hospitalizations , suggesting persistent HF risk AIMS Some patients show such an important clinical improvement and reverse remodelling after cardiac resynchronization therapy ( CRT ) that anatomy and function approach normal . These patients have been called ' super-responders ' . The aim of our study was to identify predictors of becoming a super-responder after CRT . METHODS AND RESULTS Eighty-seven consecutive patients who underwent CRT were prospect ively studied . Before CRT and 6 months after , clinical and echocardiographic evaluation was performed . Patients with a decrease in New York Heart Association functional class > or=1 , a two-fold or more increase of left ventricular ejection fraction ( LVEF ) or a final LVEF > 45 % , and a decrease in LV end-systolic volume > 15 % were classified as super-responders . There were 12 % super-responders . At baseline , there were no significant differences between super-responders and the other patients , except for the fact that super-responders had significantly smaller mitral regurgitation and LV end-diastolic diameter ( LVEDD ) and a shorter duration of heart failure symptoms . Mitral regurgitation jet area , LVEDD , and duration of heart failure symptoms were correlated with this super-response . Moreover , an evolution of symptoms for < 12 months was an independent predictor of super-response to CRT . CONCLUSION Patients in earlier phases of the cardiomyopathy , with a less altered ventricular geometry , seem to have a greater probability of becoming super-responders AIMS The aim of this study was to determine the relationship between improved ejection fraction ( EF ) and occurrence of arrhythmias in patients with cardiac resynchronization therapy devices with defibrillator function ( CRT-D ) . The hypothesis was that patients who experienced a marked improvement in EF also had fewer appropriate defibrillator interventions . METHODS AND RESULTS We analysed data of 270 patients from 2 prospect i ve registries with follow-up of ≥12 months and echocardiography performed ≥8 months after CRT-D implantation . The discriminator was whether left ventricular ejection fraction ( LVEF ) improved to > 35 % [ cut-off for primary prevention implantable cardioverter-defibrillator ( ICD ) implantation ] . Mean age was 61±11 years , LVEF 22±5 % , and follow-up 40±22 months . Ischaemic cardiomyopathy was present in 48 % , and secondary prevention indication was present in 25 % . Implantable cardioverter-defibrillator interventions were delivered to 35 % of patients . Echocardiography ( 20±15 months after implantation ) showed an improvement in LVEF from 22 % ( SD 5.4 % ) to 30 % ( SD 9.8 % ) . Improvement to > 35 % was seen in 21 % of patients . Those who improved to > 35 % had fewer ICD interventions than those who did not ( 23 vs.38 % ; P-value 0.03 ) . Analysing only patients with a primary prevention indication and stratifying again in patients with and without improvement of LVEF to > 35 % , the latter had highly significant more ICD-therapies ( 6 vs. 31 % ; P-value 0.0008 ) . CONCLUSION Patients with CRT-D for primary prevention , whose LVEF improved to > 35 % during mid-term follow-up , are at low risk of first ICD therapies beyond year 1 . If similar findings are reported in other patient cohorts , this might impact on decision-making at the time of battery depletion BACKGROUND As left ventricular ejection fraction ( LVEF ) may improve , worsen , or remain the same over time , patients ' prognosis may also be expected to change because of the change in LVEF , among other factors . OBJECTIVE To evaluate the effect of LVEF change on outcome in the Defibrillators in Non-Ischemic Cardiomyopathy Treatment Evaluation ( DEFINITE ) trial . METHODS Patients with nonischemic cardiomyopathy with LVEF<36 % , history of symptomatic heart failure , and the presence of significant ventricular ectopic activity were enrolled in the DEFINITE trial . Follow-up LVEF measurements were obtained annually in only a minority ( 17 % ) of trial participants . This study therefore evaluated survival and arrhythmic end points in patients whose LVEF was reassessed between 90 and 730 days after enrollment . RESULTS During the 90 - 730-day postr and omization period , 187 of 449 ( 42 % ) enrolled patients who survived at least 90 days had at least 1 follow-up LVEF measurement ; these patients were younger and white ; had diabetes , better 6-minute walk test results , and higher BMI ; were more likely to have appropriate shocks ; and had fewer deaths compared to those without follow-up LVEF measurements . Patients whose LVEF improved had reduced mortality compared to patients whose LVEF decreased ( hazard ratio 0.09 ; 95 % confidence interval 0.02 - 0.39 ; P = .001 ) . Survival free of appropriate shocks was not significantly related to LVEF improvement during follow-up . CONCLUSIONS LVEF improvement was associated with improved survival , but not with a significant decrease in appropriate shocks . These data highlight that appropriate caution should be exercised not to extrapolate the positive effect of improved LVEF to the elimination of arrhythmic events In recent years , several clinical trials conducted on selected middle-aged patients have documented the positive effects of new pharmacologic and nonpharmacologic treatment on chronic heart failure ( HF ) . More recently , some investigators reported cases of elderly patients who had improved clinical conditions and left ventricular ( LV ) systolic function , but neither the prevalence nor the clinical variables associated with this phenomenon have ever been characterized in this population . To assess the prevalence and the predictors of " improvement " of HF , we prospect ively analyzed 87 patients with a recent diagnosis of HF and LV systolic dysfunction , aged > 70 years , who were consecutively admitted to our center for functional class impairment ( New York Heart Association class III and IV ) . After discharge , patients underwent clinical and echocardiographic evaluations every 6 months . During follow-up ( 17 + /- 9 months ) improvement was documented in 31 subjects ( 36 % ) . The variables associated with improvement in the multivariate analysis were the absence of diabetes ( odds ratio [ OR ] 5.1 , 95 % confidence interval [ CI ] 1.3 to 19.9 , p = 0.007 ) , history of arterial hypertension ( OR 3.9 , CI 1.3 to 11.1 , p = 0.01 ) , and beta-blocker therapy ( OR 3.4 , CI 1.1 to 10.8 , p = 0.03 ) . An improvement in clinical status and LV systolic function is not infrequently observed in patients > 70 years of age who have a recent diagnosis of HF . This behavior occurs prevalently in patients receiving beta-blocker therapy who have a history of arterial hypertension , and is inversely related to the presence of diabetes mellitus INTRODUCTION Cardiac resynchronization ( CRT ) affects reverse anatomical remodeling in patients with heart failure . CRT has also been associated with fewer ventricular arrhythmias and reduced sudden death in some clinical trials , but the predictors and mechanism of the antiarrhythmic actions of CRT have not been well defined . The purpose of this study is to investigate the relationship of reverse anatomical remodeling to ventricular arrhythmias in CRT patients . METHODS AND RESULTS A retrospective analysis was performed of the InSync III Marquis study , a prospect i ve , r and omized , multicenter CRT trial . Echocardiographic data from 198 patients were obtained at baseline and after 6 months of CRT , and anatomical responders were defined as a reduction in left ventricular end systolic volume ( LVESV ) of > or=15 % . Anatomical responders ( n = 71 , 36 % ) demonstrated 29 % fewer single premature ventricular contractions beats ( PVCs ) ( P = 0.0001 ) , 48 % fewer PVC runs ( p = 0.0096 ) , and fewer treated episodes of ventricular tachycardia or fibrillation ( VT/VF ) ( P = 0.050 ) than nonresponders . Multiple regression analysis demonstrated that responder status significantly predicted single PVCs and PVC runs . Gender was the most important predictor of treated VT/VF with females having no episodes over 6 months of follow-up . CONCLUSIONS Anatomic responders to CRT demonstrate significantly fewer single PVCs and runs of PVCs . The implication of these observations is that anatomic remodeling is linked to electrical remodeling AIMS To evaluate the long-term changes of clinical and echocardiographic parameters , the incidence of cardiac events and parameters associated with late cardiac events in ' super-responders ' to cardiac resynchronization therapy ( CRT ) with [ CRT defibrillator ( CRT-D ) ] or without defibrillator back-up . METHODS AND RESULTS In all consecutive patients treated with CRT in two Italian centres ( Trieste and Udine ) with left ventricular ejection fraction ( LVEF ) ≤0.35 at implantation ( Timp ) and LVEF > 0.50 1 and /or 2 years ( Tnorm ) after implantation , the long-term outcome and the evolution of echocardiographic parameters were assessed ; factors associated with a higher risk of cardiac events , defined as hospitalization or death for heart failure ( HF ) , sudden death , or CRT-D appropriate interventions , were also analysed . Among the 259 patients evaluated , 62 ( 24 % ) had LVEF ≥ 0.50 at Tnorm ( n = 44 with at 1 year , n = 18 at 2 years ) . During a mean follow-up of 68 ± 30 months , one cardiac death ( for HF ) and eight cardiovascular events ( two hospitalization for HF and six appropriate CRT-D interventions ) occurred . At the last echo evaluation ( Tfup ) performed 51 ± 26 months after Timp , LVEF was < 0.50 in five patients ( > 0.45 in four of them ) . At univariable analysis , only LV end-systolic volume evaluated at Tfup was associated with a higher risk of cardiac events during follow-up . CONCLUSION In ' super-responders ' to CRT long-term outcome is excellent . However , cardiac events , mainly CRT-D appropriate interventions , can occur despite the persistence of LVEF > 0.50 . Early identification of these patients is still an unsolved issue |
10,701 | 26,862,005 | Conclusions : Accumulated evidence from prospect i ve cohort studies suggests that dairy consumption is inversely and longitudinally associated with the risk of childhood overweight/obesity . | Background / Objectives : Data from small-scale , short-term , clinical trials suggest a beneficial effect of dairy consumption on the risk of childhood obesity ; however , the long-term association is unclear . | OBJECTIVE To establish the first baseline of dairy and related nutrient intake in African Americans , an at-risk population of public health concern in the United States . To document dairy consumption in African Americans by age and sex during 1994 - 1998 and 1999 - 2000 and compare it with concomitant dairy , calcium , and related nutrient intakes in non-African-American adults and children . DESIGN Duplicate and single 24-hour recalls were analyzed to determine dietary intake during the Continuing Survey of Food Intakes by Individuals 1994 - 1996 , 1998 ( CSFII ) , and the National Health and Nutrition Examination Survey 1999 - 2000 ( NHANES ) , respectively . SUBJECTS African Americans and non-African Americans of all ages who participated in CSFII 1994 - 1996 , 1998 , and in NHANES 1999 - 2000 ; both surveys are a stratified r and om sample of the total civilian , noninstitutionalized US population . STATISTICAL ANALYSIS Dairy food and nutrient intake per day were quantified according to age , sex , and ethnicity/race from CSFII 1994 - 1996 , 1998 , and NHANES 1999 - 2000 . For NHANES , mean intakes from 1-day food records were sample -weighted , and st and ard errors estimated by the Taylor linearization method of SUDAAN ( version 9.0 , 2004 , RTI International , Research Triangle Park , NC ) . Usual daily intakes of calcium , magnesium , and phosphorus were based on 2-day intake data from CSFII 1994 - 1996 , 1998 , and calculated using Software for Intake Distribution from Iowa State University . The percentage of individuals categorized as not meeting the Estimated Average Requirement for magnesium and phosphorus were calculated in the same way . RESULTS CSFII 1994 - 1996 , 1998 , and NHANES 1999 - 2000 data both show that African Americans in all age groups consume fewer mean servings per day of total dairy , milk , cheese , and yogurt than non-African Americans , and have lower mean intakes of calcium , magnesium , and phosphorus . Significant differences were seen for men and women . CONCLUSIONS In this analysis , young African-American women did not meet Dietary Reference Intakes for phosphorus , and all African Americans did not meet Dietary Reference Intakes for calcium and magnesium . African Americans in all age groups did not meet dairy recommendations from the 2005 US Dietary Guidelines and the 2004 National Medical Association Consensus Report on the role of dairy and dairy nutrients in the diet of African Americans BACKGROUND Increased intake of sugar-sweetened beverages and fruit juice has been associated with overweight in children . OBJECTIVE This study prospect ively assessed beverage consumption patterns and their relationship with weight status in a cohort of children born at different risk for obesity . METHODS AND PROCEDURES Participants were children born at low risk ( n = 27 ) or high risk ( n = 22 ) for obesity based on maternal prepregnancy BMI ( kg/m(2 ) ) . Daily beverage consumption was generated from 3-day food records from children aged 3 - 6 years and coded into seven beverage categories ( milk , fruit juice , fruit drinks , caloric and non-caloric soda , soft drinks including and excluding fruit juice ) . Child anthropometric measures were assessed yearly . RESULTS High-risk children consumed a greater percentage of daily calories from beverages at age 3 , more fruit juice at ages 3 and 4 , more soft drinks ( including fruit juice ) at ages 3 - 5 , and more soda at age 6 compared to low-risk children . Longitudinal analyses showed that a greater 3-year increase in soda intake was associated with an increased change in waist circumference , whereas a greater increase in milk intake was associated with a reduced change in waist circumference . There was no significant association between change in intake from any of the beverage categories and change in BMI z-score across analyses . DISCUSSION Children 's familial predisposition to obesity may differentially affect their beverage consumption patterns . Future research should examine the extent to which dietary factors may play a role in pediatric body fat deposition over time BACKGROUND During the nutrition transition in Chile , dietary changes were marked by increased consumption of high-energy , nutrient-poor products , including sugar-sweetened beverages ( SSBs ) . Obesity is now the primary nutritional problem in posttransitional Chile . OBJECTIVE We conducted a r and omized controlled trial to examine the effects on body composition of delivering milk beverages to the homes of overweight and obese children to displace SSBs . DESIGN We r and omly assigned 98 children aged 8 - 10 y who regularly consumed SSBs to intervention and control groups . During a 16-wk intervention , children were instructed to drink 3 servings/d ( approximately 200 g per serving ) of the milk delivered to their homes and to not consume SSBs . Body composition was measured by dual-energy X-ray absorptiometry . Data were analyzed by multiple regression analysis according to the intention-to-treat principle . RESULTS For the intervention group , milk consumption increased by a mean ( + /- SEM ) of 452.5 + /- 37.7 g/d ( P < 0.0001 ) , and consumption of SSBs decreased by -711.0 + /- 33.7 g/d ( P < 0.0001 ) . For the control group , milk consumption did not change , and consumption of SSBs increased by 71.9 + /- 33.6 g/d ( P = 0.04 ) . Changes in percentage body fat , the primary endpoint , did not differ between groups . Nevertheless , the mean ( + /- SE ) accretion of lean body mass was greater ( P = 0.04 ) in the intervention ( 0.92 + /- 0.10 kg ) than in the control ( 0.62 + /- 0.11 kg ) group . The increase in height was also greater ( P = 0.01 ) in the intervention group ( 2.50 + /- 0.21 cm ) than in the control group ( 1.77 + /- 0.20 cm ) for boys but not for girls . CONCLUSION Replacing habitual consumption of SSBs with milk may have beneficial effects on lean body mass and growth in children , despite no changes in percentage body fat . This trial was registered at clinical trials.gov as NCT00149695 BACKGROUND Little is known about the relative effectiveness of calcium supplementation from food or pills with or without vitamin D supplementation for bone mass accrual during the rapid growth period . OBJECTIVE The purpose was to examine the effects of both food-based and pill supplements of calcium and vitamin D on bone mass and body composition in girls aged 10 - 12 y. DESIGN This placebo-controlled intervention trial r and omly assigned 195 healthy girls at Tanner stage I-II , aged 10 - 12 y , with dietary calcium intakes < 900 mg/d to 1 of 4 groups : calcium ( 1000 mg ) + vitamin D3 ( 200 IU ) , calcium ( 1000 mg ) , cheese ( 1000 mg calcium ) , and placebo . Primary outcomes were bone indexes of the hip , spine , and whole body by dual-energy X-ray absorptiometry and of the radius and tibia by peripheral quantitative computed tomography . RESULTS With the use of intention-to-treat or efficacy analysis , calcium supplementation with cheese result ed in a higher percentage change in cortical thickness of the tibia than did placebo , calcium , or calcium + vitamin D treatment ( P = 0.01 , 0.038 , and 0.004 , respectively ) and in higher whole-body bone mineral density than did placebo treatment ( P = 0.044 ) when compliance was > 50 % . With the use of a hierarchical linear model with r and om effects to control for growth velocity , these differences disappeared . CONCLUSIONS Increasing calcium intake by consuming cheese appears to be more beneficial for cortical bone mass accrual than the consumption of tablets containing a similar amount of calcium . Diverse patterns of growth velocity may mask the efficacy of supplementation in a short-term trial of children transiting through puberty Evidence of an association between milk intake and childhood adiposity remains inconsistent , with few data available regarding the effects of the amount of dairy fat consumed . This study examined the relation between dairy consumption ( total , full , and reduced fat ) at age 10 y on risk of excess adiposity at age 13 y in participants of the Avon Longitudinal Study of Parents and Children ( ALSPAC ; n = 2455 ) . Intakes were assessed by 3-d dietary records . Total body fat mass ( TBFM ) using dual-energy X-ray absorptiometry was examined at 13 y. Outcomes included excess TBFM ( top quintile of TBFM ) , overweight , and change in body mass index ( BMI ) . The highest vs. lowest quartile of total dairy consumers ( g/d ) at age 10 y did not have an increased risk of excess TBFM ( OR : 0.73 ; 95 % CI : 0.46 , 1.16 ; P-trend = 0.28 ) or overweight ( OR : 0.69 ; 95 % CI : 0.41 , 1.15 ; P = 0.24 ) at age 13 y. Children in the highest quartile of full-fat dairy intakes vs. those in the lowest quartile had a reduced risk of excess TBFM ( OR : 0.64 ; 95 % CI : 0.41 , 1.00 ; P = 0.04 ) and a suggestion of a reduction in overweight ( OR : 0.65 ; 95 % CI : 0.40 , 1.06 ; P = 0.19 ) at age 13 y. Furthermore , the highest vs. lowest consumers of full-fat products had smaller gains in BMI during follow-up [ 2.5 kg/m2 ( 95 % CI : 2.2 , 2.7 ) vs. 2.8 kg/m2 ( 95 % CI : 2.5 , 3.0 ) ; P < 0.01 ] . Associations with reduced-fat dairy consumption did not attain statistical significance . In this study , dairy consumption was not related to excess fat accumulation during late childhood . Estimates had wide confidence limits but generally showed inverse relations between dairy intakes and risk of excess adiposity . Additional prospect i ve research is warranted to confirm the effects of dairy intake on obesity in children OBJECTIVE To determine whether the quantity and type of milk ( whole , reduced fat , or 1%/nonfat ) consumed at age 2 years is associated with adiposity at age 3 years . DESIGN We assessed milk and dairy intake at age 2 years with food frequency question naires completed by mothers . Our primary outcomes were body mass index ( BMI ; calculated as kg/m(2 ) ) , z score and overweight at age 3 years , defined as BMI for age and sex > or=85th percentile . SUBJECTS/ SETTING Eight-hundred and fifty-two preschool-aged children in the prospect i ve US cohort Project Viva . STATISTICAL ANALYSES Linear and logistic regression models , adjusting for maternal BMI and education , paternal BMI , and child age , sex , race/ethnicity , intake of energy , nondairy beverages , television viewing , and BMI z score at age 2 years were used . RESULTS At age 2 years , mean milk intake was 2.6 ( st and ard deviation 1.2 ) servings per day . Higher intake of whole milk at age 2 , but not reduced-fat milk , was associated with a slightly lower BMI z score ( -0.09 unit per daily serving [ 95 % confidence interval : -0.16 to -0.01 ] ) at age 3 years ; when restricted to children with a normal BMI ( 5th to < 85th percentile ) at age 2 years , the association was null ( -0.05 unit per daily serving [ 95 % confidence interval : -0.13 to 0.02 ] ) . Intake of milk at age 2 years , whether full- or reduced-fat , was not associated with risk of incident overweight at age 3 years . Neither total milk nor total dairy intake at age 2 years was associated with BMI z score or incident overweight at age 3 years . CONCLUSION Neither consuming more dairy products , nor switching from whole milk to reduced-fat milk at age 2 years , appears likely to prevent overweight in early childhood Observational studies of dietary patterns and growth and studies with milk supplementation have shown that children consuming diets containing animal source foods grow better . This study evaluates the growth of 544 Kenyan schoolchildren ( median age 7.1 y ) after 23 mo of food supplementation with a meat , milk or energy supplement ( approximately 1255 kJ ) compared to a control group without a supplement . Multivariate analyses controlled for covariates compared gain in weight , height , weight-for-height Z-score ( WHZ ) , height-for-age Z-score ( HAZ ) , mid-upper-arm circumference , triceps and subscapular skinfolds , mid-upper-arm muscle and mid-upper-arm fat area . Children in each of the supplementation groups gained approximately 0.4 kg ( 10 % ) more weight than children in the Control group . Children in the Meat , Milk and Energy groups gained 0.33 , 0.19 and 0.27 cm more , respectively , in mid-upper-arm circumference than children in the Control group . Children who received the Meat supplement gained 30 - 80 % more mid-upper-arm muscle area than children in the other groups , and children who received the milk supplement gained 40 % more mid-upper-arm muscle area than children who did not receive a supplement . No statistically significant overall effects of supplementation were found on height , HAZ , WHZ or measures of body fat . A positive effect of the milk supplement on height gain could be seen in the subgroup of children with a lower baseline HAZ ( < or = -1.4 ) . The results indicate that food supplements had a positive impact on weight gain in the study children and that the addition of meat increased their lean body mass Background / objectives : Few studies have investigated the associations between flavored milk consumption and body composition in children . We aim ed to examine the prospect i ve relationships between flavored milk consumption and body fat . Subjects/ methods : Subjects included 2270 children from the Avon Longitudinal Study of Parents and Children . Flavored milk consumption at age 10 years was assessed using dietary records ; consumption was dichotomized as consumers and non-consumers . Percent body fat was measured using dual-energy X-ray absorptiometry at 11 and 13 years . Body weight at 11 and 13 years was included as a secondary outcome . Associations were also examined in a subset of plausible reporters to evaluate the influence of dietary reporting errors . There was an effect of interaction between flavored milk and baseline weight on body fat ( P-interaction < 0.02 ) . Results : In plausible reporters , overweight/obese children who consumed flavored milk had less favorable changes in body fat compared with non-consumers ( adjusted means : −0.16 % , 95 % CI : −3.8 , 3.5 vs −3.4 % , 95 % CI : −6.5 , −0.42 , P=0.02 ) . Similar associations with body weight were observed . The adjusted mean percent body fat for overweight/obese girls who consumed flavored milk was greater at age 13 compared with 11 years ( 39.7 % , 95 % CI : 32 , 47 vs 38.3 % , 95 % CI : 32 , 44 ) . The mean percent body fat for overweight/obese boys was similar between consumers and non-consumer is at 13 years ( 30.4 % , 95 % CI : 20 , 41 vs 30.1 % , 95 % CI : 21 , 40 ) . Conclusions : Overweight/obese children who consumed flavored milk had less favorable changes in body composition over time . Although more research is needed , discouraging flavored milk consumption may be one beneficial strategy to address childhood obesity Epidemiologic studies report conflicting results for the relationship between milk intake and adiposity in children . We examined prospect i ve and cross-sectional associations between milk intake and percent body fat among 2245 children from the Avon Longitudinal Study of Parents and Children . Cross-sectional analyses were performed at age 13 y between total , full-fat , and reduced-fat milk intake assessed using 3-d dietary records and body fat from DXA . Prospect i ve analyses were conducted between milk intakes at age 10 y and body fat at 11 and 13 y. Models were adjusted for age , sex , height , physical activity , pubertal status , maternal BMI , maternal education , and intakes of total fat , sugar-sweetened beverages , 100 % fruit juice , and ready-to-eat cereals ; baseline BMI was added to prospect i ve models . Subset analyses were performed for those with plausible dietary intakes . Mean milk consumption at 10 and 13 y was ( mean ± SD ) 0.90 ± 0.73 and 0.85 ± 0.78 servings/d [ 1 serving = 8 oz of milk ( 244 g of plain and 250 g flavored milk ) ] , respectively . Cross-sectional results indicated an inverse association between full-fat milk intake and body fat [ β = -0.47 ( 95 % CI = -0.76 , -0.19 ) ; P = 0.001 ] . Milk intake at age 10 y was inversely associated with body fat at 11 y [ β = -0.16 g/d ( 95%CI = -0.28 , -0.04 ) ; P = 0.01 ] , but not among those with plausible dietary intakes , suggesting that this association was influenced by dietary measurement errors . Milk intake was not associated with body fat at age 13 y after adjustment . Although our prospect i ve results corroborate other findings of a null associations between milk intake and adiposity , our inconsistent findings across analyses suggest further investigation is needed to clarify the relation , and accounting for dietary reporting errors is an important consideration We aim ed to prospect ively assess dairy intake among adolescents , and determine the predictors of adequate dairy consumption during adolescence . 634 Sydney schoolchildren ( 351 girls and 283 boys ) who had dietary data at both age 12 and 17 were included for analyses . Dairy consumption was assessed from vali date d semi-quantitative food frequency question naires . At age 12 , mean total dairy intake was 1.62 serves/day which decreased to 1.40 by age 17 ( p<0.0001 ) . Mean serves/day of milk decreased from 1.11 to 0.92 during adolescence . Moreover , 90 % of the decrease in serves/day of total dairy was due to reduced milk consumption . At age 12 , 8.5 % of children consumed > = 3.5 serves/day of total dairy and this decreased to 6.2 % , 5 years later at age 17 ( p=0.001 ) . A lower proportion of girls compared with boys consumed > =3 serves/day of total dairy at both ages 12 ( p=0.005 ) and 17 ( p=0.01 ) . Participants with tertiary qualified parents at baseline were 85 % more likely to have intakes of the dairy food group above the median during the 5 years , OR 1.85 ( 95 % CI 1.18 - 2.91 ) . Frequent flavored milk consumption ( > = 2 serves/week ) at baseline was associated with ~5-fold greater likelihood of maintaining intakes of dairy foods above the median during adolescence . Dairy food consumption decreased significantly during adolescence , driven primarily by a decrease in milk consumption . Most adolescents did not meet national recommended guidelines for the dairy food group intake . These findings highlight the need for further research into intervention strategies aim ed at sustaining dairy consumption OBJECTIVE . Our goal was to test the hypothesis that increased fruit juice intake and parental restriction of children 's eating are associated with increased adiposity gain and whether exposure to nutritional counseling predicted reduced adiposity gain among children . PATIENTS AND METHODS . A sample of parents or guardians of children aged 1 to 4 years who attended 1 of 49 Special Supplemental Nutrition Program for Women , Infants , and Children agencies in New York State were surveyed in 1999 or 2000 ( N = 2801 ) . The survey addressed children 's dietary intake , parental feeding practice s , and parental exposure to nutritional counseling messages to increase fruit , vegetable , and low-fat milk intakes . Each child 's height and weight were measured approximately every 6 months for up to 48 months . A prospect i ve cohort design was used in which survey variables were the predictors and the outcome was change in children 's adiposity , defined as change in age- and gender-st and ardized BMI per month ( ie , BMI z-score slope ) . RESULTS . Controlling for gender and ethnicity , the relationship between juice intake and adiposity gain depended on children 's initial overweight status . Among children who were initially either at risk for overweight or overweight , increased fruit juice intake was associated with excess adiposity gain , whereas parental offerings of whole fruits were associated with reduced adiposity gain . Each additional daily serving of fruit juice was associated with an excess adiposity gain of 0.009 SD per month . Feeding restriction was greater among parents whose children were initially at risk for overweight or overweight compared with those at a healthy weight . Parental exposure to nutritional messages was not associated with reduced child adiposity gain . CONCLUSION . This study supports the Institute of Medicine recommendations to reduce fruit juice intake as a strategy for overweight prevention in high-risk children BACKGROUND Obesity in adolescence has been increasing in the past several decades . Beverage habits among adolescents include increased consumption of sugar-sweetened beverages and decreased consumption of milk . OBJECTIVE This study aim ed to examine the association between beverage consumption and 5-y body weight change in 2294 adolescents . DESIGN Project EAT ( Eating Among Teens ) is a 5-y longitudinal study of eating patterns among adolescents . Surveys were completed in 1998 - 1999 ( time 1 ) and in 2003 - 2004 ( time 2 ) . Multivariable linear regression was used to examine the association between beverage consumption at time 2 and change in body mass index from time 1 to time 2 , with adjustments for age , socioeconomic status , race , cohort , physical activity , sedentary behavior , coffee , tea , time 1 body mass index , and beverage variables . RESULTS In prospect i ve analyses , consumption of beverages was not associated with weight gain , except for consumption of low-calorie soft drinks ( positive association , P = 0.002 ) and white milk ( inverse association , P = 0.03 ) , but these associations did not appear to be a monotonic linear dose-response relation . The positive association with low-calorie soft drinks was no longer present after adjustment for dieting and parental weight-related concerns , which suggests that the use of low-calorie soft drinks is a marker for more general dietary behaviors and weight concerns . CONCLUSIONS We showed no association between sugar-sweetened beverage consumption , juice consumption , and adolescent weight gain over a 5-y period . A direct association between diet beverages and weight gain appeared to be explained by dieting practice s. Adolescents who consumed little or no white milk gained significantly more weight than their peers who consumed white milk . Future research that examines beverage habits and weight among adolescents should address portion sizes , adolescent maturation , and dieting behaviors OBJECTIVE To examine prospect ively the association between beverage consumption ( fruit juice , fruit drinks , milk , soda , and diet soda ) and changes in weight and body mass index among preschool children . DESIGN A prospect i ve cohort study that collected dietary , anthropometric , and sociodemographic data .Subjects/ Setting The study population included 1,345 children age 2 to 5 years participating in the North Dakota Special Supplemental Nutrition Program for Women , Infants , and Children ( WIC ) on two visits between 6 to 12 months apart . Statistical analyses We performed linear regression analyses to examine whether beverage consumption was associated with annual change in weight and body mass index . Intakes were measured as continuous ( oz/day ) and we also dichotomized fruit juice , fruit drinks , and milk at high intakes . RESULTS In multivariate regression analyses adjusted for age , sex , energy intake , change in height , and additional sociodemographic variables , weight change was not significantly related to intakes ( per ounce ) of fruit juice ( beta=0.01 lb/year , 95 % CI : -0.01 to 0.20 , P=.28 ) , fruit drinks ( beta=-0.03 lb/year , 95 % CI : -0.07 to 0.01 , P=.28 ) , milk ( beta=0.00 lb/year , 95 % CI : -0.02 to 0.02 , P=.86 ) , soda ( beta=-0.00 lb/year , 95 % CI : -0.08 to 0.08 , P=.95 ) , or diet soda ( beta=0.01 lb/year , 95 % CI : -0.11 to 0.13 , P=.82 ) . Findings remained null when we examined associations with body mass index and when fruit juice , fruit drinks , and milk were dichotomized at high intake levels in both analyses . CONCLUSIONS Our study does not show an association between beverage consumption and changes in weight or body mass index in this population of low-income preschool children in North Dakota PURPOSE To determine whether a significant relationship exists between fat mass ( FM ) development and physical activity ( PA ) and /or sugar-sweetened drink ( SD ) consumption in healthy boys and girls aged 8 - 19 yr . METHODS A total of 105 males and 103 females were assessed during childhood and adolescence for a maximum of 7 yr and a median of 5 yr . Height was measured biannually . Fat-free mass ( FFM ) and FM were assessed annually by dual x-ray absorptiometry ( DXA ) . PA was evaluated two to three times annually using the PAQ-C/A. Energy intake and SD were assessed using a 24-h dietary intake question naire also completed two to three times per year . Years from peak height velocity were used as a biological maturity age indicator . Multilevel r and om effects models were used to test the relationship . RESULTS When controlling for maturation , FFM , and energy intake adjusted for SD , PA level was negatively related to FM development in males ( P<0.05 ) but not in females ( P>0.05 ) . In contrast , there was no relationship between SD and FM development of males or females ( P>0.05 ) . There was also no interaction effect between SD and PA ( P>0.05 ) with FM development . CONCLUSION This finding lends support to the idea that increasing PA in male youths aids in the control of FM development . Models employed showed no relationship between SD and FM in either gender |
10,702 | 28,857,713 | Conclusions The totality of high- quality clinical and cost-effectiveness data supports the use of dalteparin over other low-molecular-weight heparins for preventing recurrent venous thromboembolism in patients with cancer | Background Patients with cancer have an elevated risk of venous thromboembolism .
Importantly , patients with cancer , who have metastatic disease , renal insufficiency , or are receiving anticancer therapy , have an even higher risk of a recurrent event .
Similarly , the risk of recurrent venous thromboembolism is higher than the risk of an initial event .
To reduce the risk , extended duration of prophylaxis for up to six months with low-molecular-weight heparins such as dalteparin , enoxaparin , nadroparin , and tinzaparin is recommended by international guidelines .
In this paper , the clinical and economic literature is review ed to provide evidence d based recommendations based on clinical benefit and economic value . | BACKGROUND The use of warfarin sodium for treating venous thromboembolism in patients with cancer is associated with a significant risk of recurrence and bleeding . The use of low-molecular-weight heparin sodium for secondary prevention of venous thromboembolism in cancer patients may reduce the complication rate . OBJECTIVE To determine whether a fixed dose of subcutaneous low-molecular-weight heparin is superior to oral warfarin for the secondary prophylaxis of venous thromboembolism in patients with cancer and venous thromboembolism . METHODS In a r and omized , open-label multicenter trial performed between April 1995 and March 1999 , we compared subcutaneous enoxaparin sodium ( 1.5 mg/kg once a day ) with warfarin given for 3 months in 146 patients with venous thromboembolism and cancer . MAIN OUTCOME MEASURE A combined outcome event defined as major bleeding or recurrent venous thromboembolism within 3 months . RESULTS Of the 71 evaluable patients assigned to receive warfarin , 15 ( 21.1 % ; 95 % confidence interval [ CI ] , 12.3%-32.4 % ) experienced one major outcome event compared with 7 ( 10.5 % ) of the 67 evaluable patients assigned to receive enoxaparin ( 95 % CI , 4.3%-20.3 % ; P = .09 ) . There were 6 deaths owing to hemorrhage in the warfarin group compared with none in the enoxaparin group . In the warfarin group , 17 patients ( 22.7 % ) died ( 95 % CI , 13.8%-33.8 % ) compared with 8 ( 11.3 % ) in the enoxaparin group ( 95 % CI , 5.0%-21.0 % ; P = .07 ) . No difference was observed regarding the progression of the underlying cancer or cancer-related death . CONCLUSIONS These results confirm that warfarin is associated with a high bleeding rate in patients with venous thromboembolism and cancer . Prolonged treatment with low-molecular-weight heparin may be as effective as oral anticoagulants and may be safer in these cancer patients Background Patients with cancer are at increased risk of venous thromboembolism ( VTE ) and the risk is further elevated after a primary VTE . To reduce the risk of recurrent events , extended prophylaxis with vitamin K antagonists ( VKA ) is available for use . However , in a large r and omized trial ( Comparison of Low-Molecular-Weight Heparin versus Oral Anticoagulant Therapy for the Prevention of Recurrent Venous Thromboembolism in Patients with Cancer [ CLOT ] ; Lee et al ) , extended duration dalteparin reduced the relative risk of recurrent VTE by 52 % compared to VKA ( p=0.002 ) . A recent subgroup analysis of patients with moderate-to-severe renal impairment also revealed lower absolute VTE rates with dalteparin ( 3 % vs. 17 % ; p=0.011 ) . To measure the economic value of dalteparin as an alternative to VKA , a patient-level cost utility analysis was conducted from a Canadian perspective . Methods Re source use data captured during the CLOT trial were extracted and linked to 2015 Canadian unit cost estimates . Health state utilities were then measured using the Time-Trade-Off technique in 24 r and omly selected members of the general Canadian public to estimate the gains in quality -adjusted life years ( QALYs ) . Results For the entire CLOT trial population ( n=676 ) , the dalteparin group had significantly higher mean costs compared to the VKA group ( $ Can5,771 vs. $ Can2,569 ; p<0.001 ) . However , the utility assessment revealed that 21 of 24 respondents ( 88 % ) selected dalteparin over VKA , with an associated gain of 0.14 ( 95 % confidence interval [ CI ] : 0.10–0.18 ) QALYs . When the incremental cost of dalteparin was combined with the QALY gain , dalteparin had a cost of $ Can23,100 ( 95 % CI : $ Can19,200–$Can25,800 ) per QALY gained . The analysis in patients with renal impairment suggested even better economic value with the cost per QALY gained being < $ 14,000 . Conclusion Extended duration dalteparin is a cost-effective alternative to VKA for the prevention of recurrent VTE in patients with cancer , especially in those with renal impairment This study evaluated enoxaparin alone versus initial enoxaparin followed by warfarin in secondary prevention of venous thromboembolic events in adults with active malignancy . Cancer patients ( n = 122 ) with acute symptomatic venous thromboembolic events were r and omly allocated to receive subcutaneous enoxaparin 1.0 mg/kg every 12 hours for 5 days , followed by 1.0 mg/kg daily ( group 1a ) or 1.5 mg/kg daily ( group 1b ) for 175 days , or subcutaneous enoxaparin 1.0 mg/kg every 12 hours for at least 5 days and until a stable international normalized ratio of 2 to 3 was achieved on oral warfarin begun on day 2 and continued to day 180 ( group 2 ) . There were no significant differences in major and minor bleeding rates between treatment groups . No bleeding events were intracranial or fatal . Enoxaparin treatment was feasible , generally well tolerated , and effective for a 180-day period in the secondary prevention of venous thromboembolic events in patients with active malignancy OBJECTIVE To determine the cost and cost effectiveness of adding venous thromboembolism ( VTE ) prophylaxis with enoxaparin , a low-molecular-weight heparin , to st and ard care for acutely ill , hospitalized medical patients . METHODS A pharmacoeconomic model was developed to simulate the 6- to 14-day course of enoxaparin prophylaxis evaluated in the MEDENOX trial in a US healthcare setting . Clinical results as reported for the trial were applied to re source use and treatment costs in a US healthcare environment . The model projects hospital length of stay and cost for an acute medical admission from a third-party payer perspective , as well as costs for the course of enoxaparin . RESULTS VTE prophylaxis with enoxaparin would account for 1.2 % to 2.4 % of the cost of a hospital admission , with an additional $ 23 + /- $ 28 to $ 99 + /- $ 122 to complete the course of prophylaxis out of hospital . Incremental cost effectiveness of VTE prophylaxis relative to no prophylaxis ranges from $ 1249 to $ 3088 per VTE avoided . Venous thromboembolism prophylaxis appears to be a break-even intervention , with the cost recouped through avoided treatment , if the rate of treated VTE without prophylaxis is at least 3 - 4 % . DISCUSSION AND CONCLUSIONS The MEDENOX trial demonstrated that prophylaxis with enoxaparin substantially decreases the risk of VTE among acutely ill , hospitalized medical patients . Economic analysis indicates that this protection represents a small increase in current treatment costs . Prophylaxis is cost effective in terms of incremental cost per VTE avoided . Furthermore , there is a reasonable likelihood that the cost of prophylaxis will be offset by avoided future VTE treatment Background : In a r and omized trial ( ie , Comparison of Low-Molecular-Weight Heparin versus Oral Anticoagulant Therapy for the Prevention of Recurrent Venous Thromboembolism in Patients with Cancer [ CLOT ] ) that evaluated secondary prophylaxis of recurrent venous thromboembolism ( VTE ) in patients with cancer , dalteparin reduced the relative risk by 52 % compared to oral vitamin K antagonists ( VKAs ; hazard ratio = 0.48 , P = .002 ) . A recent subgroup analysis in patients with moderate to severe renal impairment also revealed lower absolute VTE rates with dalteparin ( 3 % vs 17 % ; P = .011 ) . To measure the economic value of dalteparin in these population s , a pharmacoeconomic analysis was conducted from the Dutch health-care system perspective . Methods : Re source utilization data contained within the CLOT trial data base were extracted and converted into direct cost estimates . Univariate analysis was then conducted to compare the total cost of therapy between patients r and omized to dalteparin or VKA therapy . Health state utilities were then measured in 24 members of the general public using the time trade-off technique . Results : When all of the cost components were combined for the entire population ( n = 676 ) , the dalteparin group had significantly higher overall costs than the VKA control group ( dalteparin = € 2375 vs VKA = € 1724 ; P < .001 ) . However , dalteparin was associated with a gain of 0.14 ( 95 % confidence interval [ CI ] : 0.10 - 0.18 ) quality -adjusted life years ( QALYs ) over VKA . When the incremental cost was combined with the utility gain , dalteparin had a cost of € 4,697 ( 95 % CI : € 3824-€4951 ) per QALY gained . Conclusion : Secondary prophylaxis with dalteparin is a cost-effective alternative to VKA for the prevention of recurrent VTE in patients with cancer OBJECTIVE To evaluate whether low-molecular-weight heparin ( LMWH ) could be equally ( or more ) effective than oral anti-vitamin-K agents ( AVK ) in the long-term treatment of deep venous thrombosis ( DVT ) . DESIGN A r and omised , open-label trial . MATERIAL AND METHODS In this trial , 241 patients with symptomatic proximal DVT of the lower limbs confirmed by duplex ultrasound scan were included . After initial LMWH , patients received 6 months of treatment with full therapeutic dosage of tinzaparin or acenocoumarol . The primary outcome was the 12-month incidence of symptomatic recurrent venous thrombo-embolism ( VTE ) . Duplex scans were performed at 6 and 12 months . RESULTS During the 12-month period , six patients ( 5 % ) of 119 who received LMWH and 13 ( 10.7 % ) of 122 who received AVK had recurrent VTE ( p=0.11 ) . In patients with cancer , recurrent VTE tended to be lower in the LMWH group ( two of 36 [ 5.5 % ] ) vs. seven of 33 [ 21.2 % ] ; p=0.06 ) . One major bleeding occurred in the LMWH group and three in the AVK group . Venous re-canalisation increased significantly at 6 months ( 73.1 % vs. 47.5 % ) and at 12 months ( 91.5 % vs. 69.2 % ) in the LMWH group . CONCLUSIONS Tinzaparin was more effective than AVK in achieving re-canalisation of leg thrombi . Long-term tinzaparin was at least as efficacious and safe as AVK for preventing recurrent VTE , especially in patients with cancer Direct oral anticoagulants may be effective and safe for treatment of venous thromboembolism ( VTE ) in cancer patients , but they have not been compared with low-molecular-weight heparin ( LMWH ) , the current recommended treatment for these patients . The Hokusai VTE-cancer study is a r and omised , open-label , clinical trial to evaluate whether edoxaban , an oral factor Xa inhibitor , is non-inferior to LMWH for treatment of VTE in patients with cancer . We present the rationale and some design features of the study . One such feature is the composite primary outcome of recurrent VTE and major bleeding during a 12-month study period . These two complications occur frequently in cancer patients receiving anticoagulant treatment and have a significant impact . The evaluation beyond six months will fill the current gap in the evidence base for the long-term treatment of these patients . Based on the observation that the risk of recurrent VTE in patients with active cancer is similar to that in those with a history of cancer , the Hokusai VTE-cancer study will enrol patients if whose cancer was diagnosed within the past two years . In addition , patients with incidental VTE are eligible because their risk of recurrent VTE is similar to that in patients with symptomatic disease . The unique design features of the Hokusai VTE-cancer study should lead to enrolment of a broad spectrum of cancer patients with VTE who could benefit from oral anticoagulant treatment |
10,703 | 31,012,483 | We found scarcity of evidence about the risk of adverse events for these interventions .
The assessment of non-pharmacological and miscellaneous interventions suggests that there is heterogeneous and even contradictory evidence related to the effectiveness of these prophylactic strategies . | BACKGROUND High altitude illness ( HAI ) is a term used to describe a group of mainly cerebral and pulmonary syndromes that can occur during travel to elevations above 2500 metres ( ˜ 8200 feet ) .
Acute mountain sickness ( AMS ) , high altitude cerebral oedema ( HACE ) , and high altitude pulmonary oedema ( HAPE ) are reported as potential medical problems associated with high altitude ascent .
In this , the third of a series of three review s about preventive strategies for HAI , we assessed the effectiveness of miscellaneous and non-pharmacological interventions .
OBJECTIVES To assess the clinical effectiveness and adverse events of miscellaneous and non-pharmacological interventions for preventing acute HAI in people who are at risk of developing high altitude illness in any setting . | Background Rhodiola crenulata ( R. crenulata ) is widely used to prevent acute mountain sickness in the Himalayan areas and in Tibet , but no scientific studies have previously examined its effectiveness . We conducted a r and omized , double-blind , placebo-controlled crossover study to investigate its efficacy in acute mountain sickness prevention . Methods Healthy adult volunteers were r and omized to 2 treatment sequences , receiving either 800 mg R. crenulata extract or placebo daily for 7 days before ascent and 2 days during mountaineering , before crossing over to the alternate treatment after a 3-month wash-out period . Participants ascended rapidly from 250 m to 3421 m on two separate occasions : December 2010 and April 2011 . The primary outcome measure was the incidence of acute mountain sickness , as defined by a Lake Louise score ≥ 3 , with headache and at least one of the symptoms of nausea or vomiting , fatigue , dizziness , or difficulty sleeping . Results One hundred and two participants completed the trial . There were no demographic differences between individuals taking Rhodiola-placebo and those taking placebo-Rhodiola . No significant differences in the incidence of acute mountain sickness were found between R. crenulata extract and placebo groups ( all 60.8 % ; adjusted odds ratio ( AOR ) = 1.02 , 95 % confidence interval ( CI ) = 0.69–1.52 ) . The incidence of severe acute mountain sickness in Rhodiola extract vs. placebo groups was 35.3 % vs. 29.4 % ( AOR = 1.42 , 95 % CI = 0.90–2.25 ) . Conclusions R. crenulata extract was not effective in reducing the incidence or severity of acute mountain sickness as compared to placebo . Trial registration Clinical Trials.govNCT01536288 The mechanism of high altitude headache ( HAH ) remains unknown . The aim of this study was to determine experimentally whether optic nerve sheath diameter ( ONSD ) , as an indicator of intracranial pressure , is related to HAH . Following sea level measurements at 3 and 12 hours ( SL ) , 23 subjects were passively transported to high altitude ( 3777 m , HA ) via cable car . HAH , ONSD , arterial oxygen saturation ( Spo(2 ) ) , and fluid balance were determined at 3 , 12 , 24 , and 36 hours . After 12 hours exposure to HA , subjects were classified by visual analogue scale ( VAS ) as either HAH positive ( HAH+ ) or HAH negative ( HAH- ) . Acetazolamide ( 250 mg ) or placebo was then r and omly prescribed at 15 , 20 , and 28 hours . Outcome means were compared via analysis of variance , and relationships between variables were analyzed by longitudinal regression . Acetazolamide had no statistically significant effect on HAH ( p=0.63 ) or ONSD ( p=0.98 ) , but produced a negative fluid balance ( p<0.01 ) ( and also increased Spo(2 ) in exploratory analyses ) . Spo(2 ) was lower in HAH+ than HAH- [ 85 (3)% versus 88 (2)% , p=0.03 ) . Nevertheless , ONSD increased similarly in HAH+ and HAH- ( interaction p=0.90 ) . ONSD also remained significantly elevated above SL values for the entire HA period [ SL , 5.2 ( 0.5 ) versus HA , 5.6 ( 0.5 ) mm , p<0.01 ] , despite headache resolving with acclimatization [ VAS : SL , 1/100 ( 3 ) mm versus HA 3 h , 9/100 ( 13 ) ; 12 h , 10/100 ( 14 ) ; 24 h , 8/100 ( 12 ) ; 36 h , 1/100 ( 4 ) mm , p<0.01 ] . Furthermore , HAH was significantly correlated with Spo(2 ) ( β=-1.39 , p<0.01 ) but not with ONSD ( β=0.59 , p=0.57 ) . These data do not support that intracranial pressure is associated with the development or amelioration of mild HAH . Clinical trial registration NCT01288781 Background The aim of this study was to assess the role of intravenous iron supplementation in the prevention of AMS . Material / Methods This was a r and omized , double-blinded , placebo-controlled study . Forty-one ( n=41 ) healthy Chinese low-altitude inhabitants living in Beijing , China ( altitude of about 50 meters ) were r and omly assigned into intravenous iron supplementation ( ISS group ; n=21 ) and placebo ( CON group ; n=20 ) groups . Participants in the ISS group received iron sucrose supplement ( 200 mg ) before flying to Lhasa , China ( altitude of 4300 meters ) . Acute mountain sickness ( AMS ) severity was assessed with the Lake Louise scoring ( LLS ) system within 5 days after l and ing on the plateau ( at high altitude ) . Routine check-ups , clinical biochemistry , and blood tests were performed before departure and 24 h after arrival . Results A total of 38 participants completed the study ( ISS group : n=19 ; CON group : n=19 ) . The rate of subjects with AMS ( LLS>3 ) was lower in the ISS group compared with the CON group , but no significant differences were obtained ( P>0.05 ) . There were no differences in patients ’ baseline characteristics . The physiological indices were similar in both groups except for serum iron concentrations ( 19.44±10.02 vs. 85.10±26.78 μmol/L ) and transferrin saturation rates ( 28.20±12.14 vs. 68.34±33.12 % ) , which were significantly higher in the ISS group ( P<0.05 ) . Finally , heart rate was identified as a contributing factor of LLS . Conclusions These preliminary findings suggest that intravenous iron supplementation has no significant protective effect on AMS in healthy Chinese low-altitude inhabitants A double-blind r and omized study of 45 climbers on Mt. Rainier was conducted to test the effectiveness of antacids in preventing acute mountain sickness . All 45 climbed to 3353 m , and 31 continued to the summit . Ten climbers listed acute mountain sickness as the reason for not attaining the summit . Of symptoms monitored throughout the climb , neither headache , nausea , dizziness , pounding heart , nor shortness of breath differed in severity between antacid-treated and placebo-treated groups . In both groups vital capacity decreased significantly with ascent ( p less than 0.05 ) , while peak flow ( p less than 0.005 ) and minute ventilation ( p less than 0.001 ) increased significantly . The 7 climbers with the most severe AMS symptom scores above 4000 m had significantly lower peak flow at sea level prior to ascent compared with the other 25 climbers who completed sea level tests ( p less than 0.005 ) . The results of this study fail to document efficacy for antacid use for the prevention of acute mountain sickness Acute mountain sickness ( AMS ) is a common and disabling condition that occurs in healthy individuals ascending to high altitude . Based on the ability of iron to influence cellular oxygen sensing pathways , we hypothesized that iron supplementation would protect against AMS . To examine this hypothesis , 24 healthy sea-level residents were r and omized to receive either intravenous iron(III)-hydroxide sucrose ( 200 mg ) or saline placebo , before ascending rapidly to Cerro de Pasco , Peru ( 4340 m ) . The Lake Louise scoring system was used to assess incidence and severity of AMS at sea level and on the first full day at altitude . No significant difference in absolute AMS score was detected between the two groups either at baseline or at high altitude . However , the mean increase in AMS score was 65 % smaller in the iron group than in the saline group ( p<0.05 ) , and the change in AMS score correlated negatively with the change in ferritin ( R=-0.43 ; p<0.05 ) . Hematocrit and arterial oxygen saturation were unaffected by iron . In conclusion , this preliminary r and omized , double-blinded , placebo-controlled trial suggests that intravenous iron supplementation may protect against the symptoms of AMS in healthy volunteers OBJECTIVE To investigate the therapeutic effect of low-concentration of nitroic oxide ( NO ) inhalation in high-altitude pulmonary edema . METHOD Sixty-five male patients with high-altitude pulmonary edema were r and omized into three groups . Patients in the conventional therapy group received oxygen , intravenous furosemide , aminophylline and dexamethasone ; patients in the nifedipine group received oral nifedipine ( 10 mg , tid ) in addition to conventional therapy ; and patients in the NO group received NO ( 10 ppm ) inhalation for 30 min , in addition to oral nifedipine . The time for which pulmonary rales on auscultation and shadows on chest radiograph lasted , and the course of disease , were compared . RESULT In the NO group , pulmonary rales disappeared in 0.4 + /- 0.3 d , shadows on chest radiograph disappeared in 0.6 + /- 0.2 d , and the course of disease was 1.8 + /- 0.7 d , all of which were significantly different from those of the nifedipine group ( 2.4 + /- 1.4 d , 4.1 + /- 1.7 d , 6.8 + /- 1.8 d , respectively ) and the conventional therapy group ( 3.7 + /- 1.2 d , 5.5 + /- 1.8 d , 9.6 + /- 3.1 d , respectively ) . CONCLUSION Low-concentration NO inhalation on the basis of conventional and nifedipine therapies was very effective in the treatment of high-altitude pulmonary edema , which deserves further and larger scale investigation “ Live High-Train Low ” ( LHTL ) training can alter oxidative status of athletes . This study compared prooxidant/antioxidant balance responses following two LHTL protocol s of the same duration and at the same living altitude of 2250 m in either normobaric ( NH ) or hypobaric ( HH ) hypoxia . Twenty-four well-trained triathletes underwent the following two 18-day LHTL protocol s in a cross-over and r and omized manner : Living altitude ( PIO2 = 111.9 ± 0.6 vs. 111.6 ± 0.6 mmHg in NH and HH , respectively ) ; training “ natural ” altitude ( ~1000–1100 m ) and training loads were precisely matched between both LHTL protocol s. Plasma levels of oxidative stress [ advanced oxidation protein products ( AOPP ) and nitrotyrosine ] and antioxidant markers [ ferric-reducing antioxidant power ( FRAP ) , superoxide dismutase ( SOD ) and catalase ] , NO metabolism end-products ( NOx ) and uric acid ( UA ) were determined before ( Pre ) and after ( Post ) the LHTL . Cumulative hypoxic exposure was lower during the NH ( 229 ± 6 hrs . ) compared to the HH ( 310 ± 4 hrs . ; P<0.01 ) protocol . Following the LHTL , the concentration of AOPP decreased ( -27 % ; P<0.01 ) and nitrotyrosine increased ( + 67 % ; P<0.05 ) in HH only . FRAP was decreased ( -27 % ; P<0.05 ) after the NH while was SOD and UA were only increased following the HH ( SOD : + 54 % ; P<0.01 and UA : + 15 % ; P<0.01 ) . Catalase activity was increased in the NH only ( + 20 % ; P<0.05 ) . These data suggest that 18-days of LHTL performed in either NH or HH differentially affect oxidative status of athletes . Higher oxidative stress levels following the HH LHTL might be explained by the higher overall hypoxic dose and different physiological responses between the NH and HH OBJECTIVE Recent trials have demonstrated the usefulness of ibuprofen in the prevention of acute mountain sickness ( AMS ) , yet the proposed anti-inflammatory mechanism remains unconfirmed . Acetaminophen and ibuprofen were tested for AMS prevention . We hypothesized that a greater clinical effect would be seen from ibuprofen due to its anti-inflammatory effects compared with acetaminophen 's mechanism of possible symptom reduction by predominantly mediating nociception in the brain . METHODS A double-blind , r and omized trial was conducted testing acetaminophen vs ibuprofen for the prevention of AMS . A total of 332 non-Nepali participants were recruited at Pheriche ( 4371 m ) and Dingboche ( 4410 m ) on the Everest Base Camp trek . The participants were r and omized to either acetaminophen 1000 mg or ibuprofen 600 mg 3 times a day until they reached Lobuche ( 4940 m ) , where they were reassessed . The primary outcome was AMS incidence measured by the Lake Louise Question naire score . RESULTS Data from 225 participants who met inclusion criteria were analyzed . Twenty-five participants ( 22.1 % ) in the acetaminophen group and 18 ( 16.1 % ) in the ibuprofen group developed AMS ( P = .235 ) . The combined AMS incidence was 19.1 % ( 43 participants ) , 14 percentage points lower than the expected AMS incidence of untreated trekkers in prior studies at this location , suggesting that both interventions reduced the incidence of AMS . CONCLUSIONS We found little evidence of any difference between acetaminophen and ibuprofen groups in AMS incidence . This suggests that AMS prevention may be multifactorial , affected by anti-inflammatory inhibition of the arachidonic-acid pathway as well as other analgesic mechanisms that mediate nociception . Additional study is needed Background — The degree of pulmonary hypertension in healthy subjects exposed to acute hypobaric hypoxia at high altitude was found to be related to increased plasma endothelin (ET)-1 . The aim of the present study was to investigate the effects of ET-1 antagonism on pulmonary hypertension , renal water , and sodium balance under acute and prolonged exposure to high-altitude – associated hypoxia . Methods and Results — In a double-blind fashion , healthy volunteers were r and omly assigned to receive bosentan ( 62.5 mg for 1 day and 125 mg for the following 2 days ; n=10 ) or placebo ( n=10 ) at sea level and after rapid ascent to high altitude ( 4559 m ) . At sea level , bosentan did not induce any significant changes in hemodynamic or renal parameters . At altitude , bosentan induced a significant reduction of systolic pulmonary artery pressure ( 21±7 versus 31±7 mm Hg , P<0.03 ) and a mild increase in arterial oxygen saturation versus placebo after just 1 day of treatment . However , both urinary volume and free water clearance ( H2OCl/glomerular filtration rate ) were significantly reduced versus placebo after 2 days of ET-1 antagonism ( 1100±200 versus 1610±590 mL ; −6.7±3.5 versus −1.8±4.8 mL/min , P<0.05 versus placebo for both ) . Sodium clearance and segmental tubular function were not significantly affected by bosentan administration . Conclusions — The present results indicate that the early beneficial effect of ET-1 antagonism on pulmonary blood pressure is followed by an impairment in volume adaptation . These findings must be considered for the prevention and treatment of acute mountain sickness Bloch , Konrad E. , Alex and er J. Turk , Marco Maggiorini , Thomas Hess , Tobias Merz , Martina M. Bosch , Daniel Barthelmes , Urs Hefti , Jacqueline Pichler , Oliver Senn , and Otto D. Schoch . Effect of ascent protocol on acute mountain sickness and success at Muztagh Ata , 7546 m. High Alt . Med . Biol . 10:25 - 32 , 2009.- Data on acclimatization during expedition-style climbing to > 5000 m are scant . We evaluated the hypothesis that minor differences in ascent protocol influence acute mountain sickness ( AMS ) symptoms and mountaineering success in climbers to Muztagh Ata ( 7546 m ) , Western China . We performed a r and omized , controlled trial during a high altitude medical research expedition to Muztagh Ata . Thirty-four healthy mountaineers ( mean age 45 yr , 7 women ) were r and omized to follow one of two protocol s , ascending within 15 or 19 days to the summit of Muztagh Ata at 7546 m , respectively . The main outcome measures , AMS symptom scores and the number of proceeding climbers , were assessed daily . Mean + /- SD AMS-C scores of 16 climbers r and omized to slow ascent were 0.06 + /- 0.18 , 0.26 + /- 0.08 , 0.41 + /- 0.45 , 0.53 + /- 0.77 at camps I ( 5533 m ) , II ( 6265 m ) , III ( 6865 m ) , and the summit ( 7546 m ) , respectively . Corresponding values in 18 climbers r and omized to fast ascent were significantly higher : 0.17 + /- 0.23 , 0.43 + /- 0.75 , 0.49 + /- 0.36 , and 0.69 + /- 0.54 ( p < 0.008 , vs. slow ascent in regression analysis accounting for weather-related protocol deviation ) . Climbers r and omized to slow ascent were able to ascend according to the protocol without AMS for significantly more days than climbers r and omized to fast ascent ( p = 0.04 , Kaplan-Meier analysis ) . More climbers r and omized to slow ascent were successful in reaching the highest camp at 6865 m without AMS ( odds ratio 9.5 ; 95 % confidence interval 1.02 to 89 ) . In climbers ascending to very high altitudes , differences of a few days in acclimatization have a significant impact on symptom severity , the prevalence of AMS , and mountaineering success . Clinical Trials.gov Identifier NCT00603122 Abstract Observations on acute mountain sickness occurring between 11,000 and 18,000 feet , in 1925 men , 18 , to 53 years old , showed no direct relation between altitude and severity of illness ; mild , moderate and severe cases occurred at all altitudes . A time lag of six to 96 hours between arrival and onset of symptoms ruled out any direct relation between hypoxia and acute mountain sickness . During this period there was clinical evidence of respiratory dysfunction with slow , irregular or Cheyne — Stokes breathing , pulmonary congestion and antidiuresis . In one biopsy and two autopsy studies there was evidence of cerebral edema . Diuresis induced with furosemide provided effective routine therapy . Morphine and betamethasone were used as additional aids in severe cases . Clinical features of acute mountain sickness were ascribed to hypoxia , pulmonary congestion , increased cerebral blood flow , increased cerebrospinal-fluid pressure and cerebral edema 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 There is an expectation that repeated daily exposures to normobaric hypoxia ( NH ) will induce ventilatory acclimatization and lessen acute mountain sickness ( AMS ) and the exercise performance decrement during subsequent hypobaric hypoxia ( HH ) exposure . However , this notion has not been tested objective ly . Healthy , unacclimatized sea-level ( SL ) residents slept for 7.5 h each night for 7 consecutive nights in hypoxia rooms under NH [ n = 14 , 24 ± 5 ( SD ) yr ] or " sham " ( n = 9 , 25 ± 6 yr ) conditions . The ambient percent O(2 ) for the NH group was progressively reduced by 0.3 % [ 150 m equivalent ( equiv ) ] each night from 16.2 % ( 2,200 m equiv ) on night 1 to 14.4 % ( 3,100 m equiv ) on night 7 , while that for the ventilatory- and exercise-matched sham group remained at 20.9 % . Beginning at 25 h after sham or NH treatment , all subjects ascended and lived for 5 days at HH ( 4,300 m ) . End-tidal Pco(2 ) , O(2 ) saturation ( Sa(O(2 ) ) ) , AMS , and heart rate were measured repeatedly during daytime rest , sleep , or exercise ( 11.3-km treadmill time trial ) . From pre- to posttreatment at SL , resting end-tidal Pco(2 ) decreased ( P < 0.01 ) for the NH ( from 39 ± 3 to 35 ± 3 mmHg ) , but not for the sham ( from 39 ± 2 to 38 ± 3 mmHg ) , group . Throughout HH , only sleep Sa(O(2 ) ) was higher ( 80 ± 1 vs. 76 ± 1 % , P < 0.05 ) and only AMS upon awakening was lower ( 0.34 ± 0.12 vs. 0.83 ± 0.14 , P < 0.02 ) in the NH than the sham group ; no other between-group rest , sleep , or exercise differences were observed at HH . These results indicate that the ventilatory acclimatization induced by NH sleep was primarily expressed during HH sleep . Under HH conditions , the higher sleep Sa(O(2 ) ) may have contributed to a lessening of AMS upon awakening but had no impact on AMS or exercise performance for the remainder of each day Abstract Objective .—To determine the efficacy of 2 different sources of Ginkgo biloba extract ( GBE ) in reducing the incidence and severity of acute mountain sickness ( AMS ) following rapid ascent to high altitude . Methods .—Two r and omized , double-blind , placebo-controlled cohort studies were conducted in which participants were treated with GBE ( 240 mg·d−1 ) or placebo prior to and including the day of ascent from 1600 m to 4300 m ( ascent in 2 hours by car ) . Acute mountain sickness was diagnosed if the Environmental Symptom Question naire III acute mountain sickness – cerebral ( AMS-C ) score was ≥0.7 and the Lake Louise Symptom ( LLS ) score was ≥3 and the participant reported a headache . Symptom severity was also determined by these scores . Results .— Results were conflicting : Ginkgo biloba reduced the incidence and severity of AMS compared to placebo in the first but not the second study . In the first study , GBE reduced AMS incidence ( 7/21 ) vs placebo ( 13/19 ) ( P = .027 , number needed to treat = 3 ) , and it also reduced severity ( AMS-C = 0.77 ± 0.26 vs 1.59 ± 0.27 , P = .029 ) . In the second study , GBE did not reduce incidence or severity of AMS ( GBE 4/15 vs placebo 10/22 , P = .247 ; AMS-C = 0.48 ± 0.13 vs 0.58 ± 0.11 , P = .272 ) . The primary difference between the 2 studies was the source of GBE . Conclusions .—The source and composition of GBE products may determine the effectiveness of GBE for prophylaxis of AMS 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 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 Numerous cases of acute mountain sickness ( AMS ) during trekking were reported to have been successfully treated with portable pressure chambers . The effect of early pressurization during acute altitude exposure in the Alps had not been previously studied . In order to test the hypothesis that an early pressurization of unacclimatized subjects for 3 h could prevent or delay the appearance of symptoms of AMS , 51 previously healthy subjects climbed from 1,030 to 4,360 m within 12 h. Upon arrival at 4,360 m , AMS scores ( Lake Louise Consensus Question naire ' 91 ) , oxygen saturation ( SaO2 ) , and heart rate ( HR ) were determined at rest . The subjects were then r and omly divided in two groups ; one group was pressurized to 200 mBar for 3 h while the other rested . AMS score , HR , and SaO2 were similar in both groups before treatment . AMS score had decreased ( from 2.44 + /- 0.41 ( S.E. ) to 0.89 + /- 0.26 , p < 0.05 ) and SaO2 had increased ( from 75.22 + /- 1.32 % to 79.07 + /- 1.27 % , p < 0.05 ) in the treatment group 15 min after leaving the pressure chamber whereas the control group had unchanged AMS score ( 2.50 + /- 0.40 vs. 2.40 + /- 0.40 , N.S. ) and SaO2 ( 77.83 + /- 1.41 vs. 76.67 + /- 1.24 , N.S. ) . The next morning , however , AMS score , HR , and SaO2 were similar for both groups . It is concluded that during acute ascent in the Alps , an early 3-h pressurization of unacclimatized subjects does slightly delay the onset of AMS but does not prevent the illness nor does it attenuate its severity upon appearance BACKGROUND Acute mountain sickness ( AMS ) commonly occurs when unacclimatized individuals ascend to altitudes above 2000 m. Acetazolamide and Ginkgo biloba have both been recommended for AMS prophylaxis ; however , there is conflicting evidence regarding the efficacy of Ginkgo biloba use . We performed a r and omized , placebo-controlled trial of acetazolamide vs Ginkgo biloba for AMS prophylaxis . METHODS We r and omized unacclimatized adults to receive acetazolamide , Ginkgo biloba , or placebo in double-blind fashion and took them to an elevation of 3800 m for 24 hours . We grade d AMS symptoms using the Lake Louise Acute Mountain Sickness Scoring System ( LLS ) and compared the incidence of AMS ( defined as LLS score > or =3 and headache ) . RESULTS Fifty-seven subjects completed the trial ( 20 received acetazolamide ; 17 , Ginkgo biloba , and 20 , placebo ) . The LLS scores were significantly different between groups ; the median score of the acetazolamide group was significantly lower than that of the placebo group ( P=.01 ; effect size , 2 ; and 95 % confidence interval [ CI ] , 0 to 3 ) , unlike that of the Ginkgo biloba group ( P=.89 ; effect size , 0 ; and 95 % CI , -2 to 2 ) . Acute mountain sickness occurred less frequently in the acetazolamide group than in the placebo group ( effect size , 30 % ; 95 % CI , 61 % to -15 % ) , and the frequency of occurrence was similar between the Ginkgo biloba group and the placebo group ( effect size , -5 % ; 95 % CI , -37 % to 28 % ) . CONCLUSIONS In this study , prophylactic acetazolamide therapy decreased the symptoms of AMS and trended toward reducing its incidence . We found no evidence of similar efficacy for Ginkgo biloba This study was performed to evaluate whether increasing hemoglobin before ascent by prophylactic erythropoietin injections prevents acute mountain sickness ( AMS ) . This open-label , r and omized , controlled trial involved 39 healthy volunteers with hemoglobin ≤15.5 g/dL who were divided r and omly into erythropoietin ( n=20 ) and control ( n=19 ) groups . Epoetin alpha 10,000 IU injections were given weekly for four consecutive weeks . On day 1 , and 7 days after the last injection ( day 29 ) , oxygen saturation ( SaO2 ) , and hemoglobin were measured . The subjects departed Seoul on day 30 and arrived at Annapurna base camp ( ABC , 4,130 m ) on day 34 . AMS was diagnosed when headache and Lake Louise score ( LLS ) of ≥3 were present . Immediate descent criteria followed US Army recommendations . Two groups differ in hemoglobin levels on day 29 ( 15.4±1.1 vs 14.2±1.0 g/dL , P=0.001 ) . At ABC , erythropoietin group had a significantly lower mean LLS , AMS incidence , and number of subjects who met immediate descent criteria . Multiple logistic regression analysis showed that SaO2<87 % and control group , but not hemoglobin<15.0 g/dL , independently predicted satisfaction of immediate descent criteria . Erythropoietin-related adverse effects were not observed . In conclusion , erythropoietin may be an effective prophylaxis for AMS . ( Clinical Trial Registry Number ; NCT 01665781 ) . Graphical BACKGROUND Acute mountain sickness may be caused by cerebrovascular fluid leakage due to oxidative damage to the endothelium . This may be reduced by oral antioxidant supplementation . AIM To assess the effectiveness of antioxidant supplementation for the prevention of acute mountain sickness ( AMS ) . DESIGN A parallel-group double blind , r and omized placebo-controlled trial . METHODS The study was conducted in a university clinical research facility and a high altitude research laboratory . Eighty-three healthy lowl and volunteers ascended to 5200 m on the Apex 2 high altitude research expedition . The treatment group received a daily dose of 1 g l-ascorbic acid , 400 IU of alpha-tocopherol acetate and 600 mg of alpha-lipoic acid ( Cultech Ltd. , Wales , UK ) in four divided doses . Prevalence of AMS was measured using the Lake Louise Consensus score sheet ( LLS ) . Secondary outcomes were AMS severity measured using a novel visual analogue scale , arterial oxygen saturation and pulmonary artery systolic pressure ( PASP ) . RESULTS Forty-one subjects were allocated to the antioxidant group , and 42 to the placebo group . There was no difference in AMS incidence or severity between the antioxidant and placebo groups using the LLS at any time at high altitude . At the pre-determined comparison point at Day 2 at 5200 m , 69 % of the antioxidant group ( 25/36 ) and 66 % of the placebo group ( 23/35 ) had AMS using the LLS criteria ( P = 0.74 ) . No differences were observed between the groups for PASP , oxygen saturation , presence of a pericardial effusion or AMS assessed by VAS . CONCLUSION This trial found no evidence of benefit from antioxidant supplementation at high altitude . TRIAL REGISTRATION NUMBER NCT00664001 Abstract In order to study the use of positive end expiratory pressure ( PEEP ) to prevent acute mountain sickness ( AMS ) , 22 subjects were exposed r and omly to 8-h hypobaric hypoxia in a hypobaric chamber ( 4500 m , 589 hPa , 22 ° C ) once being administered 5-cm H2O PEEP and once without . The prevention of AMS by PEEP was evaluated by scoring AMS according to the Lake Louise system ( self-report question naire and clinical assessment ) throughout the experiment with O2 saturation ( SO2 ) and heart rate measurements being made . Arterial blood analyses ( partial pressures of arterial O2 and CO2 , PaO2 , PaCO2 , and pH ) were made at the end of the exposure . Results showed decreased AMS scores with PEEP at the end of the 8-h hypoxia [ 1.50 ( SEM 1.32 ) vs 3.23 ( SEM 2.07 ) , P < 0.01 for self-report plus clinical assessment scores ] with a lower prevalence ( 23 % vs 55 % , P < 0.01 ) . The SO2 , PaO2 , PaCO2 and HCO3− did not change significantly . However , a smaller increase in arterial pH [ 7.47 ( SEM 0.02 ) vs 7.50 ( SEM 0.02 ) , P < 0.05 ] was observed with PEEP , attesting a lesser alkalosis . Moreover , heart rate increased with PEEP ( P < 0.05 ) . In conclusion , this study would suggest that a 5-cm H2O PEEP may help decrease AMS scores at the end of an 8-h exposure to hypoxia in a hypobaric chamber . Such a method could be used to prevent AMS in such experimental conditions without adverse effects Blood pressure increases during acute exposure to high altitude in healthy humans . However , little is known on altitude effects in hypertensive subjects or on the treatment efficacy in this condition . Objectives of High Altitude Cardiovascular Research (HIGHCARE)– And es Lowl and ers Study were to investigate the effects of acute high-altitude exposure on 24-hour ambulatory blood pressure in hypertensive subjects and to assess antihypertensive treatment efficacy in this setting . One hundred untreated subjects with mild hypertension ( screening blood pressure , 144.1±9.8 mm Hg systolic , 92.0±7.5 mm Hg diastolic ) were r and omized to double-blind placebo or to telmisartan 80 mg+modified release nifedipine 30 mg combination . Twenty-four – hour ambulatory blood pressure monitoring was performed off-treatment , after 6 weeks of treatment at sea level , on treatment during acute exposure to high altitude ( 3260 m ) and immediately after return to sea level . Eighty-nine patients completed the study ( age , 56.4±17.6 years ; 52 men/37 women ; body mass index , 28.2±3.5 kg/m2 ) . Twenty-four – hour systolic blood pressure increased at high altitude in both groups ( placebo , 11.0±9 mm Hg ; P<0.001 and active treatment , 8.1±10.4 mm Hg ; P<0.001 ) . Active treatment reduced 24-hour systolic blood pressure both at sea level and at high altitude ( 147.9±11.1 versus 132.6±12.4 mm Hg for placebo versus treated ; P<0.001 ; 95 % confidence interval of the difference 10.9–19.9 mm Hg ) and was well tolerated . Similar results were obtained for diastolic , for daytime blood pressure , and for nighttime blood pressure . Treatment was well tolerated in all conditions . Our study demonstrates that ( 1 ) 24-hour blood pressure increases significantly during acute high-altitude exposure in hypertensive subjects and ( 2 ) treatment with angiotensin receptor blocker-calcium channel blocker combination is effective and safe in this condition . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT01830530 OBJECTIVES This study evaluates the ability of positive end-expiratory pressure ( PEEP ) , a nonpharmacological method , to prevent the occurrence of acute mountain sickness during two ascents of Mount Blanc . METHODS In a r and om order ( once with PEEP and once without ) , PEEP was administered or not to eight subjects during two ascents of Mount Blanc . Scores for acute mountain sickness were quantified using the Lake Louise acute mountain sickness scoring system , and oxygen arterial blood saturation by pulse oxymetry ( SpO2 ) , heart rate , and systolic and diastolic blood pressures were also measured . RESULTS The decrease in the prevalence of acute mountain sickness indicated that the PEEP system was effective , one case ( 12.5 % ) occurring among the eight participants with PEEP and six cases ( 75 % ) occurring among the eight without PEEP ( P<0.01 ) . The severity of the cases also decreased ( P<0.01 ) . Heart rate and blood pressure did not significantly vary , whereas the SpO2 tended to be higher with PEEP ( P=0.07 ) . CONCLUSIONS This field study shows that PEEP could be an efficient method with which to prevent acute mountain sickness without adverse effects . However , the ergonomics of the PEEP system must be improved to make its use more practical in the future A controlled comparative between-group study of 48 climbers ascending Kilimanjaro ( 5895 m ) was design ed as an extension to our previous double-blind cross-over trial on the same peak in 1980 , using acetazolamide to decrease the incidence and effects of Acute Mountain Sickness . A group taking acetazolamide 500 mg each morning for one day befare reaching 3000 m were compared with 3 control groups of Caucasian subjects and lowl and and highl and Africans . Efficacy was assessed on climbing performance and scores derived from symptoms recorded daily by subjects . Those taking acetazolamide reached higher altitudes and had lower symptom scores than those in control groups . The results support the use of acetazolamide as an effective prophylactic for Acute Mountain Sickness , for most people in a dose of 500 mg in the morning starting one day before ascent above 3000 m . The optimal dose of prophylactic acetazolamide is not established , nor is the most appropiate time for medication prior to ascent In a r and omized , placebo-controlled , double-blind study , we tested a 4-week program in normobaric hypoxia that is commercially offered for the prevention of acute mountain sickness ( AMS ) . Twenty-two male and 18 female healthy subjects [ mean age 33 + /- 7 ( SD ) years ] exercised 70 min , 3 x /week for 3 weeks on a bicycle ergometer at workloads of 60 % VO2max either in normoxia ( normoxia group , NG ) or in normobaric hypoxia ( hypoxia group , HG ) , corresponding to altitudes of 2500 , 3000 , and 3500 m during weeks 1 , 2 , and 3 , respectively . Four passive exposures of 90 min in normoxia ( NG ) or hypoxia corresponding to 4500 m ( HG ) followed in week 4 . Five days after the last session , subjects ascended within 24 h from sea level to 4559 m ( one overnight stay at 3611 m ) and stayed there for 24 h. AMS was defined as LL ( Lake Louise score ) > or = 5 and AMS-C > or = 0.70 . The AMS incidence ( 70 % in NG vs. 60 % in HG , p = 0.74 ) , LL scores ( 7.1 + /- 4.3 vs. 5.9 + /- 3.4 , p = 0.34 ) , and AMS-C scores ( 1.50 + /- 1.22 vs. 0.93 + /- 0.81 , p = 0.25 ) at the study endpoint were not significantly different between the groups . However , the incidence of AMS at 3611 m ( 6 % vs. 47 % , p = 0.01 ) and the functional LL score at 4559 m were lower in HG . SpO2 at 3611 m , heart rate during ascents , and arterial blood gases at 4559 m were not different between groups . We conclude that the tested program does not reduce the incidence of AMS within a rapid ascent to 4559 m , but our data show that it prevents AMS at lower altitudes . Whether such a program would prevent AMS at higher altitudes , but with slower ascent , remains to be tested Abstract Objective To evaluate the efficacy of ginkgo biloba , acetazolamide , and their combination as prophylaxis against acute mountain sickness . Design Prospect i ve , double blind , r and omised , placebo controlled trial . Setting Approach to Mount Everest base camp in the Nepal Himalayas at 4280 m or 4358 m and study end point at 4928 m during October and November 2002 . Participants 614 healthy western trekkers ( 487 completed the trial ) assigned to receive ginkgo , acetazolamide , combined acetazolamide and ginkgo , or placebo , initially taking at least three or four doses before continued ascent . Main outcome measures Incidence measured by Lake Louise acute mountain sickness score ≥ 3 with headache and one other symptom . Secondary outcome measures included blood oxygen content , severity of syndrome ( Lake Louise scores ≥ 5 ) , incidence of headache , and severity of headache . Results Ginkgo was not significantly different from placebo for any outcome ; however participants in the acetazolamide group showed significant levels of protection . The incidence of acute mountain sickness was 34 % for placebo , 12 % for acetazolamide ( odds ratio 3.76 , 95 % confidence interval 1.91 to 7.39 , number needed to treat 4 ) , 35 % for ginkgo ( 0.95 , 0.56 to 1.62 ) , and 14 % for combined ginkgo and acetazolamide ( 3.04 , 1.62 to 5.69 ) . The proportion of patients with increased severity of acute mountain sickness was 18 % for placebo , 3 % for acetazoalmide ( 6.46 , 2.15 to 19.40 , number needed to treat 7 ) , 18 % for ginkgo ( 1 , 0.52 to 1.90 ) , and 7 % for combined ginkgo and acetazolamide ( 2.95 , 1.30 to 6.70 ) . Conclusions When compared with placebo , ginkgo is not effective at preventing acute mountain sickness . Acetazolamide 250 mg twice daily afforded robust protection against symptoms of acute mountain sickness Cerebral edema occurs in fatal cases of acute mountain sickness . Dexamethasone , commonly used to treat cerebral edema due to other causes , also reduces the symptoms of acute mountain sickness when given prophylactically . However , the efficacy of dexamethasone in the treatment of established acute mountain sickness remains uncertain . To investigate this question , we exposed six men in a hypobaric chamber to a simulated altitude of 3700 m ( barometric pressure , 64 kPa [ 481 mm Hg ] ) for 48 hours on two occasions . Acute mountain sickness was diagnosed with use of a symptoms question naire , and dexamethasone ( 4 mg every six hours ) or placebo was then given in a r and omized , double-blind , crossover fashion . Dexamethasone reduced the symptoms of acute mountain sickness by 63 percent ( P less than 0.05 ) , whereas placebo had a minimal effect ( reduction by 23 percent ; P not significant ) . In spite of this response , one subject had mild cerebral edema on brain CT after both placebo and dexamethasone . Dexamethasone had no effect on fluid shifts , oxygenation , sleep apnea , urinary catecholamine levels , the appearance of chest radiographs or perfusion scans , serum electrolyte levels , hematologic profiles , or the results of psychometric tests . Dexamethasone treatment was complicated by mild hyperglycemia in all subjects ( mean [ + /- SE ] glucose level , 7.3 + /- 1.3 mmol per liter [ 132 + /- 23 mg per deciliter ] ) . We conclude that dexamethasone effectively reduces the symptoms of acute mountain sickness . However , it did not improve objective physiologic abnormalities related to exposure to high altitudes . We therefore recommend that dexamethasone be used only when descent is impossible , or to facilitate cooperation in evacuation efforts Up to half of those who ascend rapidly to altitudes of over 3,000 m may experience symptoms of acute mountain sickness ( AMS ) and of these some 95 % may suffer from high altitude headache . We report the first controlled trial specifically to assess an oral drug therapy for this common symptom . Subjects were 21 members of mountaineering expeditions to similar altitudes in the Bolivian And es and the Himalayas in Nepal . The study was of a r and omized , placebo-controlled , double-blind , within-patient crossover design . Ibuprofen was significantly superior to placebo both in reducing headache severity and in speed of relief ( a mean difference of 94 min in time to no/minimal headache ) . Only 14 % of subjects who initially took ibuprofen felt the need for further medication compared to 83 % of those who took placebo first ( p = 0.02 ) . Of the 11 subjects completing both phases of the crossover , 8 ( 73 % ) favored ibuprofen while the remainder had no preference ( p = 0.004 ) . No attributable adverse effects occurred . The results suggest that ibuprofen is a safe and effective treatment for high altitude headache Acetazolamide and gingko biloba are the two most investigated drugs for the prevention of acute mountain sickness ( AMS ) . Evidence suggests that they may also reduce pulmonary artery systolic pressure ( PASP ) . To investigate whether these two drugs for AMS prevention also reduce PASP with rapid airlift ascent to high altitude , a r and omized controlled trial was conducted on 28 healthy young men with acetazolamide ( 125 mg bid ) , gingko biloba ( 120 mg bid ) , or placebo for 3 days prior to airlift ascent ( 397 m ) and for the first 3 days at high altitude ( 3658 m ) . PASP , AMS , arterial oxygen saturation ( Sao2 ) , mean arterial pressure ( MAP ) , heart rate ( HR ) , forced vital capacity ( FVC ) , forced expiratory volume in the first second ( FEV1 ) , and peak expiratory flow ( PEF ) were assessed both at 397 m and 3658 m. HR , PEF , and PASP increased with altitude exposure ( p<0.05 ) , and SaO2 decreased ( p<0.05 ) . PASP with acetazolamide ( mean at 3658 m , 26.2 mm Hg ; incremental change , 4.7 mm Hg , 95 % CI . , 2.6 - 6.9 mm Hg ) was lower than that with ginkgo biloba ( mean at 3658 m , 33.7 mm Hg , p=0.001 ; incremental change , 13.1 mm Hg , 95%CI . , 9.6 - 16.5 mm Hg , p=0.002 ) , and with placebo ( mean at 3658 m , 34.7 mm Hg , p<0.001 ; 14.4 mm Hg , 95 % CI . , 8.8 - 20.0 mm Hg , p=0.001 ) . The data show that a low prophylactic dosage of acetazolamide , but not gingko biloba , mitigates the early increase of PASP in a quick ascent profile RATIONALE Acute mountain sickness ( AMS ) may affect individuals who ( rapidly ) ascend to altitudes higher than 2,000 - 3,000 m. A more serious consequence of rapid ascent may be high-altitude pulmonary edema , a hydrostatic edema associated with increased pulmonary capillary pressures . Acetazolamide is effective against AMS , possibly by increasing ventilation and cerebral blood flow ( CBF ) . In animals , it inhibits hypoxic pulmonary vasoconstriction . OBJECTIVES We examined the influence of acetazolamide on the response to hypoxia of ventilation , CBF , and pulmonary vascular resistance ( PVR ) . METHODS In this double-blind , placebo-controlled , r and omized study , nine subjects ingested 250 mg acetazolamide every 8 h for 3 d. On the fourth test day , we measured the responses of ventilation , PVR , and CBF to acute isocapnic hypoxia ( 20 min ) and sustained poikilocapnic hypoxia ( 4 h ) . Ventilation was measured with pneumotachography . Hypoxia was achieved with dynamic end-tidal forcing . The maximum pressure difference across the tricuspid valve ( DeltaPmax , a good index of PVR ) was measured with Doppler echocardiography . CBF was measured by transcranial Doppler ultrasound . RESULTS In normoxia , acetazolamide increased ventilation and reduced DeltaPmax , but did not influence CBF . The ventilatory and CBF responses to acute isocapnic hypoxia were unaltered , but the rise in DeltaPmax was reduced by 57 % . The increase in DeltaPmax by sustained poikilocapnic hypoxia observed after placebo was reduced by 34 % after acetazolamide , the ventilatory response was increased , but the CBF response remained unaltered . CONCLUSIONS Acetazolamide has complex effects on ventilation , PVR , and CBF that converge to optimize brain oxygenation and may be a valuable means to prevent/treat high-altitude pulmonary edema Acetazolamide ( ACZ ) is used to prevent acute mountain sickness at altitude . Because it could affect O2 transport in several different and potentially conflicting ways , we examined its effects on pulmonary and muscle gas exchange and acid-base status during cycle exercise at approximately 30 , 50 and 90 % VO2max in normoxia ( F(IO2 ) = 0.2093 ) and acute hypoxia ( F(IO2 ) = 0.125 ) . In a double-blind , order-balanced , crossover design , six healthy , trained men ( normoxic VO2max= 59 ml kg(-1 ) min(-1 ) ) exercised at both F(IO2 ) values after ACZ ( 3 doses of 250 mg , 8 h apart ) and placebo . One week later this protocol was repeated using the other drug ( placebo or ACZ ) . We measured cardiac output ( QT ) , leg blood flow ( LBF ) , and muscle and pulmonary gas exchange , the latter using the multiple inert gas elimination technique . ACZ did not significantly affect VO2 , QT , LBF or muscle gas exchange . As expected , ACZ led to lower arterial and venous blood [ HCO3- ] , pH and lactate levels ( P < 0.05 ) , and increased ventilation ( P < 0.05 ) . In both normoxia and hypoxia , ACZ result ed in higher arterial P(O2 ) and saturation and a lower alveolar-arterial P(O2 ) difference ( AaD(O2 ) ) due to both less VA/Q mismatch and less diffusion limitation ( P < 0.05 ) . In summary , ACZ improved arterial oxygenation during exercise , due to both greater ventilation and more efficient pulmonary gas exchange . However , muscle gas exchange was unaffected OBJECTIVE To study the effect of medroxyprogesterone on blood gases and cerebral regional oxygenation at high altitude , alone and in conjunction with acetazolamide , and to assess the effect on acute mountain sickness ( AMS ) . DESIGN Two placebo-controlled trials during rapid ascent to high altitude . PARTICIPANTS In the first trial , 20 participants , and in the second trial , 24 participants . SETTING During rapid ascent to 4680 m and on rapid ascent to 5200 m. INTERVENTION In the first trial , participants were r and omized to receive medroxyprogesterone 30 mg or a placebo twice a day . In the second trial , participants were r and omly assigned to one of 4 groups : a placebo twice daily , medroxyprogesterone 30 mg twice daily , acetazolamide 250 mg plus a placebo twice daily , or acetazolamide 250 mg plus medroxyprogesterone 30 mg twice daily . MAIN OUTCOME MEASURES Blood gas changes and symptom scores of AMS in both trials and cerebral regional oxygen saturations in the first trial only . RESULTS Medroxyprogesterone improved peripheral oxygen saturations in both trials and improved PaO2 in combination with acetazolamide . Cerebral regional oxygen saturation was not altered by medroxyprogesterone . The reduction in symptom scores and in the extent of AMS was not significant in this limited study . CONCLUSIONS Medroxyprogesterone acts as a respiratory stimulant , but the clinical benefit regarding the development of AMS was unproven at high altitude . Combined medroxyprogesterone and acetazolamide gave the best PaO2 A lightweight device , design ed to supply inspired air at 12.8 % O2 concentration ( PO2 equivalent to 3960 m altitude ) by recirculating a portion of each expired breath after CO2 removal , was tested at sea-level for its ability to induce altitude acclimation . Twelve young men ( experimental group ) breathed from the device for 7.5 - 8 h each day for 10 successive days . On the morning of day 1 , inspired O2 concentrations averaged 12.8 % , as intended , but increased by noontime and remained elevated thereafter . This raised the average hypoxic stimulus to 13.8 + /- 0.9 % ( PO2 equivalent to 3370 + /- 517 m altitude ) for the entire 10-d period . Ten other young men ( control group ) breathed normoxic air from a placebo device of identical appearance on the same schedule . On day 10 , both groups were exposed for the next 2 d to 4500 m altitude in a hypobaric chamber to assess the effect of the treatment on acute mountain sickness ( AMS ) . After the sea level treatment , the experimental group showed no significant differences from control in resting ventilatory rate , respiratory frequency or end tidal PO2 , but end-tidal PCO2 was lower ; there was no indication of hemoconcentration . At altitude , both groups showed the expected decreases in end-tidal PO2 and PCO2 , and increases in hemoglobin concentration and hematocrit indicative of hemoconcentration , with no differences between them . Neither incidence nor severity of AMS differed significantly between groups , but the experimental group had a lower incidence rate than historical controls . ( ABSTRACT TRUNCATED AT 250 WORDS Acute mountain sickness ; prophylactic benefits of Free-radical-mediated damage to the blood-brain barrier may be implicated in the pathophysiology of acute mountain sickness ( AMS ) . To indirectly examine this , we conducted a r and omized double-blind placebo-controlled trial to assess the potentially prophylactic benefits of enteral antioxidant vitamin supplementation during ascent to high altitude . Eighteen subjects aged 35 + /- 10 years old were r and omly assigned double-blind to either an antioxidant ( n = 9 ) or placebo group ( n = 9 ) . The antioxidant group ingested 4 capsules/day(-1 ) ( 2 after breakfast/2 after evening meal ) that each contained 250 mg of L-ascorbic acid , 100 IU of dl-a-tocopherol acetate and 150 mg of alpha-lipoic acid . The placebo group ingested 4 capsules of identical external appearance , taste , and smell . Supplementation was enforced for 3 weeks at sea level and during a 10-day ascent to Mt. Everest base camp ( approximately 5,180 m ) . Antioxidant supplementation result ed in a comparatively lower Lake Louise AMS score at high altitude relative to the placebo group ( 2.8 + /- 0.8 points versus 4.0 + /- 0.4 points , P = 0.036 ) , higher resting arterial oxygen saturation ( 89 + /- 5 % versus 85 + /- 5 % , P = 0.042 ) , and total caloric intake ( 13.2 + /- 0.6 MJ/day(-1 ) versus 10.1 + /- 0.7 MJ/day(-1 ) , P = 0.001 ) ; the latter is attributable to a lower satiety rating following a st and ardized meal . These findings indicate that the exogenous provision of water and lipid-soluble antioxidant vitamins at the prescribed doses is an apparently safe and potentially effective intervention that can attenuate AMS and improve the physiological profile of mountaineers at high altitude OBJECTIVE The aim of this study was to test the hypothesis that administration of low-flow oxygen will improve physical performance in subjects unacclimatized to altitude . We evaluated the effects of oxygen supplementation on functional capacity and acute mountain sickness ( AMS ) symptoms in young , healthy male and female subjects who performed a 2-km fast walk test following rapid ascent to the Chajnantor plateau ( 5050 m above sea level ) in Northern Chile . METHODS The participants were r and omly distributed into 2 groups according to oxygen supplementation levels : 1 or 3 L O(2 ) · min(-1 ) . Within each group , males and females were evaluated separately . A preliminary walk test was carried out at sea level on a 100-m long , flat track with 10 U-turns . For the first walk at altitude , subjects carried the supplementary oxygen system but did not breathe the oxygen . Subjects received oxygen through a facemask the following day during the second test . The nights prior to altitude tests were spent at 2400 m in San Pedro de Atacama . RESULTS Supplementary oxygen administration during a 2-km walk test significantly improved walking times at 5050 m. We also observed a significant improvement in AMS symptoms . As expected , however , performance was poorer at altitude compared to test values at sea level , despite supplementary oxygen administration . CONCLUSIONS Our findings demonstrate the beneficial effects of supplementary oxygen administration on physical capacity , reducing the incidence of AMS and , thus , improving health and safety conditions for high altitude workers following rapid ascent , when adequate acclimatization is not possible STUDY OBJECTIVES To compare the benefits of simulated descent in a hyperbaric chamber with those of supplementary oxygen for the treatment of acute mountain sickness . DESIGN A prospect i ve study . SETTING The Snake River Health Clinic in Keystone , Colorado , which has an altitude of 2,850 m ( 9,300 ft ) . TYPE OF PARTICIPANTS Twenty-four patients who presented with acute mountain sickness . INTERVENTIONS A simulated descent of 1,432 m ( 4,600 ft ) was attained by placing the patients in a fabric hyperbaric chamber and pressurizing the chamber to 120 mm Hg ( 2.3 PSI ) above ambient pressure . Patients were r and omly assigned to either the hyperbaric treatment or treatment with 4 L of oxygen given by facemask ; both treatments lasted for two hours . MEASUREMENTS AND MAIN RESULTS Mean arterial oxygen saturation ( SaO2 ) increased 7 % ( 84 + /- 2 % to 91 + /- 1 % ) with pressurization and 14 % ( 83 + /- 4 % to 96 + /- 1 % ) with oxygen during treatment over pretreatment levels . Symptoms of acute mountain sickness decreased as rapidly with pressurization as with oxygen treatment , despite significantly higher SaO2 in the oxygen-treated group during treatment . Symptomatic improvement was retained in both groups at least one hour after treatment . CONCLUSION Simulated descent in a fabric hyperbaric chamber is as effective as oxygen therapy for the immediate relief of acute mountain sickness Previous studies suggest that 5 days of prophylactic ginkgo decreases the incidence of acute mountain sickness ( AMS ) during gradual ascent . This trial was design ed to determine if ginkgo is an effective prophylactic agent if begun 1 day prior to rapid ascent . In this double-blind , r and omized , placebo-controlled trial , 26 participants residing at sea level received ginkgo ( 60 mg TID ) or placebo starting 24 h before ascending Mauna Kea , Hawaii . Subjects were transported from sea level to the summit ( 4205 m ) over 3 hours , including 1 hour at 2835 m. The Lake Louise Self-report Question naire constituted the primary outcome measure at baseline , 2835 m , and after 4 h at 4205 m. AMS was defined as a Lake Louise Self-report Score ( LLSR ) > /= 3 with headache . Subjects who developed severe AMS were promptly transported to lower altitude for the remainder of the study . The ginkgo ( n = 12 ) and placebo ( n = 14 ) groups were well matched ( 58 % vs. 50 % female ; median age 28 yr , range 22 - 53 vs. 33 yr , range 21 - 53 ; 58 % vs. 57 % Caucasian ) . Two ( 17 % ) subjects on ginkgo and nine ( 64 % ) on placebo developed severe AMS and required descent for their safety ( p = 0.021 ) ; all recovered without sequelae . Median LLSR at 4205 m was significantly lower for ginkgo versus placebo ( 4 , range 1 - 8 vs. 5 , range 2 - 9 , p = 0.03 ) . Ginkgo use did not reach statistical significance for lowering incidence of AMS compared with placebo ( ginkgo 7/12 , 58.3 % vs. placebo 13/14 , 92.9 % , p = 0.07 ) . Twenty-one of 26 ( 81 % ) subjects developed AMS overall . This is the first study to demonstrate that 1 day of pretreatment with ginkgo 60 mg TID may significantly reduce the severity of AMS prior to rapid ascent from sea level to 4205 Abstract The influence of acetazolamide on acute mountain sickness was tested in a double-blind study of forty-three volunteers given acetazolamide or placebo , 250 mg every eight hours , for 32 hours before and 40 hours after abrupt transportation from sea level to 12,800 feet . In response to hypoxia , control subjects hyperventilated and developed mild respiratory alkalosis with increased blood pH and reduced carbon dioxide tension and bicarbonate within eight hours after arrival at altitude . These changes persisted over the five days of the study . Alkalosis was prevented in the acetazolamide-treated group , with a greater increase in ventilation and alveolar oxygen tension and a greater decrease in carbon dioxide tension and bicarbonate than in controls . Significant reductions in frequency and severity of the most prominent symptoms of acute mountain sickness — headache , insomnia and gastrointestinal symptoms — were observed in treated subjects . In control subjects , occurrence and severity of symptoms corr The study assessed physiological responses to induction to high altitude first to 3,500 m and then to 4,200 m and compared the time course of altitude acclimatization in two groups of male volunteers . The acutely inducted group was transported by aircraft ( AI ) to 3,500 m in 1 h , whereas the gradually inducted group was transported by road ( RI ) in 4 days . Baseline recordings of basal cardiovascular , respiratory , and blood gas variables were monitored at sea level as well as at 3,500 m on days 1 , 3 , 5 , and 7 . Blood gases were measured on day 10 also . After 15 days at 3,500 m , the subjects were inducted to 4,200 m by road , and measurements were repeated on days 1 , 3 , and 5 , except blood gas variables , which were done on day 10 only . Acute mountain sickness symptoms were recorded throughout . The responses of RI were stable by day 3 of induction at 3,500 m , whereas it took 5 days for AI . Four days in transit for RI appear equivalent to 2 days at 3,500 m for AI . Acclimatization schedules of 3 and 5 days , respectively , for RI and AI are essential to avoid malacclimatization and /or high-altitude illness . Both groups took 3 days at 4,200 m to attain stability for achieving acclimatization Forty-seven climbers participated in a double-blind , r and omized trial comparing acetazolamide 250 mg , dexamethasone 4 mg , and placebo every eight hours as prophylaxis for acute mountain sickness during rapid , active ascent of Mount Rainier ( elevation 4,392 m ) . Forty-two subjects ( 89.4 percent ) achieved the summit in an average of 34.5 hours after leaving sea level . At the summit or high point attained above base camp , the group taking dexamethasone reported less headache , tiredness , dizziness , nausea , clumsiness , and a greater sense of feeling refreshed ( p less than or equal to 0.05 ) . In addition , they reported fewer problems of runny nose and feeling cold , symptoms unrelated to acute mountain sickness . The acetazolamide group differed significantly ( p less than or equal to 0.05 ) from other groups at low elevations ( 1,300 to 1,600 m ) , in that they experienced more feelings of nausea and tiredness , and they were less refreshed . These drug side effects probably obscured the previously established prophylactic effects of acetazolamide for acute mountain sickness . Separate analysis of an acetazolamide subgroup that did not experience side effects at low elevations revealed a prophylactic effect of acetazolamide similar in magnitude to the dexamethasone effect but lacking the euphoric effects of dexamethasone . This study demonstrates that prophylaxis with dexamethasone can reduce the symptoms associated with acute mountain sickness during active ascent and that acetazolamide can cause side effects that may limit its effectiveness as prophylaxis against the disease Context A few small retrospective studies show associations between obesity and acute mountain sickness . Contribution This 24-hour study involving 9 obese and 10 nonobese men was conducted in a decompression chamber that simulated a rapid ascent to an altitude of 3658 m ( 12 000 ft ) . Obese men more often developed symptoms of mountain sickness and had lower nocturnal oxygen saturation values than did nonobese men . Caution s Although this elegant , short experiment suggests that obese men were more susceptible to acute mountain sickness , the study involved few people , simulated a steady rate of ascent , and did not simulate physical activity with altitude exposure . The Editors Rapid ascent from low to high altitude ( above 2500 m or 8200 ft ) often causes acute mountain sickness ( AMS ) , a syndrome characterized by headache and other systemic symptoms , such as nausea , lassitude , and difficulty sleeping . The prevalence and severity of AMS depend on the speed of ascent , the altitude attained , preacclimatization , age , sex , exertion levels while at altitude , and the ventilatory response to acute hypoxia ( 1 , 2 ) . Few retrospective field studies of high altitude have reported that obesity , as evidence d by body mass index ( BMI ) , might be associated with the development of AMS ( 3 - 7 ) . However , this association has not been studied prospect ively under controlled conditions at reasonably accessible altitudes or in individuals with mild to moderate obesity . We sought to determine whether obese individuals are more likely to develop AMS than nonobese individuals during decompression to a simulated altitude of 3658 m. We hypothesized that obese individuals were more susceptible to develop AMS than nonobese individuals during exposure to high altitudeinduced hypobaric hypoxia . Methods Participants Volunteers were recruited through local advertisements and were selected for participation on the basis of percentage body fat . Nonobese was defined as percentage body fat less than 25 % . Obese was defined as a BMI of 30 kg/m2 or greater and percentage body fat of 30 % or greater . None of the participants had a history of cardiovascular or respiratory abnormalities . No participant was taking long-term medications . All participants were nonsmokers . Nine obese men ( mean age [ SD ] , 35 8 years ) and 10 nonobese men ( mean age [ SD ] , 34 8 years ) were studied . All participants resided at sea level ( 100 m ) in Dallas , Texas . One obese and three nonobese participants previously had mild AMS . One obese participant was exposed to a 2500-m altitude 4 days before this study ; no other participant was exposed to a 1500-m or higher altitude before participating in the study . Each participant received both written and verbal explanations of the experiment before giving written consent . The Institutional Review Board of the University of Texas Southwestern Medical Center and Presbyterian Hospital of Dallas approved this study . Study Protocol The study was conducted in a large ( 40 ft long by 9 ft diameter ) multiplace ( room for > 1 person ) decompression chamber at the Institute for Exercise and Environmental Medicine in Dallas . The barometric pressure was held at 483 mm Hg , which is equivalent to an altitude of 3658 m ( 12 000 ft ) . The temperature ( 25 0.5 C ) , humidity ( 28 % 1 % ) , and concentration of CO2 ( 0.07 % 0.02 % ) in the chamber were monitored continuously by trained medical staff . Four participants at a time were studied in the chamber during the 24 hours of exposure ( Figure 3 ) . Assessment of AMS According to guidelines established by the Lake Louise AMS consensus report ( 8) , each participant completed an AMS self-report question naire at sea level ( before decompression ) and during decompression to 483 mm Hg at 6 hours , 12 hours , and 24 hours . The question naire included items for symptoms of headache , gastrointestinal symptoms , fatigue or weakness , dizziness or lightheadedness , and difficulty sleeping . Each symptom was grade d on a scale from 0 to 3 , with 0 representing no symptoms ; 1 , mild symptoms ; 2 , moderate symptoms ; and 3 , severe symptoms . A score of 15 was the maximum score possible . A self-score of 4 or more was an indication of AMS ( 8) . This scoring system has been vali date d against the U.S. Army Environmental Symptoms Question naire , demonstrating similar sensitivity and specificity ( 9 ) . Measurements of Sao 2 Daytime Sao 2 was measured by pulse oximetry ( Ohmeda 3700 Pulse Oximeter , Date x-Ohmeda , Boulder , Colorado ) at sea level and at 6 hours and 24 hours of simulated altitude . Nocturnal Sao 2 in each participant was continuously recorded in the chamber from 10:30 p.m. to 6:30 a.m. The mean nocturnal Sao 2 was calculated from values obtained every 30 minutes . Heart rate was measured at sea level and at altitude during the daytime and during sleep . Other Measurements Body composition was determined by hydrostatic weighing , and percentage body fat , fat mass , and lean mass were calculated . At sea level , all participants underwent st and ard spirometry ( measuring lung volumes , maximal flow-volume loop , and maximal voluntary ventilation ) and diffusing capacity of the lung in a whole-body plethysmograph ( Model 6200 , SensorMedics , Yorba Linda , California ) . Pulmonary function testing was performed according to the guidelines of the American Thoracic Society . Statistical Analysis Data are expressed as means ( SD ) . The parameters of AMS score and Sao 2 were analyzed by a two-way analysis of variance ( ANOVA ) using SAS software , release 8.02 ( SAS Institute , Inc. , Cary , North Carolina ) , with repeated measures on one factor ( altitude-time ) and between-participant comparisons for the other factor ( group , nonobese and obese ) . Comparisons were considered significant when the P value was less than 0.05 . Role of the Funding Sources The funding sources had no role in the design , conduct , or reporting of the study or in the decision to su bmi t the manuscript for publication . Results Participants The Table shows general characteristics of the participants . One participant in the obese group was removed from the chamber after 10 hours because of severe headache , nausea , and dizziness ( AMS score , 8) . As a result , this participant was not included in further analyses . Table . General Characteristics and Pulmonary Function of Participants at Baseline AMS Scores There was a significant interaction between altitude-time and group ( P < 0.001 ) as a result of the two-way ANOVA . This indicated that the increase in AMS scores with altitude exposure was more pronounced in the obese participants ( Figure 1 ) . Overall , after 24 hours in the chamber , seven obese participants and four nonobese participants had an AMS score of 4 or more . The frequency of AMS symptoms at 24 hours in 18 participants was as follows : headache , 89 % ; gastrointestinal upset , 36 % ; fatigue and weakness , 36 % ; dizziness , 15 % ; and difficulty sleeping , 75 % . Figure 1 . Comparison of the acute mountain sickness ( AMS ) score at sea level and at simulated altitude for 24 hours in nonobese ( n = 10 ) and obese ( n = 8) participants . P Sao 2 There was also a significant interaction between altitude-time and group ( P < 0.001 ) for Sao 2 as a result of the two-way ANOVA ( Figure 2 ) . This indicated that the decrease in Sao 2 with altitude exposure differed between the two groups . Figure 2 . Comparison of Sao at sea level , during the daytime , and during sleep at night in nonobese ( n = 10 ) and obese ( n = 8) participants . o P Figure 3 . Participants during simulated altitude exposure in decompression chamber . Discussion Our principal finding was that obese participants have higher AMS scores than nonobese participants during a 24-hour exposure to simulated altitude of 3658 m. Thus , obesity seems to be associated with the development of AMS . Also , the response of Sao 2 with exposure differed between nonobese and obese men ; obese men had lower values than nonobese men . These findings suggest that impaired breathing during sleep may be an important pathophysiologic mechanism for the increased levels of AMS in obese individuals . Limitations Although our results suggest that obese individuals may be more susceptible to AMS , these results must be interpreted with caution . Possible limitations to generalization include the small sample size , the selected nature of the study sample , the narrow spectrum of obese participants studied , the steady rate of ascent , the lack of physical activity during altitude exposure , and the simulated environment in which the participants were studied . Obesity and AMS Obesity is characterized by an abnormally large adipose tissue mass . In particular , excess weight leads to the development of various pathophysiologic disorders and , specifically , cardiovascular and respiratory abnormalities . Obesity-related respiratory function abnormalities , such as sleep-disordered breathing and nocturnal hypercapnia and hypoxia , place obese individuals at risk for illness at higher altitudes ( 10 - 13 ) . In addition , the prevalence of obesity in western society , especially in the United States ( where 22 % of the population has a BMI > 30 kg/m2 and roughly 30 % of the population is overweight [ 14 , 15 ] ) , further increases the potential for altitude-related difficulties at easily accessible high altitudes during recreational activities . A review of the literature revealed no prospect i ve data on the effect of obesity on high-altitude illness . In our study , AMS scores increased with time during altitude exposure in both nonobese and obese participants , which is consistent with previous data demonstrating that AMS symptoms are common after 24 hours of rapid ascent to high altitude ( 1 , 2 ) . The severity of symptoms , however , significantly differed between nonobese and obese men , suggesting that the occurrences of AMS at high altitude may be closely related to increased body weight . Acute mountain sickness frequently occurs in travelers who rapidly ascend to an altitude of 2500 m without acclimatizing ; the incidence and severity depend on the speed of METHOD We recruited 44 subjects to participate in a study of the preventive effect of Ginko biloba extract ( EGb 761 ) on acute mountain sickness ( AMS ) and vasomotor changes of the extremities during a Himalayan expedition . After giving their written informed consent , the subjects were r and omized to two groups . One group received 160 mg of EGb 761 per day in two divided doses and the other group received placebo . Assessment was based on the course of the Environmental Symptom Question naire ( ESQ ) score and the cold gradient measured by photoplethysmography . RESULTS The prophylactic efficacy of treatment with EGb 761 was clearly demonstrated in this study . In terms of factor 1 ( AMS-Cerebral ) , no subject in the EGb 761 group developed acute mountain sickness versus 40.9 % of subjects in the placebo group ; this difference was very significant ( p < or = 1.4 x 10(-3 ) ) . In terms of factor 2 ( AMS-Respiratory ) , 3 subjects ( 13.6 % ) in the EGb 761 group developed acute mountain sickness versus 18 ( 81.8 % ) in the placebo group ; this difference was very significant ( p = 1.2 x 10(-5 ) ) . CONCLUSION Due to its multiple pharmacological actions , EGb 761 provides an interesting response to the prevention of mountain sickness for moderate altitude ( 5400 m ) with gradual exposure . It also decreased vasomotor disorders of the extremities , as demonstrated by plethysmography ( p < 10(-8 ) ) and a specific question naire ( p < 10(-9 ) ) We investigated whether a diet of increased carbohydrate content reduces the symptoms of acute mountain sickness ( AMS ) and whether concentrations of circulating cytokines rise and correlate with hypoxia and AMS . There were 19 healthy volunteers who ingested in r and omized order both a high carbohydrate ( 68 % CHO ) or normal carbohydrate ( 45 % CHO ) diet for 4 d. On the 4th d , subjects were exposed to 8 h of 10 % normobaric oxygen . Each subject completed the Lake Louise Consensus Question naire ( LLCQ : a question naire developed to quantify the common symptoms and consequences of AMS ) at the beginning and end of each hypoxic session , at which times venous blood was obtained for the following cytokines : interleukins 1 beta , 6 and 8 ( IL-1 beta , IL-6 , IL-8 ) and tumor necrosis factor alpha ( TNF-alpha ) . AMS symptoms did not differ significantly between the diets ( LLCQ scores : 68 % CHO = 10.1 + /- 3.8 vs. 45 % CHO = 10.3 + /- 4.1 ) . Cytokine concentrations did not change with hypoxia on either diet , nor did individual changes correlate with AMS symptoms . We conclude that a high carbohydrate diet for 4 d does not reduce the symptoms of AMS ; and plasma cytokine concentrations do not change with hypoxia and the development of AMS and , thus , are not likely mediators of this syndrome Altitude exposure alters hemodynamics and sympathoadrenal function and elicits acute mountain sickness ( AMS ) . Since dexamethasone prevents AMS and influences responsiveness to catecholamines , we studied hemodynamic and sympathoadrenal responses to 4,570 m simulated altitude in 8 subjects treated with dexamethasone or placebo . Mean pulse rates were less at altitude with dexamethasone ( 96.1 for placebo and 84.1 for dexamethasone ; treatment-altitude interaction , p = 0.0045 ) . Altitude led to a postural decline in mean arterial pressure ( posture-altitude interaction , p = 0.0026 ) , but this was not affected by dexamethasone . Dexamethasone reduced urinary epinephrine to a greater extent during altitude exposure ( from 9.41 ng.mg-1 creatinine with placebo to 4.16 with dexamethasone ) when compared with sea level ( from 3.24 to 3.08 ) . Urinary excretion of norepinephrine was unchanged at altitude . We conclude that acute altitude exposure is associated with stimulation of the adrenal medulla and not the sympathetic nervous system . Dexamethasone blocks the adrenal medullary response and blunts the pulse rate increase at altitude OBJECTIVE High altitude pulmonary oedema can be successfully treated and prevented by calcium channel blockers . Moreover , calcium entering in the cells could explain the congestive phenomena of acute mountain sickness ( AMS ) . These findings led us to study the action of a calcium channel blocker , isradipine , in the prevention of non-complicated AMS . METHODS In a double blind r and omized study , 20 healthy volunteers received 5 mg of isradipine ( n = 6 ) or placebo ( n = 6 ) for 8 days . After 5 days of treatment in normoxia , the subjects were rapidly transported to an altitude of 4350 m. The efficiency of the treatment was then estimated by the AMS symptom score , haemodynamic parameters and renal function . RESULTS The administration of isradipine did not significantly modify AMS symptom score nor most of other parameters measured in high altitude hypoxia . Heart rate was an average of 15 b/min lower in the isradipine group , probably because of a direct action of isradipine on the sinus node . Otherwise , the effects of hypoxia were similar in both groups and were in accordance with the literature . There was no clear explanation for the increase in cardiac output and stroke volume when the subjects moved from supine to st and ing position . Renal blood flow , measured by Doppler or para-aminohippuric acid clearance was not modified by hypoxia . Cerebral blood flow was elevated , due to the direct vasodilator effect of hypoxia . However this increase did not seem to be the main mechanism responsible for the congestive phenomena . On the other h and , the increase in capillary permeability ( demonstrated by the increased transcapillary escape rate of albumin , and albuminuria ) appeared to play a major role in the pathogenesis of AMS and high altitude cerebral oedema . Isradipine had no protective effect on these phenomena and its use should be restricted to the treatment of high altitude pulmonary oedema Remote ischemic preconditioning ( RIPC ) has been shown to protect remote organs , such as the brain and the lung , from damage induced by subsequent hypoxia or ischemia . Acute mountain sickness ( AMS ) is a syndrome of nonspecific neurologic symptoms and in high-altitude pulmonary edema excessive hypoxic pulmonary vasoconstriction ( HPV ) plays a pivotal role . We hypothesized that RIPC protects the brain from AMS and attenuates the magnitude of HPV after rapid ascent to 3,450 m. Forty nonacclimatized volunteers were r and omized into two groups . At low altitude ( 750 m ) the RIPC group ( n = 20 ) underwent 4 × 5 min of lower-limb ischemia ( induced by inflation of bilateral thigh cuffs to 200 mmHg ) followed by 5 min of reperfusion . The control group ( n = 20 ) underwent a sham protocol ( 4 × 5 min of bilateral thigh cuff inflation to 20 mmHg ) . Thereafter , participants ascended to 3,450 m by train over 2 h and stayed there for 48 h. AMS was evaluated by the Lake Louise score ( LLS ) and the AMS-C score . Systolic pulmonary artery pressure ( SPAP ) was assessed by transthoracic Doppler echocardiography . RIPC had no effect on the overall incidence ( RIPC : 35 % , control : 35 % , P = 1.0 ) and severity ( RIPC vs. CONTROL P = 0.496 for LLS ; P = 0.320 for AMS-C score ) of AMS . RIPC also had no significant effect on SPAP [ maximum after 10 h at high altitude ; RIPC : 33 ( SD 8) mmHg ; controls : 37 ( SD 7 ) mmHg ; P = 0.19 ] . This study indicates that RIPC , performed immediately before passive ascent to 3,450 m , does not attenuate AMS and the magnitude of high-altitude pulmonary hypertension . NEW & NOTEWORTHY Remote ischemic preconditioning ( RIPC ) has been reported to improve neurologic and pulmonary outcome following an acute ischemic or hypoxic insult , yet the effect of RIPC for protecting from high-altitude diseases remains to be determined . The present study shows that RIPC , performed immediately before passive ascent to 3,450 m , does not attenuate acute mountain sickness and the degree of high-altitude pulmonary hypertension . Therefore , RIPC can not be recommended for prevention of high-altitude diseases Ibuprofen has been shown to be more effective than placebo in the treatment of high altitude headache ( HAH ) , but nonsteroidal anti-inflammatory agents have been linked to increased incidence of gastrointestinal ( GI ) side effects and high-altitude pulmonary edema ( HAPE ) . We postulated that acetaminophen , which does not share ibuprofen 's theorized causal link to GI side effects or HAPE , could provide effective HAH therapy . We conducted a prospect i ve , r and omized , double-blind , clinical trial of ibuprofen vs. acetaminophen in the Solu Khumbu , Nepal : Mt. Everest Base Camp , Pheriche , Dingboche ( 4240 m to 5315 m ) . Seventy-four consecutive patients ( ages 13 to 61 years ) were r and omized , were assessed with the Lake Louise Acute Mountain Sickness ( AMS ) criteria , and received a physical examination ( which included vital signs , oxygen saturation as measured by pulse oximetry ( SpO(2 ) ) , and assessment of clinical Lake Louise AMS criteria ) . Patients then received either 400 mg of ibuprofen ( IBU ) or 1000 mg of acetaminophen ( ACET ) , and were asked to rate their cephalgia using a 10-cm visual analog scale ( VAS ) . Thirty-nine patients received IBU , and 35 received ACET . Baseline Lake Louise AMS scores were identical in the two groups ( mean = 5.9 ) . No differences in mean VAS scores between IBU and ACET groups were noted at time 0 ( presentation ) , 30 , 60 , or 120 min . No cases of HAPE or high altitude cerebral edema were noted during the study period . In this study population , acetaminophen was as effective as ibuprofen in relieving the pain of HAH Vuyk , Jaap , Jan Van Den Bos , Kees Terhell , Rene De Bos , Ad Vletter , Pierre Valk , Martie Van Beuzekom , Jack Van Kleef , and Albert Dahan . Acetazolamide improves cerebral oxygenation during exercise at high altitude . High Alt . Med . Biol . 7:290 - 301 , 2006.--Acute mountain sickness is thought to be triggered by cerebral hypoxemia and be prevented by acetazolamide ( Actz ) . The effect of Actz on cerebral oxygenation at altitude remains unknown . In 16 members of the 2005 Dutch Cho Oyu ( 8201 m , Tibet ) expedition , the influence of Actz and exercise ( 750 mg PO daily ) on heart rate , peripheral and regional cerebral oxygen saturation ( Sa(O(2 ) ) and rS(O(2 ) ) ) , the Lake Louise score ( LLS ) , and psychomotor function were studied at 0 m 14 days prior to the expedition , after arrival at 3700 m on day 3 , after arrival at 5700 m on day 29 , and again at 5700 m before the end of the expedition on day 51 . After arrival at 3700 m , the LLS of the climbers taking Actz ( n = 8) was significantly lower compared to those who did not take Actz ( n = 8) : 0.75 + /- 1.0 versus 2.9 + /- 2.0 , p < 0.05 ( ANOVA ) . High LLSs were associated with low rS(O(2 ) ) values in rest and exercise ( p < 0.01 and p < 0.001 ) . With altitude , resting Sa(O(2 ) ) and resting rS(O(2 ) ) decreased significantly ( p < 0.001 ) , irrespective of Actz use . Exercise at 3700 m and 5700 m reduced Sa(O(2 ) ) and rS(O(2 ) ) even further compared to rest ( p < 0.001 ) , although at 3700 m the rS(O(2 ) ) was preserved better in those who took Actz ( 55.3 + /- 4.3 % versus 47.9 + /- 5.7 % , p < 0.05 ) . Irrespective of Actz use , with altitude , the percentage of omissions in the vigilance and tracking test increased while the climbers ' scores on vigor decreased ( p < 0.05 ) . In conclusion , at altitude , exercise-induced reduction in cerebral oxygenation is less in climbers on Actz compared to climbers not taking Actz . This effect is nullified after several weeks at altitude due to acclimatization in climbers not taking Actz Background Patients with COPD may experience acute mountain sickness ( AMS ) and other altitude‐related adverse health effects ( ARAHE ) when traveling to high altitudes . This study evaluated whether dexamethasone , a drug used for the prevention of AMS in healthy individuals , would prevent AMS/ARAHE in patients with COPD . Methods This placebo‐controlled , double‐blind , parallel‐ design trial included patients with COPD and Global Initiative for Obstructive Lung Disease grade 1 to 2 who were living below 800 m. Patients were r and omized to receive dexamethasone ( 8 mg/d ) or placebo starting on the day before ascent and while staying in a high‐altitude clinic at 3,100 m for 2 days . The primary outcome assessed during the altitude sojourn was the combined incidence of AMS/ARAHE , defined as an Environmental Symptoms Question naire cerebral score evaluating AMS ≥ 0.7 or ARAHE requiring descent or an intervention . Results In 60 patients r and omized to receive dexamethasone ( median [ quartiles ] age : 57 years [ 50 ; 60 ] , FEV1 86 % predicted [ 70 ; 104 ] ; PaO2 at 760 m : 9.6 kPa [ 9.2 ; 10.0 ] ) , the incidence of AMS/ARAHE was 22 % ( 13 of 60 ) . In 58 patients r and omized to receive placebo ( age : 60 y [ 53 ; 64 ] ; FEV1 94 % predicted [ 76 ; 103 ] ; PaO2 : 10.0 kPa [ 9.1 ; 10.5 ] ) , the incidence of AMS/ARAHE was 24 % ( 14 of 58 ) ( χ2 statistic vs dexamethasone , P = .749 ) . Dexamethasone mitigated the altitude‐induced PaO2 reduction compared with placebo ( mean between‐group difference [ 95 % CI ] , 0.4 kPa [ 0.0‐0.8 ] ; P = .028 ) . Conclusions In lowl and ers with mild to moderate COPD , the incidence of AMS/ARAHE at 3,100 m was moderate and not reduced by dexamethasone treatment . Based on these findings , dexamethasone can not be recommended for the prevention of AMS/ARAHE in patients with COPD undertaking high‐altitude travel , although the drug mitigated the altitude‐induced hypoxemia . Trial Registry Clinical Trials.gov ; No. : NCT02450968 ; URL : www . clinical trials.gov INTRODUCTION A higher risk of thrombosis has been reported on prolonged stay at high altitude ( HAA ) . Lowering of homocysteine ( Hcy ) has been found to reduce the risk of venous thrombosis . A r and omized field trial was conducted with primary question whether Hcy lowering agents have any effect on the incidence of thrombosis at HAA amongst Indian soldiers as compared to existing interventions . METHODS All units freshly inducted to HAA were r and omized into intervention ( Vit B12 1000 microgram/day , B6 3mg/day & folic acid 5mg/day ) and control arms , with a sample size of 12,000 person-years in each arm . RESULTS At the end of one year stay at HAA , Folate and B 12 levels decreased significantly in control arm . The levels of Hcy , fibrinogen and plasminogen activator inhibitor ( PAI 1 ) were lower and nitric oxide higher in intervention arm as compared to control arm ( p<0.05 ) . At the end of 2years , 5 thrombotic episodes occurred in the intervention arm and 17 in control arm with RR of 0.29 ( 95 % CI 0.11 - 0.80 ) , attributable fraction % ( AFe ) 70.59 % , Population attributable risk percent 54.55 % and Protective Fraction 240 % . CONCLUSION Intervention with B12 and folic acid is effective in reducing Hcy , PAI 1 , fibrinogen levels and increasing NO levels at 1yr as compared to control arm and reducing the incidence of thrombosis at 2years of stay at HAA . Thus , vitamin B 12 , B6 and folic acid intervention is safe and effective method of reducing morbidity and mortality caused by HAA induced coagulopathy BACKGROUND Inhaled budesonide has been suggested as a novel prevention for acute mountain sickness . However , efficacy has not been compared with the st and ard acute mountain sickness prevention medication acetazolamide . METHODS This double-blind , r and omized , placebo-controlled trial compared inhaled budesonide versus oral acetazolamide versus placebo , starting the morning of ascent from 1240 m ( 4100 ft ) to 3810 m ( 12,570 ft ) over 4 hours . The primary outcome was acute mountain sickness incidence ( headache and Lake Louise Question naire ≥3 and another symptom ) . RESULTS A total of 103 participants were enrolled and completed the study ; 33 ( 32 % ) received budesonide , 35 ( 34 % ) acetazolamide , and 35 ( 34 % ) placebo . Demographics were not different between the groups ( P > .09 ) . Acute mountain sickness prevalence was 73 % , with severe acute mountain sickness of 47 % . Fewer participants in the acetazolamide group ( n = 15 , 43 % ) developed acute mountain sickness compared with both budesonide ( n = 24 , 73 % ) ( odds ratio [ OR ] 3.5 , 95 % confidence interval [ CI ] 1.3 - 10.1 ) and placebo ( n = 22 , 63 % ) ( OR 0.5 , 95 % CI 0.2 - 1.2 ) . Severe acute mountain sickness was reduced with acetazolamide ( n = 11 , 31 % ) compared with both budesonide ( n = 18 , 55 % ) ( OR 2.6 , 95 % CI 1 - 7.2 ) and placebo ( n = 19 , 54 % ) ( OR 0.4 , 95 % CI 0.1 - 1 ) , with a number needed to treat of 4 . CONCLUSION Budesonide was ineffective for the prevention of acute mountain sickness , and acetazolamide was preventive of severe acute mountain sickness taken just before rapid ascent The reduced arterial oxygen tension at high altitude impairs the ability to work . Acetazolamide improves arterial oxygen saturation ( SaO2 ) by increasing ventilation but is associated with an increased work and cost of breathing . Depending on the setting s , sildenafil can also increases SaO2 possibly through a reduction in pulmonary hypertension and interstitial edema , which could improve ventilation – perfusion matching . The objective of this study is to determine the effects of acetazolamide and sildenafil on ventilatory control and breathing efficiency ( VE/VCO2 ) during submaximal steady-state hypoxic exercise in healthy individuals . Following 18 h of hypoxic exposure in an altitude tent at an oxygen concentration of 12.5 % ( simulated altitude of 4,300 m ) , 15 participants performed 10 min of hypoxic exercise on a stationary bicycle at 40 % of their sea level peak oxygen uptake ( VO2 ) while r and omly receiving sildenafil 40 mg ( SIL ) , acetazolamide 125 mg ( ACZ ) or a placebo ( PLA ) . There was no difference in VO2 during exercise between conditions while SaO2 was greater with acetazolamide compared to both placebo and sildenafil . Acetazolamide increased ventilation ( PLA 49.0 ± 3.2 , SIL 47.7 ± 3.1 , ACZ 52.1 ± 3.0 l/min ) and reduced end-tidal CO2 ( PETCO2 ) ( PLA 32.1 ± 0.8 , SIL 32.8 ± 0.9 , ACZ 29.2 ± 0.7 mmHg ) compared to placebo and sildenafil . Breathing was less efficient with acetazolamide ( increased VE/VCO2 ) in comparison to placebo and sildenafil ( PLA 41.5 ± 1.0 , SIL 40.4 ± 1.3 , ACZ 45.4 ± 1.0 ) while sildenafil did not change VE/VCO2 during hypoxic exercise . In conclusion , acetazolamide increased ventilation and reduced breathing efficiency while sildenafil did not affect breathing efficiency despite a trend toward a blunted ventilatory response , possibly due to a reduction in pulmonary hypertension and /or ventilatory drive , during submaximal hypoxic exercise in healthy individuals |
10,704 | 31,852,920 | Reductions in total and LDL cholesterol were found .
The present review supports treatment intensification with GLP-1RA in uncontrolled type 2 diabetes on SGLT2i .
This drug regimen could provide improved HbA1c control , together with enhanced weight loss and blood pressure and lipids control | GLP-1 receptor agonists ( GLP-1RA ) and SGLT2 inhibitors ( SGLT2i ) have been associated with improved glycemic control , body weight loss and favorable changes in cardiovascular risk factors and outcomes .
We conducted a systematic review and meta- analysis to evaluate the effects of the addition of GLP-1RA to SGLT2i in patients with type 2 diabetes mellitus and inadequate glycemic control . | Importance Hypoglycemia , common in patients with type 1 diabetes , is a major barrier to achieving good glycemic control . Severe hypoglycemia can lead to coma or death . Objective To determine whether insulin degludec is noninferior or superior to insulin glargine U100 in reducing the rate of symptomatic hypoglycemic episodes . Design , Setting , and Participants Double-blind , r and omized , crossover noninferiority trial involving 501 adults with at least 1 hypoglycemia risk factor treated at 84 US and 6 Polish centers ( January 2014-January 12 , 2016 ) for two 32-week treatment periods , each with a 16-week titration and a 16-week maintenance period . Interventions Patients were r and omized 1:1 to receive once-daily insulin degludec followed by insulin glargine U100 ( n = 249 ) or to receive insulin glargine U100 followed by insulin degludec ( n = 252 ) and r and omized 1:1 to morning or evening dosing within each treatment sequence . Main Outcomes and Measures The primary end point was the rate of overall severe or blood glucose-confirmed ( < 56 mg/dL ) symptomatic hypoglycemic episodes during the maintenance period . Secondary end points included the rate of nocturnal symptomatic hypoglycemic episodes and proportion of patients with severe hypoglycemia during the maintenance period . The noninferiority criterion for the primary end point and for the secondary end point of nocturnal hypoglycemia was defined as an upper limit of the 2-sided 95 % CI for a rate ratio of 1.10 or lower ; if noninferiority was established , 2-sided statistical testing for superiority was conducted . Results Of the 501 patients r and omized ( mean age , 45.9 years ; 53.7 % men ) , 395 ( 78.8 % ) completed the trial . During the maintenance period , the rates of overall symptomatic hypoglycemia were 2200.9 episodes per 100 person-years ’ exposure ( PYE ) in the insulin degludec group vs 2462.7 episodes per 100 PYE in the insulin glargine U100 group for a rate ratio ( RR ) of 0.89 ( 95 % CI , 0.85 - 0.94 ; P < .001 for noninferiority ; P < .001 for superiority ; rate difference , −130.31 episodes per 100 PYE ; 95 % CI , −193.5 to −67.16 ) . The rates of nocturnal symptomatic hypoglycemia were 277.1 per 100 PYE in the insulin degludec group vs 428.6 episodes per 100 PYE in the insulin glargine U100 group , for an RR of 0.64 ( 95 % CI , 0.56 - 0.73 ; P < .001 for noninferiority ; P < .001 for superiority ; rate difference , −61.94 episodes per 100 PYE ; 95 % CI , −83.85 to −40.03 ) . A lower proportion of patients in the insulin degludec than in the insulin glargine U100 group experienced severe hypoglycemia during the maintenance period ( 10.3 % , 95 % CI , 7.3%-13.3 % vs 17.1 % , 95 % CI , 13.4%-20.8 % , respectively ; McNemar P = .002 ; risk difference , −6.8 % ; 95 % CI , −10.8 % to −2.7 % ) . Conclusions and Relevance Among patients with type 1 diabetes and at least 1 risk factor for hypoglycemia , 32 weeks ’ treatment with insulin degludec vs insulin glargine U100 result ed in a reduced rate of overall symptomatic hypoglycemic episodes . Trial Registration clinical trials.gov Identifier : Importance Hypoglycemia , a serious risk for insulin-treated patients with type 2 diabetes , negatively affects glycemic control . Objective To test whether treatment with basal insulin degludec is associated with a lower rate of hypoglycemia compared with insulin glargine U100 in patients with type 2 diabetes . Design , Setting , and Participants R and omized , double-blind , treat-to-target crossover trial including two 32-week treatment periods , each with a 16-week titration period and a 16-week maintenance period . The trial was conducted at 152 US centers between January 2014 and December 2015 in 721 adults with type 2 diabetes and at least 1 hypoglycemia risk factor who were previously treated with basal insulin with or without oral antidiabetic drugs . Interventions Patients were r and omized 1:1 to receive once-daily insulin degludec followed by insulin glargine U100 ( n = 361 ) or to receive insulin glargine U100 followed by insulin degludec ( n = 360 ) and r and omized 1:1 to morning or evening dosing within each treatment sequence . Main Outcomes and Measures The primary end point was the rate of overall symptomatic hypoglycemic episodes ( severe or blood glucose confirmed [ < 56 mg/dL ] ) during the maintenance period . Secondary end points were the rate of nocturnal symptomatic hypoglycemic episodes ( severe or blood glucose confirmed , occurring between 12:01 AM and 5:59 AM ) and the proportion of patients with severe hypoglycemia during the maintenance period . Results Of the 721 patients r and omized ( mean [ SD ] age , 61.4 [ 10.5 ] years ; 53.1 % male ) , 580 ( 80.4 % ) completed the trial . During the maintenance period , the rates of overall symptomatic hypoglycemia for insulin degludec vs insulin glargine U100 were 185.6 vs 265.4 episodes per 100 patient-years of exposure ( PYE ) ( rate ratio = 0.70 [ 95 % CI , 0.61 - 0.80 ] ; P < .001 ; difference , −23.66 episodes/100 PYE [ 95 % CI , −33.98 to −13.33 ] ) , and the proportions of patients with hypoglycemic episodes were 22.5 % vs 31.6 % ( difference , −9.1 % [ 95 % CI , −13.1 % to −5.0 % ] ) . The rates of nocturnal symptomatic hypoglycemia with insulin degludec vs insulin glargine U100 were 55.2 vs 93.6 episodes/100 PYE ( rate ratio = 0.58 [ 95 % CI , 0.46 - 0.74 ] ; P < .001 ; difference , −7.41 episodes/100 PYE [ 95 % CI , −11.98 to −2.85 ] ) , and the proportions of patients with hypoglycemic episodes were 9.7 % vs 14.7 % ( difference , −5.1 % [ 95 % CI , −8.1 % to −2.0 % ] ) . The proportions of patients experiencing severe hypoglycemia during the maintenance period were 1.6 % ( 95 % CI , 0.6%-2.7 % ) for insulin degludec vs 2.4 % ( 95 % CI , 1.1%-3.7 % ) for insulin glargine U100 ( McNemar P = .35 ; risk difference , −0.8 % [ 95 % CI , −2.2 % to 0.5 % ] ) . Statistically significant reductions in overall and nocturnal symptomatic hypoglycemia for insulin degludec vs insulin glargine U100 were also seen for the full treatment period . Conclusions and Relevance Among patients with type 2 diabetes treated with insulin and with at least 1 hypoglycemia risk factor , 32 weeks ’ treatment with insulin degludec vs insulin glargine U100 result ed in a reduced rate of overall symptomatic hypoglycemia . Trial Registration clinical trials.gov Identifier : BACKGROUND Glucagon-like peptide-1 ( GLP-1 ) receptor agonists and sodium-glucose co-transporter-2 ( SGLT2 ) inhibitors improve glycaemic control and reduce bodyweight in patients with type 2 diabetes through different mechanisms . We assessed the safety and efficacy of the addition of the once-weekly GLP-1 receptor agonist dulaglutide to the ongoing treatment regimen in patients whose diabetes is inadequately controlled with SGLT2 inhibitors , with or without metformin . METHODS AWARD-10 was a phase 3b , double-blind , parallel-arm , placebo-controlled , 24-week study done at 40 clinical sites in Austria , Czech Republic , Germany , Hungary , Israel , Mexico , Spain , and the USA . Eligible adult patients ( ≥18 years ) with inadequately controlled type 2 diabetes ( HbA1c concentration ≥7·0 % [ 53 mmol/mol ] and ≤9·5 % [ 80 mmol/mol ] ) , a BMI of 45 kg/m2 or less , and taking stable doses ( > 3 months ) of an SGLT2 inhibitor ( with or without metformin ) were r and omly assigned ( 1:1:1 ) via an interactive web-response system to subcutaneous injections of either dulaglutide 1·5 mg , dulaglutide 0·75 mg , or placebo once per week for 24 weeks . Patients and investigators were masked to dulaglutide and placebo assignment , and those assessing outcomes were masked to study drug assignment . The primary objective was to test for the superiority of dulaglutide ( 1·5 mg or 0·75 mg ) versus placebo for change in HbA1c concentration from baseline at 24 weeks . All analyses were done in the intention-to-treat population , defined as all r and omly assigned patients who received at least one dose of study drug . This study is registered with Clinical Trials.gov , number NCT02597049 . FINDINGS Between Dec 7 , 2015 , and Feb 3 , 2017 , 424 patients were r and omly assigned to dulaglutide 1·5 mg ( n=142 ) , dulaglutide 0·75 mg ( n=142 ) , and placebo ( n=140 ) . One patient in the dulaglutide 0·75 mg group was excluded from the analysis because they did not receive any dose of the study drug . The reduction in HbA1c concentration at 24 weeks was larger in patients receiving dulaglutide ( least squares mean [ LSM ] for dulaglutide 1·5 mg -1·34 % [ SE 0·06 ] or -14·7 mmol/mol [ 0·6 ] ; dulaglutide 0·75 mg -1·21 % [ 0·06 ] or -13·2 mmol/mol [ 0·6 ] ) than in patients receiving placebo ( -0·54 % [ 0·06 ] or -5·9 mmol/mol [ 0·6 ] ; p<0·0001 for both groups vs placebo ) . The LSM differences were -0·79 % ( 95 % CI -0·97 to -0·61 ) or -8·6 mmol/mol ( -10·6 to -6·7 ) for dulaglutide 1·5 mg and -0·66 % ( -0·84 to -0·49 ) or -7·2 mmol/mol ( -9·2 to -5·4 ) for dulaglutide 0·75 mg ( p<0·0001 for both ) . Serious adverse events were reported for five ( 4 % ) patients in the dulaglutide 1·5 mg group , three ( 2 % ) patients in the dulaglutide 0·75 mg group , and five ( 4 % ) patients in the placebo group . Treatment-emergent adverse events were more common in patients treated with dulaglutide than in patients who received placebo , mainly because of an increased incidence of gastrointestinal adverse events . Nausea ( 21 [ 15 % ] patients in the dulaglutide 1·5 mg group vs seven [ 5 % ] in the dulaglutide 0·75 mg group vs five [ 4 % ] in the placebo group ) , diarrhoea ( eight [ 6 % ] vs 14 [ 10 % ] vs four [ 3 % ] ) , and vomiting ( five [ 4 % ] vs four [ 3 % ] vs one [ 1 % ] ) were more common with dulaglutide than with placebo . One episode of severe hypoglycaemia was reported in the dulaglutide 0·75 mg group . Two ( 1 % ) patients receiving dulaglutide 1·5 mg died , but these deaths were not considered to be related to study drug ; no deaths occurred in the other groups . INTERPRETATION Dulaglutide as add-on treatment to SGLT2 inhibitors ( with or without metformin ) result ed in significant and clinical ly relevant improvements in glycaemic control , with acceptable tolerability that is consistent with the established safety profile of dulaglutide . FUNDING Eli Lilly and Company OBJECTIVE Development of these guidelines is m and ated by the American Association of Clinical Endocrinologists ( AACE ) Board of Directors and the American College of Endocrinology ( ACE ) Board of Trustees and adheres to published AACE protocol s for the st and ardized production of clinical practice guidelines ( CPGs ) . METHODS Recommendations are based on diligent review of clinical evidence with transparent incorporation of subjective factors . RESULTS There are 9 broad clinical questions with 123 recommendation numbers that include 160 specific statements ( 85 [ 53.1 % ] strong [ Grade A ] ; 48 [ 30.0 % ] intermediate [ Grade B ] , and 11 [ 6.9 % ] weak [ Grade C ] , with 16 [ 10.0 % ] based on expert opinion [ Grade D ] ) that build a comprehensive medical care plan for obesity . There were 133 ( 83.1 % ) statements based on strong ( best evidence level [ BEL ] 1 = 79 [ 49.4 % ] ) or intermediate ( BEL 2 = 54 [ 33.7 % ] ) levels of scientific substantiation . There were 34 ( 23.6 % ) evidence -based recommendation grade s ( Grade s A-C = 144 ) that were adjusted based on subjective factors . Among the 1,790 reference citations used in this CPG , 524 ( 29.3 % ) were based on strong ( evidence level [ EL ] 1 ) , 605 ( 33.8 % ) were based on intermediate ( EL 2 ) , and 308 ( 17.2 % ) were based on weak ( EL 3 ) scientific studies , with 353 ( 19.7 % ) based on review s and opinions ( EL 4 ) . CONCLUSION The final recommendations recognize that obesity is a complex , adiposity-based chronic disease , where management targets both weight-related complications and adiposity to improve overall health and quality of life . The detailed evidence -based recommendations allow for nuanced clinical decision-making that addresses real-world medical care of patients with obesity , including screening , diagnosis , evaluation , selection of therapy , treatment goals , and individualization of care . The goal is to facilitate high- quality care of patients with obesity and provide a rational , scientific approach to management that optimizes health outcomes and safety . ABBREVIATIONS A1C = hemoglobin A1c AACE = American Association of Clinical Endocrinologists ACE = American College of Endocrinology ACSM = American College of Sports Medicine ADA = American Diabetes Association ADAPT = Arthritis , Diet , and Activity Promotion Trial ADHD = attention-deficit hyperactivity disorder AHA = American Heart Association AHEAD = Action for Health in Diabetes AHI = apnea-hypopnea index ALT = alanine aminotransferase AMA = American Medical Association ARB = angiotensin receptor blocker ART = assisted reproductive technology AUC = area under the curve BDI = Beck Depression Inventory BED = binge eating disorder BEL = best evidence level BLOOM = Behavioral Modification and Lorcaserin for Overweight and Obesity Management BLOSSOM = Behavioral Modification and Lorcaserin Second Study for Obesity Management BMI = body mass index BP = blood pressure C-SSRS = Columbia Suicidality Severity Rating Scale CAD = coronary artery disease CARDIA = Coronary Artery Risk Development in Young Adults CBT = cognitive behavioral therapy CCO = Consensus Conference on Obesity CHF = congestive heart failure CHO = carbohydrate CI = confidence interval COR-I = Contrave Obesity Research I CPG = clinical practice guideline CV = cardiovascular CVD = cardiovascular disease DASH = Dietary Approaches to Stop Hypertension DBP = diastolic blood pressure DEXA = dual-energy X-ray absorptiometry DPP = Diabetes Prevention Program DSE = diabetes support and education EL = evidence level ED = erectile dysfunction ER = extended release EWL = excess weight loss FDA = Food and Drug Administration FDG = 18F-fluorodeoxyglucose GABA = gamma-aminobutyric acid GERD = gastroesophageal reflux disease GI = gastrointestinal GLP-1 = glucagon-like peptide 1 HADS = Hospital Anxiety and Depression Scale HDL-c = high-density lipoprotein cholesterol HR = hazard ratio HTN = hypertension HUNT = Nord-Trøndelag Health Study ICSI = intracytoplasmic sperm injection IFG = impaired fasting glucose IGT = impaired glucose tolerance ILI = intensive lifestyle intervention IVF = in vitro fertilization LAGB = laparoscopic adjustable gastric b and ing LDL-c = low-density lipoprotein cholesterol LES = lower esophageal sphincter LSG = laparoscopic sleeve gastrectomy LV = left ventricle LVH = left ventricular hypertrophy LVBG = laparoscopic vertical b and ed gastroplasty MACE = major adverse cardiovascular events MAOI = monoamine oxidase inhibitor MI = myocardial infa rct ion MN RCT = meta- analysis of non-r and omized prospect i ve or case-controlled trials MRI = magnetic resonance imaging MUFA = monounsaturated fatty acid NAFLD = nonalcoholic fatty liver disease NASH = nonalcoholic steatohepatitis NES = night eating syndrome NHANES = National Health and Nutrition Examination Surveys NHLBI = National Heart , Lung , and Blood Institute NHS = Nurses ' Health Study NICE = National Institute for Health and Care Excellence OA = osteoarthritis OGTT = oral glucose tolerance test OR = odds ratio OSA = obstructive sleep apnea PHQ-9 = Patient Health Question naire PCOS = polycystic ovary syndrome PCP = primary care physician POMC = pro-opiomelanocortin POWER = Practice -Based Opportunities for Weight Reduction PPI = proton pump inhibitor PRIDE = Program to Reduce Incontinence by Diet and Exercise PSA = prostate specific antigen QOL = quality of life RA = receptor agonist RCT = r and omized controlled trial ROC = receiver operator characteristic RR = relative risk RYGB = Roux-en-Y gastric bypass SAD = sagittal abdominal diameter SBP = systolic blood pressure SCOUT = Sibutramine Cardiovascular Outcome Trial SG = sleeve gastrectomy SHBG = sex hormonebinding globulin SIEDY = Structured Interview on Erectile Dysfunction SNRI = serotonin-norepinephrine reuptake inhibitors SOS = Swedish Obese Subjects SS = surveillance study SSRI = selective serotonin reuptake inhibitors STORM = Sibutramine Trial on Obesity Reduction and Maintenance TCA = tricyclic antidepressant TONE = Trial of Nonpharmacologic Intervention in the Elderly TOS = The Obesity Society T2DM = type 2 diabetes mellitus UKPDS = United Kingdom Prospect i ve Diabetes Study U.S = United States VAT = visceral adipose tissue VLDL = very low-density lipoprotein WC = waist circumference WHO = World Health Organization WHR = waist-hip ratio WHtR = waist-to-height ratio WMD = weighted mean difference WOMAC = Western Ontario and McMaster Universities osteoarthritis index XENDOS = XEnical in the Prevention of Diabetes in Obese Subjects The decrement in plasma glucose concentration with SGLT2 inhibitors ( SGLT2i ) is blunted by a rise in endogenous glucose production ( EGP ) . We investigated the ability of incretin treatment to offset the EGP increase . Subjects with type 2 diabetes ( n = 36 ) were r and omized to 1 ) canagliflozin ( CANA ) , 2 ) liraglutide ( LIRA ) , or 3 ) CANA plus LIRA ( CANA/LIRA ) . EGP was measured with [3 - 3H]glucose with or without drugs for 360 min . In the pretreatment studies , EGP was comparable and decreased ( 2.2 ± 0.1 to 1.7 ± 0.2 mg/kg ⋅ min ) during a 300- to 360-min period ( P < 0.01 ) . The decrement in EGP was attenuated with CANA ( 2.1 ± 0.1 to 1.9 ± 0.1 mg/kg ⋅ min ) and CANA/LIRA ( 2.2 ± 0.1 to 2.0 ± 0.1 mg/kg ⋅ min ) , whereas with LIRA it was the same ( 2.4 ± 0.2 to 1.8 ± 0.2 mg/kg ⋅ min ) ( all P < 0.05 vs. baseline ) . After CANA , the fasting plasma insulin concentration decreased ( 18 ± 2 to 12 ± 2 μU/mL , P < 0.05 ) , while it remained unchanged in LIRA ( 18 ± 2 vs. 16 ± 2 μU/mL ) and CANA/LIRA ( 17 ± 1 vs. 15 ± 2 μU/mL ) . Mean plasma glucagon did not change during the pretreatment studies from 0 to 360 min , while it increased with CANA ( 69 ± 3 to 78 ± 2 pg/mL , P < 0.05 ) , decreased with LIRA ( 93 ± 6 to 80 ± 6 pg/mL , P < 0.05 ) , and did not change in CANA/LIRA . LIRA prevented the insulin decline and blocked the glucagon rise observed with CANA but did not inhibit the increase in EGP . Factors other than insulin and glucagon contribute to the stimulation of EGP after CANA-induced glucosuria IMPORTANCE Weight loss of 5 % to 10 % can improve type 2 diabetes and related comorbidities . Few safe , effective weight-management drugs are currently available . OBJECTIVE To investigate efficacy and safety of liraglutide vs placebo for weight management in adults with overweight or obesity and type 2 diabetes . DESIGN , SETTING , AND PARTICIPANTS Fifty-six-week r and omized ( 2:1:1 ) , double-blind , placebo-controlled , parallel-group trial with 12-week observational off-drug follow-up period . The study was conducted at 126 sites in 9 countries between June 2011 and January 2013 . Of 1361 participants assessed for eligibility , 846 were r and omized . Inclusion criteria were body mass index of 27.0 or greater , age 18 years or older , taking 0 to 3 oral hypoglycemic agents ( metformin , thiazolidinedione , sulfonylurea ) with stable body weight , and glycated hemoglobin level 7.0 % to 10.0 % . INTERVENTIONS Once-daily , subcutaneous liraglutide ( 3.0 mg ) ( n = 423 ) , liraglutide ( 1.8 mg ) ( n = 211 ) , or placebo ( n = 212 ) , all as adjunct to 500 kcal/d dietary deficit and increased physical activity ( ≥150 min/wk ) . MAIN OUTCOMES AND MEASURES Three co primary end points : relative change in weight , proportion of participants losing 5 % or more , or more than 10 % , of baseline weight at week 56 . RESULTS Baseline weight was 105.7 kg with liraglutide ( 3.0-mg dose ) , 105.8 kg with liraglutide ( 1.8-mg dose ) , and 106.5 kg with placebo . Weight loss was 6.0 % ( 6.4 kg ) with liraglutide ( 3.0-mg dose ) , 4.7 % ( 5.0 kg ) with liraglutide ( 1.8-mg dose ) , and 2.0 % ( 2.2 kg ) with placebo ( estimated difference for liraglutide [ 3.0 mg ] vs placebo , -4.00 % [ 95 % CI , -5.10 % to -2.90 % ] ; liraglutide [ 1.8 mg ] vs placebo , -2.71 % [ 95 % CI , -4.00 % to -1.42 % ] ; P < .001 for both ) . Weight loss of 5 % or greater occurred in 54.3 % with liraglutide ( 3.0 mg ) and 40.4 % with liraglutide ( 1.8 mg ) vs 21.4 % with placebo ( estimated difference for liraglutide [ 3.0 mg ] vs placebo , 32.9 % [ 95 % CI , 24.6 % to 41.2 % ] ; for liraglutide [ 1.8 mg ] vs placebo , 19.0 % [ 95 % CI , 9.1 % to 28.8 % ] ; P < .001 for both ) . Weight loss greater than 10 % occurred in 25.2 % with liraglutide ( 3.0 mg ) and 15.9 % with liraglutide ( 1.8 mg ) vs 6.7 % with placebo ( estimated difference for liraglutide [ 3.0 mg ] vs placebo , 18.5 % [ 95 % CI , 12.7 % to 24.4 % ] , P < .001 ; for liraglutide [ 1.8 mg ] vs placebo , 9.3 % [ 95 % CI , 2.7 % to 15.8 % ] , P = .006 ) . More gastrointestinal disorders were reported with liraglutide ( 3.0 mg ) vs liraglutide ( 1.8 mg ) and placebo . No pancreatitis was reported . CONCLUSIONS AND RELEVANCE Among overweight and obese participants with type 2 diabetes , use of subcutaneous liraglutide ( 3.0 mg ) daily , compared with placebo , result ed in weight loss over 56 weeks . Further studies are needed to evaluate longer-term efficacy and safety . TRIAL REGISTRATION clinical trials.gov Identifier : NCT01272232 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 Aim To explain the subadditive efficacy typically observed with initial combination treatments for type 2 diabetes . Methods Individual subject data from 1186 patients with type 2 diabetes [ mean glycated haemoglobin ( HbA1c ) = 8.8 % ] treated with metformin , canagliflozin or canagliflozin + metformin were used . The baseline HbA1c versus ΔHbA1c relationships for monotherapy arms were determined using analysis of covariance and then used to predict efficacy in the combination arms by modelling how applying one treatment lowers the ‘ effective baseline HbA1c ’ for a second treatment . The model was further tested using data from several published combination studies . Results The mean ΔHbA1c levels were −1.25 , −1.33 , −1.37 , −1.77 and −1.81 % with metformin , canagliflozin 100 mg , canagliflozin 300 mg , canagliflozin 100 mg/metformin and canagliflozin 300 mg/metformin , respectively . Using the monotherapy results , the predicted efficacy for the canagliflozin/metformin arms was within 10 % of the observed values using the new model , whereas assuming simple additivity overpredicted efficacy in the combination arms by nearly 50 % . For 10 other published initial combination studies , predictions from the new model [ mean ( st and ard error ) predicted ΔHbA1c = 1.67 % ( 0.14 ) ] were much more consistent with observed values [ ΔHbA1c = 1.72 % ( 0.12 ) ] than predictions based on assuming additivity [ predicted ΔHbA1c = 2.19 % ( 0.21 ) ] . Conclusions The less‐than‐additive efficacy commonly seen with initial combination treatments for type 2 diabetes can be largely explained by the impact of baseline HbA1c on the efficacy of individual treatments . Novel formulas have been developed for predicting the efficacy of combination treatments based on the efficacy of individual treatments and the baseline HbA1c of the target patients BACKGROUND Sodium-glucose cotransporter 2 ( SGLT2 ) inhibitors improve glycaemia in patients with type 2 diabetes by enhancing urinary glucose excretion . We compared the efficacy and safety of canagliflozin , an SGLT2 inhibitor , with glimepiride in patients with type 2 diabetes inadequately controlled with metformin . METHODS We undertook this 52 week , r and omised , double-blind , active-controlled , phase 3 non-inferiority trial at 157 centres in 19 countries between Aug 28 , 2009 , and Dec 21 , 2011 . Patients aged 18 - 80 years with type 2 diabetes and glycated haemoglobin A1c ( HbA1c ) of 7·0 - 9·5 % on stable metformin were r and omly assigned ( 1:1:1 ) by computer-generated r and om sequence via an interactive voice or web response system to receive canagliflozin 100 mg or 300 mg , or glimepiride ( up-titrated to 6 mg or 8 mg per day ) orally once daily . Patients , study investigators , and local sponsor personnel were masked to treatment . The primary endpoint was change in HbA1c from baseline to week 52 , with a non-inferiority margin of 0·3 % for the comparison of each canagliflozin dose with glimepiride . If non-inferiority was shown , we assessed superiority on the basis of an upper bound of the 95 % CI for the difference of each canagliflozin dose versus glimepiride of less than 0·0 % . Analysis was done in a modified intention-to-treat population , including all r and omised patients who received at least one dose of study drug . This study is registered with Clinical Trials.gov , number NCT00968812 . FINDINGS 1450 of 1452 r and omised patients received at least one dose of glimepiride ( n=482 ) , canagliflozin 100 mg ( n=483 ) , or canagliflozin 300 mg ( n=485 ) . For lowering of HbA1c at 52 weeks , canagliflozin 100 mg was non-inferior to glimepiride ( least-squares mean difference -0·01 % [ 95 % CI -0·11 to 0·09 ] ) , and canagliflozin 300 mg was superior to glimepiride ( -0·12 % [ -0·22 to -0·02 ] ) . 39 ( 8 % ) patients had serious adverse events in the glimepiride group versus 24 ( 5 % ) in the canagliflozin 100 mg group and 26 ( 5 % ) in the 300 mg group . In the canagliflozin 100 mg and 300 mg groups versus the glimepiride group , we recorded a greater number of genital mycotic infections ( women : 26 [ 11 % ] and 34 [ 14 % ] vs five [ 2 % ] ; men : 17 [ 7 % ] and 20 [ 8 % ] vs three [ 1 % ] ) , urinary tract infections ( 31 [ 6 % ] for both canagliflozin doses vs 22 [ 5 % ] ) , and osmotic diuresis-related events ( pollakiuria : 12 [ 3 % ] for both doses vs one [ < 1 % ] ; polyuria : four [ < 1 % ] for both doses vs two [ < 1 % ] ) . INTERPRETATION Canagliflozin provides greater HbA1c reduction than does glimepiride , and is well tolerated in patients with type 2 diabetes receiving metformin . These findings support the use of canagliflozin as a viable treatment option for patients who do not achieve sufficient glycaemic control with metformin therapy . FUNDING Janssen Research & Development , LLC OBJECTIVE Among patients with type 2 diabetes uncontrolled with metformin , exenatide once weekly ( QW ) plus dapagliflozin combination produced greater reductions in glycemia , weight , and systolic blood pressure ( SBP ) at 28 weeks than exenatide QW or dapagliflozin alone ( DURATION -8 ) . Here , we investigated the safety and maintenance of efficacy at 52 weeks , after a 24-week extension . RESEARCH DESIGN AND METHODS This phase 3 , multicenter , double-blind study r and omized adults with type 2 diabetes ( with glycated hemoglobin [ HbA1c ] 8.0–12.0 % [ 64–108 mmol/mol ] and on metformin ≥1,500 mg/day ) to exenatide QW ( 2-mg subcutaneous injection ) plus once-daily dapagliflozin ( 10-mg oral tablet ) , exenatide QW plus oral placebo , or dapagliflozin plus injected placebo . Extension-period P values were nominal . RESULTS Of 1,375 patients screened , 695 were r and omized ( mean baseline HbA1c 9.3 % [ 78 mmol/mol ] ) ; 81.2 % completed the study , and 75.3 % completed treatment . At 52 weeks , HbA1c reductions were greater with exenatide QW plus dapagliflozin ( least squares mean change −1.75 % [ −19.1 mmol/mol ] ) versus exenatide QW ( −1.38 % [ −15.1 mmol/mol ] ; P = 0.006 ) or dapagliflozin ( −1.23 % [ −13.4 mmol/mol ] ; P < 0.001 ) ; mean HbA1c values were 6.9 % ( 52 mmol/mol ) , 7.2 % ( 55 mmol/mol ) , and 7.4 % ( 57 mmol/mol ) , respectively . Weight and SBP reductions were greater with exenatide QW plus dapagliflozin ( −3.31 kg and −4.5 mmHg ) versus exenatide QW ( −1.51 kg and −0.7 mmHg ; both P < 0.001 ) but similar to those with dapagliflozin ( −2.28 kg and −2.7 mmHg ; P = 0.057 and P = 0.100 , respectively ) . The exenatide QW plus dapagliflozin regimen was well tolerated with no unexpected safety findings ; more patients treated with exenatide QW experienced gastrointestinal and injection site – related adverse events . No major hypoglycemia occurred . CONCLUSIONS Among patients with type 2 diabetes uncontrolled with metformin , exenatide QW plus dapagliflozin provided sustained improvements in glycemia , weight , and SBP over 52 weeks , with no unexpected safety findings BACKGROUND Glucagon-like peptide 1 receptor agonists differ in chemical structure , duration of action , and in their effects on clinical outcomes . The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown . We aim ed to determine the safety and efficacy of albiglutide in preventing cardiovascular death , myocardial infa rct ion , or stroke . METHODS We did a double-blind , r and omised , placebo-controlled trial in 610 sites across 28 countries . We r and omly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease ( at a 1:1 ratio ) to groups that either received a subcutaneous injection of albiglutide ( 30 - 50 mg , based on glycaemic response and tolerability ) or of a matched volume of placebo once a week , in addition to their st and ard care . Investigators used an interactive voice or web response system to obtain treatment assignment , and patients and all study investigators were masked to their treatment allocation . We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death , myocardial infa rct ion , or stroke , which was assessed in the intention-to-treat population . If non-inferiority was confirmed by an upper limit of the 95 % CI for a hazard ratio of less than 1·30 , closed testing for superiority was prespecified . This study is registered with Clinical Trials.gov , number NCT02465515 . FINDINGS Patients were screened between July 1 , 2015 , and Nov 24 , 2016 . 10 793 patients were screened and 9463 participants were enrolled and r and omly assigned to groups : 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo . On Nov 8 , 2017 , it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued , and participants returned for a final visit and discontinuation from study treatment ; the last patient visit was on March 12 , 2018 . These 9463 patients , the intention-to-treat population , were evaluated for a median duration of 1·6 years and were assessed for the primary outcome . The primary composite outcome occurred in 338 ( 7 % ) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 ( 9 % ) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group ( hazard ratio 0·78 , 95 % CI 0·68 - 0·90 ) , which indicated that albiglutide was superior to placebo ( p<0·0001 for non-inferiority ; p=0·0006 for superiority ) . The incidence of acute pancreatitis ( ten patients in the albiglutide group and seven patients in the placebo group ) , pancreatic cancer ( six patients in the albiglutide group and five patients in the placebo group ) , medullary thyroid carcinoma ( zero patients in both groups ) , and other serious adverse events did not differ between the two groups . There were three ( < 1 % ) deaths in the placebo group that were assessed by investigators , who were masked to study drug assignment , to be treatment-related and two ( < 1 % ) deaths in the albiglutide group . INTERPRETATION In patients with type 2 diabetes and cardiovascular disease , albiglutide was superior to placebo with respect to major adverse cardiovascular events . Evidence -based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes . FUNDING GlaxoSmithKline Aim To investigate the efficacy and safety of insulin degludec/liraglutide ( IDegLira ) versus insulin glargine 100 units/mL ( IGlar U100 ) as add‐on to sodium‐glucose co‐transporter‐2 ( SGLT2 ) inhibitor therapy . Material s and methods In this 26‐week , phase IIIb , open‐label , parallel‐group , treat‐to‐target trial , conducted at 74 sites in 11 countries , insulin‐naïve people aged ≥18 years with glycated haemoglobin ( HbA1c ) 53–97 mmol/mol ( 7.0–11.0 % ) , body mass index 20–40 kg/m2 and inadequately controlled type 2 diabetes ( T2D ) on SGLT2 inhibitor ± oral antidiabetic drugs were r and omized 1:1 to once‐daily IDegLira or IGlar U100 , both as add‐on to existing therapy . The primary endpoint was change in HbA1c from baseline to week 26 . Results A total of 210 participants were r and omized to each treatment arm . Mean HbA1c reductions were 21 mmol/mol ( 1.9%‐points ) with IDegLira and 18 mmol/mol ( 1.7%‐points ) with IGlar U100 ; confirming non‐inferiority ( P < 0.0001 ) and superiority of IDegLira ( difference in HbA1c change –3.90 mmol/mol ; 95 % confidence interval [ CI ] –5.45 ; –2.35 ( −0.36%‐points ; 95 % CI –0.50 , –0.21 ) ) . Superiority for IDegLira over IGlar U100 was also confirmed for : body weight ( difference −1.92 kg ; 95 % CI –2.64 , –1.19 ) ; severe or blood‐glucose‐confirmed symptomatic hypoglycaemia ( rate ratio 0.42 ; 95 % CI 0.23 , 0.75 ) ; total daily insulin dose ( difference −15.37 U ; 95 % CI –19.60 , −11.13 ) . The overall treatment‐emergent adverse event rate was higher with IDegLira as a result of higher increased lipase and nausea rates . Conclusions The favourable safety and efficacy profile of IDegLira in people with uncontrolled T2D on SGLT2 inhibitors , and lower weight gain and hypoglycaemia risk versus IGlar U100 , suggest that clinicians should consider IDegLira initiation in this population BACKGROUND Semaglutide is a once-weekly glucagon-like peptide-1 ( GLP-1 ) analogue for type 2 diabetes . Few clinical trials have reported on the concomitant use of GLP-1 receptor agonists with sodium-glucose cotransporter-2 ( SGLT-2 ) inhibitors . We aim ed to investigate the efficacy and safety of semaglutide when added to SGLT-2 inhibitor therapy in patients with inadequately controlled type 2 diabetes . METHODS The SUSTAIN 9 double-blind , parallel-group trial was done at 61 centres in six countries ( Austria , Canada , Japan , Norway , Russia , and the USA ) . Adults with type 2 diabetes and HbA1c 7·0 - 10·0 % ( 53 - 86 mmol/mol ) , despite at least 90 days of treatment with an SGLT-2 inhibitor , were r and omly assigned ( 1:1 ) to receive subcutaneous semaglutide 1·0 mg or volume-matched placebo once weekly for 30 weeks , after a dose-escalation schedule of 4 weeks of 0·25 mg semaglutide or placebo and 4 weeks of 0·5 mg semaglutide or placebo . Existing antidiabetic medications , including SGLT-2 inhibitor treatment , were continued for the duration of the trial . Rescue medication , defined as intensification of background antidiabetic treatment or the initiation of new glucose-lowering medications , could be given to patients meeting specific criteria at the discretion of the investigator . The primary outcome was change in HbA1c from baseline at week 30 , assessed in the full analysis set ( all patients r and omly allocated to treatment ) using on-treatment data collected before rescue medication was started . The confirmatory secondary outcome was change in bodyweight from baseline to week 30 . Safety was also assessed in the safety analysis set ( all patients who received at least one dose of treatment ) . The trial was registered with Clinical Trials.gov ( NCT03086330 ) . FINDINGS Between March 15 , and Dec 4 , 2017 , 302 patients were enrolled and r and omly assigned to receive semaglutide 1·0 mg or placebo ( full analysis set ) , of whom 301 received at least one dose of treatment ( safety analysis set ) . One patient was assigned to semaglutide but was not treated ( reason unknown ) . 294 ( 97·4 % ) patients completed the trial and 267 ( 88·4 % ) completed treatment . Baseline characteristics were generally comparable between groups . In addition to r and omised medication and SGLT-2 inhibitor , 216 ( 71·5 % ) patients were taking metformin and 39 ( 12·9 % ) were taking sulphonylurea . Patients given semaglutide had greater reductions in HbA1c ( estimated treatment difference -1·42 % [ 95 % CI -1·61 to -1·24 ] ; -15·55 mmol/mol [ -17·54 to -13·56 ] ) and bodyweight ( -3·81 kg [ -4·70 to -2·93 ] ) versus those r and omised to placebo ( both p<0·0001 ) . 356 adverse events were reported by 104 ( 69·3 % ) patients in the semaglutide group , and 247 adverse events were reported by 91 ( 60·3 % ) patients in the placebo group . Gastrointestinal adverse events were most common and were reported in 56 ( 37·3 % ) patients in the semaglutide group and 20 ( 13·2 % ) in the placebo group . Serious adverse events occurred in seven ( 4·7 % ) patients in the semaglutide group and six ( 4·0 % ) in the placebo group . Severe or blood glucose-confirmed hypoglycaemic events were reported in four patients on semaglutide ( 2·7 % ) . 16 patients stopped treatment early because of an adverse event , 13 of whom were in the semaglutide group . There were no deaths during the trial . INTERPRETATION Adding semaglutide to SGLT-2 inhibitor therapy significantly improves glycaemic control and reduces bodyweight in patients with inadequately controlled type 2 diabetes , and is generally well tolerated . FUNDING Novo Nordisk BACKGROUND Glucagon-like peptide-1 ( GLP-1 ) receptor agonists are effective treatments for type 2 diabetes , lowering glycated haemoglobin ( HbA1c ) and weight , but are currently only approved for use as subcutaneous injections . Oral semaglutide , a novel GLP-1 agonist , was compared with subcutaneous liraglutide and placebo in patients with type 2 diabetes . METHODS In this r and omised , double-blind , double-dummy , phase 3a trial , we recruited patients with type 2 diabetes from 100 sites in 12 countries . Eligible patients were aged 18 years or older , with HbA1c of 7·0 - 9·5 % ( 53 - 80·3 mmol/mol ) , on a stable dose of metformin ( ≥1500 mg or maximum tolerated ) with or without a sodium-glucose co-transporter-2 inhibitor . Participants were r and omly assigned ( 2:2:1 ) with an interactive web-response system and stratified by background glucose-lowering medication and country of origin , to once-daily oral semaglutide ( dose escalated to 14 mg ) , once-daily subcutaneous liraglutide ( dose escalated to 1·8 mg ) , or placebo for 52 weeks . Two estim and s were defined : treatment policy ( regardless of study drug discontinuation or rescue medication ) and trial product ( assumed all participants were on study drug without rescue medication ) in all participants who were r and omly assigned . The treatment policy estim and was the primary estim and . The primary endpoint was change from baseline to week 26 in HbA1c ( oral semaglutide superiority vs placebo and non-inferiority [ margin : 0·4 % ] and superiority vs subcutaneous liraglutide ) and the confirmatory secondary endpoint was change from baseline to week 26 in bodyweight ( oral semaglutide superiority vs placebo and liraglutide ) . Safety was assessed in all participants who received at least one dose of study drug . This trial is registered on Clinical trials.gov , number NCT02863419 , and the European Clinical Trials registry , number EudraCT 2015 - 005210 - 30 . FINDINGS Between Aug 10 , 2016 , and Feb 7 , 2017 , 950 patients were screened , of whom 711 were eligible and r and omly assigned to oral semaglutide ( n=285 ) , subcutaneous liraglutide ( n=284 ) , or placebo ( n=142 ) . 341 ( 48 % ) of 711 participants were female and the mean age was 56 years ( SD 10 ) . All participants were given at least one dose of study drug , and 277 ( 97 % ) participants in the oral semaglutide group , 274 ( 96 % ) in the liraglutide group , and 134 ( 94 % ) in the placebo group completed the 52-week trial period . Mean change from baseline in HbA1c at week 26 was -1·2 % ( SE 0·1 ) with oral semaglutide , -1·1 % ( SE 0·1 ) with subcutaneous liraglutide , and -0·2 % ( SE 0·1 ) with placebo . Oral semaglutide was non-inferior to subcutaneous liraglutide in decreasing HbA1c ( estimated treatment difference [ ETD ] -0·1 % , 95 % CI -0·3 to 0·0 ; p<0·0001 ) and superior to placebo ( ETD -1·1 % , -1·2 to -0·9 ; p<0·0001 ) by use of the treatment policy estim and . By use of the trial product estim and , oral semaglutide had significantly greater decreases in HbA1c than both subcutaneous liraglutide ( ETD -0·2 % , 95 % CI -0·3 to -0·1 ; p=0·0056 ) and placebo ( ETD -1·2 % , -1·4 to -1·0 ; p<0·0001 ) at week 26 . Oral semaglutide result ed in superior weight loss ( -4·4 kg [ SE 0·2 ] ) compared with liraglutide ( -3·1 kg [ SE 0·2 ] ; ETD -1·2 kg , 95 % CI -1·9 to -0·6 ; p=0·0003 ) and placebo ( -0·5 kg [ SE 0·3 ] ; ETD -3·8 kg , -4·7 to -3·0 ; p<0·0001 ) at week 26 ( treatment policy ) . By use of the trial product estim and , weight loss at week 26 was significantly greater with oral semaglutide than with subcutaneous liraglutide ( -1·5 kg , 95 % CI -2·2 to -0·9 ; p<0·0001 ) and placebo ( ETD -4·0 kg , -4·8 to -3·2 ; p<0·0001 ) . Adverse events were more frequent with oral semaglutide ( n=229 [ 80 % ] ) and subcutaneous liraglutide ( n=211 [ 74 % ] ) than with placebo ( n=95 [ 67 % ] ) . INTERPRETATION Oral semaglutide was non-inferior to subcutaneous liraglutide and superior to placebo in decreasing HbA1c , and superior in decreasing bodyweight compared with both liraglutide and placebo at week 26 . Safety and tolerability of oral semaglutide were similar to subcutaneous liraglutide . Use of oral semaglutide could potentially lead to earlier initiation of GLP-1 receptor agonist therapy in the diabetes treatment continuum of care . FUNDING Novo Nordisk |
10,705 | 32,358,684 | In most subtypes of interventions , mixed results on adherence ( and persistence ) were found .
Multicomponent interventions based on patient education and counseling were the most effective interventions when aim ing to increase adherence and /or persistence to osteoporosis medications .
This up date d review suggests that patient education , monitoring and supervision , change in drug regimen , and interdisciplinary collaboration have mixed results on medication adherence and persistence , with more positive effects for multicomponent interventions with active patient involvement .
Compared with the previous review , a shift towards more patient involvement , counseling and shared decision-making , was seen , suggesting that individualized solutions , based on collaboration between the patient and the healthcare provider , are needed to improve adherence and persistence to osteoporosis medications | Multicomponent interventions with active patient involvement were more effective .
This study was conducted to up date a systematic literature review on interventions to improve adherence to anti-osteoporosis medications . | Summary Using a protocol led intervention program , pharmacists can decrease nonadherence to osteoporosis medication , by continuous monitoring and tailored counseling sessions , starting at treatment initiation . In the usual care group , 32.8 % of patients initiating osteoporosis medication discontinued or were nonadherent , compared to 19.0 % of patients in the intervention group . Purpose While community pharmacies have been shown to offer a promising platform for osteoporosis management in patients with osteoporosis , more research is needed to determine pharmacists ’ effects on improving adherence . The aim of this study was to determine the effects of a community pharmacists ’ intervention program on the 1-year discontinuation and nonadherence rates of patients initiating osteoporosis medication . Methods This intervention study included 937 patients , recruited from 13 Dutch community pharmacies , initiating osteoporosis medication . The intervention group ( N = 495 ) , received the Medication Monitoring and Optimization ( MeMO ) intervention , comprising of continuous monitoring of patients ’ adherence to their osteoporosis medication and tailored counseling sessions with nonadherent patients . Results were compared to an internal ( n = 442 ) reference group , receiving usual pharmacy care . Primary study outcomes were therapy discontinuation and nonadherence ; results were adjusted for potential confounders using Cox proportional hazard analysis . Secondary outcome was patients ’ satisfaction . Results In the usual care group , 32.8 % of patients initiating osteoporosis medication discontinued or were nonadherent , compared to 19.0 % of patients in the intervention group ( P < 0.001 ) . Ninety-three percent of the respondents were satisfied with the pharmacies ’ services provided . Notably , 31 % mentioned that the pharmacy was the only place where they received information on various aspects of administration and acting of their medication . Conclusion Pharmacists can decrease nonadherence and discontinuation with osteoporosis medication by providing tailored counseling sessions and continuous monitoring of drug use . Pharmaceutical care programs , such as MeMO , contribute to more optimal use of osteoporosis medication Osteoporosis treatment rates are declining , even among those with past fractures . Novel , low-cost approaches are needed to improve osteoporosis care . We conducted a parallel group , controlled , r and omized clinical trial evaluating a behavioral intervention for improving osteoporosis medication use . A total of 2684 women with self-reported fracture history after age 45 years not using osteoporosis therapy from US Global Longitudinal Study of Osteoporosis in Women ( GLOW ) sites were r and omized 1:1 to receive a multimodal , tailored , direct-to-patient , video intervention versus usual care . The primary study outcome was self-report of osteoporosis medication use at 6 months . Other outcomes included calcium and vitamin D supplementation , bone mineral density ( BMD ) testing , readiness for behavioral change , and barriers to treatment . In intent-to-treat analyses , there were no significant differences between groups ( intervention versus control ) in osteoporosis medication use ( 11.7 % versus 11.4 % , p = 0.8 ) , calcium supplementation ( 31.8 % versus 32.6 % , p = 0.7 ) , vitamin D intake ( 41.3 % versus 41.9 % , p = 0.8 ) , or BMD testing ( 61.8 % versus 57.1 % , p = 0.2 ) . In the intervention group , fewer women were in the precontemplative stage of behavior change , more women reported seeing their primary care provider , had concerns regarding osteonecrosis of the jaw , and difficulty in taking/remembering to take osteoporosis medications . We found differences in BMD testing among the subgroup of women with no prior osteoporosis treatment , those who provided contact information , and those with no past BMD testing . In per protocol analyses , women with appreciable exposure to the online intervention ( n = 257 ) were more likely to start nonbisphosphonates ( odds ratio [ OR ] = 2.70 ; 95 % confidence interval [ CI ] 1.26 - 5.79 ) compared with the usual care group . Although our intervention did not increase the use of osteoporosis therapy at 6 months , it increased nonbisphosphonate medication use and BMD testing in select subgroups , shifted participants ' readiness for behavior change , and altered perceptions of barriers to osteoporosis treatment . Achieving changes in osteoporosis care using patient activation approaches alone is challenging . © 2018 American Society for Bone and Mineral Research Summary Telephone call intervention did not improve alendronate persistence in Fracture Liaison Service ( FLS ) patients in this study . A bone turnover marker cut-off point for alendronate persistence is proposed for individual FLS patients . Introduction FLS aims to prevent subsequent fractures , which should include improving patients ’ persistence with prescribed oral bisphosphonates . We studied the influence of telephone calls and the predictive value of changes in bone turnover markers ( BTMs ) for evaluating persistence with alendronate . Methods Postmenopausal women with a recent fracture and osteoporosis who started alendronate were r and omized to receive three phone calls ( PC ) ( after 1 , 4 , and 12 months ) or no phone calls ( no PC ) . s-CTX and P1NP were measured at baseline and after 3 , 6 , 9 , and 12 months . As a reference group , 30 postmenopausal osteopenic patients with a recent fracture were analyzed as well . Persistence was assessed using the Dutch National Switch Point Pharmacies-GPs data base and cross-referenced with PC , no PC , and BTM changes . Cut-off values of BTMs were calculated based on least significant change ( LSC ) and also on underrunning median values of the untreated osteopenic postmenopausal reference group with a recent fracture . Results Out of 119 patients , 93 ( 78 % ) completed 12 months follow-up ( 45 PC and 48 no PC ) . Mean age was 69 years . Persistence was similar in PC and no PC participants . The cut-off value > 29 % ( < 415 ng/L ) as LSC of s-CTX and > 36 % ( < 53.1 μg/L ) as LSC of P1NP was determined optimally showing alendronate persistence after 1 year ( being 93 and 88 % , respectively ) . Conclusions In this context , telephone calls did not improve persistence . In around 90 % of patients , 1-year alendronate persistence was confirmed by achieving LSC of s-CTX and of P1NP at 12 months Summary Patients often do not know or underst and their bone density test results , and pharmacological treatment rates are low . In a clinical trial of 7749 patients , we used a tailored patient-activation result letter accompanied by a bone health brochure to improve appropriate pharmacological treatment . Treatment rates , however , did not improve . Introduction Patients often do not know or underst and their dual-energy x-ray absorptiometry ( DXA ) test results , which may lead to suboptimal care . We tested whether usual care augmented by a tailored patient-activation DXA result letter accompanied by an educational brochure would improve guideline -concordant pharmacological treatment compared to usual care only . Methods We conducted a r and omized , controlled , double-blinded , pragmatic clinical trial at three health care centers in the USA . We r and omized 7749 patients ≥50 years old and presenting for DXA between February 2012 and August 2014 . The primary clinical endpoint at 12 and 52 weeks post-DXA was receiving guideline -concordant pharmacological treatment . We also examined four of the steps along the pathway from DXA testing to that clinical endpoint , including ( 1 ) receiving and ( 2 ) underst and ing their DXA results and ( 3 ) having subsequent contact with their provider and ( 4 ) discussing their results and options . Results Mean age was 66.6 years , 83.8 % were women , and 75.3 % were non-Hispanic whites . Intention-to-treat analyses revealed that guideline -concordant pharmacological treatment was not improved at either 12 weeks ( 65.1 vs. 64.3 % , p = 0.506 ) or 52 weeks ( 65.2 vs. 63.8 % , p = 0.250 ) post-DXA , even though patients in the intervention group were more likely ( all p < 0.001 ) to recall receiving their DXA results letter at 12 weeks , correctly identify their results at 12 and 52 weeks , have contact with their provider at 52 weeks , and have discussed their results with their provider at 12 and 52 weeks . Conclusion A tailored DXA result letter and educational brochure failed to improve guideline -concordant care in patients who received DXA The CONSORT ( Consoli date d St and ards of Reporting Trials ) statement is used worldwide to improve the reporting of r and omized , controlled trials . Schulz and colleagues describe the latest version , CONSORT 2010 , which up date s the reporting guideline based on new method ological evidence and accumulating experience . Objective . To evaluate 2 incremental levels of intervention design ed to increase initiation of osteoporosis treatment by primary care physicians ( PCP ) following fragility fractures ( FF ) . Methods . Women and men over age 50 years were screened for incident FF in fracture clinics , and eligible out patients were r and omly assigned to st and ard care ( SC ) or to either minimal ( MIN ) or intensive ( INT ) interventions . The MIN and INT interventions were intended to educate and motivate both patients and PCP , but differed in their frequency of contact and information content . Delivery of osteoporosis medication was confirmed with pharmacists . Treatment rates were analyzed using an intention-to-treat approach . Results . At inclusion , 74.3 % of 881 out patients with FF were untreated . Followup at 12 months was completed in 92.3 % of patients . Up to 90 % of patients treated at inclusion remained treated at 12 months . Among patients who initially were untreated , 18.8 % in the SC group , 40.4 % in the MIN , and 53.2 % in the INT groups were treated at 12 months . Change in treatment rates ( adjusted for age and initial treatment ) increased significantly after both MIN and INT . Only the INT intervention significantly increased treatment rates in patients with previous fractures . Negative predictors of change in treatment status included non-major FF , age younger than 65 years , and male sex . Conclusion . Both interventions significantly increased initiation of osteoporosis treatment . Our multidisciplinary intervention builds on existing first-line structures and uses minimal specialized re sources . Iterative and systematic interventions in the context of clinical care may modify the approach of PCP to osteoporosis management after FF and narrow the care gap in the long term Summary Following initiation of oral bisphosphonate therapy through a secondary fracture prevention program , 2-year treatment compliance and persistence remained high and were similar in patients r and omised to follow-up by either the program or primary care physician . Thus , community-based and specialist management are equally effective in supporting compliance and persistence with anti-osteoporotic treatments . Introduction The purpose of this study was to determine whether management by a secondary fracture prevention ( SFP ) program ( aka “ fracture liaison service ” ) results in better compliance and persistence to oral bisphosphonate therapy than follow-up by the primary care physician , after initiation within an SFP program . Methods This prospect i ve RCT included 102 patients with incident osteoporotic fractures referred to a SFP program in Sydney , Australia . Following oral bisphosphonate therapy initiation , patients were r and omised to either 6-monthly follow-up with the SFP program ( group A ) or referral to their primary care physician with a single SFP program visit at 24 months ( group B ) . Compliance and persistence to treatment were measured using pharmaceutical cl aims data . Predictors of compliance and persistence and associations between compliance and persistence , and changes in bone mineral density ( BMD ) or bone resorption marker , urinary deoxypyridinoline over 24 months were analysed . Results The median medication possession ratio at 24 months was 0.78 ( IQR , 0.50–0.93 ) in group A and 0.79 ( IQR , 0.48–0.96 ) in group B ( p = 0.68 ) . Persistence at 24 months was also similar in both groups ( 64 vs. 61 % , respectively ; p = 0.75 ) . After adjusting for confounders , patients in group A were not more likely to be compliant ( OR , 1.06 ; 95 % CI , 0.46–2.47 ) or persistent ( HR , 0.83 ; 95 % CI , 0.27–1.67 ) than those r and omised to group B. Time-based changes in BMD or bone turnover were not associated with compliance or persistence . Conclusion Compliance and persistence to oral bisphosphonate therapy remain high amongst patients initiated within an SFP program , with community-based and SFP program management being equally effective in maintaining therapeutic compliance and persistence over 2 years . These results indicate that one of the main functions of an SFP program may be the initiation of therapy rather than continuous patient monitoring Purpose Osteoporosis Choice , an encounter decision aid , can engage patients and clinicians in shared decision making about osteoporosis treatment . Its effectiveness compared to the routine provision to clinicians of the patient ’s estimated risk of fracture using the FRAX calculator is unknown . Methods Patient-level , r and omized , three-arm trial enrolling women over 50 with osteopenia or osteoporosis eligible for treatment with bisphosphonates , where the use of Osteoporosis Choice was compared to FRAX only and to usual care to determine impact on patient knowledge , decisional conflict , involvement in the decision-making process , decision to start and adherence to bisphosphonates . Results We enrolled 79 women in the three arms . Because FRAX estimation alone and usual care produced similar results , we grouped them for analysis . Compared to these , use of Osteoporosis Choice increased patient knowledge ( median score 6 vs. 4 , p = .01 ) , improved underst and ing of fracture risk and risk reduction with bisphosphonates ( p = .01 and p<.0001 , respectively ) , had no effect on decision conflict , and increased patient engagement in the decision making process ( OPTION scores 57 % vs. 43 % , p = .001 ) . Encounters with the decision aid were 0.8 minutes longer ( range : 33 minutes shorter to 3.0 minutes longer ) . There were twice as many patients receiving and filling prescriptions in the decision aid arm ( 83 % vs. 40 % , p = .07 ) ; medication adherence at 6 months was no different across arms . Conclusion Supporting both patients and clinicians during the clinical encounter with the Osteoporosis Choice decision aid efficiently improves treatment decision making when compared to usual care with or without clinical decision support with FRAX results . Trial Registration clinical trials.gov Long-term patient adherence to osteoporosis treatment is poor despite proven efficacy . In this study , we aim ed to assess the impact of active patient training on treatment compliance and persistence in patients with postmenopausal osteoporosis . In the present national , multicenter , r and omized controlled study , postmenopausal osteoporosis patients ( 45 - 75 years ) who were on weekly bisphosphonate treatment were r and omized to active training ( AT ) and passive training ( PT ) groups and followed-up by 4 visits after the initial visit at 3 months interval during 12 months of the treatment . Both groups received a bisphosphonate usage guide and osteoporosis training booklets . Additionally , AT group received four phone calls ( at 2nd , 5th , 8th , and 11th months ) and participated to four interactive social/training meetings held in groups of 10 patients ( at 3rd , 6th , 9th , and 12th months ) . The primary evaluation criteria were self-reported persistence and compliance to the treatment and the secondary evaluation criteria was quality life of the patients assessed by 41-item Quality of Life European Foundation for Osteoporosis ( QUALEFFO-41 ) question naire .. Of 448 patients ( mean age 62.4±7.7 years ) , 226 were r and omized to AT group and 222 were r and omized to PT group . Among the study visits , the most common reason for not receiving treatment regularly was forgetfulness ( 54.9 % for visit 2 , 44.3 % for visit 3 , 51.6 % for visit 4 , and 43.8 % for visit 5 ) , the majority of the patients always used their drugs regularly on recommended days and dosages ( 63.8 % for visit 2 , 60.9 % for visit 3 , 72.1 % for visit 4 , and 70.8 % for visit 5 ) , and most of the patients were highly satisfied with the treatment ( 63.4 % for visit 2 , 68.9 % for visit 3 , 72.4 % for visit 4 , and 65.2 % for visit 5 ) and wanted to continue to the treatment ( 96.5 % for visit 2 , 96.5 % for visit 3 , 96.9 % for visit 4 , and 94.4 % for visit 5 ) . QUALEFFO scores of the patients in visit 1 significantly improved in visit 5 ( 37.7±25.4 vs. 34.0±14.6 , p<0.001 ) ; however , the difference was not significant between AT and PT groups both in visit 1 and visit 5 . In conclusion , in addition to active training , passive training provided at the 1st visit did not improve the persistence and compliance of the patients for bisphosphonate treatment 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 INTRODUCTION To describe the rationale and design of an NIH funded r and omized controlled trial : the Patient Activation after DXA Result Notification ( PAADRN ) study . The aim of this trial is to evaluate the effect that a direct mailing of Dual-Energy X-ray Absorptiometry ( DXA ) results from bone density testing centers to patients will have on patients ' knowledge , treatment and self-efficacy . METHODS We will enroll approximately 7500 patients presenting for DXA at three study sites , the University of Iowa , the University of Alabama at Birmingham , and Kaiser Permanente of Atlanta , Georgia . We will r and omize providers ( and their respective patients ) to either the intervention arm or usual care . Patients r and omized to the intervention group will receive a letter with their DXA results and an educational brochure , while those r and omized to usual care will receive their DXA results according to st and ard practice . The seven discrete outcomes are changes from baseline to 12-weeks and /or 52-weeks post-DXA in : ( 1 ) guideline concordant pharmacologic and non-pharmacologic therapy ; ( 2 ) knowledge of DXA results ; ( 3 ) osteoporosis-specific knowledge ; ( 4 ) general health-related quality of life ; ( 5 ) satisfaction with bone-related health care , ( 6 ) patient activation ; and , ( 7 ) osteoporosis-specific self-efficacy . CONCLUSION This trial will offer evidence of the impact of a novel approach-direct-to-patient mailing of test results -to improve patient activation in their bone health care . The results will inform clinical practice for the communication of DXA and other test results OBJECTIVE To investigate the effect of pharmacist management of poorly controlled diabetes mellitus in a community-based primary care group . STUDY DESIGN R and omized controlled trial of pharmacist management of diabetes compared with usual medical care . METHODS Patients 18 years or older with glycosylated hemoglobin ( A1C ) levels of 9.0 % or higher were enrolled . Patients were r and omly assigned to an intervention group ( n = 52 ) or a control group ( n = 51 ) . Management in the control group included the use of registries and targeted patient outreach . The intervention group participated in the same outreach program plus medication management , patient education , and disease control by a pharmacist . RESULTS Nonparametric data showed median A1C decreases of 1.50 % for the intervention group and 0.40 % for the control group ( P = .06 ) . Significantly more patients in the intervention group improved their A1C level by at least 1.0 % relative to the control group ( 67.3 % vs 41.2 % , P = .02 ) . Most of this benefit was seen for patients of nonwhite race/ethnicity compared with control subjects ( 56.3 % vs 22.7 % , P = .03 ) . Male patients showed significantly greater benefit as well , with a median A1C decrease of 1.90 % vs 0.15 % for controls ( P = .03 ) . CONCLUSIONS Patients with poorly controlled diabetes improved A1C levels significantly when pharmacist management was added to an aggressive organizational diabetes management program . Our results suggest that clinical ly trained pharmacists can help primary care providers improve diabetes management , especially among male patients and among patients of nonwhite race/ethnicity OBJECTIVE The aim of this study was to examine the level of compliance and persistence in patients with postmenopausal osteoporosis ( OP ) receiving daily risedronate ( 5 mg ) with either fixed dosing of three different timing regimens ( A : before breakfast ; B : in-between meals ; C : before bedtime ) or with flexible dosing and the effect on urinary N-terminal telopeptide of Type 1 collagen ( NTX-1 ) . METHODS The study included 448 patients with postmenopausal OP . Patients were r and omly assigned into six treatment groups each with a permutation of the treatment sequence ( ABC , BCA , etc . ) in the crossover phase ( 3 x 1 week ) and r and omized to 23 weeks of either the daily flexible ( either regimen A , B or C ) or fixed timing ( only regimen A , B , or C ) in the patient 's preference phase . Urinary NTX-1 was tested . RESULTS A total of 433 patients participated in the patient 's preference phase ( 49.7 % preferred flexible and 50.3 % fixed timing ) . There was no significant difference between the proportion of responders who were both compliant and persistent in the flexible ( 54.4 % ) and fixed regimens ( 53.7 % ) ( p=0.8803 ) . A significant difference between the flexible and fixed regimens was seen in persistence in favor of the flexible regimen ( p=0.0306 ) . There was no significant difference between the flexible and fixed regimens in terms of compliance ( p=0.4611 ) . Change in urinary NTX-1 did not show any difference between the two regimens . At the final visit , 51 % of patients in the flexible and 55 % in the fixed regimen group considered the used risedronate regimen as excellent or very good ( p=0.1440 ) . CONCLUSION A flexible dosing with daily risedronate appears be a valuable option in terms of compliance and persistence for patients with postmenopausal OP Summary Osteoporosis treatment has low adherence and persistence . This study evaluated if greater patient involvement could improve them . At 12 months , only 114 out of 344 participants were “ fully adherent and persistent ” ( all drug doses taken throughout the study ) . Only frequency of drug administration had a significant influence on adherence . Introduction Osteoporosis affects millions of individuals worldwide . There are now several effective drugs , but adherence to and persistence with treatment are low . This 12-month multicenter , prospect i ve , r and omized study evaluated the efficacy of two different methods aim ed at improving adherence and persistence through greater patient involvement , compared with st and ard clinical practice . Methods Three hundred thirty-four post-menopausal women , receiving an oral prescription for osteoporosis for the first time , were recruited and r and omized into three groups : group 1 ( controls , managed according to st and ard clinical practice ) and groups 2 and 3 ( managed with greater patient and caregiver involvement and special reinforcements : group 2 , instructed to use several different “ reminders ” ; group 3 , same “ reminders ” as group 2 , plus regular phone calls from and meetings at the referring Center ) . All enrolled women had two visits ( baseline and 12 months ) . Results Of 334 enrolled women , 247 ( 74 % ) started the prescribed therapy . Of those who started , 219 ( 88.7 % ) persisted in therapy for at least 10 months . At final evaluation , only 114 women were considered as “ fully adherent and persistent ” ( all doses taken throughout the 12 months ) . There were no significant differences regarding “ full adherence ” among the three r and omized groups . The frequency of drug administration had a significant influence : weekly administration had a > 5-fold higher adherence and monthly administration an 8-fold higher adherence ( p < 0.0001 ) than daily administration . Conclusions The special effort of devising and providing additional reminders did not prove effective . Additional interventions during the follow-up , including costly interventions such as phone calls and educational meetings , did not provide significant advantages Abstract Summary The patients ’ adherence to osteoporosis treatments is low . In our study population a history of osteoporotic fractures was associated to better compliance and persistence ; however , a 12-month r and omized study carried out on 816 osteoporotic women showed that providing the patients with their individual fracture risk information did not prove effective . Purpose Several drugs are currently available for the treatment of osteoporosis , but the patients ’ compliance and persistence with these treatments are low . This study aim ed to both analyze the adherence to oral osteoporosis medications among Italian osteoporotic patients ( cross-sectional study ) and evaluate if providing patients with their individual fracture risk information may improve compliance and persistence ( prospect i ve study ) . Methods A total of 3379 osteoporotic patients referred as out patients for a visit 1 year after receiving a prescription of oral osteoporosis medications for the first time , were enrolled for the retrospective study . Moreover , 816 postmenopausal women receiving an oral prescription for osteoporosis for the first time , were r and omized into two groups : group 1 ( managed according to st and ard clinical practice ) and group 2 ( managed with greater patient involvement and information on the individual risk of major osteoporotic fractures calculated by DeFRA algorithm ) . Results In the retrospective study , a history of osteoporotic fractures , the frequency of drug administration and a condition of being overweight/obese had a significant influence on both compliance and persistence . Of the 816 patients enrolled in the longitudinal study , 731 ( 374 of group 1 and 357 of group 2 ) attended the 1 year follow-up visit . The percentage of women with high compliance or persistence was greater in group 2 ( 64.2 vs. 58.1 % and 66.8 vs. 62.6 % , respectively ) , but without reaching any statistical significance . Conclusions Although providing the patients with their individual fracture risk information was not statistically effective , further studies on additional interventions able to improve the patients ’ perceived risk of fracture are warranted Summary The r and omized , clinical trial demonstrated that switching to monthly minodronate from weekly alendronate and risedronate provides greater increases in patients ’ satisfaction and bone mineral density and more substantial decreases in a bone resorption marker than continuing weekly alendronate and risedronate in patients with systemic rheumatic diseases on glucocorticoid therapy . Purpose Osteoporosis and associated fractures are major concerns for patients with systemic rheumatic diseases on long-term glucocorticoid therapy . Bisphosphonates increase bone mineral density ( BMD ) and reduce the frequency of vertebral fractures , but they are associated with poor adherence . The effects of monthly oral minodronate on patients ’ satisfaction , BMD , and bone turnover markers were investigated in patients with systemic rheumatic diseases on glucocorticoids and weekly oral alendronate or risedronate . Methods Study patients with systemic rheumatic diseases on oral glucocorticoids and weekly alendronate 35 mg or risedronate 17.5 mg were r and omly assigned either to switch to minodronate 50 mg every 4 weeks or to continue the currently taking weekly bisphosphonate for 52 weeks after a 24-week run-in period . Patients were stratified by hospital site , sex , and menopausal status in women at enrollment . The primary endpoint was the difference between the proportions of patients who responded very satisfactory or satisfactory for the current bisphosphonate therapy at weeks 48 and 76 between the two groups . Secondary endpoints included percentage changes in lumbar spine BMD and bone turnover markers from the time of starting allocated treatment . Results Monthly minodronate was superior to weekly alendronate or risedronate for patients ’ satisfaction , the increase of lumbar spine BMD , and suppression of serum tartrate-resistant acid phosphatase 5b at week 76 . Conclusions Monthly minodronate is more acceptable and may be more effective than weekly alendronate or risedronate for prevention and treatment of bone loss in patients with systemic rheumatic diseases on glucocorticoid therapy Objectives This study examined patient adherence and persistence to oral bisphosphonates for the treatment of osteoporosis in real-world setting s. Methods A systematic review was completed according to the Preferred Reporting Items for Systematic Review s and Meta-Analyses . Medical Literature Analysis and Retrieval System Online ( MEDLINE ) , Cumulative Index to Nursing and Allied Health Literature ( CINAHL ) , Allied and Complementary Medicine Data base ( AMED ) , Data base of Abstract s of Review s of Effects ( DARE ) , Health Technology Assessment ( HTA ) and National Health Service Economic Evaluation Data base NHS EED ) data bases were search ed for studies published in English language up to April 2018 . Prospect i ve and retrospective observational studies that used prescription cl aim data bases or hospital medical records to examine patient adherence and persistence to oral bisphosphonate treatment among adults with osteoporosis were included . The Newcastle – Ottawa quality assessment scale ( NOS ) was used to assess the quality of included studies . Results The search yielded 540 published studies , of which 89 were deemed relevant and were included in this review . The mean age of patients included within the studies ranged between 53 to 80.8 years , and the follow-up varied from 3 months to 14 years . The mean persistence of oral bisphosphonates for 6 months , 1 year and 2 years ranged from 34.8 % to 71.3 % , 17.7 % to 74.8 % and 12.9 % to 72.0 % , respectively . The mean medication possession ratio ranged from 28.2 % to 84.5 % , 23 % to 50 % , 27.2 % to 46 % over 1 year , 2 years and 3 years , respectively . All studies included scored between 6 to 8 out of 9 on the NOS . The determinants of adherence and persistence to oral bisphosphonates included geographic residence , marital status , tobacco use , educational status , income , hospitalisation , medication type and dosing frequency . Conclusions While a number of studies reported high levels of persistence and adherence , the findings of this review suggest that patient persistence and adherence with oral bisphosphonates medications was poor and reduced notably over time . Overall , adherence was suboptimal . To maximise adherence and persistence to oral bisphosphonates , it is important to consider possible determinants , including characteristics of the patients BACKGROUND Multiple studies demonstrate poor adherence to medication regimens prescribed for chronic illnesses , including osteoporosis , but few interventions have been proven to enhance adherence . We examined the effectiveness of a telephone-based counseling program rooted in motivational interviewing to improve adherence to a medication regimen for osteoporosis . METHODS We conducted a 1-year r and omized controlled clinical trial . Participants were recruited from a large pharmacy benefits program for Medicare beneficiaries . All potentially eligible individuals had been newly prescribed a medication for osteoporosis . Consenting participants were r and omized to a program of telephone-based counseling ( n = 1046 ) using a motivational interviewing framework or a control group ( n = 1041 ) that received mailed educational material s. Medication regimen adherence was the primary outcome compared across treatment arms and was measured as the median ( interquartile range ) medication possession ratio , calculated as the ratio of days with filled prescriptions to total days of follow-up . RESULTS The groups were balanced at baseline , with a mean age of 78 years ; 93.8 % were female . In an intention-to-treat analysis , median adherence was 49 % ( interquartile range , 7%-88 % ) in the intervention arm and 41 % ( 2%-86 % ) in the control arm ( P = .07 , Kruskal-Wallis test ) . There were no differences in self-reported fractures . CONCLUSION In this r and omized controlled trial , we did not find a statistically significant improvement in adherence to an osteoporosis medication regimen using a telephonic motivational interviewing intervention Denosumab has been shown to reduce new vertebral , nonvertebral , and hip fractures in postmenopausal women with osteoporosis . In subjects who were treatment-naïve or previously treated with alendronate , denosumab was associated with greater gains in bone mineral density ( BMD ) and decreases in bone turnover markers when compared with alendronate-treated subjects . This trial was design ed to compare the efficacy and safety of denosumab with risedronate over 12 months in postmenopausal women who transitioned from daily or weekly alendronate treatment and were considered to be suboptimally adherent to therapy . In this r and omized , open-label study , postmenopausal women aged ≥55 years received denosumab 60 mg subcutaneously every 6 months or risedronate 150 mg orally every month for 12 months . Endpoints included percentage change from baseline in total hip BMD ( primary endpoint ) , femoral neck , and lumbar spine BMD at month 12 , and percentage change from baseline in sCTX-1 at months 1 and 6 . Safety was also assessed . A total of 870 subjects were r and omized ( 435 , risedronate ; 435 , denosumab ) who had a mean ( SD ) age of 67.7 ( 6.9 ) years , mean ( SD ) BMD T-scores of -1.6 ( 0.9 ) , -1.9 ( 0.7 ) , and -2.2 ( 1.2 ) at the total hip , femoral neck , and lumbar spine , respectively , and median sCTX-1 of 0.3 ng/mL at baseline . At month 12 , denosumab significantly increased BMD compared with risedronate at the total hip ( 2.0 % vs 0.5 % ) , femoral neck ( 1.4 % vs 0 % ) , and lumbar spine ( 3.4 % vs 1.1 % ; p<0.0001 at all sites ) . Denosumab significantly decreased sCTX-1 compared with risedronate at month 1 ( median change from baseline of -78 % vs -17 % ; p<0.0001 ) and month 6 ( -61 % vs -23 % ; p<0.0001 ) . Overall and serious adverse events were similar between groups . In postmenopausal women who were suboptimally adherent to alendronate therapy , transitioning to denosumab was well tolerated and more effective than risedronate in increasing BMD and reducing bone turnover |
10,706 | 23,985,640 | There are now excellent techniques for minimizing anesthetic injection pain , with supporting evidence varying from anecdotal to systematic review s. Medical students and residents can easily learn techniques that reliably limit the pain of local anesthetic injection to the minimal discomfort of only the first fine needlestick .
By combining many of these conclusions and techniques offered in the literature , tumescent local anesthetic can be administered to a substantial area such as a h and and forearm for tendon transfers or a face for rhytidectomy , with the patient feeling just the initial poke | BACKGROUND Local anesthetic injection is often cited in literature as the most painful part of minor procedures .
It is also very possible for all doctors to get better at giving local anesthesia with less pain for patients .
The purpose of this article is to illustrate and simplify how to inject local anesthesia in an almost pain-free manner . | AIM The aim of the study was to evaluate the effect of cooling the soft tissue of injection sites on the pain perceptions of pediatric patients during the administration of local anesthesia for routine dental procedures . METHODS AND MATERIAL S A total of 160 children aged 5 - 6 years were included in the present study . On a r and om basis , the subjects were allocated to the without ice pretreatment ( WIP ) group ( topical anesthesia + counterstimulation + distraction ) or the ice pretreatment ( IP ) group ( cooling + topical anesthesia + counterstimulation + distraction ) . During the administration of an inferior alveolar nerve block , the children 's behavior was assessed using the sound , eye , and motor ( SEM ) scale . The statistical analysis of data was performed based on the analysis of variance ( ANOVA ) . RESULTS There were no significant differences within the groups between the values of the sound , eye , and motor components for either the WIP or the IP groups ( P>0.05 ) . All three components of the SEM in the IP group were consistently lower than the WIP group ( P<0.05 ) . Moreover , the SEM value for the WIP group surpassed the IP group ( P<0.05 ) . CONCLUSIONS Cooling the site of infiltration block prior to the injection of local anesthesia significantly reduced the pain perceived during injection of local anesthetic agent in pediatric patients . CLINICAL SIGNIFICANCE Pre-cooling of the soft tissues of an injection site prior to the administration of a local anesthetic can minimize the discomfort and anxiety associated with the injection procedure and facilitates the management of pediatric patients during this phase of a dental procedure The purpose of this study was to clarify the effects of anxiety about dental treatment on pain during treatment . Subjects consisted of 57 consenting sixth- grade students at Tokyo Dental College ( male : 32 , female : 25 ) , all of whom participated in this study during their clinical training program . They knew how third molars were extracted and all had experience of assisting in tooth extraction . Prior to the study , trait anxiety in the subjects was evaluated according to the State-Trait Anxiety Inventory ( STAI , Japanese version ) . The students were asked to read one of two scenarios describing a scene in which a third molar was extracted while imagining themselves to be the patient . Scene 1 is set in an " environment where the patient feels safe and comfortable , " and the Scene 2 is set in an " environment where the patient feels strong anxiety " . The subjects were asked to imagine the anxiety and pain in that scenario and evaluate that pain according to a visual analogue scale ( VAS ) . Two scenarios were r and omly shown to the subjects in a crossover manner . No significant correlation between trait anxiety and preoperative anxiety was observed . There was no difference in level of preoperative anxiety for Scene 1 and Scene 2 between the high- and low-trait anxiety groups . This suggests that there was no relationship between sensitivity to anxiety as a characteristic of the subject and amplitude of anxiety immediately prior to treatment . Scene 2 elicited significantly higher anxiety before injection of regional anesthesia , significantly higher pain during insertion of the needle , and significantly higher pain during extraction of the tooth than Scene 1 . This difference suggests that patients feel stronger pain if anxiety in the treatment environment is high and that it is , therefore , important to reduce anxiety during treatment to reduce pain PURPOSE To examine prospect ively the incidence of digital infa rct ion and phentolamine rescue in a large series of patients in whom local anesthesia with adrenaline was injected electively into the h and and fingers . There continues to be a commonly held belief that epinephrine injection is contraindicated in the finger despite a lack of valid evidence to support this concept in the literature . METHODS From 2002 to 2004 there were 9 h and surgeons in 6 cities who prospect ively recorded each consecutive case of elective h and and finger epinephrine injection . They recorded each instance of skin or tissue loss and the number of times phentolamine reversal of adrenaline vasoconstriction was required . RESULTS There were 3,110 consecutive cases of elective injection of low-dose epinephrine ( 1:100,000 or less ) in the h and and fingers and none produced any instance of digital tissue loss . Phentolamine was not required to reverse the vasoconstriction in any patients . CONCLUSIONS The true incidence of finger infa rct ion in elective low-dose epinephrine injection into the h and and finger is likely to be remote , particularly with the possible rescue with phentolamine OBJECTIVE : The goal was to test a multifaceted distraction method design ed to reduce injection-associated pain in school-aged children . METHODS : A clinical trial evaluated 41 children , 4 to 6 years of age , who were given 3 st and ard prekindergarten immunizations ; 21 were assigned r and omly to an office routine control group , whereas 20 received a multifaceted , discomfort-reducing intervention . The intervention added verbal suggestions of diminished sensation and a visual focusing activity to the use of ethyl chloride , an established pain-reducing measure . The distraction material s used for the intervention consisted of topical ethyl chloride spray , an improvised , plastic , multipronged arm gripper , and a vibrating instrument descending on the contralateral arm , which provided the focusing task and visual distraction . RESULTS : According to patient and parent Faces Pain Scale-Revised scores and nonblinded , video-taped observations scored according to the face-legs-activity-crying-consolability method , the intervention group showed highly significant reductions in pain and discomfort , compared with the control group ( patient self-report , P < .0013 ; parent report , P < .0002 ; observation score , P < .0001 ) . CONCLUSION : This multifaceted distraction intervention reduced significantly the pain and discomfort of childhood immunizations in children 4 to 6 years of age AIM The aim of this study was to investigate the influence of anxiety and type of dental injection , a plastic syringe or an electronic computerized device , on the pain perceived by children . DESIGN Two dental injectors , a computerized device ( W and , Milestone Scientific , Livingston , NJ , USA ) and a traditional plastic syringe , were compared . Forty-one children , aged 9 - 13 years , who had registered for treatment in Marmara University , Istanbul , Turkey , were included in the study . Both anxious and non-anxious children were included in the study group . The Children 's Fear Survey Schedule-Dental Subscale , Facial Image Scale , Spielberger 's State Anxiety Index for Children , and heart rates were used to determine the anxiety levels . Participants were assigned to interventions by using r and om allocation . The first appointment was design ed as an introductive familiarization session and injections were administered in the second and third sessions , with one or the other injector . The visual analogue scale was used for pain measurement after injections . RESULTS No significant differences in injection pain scores were observed between the W and and traditional plastic injector . Higher levels of pre-injection anxiety were found to be related to more severe pain reports by the children . CONCLUSIONS Anxiety plays an important role in the pain reaction of children , and was found to be more determinative in pain perception than the injection devices preferred BACKGROUND The " gate control " theory suggests pain can be reduced by simultaneous activation of nerve fibres that conduct non-noxious stimuli . This study investigated the effects of vibration stimuli on pain experienced during local anaesthetic injections . METHODS In a preliminary study , subjects were asked to rate anticipated and actual pain from regional anaesthetic injections in the oral cavity . A second study compared , within subjects , pain from injections with and without a simultaneous vibration stimulus . Both infiltration and block anaesthetic injection techniques were assessed . In each subject , two similar injections were given and with one , a vibration stimulus was r and omly allocated . Injection pain was assessed by visual analogue scale and McGill pain descriptors . RESULTS Both infiltration and block injections were painful ( mean anticipated intensity : 31.25 , actual : 17.82 mm on 100 mm scale ) . Pain intensity with and without vibration was 12.9 mm ( range 0 - 67 ) and 22.2 mm ( range 0 - 83 ) respectively ( p = 0.00005 , paired T-test ) , and this effect was seen with both infiltration ( p = 0.032 ) and block anaesthetic ( p = 0.0001 ) injection subgroups . Furthermore , compared to no vibration-stimulus injections , injections with vibration result ed in less pain descriptors chosen ( p = 0.004 ) , and the descriptors had a lower pain rating ( p = 0.001 ) . CONCLUSIONS The results suggest that vibration can be used to decrease pain during dental local anaesthetic administration Local anesthetics can produce pain during skin infiltration . We design ed a r and omized , prospect i ve trial to determine whether needle gauge and /or solution pH affect pain during the intradermal infiltration of lidocaine . After approval by our institution 's human studies review board , 40 healthy adult volunteers gave their consent to participate in this study . All of the volunteers r and omly received four intradermal injections . Each volunteer was blinded as to the content of the intradermal injections and to which needle size was used for each injection . Each volunteer r and omly received a 0.25-mL intradermal injection of the following four solutions : 1 ) lidocaine 2 % administered through a 25-gauge needle ( lido-25 ) ; 2 ) lidocaine 2 % mixed with sodium bicarbonate ( 4 mL of 2 % lidocaine plus 1 mL of sodium bicarbonate , pH 7.26 ) administered through a 25-gauge needle ( lido-bicarb-25 ) ; 3 ) lidocaine 2 % administered through a 30-gauge needle ( lido-30 ) ; and 4 ) lidocaine 2 % mixed with sodium bicarbonate ( 4 mL of 2 % lidocaine plus 1 mL of sodium bicarbonate ) administered through a 30-gauge needle ( lido-bicarb-30 ) . In each patient , the injection site was in the same region for each of the four injections . The skin wheal was tested for appropriate anesthesia using a 19-gauge needle on the skin wheal . A visual analog pain score was recorded after each intradermal injection . The pain scores were significantly higher in the lido-25 ( 3.2 + /- 0.2 ) group than in the lido-30 ( 2.5 + /- 0.3 ) , lido-bicarb-25 ( 1.9 + /- 0.2 ) , and lido-bicarb-30 ( 1.3 + /- 0.2 ) groups . The lido-bicarb-30 injection was also rated as less painful than the lido-30 injection . We found no differences between the lido-bicarb-25 and the lido-bicarb-30 injections . Complete analgesia for the 19-gauge needle pain stimulus was achieved in all patients for each injection . We conclude that , overall , the pain intensity of an intradermal injection of 2 % lidocaine is low . The addition of sodium bicarbonate to 2 % lidocaine decreases the pain associated with an intradermal skin wheal , and although the use of a 30-gauge needle decreases the pain of injection , the addition of sodium bicarbonate seems to have a greater overall effect than needle size . Implication s : Forty volunteers r and omly received four intradermal injections consisting of 2 % lidocaine with or without sodium bicarbonate via a 25- or 30-gauge needle . The addition of bicarbonate had a greater overall effect than needle size in decreasing the pain associated with the intradermal injection of lidocaine . ( Anesth Analg 1998;86:379 - 81 This study on low contamination wounds was conducted to compare the pain of local infiltration anaesthesia administered into the skin surrounding the wound with administration directly into the incised edges of the wound . Eighty-one adult patients were r and omized by date of presentation to receive infiltration anesthesia by one of the two methods . Pain of anesthetic administration was rated on a visual analogue scale and recorded as a pain score in millimeters . The results demonstrated that the average pain score for infiltration into the wound was significantly lower than the average pain score for infiltration into skin surrounding the wound Needle insertion is a very common invasive procedure , but little has been done to study how pain is related to the mechanical properties of the needle insertion , and how pain from the procedure may be minimized . The aim of the present study was to investigate the pain evoked by st and ardized needle insertion into the human skin . Needle insertions were performed with continuous registration of the mechanical force on the needle . Forty consecutive needle insertions to the depth of 8 mm with 27 G and 30 G needles , 2 and 19 mm/s velocities , and at 45 and 90 degree angles to the skin surface were performed in a r and omized and blinded design in 30 healthy volunteers . The occurrence , intensity and quality of pain , as well as the maximum mechanical needle penetration force and the total mechanical workload were registered . The mechanical parameters of needle insertions were significantly related to needle size and velocity of insertion . Occurrence of pain and bleeding were significantly related to the needle size . High needle insertion velocity was significantly related to a higher rate of sharp and pricking pain , and low insertion velocity to a significantly higher rate of dull and burning pain . The present study provides quantitative data on pain and mechanical parameters of st and ardized needle insertions through normal human skin This study quantitatively assessed injection pressure , pain , and anxiety at the start of injection of a local anesthetic into the oral mucosa , and confirmed the relationship between injection pressure and pain , as well as between injection pressure and anxiety . Twenty-eight healthy men were selected as subjects and a 0.5-inch ( 12 mm ) 30-gauge disposable needle attached to a computer-controlled local anesthetic delivery system ( the W and ) was used . A 0.5 mL volume of local anesthetic solution was injected submucosally at a speed of either 30 or 160 s/mL. Three seconds after the start of local anesthetic injection , injection pressure was measured and pain and anxiety were assessed . Injection pressure was measured continuously in real time by using an invasive sphygmomanometer and analytical software , and pain was assessed on the Visual Analogue Scale and anxiety on the Faces Anxiety Scale . A significant correlation was evident between injection pressure and pain ( rs = .579 , P = .00124 ) and between intensity of injection pressure and state anxiety ( rs = .479 , P = .00979 ) . It is therefore recommended that local anesthetic be injected under low pressure ( less than 306 mm Hg ) to minimize pain and anxiety among dental patients Purpose : To compare the pain induced by tissue infiltration of lidocaine 2 % with epinephrine 1:100,000 versus articaine 4 % with epinephrine 1:100,000 for eyelid surgery . Methods : Thirty patients undergoing bilateral eyelid surgery were enrolled in a prospect i ve , r and omized , double-masked study . Each subject received injections of lidocaine 2 % with epinephrine 1:100,000 ( Xylocaine ) on one side and articaine 4 % with epinephrine 1:100,000 ( Septocaine ) on the other for surgical anesthesia . The patients rated the pain of infiltration using a 100-mm visual analogue scale immediately after receiving each injection . The pain scores were compared using the paired t test . Results : Twenty-two of the 30 patients ( 73.3 % ) rated the articaine injection as less painful than the lidocaine injection . The mean pain score for lidocaine was 42.60 ± 24.74 and the pain score for articaine was 31.85 ± 20.28 ( p = 0.011 ) . Conclusions : In this study , infiltration of articaine was less painful than lidocaine for eyelid surgery , making articaine an attractive alternative for local anesthesia BACKGROUND Local anesthetics are acidic and cause pain on infiltration into the skin . Two methods are commonly used by dermatologists to raise the pH of lidocaine with epinephrine : buffering with sodium bicarbonate or freshly mixing lidocaine with epinephrine on the day of use . OBJECTIVE Our purpose was to compare the pain induced by infiltration of the skin with 1 % lidocaine with epinephrine 1:100,000 buffered with sodium bicarbonate ( buffered ) versus 1 % lidocaine freshly mixed with epinephrine ( fresh ) . METHODS Sixty volunteers were recruited for this prospect i ve , double-blind study . Each subject received an intradermal injection of the buffered solution and the fresh solution . Immediately after each injection subjects rated the pain of infiltration on a 100-mm visual analog scale . The pain scores for the anesthetic solutions were compared using the paired t test . RESULTS The pain score for the buffered solution was 18.3 + /- 20.3 , and the pain score for the fresh solution was 23.5 + /- 19.1 ( P = .0543 ) . Sixty-five percent of subjects felt the fresh solution was more painful than the buffered solution . LIMITATIONS The results did not reach statistical significance . CONCLUSION In this small study , buffered lidocaine with epinephrine caused less pain on infiltration into the skin than lidocaine freshly mixed with epinephrine , but the results were not statistically significant BACKGROUND The authors compared the safety and efficacy of 4 percent articaine with epinephrine 1:100,000 with 2 percent lidocaine with epinephrine 1:100,000 . METHODS In three identical r and omized , double-blind , multicenter trials , subjects 4 to 80 years of age received either 4 percent articaine with epinephrine 1:100,000 or 2 percent lidocaine with epinephrine 1:100,000 for simple or complex dental procedures . In each trial , the authors r and omized the subjects in a 2:1 ratio to receive articaine or lidocaine . Efficacy was determined by both subject and investigator using a visual analog scale , or VAS . The authors used the Kruskal-Wallis test to analyze the data . RESULTS A total of 882 subjects received articaine , and 443 received lidocaine . The authors found no statistical differences between the groups ( P = .05 ) . They also compared drug volumes for both articaine and lidocaine groups ( 2.5 milliliters + /- 0.07 st and ard error of mean , or SEM , vs. 2.6 mL + /- 0.09 SEM for simple procedures and 4.2 mL + /- 0.15 SEM vs. 4.5 mL + /- 0.21 SEM for complex procedures ) . The procedures ' duration s were comparable for both the articaine and lidocaine groups . The authors found no statistical difference between the two treatment groups ( P = .05 ) with respect to subject or investigator pain ratings using the VAS ; the mean pain scores determined by both patients and investigators for all groups tested were less than 1.0 . CONCLUSIONS The authors found that 4 percent articaine with epinephrine 1:100,000 was well-tolerated in 882 subjects . It also provided clinical ly effective pain relief during most dental procedures and had a time to onset and duration of anesthesia appropriate for clinical use and comparable to those observed for other commercially available local anesthetics . CLINICAL IMPLICATION S Pain control is a major component of patient comfort and safety . Local anesthetics form the backbone of pain control techniques in dentistry . Four percent articaine with epinephrine is an amide local anesthetic that will meet the clinical requirements for pain control of most dental procedures in most patients STUDY OBJECTIVES We compared the pain of infiltration and anesthetic effects of.9 % benzyl alcohol with epinephrine , 1 % diphenhydramine , and .9 % buffered lidocaine . METHODS A prospect i ve , r and omized , double-blind study comparing benzyl alcohol , diphenhydramine , and lidocaine was carried out on adult volunteers . Each subject received all 3 injections in a st and ardized manner . Pain of infiltration was measured on a 100-mm visual analog pain scale and analyzed with a Kruskal-Wallis test . Duration of anesthesia was assessed at 5-minute intervals for a maximum of 45 minutes and compared with the use of survival analysis techniques by a log-rank test . Return of sensation by 45 minutes was evaluated with an exact chi2 test . All tests were 2-tailed , with significance defined as P < .05 . RESULTS Thirty subjects were enrolled . The diphenhydramine median pain score was 55 mm , compared with 12.5 mm for lidocaine and 5 mm for benzyl alcohol ( P = .001 ) . Pairwise comparisons showed that all possible combinations were statistically significant . The 3 anesthetics were different with respect to duration of anesthesia ( P < .001 ) . Pairwise comparisons revealed a longer duration of anesthesia for lidocaine than for diphenhydramine or benzyl alcohol , but no significant difference was found between diphenhydramine and benzyl alcohol . Pain sensation returned within the 45-minute study period in only 3 of 30 lidocaine injections , compared with 11 of 30 benzyl alcohol injections and 19 of 30 diphenhydramine injections ( P = .001 ) . CONCLUSION Benzyl alcohol is a better alternative than diphenhydramine as a local anesthetic for lidocaine-allergic patients AIM This paper is the report of a study to determine whether changing the needle before administering an intramuscular injection could reduce pain , and to investigate gender differences in pain perception . BACKGROUND A skilled injection technique can make the patient 's experience less painful and avoid unnecessary complications , and the use of separate needles to draw up and administer medication ensures that the tip of the needle is sharp and free from medication residue . METHOD A r and omized controlled trial was carried out between January 2009 and May 2009 with 100 patients receiving diclofenac sodium intramuscularly in an emergency and traffic hospital in İzmir , Turkey . The primary outcome was pain intensity measured on a numerical rating scale . Each patient received two injections by the same investigator using two different techniques . The two techniques were r and omly allocated and the patients were blinded to the injection technique being administered . After each injection , another investigator who had no prior knowledge of which injection technique was used immediately assessed pain intensity using a numerical rating scale . Descriptive statistics , paired t-test and t-test were used to evaluate the data . RESULTS Findings demonstrated that changing the needle prior to intramuscular medication administration significantly reduced pain intensity . A statistical difference in pain intensity was observed between the two injection techniques . CONCLUSION The results supported the hypothesis that changing the needle prior to administering the medicine significantly reduced pain intensity This study compared the pain from intradermal infiltration of ( 1 ) plain lidocaine , ( 2 ) warmed lidocaine , ( 3 ) buffered lidocaine , and ( 4 ) warmed , buffered lidocaine . A r and omized , double-blind , Latin Square design of 20 volunteers was used . Each volunteer was injected with a series of four test solutions on four separate occasions , for 16 total injections each . Each volunteer served as his or her own control . The mean pain scores for the four solutions were : 44.2 for plain lidocaine , 42.2 for warmed lidocaine , 36.7 for buffered lidocaine , and 29.2 for warmed , buffered lidocaine . Buffered lidocaine was statistically less painful than both plain lidocaine and warmed lidocaine . Warmed , buffered lidocaine was significantly less painful than all other solutions , including buffered lidocaine ( P < .005 ) . However , warmed lidocaine did not yield pain scores significantly different from plain lidocaine . In this experimental model , warmed lidocaine was not superior to plain lidocaine , but warmed , buffered lidocaine caused significantly less pain than plain lidocaine , buffered lidocaine , or warmed lidocaine . Thus , there may be benefit from heating the buffered lidocaine now in common clinical use STUDY OBJECTIVE To evaluate pain and the spread of analgesia when local anesthetics are given as an intradermal injection into the dorsal aspect of the h and . DESIGN R and omized , double-blinded , placebo-controlled study . SETTING University medical center . PATIENTS 40 consenting adult volunteers . INTERVENTIONS Volunteers were r and omly assigned to receive a 0.25-mL injection of either lidocaine hydrochloride ( 1 % ) , buffered lidocaine , diphenhydramine ( 1 % ) , or placebo ( 0.9 % sodium chloride solution ) into the dorsal aspect of both h and s. MEASUREMENTS The volunteers used a visual analog scale to compare the pain of needle insertion and solution injection . Then at 1 , 2 , 5 , 10 , 20 , and 30 minutes after intradermal injection , the extent of the analgesic area was marked on a strip of tape placed horizontally across the h and . Then at 32 minutes after intradermal injection , the extent of the analgesic area was marked on a strip of tape placed vertically across the h and . The volunteers were called each day and asked the duration of their numbness or hyperesthesia until their h and s were no longer numb or sore . MAIN RESULTS Buffered lidocaine during intradermal infiltration was found to be significantly ( p < 0.05 ) less painful than either lidocaine hydrochloride or diphenhydramine and equivalent to placebo . Diphenhydramine and lidocaine hydrochloride during intradermal infiltration induced significantly ( p < 0.05 ) more pain than buffered lidocaine or placebo . Lidocaine hydrochloride displayed a significantly ( p < 0.05 ) larger diameter of analgesia than placebo by 1 minute after the injection , buffered lidocaine by 2 minutes after injection , and diphenhydramine by 5 minutes after injection . By 20 minutes after injection , diphenhydramine diameter of analgesia was significantly ( p < 0.05 ) larger than placebo but significantly less than buffered lidocaine . By 30 minutes after injection , diphenhydramine diameter of analgesia was equivalent to placebo whereas buffered lidocaine and lidocaine diameters were still significantly ( p < 0.05 ) larger than placebo . Diphenhydramine injection result ed in numbness that lasted significantly ( p < 0.05 ) longer than other study solutions whereas buffered lidocaine and lidocaine injections result ed in numbness that lasted significantly longer than placebo . Diphenhydramine injection result ed in hyperesthesia that lasted for 2 or more days in 12 of the volunteers . CONCLUSION There is a reduction of infiltration pain using buffered lidocaine as opposed to lidocaine and diphenhydramine . Although lidocaine injection result ed in a slightly faster spread of analgesic diameter , buffered lidocaine was equivalent to lidocaine from minute 2 until minute 30 . Therefore , to obtain optimal anesthetic conditions , we recommend that buffered lidocaine be given 2 minutes before performing catheterization , whereas diphenhydramine should be given 5 minutes before catheterization , but only when buffered lidocaine can not be used OBJECTIVES To investigate the effects of warming vs buffering , and warming with buffering , on the pain of lidocaine infiltration . METHODS A r and omized , double-blind clinical trial was conducted using volunteers aged 18 years or more and without an allergy to lidocaine . The study consisted of two parts , each comparing two solutions . The solutions for Part I were warm ( 38.9 degrees C ; 102 degrees F ) plain lidocaine and room-temperature buffered lidocaine . Warm buffered lidocaine and room-temperature buffered lidocaine were used for Part II . The subjects received two st and ardized 0.5-mL intradermal injections , one study solution in each forearm . Immediately after each injection , pain was assessed using a 100-mm visual analog pain scale . Pain scores were analyzed by the sign test , with significance defined as p < 0.05 . RESULTS Part I ( n = 10 ) : Nine subjects reported room-temperature buffered lidocaine to be less painful than warm plain lidocaine . Mean pain scores were 28 mm lower for room-temperature buffered lidocaine than they were for warm plain lidocaine ( p < 0.01 ) . Part II ( n = 24 ) : Eleven subjects found warm buffered lidocaine to be the least painful , 11 reported room-temperature buffered lidocaine to be the least painful , and two reported no difference . A mean pain score difference of 2.1 mm favoring warm buffered lidocaine was not statistically significant . Part II had a power of 80 % to detect a 10-mm difference between the two solutions at alpha = 0.05 . CONCLUSION To reduce the pain of lidocane infiltration , buffering is more effective than warming . Warming does not enhance buffering Background and Objectives The aim of this study was to compare the effectiveness of 3 anesthetic creams in relieving venous puncture-related pain in children . Methods We performed a double-blind , r and omized , prospect i ve study in 300 patients , American Society of Anesthesiologists ( ASA ) I-II , aged 3 months to 10 years , scheduled for minor elective surgical procedures . These children were distributed into 3 groups , with 100 patients each , according to each type of cream applied to the back of the children ’s h and s before performing the venous puncture : Group I was given EMLA ( eutectic 2.5 % lidocaine and 2.5 % prilocaine mixture ) , group II received 4 % amethocaine ( 4 % AMET ) , and group III was treated with AMLI ( 2.5 % amethocaine and 2.5 % lidocaine ) , a new anesthetic cream developed at our hospital . Each group was further classified into 5 subgroups , with 20 patients each , according to the time length of the application of the individual cream ( group A , ≤ 30 minutes ; B , 30 minutes to 60 minutes ; C , 60 minutes to 90 minutes ; D , 90 minutes to 120 minutes ; E , ≥ 120 minutes ) . We evaluated pain , movement , and verbalization to puncture , as well as the appearance of adverse effects . Results Group I ( EMLA ) , subgroup A ( ≤ 30 minutes ) , experienced significantly more pain , movement , and verbalization than groups II and III . Patients in group II ( 4 % AMET ) exhibited a higher frequency of untoward effects . Conclusions All 3 creams proved to be effective in relieving venous puncture pain in children . EMLA presented a longer latency period , 4 % amethocaine showed the highest percentage of untoward effects , and AMLI exhibited a shorter latency period than EMLA , while having fewer adverse effects than 4 % AMET and EMLA Skin infiltration of local anesthetics causes pain . In a double-blinded protocol , 22 volunteers received r and om intradermal injections to the volar surface of the forearm with each of the following solutions : normal saline solution 0.9 % ( NSS ) , lidocaine 1 % ( L ) , lidocaine 1 % and sodium bicarbonate 8.4 % ( L+BIC ) , 2-chloroprocaine 2 % ( CP ) , 2-chloroprocaine 2 % and sodium bicarbonate 8.4 % ( CP+BIC ) , and NaCHO3 8.4 % ( BIC ) . Initially , each volunteer received an open-labeled injection of NSS . A 100-mm visual analog scale ( VAS , 1–100 ) was used to assess pain with each injection . The pH of each solution was stable for the length of the study . Repeated measures of variance were used for analysis . The VAS scores ( mean ± sd ) for open-label and blinded NSS injections were 15.5 ± 15.9 and 14.0 ± 18.1 , respectively . The scores for the studied solutions were as follows : BIC , 47.2 ± 25.5 ; L , 25.8 ± 27.6 ; L+BIC , 16.0 ± 14.2 ; CP , 8.6 ± 7.4 ; and CP+BIC , 6.8 ± 6.7 . No significant difference was found between CP and alkalinized CP , but the injection of both solutions was significantly less painful than that of all other solutions ( P < 0.05 ) . The pH of the solutions was not related to the pain score . We found that chloroprocaine caused less pain at injection than the more commonly used lidocaine Purpose : We hypothesized that the size of syringe influenced needle control in physician-performed procedures . Material s and Methods : Operators were tested for their ability to control a 1- , 3- , 5- , 10- , and 20-mL syringe and equivalent sizes of the new safety device , the reciprocating procedure device ( RPD ) , using the quantitative needle-based displacement method . Three hundred twenty clinical syringe procedures were then r and omized to either a 3- or 10-mL conventional syringe or to a 3- or 10-mL RPD . Patient pain was measured with the Visual Analog Pain Scale ( VAPS ) . Results : Increasing syringe size was associated with the undesirable characteristic of unintended forward penetration ( loss of control of the needle in the forward direction ) ( r2 = 0.97 , slope = 2.14 , 95 % CI : 1.54–2.76 , P < 0.002 ) , and unintended retraction ( loss of control of the needle in the reverse direction ) ( r2 = 0.97 , slope 2.15 , 95 % CI : 1.54–2.76 , P < 0.002 ) . In addition , 2-h and ed operation of a syringe result ed in greater control than 1-h and ed operation of a syringe ( P < 0.001 ) . When 1-h and ed operation was required , the RPD control syringe reduced unintended penetration by 52.3 % ( P ≥ 0.001 ) , unintended retraction by 56.8 % ( P ≥ 0.001 ) , and patient pain by 54.7 % ( P ≥ 0.001 ) at each device size . Conclusions : For greater safety and control when operating the conventional syringe , smaller syringe sizes and 2 h and s instead of 1 h and should be used whenever possible . If 1-h and ed operation of a syringe is necessary , a safety technology like the RPD control syringe should be used The purpose of this prospect i ve , r and omized , double-blind study was to compare the pain of injection , heart rate increase , and postinjection pain of the intraligamentary injection of 4 % articaine with 1:100,000 epinephrine and 2 % lidocaine with 1:100,000 epinephrine administered with a computer-controlled local anesthetic delivery system . Using a crossover design , intraligamentary injections of 1.4 mL of 4 % articaine with 1:100,000 epinephrine and 1.4 mL of 2 % lidocaine with 1:100,000 epinephrine were r and omly administered on the mesial and distal aspects of the m and ibular first molar with a computer-controlled local anesthetic delivery system in a double-blind manner at 2 separate appointments to 51 subjects . The results demonstrated the incidence of moderate pain was 14%-27 % with needle insertion , with 0%-4 % reporting severe pain . For solution deposition , moderate pain was reported 8%-18 % of the time , with no reports of severe pain . There were no significant differences between the articaine and lidocaine solutions . Regarding heart rate changes , neither anesthetic solution result ed in a significant increase in heart rate over baseline readings . On day 1 postinjection , there was a 31 % incidence of moderate/severe pain with the articaine solution and 20 % incidence of moderate/severe pain with the lidocaine solution . The moderate/severe pain ratings decreased over the next 2 days . There were no significant differences between the articaine and lidocaine solutions . We concluded that the intraligamentary injection of 4 % articaine with 1:100,000 epinephrine was similar to 2 % lidocaine with 1:100,000 epinephrine for injection pain and postinjection pain in the m and ibular first molar when administered with a computer-controlled local anesthetic delivery system . For both anesthetic solutions , heart rate did not significantly increase with the intraligamentary injection using the computer-controlled local anesthetic system Background : Three local anesthetics are commonly used for digital nerve block : 2 % lidocaine with 1:100,000 epinephrine , 2 % lidocaine , and 0.5 % bupivacaine . The authors have not identified a study that has compared these three agents in digital nerve block in a r and omized fashion . The goal of this study was to determine which of the three agents provided the longest duration of digital nerve blockade . Methods : Thirty volunteers had the long finger of each h and along with one of their small fingers anesthetized with one of the above agents , respectively . The local anesthetic agent to be used in each finger was r and omized . A double-blind design was used . Volunteers reported the time that each of their fingers returned to normal sensation at the tip . An analysis of variance was used to detect significant differences among the three groups , and subsequent pair-wise comparisons were performed using post hoc Tukey tests . Results : The mean duration of anesthesia was as follows : 0.5 % bupivacaine , 24.9 hours ; 2 % lidocaine with epinephrine ( 1:100,000 ) , 10.4 hours ; and 2 % lidocaine , 4.9 hours . In both the Bonferroni and Tukey tests , all three agents provided significantly different duration s of digital nerve blockade ( p = 0.01 ) . Conclusions : At an average of 24.9 hours , bupivacaine ( 0.5 % ) provides a significantly longer digital anesthesia time than the average 10.4 hours achieved by 2 % lidocaine with epinephrine ( 1:100,000 ) , which in turn provides twice as long an anesthesia time as 2 % lidocaine ( average , 4.9 hours ) STUDY OBJECTIVE To compare room-temperature unbuffered lidocaine , warm lidocaine , buffered lidocaine , and warm buffered lidocaine to determine which of the four solutions is least painful during infiltration . DESIGN R and omized , controlled , double-blinded , volunteer study . TYPE OF PARTICIPANT Thirty-two young healthy adults . MAIN RESULTS Each subject received four subcutaneous injections of 1 % lidocaine : room-temperature unbuffered , warm , buffered , and warm buffered . After each injection , participants recorded their perception of pain associated with infiltration of the solution on a visual analog scale . Mean pain scores for the four solutions were determined and analyzed . The mean perceived pain score for the warm buffered solution was significantly lower than for any of the other solutions ( versus warm : P = .0005 ; versus buffered : P = .0028 ; versus room temperature : P = .0001 ) . There was no statistically significant difference between either the warm solution or buffered solution and the room-temperature unbuffered lidocaine . The difference in mean pain score for the warm buffered solution , compared with those for the warm , buffered , and room-temperature solutions , suggests that warming and buffering have a synergistic effect . CONCLUSION Skin infiltration with warm buffered lidocaine is significantly less painful than infiltration with room-temperature unbuffered lidocaine , warm lidocaine , or buffered lidocaine A r and omised , prospect i ve trial was conducted to assess the efficacy of various means of alleviating the pain of subcutaneous lidocaine infiltration . One hundred and twenty‐two patients were r and omly allocated to different groups to receive buffered lidocaine 1 % , warmed lidocaine 1 % or infiltration by the counter‐irritation technique . A visual analogue pain score was recorded at different stages of cannulation and results showed that pain scores were significantly lower in the group receiving buffered lidocaine 1 % ( p < 0.02 ) and in the counter‐irritation group ( p < 0.05 ) . Thus buffering lidocaine 1 % and administration of lidocaine 1 % by the counter‐irritation technique is effective in relieving the pain of lidocaine infiltration A r and omised , placebo‐controlled , double‐blind study was undertaken in 111 children between the ages of 1 and 5 years to assess the efficacy of EMLA 5 % cream in the alleviation of venepuncture pain at intravenous induction of general anaesthesia using 27‐gauge needles . Pain assessment was made by an operating department assistant using both verbal rating scale and visual analogue scale methods . Seventy‐five children , of whom 24 were premedicated , were treated with EMLA cream and 36 with placebo , 14 of whom were premedicated . Significantly lower pain scores were recorded in the children treated with EMLA cream ( verbal rating scale : premedicated p < 0.05 , unpremedicated p < 0.001 ; visual analogue scale : premedicated p < 0.0005 , unpremedicated p < 0.0002 ) . No variation in analgesia was found for application times between 30 and 300 minutes and there were no serious side effects BACKGROUND Tumescent local anesthesia is widely used in dermatologic surgery . Minimizing pain associated with injections is crucial to successful surgical procedures . OBJECTIVE This study investigates the pain associated with warm and room temperatures in neutralized or nonneutralized tumescent anesthetic solutions injection . METHODS Thirty-six patients with axilla osmidrosis who underwent local anesthesia for surgery were r and omly assigned to three groups . Group A received warm neutral ( 40 ° C ) and room-temperature neutral ( 22 ° C ) tumescent injections to each axillary region . Group B received warm neutral ( pH 7.35 ) and warm nonneutral ( pH 4.78 ) tumescent injections on each side of axilla . Group C received warm nonneutral and room-temperature nonneutral tumescent injections on each side of axilla . Pain associated with infiltration of anesthesia was rated on a visual analog scale ( VAS ) . RESULTS A statistically significant decrease ( p < .001 ) in pain sensation was reported on the warm , neutral injection side ( mean rating , 32.7 mm ) compared with the room-temperature , neutral injection side ( mean rating , 53.3 mm ) . Patient-reported pain intensity was significantly lower on the side that received warm , neutral tumescent anesthesia ( mean rating , 26.8 mm ) than on the side receiving warm , nonneutral tumescent anesthesia ( mean rating , 44.9 mm ; p < .001 ) . The difference in VAS scores between warm neutral ( mean rating , 23.9 mm ) and room-temperature nonneutral ( mean rating , 61.2 mm ) was statistically significant ( p < .001 ) . CONCLUSION The warm , neutral tumescent anesthetic preparation effectively suppressed patient pain during dermatologic surgical procedures OBJECTIVE To study the effect of an active distraction technique on pain in preschool children receiving diphtheria , pertussis , and tetanus immunization . DESIGN R and omized , unblinded controlled study . SETTING Columbus Public Health Department Immunization Clinics . PARTICIPANTS One hundred forty-nine 4- to 7-year-old children . INTERVENTION Children were taught to blow out air repeatedly during the injection , as if they were blowing bubbles . RESULTS Children who were taught to blow out air during their shots had significantly fewer pain behaviors ( P < .04 ) and demonstrated a trend toward lower subjectively reported pain ( P = .06 ) . There was no significant difference in the nurse or parent visual analog scale scores . CONCLUSIONS A simple distraction technique can be effective in helping children cope with the pain of immunization . The use of such a technique to relieve the pain and distress associated with even a brief painful procedure should be encouraged The pain of infiltrating lidocaine with epinephrine into skin is reduced by the addition of sodium bicarbonate . The effect of varied concentrations of sodium bicarbonate on pain of infiltration of 1 % lidocaine with epinephrine 1:100,000 was measured . Sodium bicarbonate at 40 and 100 meq/L of anesthetic solution caused significantly less pain than did 0 or 10 meq/L. The stability of epinephrine in a solution at pH 7.3 was also determined . Epinephrine concentration declined approximately 25 % per week in anesthetic solution containing 100 meq/L sodium bicarbonate Keeping in mind the limitations of the methods , we believe that long term effects in humans are very likely to occur at levels of maternal alcohol consumption during pregnancy of 300 g or more of absolute alcohol a week . Below this level the evidence is conflicting and open to method ological objections . We continue to support the recommendation from our results of immediate outcome of pregnancy that , allowing for a margin of safety , women should not have more than one st and ard drink a day ( 70 - 85 g absolute alcohol a week ) , and only as much as this if abstinence is not feasible . Background and aim . Needle injections are used daily by millions of people around the world for the administration of various drugs ( e.g. , insulin ) , venepuncture , and some neurophysiological procedures . The aim of this paper was to study the influence of the outer needle diameter on the pain evoked by controlled needle insertion . Methods . An automated needle injection system was used to perform a series of insertions where velocity , angle of insertion , and depth of injection were controlled . The frequency of pain following needle insertions ( 23 G , 27 G , 30 G , 32 G ) was recorded together with the pain intensity ( measured using the visual analogue scale — VAS ) and the occurrence of bleeding . Results . The outer needle diameter was positively and significantly correlated to the frequency of the insertion pain ; for example , 63 % of insertions with 23 G needles caused pain , 53 % of insertions with 27 G and 31 % of insertions with the thinnest ( 32 G ) needle ( p < 0.0001 ) caused pain . The thickest needle caused most insertions associated with bleeding . Bleeding insertions were approximately 1.3 times more painful ( as indicated by VAS scores ) than insertions without concomitant bleedings ( p = 0.004 ) . Conclusion . By decreasing the outer diameter of a needle , the frequency of insertion pain can be reduced and may encourage patients to adhere to dem and ing injection regimens such as recurrent insulin administration Purpose : To evaluate whether a very slow injection of local anaesthetics during dorsal penile nerve block for circumcision causes less pain than a more rapid injection |
10,707 | 27,572,000 | Some relationships between high scores on measures consistent with media literacy constructs and low scores on body dissatisfaction and related attitudes were found .
Media literacy-based interventions revealed improvements in media literacy constructs realism scepticism , influence of media , and awareness of media motives for profit , and improvements in body-related variables , but not disordered eating . | This study comprised a systematic review of literature examining empirical relationships between levels of media literacy and body dissatisfaction and disordered eating .
The review aim ed to integrate research on this topic . | Background Positive self-esteem , emotional well-being , school achievements and family connectedness are considered protective factors against health-compromising behaviors . This study examined the effect of an interactive , community-based , media literacy and dissonance wellness program , In Favor of Myself , on the self-image , body image , eating attitudes and behavior of young adolescents . A preliminary cohort study was conducted among 972 program participants who did not take part in the controlled trial . Over 75 % of participants said they would recommend the program to their friends . Methods A controlled trial was conducted to evaluate program acceptability , efficacy and effectiveness among 259 participants ( 210 in the intervention group and 49 in the control group ) , aged 12–14 years , who completed question naires during at least two assessment times . Program material s were provided , along with leaders ' training , in order to ensure quality program delivery and creation of a wide network of committed program leaders . Results The program significantly reduced drive for thinness and self-worth contingent upon others ' approval , the gap between current body figure and ideal figure , and the impact of mood on girls ' self-image . Superiority was found among those participating in the intervention group with respect to recognizing media strategies , the influence of media on desire to change , and the influence of appearance on self-confidence and drive for thinness . Conclusions In Favor of Myself shows promising results for strengthening adolescents ' ability to cope with the challenges of their life stage . Suggestions for improving In Favor of Myself are presented The Media Ready Program was design ed as a middle school , media literacy education , preventive intervention program to improve adolescents ' media literacy skills and reduce their intention to use alcohol or tobacco products . In a short-term efficacy trial , schools in North Carolina were r and omly assigned to conditions ( Media Ready : n = 214 ; control : n = 198 ) . Boys in the Media Ready group reported significantly less intention to use alcohol in the future than did boys in the control group . Also , students in the Media Ready group who had used tobacco in the past reported significantly less intention to use tobacco in the future than did students in the control group who had previously used tobacco . Multilevel multiple mediation analyses suggest that the set of logical analysis Message Interpretation Processing variables mediated the program 's effect on students ' intentions to use alcohol or tobacco in the future Background / Objectives : This longitudinal study describes the relationship between young children ’s screen time , dietary habits and anthropometric measures . The hypothesis was that television viewing and other screen activities at baseline result in increased consumption of sugar-sweetened beverages ( SSB ) and increased BMI , BMI z-score and waist to height ratio ( WHtR ) two years later . A second hypothesis was that SSB consumption mediates the association between the screen activities and changes in the anthropometric measures .Subjects/ Methods : The study is a part of the prospect i ve cohort study IDEFICS ( “ Identification and prevention of dietary and lifestyle-induced health effects in children and infants ” ) , investigating diet , lifestyle and social determinants of obesity in 2 to 9-year-olds in eight European countries ( baseline n=16 225 , two-year follow-up ; n=11 038 ) . Anthropometry was objective ly measured , and behaviours were parent-reported . Results : The main hypothesis was supported , but the second hypothesis was not confirmed . The odds ratio of being in the highest quintile of % change in WHtR was 1.26 ( 95 % CI : 1.17–1.36 ) and in BMI 1.22 ( 95 % CI : 1.13–1.31 ) , for each hour per day watching television . The odds ratio of having increased SSB consumption was 1.19 ( 95 % CI : 1.09–1.29 ) for each hour per day watching TV . The associations for total screen time were slightly weaker . Conclusions : The results indicate substantial effects of TV viewing and other screen activities for young children , both on their consumption of sugary drinks and on an increase in BMI and central obesity . Our findings suggest that television viewing seems to have a stronger effect on food habits and anthropometry than other screen activities in this age group BACKGROUND A r and omized controlled trial of three school-based programs and a no-intervention control group was conducted to evaluate their efficacy in reducing eating disorder and obesity risk factors . METHOD A total of 1316 grade 7 and 8 girls and boys ( mean age = 13.21 years ) across three Australian states were r and omly allocated to : Media Smart ; Life Smart ; the Helping , Encouraging , Listening and Protecting Peers ( HELPP ) initiative ; or control ( usual school class ) . Risk factors were measured at baseline , post-program ( 5 weeks later ) , and at the 6- and 12-month follow-ups . RESULTS Media Smart girls had half the rate of onset of clinical ly significant concerns about shape and weight than control girls at the 12-month follow-up . Media Smart and HELPP girls reported significantly lower weight and shape concern than Life Smart girls at the 12-month follow-up . Media Smart and control girls scored significantly lower than HELPP girls on eating concerns and perceived pressure at the 6-month follow-up . Media Smart and HELPP boys experienced significant benefit on media internalization compared with control boys and these were sustained at the 12-month follow-up in Media Smart boys . A group × time effect found that Media Smart participants reported more physical activity than control and HELPP participants at the 6-month follow-up , while a main effect for group found Media Smart participants reported less screen time than controls . CONCLUSIONS Media Smart was the only program to show benefit on both disordered eating and obesity risk factors . Whilst further investigations are indicated , this study suggests that this program is a promising approach to reducing risk factors for both problems This study aim ed to evaluate the efficacy of BodyThink , a widely disseminated body image and self-esteem program . Participants were 277 , grade 7 students from 4 secondary schools in Australia . The intervention group ( 62 girls , 85 boys ) participated in BodyThink during four 50-min lessons , while the control group ( 65 girls , 65 boys ) received their usual classes . All participants completed baseline , postintervention and 3-month follow-up question naires . For girls , the intervention group reported higher media literacy and lower internalization of the thin ideal compared to the control group . For boys , the intervention group reported higher media literacy and body satisfaction than the control group . Although some positive outcomes were observed , it would be valuable to find ways to enhance the impact of BodyThink , especially in light of its wide dissemination . Suggestions for improving BodyThink are presented OBJECTIVE To evaluate a community-based intervention aim ed at the primary prevention of disordered eating among preadolescent girls . DESIGN Girl Scout troop members were r and omized into control and intervention groups . Program feasibility and effect at postintervention and 3-month follow-up were evaluated . SUBJECTS/ SETTING 226 girls ( mean age = 10.6 years , st and ard deviation = 0.7 ) from 24 Girl Scout troops . INTERVENTION Six 90-minute sessions focusing on media literacy and advocacy skills . MAIN OUTCOME MEASURES Evaluation focused on program satisfaction and short-term effect on dieting behaviors , body image attitudes , and media knowledge , attitudes , and habits . STATISTICAL ANALYSES Performed t tests , chi 2 tests , and analyses of covariance including troop as a r and om source of variation . RESULTS At baseline , 29 % of the girls were trying to lose weight . The program had a notable positive influence on media-related attitudes and behaviors including internalization of sociocultural ideals , self-efficacy to impact weight-related social norms , and print media habits . A modest program effect on body-related knowledge and attitudes was apparent at post-intervention ( i.e. , on body size acceptance , puberty knowledge , and perceived weight status ) but not at follow-up . Significant changes were not noted for dieting behaviors , but they were in the hypothesized direction . Satisfaction with the program was high among girls , parents , and leaders . APPLICATIONS/ CONCLUSIONS It is feasible to use community youth setting s , such as the Girl Scouts , to implement interventions to prevent disordered eating behaviors . The program led to positive trends in outcome variables ; however , longer and more intensive interventions are needed for lasting changes in body image and dieting behaviors Research ers used a quasi-experiment ( N = 723 ) conducted in the field and using both pretests and posttests to carry out a theory-based evaluation of the effectiveness of a media literacy curriculum implemented in Washington state . Results showed that reflective thinking concerning media message about tobacco increased for all media literacy participants , whether or not they had used tobacco previously . Changes in reflective thinking affected a range of decision-making indicators . Lesson participants who had not used tobacco demonstrated greater change at earlier stages of decision making in ways that suggested a greater underst and ing of the persuasive techniques used by tobacco manufacturers , on indicators such as perceived realism , desirability , and similarity . Lesson participants who had tried tobacco demonstrated greater change at later stages of decision making on indicators such as perceived peer norms for tobacco use , identification with tobacco-related portrayals , and expectancies for tobacco use . All participants also showed increases in their ability and motivations to resist smoking-related influences . Overall , the results suggest that media literacy has important and somewhat different effects on those who have and those who have not experimented with tobacco use . The results also show the importance of measuring cognitive and affective indicators of decision making that may change gradually as participants gain experience putting lessons learned into action OBJECTIVES Body image and eating disturbances have become global phenomena , yet prospect i ve design s have rarely been employed in research on non-Western sample s. This study tested the extent to which select features of the dual-pathway account of bulimic disturbances contributed to changes in eating disorder symptoms reported among adolescents from China . METHODS A sample of 593 Chinese middle school and high school students ( 217 boys , 376 girls ) completed measures of eating disorder symptoms , body image concerns , internalized physical appearance ideals , negative affect , and appearance-based social pressure , teasing , and comparison and returned 9 months later to complete the same measures . RESULTS For both girls and boys , increases in eating disorder symptoms between Times 1 and 2 were predicted by higher baseline levels of fatness concern and perceived social pressure . Among the girls , negative affect also contributed marginally to changes in eating disorder symptoms . CONCLUSIONS Findings suggest specific risk factors including personal concerns about being fat and negative social feedback about physical appearance , may help to explain changes in eating disturbances of adolescents over time and across specific cultures |
10,708 | 29,681,574 | mean difference = 1.81 ; 95 % CI = -0.14 to 3.77 ; P = 0.07).Compared with control intervention , palliative care intervention was found to significantly reduce readmission , ESAS , PHQ-9 , and improve heart failure question naire , but showed no influence on mortality and quality of life question naire in patients with heart failure | Palliative care might be beneficial to heart failure .
However , the results remain controversial .
We conducted a systematic review and meta- analysis to explore the effect of palliative care on heart failure . | Objective To examine the effects of home-based transitional palliative care for patients with end-stage heart failure ( ESHF ) after hospital discharge . Methods This was a r and omised controlled trial conducted in three hospitals in Hong Kong . The recruited subjects were patients with ESHF who had been discharged home from hospitals and referred for palliative service , and who met the specified inclusion criteria . The interventions consisted of weekly home visits/telephone calls in the first 4 weeks then monthly follow-up , provided by a nurse case manager supported by a multidisciplinary team . The primary outcome measures were any readmission and count of readmissions within 4 and 12 weeks after index discharge , compared using χ2 tests and Poisson regression , respectively . Secondarily , change in symptoms over time between control and intervention groups were evaluated using generalised estimating equation analyses of data collected using the Edmonton Symptom Assessment Scale ( ESAS ) . Results The intervention group ( n=43 ) had a significantly lower readmission rate than the control group ( n=41 ) at 12 weeks ( intervention 33.6 % vs control 61.0 % χ2=6.8 , p=0.009 ) . The mean number ( SE ) of readmissions for the intervention and control groups was , respectively , 0.42 ( 0.10 ) and 1.10 ( 0.16 ) and the difference was significant ( p=0.001 ) . The relative risk ( CI ) for 12-week readmissions for the intervention group was 0.55 ( 0.35 to 0.88 ) . There was no significant difference in readmissions between groups at 4 weeks . However , when compared with the control group , the intervention group experienced significantly higher clinical improvement in depression ( 45.9 % vs 16.1 % , p<0.05 ) , dyspnoea ( 62.2 % vs 29.0 % , p<0.05 ) and total ESAS score ( 73.0 % vs 41.4 % , p<0.05 ) at 4 weeks . There were significant differences between groups in changes over time in quality of life ( QOL ) measured by McGill QOL ( p<0.05 ) and chronic HF ( p<0.01 ) question naires . Conclusions This study provides evidence of the effectiveness of a postdischarge transitional care palliative programme in reducing readmissions and improving symptom control among patients with ESHF . Trial registration number HKCTR-1562 ; Results Background Readmissions are costly and have implication s for quality of care . Studies have been reported to support effects of transitional care programs in reducing hospital readmissions and enhancing clinical outcomes . However , there is a paucity of studies executing full economic evaluation to assess the cost-effectiveness of these transitional care programs . This study is therefore launched to fill this knowledge gap . Methods Cost-effectiveness analysis was conducted alongside a r and omized controlled trial that examined the effects of a Health-Social Transitional Care Management Program ( HSTCMP ) for medical patients discharged from an acute regional hospital in Hong Kong . The cost and health outcomes were compared between the patients receiving the HSTCMP and usual care . The total costs comprised the pre-program , program , and healthcare utilization costs . Quality of life was measured with SF-36 and transformed to utility values between 0 and 1 . Results The readmission rates within 28 ( control 10.2 % , study 4.0 % ) and 84 days ( control 19.4 % , study 8.1 % ) were significantly higher in the control group . Utility values showed no difference between the control and study groups at baseline ( p = 0.308 ) . Utility values for the study group were significantly higher than in the control group at 28 ( p < 0.001 ) and 84 days ( p = 0.002 ) . The study group also had a significantly higher QALYs gain ( p < 0.001 ) over time at 28 and 84 days when compared with the control group . The intervention had an 89 % chance of being cost-effective at the threshold of £ 20000/QALY . Conclusions Previous studies on transitional care focused mainly on clinical outcomes and not too many included cost as an outcome measure . Studies examining the cost-effectiveness of the post-discharge support services are scanty . This study is the first to examine the cost-effectiveness of a transitional care program that used nurse-led services participated by volunteers . Results have shown that a health-social partnership transitional care program is cost-effective in reducing healthcare costs and attaining QALY gains . Economic evaluation helps to inform funders and guide decisions for the effective use of competing healthcare re sources BACKGROUND We conducted this prospect i ve comparative study to examine the feasibility and effectiveness of a palliative care consultation along with st and ard heart failure care in an outpatient setting regarding symptom burden , depression , and quality of life ( QOL ) . METHODS AND RESULTS Thirty-six patients ( 53.6 ± 8.3 years old ) were referred for an outpatient palliative care consultation after discharge . Changes in symptom burden , depression , and QOL at 3 months were compared with 36 patients with symptomatic heart failure matched on age , sex , race , and New York Heart Association functional class . Improvements were observed in symptom burden , depression , and QOL in both groups over time ( all P < .005 ) , but were more pronounced in patients receiving a palliative care consultation ( all P < .035 ) . CONCLUSIONS A palliative care consultation may reduce symptom burden and depression and enhance QOL in patients with symptomatic heart failure . Larger-scale r and omized controlled trials sufficiently powered to assess clinical outcomes are warranted to determine the efficacy of palliative care services in outpatient setting s regarding symptom distress , depression , and QOL in patients with symptomatic heart failure BACKGROUND Ivabradine is indicated to control heart rate in otherwise optimally treated patients with chronic heart failure ( CHF ) and reduced ejection fraction . However , data on its effectiveness outside clinical trials and longer-term effects are scarce . METHODS We performed a prospect i ve cohort study involving 249 German resident cardiologists and analyzed the 1-year effectiveness and safety of ivabradine used in CHF out patients . Data on symptoms , quality of life , and hospitalizations were collected . RESULTS In total , 767 CHF patients were enrolled to receive ivabradine twice daily , of whom 684 ( 90 % ) were still on ivabradine at study end ( mean treatment duration 11.2months ) . The cohort was representative of CHF patients seen in clinical practice in terms of age , risk factor profile , and comorbidities . Concomitant beta-blocker therapy was prescribed in 497 patients ( 65 % ) . After one year , compared to baseline , heart rate in ivabradine-treated patients was 16bpm lower . This reduction was associated with a significant improvement in NYHA class , and less frequent signs of decompensation ( 36 % to 8 % ) . The proportion of hospitalized patients within 1year decreased from 23 % before treatment , to 5 % with ivabradine therapy . These improvements in clinical status were accompanied by a reduction in BNP and an increase in LVEF ( + 5.1 % at 1year ) . Quality of life was significantly improved in all measured dimensions . Adverse drug reactions were noted in 26 patients ( 3 % ) , and were in line with the known safety profile of ivabradine . CONCLUSIONS Ivabradine was effective and well-tolerated in CHF patients seen in clinical practice throughout 1year of treatment OBJECTIVES The purpose of this clinical trial was to evaluate the long-term effects of flosequinan on the morbidity and mortality of patients with severe chronic heart failure . BACKGROUND Flosequinan was the first oral vasodilator to be used in the clinic to augment the effects of digitalis , diuretics , and angiotensin-converting enzyme inhibitors in heart failure . However , the drug activated neurohormonal systems and exerted both positive inotropic and chronotropic effects , raising concerns about its safety during long-term use . METHODS Following a run-in period design ed to minimize the risk of tachycardia , we r and omly assigned 2,354 patients in New York Heart Association functional class III to IV heart failure and with an ejection fraction ≤35 % to receive long-term treatment with placebo or flosequinan ( 75 or 100 mg/day ) in addition to their usual therapy . The primary outcome was all-cause mortality . RESULTS The trial was terminated after a recommendation of the Data and Safety Monitoring Board , because during an average of 10 months of follow-up , 192 patients died in the placebo group and 255 patients died in the flosequinan group ( hazard ratio : 1.39 , 95 % confidence interval : 1.15 to 1.67 ; p = 0.0006 ) . Flosequinan also increased the risk of disease progression , which was paralleled by drug-related increases in heart rate and neurohormonal activation . However , during the first month , patients in the flosequinan group were more likely to report an improvement in well-being and less likely to experience worsening heart failure . Similarly , during the month following drug withdrawal at the end of the trial , patients withdrawn from flosequinan were more likely than those withdrawn from placebo to report symptoms of or to require treatment for worsening heart failure . CONCLUSIONS Although flosequinan produced meaningful symptomatic benefits during short- and long-term treatment , the drug increased the risk of death in patients with severe chronic heart failure CONTEXT There are few r and omized controlled trials on the effectiveness of palliative care interventions to improve the care of patients with advanced cancer . OBJECTIVE To determine the effect of a nursing-led intervention on quality of life , symptom intensity , mood , and re source use in patients with advanced cancer . DESIGN , SETTING , AND PARTICIPANTS R and omized controlled trial conducted from November 2003 through May 2008 of 322 patients with advanced cancer in a rural , National Cancer Institute- design ated comprehensive cancer center in New Hampshire and affiliated outreach clinics and a VA medical center in Vermont . INTERVENTIONS A multicomponent , psychoeducational intervention ( Project ENABLE [ Educate , Nurture , Advise , Before Life Ends ] ) conducted by advanced practice nurses consisting of 4 weekly educational sessions and monthly follow-up sessions until death or study completion ( n = 161 ) vs usual care ( n = 161 ) . MAIN OUTCOME MEASURES Quality of life was measured by the Functional Assessment of Chronic Illness Therapy for Palliative Care ( score range , 0 - 184 ) . Symptom intensity was measured by the Edmonton Symptom Assessment Scale ( score range , 0 - 900 ) . Mood was measured by the Center for Epidemiological Studies Depression Scale ( range , 0 - 60 ) . These measures were assessed at baseline , 1 month , and every 3 months until death or study completion . Intensity of service was measured as the number of days in the hospital and in the intensive care unit ( ICU ) and the number of emergency department visits recorded in the electronic medical record . RESULTS A total of 322 participants with cancer of the gastrointestinal tract ( 41 % ; 67 in the usual care group vs 66 in the intervention group ) , lung ( 36 % ; 58 vs 59 ) , genitourinary tract ( 12 % ; 20 vs 19 ) , and breast ( 10 % ; 16 vs 17 ) were r and omized . The estimated treatment effects ( intervention minus usual care ) for all participants were a mean ( SE ) of 4.6 ( 2 ) for quality of life ( P = .02 ) , -27.8 ( 15 ) for symptom intensity ( P = .06 ) , and -1.8 ( 0.81 ) for depressed mood ( P = .02 ) . The estimated treatment effects in participants who died during the study were a mean ( SE ) of 8.6 ( 3.6 ) for quality of life ( P = .02 ) , -24.2 ( 20.5 ) for symptom intensity ( P = .24 ) , and -2.7 ( 1.2 ) for depressed mood ( P = .03 ) . Intensity of service did not differ between the 2 groups . CONCLUSION Compared with participants receiving usual oncology care , those receiving a nurse-led , palliative care-focused intervention addressing physical , psychosocial , and care coordination provided concurrently with oncology care had higher scores for quality of life and mood , but did not have improvements in symptom intensity scores or reduced days in the hospital or ICU or emergency department visits . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00253383 PURPOSE This study evaluates the implementation of Disease Specific Advance Care Planning ( DS-ACP ) for heart failure patients in a large health care system . The DS-ACP model uses a trained facilitator to guide communication between patient and proxy regarding patient values and goals for treatment in worst-case scenarios , develop a disease specific documentation plan , and identify needed re sources . METHODS Referral and DS-ACP service delivery data were merged with electronic health record data . Process measures for implementation are described . Patients who participated in DS-ACP are compared with those who did not on demographics , medical characteristics , and outcomes such as inpatient readmissions , and hospice use among those who died . A chart audit was completed on a sample of patients to examine differences in advance care planning documentation between participants and non participants . RESULTS Nearly one third ( 31.8 % ) of the 1894 heart failure patients referred to DS-ACP participated . Referral method was associated with participation . A chart audit revealed 94.3 % of those completing the DS-ACP process , had a health directive compared to 24.8 % of noncompleters ( p<0.001 ) . Of the patients who died by the end of the study period ( n=286 ) , DS-ACP participants were more likely to have used hospice compared to non participants ( 56 % versus 37 % , p=0.002 ) . CONCLUSIONS These initial evaluation results indicate the DS-ACP model , previously tested in r and omized trials , can be successfully implemented among heart failure patients in a large health care system . Results demonstrate the importance of referral method and show initial positive results for participation , improved documentation , and hospice use BACKGROUND Heart failure ( HF ) is associated with a high symptom burden and reduced quality of life ( QOL ) . Models integrating palliative care ( PC ) into HF care have been proposed , but limited research is available on the outcomes of such models . OBJECTIVE Our aim was to assess if inpatient PC for HF patients is associated with improvements in symptom burden , depressive symptoms , QOL , or differential use of services . METHODS Patients hospitalized with acute HF were r and omized to receive a PC consult with follow-up as determined by provider or st and ard care . Two hundred thirty-two patients ( 116 intervention/116 control ) from a large tertiary-care urban hospital were recruited over a 10-month period . Primary outcomes were symptom burden , depressive symptoms , and QOL measured at baseline , 1 , and 3 months . Secondary outcomes included advance care planning ( ACP ) , inpatient 30-day readmission , hospice use , and death . RESULTS Improvements were greater at both 1 and 3 months in the intervention group for primary outcome summary measures after adjusting for age , gender , and marital status differences between study groups . QOL scores increased by 12.92 points in the intervention and 8 points in the control group at 1 month ( difference+4.92 , p<0.001 ) . Improvement in symptom burden was 8.39 in the intervention group and 4.7 in the control group at 1 month ( + 3.69 , p<0.001 ) . ACP was the only secondary outcome associated with the intervention ( hazard ratio [ HR ] 2.87 , p=0.033 ) . CONCLUSION An inpatient PC model for patients with acute HF is associated with short-term improvement in symptom burden , QOL , and depressive symptoms There have been no reports evaluating the impact of long-acting loop diuretics ( LLD ) on the outcome of heart failure ( HF ) and arrhythmia treatment in HF with reduced ejection fraction ( HFrEF ) patients implanted with a cardiac resynchronization therapy ( CRT ) device . This was a prospect i ve , single-blind , r and omized crossover study . We allocated 21 consecutive CRT implanted patients into 2 groups . The furosemide group received furosemide as a first treatment and azosemide as a second treatment . The azosemide group received this treatment in the reverse order . The first treatment was given to each group for 6 months and the second treatment continued for an additional 6 months . We combined the data of each medication regimen in each group and analyzed it at baseline , 6 months , and 1 year . The primary endpoints were the variation of fluid index and thoracic impedance measured by CRT at 6 months . The baseline characteristics were similar for both groups . The difference in the primary endpoints was not statistically significant between the 2 medication arms ( fluid index : -29.6 ± 64.4 versus 16.2 ± 48.2 ; P = 0.22 , thoracic impedance : -0.49 ± 17.8 versus 2.45 ± 12.5 ; P = 0.56 ) . Likewise , the clinical outcome of HF and the CRT derived parameters in both arms were comparable . HFrEF patients taking LLD after CRT implantation might be comparable to those taking short-acting loop diuretics in the treatment of HF and HF-associated arrhythmias BACKGROUND Palliative interventions are an important part of advanced heart failure ( HF ) care . However , these interventions are historically underutilized , particularly by African Americans . METHODS AND RESULTS We performed a prospect i ve r and omized intervention trial in patients with advanced HF who were hospitalized for acute decompensation at 3 urban hospitals , comparing the effect of palliative care consultation ( PCC ) with that of usual care . The primary end point was the proportion choosing comfort-oriented care ( hospice and /or " do not resuscitate " [ DNR ] order ) 3 - 6 months after r and omization . A total of 85 patients ( mean age 68 years , 91.8 % African American ) were enrolled over a 2-year period . Four of the 43 patients ( 9.3 % ) r and omized to the PCC group chose comfort-oriented care versus 0 of the 42 control group members ( risk difference = 9.3 % ; 95 % confidence interval = -11.8 % to 30.0 % ) . CONCLUSIONS In this predominantly African-American cohort of hospitalized patients with advanced HF , PCC did not lead to a greater likelihood of comfort care election compared with usual care . More robust palliative interventions should be developed to meet the needs of diverse groups of patients with HF Clinical status in heart failure is conventionally assessed by the physician 's evaluation , patients ' own perception of their symptoms , quality of life ( QoL ) tools , and a measure of functional capacity . These aspects can be measured with tools such as the New York Heart Association functional class , QoL tools such as the EuropeanQoL-5 dimension , the Kansas City Cardiomyopathy Question naire , patient global assessment ( PGA ) , and by 6-minute walk test ( 6MWT ) , respectively . The ferric carboxymaltose in patients with heart failure and iron deficiency ( FAIR-HF ) trial demonstrated that treatment with intravenous ferric carboxymaltose in iron-deficient patients with symptomatic heart failure with reduced left ventricular function , significantly improved all 5 outcome measures . This analysis assessed the correlations between the longitudinal changes in the measures of clinical status , as measured by QoL tools and the changes in the measures of functional capacity as measured by the 6MWT . This analysis used the data base from the FAIR-HF trial , which r and omized 459 patients with chronic heart failure ( reduced left ventricular ejection fraction ) and iron deficiency , with or without anemia to ferrous carboxymaltose or placebo . The degree of correlation between QoL tools and the 6MWT was assessed at 4 , 12 , and 24 weeks . The data demonstrate highly significant correlations between QoL and functional capacity , as measured by the 6MWT , at all time points ( p < 0.001 ) . Changes in PGA , Kansas City Cardiomyopathy Question naire , and EuroQoL-5D correlated increasingly over time with changes in 6MWT performance . Interestingly , the strongest correlation at 24 weeks is for the PGA , which is a simple numerical scale ( r = -0.57 , p < 0.001 ) . This analysis provides evidence that QoL assessment show a significant correlation with functional capacity , as measured by the 6MWT . The strength of these correlations increased over time AIMS We evaluated the outcome of person-centred and integrated Palliative advanced home caRE and heart FailurE caRe ( PREFER ) with regard to patient symptoms , health-related quality of life ( HQRL ) , and hospitalizations compared with usual care . METHODS AND RESULTS From January 2011 to October 2012 , 36 ( 26 males , 10 females , mean age 81.9 years ) patients with chronic heart failure ( NYHA class III-IV ) were r and omized to PREFER and 36 ( 25 males , 11 females , mean age 76.6 years ) to the control group at a single centre . Prospect i ve assessment s were made at 1 , 3 , and 6 months using the Edmonton Symptom Assessment Scale , Euro Qol , Kansas City Cardiomyopathy Question naire , and rehospitalizations . Between-group analysis revealed that patients receiving PREFER had improved HRQL compared with controls ( 57.6 ± 19.2 vs. 48.5 ± 24.4 , age-adjusted P-value = 0.05 ) . Within-group analysis revealed a 26 % improvement in the PREFER group for HRQL ( P = 0.046 ) compared with 3 % ( P = 0.82 ) in the control group . Nausea was improved in the PREFER group ( 2.4 ± 2.7 vs. 1.7 ± 1.7 , P = 0.02 ) , and total symptom burden , self-efficacy , and quality of life improved by 18 % ( P = 0.035 ) , 17 % ( P = 0.041 ) , and 24 % ( P = 0.047 ) , respectively . NYHA class improved in 11 of the 28 ( 39 % ) PREFER patients compared with 3 of the 29 ( 10 % ) control patients ( P = 0.015 ) . Fifteen rehospitalizations ( 103 days ) occurred in the PREFER group , compared with 53 ( 305 days ) in the control group . CONCLUSION Person-centred care combined with active heart failure and palliative care at home has the potential to improve quality of life and morbidity substantially in patients with severe chronic heart failure . TRIAL REGISTRATION NCT01304381 Little is known about the burden of illness associated with advanced congestive heart failure ( CHF ) . Underst and ing the needs of this population requires further information about symptoms and other factors related to quality of life . We studied a convenience sample of 103 community-dwelling patients with New York Heart Association Class III/IV CHF . The primary outcome , quality of life , was measured with the Multidimensional Index of Life Quality . Potential correlates of quality of life included overall symptom burden ( Memorial Symptom Assessment Scale , MSAS ) , including global symptom distress ( MSAS Global Distress Index , GDI ) ; psychological state ( Mental Health Inventory-5 ) ; functional status ( Sickness Impact Profile ) ; spirituality ( Functional Assessment of Chronic Illness Therapy-Spirituality Scale ) ; and co-morbid conditions ( Charlson Comorbidity Index ) . Patients had a mean age of 67.1 years ( SD=12.1 ) ; were mostly white ( 72.8 % ) , male ( 71.8 % ) , and married ( 51.5 % ) ; and had a mean ejection fraction of 22.3 % ( SD=6.8 ) . The most prevalent symptoms were lack of energy ( 66 % ) , dry mouth ( 62 % ) , shortness of breath ( 56 % ) , and drowsiness ( 52 % ) . Pain was reported by about one-third of patients . For each of these symptoms , high symptom-related distress was reported by 14.1%-54.1 % . Quality of life was moderately compromised ( Multidimensional Index of Life Quality composite , median=56 , possible range 12 - 84 ) . Impairment in quality of life was strongly associated with global symptom distress ( MSAS GDI ; r=0.74 , P<0.001 ) ; burden of comorbid conditions ( r = -0.32 , P=0.002 ) , female sex ( r=-0.22 , P=0.03 ) , functional impairment , particularly psychological impairment ( r=-0.55 , P<0.001 ) , and poorer psychological well-being ( r=0.68 , P<0.001 ) . In multivariate analyses , impairment in quality of life was significantly related to high symptom distress , poorer psychological well-being , and poor functional mobility ( R2=0.67 ; P=0.002 for all ) . Distressful symptoms related to impaired quality of life included lack of energy ( P=0.04 ) , irritability ( P=0.03 ) , and drowsiness ( P=0.02 ) . Community-dwelling patients with advanced CHF experience numerous symptoms , significant symptom distress , and a compromised quality of life . Overall quality of life was strongly associated with symptom distress , psychological well-being and functional status . A focus on ameliorating prevalent physical symptoms and psychological distress , along with supportive measures that promote functional mobility , may lead to an improvement in the overall quality of life in this patient population |
10,709 | 19,299,447 | CONCLUSIONS Isoflavone-rich soy products decrease FSH and LH in premenopausal women and may increase estradiol in post-menopausal women . | BACKGROUND Hormonal effects of soy and isoflavones have been investigated in numerous trials with equivocal findings .
We aim ed to systematic ally assess the effects of soy and isoflavones on circulating estrogen and other hormones in pre- and post-menopausal women . | The soybean is rich in isoflavone phytoestrogens , which are lig and s for estrogen receptors , but it is unknown whether soy/phytoestrogens have similar procoagulant effects to estrogen . In this r and omized double-blind trial , 40 healthy postmenopausal women of age 50 - 75 yr received soy protein isolate ( 40 g soy protein , 118 mg isoflavones ) ( n = 19 ) or casein placebo ( n = 21 ) . Plasma markers of coagulation , fibrinolysis , and endothelial dysfunction were measured at baseline and 3 months . The baseline characteristics of the two groups were similar . Compared with casein placebo , soy decreased triglycerides ( P < 0.005 ) and low-density lipoprotein/high-density lipoprotein ratio ( P < 0.001 ) and increased lipoprotein ( a ) ( P < 0.05 ) . Activity of coagulation factor VII ( VIIc ) decreased similarly in both groups ( P < 0.005 ) . Prothrombin fragments 1 + 2 ( a marker of thrombin generation ) decreased in the soy group ( P < 0.005 ) , but the change was not different from the casein group . There was no effect of soy on soluble fibrin ( a marker of fibrin production ) , plasminogen activator inhibitor-1 ( a marker of fibrinolytic inhibitory potential ) , D-dimer ( a marker of fibrin turnover ) , or von Willebr and factor ( a marker of endothelial damage ) . In conclusion , the results of the current study do not support biologically significant estrogenic effects of soy/phytoestrogens on coagulation , fibrinolysis , or endothelial function Objective : To determine the safety and efficacy of an oral soy isoflavone extract for relief of menopausal hot flushes . Design : This was a double‐blind , r and omized , parallel group , outpatient , multicenter ( 15 sites ) study . A total of 177 postmenopausal women ( mean age = 55 years ) who were experiencing five or more hot flushes per day were r and omized to receive either soy isoflavone extract ( total of 50 mg genistin and daidzin per day ) or placebo . Physical examinations and endometrial and biochemical evaluations were performed upon admission and completion . Body weight , symptoms , and safety were evaluated at all visits . Results : Relief of vasomotor symptoms was observed in both groups . Decreases in the incidence and severity of hot flushes occurred as soon as 2 weeks in the soy group , whereas the placebo group experienced no relief for the first 4 weeks . Differences between evaluable subjects in both groups were statistically significant over 6 weeks ( p = 0.03 ) . Over 12 weeks , between‐group differences approached significance ( p = 0.08 ) . Endometrial thickness evaluated by ultrasound , lipoproteins , bone markers , sex hormone‐binding globulin and follicle‐stimulating hormone , and vaginal cytology did not change in either group . Conclusions : Soy isoflavone extract was effective in reducing frequency and severity of flushes and did not stimulate the endometrium . Soy isoflavone extracts provide an attractive addition to the choices available for relief of hot flushes . ( Menopause 2000;7:236‐242 . © 2000 , The North American Menopause Society . Background . The aim of the study was to evaluate the effect , in postmenopausal women , of the phytoestrogen genistein and hormone replacement therapy ( HRT ) on circulating two independent factors of cardiovascular risk : homocysteine and C‐reactive protein ( CRP ) Phytoestrogens are thought to be beneficial to vascular health . Possible mechanisms of action could involve C-reactive protein ( CRP ) , endothelial E-selectin , and nitric oxide . We therefore design ed a r and omized , placebo-controlled , double-blind trial in which we studied the effects of isoflavonoids on CRP , E-selectin , and nitrate-nitrite ( NO(x ) ; reflecting the release of nitric oxide ) in postmenopausal women . Fifty-six postmenopausal women ( FSH > 30 U/liter ) with a history of breast cancer used ( in a r and omized order ) phytoestrogen ( 114 mg isoflavonoids ) or placebo tablets daily for 3 months ; the treatment regimens were crossed over after a 2-month washout period . The serum levels of CRP and E-selectin , and plasma levels of NO(x ) were measured before and on the last day of each treatment . The phytoestrogen regimen did not affect the levels of either CRP ( P = 0.584 ) or NO(x ) ( P = 0.270 ) , but the levels of E-selectin were reduced by 4.0 % ( 2.9 ng/ml ; P = 0.031 ) during phytoestrogen use and by 2.2 % ( 1.3 ng/ml ; P = 0.023 ) during placebo use . No difference was found at any marker at 3 months between the groups . In conclusion , our data , suggesting neutral effects of phytoestrogens on CRP , E-selectin , and nitric oxide , fail to support a vasoprotective role of phytoestrogens Background : Postmenopausia and hypercholesterolemia are related to endothelial dysfunction , a pathogenic event in atherosclerosis . Soy protein reduces plasma cholesterol , but there is scanty information about its effect on endothelial function . Objective : To evaluate the effect of isolated soy protein compared to caseinate on plasma lipoproteins and endothelial function in postmenopausal hypercholesterolemic women . Design : R and omized , double-blind , cross-over trial . Setting : Outpatient clinic of the Catholic University of Chile . Subjects : Eighteen healthy , postmenopausal women with hypercholesterolemia were recruited , included and completed the protocol . Interventions : During the trial , all patients followed a low fat/low cholesterol diet and were r and omly assigned to receive isolated soy protein or matching caseinate for 4 weeks , and then the alternative treatment until week 8 . At pre- study and at the end of the first and second period , plasma lipoprotein levels and endothelial function ( flow-mediated dilatation ( FMD ) of the brachial artery ) were evaluated . Results : Plasma total and low density lipoprotein (LDL)-cholesterol concentration were significantly lower with the low fat/low cholesterol diet compared to pre- study , either with caseinate or soy protein . No significant differences in plasma lipid concentration between caseinate or soy protein interventions were observed . FMD did not change with the caseinate . In contrast , when soy protein was administered , FMD was significantly higher compared to pre- study ( 9.471.8 % vs 5.371.2 % ; P<0.05 ) and compared to caseinate intervention ( 9.471.8 % vs 4.971.5 % ; P<0.033 ) . Conclusions : These results suggest that in postmenopausal hypercholesterolemic women , soy protein improves endothelial function , regardless of changes in plasma lipoproteins . Sponsorship : Pontificia Universidad Católica ( DIPUC99/09E ) , Protein Technology International and Gynopharm Laboratory ( Recalcine Group ) Objective : To evaluate in a 12-month , prospect i ve , r and omized , double-blind , placebo-controlled study whether pure administration of the phytoestrogen genistein ( 54 mg/d ) might reduce the number and severity of hot flushes in postmenopausal women with no adverse effect on the endometrium . Design : A total of 389 participants met the main study criteria and were r and omly assigned to receive the phytoestrogen genistein ( n = 198 ) or placebo ( n = 191 ) . About 40 % of participants in both groups did not suffer from hot flushes , and the evaluation was performed in a subgroup of 247 participants ( genistein , n = 125 ; placebo , n = 122 ) . Reductions from baseline in the frequency and severity of hot flushes were the principal criteria of efficacy . Endometrial thickness was evaluated by ultrasonography . The maturation value was also used to determine hormonal action on the vaginal cells . Results : There were no significant differences in age , time since menopause , body mass index , and vasomotor symptoms between groups at baseline ( 4.4 ± 0.33 hot flushes per day in the genistein group and 4.2 ± 0.35 hot flushes per day in the control group ) . The effect was already evident in the first month and reached its peak after 12 months of genistein therapy ( −56.4 % reduction in the mean number of hot flushes ) . Furthermore , there was a significant difference between the two groups at each evaluation time ( 1 , 3 , 6 , and 12 months ) . No significant difference was found in mean endometrial thickness and maturation value score between the two groups , either at baseline or after 12 months . Conclusions : The phytoestrogen genistein has been shown to be effective on vasomotor symptoms without an adverse effect on endometrium BACKGROUND Observational studies suggest that dietary isoflavones reduce breast cancer risk , and this may be caused in part by effects on endogenous hormone concentrations . Because intestinal bacteria metabolize isoflavones , it was hypothesized that consumption of probiotic bacteria would enhance the biologic effects of isoflavones , including effects on endogenous hormones . DESIGN Twenty ( 20 ) postmenopausal breast cancer survivors and 20 healthy postmenopausal women completed four 42-day diet periods in a r and omized , crossover design . They received one of the following : isolated soy protein ; isolated milk protein ; soy + probiotic capsules ; or milk + probiotic capsules . Each protein supplement provided 0.38 g protein/(kg body weight/day ) ( 26.6 + /- 4.5 g protein/day ) and soy protein provided 0.64 mg isoflavones/(kg body weight/day ) ( 44.4 + /- 7.5 mg isoflavones/day ) . Probiotic capsules provided 10(9 ) colony-forming units Lactobacillus acidophilus ( strain DDS-1 ) , Bifidobacterium longum , and 15 - 20 mg fructo-oligosaccharide . MEASURES Plasma sample s were collected at baseline and after each diet for analysis of estrogens , follicle-stimulating hormone ( FSH ) , and rogens , and sex hormone?binding globulin ( SHBG ) . RESULTS Hormone levels were not affected by soy , probiotic supplements , or equol producer status , and neither cancer status nor equol producer status altered the effects of soy or probiotics . Furthermore probiotics did not alter the effects of soy consumption . Soy protein tended to decrease SHBG compared to milk protein diets ( p = 0.05 ) , although both proteins significantly decreased SHBG relative to baseline ( p = 0.0001 and p = 0.03 ) . CONCLUSIONS These data suggest that short-term , moderate consumption of isoflavone-containing soy protein and consumption of these particular probiotic capsules do not significantly alter reproductive hormone concentrations in breast cancer survivors or controls , regardless of equol producer status OBJECTIVE Phytoestrogen consumption has been shown to reduce risk factors for cardiovascular disease . Type 2 diabetes confers an adverse cardiovascular risk profile particularly in women after menopause . The aim of this study was to determine whether a dietary supplement with soy protein and isoflavones affected insulin resistance , glycemic control , and cardiovascular risk markers in postmenopausal women with type 2 diabetes . RESEARCH DESIGN AND METHODS A total of 32 postmenopausal women with diet-controlled type 2 diabetes completed a r and omized , double blind , cross-over trial of dietary supplementation with phytoestrogens ( soy protein 30 g/day , isoflavones 132 mg/day ) versus placebo ( cellulose 30 g/day ) for 12 weeks , separated by a 2-week washout period . RESULTS Compliance with the dietary supplementation was > 90 % for both treatment phases . When compared with the mean percentage change from baseline seen after 12 weeks of placebo , phytoestrogen supplementation demonstrated significantly lower mean values for fasting insulin ( mean + /- SD 8.09 + /- 21.9 % , P = 0.006 ) , insulin resistance ( 6.47 + /- 27.7 % , P = 0.003 ) , HbA(1c ) ( 0.64 + /- 3.19 % , P = 0.048 ) , total cholesterol ( 4.07 + /- 8.13 % , P = 0.004 ) , LDL cholesterol ( 7.09 + /- 12.7 % , P = 0.001 ) , cholesterol/HDL cholesterol ratio ( 3.89 + /- 11.7 % , P = 0.015 ) , and free thyroxine ( 2.50 + /- 8.47 % , P = 0.004 ) . No significant change occurred in HDL cholesterol , triglycerides , weight , blood pressure , creatinine , dehydroepi and rosterone sulfate , and rostenedione , and the hypothalamic-pituitary-ovarian axis hormones . CONCLUSIONS These results show that dietary supplementation with soy phytoestrogens favorably alters insulin resistance , glycemic control , and serum lipoproteins in postmenopausal women with type 2 diabetes , thereby improving their cardiovascular risk profile Soy phytoestrogens were suggested to reduce the risk of a number of diseases including breast cancer . Given that these compounds are metabolized by bacteria , alteration of intestinal bacteria and enzymes may affect phytoestrogen metabolism . We hypothesized that probiotics , when consumed with soy protein , would increase plasma isoflavones , as well as equol producer frequency , in postmenopausal women . We further hypothesized that these effects would differ between women who have had breast cancer and women who have not . To test these hypotheses , 20 breast cancer survivors and 20 controls completed four 6-wk treatments in a r and omized , crossover design : supplementation with soy protein ( S ) ( 26.6 + /- 4.5 g protein , 44.4 + /- 7.5 mg isoflavones/d ) ; soy + probiotics ( S+P ) ( 10(9 ) colony-forming units Lactobacillus acidophilus DDS+1 and Bifidobacterium longum , 15 - 30 mg fructooligosaccharide/d ) ; milk protein ( M ) ( 26.6 + /- 4.5 g protein/d ) ; and milk + probiotics ( M+P ) . Plasma phytoestrogen concentrations did not differ between controls and survivors , although genistein tended to be lower in survivors at baseline ( P = 0.15 ) , and during soy ( P = 0.16 ) and milk protein ( P = 0.16 ) consumption . As expected , soy consumption increased plasma phytoestrogen concentrations ( P < 0.0001 ) . Plasma phytoestrogen concentrations and the number of equol producers did not differ between the S and S+P diets . At the same time , plasma equol concentrations as well as urinary equol excretion in 2 subjects were more than 7-fold different between the 2 diets . These results indicate that this particular probiotic supplement does not generally affect plasma isoflavones , although the large differences between plasma and urinary equol in some subjects suggest that equol producer status may be modifiable in some individuals Soy protein favorably alters serum lipids and lipoproteins in hypercholesterolemic individuals , thereby reducing cardiovascular disease risk . The primary purpose was to determine the effect of soy protein ( 40 g/d ) on circulating lipids and lipoproteins or coagulation and fibrinolytic factors in normocholesterolemic and mildly hypercholesterolemic perimenopausal women . We also determined the contribution of coagulation and fibrinolytic and other factors ( e.g. , body size and composition ; serum estrogens , ferritin , iron ; dietary intake ) to lipid profiles . Subjects were r and omly assigned to treatment : isoflavone-rich soy ( n = 24 ) , isoflavone-poor soy ( n = 24 ) , or whey control ( n = 21 ) protein . We measured circulating lipids and lipoproteins at baseline , wk 12 and wk 24 , and coagulation/fibrinolytic factors at baseline and wk 24 . Coagulation and fibrinolytic factors were not adversely affected by treatment . Treatment did not alter lipid profiles in mildly hypercholesterolemic ( n = 30 ) or in all subjects combined . Time significantly ( P < 0.001 ) affected serum total cholesterol , triacylglycerol , LDL cholesterol and HDL cholesterol concentrations . We could not attribute changes over time to various factors , but at baseline accounted for 57 % of the variability in HDL cholesterol ( P < or = 0.0001 ) and for 50 % in the total to HDL cholesterol ratio ( P < or = 0.0001 ) . Dietary vitamin E and % energy from fat had positive effects , whereas plasma plasminogen activator inhibitor-1 , fibrinogen , body weight and serum ferritin had negative effects on HDL and total to HDL cholesterol . Isoflavone-rich or isoflavone-poor soy protein had no effect on lipid profiles or coagulation and fibrinolytic factors , whereas the effect of time suggested that the hormonal milieu during the menopausal transition may have overridden any detectable treatment effect on lipids . The relationship between coagulation factors and serum lipids should be examined further as indices of cardiovascular disease risk in midlife women BACKGROUND Soy-protein consumption is known to reduce plasma total and LDL cholesterol concentrations . However , the responsible soy component or components and the magnitude of effects in normocholesterolemic and mildly hypercholesterolemic subjects are unclear . OBJECTIVE The present study examined the effects of soy isoflavone consumption on plasma concentrations of triacylglycerol , apolipoprotein ( apo ) A-I , apo B , lipoprotein(a ) , and total , LDL , and HDL cholesterol and on LDL peak particle diameter in normocholesterolemic and mildly hypercholesterolemic postmenopausal women . DESIGN In a r and omized crossover trial , fasting plasma sample s were obtained from 18 postmenopausal women throughout three 93-d periods of daily isolated soy protein ( ISP ) consumption providing an average of 7.1 + /- 1.1 ( control ) , 65 + /- 11 ( low isoflavone ) , or 132 + /- 22 ( high isoflavone ) mg isoflavones/d . RESULTS Compared with values measured during the control diet , the plasma LDL cholesterol concentration was 6.5 % lower ( P < 0.02 ) during the high-isoflavone diet and the ratio of LDL to HDL cholesterol was 8.5 % and 7.7 % lower during the low- and high-isoflavone diets , respectively ( P < 0.02 ) . Isoflavone consumption did not significantly affect plasma concentrations of total or HDL cholesterol , triacylglycerol , apo A-I , apo B , or lipoprotein(a ) or the LDL peak particle diameter . CONCLUSIONS Consumption of isoflavones as a constituent of ISP result ed in small but significant improvements in the lipid profile in normocholesterolemic and mildly hypercholesterolemic postmenopausal women . Although the effects were small , it is possible that isoflavones may contribute to a lower risk of coronary heart disease if consumed over many years in conjunction with other lipid-lowering strategies Numerous studies report that soy lowers cholesterol . Probiotic bacteria were also reported to lower total cholesterol ( TC ) and LDL cholesterol ( LDL-C ) . We hypothesized that by altering intestinal microflora , probiotic consumption may also change phytoestrogen metabolism and enhance the effects of soy . To evaluate the independent and interactive effects of probiotic bacteria and soy on plasma TC , LDL-C , HDL cholesterol ( HDL-C ) , and triglycerides ( TG ) , 37 women with a baseline TC of 5.24 mmol/L were given the following 4 treatments for 6 wk each in a r and omized crossover design : soy protein isolate ( 26 + /- 5 g soy protein containing 44 + /- 8 mg isoflavones/d ) ; soy protein isolate + probiotic capsules ( 10(9 ) colony-forming units Lactobacillus acidophilus DDS-1 and Bifidobacterium longum ) ; milk protein isolate ( 26 + /- 5 g milk protein/d ) ; and milk protein isolate + probiotic . Soy consumption decreased plasma TC by 2.2 % ( P = 0.02 ) and LDL-C by 3.5 % ( P = 0.005 ) , increased HDL-C by 4.2 % ( P = 0.006 ) and tended to decrease TG ( P = 0.07 ) compared with milk protein intake . When divided according to initial TC concentration , soy effects were observed only in hypercholesterolemic women ( TC > 5.17 mmol/L ) . In this subgroup , soy treatments decreased plasma TC by 3.3 % ( P = 0.01 ) , LDL-C by 4.5 % ( P = 0.004 ) , and TG by 10.6 % ( P = 0.02 ) , and increased HDL-C by 4.2 % ( P = 0.02 ) . When subjects were divided on the basis of plasma and urine concentrations of the isoflavone metabolite , equol , equol producers and nonproducers did not differ in baseline lipids or in the effects of soy . Probiotics did not lower cholesterol or enhance the effects of soy . These results confirm a beneficial effect of soy on plasma cholesterol in mildly hypercholesterolemic postmenopausal women independent of equol production status , but do not support an independent or additive effect of these particular probiotic bacteria Some epidemiologic studies reported an association between a low ratio of urinary 2-hydroxyestrogens ( 2-hydroxyestradiol + 2-hydroxyestrone ) to 16alpha-hydroxyestrone ( 2:16OHE(1 ) ) and increased breast cancer risk . Some studies show that soy consumption increases this ratio , and it is suggested that this effect may reduce breast cancer risk . We hypothesized that consumption of probiotic bacteria would alter fecal bacteria and enzymes involved in soy isoflavone metabolism , thereby increasing isoflavone bioavailability and enhancing the beneficial effects of soy on estrogen metabolism . Breast cancer survivors ( n = 20 ) and controls ( n = 20 ) were given 4 treatments for 6 wk each , separated by 2-wk washout periods , in a r and omized , crossover design : soy protein ( 26.6 + /- 4.5 g protein/d containing 44.4 + /- 7.5 mg isoflavones/d ) ; soy protein + probiotics ( 10(9 ) colony-forming units Lactobacillus acidophilus DDS(R)+1 & Bifidobacterium longum , 15 - 30 mg fructooligosaccharide/d ) ; milk protein ( 26.6 + /- 4.5 g protein/d ) ; and milk protein + probiotics . Survivors tended to have a lower baseline urine 2:16OHE(1 ) ratio than controls ( P = 0.10 ) . In the group as a whole , soy consumption tended to increase urinary 2-hydroxyestrogens ( P = 0.07 ) and 16alpha-hydroxyestrone ( P = 0.11 ) but had no effect on the urinary 2:16OHE(1 ) ratio . When subjects were divided into groups by plasma concentrations and urinary levels of the daidzein metabolite equol , soy increased urinary 2-hydroxyestrogens ( P = 0.01 ) and the 2:16OHE(1 ) ratio ( P = 0.04 ) only in subjects with high plasma equol concentrations . None of these results were influenced by probiotic consumption . These results are consistent with studies that found lower urine 2:16OHE(1 ) ratios in women with breast cancer and suggest that soy consumption increases this ratio only in women who are equol producers We assessed the independent effect of soy protein relative to animal protein and of isoflavones on various electrophoretic characteristics of LDL particles . LDL particles were characterized by polyacrylamide gradient gel electrophoresis in 36 moderately hypercholesterolemic men and women ( LDL cholesterol > 3.36 mmol/L ) . All subjects consumed in r and om order each of the four diets ( soy protein depleted of isoflavones , soy protein enriched in isoflavones , animal protein with no added isoflavones , and animal protein with added isoflavones ) for 6 wk . Consumption of soy protein was associated with a larger LDL peak particle size relative to animal protein ( P < 0.01 ) . Soy protein also decreased the cholesterol levels in LDL < 25.5 nm by 12.3 % ( P < 0.001 ) and increased cholesterol levels in LDL > 26.0 nm by 14.3 % ( P < 0.05 ) relative to animal protein . Isoflavones did not affect these LDL particle characteristics . Soy protein shifted LDL particle distribution to a less atherogenic pattern and this effect is independent of soy 's isoflavone component BACKGROUND Low intake of dietary fat and high intake of soy foods have been suggested to partly explain the lower breast cancer rates in Asia , perhaps because of lower endogenous estrogens . OBJECTIVE The objective was to assess the hormonal and nonhormonal effects of diets resembling an Asian diet in terms of total fat and soy food contents . DESIGN Fifty-seven postmenopausal women participated in a r and omized , controlled , dietary intervention study . The subjects consumed a very-low-fat diet ( VLFD ; 11 % of energy as fat ) , a Step I diet ( 25 % of energy as fat ) supplemented with soy food ( SFD ; 50 mg isoflavones/d ) , or a control Step I diet ( CD ; 27 % of energy as fat ) with no soy food . All diets were prepared at the General Clinical Research Center of the University of Southern California . Serum hormones and other markers were measured at baseline and every 2 wk during the 8 wk of intervention . RESULTS There were no significant differences in total estradiol and sex hormone binding globulin at the completion of the intervention between women in the SFD and VLFD groups and those in the CD group . Serum insulin decreased significantly in the SFD group , and leptin decreased significantly in the SFD and VLFD groups ; however , these changes did not differ significantly from the changes in the CD group . CONCLUSIONS This study does not provide evidence that ingestion of soy food or a VLFD significantly reduces estrogen concentrations in postmenopausal women . However , short-term changes in diet may have significant and beneficial effects on blood insulin and leptin concentrations BACKGROUND Dietary phytoestrogens are lig and s for the estrogen receptor and may mimic estrogenic effects in vivo . OBJECTIVE To assess the biological activity of isoflavone phytoestrogens , we analyzed the effect of dietary soy isoflavone supplementation on in vivo bioassays of estrogenicity . DESIGN Fifty healthy postmenopausal women aged 50 - 75 y participated in a double-blind , placebo-controlled trial in which they received either soy protein isolate ( 40 g soy protein , 118 mg isoflavones ) or casein placebo . Measurements were made at baseline and at 3 mo . Urinary isoflavone excretion was measured to reflect compliance . The bioassays of estrogenicity included measurement of hepatic proteins and gonadotropin concentrations . RESULTS Baseline characteristics were not significantly different between the soy and placebo groups . Urinary isoflavone excretion increased in the soy group and at the end of 3 mo was higher in the soy group than in the placebo group . In plasma sample s from both groups , C-reactive protein increased significantly over the 3-mo treatment period , whereas sex hormone-binding globulin and thyroid-binding globulin decreased significantly . However , there were no significant differences between the groups in hepatic protein synthesis ( change over 3 mo + /- SEM in the soy and placebo groups , respectively ) : C-reactive protein , 0.42 + /- 0.2 and 0.48 + /- 0.2 U/mL ; sex hormone-binding globulin , -6.9 + /- 1.5 and -10.0 + /- 2.1 micro g/mL ; thyroid-binding globulin , -16 + /- 8 and -26 + /- 7 nmol/L. Furthermore , gonadotropin and dehydroepi and rosterone sulfate concentrations did not change significantly in either group . CONCLUSIONS In healthy postmenopausal women , dietary soy isoflavones do not affect in vivo biological indicators of estrogenicity , including hepatic protein synthesis and gonadotropin concentrations . This suggests that soy isoflavones have little biologically relevant estrogenic effect in vivo in postmenopausal women BACKGROUND Elevated iron stores , oxidative stress , and estrogen deficiency may place postmenopausal women at greater risk of heart disease and cancer than premenopausal women . OBJECTIVE The objective was to determine the effect of soy-protein isolate ( SPI ) intake and iron indexes on plasma total antioxidant status ( TAS ) in perimenopausal women after control for other contributing factors . DESIGN Perimenopausal women ( n = 69 ) were r and omly assigned ( double blind ) to treatment : isoflavone-rich SPI ( SPI+ ; n = 24 ) , isoflavone-poor SPI ( SPI- ; n = 24 ) , or whey protein ( control ; n = 21 ) . Each subject consumed 40 g soy or whey protein daily for 24 wk . Plasma TAS , serum ferritin , serum iron , transferrin saturation , and hemoglobin were measured at baseline , week 12 , and week 24 . RESULTS No significant time-by-treatment interactions on iron indexes or TAS were observed , whereas time had an effect on serum ferritin ( P < or = 0.0001 ) and hemoglobin ( P = 0.004 ) but not on TAS . Multiple regression analysis showed that at week 12 , 48 % ( P < or = 0.0001 ) of the variability in TAS was accounted for by baseline TAS , alcohol intake , soy intake ( soy compared with control ; P = 0.016 ) , plasma lipoprotein(a ) , and dietary iron . At week 24 , 47 % of the variability in TAS was accounted for by baseline TAS , serum ferritin , serum estrone , dietary zinc , and dietary meat , fish , and poultry . CONCLUSIONS SPI intake had no significant effect on iron status , but our results suggest that dietary soy protein and low iron stores may protect perimenopausal women from oxidative stress BACKGROUND Clinical trial data and the results of a meta- analysis suggest a hypocholesterolemic effect of soy protein . The effect may be partially attributable to the isoflavones in soy . Few studies have examined the separate effects of soy protein and isoflavones . OBJECTIVE The objective of this study was to determine the effect of soy protein and isoflavones on plasma lipid concentrations in postmenopausal , moderately hypercholesterolemic women . DESIGN This was a r and omized , double-blind , placebo-controlled clinical trial with 3 treatment groups . After a 4-wk run-in phase during which the women consumed a milk protein supplement , the subjects were r and omly assigned to 12 wk of dietary protein supplementation ( 42 g/d ) with either a milk protein ( Milk group ) or 1 of 2 soy proteins containing either trace amounts of isoflavones ( Soy- group ) or 80 mg aglycone isoflavones ( Soy+ group ) . RESULTS LDL-cholesterol concentrations decreased more in the Soy+ group ( n = 31 ) than in the Soy- group ( n = 33 ) ( 0.38 compared with 0.09 mmol/L ; P = 0.005 ) , but neither of these changes was significantly different from the 0.26-mmol/L decrease observed in the Milk group ( n = 30 ) . The results for total cholesterol were similar to those for LDL cholesterol . There were no significant differences in HDL-cholesterol or triacylglycerol concentrations between the 3 groups . CONCLUSIONS The difference in total- and LDL-cholesterol lowering between the 2 soy-protein supplements suggests an effect attributable to the isoflavone-containing fraction . However , the unexpected LDL-cholesterol lowering observed in the Milk group , and the fact that there was no significant difference between either soy group and the Milk group , suggests that changes may have been due to other factors related to participation in the study BACKGROUND Several clinical trials have suggested that soy intake decreases oxidative stress . Soy isoflavones have antioxidant properties in vitro , but results of supplementation in clinical trials are inconclusive . OBJECTIVE The objective was to evaluate the independent effects of soy protein and soy-derived isoflavones on plasma antioxidant capacity and biomarkers of oxidative stress . DESIGN Forty-two hypercholesterolemic ( LDL cholesterol > 3.36 mmol/L ) subjects aged > 50 y were provided with each of 4 diets in r and om order in a crossover design . Diets varied in protein source ( 10 % of energy , soy or animal ) and isoflavone content ( trace or 50 mg/1000 kcal ) and were consumed for 42 d each . Plasma antioxidants , protein carbonyls , malondialdehyde , total antioxidant performance , LDL oxidizability , and urinary F(2)-isoprostanes were measured at the end of each dietary phase . RESULTS Plasma antioxidant concentrations were not significantly different , regardless of dietary treatment , except for isoflavones , which were higher after isoflavone supplementation ( P = 0.0001 ) . Although plasma total antioxidant performance was 10 % higher with soy protein intake , regardless of dietary isoflavones ( P = 0.0003 ) , soy protein did not significantly affect most individual markers of oxidative stress ( LDL oxidizability , urinary F(2)-isoprostanes , malondialdehyde , or protein carbonyls in native plasma ) . However , soy protein was associated with modestly lower concentrations of protein carbonyls in oxidized plasma . There was no significant effect of isoflavones on LDL oxidation , urinary F(2)-isoprostanes , or protein carbonyl groups , although , paradoxically , the plasma malondialdehyde concentration was significantly higher after the isoflavone-rich diets ( P = 0.04 ) . CONCLUSIONS Diets relatively high in soy protein or soy-derived isoflavones have little effect on plasma antioxidant capacity and biomarkers of oxidative stress BACKGROUND Soy consumption is known to reduce plasma total cholesterol and LDL cholesterol in hypercholesterolemic subjects , but the responsible soy components and the effects in normocholesterolemic subjects remain unclear . OBJECTIVE The effects of soy isoflavone consumption on plasma total cholesterol , HDL-cholesterol , LDL-cholesterol , triacylglycerol , apolipoprotein A-I , apolipoprotein B , and lipoprotein(a ) concentrations and on LDL peak particle diameter were examined in normocholesterolemic , premenopausal women . DESIGN Thirteen healthy , normocholesterolemic , free-living , premenopausal female volunteers took part in this r and omized , crossover-controlled trial . Each subject acted as her own control . Three soy isoflavone intakes ( control : 10.0 + /- 1.1 ; low : 64.7 + /- 9.4 ; and high : 128.7 + /- 15.7 mg/d ) , provided as soy protein isolate , were consumed for 3 menstrual cycles each . Total cholesterol , HDL cholesterol , LDL cholesterol , and triacylglycerol were measured over the menstrual cycle . Apolipoprotein A-I , apolipoprotein B , lipoprotein(a ) , and LDL peak particle diameter were evaluated in the midluteal phase . RESULTS Total cholesterol , HDL-cholesterol , and LDL-cholesterol concentrations changed significantly across menstrual cycle phases ( P < 0.005 ) . During specific phases of the cycle , the high-isoflavone diet lowered LDL cholesterol by 7.6 - 10.0 % ( P < 0.05 ) , the ratio of total cholesterol to HDL cholesterol by 10.2 % ( P < 0.005 ) , and the ratio of LDL to HDL cholesterol by 13.8 % ( P < 0.002 ) . CONCLUSIONS Isoflavones significantly improved the lipid profile across the menstrual cycle in normocholesterolemic , premenopausal women . Although of small magnitude , these effects could contribute to a lower risk of developing coronary heart disease in healthy people who consume soy over many years Soya foods may protect against the development of breast cancer . Insulin-like growth factor (IGF)-1 is under investigation as a possible link between nutrition and cancer . We examined the effect of soya foods on circulating IGF-1 and IGF binding protein (BP)-3 levels among 196 healthy premenopausal women in a 2-year r and omised nutritional trial . The intervention group consumed two daily servings of soya foods including tofu , soya milk , soya nuts and soya protein powder ( equivalent to 50 mg isoflavones and 5 - 22 g soya protein per serving ) ; the controls maintained their regular diet . Five serum sample s at baseline , 3 , 6 , 12 , and 24 months were collected in the morning during the luteal phase and analysed for IGF-1 and IGFBP-3 by double-antibody ELISA . We applied mixed models to investigate the intervention effect and predictors of serum levels while considering the repeated measurement design . Adherence with the study regimen was high and dropout rates were acceptable . R and omisation result ed in similar mean IGF-1 and IGFBP-3 levels by group . We did not observe a significant intervention effect on IGF-1 , IGFBP-3 , and their molar ratio during the entire study period . However , urinary isoflavone excretion during the study period was positively associated with IGF-1 ( P=0.04 ) and the IGF-1:IGFBP-3 ratio ( P=0.06 ) . The effect was consistent over time . Adding soya foods to the diet of premenopausal women does not appear to lower serum levels of IGF-1 and IGFBP-3 ; if anything , the greater protein intake from soya may lead to a small increase in IGF-1 serum levels Plants contain compounds with oestrogen -- like action called phytoestrogens . Soy contains daidzin , a potent phytoestrogen , and wheat flour contains less potent enterolactones . We aim ed to show in 58 postmenopausal women ( age 54 , range 30 - 70 years ) with at least 14 hot flushes per week , that their daily diet supplemented with soy flour ( n = 28 ) could reduce flushes compared with wheat flour ( n = 30 ) over 12 weeks when r and omised and double blind . Hot flushes significantly decreased in the soy and wheat flour groups ( 40 % and 25 % reduction , respectively < 0.001 for both ) with a significant rapid response in the soy flour group in 6 weeks ( P < 0.001 ) that continued . Menopausal symptom score decreased significantly in both groups ( P < 0.05 ) . Urinary daidzein excretion confirmed compliance . Vaginal cell maturation , plasma lipids and urinary calcium remained unchanged . Serum FSH decreased and urinary hydroxyproline increased in the wheat flour group OBJECTIVE Several epidemiologic studies have described protective effects of soy consumption against breast cancer . The goal of this trial among premenopausal women was to examine the effect of soy foods on menstrual cycle length and circulating sex hormone levels . METHODS This 2-year dietary intervention r and omized 220 healthy premenopausal women . The intervention group consumed two daily servings of soy foods containing approximately 50 mg of isoflavones ; the control group maintained their regular diet . Five blood sample s ( obtained in months 0 , 3 , 6 , 12 , and 24 ) were taken 5 days after ovulation as determined by an ovulation kit . The serum sample s were analyzed for estrone , estradiol , sex hormone binding globulin , and rostenedione , and progesterone by immunoassay . RESULTS At baseline , both groups had similar demographic , anthropometric , and nutritional characteristics . The dropout rates of 15.6 % ( 17 of 109 ) in the intervention group and 12.6 % ( 14 of 111 ) in the control group did not differ significantly . According to soy intake logs , 24-hour recalls , and urinary isoflavone excretion , the women closely adhered to the study regimen . Menstrual cycles became slightly shorter in both groups but did not differ by group . Mixed general linear models indicated no significant intervention effect on any of the serum hormones . However , and rostenedione and progesterone decreased significantly over time in both groups . CONCLUSIONS The results of this study suggest that the preventive effects of soy on breast cancer risk in premenopausal women may not be mediated by circulating sex hormone levels . Different mechanisms of actions or effects of exposure earlier in life are alternate hypotheses that require further investigation OBJECTIVES It has been suggested that isoflavones protect the cardiovascular system , in part by improving lipid profile . The purpose of the present research was to examine the effect of a 12-week soy isoflavone supplementation on lipoprotein status and platelet thromboxane A2 receptor density . METHODS Twenty-nine healthy postmenopausal women were invited to take part in a r and omised study to receive either 100 mg/day isoflavone supplement ( n=15 ) or identical placebo capsules ( n=14 ) . Blood sample s obtained at baseline and after 12 weeks were analysed for isoflavones , total cholesterol , high density lipoprotein cholesterol , triglycerides , glucose , insulin , estradiol , testosterone , gonadotrophins , sex hormone-binding globulin ( SHBG ) and platelet thromboxane A2 receptor density . Blood pressure measurements , body mass index , subcutaneous fat at entrance and at the end of treatment were also registered . Changes in variables between groups were compared by ANOVA for repeated measures . RESULTS Blood pressure , body mass index , subcutaneous fat , insulin , serum lipoprotein , sex hormones and SHBG did not differ among groups . However , platelet thromboxane A2 receptor density declined significantly ( from 181.9+/-30.9 to 115.2+/-16.2 fmol/10(8 ) platelets ) in the experimental group , remaining mostly unchanged in the placebo group ( 176.3+/-27.3 to 170.4+/-28.2 fmol/10(8 ) platelets ) . The dissociation constant ( Kd ) values were unchanged . The change in platelet thromboxane A2 receptors correlated negatively with isoflavones serum concentration ( r=-0.59 , p<0.001 ) . CONCLUSIONS In this study we demonstrated that the beneficial effects of isoflavones in menopausal women could be more related to platelet function than to improving classical cardiovascular risk factors Objective : The phytoestrogen genistein has been shown to be the most efficacious in clinical and experimental studies . We studied whether genistein treatment affects some cardiovascular risk markers in postmenopausal women . Design : Sixty healthy postmenopausal women , who were 52 to 60 years of age , were enrolled in a 6-month double-blind , placebo-controlled , r and omized study . After a 4-week stabilization on a st and ard fat-reduced diet , participants were r and omly assigned to receive either genistein ( n = 30 ; 54 mg/d ) or placebo ( n = 30 ) . At baseline and after a 6-month treatment , we measured fasting glucose , insulin , insulin resistance ( HOMA-IR ) , osteoprotegerin ( OPG ) , fibrinogen , and sex hormone-binding globulin ( SHBG ) . Results : By comparison with placebo , genistein treatment decreased significantly fasting glucose ( genistein = −8.7 ± 2.3 % ; placebo = 3.2 ± 2.3 % ; P < 0.001 ) , fasting insulin ( genistein = −12 ± 3.33 % ; placebo = 36 ± 3.29 % ; P < 0.001 ) , and HOMA-IR ( genistein = −14 ± 5.8 % ; placebo = 42 ± 0.6 % ; P < 0.001 ) . After genistein-treatment , fibrinogen decreased ( genistein = 3.18 ± 0.12 g/L ; placebo = 3.83 ± 0.04 g/L ; P < 0.001 ) with respect to placebo . In the genistein group , serum OPG was lower ( −2 ± 0.3 % ) than in placebo ( 9 ± 1.5 % ; P < 0.001 ) , and serum SHBG was higher ( 63 ± 3.8 nmol/L ) compared with placebo ( 53 ± 2.9 nmol/L ; P < 0.05 ) . Conclusion : Our study suggests that genistein may have a favorable effect on some cardiovascular markers Soy isoflavones are hypothesized to be responsible for changes in hormone action associated with reduced breast cancer risk . To test this hypothesis , we studied the effects of isoflavone consumption in 14 premenopausal women . Isoflavones were consumed in soy protein powders and provided relative to body weight ( control diet , 10 + /- 1.1 ; low isoflavone diet , 64 + /- 9.2 ; high isoflavone diet , 128 + /- 16 mg/day ) for three menstrual cycles plus 9 days in a r and omized cross-over design . During the last 6 weeks of each diet period , plasma was collected every other day for analysis of estrogens , progesterone , LH , and FSH . Diet effects were assessed during each of four distinctly defined menstrual cycle phases . Plasma from the early follicular phase was analyzed for and rogens , cortisol , thyroid hormones , insulin , PRL , and sex hormone-binding globulin . The low isoflavone diet decreased LH ( P = 0.009 ) and FSH ( P = 0.04 ) levels during the periovulatory phase . The high isoflavone diet decreased free T3 ( P = 0.02 ) and dehydroepi and rosterone sulfate ( P = 0.02 ) levels during the early follicular phase and estrone levels during the midfollicular phase ( P = 0.02 ) . No other significant changes were observed in hormone concentrations or in the length of the menstrual cycle , follicular phase , or luteal phase . Endometrial biopsies performed in the luteal phase of cycle 3 of each diet period revealed no effect of isoflavone consumption on histological dating . These data suggest that effects on plasma hormones and the menstrual cycle are not likely to be the primary mechanisms by which isoflavones may prevent cancer in premenopausal women The phytoestrogen genistein improves endothelial dysfunction in ovariectomized rats through a nitric oxide-dependent mechanism . We investigated whether genistein alters the balance between the nitric oxide products and endothelin-1 and influences endothelium-dependent vasodilation in postmenopausal women . Sixty healthy postmenopausal women were enrolled in the study . A double-blind , placebo controlled , r and omized design was employed . After a 4-week stabilization on a st and ard fat-reduced diet , participants to the study were r and omly assigned to receive either genistein ( n=30 ; 54 mg/day ) or placebo ( n=30 ) . Flow-mediated , endothelium-dependent vasodilation of the brachial artery , plasma nitric oxide breakdown products and endothelin-1 levels were measured at baseline and after 6 months of genistein therapy . The mean baseline level of nitrites/nitrates was 22+/-10 micromol/l and increased to 41+/-10 micromol/ml after 6 months of treatment . The mean baseline plasma endothelin-1 level was 14+/-4 pg/ml and decreased to 7+/-1 pg/ml following 6 months of treatment with genistein . The mean baseline ratio of nitric oxide to endothelin also significantly increased at the end of treatment . Flow-mediated , endothelium-dependent vasodilation of the brachial artery was 3.9+/-0.8 mm at baseline and increased to 4.4+/-0.7 mm after 6 months of treatment . Placebo-treated women showed no changes in plasma nitrites/nitrates , endothelin-1 levels and flow-mediated vasodilation . Genistein therapy improves flow-mediated endothelium dependent vasodilation in healthy postmenopausal women . This improvement may be mediated by a direct effect of genistein on the vascular function and could be the result of an increased ratio of nitric oxide to endothelin Objective —The objective of this study was to assess the independent effect of soy relative to common sources of animal protein and soy-derived isoflavones on blood lipids . Methods and Results —Forty-two subjects with LDL cholesterol levels ≥3.36 mmol/L were fed each of four diets in r and omized order for 6 weeks per phase . Diets contained a minimum of 25 g animal protein or isolated soy protein/4.2 MJ , with each containing trace amounts or 50 mg of isoflavones/4.2 MJ . Soy protein had a modest effect on total , LDL and HDL cholesterol , and triglyceride concentrations ( −2 % , P = 0.017 ; −2 % , P = 0.042 ; + 3%;P = 0.034 , −11 % , P < 0.001 , respectively ) . Soy protein had no significant effect on plasma lipids in individuals with LDL cholesterol < 4.14 mmol/L and significantly reduced total and LDL cholesterol and triglyceride concentrations in individuals with LDL cholesterol ≥4.14 mmol/L ( −4 % , P = 0.001 ; −5 % , P = 0.003 ; −15 % , P < 0.001 , respectively ) . No significant effect of isoflavones on plasma lipid levels was observed either constituent to the soy protein or supplemental to the animal protein . Conclusions —Although potentially helpful when used to displace products containing animal fat from the diet , the regular intake of relatively high levels of soy protein ( > 50 g/day ) had only a modest effect on blood cholesterol levels and only in subjects with elevated LDL cholesterol levels ( ≥4.14 mmol/L ) . Soy-derived isoflavones had no significant effect Abstract : Consumption of soy protein has been associated with altered risk of developing endocrine-regulated cancers . This study was design ed to assess the independent effect of soy relative to animal protein and soy-derived isoflavones on circulating estrogen and and rogen concentrations in postmenopausal women and older men . Forty-two subjects ( > 50 yr ) with low-density lipoprotein cholesterol levels of ≥3.36 mmol/l were fed each of 4 diets in r and omized order for 6 wk/phase . All food and drink were provided . Diets contained 25 g soy or common sources of animal protein/4.2 MJ containing trace or 50 mg isoflavones/4.2 MJ . At the end of each diet phase , concentrations of estrone sulfate , estrone , estradiol , testosterone , and rostendione , dihydrotestosterone , dehydroepi and rosterone , and dehydroepi and rosterone sulfate were measured . In postmenopausal women , concentrations of estrone were higher and its precursor , dehydroepi and rosterone , lower after consuming the soy compared with animal protein diets ( P = 0.0396 and 0.0374 , respectively ) . There was no significant effect of isoflavones on any of the hormones measured . In older men , dehydroepi and rosterone sulfate concentrations were lower after consuming the isoflavone ( P = 0.0106 ) and higher after soy , compared with the animal protein diets ( P = 0.0118 ) . These data suggest that relatively large amounts of soy protein or soy-derived isoflavones had modest and limited sex-specific effects on circulating hormone levels To examine the hormonal effects of isoflavones , of which soyabean is a rich source , fifteen healthy nonvegetarian premenopausal women were studied over 9 months . They lived in a metabolic suite for between 4 and 6 months where their diet and activity levels were kept constant and their hormonal status was measured over two or three menstrual cycles . During one ( control ) menstrual cycle a normal but constant diet containing no soyabean products was fed . Then , over a second complete cycle six subjects consumed a similar diet into which 60 g textured vegetable protein (TVP)/d , containing 45 mg conjugated isoflavones , had been incorporated . Three participants had 50 g miso ( a fermented soyabean paste ) , containing 25 mg unconjugated isoflavones , added daily to their diet over a menstrual cycle , and six others consumed 28 g TVP/d , containing 23 mg conjugated isoflavones . Five participants completed a third diet period where they were r and omly assigned to consume either the control diet over a cycle , or a similar diet incorporating 60 g of a soyabean product which had had the isoflavones chemically extracted ( Arcon F ) . Follicular phase length was significantly ( P < 0.01 ) increased and peak progesterone concentrations were delayed with 60 g TVP but no effects were observed with Arcon F. The increase in menstrual cycle length did not reach statistical significance in the three three subject who ate 50 g miso/d , but peak progesterone levels were significantly ( P < 0.05 ) delayed . Mid-cycle peaks of luteinizing hormone ( LH ) and follicle stimulating hormone ( FSH ) were suppressed with 45 mg conjugated isoflavones as 60 g TVP ( P < 0.05 and P < 0.01 respectively ) . No other changes in sex-steroid hormone levels were observed on any of the other diets . A significant reduction in total cholesterol was found with 45 mg conjugated isoflavones ( P < 0.05 ) , but not with 23 mg conjugated isoflavone-free Arcon F. There was no effect of menstrual cycle phase on transit time Soy isoflavones are hypothesized to exert hormonal effects in women and thus may play a role in bone metabolism throughout life . In 2 r and omized , cross-over studies , 14 pre- and 17 postmenopausal women were given 3 soy protein isolates containing different amounts of isoflavones [ control , 0.13 ; low isoflavone ( low-iso ) , 1.00 ; and high-iso , 2.01 mg/kg body wt/day , averaging 8 , 65 , and 130 mg/day , respectively ] , for over 3 months each . Food records , blood sample s , and 24-h urine collection s were obtained throughout the studies . The endpoints evaluated included plasma or serum concentrations of bone-specific alkaline phosphatase , osteocalcin , insulin-like growth factor-I ( IGFI ) , IGF binding protein-3 ( IGFBP3 ) , and urine concentrations of deoxypyridinoline cross-links and carboxy-terminal telopeptide of type I collagen . In premenopausal women , IGFI and IGFBP3 concentrations were increased by the low-iso diet , and deoxypyridinoline cross-links was increased by both the low- and high-iso diets during certain phases of the menstrual cycle . In postmenopausal women , bone-specific alkaline phosphatase was decreased by both the low- and high-iso diets , and there were trends toward decreased osteocalcin , IGFI , and IGFBP3 concentrations with increasing isoflavone consumption . Although soy isoflavones do affect markers of bone turnover , the changes observed were of small magnitude and not likely to be clinical ly relevant . These data do not support the hypothesis that dietary isoflavones per se exert beneficial effects on bone turnover in women Background / Objective : To investigate the effect of soy protein containing isoflavones on homocysteine ( Hcy ) , C-reactive protein ( CRP ) , soluble E-selectin ( sE-selectin ) , soluble vascular adhesion molecule-1 ( sVCAM-1 ) and soluble intercellular adhesion molecule-1 (sICAM-1).Subject/ Methods : In a r and omized crossover design , 34 postmenopausal women consumed soy protein isolate ( 26±5 g protein containing 44±8 mg isoflavones per day ) or milk protein isolate ( 26±5 g protein per day ) for 6 weeks each . Fasting blood sample s were collected at the end of each diet period and end points analyzed by enzyme-linked immunosorbent assay . Results : Concentrations of Hcy , CRP , sE-selectin , sVCAM-1 and sICAM-1 were not different between soy and milk diet treatments . Results did not differ by equol production status or by baseline lipid concentration . Adjustment for intake of folate and methionine did not alter the Hcy results . Conclusions : These data suggest that decreasing vascular inflammation and Hcy concentration are not likely mechanisms by which soy consumption reduces coronary heart disease risk OBJECTIVE To examine the change in menopausal symptoms and cardiovascular risk factors in response to 4 months of daily 100‐mg soy isoflavone in postmenopausal women . METHODS In this double‐blind , placebo‐controlled study , 80 women were r and omly assigned to isoflavone ( n = 40 ) and placebo ( n = 40 ) treatment . The menopausal Kupperman index was used to assess change in menopausal symptoms at baseline and after 4 months of treatment . Cardiovascular risk factors were assessed by evaluating plasma lipid levels , body mass index , blood pressure , and glucose levels in the participants . To examine the effects of this regime on endogenous hormone levels , follicle‐stimulating hormone ( FSH ) , luteinizing hormone ( LH ) , and 17β‐estradiol were measured . Transvaginal sonography was performed to quantify endometrial thickness . RESULTS The data showed a decrease in menopausal symptoms ( P < .01 , paired t test , two‐tailed , between baseline and isoflavone groups , and P < .01 , unpaired t test , between placebo and isoflavone groups ) . Total cholesterol and low‐density lipoprotein decreased significantly in the isoflavone group compared with the baseline or placebo group ( P < .001 , paired t test , two‐tailed , between baseline and isoflavone groups , and P < .01 , unpaired t test , between placebo and isoflavone groups ) . The isoflavone treatment appeared to have no effect on blood pressure , plasma glucose , and high‐density lipoprotein and triglyceride levels . CONCLUSION This study suggests that isoflavone 100‐mg regime treatment may be a safe and effective alternative therapy for menopausal symptoms and may offer a benefit to the cardiovascular system Objective : To compare the effects of daily ingestion of soy flour ( S ) , ground flaxseed ( F ) , or wheat flour ( W ) muffins , on quality of life and hot flash frequency and severity in postmenopausal women . Design : This was a double-blind , r and omized , controlled , intention-to-treat trial . Ninety-nine women , 1 to 8 years after menopause , ingested muffins with 25 g of flaxseed ( 50 mg of lignans ) , 25 g of soy ( 42 mg of isoflavones ) , or wheat ( control ) daily for 16 weeks . Subjects completed the Menopause-specific Quality of Life instrument monthly along with daily hot flash frequency and severity diaries . Compliance measures included a 3-day food diary and urinary isoflavone and lignan analyses at weeks 0 and 16 and returned muffin counts monthly . Results : Eighty-seven women ( 28 , ground flaxseed muffins ; 31 , soy flour muffins ; and 28 , wheat flour muffins ) completed the trial . Multivariate analysis of variance of all quality -of-life domains yielded an insignificant treatment × time interaction ( F46,122 = 0.92 , P = 0.62 ) but a significant time main effect ( P < .0001 ) . Repeated- measures analyses of covariance controlling for body mass index showed no significant group × time interaction nor time nor group differences on all quality -of-life domains and hot flash measures except severity . Hot flashes were less severe with flaxseed ( P = 0.001 ) compared to placebo ; however , the group × by time interaction was not significant . Phytoestrogen excretion analysis showed treatment group exposure as allocated and no contamination . Conclusion : Neither dietary flaxseed nor soy flour significantly affected menopause-specific quality of life or hot flash symptoms in this study To address the cardiovascular effects of dietary soy containing phytoestrogens , we measured blood pressure ( BP ) , lipids , vascular function ( systemic arterial compliance and pulse wave velocity ) , and endothelial function ( flow-mediated vasodilation ) in a r and omized , double-blind trial . Two hundred thirteen healthy subjects ( 108 men and 105 postmenopausal women ) , 50 - 75 yr old , received either soy protein isolate ( 40 g soy protein , 118 mg isoflavones ) or casein placebo for 3 months . There were 34 withdrawals ( 16 % ) , with 179 subjects ( 96 men and 83 women ) completing the protocol . After intervention in the soy group , compared with casein placebo , urinary phytoestrogens increased , accompanied by a significant fall in BP reflected by the BP model ( P < 0.01 ) encompassing mean change ( + /-SEM ) in systolic ( -7.5 + /- 1.2 vs. -3.6 + /- 1.1 mm Hg , P < 0.05 ) , diastolic ( -4.3 + /- 0.8 vs. -1.9 + /- 0.7 mm Hg , P < 0.05 ) , and mean BP ( -5.5 + /- 1 vs. -0.9 + /- 1 mm Hg , P < 0.008 ) . In the lipid model , soy induced greater changes , compared with placebo ( P < 0.001 ) . On individual analysis , significant contributors included a reduction in the low- to high-density lipoprotein ratio ( -0.33 + /- 0.1 vs. 0.04 + /- 0.1 mmol/L , P < 0.05 ) and triglycerides ( -0.2 + /- 0.05 vs. -0.01 + /- 0.05 mol/L , P < 0.05 ) and an increase in Lp(a ) lipoprotein ( + /- 95 % confidence interval ) [ 42 ( range , 17 - 67 ) vs. 4 ( range , -22 - 31 ) mg/L , P < 0.05 ] , whereas total , low-density lipoprotein , and high-density lipoprotein cholesterol improved in both groups ; but no treatment effect was demonstrated . The arterial functional model demonstrated no difference between groups ; although again , overall function improved in both groups . On individual analysis , peripheral PWV ( reflecting peripheral vascular resistance ) improved with soy ( P < 0.01 ) , whereas flow-mediated vasodilation ( reflecting endothelial function ) declined ( in males only ) , compared with casein placebo ( P < 0.02 ) . No effect of treatment on the hypothalamic-pituitary-gonadal axis was noted in males or females . In normotensive men and postmenopausal women , soy improved BP and lipids but , overall , did not improve vascular function . Potential adverse effects were noted , with a decline in endothelial function ( in males only ) and an increase in Lp(a ) . Further research in hypertensive and hyperlipidemic population s is needed Objective : The onset of climacteric symptoms ( hot flashes and night sweats ) is the primary reason for perimenopausal women to start hormone therapy . The association of a lower incidence of postmenopausal symptoms with high intake of soybeans in Asian women suggests that phytoestrogens are an alternative to estrogen therapy . The main effective compounds in soybean are isoflavones , which have a higher binding affinity to estrogen receptor & bgr ; than to estrogen receptor & agr;. The aim of present study was to evaluate the effects of isoflavone treatment in postmenopausal women . Design : This was a double-blind prospect i ve study . Sixty healthy postmenopausal women were r and omly assigned by computer into two groups to receive 60 mg isoflavones or placebo daily for 3 months . Before and after treatment , climacteric symptoms were recorded ; serum was collected to measure the levels of lipoprotein lipids , estradiol , and follicle-stimulating hormone ; and biopsy specimens from endometrium and breast were analyzed to investigate the expression level of steroid receptors and proliferation . Endometrial thickness was measured by ultrasound . Results : Fifty-one women finished the 12-week study . In women receiving 60 mg isoflavones daily , hot flashes and night sweats were reduced by 57 % and 43 % , respectively . The treatment did not change the levels of circulating estradiol or follicle-stimulating hormone . Immunohistochemical staining of endometrial and breast biopsy specimens revealed that isoflavones did not affect expression levels of steroid receptors ; estrogen receptors & agr ; , & bgr ; , and & bgr;cx ; progesterone receptors A and B ; or the proliferation marker Ki67 . No side effects on body weight or lipoprotein lipids were observed . Conclusions : This short-term prospect i ve study implies that isoflavones could be used to relieve acute menopausal symptoms Fifty four postmenopausal women with elevated cholesterol were recruited for a r and omised , double-blind controlled trial of soy protein containing isoflavones . ( ISP+ ) or a soy protein with a low isoflavone content ( ISP- ) , taken daily for 12 weeks . There was an overall reduction after 12 weeks in total cholesterol ( TC ) , LDL cholesterol ( LDL-C ) , sex hormone binding globulin ( SHBG ) , and luteinizing hormone ( LH ) . There were no significant differences between treatment groups . In a separate study 27 male subjects with a TC > 5.5 mmol/l were given ISP+ for 12 weeks . In this male study there was a significant increase in HDL cholesterol ( HDL-C ) and SHBG . Soy protein has a cholesterol lowering effect in both women and men . These studies suggest that this effect is independent of isoflavones . Soy protein also reduces SHBG levels in both sexes The estrogenic and antiestrogenic effects of isoflavones , phytoestrogens contained in soy foods , have been proposed as mechanisms for the possible involvement of soy products in the development of breast cancer . We investigated the hypothesis that isoflavones reduce mammographic density , a predictor of breast cancer risk . We conducted a double-blind r and omized trial in premenopausal women who received a daily 100 mg isoflavone supplement or a placebo over 12 months . Compliance with the study regimen was confirmed by urinary isoflavones and tablet counts . We used a computer-assisted method to measure mammographic density and paired t-tests to assess changes in mammographic characteristics from baseline to follow-up mammogram . Complete sets of mammograms were available for 30 women . The two groups differed by age and mammographic density at baseline , but were similar in body weight and nutritional intakes . We detected no significant changes either in the size of the dense areas or in the per cent densities . A non-significant decrease in breast area among intervention group subjects was probably the result of method ological issues in comparing mammograms taken under different conditions . In conclusion , our findings do not support the hypothesis that isoflavones decrease mammographic density during a one-year intervention . Although this exploratory study had limited power , it appears that isoflavones do not exert an estrogenic effect similar to hormone replacement therapy on mammographic density OBJECTIVE To evaluate the effects of isoflavones on vasomotor symptoms and blood lipids in postmenopausal women with contraindication for conventional hormone replacement therapy ( HRT ) . METHODS This prospect i ve , double-blind and placebo-controlled study included 50 postmenopausal women r and omly divided into two groups : 25 women on soy germ isoflavones ( 60 mg per day , capsules ) and 25 women on placebo . Inclusion criteria included : non-vegetarian , non-asian women whose last menstruation date d at least 12 months prior to the beginning of the study , with FSH > 40 mIU/ml , hot flushes and contraindication for HRT , not using tamoxifen or antibiotic and no disease of the gastrointestinal tract . For 6 months , the Kupperman menopausal index ( KMI ) , the vaginal cytological maturation value ( MV ) and both hormonal and lipid profiles were assessed . The t-test and analysis of variance ( ANOVA ) were employed to compare the two groups . RESULTS In both groups , a decreased KI rate was observed . However , isoflavone was significantly superior to placebo in reducing hot flushes ( 44 % versus 10 % , respectively ) ( P < 0.05 ) . After 6 months , the isoflavone group showed increased estradiol levels with unchanged FSH , LH , and vaginal cytology , and a reduction of 11.8 % in LDL and an increase of 27.3 % in HDL ( P < 0.05 ) . In the placebo group , just a reduction in MV was observed after 6 months ( P < 0.05 ) . CONCLUSIONS Soy germ isoflavone exerted favorable effects on vasomotor symptoms and lipid profile , showing itself to be an interesting alternative therapy for the postmenopausal women with contraindication for conventional HRT Objective Menopause-induced estrogen deficiency increases the risk of cardiovascular disease , which is related to a shift in regional fat distribution . We tested the hypothesis that estrogen-like isoflavones in soy protein isolate ( SPI+ ) would lessen both regional fat gain and lean loss compared with isoflavone-poor soy ( SPI− ) . Design Perimenopausal participants ( N = 69 ) were r and omly assigned ( double-blind ) to 24 weeks of treatment ( 40 g soy or whey protein per day ) : SPI+ ( n = 24 ) , SPI− ( n = 24 ) , or whey control ( n = 21 ) ; each participant had blood drawn in the fasted ( 12 hours ) state , had physical activity assessed , and kept a 5-day food diary . Dual-energy x-ray absorptiometry was used to examine the effects of SPI+ on regional fat and lean tissue distribution changes in the waist , hip , and thigh regions . Results Mean body mass increased ( P < 0.01 ) in each group , but treatment had no effect on gain in overall body mass , fat mass , or lean mass using analysis of variance . In all treatment groups combined , lean mass increased in each region ; fat mass increased only in the waist region . Treatment had an effect ( P = 0.039 ) on hip lean mass and a marginal effect ( P = 0.077 ) on thigh fat . Regression analyses revealed that SPI+ diminished the increase in thigh fat ( P = 0.018 ) and heightened the increase in hip lean ( P = 0.035 ) mass . Carbohydrate intake ( P = 0.006 ) and cohort ( reflective of season ; P = 0.011 ) contributed to the gain in thigh fat . Total protein intake ( P = 0.0012 ) , plasma insulin ( P = 0.0034 ) , and physical activity ( P = 0.047 ) contributed to the gain in hip lean mass . Conclusions Gain in hip lean mass was greater ( P = 0.014 ) in SPI+ than other groups , but SPI+ did not reduce the disease-promoting menopausal shift in regional fat mass Objectives : To assess the acceptability of the delivery of an isoflavone supplementation in the form of a powdered drink , and whether the supplementation of dietary isoflavones in this manner decreased the incidence of menopausal flushes . The secondary aims included assessment of other symptoms or parameters of estrogen deficiency and responses to isoflavones . Methods : A r and omized , double-blind , placebo-controlled , parallel-group trial comprising 24 postmenopausal women with symptoms of estrogen deficiency was performed over a 12-week period . The women were r and omized to receive a dietary beverage containing isoflavones or an isoflavone-free , isocaloric placebo preparation . Results : Although there was a high compliance rate among individual patients , there was a 25 % withdrawal rate from the study in the active group . The incidence of complaints of bad taste tended to be higher in the active group ( p = 0.07 ) , and the total number of adverse events was significantly higher in this group ( p < 0.001 ) . There was no statistically significant difference in the incidence of flushes between the groups . There was no difference between the groups in Greene Menopause Symptom Scores , vaginal maturation value , levels of follicle stimulating hormone ( FSH ) or sex hormone-binding globulin ( SHBG ) , or bone turnover markers . Conclusions : Powdered energy drinks are not commonly consumed in Australia and were poorly tolerated in this study . The high withdrawal rate and reporting of side-effects suggests that other methods of isoflavone delivery may be more appropriate in this culture , in future trials . At the dose used no benefit was seen in relief from menopausal symptoms , although for the sample size , the study could only have been expected to detect major differences between the groups Despite the safety review conducted by the U.S. Food and Drug Administration in the process of awarding a health cl aim for the cholesterol-lowering properties of soy protein , concerns about the possible goitrogenic effects of soybean isoflavones persist . Concerns are based primarily on in vitro research , animal studies , and older reports of goiter in infants fed soy formula not fortified with iodine . In a r and omized , double blind , placebo-controlled study , we investigated the effect on thyroid function of a daily supplement containing 90 mg ( aglycone weight ) of total isoflavones/day versus placebo in 38 postmenopausal women , 64 - 83 years old , not on hormone replacement therapy . Serum thyroid-stimulating hormone ( TSH ) , thyroxine ( T4 ) , and triiodothyronine ( T3 ) were measured at baseline and after 90 and 180 days . In the supplement group , at baseline and 6 months , TSH ( micro U/ml ) , T4 ( nM ) , and T3 ( nM ) levels ( mean + /- SE ) were 3.00 + /- 0.44 , 149.00 + /- 5.04 , and 1.53 + /- 0.13 , respectively , and 3.49 + /- 0.52 , 154.52 + /- 2.09 , and 1.78 + /- 0.12 , respectively . In the control group , levels at baseline and at 6 months were 3.35 + /- 0.51 , 145.39 + /- 6.69 , and 1.55 + /- 0.18 , respectively , and 3.63 + /- 0.57 , 153.77 + /- 6.64 , and 1.75 + /- 0.10 , respectively . Intragroup differences for all three measures were statistically indistinguishable at 6 months , and levels were similar between the isoflavone supplement and placebo groups at each measurement . These results indicate that in this group of healthy iodine-replete subjects , soy isoflavones do not adversely affect thyroid function Despite evidence supporting the involvement of the IGF system in the development of breast and other cancers , the major determinants of interindividual variability in circulatory IGF-I levels are not well understood . Previous research has pointed to important genetic influences as well as dietary effects through marked calorie or protein restriction . We conducted a r and omized trial to determine the effects of 2 dietary patterns on serum IGF-1 , IGFBP1 and IGFBP3 in free-living premenopausal women : phase 1 , an isocaloric low-fat , high-fiber ( LFHF ) vs. usual diet , and phase 2 , a soy supplement either with or without isoflavones ( soy+IF vs. soy-IF ) . Participants completed 12 menstrual cycles on phase 1 and then were r and omly assigned to a soy supplement for 3 cycles while maintaining the phase 1 diet . Before and after each phase , 154 women provided serum . We found no difference in the change in IGF-I , BP1 or BP3 in the LFHF group compared to the usual diet group . In phase 2 , there were no differences in any IGF protein between the soy+IF and the soy-IF groups or any evidence of interaction between isoflavone exposure and the background diet . However , there was a small but statistically significant decrease ( 2.3 % ) in BP3 and an increase in the IGF-I : BP3 molar ratio among all 153 subjects following either soy supplement . These changes were correlated with changes in intake of calcium , total vegetable protein and soy . The results are compatible with previous data suggesting that increases in dietary calcium , protein and soy , in particular , could increase circulating levels of bioavailable Isoflavones , phytoestrogens contained in soy foods , may play a role in breast cancer prevention . This r and omized double-blinded trial with 34 premenopausal women investigated whether 100 mg of isoflavones per day versus placebo affects the ovulatory cycle during 1 year . Compliance with the study regimen was confirmed by the increase of urinary isoflavone excretion among the intervention group . Blood sample s were taken 5 days after ovulation as determined by an ovulation kit , at baseline , and at months 1 , 3 , 6 , and 12 . Serum levels of estrone , estradiol , estrone sulfate , progesterone , sex hormone-binding globulin , follicle-stimulating hormone , and luteinizing hormone were quantified by immunoassay ; free estradiol was calculated . We applied the method of least squares to fit general linear models to test for an intervention effect while taking into account the repeated measurement design . Except for a small difference in age , the two groups were comparable at baseline . Menstrual cycle length did not change significantly during the intervention [ F(1,32 ) = 0.69 ; P = 0.44 ] . During 1 year , we did not observe any significant changes in hormone levels by treatment group . The difference in change between intervention and control group was -13.0 pg/ml ( 95 % confidence interval , -57.5 to 31.5 ) for estradiol and 6.9 pg/ml ( 95 % confidence interval , -17.8 to 31.5 ) for estrone . Exclusion of 22 non-ovulatory cycles , noncompliant women , or non-Asian women did not affect the results . These findings do not support the hypothesis that isoflavones affect the ovulatory cycles of premenopausal women over a 1-year period . However , isoflavones alone may have different effects on the reproductive cycle than isoflavones present in soy foods The low cardiovascular risk in Asian women has been thought to result from high isoflavonoid intake . In a double-blind , r and omized , placebo-controlled trial , we studied the effects of isolated isoflavonoids ( 114 mg/d ) on lipids , lipoproteins , insulin sensitivity , and ghrelin in 56 nondiabetic postmenopausal women with a history of breast cancer . Isoflavonoid or placebo tablets were given for 3 months , and the treatment regimens crossed over after a 2-month washout period . The concentrations of total cholesterol , high- and low-density lipoprotein cholesterol , triglycerides , apolipoproteins B and A1 , and lipoprotein ( a ) were not affected by isoflavonoids . However , during the isoflavonoid regimen , women with low-density lipoprotein cholesterol level above the median ( 4.20 mmol/liter ) showed a rise [ 0.65 + /- 0.60 ( sd ) mmol/liter ] , which was statistically different from the fall during the placebo regimen ( -0.45 + /- 0.67 mmol/liter , P = 0.009 ) . Isoflavonoids did not affect insulin sensitivity as assessed by an oral 2-h glucose tolerance test ( 75 g ) . Changes in ghrelin levels differed ( P = 0.048 ) during the isoflavonoid ( -7.1 + /- 151 micromol/liter ) and placebo regimens ( + 47.9 + /- 198 micromol/liter ) . In conclusion , we found no effects of isolated isoflavonoids on lipids , lipoproteins , or insulin sensitivity in postmenopausal women , implying no vascular benefit . Isoflavonoids may reduce ghrelin levels and thus hunger and weight OBJECTIVE To determine the effects of soy-derived isoflavones on vaginal epithelium and the endometrium . DESIGN Double-blind , r and omized , placebo-controlled crossover trial . SETTING Outpatient clinic of a university hospital . PATIENT(S ) Sixty-four postmenopausal women with a history of breast cancer . INTERVENTION(S ) The women took ( in a r and omized order ) 114 mg of isolated isoflavonoids or placebo in tablets daily for 3 months ; the treatment regimens were crossed over after a 2-month washout period . The subjects were studied before and on the last day of each treatment period . MAIN OUTCOME MEASURE(S ) Vaginal dryness , maturation index ( MI ) of vaginal epithelium , endometrial thickness , histology , and expression of estrogen ( E ) and progesterone ( P ) receptors and the proliferation marker Ki-67 in the endometrium . RESULT ( S ) Isolated isoflavones did not relieve vaginal dryness . Maturation index values remained unchanged during the isoflavone regimen , but decreased during the placebo regimen . No changes were found in any of the variables measured in the endometrium . CONCLUSION ( S ) Daily administration of 114 mg of isolated isoflavones for 3 months had no effect on the subjective perception of vaginal dryness or on objective findings in the vagina or endometrium . This implies safety with regard to the endometrium PURPOSE Genistein , a phytoestrogen found in soybeans , corrects endothelial dysfunction induced by oophorectomy in animals . Using a double-blind , controlled , r and omized design , we evaluated its effects on endothelial function in women . METHODS We enrolled 79 healthy postmenopausal women ( mean [ + /- SD ] age , 56 + /- 4 years ) and r and omly assigned them to receive continuous estrogen/progestin therapy ( n = 26 ; 17beta-estradiol [ 1 mg/d ] combined with norethisterone acetate [ 0.5 mg/d ] ) , genistein ( n = 27 ; 54 mg/d ) , or placebo ( n = 26 ) . Brachial artery flow-mediated , endothelium-dependent vasodilation and plasma levels of nitrites/nitrates ( a marker of nitric oxide metabolism ) and endothelin-1 were measured at baseline and after 1 year of therapy . RESULTS Treatment with genistein increased levels of nitrites/nitrates ( mean increase , 21 micromol/L ; 95 % confidence interval [ CI ] : 15 to 26 micromol/L ; P < 0.001 vs. placebo ) ; estrogen/progestin therapy caused similar changes ( P < 0.001 vs. placebo ) . Plasma endothelin-1 levels decreased following 12 months of genistein ( mean decrease , 7 pg/mL ; 95 % CI : 3 to 10 pg/mL ; P < 0.001 vs. placebo ) and after 12 months of estrogen/progestin ( P < 0.001 vs. placebo ) . When compared with placebo , brachial artery flow-mediated dilation was improved by genistein ( mean increase , 5.5 % ; 95 % CI : 3.9 % to 7.0 % ; P < 0.001 ) and by estrogen/progestin ( P < 0.001 ) . There were no significant differences between estrogen and genistein for any of these parameters ( all P > 0.4 ) . CONCLUSION One year of genistein therapy improves endothelium function in postmenopausal women to a similar extent as does an estrogen/progestin regimen UNLABELLED The combined intervention of isoflavone intake and walking exercise over 1 year in postmenopausal Japanese women exhibited a trend for a greater effect on prevention of bone loss at the total hip and Ward 's triangle regions . INTRODUCTION The additive effects of isoflavones and exercise on bone and lipid metabolism have been shown in estrogen-deficient animals . In this study , we determined the effects of isoflavone intake , walking exercise , and their interaction on bone , fat mass , and lipid metabolism over 1 year in postmenopausal Japanese women . MATERIAL S AND METHODS A total of 136 postmenopausal women at < 5 years after the onset of menopause were r and omly assigned to four groups : ( 1 ) placebo , ( 2 ) walking ( 45 minutes/day , 3 days/week ) with placebo , ( 3 ) isoflavone intake ( 75 mg of isoflavone conjugates/day ) , and ( 4 ) combination of isoflavone plus walking . BMD , fat mass , serum lipid , and serum and urinary isoflavone concentrations were assessed . RESULTS A significant main effect of isoflavone on the reduction in trunk fat mass was obtained at 12 months . Significant main effects of walking on the reduction in fat mass in the whole body and the trunk were observed at 3 , 6 , and 12 months and that in the legs and arms at 6 and 12 months . Serum high-density lipoprotein (HDL)-cholesterol concentration significantly increased by 12 months after the walking and the combined intervention . After 12 months , a significant main effect of isoflavone on BMD was observed only at Ward 's triangle . Walking prevented bone loss at the total hip and the Ward 's triangle to significant degrees . The effect of the combined intervention on BMD at total hip and Ward 's triangle regions was greater than that of either alone . No significant interaction was observed between isoflavone and walking in any measurements recorded during the study . CONCLUSIONS Our study suggest that combined intervention of 75 mg/day of isoflavone intake and walking exercise 3 times/week for 1 year showed a trend for a greater effect on BMD at total hip and Ward 's triangle regions than either alone . Intervention with isoflavone in postmenopausal Japanese women showed a modest effect on BMD compared with those in Westerners . Further studies over longer treatment duration that include assessment of BMD at various regions are necessary to ascertain the clinical significance of the combined intervention of isoflavone plus walking in postmenopausal women Postmenopausal women are at an increased risk of developing coronary artery disease ( CAD ) . This increase is due primarily to elevated cholesterol concentrations accompanying the loss of endogenous estrogen secretion . Recently , the consumption of soy foods has been shown to reduce serum cholesterol concentrations . Phytoestrogens ( PE ) have been proposed as the responsible agents of the hypocholesterolemic effect of soy foods . However , few studies have investigated the effect of PE supplementation on serum lipoproteins . The purpose of the present study is to investigate the effects of PE supplementation ( 150 mg ) on serum lipids and lipoproteins in moderately hypercholesterolemic , elderly , postmenopausal women . Thirty-six subjects were r and omized into two groups and received either a 150-mg PE supplement/d ( n = 20 ) or a placebo ( n = 16 ) . Serum sample s obtained at baseline and 2 months were analyzed for total triacylglycerol , total cholesterol , and high density lipoprotein cholesterol using st and ard Lipid Research Clinic procedures . In addition , total triacylglycerol and cholesterol were measured after 6 months of treatment . The t test and ANOVA were employed to compare the two groups . The results ( mean + /- SEM ) indicated no significant differences in total triacylglycerol ( 1.3 + /- 0.2 vs. 1.2 + /- 0.2 mmol/liter ) , total cholesterol ( 6.4 + /- 0.4 vs. 6.5 + /- 0.2 mmol/liter ) , or high density lipoprotein cholesterol ( 1.0 + /- 0.1 vs. 1.0 + /- 0.1 mmol/liter ) between the placebo and the PE groups , respectively , after 2 months of treatment . Moreover , total triacylglycerol and cholesterol remained unchanged after 6 months . Our findings suggest that PE supplementation with 150 mg/d over a 6-month period does not significantly alter serum lipoproteins in postmenopausal women and , therefore , may not effectively reduce the risk of CAD in this population Summary . Background : High intake of soy products has been suggested to prevent breast cancer , osteoporosis , and cardiovascular diseases . Aim of the study : To investigate the effects of isoflavone-containing soy on circulating sex hormones , biomarkers of bone turnover , and lipoprotein profiles . Methods : Fourteen young women received in a r and omized crossover design 5 soy cookies ( 52 mg isoflavones ) or 5 soy-free cookies ( no isoflavones ) per day for one menstrual cycle starting one week before menstruation . Serum and urine analyses were performed on day 3 after onset of menstruation ( t1 ) , 3 days before ovulation ( t2 ) , 3 days after ovulation ( t3 ) , during the midluteal phase ( t4 ) , and again 3 days after onset of the next menstruation ( t5 ) . Results : With the exception of higher progesterone levels at t2 , soy supplementation did not affect the physiologic fluctuations in circulating sex hormones . The ratio of C-telopeptide ( a bone resorption marker ) to osteocalcin ( a bone formation marker ) was slightly higher at t4 during the soy period compared to t4 during the control period ( P < 0.05 ) , indicating an uncoupling of bone resorption and formation processes . Serum levels of total cholesterol , LDL cholesterol , and HDL cholesterol were not influenced by soy intake . Conclusions : High short-term isoflavone-containing soy intake slightly affects physiologic fluctuations in bone turnover , but has no significant effects on most circulating sex hormones and on lipoprotein parameters in young healthy women OBJECTIVE To investigate the effect of soy isoflavone supplementation on bone mineral density ( BMD ) and markers of bone turnover in postmenopausal women . METHODS In this r and omized , placebo-controlled clinical trial , we used a crossover design to test the effect of soy isoflavone ( 110 mg/day ) ( 1.3:1.0:0.22 ratio of genistein/daidzein/ glycitein ) on bone formation , bone resorption , bone mineral content ( BMC ) , and BMD for 6 months . RESULTS Postmenopausal women ( n = 19 ) , mean age 70.6 + /- 6.3 years and mean time since menopause 19.1 + /- 5.5 years , were given isoflavone supplements for 6 months . There was a 37 % decrease in urinary concentrations of type 1 collagen alpha1-chain helical peptide ( HP ) , a marker of bone resorption , during the isoflavone supplementation compared with baseline ( p < 0.05 ) and a significant difference in mean ( SE ) HP excretion levels when isoflavone was compared with placebo ( 43.4 + /- 5.2 vs. 56.3 + /- 7.2 microg/mmol creatinine [ cr ] , p < 0.05 ) . With isoflavone supplementation , mean spine BMD at L2 and L3 was significantly greater when treatment was compared with control , with a difference between means of 0.03 + /- 0.04 g and 0.03 + /- 0.04 g ( p < 0.05 ) , respectively . There were nonsignificant increases from baseline for total spine BMC ( 3.5 % ) , total spine BMD ( 1 % ) , total hip BMC ( 3.6 % ) , and total hip BMD ( 1.3 % ) with the isoflavone treatment . CONCLUSIONS Soy isoflavone , in isolated form , was effective in this study to significantly decrease bone resorption in postmenopausal women . Further investigation needs to be done to evaluate the long-term effects of soy isoflavone on bone mass and fracture risk objective To assess the effect of a dietary soy protein supplement containing isoflavones on lipids and indices of bone resorption in postmenopausal women BACKGROUND The hypocholesterolemic effect of soy protein concentrates on normolipidemic subjects still remains unclear . Our objective is to assess the effect of soymilk supplementation , a whole soy product , with usual diet on serum lipids in normolipidemic subjects . METHODS We conducted a r and omized controlled trial on 60 premenopausal normolipidemic Japanese women . After excluding 8 subjects whose initial serum concentration of total cholesterol or triacylglycerol was higher than 220 mg/dL ( 5.69 mmol/L ) or 160 mg/dL ( 1.81 mmol/L ) , respectively , we encouraged the subjects in the soymilk-supplemented group ( n = 27 ) to consume 400 mL ( 408 g ) of commercial regular soymilk daily during two menstrual cycles . There were no significant differences in variables , including nutrient intake , between the soymilk-supplemented and control ( n = 25 ) groups before the intervention . RESULTS After the trial , we observed a significant decrease of 10.9 mg/dL , or 5.3 % , in serum concentration of total cholesterol in the soymilk-supplemented group . During the intervention , nutrient intake assessment showed significant increases in nutrient densities of vitamin E , polyunsaturated fatty acids , isoflavones , and P/S ratio and decreases in total energy and nutrient densities of vitamin C and green tea in this group . A statistically significant decrease in serum total cholesterol could still be observed even after excluding the estimated hypocholesterolemic effects of soymilk 's polyunsaturated fatty acids . CONCLUSIONS Our results suggest the hypocholesterolemic effect of soymilk , a traditional whole soy product , in Asian countries in normolipidemic subjects Fourteen premenopausal women participated in a r and omized , crossover controlled feeding study of three diets , each two menstrual cycles long . We compared a high saturated fat Western diet ( control diet ) with two other diets : the control diet plus soy protein ( soy diet ) and the control diet with polyunsaturated fat ( PUFA diet ) replacing most of the saturated fat . We measured reproductive and serum hormones , urinary estrogen metabolites and isoflavonoids , and menstrual cycle length . In the follicular phase , prolactin concentrations significantly decreased by 3.6 μg/dl ( P = 0.047 ) , follicle-stimulating hormone concentrations slightly increased by 0.1 IU/l ( P = 0.076 ) , and cortisol concentrations slightly decreased by 81.8 nmol/l ( P = 0.088 ) with the PUFA diet vs. the control diet . The soy diet slightly increased menstrual cycle length by 1.8 ± 0.7 days ( P = 0.088 ) and significantly increased ( P < 0.0001 ) urinary isoflavonoid excretion . These well-controlled diets did not affect serum estrogens or urinary estrogen metabolites , suggesting that type of fat or consumption of soy with a high saturated fat diet may not alter breast cancer risk by these mechanisms It is believed that soy isoflavone has much potential effectiveness on the postmenopausal status ; however , the optimal dose for preventing postmenopausal bone loss still remains unclear . This open-labeled , self-controlled pilot study was undertaken to determine the effect of 1-year supplementation of different high dosages of soy isoflavone in postmenopausal Taiwanese women . Forty-three women aged 45 - 67 years were enrolled and r and omly assigned into a control ( C ) , 100 mg/day isoflavone ( IF100 ) and 200 mg/day isoflavone ( IF200 ) groups for 1 year . Dual-energy X-ray absorptiometry and other related biochemical markers of bone metabolism were measured . Results indicated that the decrease in bone mineral density ( BMD ) was significant for lumbar vertebrae L1 - 3 , L1 - 4 and the femur neck in the C group ; surprisingly , the BMD of L1 - 3 was significantly elevated in the IF100 group ; however , there were no consistent responses in the IF200 group . No significant change except loss of the bone mineral content of Ward 's triangle ( P=.003 ) was found in the IF200 group after treatment . The percentage change at L1 - 3 was less ( P=.04 ) in the IF200 group when compared to the IF100 group . A relatively uniform direction of bone formation in exp and ing the weight and area with different rates of change result ed in different BMD changes . Both indicated a change of bone formation patterns with the higher-dose supplement . A protective effect of IF100 on estrogen-related bone loss was observed . A lack of a benefit such as high safety in the IF200 group for 1-year administration was ensured and lacked undesirable side effects Soy isoflavones have been hypothesized to exert hormonal effects in postmenopausal women . To test this hypothesis , we studied the effects of three soy powders containing different levels of isoflavones in 18 postmenopausal women . Isoflavones were consumed relative to bodyweight [ control : 0.11 + /- 0.01 ; low isoflavone ( low-iso ) : 1.00 + /- 0.01 ; high isoflavone ( high-iso ) : 2.00 + /- 0.02 mg/kg/day ] for 93 days each in a r and omized crossover design . Blood was collected on day 1 of the study ( baseline ) and days 36 - 38 , 64 - 66 , and 92 - 94 of each diet period , for analysis of estrogens , and rogens , gonadotropins , sex hormone binding globulin ( SHBG ) , prolactin , insulin , cortisol , and thyroid hormones . Vaginal cytology specimens were obtained at baseline and at the end of each diet period , and endometrial biopsies were performed at baseline and at the end of the high-iso diet period , to provide additional measures of estrogen action . Overall , compared with the control diet , the effects of the low-iso and high-iso diets were modest in degree . The high-iso diet result ed in a small but significant decrease in estrone-sulfate ( E1-S ) , a trend toward lower estradiol ( E2 ) and estrone ( E1 ) , and a small but significant increase in SHBG . For the other hormones , the few significant changes noted were also small and probably not of physiological importance . There were no significant effects of the low-iso or high-iso diets on vaginal cytology or endometrial biopsy results . These data suggest that effects of isoflavones on plasma hormones per se are not significant mechanisms by which soy consumption may exert estrogen-like effects in postmenopausal women . These data also show that neither isoflavones nor soy exert clinical ly important estrogenic effects on vaginal epithelium or endometrium To examine the effects of protein source and isoflavones on triglyceride ( TG ) fatty acid ( TGFA ) and cholesterol bio synthesis , subjects ( > 50 years , LDL cholesterol > 130 mg/dl ) underwent a four-phase r and omized cross-over feeding trial . Diets contained either isolated soy protein or common sources of animal protein ( 25 g/1000 kcal ) , without or with isoflavones ( 49 mg/1000 kcal ) and were each fed for 6 weeks . Blood sample s from 20 hyperlipidemic subjects ( 6 M , 14F , 62 + /- 9 years , BMI 26 + /- 3 kg/m(2 ) , LDL cholesterol > 160 mg/dl after feeding animal protein without isoflavones ) were selected to measure TGFA fractional synthetic rate ( TGFA-FSR ) and free cholesterol fractional synthetic rate ( FC-FSR ) over 24h as deuterium oxide uptake into TGFA and free cholesterol . Soy protein reduced TG by 12.4 % ( P < 0.0001 ) , total cholesterol by 4.4 % ( P < 0.001 ) , and LDL cholesterol by 5.7 % ( P = 0.003 ) compared to animal protein . The TGFA-FSR was reduced by 13.3 % ( P = 0.018 ) and FC-FSR was increased by 7.6 % ( P = 0.017 ) after the soy protein relative to the animal protein . Isoflavones had no significant effect on TG and TGFA-FSR . Isoflavones reduced total cholesterol levels by 3.1 % ( P = 0.009 ) but had no significant effect on LDL , HDL cholesterol levels , or FC-FSR . These data demonstrate that dietary protein type modulates circulating TG and cholesterol levels in hypercholesterolemic individuals by distinct mechanisms OBJECTIVE To assess the effect of soy isoflavone ingestion on plasma leptin concentrations in premenopausal and postmenopausal women . DESIGN R and omized , crossover studies , with blinding of participants and laboratory personnel . SETTING Procedures involving free-living individuals were carried out at the University of Minnesota General Clinical Research Center . PATIENT(S ) Fourteen regularly cycling premenopausal women , and 18 postmenopausal women . INTERVENTION(S ) Each premenopausal participant consumed , on a daily basis , each of three soy protein powders containing different levels of isoflavones for three menstrual cycles plus 9 days , with plasma sample s collected every other day the last 6 weeks of each diet period . Similarly , each postmenopausal participant consumed each of the three powders for 93 days , with plasma sample s collected daily on days 64 to 66 and 92 to 94 of each diet period . The powders , dosed on a per-kilogram body weight basis , provided mean isoflavone intakes of 8 , 65 , and 130 mg/day , for the control , low-isoflavone , and high-isoflavone diet periods , respectively . MAIN OUTCOME MEASURE(S ) Plasma leptin concentrations . RESULT ( S ) Isoflavone intake had essentially no effect on leptin concentrations in either premenopausal or postmenopausal participants . Concentrations in the premenopausal women were higher during the periovulatory and midluteal phases as compared to the early follicular and midfollicular phases . CONCLUSION ( S ) Despite the well-documented effect of estrogens to enhance leptin production , even high levels of isoflavone consumption do not alter leptin concentrations in women . Further studies are needed to more precisely delineate the nature of estrogenic and /or antiestrogenic effects of isoflavones in humans The effects of soy protein ( 40 g/d ) containing moderate and higher concentrations of isoflavones on blood lipid profiles , mononuclear cell LDL receptor messenger RNA , and bone mineral density and content were investigated in 66 free-living , hypercholesterolemic , postmenopausal women during a 6-mo , parallel-group , double-blind trial with 3 interventions . After a control period of 14 d , during which subjects followed a National Cholesterol Education Program Step I low-fat , low-cholesterol diet , all subjects were r and omly assigned to 1 of 3 dietary groups : Step I diet with 40 g protein/d obtained from casein and nonfat dry milk ( CNFDM ) , Step I diet with 40 g protein/d from isolated soy protein containing 1.39 mg isoflavones/g protein ( ISP56 ) , or Step I diet with 40 g protein/d from isolated soy protein containing 2.25 mg isoflavones/g protein ( ISP90 ) . Total and regional bone mineral content and density were assessed . Non-HDL cholesterol for both ISP56 and ISP90 groups was reduced compared with the CNFDM group ( P < 0.05 ) . HDL cholesterol increased in both ISP56 and ISP90 groups ( P < 0.05 ) . Mononuclear cell LDL receptor mRNA was increased in subjects consuming ISP56 or ISP90 compared with those consuming CNFDM ( P < 0.05 ) . Significant increases occurred in both bone mineral content and density in the lumbar spine but not elsewhere for the ISP90 group compared with the control group ( P < 0.05 ) . Intake of soy protein at both isoflavone concentrations for 6 mo may decrease the risk factors associated with cardiovascular disease in postmenopausal women . However , only the higher isoflavone-containing product protected against spinal bone loss OBJECTIVE Phytoestrogens are popular in treatment of menopause , although scientific evidence is insufficient as to their efficacy . We studied the effects of daily use of isoflavonoids on climacteric symptoms and quality of life in patients with a history of breast cancer . METHODS Sixty-two postmenopausal symptomatic women were r and omized to use either phytoestrogen ( tablets containing 114 mg of isoflavonoids ) or a placebo for 3 months ; the treatment regimens were reversed after a 2-month washout period . Fifty-six women completed the study . Menopausal symptoms were recorded on the Kupperman index and the visual analogue scale , and working capacity and mood changes were assessed via vali date d question naires . In addition , we followed the levels of phytoestrogens , follicle-stimulating hormone ( FSH ) , luteinizing hormone ( LH ) , estradiol , and sex hormone – binding globulin . Liver enzymes and creatinine were also assessed at each visit . RESULTS The phytoestrogen regimen raised the circulating levels of phytoestrogens ( daidzein , genistein , equol ) 19- to 106-fold . The Kupperman index was reduced by 4.2 ± 9.6 ( mean ± st and ard deviation ) ( 15.5 % ) during phytoestrogen use and similarly by 4.0 ± 8.1 ( 14.7 % ) during placebo use ( P nonsignificant ) . The quality of life parameters ( working capacity , mood changes ) were unaffected by phytoestrogen . In addition , the phytoestrogen regimen caused no changes in FSH , LH , estradiol , or sex hormone-binding globulin . Phytoestrogen treatment was well tolerated and caused no changes in liver enzymes , creatinine , body mass index , or blood pressure . Of the 56 women , 25 ( 44.6 % ) preferred the phytoestrogen regimen , 15 preferred the placebo ( 26.8 % ) , and 16 ( 28.6 % ) reported no preference ( nonsignificant ) . CONCLUSION Pure isoflavonoids did not alleviate subjective menopausal symptoms in breast cancer patients Objective This double‐blind , r and omized study was aim ed at evaluating comparatively , in postmenopausal women , the activity of a st and ardized soy extract ( SOYSELECT ) and placebo when given alone or in combination with conjugated equine estrogens ( CEE ) on early climacteric symptoms . Lipid profile , pituitary hormones , osteocalcin and endothelin levels , and vaginal and endometrial parameters were also evaluated . Design Participants in the control group were given placebo , and participants in the treated group were given 400 mg/day of a st and ardized soy extract , corresponding to 50 mg/daily of isoflavones . After 6 weeks of treatment , CEE was also then given to each participant at a dose of 0.625 mg/day for 4 weeks . At the end of this period , soy and placebo treatment were suspended , and , until the end of the study ( week 12 ) , participants were administered 10 mg/day of medroxyprogesterone acetate in association with CEE ( 0.625 mg/day ) . Results When compared with pretreatment data , on week 6 of the study , a significant ( p < 0.01 ) reduction in the mean number of hot flushes per week was observed in participants who were receiving the st and ardized soy extract , whereas a more marked relief was observed in both soy and placebo groups during CEE administration . Concurrently , the severity of hot flushes , assessed by means of the Greene climacteric scale , was also reduced in the soy group participants ( p < 0.001 , by paired t‐test ) . No soy‐related changes were observed on vaginal cytology , endometrial thickness , uterine artery pulsatility index , or metabolic and hormonal parameters tested . Finally , CEE‐related changes on genital tract , uterine vascular compartment , and pituitary hormones were not modified by soy treatment . Conclusions SOYSELECT may be a safe and efficacious therapy for relief of hot flushes in women who refuse or have contraindications for hormone replacement therapy . ( Menopause 2000;7:105‐111 . © 2000 , The North American Menopause Society . Objective We examined the change in menopausal symptoms in response to 24 weeks of isoflavone-rich ( 80.4 mg/day ) and isoflavone-poor ( 4.4 mg/day ) soy protein isolate treatment in perimenopausal women . Design In this double-blind 24-week study , 69 women were r and omized to treatment : isoflavone-rich soy protein ( n = 24 ) , isoflavone-poor soy protein ( n = 24 ) , or whey protein control ( n = 21 ) . A Menopausal Index was used to assess change in hot flushes and night sweats , as well as other symptoms , at baseline , week 12 , and week 24 . Results Repeated measures analysis of variance indicated no treatment effect on change in hot flush ( p = 0.18 ) and night sweat ( p = 0.92 ) frequency , whereas there was a significant decline in hot flush ( p = 0.0003 ) and night sweat ( p = 0.0007 ) frequency with time in all treatment groups . & khgr;2 analyses indicated no treatment effect on severity of hot flushes or night sweats at any time point , as well as no treatment effect on frequency or severity of other vasomotor symptoms . At the completion of the study , we found no treatment effect on retrospective perception of frequency , duration , or severity of hot flushes or night sweats . Since time had a significant effect on symptoms with all groups reporting a decline in overall symptoms , this indicated either a placebo effect or simply an improvement in symptoms during the study . Conclusion In this study , we found no evidence that isoflavone-rich or isoflavone-poor soy protein provided relief of vasomotor or of other menopausal symptoms Objective To analyze the impact of soy protein dietary supplements containing phytoestrogens on menopausal symptoms in healthy postmenopausal women . Methods A double-blind , placebo-controlled trial was conducted in 94 healthy postmenopausal women aged 50–75 years , with 44 r and omized to soy supplements containing 118 mg of isoflavones ( daidzein , genistein , glycitein and their respective glycosides ) , and 50 to an identically presented casein placebo . A vali date d question naire on menopausal symptoms was administered at baseline and at 3 months of treatment . Compliance was assessed by high-performance liquid chromatography assay of urinary phytoestrogens . Statistical analysis was completed using non-parametric statistical methods and multivariate analysis . Results At baseline 80 % of women recruited were experiencing menopausal symptoms , although symptom severity was mild . Those consuming phytoestrogen supplements had 13- and 17-fold increases in urinary excretion of genistein and daidzein , respectively , with no change in the placebo group . Active soy supplements did not significantly alter either individual symptoms or specific symptom category scores when compared to placebo . Within-group comparisons revealed that the active group reported a significant improvement in vaginal dryness ( p = 0.01 ) , libido ( p = 0.009 ) , facial hair ( p = 0.04 ) and dry skin ( p = 0.027 ) . However , similarly , those on placebo reported an improvement in libido ( p = 0.015 ) , facial hair ( p = 0.014 ) and dry skin ( p = 0.011 ) but not vaginal dryness . Conclusions In this group of 94 older postmenopausal women with a high frequency of mild menopausal symptoms , 3 months of soy supplements containing phytoestrogens did not provide symptomatic relief compared with placebo Objective : Based on the low cardiovascular risk in Asian population s , phytoestrogens are believed to provide vascular benefits . To eluci date the mechanisms behind the possible cardiovascular effects of phytoestrogens , we evaluated reverse cholesterol transport by assessing the capacity of serum to promote cholesterol efflux in postmenopausal women treated with isolated isoflavones . Design : Thirty postmenopausal women were treated in a r and omized , placebo-controlled , crossover trial with isoflavones or placebo for 3 months interrupted by a 2-month washout period . Serum sample s were collected before and after each treatment period , and the cholesterol efflux potential was investigated by using 3H-cholesterol -- labeled Fu5AH cells in culture . Results : Serum promoted 20.2 % ± 3.0 % and 19.9 % ± 3.4 % ( mean ± SD ) cholesterol efflux after isoflavonoid treatment and after placebo treatment , respectively . Thus , the isoflavone treatment did not affect serum cholesterol efflux . We also studied separately women who produced high concentrations of the isoflavone metabolite equol into serum because some studies suggest that equol could exert favorable vascular effects . However , there was no difference in serum cholesterol efflux capacity between the equol producers ( n = 15 ) and non-equol producers ( n = 15 ) . Conclusions : In conclusion , isoflavone treatment did not affect serum cholesterol efflux potential in postmenopausal women . Based on our findings , isolated isoflavones do not provide vascular benefits by improving cholesterol efflux High phytoestrogen intake among Asian women has been thought to explain the low risk of bone fractures in these population s. In a r and omized placebo-controlled trial we studied the effects of isoflavonoids on urinary output of the N-terminal cross-linked telopeptide of type I collagen , pyridinoline ( Pyr ) , and deoxypyridinoline ( Dpyr ) ( bone resorption markers ) and serum levels of bone-specific alkaline phosphatase and N-terminal and C-terminal procollagen type I ( bone formation markers ) . Fifty-five postmenopausal women with a history of breast cancer used phytoestrogens ( 114 mg of isoflavonoids ) or placebo tablets daily for 3 months ; the treatment regimens were then crossed over after a 2-month washout period . The markers were measured before and on the last day of each treatment period . Bone resorption was reduced during phytoestrogen use , as reflected in falls in the urinary output of Pyr ( 9 % ; P = 0.001 ) and Dpyr ( 5 % ; P = 0.008 ) . Compared with the placebo group , the fall in Dpyr was significant ( P = 0.022 ) and the falls in Pyr ( P = 0.084 ) and N-terminal cross-linked telopeptide of type I collagen ( P = 0.082 ) showed a trend toward significance . Bone formation markers were not affected by this regimen . Thus , isoflavonoid-induced inhibition of bone resorption may contribute to the low risk of osteoporosis in Asian women |
10,710 | 27,797,116 | There was no evidence of differences in most of the comparisons , and where there was , these differences were in single trials , mostly of small sample size .
When direct and indirect comparisons were available , network meta- analysis provided additional effect estimates for comparisons where there were no direct comparisons .
Low- quality evidence suggests that liver resection using a radiofrequency dissecting sealer may be associated with more adverse events than with the clamp-crush method .
Low- quality evidence also suggests that the proportion of people requiring a blood transfusion is higher with low central venous pressure than with acute normovolemic haemodilution plus low central venous pressure ; very low- quality evidence suggests that blood transfusion quantity ( red blood cells ) was lower with fibrin sealant than control ; blood transfusion quantity ( fresh frozen plasma ) was higher with oxidised cellulose than with fibrin sealant ; and blood loss , total hospital stay , and operating time were lower with low central venous pressure than with control .
There is no evidence to suggest that using special equipment for liver resection is of any benefit in decreasing the mortality , morbidity , or blood transfusion requirements ( very low- quality evidence ) .
In addition , it should be noted that the sample size was small and the credible intervals were wide , and we can not rule out considerable benefit or harm with a specific method of liver resection | BACKGROUND Liver resection is a major surgery with significant mortality and morbidity .
Specialists have tested various methods in attempts to limit blood loss , transfusion requirements , and morbidity during elective liver resection .
These methods include different approaches ( anterior versus conventional approach ) , use of autologous blood donation , cardiopulmonary interventions such as hypoventilation , low central venous pressure , different methods of parenchymal transection , different methods of management of the raw surface of the liver , different methods of vascular occlusion , and different pharmacological interventions .
A surgeon typically uses only one of the methods from each of these seven categories .
The optimal method to decrease blood loss and transfusion requirements in people undergoing liver resection is unknown .
OBJECTIVES To assess the effects of different interventions for decreasing blood loss and blood transfusion requirements during elective liver resection . | Background Intraoperative haemorrhage is a known predictor for perioperative outcome of patients undergoing hepatic resection . While anaesthesiological lowering of central venous pressure ( CVP ) by fluid restriction is known to reduce bleeding during transection of the hepatic parenchyma its potential side effects remain poorly investigated . In theory it may have negative effects on kidney function and tissue perfusion and bears the risk to result in severe haemodynamic instability in case of profound intraoperative blood loss . The present r and omised controlled trial evaluates efficacy and safety of infrahepatic inferior vena cava ( IVC ) clamping as an alternative surgical technique to reduce CVP during hepatic resection . Methods / Design The proposed IVC CLAMP trial is a single-centre r and omised controlled trial with a two-group parallel design . Patients and outcome -assessors are blinded for the treatment intervention . Patients undergoing elective hepatic resection due to any reason are enrolled in IVC CLAMP . All patients admitted to the Department of General- , Visceral- , and Transplant Surgery , University of Heidelberg for elective hepatic resection are consecutively screened for eligibility and written informed consent is obtained on the day before surgery . The primary objective of this trial is to assess and compare the amount of blood loss during hepatic resection in patients receiving surgical CVP reduction by clamping of the IVC as compared to anaesthesiological CVP without infrahepatic IVC clamping reduction . In addition to blood loss a set of general as well as surgical variables are analysed . Discussion This is a r and omised controlled patient and observer blinded two-group parallel trial design ed to assess efficacy and safety of infrahepatic IVC clamping during elective hepatectomy . Trial registration Clinical Trials AIM To investigate the effect of low central venous pressure ( LCVP ) on blood loss during hepatectomy for hepatocellular carcinoma ( HCC ) . METHODS By the method of sealed envelope , 50 HCC patients were r and omized into LCVP group ( n=25 ) and control group ( n=25 ) . In LCVP group , CVP was maintained at 2 - 4 mmHg and systolic blood pressure ( SBP ) above 90 mmHg by manipulation of the patient 's posture and administration of drugs during hepatectomy , while in control group hepatectomy was performed routinely without lowering CVP . The patients ' preoperative conditions , volume of blood loss during hepatectomy , volume of blood transfusion , length of hospital stay , changes in hepatic and renal functions were compared between the two groups . RESULTS There were no significant differences in patients ' preoperative conditions , maximal tumor dimension , pattern of hepatectomy , duration of vascular occlusion , operation time , weight of resected liver tissues , incidence of post-operative complications , hepatic and renal functions between the two groups . LCVP group had a markedly lower volume of total intraoperative blood loss and blood loss during hepatectomy than the control group , being 903.9+/-180.8 mL vs 2 329.4+/-2 538.4 ( W=495.5 , P<0.01 ) and 672.4+/-429.9 mL vs 1 662.6+/-1 932.1 ( W=543.5 , P<0.01 ) . There were no remarkable differences in the pre-resection and post-resection blood losses between the two groups . The length of hospital stay was significantly shortened in LCVP group as compared with the control group , being 16.3+/-6.8 d vs 21.5+/-8.6 d ( W=532.5 , P<0.05 ) . CONCLUSION LCVP is easily achievable in technique . Maintenance of CVP < or= 4 mmHg can help reduce blood loss during hepatectomy , shorten the length of hospital stay , and has no detrimental effects on hepatic or renal function Background : Hepatic resection is the most effective treatment for many malignant and benign conditions affecting the liver and biliary tree . Despite improvements , major partial hepatectomy can be associated with considerable blood loss and transfusion requirements . Transfusion of allogeneic blood products , although potentially life-saving , is associated with many potential complications . The primary aim of this study was to determine if acute normovolemic hemodilution ( ANH ) , an established blood conservation technique , reduces the requirement for allogeneic red cell transfusions in patients undergoing major hepatic resection . Methods : One hundred thirty patients undergoing major hepatic resection ( ≥3 segments ) were prospect ively r and omized to undergo either ANH or st and ard anesthetic management ( STD ) . In the ANH group , intraoperative blood collection was performed to a target hemoglobin of 8.0 g/dL. Low central venous pressure anesthetic technique was used intraoperatively for both groups . A st and ardized transfusion protocol was applied to all patients intraoperatively and throughout the hospital stay . Results : From April 2004 to March 2007 , 63 patients were r and omized to ANH and 67 to STD . Demographics , diagnoses , liver function , extent of resection , intraoperative blood loss , operative time , incidence and grade of complications , and length of hospital stay were similar between the 2 groups . ANH reduced the overall allogeneic red cell transfusion rate by 50 % compared with STD [ 12.7 % ( n = 8) vs. 25.4 % ( n = 17 ) , respectively ; P = 0.067 . ANH patients were less often transfused intraoperatively ( n = 1 , 1.6 % ) compared with the STD group ( n = 7 , 10.4 % ) ( P = 0.036 ) , had higher postoperative hemoglobin levels ( P = 0.01 ) , and tended to require fewer red cell units overall ( 28 vs. 47 units ) . In patients with intraoperative blood loss ≥800 mL , ANH reduced not only the allogeneic red cell transfusion rate ( 18.2 % vs. 42.4 % , P = 0.045 ) but also the proportion of patients requiring fresh frozen plasma ( 21.1 % vs. 48.3 % , P = 0.025 ) . Conclusion : For patients undergoing major liver resection , ANH is safe , effectively reduces the need for allogeneic transfusions , and should be considered for routine use . Given the modest transfusion rate in the STD arm , future efforts should attempt to target ANH use to patients most likely to benefit Objective This prospect i ve r and omized study determined the influence of closed-suction drainage on the incidence of postoperative complications after elective hepatic resection . Summary Background Data Routine drainage is no longer advocated after several intra-abdominal surgical procedures . Methods A series of 81 patients who underwent elective hepatic resection were r and omly allocated to either a nondrainage group ( n = 39 ) and a drainage group with closed-suction drainage ( n = 42 ) . Indications for resection were 42 benign lesions and 39 malignant tumors , including 19 with cirrhosis . Major hepatic resection was performed in 25 patients and minor resection , in 56 . All patients underwent ultrasonography with puncture for bacteriologic cultures of all fluid collection s within the first 5 postoperative days . Results One patient died in each group . Ultrasonography found a significantly higher rate of subphrenic collection s in the drainage group compared with the nondrainage group ( respectively , 36 % vs. 15 % , p < 0.05 ) . These collection s were more frequently infected in the drainage group ( n = 6 ) than in the nondrainage group ( n = 2 ) . After major liver resection , the rate of intra-abdominal postoperative complications ( i.e. , subphrenic fluid collection s , hematomas , and bilomas ) was similar between the two groups . Conclusion Minor liver resection is safer without drainage . Major liver resection can be performed with or without abdominal drainage Background : Dye-enhanced laser ablation ( DLA ) using a low-power diode laser for indocyanine green (ICG)-stained tissue has proven its effectiveness in dye-enhanced laser photocoagulation of retinal vessels or endoscopic surgical mucosectomy . We have applied DLA in hepatectomy and described its histological distinction in comparison with the cavitron ultrasonic surgical aspirator ( CUSA ) . Methods : A diode laser ( UDL-60 Laser unit , Olympus , Tokyo , Japan ) with 810 ± 20 nm wavelength was employed for this study . The ICG dye ( Diagnogreen ® , Daiichi Pharmaceutical , Tokyo , Japan ) with a peak absorption wavelength at 800–810 nm was injected topically into the resection plane of the liver . The liver tissue was divided by touching the tip of the diode laser . Three different concentrations of ICG solution such as 2.0 , 1.0 and 0.5 mg/ml were tested in the preliminary animal experiment . The use of a low-power diode laser at 10 W with an ICG concentration of 0.5 mg/ml was the appropriate combination for liver resection . In the clinical series , 27 hepatectomies were performed by DLA , and 10 with CUSA . Results : DLA demonstrated smooth cutting and good hemostasis in liver resection . Among the hepatectomy cases given DLA , no postoperative hemorrhage or bile leakage was noted . The postoperative hospital stay was significantly shorter in the DLA than the CUSA group . The cut surface of the liver was sealed microscopically with a layer of protein coagulum . Conclusions : A layer of protein sealant on the cut surface of the liver contributes to the short postoperative hospital stay when using DLA Purpose This r and omized , controlled , single-blinded multicenter study evaluated the efficacy of latest-generation fibrin sealant containing synthetic aprotinin as fibrinolysis inhibitor as supportive treatment for hemostasis after elective partial hepatectomy . Methods Adult subjects undergoing resection of at least one liver segment were assigned to treatment with fibrin sealant or manual compression with a surgical gauze swab if persistent oozing necessitated additional hemostatic measures after primary control of arterial and venous bleeding . The primary outcome measure was the proportion of subjects with intraoperative hemostasis at 4 min after start of r and omized treatment application . Secondary efficacy outcome measures included intraoperative hemostasis at 6 , 8 , and 10 min , intra- and postoperative rebleedings , transfusion requirements , and drainage volume . Results Seventy subjects were r and omized . Hemostasis at 4 min was achieved in 29/35 ( 82.9 % ) fibrin sealant subjects compared with 13/35 ( 37.1 % ) control subjects ( p < 0.001 ) . Significantly more fibrin sealant subjects achieved hemostasis at 6 ( p < 0.001 ) , 8 ( p = 0.028 ) , and 10 min ( p = 0.017 ) . The number of rebleedings was low in both study arms . Transfusion requirements and 48-h drainage volumes were similar between the study arms . No adverse events related to study treatment were reported . Conclusions Fibrin sealant was shown to be safe and superior to manual compression in the control of parenchymal bleeding after hepatic resection . The use of synthetic aprotinin as fibrinolysis inhibitor further improves the safety margin of fibrin sealant by eliminating the risk of transmission of bovine spongiform encephalopathy and other bovine pathogens Background Despite improvements in liver surgery over the past decades , hemostasis during hepatic resections remains challenging . This multicenter r and omized study compares the hemostatic effect of a collagen hemostat vs. a carrier-bound fibrin sealant after hepatic resection . Methods Patients scheduled for elective liver resection were r and omized intraoperatively to receive either the collagen hemostat ( COLL ) or the carrier-bound fibrin sealant ( CBFS ) for secondary hemostasis . The primary endpoint was the proportion of patients with hemostasis after 3 min . Secondary parameters were the proportions of patients with hemostasis after 5 and 10 min , the total time to hemostasis , and the complication rates during a 3 months follow-up period . Results A total of 128 patients were included . In the COLL group , 53 out of 61 patients ( 86.9 % ) achieved complete hemostasis within 3 min after application of the hemostat compared to 52 out of 65 patients ( 80.0 % ) in the CBFS group . The 95 % confidence interval for this difference [ −6.0 % , 19.8 % ] does not include the lower noninferiority margin ( −10 % ) . Thus , the COLL treatment can be regarded as noninferior to the comparator . The proportions of patients with hemostasis after 3 , 5 , and 10 min were not significantly different between the two study arms . Postoperative mortality and morbidity were similar in both treatment groups . Conclusion The collagen hemostat is as effective as the carrier-bound fibrin sealant in obtaining secondary hemostasis during liver resection with a comparable complication rate Background Hepatic resection is still associated with significant morbidity . Although the period of parenchymal transection presents a crucial step during the operation , uncertainty persists regarding the optimal technique of transection . It was the aim of the present r and omized controlled trial to evaluate the efficacy and safety of hepatic resection using the technique of stapler hepatectomy compared to the simple clamp-crushing technique . Methods / Design The CRUNSH Trial is a prospect i ve r and omized controlled single-center trial with a two-group parallel design . Patients scheduled for elective hepatic resection without extrahepatic resection at the Department of General- , Visceral- and Transplantation Surgery , University of Heidelberg are enrolled into the trial and r and omized intraoperatively to hepatic resection by the clamp-crushing technique and stapler hepatectomy , respectively . The primary endpoint is total intraoperative blood loss . A set of general and surgical variables are documented as secondary endpoints . Patients and outcome -assessors are blinded for the treatment intervention . Discussion The CRUNSH Trial is the first r and omized controlled trial to evaluate efficacy and safety of stapler hepatectomy compared to the clamp-crushing technique for parenchymal transection during elective hepatic resection . Trial Registration Clinical Trials.gov : BACKGROUND / AIMS To clarify the clinical benefits of the maneuver in right-side hepatectomy . METHODOLOGY Eighty-one patients with liver tumor ( 54 hepatocellular carcinoma , 17 metastatic liver tumor and 10 other tumors ) treated with a right-side hepatectomy were prospect ively analyzed . The patients were divided into the following three groups : a conventional approach ( group A , n=21 ) ; liver dissection under the hanging maneuver after liver mobilization ( group B , n=19 ) and liver dissection under the hanging maneuver prior to liver mobilization ( group C , n=41 ) . RESULTS The liver hanging maneuver was safely performed in all the patients in groups B and C. Tumor size had a significantly positive correlation with the amount of intraoperative blood loss ( R=0.52 , p<0.05 ) in group A only . The patients in groups B and C had a significantly lower intraoperative use of blood loss ( both p<0.01 ) , operation time ( p<0.05 and p<0.01 ) and the frequency of blood product ( both p<0.05 ) , in comparison to group A , respectively . The postoperative morbidity and the mortality rates were similar in the three groups . CONCLUSIONS Liver hanging maneuver is a safe procedure , which can decrease intraoperative blood loss and administration of blood product in right-side hepatectomy INTRODUCTION Local haemostatic agents are used for the control of surgical haemorrhage when st and ard techniques are inadequate , but there are few studies of these products in children . PATIENTS AND METHODS This was a prospect i ve , open-label study in which children ( aged 4 weeks to 6 years ) undergoing liver resection with or without segmental liver transplantation were treated with TachoSil , a collagen patch coated with a dry layer of human fibrinogen and human thrombin , if minor ( i. e. , oozing ) or moderate bleeding was present after primary haemostatic treatment . Time to haemostasis after TachoSil application was the primary endpoint . Safety was assessed by adverse events ( AEs ) , including post-operative infections , symptoms of graft rejection and re-operations . RESULTS Enrolment was stopped early after 16 children had entered the study . 13 children underwent whole liver resection and transplantation and 3 patients underwent segmental resection . Satisfactory haemostasis was achieved in 13 children ( 81.3 % ; 95 % CI : 61.8 - 100 % ) at 3 min and in 1 child at 8 min . Occurrence of AEs was as expected , with most being known complications of the underlying disease , surgical procedure , or use of immunosuppressive medication . No AEs were considered to be related to the use of TachoSil . CONCLUSIONS The use of TachoSil for haemostasis after primary haemostatic treatment appears to be safe and effective in children undergoing liver resection BACKGROUND Coagulopathy caused by cirrhosis may contribute to excessive bleeding during hepatectomy . We evaluated the hemostatic effect and safety of recombinant factor VIIa ( rFVIIa ) in cirrhotic patients undergoing partial hepatectomy . METHODS Patients were r and omized to rFVIIa 50 or 100 mug/kg or placebo , administered intravenously 10 minutes before surgery and every second hour during surgery . The primary efficacy end points were the proportion of patients receiving red blood cell ( RBC ) transfusions and the amount of RBCs transfused . The RBC transfusion trigger was blood loss of 500 mL. Safety end points included thromboembolic and adverse events . RESULTS No statistically significant effect of rFVIIa treatment on efficacy end points was observed . Serious and thromboembolic adverse events occurred at similar incidences in the study groups . CONCLUSIONS Using blood loss as a transfusion trigger , the efficacy of rFVIIa in reducing the requirement for RBC transfusion was not established in this study . No safety concerns were identified OBJECTIVE To compare the efficacy of selective hepatic vascular exclusion versus Pringle manoeuvre in partial hepatectomy for tumours adjacent to the hepatocaval junction . METHODS A r and omized comparative trial was carried out . The primary endpoint was intraoperative blood loss . The secondary endpoints were operation time , blood transfusion , postoperative liver function recovery , procedure-related morbidity and in-hospital mortality . RESULTS 160 patients were r and omized into 2 groups : the Pringle manoeuvre group ( n = 80 ) and the selective hepatic vascular exclusion ( SHVE ) group ( n = 80 ) . Intraoperative blood loss and transfusion requirements were significantly less in the SHVE group . In the SHVE group , laceration of hepatic veins happened in 18 patients . Profuse intraoperative blood loss of over 2 L happened in 2 patients but no patient suffered from air embolism because the hepatic veins were controlled . In the Pringle group , the hepatic veins were lacerated in 20 patients , with profuse blood loss of over 2 L in 7 patients and air embolism in 3 patients . The rates of postoperative bleeding , reoperation , liver failure and mortality were significantly higher and the ICU stay and hospital stay were significantly longer in the Pringle group . CONCLUSIONS SHVE was more efficacious than Pringle manoeuvre for partial hepatectomy in patients with tumours adjacent to the hepatocaval junction Objective : To compare the results of percutaneous local ablative therapy ( PLAT ) with surgical resection in the treatment of solitary and small hepatocellular carcinoma ( HCC ) . Summary Background Data : PLAT is effective in small HCC . Whether it is as effective as surgical resection in the long-term survivals remains unknown . Methods : We conducted a prospect i ve r and omized trial on 180 patients with a solitary HCC ≦5 cm to receive either PLAT or surgical resection . The patients were regularly followed up after treatment with physical examination , blood , and radiologic tests . Results : Of the 90 patients who were r and omized to PLAT , only 71 received PLAT because 19 withdrew their consent . Of the 90 patients who were r and omized to surgical resection , a single Couinaud liver segment resection was carried out in 69 patients , 2 segments in 16 patients , and 3 or more segments in 3 patients . Ethanol injection was given during open surgery in 2 patients . Only 1 patient died after surgical resection within the same hospital admission . Posttreatment complications were more often and severe after surgery than PLAT . The 1- , 2- , 3- , and 4-year overall survival rates after PLAT and surgery were 95.8 % , 82.1 % , 71.4 % , 67.9 % and 93.3 % , 82.3 % , 73.4 % , 64.0 % , respectively . The corresponding disease-free survival rates were 85.9 % , 69.3 % , 64.1 % , 46.4 % and 86.6 % , 76.8 % , 69 % , 51.6 % , respectively . Statistically , there was no difference between these 2 treatments . Conclusion : PLAT was as effective as surgical resection in the treatment of solitary and small HCC . PLAT had the advantage over surgical resection in being less invasive HYPOTHESIS A novel collagen-based composite of bovine microfibrillar collagen and bovine thrombin combined with autologous plasma is more effective than st and ard hemostasis ( collagen sponge applied with pressure ) in controlling diffuse hepatic bleeding after hemihepatectomy or segmental resection of the liver . DESIGN R and omized controlled trial . SETTING Seven university-affiliated medical centers . PATIENTS Sixty-seven adult patients scheduled for hemihepatectomy or segmental resection who received hemostatic intervention with an investigational treatment ( n = 38 ) or control ( n = 29 ) . INTERVENTION Bleeding hepatic tissue was managed in all control subjects with a collagen sponge with manual pressure . Subjects in the experimental group had the sprayable liquid composite intraoperatively applied to the surgical site . The liquid immediately formed a collagen-fibrin gel that was used without concomitant tamponade . MAIN OUTCOME MEASURES Hemostatic success was defined as the proportion of subjects in each treatment group who achieved complete hemostasis within 10 minutes . Success rates and median times required to achieve controlled bleeding ( ie , slight oozing ) and complete hemostasis were compared between treatment groups . RESULTS All 38 subjects in the experimental group achieved complete hemostasis within 10 minutes compared with only 69 % ( 20/29 ) of control subjects ( P<.001 ) . The median time to controlled bleeding was approximately 4 times longer ( 250 vs 62 seconds ) for control subjects than for experimental group subjects ( P<.001 ) . The median time required to achieve complete hemostasis also favored the experimental group ( 150 vs 360 seconds ; P<.001 ) . No adverse events related to the use of the experimental hemostatic agent were detected . CONCLUSIONS The experimental composite is more effective at controlling and stopping diffuse hepatic bleeding than a collagen sponge applied with pressure ; it may be a useful hemostatic agent for patients undergoing hemihepatectomy , segmental resection , and related surgical procedures BACKGROUND & AIMS Aminotransferases are commonly used to determine the optimal duration of ischemic intervals during intermittent Pringle maneuver ( IPM ) . However , they might not be responsive enough to detect small differences in hepatocellular damage . Liver fatty acid-binding protein ( L-FABP ) has been suggested as a more sensitive marker . This r and omized trial aim ed to compare hepatocellular injury reflected by L-FABP in patients undergoing liver resection with IPM using 15 or 30 min ischemic intervals . METHODS Twenty patients undergoing liver surgery were r and omly assigned to IPM with 15 ( 15IPM ) or 30 ( 30IPM ) minutes ischemic intervals . Ten patients not requiring IPM ( noIPM ) served as controls . Primary endpoint was hepatocellular injury during liver surgery reflected by systemic L-FABP plasma levels . Between group comparisons were performed using area under the curve and repeated measures two-way ANOVA . RESULTS The IPM groups had similar characteristics . Aminotransferases did not differ significantly between 15IPM and 30IPM at any time point . L-FABP levels rose up to 1853±708 ng/ml in the 15IPM and 3662±1355 ng/ml in the 30IPM group after finishing liver transection and decreased rapidly thereafter . There were no significant differences between 15IPM and 30IPM in cumulative L-FABP level ( p=0.378 ) or L-FABP level at any time point ( p=0.149 ) . Blood loss , remnant liver function and morbidity were comparable . CONCLUSIONS IPM with 15 or 30 min ischemic intervals induced similar hepatocellular injury measured by the sensitive marker L-FABP . The present study confirms the results of earlier trials , suggesting that IPM with 30 min ischemic intervals may be used To evaluate the effects of intermittent hepatic inflow occlusion ( IHIO ) during donor hepatectomy for living donor liver transplantation ( LDLT ) in recipients and donors , we performed a single-center , open-label , prospect i ve , parallel , r and omized controlled study . Adult donor-recipient pairs undergoing LDLT with right hemiliver grafts were r and omized into IHIO and control groups ( 1:1 ) . In the IHIO group , IHIO was performed during donor hepatectomy . The primary endpoint was the peak serum alanine aminotransferase ( ALT ) concentration in the recipients within 5 days after the operation . Blood sample s for measurements of interleukin-6 ( IL-6 ) , IL-8 , tumor necrosis factor α ( TNF-α ) , and hepatocyte growth factor ( HGF ) were taken from the donors and the recipients during the operation and postoperatively . Biopsy sample s for measurements of caspase-3 and malondialdehyde ( MDA ) were taken from the donors and the recipients . In all , 50 donor-recipient pairs ( ie , 25 pairs in each group ) completed this study . The mean peak serum ALT levels within 5 days after the operation did not differ in the recipients between the 2 groups ( P = 0.32 ) but were higher in the donors of the IHIO group ( P = 0.002 ) . There were no differences in the prothrombin times or total bilirubin levels in the recipients or donors between the 2 groups . The amount of blood loss during donor hepatectomy was significantly lower in the IHIO group versus the control group ( P = 0.02 ) . The mean hospital stay for donors was 19.3 ± 7.2 days in the control group and 15.8 ± 4.6 days in the IHIO group ( P = 0.046 ) . There were no in-hospital deaths within 1 month and no cases of primary nonfunction or initially poor function in the 2 groups . The concentrations of IL-6 , IL-8 , TNF-α , and HGF did not differ between the 2 groups , nor did the concentrations of caspase-3 and MDA . In conclusion , although we found differences in postoperative peak serum ALT levels in donors , donor hepatectomy with IHIO for LDLT using a right hemiliver graft with a graft-to-recipient body weight ratio > 0.9 % and < 30 % steatosis can be a tolerable procedure for donors and recipients The aim of this study was to compare the Cavitron ultrasonic surgical aspirator ( CUSA ) with bipolar cautery ( BP ) to CUSA with a radiofrequency coagulator [ TissueLink ( TL ) ] in terms of efficacy and safety for hepatic transection in living donor liver transplantation . Twenty-four living liver donors ( n = 12 for each group ) were r and omized to undergo hepatic transection using CUSA with BP or CUSA with TL . Blood loss during parenchymal transection and speed of transection were the primary endpoints , whereas the degree of postoperative liver injury and morbidity were secondary endpoints . Median blood loss during liver transection was significantly lower in the TL group than in the BP group ( 195.2 + /- 84.5 versus 343.3 + /- 198.4 mL ; P = 0.023 ) , and liver transection was significantly faster in the TL group than in the BP group ( 0.7 + /- 0.2 versus 0.5 + /- 0.2 cm(2)/minute ; P = 0.048 ) . Significantly fewer ties were required during liver transection in the TL group than in the BP group ( 15.8 + /- 4.8 versus 22.8 + /- 7.9 ties ; P = 0.023 ) . The morbidity rates were similar for the 2 groups . In conclusion , CUSA with TL is superior to CUSA with BP for donor hepatectomy in terms of blood loss and speed of transection with no increase in morbidity Purpose To determine the effects of desmopressin on coagulation and blood loss in patients undergoing elective partial hepatectomy . Methods A r and omized , controlled and double-blind study on 59 patients who received either 0.3 μg·kg−1 of desmopressin or an equal volume of normal saline ( control ) infused intravenously over 20 min after induction of general anesthesia . Results There was an increase in plasma levels of factors VIII and von Willebr and after the infusion of study drug in both groups ( P < 0.001 ) . The activated partial thromboplastin time was shortened in Group D whereas prothrombin time was prolonged in Group C ; ( P = 0.02 ) . A large range of intraoperative blood loss ( 400–7128 mL ) was observed , with no significant differences between groups . There were no changes in plasma electrolyte levels or osmolality . Transfusion requirements were similar in both groups . Conclusion Desmopressin did not reduce intraoperative blood loss or transfusion requirements during hepatectomy despite raising clotting factor levels and improving tests of hemostasis . RésuméObjectifDéterminer les effets de la desmopressine sur la coagulation et les pertes sanguines pendant une hépatectomie partielle réglée . MéthodeIl s’agit d’une étude r and omisée , contrôlée et à double insu auprès de 59 patients qui ont reçu , soit 0,3 μg·kg−1 de desmopressine ou un volume égale de soluté normal ( témoin ) administré par voie intraveineuse 20 min au moins après l’induction de l’anesthésie générale . RésultatsOn a noté une augmentation des niveaux plasmatiques des facteurs VIII et von Willebr and à la suite de la perfusion du médicament expérimenté chez les patients des deux groupes ( P < 0,001 ) . Le temps de céphaline activé a été plus court dans le groupe D t and is que le temps de prothrombine a été plus long dans le groupe T ; ( P = t0,02 ) . D’importants écarts ont été observés pour les pertes sanguines peropératoires ( 400–7128 mL ) , mais sans différence significative intergroupe . Aucune modification des niveaux plasmatiques d’électrolyte ou d’osmolalité n’a été notée . Les besoins de transfusion ont été comparables dans les deux groupes . Conclusion La desmopressine ne réduit pas les pertes sanguines ou les besoins de transfusion peropératoires pendant l’hépatectomie , malgré l’élévation des niveaux de facteurs de coagulation et l’amélioration de l’hémostase INTRODUCTION Haemostasis after liver resection may be difficult to achieve as a result of the presence of challenging bleeding , the anatomic l and scape of the liver and the quality of tissue making up the hepatic parenchyma . The fibrin pad ( FP ) is a topical absorbable haemostat design ed to be effective in a variety of tissues and across multiple bleeding intensities . This is the first clinical trial to evaluate the hemostat 's safety and effectiveness in controlling bleeding during elective hepatic resection . METHODS This prospect i ve , r and omized , controlled superiority trial enrolled 104 subjects undergoing elective hepatectomy in 5 countries . After parenchymal transection , subjects with an appropriately defined target bleeding site ( TBS ) were stratified according to the type of hepatic parenchyma and immediately r and omized 1:1 : FP versus St and ard of Care ( SoC ) . SoC comprised manual compression with the use of an approved topical absorbable haemostat . The primary endpoint was haemostasis at 4 min from identification of the TBS , with no re-bleeding requiring re-treatment prior to abdominal closure . Results were stratified for both normal and abnormal ( steatosis or cirrhosis ) hepatic parenchyma . All subjects were followed for 60 days post-operatively . RESULTS The intent-to-treat ( ITT ) analysis showed an overall treatment difference of 53.0 % ( P < 0.001 ) , 82.5 % ( 33/40 FP ) versus 29.5 % ( 13/44 SoC ) in achieving haemostasis at 4 min with no re-bleeding requiring treatment up to wound closure . The per protocol analysis showed an overall treatment difference of 65.7 % ( P < 0.001 ) , with 33/35 successes ( 94.3 % ) in the FP group and 12/42 in the SoC group ( 28.6 % ) . The stratification results showed treatment differences between the normal parenchyma group , 63.6 % ( 95.8 % FP versus 32.3 % SoC P < 0.001 ) and a larger difference of 72.7 % in the abnormal parenchyma group ( 90.9 % FP versus 18.2 % SoC P = 0.0003 ) . Post-operative intra-abdominal fluid collection s were less frequent in the FP group ( 3.4 % FP versus 13.3 % SoC P = 0.059 ) . There was no difference in the safety profile between the FP or SoC groups . CONCLUSIONS The FP is safe and effective when used as an adjunct to achieve haemostasis during hepatic surgery . The success rate of achieving haemostasis with a FP remained high compared with the SOC group , especially in steatotic or cirrhotic liver tissue where the control success rates diminish . In addition , FP treatment of hepatic parenchymal surfaces may reduce the risk of post-operative biliary and fluid collection Trial Design A prospect i ve r and omised controlled trial was design ed to evaluate the advantages of routine application of the anterior approach during right hepatectomy . Methods The study was conducted between March 2005 and April 2009 in a tertiary hepatobiliary – pancreatic centre . Patients scheduled for right hepatectomy for primary or metastatic tumours , without infiltration of segment 1 , inferior vena cava or main bile duct , were r and omly assigned to right hepatectomy using either an anterior or a classic approach . The primary study endpoint was overall blood loss . Results Sixty-six patients were r and omly allocated to undergo right hepatectomy with an anterior ( AA group n = 33 ) or a classic approach ( CA group n = 33 ) . Sixty-five patients were included in the analysis ( 33 in AA group and 32 in CA group ) . There was no significant difference in patient age , diagnosis , preoperative hepatic biochemistry and tumour size between the two groups . Overall blood loss ( 437 ml ± 664 in AA group vs.500 ml ± 532.3 in CA group ; p = 0.960 ) and bleeding during transection ( p = 0.973 ) were similar between two groups . Perioperative blood transfusion rates were 18 % in the AA group and 9.3 % in the CA group ( p = 0.253 ) . Time of parenchymal transsection was significantly longer in AA group ( 75.1 ± 26.6 min vs. 56.7 ± 17.5 min , p = 0.01 ) . There was no difference between both groups for postoperative prothrombin time , serum transaminase and total bilirubin levels . One patient died in each group ( p = 0.746 ) . The two groups had similar morbidity rates . Conclusion Routine application of the anterior approach during right hepatectomy does not decrease intraoperative blood loss and morbidity rate BACKGROUND Bleeding during hepatic surgery is associated with prolonged hospitalization and increased morbidity and mortality . The Veriset ™ haemostatic patch is a topical haemostat comprised of an absorbable backing made of oxidized cellulose and self-adhesive hydrogel components . It is design ed to achieve haemostasis quickly and adhere to tissues without fixation . METHODS A prospect i ve , r and omized , multicentre , single-blinded study ( n = 50 ) was performed to compare the use of a Veriset ™ haemostatic patch with a fibrin sealant patch ( TachoSil ( ® ) ) ( control ) in the management of diffuse bleeding after hepatic surgery . Patients were r and omized following the confirmation of diffuse bleeding requiring the use of a topical haemostat . Time to haemostasis was assessed at preset intervals until haemostasis was achieved . RESULTS Both groups were similar in comorbidities and procedural techniques . The median time to haemostasis in the group using the Veriset ™ haemostatic patch was 1.0 min compared with 3.0 min in the control group ( P < 0.001 ; 3-min minimum application time for the control patch ) . This result was independent of bleeding severity and surface area . Both products had similar safety profiles and no statistical differences were observed in the occurrence of adverse or device-related events . CONCLUSIONS Regardless of bleeding severity or surface area , the Veriset ™ haemostatic patch achieved haemostasis in this setting significantly faster than the control device in patients undergoing hepatic resection . It was safe and easy to h and le in open hepatic surgery Background Surgical resection remains the optimal therapy for cirrhotic patients with hepatocellular carcinoma ( HCC ) that are not suitable for liver transplantation ( LT ) . Recently , various innovative techniques for liver resection have been developed . Aim The aim of the study was to compare radiofrequency-assisted parenchyma transection ( RF-PT ) with the traditional clamp-crushing ( CC ) technique to explore the preferred therapy in cirrhotic patients with HCC . Methods From January 2009 to December 2010 , 75 cirrhotic patients with HCC who underwent hepatectomy were r and omized to RF-PT ( group 1 , n = 38 ) or CC-PT ( group 2 , n = 37 ) groups . The primary endpoint was intraoperative blood loss . The secondary endpoints included hepatic transection time , total operating time , postoperative morbidity , mortality , length of intensive care unit and hospital stays , and liver function . Results The characteristics of the two patient groups were closely matched . The Pringle maneuver was not used in RF-PT patients . The blood loss of the RF-PT group , total or during transection , was significantly lower than that of the CC-PT group ( 385 vs. 545 ml , p = 0.001 ; 105 vs. 260 ml , p = 0.000 , respectively ) . Compared with CC-PT patients , the morbidity of the RF-PT group was lower though not statistically significant ( 28.9 vs. 38.8 % , p = 0.197 ) . One death occurred in the RF-PT group 12 days postoperative due to a large area cerebral embolism . Conclusion RF-PT is a safe and feasible surgical resection method for patients with cirrhosis and concomitant HCC . In addition , RF-PT results in lower blood loss and lower morbidity than the CC technique during liver resection Liver surgery is still associated with a high rate of morbidity and mortality . We aim ed to compare different haemodynamic treatments in liver surgery . In a prospect i ve , blinded , r and omised , controlled pilot trial patients undergoing liver resection were r and omised to receive haemodynamic management guided by conventional haemodynamic parameters or by oesophageal Doppler monitor ( ODM , CardioQ-ODM ) or by pulse power wave analysis ( PPA , LiDCOrapid ) within a goal -directed algorithm adapted for liver surgery . The primary endpoint was stroke volume index before intra-operative start of liver resection . Secondary endpoints were the haemodynamic course during surgery and postoperative pain levels . Due to an unbalance in the extension of the surgical procedures with a high rate of only minor procedures the conventional group was dropped from the analysis . Eleven patients in the ODM group and 10 patients in the PPA group were eligible for statistical analysis . Stroke volume index before start of liver resection was 49 ( 37 ; 53 ) ml/m2 and 48 ( 41 ; 56 ) ml/m2 in the ODM and PPA group , respectively ( p=0.397 ) . The ODM guided group was haemodynamically stable as shown by ODM and PPA measurements . However , the PPA guided group showed a significant increase of pulse-pressure-variability ( p=0.002 ) that was not accompanied by a decline of stroke volume index displayed by the PPA ( p=0.556 ) but indicated by a decline of stroke volume index by the ODM ( p<0.001 ) . The PPA group had significantly higher postoperative pain levels than the ODM group ( p=0.036 ) . In conclusion , goal -directed optimization by ODM and PPA showed differences in intraoperative cardiovascular parameters indicating that haemodynamic optimization is not consistent between the two monitors . Trial Registration IS RCT N.com IS RCT Use of a saline‐linked radiofrequency coagulator ( dissecting sealer ) has been suggested to reduce blood loss during hepatic resection . A r and omized clinical trial was conducted to assess the effects of using the device on the amount of blood loss BACKGROUND / AIMS There is experimental evidence that the liver can safely tolerate a cycle involving application of the Pringle maneuver for 30 minutes each time . METHODOLOGY One hundred and twenty patients who underwent elective hepatectomy were r and omly assigned to two groups of intermittent occlusion ( 30-min or 15-min Pringle group , n=60 each ) . A synthetic protease inhibitor ( gabexate mesilate , GM , 2 mg/kg/h ) was administered to pharmacologically alleviate visceral congestion , accompanied by hepatic pedicle clamping . Intraoperative data , liver function parameters and portal plasma levels of the inflammatory cytokine , interleukin (IL)-6 ( a marker reflecting the status of visceral congestion ) , were examined as well as the postoperative course . Additionally , ten more patients r and omly underwent right hepatectomy without GM , in order to clarify the influence of this agent on the present outcomes . RESULTS The two groups of patients were comparable in terms of preoperative assessment s , hepatic inflow occlusion time , extent of resection and background liver conditions . The 30-min Pringle group showed less blood loss during surgery ( p=0.02 ) with a tendency for better postoperative mortality and morbidity . The postoperative liver functions were similar between the two groups . The portal plasma levels of IL-6 during pedicle clamping did not differ significantly between the two groups . When GM was not used , the 30-min intermittent Pringle maneuver induced a two-fold rise in serum transaminase levels on day 1 compared with the 15-min group . CONCLUSIONS Our study indicates that intermittent application of the Pringle maneuver for 30 minutes each time can be accomplished effectively and safely for human hepatectomy , when combined with use of a protease inhibitor Background Blood loss and the requirement of blood transfusions during liver transection have been shown to correlate well with higher morbidity and mortality rates and a worse prognosis . Various devices for liver parenchymal transection have been developed to reduce intraoperative blood loss . The goal of this study is to evaluate the safety and effectiveness of BiClamp ® forcep transection compared to a clamp crushing technique in patients undergoing liver resection . Methods / Design This study will include patients 18 years and older scheduled for hepatectomy with hepatic vascular exclusion who give informed consent . A sample size of 48 patients in each r and omization arm will be calculated to detect a difference in the reduction of blood loss of approximately 200 ml ( 90 % power and α = 0.05 ( two-tailed ) ) . The primary efficacy endpoint of the trial will be the total intraoperative blood loss based on the r and omized dissection technique . The statistical analysis is based on the intention-to-treat population . Patients will be followed up on for three months for complications and adverse events . Discussion This prospect i ve , single-center , r and omized controlled , single-blinded , two-group parallel trial is design ed to assess the efficacy and safety of BiClamp forcep hepatectomy versus clamp crushing for parenchymal transection during elective hepatic resection . Trial registration This trial was registered with Clinical trials.gov ( identifier : NCT02197481 ) on 15 July 2014 Fast-track ( FT ) programs have been applied in colorectal surgery for years . But in liver surgery , role of FT programs has not been fully established . So , a perspective study was performed in our center . A total of 297 hepatocellular carcinoma patients were r and omized into FT and non-FT ( NFT ) group ( n = 135 and 162 , respectively ) according to perioperative managements . Operation time , anhepatic phase and intraoperative blood loss were all significantly reduced in FT group ; besides , first exhaust time after operation and hospital stay were also shortened significantly . Spearman correlation showed that operation time was positively correlated with four parameters , including the anhepatic phase , the intraoperative blood loss during surgery , the hospital day and the first exhaust time after surgery . The anhepatic phase was also positively correlated with the intraoperative blood loss during surgery . Besides , the hospital day was positively correlated with the intraoperative blood loss during surgery and the first exhaust time after surgery . FT postoperative management was the only predictor of the shorter first exhaust time after operation and the shorter hospital day . No total postoperative complication , readmission and postoperative mortality were observed . Our data indicated that FT programs were safe and effective in hepatectomy Background The success of hepatectomy can be associated with intraoperative blood loss because massive blood loss causes a poor prognosis . This study was design ed to evaluate the effect of infrahepatic inferior vena cava ( IVC ) clamping on the bleeding amount during hepatectomy . Methods Eighty-five patients scheduled to undergo hepatic resection were r and omly assigned to the IVC clamping or an IVC nonclamping group according to age , indocyanine green retention rate at 15 minutes , operative procedure , and number of tumors by prospect i ve , r and omized method . All analyses were compared by Mann-Whitney U test . Results Forty-three patients were assigned to the IVC clamping group and 42 to the nonclamping group ( IVC clamping group vs. non-clamping ) : total blood loss ( 499 vs. 584 ml ; p = 0.567 ) , amount of bleeding during hepatectomy ( 233 vs. 285 ml ; p = 0.474 ) , amount of bleeding during hepatectomy/area of dissection ( 4.9 vs. 6.6 ml/cm2 ; p = 0.63 ) , CVP difference ( −3 cmH2O vs. −1 cmH2O ; p < 0.01 ) , and diameter of the right hepatic vein ( −2.2 cm vs. 0 ; p < 0.01 ) . Conclusions Although we had speculated that infrahepatic IVC clamping would reduce blood loss during hepatectomy , we failed to demonstrate any beneficial effects in this clinical setting with low CVP Objective : To evaluate the efficacy of fibrin sealant in reducing resection surface-related complications in liver surgery . Background : Bile leakage , bleeding , and abscess formation are major resection surface-related complications after liver resection . It is unclear whether application of fibrin sealant to the resection surface is effective in reducing these complications . Methods : In a multicenter , r and omized trial in 310 noncirrhotic patients undergoing liver resection , we compared prophylactic application of fibrin sealant to the resection surface ( 156 patients ) with no application of fibrin sealant ( 154 patients ) . In addition to clinical assessment s , patients underwent protocol ized computerized tomography ( CT ) scan 1 week postoperatively . Primary endpoint was a composite of postoperative resection surface-related complications ( bile leakage , bleeding , or abscess ) , as adjudicated by a clinical -events committee that was unaware of the study -group assignments . Results : Overall rate of resection surface-related complications was not different between the 2 groups : 24 % ( 38/156 patients ) in the fibrin sealant group and 24 % ( 37/154 patients ) in the control group . Bile leakage was detected in 14 % of patients in the fibrin sealant group and in 14 % of controls . CT scans showed a fluid collection at the resection surface 100 mL or more in 28 % of patients in the fibrin sealant group and in 26 % of controls ( P = 0.800 ) . The rate of re interventions for resection surface-related complications ( 12 % vs 10 % ; P = 0.492 ) and severity of complications did also not differ between the 2 groups . Conclusions : This r and omized multicenter trial shows that prophylactic application of fibrin sealant at the resection surface after liver resections does not lead to a reduction in the incidence or severity of postoperative bile leakage or other resection surface-related complications ( Controlled trial number , IS RCT N85205641 ) Mixed treatment comparison ( MTC ) meta- analysis is a generalization of st and ard pairwise meta- analysis for A vs B trials , to data structures that include , for example , A vs B , B vs C , and A vs C trials . There are two roles for MTC : one is to strengthen inference concerning the relative efficacy of two treatments , by including both ' direct ' and ' indirect ' comparisons . The other is to facilitate simultaneous inference regarding all treatments , in order for example to select the best treatment . In this paper , we present a range of Bayesian hierarchical models using the Markov chain Monte Carlo software WinBUGS . These are multivariate r and om effects models that allow for variation in true treatment effects across trials . We consider models where the between-trials variance is homogeneous across treatment comparisons as well as heterogeneous variance models . We also compare models with fixed ( unconstrained ) baseline study effects with models with r and om baselines drawn from a common distribution . These models are applied to an illustrative data set and posterior parameter distributions are compared . We discuss model critique and model selection , illustrating the role of Bayesian deviance analysis , and node-based model criticism . The assumptions underlying the MTC models and their parameterization are also discussed 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 Various devices have been developed to facilitate liver transection and reduce blood loss in liver resections . None of these has proven superiority compared with the classical clamp‐crushing technique . This r and omized clinical trial compared the effectiveness and safety of stapler transection with that of clamp‐crushing during open liver resection BACKGROUND In patients with cirrhosis excessive hemorrhage and the need for blood transfusion are associated with increased postoperative morbidity and mortality as well as a poor long-term outcome . Saline-linked radiofrequency dissecting sealer ( TissueLink ) is a recent advance in technology that improves hemostasis during difficult liver resections . Preliminary studies have shown that this technique reduces blood loss without inflow occlusion . PATIENTS AND METHODS A controlled study was performed on 122 consecutive patients with cirrhosis who underwent liver resection for hepatocytotic carcinoma . The outcomes of liver transection with clamp crushing and TissueLink were compared to evaluate which strategy is most beneficial to the patients . RESULTS Both intraoperative blood loss and blood transfusion requirements were significantly higher in the crushing clamp group than in the TissueLink group ( P = 0.047 and P = 0.031 , respectively ) . In addition , a significantly higher number of patients required a blood transfusion in the crushing clamp group ( P < 0.001 ) . However , the transection time was significantly faster in the crushing clamp group than in the TissueLink group ( P < 0.001 ) . The number of patients that required Pringle 's maneuver was markedly higher in the crushing clamp group ( P < 0.001 ) . In addition , the hemostasis time was significantly longer in the crushing clamp group ( P < 0.001 ) . The serum aspartate aminotransferase levels 3 and 7 days after surgery were significantly higher in the crushing clamp group than in the TissueLink group ( P = 0.035 and P = 0.003 , respectively ) . Serum total bilirubin levels were markedly increased 3 days after surgery in the crushing clamp group than in the TissueLink group ( P = 0.011 ) . Biliary leakage occurred in a higher number of crushing clamp patients ( six ) than TissueLink patients ( three ) , although this difference was not significant . The operative morbidity not including biliary leakage was higher in the crushing clamp group than the TissueLink group ( nine patients versus five patients , respectively ) . CONCLUSION This study reveals that the TissueLink procedure has beneficial effects during liver transection under cirrhotic conditions in terms of blood loss and reperfusion-related liver injury . However , this procedure requires a significantly longer transection time of the parenchyma Ninety-seven patients undergoing elective liver resection through a subcostal incision were assigned to large-dose aprotinin treatment or placebo in a double-blind , prospect i ve , r and omized fashion . R and omization was stratified by diagnosis : ( a ) cancer in cirrhosis , ( b ) cancer in healthy liver , and ( c ) benign tumor in healthy liver . Intraoperative blood loss , percentage of transfused patients , and total transfusion requirement per group were significantly lower in the aprotinin group than in the placebo group ( 1217 + /- 966 mL vs 1653 + /- 1221 mL , P = 0.048 ; 17 % vs 39 % , P = 0.02 ; 30 vs 77 red blood cell packs , P = 0.015 , respectively ) . Assessment of hematological markers ( a ) prior to surgery , ( b ) at the end of surgery , and ( c ) 24 h after surgery showed an identical intraoperative increase in thrombin-antithrombin III complexes in patients of both groups ( P = 0.86 ) , which indicates a similar activation of coagulation . Intraoperative hyperfibrinolysis was significantly less pronounced in the aprotinin group than in the placebo group ( P = 0.0002 and P = 0.004 for D-dimers and fibrinogen , respectively ) . No adverse drug effects were detected ( circulatory disturbances , deep venous thrombosis , increase in serum creatinine ) . These results suggest that aprotinin significantly reduces blood loss and transfusion requirement in patients undergoing elective liver resection through a subcostal incision . ( Anesth Analg 1997;84:875 - 81 BACKGROUND The Pringle manoeuvre and ischaemic preconditioning are applied to prevent blood loss and ischaemia-reperfusion injury , respectively , during liver surgery . In this prospect i ve clinical trial we report on the intraoperative haemodynamic effects of the Pringle manoeuvre alone or in combination with ischaemic preconditioning . METHODS Patients ( n=68 ) were assigned r and omly to three groups : ( i ) resection with the Pringle manoeuvre ; ( ii ) with ischaemic preconditioning before the Pringle manoeuvre for resection ; ( iii ) without pedicle clamping . RESULTS Following the Pringle manoeuvre the mean arterial pressure increased transiently , but significantly decreased after unclamping as a result of peripheral vasodilation . Ischaemic preconditioning improved cardiovascular stability by lowering the need for catecholamines after liver reperfusion without affecting the blood sparing benefits of the Pringle manoeuvre . In addition , ischaemic preconditioning protected against reperfusion-induced tissue injury . CONCLUSIONS Ischaemic preconditioning provides both better intraoperative haemodynamic stability and anti-ischaemic effects thereby allowing us to take full advantage of blood loss reduction by the Pringle manoeuvre HYPOTHESIS Blood loss in hepatic resection is an important determinant of operative outcome . OBJECTIVE To clarify whether reducing the tidal volume would be effective in decreasing blood loss during liver transection . DESIGN R and omized controlled trial . SETTING University hospital . PATIENTS Eighty patients scheduled to undergo hepatic resection were r and omly assigned to receive liver transection under normoventilation ( n = 40 ) or hypoventilation ( n = 40 ) . INTERVENTIONS During liver transection , in the normoventilation group , the tidal volume was 10 mL/kg and the respiratory rate was 10/min ; in the hypoventilation group , the tidal volume was reduced to 4 mL/kg and respiratory rate was increased to 15/min . Liver transection was performed under total or selective inflow occlusion . MAIN OUTCOME MEASURE Blood loss . RESULTS Between the normoventilation and hypoventilation groups , no significant difference was found in total blood loss ( median [ range ] : 630 mL [ 72 - 3600 mL ] vs 630 mL [ 120 - 3520 mL ] ; P = .44 ) or blood loss per transection area ( median [ range ] : 7.3 mL/cm(2 ) [ 1.2 - 55.4 mL/cm(2 ) ] vs 9.8 mL/cm(2 ) [ 0.9 - 79.9 mL/cm(2 ) ] ; P = .55 ) . During liver transection , the central venous pressure was significantly reduced in the hypoventilation group than in the normoventilation group ( median [ range ] : -0.7 cm H(2)O [ -3.0 to 1.8 cm H(2)O ] vs -0.2 cm H(2)O [ -4.0 to 2.0 cm H(2)O ] ; P = .007 ) . The maximum end-tidal carbon dioxide level in the hypoventilation group was significantly higher than that in the normoventilation group ( maximum [ range ] : 50 mm Hg [ 28 - 66 mm Hg ] vs 37 mm Hg [ 27 - 60 mm Hg ] ; P<.001 ) . Transection time , postoperative liver function , hospitalization length , morbidity , and mortality were similar in the 2 groups . CONCLUSION This r and omized trial suggested no beneficial effect of reduction of tidal volume on bleeding during hepatic resection Objective : To evaluate whether ischemic preconditioning ( IP ) with continuous clamping or intermittent clamping ( IC ) of the portal triad confers better protection during liver surgery . Summary Background Data : IP and IC are distinct protective approaches against ischemic injury . Since both strategies proved to be superior in r and omized controlled trials ( RCTs ) to continuous inflow occlusion alone , we design ed a RCT to compare IP and IC in patients undergoing major liver resection . Methods : Noncirrhotic patients undergoing major liver resection were r and omized to receive IP with inflow occlusion ( n = 36 ) or IC ( n = 37 ) . Primary endpoints were postoperative liver injury and intraoperative blood loss . Postoperative liver injury was assessed by peak values of AST ( alanine aminotransferase ) and ALT ( aspartate aminotransferase ) , as well as the area under the curve ( AUC ) of the postoperative transaminase course . Secondary endpoints included resection time , the need of blood transfusion , ICU , and hospital stay as well as postoperative complications and mortality . Results : Both groups were comparable regarding demographics , ASA score , type of hepatectomy , duration of inflow occlusion ( range , 30–75 minutes ) , and resection surface . The transection-related blood loss was 146 versus 250 mL ( P = 0.008 ) , and when st and ardized to the resection surface 1.2 versus 1.8 mL/cm2 ( P = 0.01 ) for IP and IC , respectively . Although peak AST , AUCAST , and AUCALT were lower for IC , the differences did not reach statistical significance . Overall ( 42 % vs. 38 % ) and major ( 33 vs. 27 % ) postoperative complications as well as median ICU ( 1 vs. 1 day ) and hospital stay ( 10 vs. 11 days ) were similar between both groups . Conclusions : Both IP and IC appear to be equally effective in protecting against postoperative liver injury in noncirrhotic patients undergoing major liver resection . However , IP is associated with lower blood loss and shorter transection time . Therefore , both strategies can be recommended for noncirrhotic patients undergoing liver resection OBJECTIVE To evaluate the effects of acute normovolemic hemodilution ( ANH ) combined with controlled hypotension on reducing heterogeneous transfusion and safety during liver tumorectomy . METHODS Thirty patients undergoing elective liver tumorectomy were r and omly divided into 3 groups ( 10 each ) , namely ANH group ( group A ) , ANH combined with controlled hypotension group ( group B ) and control group ( group C ) . All the patients were anesthetized via endotracheal intubation . Before the operation , ANH was performed in groups A and B after anesthesia induction , and controlled hypotension was initiated in group B during tumorectomy . Blood transfusion and fluid infusion were carried out routinely in group C. Hb and Hct were measured before operation , after ANH , and immediately , 1 day and 7 days after the operation . The difference in intraoperative blood loss and heterogeneous blood transfusion volume in the 3 groups was observed . RESULTS In group A , heterogeneous blood transfusion was avoided in 6 cases and but given in the other cases for an average of 400 ml . In group C , every patient received heterogeneous blood transfusion ( 664.8-/+248.1 ml ) , but none of the patients received heterogeneous blood in group B. The difference in transfusion volume between the 3 groups was significant ( P<0.01 ) . Hemodynamics was basically stable during operation in the 3 groups . CONCLUSION ANH combined with controlled hypotension is safe and effective for decreasing and even avoiding homologous blood transfusion in liver tumorectomy BACKGROUND Acute normovolemic hemodilution ( ANH ) decreases transfusion rates but adds to the complexity of anesthetic management during hepatectomy . A r and omized controlled trial was conducted to determine if selecting patients for ANH using a transfusion nomogram improves management and re source use compared with selection using extent of resection . STUDY DESIGN One hundred fourteen patients undergoing partial hepatectomy were r and omized to a clinical arm ( ANH used for resection of ≥ 3 liver segments ) or a nomogram arm ( ANH used for predicted probability of transfusion ≥ 50 % based on a previously vali date d nomogram ) . The primary end point was appropriate management , defined as avoidance of ANH in patients at low risk or use of ANH in patients at high risk for allogeneic red blood cell transfusions . RESULTS Between September 2009 and May 2011 , 58 patients were r and omized to the clinical arm and 56 to the nomogram arm . Demographics , diagnoses , extent of resection , blood loss , and incidence and grade of complications did not differ between the 2 groups . There were no differences in perioperative transfusions or laboratory values . Nomogram-based allocation did not change appropriate management overall ( 80 % vs 76 % in the clinical arm ; p = 0.65 ) , but did result in comparable perioperative outcomes and a trend toward decreased ANH use ( 30 % vs 47 % ; p = 0.09 ) , particularly in low blood loss ( estimated blood loss ≤ 400 mL ) cases ( 12 % vs 25 % ; p = 0.04 ) . CONCLUSIONS Although allocation of intraoperative management using a transfusion nomogram did not improve appropriate management overall , it more effectively identified low blood loss cases and reduced ANH use in patients least likely to benefit We introduce the series of 7 tutorial papers on evidence synthesis methods for decision making , based on the Technical Support Documents in Evidence Synthesis prepared for the National Institute for Health and Clinical Excellence ( NICE ) Decision Support Unit . Although oriented to NICE ’s Technology Appraisal process , which examines new pharmaceutical products in a cost-effectiveness framework , the methods presented throughout the tutorials are equally relevant to clinical guideline development and to comparisons between medical devices , or public health interventions . Detailed guidance is given on how to use the other tutorials in the series , which propose a single evidence synthesis framework that covers fixed and r and om effects models , pairwise meta- analysis , indirect comparisons , and network meta- analysis , and where outcomes expressed in several different reporting formats can be analyzed without recourse to normal approximations . We describe the principles of evidence synthesis required by the 2008 revision of the NICE Guide to the Methods of Technology Appraisal and explain how the approach proposed in these tutorials was design ed to conform to those requirements . We finish with some suggestions on how to present the evidence , the synthesis methods , and the results We have studied the use of ultrapurified polymerized bovine haemoglobin ( HBOC-201 ) in patients undergoing preoperative haemodilution before liver resection . After autologous blood donation of 1 litre , 12 patients ( six males , six females , mean age 59 ( 35 - 69 ) yr ) received Ringer 's lactate solution 2 litre and , in a r and om design , 6 % hydroxyethyl starch 70,000/0.5 ( HES ) 3 ml kg-1 or HBOC-201 0.4 g kg-1 within 30 min . Blood sample s were obtained for blood chemistry , co-oximetry , haematology , coagulation profiles and immunology examinations before operation , on the day of surgery , on days 2 - 4 and 7 after operation , on the discharge day and 3 months after operation . There were no differences in patient characteristics , blood loss , amount of solutions infused , transfused allogeneic blood or duration of hospital stay . There were no local or systemic allergic reactions with infusion of HES or HBOC-201 . Patients receiving HBOC-201 developed more pronounced leucocytosis and reticulocytosis during the early postoperative days compared with HES-treated patients . The mean maximum plasma haemoglobin concentration was 1.0 ( SD 0.2 ) g dl-1 at the end of infusion of HBOC-201 was 8.5 h. Patients in both groups experienced temporary changes in liver enzymes and coagulation variables which returned to normal before discharge . Urinalysis revealed no difference between groups and no free haemoglobin was detected in urine . Patients receiving HBOC-201 showed no IgE and only a slight increase in IgG titres to HBOC-201 on the day of discharge ; these were not detectable at 3 months . Single-dose administration of HBOC-201 was well tolerated by patients undergoing elective liver resection surgery and appears to be safe as a substitute during preoperative haemodilution Background Haemostasis in liver surgery remains a challenge despite improved resection techniques . Oozing from blood vessels too small to be ligated necessitate a treatment with haemostats in order to prevent complications attributed to bleeding . There is good evidence from r and omised trials for the efficacy of fibrin sealants , on their own or in combination with a carrier material . A new haemostatic device is Sangustop ® . It is a collagen based material without any coagulation factors . Pre- clinical data for Sangustop ® showed superior haemostatic effect . This present study aims to show that in the clinical situation Sangustop ® is not inferior to a carrier-bound fibrin sealant ( Tachosil ® ) as a haemostatic treatment in hepatic resection . Methods / Design This is a multi-centre , patient-blinded , intra-operatively r and omised controlled trial . A total of 126 patients planned for an elective liver resection will be enrolled in eight surgical centres . The primary objective of this study is to show the non-inferiority of Sangustop ® versus a carrier-bound fibrin sealant ( Tachosil ® ) in achieving haemostasis after hepatic resection . The surgical intervention is st and ardised with regard to devices and techniques used for resection and primary haemostasis . Patients will be followed-up for three months for complications and adverse events . Discussion This r and omised controlled trial ( ESSCALIVER ) aims to compare the new collagen haemostat Sangustop ® with a carrier-bound fibrin sealant which can be seen as a " gold st and ard " in hepatic and other visceral organ surgery . If non-inferiority is shown other criteria than the haemostatic efficacy ( e.g. costs , adverse events rate ) may be considered for the choice of the most appropriate treatment . Trial Registration BACKGROUND Acute normovolemic hemodilution ( ANH ) has been widely used to prevent the massive blood loss during hepatic carcinoma . The influences of ANH on coagulation function are still controversy , especially in elderly patients . The study observed ANH effects on coagulation function and fibrinolysis in elderly patients undergoing the disease . MATERIAL S AND METHODS Thirty elderly patients ( aged 60 - 70 yr ) with liver cancer ( ASA I or II ) taken hepatic carcinectomy from February 2007 to February 2008 were r and omly divided into ANH group ( n=15 ) and control group ( n=15 ) . After tracheal intubation , patients in ANH group and control group were infused with 6 % hydroxyethyl starch ( 130/0.4 ) and Ringer 's solution , respectively . Blood sample s were drawn from patients in both groups at five different time points : before anesthesia induction ( T1 ) , 30 min after ANH ( T2 ) , 1 h after start of operation ( T3 ) , immediately after operation ( T4 ) , and 24 h after operation ( T5 ) . Then coagulation function , soluble fibrin monomer complex ( SFMC ) , prothrombin fragment ( F1 + 2 ) , and platelet membrane glycoprotein ( CD62P and activated GP IIb/GP IIIa ) were measured . RESULTS The perioperative blood loss and allogeneic blood transfusion were recorded during the surgery . The perioperative blood loss was not significantly different between two groups ( p>0.05 ) , but the volume of allogeneic blood transfusion in ANH group was significantly less than in control group ( 350.0±70.7 ) mL vs. ( 457.0±181.3 ) mL ( p<0.01 ) . Compared with the data of T1 , the prothrombin time ( PT ) and activated partial thromboplastin time ( APTT ) measured after T3 were significantly longer ( p<0.05 ) in both groups , but within normal range . There were no significant changes of thrombin time ( TT ) and D-dimer between two groups at different time points ( p>0.05 ) . SFMC and F1 + 2 increased in both groups , but were not statistically significant . PAC-1-positive cells and CD62P expressions in patients of ANH group were significantly lower than those at T1 ( p<0.05 ) and T2-T5 ( p>0.05 ) . CONCLUSIONS ANH has no obvious impact on fibrinolysis and coagulation function in elderly patients undergoing resection of liver cancer . The study suggested that ANH is safe to use in elderly patients and it could reduce allogeneic blood transfusion Introduction . Operative blood loss is still a great obstacle to liver resection , and various topical hemostatic agents were introduced to reduce it . The aim of the current study is to evaluate effects of 3 different types of these agents . Methods . In this r and omized clinical trial , 45 patients undergoing liver resection were assigned to receive TachoSil , Surgicel , and Glubran 2 for controlling bleeding . Intraoperative and postoperative findings were compared between groups . Results . Postoperative bleeding ( 0 versus 33.3 % , P = 0.04 ) and drainage volume first day after surgery ( 281.33 ± 103.98 versus 150.00 ± 60.82 mL , P = 0.02 ) were significantly higher in Surgicel than in TachoSil group . Postoperative complications included bile leak ( 3 cases in Surgicel , 1 case in TachoSil and Glubran 2 ) , noninfectious collection ( 2 cases in TachoSil and Surgicel and 1 case in Glubran 2 ) , perihepatic abscess , and massive hematoma around hepatectomy site both in Surgicel group . There was no death during the study period . Conclusion . Due to higher complications in Surgicel group , its application as hemostatic agent after liver resection is not recommended . Better results in TachoSil in comparison to the other two are indicative of its better efficacy and superiority in controlling hemostasis BACKGROUND The aim of this trial was to confirm previous results demonstrating the efficacy and safety of a fixed combination tissue sealant versus argon beam coagulation ( ABC ) treatment in liver resection . METHODS This trial was design ed as an international , multicenter , r and omized , controlled surgical trial with 2 parallel groups . Patients were eligible for intra-operative r and omization after elective resection of ≥ 1 liver segment and primary hemostasis . The primary end point was the time to hemostasis after starting the r and omized intervention to obtain secondary hemostasis . Secondary end points were drainage duration , volume , and content . Adverse events were collected to evaluate the safety of treatments . The trial was registered internationally ( Eudract number 2008 - 006407 - 23 ) . RESULTS Among 119 patients ( 60 TachoSil and 59 ABC ) r and omized in 10 tertiary care centers in Europe , the mean time to hemostasis was less when TachoSil was used ( 3.6 minutes ) compared with ABC ( 5.0 minutes ; P = .0018 ) . The estimated ratio of mean time to hemostasis for TachoSil/ABC was 0.61 ( 95 % confidence interval , 0.47 - 0.80 ; P = .0003 ) . Postoperative drainage volume , drainage fluid , and drainage duration did not differ between the 2 groups . Mortality ( 2 vs 4 patients ) and adverse reactions ( 24 vs 28 patients ) for TachoSil versus ABC did not differ . CONCLUSION This trial confirmed that TachoSil achieved significantly faster hemostasis after liver resection compared with ABC . Postoperative morbidity and mortality remained unchanged between both groups OBJECTIVE To evaluate whether vascular inflow occlusion by the Pringle maneuver during hepatectomy can be safe and effective in reducing blood loss . SUMMARY BACKGROUND DATA Hepatectomy can be performed with a low mortality rate , but massive hemorrhage during surgery remains a potentially lethal problem . The Pringle maneuver is traditionally used during hepatectomy to reduce blood loss , but there is a potential harmful effect on the metabolic function of hepatocytes . There has been no prospect i ve r and omized study to determine whether the Pringle maneuver can decrease blood loss during hepatectomy , improve outcome , or affect the metabolism of hepatocytes . METHODS From July 1995 to February 1997 , we studied 100 consecutive patients who underwent hepatectomy for liver tumors . The patients were r and omly assigned to liver transection under intermittent Pringle maneuver of 20 minutes and a 5-minute clamp-free interval ( n = 50 ) , or liver transection without the Pringle maneuver ( n = 50 ) . The surface area of liver transection was measured and blood loss during transection per square centimeter of transection area was calculated . Routine liver biochemistry , arterial ketone body ratio ( AKBR ) , and the indocyanine green ( ICG ) clearance test were done . RESULTS The two groups were comparable in terms of preoperative liver function and in the proportion of patients having major hepatectomy . The Pringle maneuver result ed in less blood loss per square centimeter of transection area ( 12 mL/cm2 vs. 22 mL/cm2 , p = 0.0001 ) , a shorter transection time per square centimeter of transection area ( 2 min/cm2 vs. 2.8 min/cm2 , p = 0.016 ) , a significantly higher AKBR in the first 2 hours after hepatectomy , lower serum bilirubin levels in the early postoperative period , and , in cirrhotic patients , higher serum transferrin levels on postoperative days 1 and 8 . The complication rate , the hospital mortality rate , and the ICG retention at 15 minutes on postoperative day 8 were equal for the two groups . CONCLUSION Performing the Pringle maneuver during liver transection result ed in less blood loss and better preservation of liver function in the early postoperative period . This is probably because there was less hemodynamic disturbance induced by the bleeding The intermittent Pringle manoeuvre ( IPM ) is commonly applied during liver resection . Few r and omized trials have addressed its effectiveness in reducing blood loss and the results have been conflicting . The present study investigated the hypothesis that IPM could reduce blood loss during liver resection by 50 per cent Several techniques have been described for safe dissection of the liver parenchyma . The aim of this study was to evaluate the feasibility and effectiveness of combining two different electronic devices , the ultrasonic dissector and the harmonic scalpel , during hepatic resection . One hundred consecutive patients who underwent liver resection between January and December 2004 were enclosed in the study . Patients requiring concomitant colic resection or biliary-enteric anastomosis were excluded from the study . Operative variables ( type of procedure , operating time , Pringle time , blood losses , transfusions , and histological tumor exposure at the transection surface ) , hospital stay , and complications were recorded . The extent of hepatic resection was a minor resection in 31 and major in 69 cases . Median blood loss was 500 mL ( range , 100–2000 mL ) and the Pringle maneuver was used in 58 patients . Median operative time was 367 minutes ( range , 150–660 minutes ) . Hepatic resection was performed in 32 cirrhotic livers . Surgical complications included one postoperative hemorrhage and two bile leaks . The overall morbidity and mortality rate was 14 and 1 per cent , respectively . In conclusion , the combined use of these electronic devices allows liver resection to be safely performed , even in cirrhotic patients , with the advantage of reducing surgical complications . A prospect i ve r and omized trial is needed to clarify the clinical benefits of liver resections performed combining these two devices BACKGROUND Excessive intraoperative blood loss and the possible requirement for blood transfusion are major problems in hepatic resection for liver tumors . The decrease of blood loss is a goal in liver surgery , and several technical developments have been introduced for this purpose . The aim of this prospect i ve r and omized study was to compare the use of the Cavitron Ultrasonic Surgical Aspirator ( CUSA ) with a radiofrequency-based bipolar hemostatic sealer versus CUSA with st and ard bipolar cautery ( BC ) in patients undergoing hepatic resection . METHODS One hundred nine patients with liver tumors were r and omized to undergo hepatic transection via CUSA with a bipolar sealer ( Aquamantys 2.3 Bipolar Sealer ; n = 55 ) or BC ( n = 54 ) . Blood loss during parenchymal transection and speed of transection were the primary end points , whereas the degree of postoperative liver injury and morbidity were secondary end points . RESULTS Compared with the BC group , the bipolar sealer showed lesser blood loss during transection and blood loss divided by resection area ( P = .0079 and .0008 , respectively ) , shorter transection time ( P = .0025 ) , faster speed of transection ( P < .0001 ) , and fewer ties and ties divided by resection area required during transection ( P < .0001 ) . CONCLUSION CUSA with a bipolar sealer is superior to CUSA with st and ard BC for various hepatectomy in terms of less blood loss and faster speed of transection , with no increase in morbidity Introduction : Strategies to reduce red blood transfusion utilization in cancer patients undergoing operation are needed . Hypothesis : Postoperative epoetin alfa ( 40,000 units subcutaneous on postoperative days 1 and 7 ) is associated with improved hematologic parameters in patients undergoing major abdominal surgery for malignancy . Material s and Methods : Prospect i ve , blinded , r and omized trial of epoetin alfa ( 40,000 units subcutaneous on postoperative days 1 and 7 ) versus placebo in patients undergoing major abdominal operation for malignancy . Primary endpoints were immature reticulocyte fraction , reticulocyte count , and hemoglobin , which were measured on postoperative days 4 , 7 , and between 14 and 20 . Secondary endpoints were transfusions and complications in the 2 groups . Results : Forty patients were enrolled . There were no significant differences in immature reticulocyte fraction ( P = 0.78 ) , reticulocyte count ( P = 0.42 ) , or hemoglobin ( 0.35 ) in patients r and omized to receive epoetin alfa versus placebo . There was no significant difference in red blood cell transfusion rate or postoperative complications in patients who received epoetin alfa compared with placebo . Discussion : The use of postoperative epoetin alfa ( 40,000 units subcutaneous on postoperative days 1 and 7 ) in patients undergoing major operation for abdominal or pelvic malignancy is not supported by this r and omized trial BACKGROUND Control of hepatic inflow is a key manoeuvre during right hepatectomy and has traditionally been achieved by extrahepatic dissection of the component right portal inflow structures at the hepatic hilum . An alternative technique is the anterior intrahepatic approach ( AIA ) , in which the Glissonian sheath is isolated within the substance of the liver during parenchymal transection and secured using an endovascular stapling device . This study evaluates the intrahepatic , extra-Glissonian technique in comparison with classical extrahepatic dissection ( EHD ) in right hepatectomy . METHODS A retrospective case-controlled study referring to a 20-year period identified 342 consecutive patients who underwent right hepatectomy for colorectal liver metastases from a prospect ively compiled data base . The AIA to right hepatectomy was used in 182 of these patients and the extrahepatic approach in 160 . The two groups were matched for age , gender , stage of primary tumour and number and size of metastases . Outcome measures included safety factors ( bleeding , bile duct injury and gun failure ) , operative duration , oncological margin , morbidity and mortality . RESULTS There were no significant differences between the two groups in terms of operative duration ( 240 min vs. 260 min ) or postoperative change in haemoglobin ( 1.3 g/dl vs. 1.4 g/dl ) . The AIA was associated with lower operative blood loss ( 355 ml vs. 425 ml ; P < or = 0.001 ) , a reduced rate of significant morbidity ( 14.6 % vs. 23.1 % ; P = 0.005 ) , better R0 resection rates ( 93 % vs. 89 % ; P = 0.014 ) and a lower 90-day mortality rate ( 3 % vs. 7 % ; P = 0.046 ) . There was one minor bile leak in each group , two clinical ly significant bile leaks requiring endoscopic retro grade cholangiopancreatography and stenting in the extrahepatic group , and a further persistent bile leak requiring biliary reconstruction in each group . In two instances the endovascular stapler misfired . Both cases were dealt with at the time of surgery with no further sequelae . The length of hospital stay was equivalent in the two groups ( 8 days vs. 9 days ) . CONCLUSIONS In selected patients , intrahepatic , extra-Glissonian stapled right hepatectomy is feasible , safe and avoids the need for EHD . The anterior approach to right hepatectomy may achieve outcomes at least as good as those associated with the classical extrahepatic approach Background Hepatic veins remain patent during complete inflow occlusion ( CIO ) and bleeding from them may continue . Occlusion of the inferior vena cava ( ICV ) during CIO may reduce blood loss from hepatic veins . This study was design ed to compare the overall outcomes after application of CIO with or without occlusion of the ICV below the liver in complex mesohepatectomy for hepatocellular carcinoma ( HCC ) patients with cirrhosis . Material s and methods One hundred and eighteen ( 118 ) patients were r and omly assigned to CIO or a modified technique of hepatic vascular exclusion ( MTHVE ) . Hemodynamic parameters were evaluated and the amount of blood loss , measurement of liver enzymes , and postoperative progress were recorded . Results Blood loss during liver transection in CIO groups was significantly greater than that in MTHVE group ( P=0.046 ) . Thus , incidence of blood transfusion was significantly greater in patients of the CIO group ( P=0.041 ) . There were no significant differences in liver enzyme changes , bilirubin , or morbidity in the postoperative period between the two groups . Conclusions CIO with occlusion of the ICV below the liver is a safe , effective , and feasible technique during mesohepatectomy in HCC patients with cirrhosis . Excellent results were obtained with minimized bleeding , limited hepatic function damage , and low rate of postoperative complications OBJECTIVE The authors compared the intra- and postoperative course of patients undergoing liver resections under continuous pedicular clamping ( CPC ) or intermittent pedicular clamping ( IPC ) . SUMMARY BACKGROUND DATA Reduced blood loss during liver resection is achieved by pedicular clamping . There is controversy about the benefits of IPC over CPC in humans in terms of hepatocellular injury and blood loss control in normal and abnormal liver parenchyma . METHODS Eighty-six patients undergoing liver resections were included in a prospect i ve r and omized study comparing the intra- and postoperative course under CPC ( n = 42 ) or IPC ( n = 44 ) with periods of 15 minutes of clamping and 5 minutes of unclamping . The data were further analyzed according to the presence ( steatosis > 20 % and chronic liver disease ) or absence of abnormal liver parenchyma . RESULTS The two groups of patients were similar in terms of age , sex , nature of the liver tumors , results of preoperative assessment , proportion of patients undergoing major or minor hepatectomy , and nature of nontumorous liver parenchyma . Intraoperative blood loss during liver transsection was significantly higher in the IPC group . In the CPC group , postoperative liver enzymes and serum bilirubin levels were significantly higher in the subgroup of patients with abnormal liver parenchyma . Major postoperative deterioration of liver function occurred in four patients with abnormal liver parenchyma , with two postoperative deaths . All of them were in the CPC group . CONCLUSIONS This clinical controlled study clearly demonstrated the better parenchymal tolerance to IPC over CPC , especially in patients with abnormal liver parenchyma BACKGROUND The aim of this study was to investigate the effects of ulinastatin , a protease inhibitor , and blood transfusion on perioperative surgical complications , changes of systemic inflammatory response syndrome ( SIRS ) scores , and levels of interleukin-6 ( IL-6 ) , interleukin-8 ( IL-8 ) and tumour necrosis factor-α ( TNF-α ) in patients undergoing liver resection . MATERIAL S AND METHODS Patients aged 18 - 65 years were enrolled and divided into four groups ( 12 patients in each group ) : a control group , a group given ulinastatin ( UTI group ) , a group given blood transfusion ( BT group ) , and a group given both blood transfusion and ulinastatin ( BT+UTI group ) . Patients were r and omised to receive ulinastatin or not , whereas blood transfusion was administered based on a transfusion trigger . Ulinastatin was given at a dose of 100,000 units/10 kg , infused 15 min before allogeneic blood transfusion or after completion of the liver resection . The patients were followed up for 3 days to record surgical complications , SIRS scores and levels of IL-6 , IL-8 and TNF-α . RESULTS Forty-four patients were included in the data analysis . The SIRS rate ( SIRS scores≥2 ) was significantly higher in the BT groups than in the control group at 6 hours and on day 3 after surgery and was significantly lower in the BT+UTI group than in the BT group on day 3 after surgery . Allogeneic blood transfusion significantly increased and ulinastatin significantly decreased postoperative levels of IL-6 , IL-8 , and TNF-α . The length of stay in hospital was significantly longer in the BT groups than in the control group but was not significantly different between the BT+UTI and BT groups . CONCLUSION A single dose of ulinastatin before allogeneic blood transfusion may lower the rate of postoperative SIRS and levels of IL-6 , IL-8 and TNF-α associated with allogeneic blood transfusion and improve patients ' postoperative recovery Background Hepatic transection by Pean-clasia is the mainstream technique that can be used with different coagulators . Monopolar floating ball ( MFB ) is proposed for liver transection . Whether its value for liver transection is unclear , its efficiency as a coagulator only seems high . We compared in a prospect i ve r and omized study the st and ard Pean-clasia with bipolar forceps ( BF ) versus Pean-clasia with MFB in patients undergoing hepatic resection . Methods Seventy-six patients scheduled for hepatectomy were r and omized in two groups , according to the coagulator device : group A ( MFB , n = 38 ) and group B ( BF , n = 38 ) . The two groups were homogeneous in terms of tumor presentation and background liver features . Blood loss , blood transfusions , transection time , number of ligatures , drain discharge , drain bilirubin levels at third , fifth , and seventh postoperative day , and postoperative morbidity and mortality were prospect ively evaluated . Results No significant differences between groups A and B were seen in terms of blood transfusions ( 11.5 % versus 16.5 % ; p = 0.450 ) , blood loss/cm2 ( mean 7.2 versus 7.6 ml ; p = 0.450 ) , transection time/cm2 ( mean 2.1 versus 2.3 ; p = 0.070 ) , number of ligatures/cm2 ( mean 0.7 versus 0.7 ; p = 1 ) , drain discharge ( mean 55 versus 66.7 ml ; p = 0.451 ) , and drain bilirubin levels ( mean 1.9 versus 2.1 mg/dl ; p = 0.664 ) . No mortality or major morbidity was recorded in both groups . Conclusions This study showed that association of Pean-clasia with MFB was safe and minimized the blood loss during hepatic resection . However , MFB did not offer significant benefits over BF , while its cost is not negligible Background The duration of hepatic vascular inflow occlusion and the amount of intraoperative blood loss have significant negative impacts on postoperative morbidity , mortality and long-term survival outcomes of patients who receive partial hepatectomy for hepatocellular carcinoma ( HCC ) with cirrhosis . Aim This study aim ed to compare the perioperative outcomes of partial hepatectomy for HCC superimposed on hepatitis B-related cirrhosis using two different occlusion techniques . Methods A r and omized controlled trial was carried out to evaluate the impact of two different vascular inflow occlusion techniques . The postoperative short-term results were compared . Results During the study period , 252 patients received partial hepatectomy for HCC with cirrhosis . Of these patients , 120 were r and omized equally into two groups : the Pringle manoeuvre group ( n = 60 ) and the hemi-hepatic vascular inflow occlusion group ( n = 60 ) . The number of patients who had poor liver function on postoperative day 5 with ISLGS grade B or worse was 24 and 13 , respectively ( P = 0.030 ) . The postoperative complication rate was significantly higher in the Pringle manoeuvre group ( 40 versus 22 % , P = 0.030 ) . However , the Pringle manoeuvre group had significantly shorter operating time ( 116 versus 136 min , P = 0.012 ) although there was no significant difference in intraoperative blood loss between the two groups [ 200 ml ( range 10–5,000 ml ) versus 300 ml ( range 100–1,000 ml ) ; P = 0.511 ] . There was no perioperative mortality . Conclusions The results indicated that for patients with HCC with cirrhosis , hemi-hepatic vascular inflow occlusion was a better inflow occlusion method than Pringle manoeuvre BACKGROUND / AIMS To evaluate whether continuous hemihepatic inflow occlusion ( HHO ) during hepatectomy can be safer than and be as effective as intermittent total hepatic inflow occlusion ( THO ) in reducing blood loss . METHODOLOGY Eighty patients undergoing liver resections were included in a prospect i ve r and omized study comparing the intra- and postoperative course under THO ( n=40 ) or HHO ( n=40 ) . THO was performed with periods of 20 minutes of occlusion and 5 minutes of releasing , while HHO was performed with continuous occlusion . The surface area of liver transection , amount of blood loss , measurements of alanine aminotransferase ( ALT ) and aspartate aminotransferase ( AST ) , and postoperative evolution were recorded . RESULTS The two groups were similar at entry in terms of preoperative liver function and in the proportion of patients experiencing major hepatectomy . The total ischemic time of the two groups was similar ( p=0.37 ) , but the operative time in the THO group was longer than in the HHO group ( p=0.02 ) . No significant difference was found between the HHO and THO group in blood loss during liver parenchyma transection ( p=0.14 ) , the elevations of ALT and AST on the first postoperative day ( ALT : p=0.12 ; AST : p=0.66 ) and postoperative morbidity ( p=0.35 ) . CONCLUSIONS On the basis of our findings , if it is feasible , continuous HHO is recommended for complex liver resection Methods for combining data from several studies exist and appear to be quite useful . None satisfactorily addresses the question of what studies should be combined . This issue is the most serious method ological limitation . Even studies with statistically significant interaction might still be combined if the effect were in the same direction . Thus , substantial scientific input is required as to what criteria must be met by each potential study . Much can be learned from combining or pooling data but it must be done cautiously . Pooling exercises do not replace well design ed prospect i ve clinical trials . Efforts for establishing basic design criteria to allow for multicentre and multicountry trials to be more easily combined might be useful . Background Perioperative hemorrhage and postoperative bile leakage are severe complications of liver surgery . They may be related to the techniques used to divide the tissue . We design ed a r and omized clinical trial to compare the cavitron ultrasonic surgical aspirator ( CUSA ) and an endoscopic stapler device applied in routine clinical hepatic surgical practice . Methods All consecutive patients admitted for elective hepatic resective surgery — at least bisegmentectomy of the liver — were assessed for enrollment in the study . A total of 100 patients were subsequently r and omized . There was a good balance between the study groups concerning issues that may be of relevance for the perioperative and postoperative courses . The primary objective of the study was to achieve an approximately 25 % reduction in perioperative blood loss and postoperative bile leakage . Secondary outcome variables were operating time , general postoperative morbidity , length of hospital stay , and direct medical costs . Results The amount of perioperative or postoperative blood loss did not differ significantly between the two groups . We observed a trend toward shorter transection and operating time for patients in whom staplers were used , but the difference did not reach statistical signifcance . The postoperative courses were close to identical in the respective study arms with no difference in bile leakage rates or in the total morbidity profiles . The direct medical costs were nonsignificantly lower in the group where staplers were used for liver transection . Conclusions The results show that the use of endoscopic vascular staplers in liver surgery is feasible and safe . It offers an attractive alternative for division of the liver parenchyma during routine hepatic surgery , being comparable to the use of CUSA without adding extra costs A single center prospect i ve study was done to evaluate the role of hepatic portal pedicle clamping ( PC ) during right hepatectomy ( RH ) in patients with primary and secondary liver tumors . Cirrhotics were excluded . Two groups were compared for preoperative demographics including diagnosis , tumor size , portal vein embolization and liver enzymes , pre and postoperative hemoglobin levels , percentage of residual liver mass , morbidity and mortality , pedicle clamp time , intensive care unit stay , length of hospital stay and blood loss . We observed no significant difference in the analysis of the post-operative hemoglobin , liver enzymes , residual liver size , size of tumor resected , need for postoperative monitoring in ICU stay , length of hospital stay and blood loss . Mortality and morbidity were the same . None of the patients were transfused during surgery . Our findings show that pedicle clamping was beneficial 15 % of the time when uncontrolled intra-operative bleeding was encountered or in a subset of patients with peliosis , steatohepatitis , Jehovah Witness patient , and post-chemotherapy patients . However , its advantage has to be weighed against the disadvantages AIM To determine whether absorbable sutures or non-absorbable sutures are better in preventing surgical site infection ( SSI ) , in this paper we discuss the results of a r and omized clinical trial which examined the type of sutures used during hepatectomy . METHODS All hepatic resections performed from January 2007 to November 2008 at the Department of Surgery at Iizuka Hospital in Japan were included in this study . There were 125 patients r and omly assigned to an absorbable sutures ( Vicryl ) group or non-absorbable sutures ( Silk ) group . RESULTS SSI was observed in 13.6 % ( 17/125 ) patients participating in this study , 11.3 % in the Vicryl group and 15.8 % in the Silk group . Incisional SSI including superficial and deep SSI , was observed in 8 % of the Vicryl group and 9.5 % of the Silk group . Organ/space SSI was observed in 3.2 % of the Vicryl group and 6.0 % of the Silk group . There were no significant differences , but among the patients with SSI , the period for recovery was significantly shorter for the Vicryl group compared to the Silk group . CONCLUSION The incidence of SSI in patients receiving absorbable sutures and silk sutures is not significantly different in this r and omized controlled study ; however , the period for recovery in patients with SSI was significantly shorter for absorbable sutures Objective : The aim of this trial was to verify the new surgical device ( the LigaSure vessels sealing system ) decrease liver transection time . Summary Background Data : Among the major goals in hepatic resection are minimization of the operation time and of the blood loss . Preliminary reports have suggested that the vessel sealing system might decrease the liver transection time , which is directly associated with the amount of blood loss . Methods : Patients who were scheduled to undergo hepatic resection at the Tokyo University Hospital were assigned , by the minimization method , to either use of the new vessel sealing system ( VS group ) or the conventional clamp crushing method ( CC group ) for liver transection . The primary end point was the liver transection time , and the secondary endpoints were the amount of blood loss during the entire operation and during liver transection , length of hospital stay , postoperative liver function , and the incidence of various adverse events . An English- language summary of the protocol was su bmi tted ( registration ID : C000000337 ) to the Clinical Trials Registry managed by the University Hospital Medical Information Network in Japan , which can be accessed commission-free on the internet ( Available at : http://www.umin.ac.jp/ctr/index.htm ) . Results : From February to December in 2006 , a total of 165 patients underwent liver resection for some benign or malignant disease of the liver . Among these patients , 120 were r and omly assigned to the CC ( n = 60 ) or the VS ( n = 60 ) group . There was no mortality in either of the 2 groups . The median liver transection time in the VS group was 57 minutes ( range : 11–127 ) , similar to that in the CC group ( 56 [ range : 9–269 ] min , P = 0.64 ) , while there was no difference in the transection speed between the 2 groups ( 1.16 [ 0.15–2.26 ] cm2/min vs. 1.10 [ 0.15–2.66 ] cm2/min , P = 0.95 ) . The amount of blood loss and blood loss per transection area during liver transaction in the VS group was also similar to that in the CC group ( median : 315 [ 25–2415 ] mL vs. 315 [ 10–1700 ] mL ; P = 0.80 ) and ( 5.04 [ 1.01–44.2 ] mL/cm2 vs. 4.36 [ 0.15–50.5 ] mL/cm2 ; P = 0.14 ) , respectively . Conclusions : This r and omized controlled trial showed that while the vessel sealing system was safe , its use was not associated with any significant decrease of the operation time or blood loss during liver transaction as compared with that of the clamp crushing method BACKGROUND / AIMS Liver resection is a dem and ing procedure due to the risk of massive blood loss . Different instruments for liver transection are available today . The aim of this r and omized clinical trial was to analyze the efficacy of three different parenchyma transection techniques of liver resection . METHODOLOGY A total of 60 non-cirrhotic patients undergoing hepatectomy were r and omly selected for clamp crushing technique ( CRUSH ) , ultrasonic dissection ( CUSA ) or bipolar device ( LigaSure ) , n=20 in each group . All patients had liver resection under low central venous pressure anaesthesia ( CVP ) , with ischemic preconditioning and intermittent inflow occlusion . Primary endpoints were surgery duration , transection duration , cumulative pedicle clamping time , intraoperative blood loss and blood transfusion . Secondary endpoints included the postoperative liver injury , postoperative morbidity and mortality . RESULTS Overall surgery duration was 295 vs. 270 vs. 240min for LigaSure , CUSA and Clamp Crushing Technique , respectively . The transection duration was 85 vs. 52.5 vs. 40 minutes , respectively . These three different resection techniques of non-cirrhotic liver produced similar outcome in terms of intraoperative blood loss , blood transfusion , postoperative complications and mortality . CONCLUSIONS The Clump Crushing Technique , CUSA and Liga Sure are equally safe for resection of non-cirrhotic liver . Liver resections can be performed safely if the entire concept is well design ed and the choice of dissection device does not affect the outcome of hepatectomy To compare the difference in efficacy of microcrystalline collagen powder ( CL ) and fibrin glue ( FG ) in elective hepatic resection , 62 patients ( female 14 , male 48 ) with ages ranging from 51 to 75 years were r and omly allocated to receive either CL or FG as a topical agent during hepatectomy . There were no significant differences between the patients treated with CL ( n=31 ) and those treated with FG ( n=31 ) regarding sex , age , liver function , coagulation function , platelet counts , type of liver resection , and operative duration . A dry cut surface of the liver was obtained during surgery in 27 ( 87 % ) patients and 25 ( 81 % ) patients treated with CL and FG , respectively . Both CL and FG showed similar hemostatic effects . The CL and FG groups were not different in terms of postoperative rebleeding , bile leakage , or morbidity and mortality rates ( 6 % vs. 6 % , 6 % vs. 6 % , 45 % vs. 39 % , and 13 % vs. 10 % , respectively ) . Of the 52 patients with a dry cut surface of the liver during surgery , 3 patients in the CL group encountered rebleeding ( n=1 ) or bile leakage ( n=2 ) from the cut surface postoperatively , while no such complications were noted in the FG group . The results seem to favor FG for reliability in the postoperative period . The application of CL or FG may be better performed with consideration of the characteristics of each agent . RésuméPour comparer les efficacités respectives de la poudre de collagène micocristalline ( PCM ) et de la colle de fibrine ( CF ) dans les résections électives du foie , 62 patients ( 14 femmes , 48 hommes ) , do nt les âges variaient de 51 à 75 ans , ont été r and omisés . Ils ont reçu soit la PCM ( n=31 ) soit la CF ( n=31 ) comme agent d'hémostase locale après hépatectomie . Il n'y avait pas de différence significative entre les patients des deux groupes en ce qui concerne le sexe , l'âge , la fonction hépatique , le bilan de coagulation , la numération plaquettaire , le type de résection ou la durée de l'opération . Une section hépatique séche a pu être obtenue en peropératoire dnas 27 ( 87 % ) et 25 ( 81 % ) cas , respectivement . Les effets hémostatiques des deux agents ont été similaires . Il n'y a pas eu de différence en ce qui concerne l'hémorragie post-opératoire ( 6 % vs 6 % ) , les fuites biliaires ( 6 % vs 6 % ) , la morbidité ( 45 % vs 39 % ) ou la mortalité ( 13 vs 10 % ) . Parmi les 52 patients pour lesquels une surface sèche avait été obtenue en peropératoire , un patient a eu une nouvelle hémorragie , et deux ont eu une fuite biliaire dans le groupe PCM , alors qu'aucune de ces complicaitons n'est survenue dans le groups CF . Ces résultats sont en faveur de la CF en ce qui concern la fiabilité des résultats , mais la CF est plus de deux fois plus chère . Le choix entre la CF ou la PCM pourrait dépendre des caractéristiques spécifiques de chaque agent . ResumenCon el propósito de comparar la differencia en cuanto a eficacia hemostásica entre el polvo de colágeno microcristalino ( CL ) y la goma de fibrina ( FG ) en la resección hepática electiva , 62 pacientes ( 14 mujeres , 48 hombres ) con edades entre 51 y 75 años fueron asignados en forma aleatoria para recibir CL o FG como agente hemostático tópico en el curso de la hepatectomía . No hubo diferencias significativas en cuanto a sexo , edad , función hepática , función de coagulación , recuento de plaquetas , tipo de la resección hepática y duración de la operación entre los pacientes en quienes se utilizó CL ( grupo CL , n=31 ) . El CL y la FG exhibieron efectos hemostásicos similares ; no se observaron diferencias en cuanto a sangrado postoperatorio , escape biliar , tasas de morbilidad y de mortalidad ( 6 % vs 6 % , 6 % vs 6 % , 45 % vs 39 % y 13 % vs 10 % , respectivamente ) . Entre 52 casos con superficie seca de sección durante la cirugía , a pacientes del grupo CL presentaron resangrado ( n=1 ) o escape biliar ( n=2 ) a partir de la superficie de sección , contra ninguno en el grupo FG . Los result ados parecen estar a favor del FG en relación a la confiabilidad en el período postoperatorio pero debe tenerse en cuenta el elevado costo . La aplicación de CL o FG debe ser realizada en consideración a las características particulares de estos dos agentes BACKGROUND Experimental findings have demonstrated a beneficial role of retro grade blood flow from hepatic veins that takes place during the Pringle maneuver in liver resections . The cytoprotective effect of hepatovenous back-perfusion has not been evaluated in humans . A r and omized prospect i ve study was design ed to compare the response of liver cells to ischemic-reperfusion injury during the application of two different ischemic procedures : inflow versus inflow plus outflow vascular occlusion of the liver . STUDY DESIGN Forty patients were r and omly allocated to undergo liver resection using the continuous Pringle maneuver ( n = 20 ) or inflow plus outflow vascular occlusion of the liver by selective hepatic vascular exclusion ( n = 20 ) . Liver function was assessed on postoperative days 1 to 6 . Response of liver cells to I/R injury was evaluated by measuring interleukins IL-6 and IL-8 at 3 , 12 , 24 , and 48 hours after reperfusion . Oxidative stress was assessed by measuring malondialdehyde levels . RESULTS Both groups were comparable regarding ischemic time , operative time , and extent of liver resection . Patients in whom retro grade blood flow to the liver took place during the Pringle maneuver showed better liver function postoperatively and less severe hepatic I/R injuries compared with those undergoing liver resection using both inflow and outflow vascular occlusion . Oxidative stress was significantly lower in the Pringle maneuver group compared with the inflow plus outflow vascular occlusion group ( mean [ + /- SD ] malondialdehyde 8 + /- 2.1 micromol/L in the Pringle group versus 14.7 + /- 1.8 micromol/L in the selective hepatic vascular exclusion group 30 min after reperfusion , p < 0.01 ) . CONCLUSIONS Back perfusion via hepatic veins contributes to attenuation of I/R damage during the Pringle maneuver and should be preferred if possible during liver resection BACKGROUND Hemorrhage and liver failure are the two major complications in partial hepatectomy . The finger fracture or clamp crushing technique has been a st and ard technique used for transection of liver parenchyma . Hepatic vascular Inflow occlusion ( Pringle maneuver , PM ) is often used to minimize blood loss , but hepatic ischemia-reperfusion may result with an increased risk of post-operative liver failure . The Harmonic scalpel ( HS ) has been shown to be effective in reducing blood loss during liver parenchymal transection without any hepatic vascular inflow occlusion . METHODS A r and omized controlled trial was carried out to evaluate the impact of the two different hepatic transection techniques . The post-operative short-term results were compared . RESULTS During the study period , 160 of 212 patients who received partial hepatectomy in our hospital were r and omized into 2 groups : the PM group ( n = 80 ) and the HS group ( n = 80 ) . The numbers of patient who had a poor liver function on post-operative day 5 ( ISLGS Grade B ) were 30 , and 18 , respectively ( p < 0.05 ) . The post-operative complication rate was significantly higher in the PM group ( 41.3 % versus 22.5 % , p < 0.05 ) . The HS group had significantly less blood loss and blood transfusion requirements than the PM group ( p < 0.05 ) . CONCLUSIONS In conclusion , liver resection carried out using HS without hepatic vascular occlusion was better than using finger fracture or clamp crushing technique with Pringle maneuver . The use of HS allowed liver resection to be safely performed , with earlier recovery of liver function , and less surgical complication Objective A r and omized study was conducted of hilar dissection and the “ glissonean ” approach and stapling of the pedicle for major hepatectomies to contrast their feasibility , safety , amount of hemorrhage , postoperative complications , operative times , and costs . Summary Background Data The “ glissonean ” approach is reported as requiring a shorter portal triad closure time ; furthermore , the procedure seems to expedite the transection of the liver . Patients and Methods Between 1998 and 2001 , 80 patients were enrolled in this study . The major liver resections included 15 extended right , 7 extended left , 42 right , and 16 left hepatectomies . The patients were r and omly assigned to the hilar dissection group ( G1 ; n = 40 ) or to the “ glissonean ” approach and stapling of the portal triad group ( G2 ; n = 40 ) . Results The groups were equally matched for age , sex , diagnosis , mean resected specimen weight , number of tumoral lesions , type of liver resection performed , and percentage of patients with margin invasion ( G1 : 4 ; 10 % vs G2 : 5 ; 12.5 % ) . The duration of the 2 procedures was similar ( G1 : 247 ± 54 min vs G2 : 236 ± 43 min ; P = 0.4 ) . However , the duration of the hilar dissection was shorter for G2 ( 50 ± 17 min ) versus G1 ( 70 ± 26 min ; P < 0.001 ) . By contrast , the duration of pedicular clamping was shorter for G1 ( 43 ± 15 min ) versus G2 ( 51 ± 15 min ; P = 0.015 ) . No differences were observed in the amount of hemorrhage ( G1 : 887 ± 510 mL vs G2 : 937 ± 636 mL ; P = 0.7 ) , and only 6 patients in G1 and 10 in G2 were transfused ( P = 0.26 ) . Morbidity rates were similar for both groups ( G1 : 23 % vs G2 : 33 % ; P = 0.3 ) . Surgical injury of the contralateral biliary duct was not observed . However , 3 patients in G1 and 4 patients in G2 presented a biliary fistula that resolved spontaneously . Postoperative hospital stay was similar ( G1 : 8 [ range , 6 - 24 ] vs G2 : 9 [ range , 5 - 31 ] days ; P = 0.6 ) . The postoperative levels of alanine transaminase ( ALT ) during the 2 first postoperative days were lower for G1 than G2 . Cost of the surgical material was 1235.80 US for G1 and 1301.10 US for G2 . Conclusions The 2 techniques are equally effective procedures for treating hilar structures . Although en bloc stapling transection is faster , hilar dissection was associated with a shorter pedicular clamping time , less cytolysis , and the material s required were less expensive BACKGROUND Fibrocaps , a ready-to-use , dry-powder fibrin sealant containing human plasma-derived thrombin and fibrinogen , is being developed as an adjunct for surgical hemostasis . MATERIAL S AND METHODS Safety and efficacy of Fibrocaps applied directly or by spray device , in combination with gelatin sponge , was compared with that of gelatin sponge-alone in two r and omized , single-blind controlled trials : FC-002 US ( United States ) and FC-002 NL ( the Netherl and s ) . A total of 126 adult patients were r and omized ( Fibrocaps : n = 47 [ FC-002 US ] , n = 39 [ FC-002 NL ] ; gelatin sponge alone : n = 23 [ FC-002 US ] , n = 17 [ FC-002 NL ) . One bleeding site was treated during a surgical procedure ( n = 125 ) . Time to hemostasis ( primary end point ) was measured , with a 28-d safety follow-up . Four surgical indications included hepatic resection ( n = 58 ) , spinal procedures ( n = 37 ) , peripheral vascular procedures ( n = 30 ) , and soft tissue dissection ( n = 1 ) . RESULTS Mean ( st and ard deviation ) time to hemostasis was significantly shorter after Fibrocaps treatment than after gelatin sponge alone ( FC-002 US : 1.9 [ 1.3 ] versus 4.8 min [ 3.1 ] , P < 0.001 ; FC-002 NL : 2.2 [ 1.3 ] versus 4.4 min [ 3.1 ] , P = 0.004 ) . The incidence of hemostasis was greater after Fibrocaps compared with that of gelatin sponge alone within 3 min ( FC-002 US : 83 % versus 35 % , P < 0.001 ; FC-002 NL : 77 % versus 53 % , P = 0.11 ) , 5 min ( 94 % versus 61 % , P = 0.001 ; 95 % versus 71 % , P = 0.022 ) , and 10 min ( 100 % versus 78 % , P = 0.003 ; 100 % versus 82 % , P = 0.025 ) . Adverse events were consistent with surgical procedures performed and patients ' underlying diseases and generally similar between treatment arms ; most were mild or moderate in severity . Non-neutralizing antithrombin antibodies were detected in 5 % of Fibrocaps-treated patients on day 29 . CONCLUSIONS Fibrocaps had good safety and efficacy profiles , supporting continuing clinical development as a novel fibrin sealant BACKGROUND The goal of the present study was to evaluate the efficacy of the novel LigaSure Vessel Sealing System ( Valleylab , Boulder , CO ) when used for liver resection . METHODS Sixty patients ( n = 30 in each group ) with liver pathology from a single center were r and omized to undergo liver resection with either the LigaSure system or with conventional clamping methods . Patients were stratified according to tumor size ( < 5 or > 5 cm ) , type of hepatectomy ( minor or major ) , and liver damage ( normal or injured ) . Estimated blood loss during liver transection was used as the primary end point , whereas liver transection speed and morbidity rate were used as secondary end points . RESULTS There were no hospital deaths . The median blood loss during liver transection was less in the LigaSure than in the conventional group ( 200 vs 322 mL ; P = .185 ) . The amount of blood loss during minor hepatectomy was significantly less in the LigaSure than in the conventional group ( 186 vs 412 mL , P = .012 ) . The liver transection speed was significantly faster in the LigaSure than in the conventional group ( 2.3 vs 1.6 cm(2)/min , P < .001 . The number of ties required during liver transection was significantly less in the LigaSure than in the conventional group ( 6 vs 69 ties , P < .001 ) . The morbidity rate was similar when comparing the 2 groups , indicating that the LigaSure sealing device and conventional methods had comparable efficacy in sealing the bile duct in the portal triad . Postoperative bile leak was observed in 1 patient ( 3 % ) in the LigaSure group and in 3 patients ( 9 % ) in the conventional group ( P = .301 ) . CONCLUSIONS The LigaSure system is an effective and safe tool for decreasing liver resection time Objective : A r and omized controlled trial was conducted to clarify the effectiveness of intraoperative blood salvage in reducing blood loss . Background : Although reduction of central venous pressure ( CVP ) is thought to decrease blood loss during liver resection , no consistently effective and safe method for obtaining the desired reduction of CVP has been established . Methods : Living liver donors scheduled to undergo liver graft procurement were r and omly assigned to a blood salvage group , in which a blood volume equal to approximately 0.7 % of the patient 's body weight was collected before the liver transection , or a control group . The surgeons were blinded to the r and omization results . The primary outcome measure was blood loss during liver parenchymal division . A multivariate analysis was also performed . Results : Seventy-nine donors were allocated intraoperatively to the blood salvage group ( n = 40 ) or the control group ( n = 39 ) . The amount of blood loss during liver transection was significantly smaller in the blood salvage group than in the control group ( median loss during transection , 140 mL vs. 230 mL , P = 0.034 ) . The CVP at the beginning of the liver parenchymal division was significantly lower in the blood salvage group than in the control group ( median , 5 cm H2O vs. 6 cm H2O , P = 0.005 ) . The results of a multivariate analysis revealed that intraoperative blood salvage offered the advantage of reduced blood loss during liver parenchymal division ( adjusted OR , 0.31 ; 95 % CI , 0.11–0.85 , P = 0.025 ) . Conclusion : Modest intraoperative blood salvage significantly and safely reduced blood loss during hepatic parenchymal transection The optimal ischaemic interval during hepatectomy with intermittent pedicle occlusion ( IPO ) remains to be established . The aim of the present r and omized clinical trial was to compare the short‐term outcome of hepatectomy using IPO with an ischaemic interval of 15 versus 30 min BACKGROUND Intermittent Pringle manoeuvre result ed in less blood loss and better preservation of liver function when it was applied for fewer than 120 minutes . The mechanism of better preservation of liver function under intermittent Pringle manoeuvre at molecular level remains unclear . Furthermore , the ultrastructural features in the liver with chronic diseases under intermittent Pringle manoeuvre have not been studied . The aim of the study is to investigate the expression of stress genes and ultrastructural change of the liver under intermittent Pringle manoeuvre . METHODS From July 1995 to February 1998 , 131 patients underwent hepatectomy for liver tumours ( 61 patients without Pringle manoeuvre and 70 patients with intermittent Pringle manoeuvre ) . Twenty-five patients ( 15 with Pringle manoeuvre and 10 without Pringle manoeuvre ) were included in the study of hepatic stress gene expression during hepatectomy . Twenty-two patients ( 18 patients with intermittent Pringle manoeuvre and four patients without Pringle manoeuvre ) were r and omly assigned for electron microscopic examination . RESULTS For the expression of stress genes , both the heat shock genes ( HSP 70A and HSC 70 ) and acute phase genes ( TNF-alpha and interleukin-6 ) were detected simultaneously in the patients with or without intermittent Pringle manoeuvre . The patients under intermittent Pringle manoeuvre had relatively higher mRNA levels of heat shock gene 70 family , which is related to intracellular repair and protection . Induction of TNF-alpha and interleukin-6 genes , which contributed to ischaemia-reperfusion injury and postoperative complication , was not found in the patients under intermittent Pringle manoeuvre . Under the electron microscopy , the hepatic ultrastructure was well maintained under intermittent Pringle manoeuvre whatever the liver status , even when the accumulated ischaemic duration was extended to 120 min . CONCLUSION Intermittent Pringle manoeuvre induced relatively higher expression of heat shock genes , which are related to intracellular homeostasis , and is consistent with the well maintenance of liver ultrastructure BACKGROUND / AIMS Routine use of abdominal drainage after liver resection is controversial . The aim of this study was to investigate the practical application of a " no abdominal drainage " policy for consecutive patients undergoing hepatic resection . METHODOLOGY The present trial included 60 consecutive patients who underwent elective hepatic resection . Fifty-two patients underwent no abdominal drainage , and in the remaining eight drainage was necessary because of gross contamination of the surgical field associated with bilioenteric anastomosis , uncontrollable bile leakage from the cut surface of the liver , or the surgeon 's preference . Patient demographics , intraoperative data , and postoperative complications and mortality were evaluated . RESULTS There was no hospital death . Eight complications occurred in 8 patients in the no-drainage group ( morbidity rate 15.4 % , 8/52 ) : bleeding , abscess , ascites requiring peritoneal tap , pleural effusion requiring thoracentesis , and pneumonia in one case each , and three cases of wound infection . Three complications were encountered in 2 patients in the drainage group ( morbidity rate 25 % , 2/8 ) : bleeding , infected biloma and pleural effusion in one case each . Postoperative hospital stay tended to be shorter in the no-drainage group ( 10.7 + /- 3.9 days ) than in the drainage group ( 15.6 + /- 6.4 days ) ( p = 0.07 ) . Considering early uneventful removal of the drain on the morning of postoperative day 1 , half of the drained patients might have not required drainage . Furthermore , in the setting of concomitant bilioenteric anastomosis ( n=4 ) , one patient underwent hepatectomy uneventfully without drainage , and two of three patients with drainage had their drains removed successfully on day 1 . The third patient retained the drain for an unnecessarily long period , but did not develop subsequent complications . CONCLUSIONS Our data support the view that prophylactic abdominal drainage is unnecessary in most patients who undergo elective hepatic resection . Bilioenteric anastomosis may not be a contraindication for a no abdominal drainage policy BACKGROUND The aim of this study was to compare ischemic preconditioning with the intermittent vascular occlusion technique in liver resections performed under inflow and outflow occlusion . METHODS Fifty-four patients with resectable liver tumors assigned were r and omly to undergo surgery with either ischemic preconditioning ( IP group , n = 27 ) or with intermittent vascular occlusion ( IVO group , n = 27 ) . Both groups were compared regarding surgical parameters , aspartate transaminase levels , and apoptosis . RESULTS For warm ischemic time less than 40 minutes , no significant difference was noticed between the 2 groups apart from caspase-3 activity , which was higher in the IVO group than in the IP group ( 17.2 + /- 3.4 vs. 10.3 + /- 5.2 , P < .05 ) . When warm ischemia exceeded 40 minutes , the IP group showed higher levels in blood aspartate transaminase levels on day 3 ( 442 + /- 178 IU/L vs. 305 + /- 104 IU/L , P < .05 ) and higher caspase-3 levels ( 26.5 + /- 5.7 count/high-power field [ hpf ] vs. 20.7 + /- 3.6 count/hpf , P < .05 ) and apoptotic activity ( 28.5 + /- 7.5 count/hpf vs. 20.2 + /- 4.1 count/hpf , P < .05 ) , as compared with the IVO group . CONCLUSIONS Although both techniques showed comparable efficacy for short ischemic times , intermittent vascular occlusion provided better cytoprotection when ischemia exceeded 40 minutes BACKGROUND Plasma-derived bovine thrombin is used as a topical agent to improve surgical hemostasis , but development of antibodies to bovine hemostatic proteins has been associated with increased bleeding and thrombotic complications . Recombinant human thrombin could reduce the risk of these complications . STUDY DESIGN The objective of this r and omized , double-blind , comparative trial was to compare the efficacy , safety , and antigenicity of recombinant human thrombin ( rhThrombin ) and bovine thrombin as adjuncts to hemostasis in liver resection , spine , peripheral arterial bypass , and dialysis access surgery . Blinded study drug was applied topically to bleeding sites with an absorbable gelatin sponge . The primary efficacy end point was time to hemostasis , summarized as the incidence of hemostasis within 10 minutes . Safety analyses were conducted for 1 month after operation , and the development of antibodies to rhThrombin or to the bovine product was evaluated . RESULTS Four hundred one patients completed this trial . Hemostasis was achieved at the time-to-hemostasis evaluation site within 10 minutes in 95 % of patients in each treatment group . Overall complications , including operative mortality , adverse events , and laboratory abnormalities , were similar between groups . Forty-three ( 21.5 % ) patients receiving bovine thrombin developed antibodies to the product ; three patients ( 1.5 % ; p < 0.0001 ) in the rhThrombin group developed antibodies to rhThrombin . None of the three patients who developed antirhThrombin antibodies had abnormal coagulation laboratory results or bleeding , thromboembolic , or hypersensitivity events . CONCLUSIONS Results of this trial suggest that rhThrombin has comparable efficacy , a similar safety profile , and is considerably less immunogenic than bovine thrombin when used for surgical hemostasis Objective To clarify the benefit of energy devices such as ultrasonically activated device and bipolar vessel sealing device in liver surgeries . Background Several studies have suggested the benefit of energy devices in liver transection , while a r and omized trial has found no association between their use and surgical outcomes . Patients and methods Patients scheduled to undergo open liver resection were eligible for this multicenter non-blinded r and omized study . They were r and omized to receive an energy device ( experimental group ) or not ( control group ) during liver transection . The primary endpoint was the proportion of patients with intraoperative blood loss > 1,000 mL. The primary aim was to show non-inferiority of hepatectomy with energy device to that without energy device . Results A total of 212 patients were r and omized and 211 ( 105 and 106 in the respective groups ) were analyzed . Intraoperative blood loss > 1,000 mL occurred in 15.0 % patients with energy device and 20.2 % patients without energy device . The experimental minus control group difference was −5.2 % ( 95 % confidence interval −13.8 to 3.3 % ; non-inferiority test , p = 0.0248 ) . Hepatectomy with energy device result ed in a shorter median liver transection time ( 63 vs. 84 min ; p < 0.001 ) and a lower rate of postoperative bile leakage ( 4 vs. 16 % ; p = 0.002 ) . Conclusions The hypothesis that hepatectomy with energy device is not inferior to that without energy device in terms of blood loss has been demonstrated . The use of energy devices during liver surgery is clinical ly meaningful as it shortens the liver transection time and reduces the incidence of postoperative bile leakage Maintaining a low central venous pressure ( CVP ) has been frequently used in liver resections to reduce blood loss . However , decreased preload carries potential risks such as hemodynamic instability . We hypothesized that a low CVP with milrinone would provide a better surgical environment and hemodynamic stability during living donor hepatectomy . Thirty‐eight healthy adult liver donors were r and omized to receive either milrinone ( milrinone group , n = 19 ) or normal saline ( control group , n = 19 ) infusion during liver resection . The surgical field was assessed using a four‐point scale . Intraoperative vital signs , blood loss , the use of vasopressors and diuretics and postoperative laboratory data were compared between groups . The milrinone group showed a superior surgical field ( p < 0.001 ) and less blood loss ( 142 ± 129 mL vs. 378 ± 167 mL , p < 0.001 ) . Vital signs were well maintained in both groups but the milrinone group required smaller amounts of vasopressors and less‐frequent diuretics to maintain a low CVP . The milrinone group also showed a more rapid recovery pattern after surgery . Milrinone‐induced low CVP improves the surgical field with less blood loss during living donor hepatectomy and also has favorable effects on intraoperative hemodynamics and postoperative recovery OBJECTIVE The authors compared operative course of patients undergoing major liver resections under portal triad clamping ( PTC ) or under hepatic vascular exclusion ( HVE ) . SUMMARY BACKGROUND DATA Reduced blood loss during liver resection is achieved by PTC or HVE . Specific complications and postoperative hepatocellular injury mediated with two procedures have not been compared . METHODS Fifty-two noncirrhotic patients undergoing major liver resections were included in a prospect i ve r and omized study comparing both the intraoperative and postoperative courses under PTC ( n = 24 ) or under HVE ( n = 28 ) . RESULTS The two groups were similar at entry , but eight patients were crossed over to the other group during resection . In the HVE group , hemodynamic intolerance occurred in four ( 14 % ) patients . In the PTC group , pedicular clamping was not efficient in four patients , including three with involvement of the cavohepatic intersection and one with persistent bleeding due to tricuspid insufficiency . Intraoperative blood losses and postoperative enzyme level reflecting hepatocellular injury were similar in the two groups . Mean operative duration and mean clampage duration were significantly increased after HVE . Postoperative abdominal collection s and pulmonary complications were 2.5-fold higher after HVE but without statistical significance , whereas the mean length of postoperative hospital stay was longer after HVE . CONCLUSIONS This study shows that both methods of vascular occlusion are equally effective in reducing blood loss in major liver resections . The HVE is associated with unpredictable hemodynamic intolerance , increased postoperative complications with a longer hospital stay , and should be restricted to lesions involving the cavo-hepatic intersection In a prospect i ve controlled trial hemostatic effectiveness of a novel collagen-based composite ( CoStasis ) was compared with a collagen sponge applied with manual pressure at diffusely bleeding sites after surgical tumor resection . The proportion of subjects achieving complete cessation of bleeding within 10 minutes ( i.e. , hemostatic success ) and the time to " complete hemostasis " were determined at raw surgical sites after tumor resection among 23 experimental and 30 control subjects . There was a similar distribution in tumor types ( e.g. , benign vs malignant ) evaluated between treatment groups . A significantly greater proportion of experimental subjects achieved complete hemostasis within 10 minutes of observation compared with controls [ 23 of 23 ( 100 % ) vs 21 of 30 ( 70 % ) ; P = 0.003 ] . The median time required to achieve complete hemostasis was more than three times longer for subjects treated with the collagen sponge compared with subjects treated with CoStasis ( 243 vs 78 seconds ; P = 0.0001 ) . Approximately 80 per cent of experimental subjects achieved complete hemostasis within 2 minutes compared with only 35 per cent of controls . There were no adverse events related to the experimental treatment in this study . These results support the use of this novel hemostatic agent to control diffuse surgical site bleeding after tumor resection at diverse anatomical locations Objective : To evaluate the effectiveness and safety of infrahepatic inferior vena cava ( IVC ) clamping for reduction of central venous pressure ( CVP ) and blood loss during hepatic resection . Background : Low CVP during parenchymal transection has been widely accepted to reduce intraoperative hemorrhage via the hepatic veins and is commonly achieved by anesthesiological interventions such as fluid restriction . We hypothesized that infrahepatic clamping of the IVC may lower the intraoperative blood loss more effectively and , moreover , prevent potential adverse effects of fluid restriction such as hemodynamic instability . Methods : Patients scheduled for elective hepatic resection were enrolled and allocated r and omly to CVP reduction by infrahepatic IVC clamping or anesthesiological interventions including primarily fluid restriction with additional use of diuretics , nitro compounds , and opioids ( control group ) . The primary efficacy endpoint was total intraoperative blood loss . Analyses were done following intention-to-treat principles . The protocol was su bmi tted to the clinical trials.gov registry ( NCT00732979 ) . Results : From April 2007 to December 2009 , a total of 152 patients were r and omized and 128 were eligible for final analyses . Baseline data were similar between both study groups . Despite higher CVP values during resection ( 4.0 ± 3.2 vs. 2.6 ± 1.8 mm Hg ; P = 0.003 ) , infrahepatic IVC clamping significantly reduced total intraoperative blood loss [ 550 ( 350.0–1150 ) mL vs. 900 ( 500–1500 ) mL ; P = 0.02 ] and blood loss during parenchymal transection [ 150 ( 85–500 ) mL vs. 400 ( 200–700 ) mL ; P = 0.006 ] compared with the control group . Postoperative mortality [ 4 ( 6.1 % ) vs. 2 ( 3.2 % ) ; P = 0.42 ] and total morbidity rates [ 38 ( 58.5 % ) vs. 37 ( 58.7 % ) ; P = 0.97 ] were comparable between both study groups . Although intraoperative hemodynamic instability occurred less frequently in patients with infrahepatic IVC clamping [ 0 vs. 4 ( 6.3 % ) ; P = 0.04 ] , the incidence of pulmonary embolism was increased in this study arm [ 4 ( 6.1 % ) vs. 0 ; P = 0.04 ] . Conclusions : Infrahepatic IVC clamping is associated with significantly less intraoperative blood loss and may reduce the incidence of intraoperative hemodynamic instability . The potential association with postoperative pulmonary embolism represents a significant concern INTRODUCTION Bleeding during liver surgery is often routinely controlled by the Pringle maneuver consisting in the temporary clamping of hepatic artery , portal vein , and bile duct . This study aim ed at investigating a possible influence of the Pringle maneuver on tissue hypoxia during liver resection . METHODS Twenty-five consecutive patients undergoing elective liver resection were prospect ively r and omized either to be treated with the Pringle maneuver ( Pringle group , n = 14 ) or without clamping ( Controls , n = 11 ) . Blood lactate levels , pyruvate levels , and hepatic vein oxygen saturation were monitored perioperatively . RESULTS Patients were comparable with respect to resection time , intraoperative blood loss , and duration of surgery . The Pringle maneuver induced a significant increase in arterial lactate levels during liver resection when compared to Controls ( 2.6 + /- 0.3 vs 1.8 + /- 0.2 mmol/l ; p < 0.05 ) . Further , the Pringle maneuver significantly increased hepatic venous lactate ( 3.3 + /- 0.3 vs 1.6 + /- 0.3 mmol/l ; p < 0.05 ) and lactate/pyruvate ratio in hepatic venous blood ( 43 + /- 8 vs 21 + /- 5 ; p < 0.05 ) during surgery . This was paralleled by a temporal decrease in hepatic venous oxygen saturation in the Pringle group ( 61 + /- 4 vs 73 + /- 4 % ; p < 0.05 ) . CONCLUSION Our findings demonstrate that liver metabolism and tissue oxygenation were markedly affected by occlusion of the liver hilus . Restricting the use of the Pringle maneuver to cases with severe bleeding might therefore be beneficial in patients undergoing liver resection Background Many techniques and devices are available for performing liver resection , such as clamp crushing , Cavitron Ultrasonic Surgical Aspirator ( CUSA ) , Hydrojet and dissecting sealer , ultrasonic shears , and , more recently , electrothermal bipolar vessel sealing system ( EBVS ) . In this prospect i ve trial we sought to evaluate the impact of EBVS on hepatic resections . Methods From March 2004 to December 2005 , 24 patients from our consecutive liver resection series were enrolled in the present study . There were 17 males and 7 females with a mean age of 59.6 years ( range = 41–80 ) who had colonic cancer metastases ( 18 ) , hepatocarcinoma ( 3 ) , angioma ( 2 ) , and intrahepatic lithisasis ( 1 ) . Patients were prospect ively r and omized to undergo liver resection via EBVS LigaSure V ( 12 patients , group A ) or ultrasonic shears harmonic scalpel ( HS ) ( 12 patients , group B ) . Hepatic procedures did not differ significantly between the two groups and were as follows : right hepatectomy ( 2 ) , left hepatectomy ( 1 ) , bisegmentectomy ( 14 ) , and segmentectomy ( 7 ) . Results There was no mortality in either group . The mean operative time was 136.7 min ( range = 90–210 ) in group A and 187.9 min ( range = 130–360 ) in group B. The Pringle maneuver was done in five patients in group A [ mean time = 11.4 min ( range = 6–12 ) ] and in four patients in group B [ mean time = 16 min ( range = 9–26 ) ] . The mean blood loss , total bile salts , and hemoglobin concentration from drained fluid on the second postoperative day were 205.8 vs. 506.7 ml , 0.6 vs. 1.1 mmol/L , and 1.0 vs. 2.1 g/L ( p < 0.05 ) for groups A and B , respectively . Mean postoperative hospital stay was 6.1 vs. 7.8 days . In group B a patient who underwent right hepatectomy for colon cancer metastases had transient hepatic failure . No patients received blood transfusions in group A , while two or more blood units were administered in two cases in group B. Conclusions In the present study EBVS proved to be safe and effective for liver resection . By means of this device , statistically significant benefits concerning blood loss , total bile salts , and hemoglobin postoperative leakage were found Background and aims A new carrier-bound fibrin sealant , TachoSil , is expected to be efficacious and safe as a haemostatic treatment in hepatic resection . Design A prospect i ve , r and omised , open and controlled multicentre trial with intraoperative as well as postoperative assessment of efficacy and a 1 month follow-up period . Setting Tertiary care centres . Patients / methods One hundred and twenty-one patients requiring secondary haemostasis during planned liver resection . Patients with coagulation disorders and patients with persistent major bleeding after primary haemostatic measures were excluded . InterventionApplication of either carrier-bound fibrin sealant ( n=59 ) or argon beamer ( argon beam coagulator ) ( n=62 ) as secondary haemostatic treatment . Main outcome measureTime to intraoperative haemostasis . Results There was a significant superiority of TachoSil over argon beamer with regard to time to haemostasis ( 3.9 min , median 3.0 , range 3–20 min vs 6.3 min , median 4.0 , range 3–39 min ) ( P=0.0007 ) . Haemoglobin concentration of drainage fluid was significantly lower on day 2 after surgery in TachoSil patients ( 1.1 mmol/l ) than in argon beamer patients ( 2.3 mmol/l ) ( P=0.012 ) . Overall , the frequency and causality of adverse events did not differ between the two treatment groups . Conclusion TachoSil is superior to argon beamer in obtaining effective and fast intraoperative haemostasis . The safety data show TachoSil to be tolerable and safe for haemostatic treatment in liver resection BACKGROUND Bleeding following liver resection continues to be a significant morbidity of the procedure . Fibrin sealants represent an improvement over conventional topical hemostatic agents , because they contain components that actively form clot . However , most available agents contain nonhuman protein , which represents an immunologic risk . HYPOTHESIS An investigational surgical fibrin sealant ( Crosseal ; American Red Cross , Washington , DC ) composed of human clottable proteins and human thrombin is more effective than st and ard topical hemostatic agents in reducing the time required to achieve hemostasis after liver resection . DESIGN Prospect i ve , r and omized , controlled trial . SETTING Fifteen major referral centers in the United States and the United Kingdom . METHODS After liver resection using st and ard surgical techniques , 121 patients seen between May 1999 and May 2000 were r and omized to treatment with a 2-component fibrin sealant ( n=58 ) or to st and ard topical hemostatic agents , used singly or in combination ( n=63 ) . Up to 10 mL of Crosseal was administered by a spray applicator , as recommended by the manufacturer , whereas agents used in the control group were applied according to their instructions for use . MAIN OUTCOME MEASURES The primary outcome measured was time to hemostasis . Secondary outcomes measured included blood loss between application of the hemostatic agent and closure of the abdomen , duration of postoperative biliary drainage , and the occurrence of complications , defined a priori as reoperation for any reason , development of abdominal fluid collection s , or bilious appearance of drained fluid for at least 1 day postoperatively . RESULTS The mean time to hemostasis was 282 seconds with Crosseal , compared with 468 seconds with st and ard agents ( 2-sided ; P = .06 ) , for the 116 efficacy-evaluable patients . Hemostasis was achieved within 10 minutes in 53 patients ( 91.4 % ) treated with the study fibrin sealant and in 44 control patients ( 69.8 % ) ( 2-sided ; P = .003 ) . Intraoperative blood loss was similar in the 2 groups . In the Crosseal group , the percentage of patients developing postoperative complications was 17.2 % , compared with 36.5 % in the control group ( 2-sided ; P = .02 ) . CONCLUSIONS Compared with the use of st and ard topical hemostatic agents , Crosseal fibrin sealant significantly reduced the time to achieve hemostasis following liver resection . Patients treated with the new fibrin sealant also experienced significantly fewer postoperative complications The Cavitron Ultrasonic Surgical Aspirator ( CUSA ® ) is an innovative tool for resecting hepatic parenchyma , which reduces intraoperative blood loss and perioperative morbidity . We design ed this study to compare the incidence and severity of venous air embolism ( VAE ) detected via transesophageal echocardiography ( TEE ) during hepatic resection by using either the clamp-crushing method or the CUSA ® method . Fifty patients scheduled for hepatic resection were r and omly assigned to receive hepatic resection by the clamp-crushing method ( CC group ) or by CUSA ® ( CUSA ® group ) . After the induction of anesthesia , the TEE probe was inserted into the patient ’s esophagus . An independent anesthesiologist grade d VAE shown in the 4-chamber view of TEE . All patients in the CUSA ® group showed VAE during hepatic resection and 44 % of the patients had air embolism filling more than half the right heart diameter . In CC group , 68 % of the patients showed VAE , which filled less than half the right heart diameter . There were no significant differences in hemodynamics and end-tidal CO2 partial pressure between the two groups . In conclusion , hepatic resection by CUSA ® increases the incidence and severity of VAE BACKGROUND Hepatectomy can be performed with a low mortality rate , but massive hemorrhage during the operation remains a potentially lethal problem . The Pringle maneuver is traditionally used during hepatectomy to reduce blood loss , but the effect on the metabolic function of hepatocytes is potentially harmful . Although our r and omized study showed that an intermittent Pringle maneuver is safe and effective during hepatectomy , the upper limit of the duration of the Pringle maneuver is not known . HYPOTHESIS The liver can tolerate intermittent Pringle maneuver if the duration is not excessive . DESIGN From July 20 , 1995 , to November 25 , 1997 , 112 patients underwent hepatectomy for liver tumors . The data of 50 patients who had hepatectomy without the Pringle maneuver were compared with those of 62 patients who had a liver transection using a Pringle maneuver for 20 minutes and a 5-minute clamp-free interval . The data were collected prospect ively . MAIN OUTCOME MEASURES The surface area of liver transection was measured , and blood loss during liver transection per centimeter square of transection area was calculated . Routine liver biochemical tests , arterial ketone body ratio ( AKBR ) , and plasma cytokine-interleukin ( IL ) 1alpha , 1beta , 2 , and 6 , and tumor necrosis factor alpha -- levels were measured before and after the operation . The morbidity and hospital mortality rates were also compared among the patients with different ischemic duration s and those without an intermittent Pringle maneuver . SETTING Tertiary referral center . RESULTS The cutoff point of accumulated ischemic time that induced substantial liver damage , as shown by the postoperative recovery rate of the AKBR , was found to be 120 minutes . Compared with the control group , the patients whose accumulated ischemic time was shorter than 120 minutes had less blood loss related to transection area ( 10 mL/cm2 vs 22 mL/cm2 ; P<.001 ) , less blood transfused ( 0 L vs 0.6 L ; P = .004 ) , a shorter transection time related to transection area ( 2.0 min/cm2 vs 2.8 min/ cm2 ; P = .002 ) , a significantly higher AKBR in the first 2 hours after liver transection , an equal recovery rate of the AKBR , and a comparable increase of the plasma level of IL-6 postoperatively . For the patients whose accumulated ischemic time was longer than 120 minutes , blood loss from the transection area was less than for the control group ( 14 mL/cm2 vs 22 mL/cm2 ; P<.05 ) , but the transection time related to the transection area and the blood transfusion volume did not differ from those of the control group . Furthermore , they had a significantly lower recovery rate of the AKBR and higher plasma levels of IL-6 postoperatively than the control group Objective : To identify the most efficient parenchyma transection technique for liver resection using a prospect i ve r and omized protocol . Summary Background Data : Liver resection can be performed by different transection devices with or without inflow occlusion ( Pringle maneuver ) . Only limited data are currently available on the best transection technique . Methods : A r and omized controlled trial was performed in noncirrhotic and noncholestatic patients undergoing liver resection comparing the clamp crushing technique with Pringle maneuver versus CUSA versus Hydrojet versus dissecting sealer without Pringle maneuver ( 25 patients each group ) . Primary endpoints were intraoperative blood loss , resection time , and postoperative liver injury . Secondary end points included the use of inflow occlusion , postoperative complications , and costs . Results : The clamp crushing technique had the highest transection velocity ( 3.9 ± 0.3 cm2/min ) and lowest blood loss ( 1.5 ± 0.3 mL/cm2 ) compared with CUSA ( 2.3 ± 0.2 cm2/min and 4 ± 0.7 mL/cm2 ) , Hydrojet ( 2.4 ± 0.3 cm2/min and 3.5 ± 0.5 mL/cm2 ) , and dissecting sealer ( 2.5 ± 0.3 cm2/min and 3.4 ± 0.4 mL/cm2 ) ( velocity : P = 0.001 ; blood loss : P = 0.003 ) . Clamp crushing technique was associated with the lowest need for postoperative blood transfusions . The degree of postoperative reperfusion injury and complications were not significantly different among the groups . The clamp crushing technique proved to be most cost-efficient device and had a cost-saving potential of 600 & U20AC ; to 2400 & U20AC ; per case . Conclusions : The clamp crushing technique was the most efficient device in terms of resection time , blood loss , and blood transfusion frequency compared with CUSA , Hydrojet , and dissecting sealer , and proved to be also the most cost-efficient device Background Liver resection is a major operation for which , even with the improvements in surgical and anesthetic techniques , the reported rate of blood transfusion was rarely less than 30 % . About 60 % of transfused patients require only 1 or 2 units of blood , a blood requirement that may be accommo date d by the use of acute normovolemic hemodilution ( ANH ) . Methods The efficacy , hemodynamic effects , and safety of ANH were investigated in a r and omized , active-control study in patients with American Society of Anesthesiologists status I – II who were undergoing major liver resection with fentanyl – nitrous oxide – isoflurane anesthesia . Patients were r and omized to the ANH ( n = 39 ) or control group ( n = 39 ) . Patients in the ANH group underwent hemodilution to a target hematocrit of 24 % . The indication for blood transfusion was st and ardized . In both groups transfusion was started at a hematocrit of 20 % . The primary efficacy endpoint was the avoidance of allogeneic blood transfusion in the intraoperative period and first 72 h after surgery . Various laboratory and hemodynamic parameters as well as postoperative morbidity were monitored to define the safety of ANH in this patient population . Results During the perioperative period , 14 control patients ( 36 % ) received at least one unit of allogeneic blood compared with 4 patients ( 10 % ) in the ANH group ( P < 0.05 ) . The hemodilution process was not associated with significant changes in patients ’ hemodynamics . Morbidity was similar between the control and the ANH groups . Postoperative hematocrit levels and biochemical liver , renal , and st and ard coagulation test results were similar in both groups . Conclusions Acute normovolemic hemodilution in patients with American Society of Anesthesiologists status I – II undergoing major liver resection may allow a significant number of patients to avoid exposure to allogeneic blood BACKGROUND AND AIM Selective hepatic vascular exclusion ( SHVE ) has not been widely used because of difficulty in extrahepatic isolation of hepatic veins . This study aims to compare the results of SHVE using tourniquets or Satinsky clamps on major hepatic veins in partial hepatectomy for liver tumors involving the roots of hepatic veins . METHODS Between June 2008 and March 2012 , a r and omized controlled trial was performed on patients undergoing liver resection to compare selective hepatic vascular exclusion using tourniquets or Satinsky clamps in partial hepatectomy . In the tourniquet group , the hepatic veins were completely isolated and occluded with tourniquets . In the Satinsky clamp group , the hepatic veins were dissected on the anterior and side walls only and they were clamped directly by Satinsky clamps . RESULTS The time for dissecting hepatic veins was significantly shorter in the Satinsky clamp group ( 7.5 ± 6.6 min vs 21.3 ± 7.4 min ) than the tourniquet group . In the tourniquet group , 5 hepatic veins could not be completely isolated and encircled . In 4 additional patients the hepatic vein was slightly torn during dissection . These 9 patients received successful occlusion using Satinsky clamps . In the Satinsky group , all occlusion of the hepatic vein was successful . There was a significant difference in the success rate in hepatic vein occlusion using the Satinsky and the tourniquet groups 60/60 vs 51/60 , P = 0.0018 . CONCLUSIONS Both techniques of hepatic vein occlusion were safe and efficacious . As the use of Satinsky clamps is safer , easier and took less time , it is recommended A r and omized prospect i ve control trial for determining the efficacy of antithrombin III concentrates in hepatic resection was performed using 24 patients with hepatocellular carcinoma . Thirteen patients were given antithrombin III concentrates ( 1,500 IU ) immediately before operation , during hepatectomy and immediately after operation . Coagulant and fibrinolytic profiles were determined by molecular markers such as thrombin-antithrombin III complex and plasmin-alpha 2plasmin inhibitor complex . During hepatic resection , both hypercoagulability and mainly primary hyperfibrinolysis occurred . Regarding the effectiveness of antithrombin III concentrates , in the antithrombin III treatment group , only a significant lower incidence of positive soluble fibrin monomer complex at postoperative days 1 and 5 was found among all the parameters studied . Therefore , no definite evidence of clinical usefulness of the perioperative administration of antithrombin III concentrates in hepatic resection was proved BACKGROUND blood loss during liver resection and the need for perioperative blood transfusions have negative impact on perioperative morbidity , mortality , and long-term outcomes . METHODS a r and omized controlled trial was performed on patients undergoing liver resection comparing hemihepatic vascular inflow occlusion , main portal vein inflow occlusion , and Pringle maneuver . The primary endpoints were intraoperative blood loss and postoperative liver injury . The secondary outcomes were operating time , morbidity , and mortality . RESULTS a total of 180 patients were r and omized into 3 groups according to the technique used for inflow occlusion during hepatectomy : the hemihepatic vascular inflow occlusion group ( n = 60 ) , the main portal vein inflow occlusion group ( n = 60 ) , and the Pringle maneuver group ( n = 60 ) . Only 1 patient in the hemihepatic vascular occlusion group required conversion to the Pringle maneuver because of technical difficulty . The Pringle maneuver group showed a significantly shorter operating time . There were no significant differences between the 3 groups in intraoperative blood loss and perioperative mortality . The degree of postoperative liver injury and complication rates were significantly higher in the Pringle maneuver group , result ing in a significantly longer hospital stay . CONCLUSIONS all 3 vascular inflow occlusion techniques were safe and efficacious in reducing blood loss . Patients subjected to hemihepatic vascular inflow occlusion , or main portal vein inflow occlusion responded better than those with Pringle maneuver in terms of earlier recovery of postoperative liver function . As hemihepatic vascular inflow occlusion was technically easier than main portal vein inflow occlusion , it is recommended BACKGROUND The optimal perioperative fluid resuscitation strategy for liver resections remains undefined . Goal -directed therapy ( GDT ) embodies a number of physiologic strategies to achieve an ideal fluid balance and avoid the consequences of over- or under-resuscitation . STUDY DESIGN In a prospect i ve r and omized trial , patients undergoing liver resection were r and omized to GDT using stroke volume variation as an end point or to st and ard perioperative resuscitation . Primary outcomes measure was 30-day morbidity . RESULTS Between 2012 and 2014 , one hundred and thirty-five patients were r and omized ( GDT : n = 69 ; st and ard perioperative resuscitation : n = 66 ) . Median age was 57 years and 56 % were male . Metastatic disease comprised 81 % of patients . Overall ( 35 % GDT vs 36 % st and ard perioperative resuscitation ; p = 0.86 ) and grade 3 morbidity ( 28 % GDT vs 18 % st and ard perioperative resuscitation ; p = 0.22 ) were equivalent . Patients in the GDT arm received less intraoperative fluid ( mean 2.0 L GDT vs 2.9 L st and ard perioperative resuscitation ; p < 0.001 ) . Perioperative transfusions were required in 4 % ( 6 % GDT vs 2 % st and ard perioperative resuscitation ; p = 0.37 ) and boluses in the postanesthesia care unit were administered to 24 % ( 29 % GDT vs 20 % st and ard perioperative resuscitation ; p = 0.23 ) . Mortality rate was 1 % ( 2 of 135 patients ; both in GDT ) . On multivariable analysis , male sex , age , combined procedures , higher intraoperative fluid volume , and fluid boluses in the postanesthesia care unit were associated with higher 30-day morbidity . CONCLUSIONS Stroke volume variation-guided GDT is safe in patients undergoing liver resection and led to less intraoperative fluid . Although the incidence of postoperative complications was similar in both arms , lower intraoperative resuscitation volume was independently associated with decreased postoperative morbidity in the entire cohort . Future studies should target extensive resections and identify patients receiving large resuscitation volumes , as this population is more likely to benefit from this technique HYPOTHESIS Hepatic parenchymal transection is a technical priority in liver surgery . The use of an ultrasonic dissector for hepatectomy may result in less blood loss than conventional clamp crushing . DESIGN R and omized controlled trial . SETTING University teaching hospital . PATIENTS The 132 patients scheduled to undergo partial hepatectomies were r and omly assigned to receive hepatic transection by ultrasonic dissector or by clamp crushing ( 66 patients by each method ) . INTERVENTIONS All resections were performed with inflow occlusion and were guided ultrasonographically . Hepatectomies were grade d according to a predefined system based on 6 criteria ( blood loss , transection time , technical error , surgical margin , l and mark appearance , and postoperative morbidity ) , each with 3 scores ( lower scores indicating higher quality ) . MAIN OUTCOME MEASURES Blood loss and hepatectomy grade . RESULTS No difference was found between the ultrasonic and clamp groups in median blood loss ( 515 mL [ range , 15 - 2527 mL ] vs 452 mL [ range , 17 - 1912 mL ] ; P = .63 ) , transection time ( 61 minutes [ range , 16 - 177 minutes ] vs 54 minutes [ range , 7 - 205 minutes ] ; P = .58 ) , or transection speed ( 1.1 cm(2)/min [ range , 0.4 - 4.0 cm(2)/min ] vs 1.0 cm(2)/min [ range , 0.4 - 3.0 cm(2)/min ] ; P = .90 ) . Ultrasonic dissection caused more frequent histologically proven tumor exposure at the surgical margin ( 9 vs 3 patients ; P = .09 ) , incomplete appearance of l and mark hepatic veins on the cut surface after anatomical resection ( 12 vs 4 patients ; P = .03 ) , and postoperative morbidity ( 20 vs 14 patients ; P = .32 ) than did clamp crushing . The hepatectomies with clamp crushing had significantly higher grade s than those with ultrasonic dissection ( P = .05 ) , as indicated by the lower median sum score ( 4.0 [ range , 0 - 12 ] vs 5.0 [ range , 0 - 19 ] ; 95 % confidence interval for difference , -2.0 to 0 ; P = .03 ) . The transection method independently influenced hepatectomy grade ( adjusted odds ratio = 3.06 ; 95 % confidence interval , 1.35 - 6.92 ; P = .01 ) . CONCLUSIONS Ultrasonic dissection offers no reduction in blood loss compared with clamp crushing for transection of the liver . Clamp crushing results in a higher quality of hepatectomy and is therefore the option of choice BACKGROUND Parenchymal liver transection constitutes an important phase of liver resection . Serious intraoperative bleeding , together with injuries to vital structures of the liver remnant , can occur during this stage . A method of sharp liver parenchymal transection with scalpel is compared in a prospect i ve r and omized manner with the widely used clamp crushing technique . METHODS Patients scheduled for hepatectomy under selective hepatic vascular exclusion ( N = 82 ) were allocated r and omly to either the sharp transection group ( n = 41 ) or the clamp crushing group ( n = 41 ) . Warm ischemic time , blood loss and transfusions , postoperative morbidity and mortality , and tumor-free margins were recorded in both groups and analyzed . RESULTS When the sharp transection group was compared with the clamp crushing group , the two groups were similar in warm ischemic time ( median 36 vs 34 minutes ) , total operative time ( median 205 vs 211 minutes ) , intraoperative blood loss ( median 500 vs 460 mL ) , blood transfusion requirements ( median value 0 in both groups ) , and overall complication rate ( 44 % vs 39 % ) . However , sharp transection yielded better tumor-free margins compared with the clamp crushing technique ( 12 + /- 1.4 mm vs 8 + /- 1.5 mm , mean + /- SD , P < .05 ) . CONCLUSION Sharp liver parenchymal transection with a scalpel is equally safe in terms of blood loss and mortality compared with the clamp crushing method . Although it is a technically dem and ing method , requiring selective hepatic vascular occlusion , it may be recommended when the tumor-free margins are anticipated to be narrow OBJECTIVE To observe the effects of acute normovolemic hemodilution ( ANH ) on coagulation function and fibrinolysis in elderly patients undergoing hepatic carcinectomy . METHODS Thirty elderly patients ( aged 60 - 70 years ) with liver cancer ( American Society of Anesthesiologists physical status I-II ) scheduled for hepatic carcinectomy from February 2007 to February 2008 were r and omly divided into ANH group ( n = 15 ) and control group ( n = 15 ) . After tracheal intubation , patients in ANH group and control group were infused with 6 % hydroxyethyl starch ( HES ) ( 130/0.4 ) , and basic liquid containing 6 % HES and routine Ringer 's solution , respectively . In all the studied patients , blood sample s were drawn at five different time points : before anesthesia induction ( T1 ) , 30 minutes after ANH ( T2 ) , 1 hour after start of operation ( T3 ) , immediately after operation ( T4 ) , and 24 hours after operation ( T5 ) . Then coagulation function , soluble fibrin monomer complex ( SFMC ) , prothrombin fragment ( F1 + 2 ) , and platelet membrane glycoprotein ( activated GPIIb/GPIIIa and P-selectin ) were measured . RESULTS The perioperative blood loss was not significantly different between the two groups ( P > 0.05 ) . The volume of allogeneic blood transfusion in ANH group was significantly smaller than that in control group ( 350.5 + /- 70.7 mL vs. 457.8 + /- 181.3 mL , P < 0.01 ) . Compared with the data of T1 , prothrombin time ( PT ) and activated partial thromboplastin time in both groups prolonged significantly after T3 ( P < 0.05 ) , but still within normal range . There were no significant changes in thrombin time and D-dimer between the two groups and between different time points in each group ( all P > 0.05 ) . SFMC and F1 + 2 increased in both groups , but without statistical significance . P-selectin expression on the platelet surface of ANH group was significantly lowered at T2 and T3 compared with the level at T1 ( P < 0.05 ) . Compared with control group , P-selectin was significantly lower in ANH group at T2-T5 ( all P < 0.05 ) . CONCLUSIONS In elderly patients undergoing resection of liver cancer , ANH may not hamper fibrinolysis and coagulation function . It could therefore be safe to largely reduce allogeneic blood transfusion BACKGROUND Allogeneic blood transfusion during liver resection for malignancies has been associated with an increased incidence of tumor recurrence and decreased survival in some series . Isovolemic hemodilution ( IH ) has been utilized in cardiac , orthopedic , and major general surgery procedures to reduce the use of banked blood products . We therefore sought to determine the safety and efficacy of IH during major hepatic resection in an adult population . METHODS Thirteen consecutive patients undergoing major hepatic resection with IH were compared with 13 age- and disease-matched controls . The diseases included metastatic colorectal adenocarcinoma ( 8 versus 9 ) , hepatoma ( 2 in each group ) and other ( 3 versus 2 ) ; and the procedures included total ( right or left ) hepatic lobectomy ( 8 versus 11 ) , partial lobectomy ( 3 versus 1 ) and trisegmentectomy ( 2 versus 1 ) . RESULTS There was no significant difference in operating time , estimated blood loss , fresh frozen plasma , platelets , amount of crystalloid or colloid infused between the two groups . There was no perioperative morbidity related to IH . The use of IH result ed in a 60 % reduction in mean packed red blood cells transfusion during major hepatic resection . Only 38 % of patients undergoing IH required packed red cells transfusion , whereas 77 % of historical control patients required allogenic transfusion . CONCLUSION The use of IH reduces the need for homologous transfusion during major hepatic resection . IH is a safe technique during hepatic resection and is not associated with perioperative morbidity BACKGROUND Intermittent occlusion of hepatic blood inflow by means of a hemihepatic or total hepatic occlusion technique is essential for reducing operative blood loss . Central liver resection to preserve more functioning liver parenchyma is m and atory for central ly located liver tumors in patients with cirrhosis , but it requires a longer overall hepatic ischemic time because of a wide transection plane . No controlled comparison has been performed for the 2 techniques in these operations . HYPOTHESIS Hemihepatic inflow occlusion may be beneficial in cirrhotic patients who undergo complex central hepatectomy with a wide liver transection plane . DESIGN A prospect i ve , r and omized study . SETTING University hospital and tertiary referral center . PATIENTS During liver parenchymal transection , 58 cirrhotic patients who underwent complex central liver resections with a wide transection plane were prospect ively r and omized into 2 groups . In the group undergoing total hepatic inflow clamping ( group T ; n = 28 ) , occlusion of hepatic blood inflow was performed for 15 minutes with declamping for 5 minutes . In the group undergoing selective clamping of ipsilateral blood inflow ( group H ; n = 30 ) , clamping was performed for 30 minutes with declamping for 5 minutes . INTERVENTION Comparison of patient background s , operative procedures , and early postoperative results . MAIN OUTCOME MEASURES Operative blood loss , need for blood transfusion , and postoperative morbidity . RESULTS The patients ' background s , operative procedures , and area of liver transection plane were not significantly different between the 2 groups . In all patients , the liver transection areas were greater than 60 cm(2 ) and overall liver ischemic times were greater than 60 minutes . The amount of operative blood loss and incidence of blood transfusion were significantly greater in group T because of greater blood loss during declamping . Overall liver ischemic and total operative times , postoperative morbidity , and postoperative changes in liver enzyme levels were not significantly different between groups . No in-hospital deaths occurred in either group . CONCLUSIONS Intermittent hemihepatic and total occlusion of hepatic blood inflow are safe in cirrhotic patients with an overall ischemic time of greater than 60 minutes . However , for complex liver resections with an estimated liver transection plane of greater than 60 cm(2 ) , hemihepatic occlusion of blood inflow , if feasible , may be recommended in cirrhotic patients to reduce operative blood loss and the incidence of blood transfusion under our defined occlusion time Our study aim ed at evaluating the effect of blood transfusion - allogeneic or autologous - on plasma levels of fibronectin during liver resections . Thirty-five patients scheduled for liver resection were r and omly allocated to receive autologous ( group autologous blood transfusion ( ABT ) , n= 19 ) or allogeneic ( homologous ) ( homologous blood transfusion ( HBT ) , n= 16 ) packed red blood cell to maintain serum haemoglobin concentration above 9 g. Serum levels of fibronectin were measured before induction of anaesthesia , at the end of operation and at first , third and sixth postoperative day . Perioperative morbidity and survival rate were also recorded . Serum fibronectin levels were significantly higher ( P < 0.05 ) in the autologous group than in the allogeneic , at the first ( 134 + /- 49 microg mL(-1 ) vs. 89 + /- 31 microg mL(-1 ) ) and third ( 178 + /- 51 microg mL(-1 ) vs. 96 + /- 41 microg mL(-1 ) ) postoperative day . No differences in survival and complication rate between the two groups were observed . Concentrations of serum fibronectin seem to be adversely affected by allogeneic blood transfusion during liver resection surgery , although this does not seem to affect patients ' morbidity and mortality Objective : To evaluate whether major right hepatectomy using the anterior approach technique for large hepatocellular carcinoma ( HCC ) results in better operative and long-term survival outcomes when compared with the conventional approach technique . Summary Background Data : The anterior approach technique has been advocated recently for large right liver tumors . However , its beneficial effects on the operative and survival outcomes of the patients have not been evaluated prospect ively . Methods : A prospect i ve r and omized controlled study was performed on 120 patients who had large ( ≥5 cm ) right liver HCC and underwent curative major right hepatic resection during a 57-month period . The patients were r and omized to undergo resection of the tumor using the anterior approach technique ( AA group , n = 60 ) or the conventional approach technique ( CA group , n = 60 ) . The anterior approach technique involved initial vascular inflow control , completion of parenchymal transection , and complete venous outflow control before the right liver was mobilized . Operative and long-term survival outcomes of the two groups were analyzed . Quantitative assessment s of markers of circulating tumor cells at various stages of surgery of the two techniques were also assessed by plasma albumin-mRNA . Results : The overall operative blood loss , morbidity , and duration of hospital stay were comparable in both groups . Major operative blood loss of ≥2 L occurred less frequently in the AA group ( 8.3 % vs. 28.3 % , P = 0.005 ) . As a result , blood transfusion requirement and number of patients requiring blood transfusion were significantly lower in the AA group . Hospital mortality occurred in 1 patient in the AA group and 6 patients in the CA group ( P = 0.114 ) . Median disease-free survival was 15.5 months in the AA group and 13.9 months in the CA group ( P = 0.882 ) . Overall survival was significantly better in the AA group ( median > 68.1 months ) than in the CA group ( median = 22.6 months , P = 0.006 ) . The survival benefit appeared more obvious in patients with stage II disease and patients with lymphovascular permeation of the tumor . The anterior approach was also found to associate with significantly lower plasma albumin-mRNA levels at various stages of surgery compared with the CA technique . On multivariate analysis , tumor staging , anterior approach hepatic resection , and resection margin involved by the tumor were independent factors affecting overall survival . Conclusion : The anterior approach results in better operative and survival outcomes compared with the conventional approach . It is the preferred technique for major right hepatic resection for large HCC BACKGROUND / AIMS It has been shown that hepatic pedicle clamping is a safe and effective technique to control bleeding during liver resection . A major drawback can be the induction of liver ischemia and splanchnic venous stasis . METHODOLOGY This r and omized controlled clinical trial compared continuous and intermittent hepatic pedicle clamping during resection of the cirrhotic liver in order to determine which technique is more effective in reducing operative blood loss and producing less ischemic injury . In 18 patients we performed continuous portal triad clamping during liver transection while in 17 patients we performed intermittent clamping . The two groups matched for extent of resection . Serial hepatic function tests were performed on postoperative day 1 , 3 and 7 . RESULTS No significant difference was found between the two groups in terms of operative findings . Operative mortality was 5.7 % ( 2 patients ) . Six patients ( 17.3 % ) had postoperative complications . There were no significant differences between the two groups with regard to postoperative liver function tests and coagulation profile . CONCLUSIONS Continuous and intermittent clamping are both effective in reducing blood loss during hepatectomy in cirrhosis . The two techniques seem to be comparable in terms of ischemic injury . Our findings suggest that intermittent portal triad clamping may not be necessary . As this is contrary to the normal expectancy , additional studies may be needed The intermittent Pringle manoeuvre during hepatectomy results in a better clinical outcome when the accumulated ischaemia time is less than 120 min . The aim of this study was to investigate hepatic gene expression related to microcirculatory modulation and ultrastructural changes in patients having the intermittent Pringle manoeuvre BACKGROUND Total hepatic vascular exclusion ( THVE ) and selective hepatic vascular exclusion ( SHVE ) are two effective techniques for bleeding control in major hepatic resections . Outcomes of the two procedures were compared . METHODS Patients undergoing major liver resection were r and omly allocated to the THVE and SHVE groups . Intraoperative hemodynamic changes and the postoperative course of the two groups were compared . RESULTS During vascular clamping , the THVE group showed a significant elevation in pulmonary vascular resistance , systemic vascular resistance , intrapulmonary shunts , and a significant reduction in cardiac index , compared with the SHVE group ( P < 0.05 ) . Patients undergoing THVE received more crystalloids and blood , showed more severe liver , renal and pancreatic dysfunction , and had a longer hospital stay than the SHVE group ( P < 0.05 ) . CONCLUSIONS Both techniques are equally effective in bleeding control in major liver resections . THVE is associated with cardiorespiratory and hemodynamic alterations and may be not tolerated by some patients . SHVE is well tolerated with fewer postoperative complications and shorter hospitalization time BACKGROUND / AIMS The propensity of fibrin glue to achieve ultimate control of the liver raw surface and its tolerance after hepatic resection , were evaluated by a prospect i ve study . MATERIAL S AND METHODS Seventy seven patients undergoing elective liver resection for benign lesions ( n = 35 ) and malignant lesions ( n = 42 ) including 7 with cirrhosis were studied . R and omization took place only at peritoneal closure and after completion of hemostasis and biliostasis . RESULTS In the group with fibrin glue ( n = 38 ) , a single dose of 5 ml was applied to the liver cut surface . The appearance of the liver margin at abdominal closure was judged as dry in 34/35 ( 97 % ) patients with fibrin glue , versus 34/42 ( 81 % ) in those without ( p = 0.016 ) . Although postoperative morbidity and mortality were not different between the 2 groups , the mean total fluid drainage during the three postoperative days and bilirubin concentration were significantly lower in the group with fibrin glue ; respectively 242 + /- 249 ml vs 505 + /- 666 ml and 24 + /- 21 mmoles/l vs 65 + /- 47 mmoles/l . CONCLUSIONS Our results indicate that fibrin glue application to the hepatic stump after hepatic resection provides effective sealing with good systemic and local compatibility In a prospect i ve study 116 patients underwent liver resection . Three different resection techniques , blunt dissection ( n = 61 ) , ultrasonic aspirator ( CUSA ) ( n = 27 ) and jet-cutter ( n = 28 ) were compared . Speed of resection , blood loss , transfusion rate , liver hilus clamping time and tissue damage were evaluated on the basis of area of transected liver surface . Liver resection with the jet-cutter was significantly faster with a resection time of 0.33 min/cm2 in comparison to blunt dissection ( 0.57 min/cm2 ) and CUSA ( 0.50 min/cm2 ) ( P < 0.01 ) and associated with lower blood loss of 17.7 ml/cm2 ( P < 0.01 ) than the other techniques ( blunt dissection 32.5 ml/cm2 , CUSA 24.3 ml/cm2 ) . Tissue damage with respect to transaminases SGOT and SGPT was comparable to the other techniques . The jet-cutter is a promising new instrument in liver surgery Background : Prevention of bleeding episodes in noncirrhotic patients undergoing partial hepatectomy remains unsatisfactory in spite of improved surgical techniques . The authors conducted a r and omized , placebo-controlled , double-blind trial to evaluate the hemostatic effect and safety of recombinant factor VIIa ( rFVIIa ) in major partial hepatectomy . Methods : Two hundred four noncirrhotic patients were equally r and omized to receive either 20 or 80 & mgr;g/kg rFVIIa or placebo . Partial hepatectomy was performed according to local practice at the participating centers . Patients were monitored for 7 days after surgery . Key efficacy parameters were perioperative erythrocyte requirements ( using hematocrit as the transfusion trigger ) and blood loss . Safety assessment s included monitoring of coagulation-related parameters and Doppler examination of hepatic vessels and lower extremities . Results : The proportion of patients who required perioperative red blood cell transfusion ( the primary endpoint ) was 37 % ( 23 of 63 ) in the placebo group , 41 % ( 26of 63 ) in the 20-&mgr;g/kg group , and 25 % ( 15 of 59 ) in the 80-&mgr;g/kg dose group ( logistic regression model ; P = 0.09 ) . Mean erythrocyte requirements for patients receiving erythrocytes were 1,024 ml with placebo , 1,354 ml with 20 & mgr;g/kg rFVIIa , and 1,036 ml with 80 & mgr;g/kg rFVIIa ( P = 0.78 ) . Mean intraoperative blood loss was 1,422 ml with placebo , 1,372 ml with 20 & mgr;g/kg rFVIIa , and 1,073 ml with 80 & mgr;g/kg rFVIIa ( P = 0.07 ) . The reduction in hematocrit during surgery was smallest in the 80-&mgr;g/kg group , with a significant overall effect of treatment ( P = 0.04 ) . Conclusions : Recombinant factor VIIa dosing did not result in a statistically significant reduction in either the number of patients transfused or the volume of blood products administered . No safety issues were identified Selective hepatic vascular exclusion ( SHVE ) and the Pringle maneuver are two methods used to control bleeding during hepatectomy . They are compared in a prospect i ve r and omized study , where 110 patients undergoing major liver resection were r and omly allocated to the SHVE group or the Pringle group . Data regarding the intraoperative and postoperative courses of the patients are analyzed . Intraoperative blood loss and transfusion requirements were significantly decreased in the SHVE group , and postoperative liver function was better in that group . Although there was no difference between the two groups regarding the postoperative complications rate , patients offered the Pringle maneuver had a significantly longer hospital stay . The application of SHVE did not prolong the warm ischemia time or the total operating time . It is evident from the present study that SHVE performed by experienced surgeons is as safe as the Pringle maneuver and is well tolerated by the patients . It is much more effective than the Pringle maneuver for controlling intraoperative bleeding , and it is associated with better postoperative liver function and shorter hospital stay In recent decades a variety of instruments for liver dissection has become available . This r and omized controlled trial analysed the efficacy and costs of three different liver dissection devices Bleeding , biliary fistula and subphrenic abscess represent the major postoperative complications after liver surgery . Many different adjuvant methods have been developed for control of hemorrhage from the raw surface of liver , but the superiority of any single method remains to be proved . The use of a two-component fibrin adhesive for the control of solid organ bleeding seems to be promising . This study was to evaluate the efficacy of this fibrin adhesive for control of postoperative bleeding in liver surgery . Forty patients were r and omized into two groups , similar in all demographic and clinical conditions . Fibrin adhesive was applied to the raw surface of liver resections at the end of operations for 20 patients . Nothing was applied for the control group . Postoperative bleeding was estimated by multiplying the drain amount by the free hemoglobin concentration , every day . Estimated postoperative bleeding was 8.12 + /- 5.65 gm for patients with fibrin adhesive , 15.57 + /- 14.43 gm for control group . Fibrin adhesive has been used in the treatment of injury to the liver and spleen . In this study , it proved to be useful in the control of postoperative bleeding in liver resection , and hopefully decreasing morbidity AIM OF THE STUDY For all resection-techniques of liver tissue intra- and post-operative blood-loss remains an important problem . Two novel resection-techniques the ultrasound-aspirator ( CUSA ) and the water-jet dissector ( Jet-Cutter ) appear to offer significant advantages regarding this problem . Aim of the present prospect i ve clinical study was the comparison of these dissection techniques . MATERIAL AND METHODS Prospect i ve r and omized study with the end points blood-loss , length of surgery , tissue trauma and long-term survival . FINDINGS Significant differences between both procedures with Jet-Cutter ( n = 31 ) versus ultrasonic surgical aspirator CUSA ( n = 30 ) were observed regarding length of resection and complete liver ischemia time ( Pringle-time ) . Here significant advantages of the jet-cutter-technique were observed with 28 + /- 11 minutes length of resection versus 46 + /- 19 minutes and 29 + /- 12 minutes Pringle-time versus 39 + /- 16 minutes . Furthermore , significant fewer blood transfusions were required following jet-cutter-resection with a mean of 1.5 blood units vs. 2.5 blood units using the CUSA . No differences were observed regarding postoperative long-term survival . CONCLUSIONS The jet-cutter-technique is a fast and safe surgical procedure for liver resections and offers an attractive therapeutic alternative for various indications in liver surgery Objective : To examine the feasibility of a real “ blood transfusion”-free hepatectomy in a large group of patients with liver tumors . Summary Background Data : Bleeding control and blood transfusion remains problematic in liver resection . A real “ blood transfusion”-free hepatectomy in a large group of patients has rarely been reported . The impact of tranexamic acid ( TA ) , an antifibrinolytic agent , on blood transfusion in liver resection is unknown . Methods : A prospect i ve double-blind r and omized trial was performed on elective liver tumor resections . In group A , TA 500 mg was intravenously administered just before operation followed by 250 mg , every 6 hours , for 3 days . In group B , only placebo was given . The patients ' background , blood transfusion rates , and early postoperative results in the 2 groups were compared . Factors that influenced blood requirement were analyzed . Results : There were 108 hepatectomies in group A and 106 hepatectomies in group B. The patients ' background s , operative procedures , and hepatectomy extent did not significantly differ between the 2 groups . Although the differences of the operative morbidity and postoperative stay were not significant , a significantly lower amount of operative blood loss , lower blood transfusion rate , shorter operative time , and lower hospital costs were found in group A patients . No patient in group A received blood transfusion . No hospital mortality occurred in either group . Tumor size and use of TA were independent factors that influenced blood transfusion . Conclusions : Perioperative parenteral use of TA reduced the amount of operative blood loss and the need for blood transfusion in elective liver tumor resection . A real “ blood transfusion”-free hepatectomy may be feasible with the assistance of parenteral TA BACKGROUND We evaluated the benefit of autologous blood transfusion and the effect of recombinant human erythropoietin ( rh-EPO ) on preoperative autologous blood donation for hepatectomy in patients with cirrhosis . METHODS Forty-two patients with cirrhosis and hepatocellular carcinoma underwent hepatectomy , 21 of whom ( group A ) donated autologous blood before operation . Eleven of these patients ( group A1 ) were administered rh-EPO before operation , and ten patients ( group A2 ) were untreated . Twenty-one patients ( group B ) did not donate autologous blood . RESULTS The frequency of homologous blood transfusion was 24 % in group A and 62 % in group B ( p < 0.05 ) . Preoperative erythropoiesis increased markedly in group A1 , and postoperative erythropoietin production was not suppressed in this group . Postoperative hematocrits recovered significantly more rapidly in patients transfused with only autologous blood . Postoperative serum total bilirubin concentrations were significantly higher in patients with transfused homologous blood . CONCLUSIONS Autologous blood transfusion yields clinical ly superior results for hepatectomy in patients with cirrhosis when compared with homologous transfusion . Preoperative rh-EPO administration minimizes presurgical decreases in hematocrit caused by autologous blood donation Objective : To evaluate the efficacy , amount of hemorrhage , biliary leakage , complications , and postoperative evolution after fibrin glue sealant application in patients undergoing liver resection . Summary Background Data : Fibrin sealants have become popular as a means of improving perioperative hemostasis and reducing biliary leakage after liver surgery . However , trials regarding its use in liver surgery remain limited and of poor method ologic quality . Patients and Methods : A total of 300 patients undergoing hepatic resection were r and omly assigned to fibrin glue application or control groups . Characteristics and debit of drainage and postoperative complications were evaluated . The amount of blood loss , measurements of hematologic parameters liver test , and postoperative evolution ( particularly involving biliary fistula and morbidity ) was also recorded . Results : Postoperatively , no differences were observed in the amount of transfusion ( 0.15 ± 0.66 vs. 0.17 ± 0.63 PRCU ; P = 0.7234 ) or in the patients that required transfusion ( 18 % vs. 12 % ; P = 0.2 ) , respectively , for the fibrin glue or control group . There were no differences in overall drainage volumes ( 1180 ± 2528 vs. 960 ± 1253 mL ) or in days of postoperative drainage ( 7.9 ± 5 vs. 7.1 ± 4.7 ) . Incidence of biliary fistula was similar in the fibrin glue and control groups , ( 10 % vs. 11 % ) . There were no differences regarding postoperative morbidity between groups ( 23 % vs. 23 % ; P = 1 ) . Conclusions : Application of fibrin sealant in the raw surface of the liver does not seem justified . Blood loss , transfusion , incidence of biliary fistula , and outcome are comparable to patients without fibrin glue . Therefore , discontinuation of routine use of fibrin sealant would result in significant cost saving BACKGROUND This Phase 3 , international , r and omized , single-blind , controlled trial ( FINISH-3 ) compared the efficacy and safety of Fibrocaps , a ready-to-use , dry-powder fibrin sealant containing human plasma-derived thrombin and fibrinogen , vs gelatin sponge alone for use as a hemostat for surgical bleeding in 4 indications ( ie , spinal , hepatic , vascular , soft tissue dissection ) . STUDY DESIGN Adults with mild to moderate surgical bleeding ( r and omized 2:1 ; Fibrocaps vs gelatin sponge ) were treated at a single bleeding site ( day 1 ) . Time to hemostasis ( TTH ) during 5 minutes was compared ( log-rank statistic ) within each indication . Safety follow-up continued to day 29 . RESULTS Patients were treated ( Fibrocaps , n = 480 ; gelatin sponge , n = 239 ) when undergoing spinal ( n = 183 ) , vascular ( n = 175 ) , hepatic ( n = 180 ) , or soft-tissue ( n = 181 ) procedures . Fibrocaps was applied by spray device in 53 % of all procedures ( 94 % of hepatic and soft-tissue procedures ) . Fibrocaps significantly reduced TTH compared with gelatin sponge ; estimated hazard ratios were 3.3 , 2.1 , 2.3 , and 3.4 for the 4 surgical indications , respectively ( each p < 0.001 ; primary end point ) . Fibrocaps significantly reduced median TTH for each indication ( p < 0.001 ) and was superior for secondary efficacy end points of restricted mean TTH ( p < 0.001 ) and probability of hemostasis at 3 ( p < 0.001 ) and 5 ( p ≤ 0.002 ) minutes . Adverse event incidences were generally similar between treatment arms . Non-neutralizing , anti-thrombin antibodies developed in 2 % of Fibrocaps-treated and 3 % of gelatin sponge-treated patients . CONCLUSIONS Fibrocaps was well tolerated and significantly reduced TTH relative to gelatin sponge alone in all 4 surgical indications . These findings demonstrate the broad utility of Fibrocaps as a hemostatic agent for mild to moderate surgical bleeding BACKGROUND / AIMS In order to reduce the rate of bleeding and bile leakage after hepatic resection , different operative techniques have been used such as selective suture , electrocautery , topical hemostatic agents , argon beam coagulation , omentoplasty and application of fibrin glue . METHODOLOGY The PlasmaJet , a recent tool that provides a high energy flow of ionized gas which seals small blood and lymph vessels has been recently introduced into clinical practice . We have conducted a r and omized trial comparing the application of 5mL of fibrin glue ( Tissucol ) and the treatment by PlasmaJet ( Plasma Surgical Limited , Theale , UK ) on the raw surface of the liver stump after elective hepatic resection . RESULTS Fifty-eight consecutive hepatic resections were performed and the postoperative mortality , blood transfusions and reoperations were not statistically different between the groups . However , there was a significant reduction of the incidence of collection s requiring percutaneous drainage in the PlasmaJet group ( p<0.001 ) . CONCLUSIONS Compared to fibrin glue application , the employment of PlasmaJet on the raw surface of the liver stump led to a significant reduction of postoperative complications requiring percutaneous drainage after elective hepatectomy Animal studies suggest that acute phase reactant cytokines and polymorphonuclear leukocytes ( PMN ) may play a critical role in ischemia‐ reperfusion injury . To evaluate whether similar mechanisms are operative in human liver , six cirrhotic and nine noncirrhotic patients undergoing right hepatectomy were r and omized for utilization of hepatic vascular exclusion ( HVE ) as a model of ischemia‐reperfusion injury . Portal and systemic levels of acute reactant cytokines ( interleukin 6 [ IL‐6 ] , interleukin 1 [ IL‐1 ] , tumor necrosis factor α [ TNF‐α ] ) and neutrophil adhesion in serial liver biopsy specimens were studied . Correlations among mediators , leukocyte adhesion , and markers of liver injury were also evaluated . Hepatic vascular exclusion result ed in substantial and reproducible changes in portal and arterial IL‐6 levels in both cirrhotic and noncirrhotic patients . Portal and systemic cytokine levels were comparable in most instances , whereas levels were usually higher in cirrhotic patients than in noncirrhotic patients . Negative correlations were found between IL‐6 levels at the time of reperfusion and later TNF‐α levels . IL‐6 levels correlated negatively with numerous markers of hepatocellular injury and the number of postoperative complications . Hepatic vascular exclusion increased neutrophils adhesion after reperfusion in cirrhotic patients but not in noncirrhotic patients . In cirrhotic patients , the degree of leukocyte adhesion after reperfusion correlated with several postoperative markers of liver injury . This study in humans shows that acute reactant cytokines are released during liver ischemia and , interestingly , that IL‐6 levels strongly correlate with clinical and laboratory measures of injury . Further studies to evaluate possible causal relationship with hepatic injury are warranted , with emphasis on the role of IL‐6 and PMN adhesion BACKGROUND Liver transection is considered a critical factor influencing intra-operative blood loss . A increase in the number of complex liver resections has determined a growing interest in new devices able to ' optimize ' the liver transection . The aim of this r and omized controlled study was to compare a radiofrequency vessel-sealing system with the ' gold-st and ard ' clamp-crushing technique . METHODS From January to December 2012 , 100 consecutive patients undergoing a liver resection were r and omized to the radiofrequency vessel-sealing system ( LF1212 group ; N = 50 ) or to the clamp-crushing technique ( Kelly group , N = 50 ) . RESULTS Background characteristics of the two groups were similar . There were not significant differences between the two groups in terms of blood loss , transection time and transection speed . In spite of a not-significant larger transection area in the LF1212 group compared with the Kelly group ( 51.5 versus 39 cm(2 ) , P = 0.116 ) , the overall and ' per cm(2 ) ' blood losses were similar whereas the transection speed was better ( even if not significantly ) in the LF1212 group compared with the Kelly group ( 1.1 cm(2 ) /min versus 0.8 , P = 0.089 ) . Mortality , morbidity and bile leak rates were similar in both groups . CONCLUSIONS The radiofrequency vessel-sealing system allows a quick and safe liver transection similar to the gold-st and ard clamp-crushing technique Control of bleeding remains key to successful hepatic resection . The present r and omized clinical trial compared infrahepatic inferior vena cava ( IVC ) clamping with low central venous pressure ( CVP ) during complex hepatectomy using portal triad clamping ( PTC ) 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 |
10,711 | 10,759,789 | Sentinel lymph node biopsy and systemic interferon remain promising modalities in the management of melanoma , although there is no affinitive evidence to support their efficacy | BACKGROUND There is conflicting data regarding the efficacy of systemic interferon as adjuvant therapy for high-risk cutaneous melanoma .
Sentinel lymph node biopsy has recently gained acceptance in the surgical management of high-risk melanoma , despite a lack of data supporting its efficacy .
OBJECTIVE To review the evidence concerning interferon and lymph node biopsy in the management of melanoma . | OBJECTIVE A prospect i ve multi-institutional r and omized surgical trial involving 740 stage I and II melanoma patients was conducted by the Intergroup Melanoma Surgical Program to determine whether elective ( immediate ) lymph node dissection ( ELND ) for intermediate-thickness melanoma ( 1 - 4 mm ) improves survival rates compared with clinical observation of the lymph nodes . A second objective was to define subgroups of melanoma patients who would have a higher survival with ELND . METHODS The eligible patients were stratified according to tumor thickness , anatomic site , and ulceration , and then were prer and omized to either ELND or nodal observation . Femoral , axillary , or modified neck dissections were performed using st and ardized surgical guidelines . RESULTS The median follow-up was 7.4 years . A multifactorial ( Cox regression ) analysis showed that the following factors independently influenced survival : tumor ulceration , trunk site , tumor thickness , and patient age . Surgical treatment results were first compared based on r and omized intent . Overall 5-year survival was not significantly different for patients who received ELND or nodal observation . However , the 552 patients 60 years of age or younger ( 75 % of total group ) with ELND has a significantly better 5-year survival . Among these patients , 5-year survival was better with ELND versus nodal observation for the 335 patients with tumors 1 to 2 mm thick , the 403 patients without tumor ulceration , and the 284 patients with tumors 1 to 2 mm thick and no ulceration . In contrast , patients older than 60 years of age who had ELND actually had a lower survival trend than those who had nodal observation . When survival rates were compared based on treatment actually received ( i.e. , including crossover patients ) , the patients with significantly improved 5-year survival rates after ELND included those with tumors 1 to 2 mm thick , those without tumor ulceration , and those 60 years of age or younger with tumors 1 to 2 mm thick or without ulceration . CONCLUSION This is the first r and omized study to prove the value of surgical treatment for clinical ly occult regional metastases . Patients 60 years or age or younger with intermediate-thickness melanomas , especially with nonulcerative melanoma and those with tumors 1 to 2 mm thick , may benefit from ELND . However , because some patients still are developing distant disease , these results should be considered an interim analysis Results of a prospect i ve r and omized clinical trial conducted by the WHO Collaborating Centers for the Evaluation of Methods of Diagnosis and Treatment of Melanoma are reported . Five‐hundred‐fifty‐three Stage I patients whose limbs were affected entered the study ; 267 were su bmi tted to wide excision and immediate node dissection and 286 had wide excision and node dissection at the time clinical ly positive nodes were detected . Survival curves of the two treatment groups could be superimposed . No subsets of patients benefitted from immediate node dissection . The authors conclude that delayed node dissection is as effective as the immediate dissection in Stage I melanoma of the extremities if the patient can be checked every three months . If the quarterly follow‐up is not guaranteed , immediate node dissection is advisable , at least for melanomas thicker than 2 mm PURPOSE Interferon alfa-2b ( IFN alpha-2b ) exhibits antitumor activity in metastatic melanoma and on this basis has been evaluated as an adjuvant therapy following surgery for deep primary ( T4 ) or regionally metastatic ( N1 ) melanoma . METHODS A r and omized controlled study of IFN alpha-2b ( Schering-Plough , Kenilworth , NJ ) administered at maximum-tolerated doses of 20 MU/m2/d intravenously ( i.v . ) for 1 month and 10 MU/m2 three times per week subcutaneously ( SC ) for 48 weeks versus observation , was conducted by the Eastern Cooperative Oncology Group ( ECOG ) in 287 patients . RESULTS A significant prolongation of relapse-free survival ( P = .0023 , one-sided ) and prolongation of overall survival ( P = .0237 , one-sided ) was observed with IFN alpha-2b therapy in this trial , which is now mature with a median follow-up time of 6.9 years . The impact of treatment on relapse rate is most pronounced early during the treatment interval . The overall benefit of treatment in this trial was analyzed stratified by tumor burden and the presence or absence of microscopic nonpalpable and palpable regional lymph node metastasis . The benefit of therapy with IFN alpha-2b was greatest among node-positive strata . Toxicity of IFN alpha-2b required dose modification in the majority of patients , but treatment at > or = 80 % of the scheduled dose was feasible in the majority of patients through the IV phase of treatment , and for more than 3 months of SC maintenance therapy . Discontinuation of treatment due to toxicity was infrequent after the fourth month of therapy . CONCLUSION IFN alpha-2b prolongs the relapse-free interval and overall survival of high-risk resected melanoma patients . The increment in median disease-free survival ( from 1 to 1.7 years ) and overall survival ( from 2.8 to 3.8 years ) that results from this therapy is associated with a 42 % improvement in the fraction of patients who are continuously disease-free after treatment with IFN ( from 26 % to 37 % ) in comparison to observation . IFN alpha-2b is the first agent to show a significant benefit in relapse-free and overall survival of high-risk melanoma patients in a r and omized controlled trial A prospect i ve r and omized study was initiated at our institution in 1972 to determine the efficacy of routine elective lymphadenectomy in localized ( stage I ) melanoma . Included in the study were 171 patients , 62 of whom had no lymphadenectomy , 55 of whom had delayed lymphadenectomy , and 54 of whom had immediate lymphadenectomy . No significant difference was found among the three treatment groups with respect to survival or metastasis-free survival . Multifactorial analysis indicated that the level of invasion and the thickness of the lesion were the most important prognostic factors , followed by age ( 60 years or older ) , site ( legs ) , and tumor type ( nodular ) . A prognostic index based on these variables was highly predictive of metastasis or death . Even when this score was considered , no significant variation was noted among the three treatment groups . More subsequent complications of melanoma , however , occurred in the group with no lymphadenectomy--36 in this group but only 19 in each of the other treatment groups . This finding was not statistically significant but does indicate that a few additional problems may be associated with leaving regional nodes intact . Further studies are needed , and indeed are being conducted , to determine whether elective lymphadenectomy improves survival sufficiently to offset the costs and the complications associated with this approach PURPOSE To compare the effect of pathologic sentinel lymph node ( SLN ) status with that of other known prognostic factors on recurrence and survival in patients with stage I or II cutaneous melanoma . PATIENTS AND METHODS We review ed the records of 612 patients with primary cutaneous melanoma who underwent lymphatic mapping and SLN biopsy between January 1991 and May 1995 to determine the effects of tumor thickness , ulceration , Clark level , location , sex , and SLN pathologic status on disease-free and disease-specific survival . RESULTS In the 580 patients in whom lymphatic mapping and SLN biopsy were successful , the SLN was positive by conventional histology in 85 patients ( 15 % ) but negative in 495 patients ( 85 % ) . SLN status was the most significant prognostic factor with respect to disease-free and disease-specific survival by univariate and multiple covariate analyses . Although tumor thickness and ulceration influenced survival in SLN-negative patients , they provided no additional prognostic information in SLN-positive patients . CONCLUSION Lymphatic mapping and SLN biopsy is highly accurate in staging nodal basins at risk for regional metastases in primary melanoma patients and identifies those who may benefit from earlier lymphadenectomy . Furthermore , pathologic status of the SLN in these patients with clinical ly negative nodes is the most important prognostic factor for recurrence . The information from SLN biopsy is particularly helpful in establishing stratification criteria for future adjuvant trials |
10,712 | 17,636,632 | There was insufficient evidence of effectiveness to recommend or advise against IUI with or without OH above TI , or vice versa . | BACKGROUND Intra-uterine insemination ( IUI ) is one of the most frequently used fertility treatments for couples with male subfertility .
Its use , especially when combined with ovarian hyperstimulation ( OH ) has been subject of discussion .
Although the treatment itself is less invasive and expensive than others , its efficacy has not been proven .
Furthermore , the adverse effects of OH such as ovarian hyperstimulation syndrome ( OHSS ) and multiple pregnancy are a concern .
OBJECTIVES The aim of this review is to determine whether for couples with male subfertility , IUI improves the live birth rates or ongoing pregnancy rates compared with timed intercourse ( TI ) , with or without OH . | Ovarian stimulation combined with intra-uterine insemination ( IUI ) is an effective treatment of non-tubal infertility but most women undergo several cycles of treatment to achieve a pregnancy . This prospect i ve study was design ed to assess the consistency ( or variation ) of ovarian responses and the effect of various ovarian stimulation protocol s on this consistency in consecutive cycles of ovarian stimulation and IUI in women with non-ovulatory infertility . A total of 86 regularly menstruating ovulating patients each completed three to six cycles of ovarian stimulation and IUI ( n = 347 cycles ) . Ovarian stimulation was achieved by sequential clomiphene citrate/human menopausal gonadotrophin ( HMG ) , HMG-only or combined gonadotrophin-releasing hormone analogue -- HMG protocol s in 33 , 29 and 24 patients respectively , and each patient used the same protocol consistently throughout the study . St and ard methods were used to monitor ovarian response and to perform IUI . Using each patient as her own control , repeated measurements analysis of variance revealed consistency of ovarian response in consecutive ovarian stimulation cycles , as shown by the number and mean diameter of maturing pre-ovulatory follicles , peak plasma oestradiol , duration of stimulation and mean HMG requirements . This consistency existed using any of the ovarian stimulation protocol s. We conclude that regularly menstruating and ovulating women are likely to have similar ovarian responses in consecutive cycles of ovarian stimulation and IUI if the same ovarian stimulation protocol is used consistently . ( ABSTRACT TRUNCATED AT 250 WORDS Superovulation was performed prospect ively with pure follicle stimulating hormone ( FSH ) to a group of 224 infertile patients with ovulatory factor ( 51 ) , male factor ( 60 ) , mild/moderate endometriosis ( 24 ) and unexplained infertility ( 72 ) . The aim was to produce three or four leading follicles in order to compensate for a ' deficient ' factor . Ovulation was induced with human chorionic gonadotrophin ( HCG ) and monitoring was performed entirely by serial transvaginal ultrasound on alternate cycles up to a maximum of six cycles ( 1120 treatment cycles ) with intervening cycles being used as self-controls ( 932 rest cycles ) . A further control group of 56 patients was matched for age , category and duration of infertility and was only scanned serially ( 336 control cycles ) . Seventy-four pregnancies were achieved and 54 delivered , giving a cumulative pregnancy rate per couple of 33 % and a cumulative take home baby rate of 24 % per couple after a maximum of six cycles of treatment . When compared with the rest or control cycles , treatment was significantly effective for ovulatory ( P < 0.001 ) , mild/moderate endometriosis ( P < 0.01 ) and unexplained infertility ( P < 0.01 ) but not for male infertility . Furthermore , pregnancy was five times more likely during the first four treatment cycles ( P = 0.00006 , odds ratio = 5 ) at the expense of a significant multiple pregnancy rate ( 18.9 % ) and mild/moderate ovarian hyperstimulation rate ( 12 % ) . We conclude that four cycles of superovulation should be routinely offered to couples on waiting lists for assisted conception or to those unable to afford it , in anovulatory , mild/moderate endometriosis and unexplained infertility . These results need confirmation by a prospect i ve multi-centre r and omized study OBJECTIVE To determine whether crossover trials with simple pooling of data over different study periods leads to a different estimate of treatment effect compared with parallel group trials in infertility research using pregnancy as the outcome measure . DESIGN An observational study using nine overviews that included trials with both crossover and parallel group design s. These overviews comprised 17 crossover and 17 parallel group trials . In total , there were 5,291 outcomes including 775 pregnancies . The association between study design and treatment effect estimate was analyzed using multiple logistic regression , controlling for differences in the therapeutic interventions and variations in the method ological quality of the trials . SETTING Infertile patients in an academic research environment . PATIENTS Infertile patients undergoing treatment efficacy evaluation in controlled trials . INTERVENTIONS R and om allocation to a variety of treatments including clomiphene citrate , hCG , IUI , tamoxifen , and bromocriptine . MAIN OUTCOME MEASURE Estimate of bias between study design s , based on the interaction of study design and treatment in the logistic regression model . RESULTS Crossover trials produced a larger average estimate of treatment effect compared with trials with a parallel group design , overestimating the odds ratio by 74 % ( 95 % confidence interval , 2 % to 197 % ) . CONCLUSION The use of a crossover design for evaluating infertility treatments with outcomes that prevent patients from completing later phases of the trial should be avoided because it leads to exaggerated estimates of treatment effect and may result in erroneous inferences and clinical decisions . Furthermore , the type of study design should be taken into account when assessing the method ological quality of therapy trials in infertility OBJECTIVE To assess the prognostic value of strict sperm morphology analysis in intrauterine insemination with husb and 's sperm ( IUI ) cycles performed because of male infertility . DESIGN Prospect i ve study . SETTING Academic tertiary hospital . PATIENTS Seventy-four consecutive couples subjected to 271 IUI cycles because of male infertility . MAIN OUTCOME MEASURE Strict morphology analysis 1 month before the beginning of IUI following the criteria of Kruger et al. RESULTS Pregnancy and no pregnancy couples were similar regarding strict normal forms ( 2.85 % + /- 2.07 % versus 3.13 % + /- 2.63 % ) , slightly amorphous forms , and the morphology index ( 11.79 + /- 6.06 versus 12.04 + /- 7.13 ) . Pregnancy rates ( PRs ) were similar when normal forms were < 4 % ( 39.1 % ) or > 4 % ( 35.7 % ) . The PR , although higher in the group with morphology index > 10 % ( 41.4 % ) than in the group < 10 % ( 33.3 % ) , lacked statistical significance . In pure male infertility group , mean values of morphology were similar in pregnancy and nonpregnancy group . A not significant trend was detected toward higher PRs in morphology index > 10 % ( 50.0 % ) than in the group < 10 % ( 33.3 % ) . CONCLUSION Strict morphology analysis 1 month before the beginning of IUI is not a useful prognostic factor in IUI performed because of male infertility A prospect i ve trial was undertaken to evaluate the efficacy of stimulated in-vitro fertilization ( SIVF ) and stimulated intrauterine insemination ( SIUI ) in couples with unexplained and mild male factor infertility . In all , 80 couples were allocated to treatment with SIVF or SIUI , both treatments following the same protocol [ clomiphene citrate and follicle stimulating hormone ( FSH ) injection ] , except that higher doses of FSH were used in the SIVF treatment cycles . Initially , 41 couples were allocated to and started treatment with SIVF but eight cases were eventually converted to SIUI because of under-response . Similarly , although 39 couples were initially allocated to SIUI treatment , five of these converted to SIVF because of over-response . The treatment cycles that were converted either to SIUI or to SIVF were not considered as treatment failures but as treatment changes and so were included in the analyses . Of the final 38 SIVF cycles , four were cancelled ( dysfunctional response ) , failed fertilization occurred in five cycles and 29 subjects reached embryo transfer . There were two biochemical pregnancies [ positive human chorionic gonadotrophin ( HCG ) only ] , two clinical abortions and seven live births . Of the final 42 SIUI cycles , only two were cancelled , insemination being performed in the remaining 40 cases . The result was one clinical abortion , three ectopics and eight live births . The proportion of cycles with positive HCG was identical ( 28.9 % per cycle treated for SIVF and 28.6 % for SIUI ) and the livebirth rates were also not different ( 18.4 % per cycle treated for SIVF and 19.0 % for SIUI ) . The cost per maternity of SIUI was approximately half that of SIVF ( Pounds Sterling 1923 versus Pounds Sterling 4611 ) and so we conclude that , as SIUI had an efficacy that was not significantly different from SIVF ( using similar protocol s ) but was more cost-effective , it must be considered the more appropriate form of management for the treatment of unexplained and mild male factor infertility . Indeed , it is hard to justify the routine use of IVF , as a first approach , in unexplained infertility BACKGROUND We aim ed to investigate whether sperm DNA quality may predict intrauterine insemination ( IUI ) outcome . METHODS The study was design ed in a prospect i ve cohort fashion , at a tertiary centre for reproductive medicine . A total of 119 patients underwent 154 cycles of IUI . Parameters related to demography , cycle management and semen sample used for IUI were evaluated . Conventional semen parameters , morphology ( strict criteria ) , sperm DNA fragmentation and stability [ evaluated by terminal deoxynucleotidyl transferase-mediated dUDP nick-end labelling ( TUNEL ) and acridine orange staining under both acid and acid + heat denaturing conditions respectively ] were measured . The main outcome measure was clinical pregnancy , defined as ultrasonographic visualization of intrauterine gestational sac(s ) . RESULTS Logistic regression analyses were done on six sets of data , including all cycles combined , cycles with washed sample s , first cycle of each couple , first cycle of each couple with washed sample s , cycles stimulated with gonadotrophins and finally gonadotrophin-stimulated cycles with washed sample s. The number of pre-ovulatory follicles on day of hCG , the age of the woman and the percentage of sperm with acid- + heat-resistant DNA were the parameters that predicted IUI outcome in most of these data subsets . For the gonadotrophin-stimulated cycles , age of the man appeared as a predictor as opposed to that of the woman ; and for the cycles within this subgroup , where the semen sample was washed , sperm DNA fragmentation and age of the man were the only two parameters to predict IUI outcome . No sample s with > 12 % of sperm having DNA fragmentation result ed in pregnancy . CONCLUSIONS The number of follicles , age of the woman/man and sperm DNA quality may predict IUI outcome Crossover studies have been successfully conducted in the case of continuous responses . Existing procedures of analysis for ordinal responses , on the other h and , are rarely satisfactory unless strict , usually unrealistic , assumptions are made . In this paper we investigate a r and om effects model and show that the model is simple and general . Interpretation of parameters is easy , though with a complicated fitting procedure BACKGROUND The high iatrogenic multiple pregnancy rate associated with intrauterine insemination ( IUI ) in hyperstimulated cycles is becoming less acceptable . Therefore we investigated data from an earlier prospect i ve trial with regard to the specific question of whether the application of mild hyperstimulation in IUI cycles could be an alternative strategy for obtaining acceptable pregnancy rates while preventing a high multiple pregnancy rate , compared with natural cycles for IUI . METHODS Pregnancy outcome of 310 natural and 334 mildly hyperstimulated cycles for IUI in 171 couples with unexplained or mild male factor subfertility was analysed on a patient level with r and om coefficient models . RESULTS Pregnancy rates were similar : 35 and 39.8 % per couple in the natural and mildly hyperstimulated cycles respectively ( P = 0.60 ) . Multiple pregnancies , all twin pregnancies , were conceived significantly more frequently in the mild hyperstimulation group ( 27 % of the pregnancies ) than in the natural cycle group ( 4 % of the pregnancies ) ( P = 0.01 ) . All multiple pregnancies in the hyperstimulation group were conceived in multifollicular cycles . Multifollicular development was strongly associated with the application of mild hyperstimulation only ( odds ratio 21.14 , 95 % confidence interval 8.15 - 54.79 ) . CONCLUSION The application of a mild hyperstimulation protocol as an alternative to a st and ard hyperstimulation protocol for IUI does not result in higher pregnancy rates than IUI in the natural cycle , while at the same time multiple pregnancies can not be avoided . Therefore , there is no place for the use of gonadotrophins in IUI treatment BACKGROUND With the occasional reports of unexpectedly poor ovarian response to controlled ovarian hyperstimulation ( COH ) for IVF in young normally cyclic women in mind , we studied age-related ovarian response to COH in a group of women who underwent st and ard IVF . METHODS Ovarian response to COH was defined as the number of follicles > or = 14 mm on the day of hCG administration . Ovarian response to COH was analysed by multiple regression analysis with woman 's age and basal FSH concentration as explanatory variables in a prospect i ve cohort of patients with idiopathic and mild male factor subfertility ( n = 85 ) , and additionally in a large retrospective cohort of women with unexplained , mild male and tubal subfertility ( n = 1155 ) , with age as explanatory variable . RESULTS Ovarian response to COH was associated significantly with age ( P < 0.001 ) and basal FSH concentration ( P = 0.002 ) . However , in women with idiopathic or mild male subfertility , in both cohorts the relationship took the form of an inverted U-shape with both older and --surprisingly -- young women having a reduced ovarian response ( P < 0.001 ) . Maximum ovarian response was around the age of 28 years . In women with tubal infertility , there was only a linear decline of ovarian response with age . CONCLUSION It is hypothesized that diminished ovarian response to COH in IVF is the very first sign of ovarian ageing in young women diagnosed with idiopathic and mild male subfertility Efficacy of intrauterine insemination ( IUI ) using washed spermatozoa for treatment of oligozoospermia was evaluated by a prospect i ve r and omized study in 50 couples , using LH-timed natural intercourse in the alternate menstrual cycles as a control . The quality of spermatozoa in terms of their concentration and motility before and after sperm washing was compared . Sperm motility increased significantly after sperm preparation but the number of sperm was reduced . Eight pregnancies occurred in 253 cycles of IUI with washed spermatozoa and clomiphene citrate-stimulated cycles ( 3.16 % per cycle ) . Only one patient conceived in 242 LH-timed natural intercourse cycles ( 0.41 % per cycle ) . Compared with LH-timed natural intercourse , IUI provided a significantly improved pregnancy rate . When the sperm count was < 5 x 10(6 ) per ml , no pregnancy occurred with the IUI method . Therefore , IUI is a of rather limited usefulness when the sperm quality is very poor . Few complications occurred after IUI , but included slight cervical contact bleeding and mild abdominal discomfort and /or cramps . In conclusion , IUI should be considered as a useful and relatively non-invasive therapeutic modality for treating caused by moderate oligozoospermia ( > 5 x 10(6)/ml ) , when sexual intercourse fails BACKGROUND The study was carried out to determine the most likely time of day for the onset of the LH surge as detected using urine LH dipsticks , and to calculate the optimum time interval from the onset of the LH surge to intrauterine insemination ( IUI ) . METHODS A prospect i ve study of 1540 cycles of IUI with donor sperm at Clevel and Fertility Centre , Middlesbrough , between June 1990 and February 2004 . Only 951 cycles ( where a positive urine LH dipstick result was immediately preceded by a negative result ) were included in our study . To determine the best time interval between the onset of the LH surge and IUI , women were divided into five subgroups according to the positive urine test-IUI time interval and the pregnancy rate and live birth rate per cycle were calculated for each group . RESULTS The first positive test was most frequently ( 44.5 % ) found at lunch-time ( 11:00 - 15:00 ) . The live birth per cycle achieved was 5.6 % when the insemination was performed 18 - 23 h from the first detection of the LH surge , and 11.7 % when it was performed between 24 and 42 h. The live birth rate declined to 6.5 % when IUI was performed later than that . Overall , no significant differences were discovered in live birth or pregnancy rate when insemination was performed at any of the time points between 18 and 53 h. CONCLUSION Our study suggested that lunch-time is the best time to check for the LH surge using urine dipsticks and insemination at any time between 18 and 53 h after the onset of the surge will produce optimal results In the present prospect i ve study we compared , in terms of pregnancy rates , the differences between intrauterine insemination ( IUI ) of in vitro capacitated husb and 's semen and timed natural intercourse in spontaneous or clomiphene citrate ( CC ) stimulated cycles . A rapid urinary luteinizing hormone peak detection test was used for timing of ovulation . Forty patients suffering from longst and ing infertility of male ( n = 17 ) , cervical ( n = 2 ) , and idiopathic ( n = 21 ) origin were r and omly assigned into four distinct treatment modalities during 4 consecutive cycles . A total of 132 cycles were analyzed . In 35 cycles treated with CC plus IUI , five conceptions were achieved , whereas three pregnancies occurred in 32 inseminated spontaneous cycles . Only 1 patient conceived after timed intercourse in 31 CC stimulated cycles , and no pregnancy result ed from 34 spontaneous cycles combined with timed intercourse . There was a statistically significant higher conception rate in cycles in which IUI was performed , whereas the use of CC does not seem to improve the pregnancy rate . Analysis of results for other modifying factors did not substantially affect the relative risk ( odds ratio ) of pregnancy OBJECTIVE To compare two methods of timing IUI , urinary LH monitoring and transvaginal ultrasonography/ hCG timing of ovulation , in patients receiving clomiphene citrate . DESIGN Prospect i ve , r and omized , crossover study . SETTING Yale University Reproductive Medicine Center . PATIENT(S ) Infertile couples undergoing IUI because of unexplained infertility , anovulation , or male factor infertility . INTERVENTION(S ) Patients received clomiphene citrate on days 3 - 7 of the menstrual cycle and were r and omized initially to one of two monitoring protocol s. In protocol A , urinary LH monitoring was used to time IUI . Urinary LH levels were determined daily with the use of commercial kits , starting on day 10 of the cycle . When urinary LH was detected , IUIs were performed daily for the next 2 days . In protocol B , ultrasound monitoring of folliculogenesis was performed until a leading follicle of > or = 18 mm was noted , at which time hCG ( 10,000 IU ) was given intramuscularly and IUIs were performed daily for the next 2 days . If no pregnancy occurred , the couple crossed over to the alternate protocol for the next cycle and continued this alternating therapy for a total of four cycles . MAIN OUTCOME MEASURE(S ) Pregnancy rate per cycle . RESULT ( S ) One hundred forty-one cycles were completed . In these cycles , six pregnancies occurred , for an overall pregnancy rate of 4.26 % per cycle . The pregnancy rate with LH-timed IUI was 4.29 % ( 3/70 ) and that with hCG-induced ovulation was 4.23 % ( 3/71 ) ; the difference was not statistically significant . CONCLUSION ( S ) Timing IUI with the use of a relatively expensive and time-consuming method such as ultrasound monitoring of folliculogenesis and hCG induction of ovulation does not appear to produce an increased pregnancy rate over urinary LH monitoring of ovulation OBJECTIVE To assess if ovulation induction with gonadotropins alone is an appropriate treatment in couples affected by unexplained and mild male factor-related infertility and if the concomitant IUI improves the pregnancy rate ( PR ) . DESIGN Prospect i ve and r and omized trial . SETTING Infertility Centre of Department of Obstetrics and Gynecology of the University of Cagliari , Cagliari , Italy . PATIENTS Two hundred couples affected by unexplained or mild male factor-related infertility were assigned r and omly to one of two treatment groups : group A ( n = 100 ) , treated with three consecutive cycles of ovulation induction with gonadotropins associated with timed vaginal intercourse ; group B ( n = 100 ) , treated with three consecutive cycles of ovulation induction with gonadotropins associated with IUI . MAIN OUTCOME MEASURE Pregnancy rate . RESULTS The PRs obtained with ovulation induction with gonadotropins associated with IUI were similar to those obtained with ovulation induction with gonadotropins associated with timed vaginal intercourse . CONCLUSION Ovulation induction with gonadotropins alone may be as effective as ovulation induction with gonadotropins associated with IUI in couples with unexplained and mild male factor infertility and can represent the initial treatment option for its minimal invasivity and reduced cost and organizational problems OBJECTIVE To compare the pregnancy rates achieved by intrauterine insemination or timed intercourse in gonadotrophin stimulated cycles in couples whose only detectable abnormality was poor sperm quality . DESIGN Sixty-two couples with primary or secondary infertility due to male factor entered the study . The 62 couples were r and omly equally divided into two groups . Each group began one of the two treatment modalities ( controlled ovarian hyperstimulation in conjunction with timed intercourse or intrauterine insemination ) for three consecutive cycles and then switched to the alternative treatment after one rest cycle , if pregnancy was not achieved . RESULTS Five pregnancies ( 3.9 % ) were achieved after 128 cycles with timed intercourse and 15 pregnancies ( 11.5 % ) after 130 cycles with intrauterine insemination . The difference was found to be statistically significant ( P < 0.05 ) . CONCLUSION We suggest that intrauterine insemination during hMG stimulated cycles improves the pregnancy rates of couples whose only detectable abnormality is poor sperm quality OBJECTIVE To determine how diagnosis , age , sperm quality , and number of preovulatory follicles affect pregnancy rates when multiple cycles of clomiphene citrate (CC)-IUI are performed . DESIGN Fifteen-year prospect i ve observational study . SETTING Private infertility clinic . PATIENT(S ) Three thous and , three hundred eighty-one cycles of husb and or donor IUI . INTERVENTION(S ) Ovulation induction with CC and IUI . MAIN OUTCOME MEASURE(S ) Per-cycle pregnancy rate ( PR ) , cumulative pregnancy rate ( CPR ) . RESULT ( S ) Pregnancy rates remained constant through four cycles , then fell significantly for diagnoses other than ovulatory dysfunction . Mean PRs for cycles 1 - 4 were significantly lower for patients with the following characteristics : age > /=43 years , poor semen quality , single preovulatory follicles , and diagnoses other than ovulatory dysfunction . Additional cycles of CC-IUI compensated for low PRs because of age , semen quality , or number of follicles . After four cycles , CPRs were 46 % for ovulatory dysfunction ; 38 % for cervical factor , male factor , and unexplained infertility ; 34 % for endometriosis ; and 26 % for tubal factor . After six cycles , CPRs were 65 % for ovulation dysfunction , 35 % for endometriosis , and unchanged for other diagnoses . CONCLUSION ( S ) Clomiphene citrate-intrauterine insemination should be performed for a minimum of four cycles . Additional cycles of CC-IUI can compensate for low pregnancy rates due to age , semen quality , or follicle number in patients with ovulation dysfunction OBJECTIVE To test the hypothesis that in couples undergoing IUI , actively managed cycles using clomiphene citrate ( CC ) stimulation , ultrasound monitoring , and hCG timing will result in increased pregnancy rate ( PR ) per cycle compared with unstimulated urinary LH-timed cycles . PATIENTS Fifty-six couples with unexplained infertility ( n = 26 ) or male factor infertility ( n = 30 ) participated in the study . SETTING Tertiary academic medical center . DESIGN Prospect i ve , r and omized , crossover . Couples were r and omized initially to one of the two study groups ( treatment A : LH-timed IUI ; treatment B : CC-stimulated , hCG-timed IUI ) . If no pregnancy occurred , each couple alternated between the two regimens during subsequent cycles , up to a total of four cycles . RESULTS Twenty-nine couples completed the study and the analysis of 95 cycles revealed that among the male factor infertility group , one pregnancy occurred during the 26 cycles of each treatment group ( PR per cycle of 3.9 % for both treatment groups ) . In contrast , among the unexplained infertility group , there was a marked difference in the effect of treatments . During treatment A only one pregnancy occurred in 20 cycles ( PR of 5 % per cycle ) whereas during treatment B , six pregnancies occurred in 23 cycles ( PR of 26.1 % per cycle ) . CONCLUSIONS If IUI is chosen as the treatment modality in unexplained infertility , the addition of active ovulation management that includes CC stimulation , ultrasound monitoring of folliculogenesis , and hCG timing of ovulation increases the PR per cycle . In couples with male infertility , PR per cycle is low and is apparently not affected by the addition of active ovulation management OBJECTIVE To determine if a simple screening test of sperm recovery through a density gradient preparation and sperm survival after a 24-hour incubation is predictive of IUI success . DESIGN Prospect i ve nonr and omized descriptive study . SETTING Tertiary assisted reproductive technology center . PATIENT(S ) Four hundred fourteen couples undergoing IUI for male factor and unexplained infertility . INTERVENTION(S ) An advanced semen analysis , which consisted of a basic semen analysis , sperm processing through a density gradient preparation , and a 24-hour sperm incubation , was performed on all couples before beginning IUIs . MAIN OUTCOME MEASURE(S ) Cumulative and per cycle pregnancy rates ( PRs ) were calculated for routine semen parameters , number of sperm processed through density gradient , and percent motile sperm after a 24-hour incubation . RESULT ( S ) None of the basic semen analysis parameters accurately predicted IUI success . When the processed total motile sperm available for insemination was > or = 10 x 10(6 ) and their 24-hour survival was > or = 70 % , 89 % ( 162 of 182 ) of couples achieved a pregnancy with a 21.4 % ( 162 of 757 ) per cycle PR compared to a 2.8 % ( 11 of 403 ) per cycle PR and 4.7 % total PR when survival was < 70 % . With use of these cutoff values for the advanced semen analysis , the test had a sensitivity of 94 % and specificity of 86 % . CONCLUSION ( S ) The number of motile sperm available for insemination and especially their 24-hour survival are highly predictive of IUI success . This advanced semen analysis is an excellent screening test to evaluate couples considering IUI OBJECTIVE To avoid multiple pregnancies caused by ovulation induction . SETTING Infertile couples treated in the Women 's Hospital and the Institute of Reproductive Medicine of the University of Münster , Münster , Germany . DESIGN The outcome of ovulation induction in patients in whom supernumerary ovarian follicles were aspirated transvaginally was compared with the outcome in patients in whom this intervention was not necessary . In a second r and omized prospect i ve study , the efficacy of a low dosage of gonadotropins was compared with a higher dosage . PATIENTS Two hundred twenty-seven couples suffering from male infertility , unexplained infertility , incipient ovarian failure , and polycystic ovaries . INTERVENTIONS Aspirations were performed if more than three follicles were sized > 14 mm . MAIN OUTCOME MEASURE Number of ( multiple ) pregnancies . RESULTS During 232 ovulation inductions , 127 aspirations of supernumerary follicles were performed ( 54.7 % ) . The pregnancy rate ( PR ) in these cycles was similar to cycles in which aspirations were unnecessary ( 24.4 % versus 21.9 % ) . The efficacy of 75 units of FSH administered daily during the recruitment phase of follicular development was equivalent to 150 units of FSH ( PR : 32.4 % versus 31.6 % ) , but supernumerary follicles were fewer ( 26.5 % versus 76.3 % ) . Six twins , two triplets ( multiple PR : 10.4 % ) , and no ovarian hyperstimulation syndrome occurred . CONCLUSIONS Transvaginal aspiration of supernumerary follicles does not reduce the PR in ovulation induction . Supernumerary follicles can be avoided by low-dose administration of gonadotropins without compromising the PR Forty-eight patients with male ( n = 16 ) or idiopathic ( n = 32 ) infertility were stimulated with human menopausal gonadotropin . Intrauterine insemination ( IUI ) or natural intercourse were performed after either human chorionic gonadotropin (hCG)-induced or spontaneous , urinary luteinizing hormone ( LH ) surge-monitored ovulation . A total of 148 cycles were analyzed . In 40 cycles treated with hCG-induced ovulation and IUI , 3 ( 7.5 % ) patients conceived , whereas 37 women accomplished natural intercourse after hCG-induced ovulation and 2 ( 5.5 % ) became pregnant . When inseminated after a spontaneous LH surge , 3 ( 8.8 % ) of 34 patients achieved a pregnancy ; no conception occurred in 37 spontaneously ovulatory cycles combined with timed intercourse . Pregnancy rates did not substantially differ between the treatment modalities or between mono-ovulatory and polyovulatory cycles . The cycle characteristics between spontaneous ovulatory and hCG-induced cycles significantly did differ BACKGROUND The precise role of GnRH antagonists in the armamentarium of drugs for stimulation of ovulation associated with intrauterine insemination remains to be clarified . In this study , we have compared two different protocol s employing GnRH antagonists in order to determine the lower effective dose of gonadotrophins to use . METHODS Sixty-six couples with unexplained infertility or moderate male subfertility were recruited . Starting on day 3 of the cycle , 32 patients were r and omized to receive 50 IU of recombinant FSH per day , whereas 34 were treated with 50 IU of recombinant FSH on alternate days . Women received the GnRH antagonist Ganirelix at a dose of 0.25 mg per day starting on the day in which a leading follicle > or = 14 mm in mean diameter was visualized , until HCG administration . Insemination was performed 34 h after HCG injection . RESULTS The regimen with daily recombinant FSH was associated with a lower rate of mono-ovulation ( 53.3 % versus 78.8 % , P=0.06 ) but also with a higher clinical pregnancy rate per initiated cycle ( 34.4 % versus 5.9 % , P=0.005 ) . CONCLUSIONS A protocol of recombinant FSH 50 IU daily and GnRH antagonist may represent an effective and safe regimen for ovulation induction associated with intrauterine insemination The efficacy of high intrauterine insemination of a washed motile fraction of spermatozoa from men with poor quality semen on the day after the luteinising hormone ( LH ) surge was compared with that of natural intercourse based on symptothermal methods and a single act of intercourse timed on the day after the LH surge in the same 35 couples in a controlled and r and omised trial of the three types of cycle . Each couple had been trying to conceive for at least 3 years , the woman being potentially fertile and the only detectable defect related to poor semen quality . After 39 intrauterine insemination cycles , 8 women conceived ( all in their first insemination cycle ) ; this procedure was significantly more successful than LH-timed intercourse ( 0/38 ; p less than 0.05 ) and natural intercourse timed by symptothermal methods ( 1/34 ; p = 0.022 ) . The technique of intrauterine AIH , with a ' Tomcat ' catheter , was simple , painless , and uncomplicated In a prospect i ve comparison of IP , IUI , and natural intercourse following superovulation in couples diagnosed as having unexplained infertility , semen factors , or sperm antibodies , pregnancy rates were found to be significantly higher after IP . Pregnancy rates were also higher in the unexplained infertility group when compared with those with semen factors . It was concluded that IP in combination with superovulation offered a simple , inexpensive , safe alternative to GIFT OBJECTIVE To compare IUI with timed intercourse in men receiving oral steroid therapy for the treatment of infertility associated with antisperm antibodies . DESIGN A prospect i ve , r and omized , cross-over trial . SETTING All patients were managed and treated at the And rology Unit , Churchill Hospital , Oxford , United Kingdom . PATIENTS AND PARTICIPANTS Thirty males who were found to have antisperm levels of > or = 50 % [ using the indirect immunobead test with isotypes immunoglobulin ( Ig ) G , IgA , and IgM ( GAM ) beads ] in either seminal plasma or serum on routine testing were recruited with their partners into the study . MAIN OUTCOME MEASURES Antisperm antibody levels in seminal plasma and serum , sperm parameters , conception rates , and pregnancy outcome . RESULTS There was a statistically significant reduction in seminal plasma antisperm antibody levels associated with steroid therapy . There was a significant improvement in certain spermatozoan parameters during steroid therapy . The cumulative pregnancy rate over four cycles of IUI was 39.4 % . The cumulative pregnancy rate over four cycles of natural intercourse was 4.8 % . There was a significantly higher chance of achieving a pregnancy with IUI . CONCLUSION Intrauterine insemination significantly improves the chance of achieving a conception when used as an adjuvant therapy to cyclical intermediate dose steroid therapy . Antisperm antibody levels in seminal plasma are significantly reduced during treatment with cyclical intermediate dose steroid therapy , although levels in serum appear to be unaffected . Cyclical intermediate dose steroid therapy significantly improves certain sperm parameters but , when used in isolation , is associated with a low pregnancy rate BACKGROUND The quality of clinical trials has received increasing attention with the growth of evidence -based medicine and systematic review s. We aim ed to identify whether errors and omissions commonly encountered when undertaking Cochrane review s in this field are still passing peer review . METHODS We undertook a review of trials published in 2001 by two major journals . We selected from Medline only trials in which authors compared pregnancy rates under two interventions by allocating women to different groups . RESULTS We identified 39 trials meeting our criteria . Six trials were fatally flawed by design , either by inappropriate use of a cross-over design or by systematic allocation described by the authors as ' r and om ' . Only six reports cl aim ed to apply the intention-to-treat principle , and the principle was misunderstood by four of these . Only five trials reported live birth rates sufficiently to allow valid meta- analysis . Most trials ( 82 % ) included at least one ' unit of analysis ' error . CONCLUSIONS We selected simple trials from respected journals , assuming that our sample would represent trials of highest method ological quality in the field . Nevertheless , the st and ards of design , analysis and reporting of many subfertility trials are not sufficient to allow reliable interpretation of results , or inclusion in meta-analyses We performed intrauterine insemination with washed husb and 's spermatozoa in 27 couples with clear evidence of impaired sperm mucus interaction due to cervical hostility or immunologic male subfertility and in 30 couples with subnormal semen , but optimal cervical mucus qualities . In each couple insemination cycles were alternated with cycles during which normal intercourse took place . Both types of cycles were monitored for LH . When a clear rise of LH levels could be detected , either IUI was scheduled or intercourse advised for the following day . In the male subfertility group no difference between the pregnancy rates of insemination and intercourse cycles was present . In the group with impairment of sperm-mucus interaction , the pregnancy rate of the insemination cycles was 16 % , whereas no pregnancies occurred during intercourse cycles In this r and omized crossover trial we investigated whether the use of controlled ovarian hyperstimulation with low-dose human menopausal gonadotrophin in couples with male subfertility leads to a higher probability of conception when intrauterine insemination ( IUI ) is applied . We also investigated whether the efficacy of IUI in natural or stimulated cycles was related to the severity of male subfertility . Seventy-four couples completed 308 treatment cycles . Thirteen pregnancies occurred after IUI in a natural cycle ( pregnancy rate per completed cycle : 8.4 % ) and 21 after IUI in a stimulated cycle ( pregnancy rate per completed cycle : 13.7 % ) . The difference between the two treatment modalities was not statistically significant . The efficacy of IUI in stimulated cycles was related to the severity of the semen defect . In couples with a total motile sperm count < 10 x 10(6 ) , ovarian stimulation did not improve treatment outcome , while it did in couples with a total motile sperm count > or = 10 x 10(6 ) . Compared with the expected chance of conceiving spontaneously without treatment , both natural and stimulated cycles improved the probability of conception . We conclude that , for the group as a whole , ovarian stimulation did not improve the probability of conception . However , in couples with less severe semen defects , ovarian stimulation did improve the probability of conception BACKGROUND This study was design ed to assess whether the use of ganirelix in women undergoing stimulated IUI could prevent the occurrence of premature LH rises and luteinization ( LH+progesterone rises ) . METHODS Women of infertile couples , diagnosed with unexplained or male factor infertility , were r and omized to receive either ganirelix ( n=103 ) or placebo ( n=100 ) in a double-blind design . All women were treated with an individualized , low-dose rFSH regimen started on day 2 - 3 of cycle . Ganirelix ( 0.25 mg/day ) was started if one or more follicles > or=14 mm were visualized . Ovulation was triggered by HCG injection when at least one follicle > or=18 mm was observed and a single IUI was performed 34 - 42 h later . The primary efficacy outcome was the incidence of premature LH rises ( + /-progesterone rise ) . RESULTS In the ganirelix group , four subjects had a premature LH rise ( value > or=10 IU/l ) , one LH rise prior to the start of ganirelix and three LH rises during ganirelix treatment , whereas in the placebo group 28 subjects had a premature LH rise , six subjects prior to the start of placebo and 22 subjects during placebo treatment . The incidence of LH rises was significantly lower in ganirelix cycles compared to placebo cycles ( 3.9 versus 28.0 % ; P=0.003 for ITT analysis ) . When excluding subjects with an LH value > or=10 IU/l before the start of ganirelix/placebo the incidence of LH rises was also significantly lower in ganirelix cycles compared to placebo cycles ( 2.9 versus 23.4 % ; P=0.003 for ITT analysis ) . Premature luteinization ( LH rise with concomitant progesterone rise > or=1 ng/ml ) was observed in one subject in the ganirelix group and in 17 subjects in the placebo group of which three subjects had a premature spontaneous ovulation . Ongoing pregnancy rates per attempt were 12.6 and 12.0 % for the ganirelix and placebo groups respectively . CONCLUSIONS Treatment with ganirelix effectively prevents premature LH rises , luteinization in subjects undergoing stimulated IUI . Low-dose rFSH regimen combined with a GnRH antagonist may be an alternative treatment option for subjects with previous proven luteinization or in subjects who would otherwise require insemination when staff are not working OBJECTIVE The hemizona assay ( HZA ) is an established functional test that examines in vitro sperm-zona pellucida binding capacity with high predictive power for fertilization outcome in IVF . The objective of this study was to evaluate the value of the HZA as a predictor of pregnancy in patients undergoing controlled ovarian hyperstimulation ( COH ) and intrauterine insemination ( IUI ) . DESIGN Prospect i ve clinical study . SETTING Academic center . PATIENT(S ) Eighty-two couples with unexplained or male factor infertility that underwent 313 IUI cycles . INTERVENTION(S ) Basic semen analysis and HZA were performed within three months of starting COH/IUI therapy . MAIN OUTCOME MEASURE(S ) Hemizona index ( HZI ) and clinical pregnancy . RESULT ( S ) Overall , patients with an HZI of < 30 had a significantly lower pregnancy rate compared to patients with an HZI of > or = 30 ( 11.1 % vs. 40.6 % , respectively ; P<.05 ; relative risk for failure to conceive : 1.5 ( confidence interval 1.2 - 1.9 ) ) . In all patients combined , and in the range of HZI 0 - 60 , the duration of infertility ( P=.000 ) and the HZI ( P=.004 ) were significant determinants of conception ( receiver operating characteristics ( ROC ) analysis ) . In couples with male infertility , the average path velocity and HZI were significant predictors of conception ( P=.001 and P=.005 , respectively , ROC analysis ) . The negative and positive predictive values of the HZA for pregnancy were 93 % and 69 % , respectively . Logistic regression analysis provided models of HZI ( P=.021 ) and duration of infertility ( P=.037 ) with highest predictability of conception in male factor and unexplained infertility groups , respectively . CONCLUSION ( S ) The HZA predicted pregnancy in the IUI setting with high sensitivity and negative predictive value in couples with male infertility . Results of this sperm function test are useful in counseling couples before allocating them into COH/IUI therapy Homologous artificial insemination ( AIH ) is used to treat infertility caused by oligoasthenospermia , despite the lack of controlled studies confirming its benefit . This prospect i ve r and omized controlled trial was undertaken to determine whether intracervical ( IC-AIH ) or intrauterine ( IU-AIH ) homologous artificial insemination improves pregnancy rates in couples with infertility attributable to oligoasthenospermia alone . Twenty couples were r and omized to receive IC-AIH or IU-AIH . Sixty-three insemination cycles were completed . During the same study period , 35 cycles with timed vaginal intercourse alone were assessed . Four pregnancies occurred , all following timed vaginal intercourse . No pregnancies result ed from IC-AIH or IU-AIH . This suggests that neither IC-AIH nor IU-AIH is of benefit when oligoasthenospermia is the cause of infertility . Pregnancies previously attributed to AIH may also have been conceived as a result of vaginal intercourse . This confounding effect on the results of AIH should always be considered The effectiveness of intrauterine insemination ( IUI ) was compared with that of intracervical insemination ( ICI ) in 49 infertile couples , in whom the major cause for infertility was oligoasthenospermia . All women had ovulation stimulated with either a clomiphene citrate (CC)-human gonadotropin combination or human gonadotropins alone . The ovulatory dose of human chorionic gonadotropin ( hCG ) was given after adequate estradiol levels were reached . The timing of inseminations was st and ardized -- IUI was 28 hours after hCG and ICI was immediately after hCG administration . Only one insemination per month was performed with either IUI or ICI . The first treatment cycle was assigned r and omly to be either IUI or ICI , and subsequent inseminations were alternated . A total of 182 cycles were completed , with 96 IUIs and 86 ICIs . Pregnancy occurred in eight patients , seven with IUI ( 14.3 % ) and one with ICI ( 2.0 % ) ; the difference is significant at P less than 0.05 . The pregnancy rate per treatment cycle was 7.3 % versus 1.2 % ( P less than 0.001 ) . This study supports the use of IUI with processed sperm in the treatment of infertility due to oligoasthenospermia In this r and omized trial we investigated whether intra-uterine insemination ( IUI ) in couples with male subfertility leads to a higher probability of conception than timed intercourse after ovarian stimulation with human menopausal gonadotrophin ( HMG ) and human chorionic gonadotrophin ( HCG ) . A total of 76 couples started 249 cycles , of which 47 were cancelled to prevent multiple pregnancies or hyperstimulation . After 202 completed treatment cycles , 15 pregnancies occurred , 11 after IUI and four after timed intercourse . The pregnancy rate per completed cycle with IUI was 10.3 % ( 95 % confidence interval : 5.5 - 17.5 % ) and 4.2 % ( 1.2 - 10.1 % ) with timed intercourse . Compared with the estimated spontaneous chance to conceive , IUI after ovarian stimulation appeared to be more effective in the first three cycles . We conclude that in subfertile couples with a male factor , IUI tends to improve the probability of conception as compared to timed intercourse when ovarian stimulation is applied , and we advise such treatment for three cycles At present , there is general agreement that ovarian stimulation improves pregnancy rates after intra-uterine insemination ( IUI ) . Also , ovulation induction with gonadotrophins is associated with higher success rates than clomiphene citrate in IUI cycles . However , the drawbacks to the use of gonadotrophin stimulation before IUI include the risks of ovarian hyperstimulation and multiple gestation , and the relative cost of a treatment cycle in a view of the medication costs and the need for increased monitoring by hormone assays and ultrasonographic measurements . In the present prospect i ve r and omized trial , the efficacy and safety of ovarian stimulation with clomiphene citrate ( 50 mg/day for 5 days ) and IUI ( clomiphene/IUI group ) were compared with those of late low-dose pure follicle stimulating hormone ( FSH , 75 IU/day from day cycle 7 until the leading follicle reached > 17 mm in diameter ) and IUI ( FSH/IUI group ) in ovulatory women who were infertile because of unexplained infertility ( n = 40 ) or male subfertility ( n = 60 ) . The mean length of treatment in the FSH group was 6.4 + /- 2.5 days . Multiple follicular development was seen in 25 % of clomiphene-stimulated cycles but only in 8 % of those treated with FSH . Pregnancy rate per cycle in clomiphene/IUI and FSH/IUI groups was 4 % ( 4/98 ) and 13 % ( 12/94 ) respectively ( P = 0.02 ) . All pregnancies obtained were singleton . There were two and one clinical abortions in the clomiphene/IUI ( 50 % ) and FSH/IUI ( 8 % ) groups respectively . No patient developed ovarian hyperstimulation syndrome . Use of our therapeutic scheme , which proved to be efficacious , safe and economic for ovarian stimulation in IUI cycles , is advocated before the institution of in-vitro fertilization ( IVF ) or gamete intra-Fallopian transfer ( GIFT ) therapy in infertile patients with patient Fallopian tubes . This late low-dose technique of administering pure FSH is suitable for use in offices without immediate access to oestradiol results OBJECTIVE To compare the efficacy of GnRH antagonist vs. GnRH agonist administration for controlled ovarian hyperstimulation ( COH ) in assisted reproduction . DESIGN A prospect i ve , r and omized trial . SETTING Clinical research unit at a tertiary care medical center . PATIENT(S ) Sixty-five patients with unexplained infertility or mild male subfertility undergoing COH for IUI . INTERVENTION(S ) Twenty-nine women ( group A ) were r and omized to receive 600 microg of busereline acetate per day starting in the midluteal phase of the cycle ( long protocol ) , whereas 36 women ( group B ) were treated with 0.25 mg/d of the GnRH antagonist Cetrorelix starting from day 6 of the cycle . The starting dose of recombinant FSH was 150 IU in women of both groups . Insemination was performed 34 hours after hCG injection . MAIN OUTCOME MEASURE(S ) Clinical and successful ongoing pregnancy rate ( PR ) , measurements of serum FSH , LH , E2 , and P , number of recruited follicles , duration of stimulation period , and amount of gonadotropins used . RESULT ( S ) Women in group A required significantly more days of treatment ( median : 12.0 vs. 9.0 ) and significantly more total units of recombinant FSH ( median 1,800 vs. 1,550 ) as compared with the corresponding values of the antagonist group ( group B ) . Serum FSH , LH , E2 , and P were significantly higher on the antagonist group on days 2 and 6 of stimulation . However , these differences regress until the day of hCG administration . CONCLUSION ( S ) The GnRH antagonists have facilitated short and simple treatment , and are particularly attractive for administration in women undergoing COH , achieving comparable PR with the long protocol regimen OBJECTIVE To determine whether intrauterine insemination ( IUI ) after ovarian stimulation with human menopausal gonadotropin ( hMG ) gives a better pregnancy rate ( PR ) than natural intercourse in couples with subfertility because of subnormal semen . DESIGN Prospect i ve r and omized controlled trial . SETTING University based subfertility clinic . PATIENTS Couples with subnormal semen as the only identifiable cause of subfertility . INTERVENTIONS In control cycles , the couples had natural intercourse . In IUI cycles , IUI was performed after ovarian stimulation with hMG and human chorionic gonadotropin . MAIN OUTCOME MEASURE The clinical PRs and complications of IUI cycles and control cycles were compared . RESULTS There were six clinical pregnancies in the 42 IUI cycles , whereas there was no clinical pregnancy in the 42 control cycles . The clinical PR in IUI cycles ( 14.3 % per cycle ) was significantly higher than that in control cycles ( 0 % ) . Six patients ( 14.3 % ) developed moderate degree of ovarian hyperstimulation syndrome in IUI cycles . CONCLUSION Intrauterine insemination after ovarian stimulation with hMG is useful in treatment of subfertile couples with subnormal semen BACKGROUND Couples affected by idiopathic subfertility or male subfertility have an estimated spontaneous conception rate of about 2 % per cycle . Although various infertility treatments are available , counselling of a couple in their choice of treatment is difficult because of the lack of consistent data from good- quality comparative studies . We compared the results of treatment with intrauterine insemination ( IUI ) with those of in-vitro fertilisation ( IVF ) , and did a cost-effectiveness analysis . METHODS In a prospect i ve , r and omised , parallel trial , 258 couples with idiopathic subfertility or male subfertility were treated for a maximum of six cycles of either IUI in the spontaneous cycle ( IUI alone ) , IUI after mild ovarian hyperstimulation , or IVF . The primary endpoint was a pregnancy result ing in at least one livebirth after treatment . Cost-effectiveness based on real costs was studied by Markov chain analysis . FINDINGS 86 couples were assigned IUI alone , 85 IUI plus ovarian hyperstimulation , and 87 IVF . Ten couples dropped out before treatment began . Although the pregnancy rate per cycle was higher in the IVF group than in the IUI groups ( 12.2 % vs 7.4 % and 8.7 % , respectively ; p=0.09 ) , the cumulative pregnancy rate for IVF was not significantly better than that for IUI . Couples in the IVF group were more likely than those in the IUI groups to give up treatment before their maximum of six attempts ( 37 [ 42 % ] drop-outs vs 13 [ 15 % ] and 14 [ 16 % ] , respectively ; p<0.01 ) . The woman 's age was the only factor that influenced a couple 's chance of success . IUI was a more cost-effective treatment than IVF ( costs per pregnancy result ing in at least one livebirth 8423 - 10661 Dutch guilders [ US$ 4511 - 5710 ] for IUI vs 27409 Dutch guilders [ US$ 14679 ] for IVF ) . INTERPRETATION Couples with idiopathic or male subfertility should be counselled that IUI offers the same likelihood of successful pregnancy as IVF , and is a more cost-effective approach . IUI in the spontaneous cycle carries fewer health risks than does IUI after mild hormonal stimulation and is therefore the first-choice treatment |
10,713 | 24,316,019 | Construct validation studies performed on temporal bone and endoscopic sinus surgery simulators showed that performance measures reliably discriminated between different experience levels .
Simulation training improved cadaver temporal bone dissection skills and operating room performance in sinus surgery .
Several simulator platforms particularly in temporal bone surgery and endoscopic sinus surgery are worthy of incorporation into training programmes . | OBJECTIVE To conduct a systematic review of the validity data for the virtual reality surgical simulator platforms available in Otolaryngology . | Objectives To evaluate construct validity of the Voxelman TempoSurg Virtual Reality ( VR ) temporal bone simulator by determining whether generated objective metrics can distinguish experienced otologic surgeons from intermediate and novice surgeons . Design Prospect i ve assessment study . Setting Two university-affiliated teaching hospitals . Participants Sixty-five participants were recruited ; 40 novice surgeons , 15 trainees in otolaryngology , and 10 experienced otolaryngology consultants with a specialist interest in otology were individually assessed on a st and ardized simulated temporal bone task . The task involved identification and delineation of the sigmoid sinus in a virtual left-sided temporal bone . Main Outcome Measures Objective data were produced using a scoring matrix incorporated into the VOXEL MAN TempoSurg software . The simulator measured the total time taken to complete the task , the volume and efficiency of bone removal and error data for excessive force or injury to the facial nerve , dura , and sigmoid sinus . Results Experts and intermediates outperformed novices with respect to the total time taken to complete the task ( expert versus novice : p < 0.001 ; intermediate versus novice : p < 0.001 ) , total volume of bone removed ( p < 0.001 and p = 0.03 ) , efficiency of bone removal ( p < 0.001 and p < 0.001 ) , time spent with the drill tip obscured ( p = 0.002 and p < 0.001 ) , and number of injuries to the sigmoid sinus ( p < 0.001 and p < 0.001 ) . The intermediate group injured the sigmoid sinus on more occasions than the experts ( p = 0.008 ) and were less efficient than experienced surgeons ( p = 0.005 ) . Conclusion Simulator-generated objective metrics can be used to differentiate individuals of differing levels of experience using a st and ardized temporal bone task . VR simulation has potential as a training tool and may have a role in both formative and summative assessment OBJECTIVES /HYPOTHESIS Surgical simulation is becoming an increasingly common training tool in residency programs . The first objective was to implement real-time soft-tissue deformation and cutting into a virtual reality myringotomy simulator . The second objective was to test the various implemented incision algorithms to determine which most accurately represents the tympanic membrane during myringotomy . STUDY DESIGN Descriptive and face-validity testing . METHODS A deformable tympanic membrane was developed , and three soft-tissue cutting algorithms were successfully implemented into the virtual reality myringotomy simulator . The algorithms included element removal , direction prediction , and Delaunay cutting . The simulator was stable and capable of running in real time on inexpensive hardware . A face-validity study was then carried out using a vali date d question naire given to eight otolaryngologists and four senior otolaryngology residents . Each participant was given an adaptation period on the simulator , was blinded to the algorithm being used , and was presented the three algorithms in a r and omized order . RESULTS A virtual reality myringotomy simulator with real-time soft-tissue deformation and cutting was successfully developed . The simulator was stable , ran in real time on inexpensive hardware , and incorporated haptic feedback and stereoscopic vision . The Delaunay cutting algorithm was found to be the most realistic algorithm representing the incision during myringotomy ( P < .05 ) . The Likert and visual analog scales had strong correlations , suggesting good internal reliability . CONCLUSIONS The first virtual reality myringotomy simulator is being developed and now integrates a real-time deformable tympanic membrane that appears to have face validity . Further development and validation studies are necessary before the simulator can be studied with respect to training efficacy and clinical impact Objective : To assess the impact of warm-up on laparoscopic performance in the operating room ( OR ) . Background : Implementation of simulation-based training into clinical practice remains limited despite evidence to show that the improvement in skills is transferred to the OR . The aim of this study was to evaluate the impact of a short virtual reality warm-up training program on laparoscopic performance in the OP . Methods : Sixteen Laparoscopic Cholecystectomies were performed by 8 surgeons in the OR . Participants were r and omized to a group which received a preprocedure warm-up using a virtual reality simulator and no warm-up group . After the initial laparoscopic cholecystectomy all surgeons served as their own controls by performing another procedure with or without preoperative warm-up . All OR procedures were videotaped and assessed by 2 independent observers using the generic OSATS global rating scale ( from 7 to 35 ) . Results : There was significantly better surgical performance on the laparoscopic Cholecystectomy following preoperative warm-up , median 28.5 ( range = 18.5–32.0 ) versus median 19.25 ( range = 15–31.5 ) , P = 0.042 . The results demonstrated excellent reliability of the assessment tool used ( Cronbach 's & agr ; = 0.92 ) . Conclusion : This study showed a significant beneficial impact of warm-up on laparoscopic performance in the OP . The suggested program is short , easy to perform , and therefore realistic to implement in the daily life in a busy surgical department . This will potentially improve the procedural outcome and contribute to improved patient safety and better utilization of OR re sources Objective . To vali date the VOXEL-MAN TempoSurg simulator for temporal bone dissection . Study Design . Prospect i ve international study . Setting . Otolaryngology departments of 2 academic health care institutions in the United Kingdom and United States . Subjects and Methods . Eighty-five subjects were recruited consisting of an experienced and referent group . Participants performed a st and ardized familiarization session and temporal bone dissection task . Realism , training effectiveness , and global impressions were evaluated across 21 domains using a 5-point Likert-type scale . A score of 4 was the minimum threshold for acceptability . Results . The experienced group comprised 25 otolaryngology trainers who had performed 150 mastoid operations . The referent group comprised 60 trainees ( mean otolaryngology experience of 2.9 years ) . Familiarization took longer in the experienced group ( P = .01 ) . User-friendliness was positively rated ( mean score 4.1 ) . Seventy percent of participants rated anatomical appearance as acceptable . Trainers rated drill ergonomics worse than did trainees ( P = .01 ) . Simulation temporal bone training scored highly ( mean score 4.3 ) . Surgical anatomy , drill navigation , and h and -eye coordination accounted for this . Trainees were more likely to recommend temporal bone simulation to a colleague than were trainers ( P = .01 ) . Transferability of skills to the operating room was undecided ( mean score 3.5 ) . Conclusion . Realism of the VOXEL-MAN virtual reality temporal bone simulator is suboptimal in its current version . Nonetheless , it represents a useful adjunct to existing training methods and is particularly beneficial for novice surgeons before performing cadaveric temporal bone dissection . Improvements in realism , specifically drill ergonomics and visual-spatial perception during deeper temporal bone dissection , are warranted OBJECTIVE The objective of this study is to determine the feasibility of computerized evaluation of resident performance using h and motion analysis on a virtual reality temporal bone ( VR TB ) simulator . We hypothesized that both computerized analysis and expert ratings would discriminate the performance of novices from experienced trainees . We also hypothesized that performance on the virtual reality temporal bone simulator ( VR TB ) would differentiate based on previous drilling experience . STUDY DESIGN The authors conducted a r and omized , blind assessment study . METHODS Nineteen volunteers from the Otolaryngology-Head and Neck Surgery training program at the University of Toronto drilled both a cadaveric TB and a simulated VR TB . Expert review ers were asked to assess operative readiness of the trainee based on a blind video review of their performance . Computerized h and motion analysis of each participant 's performance was conducted . RESULTS Expert raters were able to discriminate novices from experienced trainees ( P < .05 ) on cadaveric temporal bones , and there was a trend toward discrimination on VR TB performance . H and motion analysis showed that experienced trainees had better movement economy than novices ( P < .05 ) on the VR TB . CONCLUSION Performance , as measured by h and motion analysis on the VR TB simulator , reflects trainees ' previous drilling experience . This study suggests that otolaryngology trainees could accomplish initial temporal bone training on a VR TB simulator , which can provide feedback to the trainee , and may reduce the need for constant faculty supervision and evaluation OBJECTIVES To establish discriminant validity of the endoscopic sinus surgery simulator ( ES3 ) ( Lockheed Martin , Akron , Ohio ) between various health care provider experience levels and to define benchmarking criteria for skills assessment . DESIGN Prospect i ve multi-institutional comparison study . SETTING University-based tertiary care institution . PARTICIPANTS Ten expert otolaryngologists , 14 otolaryngology residents , and 10 medical students . INTERVENTIONS Subjects completed the ES3 's virtual reality curriculum ( 10 novice mode , 10 intermediate mode , and 3 advanced mode trials ) . Performance scores were recorded on each trial . Performance differences were analyzed using analysis of variance for repeated measures ( experience level as between-subjects factor ) . MAIN OUTCOME MEASURES Simulator performance scores , accuracy , time to completion , and hazard disruption . RESULTS The novice mode accurately distinguished the 3 groups , particularly at the onset of training ( mean scores : senior otolaryngologists , 66.0 ; residents , 42.7 ; students , 18.3 ; for the paired comparisons between groups 1 and 2 and groups 1 and 3 , P = .04 and .03 , respectively ) . Subjects were not distinguished beyond trial 5 . The intermediate mode only discriminated students from other subjects ( P = .008 ) . The advanced mode did not show performance differences between groups . Scores on the novice mode predicted those on the intermediate mode , which predicted advanced mode scores ( r = 0.687 ) , but no relationship was found between novice and advanced scores . All groups performed equally well and with comparable consistency at the outset of training . Expert scores were used to define benchmark criteria of optimal performance . CONCLUSIONS This study completes the construct validity assessment of the ES3 by demonstrating its discriminant capabilities . It establishes expert surgeon benchmark performance criteria and shows that the ES3 can train novice subjects to attain those . The refined analysis of trial performance scores could serve educational and skills assessment purpose s. Current studies are evaluating the transfer of surgical skills acquired on the ES3 to the operating room ( predictive validity ) Objective : Establish the feasibility of a predictive validity study in sinus surgery simulation training and demonstrate the effectiveness of the Endoscopic Sinus Surgery Simulator ( ES3 ) as a training device . Study Design : Prospect i ve , multi-institutional controlled trial . Setting : Four tertiary academic centers with accredited otolaryngology-head and neck surgery residency programs . Subjects : Twelve ES3-trained novice residents were compared with 13 control novice residents . Methods : Subjects were assessed on the performance of basic sinus surgery tasks . Their first in vivo procedure was video recorded and su bmi tted to a blinded panel of independent experts after the panel established a minimum inter-rater reliability of 80 percent . The recordings were review ed by using a st and ardized computer-assisted method and customized metrics . Results were analyzed with the Mann-Whitney U test . Internal rater consistency was verified with Pearson moment correlation . Results : Completion time was significantly shorter in the experimental group ( injection P = 0.003 , dissection P < 0.001 ) , which , according to the rater panel , also demonstrated higher confidence ( P = 0.009 ) , demonstrated skill during instrument manipulation ( P = 0.011 ) , and made fewer technical mistakes during the injection task ( P = 0.048 ) compared with the control group . The raters ' post hoc internal consistency was deemed adequate ( r > 0.5 between serial measurements ) . Conclusion : The validity of the ES3 as an effective surgical trainer was verified in multiple instances , including those not depending on subjective rater evaluations . The ES3 is one of the few virtual reality simulators with a comprehensive validation record . Advanced simulation technologies need more rapid implementation in otolaryngology training , as they present noteworthy potential for high- quality surgical education while meeting the necessity of patient safety OBJECTIVES /HYPOTHESIS To assess whether practice on a virtual-reality ( VR ) temporal bone simulator improves acquisition of technical skills in mastoid surgery . STUDY DESIGN Prospect i ve blinded study . METHODS Using a previously vali date d objective structured assessment of technical skills ( OSATS ) tool , performance was assessed in 12 residents for two tasks of cortical mastoidectomy : 1 ) identifying and defining the tegmen and 2 ) defining the sigmoid sinus and sinodural angle . These surgical tasks were chosen as key steps in mastoid dissection because they were of intermediate complexity . Videos of virtual dissections were captured at baseline and again after practicing each task four to six times . RESULTS OSATS scores for the tegmen task increased from 2.125 ± 1.25 to 3.1 ± 0.85 ( P = .026 ) , whereas for the sigmoid task scores increased from 2 ± 0.45 to 2.75 ± 1.125 ( P = .0098 ) . The time to complete the tasks decreased from 8.37 ± 4.78 minutes to 5.39 ± 3.06 minutes ( P = .018 ) for the tegmen task and from 8.99 ± 6.7 minutes to 8.68 ± 5.98 minutes ( P = .594 ) for the sigmoid task . There was a decline in number of injuries from 0.5 ± 1.5 to 0 ± 0.5 ( P = .594 ) for the tegmen task and from 2.5 ± 4 to 0.5 ± 1 ( P = .029 ) for the sigmoid task . CONCLUSIONS Technical skills in mastoidectomy surgery can be acquired during even brief practice on the VR temporal bone simulator . It is anticipated that longer periods of practice presented within the fundamentals of comprehensive curriculum will facilitate procedural learning . Further studies are required to eluci date evidence of transference of these skills to the operating room and to procedures of greater complexity OBJECTIVES /HYPOTHESIS This study aims to determine whether there are improved performances in cadaver temporal bone dissection after training using a VR simulator as a teaching aid compared with traditional training methods STUDY DESIGN R and omized control trial . METHODS Twenty participants with minimal temporal bone experience were recruited for this r and omized control trial . After receiving the same didactic teaching they were r and omized into two groups . The traditional group were to receive addition teaching via traditional teaching methods such as small group tutorials , videos , and models . The VR group received supervised teaching on the VR simulator . At the end of their teaching they were asked to perform a cadaveric temporal bone dissection and had their performance videoed and assessed by blinded assessors . The assessors judged the videos on four domains of assessment s looking at the end product , injury size , overall performance , and technique . These assessment s were based on the Welling 's scale and OSATS . RESULTS The VR group performed significantly better in the end product of the dissection ( VR 80 % vs. traditional 45 % , P-value < .001 ) and caused smaller injuries to anatomic structures ( VR 19 % vs. traditional 36 % , P-value = .01 ) . They also did better in the overall performance score ( VR 55 % vs. traditional 35 % , P-value = .04 ) There were no differences in the technique score . There was a fair to moderate degree of interrater reliability between the assessors ( kappa = 0.33 - 0.47 ; Intraclass correlation coefficient = 0.34 - 0.76 ) . CONCLUSION Supervised teaching using a VR simulator seems to improve cadaveric temporal bone dissection performance compared with traditional teaching methods OBJECTIVES /HYPOTHESIS The objective of this project was to develop a virtual temporal bone dissection system that would provide an enhanced educational experience for the training of otologic surgeons . STUDY DESIGN A r and omized , controlled , multi-institutional , single-blinded validation study . METHODS The project encompassed four areas of emphasis : structural data acquisition , integration of the system , dissemination of the system , and validation . RESULTS Structural acquisition was performed on multiple imaging platforms . Integration achieved a cost-effective system . Dissemination was achieved on different levels including casual interest , downloading of software , and full involvement in development and validation studies . A validation study was performed at eight different training institutions across the country using a two-arm r and omized trial where study subjects were r and omized to a 2-week practice session using either the virtual temporal bone or st and ard cadaveric temporal bones . Eighty subjects were enrolled and r and omized to one of the two treatment arms ; 65 completed the study . There was no difference between the two groups using a blinded rating tool to assess performance after training . CONCLUSIONS A virtual temporal bone dissection system has been developed and compared to cadaveric temporal bones for practice using a multicenter trial . There was no statistical difference between practice on the current simulator compared to practice on human cadaveric temporal bones . Further refinements in structural acquisition and interface design have been identified , which can be implemented prior to full incorporation into training programs and used for objective skills assessment Objective . A significant benefit of virtual reality ( VR ) simulation is the ability to provide self-direct learning for trainees . This study aims to determine whether there are any differences in performance of cadaver temporal bone dissections between novices who received traditional teaching methods and those who received unsupervised self-directed learning in a VR temporal bone simulator . Study Design . R and omized blinded control trial . Setting . Royal Victorian Eye and Ear Hospital . Subjects . Twenty novice trainees . Methods . After receiving an hour lecture , participants were r and omized into 2 groups to receive an additional 2 hours of training via traditional teaching methods or self-directed learning using a VR simulator with automated guidance . The simulation environment presented participants with structured training tasks , which were accompanied by real-time computer-generated feedback as well as real operative videos and photos . After the training , trainees were asked to perform a cortical mastoidectomy on a cadaveric temporal bone . The dissection was videotaped and assessed by 3 otologists blinded to participants ’ teaching group . Results . The overall performance scores of the simulator-based training group were significantly higher than those of the traditional training group ( 67 % vs 29 % ; P < .001 ) , with an intraclass correlation coefficient of 0.93 , indicating excellent interrater reliability . Using other assessment s of performance , such as injury size , the VR simulator-based training group also performed better than the traditional group . Conclusions . This study indicates that self-directed learning on VR simulators can be used to improve performance on cadaver dissection in novice trainees compared with traditional teaching methods alone OBJECTIVES /HYPOTHESIS The aim of this study is to evaluate an endoscopic sinus surgical simulator ( ESS ) as a training device and to introduce a methodology to assess its impact on actual operating room performance . STUDY DESIGN Prospect i ve evaluation of the endoscopic sinus surgical simulator as a trainer . METHODS Ten junior and senior ear , nose and throat residents served as subjects , some of whom had prior training with the simulator . The evaluation team collected several measures , which were analyzed for a statistical correlation , including simulator scores , operating room performance rating , ratings of videotaped operating room procedures , and surgical competency rating . RESULTS These findings suggest the ESS simulator positively affects initial operating room performance across all measures as judged by senior surgeons rating anonymous videotapes of those procedures . The two simulation-trained residents were rated consistently better than the other two residents across all measures . These differences approached statistical significance for two items : anterior ethmoidectomy ( P = .06 ; P < .05 ) and surgical confidence ( P = .09 ; P < .05 ) . In addition , the 3 subjects with the highest overall scores on the competency evaluation also had 3 of the 4 highest cumulative simulation times . CONCLUSIONS The endoscopic sinus surgical simulator is a valid training device and appears to positively impact operating room performance among junior otolaryngology residents |
10,714 | 25,259,676 | Immunotherapy was associated with a significantly longer OS and 2-year survival compared to conventional therapy .
CONCLUSION Immunotherapy may improve the survival of patients with GBM | OBJECTIVE Glioblastoma multiforme ( GBM ) has a poor prognosis .
The purpose of this systematic review and meta- analysis was to analyze the outcomes of clinical trials which compared immunotherapy with conventional therapy for the treatment of malignant gliomas . | Purpose : To assess the feasibility , safety , and toxicity of autologous tumor lysate – pulsed dendritic cell ( DC ) vaccination and toll-like receptor ( TLR ) agonists in patients with newly diagnosed and recurrent glioblastoma . Clinical and immune responses were monitored and correlated with tumor gene expression profiles . Experimental Design : Twenty-three patients with glioblastoma ( WHO grade IV ) were enrolled in this dose-escalation study and received three biweekly injections of glioma lysate-pulsed DCs followed by booster vaccinations with either imiquimod or poly-ICLC adjuvant every 3 months until tumor progression . Gene expression profiling , immunohistochemistry , FACS , and cytokine bead arrays were performed on patient tumors and peripheral blood mononuclear cells . Results : DC vaccinations are safe and not associated with any dose-limiting toxicity . The median overall survival from the time of initial surgical diagnosis of glioblastoma was 31.4 months , with a 1- , 2- , and 3-year survival rate of 91 % , 55 % , and 47 % , respectively . Patients whose tumors had mesenchymal gene expression signatures exhibited increased survival following DC vaccination compared with historic controls of the same genetic subtype . Tumor sample s with a mesenchymal gene expression signature had a higher number of CD3 + and CD8 + tumor-infiltrating lymphocytes compared with glioblastomas of other gene expression signatures ( P = 0.006 ) . Conclusion : Autologous tumor lysate – pulsed DC vaccination in conjunction with TLR agonists is safe as adjuvant therapy in newly diagnosed and recurrent glioblastoma patients . Our results suggest that the mesenchymal gene expression profile may identify an immunogenic subgroup of glioblastoma that may be more responsive to immune-based therapies . Clin Cancer Res ; 17(6 ) ; 1603–15 . © 2010 AACR Nine cancer patients were treated with adoptive cell therapy using autologous anti-MAGE-A3 T-cell receptors (TCR)-engineered T cells . Five patients experienced clinical regression of their cancers including 2 on-going responders . Beginning 1–2 days postinfusion , 3 patients ( # ’s 5 , 7 , and 8) experienced mental status changes , and 2 patients ( 5 and 8) lapsed into comas and subsequently died . Magnetic resonance imagining analysis of patients 5 and 8 demonstrated periventricular leukomalacia , and examination of their brains at autopsy revealed necrotizing leukoencephalopathy with extensive white matter defects associated with infiltration of CD3+/CD8 + T cells . Patient 7 , developed Parkinson-like symptoms , which resolved over 4 weeks and fully recovered . Immunohistochemical staining of patient and normal brain sample s demonstrated rare positively staining neurons with an antibody that recognizes multiple MAGE-A family members . The TCR used in this study recognized epitopes in MAGE-A3/A9/A12 . Molecular assays of human brain sample s using real-time quantitative-polymerase chain reaction , Nanostring quantitation , and deep-sequencing indicated that MAGE-A12 was expressed in human brain ( and possibly MAGE-A1 , MAGE-A8 , and MAGE-A9 ) . This previously unrecognized expression of MAGE-A12 in human brain was possibly the initiating event of a TCR-mediated inflammatory response that result ed in neuronal cell destruction and raises caution for clinical applications targeting MAGE-A family members with highly active immunotherapies Previous clinical trials of dendritic cell (DC)-based immunotherapy in patients with glioblastoma multiforme ( GBM ) have reported induction of systemic immune responses and prolonged survival . From 2003 to 2005 , we performed a clinical trial in which patients with malignant glioma underwent surgery for maximal cytoreduction followed by a 6-month 10-injection course of autologous DC-tumor vaccine therapy , each injection containing 1 - 6 × 10(7 ) DC . Of the 17 treated patients ( 16 with World Health Organization grade IV and one with grade III glioma ) , eight ( 47.1 % ) had an initial transient elevation in aspartate aminotransferase (AST)/alanine aminotransferase ( ALT ) . Vaccination caused some tumor shrinkage and increased concentration of tumor-infiltrating CD8(+ ) lymphocytes . Median survival and 5-year survival were 525 days and 18.8 % , respectively , for 16 patients with grade IV glioma ( 381 days and 12.5 % for eight newly diagnosed ; 966 days and 25 % for eight relapsed patients ) compared to 380 days and 0 % for 63 historical control patients . We concluded that autologous DC-tumor immunotherapy benefits patients with malignant glioma but may cause transient but reversible elevation of serum AST/ALT levels PURPOSE To investigate the safety and the immunologic and clinical responses of dendritic cell therapy for patients with recurrent malignant glioma . EXPERIMENTAL DESIGN Twenty-four patients with recurrent malignant glioma ( 6 grade 3 and 18 grade 4 patients ) were evaluated in a phase I/II clinical study of dendritic cell therapy . All patients were resistant to the st and ard maximum therapy . The patient 's peripheral blood dendritic cells were generated with granulocyte macrophage colony-stimulating factor , plus interleukin 4 with or without OK-432 , and pulsed with an autologous tumor lysate . Dendritic cells were injected intradermally , or both intratumorally and intradermally every 3 weeks . RESULTS The protocol s were well tolerated with only local redness and swelling at the injection site in several cases . Clinical responses were as follows : 1 patient with partial response , 3 patients with minor response , 10 patients with stable disease , and 10 patients with progressive disease . The patients whose dendritic cells were matured with OK-432 had longer survival times than the dendritic cells from patients without OK-432 maturation . The patients with both intratumoral and intradermal administrations had a longer survival time than the patients with intradermal administration only . Increased ELISPOT and delayed-type hypersensitivity responses after vaccination could provide good laboratory markers to predict the clinical outcome of patients receiving dendritic cell vaccination . The overall survival of patients with grade 4 glioma was 480 days , which was significantly better than that in the control group . CONCLUSIONS This study showed the safety and clinical response of autologous tumor lysate-pulsed dendritic cell therapy for patients with malignant glioma . Dendritic cell therapy is recommended for further clinical studies in malignant glioma patients Background This study evaluated the safety and immune responses to an autologous dendritic cell vaccine pulsed with class I peptides from tumor-associated antigens ( TAA ) expressed on gliomas and overexpressed in their cancer stem cell population ( ICT-107 ) . Methods TAA epitopes included HER2 , TRP-2 , gp100 , MAGE-1 , IL13Rα2 , and AIM -2 . HLA-A1- and /or HLA-A2-positive patients with glioblastoma ( GBM ) were eligible . Mononuclear cells from leukapheresis were differentiated into dendritic cells , pulsed with TAA peptides , and administered intradermally three times at two-week intervals . Results Twenty-one patients were enrolled with 17 newly diagnosed ( ND-GBM ) and three recurrent GBM patients and one brainstem glioma . Immune response data on 15 newly diagnosed patients showed 33 % responders . TAA expression by qRT-PCR from fresh-frozen tumor sample s showed all patient tumors expressed at least three TAA , with 75 % expressing all six . Correlations of increased PFS and OS with quantitative expression of MAGE1 and AIM -2 were observed , and a trend for longer survival was observed with gp100 and HER2 antigens . Target antigens gp100 , HER1 , and IL13Rα2 were downregulated in recurrent tumors from 4 HLA-A2 + patients . A decrease in or absence of CD133 expression was seen in five patients who underwent a second resection . At a median follow-up of 40.1 months , six of 16 ND-GBM patients showed no evidence of tumor recurrence . Median PFS in newly diagnosed patients was 16.9 months , and median OS was 38.4 months . Conclusions Expression of four ICT-107 targeted antigens in the pre-vaccine tumors correlated with prolonged overall survival and PFS in ND-GBM patients . The goal of targeting tumor antigens highly expressed on glioblastoma cancer stem cells is supported by the observation of decreased or absent CD133 expression in the recurrent areas of gadolinium-enhanced tumors The primary goal of this Phase I study was to assess the safety and bioactivity of tumor lysate-pulsed dendritic cell ( DC ) vaccination to treat patients with glioblastoma multiforme and anaplastic astrocytoma . Adverse events , survival , and cytotoxicity against autologous tumor and tumor-associated antigens were measured . Fourteen patients were thrice vaccinated 2 weeks apart with autologous DCs pulsed with tumor lysate . Peripheral blood mononuclear cells were differentiated into phenotypically and functionally confirmed DCs . Vaccination with tumor lysate-pulsed DCs was safe , and no evidence of autoimmune disease was noted . Ten patients were tested for the development of cytotoxicity through a quantitative PCR-based assay . Six of 10 patients demonstrated robust systemic cytotoxicity as demonstrated by IFN-γ expression by peripheral blood mononuclear cells in response to tumor lysate after vaccination . Using HLA-restricted tetramer staining , we identified a significant expansion in CD8 + antigen-specific T-cell clones against one or more of tumor-associated antigens MAGE-1 , gp100 , and HER-2 after DC vaccination in four of nine patients . A significant CD8 + T-cell infiltrate was noted intratumorally in three of six patients who underwent reoperation . The median survival for patients with recurrent glioblastoma multiforme in this study ( n = 8) was 133 weeks . This Phase I study demonstrated the feasibility , safety , and bioactivity of an autologous tumor lysate-pulsed DC vaccine for patients with malignant glioma . We demonstrate for the first time the ability of an active immunotherapy strategy to generate antigen-specific cytotoxicity in brain tumor patients Convection-enhanced delivery ( CED ) of cintredekin besudotox ( CB ) was compared with Gliadel wafers ( GW ) in adult patients with glioblastoma multiforme ( GBM ) at first recurrence . Patients were r and omized 2:1 to receive CB or GW . CB ( 0.5 microg/mL ; total flow rate 0.75 mL/h ) was administered over 96 hours via 2 - 4 intraparenchymal catheters placed after tumor resection . GW ( 3.85%/7.7 mg carmustine per wafer ; maximum 8 wafers ) were placed immediately after tumor resection . The primary endpoint was overall survival from the time of r and omization . Prestated interim analyses were built into the study design . Secondary and tertiary endpoints were safety and health-related quality -of-life assessment s. From March 2004 to December 2005 , 296 patients were enrolled at 52 centers . Demographic and baseline characteristics were balanced between the 2 treatment arms . Median survival was 36.4 weeks ( 9.1 months ) for CB and 35.3 weeks ( 8.8 months ) for GW ( P = .476 ) . For the efficacy evaluable population , the median survival was 45.3 weeks ( 11.3 months ) for CB and 39.8 weeks ( 10 months ) for GW ( P = .310 ) . The adverse-events profile was similar in both arms , except that pulmonary embolism was higher in the CB arm ( 8 % vs 1 % , P = .014 ) . This is the first r and omized phase III evaluation of an agent administered via CED and the first with an active comparator in GBM patients . There was no survival difference between CB administered via CED and GW . Drug distribution was not assessed and may be crucial for evaluating future CED-based therapeutics BACKGROUND Sipuleucel-T , an autologous active cellular immunotherapy , has shown evidence of efficacy in reducing the risk of death among men with metastatic castration-resistant prostate cancer . METHODS In this double-blind , placebo-controlled , multicenter phase 3 trial , we r and omly assigned 512 patients in a 2:1 ratio to receive either sipuleucel-T ( 341 patients ) or placebo ( 171 patients ) administered intravenously every 2 weeks , for a total of three infusions . The primary end point was overall survival , analyzed by means of a stratified Cox regression model adjusted for baseline levels of serum prostate-specific antigen ( PSA ) and lactate dehydrogenase . RESULTS In the sipuleucel-T group , there was a relative reduction of 22 % in the risk of death as compared with the placebo group ( hazard ratio , 0.78 ; 95 % confidence interval [ CI ] , 0.61 to 0.98 ; P=0.03 ) . This reduction represented a 4.1-month improvement in median survival ( 25.8 months in the sipuleucel-T group vs. 21.7 months in the placebo group ) . The 36-month survival probability was 31.7 % in the sipuleucel-T group versus 23.0 % in the placebo group . The treatment effect was also observed with the use of an unadjusted Cox model and a log-rank test ( hazard ratio , 0.77 ; 95 % CI , 0.61 to 0.97 ; P=0.02 ) and after adjustment for use of docetaxel after the study therapy ( hazard ratio , 0.78 ; 95 % CI , 0.62 to 0.98 ; P=0.03 ) . The time to objective disease progression was similar in the two study groups . Immune responses to the immunizing antigen were observed in patients who received sipuleucel-T. Adverse events that were more frequently reported in the sipuleucel-T group than in the placebo group included chills , fever , and headache . CONCLUSIONS The use of sipuleucel-T prolonged overall survival among men with metastatic castration-resistant prostate cancer . No effect on the time to disease progression was observed . ( Funded by Dendreon ; Clinical Trials.gov number , NCT00065442 . Establishment of a detection platform for glioblastoma-dendritic cell ( DC ) vaccine preparation and to determine the efficacy of the vaccine in a clinical trial . Autologous glioblastoma-DC vaccine was prepared from a glioblast specimen procured from surgical resection . The specimen was used to enrich the vaccine with peripherally blood-derived DCs after heat-shock induced , glioblastoma apoptosis . The control group received conventional treatment of surgery and radio-chemotherapy post-operation . The therapeutic group received a combination of glioblastoma-DC vaccine and conventional therapy . A comparison of the functional immune parameters , including tumor control , rate live time , Karnofsky scores , and complications occurring in each group were observed and recorded . The proportions of peripheral CD3 + , CD3+CD4 + , CD4+/CD8 + , and NK cells were significantly higher after DC vaccination than the control group ( P < 0.05 ) . Serum levels of IL-2 , IL-12 , and IFN-γwere significantly higher after DC vaccination than in the control group ( P < 0.05 ) . Nine months after vaccination , tumor control rate is significantly improved in the DC group compared with the control group ( P < 0.05 ) ; survival rate was significantly higher in DC group than in control group ( P < 0.05 ) and the time to relapse was significantly longer in DC group than that in control group ( P < 0.05 ) . Karnofsky scores were better in DC vaccination group 6 and 9 months post-treatment compared with the control group ( P < 0.05 ) . The combination of glioma DC vaccine and radiotherapy/chemotherapy post-operatively enhances the immune function of patients , increases the tumor control rate , prolongs the survival time and relapse duration , improves the quality of life , and therefore provides a more effective intervention of treating glioblastoma OBJECTIVE Cintredekin besudotox ( CB ) , a recombinant cytotoxin consisting of interleukin-13 and truncated Pseudomonas exotoxin , binds selectively to interleukin-13Rα2 receptors overexpressed by malignant gliomas . This study assessed the safety of CB administered by convection-enhanced delivery followed by st and ard external beam radiation therapy ( EBRT ) with or without temozolomide ( Temodar ; Schering-Plough , Kenilworth , NJ ) in patients with newly diagnosed malignant gliomas . METHODS After gross total resection of the tumor , two to four intraparenchymal catheters were stereotactically placed and CB ( 0.25 or 0.5 μg/mL ) was infused for 96 hours . This was followed , 10 to 14 days later , by EBRT ( 5940–6100 cGy , 5 d/wk for 6–7 wk ) with or without temozolomide ( 75 mg/m2/d , 7 d/wk during EBRT ) . Safety was assessed during an 11-week observation period after catheter placement RESULTS Twenty-two patients ( 12 men , 10 women ; median age , 55 yr ; 21 with glioblastoma multiforme and one with an anaplastic mixed oligoastrocytoma ) were enrolled . None of the patients experienced dose-limiting toxicities in the first two cohorts ( 0.25 μg/mL CB + EBRT [ n = 3 ] and 0.25 μg/mL CB + EBRT + temozolomide [ n = 3 ] ) . One patient experienced a dose-limiting toxicity ( Grade 4 seizure ) in the third cohort ( 0.5 μg/mL CB + EBRT [ n = 6 ] ) . Six patients in the final cohort ( 0.5 μg/mL CB + EBRT + temozolomide [ n = 10 ] ) completed treatment , and one patient experienced a dose-limiting toxicity ( Grade 3 aphasia and confusion ) . Four patients were not considered evaluable for a dose decision and were replaced . CB related adverse events occurring in more than one patient were fatigue , gait disturbance , nystagmus , and confusion . No Grade 3 to 4 hematological toxicities were observed . CONCLUSION CB ( 0.5 μg/mL ) administered via convection-enhanced delivery before st and ard radiochemotherapy seems to be well tolerated in adults with newly diagnosed malignant gliomas . Further clinical study assessment is warranted OBJECT A minority of patients with recurrent glioblastomas multiforme ( GBMs ) responds to systemic chemotherapy . The authors investigated the safety and efficacy of intratumoral convection-enhanced delivery ( CED ) of paclitaxel in patients harboring histologically confirmed recurrent GBMs and anaplastic astrocytomas . METHODS Fifteen patients received a total of 20 cycles of intratumoral CED of paclitaxel . The patients were observed daily by performing diffusion-weighted ( DW ) magnetic resonance ( MR ) imaging to assess the convective process and routine diagnostic MR imaging to identify the tumor response . Effective convection was determined by the progression of the hyperintense signal within the tumor on DW MR images , which corresponded to a subsequent lytic tumor response displayed on conventional MR images . Of the 15 patients , five complete responses and six partial responses were observed , giving a response rate of 73 % . The antitumor effect was confirmed by one biopsy and three en bloc resections of tumors , which showed a complete response , and by one tumor resection , which demonstrated a partial response . Lack of convection and a poor tumor response was associated with leakage of the convected drug into the subarachnoid space , ventricles , and cavities formed by previous resections , and was seen in tumors containing widespread necrosis . Complications included transient chemical meningitis in six patients , infectious complications in three patients , and transient neurological deterioration in four patients ( presumably due to increased peritumoral edema ) . CONCLUSIONS On the basis of our data we suggest that CED of paclitaxel in patients with recurrent malignant gliomas is associated with a high antitumor response rate , although it is associated with a significant incidence of treatment-associated complications . Diffusion-weighted MR images may be used to predict a response by demonstrating the extent of convection during treatment . Optimization of this therapeutic approach to enhance its efficacy and reduce its toxicity should be explored further OBJECT Convection-enhanced delivery ( CED ) is a novel method for delivering therapeutic agents to infiltrative brain tumor cells . For agents administered by CED , changes on magnetic resonance ( MR ) imaging directly result ing from catheter placement , infusion , and the therapeutic compound may confound any interpretation of tumor progression . As part of an ongoing multiinstitutional Phase I study , 14 patients with recurrent malignant glioma underwent CED of interleukin ( IL ) 13-PE38QQR , a recombinant cytotoxin consisting of human IL-13 conjugated with a truncated Pseudomonas exotoxin . Serial neuroradiographic changes were assessed in this cohort of patients . METHODS Patients were treated in two groups : Group 1 patients received IL13-PE38QQR before and after tumor resection ; Group 2 patients received infusion only after tumor resection . Preoperative and postinfusion MR images were obtained prospect ively at specified regular intervals . Changes were noted along catheter tracks on postresection MR images obtained in all patients . A simple grading system was developed to describe these changes . When MR imaging changes appeared to be related to IL1 3-PE38QQR , patients were followed up without instituting new antitumor therapy . CONCLUSIONS As CED of therapeutic agents becomes more common , clinicians and investigators must become aware of associated neuroimaging changes that should be incorporated into toxicity assessment . We have developed a simple grading system to facilitate communication about these changes among investigators . Biological imaging modalities that could possibly distinguish these changes from recurrent tumor should be evaluated . In this study the authors demonstrate the challenges in determining efficacy when surrogate end points such as time to tumor progression as defined by new or progressive contrast enhancement on MR imaging are used with this treatment modality PURPOSE Immunologic targeting of tumor-specific gene mutations may allow precise eradication of neoplastic cells without toxicity . Epidermal growth factor receptor variant III ( EGFRvIII ) is a constitutively activated and immunogenic mutation not expressed in normal tissues but widely expressed in glioblastoma multiforme ( GBM ) and other neoplasms . PATIENTS AND METHODS A phase II , multicenter trial was undertaken to assess the immunogenicity of an EGFRvIII-targeted peptide vaccine and to estimate the progression-free survival ( PFS ) and overall survival ( OS ) of vaccinated patients with newly diagnosed EGFRvIII-expressing GBM with minimal residual disease . Intradermal vaccinations were given until toxicity or tumor progression was observed . Sample size was calculated to differentiate between PFS rates of 20 % and 40 % 6 months after vaccination . RESULTS There were no symptomatic autoimmune reactions . The 6-month PFS rate after vaccination was 67 % ( 95 % CI , 40 % to 83 % ) and after diagnosis was 94 % ( 95 % CI , 67 % to 99 % ; n = 18 ) . The median OS was 26.0 months ( 95 % CI , 21.0 to 47.7 months ) . After adjustment for age and Karnofsky performance status , the OS of vaccinated patients was greater than that observed in a control group matched for eligibility criteria , prognostic factors , and temozolomide treatment ( hazard ratio , 5.3 ; P = .0013 ; n = 17 ) . The development of specific antibody ( P = .025 ) or delayed-type hypersensitivity ( P = .03 ) responses to EGFRvIII had a significant effect on OS . At recurrence , 82 % ( 95 % CI , 48 % to 97 % ) of patients had lost EGFRvIII expression ( P < .001 ) . CONCLUSION EGFRvIII-targeted vaccination in patients with GBM warrants investigation in a phase III , r and omized trial BACKGROUND Glioblastoma , the most common primary brain tumor in adults , is usually rapidly fatal . The current st and ard of care for newly diagnosed glioblastoma is surgical resection to the extent feasible , followed by adjuvant radiotherapy . In this trial we compared radiotherapy alone with radiotherapy plus temozolomide , given concomitantly with and after radiotherapy , in terms of efficacy and safety . METHODS Patients with newly diagnosed , histologically confirmed glioblastoma were r and omly assigned to receive radiotherapy alone ( fractionated focal irradiation in daily fractions of 2 Gy given 5 days per week for 6 weeks , for a total of 60 Gy ) or radiotherapy plus continuous daily temozolomide ( 75 mg per square meter of body-surface area per day , 7 days per week from the first to the last day of radiotherapy ) , followed by six cycles of adjuvant temozolomide ( 150 to 200 mg per square meter for 5 days during each 28-day cycle ) . The primary end point was overall survival . RESULTS A total of 573 patients from 85 centers underwent r and omization . The median age was 56 years , and 84 percent of patients had undergone debulking surgery . At a median follow-up of 28 months , the median survival was 14.6 months with radiotherapy plus temozolomide and 12.1 months with radiotherapy alone . The unadjusted hazard ratio for death in the radiotherapy-plus-temozolomide group was 0.63 ( 95 percent confidence interval , 0.52 to 0.75 ; P<0.001 by the log-rank test ) . The two-year survival rate was 26.5 percent with radiotherapy plus temozolomide and 10.4 percent with radiotherapy alone . Concomitant treatment with radiotherapy plus temozolomide result ed in grade 3 or 4 hematologic toxic effects in 7 percent of patients . CONCLUSIONS The addition of temozolomide to radiotherapy for newly diagnosed glioblastoma result ed in a clinical ly meaningful and statistically significant survival benefit with minimal additional toxicity BACKGROUND This study sought to evaluate effectiveness of autologous dendritic cell vaccine ( immunotherapy ) for glioblastoma multiforme ( GBM ) . METHODS Patients 14 to 70 years of age with newly diagnosed GBM and Karnofsky Performance Scale ( KPS ) score > 70 who were receiving initial treatment were enrolled and were r and omized into 2 groups during the 5-year study period . Eighteen patients underwent conventional treatment ( surgery , radiotherapy , and chemotherapy ) and received adjuvant autologous dendritic cell vaccine , and 16 patients ( control group ) underwent conventional treatment only . Administration of the vaccine was begun within 1 to 2 months postoperatively , with 10 inoculations given over 6 months . Outcome measures were overall survival ( OS ) ; progression-free survival ( PFS ) ; 1- , 2- , and 3-year survival rates , and quality of life ( QoL ) . RESULTS Follow-up time ranged from 14 to 56 months ( median , 33 months ) . The 1- , 2- , and 3-year survival rates were 88.9 % , 44.4 % , and 16.7 % for the vaccine group , respectively , and 75.0 % , 18.8 % , and 0 % , respectively , for the control group , ( P = 0.299 , 0.0035 , 0.0014 , respectively ) . The median OS for the vaccine group was 31.9 months and for the control group was 15.0 months ( P < 0.002 ) . The median progression-free survival ( PFS ) for the vaccine group was 8.5 months , and 8.0 months for the control group ( P = 0.075 ) . The surviving fraction was significantly higher in the vaccine group based on Kaplan-Meier analysis . CONCLUSIONS Adjuvant immunotherapy with whole-cell lysate dendritic cell vaccine may improve short-term survival . It seems to be safe , and its long-term effectiveness is worthy of further investigation Dendritic cell ( DC ) vaccination is emerging as a promising therapeutic option for malignant glioma patients . However , the optimal antigen formulation for loading these cells has yet to be established . The objective of this study was to compare the safety , feasibility , and immune responses of malignant glioma patients on 2 different DC vaccination protocol s. Twenty-eight patients were treated with autologous tumor lysate (ATL)-pulsed DC vaccination , whereas 6 patients were treated with glioma-associated antigen ( GAA ) peptide-pulsed DCs . Safety , toxicity , feasibility , and correlative immune monitoring assay results were compared between patients on each trial . Because of HLA subtype restrictions on the GAA-DC trial , 6/15 screened patients were eligible for treatment , whereas 28/32 patients passed eligibility screening for the ATL-DC trial . Elevated frequencies of activated natural killer cells were observed in the peripheral blood from GAA-DC patients compared with the ATL-DC patients . In addition , a significant correlation was observed between decreased regulatory T lymphocyte ( Treg ) ratios ( postvaccination/prevaccination ) and overall survival ( P=0.004 ) in patients on both trials . In fact , Treg ratios were independently prognostic for overall survival in these patients , whereas tumor pathology was not in multivariate analyses . In conclusion , these results suggest that ATL-DC vaccination is associated with wider patient eligibility compared with GAA-DC vaccination . Decreased postvaccination/prevaccination Treg ratios and decreased frequencies of activated natural killer cells were associated with prolonged survival in patients from both trials , suggesting that these lymphocyte subsets may be relevant immune monitoring endpoints for immunotherapy protocol s in malignant glioma patients |
10,715 | 20,008,762 | Contribution Authors of this systematic review concluded that ACE inhibitors reduce risk for mortality , stroke , and myocardial infa rct ion in patients with stable ischemic heart disease and preserved left ventricular function who already receive st and ard treatments , such as -blockers , statins , and aspirin . | Context Do patients already receiving st and ard therapy for ischemic heart disease benefit from additional treatment with angiotensin-converting enzyme ( ACE ) inhibitors or angiotensin IIreceptor blockers ( ARBs ) ?
Evidence about effects of ARBs was scant .
Combining ACE inhibitors and ARBs increased risks for hypotension and syncope compared with ACE inhibitor therapy alone .
The Editors An estimated 16800000 adults have ischemic heart disease ( 1 ) .
St and ard medical therapy for these patients includes aspirin , -blockers , and aggressive modification of risk factors ( 2 , 3 ) .
Angiotensin-converting enzyme ( ACE ) inhibitors or angiotensin IIreceptor blockers ( ARBs ) have established benefit in patients with heart failure and those who have had a myocardial infa rct ion with ventricular dysfunction ( 411 ) .
Their use , however , in patients with preserved ventricular function is less certain .
In patients with stable ischemic heart disease who have preserved ventricular function , what are the benefits and harms of adding ACE inhibitors or ARBs to st and ard medical therapy compared with st and ard medical therapy alone ?
2 .
In patients with stable ischemic heart disease who have preserved ventricular function and are receiving st and ard medical therapy , what are the benefits and harms of combining ACE inhibitors and ARBs compared with either an ACE inhibitor or an ARB alone ?
3 .
What is the evidence that benefits or harms differ in prespecified sub population s ? | Cardiovascular events ( CVEs ) are the leading cause of death in chronic hemodialysis patients . Results of trials in non-end-stage renal disease ( ESRD ) patients can not be extrapolated to patients with ESRD . It is critical to test cardiovascular therapies in these high-risk patients who are usually excluded from major cardiovascular trials . The study objective was to evaluate the effect of fosinopril on CVEs in patients with ESRD . Eligible patients were r and omized to fosinopril 5 mg titrated to 20 mg daily ( n=196 ) or placebo ( n=201 ) plus conventional therapy for 24 months . The primary end point was combined fatal and nonfatal first major CVEs ( cardiovascular death , resuscitated death , nonfatal stroke , heart failure , myocardial infa rct ion , or revascularization ) . No significant benefit for fosinopril was observed in the intent to treat analysis ( n=397 ) after adjusting for independent predictors of CVEs ( RR=0.93 , 95 % confidence interval ( CI ) 0.68 - 1.26 , P=0.35 ) . The per protocol secondary supportive analysis ( n=380 ) found a trend towards benefit for fosinopril ( adjusted RR=0.79 ( 95 % CI 0.59 - 1.1 , P=0.099 ) ) . In the patients who were hypertensive at baseline , systolic and diastolic blood pressures were significantly decreased in the fosinopril as compared to the placebo group . After adjustment for risk factors , trends were observed suggesting fosinopril may be associated with a lower risk of CVEs . These trends may have become statistically significant had the sample size been larger , and these findings warrant further study Background — Patients with reduced renal function are at increased risk for adverse cardiovascular outcomes . In the post – myocardial infa rct ion setting , angiotensin-converting enzyme ( ACE ) inhibitors have been shown to be as effective in patients with impaired renal function as in those with preserved renal function . Methods and Results — We assessed the relation between renal function and outcomes , the influence of ACE inhibition on this relation , and whether renal function modifies the effectiveness of ACE inhibition in patients with stable coronary artery disease and preserved systolic function enrolled in the Prevention of Events with ACE inhibition trial ( PEACE ) . Patients ( n=8290 ) were r and omly assigned to receive tr and olapril ( target , 4 mg/d ) or placebo . Clinical creatinine measures were available for 8280 patients before r and omization . The estimated glomerular filtration rate ( eGFR ) was calculated with the 4-point Modification of Diet in Renal Disease equation . Renal function was related to outcomes , and the influence of ACE-inhibitor therapy was assessed with formal interaction modeling . The mean eGFR in PEACE was 77.6±19.4 , and 1355 ( 16.3 % ) patients had reduced renal function ( eGFR < 60 mg · mL−1 · 1.73 m−2 ) . We observed a significant interaction between eGFR and treatment group with respect to cardiovascular and all-cause mortality ( P=0.02 ) . Tr and olapril was associated with a reduction in total mortality in patients with reduced renal function ( adjusted HR , 0.73 ; 95 % CI , 0.54 to 1.00 ) but not in patients with preserved renal function ( adjusted HR , 0.94 ; 95 % CI , 0.78 to 1.13 ) . Conclusions — Although tr and olapril did not improve survival in the overall PEACE cohort , in which mean eGFR was relatively high , tr and olapril reduced mortality in patients with reduced eGFR . These data suggest that reduced renal function may define a subset of patients most likely to benefit from ACE-inhibitor therapy for cardiovascular protection BACKGROUND Coprescription of aspirin and ACE inhibitors is frequent in heart failure caused by coronary artery disease . Negative interaction between aspirin and enalapril has been reported , presumably through inhibition by aspirin of ACE inhibitor-induced prostagl and in synthesis . Ticlopidine is a potent antiplatelet agent without interaction with prostagl and in synthesis . METHODS AND RESULTS The objective of this study was to compare the influence of a coadministration of ticlopidine or aspirin on the hemodynamic effects of an ACE inhibitor ( enalapril ) in patients with chronic heart failure . Twenty patients with severe heart failure were enrolled in a double-blind comparative trial and allocated to ticlopidine ( 500 mg daily , 12 patients ) or aspirin ( 325 mg daily , 8 patients ) . Hemodynamic evaluation was performed after 7 days of treatment , every hour for 4 hours after an oral administration of 10 mg of enalapril . Significant reductions in systemic vascular resistance were observed in the ticlopidine group , in contrast to no significant decrease in the aspirin group . A significant ( P=0.03 ) time-by-treatment interaction indicated significant aspirin-enalapril drug interaction . Total pulmonary resistance decreased significantly in both groups , with no difference between patients assigned to aspirin or ticlopidine . CONCLUSIONS Enalapril reduced systemic vascular resistance more effectively when given in combination with ticlopidine than with aspirin . In contrast , the reduction in total pulmonary resistance is similar when enalapril is administered in combination with aspirin or ticlopidine . Negative aspirin-enalapril interaction on prostagl and in synthesis presumably alters vasodilatation in systemic vessels , whereas prostagl and in-independent actions of ACE inhibition such as pulmonary arterial vasodilatation are maintained BACKGROUND Both hyper- and hypokalemia increase cardiovascular risk . Modest hyperkalemia is common with angiotensin-converting enzyme inhibition . We studied post-hoc the association of an initial , on-treatment serum potassium measurement with subsequent cardiovascular outcomes over 4.5 years in 9297 individuals at high cardiovascular risk , r and omized to an ACE inhibitor or to placebo . METHODS Post-hoc analysis of cardiovascular outcomes , as related to serum potassium levels , in the HOPE ( Heart Outcomes and Prevention Evaluation ) study which compared ramipril to placebo , and included 692 patients with a serum potassium level > 5.0 mM and 137 with a serum potassium level < 3.5 mM , defined as hyper- and hypokalemia , respectively . Serum potassium was measured 1 month after start of r and omized treatment . RESULTS With hyperkalemia , the primary event rate was unchanged compared to normokalemia ( 15.5 vs 15.7 % , p > 0.4 , respectively ) , with hypokalemia , the primary event rate was higher ( 22.6 % vs 15.5 % , respectively , p = 0.023 ) . The hazard ratio for the primary outcome associated with this initial hypokalemia was 1.44 ( 1.00 - 2.06 ) on multivariate analysis . The combined primary outcome ( myocardial infa rct ion , cardiovascular death , stroke ) was not different throughout deciles of serum potassium but the lowest and highest deciles included many with normokalemia . R and omized treatment was withheld because of hyperkalemia in 8 and 6 people allocated to ramipril and placebo , respectively . The benefit of ramipril on cardiovascular outcomes was independent of serum potassium , but ramipril reduced hypokalemia in the entire cohort ( 1.15 vs 1.86 % with placebo , p = 0.005 ) , particularly in those participants on diuretics ( 3.8 % vs 6.5 % , p = 0.07 ) . CONCLUSIONS In patients at high cardiovascular risk , modest hypokalemia predicts a less favorable outcome while modest hyperkalemia does not . Ramipril reduces hypokalemia and decreases risk BACKGROUND Diabetes mellitus is a strong risk factor for cardiovascular and renal disease . We investigated whether the angiotensin-converting-enzyme ( ACE ) inhibitor ramipril can lower these risks in patients with diabetes . METHODS 3577 people with diabetes included in the Heart Outcomes Prevention Evaluation study , aged 55 years or older , who had a previous cardiovascular event or at least one other cardiovascular risk factor , no clinical proteinuria , heart failure , or low ejection fraction , and who were not taking ACE inhibitors , were r and omly assigned ramipril ( 10 mg/day ) or placebo , and vitamin E or placebo , according to a two-by-two factorial design . The combined primary outcome was myocardial infa rct ion , stroke , or cardiovascular death . Overt nephropathy was a main outcome in a sub study . FINDINGS The study was stopped 6 months early ( after 4.5 years ) by the independent data safety and monitoring board because of a consistent benefit of ramipril compared with placebo . Ramipril lowered the risk of the combined primary outcome by 25 % ( 95 % CI 12 - 36 , p=0.0004 ) , myocardial infa rct ion by 22 % ( 6 - 36 ) , stroke by 33 % ( 10 - 50 ) , cardiovascular death by 37 % ( 21 - 51 ) , total mortality by 24 % ( 8 - 37 ) , revascularisation by 17 % ( 2 - 30 ) , and overt nephropathy by 24 % ( 3 - 40 , p=0.027 ) . After adjustment for the changes in systolic ( 2.4 mm Hg ) and diastolic ( 1.0 mm Hg ) blood pressures , ramipril still lowered the risk of the combined primary outcome by 25 % ( 12 - 36 , p=0.0004 ) . INTERPRETATION Ramipril was beneficial for cardiovascular events and overt nephropathy in people with diabetes . The cardiovascular benefit was greater than that attributable to the decrease in blood pressure . This treatment represents a vasculoprotective and renoprotective effect for people with diabetes BACKGROUND Treatment with angiotensin-converting-enzyme ( ACE ) inhibitors reduces mortality among survivors of acute myocardial infa rct ion , but whether to use ACE inhibitors in all patients or only in selected patients is uncertain . METHODS We screened 6676 consecutive patients with 7001 myocardial infa rct ions confirmed by enzyme studies . A total of 2606 patients had echocardiographic evidence of left ventricular systolic dysfunction ( ejection fraction , < or = 35 percent ) . On days 3 to 7 after infa rct ion , 1749 patients were r and omly assigned to receive oral tr and olapril ( 876 patients ) or placebo ( 873 patients ) . The duration of follow-up was 24 to 50 months . RESULTS During the study period , 304 patients ( 34.7 percent ) in the tr and olapril group died , as compared with 369 ( 42.3 percent ) in the placebo group ( P = 0.001 ) . The relative risk of death in the tr and olapril group , as compared with the placebo group , was 0.78 ( 95 percent confidence interval , 0.67 to 0.91 ) . Tr and olapril also reduced the risk of death from cardiovascular causes ( relative risk , 0.75 ; 95 percent confidence interval , 0.63 to 0.89 ; P = 0.001 ) and sudden death ( relative risk , 0.76 ; 95 percent confidence interval , 0.59 to 0.98 ; P = 0.03 ) . Progression to severe heart failure was less frequent in the tr and olapril group ( relative risk , 0.71 ; 95 percent confidence interval , 0.56 to 0.89 ; P = 0.003 ) . In contrast , the risk of recurrent myocardial infa rct ion ( fatal or nonfatal ) was not significantly reduced ( relative risk , 0.86 ; 95 percent confidence interval , 0.66 to 1.13 ; P = 0.29 ) . CONCLUSIONS Long-term treatment with tr and olapril in patients with reduced left ventricular function soon after myocardial infa rct ion significantly reduced the risk of overall mortality , mortality from cardiovascular causes , sudden death , and the development of severe heart failure . That mortality was reduced in a r and omized study enrolling 25 percent of consecutive patients screened should encourage the selective use of ACE inhibition after myocardial infa rct ion AIMS Cardiovascular ( CV ) disease is the leading cause of death in the elderly . The use of ACE-inhibitors in elderly patients with chronic stable vascular disease has not been previously reported . METHODS AND RESULTS The HOPE trial evaluated the effects of ramipril and vitamin E in high-risk vascular disease patients . We report the effects of ramipril in the elderly HOPE study patients , defined as those > or = 70 years of age . A total of 2755 elderly patients with vascular disease or diabetes and at least one additional CV risk factor and without heart failure or low ejection fraction were r and omized to ramipril 10 mg daily or placebo . Those assigned to ramipril had fewer major vascular events compared to those assigned to placebo [ 18.6 vs. 24.0 % , hazard ratio ( HR ) = 0.75 , P = 0.0006 ] , CV deaths ( 9.3 vs. 13.0 % , HR = 0.71 , P = 0.003 ) , myocardial infa rct ions ( 12.0 vs. 15.6 % , HR = 0.75 , P = 0.006 ) , and strokes ( 5.4 vs. 7.7 % , HR = 0.69 , P = 0.013 ) . Treatment was safe and generally well tolerated . CONCLUSION Ramipril reduces the risk of major vascular events in elderly patients with vascular disease and is safe and well tolerated by most The Japan Multicenter Investigation for Cardiovascular Diseases-B was performed to investigate whether nifedipine retard treatment was associated with a significantly higher incidence of cardiac events than angiotensin converting enzyme inhibitor treatment in Japanese patients . The study used a prospect i ve , r and omized , open , blinded endpoint ( PROBE ) design . Patients were enrolled at 354 Japanese hospitals specializing in cardiovascular disease . The subjects were 1,650 out patients aged under 75 years who had diagnoses of both hypertension and coronary artery disease . There were 828 patients subjected to intention-to-treat analysis in the nifedipine retard group and 822 patients in the angiotensin converting enzyme inhibitor group . The patients were r and omized to 3 years of treatment with either nifedipine retard or angiotensin converting enzyme inhibitor . The primary endpoint was the overall incidence of cardiac events ( cardiac death or sudden death , myocardial infa rct ion , hospitalization for angina pectoris or heart failure , serious arrhythmia , and coronary interventions ) . The primary endpoint occurred in 116 patients ( 14.0 % ) from the nifedipine retard group and 106 patients ( 12.9 % ) from the angiotensin converting enzyme inhibitor group ( relative risk , 1.05 ; 95 % confidence interval , 0.81 - 1.37 ; p = 0.75 ) . In the Kaplan-Meier estimates , there were no significant differences between the two groups ( log-rank test : p = 0.86 ) . The incidence of cardiac events and mortality did not differ between the nifedipine retard and angiotensin converting enzyme inhibitor therapies . Nifedipine retard seems to be as effective as angiotensin converting enzyme inhibitors in reducing the incidence of cardiac events and mortality Abstract Background : Angiotensin-converting enzyme inhibitors do reduce both mortality and morbidity in patients with left ventricular dysfunction , recent myocardial infa rct ion and hypertension . However , the long-term effects in patients with coronary artery disease have not been established . The EUROPA study is design ed to assess the long-term ( 3–4 years ) effects of perindopril on the reduction of cardiac events in patients with proven stable coronary artery disease but with no evidence of heart failure . Study Design and Methods : EUROPA is a 12236 patient , r and omised , double-blind , placebo-controlled and multicentre trial . EUROPA had an initial run-in period of 4 weeks during which patients received 4 and then 8 mg of perindopril daily to assess tolerance to maximum dose . This was followed by a double-blind r and omisation to either perindopril or placebo . Patients were followed-up at 3 and 6 months and then 6 monthly until the last patient included in the main study completes the 3-year follow-up . EUROPA includes five sub- studies . Each of these sub- studies investigates the effects of perindopril on a different aspect of coronary artery disease : endothelial dysfunction , atherosclerosis progression or regression , diabetes mellitus , inflammation , thrombosis , neurohormonal activation . Patients are characterised genetically to assess characteristics associated with improved or unfavourable outcome . The final results of EUROPA will be available in 2002 BACKGROUND Angiotensin II type 1 receptor blockers have favourable effects on haemodynamic measurements , neurohumoral activity , and left-ventricular remodelling when added to angiotensin-converting-enzyme ( ACE ) inhibitors in patients with chronic heart failure ( CHF ) . We aim ed to find out whether these drugs improve clinical outcome . METHODS Between March , 1999 , and November , 1999 , we enrolled 2548 patients with New York Heart Association functional class II-IV CHF and left-ventricular ejection fraction 40 % or lower , and who were being treated with ACE inhibitors . We r and omly assigned patients c and esartan ( n=1276 , target dose 32 mg once daily ) or placebo ( n=1272 ) . At baseline , 55 % of patients were also treated with beta blockers and 17 % with spironolactone . The primary outcome of the study was the composite of cardiovascular death or hospital admission for CHF . Analysis was done by intention to treat . FINDINGS The median follow-up was 41 months . 483 ( 38 % ) patients in the c and esartan group and 538 ( 42 % ) in the placebo group experienced the primary outcome ( unadjusted hazard ratio 0.85 [ 95 % CI 0.75 - 0.96 ] , p=0.011 ; covariate adjusted p=0.010 ) . C and esartan reduced each of the components of the primary outcome significantly , as well as the total number of hospital admissions for CHF . The benefits of c and esartan were similar in all predefined subgroups , including patients receiving baseline beta blocker treatment . INTERPRETATION The addition of c and esartan to ACE inhibitor and other treatment leads to a further clinical ly important reduction in relevant cardiovascular events in patients with CHF and reduced left-ventricular ejection fraction BACKGROUND In patients who have vascular disease or high-risk diabetes without heart failure , angiotensin-converting-enzyme ( ACE ) inhibitors reduce mortality and morbidity from cardiovascular causes , but the role of angiotensin-receptor blockers ( ARBs ) in such patients is unknown . We compared the ACE inhibitor ramipril , the ARB telmisartan , and the combination of the two drugs in patients with vascular disease or high-risk diabetes . METHODS After a 3-week , single-blind run-in period , patients underwent double-blind r and omization , with 8576 assigned to receive 10 mg of ramipril per day , 8542 assigned to receive 80 mg of telmisartan per day , and 8502 assigned to receive both drugs ( combination therapy ) . The primary composite outcome was death from cardiovascular causes , myocardial infa rct ion , stroke , or hospitalization for heart failure . RESULTS Mean blood pressure was lower in both the telmisartan group ( a 0.9/0.6 mm Hg greater reduction ) and the combination-therapy group ( a 2.4/1.4 mm Hg greater reduction ) than in the ramipril group . At a median follow-up of 56 months , the primary outcome had occurred in 1412 patients in the ramipril group ( 16.5 % ) , as compared with 1423 patients in the telmisartan group ( 16.7 % ; relative risk , 1.01 ; 95 % confidence interval [ CI ] , 0.94 to 1.09 ) . As compared with the ramipril group , the telmisartan group had lower rates of cough ( 1.1 % vs. 4.2 % , P<0.001 ) and angioedema ( 0.1 % vs. 0.3 % , P=0.01 ) and a higher rate of hypotensive symptoms ( 2.6 % vs. 1.7 % , P<0.001 ) ; the rate of syncope was the same in the two groups ( 0.2 % ) . In the combination-therapy group , the primary outcome occurred in 1386 patients ( 16.3 % ; relative risk , 0.99 ; 95 % CI , 0.92 to 1.07 ) ; as compared with the ramipril group , there was an increased risk of hypotensive symptoms ( 4.8 % vs. 1.7 % , P<0.001 ) , syncope ( 0.3 % vs. 0.2 % , P=0.03 ) , and renal dysfunction ( 13.5 % vs. 10.2 % , P<0.001 ) . CONCLUSIONS Telmisartan was equivalent to ramipril in patients with vascular disease or high-risk diabetes and was associated with less angioedema . The combination of the two drugs was associated with more adverse events without an increase in benefit . ( Clinical Trials.gov number , NCT00153101 [ Clinical Trials.gov ] . ) Arthritis and hypertension are frequent comorbidities in the elderly hypertensive population . Nonsteroidal anti-inflammatory drugs are often used to relieve pain in arthritic patients but a side effect is sodium retention and consequent elevation of blood pressure ( BP ) . The effect of dihydropyridine calcium blocking drugs is relatively independent of sodium intake , whereas the angiotensin-converting enzyme ( ACE ) inhibitors ' effects can be blunted by a high-sodium diet . This study compared the effects of indomethacin with placebo in elderly patients with essential hypertension who had been controlled with amlodipine or enalapril . Indomethacin 50 mg twice daily or placebo was administered for 3 weeks in a double-blind crossover study to patients controlled with amlodipine or enalapril . The response was assessed by ambulatory BP measurement . Indomethacin raised BP and lowered pulse rates in patients taking enalapril but had little effect in patients receiving amlodipine . The difference caused by indomethacin between the two groups was 10.1/4.9 mm Hg increase in BP and a 5.6 beats/min fall in pulse in people taking enalapril . Addition of indomethacin to patients taking either drug caused a rise in weight and a fall in plasma renin . It is postulated that the effect is due to inhibition of prostagl and in synthesis , which causes sodium retention . In patients taking amlodipine , the fall in plasma renin ameliorates the effect of sodium retention on BP . In patients taking enalapril , plasma renin falls but this is not translated into an effect because of the blockage of converting enzyme . Thus , the full effect of sodium retention on BP is expressed . In patients treated with indomethacin , fewer patients may respond to ACE inhibitors . However , the major problem is the patient who intermittently takes indomethacin or other nonsteroidal anti-inflammatory drugs , which , if a person is treated by an ACE inhibitor causes BP to go out of control . In such patients amlodipine would appear to be a preferred choice to enalapril Background —Activation of the renin-angiotensin-aldosterone system and oxidative modification of LDL cholesterol play important roles in atherosclerosis . The Study to Evaluate Carotid Ultrasound changes in patients treated with Ramipril and vitamin E ( SECURE ) , a sub study of the Heart Outcomes Prevention Evaluation ( HOPE ) trial , was a prospect i ve , double-blind , 3 × 2 factorial design trial that evaluated the effects of long-term treatment with the angiotensin-converting enzyme inhibitor ramipril and vitamin E on atherosclerosis progression in high-risk patients . Methods and Results —A total of 732 patients ≥55 years of age who had vascular disease or diabetes and at least one other risk factor and who did not have heart failure or a low left ventricular ejection fraction were r and omly assigned to receive ramipril 2.5 mg/d or 10 mg/d and vitamin E ( RRR-&agr;-tocopheryl acetate ) 400 IU/d or their matching placebos . Average follow-up was 4.5 years . Atherosclerosis progression was evaluated by B-mode carotid ultrasound . The progression slope of the mean maximum carotid intimal medial thickness was 0.0217 mm/year in the placebo group , 0.0180 mm/year in the ramipril 2.5 mg/d group , and 0.0137 mm/year in the ramipril 10 mg/d group ( P = 0.033 ) . There were no differences in atherosclerosis progression rates between patients on vitamin E and those on placebo . Conclusions —Long-term treatment with ramipril had a beneficial effect on atherosclerosis progression . Vitamin E had a neutral effect on atherosclerosis progression Background —We have previously demonstrated that ramipril reduces vascular events and new diagnoses of diabetes when given for a 4.5-year period . However , it is not known whether the benefits are observed in subgroups of patients at varying risk or on other proven therapies and whether the benefits are sustained beyond the current trial . The 2 aims of this investigation were to assess whether the benefits observed during the HOPE trial were ( 1 ) maintained after trial cessation during an additional 2.6 years of follow-up and ( 2 ) observed in subgroups based on risk and ancillary treatments . Methods and Results —Of the initial 267 study centers and 9297 patients , 174 centers and 4528 patients agreed to further follow-up . The rates of use of angiotensin-converting-enzyme inhibitors ( ACEIs ) in the 2 groups ( 72 % ramipril versus 68 % placebo ) were similar after the end of the trial . During the posttrial follow-up , patients allocated to ramipril had a 19 % further lower relative risk ( RR ) of myocardial infa rct ion ( 95 % confidence interval [ CI ] , 0.65 to 1.01 ) , a 16 % lower RR ( 95 % CI , 0.70 to 0.99 ) of revascularization , and a 34 % lower RR of a new diagnosis of diabetes ( 95 % CI , 0.46 to 0.95 ) . Similar RR reductions in vascular events were observed during and after the active phase of the trial , regardless of baseline risk ( RR of 0.76 , 0.89 , and 0.83 for low- , medium- , and high-risk patients , respectively ) or ancillary treatments ( RR of 0.90 for aspirin , 0.76 for & bgr;-blockers , and 0.84 for lipid-lowering medication ) . Conclusions —The benefits of ramipril observed during the active period of the HOPE trial were maintained during posttrial follow-up for cardiovascular death , stroke , and hospitalization for heart failure . Additional reductions in myocardial infa rct ion , revascularization , and the development of diabetes were observed during the follow-up phase despite similar rates of ACEI use in the 2 r and omized groups . These benefits were consistent regardless of patient risk or ancillary treatments BACKGROUND Cardiovascular events are the major determinants of the prognosis of patients on chronic haemodialysis . The present study was design ed to investigate whether c and esartan , an angiotensin II type-1 receptor blocker , reduces the incidence of cardiovascular events in these patients . METHODS A total of 80 chronic haemodialysis patients ( male/female , 47/33 ; mean age + /- SEM , 61 + /- 1 years ) in stable condition and with no clinical evidence of cardiac disorders were enrolled . Patients were r and omly assigned c and esartan 4 - 8 mg/day ( c and esartan group ; n = 43 ) or nothing ( control group ; n = 37 ) , and followed for 19.4 + /- 1.2 months with as endpoint cardiovascular events such as fatal/nonfatal myocardial infa rct ion , unstable angina pectoris , congestive heart failure , severe arrhythmia and sudden death . RESULTS Both groups exhibited similar clinical characteristics at baseline . During follow-up , cardiovascular events occurred in seven patients in the c and esartan group and 17 in the control group . Kaplan-Meier analysis revealed that cardiovascular events and mortality rates were significantly ( P < 0.01 ) higher in the control group than in the c and esartan group ( 45.9 vs 16.3 % and 18.9 vs 0.0 % , respectively ) . CONCLUSIONS C and esartan therapy significantly reduces cardiovascular events and mortality in patients on chronic maintenance haemodialysis and therefore improves the prognosis of these patients OBJECTIVES This study sought to examine whether the cardioprotective effects of angiotensin-converting enzyme ( ACE ) inhibitor therapy by perindopril are modified by renal function in patients with stable coronary artery disease . BACKGROUND A recent study reported that an impaired renal function identified a subgroup of patients with stable coronary artery disease more likely to benefit from ACE inhibition therapy . In light of the growing interest in tailored therapy for targeting medications to specific subgroups , remarks on the consistency of the treatment effect by ACE inhibitors are highly important . METHODS The present study involved 12,056 patients with stable coronary artery disease without heart failure r and omized to perindopril or placebo . Estimated glomerular filtration rate ( eGFR ) was calculated using the abbreviated Modification of Diet in Renal Disease equation . Cox regression analysis was used to estimate multivariable-adjusted hazard ratios . RESULTS The mean eGFR was 76.2 ( + /-18.1 ) ml/min/1.73 m2 . During follow-up , the primary end point ( cardiovascular death , nonfatal myocardial infa rct ion , or resuscitated cardiac arrest ) occurred in 454 of 5,761 patients ( 7.9 % ) with eGFR > or = 75 and in 631 of 6,295 patients ( 10.0 % ) with eGFR < 75 . Treatment benefits of perindopril were apparent in both patient groups either with eGFR > or = 75 ( hazard ratio 0.77 ; 95 % confidence interval 0.64 to 0.93 ) or eGFR < 75 ( hazard ratio 0.84 ; 95 % confidence interval 0.72 to 0.98 ) . We observed no significant interaction between renal function and treatment benefit ( p = 0.47 ) . Using different cutoff points of eGFR at the level of 60 or 90 result ed in similar trends . CONCLUSIONS The treatment benefit of perindopril is consistent and not modified by mild to moderate renal insufficiency Background —In trials of patients with left ventricular dysfunction or heart failure , ACE inhibitor use was unexpectedly associated with reduced myocardial infa rct ion ( MI ) . Using the Heart Outcomes Prevention Evaluation ( HOPE ) trial data , we tested prospect ively whether ramipril , an ACE inhibitor , could reduce coronary events and revascularization procedures among patients with normal left ventricular function . Methods and Results —In the HOPE trial , 9297 high-risk men and women , ≥55 years of age with previous cardiovascular disease or diabetes plus 1 risk factor , were r and omly assigned to ramipril ( up to 10 mg/d ) , vitamin E ( 400 IU/d ) , their combination , or matching placebos . During the mean follow-up of 4.5 years , there were 482 ( 10.4 % ) patients with clinical MI and unexpected cardiovascular death in the ramipril group compared with 604 ( 12.9 % ) in the placebo group [ relative risk reduction ( RRR ) , 21 % ( 95 % CI ) (11,30);P < 0.0003 ] . Ramipril was associated with a trend toward less fatal MI and unexpected death [ 4.0 % versus 4.7 % ; RRR , 16 % ( −3 , 31 ) ] and with a significant reduction in nonfatal MI [ 5.6 % versus 7.2 % ; RRR , 23 % ( 9,34 ) ] . Risk reductions in MI were documented in participants taking or not taking & bgr;-blockers , lipid lowering , and /or antiplatelet agents . Although ramipril had no impact on hospitalizations for unstable angina [ 11.9 % versus 12.2 % ; RRR , 3 % ( −9,14 ) ] , it reduced the risk of worsening and new angina [ 27.2 % versus 30.0 % ; RRR , 12 % (5,18);P < 0.0014 ] and coronary revascularizations [ 12.5 % versus 14.8 % ; RRR , 18 % ; ( 8,26 ) P < 0.0005 ] . Conclusions —In this high-risk cohort , ramipril reduced the risk of MI , worsening and new angina , and the occurrence of coronary revascularizations BACKGROUND Angiotensin-converting enzyme ( ACE ) inhibitors reduce mortality , myocardial infa rct ion , stroke , heart failure , need for revascularization , nephropathy , and diabetes and its complications . Although angiotensin-II receptor blockers ( ARBs ) have been less extensively evaluated , theoretically they may have " protective " effects similar to those of ACE inhibitors , but with better tolerability . Currently , there is uncertainty about the role of ARBs when used alone or in combination with an ACE inhibitor in high-risk population s with controlled hypertension . OBJECTIVES Primary objectives of the ONgoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial ( ONTARGET ) are to determine if the combination of the ARB telmisartan and the ACE inhibitor ramipril is more effective than ramipril alone , and if telmisartan is at least as effective as ramipril . The Telmisartan R and omized AssessmeNt Study in aCE iNtolerant subjects with cardiovascular Disease ( TRANSCEND ) will determine if telmisartan is superior to placebo in patients who are intolerant of ACE inhibitors . The primary outcome for both trials is the composite of cardiovascular death , myocardial infa rct ion , stroke , or hospitalization for heart failure . METHOD High-risk patients with coronary , peripheral , or cerebrovascular disease or diabetes with end-organ damage are being recruited and followed for 3.5 to 5.5 years in 2 parallel , r and omized , double-blind clinical trials . PROGRESS Recruitment from 730 centers in 40 countries for ONTARGET ( n = 25,620 ) was completed in July 2003 . For TRANSCEND , 5776 patients ( out of a projected total of 6000 ) have been recruited ( by May 10 , 2004 ) . Baseline patient characteristics are comparable to the Heart Outcomes Prevention Evaluation ( HOPE ) trial , the basis of the design of the current study , confirming that patients are at high-risk The degree of arterial stiffness is correlated with the risk of cardiovascular diseases and it is a powerful predictor for morbidity and mortality . Studies have shown that arterial stiffness reduction is associated with an improvement in survival . Reduction of arterial stiffness by pharmacological drugs varies according to the drugs and doses used and duration of treatment . This effect on the arteries differs among the various classes of drugs and among individual drugs in the same class . Quantification of the stiffness and other properties of the arterial wall can be used to monitor the responses to therapy in individuals with hypertension and other cardiovascular diseases . These measures can then be used as surrogate markers for the risk of clinical events . Inhibition of the renin-angiotensin system ( RAS ) is associated with an important decrease in cardiovascular risk . Findings from clinical trials support the hypothesis that the protective effects of RAS inhibition are partly independent from blood pressure reduction and related to several mechanisms including vascular protective effects . The aim of the TRanscend Arterial stiffNess Sub study ( TRANS ) is to assess the effect of an angiotensin II receptor blocker ( ARB ) , telmisartan , on the arterial stiffness in a subgroup of patients from the Telmisartan R and omized Assessment Study in aCE iNtolerant subjects with cardiovascular Disease ( TRANSCEND ) trial . The TRANSCEND trial is an international , multicenter , r and omized double blind placebo controlled trial of telmisartan that enrolled patients at high risk for cardiovascular events . Some clinical baseline data of the TRANS sub study are reported . When completed , the results of the TRANS sub study will show whether the beneficial effects of treatment with telmisartan on cardiovascular outcome may be related to an improvement in arterial stiffness OBJECTIVES The primary objective of this study was to investigate the effects of the angiotensin-converting enzyme ( ACE ) inhibitor , ramipril , on carotid atherosclerosis in patients with coronary , cerebrovascular or peripheral vascular disease . BACKGROUND Angiotensin-converting enzyme inhibitors have been shown to reduce the risk of coronary events in various patient groups and to prevent the development of atherosclerosis in animal models . It has been hypothesized that the clinical benefits of ACE inhibitors may , therefore , be mediated by effects on atherosclerosis . METHODS Six hundred seventeen patients were r and omized in equal proportions to ramipril ( 5 - 10 mg daily ) or placebo . At baseline , two years and four years , carotid atherosclerosis was assessed by B-mode ultrasound , and left ventricular mass was assessed by M-mode echocardiography . RESULTS Blood pressure ( BP ) was reduced by a mean of 6 mm Hg systolic and 4 mm Hg diastolic in the ramipril group compared with the placebo group ( p<0.001 ) . There was no difference between groups in the changes in common carotid artery wall thickness ( p = 0.58 ) or in carotid plaque ( p = 0.93 ) . Left ventricular mass index decreased by 3.8 g/m2 ( 4 % ) in the ramipril group compared with the placebo group ( 2p = 0.04 ) . CONCLUSIONS The results provide no support for the hypothesis that reduced atherosclerosis is responsible for the beneficial effects of ACE inhibitors on major coronary events . It is more likely that the benefits are due to lower BP , reduced left ventricular mass or other factors such as reversal of endothelial dysfunction OBJECTIVE To describe the design of the HOPE ( Heart Outcomes Prevention Evaluation ) study . DESIGN Description of the key design features of HOPE , a large , simple r and omized trial of two widely applicable treatments -- ramipril , an angiotensin-converting enzyme inhibitor ; and vitamin E , a naturally occurring antioxidant vitamin -- in the prevention of myocardial infa rct ion , stroke or cardiovascular death . SETTING Two-hundred and sixty-seven hospitals , physician offices and clinics in Canada , the United States , Mexico , Europe and South America . PATIENTS Over 9000 women and men aged 55 years and above at high risk for cardiovascular events such as myocardial infa rct ion and stroke were recruited over 18 months . INTERVENTIONS A 2X2 factorial design with ramipril and vitamin E with follow-up for up to four years . CONCLUSIONS HOPE will be one of the largest trials of two new interventions to prevent myocardial infa rct ion , stroke or cardiovascular death in high risk patients . The results of HOPE will have direct public health impact and are likely to be readily incorporated into clinical practice . Key design features of HOPE are inclusion of individuals at high risk of cardiovascular disease , inclusion of a substantial proportion of patients with diabetes ( 36 % ) and women ( 27 % ) , and detailed sub studies to provide data on mechanisms of benefit The Prevention of Events with Angiotensin-Converting Enzyme Inhibition ( PEACE ) trial is an 8,100 patient , r and omized , double-blind , placebo-controlled trial design ed to determine the usefulness of angiotensin-converting enzyme ( ACE ) inhibitors in treating coronary patients with preserved left ventricular ejection fraction . The hypothesis being tested in this trial is that patients with coronary disease and ejection fraction > or = 40 % who are treated with ACE inhibitors will experience a reduction in the incidence of cardiovascular death , nonfatal myocardial infa rct ion , or a revascularization procedure compared with patients treated with conventional therapy . The design of the PEACE trial is described herein BACKGROUND Angiotensin-converting-enzyme inhibitors improve the outcome among patients with left ventricular dysfunction , whether or not they have heart failure . We assessed the role of an angiotensin-converting-enzyme inhibitor , ramipril , in patients who were at high risk for cardiovascular events but who did not have left ventricular dysfunction or heart failure . METHODS A total of 9297 high-risk patients ( 55 years of age or older ) who had evidence of vascular disease or diabetes plus one other cardiovascular risk factor and who were not known to have a low ejection fraction or heart failure were r and omly assigned to receive ramipril ( 10 mg once per day orally ) or matching placebo for a mean of five years . The primary outcome was a composite of myocardial infa rct ion , stroke , or death from cardiovascular causes . The trial was a two-by-two factorial study evaluating both ramipril and vitamin E. The effects of vitamin E are reported in a companion paper . RESULTS A total of 651 patients who were assigned to receive ramipril ( 14.0 percent ) reached the primary end point , as compared with 826 patients who were assigned to receive placebo ( 17.8 percent ) ( relative risk , 0.78 ; 95 percent confidence interval , 0.70 to 0.86 ; P<0.001 ) . Treatment with ramipril reduced the rates of death from cardiovascular causes ( 6.1 percent , as compared with 8.1 percent in the placebo group ; relative risk , 0.74 ; P<0.001 ) , myocardial infa rct ion ( 9.9 percent vs. 12.3 percent ; relative risk , 0.80 ; P<0.001 ) , stroke ( 3.4 percent vs. 4.9 percent ; relative risk , 0.68 ; P<0.001 ) , death from any cause ( 10.4 percent vs. 12.2 percent ; relative risk , 0.84 ; P=0.005 ) , revascularization procedures ( 16.3 percent vs. 18.8 percent ; relative risk , 0.85 ; P<0.001 ) , cardiac arrest ( 0.8 percent vs. 1.3 percent ; relative risk , 0.62 ; P=0.02 ) , [ corrected ] heart failure ( 9.1 percent vs. 11.6 percent ; relative risk , 0.77 ; P<0.001 ) , and complications related to diabetes ( 6.4 percent vs. 7.6 percent ; relative risk , 0.84 ; P=0.03 ) . CONCLUSIONS Ramipril significantly reduces the rates of death , myocardial infa rct ion , and stroke in a broad range of high-risk patients who are not known to have a low ejection fraction or heart failure BACKGROUND Non-steroidal anti-inflammatory drugs ( NSAIDs ) may increase blood pressure ( BP ) and blunt the effects of many antihypertensives . It seems that NSAIDs and the antihypertensive drugs differ in their propensity to such an interaction . OBJECTIVES To determine the extent of the interaction between two antihypertensives and three NSAIDs . METHODS A prospect i ve clinical trial in a family practice included 88 treated hypertensives aged over 55 years ; 39 controls and 49 , also taking NSAIDs for osteoarthritis . During this 3-month study , two antihypertensives , lisinopril/hydrochlorothiazide and amlodipine , were compared with three NSAIDs : ibuprofen , acetaminophen , and piroxicam . BP was measured with st and ard mercury sphygmomanometer and with an automatic device , in st and ing , sitting , and supine position . RESULTS The average starting blood pressure in the study group was 149.3A+/-9.8/88.6A+/-6.8 mm Hg . In the lisinopril/hydrochlorothiazide subgroup , both ibuprofen and piroxicam elevated systolic BP by 7.7 - 9.9 % ( p<0.001 ) , which , during the acetaminophen period , decreased by 6.9 - 9.4 % to 0.3 - 0.9 % above baseline ( p<0.001 ) , increasing again by 7.0 - 7.7 % ( p<0.001 ) during the second exposition to these drugs . In the amlodipine subgroup , ibuprofen or piroxicam increased BP by 1.1 - 1.6 % ( p>0.290 ) only , and there were no significant shifts in the follow-up periods . Analogous deviations were observed with both measurement devices , in all the examinee 's positions . In the control group , BP did not change appreciably . CONCLUSIONS Piroxicam and ibuprofen markedly blunt the effects of antihypertensive drugs while acetaminophen is almost inert . Lisinopril/hydrochlorothiazide combination is much more affected by this interaction than amlodipine ( Clinical Trials.gov # NCT00631514 ) Context Do all angiotensin-converting enzyme ( ACE ) inhibitors similarly improve survival after myocardial infa rct ion ? Contribution This retrospective study linked hospital and prescription data from 18 453 patients 65 years of age and older who were admitted to 109 Canadian hospitals for myocardial infa rct ion in the late 1990s . Patients who filled prescriptions for ramipril had lower mortality rates within the first year of hospital discharge than did those who filled prescriptions for several other ACE inhibitors , including captopril , enalapril , fosinopril , and quinapril . Caution s Although analyses controlled for multiple potential confounders , the authors could not adjust for unmeasured factors that might make the risk for death seem related to a particular ACE inhibitor . The Editors Many r and omized , controlled trials have shown that the use of angiotensin-converting enzyme ( ACE ) inhibitors after the occurrence of an acute myocardial infa rct ion improves survival and reduces the risk for a subsequent acute myocardial infa rct ion ( 1 - 7 ) . Although not all ACE inhibitors have been studied , they are invariably used in practice because physicians probably assume a class effect . A class effect implies that all drugs in a class exert the same effects , whether positive or negative , on their target population ( 8) . Angiotensin-converting enzyme inhibitors have been shown to be effective in treating essential hypertension ( 9 ) , renal disease ( 10 ) , and left ventricular dysfunction ( 11 ) , as well as in improving survival after acute myocardial infa rct ion ( 12 ) . Although beneficial effects might occur with all drugs in this class , the extent of benefit may vary with each drug ( 13 ) . Moreover , the varying pharmacologic and structural characteristics of ACE inhibitors influence the potency and bioavailability of each drug and could result in varying effectiveness . Several other classes of medications , including cardiac medications , have shown heterogeneous effects ( 14 ) . The lipid-lowering agent cerivastatin has been removed from the market because an unusually high proportion of patients experienced rhabdomyolysis ( 15 ) . Individual calcium-channel blockers have also differed in terms of their beneficial and side effects ( 16 , 17 ) . In fact , research ers have suggested that within the classes of both nitrates ( 18 ) and calcium-channel blockers ( 19 ) , short-acting and long-acting drugs exhibit different properties . The tendency for physicians to assume a class effect can be seen by the increase in prescriptions for ramipril in patients who have had acute myocardial infa rct ion ( 20 ) since the publication of the Heart Outcomes Prevention Evaluation ( HOPE ) ( 21 ) . However , the protocol for this trial did not specifically target patients in the period immediately after acute myocardial infa rct ion . In practice , physicians seem to assume that ramipril is indicated for secondary prevention after acute myocardial infa rct ion , even in patients without congestive heart failure ( CHF ) ( 22 - 24 ) . Our study examined the class effect of ACE inhibitors on 1-year mortality when the ACE inhibitors were prescribed to elderly patients immediately after acute myocardial infa rct ion . Methods Study Group and Data Sources We used the administrative data base that stores the information on hospital discharge summaries for the province of Quebec ( Maintenance et Exploitation des Donnes pour l'tude de la Clientle Hospitalire [ Med-Echo ] ) to create a cohort of patients 65 years of age or older who were hospitalized for acute myocardial infa rct ion and were alive at discharge . Patients were identified on the basis of a discharge diagnosis of acute myocardial infa rct ion ( International Classification of Diseases , Ninth Revision , code 410 ) between 1 April 1996 and 31 March 2000 . Using encrypted Medicare numbers , we then linked this cohort with the physician and drug cl aims data base for the province of Quebec ( the Rgie de l'Assurance Maladie du Qubec [ RAMQ ] ) . This latter data base contains information on all outpatient prescriptions for patients 65 years of age or older as well as all inpatient and outpatient diagnostic and therapeutic procedures in Quebec . This data base provides survival status for more than 99 % of patients ( 25 ) . We identified a total of 18 453 patients who had had an acute myocardial infa rct ion ; 41 % were prescribed ACE inhibitors at discharge after the acute myocardial infa rct ion ( Figure 1 ) . Figure 1 . Flow diagram . Demographic , Clinical , and Hospital Characteristics As many as 15 secondary diagnoses can be included in the hospital discharge summary data base ; these secondary diagnoses were used to obtain data about patient comorbid conditions at discharge . We also identified the following in-hospital invasive procedures : cardiac catheterization , percutaneous coronary intervention , and coronary artery bypass graft surgery . In addition , cardiac medications that may influence survival after acute myocardial infa rct ion were identified . Finally , we obtained information on the specialty of the treating physician ( 3 categories [ cardiologist , internist , or general practitioner and others ] ) , as well as on the following characteristics of the hospital in which the acute myocardial infa rct ion was treated : availability of cardiac catheterization , annual acute myocardial infa rct ion volume ( 100 or < 100 acute myocardial infa rct ions per year ) , and urban or rural location . Prescription Groups We identified patients who filled at least 1 prescription for an ACE inhibitor within 30 days of discharge . This time frame was used to include patients who may not have filled their prescriptions immediately , despite receiving them at discharge . Almost all patients who have an acute myocardial infa rct ion fill their first prescription within 30 days of discharge ( 26 ) . The patients were categorized into groups according to the ACE inhibitor on their first prescription filled after discharge . Patients who were switched to another ACE inhibitor during the first year after discharge were excluded because switching often indicates worse prognosis ( 27 ) . To determine the extent to which patients followed their treatment regimens for each ACE inhibitor , we calculated several measures of treatment adherence . Among patients with discharge prescriptions , we calculated the proportion of patients who also filled at least 1 prescription during the period 275 to 365 days ( that is , 9 to 12 months ) after discharge . In addition , we calculated persistence of filled prescriptions as the proportion of time for which a patient was covered by prescriptions during the first year after discharge or the proportion of time until death if the patient died earlier . These measures were calculated on the basis of a variable indicating the duration of each filled prescription available in the drug cl aims data base . We also calculated the proportion of patients for whom persistence was 80 % or higher . Time-Dependent Covariates We created 2 time-dependent variables . One indicated periods of exposure and nonexposure for each patient , according to information on date s when subsequent prescriptions were filled and on duration of these prescriptions . The other indicated dosage category ( no drug , below target , or at- or above-target ) . The target dosage of each drug was identified from r and omized , controlled trials ( 26 , 28 ) . Administrative data bases do not have a code for missing variables . We assumed that patients with a missing variable for a secondary diagnosis did not have that diagnosis . Validity studies have been performed specifically for the Quebec administrative data base and for other similar Canadian data bases in general ( 29 ) . Overall , few data seem to be missing when the data bases are vali date d against chart review , especially for variables that are linked to reimbursement , such as prescriptions and physicians services . The variables for prescriptions include type of drug , dosage category , frequency , and duration . For prescriptions , the variable for dosage was missing for 69 patients ( 0.9 % ) , and we have attributed the most frequently used dosage of the particular ACE inhibitor to the missing value . Statistical Analysis We compared demographic , clinical , physician , and hospital characteristics of patients according to the type of ACE inhibitor prescribed at discharge . Unadjusted mortality throughout 1 year of follow-up for users of each ACE inhibitor was summarized by using KaplanMeier curves and compared by using the log-rank test . To account for differences in follow-up and to control for differences among patients ' characteristics , a multivariable Cox proportional hazards model ( 27 ) was used . In all Cox models , the associations between particular ACE inhibitors and mortality within the first year were adjusted for the following fixed variables : age , sex , CHF , diabetes , cardiac dysrhythmia , cerebrovascular disease , acute renal failure , malignant conditions , shock , in-hospital procedures ( cardiac catheterization , percutaneous coronary intervention , coronary artery bypass graft surgery ) , discharge medications ( -blockers , lipid-lowering agents , nitrates , aspirin , calcium-channel blockers , diuretics , warfarin ) , the year of acute myocardial infa rct ion to account for temporal trends , physician specialty , and 2 hospital characteristics ( availability of cardiac catheterization and acute myocardial infa rct ion volume ) . Forced-entry regression was used to include these variables in all multivariable models in order to adjust the between-drug comparisons for potential confounders . Because ramipril has increasingly been used in the period immediately after acute myocardial infa rct ion ( as a result of the HOPE study ) it was a priori selected as a reference category , and adjusted hazard ratios were estimated for the other ACE inhibitors in comparison with ramipril . The date of 31 March 2001 was used as a censoring point for patients still alive , which enabled us to have 1 year of follow-up information for all patients . As in our The prevalence of end stage renal disease ( ESRD ) is growing in western countries . Patients with ESRD are more frequently elderly and diabetic and are exposed to very high cardiovascular morbidity and mortality . The main aim of the FOSIDIAL study is to assess the efficacy and safety of fosinopril , an angiotensin converting enzyme ( ACE ) inhibitor , in reducing the mortality and cardiovascular events in haemodialysis patients presenting with left ventricular hypertrophy . A total number of 397 patients are included in the study . They are aged 50 - 80 years ( average 66.7 years ) and have been undergoing haemodialysis for 4.8 years . All have left ventricular hypertrophy with cardiac mass index > 100 g/m2 in women and > 130 g/m2 in men , measured within 3 months prior to inclusion . Baseline cardiac mass index is 174 g/m2 . After a 2 week placebo period , the patients are r and omised into two groups receiving either fosinopril 5 - 20 mg/day , or a placebo for a duration of 24 months . The target dose is reached at the sixth , seventh or eighth week of treatment . Depending on tolerance , 300 patients reached the maximum recommended dose . Patients are subsequently assessed clinical ly every 3 months until the end of the study . The primary outcome is a composite endpoint of fatal and nonfatal major cardiovascular events . Secondary endpoints are individual cardiovascular events , event-free survival , overall mortality and all-cause hospitalisations . The trial began in October 1998 . All patients were included by December 2000 and follow-up is ongoing . The last visit for the last patient is scheduled for 30 December 2002 . We report here on the study design and the baseline characteristics of the study population We stratified findings from the Japan Multicenter Investigation for Cardiovascular Diseases-B according to whether or not the patients had diabetes and compared the incidence of cardiac events occurring over a 3-year period between treatment with nifedipine retard and angiotensin converting enzyme ( ACE ) inhibitor . The primary endpoint was the overall incidence of cardiac events ( cardiac death or sudden death , myocardial infa rct ion , hospitalization for angina pectoris or heart failure , serious arrhythmia , and coronary interventions ) , and the secondary endpoints were a composite of other events ( cerebrovascular accidents , worsening of renal dysfunction , non-cardiovascular events , and total mortality ) . The results showed no significant difference in the incidence of the primary endpoint between the nifedipine group ( n=199 ) and the ACE inhibitor group ( n=173 ) in diabetic patients : 15.08 % vs. 15.03 % , relative risk 1.06 , p=0.838 . Also in nondiabetic patients , no significant difference was observed between the former ( n=629 ) and the latter ( n=649 ) : 13.67 % vs. 12.33 % , relative risk 1.04 , p=0.792 . Similar results were obtained for the incidence of the secondary endpoints : in diabetic patients , 5.03 % vs. 5.20 % , relative risk 0.89 , p=0.799 ; in nondiabetic patients , 2.70 % vs. 2.47 % , relative risk 1.07 , p=0.842 . Achieved blood pressure levels were 138/76 and 136/77 mmHg in the nifedipine group and 140/78 and 138/79 mmHg in the ACE inhibitor group in diabetic and nondiabetic patients , respectively . This study showed that nifedipine retard was as effective as ACE inhibitors in reducing the incidence of cardiac events in extremely high-risk hypertensive patients with complications of diabetes and coronary artery disease BACKGROUND The aim of the study was to investigate the cardioprotective effects of the angiotensin-converting enzyme inhibitor zofenopril in post-myocardial infa rct ion ( MI ) patients with preserved left ventricular function ( LVF ) . METHODS Three hundred forty-nine post-MI patients with preserved LVF ( LV ejection fraction > 40 % ) were treated for 6 months with zofenopril 30 to 60 mg ( n = 177 ) or placebo ( n = 172 ) according to a double-blind , r and omized study design . The primary end point of the study was the combined occurrence of significant ST-T abnormalities on ambulatory electrocardiography ( ECG ) , ECG abnormalities or symptoms of angina during st and ard exercise test , recurrence of MI , and need for revascularization procedures for angina . RESULTS The primary end point occurred in 20.3 % of zofenopril-treated and 35.9 % of placebo-treated patients ( P = .001 ) , despite no differences in blood pressure control , LVF , and concomitant therapy . ST-T depression during ambulatory ECG occurred in 22.7 % of patients treated with placebo and 10.7 % of those undergoing ACE-inhibition treatment ( P = .027 ) . ST-T depression in response to exercise test occurred in 14.2 % and 26.7 % of patients treated with zofenopril or placebo , respectively , ( P = .024 ) , with a lower proportion of zofenopril-treated patients who complained of anginal pain ( 4.7 vs 14.3 % ; P = .017 ) , significant ST depression ( 14.2 vs 26.7 % ; P = .024 ) , and major ventricular arrhythmias ( 3.8 vs 10.5 % ; P = .048 ) . The rate of major cardiovascular events was reduced in patients treated with ACE inhibitor , with a lower rate of development and progression of congestive heart failure . CONCLUSIONS The results of the SMILE-ISCHEMIA study support the cardioprotective role of zofenopril when given to patients with normal LVF after acute MI BACKGROUND The EUROPA trial has demonstrated that an ACE inhibitor perindopril , was able to significantly decrease the risk of major cardiac events in patients with stable coronary heart disease without apparent heart failure . AIM To assess the long-term clinical outcome of patients with stable coronary heart disease and preserved left ventricular function ( left ventricular ejection fraction ( LVEF > or = 40 % ) . METHODS A retrospective evaluation of LVEF was performed in the EUROPA study population . Among the 12,218 patients of EUROPA , we identified 7096 ( 58 % ) patients who had LVEF measurement before r and omization . The measurements were obtained mainly by echocardiography in 5214 cases ( 73 % ) or by angiography in 1470 cases ( 21 % ) . Two groups of patients were studied : 6878 ( 97 % ) patients with LVEF > or = 40 % ( 3429 received 8 mg of perindopril and 3449 received a placebo ) and 218 patients ( 3 % ) with a LVEF<40 % ( 111 received perindopril and 107 a placebo ) . RESULTS The baseline characteristics of patients with documented LVEF were similar to the whole EUROPA population in terms of demographics , medical history , physical examination ( heart rate , blood pressure ) , and medications at screening . The mean LVEF of this population was 57.0+/-10.4 % . In patients ( n=6878 ) with preserved LV function ( LVEF > or = 40 % ) , there was a significant relative risk reduction of 16 % of the primary endpoint ( a composite of cardiovascular death , non-fatal myocardial infa rct ion and resuscitated cardiac arrest ) in the group treated with perindopril ( 8.3 % ) in comparison to the group treated with placebo ( 9.8 % ) : Hazard ratio (HR)=0.84 [ 95 % CI : 0.72 - 0.99 ] p=0.033 ) . Similar results were obtained for the first secondary endpoint ( total mortality , non-fatal myocardial infa rct ion , hospital admission for unstable angina and cardiac arrest with successful resuscitation ) : HR=0.85 [ 95 % CI : 0.76 - 0.96 ] p=0.008 , for cardiovascular mortality and non-fatal MI : HR=0.84 [ 95 % CI : 0.72 - 0.99 ] p=0.036 . Similar benefits were observed in patients with an LVEF > or = 40 % and a history of previous myocardial infa rct ion and in patients with an LVEF<40 % . CONCLUSIONS LVEF was documented in 58 % of the EUROPA study population and only 3 % had an impaired LV function , confirming that EUROPA patients did not have asymptomatic LV dysfunction . Results in patients with preserved LV function are consistent with those of the whole EUROPA study population and perindopril 8 mg is beneficial in the broad spectrum of patients with stable coronary artery disease without evidence of heart failure BACKGROUND Angiotensin-converting-enzyme ( ACE ) inhibitors are effective in reducing the risk of heart failure , myocardial infa rct ion , and death from cardiovascular causes in patients with left ventricular systolic dysfunction or heart failure . ACE inhibitors have also been shown to reduce atherosclerotic complications in patients who have vascular disease without heart failure . METHODS In the Prevention of Events with Angiotensin Converting Enzyme Inhibition ( PEACE ) Trial , we tested the hypothesis that patients with stable coronary artery disease and normal or slightly reduced left ventricular function derive therapeutic benefit from the addition of ACE inhibitors to modern conventional therapy . The trial was a double-blind , placebo-controlled study in which 8290 patients were r and omly assigned to receive either tr and olapril at a target dose of 4 mg per day ( 4158 patients ) or matching placebo ( 4132 patients ) . RESULTS The mean ( + /-SD ) age of the patients was 64+/-8 years , the mean blood pressure 133+/-17/78+/-10 mm Hg , and the mean left ventricular ejection fraction 58+/-9 percent . The patients received intensive treatment , with 72 percent having previously undergone coronary revascularization and 70 percent receiving lipid-lowering drugs . The incidence of the primary end point -- death from cardiovascular causes , myocardial infa rct ion , or coronary revascularization -- was 21.9 percent in the tr and olapril group , as compared with 22.5 percent in the placebo group ( hazard ratio in the tr and olapril group , 0.96 ; 95 percent confidence interval , 0.88 to 1.06 ; P=0.43 ) over a median follow-up period of 4.8 years . CONCLUSIONS In patients with stable coronary heart disease and preserved left ventricular function who are receiving " current st and ard " therapy and in whom the rate of cardiovascular events is lower than in previous trials of ACE inhibitors in patients with vascular disease , there is no evidence that the addition of an ACE inhibitor provides further benefit in terms of death from cardiovascular causes , myocardial infa rct ion , or coronary revascularization BACKGROUND In the treatment of coronary atherosclerotic artery disease ( CAD ) , the mechanisms by which lipid lowering , a proven therapy , produces beneficial clinical effects remain unclear . Moreover , although potential mechanisms of benefit are well known and increasingly applied clinical ly , there are no conclusive data from clinical trials study ing primarily the antiischemic effects of angiotensin-converting enzyme ( ACE ) inhibition in patients with normal heart function . The Simvastatin/Enalapril Coronary Atherosclerosis Trial ( SCAT ) is design ed to clarify some of these issues in CAD patients with normal or mildly elevated cholesterol . DESIGN AND OBJECTIVES : SCAT is a three- to five-year , multicentre , r and omized , double-blind , placebo controlled , 2 x 2 factorial trial evaluating the effects of cholesterol lowering therapy by simvastatin and /or ACE inhibition by enalapril on anatomic coronary atherosclerosis progression assessed by quantitative coronary angiography in CAD patients with preserved left ventricular function and total cholesterol levels between 4.1 and 6.2 mmol/L. PATIENTS Of 460 patients ( age 61 + /- 9 years ; 409 males , 51 females ) enrolled between June 1991 and July 1995 , 230 were r and omized to simvastatin and 230 to placebo , and 229 to enalapril and 231 to placebo . Average baseline total cholesterol level was 5.20 + /- 0.61 mmol/L , high density lipoprotein cholesterol was 0.99 + /- 0.25 mmol/L , low density lipoprotein cholesterol was 3.36 + /- 0.57 mmol/L and triglycerides were 1.82 + /- 0.75 mmol/L. The trial will be completed in June 1998 . SIGNIFICANCE Insights gained from this long term angiographic trial will lead to a better underst and ing of the mechanisms of benefits of these two treatments , both alone and in combination . Of particular interest is that this trial will be able to examine a suspected beneficial interaction , if present , between these two treatments BACKGROUND Angiotensin-converting enzyme ( ACE ) inhibitors have an accepted place in the treatment of hypertension and heart failure . However , at present they have no specific role in the prevention or treatment of coronary artery disease : evidence from animal experiments and some of the large ACE inhibitor cardiac studies makes this effect well worth testing . OBJECTIVE The objective of EUROPA is to assess the effects of perindopril ( an ACE inhibitor ) on outcome in patients with stable coronary artery disease , but no clinical heart failure . METHODS This is a double-blind , placebo-controlled , multicentre study with a duration of 3.5 years . It is proposed to recruit 10500 patients from 24 countries in Europe . The primary end-point is a combined one : total mortality , non-fatal acute myocardial infa rct ion , unstable angina pectoris and cardiac arrest with successful resuscitation are included ; the outcome is studied in patients with proven coronary artery disease and no clinical heart failure . Secondary end-points consist of these events individually calculated . The first patient was recruited in October 1997 , and it is planned to finish recruitment by the end of 1998 Invasive revascularization improves prognosis , functional status and quality of life in patients with severe angina pectoris and impaired left ventricular function , and treatment with ACE-I reduces the development of cardiac events and left ventricular dysfunction in patients without or with mild angina pectoris . However , the effects of a combined treatment strategy with invasive revascularization and subsequent long-term ACE-I therapy in patients with limiting angina pectoris and impaired left ventricular function have not previously been investigated . APRES is a long-term , prospect i ve , r and omized double-blind study that evaluates the effects of ramipril 10 mg o.d . on the long-term development of cardiac events , left ventricular function , functional status and quality of life following invasive revascularization in patients without recent AMI or clinical heart failure and with preoperative ejection fraction in the range 0.30 - 0.50 . The rationale , design and power of APRES and the choice and relevance of outcome measures are discussed . Based on experience and results from the first year of the study for screening procedure , inclusion rate , patient compliance , reproducibility analyses and the magnitude of outcome measures , we conclude that the study is feasible and safe . The included patients match with the target population , the outcome measures seem appropriate and the power considerations valid for the majority of the outcome measures BACKGROUND Angiotensin-converting-enzyme ( ACE ) inhibitors such as captopril reduce mortality and cardiovascular morbidity among patients with myocardial infa rct ion complicated by left ventricular systolic dysfunction , heart failure , or both . In a double-blind trial , we compared the effect of the angiotensin-receptor blocker valsartan , the ACE inhibitor captopril , and the combination of the two on mortality in this population of patients . METHODS Patients receiving conventional therapy were r and omly assigned , 0.5 to 10 days after acute myocardial infa rct ion , to additional therapy with valsartan ( 4909 patients ) , valsartan plus captopril ( 4885 patients ) , or captopril ( 4909 patients ) . The primary end point was death from any cause . RESULTS During a median follow-up of 24.7 months , 979 patients in the valsartan group died , as did 941 patients in the valsartan- and -captopril group and 958 patients in the captopril group ( hazard ratio in the valsartan group as compared with the captopril group , 1.00 ; 97.5 percent confidence interval , 0.90 to 1.11 ; P=0.98 ; hazard ratio in the valsartan- and -captopril group as compared with the captopril group , 0.98 ; 97.5 percent confidence interval , 0.89 to 1.09 ; P=0.73 ) . The upper limit of the one-sided 97.5 percent confidence interval for the comparison of the valsartan group with the captopril group was within the prespecified margin for noninferiority with regard to mortality ( P=0.004 ) and with regard to the composite end point of fatal and nonfatal cardiovascular events ( P<0.001 ) . The valsartan- and -captopril group had the most drug-related adverse events . With monotherapy , hypotension and renal dysfunction were more common in the valsartan group , and cough , rash , and taste disturbance were more common in the captopril group . CONCLUSIONS Valsartan is as effective as captopril in patients who are at high risk for cardiovascular events after myocardial infa rct ion . Combining valsartan with captopril increased the rate of adverse events without improving survival BACKGROUND The European trial on Reduction Of cardiac events with Perindopril in patients with stable coronary Artery disease ( EUROPA ) demonstrated the benefits of perindopril with respect to secondary prevention of cardiovascular risk in patients with stable coronary artery disease . AIMS To describe the clinical effects of perindopril in a sub population of patients from EUROPA with a history of myocardial infa rct ion and /or revascularization . PATIENTS AND METHODS Of the 12,218 patients in the EUROPA study , 10,962 had a history of myocardial infa rct ion and /or revascularization . In this EUROPA sub population , 7910 patients had a history of myocardial infa rct ion and 6709 had a history of revascularization . Patients were r and omized to treatment with perindopril 8mg/day or placebo . The primary endpoint was a composite of cardiovascular mortality , myocardial infa rct ion and resuscitated cardiac arrest . RESULTS After a mean follow-up of 4.2 years , treatment with perindopril 8mg/day was associated with a 22.4 % reduction in the primary endpoint compared with placebo ( p<0.001 ) in patients with a history of myocardial infa rct ion . Patients with a history of myocardial revascularization showed a 17.3 % reduction in the primary endpoint with perindopril versus placebo ( p<0.05 ) . In the combined population of patients with a history of myocardial infa rct ion and /or revascularization , treatment with perindopril produced a 22.4 % reduction in the primary endpoint compared with placebo ( p<0.001 ) . CONCLUSIONS This study confirms the benefits of a high dose of angiotensin-converting enzyme inhibitor for the secondary prevention of cardiovascular risk among patients with a history of myocardial infa rct ion and /or revascularization The future rate of cardiovascular events can be predicted by several well-established risk factors . Even in the absence of classic risk factors , patients with renal disease have an elevated risk for cardiovascular disease ( 1 , 2 ) . This renalcardiovascular association is well established in patients with advanced renal insufficiency ( 2 ) . It has also been reported in patients in the Hypertension Detection and Follow-up Program ( HDFP ) ( 3 ) , in which a serum creatinine concentration greater than 133 mol/L ( 1.5 mg/dL ) was a strong predictor of cardiovascular disease . However , HDFP included only patients with hypertension . In contrast , a recent analysis of data from the Framingham Study did not detect a relationship between mild renal insufficiency ( defined as a serum creatinine concentration of 124 to 265 mol/L [ 1.4 to 3.0 mg/dL ] ) and cardiovascular events ( 4 ) . The Heart Outcomes and Prevention Evaluation ( HOPE ) study investigated the effects of ramipril and vitamin E on major cardiovascular outcomes in 9297 patients at high risk , including those with serum creatinine concentrations up to 200 mol/L ( 2.3 mg/dL ) ( 5 - 7 ) . Our study examined the hypothesis that previous evidence of renal disease ( that is , an elevated serum creatinine concentration 124 mol/L [ 1.4 mg/dL ] ) would independently predict future cardiovascular disease . Since the connection between renal and cardiovascular disease is known to exist in patients with diabetes mellitus and those with hypertension , we analyzed nondiabetic and normotensive patients separately . We also examined whether ramipril continued to be effective in patients with impaired renal function . This was done to determine whether the common clinical practice of withholding angiotensin-converting enzyme ( ACE ) inhibitors in patients with impaired renal excretory function is justified . Methods Patients The design and primary outcomes of the HOPE study have been described elsewhere ( 5 - 7 ) . Briefly , men and women at least 55 years of age from 267 centers were included if they had objective evidence of vascular disease or diabetes combined with another cardiovascular risk factor . The main exclusion criteria were heart failure , intolerance of ACE inhibitors or vitamin E , a serum creatinine concentration greater than 200 mol/L ( 2.3 mg/dL ) , or dipstick-positive proteinuria ( > 1 + ) . Patients were treated with ramipril , vitamin E , or placebo in a double-blind , 2 2 factorial design . Follow-up was 3.5 to 5.5 years ( median , 4.5 years ) , and the primary outcome measure was the incidence of cardiovascular death , myocardial infa rct ion , or stroke . Secondary outcome measures included total mortality , hospitalization for heart failure , and revascularization . At the time of r and omization , urine albumin level and creatinine concentration were measured once in all patients at four central laboratories . The ratio of urine albumin to creatinine was calculated , and a value of at least 2 mg/mmol was defined as microalbuminuria . Serum creatinine concentration was measured in all patients at local laboratories at the time of r and omization . Renal Insufficiency Recent data suggest that in patients older than 55 years of age , a serum creatinine concentration of at least 124 mol/L ( 1.4 mg/dL ) is a good indicator of a glomerular filtration rate less than 80 mL/min ( 8) . Therefore , before beginning this post hoc analysis , we used a serum creatinine concentration of at least 124 mol/L ( 1.4 mg/dL ) to differentiate between patients with and those without renal insufficiency . We also estimated creatinine clearance from serum creatinine concentrations by using the CockcroftGault formula ( 8) , which derives the value from creatinine concentration , age , and body weight ( 140 age [ in years ] body weight [ in kg]/serum creatinine concentration [ in mg/dL ] 72 [ in men ] or 0.85 [ in women ] ) . For calculated creatinine clearance , an a priori value of 65 mL/min was arbitrarily chosen as a definite indicator of renal insufficiency . Statistical Analysis Baseline serum creatinine values were missing in 10 of 9297 patients who were r and omly assigned to receive ramipril , 10 mg/d , or placebo . Only data from the original intention-to-treat analysis ( 5 ) were included in our study . We compared baseline characteristics in patients with and those without renal insufficiency by using chi-square tests for discrete variables and t-tests for continuous variables . Because the ratio of albumin to creatinine was not normally distributed , it was compared by using a Wilcoxon test . In the final analysis , time-to-event in each group was estimated by using Cox regression stratified by center ; this was done because rates of renal insufficiency varied significantly by center ( P=0.006 ) but event rates did not . Association by center was tested by using logistic regression for renal insufficiency and Cox regression for events . Center was treated as a fixed effect in these models ( 9 ) . Multivariate models to predict events were developed by using Cox regression and a backward elimination technique , beginning with univariate significant risk factors , including age ; sex ; waist-to-hip ratio ; body mass index ; and history of hypertension , diabetes , coronary artery disease , peripheral vascular disease , smoking , ramipril use , and renal insufficiency . Age , body mass index , waist-to-hip ratio , and blood pressure were treated as continuous variables . All covariates were tested for possible confounding with renal insufficiency , but no such pattern was found . We used Cox regression models to assess the effect of r and omization to ramipril after controlling for serum creatinine concentration . Statistical tests for interaction were done in the Cox regression analysis to determine whether the effect of ramipril differed in patients with and those without renal insufficiency . We classified patients according to quartiles of serum creatinine concentration and then determined the effect of renal insufficiency on risk for the primary outcome . To do this , we analyzed the rate of the primary outcome across quartiles using Cox regression and testing linearity of the hazard ratios ( HRs ) . Creatinine clearance was also estimated from serum creatinine concentration by using the CockcroftGault formula ( 8) . Because age is used to calculate this value , age was excluded from all multivariate analyses that included creatinine clearance as a variable . All analyses were done by using SAS software for Unix , version 6.12 ( SAS Institute , Inc. , Cary , North Carolina ) . Role of the Funding Sources The funding sources had no role in the collection , analysis , or interpretation of the data or in the decision to su bmi t the manuscript for publication . Results Baseline Characteristics of Patients with Renal Disease As shown in Table 1 , 980 patients had a serum creatinine concentration at least 124 mol/L ( 1.4 mg/dL ) and 8307 patients did not . Baseline variables did not differ between the placebo and ramipril subgroups . Compared with patients who had no evidence of renal insufficiency , those with renal insufficiency were older ; were more likely to be male ; and had a higher baseline prevalence of hypertension , coronary artery disease , peripheral vascular disease , low high-density lipoprotein cholesterol level , and use of antiplatelet and antihypertensive agents . Systolic blood pressure , urine albumin level , and waist-to-hip ratio were also higher in this group . Table 1 . Baseline Characteristics of Patients with and Those without Renal Insufficiency Event Rates in Patients with Renal Insufficiency Renal insufficiency was an important predictor of the primary outcome for all patients , as well as for the ramipril and placebo groups separately . The extent to which renal insufficiency was associated with the primary outcome is shown in Figure 1 and Table 2 . Most impressive is the fact that cardiovascular and all-cause mortality rates were nearly twice as high in patients with renal insufficiency ( HR , 1.90 [ 95 % CI , 1.53 to 2.36 ] and 1.83 [ CI , 1.54 to 2.17 ] , respectively , by Cox regression controlling for ramipril use ; P<0.001 for both comparisons ) , as were hospitalizations for heart failure ( HR , 2.11 [ CI , 1.56 to 2.81 ] ; P<0.001 ) . This effect of renal insufficiency was also observed when calculated creatinine clearance was used instead of serum creatinine concentration ( Table 3 ) . Figure 1 . Primary outcome , myocardial infa rct ion , cardiovascular death , and all death for patients with a serum creatinine concentration less than 1.4 mg/dL ( < 124 mol/L ) or at least 1.4 mg/dL ( 124 mol/L ) . Table 2 . Outcomes in Patients with and Those without Renal Insufficiency Table 3 . Outcomes in Patients with a Creatinine Clearance 65 mL/min or > 65 mL/min Analysis of the group risk for the primary outcome clearly showed that as serum creatinine concentration increases , so does cardiovascular risk . As shown in Figure 2 , the incidence of the primary outcome increased with each quartile of serum creatinine concentration ( P<0.001 for linear trend of HR across quartiles ) . Figure 2 . Primary outcome according to quartiles of serum creatinine concentration . P P We performed a multivariate analysis to determine whether the observed relationship between the incidence of the primary outcome and renal insufficiency could be explained by the association of impaired renal function with the variables identified in Table 1 . In this analysis , an elevated serum creatinine concentration and microalbuminuria were highly significant , independent renal risk factors for the aggregate primary outcome of cardiovascular death , myocardial infa rct ion , or stroke ( HR , 1.40 [ CI , 1.16 to 1.69 ] and 1.59 [ CI , 1.37 to 1.84 ] , respectively ; P<0.001 for both comparisons ) . Other factors that independently and significantly predicted the primary outcome measure were coronary artery disease ( HR , 1.51 [ CI , 1.22 to 1.85 ] ) , peripheral vascular disease ( HR , 1.49 [ CI , 1.29 to 1.70 ] ) , diabetes mellitus ( HR , 1.42 [ CI , 1.23 to 1.65 ] ) , male sex ( HR , 1.20 [ CI , 1.01 to 1.43 ] ) , 1-year increase in age ( OBJECTIVES The purpose of this study was to investigate the effects of angiotensin II receptor blockers on the prevention of cardiovascular events in patients with coronary artery disease ( CAD ) . BACKGROUND Angiotensin II may contribute to the pathogenesis of CAD . Long-term clinical trials have shown that blockade of the renin-angiotensin system can reduce cardiovascular events in patients with acute myocardial infa rct ion complicated by heart failure . METHODS Patients with a history of coronary intervention and no significant coronary stenosis on follow-up angiography 6 months after intervention were r and omly assigned into a c and esartan group ( n = 203 ; baseline treatment plus c and esartan 4 mg/d ) or a control group ( n = 203 ; baseline treatment alone ) . The primary end point was a composite of revascularization , nonfatal myocardial infa rct ion , or cardiovascular death . The secondary end point was hospitalization for cardiovascular causes . RESULTS There were no changes in blood pressure and in other coronary risk factors in either group during a mean follow-up of 24 months . Primary end point risk was significantly lower in the c and esartan group ( n = 12 ) than in control group patients ( n = 25 ) ( P = .03 ) . C and esartan treatment reduced primary end point risk ( 5.9 % vs 12.3 % for control subjects ; relative risk , 0.47 ; 95 % CI , 0.24 to 0.93 ) . The incidence of all events including secondary end points and noncardiovascular death was significantly lower in the c and esartan group than in control group patients ( 23 vs 40 cases ) ( P = .02 ) . CONCLUSIONS Relatively low-dose c and esartan , which did not alter blood pressure levels , reduces cardiovascular risk in high-risk patients with CAD Background This long-term , multicenter , r and omized , double-blind , placebo-controlled , 2 × 2 factorial , angiographic trial evaluated the effects of cholesterol lowering and angiotensin-converting enzyme inhibition on coronary atherosclerosis in normocholesterolemic patients . Methods and Results There were a total of 460 patients : 230 received simvastatin and 230 , a simvastatin placebo , and 229 received enalapril and 231 , an enalapril placebo ( some subjects received both drugs and some received a double placebo ) . Mean baseline measurements were as follows : cholesterol level , 5.20 mmol/L ; triglyceride level , 1.82 mmol/L ; HDL , 0.99 mmol/L ; and LDL , 3.36 mmol/L. Average follow-up was 47.8 months . Changes in quantitative coronary angiographic measures between simvastatin and placebo , respectively , were as follows : mean diameters , −0.07 versus −0.14 mm ( P = 0.004 ) ; minimum diameters , −0.09 versus −0.16 mm ( P = 0.0001 ) ; and percent diameter stenosis , 1.67 % versus 3.83 % ( P = 0.0003 ) . These benefits were not observed in patients on enalapril when compared with placebo . No additional benefits were seen in the group receiving both drugs . Simvastatin patients had less need for percutaneous transluminal coronary angioplasty ( 8 versus 21 events;P = 0.020 ) , and fewer enalapril patients experienced the combined end point of death/myocardial infa rct ion/stroke ( 16 versus 30;P = 0.043 ) than their respective placebo patients . Conclusions This trial extends the observation of the beneficial angiographic effects of lipid-lowering therapy to normocholesterolemic patients . The implication s of the neutral angiographic effects of angiotensin-converting enzyme inhibition are uncertain , but they deserve further investigation in light of the positive clinical benefits suggested here and seen elsewhere AIMS The aim of this study was to assess the effect of the angiotensin converting enzyme inhibitor perindopril on cardiovascular events in diabetic patients with coronary artery disease . METHODS AND RESULTS A total of 1502 diabetic patients with known coronary artery disease and without heart failure of 12 218 overall in the EUropean trial on Reduction Of cardiac events with Perindopril in stable coronary Artery ( EUROPA ) disease were r and omized in a double-blinded manner to perindopril 8 mg once daily or placebo . Follow-up was for a median of 4.3 years . The primary end point was cardiovascular death , non-fatal myocardial infa rct ion , and resuscitated cardiac arrest . Perindopril treatment was associated with a non-significant reduction in the primary endpoint in the diabetic population , 12.6 vs. 15.5 % , relative risk reduction 19 % [ ( 95 % CI , -7 to 38 % ) , P=0.13 ] . This was of similar relative magnitude to the 20 % risk reduction observed in the main EUROPA population . CONCLUSION Perindopril tends to reduce major cardiovascular events in diabetic patients with coronary disease in addition to other preventive treatments and the trend towards reduction was of a similar relative magnitude to that observed the general population with coronary artery disease OBJECTIVES --To investigate the role of prostagl and ins in maintaining circulatory homoeostasis in chronic heart failure and the hypothesis that an increase in vasodilatory prostagl and in synthesis may contribute to the actions of angiotensin converting enzyme inhibitors in heart failure . DESIGN --R and omised , double blind , placebo controlled studies . Cardiac output and renal and limb blood flow were measured after oral indomethacin 50 mg or placebo followed by " open " intravenous infusion of prostagl and in E2 ( study A ) . In a second study the same measurements were made after oral indomethacin 50 mg or placebo was given 30 min before " open " captopril ( study B ) . METHODS --Blood pressure was measured using a mercury sphygmomanometer . Cardiac output was determined by Doppler interrogation of blood flow in the ascending aorta and echocardiographic measurement of aortic root diameter . Renal blood flow was calculated from the effective renal plasma flow measured by p-aminohippurate clearance and the haematocrit , and glomerular filtration rate by endogenous creatinine clearance . Limb blood flow was measured by venous occlusion plethysmography using mercury in silastic strain gauges . The concentration of plasma prostagl and in E2 was measured by radioimmunoassay . SETTING --University department of cardiovascular medicine . PATIENTS --12 patients with chronic stable heart failure before starting treatment with angiotensin converting enzyme inhibitors . RESULTS --Indomethacin result ed in adverse effects on cardiac output , systemic vascular resistance , renal blood flow , glomerular filtration , urinary sodium excretion , and calf vascular resistance . Changes were reversed with infusion of prostagl and in E2 . Pretreatment with indomethacin result ed in the attenuation of the acute increase in cardiac output and decrease in systemic vascular resistance that occurred with captopril . Similarly , an increase in renal blood flow with captopril was attenuated by indomethacin . CONCLUSIONS --The acute adverse effects of indomethacin on central and peripheral haemodynamic and renal function suggest that prostagl and ins have a significant role in the regulation of peripheral blood flow and renal function in patients with stable chronic heart failure . The attenuation by indomethacin of captopril induced improvements in haemodynamic function and renal blood flow is consistent with the hypothesis that captopril may act in part via an increase in prostagl and in synthesis BACKGROUND The ELITE study showed an association between the angiotensin II antagonist losartan and an unexpected survival benefit in elderly heart-failure patients , compared with captopril , an angiotensin-converting-enzyme ( ACE ) inhibitor . We did the ELITE II Losartan Heart Failure Survival Study to confirm whether losartan is superior to captopril in improving survival and is better tolerated . METHODS We undertook a double-blind , r and omised , controlled trial of 3,152 patients aged 60 years or older with New York Heart Association class II-IV heart failure and ejection fraction of 40 % or less . Patients , stratified for beta-blocker use , were r and omly assigned losartan ( n=1,578 ) titrated to 50 mg once daily or captopril ( n=1,574 ) titrated to 50 mg three times daily . The primary and secondary endpoints were all-cause mortality , and sudden death or resuscitated arrest . We assessed safety and tolerability . Analysis was by intention to treat . FINDINGS Median follow-up was 555 days . There were no significant differences in all-cause mortality ( 11.7 vs 10.4 % average annual mortality rate ) or sudden death or resuscitated arrests ( 9.0 vs 7.3 % ) between the two treatment groups ( hazard ratios 1.13 [ 95.7 % CI 0.95 - 1.35 ] , p=0.16 and 1.25 [ 95 % CI 0.98 - 1.60 ] , p=0.08 ) . Significantly fewer patients in the losartan group ( excluding those who died ) discontinued study treatment because of adverse effects ( 9.7 vs 14.7 % , p<0.001 ) , including cough ( 0.3 vs 2.7 % ) BACKGROUND Actions of angiotensin II may contribute to the progression of heart failure despite treatment with currently recommended drugs . We therefore evaluated the long-term effects of the addition of the angiotensin-receptor blocker valsartan to st and ard therapy for heart failure . METHODS A total of 5010 patients with heart failure of New York Heart Association ( NYHA ) class II , III , or IV were r and omly assigned to receive 160 mg of valsartan or placebo twice daily . The primary outcomes were mortality and the combined end point of mortality and morbidity , defined as the incidence of cardiac arrest with resuscitation , hospitalization for heart failure , or receipt of intravenous inotropic or vasodilator therapy for at least four hours . RESULTS Overall mortality was similar in the two groups . The incidence of the combined end point , however , was 13.2 percent lower with valsartan than with placebo ( relative risk , 0.87 ; 97.5 percent confidence interval , 0.77 to 0.97 ; P=0.009 ) , predominantly because of a lower number of patients hospitalized for heart failure ; 455 ( 18.2 percent ) in the placebo group and 346 ( 13.8 percent ) in the valsartan group ( P<0.001 ) . Treatment with valsartan also result ed in significant improvements in NYHA class , ejection fraction , signs and symptoms of heart failure , and quality of life as compared with placebo ( P<0.01 ) . In a post hoc analysis of the combined end point and mortality in subgroups defined according to base-line treatment with angiotensin-converting-enzyme ( ACE ) inhibitors or beta-blockers , valsartan had a favorable effect in patients receiving neither or one of these types of drugs but an adverse effect in patients receiving both types of drugs . CONCLUSIONS Valsartan significantly reduces the combined end point of mortality and morbidity and improves clinical signs and symptoms in patients with heart failure , when added to prescribed therapy . However , the post hoc observation of an adverse effect on mortality and morbidity in the subgroup receiving valsartan , an ACE inhibitor , and a beta-blocker raises concern about the potential safety of this specific combination BACKGROUND Angiotensin-converting enzyme ( ACE ) inhibitors reduce major cardiovascular events , but are not tolerated by about 20 % of patients . We therefore assessed whether the angiotensin-receptor blocker telmisartan would be effective in patients intolerant to ACE inhibitors with cardiovascular disease or diabetes with end-organ damage . METHODS After a 3-week run-in period , 5926 patients , many of whom were receiving concomitant proven therapies , were r and omised to receive telmisartan 80 mg/day ( n=2954 ) or placebo ( n=2972 ) by use of a central automated r and omisation system . R and omisation was stratified by hospital . The primary outcome was the composite of cardiovascular death , myocardial infa rct ion , stroke , or hospitalisation for heart failure . Analyses were done by intention to treat . This trial is registered with Clinical Trials.gov , number NCT00153101 . FINDINGS The median duration of follow-up was 56 ( IQR 51 - 64 ) months . All r and omised patients were included in the efficacy analyses . Mean blood pressure was lower in the telmisartan group than in the placebo group throughout the study ( weighted mean difference between groups 4.0/2.2 [ SD 19.6/12.0 ] mm Hg ) . 465 ( 15.7 % ) patients experienced the primary outcome in the telmisartan group compared with 504 ( 17.0 % ) in the placebo group ( hazard ratio 0.92 , 95 % CI 0.81 - 1.05 , p=0.216 ) . One of the secondary outcomes -a composite of cardiovascular death , myocardial infa rct ion , or stroke-occurred in 384 ( 13.0 % ) patients on telmisartan compared with 440 ( 14.8 % ) on placebo ( 0.87 , 0.76 - 1.00 , p=0.048 unadjusted ; p=0.068 after adjustment for multiplicity of comparisons and overlap with primary outcome ) . 894 ( 30.3 % ) patients receiving telmisartan were hospitalised for a cardiovascular reason , compared with 980 ( 33.0 % ) on placebo ( relative risk 0.92 , 95 % CI 0.85 - 0.99 ; p=0.025 ) . Fewer patients permanently discontinued study medication in the telmisartan group than in the placebo group ( 639 [ 21.6 % ] vs 705 [ 23.8 % ] ; p=0.055 ) ; the most common reason for permanent discontinuation was hypotensive symptoms ( 29 [ 0.98 % ] in the telmisartan group vs 16 [ 0.54 % ] in the placebo group ) . INTERPRETATION Telmisartan was well tolerated in patients unable to tolerate ACE inhibitors . Although the drug had no significant effect on the primary outcome of this study , which included hospitalisations for heart failure , it modestly reduced the risk of the composite outcome of cardiovascular death , myocardial infa rct ion , or stroke . FUNDING Boehringer Ingelheim |
10,716 | 30,915,627 | Discussion Compared to high-income setting s , episiotomy rates are high in LMIC medical facilities . | Introduction Birth-related perineal trauma ( BPT ) is a common consequence of vaginal births .
When poorly managed , BPT can result in increased morbidity and mortality due to infections , haemorrhage , and incontinence .
This review aims to collect data on rates of BPT in low- and middle-income countries ( LMICs ) , through a systematic review and meta- analysis . | BACKGROUND : The objective of the present study was to evaluate the effect of the two methods of delivery , “ h and s-on ” vs. “ h and s poised ” , on perineal trauma and delivery outcome in primiparous women referred to Shariati Hospital of Isfahan during 2007 - 2008 . METHODS : In a clinical trial study , 100 low risk primiparous pregnant women were r and omly assigned to two h and s-on and h and -poised ( h and s-off ) groups . In the h and s-on group , this method was used to control fetal head in the second stage of labor . It means that the fingers of one h and supported fetal occiput and the other h and applied slight pressure on the head to control the delivery of the head during the crowning process . In the h and s-poised group , midwife observed the parturient woman and do not touch perineum during the second labor stage while fetal head was delivering . Then , the two groups were compared in terms of perineal trauma , as well as neonatal and delivery outcome . RESULTS : Demographic characteristics of all studied women were similar in two groups . The rate of episiotomy was higher in h and s-on group ( 84 % vs. 40 % , p = 0.001 ) . The rate of postpartum hemorrhage ( 4th stage ) was higher in h and s-on group ( 12 % vs. 4 % , p = 0.04 ) . The rate of mild and moderate postpartum pain in h and s-on group was higher than h and s-off group ( 70 % vs. 58 % and 29 % vs. 10 % , p < 0.001 ) but sever pain was not different in two groups . CONCLUSIONS : It seems that h and s-poised method is associated with less perineal trauma , particularly regarding the lower need for episiotomy and postpartum hemorrhage Background : Obstetric anal sphincter injuries ( OASIS ) can cause an adverse impact on women 's physical and mental health . There was lack of published data in Chinese population particularly on study ing the risk of OASIS for nonrotational outlet forceps . This study was to determine the incidence and risk factors of OASIS . Methods : This is a retrospective cohort study carried out in a tertiary referral hospital in Hong Kong . The control group was selected r and omly . Univariate and multivariate logistic regression analysis was performed to evaluate the influence of potential risk factors on OASIS . This study review ed the obstetric records of OASIS women and r and om control from January 2011 to June 2014 . Univariate and multivariate logistic regression analysis was performed to evaluate the influence of potential risk factors on OASIS . Results : Of 15,446 women delivered , 49 had OASIS . The percentage of OASIS increased from 0.3 % ( 2011 ) to 0.38 % ( 2014 ) . There was an increasing trend of OASIS in attempted spontaneous vaginal delivery without episiotomy ( P < 0.01 ) , but it did not increase the OASIS risk ( P = 0.46 ) . Univariate analysis of 49 cases and 438 control subjects showed that forceps delivery ( odds ratio [ OR ] = 8.73 , P < 0.01 ) , prolong second stage of labor ( OR = 1.43 , P < 0.01 ) increased the risk for OASIS . In multivariate regression models , only forceps delivery ( OR = 6.28 , P < 0.01 ) proved to be independent risk factor . Conclusions : The incidence of OASIS in Chinese women was increased after 2012 , but still lower than the reported figures in the literature . Outlet forceps delivery could be a possible associated risk factor Background Fetal and neonatal mortality rates in low-income countries are at least 10-fold greater than in high-income countries . These differences have been related to poor access to and poor quality of obstetric and neonatal care . Methods This trial tested the hypothesis that teams of health care providers , administrators and local residents can address the problem of limited access to quality obstetric and neonatal care and lead to a reduction in perinatal mortality in intervention compared to control locations . In seven geographic areas in five low-income and one middle-income country , most with high perinatal mortality rates and substantial numbers of home deliveries , we performed a cluster r and omized non-masked trial of a package of interventions that included community mobilization focusing on birth planning and hospital transport , community birth attendant training in problem recognition , and facility staff training in the management of obstetric and neonatal emergencies . The primary outcome was perinatal mortality at ≥28 weeks gestation or birth weight ≥1000 g. Results Despite extensive effort in all sites in each of the three intervention areas , no differences emerged in the primary or any secondary outcome between the intervention and control clusters . In both groups , the mean perinatal mortality was 40.1/1,000 births ( P = 0.9996 ) . Neither were there differences between the two groups in outcomes in the last six months of the project , in the year following intervention cessation , nor in the clusters that best implemented the intervention . Conclusions This cluster r and omized comprehensive , large-scale , multi-sector intervention did not result in detectable impact on the proposed outcomes . While this does not negate the importance of these interventions , we expect that achieving improvement in pregnancy outcomes in these setting s will require substantially more obstetric and neonatal care infrastructure than was available at the sites during this trial , and without them provider training and community mobilization will not be sufficient . Our results highlight the critical importance of evaluating outcomes in r and omized trials , as interventions that should be effective may not be . Trial registration Clinical Trials.gov OBJECTIVE To evaluate the prevalence of obstetrical anal sphincter injuries ( OASIS ) , which include third and fourth degree perineal tears in primigravida in routine versus selective mediolateral episiotomy . Secondly , to determine the rate of episiotomy in local setting s. METHODS This r and omized control trial was carried out in the labor ward of a tertiary hospital of the Universiti Kebangsaan Malaysia Medical Center , Kuala Lumpur , Malaysia between May and October 2009 . The trial included 171 primigravida beyond 38 weeks gestation who achieved vaginal delivery , and r and omly assigned to selective and routine episiotomy groups . The type of perineal injuries following childbirth among 171 women were evaluated . RESULTS The overall episiotomy rate from both groups was 76.6 % . The prevalence of third degree perineal tears was 3.7 % in the routine compared with selective mediolateral episiotomy at 1.1 % . There was no occurrence of fourth degree tears in both groups . However , selective mediolateral episiotomy was associated with an increased risk of periurethral and labial injury compared with the routine group ( 4.5 % versus 0 % ) . CONCLUSION Routine mediolateral episiotomy in primigravida is associated with a higher prevalence of obstetrical anal sphincter injuries . As anal sphincter injuries are known to have morbidities , selective mediolateral episiotomy in primigravida is therefore recommended in the implementation of new delivery practice , and in an attempt to reduce our high episiotomy rate OBJECTIVE To observe the frequency and severity of perineal tears during vaginal delivery . METHODS It was a prospect i ve observational study done at the Countess Lady Duffrin Fund Hospital , Hyderabad , Pakistan , from December 1 , 2009 to May 31 , 2010 . Women with full-term singleton pregnancy primigravida or multigravida , in active labour were included in the study . Patients with pre-term labour , breech presentation and antepartum haemorrhage were excluded , leaving the study population to be 147/1488 . A pre design ed structured proforma was used after informed verbal consent by the patient . All results were analysed on SPSS version 11 . Frequencies and percentages were calculated , while Spearman 's rho test ( two-tailed ) was applied for categorical variables . A p-value of less than or equal to 0.05 was considered significant . RESULTS The frequency of perineal tears in our study was 147/1488 ( 9.8 % ) . The mean age was 28.08 + /- 7.47 , ranging between 17 - 42 years . The vast majority , 100 ( 68 % ) delivered spontaneously , 45 ( 30.6 % ) were delivered with help of the forceps , and only 2 ( 1.4 % ) had vacuum delivery . Parity , oxytocin use , mediolateral episiotomy , forceps use , weight of babies > 3.6 kg were significantly associated with perineal tears . CONCLUSION Perineal tears cause considerable post-natal morbidity . Identification of risk factors , vigilant monitoring during labour and good perineal support is recommended for minimising the risk of perineal trauma as well as morbidity Objective . To evaluate the impact of Advanced Life Support in Obstetrics ( ALSO ) training on staff performance and the incidences of post‐partum hemorrhage ( PPH ) at a regional hospital in Tanzania . Design . Prospect i ve intervention study . Setting . A regional , referral hospital . Population . A total of 510 women delivered before and 505 after the intervention . Methods . All high‐ and mid‐level providers involved in childbirth at the hospital attended a two‐day ALSO provider course . Staff management was observed and post‐partum bleeding assessed at all vaginal deliveries for seven weeks before and seven weeks after the training . Main Outcome Measures . PPH ( blood loss ≥500ml ) , severe PPH ( blood loss ≥1000ml ) and staff performance to prevent , detect and manage PPH . Results . The incidence of PPH was significantly reduced from 32.9 to 18.2%[RR 0.55 ( 95%CI : 0.44–0.69 ) ] , severe PPH from 9.2 to 4.3%[RR 0.47 ( 95%CI : 0.29–0.77 ) ] . The active management of the third stage of labor was also significantly improved . There was a significant decrease in episiotomies . By visual estimation , staff identified one in 25 of the PPH cases before the ALSO training and one in five after the training . A significantly higher proportion of women with PPH had continuous uterine massage , oxytocin infusion and bimanual compression of the uterus after the training . Conclusions . A two‐day ALSO training course can significantly improve staff performance and reduce the incidence of PPH , at least as evaluated by short‐term effects Background Our aim was to describe the range of perineal trauma in women with a singleton vaginal birth and estimate the effect of maternal and obstetric characteristics on the incidence of perineal tears . Methods We conducted a prospect i ve observational study on all women with a planned singleton vaginal delivery between May and September 2006 in one obstetric unit , three freest and ing midwifery-led units and home setting s in South East Engl and . Data on maternal and obstetric characteristics were collected prospect ively and analysed using univariable and multivariable logistic regression . The outcome measures were incidence of perineal trauma , type of perineal trauma and whether it was sutured or not . Results The proportion of women with an intact perineum at delivery was 9.6 % ( 125/1,302 ) in nulliparae , and 31.2 % ( 453/1,452 ) in multiparae , with a higher incidence in the community ( freest and ing midwifery-led units and home setting s ) . Multivariable analysis showed multiparity ( OR 0.52 ; 95 % CI : 0.30–0.90 ) was associated with reduced odds of obstetric anal sphincter injuries ( OASIS ) , whilst forceps ( OR 4.43 ; 95 % CI : 2.02–9.71 ) , longer duration of second stage of labour ( OR 1.49 ; 95 % CI : 1.13–1.98 ) , and heavier birthweight ( OR 1.001 ; 95 % CI : 1.001–1.001 ) , were associated with increased odds . Adjusted ORs for spontaneous perineal truama were : multiparity ( OR 0.42 ; 95 % CI : 0.32–0.56 ) ; hospital delivery ( OR 1.48 ; 95 % CI : 1.01–2.17 ) ; forceps delivery ( OR 2.61 ; 95 % CI : 1.22–5.56 ) ; longer duration of second stage labour ( OR 1.45 ; 95 % CI : 1.28–1.63 ) ; and heavier birthweight ( OR 1.001 ; 95 % CI : 1.000–1.001 ) . Conclusions This large prospect i ve study found no evidence for an association between many factors related to midwifery practice such as use of a birthing pool , digital perineal stretching in the second stage , h and s off delivery technique , or maternal birth position with incidence of OASIS or spontaneous perineal trauma . We also found a low overall incidence of OASIS , and fewer second degree tears were sutured in the community than in the hospital setting s. This study confirms previous findings of overall high incidence of perineal trauma following vaginal delivery , and a strong association between forceps delivery and perineal trauma Background Episiotomy is the surgical enlargement of the vaginal orifice by an incision of the perineum during the second stage of labor or just before delivery of the baby . During the 1970s , it was common to perform an episiotomy for almost all women having their first delivery , ostensibly for prevention of severe perineum tears and easier subsequent repair . However , there are no data available to indicate if an episiotomy should be midline or medio-lateral . We compared midline versus medio-lateral episiotomy for complication such as extended perineal tears , pain scores , wound infection rates and other complications . Methods We conducted a prospect i ve cohort including 1,302 women , who gave birth vaginally between April 2005 and February 2006 at Srinagarind Hospital – a tertiary care center in Northeast Thail and . All women included had low risk pregnancies and delivered at term . The outcome measures included deep perineal tears ( including perineal tears with anal sphincter and /or rectum tears ) , other complications , and women 's satisfaction at 48 hours and 6-weeks postpartum . Results In women with midline episiotomy , deep perineal tears occurred in 14.8 % , which is statistically significantly higher compared to 7 % in women who underwent a medio-lateral episiotomy ( p-value < 0.05 ) . There was no difference between the groups for other outcomes ( such as blood loss , vaginal hematoma , infection , pain , dyspareunia , and women 's satisfaction with the method ) . The risk factors for deep perineal tears were : midline episiotomy , primiparity , maternal height < 145 cm , fetal birth weight > 3,500 g and forceps extraction . Conclusion Midline compared to medio-lateral episiotomy result ed in more deep perineal tears . It is more likely deep perineal tears would occur in cases with additional risk factors OBJECTIVE To determine the impact of introducing an emergency obstetric and neonatal care training program on maternal and perinatal morbidity and mortality at Moi Teaching and Referral Hospital , Eldoret , Kenya . METHODS A prospect i ve chart review was conducted of all deliveries during the 3-month period ( November 2009 to January 2010 ) before the introduction of the Advances in Labor and Risk Management International Program ( AIP ) , and in the 3-month period ( August-November 2011 ) 1 year after the introduction of the AIP . All women who were admitted and delivered after 28 weeks of pregnancy were included . The primary outcome was the direct obstetric case fatality rate . RESULTS A total of 1741 deliveries occurred during the baseline period and 1812 in the postintervention period . Only one mother died in each period . However , postpartum hemorrhage rates decreased , affecting 59 ( 3.5 % ) of 1669 patients before implementation and 40 ( 2.3 % ) of 1751 afterwards ( P=0.029 ) . The number of patients who received oxytocin increased from 829 ( 47.6 % ) to 1669 ( 92.1 % ; P<0.001 ) . Additionally , the number of neonates with 5-minute Apgar scores of less than 5 reduced from 133 ( 7.7 % ) of 1717 to 95 ( 5.4 % ) of 1745 ( P=0.006 ) . CONCLUSION The introduction of the AIP improved maternal outcomes . There were significant differences related to use of oxytocin and postpartum hemorrhage Purpose Maintaining an intact perineum is a highly regarded aim in delivery procedures today . Since perineal massage is a common practice during delivery , the present study aims to investigate the effect of perineal massage with Vaseline on perineal trauma ( rate of episiotomy procedures and perineal tears ) . Method Ninety primiparous women ( aged between 18 and 30 years with gestational age of 38–42 weeks ) were selected sequentially in Tehran in 2009 . Once participants ’ characteristics were registered , they were r and omly assigned to the intervention ( perineal massage with Vaseline ) or control groups . In the massage group , perineal massage was performed in the second stage of delivery once the genitalia were treated with sterilized Vaseline . The perineum was examined after the delivery in terms of episiotomy or tear and its severity degree . Results The two groups were homogeneous in terms of demographic data , weight gain during pregnancy , gestational age , abortion history and fetal weight . The second stage of delivery was significantly shorter in the massage group than the control group and the massage group had significantly more intact perineum ( P = 0.004 ) . In addition , lower episiotomy and higher first- and second-degree perineal tears were seen in the massage group in comparison with the control one ( P < 0.001 ) . Neither of the groups suffered from third- and fourth-degree tears . Conclusion The findings showed that the perineal massage with Vaseline in the second stage of labor increases perineal integrity and decreases perineal traumas ( episiotomy and tears ) . So , it seems that the perineal massage could be an effective way to preserve an intact perineum in labor Objective To compare maternal and neonatal outcomes of vacuum versus forceps application in assisted vaginal delivery . Material and Method Women in labor with vertex presentation were delivered by vacuum and forceps . A total of 120 cases were included in this prospect i ve study . Maternal and neonatal morbidity were compared in terms of perineal lacerations , episiotomy extension , post-partum hemorrhage , Apgar score , instrumental injuries , NICU admissions PNM etc . χ2 test was used to analyze the data .ObservationsMaternal morbidity viz . episiotomy extension as well as first and second degree perineal tear were significant in the forceps group ( P = 0.0001 and P = 0.02 , respectively ) . With regards to neonatal morbidity , no statistically significant difference was noted . Conclusion Vacuum and forceps should remain appropriate tools in the armamentarium of the modern obstetrician . However , ventouse may be chosen first ( if there is no fetal distress ) as it is significantly less likely to injure the mother The burden of maternal ill-health includes not only the levels of maternal mortality and complications during pregnancy and around the time of delivery but also extends to the st and ard postpartum period of 42 days with consequences of obstetric complications and poor management at delivery . There is a dearth of reliable data on these postpartum maternal morbidities and disabilities in developing countries , and more research is warranted to investigate these and further strengthen the existing safe motherhood programmes to respond to these conditions . This study aims at identifying the consequences of pregnancy and delivery in the postpartum period , their association with acute obstetric complications , the sociodemographic characteristics of women , mode and place of delivery , nutritional status of the mother , and outcomes of birth . From among women who delivered between 2007 and 2008 in the icddr , b service area in Matlab , we prospect ively recruited all women identified with complicated births ( n=295 ) ; a perinatal mortality ( n=182 ) ; and caesarean-section delivery without any maternal indication ( n=147 ) . A r and om sample of 538 women with uncomplicated births , who delivered at home or in a facility , was taken as the control . All subjects were clinical ly examined at 6 - 9 weeks for postpartum morbidities and disabilities . Postpartum women who had suffered obstetric complications during birth and delivered in a hospital were more likely to suffer from hypertension [ adjusted odds ratio (AOR)=3.44 ; 95 % confidence interval (CI)=1.14 - 10.36 ] , haemorrhoids ( AOR=1.73 ; 95 % CI=1.11 - 3.09 ) , and moderate to severe anaemia ( AOR=7.11 ; 95 % CI=2.03 - 4.88 ) than women with uncomplicated normal deliveries . Yet , women who had complicated births were less likely to have perineal tears ( AOR=0.05 ; 95 % CI=0.02 - 0.14 ) and genital prolapse ( AOR=0.22 ; 95 % CI=0.06 - 0.76 ) than those with uncomplicated normal deliveries . Genital infections were more common amongst women experiencing a perinatal death than those with uncomplicated normal births ( AOR=1.92 ; 95 % CI=1.18 - 3.14 ) . Perineal tears were significantly higher ( AOR=3.53 ; 95 % CI=2.32 - 5.37 ) among those who had delivery at home than those giving birth in a hospital . Any woman may suffer a postpartum morbidity or disability . The increased likelihood of having hypertension , haemorrhoids , or anaemia among women with obstetric complications at birth needs specific intervention . A higher quality of maternal healthcare services generally might alleviate the suffering from perineal tears and prolapse amongst those with a normal uncomplicated delivery INTRODUCTION The purpose of this study was to compare the frequency and severity of perineal trauma during spontaneous birth with or without perineal injections of hyaluronidase ( HAase ) . METHODS A r and omized , placebo-controlled , double-blind clinical trial was conducted in a midwife-led , in-hospital birth center in São Paulo , Brazil . Primiparous women ( N = 160 ) were r and omly assigned to an experimental ( n = 80 ) or control ( n = 80 ) group . During the second stage of labor , women in the experimental group received an injection of 20.000 turbidity-reducing units of HAase in the posterior region of the perineum , and those in the control group received a placebo injection . The assessment of perineal outcome was performed by 2 independent nurse-midwives . A 1-tailed Fisher exact test was performed , and a P value < .025 was considered statistically significant . RESULTS Perineal integrity occurred in 34.2 % of the experimental group and in 32.5 % of the control group , which was not a statistically significant difference ( P= .477 ) . First-degree laceration was the most common trauma in the posterior region of the perineum in women in both groups ( experimental = 56 % , control = 42.6 % ) . Severe perineal trauma occurred in 28.9 % of the experimental group and 38.8 % of the control group , which also was not a statistically significant difference ( P= .131 ) . The depth of second-degree perineal lacerations in the experimental and control groups , measured by the Peri-Rule , was 1.9 cm and 2.3 cm , respectively . An episiotomy was performed in 11 women ( experimental group = 3 , control group = 8) , and 4 ( all in control group ) had third-degree lacerations . DISCUSSION The use of injectable HAase did not increase the proportion of intact perineum and did not reduce the proportion of severe perineal trauma in our sample OBJECTIVE to evaluate the effects of low-level laser therapy for perineal pain and healing after episiotomy . DESIGN a double-blind , r and omised , controlled clinical trial comparing perineal pain scores and episiotomy healing in women treated with low-level laser therapy ( LLLT ) and with the simulation of the treatment . SETTING the study was conducted in the Birth Centre and rooming-in units of Amparo Maternal , a maternity service located in the city of São Paulo , Brazil . PARTICIPANTS fifty-two postpartum women who had had mediolateral episiotomies during their first normal delivery were r and omly divided into two groups of 26 : an experimental group and a control group . INTERVENTION in the experimental group , the women were treated with LLLT . Irradiation was applied at three points directly on the episiotomy after the suture and in three postpartum sessions : up to 2 hrs postpartum , between 20 and 24 hrs postpartum and between 40 and 48 hrs postpartum . The LLLT was performed with diode laser , with a wavelength of 660 nm ( red light ) , spot size of 0.04 cm(2 ) , energy density of 3.8 J/cm(2 ) , radiant power of 15 mW and 10s per point , which result ed in an energy of 0.15 J per point and a total energy of 0.45 J per session . The control group participants also underwent three treatment sessions , but without the emission of radiation ( simulation group ) , to assess the possible effects of placebo treatment . MAIN OUTCOMES perineal pain scores , rated on a scale from 0 to 10 , were evaluated before and immediately after the irradiation in the three sessions . The healing process was assessed using the REEDA scale ( Redness , Edema , Echymosis , Discharge Aproximation ) before each laser therapy session and 15 and 20 days after the women 's discharge . FINDINGS comparing the pain scores before and after the LLLT sessions , the experimental group presented a significant within-group reduction in mean pain scores after the second and third sessions ( p=0.003 and p<0.001 , respectively ) , and the control group showed a significant reduction after the first treatment simulation ( p=0.043 ) . However , the comparison of the perineal pain scores between the experimental and control groups indicated no statistical difference at any of the evaluated time points . There was no significant difference in perineal healing scores between the groups . All postpartum women approved of the low-level laser therapy . CONCLUSIONS this pilot study showed that LLLT did not accelerate episiotomy healing . Although there was a reduction in perineal pain mean scores in the experimental group , we can not conclude that the laser relieved perineal pain . This study led to the suggestion of a new research proposal involving another irradiation protocol to evaluate LLLT 's effect on perineal pain relief INTRODUCTION Episiotomy is a common obstetrical practice that is believed to prevent severe lacerations . Principles of evidence based medicine raises questions on the utility of routine episiotomy . METHODS A prospect i ve observational study was conducted in primi gravidas coming to Tansen Mission Hospital for delivery who were not offered episiotomy sticking to the protocol of restrictive use of episiotomy and the subsequent perineal tear was evaluated in terms of its length , degree and complications . Risk factors associated with significant degrees of perineal tear was investigated . RESULTS The episiotomy rate during the time of study was only 22 % . Among those included in the study , 16.2 % of women had intact perineum and majority of women ( 43.2 % ) had first degree of tear . Only one ( 1.4 % ) had third degree tear without any long term complications . Having a baby weighing 2.5 kg increases the mean tear length significantly ( P = 0.019 ) and increases the risk of having second or third degree of tear by almost two times ( Relative Risk = 1.95 ) . No clinical ly significant complications were observed in any of the women after the delivery . CONCLUSIONS This study provides some evidence that the principle of restrictive use of episiotomy with a total episiotomy rate being around 20 % can be carried out successfully even in an under-re source d setting of our country OBJECTIVE To examine the effects of perineal massage during active labor on the frequency of episiotomy and perineal tearing . METHODS A r and omized controlled study was conducted at a center in Sivas , Turkey , between January 1 , 2010 , and May 31 , 2011 . Healthy pregnant women presenting for their first or second delivery at 37 - 42 weeks of pregnancy were enrolled during the first stage of labor . Participants were r and omly assigned ( 1:1 ) to the massage group ( 10-minute perineal massage with glycerol four times during the first stage and once during the second stage of labor ) or control group ( routine care ) . The frequency of episiotomy and perineal tearing were compared between the groups . Participants and investigators were not masked to group assignment . RESULTS Both groups contained 142 participants . Episiotomy was performed among 44 ( 31.0 % ) women in the massage group and 99 ( 69.7 % ) in the control group ( P = 0.001 ) . Lacerations were recorded among 13 ( 4.2 % ) women in the massage group and 6 ( 4.2 % ) in the control group ( P = 0.096 ) . CONCLUSION Application of perineal massage during active labor decreased the frequency of episiotomy procedures . Clinical Trials.gov : NCT02201615 OBJECTIVE to investigate the use of local anaesthetics , in the presence or absence of vasoconstrictors , for perineal repair during spontaneous delivery . DESIGN double-blind , r and omised-controlled trial . SETTING a birth centre , in the city of Sao Paulo , Brazil . PARTICIPANTS from June to December 2004 , a total of 96 women were allocated into three groups ( first-degree perineal lacerations , second-degree perineal lacerations or episiotomy ) , and treated with local anaesthesia ( 1 % lidocaine or 1 % lidocaine with epinephrine ) ( n=16 per treatment per group ) . INTERVENTIONS an initial local infiltration of the anaesthetic solution was given so that episiotomy could be carried out ( 5ml ) and to suture spontaneous lacerations ( 1ml ) , followed by repeated doses ( 1ml ) until pain was completely inhibited . MEASUREMENTS AND FINDINGS the main outcome measurement was the volume of anaesthetic used during episiotomy and perineal suture . Our data suggest that the concomitant use of the vasoconstrictor result ed in a significantly lower average volume used in the treatment of first-degree ( 1ml , 95 % confidence interval ( CI ) 0.4 - 1.6 ) and second-degree ( 3.7ml , 95 % CI 1.6 - 5.8 ) lacerations ( p=0.002 and 0.001 , respectively ) . A 0.3ml ( 95 % CI 1.5 - 2.1 ) average decrease in anaesthetic volume was observed with episiotomy ( p=0.724 ) . The maximum volume of anaesthetic used with and without vasoconstrictor was 1 - 2ml in 95 % and 3 - 4ml in 50 % of first-degree lacerations , respectively , and 1 - 6ml in 88 % and 7 - 15ml in 81 % of second-degree lacerations , respectively . For episiotomy , the maximum dose was 15ml , regardless of anaesthetic solution used . KEY CONCLUSIONS our data confirm the hypothesis that the use of anaesthetics in conjunction with vasoconstrictors is more effective than anaesthetics alone in the repair of perineal lacerations , but not for episiotomy BACKGROUND Episiotomy is the commonest obstetric surgical operation performed to increase the introitus to enhance vaginal delivery . This study was to compare the effect of two local anaesthetic agents on postpartum perineal pain and time for dem and for oral analgesics . METHODS A r and omized double-blinded controlled clinical trial was conducted in primiparous women who had spontaneous vaginal delivery , comparing 1 % plain lidocaine and 0.25 % plain bupivacaine infiltration for the repair of selective episiotomy or perineal injury . RESULTS The two groups were comparable in sociodemographic characteristics . At 2 and 4 hours , women who had perineorraphy under lidocaine had significantly higher pain scores on the Visual Analogue Scale ( VAS ) than those who had the repair under bupivacaine , ( 4.0 v. 2.0 ) and ( 6.0 v. 3.0)respectively . At the 6h hour , the mean pain score for the bupivacaine group was 4.0 on the VAS while the lidocaine group had already received a dose of oral analgesic ( Ibuprofen 400 mg ) following severe pain from the repair . There was however no statistically significant difference in the pain score on the VAS between the two groups at the time of request for oral analgesics . The mean time lapse before dem and for oral analgesics for the lidocaine group was 2.25 + /- 0.46 hrs ( Mean+St and ard deviation ) while that for the bupivacaine group was 7.13 1.56 hrs ( Mean St and ard deviation ) . The P value was P < 0.0000 ( Student 's t-test ) and statistically significant . CONCLUSION It is concluded that the patients in the bupivacaine group had a prolonged analgesia and needed fewer doses of oral analgesics in the immediate postpartum perineal repair period AIMS AND OBJECTIVES ( 1 ) To evaluate the influence of local cold on severity of labour pain and ( 2 ) to identify the effect of local cold on maternal and neonatal outcomes . BACKGROUND Fear of labour pain results in an increase in pain and duration of labour , maternal discontent and dem and for caesarean section . Regarding maternal and foetal complications of analgesic medications , the attention to application of nonpharmacological methods including cold therapy is increased . DESIGN R and omised controlled trial . METHODS Sixty-four pregnant women , at initiation of active phase of labour , were allocated r and omly to cold therapy and control groups ( n = 64 ) . Null parity , term pregnancy , presence of single foetus , cephalic presentation and completing informed consent were considered as inclusion criteria . Administration of analgesic and anaesthesia , foetal distress , skin lesions in regions of cold therapy and high-risk pregnancy provided exclusion criteria . Cold pack was applied over abdomen and back , for 10 minutes every 30 minutes during first phase of labour . Additionally , cold pack was placed over perineum , for 5 minutes every 15 minutes during second phase . Pain severity was assessed based on the visual analogue scale . RESULTS The two groups were not significantly different considering demographic data , gestational age , foetal weight , rupture of membranes and primary severity of pain . Degree of pain was lower in cold therapy group during all parts of active phase and second stage . Duration of all phases was shorter in cold therapy group in all phases . Foetal heart rate , perineal laceration , type of birth , application of oxytocin and APGAR score were not significantly different between two groups . CONCLUSION Labour pain is probably reduced based on gate theory using cold . Pain control by cold maybe improves labour progression without affecting mother and foetus adversely . RELEVANCE TO CLINICAL PRACTICE Local cold therapy could be included in labour pain management |
10,717 | 26,133,124 | Three of the six trials had adequate sequence generation while all the trials had unclear allocation concealment There was no evidence of any difference in pain perception during surgery with either retrobulbar or peribulbar anaesthesia .
Both were largely effective .
There was no evidence of any difference in complete akinesia or the need for further injections of local anaesthetic .
There is little to choose between peribulbar and retrobulbar block in terms of anaesthesia and akinesia during surgery measuring acceptability to patients , need for additional injections and development of severe complications .
Severe local or systemic complications were rare for both types of block | BACKGROUND Cataract is a major cause of blindness worldwide .
Unless medically contraindicated , cataract surgery is usually performed under local ( regional ) anaesthesia .
Local anaesthesia involves the blockage of a nerve subserving a given part of the body .
It involves infiltration of the area around the nerve with local anaesthetic .
The two main approaches in the eye are retrobulbar and peribulbar .
There is debate over whether the peribulbar approach provides more effective , safer anaesthesia for cataract surgery than retrobulbar block .
OBJECTIVES The objective of this review was to assess the effects of peribulbar anaesthesia ( PB ) compared to retrobulbar anaesthesia ( RB ) on pain scores , ocular akinesia , patient acceptability and ocular and systemic complications . | OBJECTIVES To evaluate and compare levels of patient discomfort and perioperative complications during phacoemulsification and implantation of a foldable intraocular lens under topical lidocaine hydrochloride and retrobulbar anesthesia in patients with cataract who also had exfoliation syndrome , uveitis , posterior synechia , phacodonesis , or previous intraocular surgery . DESIGN A prospect i ve , r and omized , controlled trial was carried out at 2 institutions . PARTICIPANTS A total of 476 eyes of 476 patients with various well-established risk factors fulfilled the inclusion criteria . In 238 eyes , phacoemulsification was performed under retrobulbar anesthesia , while the other 238 eyes received topical anesthesia . INTERVENTIONS All patients underwent temporal clear corneal phacoemulsification and implantation of a foldable intraocular lens . Patients under retrobulbar anesthesia received a single injection ( 3 . 5 - 5.5 mL ) of a combination of 0.75 % bupivacaine hydrochloride , 2 % lidocaine , and hyaluronidase into the retrobulbar space . Patients in the topical anesthesia group received a minimum of 5 doses ( approximately 40 microL per dose ) of 2 % topical lidocaine . No intracameral injection of any anesthetic was given . MAIN OUTCOME MEASURES The number of complications and adverse events . The intraoperative conditions were judged by the surgeon ( P.C.J. or F.K. J. ) , and a 10-point visual analog scale was used immediately after surgery to assess each patient 's overall severity of intraoperative pain . RESULTS The overall intraoperative complication rate was 1.9 % for capsular tear , 3.8 % for zonular tear , 1.5 % for vitreous loss , and 1.0 % for iris prolapse . Apart from the incidence of vitreous loss , which was significantly ( P = .041 ) lower in the topical anesthesia group , no statistically significant differences in intraoperative and early postoperative complications were found between the groups . A supplemental posterior sub-Tenon space injection was required in 1.3 % of the topical anesthesia group and in 0.8 % of the retrobulbar anesthesia group . Chemosis ( 2.5 % ) , subconjunctival hemorrhage ( 1.7 % ) , and periorbital hematoma ( 0.8 % ) were seen only in the retrobulbar anesthesia group . The mean + SE pain scores estimated by the patients were 0.84 + 1.30 in the topical anesthesia group and 0.73 + 1.50 in the retrobulbar anesthesia group ( P = .41 ) . Patient preference for topical anesthesia ( 91 % ) appeared to be significantly ( P = .01 ) higher than for retrobulbar anesthesia ( 62 % ) . The surgeons found anesthesia-related intraoperative difficulty to be slightly lower in the retrobulbar anesthesia group ( 8 % ) than in the topical anesthesia group ( 14 % ) . CONCLUSIONS Surgery-related complications and patient discomfort were similar for the 2 methods of anesthesia . Topical anesthesia is justified as a means of improving safety without causing discomfort to the patient even in complicated cases of cataract surgery . Arch Ophthalmol . 2000;118:1037 - AIMS The effect of local anaesthetics on optic nerve function can be investigated by quantifying the relative afferent pupillary defect ( RAPD ) . METHODS The study compared the depth of induced RAPD following posterior sub-Tenon 's , retrobulbar , and peribulbar local anaesthetics using crossed polarising filters before cataract surgery ( time 1 = 5 minutes ) , immediately after surgery ( time 2 = 42 minutes ( av ) ) , and once again on the ward ( time 3 = 107 minutes ( av ) ) . RESULTS All patients developed a RAPD . There was no significant difference in the depth of RAPD between the groups at any one time period . The peribulbar group had a significantly steeper decay in RAPD from time 1 to time 2 ( p = 0.014 ) . This effect was reduced when the shorter operation time for this group was entered as a cofactor ( p = 0.063 ) . By time 3 the RAPDs for all groups had decayed similarly so that no differences could be detected . CONCLUSION All three anaesthetic methods caused a similar level of disruption to optic nerve conduction immediately following administration and at the time of day case discharge BACKGROUND AND OBJECTIVE To evaluate the response of intraocular pressure ( IOP ) to retrobulbar and peribulbar anesthesia . PATIENTS AND METHODS Patients were prospect ively masked and r and omized to receive either 4 cc of retrobulbar anesthesia ( X = 29 ) or 6 cc of peribulbar anesthesia ( X = 30 ) , each consisting of a 50:50 mixture of 2 % xylocaine and 0.75 % bupivacaine with 150 units of hyaluronidase . IOPs were measured pre-anesthesia and 1 , 2 , and 5 minutes post-anesthesia in nonglaucoma patients undergoing cataract extraction and intraocular lens implantation . RESULTS Mean IOPs in the retrobulbar group as determined with a tonometer were 18.24 , 18.66 , 19.14 , and 17.86 mm Hg pre-anesthesia and 1 , 2 , and 5 minutes post-anesthesia , respectively . In the peribulbar group , the mean IOPs were 18.53 , 21.20 , 20.40 , and 19.20 mm Hg , respectively . The 1-minute pressures in the two groups were statistically different ( P = .023 ) . Within the peribulbar group , the 1- and 2-minute pressures were statistically different from the pre-anesthesia IOP ( P = .001 and P = .018 , respectively ) . CONCLUSION Peribulbar anesthesia , with its higher volume of anesthetic ( 6 vs 4 cc ) , results in a higher initial IOP . This difference was slight and short lived , and occurred in the absence of any external ocular compression . This study may have application in avoiding elevation of IOP in select patients undergoing a local procedure ABSTRACT One hundred patients having elective cataract surgery were evaluated in a prospect i ve , r and omized , double‐blinded study comparing retrobulbar and peribulbar anesthesia . Patients were divided into two study groups and evaluated on three criteria felt to be critical to intraocular surgery . Results showed that the efficacy of the oneinjection‐site peribulbar block was similar to that of the retrobulbar block for all three criteria . Because the one‐injection‐site anesthetic is administered outside the muscle cone , the potential for optic nerve and central nervous system complications should be minimized Abstract Although usually safe , retrobulbar anesthesia and peribulbar anesthesia have potentially sight‐ and life‐threatening complications . Although it has been suggested that peribulbar anesthesia is as effective and safer than retrobulbar anesthesia , no large study has addressed the true rate of complications . To determine the efficacy and safety of peribulbar anesthesia , this study prospect ively examined 16,224 consecutive peribulbar blocks . Twelve centers in the United States , Germany , and Chile participated in the study . After a peribulbar block was administered , the degree of akinesia , amaurosis , percentage of supplemental blocks required , and side effects and complications occurring after the block and for six weeks were recorded . Perioperative and late optic nerve complications were included . To approximate a real‐life situation , ophthalmologists , anesthesiologists , and certified registered nurse anesthetists performed the blocks . Ninety‐five percent of patients achieved a 95 % or greater degree of akinesia . The incidence of complications in the consecutive cases was low . Orbital hemorrhage occurred in 12 cases ( 0.74 % ) . There was one globe perforation ( 0.006 % ) , two expulsive hemorrhages ( 0.013 % ) , one gr and mal seizure ( 0.006 % ) , and no cases of cardiac or respiratory depression or deaths . Peribulbar is as effective as retrobulbar anesthesia and appears to lead to fewer sight‐ and life‐threatening complications , even when slightly different peribulbar techniques are used . This is especially true when the anesthetic is administered with a 1 1/4‐inch or shorter needle with the eye in the primary position , followed by ten to 15 minutes of ocular compression Complications of retrobulbar anesthesia are rare but significant . Periocular anesthesia has been advocated as an alternative to retrobulbar injections . In a prospect i ve , r and omized , masked study of 79 consecutive cataract extraction s with intraocular lens implantations , 40 patients received retrobulbar injections and 39 patients received periocular injections . In every instance , the volume of the injection was 5 mL. No significant difference in surgeon 's assessment of akinesia and anesthesia was found . Supplemental anesthesia was required in eight ( 21 % ) of the patients who received retrobulbar injections and in 11 ( 28 % ) of the patients who received periocular injections . A significant increase in chemosis was found with periocular injections . There was one complication with retrobulbar anesthesia and none with periocular anesthesia . No significant difference in patient assessment of comfort was found . The efficacy of periocular anesthesia appears to be comparable to that of retrobulbar anesthesia Two methods of periocular anaesthesia ( PI and PII ) were compared with the traditional retrobulbar block in a prospect i ve study of 450 patients undergoing elective cataract extraction and intraocular lens implantation . A solution of local anaesthetic containing equal amounts of 2 % lignocaine and 0.5 % bupivacaine was used in all the groups . Hyaluronidase ( 75 IU/10 ml of local anaesthetic solution ) was added . Three groups of patients were studied , with 150 patients in each group . The retrobulbar injection ( group R ) was performed with 4 ml of the anaesthetic solution through the lower eyelid inferotemporally and a further 6 ml was injected for seventh cranial nerve block . In the first periocular technique ( group PI ) the local anaesthetic was injected inferotemporally ( 5 ml ) through the lower lid and superonasally ( 5 ml ) through the upper lid . In the second periocular technique ( PII ) the injections were performed inferotemporally ( 5 ml ) and into the medial compartment ( 2 ml ) of the orbit at the medial canthus . Satisfactory anaesthesia could be achieved with all of these methods . Additional block because of insufficient akinesia of the muscles was required in 12 % ( 18/150 ) in group R , in 19 % ( 28/150 ) in group PI , and in 11 % ( 16/150 ) in PII . The medial compartment technique ( PII ) was associated with the highest percentage of total akinesia of the muscles and lowest reblock rate . All three methods produced sufficient analgesia during surgery and there were no differences in the requirements for additional analgesic drugs during surgery . It is concluded that the medial compartment technique represents a good alternative to retrobulbar block A prospect i ve trial was conducted on 142 patients who underwent cataract surgery , to compare the efficacy of a single point , low volume peribulbar with that of retrobulbar anaesthesia . It was found that peribulbar anaesthesia is as efficacious as retrobulbar anaesthesia without the associated complications . It also avoids the facial block used by most ophthalmologists to supplement a retrobulbar block , thus markedly reducing the post-operative patient discomfort as well as the total volume of anaesthetic used Purpose : To assess the effects of retrobulbar and peribulbar anesthesia on nerve function as detected by visual‐evoked potentials ( VEPs ) . Setting : University hospital in southern Brazil . Methods : In a prospect i ve study , 7 patients had peribulbar anesthesia and 9 had retrobulbar anesthesia for extracapsular cataract extraction . Visual‐evoked potentials with pattern reversal and flash stimulation were performed at least 1 month before and 1 month after surgery . Study participants did not have ocular pathology other than cataract . The Lens Classification System III was used to grade the opacities before surgery . Results : No significant difference was found between preoperative and postoperative evaluations in VEP flash and pattern‐reversal amplitude and latency in either group ( P > .05 ) . Postoperative amplitude and latency was not significantly different between the peribulbar and retrobulbar groups . Two cases in the peribulbar group had altered wave morphology without clinical manifestation postoperatively . All patients had a final best spectacle‐corrected visual acuity of 20/20 . Conclusion : Block anesthetic procedures were safely used in cataract surgery , with no clinical sequelae to the optic nerve Peribulbar anaesthesia is now established as an alternative to retrobulbar anaesthesia for cataract surgery . However , the larger volume of anaesthetic solution in the extraconal orbit with the peribulbar technique might carry a higher risk of systemic side-effects . To assess this risk we carried out a prospect i ve r and omised comparison of plasma catecholamine and pressor effects between the two methods of anaesthesia in 40 patients . Plasma adrenaline and noradrenaline , heart rate , blood pressure , pain and anxiety were documented before and after local anaesthesia and during surgery . There were no statistically significant differences between the responses of the two groups . Both groups demonstrated a statistically significant rise in plasma adrenaline and heart rate . However , this change was minimal compared with the effects reported after severe stress or general anaesthesia , emphasising the importance of allaying patient anxiety during local anaesthesia . We have therefore shown that the larger volume of extraconal orbital anaesthetic solution with the peribulbar technique produces no greater risk of systemic pressor effects A prospect i ve clinical trial comparing peribulbar with retrobulbar anaesthesia is reported . Ninety-nine consecutive patients for cataract extraction under local anaesthesia were r and omly allocated to a peribulbar or retrobulbar technique . The effectiveness of the anaesthetic , the operative conditions , and the degree of patient discomfort were recorded . Pain scores ( as assessed separately by the patient , surgeon , and attendant nurse ) demonstrated that anaesthetic administration and surgery were less painful with the peribulbar method . This technique gave more reliable ocular akinesia and orbic-ularis oculi paralysis in addition to a lower operative complication rate A modified retrobulbar block ( MRB ) using a single superomedial injection was compared with the classical retrobulbar block ( RB ) and peribulbar block ( PB ) in a r and omized , prospect i ve , surgeon-blinded study involving 150 patients undergoing cataract surgery . No serious complication occurred in any of the patients , The MRB produced higher rates of total akinesia in the orbicularis and all the extraocular muscles , which were statistically significant for the orbicularis , superior , inferior and lateral rectus and oblique muscles when compared with RB , and for the superior rectus and oblique muscles when compared with PB . MRB required less supplemental blocks , provided good operating conditions for the surgeon , and achieved high patient acceptance . It is concluded that MRB is a useful alternative method of ocular block for cataract surgery . RésuméLe bloc retrobulbaire modifie ( BRM ) a une seule injection supero-interne est compare au bloc retrobulbaire classique ( BR ) et au bloc peribulbaire ( BP ) . L’étude r and omisée , prospect i ve , à l’insu du chirurgien comprend 150 patients opérés pour cataracte . La chirurgie se déroule sans complications . Le BRM produit plus d’akinésie totale de l’orbiculaire et de tous les muscles extra-oculaires : elle est significative pour l’orbiculaire , les muscles droits inférieurs , supérieurs , latéraux et les muscles obliques comparativement au BP . Le BRM requiert moins souvent de supplement anesthésique , fournit des bonnes conditions opératoires et est bien accepté par le patient . On conclut que le BRM représente une alternative valable pour la chirurgie oculaire PURPOSE A r and omized , double-masked study of 317 patients was conducted to determine if the incidence of postcataract ptosis is greater with retrobulbar or two-injection peribulbar injection anesthesia . METHODS Surgery consisted of a planned extracapsular extraction with posterior chamber lens implantation , and no superior rectus bridle suture was used . Ptosis was quantitatively documented preoperatively and postoperatively at 1 , 2 , 5 , and 90 days by the surgeon , photographically at 90 days by a masked observer , and subjectively by the patients . Postcataract ptosis was defined as a drop in the lid margin of 2 mm or greater after correcting for any change in the fellow eye . RESULTS The incidence of ptosis at 90 days in patients given peribulbar anesthesia was 5.8 % and in patients given retrobulbar anesthesia 5.5 % , and this difference was not statistically significant ( P = 0.90 ) . Eighteen percent of patients in both groups reported a change in the appearance of their eyelids . There was a moderate , positive correlation among patients who reported a change in their lid position and objective measurements of ptosis . Preoperative clinical measurements of vertical lid fissure width and levator function , and the appearance of the lid crease or superior sulcus were not predictive for the development of postoperative ptosis at 90 days ; the best predictor was the presence of ptosis in the immediate postoperative period . CONCLUSION The incidence of postcataract ptosis is the same whether two injection peribulbar or retrobulbar anesthesia is used Prilocaine ( Citanest ) has been shown to be a satisfactory alternative to lignocaine , with certain important advantages , including superior diffusion . The latter may be especially important in peribulbar anesthesia , where the level of diffusion is a critical factor in providing a timely , high- quality block . In a prospect i ve r and omized study , we compared the effectiveness of peribulbar vs retrobulbar administration of prilocaine . Eighty-seven patients undergoing elective intraocular surgery were r and omized to receive either retrobulbar or peribulbar anesthesia with prilocaine 3 % with felypressin and hyaluronidase . Pain of injection , akinesia , and anesthesia were evaluated at predetermined intervals after injection . Except for the fact that lid akinesia occurred earlier in the peribulbar group , there was no difference in the quality or rate of onset of overall akinesia in the two groups . Nor were there any differences in the pain associated with injection . Both groups had excellent operative anesthesia and akinesia A prospect i ve r and omized study was done in 79 patients undergoing elective routine cataract surgery in which the Kelman phacoemulsification technique was used with placement of an intraocular lens . In all the patients anesthesia was induced with both a peribulbar and a retrobulbar injection of a large volume ( total 10.5 mL ) of local anesthetic . The patients were r and omly assigned to receive either the peribulbar ( 39 patients ) ( group 1 ) or the retrobulbar ( 40 patients ) ( group 2 ) injection first . The intraocular pressure ( IOP ) was measured five times during anesthesia . The mean elevation in IOP immediately after the first injection was 0.4 mm Hg in group 1 , compared with 2.0 mm Hg in group 2 . Twenty minutes after both injections had been given and a Super Pinky pressure device had been placed on the eye , the mean decrease in IOP from the preoperative value was 3.1 mm Hg in group 1 and 4.8 mm Hg in group 2 . We conclude that a combined peribulbar and retrobulbar approach is a safe and effective alternative method of regional anesthesia for cataract surgery Methods . The features of retrobulbar and peribulbar blocks were compared prospect ively in 300 patients undergoing elective , ambulatory cataract surgery . Both techniques were clinical ly applicable , but to achieve total akinesia of the eye muscles , an additional injection was needed in 13 % of the patients with retrobulbar block and in 35 % with periocular block . Results . In younger patients ( < 65 years ) , the number of injections and the volume of the local anesthetic needed to produce a total akinesia of the eye were significantly higher when compared with the elderly |
10,718 | 23,881,791 | Meta- analysis suggested a modest but statistically significant reduction in the incidence of chronic pain after surgery following treatment with ketamine but not gabapentin or pregabalin .
Furthermore , available evidence does not support the efficacy of gabapentin , pregabalin , non-steroidal anti-inflammatories , intravenous steroids , oral NMDA blockers , oral mexiletine , intravenous fentanyl , intravenous lidocaine , oral venlafaxine or inhaled nitrous oxide for the prevention of chronic postoperative pain | BACKGROUND Chronic pain can often occur after surgery , substantially impairing patients ' health and quality of life .
It is caused by complex mechanisms that are not yet well understood .
The predictable nature of most surgical procedures has allowed for the conduct of r and omized controlled trials of pharmacological interventions aim ed at preventing chronic postsurgical pain .
OBJECTIVES The primary objective was to evaluate the efficacy of systemic drugs for the prevention of chronic pain after surgery by examining the proportion of patients reporting pain three months or more after surgery .
The secondary objective was to evaluate the safety of drugs administered for the prevention of chronic pain after surgery . | Abstract We studied the prevalence of chronic pain and long term sensory changes after cosmetic augmentation mammoplasty and the effects of a single i.v . preoperative dose of methylprednisolone 125 mg ( n = 74 ) , parecoxib 40 mg ( n = 71 ) , or placebo ( n = 74 ) . A question naire was mailed 6 weeks and 1 year after surgery . Response rate after 1 year was 80 % . At 1 year non‐evoked pain was present in 13 % , and evoked pain was present in 20 % with no statistically significant differences between the groups . Methylprednisolone was associated with reduced odds for hyperesthesia at 1 year ( OR 0.3 , 95 % CI 0.1–0.6 ) , and significantly reduced the prevalence of hyperesthesia ( 30 % ) compared with placebo ( 56 % , P < 0.01 ) and parecoxib ( 51 % , P < 0.04 ) . Factors associated with increased odds for pain at 1 year were intensity of pain during the first 6 days after surgery ( OR 1.3 , 95 % CI 1.1–1.6 ) , pain at 6 weeks ( OR 18.4 , 95 % CI 6.9–49.3 ) , hyperesthesia at 6 weeks ( OR 2.3 , 95 % CI 1.1–5.1 ) and present hyperesthesia ( OR 3.1 , 95 % CI 1.4–6.7 ) . We conclude that persistent pain and sensory changes are common after augmentation mammoplasty , and that patients having pain at 6 weeks most likely will have pain also at 1 year . Acute postoperative pain , hyperesthesia at 6 weeks , and the presence of hyperesthesia increased the odds for pain at 1 year . Preoperative methylprednisolone result ed in significantly less hyperesthesia compared with both parecoxib and placebo , but did not significantly reduce the prevalence of persistent spontaneous or evoked pain Background and objective : Gabapentin has been suggested to decrease acute postoperative pain . We evaluated the effect of gabapentin on pain after abdominal hysterectomy . Methods : Sixty patients scheduled for abdominal hysterectomy were r and omized to receive orally gabapentin 400 mg 6 hourly or placebo . Treatment started 18 h preoperatively and continued for 5 postoperative days . Pain ( visual analogue score ) and consumption of morphine for 48 h and of oral paracetamol/codeine were recorded after 2 , 4 , 8 , 24 and 48 h and on days 3‐5 postoperatively . After 1 month , patients were interviewed by phone for pain , and analgesic intake after hospital discharge . Results : Morphine consumption ( mean ± SD ) was 35 ± 15.7 mg in the control and 28 ± 12.1 mg in the gabapentin group ( P = 0.21 ) . Median number ( range ) of paracetamol 500 mg/codeine 30 mg tablets taken during days 3‐5 was 1.0 ( 0‐6 ) in the control and 2.0 ( 0‐9 ) in the gabapentin group ( P = 0.35 ) . The visual analogue scores at rest and after cough did not differ between the two groups ( F = 0.92 , df = 1 , P = 0.34 and F = 0.56 , df = 1 , P = 0.46 , respectively ) . One month after surgery , 22/27 ( 81 % ) of the control group and 9/25 ( 36 % ) of the gabapentin group reported pain in the surgical area ( χ2 = 11.15 , P = 0.002 ) , while 11/27 ( 41 % ) of controls and 7/25 ( 28 % ) of gabapentin patients consumed analgesics for pain ( χ2 = 0.93 , P = 0.39 ) . The intensity of pain was decreased in the gabapentin group ( χ2 = 12.6 , P = 0.003 ) . Conclusions : Gabapentin has no effect on immediate pain after abdominal hysterectomy but decreases pain 1 month postoperatively Abstract Variability in patients ' response to interventions in pain and other clinical setting s is large . Many explanations such as trial methods , environment or culture have been proposed , but this paper sets out to show that the main cause of the variability may be r and om chance , and that if trials are small their estimate of magnitude of effect may be incorrect , simply because of the r and om play of chance . This is highly relevant to the questions of ‘ How large do trials have to be for statistical accuracy ? ’ and ‘ How large do trials have to be for their results to be clinical ly valid ? ’ The true underlying control event rate ( CER ) and experimental event rate ( EER ) were determined from single‐dose acute pain analgesic trials in over 5000 patients . Trial group size required to obtain statistically significant and clinical ly relevant ( 0.95 probability of number‐needed‐to‐treat within ±0.5 of its true value ) results were computed using these values . Ten thous and trials using these CER and EER values were simulated using varying group sizes to investigate the variation due to r and om chance alone . Most common analgesics have EERs in the range 0.4–0.6 and CER of about 0.19 . With such efficacy , to have a 90 % chance of obtaining a statistically significant result in the correct direction requires group sizes in the range 30–60 . For clinical relevance nearly 500 patients are required in each group . Only with an extremely effective drug ( EER>0.8 ) will we be reasonably sure of obtaining a clinical ly relevant NNT with commonly used group sizes of around 40 patients per treatment arm . The simulated trials showed substantial variation in CER and EER , with the probability of obtaining the correct values improving as group size increased . We contend that much of the variability in control and experimental event rates is due to r and om chance alone . Single small trials are unlikely to be correct . If we want to be sure of getting correct ( clinical ly relevant ) results in clinical trials we must study more patients . Credible estimates of clinical efficacy are only likely to come from large trials or from pooling multiple trials of conventional ( small ) size BACKGROUND Unrelieved postoperative pain may impair rehabilitation , delay recovery , and result in poor outcomes . Preventive multimodal analgesic techniques may improve long-term outcome after surgery . METHODS We r and omized 200 consecutive patients to receive acetaminophen 1000 mg and either celecoxib 400 mg or placebo 1 - 2 h before anterior cruciate ligament surgery . All patients received intraarticular analgesics and had an external cooling system applied to the operative knee . After discharge patients were instructed to take acetaminophen 1000 mg every 6 h and either celecoxib 200 mg every 12 h or matching placebo for the first 14 days postoperatively . All patients were enrolled in an accelerated rehabilitation program . Six months postoperatively , the level of activity was assessed , as was the presence of patellofemoral complications including : anterior knee pain , flexion contracture , quadriceps weakness , and complex regional pain syndrome . RESULTS More patients in the control group developed patellofemoral complications compared to the celecoxib group ( P = 0.001 ) including anterior knee pain ( 14/96 ; 15 % ) vs ( 4/95 ; 1 % ) , complex regional pain syndrome ( 7/96 ; 7 % ) vs ( 1/95 ; 1 % ) , flexion contractures ( 9/96 ; 9 % ) vs ( 2/95 ; 2 % ) , and scar tissue requiring re-arthroscopy ( 8/96 ; 8 % ) vs ( 2/95 ; 2 % ) respectively . More patients in the celecoxib group returned to a higher activity level ( 84 % vs 65 % ) ( P < 0.01 ) , were able to participate at a more intense level ( P < 0.02 ) , and return to full sports activity ( P < 0.05 ) . CONCLUSIONS The administration of celecoxib as a component of a preventive multimodal analgesic technique for anterior cruciate ligament reconstruction reduces long-term patellofemoral complications and increases the likelihood of returning to a preinjury level of activity BACKGROUND : Ketamine has been shown to have a morphine-sparing effect soon after surgery . Nevertheless , whether this effect still exists after being combined with nonsteroidal antiinflammatory drugs and acetaminophen , and whether ketamine can decrease chronic pain after nononcologic surgery remain unclear . Thus , we design ed a study to assess ketamine ’s effect on acute and chronic postoperative pain when combined with multimodal analgesia after total hip arthroplasty ( THA ) . METHODS : Patients scheduled for primary nononcologic THA using st and ardized general anesthesia were r and omized . They received IV ketamine before incision ( 0.5 mg/kg ) , and a 24-h infusion ( 2 & mgr;g · kg−1 · min−1 ) or a similar blinded saline bolus and infusion . Postoperative analgesia included IV acetaminophen , ketoprofen , plus morphine/droperidol patient-controlled analgesia for 48 h. Data pertaining to pain scores , morphine consumption , and need for crutches were collected for 6 mo after THA . Our primary outcome was 24-h morphine consumption . RESULTS : One hundred fifty-four patients were included ( placebo , 75 ; ketamine , 79 ) . Patients and operative data were similar in both groups . Ketamine decreased morphine consumption at 24 h from 19 ± 12 mg to 14 ± 13 mg ( P = 0.004 ) . At Day 30 , ketamine decreased the proportion of patients needing 2 crutches or a walking frame from 56 % to 31 % ( P = 0.0035 ) . From Day 30 to Day 180 , ketamine decreased the proportion of patients with persistent pain at rest in the operated hip ( P = 0.008 ) . At Day 180 , 21 % of placebo group patients ( 15 of 70 ) experienced pain at rest in the operated hip versus 8 % ( 6 of 72 ) in the ketamine group ( P = 0.036 , odds ratio 0.33 , 95 % confidence interval 0.12–0.91 , risk reduction 67 % ) . CONCLUSIONS : Ketamine had a morphine-sparing effect after THA , even when morphine was combined with multimodal systemic analgesia . It also facilitated rehabilitation at 1 mo and decreased postoperative chronic pain up to 6 mo after surgery Background Perioperative administration of pregabalin , which is effective for neuropathic pain , might reduce early postoperative and chronic pain . This r and omized , double-blinded , placebo-controlled trial ( Clinical Trials.gov ID NCT00905580 ) was design ed to investigate the efficacy and safety of pregabalin for reducing both acute postoperative pain and the development of chronic pain in patients after robot-assisted endoscopic thyroidectomy . Methods Ninety-nine patients were r and omly assigned to groups that received pregabalin 150 mg or placebo 1 h before surgery , with the dose repeated after 12 h. Assessment s of pain and side effects were performed 48 h postoperatively . The incidences of chronic pain and hypoesthesia in the anterior chest were recorded 3 months after surgery . Results Ninety-four patients completed the study . Verbal numerical rating scale scores for pain and the need for additional analgesics were lower in the pregabalin group ( n = 47 ) than the placebo group ( n = 47 ) during 48 h postoperatively ( P < 0.05 ) . However , incidences of sedation and dizziness were higher in the pregabalin group ( P < 0.05 ) . There were no differences between the groups in the incidences of chronic pain and chest hypoesthesia at 3 months after surgery . Conclusions Perioperative administration of pregabalin ( 150 mg twice per day ) was effective in reducing early postoperative pain but not chronic pain in patients undergoing robot-assisted endoscopic thyroidectomy . Caution should be taken regarding dizziness and sedation Background and objective To find out whether preoperative gabapentin use had a favourable effect on long-term postoperative pain in patients undergoing inguinal herniorrhaphy . Methods Sixty male patients – aged 20–40 years – who were scheduled for unilateral inguinal herniorrhaphy under spinal anaesthesia were included in this prospect i ve , r and omized , double-blind study . The patients were r and omly allocated to two groups : the gabapentin group ( n = 30 ) received single-dose 1.2 g oral gabapentin 1 h before surgery , and the placebo group received a placebo capsule instead . Spinal anaesthesia was performed with heavy bupivacaine , and all operations were performed by the same surgeon with the same technique . Postoperative analgesia was evaluated during sitting and lying with a visual analogue scale . Assessment of postoperative pain at 1 , 3 and 6 months was carried out with an 11-point numerical rating scale ; 0 indicating ‘ no pain ’ and 10 indicating ‘ worst pain imaginable ’ . Patients who had numerical rating scale scores of more than 0 were further evaluated with regard to the impact of pain on their daily activities . Results When compared with the placebo group , the gabapentin group displayed significantly lower visual analogue scale scores ( lying and sitting ) and total tramadol consumption at 8 , 12 , 16 , 20 and 24 h after surgery ( P < 0.05 ) and higher postoperative patient satisfaction scores ( P < 0.05 ) . Numerical rating scale scores at 1 , 3 and 6 months after surgery were lower in the gabapentin group than in the placebo group ( P < 0.05 ) . The number of patients whose daily activities were adversely affected by pain was smaller in the gabapentin group at the first month ; however , the two groups were found to be similar at 3 and 6 months . Conclusion We conclude that preoperative single-dose gabapentin decreases the intensity of acute postoperative pain , tramadol consumption and the incidence and intensity of pain in the first 6 months after inguinal herniorrhaphy Abstract Current trends in orthopaedic surgery have explored different forms of adjuvant treatments to minimize postoperative pain and the risk of nausea and vomiting . A small single preoperative dose of dexamethasone , as part of a comprehensive multimodal analgesic regimen in low-risk patients undergoing total hip arthroplasty ( THA ) , provides antiemetic and opioid-sparing effects but the longer-term effects on pain , complications , or function are not known . We therefore asked whether such a routine would affect longer-term pain , complications , or function . Fifty patients undergoing elective primary THA using spinal anesthesia were initially r and omized to receive either dexamethasone ( 40 mg intravenous ) or saline placebo . The patients , anesthesiologists , nurses , and research coordinators were blinded to the study arms . The functional outcome was measured using the Harris hip score . Outcomes were assessed 6 weeks and 1 year postoperatively . We observed no difference in resting pain between the two groups at either time period . Both groups had similar functional outcome scores for the total Harris hip score and individual scoring items at each followup interval . There were no wound complications , deep infections , or osteonecrosis in the contralateral hip at 1-year followup . We recommend the addition of a small single preoperative dose of dexamethasone to a comprehensive multimodal analgesic regimen in low-risk patients given its immediate antiemetic and opioid-sparing effects , and absence of subsequent effects . Level of Evidence : Level II , therapeutic study ( prospect i ve comparative study ) . See the Guidelines for Authors for a complete description of levels of evidence BACKGROUND : Chronic postsurgical pain ( CPSP ) affects between 5 % and 70 % of surgical patients , depending on the surgery . There is no reliable treatment for CPSP , which has led to an increased emphasis on prevention . In this study , we sought to determine whether preventive etanercept can decrease the magnitude of postoperative pain and reduce the incidence of CPSP . METHODS : We performed a multicenter , r and omized study in 77 patients comparing subcutaneous etanercept 50 mg administered 90 minutes before inguinal hernia surgery with saline . Patients , surgeons , anesthesiologists , the injecting physician , nursing staff , and evaluators were blinded . The primary outcome measure was a 24-hour numerical rating scale pain score . Secondary outcome measures were postanesthesia care unit pain scores , 24-hour opioid requirements , time to first analgesic , and pain scores recorded at 1 month , 3 months , 6 months , and 12 months . RESULTS : Mean 24-hour pain scores were 3.3 ( 95 % confidence interval [ CI ] , 3.2–4.6 ) in the etanercept and 3.9 ( 95 % CI , 2.6–4.0 ) in the control group ( P = 0.22 ) . The mean number of analgesic pills used in the first 24 hours was 4.0 ( SD , 2.8 ) in the treatment versus 5.8 ( SD , 4.2 ) in the control group ( P = 0.03 ) . At 1 month , 10 patients ( 29 % ) in the treatment group reported pain versus 21 ( 49 % ) control patients ( P = 0.08 ) . The presence of pain at 1 month was significantly associated with pain at 3 months ( hazard ratio , 0.74 ; 99 % CI , 0.52–0.97 ; P = 0.03 ) . CONCLUSION : Although preventive etanercept was superior to saline in reducing postoperative pain on some measures , the effect sizes were small , transient , and not statistically significant . Different dosing regimens in a larger population should be explored in future studies Summary Chronic postsurgical pain was common after major surgery in the Evaluation of Nitrous Oxide in the Gas Mixture for Anaesthesia ( ENIGMA ) trial . Nitrous oxide administration was associated with a decrease in the risk of chronic wound pain after surgery . ABSTRACT Nitrous oxide is an antagonist at the N‐methyl‐D‐aspartate receptor and may prevent the development of chronic postsurgical pain . We conducted a follow‐up study in the Evaluation of Nitrous Oxide in the Gas Mixture for Anaesthesia ( ENIGMA ) trial patients to evaluate the preventive analgesic efficacy of nitrous oxide after major surgery . The ENIGMA trial was a r and omized controlled trial of nitrous oxide‐based or nitrous oxide‐free general anesthesia in patients presenting for noncardiac surgery lasting more than 2 hours . Using a structured telephone interview , we contacted all ENIGMA trial patients recruited in Hong Kong ( n = 640 ) . We recorded the severity of postsurgical pain of at least 3 months ’ duration that was not due to disease recurrence or a pre‐existing pain syndrome , using the modified Brief Pain Inventory . The impact of postsurgical pain on quality of life was also measured . Pain intensity , opioid and other analgesic requirements during the first week of surgery , were retrieved from the trial case report form and medical records . A total of 46 ( 10.9 % ) patients reported pain that persisted from the index surgery , and 39 ( 9.2 % ) patients had severe pain . In addition , patients with chronic pain rated poorly in all attributes of the quality ‐of‐life measures compared with those who were pain free . In a multivariate analysis , nitrous oxide decreased the risk of chronic postsurgical pain . In addition , severe pain in the first postoperative week , wound complication , and abdominal incision increased the risk of chronic pain . In conclusion , chronic postsurgical pain was common after major surgery in the ENIGMA trial . Intraoperative nitrous oxide administration was associated with a reduced risk of chronic postsurgical pain BACKGROUND Endometriosis is associated with an inflammatory response . Hence infliximab , an anti-TNF-α monoclonal antibody , might relieve pain . METHODS A r and omized placebo-controlled trial was design ed with 21 women with severe pain and a rectovaginal nodule of at least 1 cm . After 1 month of observation , three infusions of infliximab ( 5 mg/kg ) or placebo were given . Surgery was performed 3 months later and follow-up continued for 6 months . The primary end-point was pain ( dysmenorrhea , deep dyspareunia and non-menstrual pain ) rated at each visit by the clinician and on a daily basis by the patient who in addition scored pain by visual analog pain scale and analgesia intake . Secondary end-points included the volume of the endometriotic nodule , pelvic tenderness and the visual appearance of endometriotic lesions at laparoscopy . RESULTS Pain severity decreased during the treatment by 30 % in both the placebo ( P < 0.001 ) and infliximab groups ( P < 0.001 ) . However , no effect of infliximab was observed for any of the outcome measures . After surgery , pain scores decreased in both groups to less than 20 % of the initial value . CONCLUSIONS Infliximab appears not to affect pain associated with deep endometriosis . Treatment is associated with an important placebo effect . After surgery , pain decreases to less than 20 % . Trials registration number Clinical Trials.gov : NCT00604864 Background : Ketamine potentiates intravenous or epidural morphine analgesia . The authors hypothesized that very-low-dose ketamine infusion reduces acute and long-term postthoracotomy pain . Methods : Forty-nine patients scheduled to undergo open thoracotomy were r and omly assigned to receive one of two anesthesia regimens : continuous epidural infusion of ropivacaine and morphine , along with intravenous infusion of ketamine ( 0.05 mg · kg−1 · h−1 [ approximately 3 mg/h ] , ketamine group , n = 24 ) or placebo ( saline , control group , n = 25 ) . Epidural analgesia was continued for 2 days after surgery , and infusion of ketamine or placebo was continued for 3 days . Pain was assessed at 6 , 12 , 24 , and 48 h after surgery . Patients were asked about their pain , abnormal sensation on the wound , and inconvenience in daily life at 7 days and 1 , 3 , and 6 months after surgery . Results : The visual analog scale scores for pain at rest and on coughing 24 and 48 h after thoracotomy were lower in the ketamine group than in the control group ( pain at rest , 9 ± 11 vs. 25 ± 20 and 9 ± 11 vs. 18 ± 13 ; pain on coughing , 26 ± 16 vs. 50 ± 17 and 30 ± 18 vs. 43 ± 18 , mean ± SD ; P = 0.002 and P = 0.01 , P < 0.0001 and P = 0.02 , respectively ) . The numerical rating scale scores for baseline pain 1 and 3 months after thoracotomy were significantly lower in the ketamine group ( 0.5 [ 0–4 ] vs. 2 [ 0–5 ] and 0 [ 0–5 ] vs. 1.5 [ 0–6 ] , median [ range ] , respectively ; P = 0.02 ) . Three months after surgery , a higher number of control patients were taking pain medication ( 2 vs. 9 ; P = 0.03 ) . Conclusions : Very-low-dose ketamine ( 0.05 mg · kg−1 · h−1 ) potentiated morphine-ropivacaine analgesia and reduced postthoracotomy pain UNLABELLED Postmastectomy pain syndrome ( PMPS ) is a neuropathic pain syndrome that might develop after breast surgery . Like many other forms of neuropathic pain , it is relatively resistant to treatment and negatively affects the quality of life . A double-blind , r and omized , placebo-controlled pilot trial was conducted to study the analgesic efficacy of perioperative administration of the N-methyl-D-aspatrate ( NMDA ) receptor antagonist amantadine in preventing PMPS after mastectomy plus axillary lymph node dissection ( ALND ) . In the study group , a regimen of 200 mg/day of amantadine was started 1 day before surgery and continued for 14 days , whereas the control group received a placebo . Patients were required to indicate the exact location of their pain and to record its level at 1 , 3 , and 6 months after surgery . Neurologic examination and Quantitative Thermal Testing ( QTT ) were performed 1 and 6 months after surgery . On both the neurologic examination and the QTT , all patients , regardless of the perioperative intervention ( amantadine or placebo ) , presented evidence for nerve injury , manifested primarily by painful hypoesthesia ( anesthesia dolorosa ) in the axilla or inner arm . PMPS persisted for the entire duration of the study in 82 % of the patients who were available for follow-up . The average intensity of the pain was moderate in both groups and tended not to decline over time . No differences between the 2 groups in any of the outcome parameters reached statistical significance . According to the results of the present pilot study , the NMDA antagonist amantadine does not prevent the development of PMPS in patients who undergo breast surgery with ALND . PERSPECTIVE Breast surgery that involves ALND seems to uniformly cause nerve injury , which can not be prevented by the perioperative administration of 200 mg of amantadine . It is most commonly presented by painful hypoesthesia or anesthesia dolorosa in the axillary/inner arm area , which is moderate in intensity and likely to persist for at least 6 months BACKGROUND Chronic postsurgical thoracic pain ( CPTP ) represents a major therapeutic challenge characterized by an absence of clinical studies to guide treatment . Recently , the implementation of pulsed radiofrequency ( RF ) has generated intense interest in the medical community as a safe and potentially effective treatment for neuropathic pain . To date , there are no studies comparing pulsed RF to more conventional therapeutic modalities for any pain condition . OBJECTIVES To compare treatment outcomes between pharmacotherapy , pulsed RF of the intercostal nerves ( ICN ) and pulsed RF of the dorsal root ganglia ( DRG ) in CPTP . METHODS Retrospective data analysis involving 49 patients . RESULTS At 6-week follow-up , 61.5 % of the pulsed RF DRG group reported > or = 50 % pain relief vs. 27.3 % in the medical management ( MM ) group and 21.4 % in the IC group ( P = 0.12 ) . At 3-month follow-up , 53.8 % in the DRG group continued to report > or = 50 % pain relief vs. 19.9 % in the MM and 6.7 % in the ICN groups , respectively ( P = 0.02 ) . Among the pulsed RF patients who did report a successful outcome , the mean duration of pain relief was 2.87 months in the ICN group and 4.74 months in the DRG group ( P = 0.01 ) . CONCLUSIONS Pulsed RF of the DRG was a superior treatment to pharmacotherapy and pulsed RF of the ICN in patients with CPTP . Prospect i ve studies are needed to confirm these results and identify the best c and i date s for this treatment Purpose Much remains unknown about the relationship between acute postoperative pain and the development of pathologic chronic postsurgical pain ( CPSP ) . The purpose of this project was to identify the extent to which maximum pain scores on movement over the first two days after total hip arthroplasty predicted the presence of chronic pain 6 months later after controlling for potentially important covariates . Methods The sample comprised 82 of 114 patients who participated in a double-blinded r and omized controlled trial in which all patients received acetaminophen 1 g p.o . , celecoxib 400 mg p.o . , and dexamethasone 8 mg i.v . , 1–2 h preoperatively . In addition , patients received gabapentin ( GBP ) 600 mg ( G2 ) or placebo ( G1 and G3 ) 2 h prior to surgery [ G1 : placebo/placebo ( n = 38 ) ; G2 : GBP/placebo ( n = 38 ) ; G3 : placebo/GBP ( n = 38 ) ] . In the PACU , patients received gabapentin 600 mg ( G3 ) or placebo ( G1 and G2 ) . Follow-up data from the 82 patients who were contacted by telephone 6 months postsurgery were used for the current study . Results Maximal movement-evoked pain intensity over the first two postoperative days ( P = 0.38 ) failed to predict the presence of CPSP 6 months later after controlling for age ( P = 0.09 ) , treatment group ( P = 0.91 ) , and cumulative morphine consumption ( P = 0.8 ) ( multivariate logistic regression likelihood ratio test against the intercept only model P = 0.59 ) . Conclusion Neither maximum movement-evoked acute pain , nor any other factor measured , predicted the presence of CPSP at 6 months . Further research is needed to identify risk factors for CPSP after total hip arthroplasty Purpose To assess the analgesic efficacy and functional outcome of postoperative epidural infusion of ropivacaine combined with sufentanil in a r and omized , controlled trial . Methods Thirty-two ASA I – III patients undergoing elective total hip replacement ( THR ) were included . Lumbar epidural block using 0.75 % ropivacaine was combined with either propofol sedation or general anesthesia for surgery . On arrival in the recovery room , the epidural infusion was commenced at a rate in mL calculated as follows : ( height in cm −100 ) × 0.1 . Eleven patients received an epidural infusion of ropivacaine 0.1 % with 0.5 μg·mL−1 sufentanil ( Group R+S0.5 ) , ten patients ropivacaine 0.1 % with 0.75 μg·mL−1 sufentanil ( Group R+S0.75 ) , and 11 patients ropivacaine 0.1 % with 1 μg·mL−1 sufentanil ( Group R+S1 ) over a postoperative study period of 44 hr . All patients had access to iv piritramide via a patient-controlled analgesia ( PCA ) device . Postel-Merle-d’Aubigné scoring system ( PMA score ) was assessed preoperatively , three weeks after surgery , and three months after surgery by an orthopedic surgeon blinded to study group . Results Motor block was negligible in all three groups . After eight hours of epidural infusion , sensory block had regressed completely in all patients . There was no significant difference with regard to visual analogue scale ( VAS ) scores ( at rest : P = 0.55 , on movement : P = 0.63 ) , consumption of rescue medication ( P = 0.99 ) , patient satisfaction ( P = 0.22 ) , and the incidence of adverse events . All treatment regimens provided effective postoperative analgesia with only a minimal use of supplemental opioid PCA . There was no difference between groups regarding orthopedic PMA score ( pain : P = 0.24 , mobility : P = 0.65 , and ability to walk : P = 0.44 ) . Conclusion Ropivacaine 0.1 % with 0.5 μg·mL−1 sufentanil for postoperative analgesia after THR provides efficient pain relief and , compared with 0.75 and 1 μg·mL−1 sufentanil , reduces sufentanil consumption without compromise in patient satisfaction , VAS scores , and functional outcome .RésuméObjectifÉvaluer , par une étude r and omisée et contrôlée , l’efficacité analgésique et les effets fonctionnels d’une perfusion péridurale postopératoire de ropivacaïne combinée au sufentanil . MéthodeL’étude a été menée auprès de 32 patients d’état physique ASA I – III , devant subir une arthroplastie totale de hanche ( ATH ) . Le bloc péridural lombaire réalisé avec de la ropivacaïne à 0,75 % , a été combiné à une sédation au propofol ou à une anesthésie générale pour l’intervention chirurgicale . La perfusion péridurale , débutée dès l’arrivée en salle de réveil , avait un débit en mL calculé comme suit : ( la taille en cm −100 ) × 0,1 . Onze patients ont reçu une perfusion péridurale de ropivacaïne à 0,1 % combinée à 0,5 μg·mL−1 de sufentanil ( Groupe R+S0,5 ) , dix ont eu de la ropivacaïne à 0,1 % et 0,75μg·mL−1 de sufentanil ( Groupe R+S0,75 ) et onze , de la ropivacaïne à 0,1 % avec 1 μg·mL−1 de sufentanil ( Groupe R+S1 ) pendant les 44 h postopératoires de l’étude . Tous les patients avaient accès à une analgésie autocontrôlée ( AAC ) iv avec piritramide . Le score de Postel-Merle d’Aubigné ( score PMA ) a été évalué avant l’opération , trois semaines et trois mois après l’opération , par un chirurgien orthopédique impartial . RésultatsLe blocage moteur a été négligeable dans les trois groupes . Après huit heures de perfusion péridurale , le bloc sensitif avait complètement régressé chez tous les patients . Il n’y a pas eu de différence significative des scores de l’échelle visuelle analogique ( au repos : P = 0,55 , au mouvement : P = 0,63 ) , de consommation de médication de secours ( P = 0,99 ) , de satisfaction des patients ( P = 0,22 ) et d’incidence d’événements indésirables . Tous les schémas posologiques ont produit une analgésie postopératoire efficace et n’ont nécessité qu’un usage minimal d’opioïde supplémentaire en AAC . Le score orthopédique PMA était similaire entre les groupes ( douleur : P = 0,24 , mobilité : P = 0,65 et capacité de marcher : P = 0,44 ) . Conclusion De la ropivacaïne à 0,1 % combinée à 0,5μg·mL−1 de sufentanil , utilisée comme analgésie postopératoire après une ATH , réduit efficacement la douleur et , comparé à 0,75 et 1 μg·mL−1 de sufentanil , réduit la consommation de sufentanil sans compromettre la satisfaction des patients , les scores à l’EVA et les effets fonctionnels Background and objective Local anaesthetics administered intraabdominally have been found to reduce analgesic requirements postoperatively after hysterectomy . This study was design ed to assess the optimal dose of local anaesthetics for best pain relief . Methods Sixty patients undergoing abdominal hysterectomy were r and omly divided into three groups to receive 10 ml h−1 infusion of levobupivacaine intraabdominally postoperatively for 48 h in a double-blind manner : group L , 7.5 mg h−1 ; group M , 12.5 mg h−1 and group H , 17.5 mg h−1 . Pain intensity was measured using the numeric rating scale , ketobemidone consumption over 48 h was measured with a patient-controlled analgesia pump , recovery parameters , expiratory muscle strength , time to home readiness , plasma concentration of levobupivacaine and health-related quality of life were all measured at defined time points postoperatively . Results No differences were found between the active groups in pain intensity , recovery parameters or health-related quality of life . Pain intensity was maximal during 0–4 h and during coughing . Expiratory muscle strength decreased significantly during 0–4 h in all active groups , with no differences between the groups . Plasma concentration of levobupivacaine was below known toxic concentrations in humans , and no patient had symptoms of local anaesthetic toxicity . Health-related quality of life showed improved scores at 3 months after the operation compared with preoperative values , but no differences between the groups were found in any of the parameters . Conclusion Satisfactory analgesia can be achieved with low doses of levobupivacaine administered intraabdominally , except during the early postoperative period . No advantages were seen in this study when higher doses of levobupivacaine were administered as a continuous infusion for postoperative pain relief BACKGROUND : Gabapentin and ketamine are popular analgesic adjuvants for improving perioperative pain management . We design ed this double-blind , placebo-controlled study to test and compare the preventive effects of perioperative ketamine and gabapentin on early and chronic pain after elective hysterectomy . METHODS : Sixty patients undergoing abdominal hysterectomy were r and omly assigned to 1 of the following 3 groups : control group received oral placebo capsules and bolus plus infusion of saline ; ketamine group received oral placebo capsules and , before incision , 0.3 mg/kg IV bolus and 0.05 mg·kg−1·h−1 infusion of ketamine until the end of surgery ; and gabapentin group received oral gabapentin 1.2 g and bolus plus infusion of saline . The anesthetic technique was st and ardized , and the postoperative assessment s included verbal rating scales for pain and sedation , IV morphine usage , quality of recovery assessment , recovery of bowel function , resumption of normal activities , and patient satisfaction with their pain management . Patients were question ed at 1 , 3 , and 6 mo after surgery for chronic postoperative pain . RESULTS : Postoperative pain scores were significantly lower in the gabapentin group compared with the ketamine and control groups , and patient-controlled analgesia morphine use was significantly reduced in both treatment groups ( versus control group ) ( P < 0.001 ) . Total patient-controlled analgesia morphine use was decreased by 35 % and 42 % in the ketamine and gabapentin groups , respectively , compared with the control group ( P < 0.001 ) . Patient satisfaction with pain treatment was significantly improved in the ketamine and gabapentin groups compared with the control group ( P < 0.001 ) . The incidence of incisional pain and related pain scores at the 1- , 3- , and 6-mo follow-up were significantly lower in the gabapentin group compared with the ketamine and control groups ( P < 0.001 ) . CONCLUSION : Gabapentin and ketamine are similar in improving early pain control and in decreasing opioid consumption ; however , gabapentin also prevented chronic pain in the first 6 postoperative months In this clinical , r and omized , prospect i ve study , we compared the effects of three different analgesia techniques ( thoracic epidural analgesia [ TEA ] with and without preoperative initiation and IV patient-controlled analgesia [ IV-PCA ] ) on postthoracotomy pain in 69 patients . In two groups , a thoracic epidural catheter was inserted preoperatively . Group Pre-TEA had bupivacaine and morphine solution preoperatively and intraoperatively . Postoperative analgesia was maintained with epidural PCA with a similar solution . Group Post-TEA , with no intraoperative medication , had the same postoperative analgesia as Group Pre-TEA plus the bolus dose . Group IV-PCA received only IV-PCA with morphine for postoperative analgesia . Pain was evaluated every 4 h during the first 48 h at rest , cough , and movement . Pre-TEA was associated with decreased pain compared with the other groups . Six months later , the patients were asked about their pain . The incidence and the intensity of pain were most frequent in Group IV-PCA ( 78 % ) and were the least in Group Pre-TEA ( 45 % ) ( Group Pre-TEA versus Group IV-PCA , P = 0.0233 ; Group Pre-TEA versus Group IV-PCA , P = 0.014 ) . Patients having pain on the second postoperative day had 83 % chronic pain . TEA with preoperative initiation is a preferable method in preventing acute and long-term thoracotomy pain Abstract Objectives To determine the benefits and risks of a non-steroidal anti-inflammatory drug ( NSAID ) as prophylaxis for ectopic bone formation in patients undergoing total hip replacement ( or revision ) surgery . Design Double blind r and omised placebo controlled clinical trial , stratified by treatment site and surgery ( primary or revision ) . Setting 20 orthopaedic surgery centres in Australia and New Zeal and . Participants 902 patients undergoing elective primary or revision total hip replacement surgery . Intervention 14 days ' treatment with ibuprofen ( 1200 mg daily ) or matching placebo started within 24 hours of surgery . Main outcome measures Changes in self reported hip pain and physical function 6 to 12 months after surgery ( Western Ontario and McMaster University Arthritis index ) . Results There were no significant differences between the groups for improvements in hip pain ( mean difference −0.1 , 95 % confidence interval −0.4 to 0.2 , P = 0.6 ) or physical function ( −0.1 , −0.4 to 0.2 , P = 0.5 ) , despite a decreased risk of ectopic bone formation ( relative risk 0.69 , 0.56 to 0.83 ) associated with ibuprofen . There was a significantly increased risk of major bleeding complications in the ibuprofen group during the admission period ( 2.09 , 1.00 to 4.39 ) . Conclusions These data do not support the use of routine prophylaxis with NSAIDs in patients undergoing total hip replacement surgery . Trial registration NCT00145730 [ Clinical Trials.gov ] Background and purpose The degree of postoperative pain is usually moderate to severe following knee arthroplasty . We investigated the efficacy of local administration of analgesics into the operating area , both intraoperatively and postoperatively . Methods 40 patients undergoing unicompartmental knee arthroplasty ( UKA ) were r and omized into 2 groups in a double – blind study ( Clinical Trials.gov identifier : NCT00653926 ) . In group A ( active ) , 200 mg ropivacaine , 30 mg ketorolac , and 0.5 mg epinephrine ( total volume 106 mL ) were infiltrated intraoperatively into the soft tissue , while in group P ( placebo ) , no injections were given . 21 hours postoperatively , 150 mg ropivacain , 30 mg ketorolac , and 0.1 mg epinephrine were injected intraarticularly via a catheter in group A , whereas patients in group P were injected with the same volume of saline ( 22 mL ) . Results Median hospital stay was shorter in group A than in group P : 1 ( 1–6 ) days as opposed to 3 ( 1–6 ) days ( p < 0.001 ) . Postoperative pain in group A was statistically significantly lower at rest after 6 h and 27 h and on movement after 6 , 12 , 22 , and 27 h. Morphine consumption was statistically significantly lower in group A for the first 48 h , result ing in a lower frequency of nausea , pruritus , and sedation . Postoperatively , there were improved functional scores ( Oxford knee score and EQ–5D ) in both groups relative to the corresponding preoperative values . Interpretation Local injection of analgesics periarticularly at the end of the operation and intraarticularly at 21 h postoperatively provided excellent pain relief and earlier home discharge following UKA . There was a high degree of patient satisfaction in both groups after 6 months ( Clinical Trials.gov : NCT 00653926 ) 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 AFTER surgical procedures such as amputation , mastectomy , and thoracotomy , as many as 60 % of patients continue to experience pain for at least 6 months , with approximately 10 % reporting severe pain . These chronic postsurgical pain conditions have major adverse effects on health-related quality of life , including physical functioning and emotional well-being . Unfortunately , the efficacy of existing treatments is limited and many patients remain refractory to currently available therapies . For this reason , the development of interventions that prevent chronic pain after surgery has the potential to have a major impact on public health . Substantial attention has been devoted to the hypothesis that the incidence of chronic postsurgical pain can be reduced by “ preventive ” analgesia , and the benefits of preoperative , intraoperative , and postoperative analgesic interventions have been investigated alone and in various combinations . Although the results of these studies suggest that reduced acute pain and analgesic consumption can extend beyond the duration of action of the preventive analgesic interventions , there is little evidence that chronic postsurgical pain can be prevented . Placebocontrolled r and omized clinical trials are needed to determine what specific analgesic interventions are efficacious for preventing chronic pain after what types of surgery for which patients . – 6 A critical component of future clinical trials will involve determining the clinical importance of the benefits of preventive analgesia . The results of recent studies and consensus recommendations provide a foundation for interpreting the benefits of chronic pain treatment ; however , little attention has been paid to determining what magnitudes of chronic pain prevention are clinical ly meaningful . As is true of treatment benefits , evaluating the importance of preventive benefits involves a frequently misunderstood distinction between the interpretation of the clinical importance of individual patient benefits and the interpretation of the clinical importance of group differences . The results of multiple studies have shown that individual patients consider chronic pain reductions of at least 30 % on numerical or visual analog scales to be moderately clinical ly important , whereas reductions of at least 50 % represent substantial improvements . These thresholds are based on ratings by patients of their own improvement at the end of chronic pain trials , and consistent results have been found across different chronic pain conditions and in patients administered active treatments as well as placebo . Criteria for identifying clinical ly meaningful individual improvements are necessary to categorize patients as “ responders ” or “ nonresponders , ” which makes it possible to compare the percentages of patients who achieve clinical ly important outcomes between different treatment and comparison groups . Unfortunately , criteria for determining clinical ly important improvements in patients being treated for chronic pain can not be extrapolated to those undergoing perioperative analgesic interventions to prevent chronic pain . Currently , there are no data that make it possible to determine whether patients who have not experienced chronic pain would consider its prevention after surgery important enough to undergo preoperative , intraoperative , and postoperative analgesic interventions . Evaluations of individual patient improvements associated with chronic pain treatments have emphasized pain reduction , but patients considering the prevention of conditions for which their risk is relatively low can also be expected to be particularly concerned with the adverse effects , safety risks , inconvenience , and costs of the preventive intervention . It is likely that an efficacious preventive analgesia would not completely prevent chronic pain but would instead partially reduce its incidence , intensity , or duration . Such partial preventive benefits would , of course , be even harder for patients to evaluate ; for example , would patients consider reducing pain intensity 6 months after surgery from a daily average of 4 to 2 on a 0–10 scale a clinical ly important benefit ? Would this evaluation change if this reduction in pain intensity at 6 months is known to last for another 2 yr , or if the preventive intervention requires that patients take a medication that causes sedation , nausea , and constipation for 7 days before and 30 days after their operation ? Evaluations of the clinical importance of preventive analgesia must reflect the magnitude of the reductions in chronic pain incidence , intensity , or duration that the intervention would provide . However , even small reductions in the incidence or intensity of a chronic pain condition that can last for months or even years might be considered clinical ly important by patients if Accepted for publication November 17 , 2009 . The authors are not supported by , nor maintain any financial interest in , any commercial activity that may be associated with the topic of this article Before implementing a new therapy , we should ascertain the benefits and risks of the therapy and assure ourselves that the re sources consumed during the intervention will not be exorbitant . In the hierarchy of research design s , the results of r and omized controlled trials , especially if systematic ally review ed , are considered the highest level of evidence . We suggest a three-step approach to using an article from the medical literature to guide your patient care . We recommend that readers ask whether the study can provide valid results , review the results , and consider how the results can be applied to patient care . Given the time constraints of busy surgical practice s and surgical training programs , applying this analysis to every relevant article will be challenging . However , the basis of this process is essentially what we all do many times each week when making decisions about whether and how to treat patients . Making this process explicit with guidelines to assess the strength of the available evidence can serve to improve patient care . It also allow us to defend therapeutic interventions based on available evidence and not anecdote Purpose Non-opioid analgesics are increasingly used as part of a multimodal regimen for pain management . This prospect i ve , r and omized , double-blinded , placebo-controlled study was design ed to evaluate the effect of short-term postoperative administration of celecoxib on pain management and recovery outcomes following laparoscopic surgery . Methods Eighty consenting ASA I-III out patients undergoing laparoscopic surgery were r and omly assigned to one of two treatment groups : Control ( placebo ) or Celecoxib ( celecoxib , 400 mg·day-1 ) . The initial dose ( celecoxib 400 mg or placebopo ) was administered in the recovery room , and celecoxib 200 mg ( or a placebo)po bid was continued for three additional days after surgery . Postoperative pain scores and the need for opi-oid-containing analgesics were recorded at specific intervals in the recovery room . Follow-up evaluations were performed at 24 hr , 48 hr , 72 hr and seven days and one month after surgery to assess post-discharge pain , analgesic requirements , complications , quality of recovery , and resumption of normal activities , as well as patient satisfaction with their pain management . Results Celecoxib reduced mean pain scores and the need for analgesics at 24 hr and 48 hr postoperatively . Patient satisfaction with their postoperative pain management was also higher in the Celecoxib group ( 94 ± 8 vs 80 ± 25,P < 0.05 ) . Quality of recovery scores were significantly higher in the Celecoxib group on the first and second postoperative days ( 17 ± 1 vs 15 ± 2 , and 18 ± 1 vs 16 ± 2 , respectively ) . Finally , bowel function recovered an average of one day earlier and patients resumed activities of daily living two days earlier in the Celecoxib group ( P < 0.05 ) . ConclusionS hort-term administration of celecoxib , 400 mg·day−1po , decreased postoperative pain and the need for opioid-containing analgesic medication , leading to an improved quality of recovery after outpatient laparoscopic surgery . RésuméObjectifLes analgésiques non-opiacés sont de plus en plus utilisés dans le cadre d’un régime multimodal pour le traitement de la douleur . Cette étude prospect i ve , r and omisée , à double insu et contrôlée par placebo a été effectuée afin de déterminer l’effet de l’administration postopératoire à court terme de célécoxib sur le traitement de la douleur et la convalescence suite à une chirurgie laparoscopique . MéthodeQuatre-vingt patients ASA I-III non hospitalisés subissant une chirurgie laparoscopique ont été r and omisés en deux groupes de traitement : Témoin ( placebo ) ou Célécoxib ( célécoxib , 400 mg·jour−1 ) . La dose initiale ( célécoxib 400 mg ou placebo po ) a été administrée à la salle de réveil , et l’administration de célécoxib 200 mg ( ou un placebo ) po a été continuée deux fois par jour pendant trois jours suivant l’opération . La douleur postopératoire et les besoins en analgésiques à base d’opiacés ont été mesurés à des intervalles spécifiques à la salle de réveil . Des examens de contrôle ont été effectués 24 h , 48 h , 72 h , sept jours et un mois après la chirurgie afin d’évaluer la douleur suite au congé de l’hôpital , les besoins analgésiques , les complications , la qualité du rétablissement et la reprise des activités normales , ainsi que la satisfaction des patients quant au traitement de la douleur . RésultatsLe célécoxib a réduit les scores moyens de douleur ainsi que le besoin d’analgésiques à 24h et 48h après l’opération . La satisfaction des patients quant au traitement postopératoire de la douleur qu’ils ont reçu était également plus élevée dans le groupe célécoxib ( 94 ±8 vs 80 ± 25,P < 0,05 ) . Les résultats de la qualité du rétablissement étaient significativement plus élevés dans le groupe célécoxib le premier et le deuxième jour après l’opération ( 17±1vs15±2,et18 ± 1 vs 16 ± 2 , respectivement ) . Finalement , la fonction intestinale a été rétablie en moyenne un jour plus tôt et les patients ont repris leurs activités quotidiennes deux jours plus tôt dans le groupe célécoxib ( P < 0,05 ) . Conclusion L’administration à court terme de célécoxib 400 mg·jour−1 po a diminué la douleur postopératoire et le besoin de médication analgésique à base d’opiacés , ce qui a engendré une qualité de rétablissement améliorée après la chirurgie laparoscopi-que sans hospitalisation OBJECTIVE To evaluate the effectiveness for the outcomes of endometriosis-related pain and quality of life of conservative surgery plus placebo compared with conservative surgery plus hormonal suppression treatment or dietary therapy . DESIGN R and omized comparative trial . SETTING University hospital . PATIENT(S ) Two hundred twenty-two consecutive women who underwent conservative pelvic surgery for symptomatic endometriosis stage III-IV ( r-AFS ) . INTERVENTION(S ) Six months of placebo ( n = 110 ) versus GnRH-a ( tryptorelin or leuprorelin , 3.75 mg every 28 days ) ( n = 39 ) or continuous estroprogestin ( ethynilestradiol , 0.03 mg plus gestoden , 0.75 mg ) ( n = 38 ) versus dietary therapy ( vitamins , minerals salts , lactic ferments , fish oil ) ( n = 35 ) . MAIN OUTCOME MEASURE(S ) Painful symptoms ( visual analogue scale score ) and quality -of-life endometriosis-related symptoms ( SF-36 score ) at 12 months ' follow-up . RESULT ( S ) Patients treated with postoperative hormonal suppression therapy showed less visual analogue scale scores for dysmenorrhoea than patients of the other groups . Hormonal suppression therapy and dietary supplementation were equally effective in reducing nonmenstrual pelvic pain . Surgery plus placebo showed significative decrease in dyspareunia scores . Postoperative medical and dietary therapy allowed a better quality of life than placebo . CONCLUSION ( S ) Postoperative hormonal suppression treatment or dietary therapy are more effective than surgery plus placebo to obtain relief of pain associated with endometriosis stage III-IV and improvement of quality of life Objectives Postmastectomy pain syndrome is a neuropathic pain syndrome that is known to develop after breast surgery . Preemptive analgesia has been shown to be efficacious in reducing postoperative pain , and may be effective in reducing the incidence of certain types of neuropathic pain . We investigated the analgesic efficacy of Venlafaxine and gabapentin on acute and chronic pain associated with cancer breast surgery . Patients and Methods The study was carried out on 150 patients scheduled for either partial or radical mastectomy with axillary dissection . They were r and omized in a double-blinded manner to receive , extended release Venlafaxine 37.5 mg/d , gabapentin 300 mg/d , or placebo for 10 days starting the night before operation . Pain scores were recorded at rest and movement ( visual analog scale ) at 4 , 12 , and 24 hours on the first day postoperatively , daily from the second to tenth day postoperatively and visual analog scale in addition to pain character 6 months later . Analgesic requirements were compared between the 3 groups . Results Pain after movement was reduced by gabapentin from the second to tenth postoperative day and venlafaxine group in the last 3 days but no difference was found between the groups regarding pain during rest . Gabapentin reduced morphine consumed in the first 24 hours postoperatively . The analgesic requirements from the second to tenth days for codeine and paracetamol were reduced in venlafaxine and gabapentin groups compared to the control group . Six months later , the incidence of chronic pain , its intensity , and need for analgesics were reduced in venlafaxine compared to gabapentin and the placebo group . However , burning pain was more frequent in the control groups than in the gabapentin . Conclusion Venlafaxine 37.5 mg/d extended release or gabapentin 300 mg/d have equipotent effects ( except on the first day in venlafaxine group ) in reducing analgesic requirements , although gabapentin is more effective in reducing pain after movement . Venlafaxine significantly reduced the incidence of postmastectomy pain syndromes ( chronic pain ) 6 months in women having breast cancer surgery . Gabapentin had no effect on chronic pain except decreasing incidence of burning pain BACKGROUND : Despite the enormous success of total knee arthroplasty ( TKA ) , chronic neuropathic pain can develop postoperatively and is both distressing and difficult to treat once established . We hypothesized that perioperative treatment with pregabalin , a chronic pain medication , would reduce the incidence of postsurgical neuropathic pain . METHODS : We performed a r and omized , placebo-controlled , double-blind trial of pregabalin ( 300 mg ) administered before TKA and for 14 days after TKA ( 150–50 mg twice daily ) . Patients were screened for the presence of neuropathic pain at 3 and 6 mo postoperatively using the Leeds Assessment of Neuropathic Symptoms and Signs scale . Secondary outcomes included postsurgical recovery and rehabilitation measures , including knee range of motion , opioid consumption , postoperative pain scores , sleep disturbance , and time to discharge as well as the occurrence of postoperative systemic complications . RESULTS : Of the 240 patients r and omly assigned to the 2 treatment groups ( 120 in each ) , data for the primary outcome were obtained from 113 pregabalin patients and 115 placebo patients . At both 3 and 6 mo postoperatively , the incidence of neuropathic pain was less frequent in the pregabalin group ( 0 % ) compared with the placebo group ( 8.7 % and 5.2 % at 3 and 6 mo , respectively ; P = 0.001 and P = 0.014 ) . Patients receiving pregabalin also consumed less epidural opioids ( P = 0.003 ) , required less oral opioid pain medication while hospitalized ( P = 0.005 ) , and had greater active flexion over the first 30 postoperative days ( P = 0.013 ) . There were no differences in the actual recorded duration of hospitalization between the 2 groups , although time to achieve hospital discharge criteria was longer for placebo patients , 69.0 ± 16.0 h ( mean ± sd ) , than that of pregabalin patients , 60.2 ± 15.8 h ( P = 0.001 ) . Sedation ( P = 0.005 ) and confusion ( P = 0.013 ) were more frequent on the day of surgery and postoperative day 1 in patients receiving pregabalin . CONCLUSION : Perioperative pregabalin administration reduces the incidence of chronic neuropathic pain after TKA , with less opioid consumption and better range of motion during the first 30 days of rehabilitation . However , in the doses tested , it is associated with a higher risk of early postoperative sedation and confusion Purpose To examine the effect of continuous epidural block initiated before thoracic surgery upon early and long-term postoperative pain . Methods In a double-blind study , 70 patients scheduled for thoracic surgery under general anesthesia were assigned r and omly to receive continuous epidural block with mepivacaine 1.5 % initiated either 20 min before surgical incision ( Pre group ) or at completion of surgery ( Post group ) . In both groups the initial dose was 4 ml , followed by a continuous infusion at 4 ml·hr−1 until 72 hr after operation . Indomethadn suppositories , 50 mg , were administered on request as supplementary analgesics . Visual analogue scale at rest was assessed four hours after operation , and then every 24 hr after operation on postoperative days 1 through 7 , and also days 14 and 30 . At three and six months after operation , all patients were interviewed by telephone with respect to postoperative pain . The most severe pain was assessed using modified numerical rating scale . Results By a visual analogue scale , postoperative pain was less in the Pre group than in the Post group at four hours , two and three days after operation ( P < 0.05 ) . By a numerical rating scale six months after operation , pain was less in the Pre group than in the Post group ( P = 0.015 ) . The percentage of pain-free patients was higher in the Pre group than in the Post group at three ( P = 0.035 ) and six ( P = 0.0086 ) months after operation . Conclusion Continuous epidural block initiated prior to surgery may reduce long-term post-thoracotomy pain . RésuméObjectifExaminer l’effet d’un blocage épidural continu , amorcé avant une intervention chirurgicale thoracique , sur la douleur postopératoire précoce et de long terme . MéthodeLétude à double insu a porté sur 70 patients qui devaient subir une opération thoracique sous anesthésie générale . Répartis au hasard , ils ont reçu un blocage épidural continu avec de la mépivacaïne à 1,5 % , administrée soit 20 min avant l’incision chirurgicale ( groupe Pré ) , soit à la fin de l’intervention ( groupe Post ) . Pour tous , la dose initiale a été de 4 ml suivie d’une perfusion continue à 4 ml·hr−1 jusqu’à 72 h après l’opération . Des suppositoires de 50 mg d’indométhacine ont été administrés sur dem and e pour compléter l’analgésie . La douleur a été évaluée au repos selon l’échelle visuelle analogique , 4 h après l’opération et puis à toutes les 24 h des jours 1 à 7 et aussi les jours 14 et 30 . Trois mois et six mois après l’opération , tous les patients ont été interrogés par téléphone au sujet de la douleur postopératoire . La douleur la plus sévère a été évaluée en utilisant une échelle d’estimation numérique modifiée . RésultatsSelon l’échelle visuelle analogique , la douleur postopératoire était plus faible chez les patients du groupe Pré que chez ceux du groupe Post à 4 h , deux et trois jours après l’opération ( P < 0,05 ) . Selon une échelle d’estimation numérique , la douleur était moins intense chez les patients du groupe Pré que chez ceux du groupe Post ( P = 0,015 ) six mois après l’opération . Le pourcentage de patients sans douleur était plus élevé dans le groupe Pré que dans le groupe Post à trois mois ( P = 0,035 ) et à six mois ( P = 0,0086 ) après l’opération . Conclusion Le blocage épidural continu amorcé avant l’intervention chirurgicale peut réduire la douleur qui se prolonge après une thoracotomie Background and Objectives Acute stump pain and phantom limb pain after amputation is a significant problem among amputees with a reported incidence of phantom limb pain in the first year following amputation as high as 70 % . Epidural analgesia before limb amputation is commonly used to reduce postamputation acute stump pain in the immediate postoperative period and phantom pain in the first year . We investigated whether immediate postamputation stump pain and phantom pain in the first year is reduced by preoperative epidural block with bupivacaine and diamorphine compared with intraoperative placement of a perineural catheter infusing bupivacaine . Methods In a r and omized prospect i ve trial , 30 patients scheduled for lower limb amputation were r and omly assigned epidural bupivacaine at the st and ard rate used in our hospital ( 0.166 % , 2 to 8 mL/h ) and diamorphine ( 0.2 to 0.8 mg/h ) for 24 hours before and during operation ( 14 patients ; epidural group ) and 3 days postoperatively , or an intraoperatively placed perineural catheter ( 16 patients ; perineural group ) for intra and postoperative administration of bupivacaine ( 0.25 % , 10 mL/h ) . All patients had general anesthesia for the amputation and were asked about stump and phantom pain in the first 3 days and then at 6 and 12 months by an independent examiner . Study endpoints were rate of stump and phantom pain , intensity of stump and phantom pain , and consumption of opioids . The groups were well matched in baseline characteristics . Results Stump pain scores in the first 3 days were significantly higher in the perineural group compared with the epidural group ( P < .01 ) . After 3 days , 4 ( 29 % ) patients in the epidural group and 7 ( 44 % ) in the perineural group had phantom pain ( P = .32 ) . Numbers of patients with phantom pain for epidural versus perineural group were : 5 ( 63 % ) versus 7 ( 88 % ) ( P = .25 ) at 6 months ; 3 ( 38 % ) versus 4 ( 50 % ) ( P = .61 ) at 12 months . Stump pain and phantom sensation were similar in both groups at 6 and 12 months . Conclusions Using our regimen , perioperative epidural block started 24 hours before the amputation is not superior to infusion of local anaesthetic via a perineural catheter in preventing phantom pain , but gives better relief of stump pain in the immediate postoperative period BACKGROUND Chronic post-thoracotomy pain ( CPTP ) consists of different types of pain . Some characteristics of CPTP are the same as those of recognized neuropathic pain syndromes . OBJECTIVE We aim ed to determine the safety and efficacy of gabapentin ( GP ) in comparison to naproxen sodium ( NS ) in patients with CPTP . METHODS Forty consecutive patients with CPTP after posterolateral/lateral thoracotomy were prospect ively evaluated . Twenty patients were given GP and another 20 were given NS treatment . Visual Analogue Scale ( VAS ) and the Leeds Assessment of Neuropathic Symptoms and Signs ( LANSS ) scorings were performed pretreatment ( day 0 ) and on the 15th , 30th , 45th and 60th days . Adverse events were question ed . The mean ages were 45.7+/-14.9 and 49.8+/-15.2 years and the mean duration s of pain were 3.8+/-0.9 and 3.8+/-1.1 months , respectively . RESULTS The mean pretreatment VAS scores ( VAS0 ) were 6.4+/-0.6 and 6.8+/-0.6 , the mean pretreatment LANSS scores ( LANSS0 ) were 18.85+/-1.6 and 20.75+/-2.6 in GP and NS groups , respectively ( p>0.05 ) . Minor adverse events which did not m and ate discontinuation of treatment were observed in seven patients ( 35 % ) in the GP and in four patients ( 20 % ) in the NS group . The number of patients with a VAS score < 5 at the latest follow-up ( VAS60 < 5 ) was 17 ( 85 % ) and 3 ( 15 % ) in GP and NS groups , respectively ( p<0.001 ) . Seventeen patients ( 85 % ) in the GP and 0 patients ( 0 % ) in the NS group had a LANSS score < 12 at the latest follow-up . CONCLUSION Gabapentin is safe and effective in the treatment of CPTP with minimal side effects and a high patient compliance . These results should be supported with multidisciplinary studies with larger sample sizes and longer follow-ups BACKGROUND Continuous passive motion after major knee surgery optimizes the functional prognosis but causes severe pain . The authors tested the hypothesis that postoperative analgesic techniques influence surgical outcome and the duration of convalescence . METHODS Before st and ardized general anesthesia , 56 adult scheduled for major knee surgery were r and omly assigned to one of three groups , each to receive a different postoperative analgesic technique for 72 h : continuous epidural infusion , continuous femoral block , or intravenous patient-controlled morphine ( dose , 1 mg ; lockout interval , 7 min ; maximum dose , 30 mg/4 h ) . The first two techniques were performed using a solution of 1 % lidocaine , 0.03 mg/ml morphine , and 2 microg/ml clonidine administered at 0.1 ml x kg(-1 ) x h(-1 ) . Pain was assessed at rest and during continuous passive motion using a visual analog scale . The early postoperative maximal amplitude of knee flexion was measured during continuous passive motion at 24 h and 48 h and compared with the target levels prescribed by the surgeon . To evaluate functional outcome , the maximal amplitudes were measured again on postoperative day 5 , at hospital discharge ( day 7 ) , and at 1- and 3-month follow-up examinations . When the patients left the surgical ward , they were admitted to a rehabilitation center , where their length of stay depended on prospect ively determined discharge criteria RESULTS The continuous epidural infusion and continuous femoral block groups showed significantly lower visual analog scale scores at rest and during continuous passive motion compared with the patient-controlled morphine group . The early postoperative knee mobilization levels in both continuous epidural infusion and continuous femoral block groups were significantly closer to the target levels prescribed by the surgeon than in the patient-controlled morphine group . On postoperative day 7 , these values were 90 degrees ( 60 - 100 degrees)(median and 25th-75th percentiles ) in the continuous epidural infusion group , 90 degrees ( 60 - 100 degrees ) in the continuous femoral block group , and 80 degrees ( 60 - 100 degrees ) in the patient-controlled morphine group ( P < 0.05 ) . The duration s of stay in the rehabilitation center were significantly shorter : 37 days ( range , 30 - 45 days ) in the continuous epidural infusion group , 40 days ( range , 31 - 60 days ) in the continuous femoral block group , and 50 days ( range , 30 - 80 days ) in the patient-controlled morphine group ( P < 0.05 ) . Side effects were encountered more frequently in the continuous epidural infusion group . CONCLUSION Regional analgesic techniques improve early rehabilitation after major knee surgery by effectively controlling pain during continuous passive motion , thereby hastening convalescence & NA ; The aim of the study was to evaluate post‐operative pain and analgesic use after pre‐operative or post‐incisional i.v . fentanyl plus low dose i.v . ketamine vs. a st and ard treatment receiving i.v . fentanyl but not ketamine . Men undergoing radical prostatectomy under general anesthesia were r and omly assigned in a double‐blinded manner to one of three groups . Patients received i.v . fentanyl before incision followed by an i.v . bolus dose ( 0.2 ml kg−1 ) and an i.v . infusion ( 0.0025 ml kg−1 min−1 ) of 1 mg ml−1 ketamine ( group 1 ) or normal saline ( groups 2 and 3 ) . Seventy minutes after incision , patients received i.v . fentanyl followed by an i.v . bolus dose ( 0.2 ml kg−1 ) and an i.v . infusion ( 0.0025 ml kg−1 min−1 ) of saline ( groups 1 and 3 ) or ketamine ( group 2 ) . Pain , von Frey pain thresholds , and cumulative morphine consumption using patient‐controlled analgesia ( PCA ) were assessed up to 72 h after surgery . 143 patients completed the study ( group 1 , n=47 ; group 2 , n=50 ; group 3 , n=46 ) . Cumulative PCA morphine ( mean±SD ) did not differ significantly among groups ( group 1 , 92.3±45.9 mg ; group 2 , 107.2±58.4 mg ; group 3 , 103.6±50.4 mg ; P=0.08 for groups 1 vs. 2 , and groups 1 vs. 3 ) . On day 3 , the hourly rate ( mean±SEM ) of morphine consumption was significantly lower ( P<0.0009 ) in group 1 ( 0.61±0.013 mg h−1 ) than group 2 ( 0.86±0.011 mg h−1 ) and group 3 ( 0.89±0.008 mg h−1 ) . Pain scores and von Frey pain thresholds did not differ significantly among groups . Two‐week and 6‐month follow‐ups did not reveal significant group differences in pain incidence , intensity , disability or mental health . Pre‐operative , low‐dose administration of i.v . ketamine did not result in a clinical ly meaningful reduction in pain or morphine consumption when compared with post‐incisional administration of ketamine or a saline control condition Background : Most studies of preemptive or preventive analgesia restrict outcomes to pain and analgesic consumption in the acute postoperative period . The potential longer-term effects on these and other domains of functioning have received little empirical attention . The purpose of this study was to follow up patients who had received general anesthesia plus epidural fentanyl and lidocaine before ( group 1 ) or after ( group 2 ) incision or general anesthesia plus a sham epidural ( group 3 ) . Methods : Patients were contacted approximately 3 weeks and 6 months after surgery . A follow-up pain question naire and the McGill Pain Question naire were administered by telephone . The Mental Health Inventory and Pain Disability Index were mailed to patients , completed , and mailed back . Results : One hundred thirty-one of the 141 patients ( 93 % ) were reached 3 weeks after surgery ( n = 41 , n = 48 , and n = 42 in groups 1 , 2 , and 3 , respectively ) , and 109 ( 77 % ) were reached at 6 months ( n = 35 , n = 37 , and n = 37 in groups 1 , 2 , and 3 , respectively ) . Multivariate analysis of covariance indicated that that even after controlling for age and presence or absence of preoperative pain , Pain Disability Index scores ( mean ± SD ) at the first follow-up were significantly lower in group 1 ( 17.3 ± 12.8 ) and group 2 ( 18.1 ± 17.0 ) compared with group 3 ( 26.3 ± 18.3 ) . McGill Pain Question naire and Mental Health Inventory scores did not differ significantly among the groups . There were no significant differences at the 6-month follow-up . Conclusion : The short-term beneficial effects of preventive epidural analgesia translated into less pain disability 3 weeks after surgery . Progress in underst and ing the processes involved in postsurgical recovery and the risk factors for chronic postsurgical pain would be aided by baseline and postsurgical measures of relevant psychological , emotional , and physical variables Background and purpose Postoperative pain is often severe after total knee arthroplasty ( TKA ) . We investigated the efficacy of the local infiltration analgesia ( LIA ) technique , both intraoperatively and postoperatively . Methods 48 patients undergoing TKA were r and omized into 2 groups in a double-blind study . In group A , 400 mg ropivacaine , 30 mg ketorolac , and 0.5 mg epinephrine were infiltrated periarticularly during operation . In group P , no injections were given . 21 h postoperatively , 200 mg ropivacaine , 30 mg ketorolac , and 0.1 mg epinephrine were injected intraarticularly in group A , and the same volume of saline was injected in group P. All patients were followed up for 3 months . Results Median morphine consumption was lower in group A during the first 48 h : 18 ( 1–74 ) mg vs. 87 ( 36–160 ) mg in group P. Postoperative pain was lower at rest in group A during the first 27 h , and on movement during the first 48 h , except at 21 h. Time to fulfillment of discharge criteria was shorter in group A than in group P : 3 ( 1–7 ) vs. 5 ( 2–8 ) days . Patient satisfaction was higher in group A than in group P on days 1 and 7 . The unbound venous blood concentration of ropivacaine was below systemic toxic blood concentrations . Interpretation The local infiltration analgesia ( LIA ) technique provides excellent pain relief and lower morphine consumption following TKA , result ing in shorter time to home readiness and higher patient satisfaction . There were few side effects and systemic LA concentrations were low Background Inguinal hernia repair is one of the most frequently performed procedures in Switzerl and ( 15'000/year ) . The most common complication postoperatively is development of chronic pain in up to 30 % of all patients irrespective of the operative technique . Methods / Design 264 patients scheduled for an inguinal hernia repair using one of three procedures ( Lichtenstein , Barwell and TEP = total extraperitoneal hernioplasty ) are being r and omly allocated intra-operatively into two groups . Group I patients receive a local injection of 20 ml Carbostesin ® 0.25 % at the end of the operation according to a st and ardised procedure . Group II patients get a 20 ml placebo ( 0.9 % Saline ) injection . We use pre-filled identically looking syringes for blinded injection , i.e. the patient , the surgeon and the examinator who performs the postoperative clinical follow-ups remain unaware of group allocation . The primary outcome of the study is the occurrence of developing chronic pain ( defined as persistent pain at 3 months FU ) measured by VAS and Pain Matcher ® device ( Cefar Medical AB , Lund , Sweden).The study started on July 2006 . In addition to a sample size re-evaluation three interim analyses are planned after 120 , 180 and 240 patients had finished their 3-months follow-up to allow for early study termination . Discussion Using a group sequential study design the minimum number of patients are enrolled to reach a valid conclusion before the end of the study .To limit subjectivity , both a VAS and the Pain Matcher ® device are used for the evaluation of pain . This allows us also to compare these two methods and further assess the use of Pain Matcher ® in clinical routine . The occurrence of chronic pain after inguinal hernia repair has been in focus of several clinical studies but the reduction of it has been rarely investigated . We hope to significantly reduce the occurrence of this complication with our investigated intervention . Trial Registration Our trial has been registered at Clinical Trials.gov . The trial registration number is : [ NCT00484731 ] & NA ; Phantom limb pain ( PLP ) associated neuroplastic changes are partly mediated by excitatory amino acids at NMDA receptor sites . This study was undertaken to deduce if NMDA‐receptor antagonists may be effective in patients with chronic PLP . Therefore a four week double‐blinded , r and omized placebo‐controlled trial was performed to evaluate the efficacy of 30 mg memantine/day , an orally administrable NMDA receptor antagonist . Thirty‐six patients , 18 per group , with a history of at least 12 months PLP and an average pain of at least 4 on the 11‐point numeric rating scale ( NRS ) were enrolled . The patients completed a st and ardized question naire before the trial . PLP intensity and the level of eight complaints were assessed during the trial . Number needed to treat ( NNT ) was calculated based on the average PLP during the 3rd week ( steady state ) . In both groups , PLP declined significantly in comparison with the baseline ( verum : 5.1 ( ±2.1 ) to 3,8 ( ±2,3 ) , placebo from 5.1 ( ±2.0 ) to 3.2 ( ±1,46 ) NRS ) without a re‐rising of the PLP during the washout period . Mean pain relief was 47 % in the memantine group ( 10 patients reported more than 50 % relief ) , 40 % in the placebo group ( 6>50 % ) : NNT were 4.5 ( KI : 2.1–10.6 ) . Analysis of covariance demonstrated a significant impact only on the prior PLP intensity , but no treatment effect . Two patients have demonstrated long‐term pain relief under memantine until now ( 16 months ) . The total number of slight adverse events were comparable in both groups , but the overall number of severe events was higher in the memantine group ( P<0.05 ) . This trial failed to demonstrate a significant clinical benefit of the NMDA‐receptor antagonist memantine in chronic PLP . The administration of a higher dosage is probably not tolerable Thoracotomy is often responsible for chronic pain , possibly of neuropathic origin . To confirm pre clinical studies , the preventive effects of perioperative ketamine were tested in a r and omized , double‐blind , placebo‐controlled clinical trial on persistent neuropathic pain after thoracotomy . Eighty‐six patients scheduled for thoracotomy under st and ardised general anaesthesia were r and omised to receive either ketamine ( 1mgkg−1 at the induction , 1mgkg−1h−1 during surgery , then 1mgkg−1 during 24h ; n=42 ) or normal saline ( n=44 ) . Postoperative analgesia included a single dose of intrapleural ropivacaine , intravenous paracetamol and nefopam , and patient‐controlled intravenous morphine . Vital parameters and analgesia were recorded during the 48 first postoperative hours . Seventy‐three patients were followed up . The patient 's chest was examined 1–2 weeks , 6 weeks and 4 months after surgery . At the last two observations , spontaneous pain score over a one‐week period ( visual analogue scale ) , neuropathic pain score ( NPSI ) , and intake of analgesics , were assessed . No drug affecting neuropathic pain ( except opiates ) was given during the follow‐up . Two patients in each group were lost to follow‐up after the 6 week visit . Ketamine improved immediate postoperative pain , but the groups were similar in terms of neuropathic pain and intake of analgesics , 6 weeks ( NPSI score : ketamine : 1.25 [ 0–4.125 ] ; placebo : 1 [ 0–4 ] ) and 4 months after surgery . Thus , ketamine given in 24‐h infusion failed to prevent chronic neuropathic pain after thoracotomy . Other perioperative preventive long‐lasting treatments or techniques could be tested in this context BACKGROUND In this prospect i ve , r and omized , double-blind , placebo-controlled study , we investigated the effect of pregabalin on oxycodone consumption , postoperative confusion , and pain in elderly cardiac surgery patients . METHODS Seventy patients , aged ≥75 yr , were r and omized to receive either 150 mg of pregabalin before operation and 75 mg of pregabalin twice daily for 5 postoperative days or placebo . Pain intensity was measured with the Verbal Rating Scale ( VRS ) . When pain intensity was ≥2 on the VRS , patients received oxycodone either i.v . ( 0.05 mg kg(-1 ) ) or orally ( 0.10 - 0.15 mg kg(-1 ) ) . Postoperative confusion was measured with the Confusion Assessment Method for the intensive care unit ( CAM-ICU ) . Postoperative pain was assessed by a telephone interview 1 and 3 months after operation . RESULTS Cumulative consumption of parenteral oxycodone during 16 h after extubation was reduced by 44 % and total oxycodone consumption from extubation to the end of the fifth postoperative day was reduced by 48 % in the pregabalin group . Time to extubation was 138 min shorter and CAM-ICU scores were significantly lower on the first postoperative day in the placebo group , although there was no significant difference with respect to the Mini-Mental State Examination or the Richmond Agitation Sedation Score . The incidence of pain during movement was significantly lower in the pregabalin group at 3 months postoperative . CONCLUSIONS The administration of pregabalin reduced postoperative opioid consumption after cardiac surgery reduced the incidence of confusion on the first postoperative day and increased time to extubation when compared with placebo . Three months after operation , patients in the pregabalin group experienced less pain during movement STUDY OBJECTIVE To determine whether intrathecal baclofen is an effective adjunctive agent to decrease acute and chronic postoperative pain after total knee arthroplasty . DESIGN Prospect i ve , r and omized , double-blind controlled trial . SETTING Operating room and inpatient units of a university hospital . PATIENTS 60 adult , ASA physical status I , II , and III patients presenting for total knee arthroplasty . INTERVENTIONS Anesthesia was provided by spinal injection of 15 mg of 0.75 % hyperbaric bupivacaine combined with either 100 mcg baclofen or saline . Sedation was provided with intravenous midazolam and propofol . MEASUREMENTS Data were collected on adverse effects , opioid usage , and verbal pain scale ( VPS ) from 0 to 10 . The study period was divided into six discrete time intervals that included the 1(st ) 72-hour postoperative period and a three-month post-discharge follow-up telephone call . MAIN RESULTS The baclofen group used less morphine in the PACU than the control group ( 5 mg vs. 9.3 mg ; P = 0.04 ) . VPS were lower in the baclofen group than the treatment group , but significant differences could be demonstrated only in the time periods 48 - 72 hours and three months postoperatively . At three months , fewer patients in the baclofen group reported pain than the control group ( 8/27 vs. 19/29 ; P = 0.009 ) . Regression analysis showed that the baclofen group was 4.5 times less likely to report pain at three months ( 95 % CI : 1.5 - 16.6 ) . CONCLUSIONS IT baclofen used as an adjuvant to spinal anesthesia for total knee arthroplasty allows for less postoperative opioid usage and less chronic pain at three months BACKGROUND AND OBJECTIVES The development of chronic pain after spinal-fusion surgery represents a significant source of morbidity . One of the predictive factors for the development of chronic postsurgical pain is inadequate acute postoperative pain management . Further , the up-regulation of cyclooxygenase-2 ( COX-2 ) after surgery may result in neuro-plastic changes that may contribute to a progression from acute to chronic pain . The goal of this prospect i ve , r and omized , double-blind study was to examine the effect of perioperative COX-2 inhibition on acute and chronic donor-site pain in patients undergoing spinal-fusion surgery . METHODS Eighty patients scheduled to undergo instrumented posterior spinal fusion were r and omized to either receive celecoxib 400 mg 1 hour before surgery , and then 200 mg every 12 hours after surgery for the first 5 days or receive matching placebo at similar time intervals . Patients were administered morphine via patient-controlled analgesia pump for the first 24 hours , and then acetaminophen and oxycodone tablets . Patients were asked to quantify their average pain on postoperative days 1 to 5 . At 1 year after surgery , patients were question ed about the presence and subjective characteristics of any residual donor-site pain . RESULTS Patients administered celecoxib reported lower pain scores and less opioid use during the first 5 postoperative days . Chronic donor-site pain was significantly higher ( P<.01 ) in the placebo group ( 12 of 40 , or 30 % ) compared with the celecoxib group ( 4 of 40 , or 10 % ) at 1 year after surgery . CONCLUSIONS The administration of celecoxib for the first 5 days after spinal-fusion surgery result ed in improved analgesia and a reduction in chronic donor-site pain at 1 year after surgery BACKGROUND : Patient outcome after lumbar discectomy for radicular low back pain is variable and the benefit is inconsistent . Many patients continue to experience pain 3 months after surgery . Pregabalin , a membrane stabilizer , may decrease perioperative central sensitization and subsequent persistent pain . METHODS : Forty patients undergoing lumbar discectomy were r and omly allocated to receive either pregabalin ( 300 mg at 90 minutes preoperatively and 150 mg at 12 and 24 hours postoperatively ) or placebo at corresponding times in a double-blinded manner . Our primary outcome was the change in the present pain intensity ( PPI ) ( visual analog scale [ VAS ] , 0–100 mm [ PPI-VAS , McGill Pain Question naire ] ) from preoperatively to 3 months postoperatively . RESULTS : The decrease in PPI-VAS score at 3 months was greater in patients who received pregabalin ( 37.6 ± 19.6 mm ) ( mean ± SD ) than those who received placebo ( 25.3 ± 21.9 mm ) ( P = 0.08 ) . The Rol and Morris disability score at 3 months was less in patients who received pregabalin ( 2.7 ± 2.4 ) than in those who received placebo ( 5.6 ± 4.8 ) ( P = 0.032 ) . Pregabalin administration was associated with greater pain tolerance thresholds in both lower limbs compared with placebo at 24 hours postoperatively . CONCLUSION : Perioperative pregabalin administration is associated with less pain intensity and improved functional outcomes 3 months after lumbar discectomy & NA ; The efficacy of oral retarded morphine sulphate ( MST ® ) was tested against placebo in a double‐blind crossover design in 12 patients with phantom limb pain after unilateral leg or arm amputation . Two counterbalanced treatment phases of 4 weeks each were initiated with an intravenous test infusion of MST ® or Placebo . The titration phase was 2 weeks . The dose of MST ® was titrated to at least 70 mg/day and at highest 300 mg/day . Pain intensity was assessed hourly on visual analog scales during a 4‐week treatment‐free phase , both treatment phases and at two follow‐ups ( 6 and 12 months ) . Reorganization of somatosensory cortex , electric perception and pain thresholds as well as selective attention were measured pre‐ and post‐treatment . A significant pain reduction was found during MST ® but not during placebo . A clinical ly relevant response to MST ® ( pain reduction of more than 50 % ) was evident in 42 % , a partial response ( pain reduction of 25–50 % ) in 8 % of the patients . Neuromagnetic source imaging of three patients showed initial evidence for reduced cortical reorganization under MST ® concurrent with the reduction in pain intensity . Perception and pain thresholds were not significantly altered whereas attention was significantly lower under MST ® . Thus , opioids show efficacy in the treatment of phantom limb pain and may potentially influence also cortical reorganization . These data need to be replicated in larger patient sample CONTEXT Controlling postoperative pain after knee replacement while reducing opioid-induced adverse effects and improving outcomes remains an important challenge . OBJECTIVE To assess the effect of combined preoperative and postoperative administration of a selective inhibitor of cyclooxygenase 2 on opioid consumption and outcomes after total knee arthroplasty ( TKA ) . DESIGN , SETTING , AND PATIENTS R and omized , placebo-controlled , double-blind trial conducted June 2001 through September 2002 , enrolling 70 patients aged 40 to 77 years and undergoing TKA at a university hospital in the United States . INTERVENTIONS Patients were r and omly assigned to receive 50 mg of oral rofecoxib at 24 hours and at 1 to 2 hours before TKA , 50 mg daily for 5 days postoperatively , and 25 mg daily for another 8 days , or matching placebo at the same times . MAIN OUTCOME MEASURES Postoperative outcomes including postsurgical analgesic consumption and pain scores achieved , nausea and vomiting , joint range of motion , sleep disturbance , patient satisfaction with analgesia , and hematologic and coagulation parameters . RESULTS Total epidural analgesic consumption and in-hospital opioid consumption were less in the group receiving rofecoxib compared with the group receiving placebo ( P<.05 ) . Median pain score ( visual analog scale [ VAS ] , 0 - 10 ) achieved for the knee was lower in the rofecoxib group compared with the placebo group during hospital stay ( 2.2 [ interquartile range [ IQR ] , 1.4 - 3.2 ] vs 3.5 [ IQR , 2.7 - 4.3 ] , P<.001 ) and 1 week after discharge ( 2.6 [ IQR , 1.4 - 3.5 ] vs 3.7 [ IQR , 2.9 - 4.7 ] , P = .03 ) . There was less postoperative vomiting in the rofecoxib group ( 6 % ) compared with the placebo group ( 26 % ) ( P = .047 ) , as well as a decrease in sleep disturbance compared with the placebo group on the night of surgery ( P = .006 ) and on the first ( P = .047 ) and second ( P<.001 ) days postoperatively . Knee flexion was increased in the rofecoxib group compared with the placebo group at discharge ( active flexion : mean [ SD ] , 84.2 degrees [ 11.1 degrees ] vs 73.2 degrees [ 13.6 degrees ] , P = .03 ; passive flexion : 90.5 degrees [ 6.8 degrees ] vs 81.8 degrees [ 13.4 degrees ] , P = .05 ) and at 1 month postoperatively ( 109.3 degrees [ 8.5 degrees ] vs 100.8 degrees [ 11.8 degrees ] , P = .01 ) , with shorter time in physical therapy to achieve effective joint range of motion . The rofecoxib group was more satisfied with analgesia and anesthesia at discharge compared with the placebo group ( median satisfaction score , 4.3 [ IQR , 3.0 - 4.7 ] vs 3.3 [ IQR , 2.3 - 4.3 ] , respectively ; P = .03 ) , and the differences persisted at 2-week and at 1-month follow-up . There was no intergroup difference in surgical blood loss ( P>.05 for both intraoperative and postoperative blood loss ) . CONCLUSION Perioperative use of an inhibitor of cyclooxygenase 2 is an effective component of multimodal analgesia that reduces opioid consumption , pain , vomiting , and sleep disturbance , with improved knee range of motion after TKA Background and Objectives Continuous femoral nerve block is a well-accepted technique for regional analgesia after total-knee replacement . However , many patients still experience considerable pain at the popliteal space and at the medial aspect of the knee . The goal of this study is to evaluate whether a psoas compartment catheter provides better postoperative analgesia than a femoral nerve catheter does and whether it is as effective as the combination of a femoral and a sciatic nerve catheter and , thus , improves functional outcome . Methods Ninety patients who underwent total-knee replacement under st and ardized general anesthesia participated in this prospect i ve r and omized study . Group FEM received a continuous femoral nerve block , group FEM/SCI received a combination of a femoral and a sciatic continuous nerve block , and group PSOAS received a continuous psoas compartment block . Patient-controlled analgesia with piritramide was available for 48 hours . Maximal bending and extending of the knee and walking distance was assessed during the first 7 days . A st and ardized telephone survey was conducted after 9 to12 months to evaluate residual pain and functional outcome . Results Postoperative opioid consumption during 48 hours was significantly less in the FEM/SCI group ( median : 18 mg ; 25th/75th percentile : 6/40 ) compared with the FEM group ( 49 mg ; 25/66 ) and the PSOAS group ( 44 mg ; 30/62 ) ( P = .002 ) . Postoperative pain scores were not different , and no differences occurred with respect to short-term or long-term functional outcome . Conclusion The FEM/SCI catheter is superior to FEM and PSOAS catheter with respect to reduced analgesic requirements after total-knee replacement , but functional outcome does not differ with those 3 continuous regional analgesia techniques BACKGROUND Postoperative pain in patients with bone and soft tissue cancer is different from that of other surgical patients due to the severity of the pain generated during surgery and because many of them have already been in pain preoperatively . The search for optimal intravenous pharmacologic management for this population is an ongoing one . We conducted a 10-month prospect i ve , r and omised , double blind study to compare the effects of a st and ard morphine dose to a 35%-lower dose plus a subanaesthetic dose of ketamine for postoperative pain control in patients undergoing bone and soft tissue cancer surgery under st and ardised general anaesthesia . METHODS After extubation , when objective ly awake ( > or=5/10 on a 0 - 10 visual analogue scale ( VAS ) ) and complaining of pain ( > or=5/10 VAS ) , patients were connected to an intravenous patient-controlled analgesia ( IV-PCA ) device that delivered 1.5 mg morphine/bolus ( MO group ) or 1 mg morphine+5 mg ketamine/bolus ( MK group ) , with a 7 min lockout time . Rescue intramuscular diclofenac 75 mg was available Q4/day . Follow-up lasted 96 h. RESULTS Fifty-seven patients ( 24 males , aged 18 - 74 years ) completed the study . Pain scores were lower in the MK group compared to the MO patients , although MO patients ( n=29 ) used 32.9+/-24.9 mg/patient morphine during the first 24 postoperative h compared to 14.6+/-11.4 mg/patient ( P<0.05 ) for the MK patients ( n=28 ) . At that time point , 11 MO versus 4 MK patients still required IV-PCA ( P<0.05 ) . Diclofenac was also used more in the MO group . All vital signs were similar between the groups . The physiotherapy score was 35 % higher for the MK patients ( P<0.05 ) . No patient had hallucinations . Postoperative nausea and vomiting rates were higher in the MO group . CONCLUSIONS The use of subanaesthetic ketamine plus 2/3 the st and ard dose of morphine following bone and tissue resections results in 1 ) lower and more stable pain score , 2 ) approximately 60 % morphine sparing effect , 3 ) a shorter period of postoperative IV-PCA dependence . Such therapy is also associated with better early physical performance Background and objective : Gabapentin and local anaesthetics may decrease postoperative pain and analgesic needs . The aim of the study was to investigate the effect of the combination of these drugs on the analgesic needs as well as on acute and late pain after abdominal hysterectomy . Methods : Sixty patients undergoing abdominal hysterectomy were r and omly assigned to receive postoperatively oral gabapentin 400 mg 6 hourly for 7 days plus continuous wound infusion of ropivacaine 0.75 % for 30 h or placebo capsules identical to those of gabapentin for 7 days and continuous wound infusion of normal saline for 30 h. Morphine consumption ( PCA ) for 48 h , paracetamol 500 mg plus codeine 30 mg ( Lonalgal ® tablets ) intake on days 3–7 , visual analogue pain scores at rest and after cough during the first 7 postoperative days , the need for analgesics at home and the presence and incidence of pain after 1 month were recorded . Results : The treatment group consumed less cumulative morphine over the first 48 h ( 31 ± 13.2 mg vs. 50 ± 20.5 mg in controls , P < 0.001 ) and less Lonalgal ® tablets on days 3–7 ( z = 2.54 , P = 0.011 ) . The visual analogue score values at rest and after cough did not differ between the groups during the first 7 postoperative days . One month postoperatively , fewer patients in the treatment group experienced pain due to surgery than in the control group ( 17/27 vs. 21/24 , P = 0.045 ) . Conclusion : Gabapentin and continuous wound infusion with ropivacaine 0.75 % decreased analgesic needs and late pain in patients undergoing abdominal hysterectomy Background : As a broader definition of preemptive analgesia , preventive analgesia aims to prevent the sensitization of central nervous system , hence the development of pathologic pain after tissular injury . To demonstrate benefits from preventive treatment , objective measurement of postoperative pain such as wound hyperalgesia and persistent pain should be evaluated . The current study assessed the role and timing of epidural analgesia in this context . Methods : In a r and omized , double-blinded trial , 85 patients scheduled to undergo neoplastic colonic resection were included . All the patients received a thoracic epidural catheter , systemic ketamine at a antihyperalgesic dose , and general anesthesia . Continuous infusion of analgesics belonging to the same class was administered by either intravenous or epidural route before incision until 72 h after surgery . Patients were allocated to four groups to receive intraoperative intravenous lidocaine – sufentanil – clonidine or epidural bupivacaine – sufentanil – clonidine followed postoperatively by either intravenous ( lidocaine – morphine – clonidine ) or epidural ( bupivacaine – sufentanil – clonidine ) patient-controlled analgesia . Postoperative pain scores ( visual analog scale ) , analgesic consumption , wound area of punctuate hyperalgesia , residual pain , and analgesics needed from 2 weeks until 12 months were recorded . Results : Analgesic requirements , visual analog scale scores , and area of hyperalgesia were significantly higher in the intravenous treatment group ( intravenous – intravenous ) , and more patients reported residual pain from 2 weeks until 1 yr ( 28 % ) . Although postoperative pain measurements did not differ , postoperative epidural treatment ( intravenous – epidural ) was less effective to prevent residual pain at 1 yr ( 11 % ; P = 0.2 with intravenous – intravenous group ) than intraoperative one ( epidural – epidural and epidural – intravenous groups ) ( 0 % ; P = 0.01 with intravenous – intravenous group ) . Conclusion : Combined with an antihyperalgesic dose of ketamine , intraoperative epidural analgesia provides effective preventive analgesia after major digestive surgery OBJECTIVES Improvement in health-related quality of life is a major object of cardiac surgery . However , high stress exposure during the perioperative period of cardiac surgery can result in the formation of traumatic memories and symptoms of chronic stress or even posttraumatic stress disorder , which can have negative effects on health-related quality -of-life outcome . In this controlled study we examined whether exogenously administered stress doses of hydrocortisone during cardiac surgery reduce perioperative stress exposure and the long-term incidence of chronic stress symptoms and improve health-related quality of life after cardiac surgery . METHODS Thirty-six high-risk patients undergoing cardiac surgery were prospect ively r and omized to receive either stress doses of hydrocortisone or placebo . Of 28 available patients at 6 months after cardiac surgery , 14 had received hydrocortisone , and 14 had received placebo . Traumatic memories , chronic stress symptoms ( posttraumatic stress disorder scores ) , and health-related quality of life were measured by using vali date d question naires . RESULTS Compared with patients from the placebo group , patients from the hydrocortisone group had a significantly shorter duration of intensive care unit treatment , required lower doses of the stress hormone norepinephrine during cardiac surgery , and had significantly fewer stress symptoms and a better health-related quality of life regarding physical function , chronic pain , general health , vitality , and mental health during follow-up . The groups did not differ with regard to the number or type of intensive care unit-related traumatic memories . CONCLUSIONS The use of stress doses of hydrocortisone in high-risk cardiac surgical patients reduces perioperative stress exposure , decreases chronic stress symptoms , and improves health-related quality of life at 6 months after cardiac surgery OBJECTIVE To evaluate the efficacy and safety of a cyclooxygenase (COX)-2 specific inhibitors versus placebo in the treatment of endometriosis-associated pelvic pain . STUDY DESIGN A group of women ( n = 28 ) with pelvic pain after conservative surgery for symptomatic endometriosis ( Stage I and II ) were enrolled at the Department of Pediatric , Obstetrics and Reproductive Medicine of University of Siena . A treatment with a COX-2 specific inhibitors ( rofecoxib , 25 mg per day ) ( n = 16 ) or placebo ( n = 12 ) was given for 6 months . Pelvic pain quantification with a clinical evaluation , including Visual Analogue Scale ( VAS ) for pain , was performed before and up to 6 months after treatment . RESULTS A significant improvement of both pelvic pain and dyspareunia was observed after a 6 months persisting since the end of the treatment ( P < 0.0001 ) . The efficacy of rofecoxib was higher than placebo and no recurrence occurred , while in the placebo-treatment a 16 % ( 2/12 ) occurred . No significant side effects have been found with the use of rofecoxib . CONCLUSIONS The use of COX-2 specific inhibitors was effective , safe and low cost therapy in the management of pelvic pain associated to endometriosis and might be also proposed in early stage of endometriosis & NA ; Adenosine analogs produce analgesic actions in nociceptive paradigms and alleviate manifestations of neuropathic pain in nerve injury models in rodents . In humans , previous work indicates an analgesic effect for adenosine administered intravenously in postoperative and neuropathic pain . In this double blind placebo controlled crossover trial , we used an enriched enrolment design to determine the effects of intravenous adenosine ( 50 & mgr;g/kg/min over 60 min ) on neuropathic pain . In Phase 1 of the trial , adenosine was administered in an open label manner , while in Phase 2 adenosine was administered in a double blind placebo controlled manner to 23 adenosine responders who had experienced a 30 % or greater response in the open trial . Outcome measures included the McGill pain question naire ( MPQ ) , which generates a pain rating index ( PRI ) , and contains a visual analog scale ( VAS ) of pain intensity , the neuropathy pain scale ( NPS ) , and a VAS for pain relief . Subjects also grade d the degree of allodynia and hyperalgesia using a VAS . Adenosine led to a significant reduction in spontaneous pain according to the MPQ‐PRI , the MPQ‐VAS and the VAS for pain relief . The NPS showed a pattern similar to the MPQ‐PRI , with statistically significant reductions in scales 1 ( intensity ) , 3 ( hot ) , 6 ( sensitive ) , 7 ( itchy ) and 9 ( unpleasant ) . Adenosine also led to a significant reduction in pinprick hyperalgesia , but not in allodynia . Three patients from Phase 1 of the trial experienced long term resolution of their pain following intravenous adenosine ( 5,16,25 months ) . The results of this study support previous reports that indicate intravenous adenosine alleviates neuropathic pain and hyperalgesia BACKGROUND Total knee arthroplasty ( TKA ) is associated with considerable postoperative pain , which , if unrelieved , may result in prolonged hospital stay , inability to participate in rehabilitation programs , poor outcomes , and greater use of healthcare re sources . The hypothesis of this study is that perioperative administration of celecoxib will improve analgesic efficacy , with a result ant improvement in short- and long-term clinical outcomes after TKA . METHODS We studied 200 patients undergoing elective TKA in a prospect i ve , r and omized , double-blind , placebo-controlled fashion . All patients underwent a similar perioperative anesthetic/analgesic procedure . After completion of surgery , patients were started on an epidural infusion with patient-controlled epidural analgesia . Patients were instructed to keep their numerical rating score pain < or = 3 . Patients were r and omly assigned to one of two groups : celecoxib or placebo . The celecoxib group received celecoxib 100 mg orally twice a day 7 days before surgery . On the day of surgery , celecoxib 400 mg was administered 1 - 2 h before surgery and then 200 mg every 12 h for 10 postoperative days . The control group received matching placebo capsules at the same times . The primary objective of this study was to determine whether the perioperative use of celecoxib reduces the amount of postoperative opioid consumption . Secondary objectives were to determine whether celecoxib is associated with improved clinical outcomes and a reduction in opioid-related adverse effects . RESULTS The celecoxib group required less patient-controlled epidural analgesia over the 40-h postoperative period : placebo 232.8 + /- 2.0 mL , celecoxib 209.1 + /- 1.8 mL ( P < 0.001 ) . At home over days 4 - 10 after surgery , the celecoxib group had reduced pain intensity with movement ( F = 109.7 , P < 0.001 ) at all time points . The celecoxib group also consumed less oxycodone at home than placebo group ( F = 417.8 , P < 0.001 ) . With active movement , range of motion ( ROM ) differed between the two groups over postoperative days 1 - 3 ( F = 50.7 , P < 0.001 ) , with the celecoxib group having greater ROM at all time points . There was earlier achievement of 90 degrees knee flexion with celecoxib compared with placebo ( P < 0.001 ) . Celecoxib patients had a better overall Knee Society Score ( 93.3 + /- 0.6 ) than placebo patients ( 86.4 + /- 0.9 ) at 12-mo follow-up ( P < 0.001 ) . The incidence of side effects ( nausea , vomiting , and pruritus ) in the immediate postoperative period was less in the celecoxib group . CONCLUSIONS Perioperative use of celecoxib reduces postoperative pain , opioid consumption , opioid-related adverse effects , and is associated with long-term benefits including improved knee function and less time to achieve effective knee ROM after TKA BACKGROUND : The addition of ketamine to morphine for patient-controlled analgesia ( PCA ) is supported by previous basic and clinical research , but has been challenged by subsequent negative studies . Important limitations of previous studies are the low number of patients analyzed , the use of morphine-ketamine combinations that may not the optimal , and that not all the relevant outcomes have been analyzed . In this study , we compared the combination of morphine and ketamine with morphine alone for postoperative PCA in large patient groups . We used a morphine-ketamine combination identified by an optimization procedure in our previous study . METHODS : After major elective orthopedic surgery , 352 patients received either PCA with morphine bolus 1.5 mg ( Group M , n = 176 ) or a bolus of morphine plus ketamine 1.5 mg each ( Group MK , n = 176 ) in a r and omized , double-blind fashion . Unsatisfactory treatment was defined as the occurrence of either inadequate analgesia or unacceptable side effects . In addition , total consumption of PCA drugs , duration of PCA use , direct medical costs , and number of patients with chronic postoperative pain 3 and 6 mo after operation were recorded . RESULTS : The incidence of unsatisfactory treatment was 33.0 % in Group M and 36.9 % in Group MK ( P = 0.50 ) . No significant differences were found between the groups with respect to secondary end points . CONCLUSIONS : Small-dose ketamine combined with morphine for PCA provides no benefit to patients undergoing major orthopedic surgery and can not be recommended for routine use Evidence has accumulated that the N-methyl-d-aspartate receptor system plays a role in continuous and particularly , in stimulus-evoked pain after nerve injury . We examined , in a r and omized , double-blinded , cross-over fashion , the analgesic effect of memantine ( a N-methyl-d-aspartate receptor antagonist ) in a group of patients with chronic pain after surgery . We r and omized 19 patients to receive either memantine or placebo in the first 5-wk treatment period . A washout period of 4 wks was followed by another 5-wk treatment period with the opposite drug . The dosage of drug was increased from 5 to 20 mg/d . Pain was recorded daily , with the use of a 0–10 numeric rating scale . Before and at the end of each treatment period , pain and sensitivity were also assessed by using the McGill Pain Question naire , allodynia to touch , brush and cold , wind-up-like pain , and thresholds to mechanical stimuli ( pressure and von Frey hair ) . A total of 15 patients ( 12 amputees and three patients with other nerve injuries ) completed the study . There was no difference between memantine and placebo on any of the outcome measures . We conclude that memantine at a dosage of 20 mg/d does not reduce spontaneous or evoked pain in patients with nerve injury pain . Implication s In a r and omized , double-blinded and cross-over study , the analgesic effect of memantine ( a drug which reduces the excitability of sensitized neurons in the dorsal horn ) was examined in 19 patients with chronic pain after nerve injury Background : Pain after amputation is common but difficult to treat . Therefore , the authors examined whether postoperative treatment with gabapentin could reduce postamputation stump and phantom pain . Methods : Forty-six patients scheduled to undergo lower limb amputation were r and omly assigned to receive oral gabapentin or placebo . Treatment was started on the first postoperative day and continued for 30 days . The daily dose of gabapentin or placebo was gradually increased to 2,400 mg/day . The intensity of stump and phantom pain was recorded every day on a numeric rating scale ( 0–10 ) during the 30-day treatment period . Five interviews were performed after 7 , 14 , and 30 days and after 3 and 6 months . Results : Results from 41 patients were included in the data analysis . The risk of phantom pain ( gabapentin vs. placebo ) was 55.0 % versus 52.6 % ( risk difference , 2.4 % ; 95 % confidence interval , −28.9 to 33.7 % ; P = 0.88 ; 30 days ) and 58.8 % versus 50.0 % ( risk difference , 8.8 % ; 95 % confidence interval , −23.3 to 40.9 % ; P = 0.59 ; 6 months ) . The median intensity of phantom pain ( gabapentin vs. placebo ) was 1.5 ( range , 0–9.0 ) versus 1.2 ( range , 0–6.6 ) ( P = 0.60 ; 30 days ) and 1.0 ( range , 0–6.0 ) versus 0.5 ( range , 0–5.0 ) ( P = 0.77 ; 6 months ) . The median intensity of stump pain was 0.85 ( range , 0–8.2 ) versus 1.0 ( range , 0–5.4 ) ( P = 0.68 ; 30 days ) and 0 ( range , 0–8.0 ) versus 0 ( range , 0–5.0 ) ( P = 0.58 ; 6 months ) . Conclusion : Gabapentin administered in the first 30 postoperative days after amputation does not reduce the incidence or intensity of postamputation pain BACKGROUND : Harvesting of iliac crest graft for spinal fusions is associated with a number of patients reporting residual or chronic pain at the harvest site . Various interventions , including morphine infiltration , have been proposed to minimize the associated pain . METHODS : We performed a prospect i ve , double-blind , r and omized , placebo-controlled study comparing intraoperative infiltration of 5 mg morphine ( treatment ) versus saline ( placebo ) into the iliac crest harvest site for patients undergoing elective spinal surgery . Patients with myelopathy , excessive perioperative opioid use ( 60 mg equivalent morphine/d or more ) , or multilevel ( > 3 levels ) spinal surgery were excluded . Postoperative administration of morphine ( recovery room and patient-controlled analgesia ) was st and ardized . Numerical pain scores specific for the iliac crest site were determined in the immediate postoperative period and at 3 , 6 , and 12 months . RESULTS : Of the 54 patients r and omized , 47 ( 87 % ) were available for review with a minimum of 1-year follow-up . The groups were similar in baseline age , gender , and comorbidities . There was no significant difference between groups in total use of postoperative morphine during the first 24 hours ( P = 0.48 ) . Repeated measures analysis of variance demonstrated no interacting effect of group over time for hip pain at rest ( P = 0.94 ) , hip pain while moving ( P = 0.90 ) , spine pain at rest ( P = 0.99 ) , or spine pain while moving ( P = 0.83 ) . The proportion of patients reporting iliac crest pain at 1-year follow-up was the same between groups ( P = 0.95 ) . CONCLUSIONS : This study has demonstrated that there are no additional benefits for the use of intraoperative infiltration of morphine into the iliac crest harvest site during spinal fusions BACKGROUND : A single preoperative dose of 600 mg gabapentin , combined with multimodal analgesia , has previously been shown to reduce postcesarean pain and improve maternal satisfaction but was associated with increased maternal sedation . We hypothesized that a lower dose of gabapentin may be effective with less sedation . METHODS : We conducted a doubleblind , r and omized , placebo-controlled study . Women undergoing elective cesarean delivery were r and omized into 3 groups to receive 300 or 600 mg oral gabapentin , or placebo , 1 hour before surgery . Temporal summation ( TS ) testing was performed at the time of study drug administration , and a visual analog scale ( 0 to 100 mm ) difference ≥10 mm between the 1st and 10th stimuli was considered TS+ . Spinal anesthesia and postoperative analgesia were instituted , including intrathecal fentanyl and morphine , oral diclofenac and acetaminophen , and systemic morphine as required . Pain assessment s at rest and on movement ( visual analog scale 0 to 100 mm ) were conducted at 6 , 12 , 24 , and 48 hours after surgical incision . The primary outcome was pain on movement at 24 hours . Secondary outcomes included satisfaction with analgesia , supplemental opioid consumption , lactation difficulties , neonatal outcomes , maternal sedation , and other adverse effects . Three months after delivery , patients were contacted for assessment of chronic pain . RESULTS : One hundred thirty-two women were r and omized and 6 were excluded . The difference in mean pain scores at 24 hours ( 95 % confidence intervals [ CI ] ) were as follows : 600 mg versus 300 mg mean difference : 5 mm ( 95 % adjusted CI , −7 to 17 ) ; 600 mg versus placebo : 3 mm ( −9 to 15 ) ; 300 mg versus placebo : −2 mm [ −14 to 10 ] ; overall P value = 0.61 . There was no apparent benefit of gabapentin in TS+ women , although overall pain scores were significantly higher in these women irrespective of the study group . CONCLUSION : Given the wide confidence intervals of the differences in mean pain scores , the current study did not allow us to determine whether a single preoperative dose of gabapentin ( 300 mg and 600 mg ) improved postcesarean analgesia compared to placebo in the context of a multimodal analgesic regimen . A larger study is required Objectives : Breast cancer surgery is associated with a high incidence of persistent postsurgical pain ( PPSP ) . The aim of this study was to evaluate the impact of intravenous ( IV ) lidocaine on acute and PPSP , analgesic requirements , and sensation abnormalities in patients undergoing surgery for breast cancer . Methods : Thirty-six patients participated in this r and omized , double-blinded study . Before induction of general anesthesia , patients received a bolus of intravenous lidocaine 1.5 mg/kg followed by a continuous infusion of lidocaine 1.5 mg/kgh ( lidocaine group ) or an equal volume of saline ( control group ) . The infusion was stopped 1 hour after the skin closure . Pain scores and analgesic consumption were recorded at 2 , 4 , 24 hours , and then daily for 1 week postoperatively . Three months later , patients were assessed for PPSP and secondary hyperalgesia . Results : Two ( 11.8 % ) patients in the lidocaine group and 9 ( 47.4 % ) patients in the control group reported PPSP at 3 months follow-up ( P=0.031 ) . McGill Pain Question naire revealed greater present pain intensity-visual analog scale in the control group ( 14.6±22.5 vs. 2.6±7.5 ; P=0.025 ) . Secondary hyperalgesia ( area of hyperalgesia/length of surgical incision ) was significantly less in the lidocaine group compared with control group ( 0.2±0.8 vs. 3.2±4.5 cm ; P=0.002 ) . The 2 groups were similar in terms of analgesic consumption during the early postoperative period . Discussion : Intravenous perioperative lidocaine decreases the incidence and severity of PPSP after breast cancer surgery . Prevention of the induction of central hyperalgesia is a potential mechanism Evidence about the effectiveness of the N-methyl-D-aspartate antagonist ketamine to reduce postoperative acute and long-lasting pain is inconclusive . The aim of this study was to investigate effects of adding an intraoperative , pre-incision single intravenous dose of ketamine to a routine anaesthesia regimen on postoperative analgesic requirements , side-effects and persisting pain up to three months . After obtaining Ethical Committee approval and written informed patient consent , 120 patients were included in this prospect i ve , r and omised , double-blinded , placebo-controlled study . Patients were r and omised into three groups , receiving 0.15 mg/kg ketamine intravenously , 0.5 mg/kg ketamine intravenously or normal saline in groups low-dose ketamine , moderate-dose ketamine and placebo , respectively . Anaesthesia maintenance , intraoperative pain management and postoperative pain therapy were st and ardised . The primary study endpoint was consumption of morphine during the first 24 hours after surgery . Three months after surgery , pain scores were assessed . Data were compared by t-test and Kruskall-Wallis test with alpha = 0.05 . There was no difference between the groups in the assessed variables . These findings indicate that with the anaesthesia regimen described , and in the doses used , a single intravenous dose of ketamine does not reduce postoperative analgesic requirement or postoperative pain at three months BACKGROUND : Gabapentin is effective for preventing and treating acute and chronic postoperative pain ; however , it has not been described for use in cesarean delivery . We hypothesized that preoperative gabapentin would reduce postcesarean delivery pain . METHODS : Women undergoing scheduled cesarean delivery were r and omized to receive preoperative gabapentin 600 mg , or placebo . Spinal anesthesia was achieved with 0.75 % hyperbaric bupivacaine 12 mg , fentanyl 10 & mgr;g , and morphine 100 & mgr;g . Postoperative analgesia was initiated with intraoperative ketorolac and acetaminophen , and continued with postoperative diclofenac , acetaminophen , and morphine . Patients were assessed at 6 , 12 , 24 , and 48 hours after spinal anesthesia for pain at rest and on movement using a visual analog scale ( 0 to 100 mm ) , satisfaction , opioid consumption , and side effects . Neonatal interventions , Apgar scores , umbilical artery blood gases , and breastfeeding difficulties were assessed . Chronic pain was assessed 3 months after delivery . Maternal and umbilical vein gabapentin plasma concentrations were measured in a subgroup of patients . Mixed-model analysis was used to compare the primary outcome of visual analog scale pain scores at 24 hours between groups . RESULTS : Forty-six patients were r and omized , and 2 were excluded from analysis . The mean ( 95 % confidence interval , CI ) pain scores on movement at 24 hours were 21 mm ( CI = 13–28 ) in the gabapentin and 41 mm ( CI = 31–50 ) in the placebo group ( P = 0.001 ) . Maternal satisfaction was higher in the gabapentin group . There was no difference in opioid consumption . Severe maternal sedation was more common in the gabapentin group ( 19 % vs. 0 % , P = 0.04 ) . There was no difference in neonatal Apgar scores , interventions , or umbilical artery pH. The mean ( SD ) maternal vein : umbilical vein plasma gabapentin ratio was 0.86 ( 0.12 ) . The incidence of pain at 3 months was similar in both groups . CONCLUSION : Preoperative gabapentin 600 mg in the setting of multimodal analgesia reduces postcesarean delivery pain and increases maternal satisfaction in comparison with placebo PURPOSE To evaluate oral gabapentin for postoperative pain after photorefractive keratectomy ( PRK ) . DESIGN Prospect i ve , nonr and omized clinical trial . METHODS In additional to a st and ard regimen of topical antibiotics , topical steroids , and topical tetracaine as required , all PRK patients at our laser vision center were treated after surgery for pain for a two-month period with Percocet ( oxycodone/acetaminophen ) [ Endo Pharmaceuticals ; Chadds Ford , Pennsylvania , USA ] 5 mg/325 mg as required for three days ( control group ) . Patients completed a pain assessment survey using a faces pain scale ( from zero through 6 ) on the evening of surgery and each subsequent morning and evening until postoperative day 3 . A successive cohort of patients received Neurontin ( gabapentin ) [ Pfizer , New York , New York , USA ] 300 mg thrice daily ( first dose administered two hours or more before the procedure ) as an oral pain medication for three days , and the same survey data were collected . RESULTS Data were collected on 141 patients in each cohort . Successful pain management score ( defined as faces zero through 2 on the scale ) differences did not reach statistical significance between the two cohorts except on the morning of the second postoperative day , when gabapentin was superior . On all postoperative days , patients in the oxycodone/acetaminophen cohort used significantly less tetracaine eye drops as required . The percent of patients rating overall pain experience as better than expected was 35 % and 36 % , those rating pain experience as about what was expected was 50 % and 49 % , and those rating pain experience as worse than expected was 15 % and 15 % in the oxycodone/acetaminophen and gabapentin cohorts , respectively . CONCLUSIONS We found no difference in overall subjective pain management ratings between gabapentin and oxycodone/acetaminophen for postoperative PRK pain , although gabapentin was associated with significantly more frequent use of anesthetic eye drops as required We hypothesized that perioperative ketamine administration would modify acute central sensitization following amputation and hence reduce the incidence and severity of persistent post-amputation pain ( both phantom limb and stump pain ) . In a r and omized , controlled trial , 45 patients undergoing above- or below-knee amputation received ketamine 0.5 mg.kg–1 or placebo as a pre-induction bolus followed by an intravenous infusion of ketamine 0.15 mg.kg–1.h–1 or normal saline for 72 hours postoperatively . Both groups received st and ardized general anaesthesia followed by patient-controlled intravenous morphine . The surface area of allodynia over the stump was mapped at days 3 and 6 . Postamputation pain was assessed at days 3 and 6 and at 6 months postoperatively . We found no significant difference between groups in the surface area of stump allodynia or in morphine consumption . There was an unexplained , but significant , increase in the incidence of stump pain in the ketamine group at day 3 . At six-month review , the incidence of phantom pain was 47 % in the ketamine group and 71 % in the control group . This did not reach statistical significance ( P=0.28 ) as the power of the study was based on the search for a large treatment effect . The incidence of stump pain at six months was 47 % in the ketamine group and 35 % in the control group ( P=0.72 ) . There were no significant between-group differences in pain severity throughout the study period . Ketamine at the dose administered did not significantly reduce acute central sensitization or the incidence and severity of post-amputation pain BACKGROUND Ketamine is an analgesic suitable for the induction of anesthesia during Caesarean delivery . This double blind , r and omized trial examined the effect of intravenous ketamine used before the induction of general anesthesia on morphine consumption , immediate and long term postoperative pain after Cesarean delivery . METHODS One hundred and forty term pregnant women undergoing elective Cesarean delivery were r and omized into four groups ( N.=35 each ) , placebo ( 0.9 % normal saline ) , ketamine 0.25 , 0.5 , or 1 mg kg(-1 ) intravenously . In all patients 2 - 2.5 mg kg(-1 ) propofol was used for the induction of anesthesia , 0.6 mg kg(-1 ) rocuronium to facilitate the tracheal intubation and 50 % oxygen in N2O and sevoflurane ( end-tidal concentration of 1.2 - 1.3 % ) for the maintenance of anesthesia . Postoperative analgesia was provided with intravenous morphine chloride patient-controlled analgesia ( PCA ) and rescue analgesia with intramuscular diclofenac sodium in the postoperative period . Apgar scores of the neonates and hemodynamic variables of the mothers were recorded during anaesthesia . Groups were compared regarding the cumulative morphine consumption and pain scores assessed with a numerical rating ( 0 - 10 ) scale at 2 , 6 , 12 , 18 , 24 , and 48 h postoperatively . Postoperative side effects were recorded . Patients were evaluated for persistent postoperative pain at 2 weeks , 1 and 6 months , and 1 year . RESULTS The cumulative morphine consumption at 48 hours after the surgery was the primary outcome of the study . There was no significant difference in terms of acute pain at 2 ( P=0.3 ) , 6 ( P=0.7 ) , 12 ( P=0.4 ) , 18 ( P=0.4 ) , 24 ( P=0.8 ) , and 48 ( P=0.5 ) hours postoperatively . Cumulative morphine consumption obtained at 2 ( P=0.9 ) , 6 ( P=0.5 ) , 12 ( P=0.4 ) , 18 ( P=0.4 ) , 24 ( P=0.1 ) , and 48 ( P=0.2 ) hours was also similar among the groups . Prolonged postoperative pain evaluated 2 weeks ( P=0.3 ) , 1 month ( P=0.7 ) , 6 months ( P=0.1 ) and 1 year ( P=0.3 ) after the operation was also similar among the groups . There was no significant difference in side effects among the groups during the postoperative 48 hours . Apgar scores at 1 min ( P=0.5 ) and 5 mins ( P=0.5 ) were similar among the groups . Maternal intraoperative hemodynamic parameters were similar among the groups . CONCLUSION There was no difference regarding early and late postoperative pain and morphine consumption with ketamine at doses of 0.25 , 0.5 , and 1 mg kg(-1 ) in women undergoing Caesarean delivery under general anaesthesia , compared with the control group Background : Postoperative pain after radical retropubic prostatectomy can be severe unless adequately treated . Low thoracic epidural analgesia and patient-controlled intravenous analgesia were compared in this double-blind , r and omized study . Methods : Sixty patients were r and omly assigned to receive either low thoracic epidural analgesia ( group E ) or patient-controlled intravenous analgesia ( group P ) for postoperative pain relief . All patients had general anesthesia combined with thoracic epidural analgesia during the operation . Postoperatively , patients in group E received an infusion of 1 mg/ml ropivacaine , 2 & mgr;g/ml fentanyl , and 2 & mgr;g/ml adrenaline , 10 ml/h during 48 h epidurally , and a placebo patient-controlled intravenous analgesia pump intravenously . Patients in group P received a patient-controlled intravenous analgesia pump with morphine intravenously and 10 ml/h placebo epidurally . Pain , the primary outcome variable , was measured using the numeric rating scale at rest ( incision pain and “ deep ” visceral pain ) and on coughing . Secondary outcome variables included gastrointestinal function , respiratory function , mobilization , and full recovery . Health-related quality of life was measured using the Short Form-36 question naire , and plasma concentration of fentanyl was measured in five patients to exclude a systemic effect of fentanyl . Results : Incisional pain and pain on coughing were lower in group E compared with group P at 2–24 h , as was deep pain between 3 and 24 h postoperatively ( P < 0.05 ) . Maximum expiratory pressure was greater in group E at 4 and 24 h ( P < 0.05 ) compared with group P. No difference in time to home discharge was found between the groups . The mean plasma fentanyl concentration varied from 0.2 to 0.3 ng/ml during 0–48 h postoperatively . At 1 month , the scores on emotional role , physical functioning , and general health of the Short Form-36 were higher in group E compared with group P. However , no group × time interaction was found in the Short Form-36 . Conclusions : The authors found evidence for better pain relief and improved expiratory muscle function in patients receiving low thoracic epidural analgesia compared with patient-controlled analgesia for radical retropubic prostatectomy . Low thoracic epidural analgesia can be recommended as a good method for postoperative analgesia after abdominal surgery OBJECTIVE This prospect i ve r and omized double-blind study examined the effect of local wound infusion of anesthetics on pain control in the thoracotomy wound of patients undergoing minimally invasive cardiac surgery . METHODS Patients who underwent coronary artery bypass grafting or cardiac valvular procedures via a minimally invasive thoracotomy were studied . Patients were enrolled and r and omly allocated to two groups with different modalities of postoperative analgesia . The thoracotomy wound infusion group received 0.15 % bupivacaine infused continuously at 2 mL/h through a catheter embedded in the wound , as well as intravenous patient-controlled analgesia . The control group had patient-controlled analgesia alone with a sham thoracotomy wound infusion of normal saline . Verbal analog pain scores ( 0 - 10 points ) and recovery profiles were investigated . RESULTS There were 19 patients in each group for complete data analysis . On the first day after the operation , infusion of local anesthetics significantly reduced the verbal analog pain scores both at rest and during motion ( thoracotomy wound infusion vs control ) . The improved pain relief with thoracotomy wound infusion persisted at day 3 and even at 3 months after the operation . No difference was noted about time to extubation , length of intensive care unit stay , or hospital stay . CONCLUSION In this controlled double-blind study , thoracotomy wound infusion and patient-controlled analgesia were superior to patient-controlled analgesia alone in reducing pain at 1 , 3 , and 90 days after minimally invasive cardiac surgery Background and Objectives Severe phantom limb pain after surgical amputation affects 50 % to 67 % of patients and is difficult to treat . Gabapentin is effective in several syndromes of neuropathic pain . Therefore , we evaluated its analgesic efficacy in phantom limb pain . Methods Patients attending a multidisciplinary pain clinic with phantom limb pain were enrolled into this r and omized , double-blind , placebo-controlled , cross-over study . Other anticonvulsant therapy was discontinued . Each treatment was 6 weeks separated by a 1-week washout period . Codeine/paracetamol was allowed as rescue analgesia . The daily dose of gabapentin was titrated in increments of 300 mg to 2,400 mg or the maximum tolerated dose . Patients were assessed at weekly intervals . The primary outcome measure was visual analog scale ( VAS ) pain intensity difference ( PID ) compared with baseline at the end of each treatment . Secondary measures were indices of sleep interference , depression ( Hospital Anxiety and Depression [ HAD ] scale ) , and activities of daily living ( Bartel Index ) . Results Nineteen eligible patients ( mean age , 56 years ; range , 24 to 68 years ; 16 men ) were r and omized , of whom 14 completed both arms of the study . Both placebo and gabapentin treatments result ed in reduced VAS scores compared with baseline . PID was significantly greater than placebo for gabapentin therapy at the end of the treatment ( 3.2 ± 2.1 v 1.6 ± 0.7 , P = .03 ) . There were no significant differences between placebo and gabapentin therapy in terms of the number of tablets of rescue medication required , sleep interference , HAD scale , or Bartel Index . The medication was well tolerated with few reports of adverse effects . Conclusions After 6 weeks , gabapentin monotherapy was better than placebo in relieving postamputation phantom limb pain . There were no significant differences in mood , sleep interference , or activities of daily living , but a type II error can not be excluded for these variables The clinical effects of allopurinol on the attenuation of reperfusion injury in thumb replantations after prolonged ischaemic time were studied in a r and omized control trial with a 2-year follow-up . There were 60 patients , in the trial group , and 38 patients in the control group . All were young , healthy labourers who had sharp or locally crushed amputations of the thumb at the proximal phalanx with a total ischaemic time of more than 10 hours . The st and ard management for thumb replantation was used in these patients , except that 300 mg allopurinol was given orally in the trial group on admission and a further 300 mg for another 5 days . After operation , the trial group had a lower infection rate , and less postoperative pain and chronic swelling than the control group . Recovery of sensation was also better in the trial group OBJECTIVE To evaluate whether persistence of pelvic pain after excision of endometriosis was associated with adenomyosis as defined by a thickened uterine junctional zone ( JZ ) on magnetic resonance ( MR ) imaging . DESIGN Prospect i ve clinical trial . SETTING Government research hospital . PATIENT(S ) Fifty-three women with chronic pelvic pain . INTERVENTION(S ) Preoperative MR imaging to measure uterine JZ thickness , surgical excision , and pathologic diagnosis of endometriosis . Those with biopsy-proven endometriosis were r and omized to raloxifene or placebo . Visual analog scale ( VAS ) was used to rate dysmenorrhea and nonmenstrual pain severity before surgery and 3 months later . MAIN OUTCOME MEASURE(S ) Comparison of JZ thickness and pain severity before and 3 months after surgery in women with endometriosis controlling for medical treatment . RESULT ( S ) Forty of the 53 patients had biopsy-proven endometriosis , and 6 of these 40 women with endometriosis had a thickened JZ . Overall , dysmenorrhea at 3 months was positively correlated with preoperative JZ thickness ( r = 0.47 , P=.01 ) . Dysmenorrhea pain severity showed no significant decrease in those patients whose JZ measured > or=11 mm compared with those with JZ < 8 mm ( P<.0001 ; VAS decreased 4.3 + /- 0.6 ) , or > or=8 and < 11 mm ( P<.02 ; VAS decreased 4.8 + /- 1.3 ) . Nonmenstrual pain severity was correlated with JZ thickness ( r = 0.51 , P=.004 ) at 3 months with a significant decrease in nonmenstrual pain only in women with a JZ < 8 mm ( VAS decreased 4.0 + /- 0.7 , P<.0001 ) . The association between dysmenorrhea and nonmenstrual pain reduction and thinner JZ remained after controlling for medical treatment . CONCLUSION ( S ) Following surgical excision of endometriosis , chronic pelvic pain was significantly more likely to persist with JZ thickness > 11 mm on preoperative MR imaging . This suggests that myometrial JZ abnormalities or adenomyosis may contribute to chronic pelvic pain in women with endometriosis BACKGROUND The role of preoperative gabapentin in postoperative pain management is not clear , particularly in patients receiving regional blockade . Patients undergoing thoracotomy benefit from epidural analgesia but still may experience significant postoperative pain . We examined the effect of preoperative gabapentin in thoracotomy patients . METHODS Adults undergoing elective thoracotomy were enrolled in this prospect i ve , r and omized , double-blinded , placebo-controlled study , and r and omly assigned to receive 600 mg gabapentin or active placebo ( 12.5 mg diphenhydramine ) orally within 2 hours preoperatively . St and ardized management included thoracic epidural infusion , intravenous patient-controlled opioid analgesia , acetaminophen and ketorolac . Pain scores , opioid use and side effects were recorded for 48 hours . Pain was also assessed at 3 months . RESULTS One hundred twenty patients ( 63 placebo and 57 gabapentin ) were studied . Pain scores did not significantly differ at any time point ( P = 0.53 ) . Parenteral and oral opioid consumption was not significantly different between groups on postoperative day 1 or 2 ( P > 0.05 in both cases ) . The frequency of side effects such as nausea and vomiting or respiratory depression was not significantly different between groups , but gabapentin was associated with decreased frequency of pruritus requiring nalbuphine ( 14 % gabapentin vs. 43 % control group , P < 0.001 ) . The frequency of patients experiencing pain at 3 months post-thoracotomy was also comparable between groups ( 70 % gabapentin vs. 66 % placebo group , P = 0.72 ) . CONCLUSIONS A single preoperative oral dose of gabapentin ( 600 mg ) did not reduce pain scores or opioid consumption following elective thoracotomy , and did not confer any analgesic benefit in the setting of effective multimodal analgesia that included thoracic epidural infusion Background : There is a need for new clinical models to investigate effectively the development of pain after surgery and the effect , if any , of pre‐emptive treatment . Bilateral models are of special interest , since the patient serves as his/her own control . The objective of this preliminary study was to test a clinical model for the study of acute and chronic pain after bilateral reduction mammoplasty Background : Stump and phantom pains are debilitating sequelae of amputations that are often resistant to treatment . The efficacy of pharmacologic therapies , including opioids and sodium channel blockers , for postamputation pain is uncertain . Methods : The authors conducted a double-blind , r and omized , placebo-controlled , crossover study in adult patients with postamputation pain of 6 months or longer and greater than 3 on a 0–10 numeric pain rating scale . Each of the three treatment periods ( morphine , mexiletine , or placebo ) included a 1-week drug-free interval followed by 4-week titration , 2-week maintenance , and 2-week drug-taper phases . The primary outcome measure was change in average pain intensity from the drug-free baseline to the last week of maintenance . Results : Sixty amputees were enrolled ; data were analyzed from 56 subjects for one drug period , 45 subjects for two drug periods , and 35 subjects who completed all three drug periods . The mean morphine and mexiletine dosages were 112 and 933 mg , respectively . Morphine treatment provided lower pain scores compared with placebo and mexiletine ( P = 0.0003 ) . The mean percent pain relief during treatment with placebo , mexiletine , and morphine was 19 , 30 , and 53 % , respectively ( P < 0.0001 , morphine vs. placebo and mexiletine ) . The numbers needed to treat to obtain 50 % and 33 % decreases in pain intensity with morphine were 5.6 and 4.5 , respectively . Treatment with morphine was associated with a higher rate of side effects . Conclusions : Therapy with morphine , but not mexiletine , result ed in a decrease in intensity of postamputation pain but was associated with a higher rate of side effects and no improvement in self-reported levels of overall functional activity and pain-related interference in daily activities Over a 6‐year period 264 cholecystokinin ( CCK ) provocation tests have been performed in 174 patients with undiagnosed right upper quadrant pain . All were carried out by one person ( T.W.J.L. ) as part of a prospect i ve placebo‐controlled crossover study . Following infusion of CCK but not saline , 103 patients developed pain ( CCK + ve ) . These patients were offered cholecystectomy and 90 accepted . Seventy patients developed no pain during either infusion ( CCK − ve ) , and one patient experienced pain with both CCK and saline infusions . Of the 90 patients who underwent cholecystectomy , 81 ( 90 per cent ) have been followed up for a mean of 35 months ( range 12 months to 5 1/2 years ) , 67 percent have had complete resolution of symptoms and a further 24 percent have had a marked improvement in symptoms . Only 9 per cent of patients did not benefit from cholecystectomy . This compares well with patients undergoing cholecystectomy for uncomplicated calculous gallbladder disease , 88 per cent of whom , in our study , were improved by surgery . Patients with a positive CCK test have an excellent chance of symptomatic improvement following cholecystectomy Background and Purpose — We performed a double-blind , placebo-controlled study to investigate the effectiveness of amitriptyline for the prophylactic treatment of patients with acute thalamic stroke in preventing central poststroke pain . Methods — Subject received , in a r and omized sequence , either amitriptyline titrated from 10 to 75 mg in extended-release form or placebo over a therapy period of 365 days . We documented the time when pain developed ; the intensity , type , site , and distribution of pain ; and the presence/absence and type of allodynia . Results — Thirty-nine patients ( 23 women and 16 men ; age range , 36 to 68 years ) with central poststroke pain participated . The placebo group showed a pain rate of 21 % within 1 year after the diagnosis of thalamic stroke compared with 17 % in the group under prophylactic treatment with amitriptyline . Average ( SE ) time to pain was 318 ( 23 ) days for patients in the placebo group and 324 ( 24 ) days for patients in the amitriptyline group . Conclusions — With the achieved sample sizes of this study and a pain rate of approximately 21 % in the placebo group , any near-perfect pain protection would have been detected . Near-perfect pain protection , in this context , refers to pain in < 2.4 % of the recruited patients treated with amitriptyline or in approximately 89 % of placebo-treated patients . Larger studies are recommended to test the hypothesis that prophylactic amitriptyline reduces but does not completely prevent central poststroke pain Background : Pregabalin is used for the treatment of neuropathic pain and has shown analgesic efficacy in post‐operative pain . The aim of this r and omized , double‐blinded , placebo‐controlled trial ( Clinical Trials.gov ID NCT00938548 ) was to investigate the efficacy and safety of pregabalin for reducing post‐operative pain in patients after mastectomy Study Design . A r and omized , double-blind placebo controlled trial in multimodal analgesia for postoperative pain was conducted . Objective . To examine whether combination of corticosteroid and bupivacaine administered in patients undergoing posterior lumbosacral spine surgery reduces postoperative morphine consumption , back and leg pain relief , and improves functional disability and general health status . Summary of Background Data . Patients with lumbar spine surgery had moderate to severe postoperative pain . Administration of corticosteroid or injection of local anesthetic agent has been additive treatment methods for opioid drugs . There is uncertainty as to whether corticosteroid and bupivacaine combination improves outcomes in lumbosacral spine surgery . Methods . A total of 103 patients who were scheduled to undergo elective posterior lumbar discectomy , decompressive laminectomy with or without instrumented fusion for degenerative spinal diseases , received either methylprednisolone locally applied to the affected nerve roots ( and bupivacaine was infiltrated into the wound ) or injected placebo . Morphine consumption and pain scores were recorded at 1 , 2 , 3 , 6 , 12 , 24 , and 48 hours after surgery . Oswestry Index and Short Form SF-36 scores were recorded before surgery and at 1 and 3 months later . Results . Demographic data between the 2 groups were comparable . The cumulative morphine dose and postoperative pain was significantly lower in the study group than in the placebo group ( P = 0.01 and P = 0.001 , respectively ) . When performing subgroup analyses , the beneficial effects were found in all groups of surgery but could not demonstrated statistically significant difference for all subgroup comparisons . There was no significant difference between the 2 groups with regard to pain on cough , Oswestry Index , and SF-36 scores . No complications were associated with the perioperative use of methylprednisolone or bupivacaine . Conclusions . Administration of methylprednisolone-bupivacaine provided a favorable effect immediately after posterior lumbosacral spine surgery for discectomy , decompression , and /or spinal fusion without complication Postoperative ectopic bone formation affects about 40 % of people undergoing elective hip replacement surgery . Despite clear evidence that a short course of perioperative nonsteroidal anti-inflammatory drugs ( NSAIDs ) can substantially reduce the occurrence of ectopic bone , the use of NSAID-based prophylactic therapy is uncommon in Australia or New Zeal and . In part , this reflects surgeons ' uncertainty about the importance of ectopic bone as a cause of impaired long-term outcome , and in part , concerns about possible increased risk for gastrointestinal complications and excess wound bleeding in patients undergoing orthopedic surgery . To address this uncertainty , a multicenter r and omized controlled clinical trial is being conducted amongst 1000 patients undergoing elective total hip replacement ( or revision ) surgery . Patients are r and omly allocated to 14 days of treatment with either 1200 mg ibuprofen ( a commonly used NSAID ) or matching placebo commencing within 24 h of surgery . Treatment outcomes will be assessed 6 - 12 months later . The primary outcome will be self-reported pain and physical function . Secondary outcomes include quality of life and physical performance measures . Patient recruitment has commenced in more than 20 orthopedic centers throughout Australia and New Zeal and and will be complete by the end of October 2003 . The prevention of chronic ectopic bone-related pain and disability after hip replacement surgery with anti-inflammatory drugs study ( HIPAID ) has been design ed to provide precise and reliable information about the overall balance of risks and benefits associated with a short 14-day perioperative course of ibuprofen among individuals undergoing elective total hip replacement surgery OBJECTIVE Chronic post-sternotomy chest pain and paresthesia ( PCPP ) are frequently seen and reduce the quality of life . We aim ed to demonstrate the efficacy and safety of gabapentin compared with diclofenac in the treatment of PCPP and to eluci date the similarities of PCPP to neuropathic pain syndromes . METHODS The prospect i ve , r and omized , open-label , blinded end-point design of study was used . One hundred and ten patients having PCPP lasting three months or more were r and omized to receive 800 mg/daily gabapentin ( n=55 ) and 75 mg/daily diclofenac ( n=55 ) for thirty days . All patients have undergone cardiac surgery and median sternotomy . The perception of pain or paresthesia was evaluated as 0 - -Normal ( no pain or paresthesia ) , 1 - -Mild , 2 - -Moderate , 3 - -Severe at baseline and after thirty days of treatment . Recurrences were question ed after three months . Statistical analyses were performed using independent sample s t , Chi-square , continuity correction , Fisher 's exact , Mann Whitney U and Kruskal Wallis tests . RESULTS In gabapentin group , mean pain and paresthesia scores regressed from 2.12+/- 0.76 to 0.54+/- 0.83 ( p<0.001 ) and from 1.72+/- 0.74 to 0.49+/- 0.62 ( p<0.001 ) , respectively . Mean pain and paresthesia scores regressed in diclofenac group from 1.93+/- 0.8 to 1.0+/- 1.13 ( p<0.001 ) and from 1.76+/- 0.74 to 1.24+/- 0.96 ( p=0.002 ) , respectively . Although , both gabapentin and diclofenac were found to be effective without obvious side effects in the treatment of PCPP ( p<0.001 ) , gabapentin was found to be superior to diclofenac ( p=0.001 and p<0.001 , respectively ) . Adverse effects were seen in 7 % of patients on gabapentin and 4 % of patients on diclofenac . Results also showed that symptomatic relief with gabapentin lasts longer than diclofenac ( p<0.001 ) . CONCLUSION Both gabapentin and diclofenac are effective in the treatment of chronic PCPP , without obvious side effects . However , gabapentin is found to be superior to diclofenac and its effects sustain longer . The results show that there may be some evidence in PCPP as a kind of neuropathic pain PURPOSE In patients with critical limb ischemia ( CLI ) , distal revascularization remains the procedure of choice for preventing limb loss , but long-term outcomes for pain relief , wound healing , and prevention of amputation remain suboptimal . Prostagl and in drug therapy as an adjuvant to revascularization may improve these outcomes . The current trial was design ed to test the hypothesis that the use of lipo-ecraprost , a lipid encapsulated prostagl and in E(1 ) prodrug , as an adjunctive therapy after distal revascularization would improve amputation-free survival in patients with CLI . METHODS The study was r and omized , multicenter , double blind , and placebo controlled . Patients meeting clinical and hemodynamic criteria for CLI who were undergoing either bypass or endovascular revascularization of the below knee popliteal or more distal arteries were r and omized to receive placebo or a 60-microg dose of lipo-ecraprost administered intravenously starting < or=72 hours of the index revascularization and then 5 days per week for 8 weeks . The study primary end point was the composite end point of death or amputation at or above the level of the ankle at 180 days . RESULTS The study r and omized 322 patients , and 284 received at least one dose of study medication and were included in the intention-to-treat population . A total of 213 patients underwent surgical bypass , and 71 underwent endovascular revascularization before receiving study medication . The distribution of index revascularization procedures and location of distal target arteries were similar for both placebo and lipo-ecraprost groups . At 180 days , 21 patients ( 7.4 % ) were lost to follow-up before reaching the primary end point . Seventy-one percent of the patients taking the placebo completed at least half the doses of the study medication compared with 48 % of those taking lipo-ecraprost . Index leg revascularization-assisted primary patency was 82 % in the placebo group and 84 % in the lipo-ecraprost group ( P = .874 ) . Changes in lower extremity hemodynamics as a result of the revascularization during the study period did not differ between the placebo and lipo-ecraprost treatment arms . For the primary event of amputation-free survival , there were no differences between groups : 19 major amputations occurred in the placebo group and 17 in the lipo-ecraprost group ; 19 deaths occurred in the placebo group and 13 in the lipo-ecraprost group . CONCLUSION Eight weeks of parenteral therapy with lipo-ecraprost after distal revascularization in patients with CLI provided no additional benefit in the reduction of major amputation or death at 180 days & NA ; We investigated whether intraoperative ‘ subanesthetic doses ’ of ketamine have a postoperative anti‐hyperalgesic and an analgesic effect and which is the preferential route of administration , either systemic ( intravenous , i.v . ) or epidural . One hundred patients scheduled for rectal adenocarcinoma surgery under combined epidural/general anesthesia were included . Before skin incision all the patients received an epidural bolus followed by an infusion of continuous bupivacaine/sufentanil/clonidine mixture . They were r and omly assigned to receive no ketamine ( group 1 ) , i.v . ketamine at the bolus dose of 0.25 mg/kg followed by an infusion of 0.125 mg/kg per h ( group 2 ) , 0.5 mg/kg and 0.25 mg/kg per h ( group 3 ) , epidural ketamine 0.25 mg/kg and 0.125 mg/kg per h ( group 4 ) , or 0.5 mg/kg and 0.25 mg/kg per h ( group 5 ) . All i.v . and epidural analgesics were stopped at the end of surgery and patients were connected to an i.v . morphine patient‐controlled analgesia ( PCA ) device . Short‐term postoperative analgesia ( 72 h ) was assessed by pain visual analog scale scores at rest , cough , and movements as well as by PCA requirements . Wound mechanical hyperalgesia was evaluated and residual pain was assessed by asking the patients at 2 weeks , and 1 , 6 , and 12 months . The area of hyperalgesia and morphine PCA requirements were significantly reduced in group 3 . These patients reported significantly less residual pain until the sixth postoperative month . These observations support the theory that subanesthetic doses of i.v . ketamine ( 0.5 mg/kg bolus followed by 0.25 mg/kg per h ) given during anesthesia reduce wound hyperalgesia and are a useful adjuvant in perioperative balanced analgesia . Moreover , they show that the systemic route clearly is the preferential route Study Design . Parallel design , prospect i ve , double-blinded , r and omized , controlled trial composed of 2 independent groups treated with a continuous infusion catheter ( saline vs. Marcain ) placed into the iliac crest bone graft site ( ICBG ) . Objective . To determine the long-term effects of postoperative continuous local anesthetic agent infusion at the ICBG harvest site in reducing chronic pain , narcotic usage and improving long-term , postoperative function and satisfaction with the surgical procedure . Summary of Background Data . Harvesting iliac crest bone has been shown to be a source of pain and morbidity . In our initial study , we reported that patients who received local anesthetic at the graft site noted a reduction in acute postoperative pain ( VAS ) and narcotic usage . Methods . Twenty-six patients underwent posterior iliac crest bone graft harvesting . Patients were r and omly assigned to receive 96 mL ( 2 mL/h × 48 hours ) of either 0.5 % Marcain or normal saline delivered via a continuous infusion catheter placed at the ICBG harvest site . Postoperative pain scores , narcotic use/frequency , activity level , and length of stay ( LOS ) were recorded and reported previously . At a minimum of 4 years after surgery ( mean , 4.7 years ; range , 4.5–5.4 years ) , all patients completed a question naire documenting their current VAS pain score ( iliac crest ) , frequency of pain ( days per month ) , level of activity , chronic pain at the ICBG site , and overall satisfaction with the procedure . Results . Nine of 11 patients ( 82 % ) in the treatment group and 10 of 14 patients ( 71 % ) in the control group were available at final follow-up ( 1 death occurred in the control group unrelated to the study ) . The treatment group had a statistically significant decrease in the graft site pain VAS score ( 1.4 vs. 4.8 ) and increased satisfaction with the procedure at a minimum of 4 years postprocedure ( P < 0.05 ) . Additionally , no patient in the treatment group developed chronic iliac crest dysesthesias ( 0 of 9 ) versus 7 of 10 patients ( 70 % ) in the control group ( P < 0.05 ) . Conclusion . Continuous infusion of 0.5 % Marcain at the ICBG harvest site significantly reduced chronic dysesthesias . Overall satisfaction with the procedure , number of painful days per month , and VAS scores were significantly better in the treatment group at 4 years . No long-term complications were attributed to either the ICBG site or the catheter-infusion system . The use of continuous local anesthetic infusion at the iliac crest may help in alleviating graft-related pain beyond the perioperative phase & NA ; Salmon calcitonin ( S‐CT ) has been shown to be a valuable analgesic in phantom limb pain ( PLP ) in several case reports . To evaluate these findings a double‐blind crossover comparison of S‐CT treatment versus placebo was initiated . Twenty‐one out of 161 patients who had undergone major amputations and developed severe PLP 0–7 days after surgery were included in the study . For each patient a matched pair of infusions was prepared containing either 200 IU of s‐CT or placebo . Group I ( n = 11 ) was first given s‐CT and group II ( n = 10 ) placebo . When PLP reached a level of more than 3 on a numeric analogue scale ( NAS ) the first infusion was administered . The second infusion ( crossover ) or more infusions were given when the pain level again exceeded more than 3 on NAS . Using S‐CT infusion , PLP was eased from a median of 7 to 4 on NAS in both groups ( P < 0.001 ) , regardless of whether S‐CT or placebo was given first . Placebo , however , did not change pain scores ( median 7 on NAS , P > 0.1 ) . In the S‐CT group , but not in the placebo group , 4 individuals remained pain free without a second infusion . Any further treatment was performed with S‐CT . One week after the first PLP treatment 19 patients ( 90 % ) had pain relief of more than 50 % , 16 ( 76 % ) were completely pain free , and 15 ( 71 % ) never experienced PLP again . One year later 8 out of the 13 surviving patients ( 62 % ) still had more than 75 % PLP relief . After 2 years PLP exceeded 3 on NAS in 5 individuals ( 42 % ) , and the remaining 12 patients presented the same PLP as after 1 year . In conclusion , S‐CT is a valuable treatment for PLP in the early postoperative period BACKGROUND Irritable bowel syndrome ( IBS ) is a common gastrointestinal disorder seen in primary care practice . The symptoms of IBS , including abdominal pain , discomfort , and abnormal bowel function , may be modulated by activity of the serotonin type 3 receptor ( 5-HT(3 ) ) . The efficacy and tolerability of the 5-HT(3 ) receptor antagonist alosetron hydrochloride in nonconstipated female patients with IBS were evaluated in a double-blind , r and omized , placebo-controlled trial . METHODS Patients received either 1 mg of alosetron hydrochloride ( n = 309 ) or placebo ( n = 317 ) twice daily for 12 weeks , followed by a 4-week posttreatment period . Adequate relief of IBS pain and discomfort was the primary end point . Secondary end points included improvements in urgency , stool frequency , stool consistency , incomplete evacuation , and bloating . RESULTS Seventy-one percent of patients were classified as having diarrhea-predominant IBS . Forty-three percent of alosetron-treated patients with diarrhea-predominant IBS reported adequate relief for all 3 months compared with 26 % of placebo-treated patients ( P<.001 ; percentage point difference = 17 ; 95 % confidence interval , 8.0 - 25.4 ) . Improvement with alosetron compared with placebo was observed by the end of the fourth week of treatment and persisted throughout the remainder of treatment . Alosetron significantly decreased urgency and stool frequency and caused firmer stools within 1 week of starting treatment . Effects were sustained throughout treatment and symptoms returned following treatment cessation . No significant improvement in the percentage of days with sense of incomplete evacuation or bloating was observed compared with placebo during the first month of treatment . Constipation was the most commonly reported adverse event . CONCLUSION Alosetron hydrochloride , 1 mg twice daily for 12 weeks , is effective in relieving pain and some bowel-related symptoms in diarrhea-predominant female patients with IBS BACKGROUND Epidural analgesia before limb amputation is commonly used to reduce postamputation pain . But there have been no controlled studies with large numbers of patients to prove such a pre-emptive effect . We investigated whether postamputation stump and phantom pain in the first year is reduced by preoperative epidural blockade with bupivacaine and morphine . METHODS In a r and omised , double-blind trial , 60 patients scheduled for lower-limb amputation were r and omly assigned epidural bupivacaine ( 0.25 % 4 - 7 mL/h ) and morphine ( 0.16 - 0.28 mg/h ) for 18 h before and during the operation ( 29 patients ; blockade group ) or epidural saline ( 4 - 7 mL/h ) and oral or intramuscular morphine ( 31 patients ; control group ) . All patients had general anaesthesia for the amputation and were asked about stump and phantom pain after 1 week and then after 3 , 6 , and 12 months by two independent examiners . Study endpoints were rate of stump and phantom pain , intensity of stump and phantom pain , and consumption of opioids . FINDINGS Two patients in each group were withdrawn before amputation . The groups were well matched in baseline characteristics . Median duration of preoperative saline treatment was 18.5 h ( IQR 17 - 20 ) . Median duration of preoperative epidural blockade in the blockade group was 18 h ( 15 - 20.3 ) . The combined median duration of postoperative epidural pain treatment in both groups was 166 h ( 89.3 - 308.3 ) . After 1 week , 14 ( 52 % ) patients in the blockade group and 15 ( 56 % ) in the control group had phantom pain ( 95 % CI - 30.6 to 22.7 , p = 0.9 ) . The figures for blockade versus control group were : 14 ( 82 % ) vs ten ( 50 % ; 4.0 to 60.8 , p = 0.09 ) at 3 months ; 13 ( 81 % ) vs 11 ( 55 % ; -2.7 to 55.3 , p = 0.2 ) at 6 months ; and nine ( 75 % ) vs 11 ( 69 % ; -27.0 to 39.6 , p = 1.0 ) at 12 months . Intensity of stump and phantom pain and consumption of opioids were similar in both groups at all four postoperative interviews . INTERPRETATION Perioperative epidural blockade started a median of 18 h ( 15 - 20.3 ) before the amputation and continued into the postoperative period does not prevent phantom or stump pain BACKGROUND Thoracotomy is associated with severe pain . We hypothesized that the concomitant use of a subanesthetic dose of ketamine plus a two-third-st and ard morphine dose might provide more effective analgesia with fewer side effects than a st and ard morphine dose for early pain control . METHODS We conducted a 6-month r and omized , double-blind study in patients undergoing thoracotomy for minimally invasive direct coronary artery bypass or for lung tumor resection . After extubation , when objective ly awake ( > or= 5/10 visual analogue scale [ VAS ] ) and complaining of pain ( > or= 5/10 VAS ) , patients were connected to patient-controlled IV analgesia delivering 1.5 mg of morphine plus saline solution ( MO ) or 1.0 mg of morphine plus a 5-mg ketamine bolus ( MK ) , with a 7-min lockout time . Rescue IM diclofenac , 75 mg , was available . Follow-up lasted 4 h. RESULTS Forty-one patients completed the study . MO patients ( n = 20 ) used 6.8 + /- 1.9 mg/h ( mean + /- SD ) and 5.5 + /- 3.6 mg/h of morphine during the first and second hours , respectively ; MK patients ( n = 21 ) used 3.7 + /- 1.2 mg/h and 2.8 + /- 2.3 mg/h , respectively ( p < 0.01 ) . The 4-h activation rate of the device was double in the MO patients than in the MK patients ( 66 + /- 54 vs 28 + /- 20 , p < 0.001 ) . The maximal self-rated pain score was 5.6 + /- 1.0 for the MO group vs 3.7 + /- 0.7 for the MK group ( p < 0.01 ) . Four MO patients vs one MK patient required diclofenac ; 6 MO patients but no MK patients had oxygen saturation by pulse oximetry < 94 % on a fraction of inspired oxygen of 0.4 ( p < 0.01 ) ; two MO patients required reintubation . Paco(2 ) was higher in the MO group ( 40 + /- 6 mm Hg vs 33 + /- 5 mm Hg , p < 0.05 ) . Heart rate , BP , and incidence of nausea/vomiting were similar ; no ketamine-related hallucinations were detected . CONCLUSIONS Subanesthetic ketamine combined with a 35%-lower morphine dose provided equivalent pain control compared to the st and ard morphine dose alone , with fewer adverse side effects and a 45 % reduction in morphine consumption . TRIAL REGISTRATION Clinical Trials.gov Identifier : NCT00625911 CHRONIC pain continues to be a major humanitarian and socioeconomic burden with slow progress in the development of new preventive and therapeutic options . Persistent postsurgical pain ( PPP ) is a well-known and common clinical entity with a reported incidence between 5 and 50 % of patients after various common operations . PPP has received increased interest during the past 10–15 yr . These patients can be studied before injury is inflicted , and thus , PPP provides a special opportunity to underst and pathogenic mechanisms for developing a chronic pain state or the transition from an acute to a chronic pain state . What have we learned from clinical trials regarding pathogenic mechanisms of PPP and the effects of preventive or therapeutic interventions ? Despite the increased attention to PPP , most studies have done little more than codify the striking frequency with which this problem occurs after many disparate types of surgery : from inguinal herniorrhaphy to thoracotomy to breast surgery . It is likely that the pathogenic mechanisms leading to PPP are multiple , and thus , more rigorous study design will be required to better underst and how the problem evolves and who is at greatest risk . Such careful study design has been the exception rather than the rule . What we do know is that those that seem to be most relevant are gender , psychosocial factors , preoperative pain at the site of surgery or in other body regions , the type of surgical trauma , nerve damage , acute postoperative pain and inflammatory responses , perioperative analgesia , type of disease , recurrence of malignancy , and adjuvant therapy . Several years ago , the International Association for the Study of Pain defined PPP as a persistent pain state that is apparent more than 2 months postoperatively that can not be explained by other causes ( recurrence of disease , inflammation , and others ) . Most of the available literature has followed the lead of this overly simplistic definition and is composed of reports with insufficient pain assessment and little information regarding its consequences . Too often , studies on PPP have been conducted using a single assessment , asking patients simply to report whether they have persistent pain at one point in time using only a simple yes or no answer . Future studies should include not only a detailed assessment of the location , characteristics , and evolution of painful symptoms and associated changes in neurologic function but also assessment s of the consequences of persistent pain on physical and social function . These studies must be performed on a procedure-specific basis because the type of surgery has different consequences on specific organ functions , and new assessment scales must be developed and vali date d for individual procedures . We have only limited information from vali date d procedure-specific scoring systems , the most comprehensive example being the post groin hernia surgery pain scale . Finally , previous classifications of PPP as neuropathic and nociceptive pain have lacked specific objective criteria for such subgroupings , leading to the artificial concept that these two types of pain can be easily teased apart — even more damaging is the concept that the treatment for these two interwoven pain syndromes somehow differs . Indeed , many patients with PPP report both sensory abnormalities and localized stimulus-evoked pain , suggesting that both abnormal nerve function and ongoing nociception play a role in PPP . Less than a h and ful of studies have included detailed neurophysiologic assessment of PPP . There is a dramatic need for similar procedure-specific studies that are conducted prospect ively to detail the evolution and characteristics of PPP and include pain-related functional impairment scales to assess the real impact of this problem . The pathogenic factors involved in PPP may be divided into patient and surgery-related factors , of which preoperative factors to be assessed in detail include psychosocial factors , pain and its consequences , nociceptive function , and gender . Of the intraoperative factors , type of anesthesia , surgical approach ( magnitude of tissue damage ) , nerve identification , and nerve injury are obviously important , and postoperative factors should include a detailed description of the type of analgesia , duration , early follow-up with neurophysiologic assessment s , disease data , and detailed assessment of pain and its functional consequences . Although 2 months postoperatively has been proposed as a criterion for PPP , the definition was not based on procedure-specific data , and after some operations , a continuous inflammatory response may be apparent calling for assessment s for at least 3–6 months postoperatively to provide useful information . Although these requirements for study design may seem obvious and easy to include in clinical trials , an example from a Accepted for publication November 17 , 2009 . The authors are not supported by , nor maintain any financial interest in , any commercial activity that may be associated with the topic of this article OBJECTIVE To investigate the relationships between 2 anesthetic techniques , or the extent of allodynia around the surgical wound , and the occurrence of chronic post-thoracotomy pain . DESIGN Prospect i ve , r and omized study . SETTING A single-institution , university hospital . PARTICIPANTS Thirty-eight patients who underwent elective thoracotomy under general anesthesia . INTERVENTIONS High-dose remifentanil ( average effect-site concentration 5.61 + /- 0.84 ng/mL ) with epidural analgesia started and at the end of surgery or low-dose remifentanil ( average effect site concentration 1.99 + /- 0.02 ng/mL ) with epidural analgesia with 0.5 % ropivacaine started at the beginning of anesthesia . MEASUREMENTS AND MAIN RESULTS Pain intensity and the extent of allodynia around the wound were measured during the hospital stay . The presence and intensity of residual pain were assessed 1 , 3 , and 6 months after surgery and at the end of the study ( 6 - 13 months , average 9 months ) . A DN4 neuropathic pain diagnostic question naire was conducted at the same times . In the high-dose group , the area with allodynia was three times larger than the area in the low-dose group . The increased allodynia was associated with a higher incidence of chronic pain ( RR : 2.7 - 4.2 ) 3 and 6 months after surgery and at the end of the study ( median follow-up : 9.5 months ) . CONCLUSIONS High-dose remifentanil ( 0.14 - 0.26 microg/kg/min ) without epidural analgesia during surgery is associated with a large area of allodynia around the wound . These patients develop a much higher incidence of chronic pain than those receiving low-dose remifentanil with epidural analgesia during surgery OBJECTIVES The purpose of this study was to evaluate the analgesic effects of perioperative gabapentin on postoperative acute and chronic pain after coronary artery bypass graft ( CABG ) surgery with median sternotomy and internal mammary artery harvesting . DESIGN A double-blind r and omized clinical study . SETTING A single-academic hospital . PARTICIPANTS Patients with ischemic heart disease who were scheduled to undergo CABG surgery . INTERVENTIONS Forty patients were allocated r and omly into 2 groups ; the gabapentin group ( n = 20 ) received 1.2 g/d of oral gabapentin before and for 2 days after surgery , and the placebo group ( n = 20 ) received a placebo capsule instead . The primary outcome was to evaluate the effects of gabapentin on acute and chronic pain after surgery . The postoperative evaluation included the assessment of pain at rest and when coughing , intravenous tramadol usage , postoperative morbidities , and side effects of gabapentin . Postoperative analgesia at 6 , 12 , 18 , 24 , 48 , and 72 hours after extubation and at discharge was evaluated with the visual analog scale . The assessment of postoperative pain at the 1- and 3-month follow-ups was performed using a numeric rating scale . MAIN RESULTS Postoperative pain scores at 1 , 2 , and 3 days were significantly lower in the gabapentin group when compared with the placebo group ( p < 0.05 ) . Pain scores at 1 and 3 months postoperatively were lower in the gabapentin group than in the placebo group ( p > 0.05 ) . Consumption of intravenous tramadol given as rescue analgesic within 24 hours after extubation in the gabapentin group was 99.0 ± 53.8 mg versus 149.4 ± 72.5 mg in the placebo group ( p < 0.05 ) . There were no differences in the incidence of side effects and time to extubation between the groups . CONCLUSIONS Gabapentin significantly reduced the intensity of pain and tramadol consumption in the early postoperative period after CABG surgery . Pain scores at 1 and 3 months after surgery were low in both groups , with no significant difference between the groups BACKGROUND : Preoperative oral gabapentin has been shown to reduce postoperative pain . However , the effects of gabapentin as an adjunct to regional anesthesia is unclear and its effects on chronic pain remains unknown . In patients undergoing thyroidectomy , we investigated the effects on early and late ( at 6 mo ) postoperative pain of preoperative oral gabapentin as an adjunct to superficial cervical plexus block ( SCPB ) . METHOD : Fifty consecutive consenting patients were r and omized to receive either 1200 mg of gabapentin ( Group G ) or placebo ( Group P ) 2 h preoperatively . Preoperative anxiety was assessed on a numeric scale from 0 to 6 . A SCPB was performed after a st and ardized induction of anesthesia . The primary outcome , analgesic drug consumption , was assessed during the procedure and postoperatively in the postanesthesia care unit and after discharge to the ward . Over the first 24 h , pain levels at rest and during swallowing were measured on a numeric scale from 0 to 10 . If the pain level was more than 4/10 at rest , patients received 1 g/6 h of IV paracetamol and /or 50 mg/6 h of IV tramadol as a rescue analgesic treatment in the interval . The day before operation and 6 mo after thyroidectomy , included patients were asked to answer a neuropathic pain diagnostic question naire . RESULTS : Population characteristics , preoperative anxiety , intraoperative drug consumption , procedure duration , and postoperative care unit stay were comparable in both groups . Analgesic consumption during the first 24 postoperative hours was similar in both groups ( G : 3 [ 0–5 ] doses/24 h ; P : 3 [ 1–5 ] doses/24 h ; P = NS ) , as well as pain at rest ( G : 2,2 [ 0.2–3.7 ] ; P : 2 [ 0–6.3 ] ; P = NS ) , and during swallowing ( G : 2.8 [ 0.4–8.9 ] ; P : 3 [ 1.4–6.3 ] ; P = NS ] ) . Eight patients had a diagnostic question naire score more than 3 , 6 mo after operation versus 2 in preoperative period ( P = 0.04 ) . Such delayed neuropathic pain complaints were reported in seven patients receiving SCPB alone and only in one patient receiving both SCPB and preoperative adjunctive oral gabapentin . ( P = 0.01 ) . CONCLUSION : Oral preoperative administration of gabapentin did not modify immediate pain management in thyroidectomy patients receiving SCPB , but prevented delayed neuropathic pain at 6 mo Context The antiepileptics gabapentin and pregabalin are used as adjuvants to control postoperative pain . Objective The aim of the present study was to investigate the effect of perioperative administration of pregabalin on postoperative acute and chronic pain and analgesic requirements . Setting Department of Anaesthesiology , Aretaieio University Hospital , Athens , Greece . Patients Eighty patients scheduled for abdominal hysterectomy or myomectomy were r and omly assigned to the pregabalin or to the control group . Intervention The pregabalin group received 150 mg of pregabalin 8-hourly , starting on the afternoon before surgery and continued until the fifth postoperative day . The control group was similarly treated , but received placebo capsules instead . Measurements Postoperative intravenous morphine and Lonalgal ( 30 mg codeine with 500 mg paracetamol ) tablet consumption , visual analogue pain scores at rest and on coughing , sedation , anxiety , dizziness , ataxia , blurred vision and diplopia were recorded . One and 3 months postoperatively patients were interviewed for the presence of pain and analgesic needs due to surgery . Results The pregabalin-treated patients consumed less morphine during the first 48 h postoperatively ( P = 0.0001 ) . However , consumption of Lonalgal tablets and visual analogue scores for pain at rest and on coughing did not differ between the groups . No difference was found in sedation and anxiety scores between the patients who received placebo or pregabalin . Patients in the control group had lower incidences of dizziness ( 29 versus 58 % , P = 0.015 ) , ataxia ( 0 versus 18 % , P = 0.011 ) , blurred vision ( 6 versus 26 % , P = 0.028 ) and diplopia ( 0 versus 16 % , P = 0.023 ) . Presence of pain , analgesic intake due to surgery and decreased or absent sensation around the wound did not differ between the groups 1 and 3 months postoperatively . Conclusion Pregabalin in the doses given decreased morphine requirements for the first 48 h postoperatively , but neither altered the analgesic requirements beyond 48 h nor had any effect on acute , late or chronic pain BACKGROUND Pain following total knee arthroplasty ( TKA ) interferes with rehabilitation . Capsaicin applied in high concentration to nociceptors can cause relatively selective C-fibre desensitization for a period of weeks to months . Result ant long-lasting analgesia might facilitate rehabilitation . OBJECTIVE The objective of this study was to determine if direct instillation of a high-concentration capsaicin preparation into the wound following TKA would provide pain relief , improve physical functioning and rehabilitation , and reduce opioid requirements . METHODS This was a r and omized , double-blind , parallel-group , placebo-controlled , multicentre , phase II trial carried out in a teaching hospital system . Non-opioid-tolerant males or females aged 18 - 85 years with a body mass index ( BMI ) ≤45 kg/m2 , American Society of Anesthesiologists ( ASA ) physical status 1 - 3 and end-stage osteoarthritis who were scheduled for primary unilateral TKA were included . Patients received placebo vehicle or capsaicin 15 mg ( Anesiva 4975 ) by instillation immediately prior to wound closure . Surgery was conducted under spinal anaesthesia and femoral nerve block . Postoperative rescue analgesia consisted of intravenous patient-controlled analgesia with morphine for 24 hours ; oral oxycodone was provided thereafter as needed . It was hypothesized prior to data collection that capsaicin instillation would reduce postoperative pain scores and result in improved patient satisfaction and ambulation . The primary outcome was the area under the numerical rating scale ( NRS ) for pain score-time curve from 4 to 24 hours ( AUC(4 - 24 ) ) . NRS for pain scores were obtained every 4 hours for 24 hours then daily with ambulation and physical therapy for 3 days . Function and patient satisfaction were assessed at 14 , 28 and 42 days . RESULTS Data from 14 patients ( seven per group ) from a single centre ( data were not available from other sites because of sponsor bankruptcy ) were available for this preliminary report . AUC(4 - 24 ) was not significantly different clinical ly ( placebo 70.3 ; capsaicin 65.7 ) in this sample ; however , a significant opioid-sparing effect was seen in the capsaicin group despite the fact that patients in this group had higher BMI s. Pain scores tended to be lower in the capsaicin group , despite the fact that patients in this group received significantly less rescue opioid medication . Morphine use from 12 - 24 hours was lower ( capsaicin group mean 13.4 mg ; 95 % confidence interval [ CI ] 7.4 , 19.5 ; range 10 - 21 mg vs placebo group mean 25.9 mg ; 95 % CI 19.8 , 32.0 ; range 15 - 36 mg ; p = 0.009 ) . Total intravenous and oral opioid in morphine equivalents over 72 hours was also lower with capsaicin compared with placebo ( p = 0.03 ) . Active range of motion ( ROM ) was also significantly improved at day 14 in the capsaicin group compared with the placebo group ( p = 0.0014 ) . A higher percentage of patients in the capsaicin group reported being extremely satisfied with their treatment . The only statistically significant difference in treatment-emergent adverse events was for pruritus , which was more frequent in the placebo group ( p = 0.03 ) . CONCLUSION Despite having higher BMI s , patients in the capsaicin group achieved comparable or better pain scores with significantly less opioid use in the first 3 postoperative days . They also had less pruritus , which may have been a consequence of the opioid-sparing effect . The effects of capsaicin with respect to function , however , appeared to be longer lasting , with improved active ROM reported at 14 days We evaluated the effect of multimodal analgesia on acute and chronic pain after breast surgery for cancer . Fifty patients scheduled for breast cancer surgery were blindly r and omized to receive gabapentin , eutectic mixture of local anesthetics cream , and ropivacaine in the wound or three placebos . Pain ( visual analog scale ) and analgesics were recorded in the postanesthesia care unit ( PACU ) 3 , 6 , and 9 h and 8 days after surgery . Three and 6 mo later , patients were assessed for chronic pain . The treatment group consumed less paracetamol in the PACU ( 469 versus 991 mg ; P < 0.002 ) and less Lonalgal ® ( 1.0 versus 4.4 tablets ; P = 0.003 ) than the controls , exhibited lower visual analog scale scores at rest in the PACU ( P = 0.001 ) and on postoperative Days 1 , 3 , and 5 ( P = 0.040 , P = 0.015 , and P = 0.045 , respectively ) , and after movement in the PACU ( P = 0.001 ) and on postoperative Days 2 , 4 , and 8 ( P = 0.028 , P = 0.007 , and P = 0.032 , respectively ) . Three and 6 mo after surgery , 18 of 22 ( 82 % ) and 12 of 21 ( 57 % ) of the controls reported chronic pain versus 10 of 22 ( 45 % ) and 6 of 20 ( 30 % ) in the treatment group ( P = 0.028 and P = 0.424 , respectively ) ; 5 of 22 and 4 of 21 of the controls required analgesics versus 0 of 22 and 0 of 20 of those treated ( P = 0.048 and P = 0.107 , respectively ) . Multimodal analgesia reduced acute and chronic pain after breast surgery for cancer & NA ; Dextromethorphan is a noncompetitive N‐methyl‐D‐aspartate ( NMDA ) receptor antagonist known to inhibit wind‐up and NMDA‐mediated nociceptive responses of dorsal horn neurons . Experimental and clinical studies indicate that NMDA‐receptor antagonists may potentiate the effect of analgesics such as morphine , local anesthetics and NSAIDs . Results from previous clinical studies of dextromethorphan in postoperative pain are conflicting , possibly related to administration of insufficient doses of the drug . Fifty patients scheduled for non‐malignant elective abdominal hysterectomy in general anesthesia were r and omized to receive oral dextromethorphan 150 mg , or placebo 1 h before surgery . The patients received patient‐controlled analgesia with morphine for 24 h postoperatively as the only analgesic . Patient‐controlled analgesia ( PCA ) morphine consumption was reduced with 30 % from 0–4 h after operation in patients receiving dextromethorphan compared with placebo ( P=0.02 ) ; no differences were observed from 5–24 h postoperatively . There were no significant differences between groups for visual analogue scale scores at rest , during cough , or during mobilization , pressure pain detection thresholds , von Frey hair pain detection thresholds , or peak flow . At 24 h after operation , hyperalgesia to von Frey hair stimulation proximal to the surgical wound was easily detected in 23 of 25 patients receiving dextromethorphan , and in 22 of 25 patients receiving placebo , with no significant difference between groups . Pooled data from both groups showed a weak but significant correlation between the extent of hyperalgesia at 24 h after operation , and total 24 h postoperative PCA morphine consumption ( Rs=0.28 , P=0.05 ) . Three months postoperatively , hyperalgesia was still detectable in 18 of 22 examined patients in the dextromethorphan group , and in 16 of 23 patients in the placebo group , without statistical differences between groups . There were no significant differences in side‐effects ( nausea , vomiting , sedation ) . In conclusion , oral dextromethorphan 150 mg reduced PCA morphine consumption immediately ( 0–4 h ) after hysterectomy , without prolonged effects on pain or wound hyperalgesia . A positive correlation between the magnitude of wound hyperalgesia at 24 h after operation , and total 24 h postoperative PCA morphine consumption was demonstrated We investigated the analgesic efficacy of mexiletine and gabapentin on acute and chronic pain associated with cancer breast surgery in 75 patients . They were r and omized to receive , in a double-blinded manner , mexiletine 600 mg/d , gabapentin 1200 mg/d , or placebo for 10 days . Anesthesia was st and ardized , and all patients had access to routine postoperative analgesics on dem and . The visual analog scale score assessed pain at rest and after movement . Three months later , all patients were interviewed to identify intensity of chronic pain and analgesic requirements . Mexiletine and gabapentin reduced codeine consumed from the second to tenth day by 50 % ( P = 0.029;P = 0.018 and P = 0.035 for mexiletine versus control and gabapentin versus control comparisons , respectively ) . Total paracetamol consumption was also reduced during the same time ( P = 0.0085;P = 0.007 and P = 0.011 for the mexiletine and gabapentin groups when compared with the control , respectively ) . Pain at rest and after movement was reduced by both drugs on the third postoperative day . Pain after movement also was reduced by gabapentin between the second and fifth postoperative day . Three months later , the incidence of chronic pain , its intensity , and need for analgesics were not affected by either treatment . However , burning pain was more frequent in the control group ( P = 0.033 ) Background and Objectives A significant percentage of women undergoing breast surgery for cancer may develop neuropathic pain in the chest , and /or ipsilateral axilla and /or upper medial arm , with impairment in performing daily occupational activities . We design ed this study to determine if the perioperative application of EMLA ( eutectic mixture of local anesthetics ; AstraZeneca ) cream in the breast and axilla area reduces analgesic requirements , as well as the acute and chronic pain after breast surgery . Methods Forty-six female patients scheduled for breast surgery received r and omly 5 g of EMLA or placebo on the sternal area 5 minutes before surgery , and 15 g on the supraclavicular area and axilla at the end of the operation . Treatment with EMLA cream ( 20 g ) or placebo was also applied daily on the 4 days after surgery . In the postanesthesia care unit ( PACU ) , 3 , 6 , 9 , and 24 hours after surgery , and on the second to sixth day postoperatively , pain was assessed by visual analogue scale ( VAS ) at rest and after movement , and postoperative analgesic requirements were recorded . Three months later , patients were asked if they had pain in the chest wall , axilla and /or medial upper arm , decreased sensation , if they required analgesics at home , and for the intensity of pain . Results Acute pain at rest and with movement did not differ between the EMLA and control groups , and the analgesics consumed during the first 24 hours were the same for the EMLA and control groups . However , time to the first analgesia requirement was longer ( P = .04 ) , and codeine and paracetamol consumption during the second to fifth days was less ( P = .001 , and P = .004 , respectively ) in the EMLA versus the control group . Three months postoperatively , pain in the chest wall , axilla , and the total incidence and the intensity of chronic pain were significantly less in the EMLA versus the control group ( P = .004 , P = .025 , P = .002 and P = .003 , respectively ) . The use of analgesics at home and abnormal sensations did not differ between the 2 groups . Conclusions The application of EMLA to patients undergoing breast surgery for cancer reduced the postoperative analgesic requirements and the incidence and intensity of chronic pain Postmastectomy pain syndrome ( PMPS ) is a neuropathic pain syndrome that may develop following breast surgery . Venlafaxine has been shown to be efficacious in the management of PMPS . The preemptive administration of venlafaxine has been shown to be efficacious in reducing the incidence of neuropathic pain in the rat model . We examined the efficacy of administering either venlafaxine or placebo for two weeks starting the night before surgery to 100 patients scheduled for either partial or radical mastectomy with axillary dissection . Patients were administered PCA morphine for the first 24 hours following surgery and then acetaminophen/oxycodone tablets . Pain scores were recorded at rest and movement on day 1 , at 1 month , and at 6 months after surgery . At 6 months postoperatively , the presence of pain in the chest , arm , and axilla ; edema ; decreased sensation in the operative area ; and phantom breast pain were recorded . There was no difference in postoperative opioid use . Pain scores with movement were lower in the venlafaxine group at 6 months . Pain scores at all other time intervals were similar . There was a significant decrease in the incidence of chest wall pain ( 55 % vs. 19 % , P = 0.0002 ) , arm pain ( 45 % vs. 17 % , P = 0.003 ) , and axilla pain ( 51 % vs. 19 % , P = 0.0009 ) between the control group and the venlafaxine group , respectively . No significant differences were noted between the two groups with regard to edema , phantom pain , or sensory changes . We conclude that the perioperative administration of venlafaxine beginning the night prior to surgery significantly reduces the incidence of PMPS following breast cancer surgery Abstract Background and objective Perioperative low-dose ketamine has been useful for postoperative analgesia . In this study we wanted to assess the analgesic effect and possible side-effects of perioperative low-dose S ( + ) ketamine when added to a regime of non-opioid multimodal pain prophylaxis . Methods Seventy-seven patients scheduled for haemorrhoidectomy were enrolled in this r and omized , double-blind , controlled study . They received oral paracetamol 1–2 g , total intravenous anaesthesia , intravenous 8 mg dexamethasone , 30 mg ketorolac and local infiltration with bupivacaine/epinephrine . Patients r and omized to S ( + ) ketamine received an intravenous bolus dose of 0.35 mg kg−1 S ( + ) ketamine before start of surgery followed by continuous infusion of 5 μg kg−1 min−1 until 2 min after end of surgery . Patients in the placebo group got isotonic saline ( bolus and infusion ) . BISTM monitoring was used . Pain intensity and side-effects were assessed by blinded nursing staff during PACU stay and by phone 1 , 7 and 90 days after surgery . Results In patients r and omized to S ( + ) ketamine emergence from anaesthesia was significantly longer ( 13.1 min vs. 9.3 min ; p < 0.001 ) . BIS values were significantly higher during anaesthesia ( maximal value during surgery : 62 vs. 57 ; p = 0.01 ) and when opening eyes ( 81 vs. 70 , p < 0.001 ) . Pain scores ( NRS and VAS ) did not differ significantly between groups . Conclusions The addition of perioperative S ( + ) ketamine for postoperative analgesia after haemorrhoidectomy on top of multimodal non-opioid pain prophylaxis does not seem to be warranted , due to delayed emergence and recovery , more side-effects , altered BIS readings and absence of additive analgesic effect Objectives Chronic postthoracotomy pain is the most common long-term complication that occurs after a thoracotomy with a reported incidence of up to 80 % . Although thoracic epidural analgesia is a widely used method for managing acute postthoracotomy pain , its effects seems question able . The objective of this prospect i ve , double-blinded , r and omized , controlled trial was to assess the effect of preemptive low-dose epidural ketamine in addition to preemptive thoracic epidural analgesia on the incidence of chronic postthoracotomy pain . Methods We analyzed 133 patients who were r and omized to preemptive thoracic epidural analgesia either with or without ketamine ( Group K : 0.12 % levobupivacaine , 2 & mgr;g/mL of fentanyl , 0.2 mg/mL ketamine , total volume of 500 mL vs. Group KF : 0.12 % levobupivacaine , 2 & mgr;g/mL of fentanyl , total volume of 500 mL ) . Pain at the thoracotomy scar site during rest and movement ( coughing ) was assessed at 2 weeks and 3 months after surgery using a visual analog scale . The incidence of allodynia and numbness was also evaluated . Results There was no difference in the incidence of chronic postthoracotomy pain at 3 months between the 2 groups ( 67.7 % in group K vs. 75 % in group KF ) . The incidences of allodynia or numbness were not different between the 2 groups . Discussion The addition of preemptive low-dose epidural ketamine ( 1.2 mg/h ) to preemptive thoracic epidural analgesia did not have any beneficial effects in preventing chronic postthoracotomy pain STUDY OBJECTIVE To compare outcomes after conservative surgery for endometriosis with and without pentoxifylline and to assess the efficacy of pentoxifylline in preventing recurrence of endometriosis after conservative surgery . DESIGN Parallel-group , r and omized , controlled trial ( Canadian Task Force classification I ) . SETTING Tertiary care hospital . PATIENTS Women undergoing conservative surgery for endometriosis . INTERVENTIONS Laparoscopic conservative surgery for endometriosis was completed by a single surgeon ( J.A.T. ) , and all suspected endometriotic lesions were widely excised using monopolar coagulation and scissors . All specimens were su bmi tted to pathology for confirmation of the diagnosis . R and omization to the treatment or control groups was completed preoperatively in the outpatient surgery unit by drawing colored marbles . A preoperative visual analog pain scale ( VAS ) was completed . After surgery , patients were discharged home with prescriptions for naproxen , hydromorphone , and pentoxifylline . MEASUREMENTS AND MAIN RESULTS Visual analog scale scoring was completed monthly by each patient , and each patient was seen monthly for review and pelvic examination . Analgesic use was recorded daily using an individual medication log . Ongoing treatment choice after completion of the 3-month follow-up was recorded . The relationship between the group receiving pentoxifylline and the control group as well as analysis of the VAS scores at time of surgery and 1 , 2 , and 3 months postoperatively was determined using a covariate mixed-model ANOVA . Forty-nine patients were enrolled in the trial . One patient became pregnant before surgery , and 1 patient 's chart was not available for analysis . Of the 47 who underwent conservative surgery for endometriosis , 9 ( 19 % ) had no endometriosis noted in the pathology specimens su bmi tted . Two patients withdrew from the trial after surgery , and 2 patients were lost to follow-up after relocating to a different city . Nineteen women completed the 3-month follow-up in the control group , 15 in the group receiving pentoxifylline . The mean age , gravidity , parity , body mass index , previous surgery for endometriosis , menstrual cycle , and preoperative analgesic use did not differ significantly between the control and treatment groups . The time to complete the conservative surgery did not vary between the 2 groups . There were no intraoperative complications : two patients were admitted postoperatively , one for nausea and vomiting , one for pain that resolved 24 hours after admission . The VAS scores did not differ at the time of surgery ; and in both the control and the pentoxifylline groups , there was significant improvement at each monthly interval ( p < .05 ) . The patients receiving pentoxifylline had significantly better VAS scores at 2 and 3 months after surgery ( p < .03 ) . CONCLUSIONS The use of pentoxifylline after conservative surgery for endometriosis result ed in improved VAS scores at 2 and 3 months after the procedure when compared with patients having conservative surgery only . The longer-term use of pentoxifylline after conservative surgery may improve long-term outcomes after surgical treatment for endometriosis & NA ; Perioperative minocycline administration for 8 days after lumbar discectomy does not improve persistent pain . & NA ; Minocycline strongly inhibits microglial activation , which contributes to central sensitization , a major mechanism underlying chronic pain development . We hypothesized that the perioperative administration of minocycline might decrease persistent pain after lumbar discectomy . We r and omly assigned 100 patients undergoing scheduled lumbar discectomy to placebo and minocycline groups . The minocycline group received 100 mg minocycline orally , twice daily , beginning the evening before surgery and continuing for 8 days . The primary outcome was the change in lower limb pain intensity at rest between baseline and 3 months . Secondary outcomes were pain intensity on movement , the incidence of persistent pain and chronic neuropathic pain , back pain intensity at rest and on movement , and changes in Neuropathic Pain Symptom Inventory , Brief Pain Inventory , and Rol and ‐Morris scores at 3 months . An intention‐to‐treat analysis was performed for patients assessed from the day before surgery to 3 months . The decrease in lower limb pain intensity was similar in the placebo and minocycline groups , both at rest −1.7 ± 1.6 vs −2.3 ± 2.4 and on movement −2.5 ± 2.1 vs −3.4 ± 2.9 . The incidence and intensity of neuropathic pain and functional scores did not differ between the minocycline and placebo groups . Exploratory analysis suggested that minocycline might be effective in a subgroup of patients with predominantly deep spontaneous pain at baseline . Perioperative minocycline administration for 8 days does not improve persistent pain after lumbar discectomy BACKGROUND Thoracotomy is associated with severe pain . Large doses of morphine can depress respiratory drive and compromise hemodynamic stability . Ketamine reduces hyperalgesia , prevents opioid tolerance and resistance and lowers morphine consumption . At sub-anesthetic ( < or = 500 microg/kg ) doses , ketamine rarely produces undesirable hemodynamic alterations . We hypothesized that by combining a sub-anesthetic dose of ketamine with morphine , we could effectively control pain with less morphine and minimize drowsiness , while maintaining safe hemodynamic and respiratory parameters . METHODS Sequential patients undergoing anterolateral thoracotomy for MIDCAB , lung tumor resection , or median sternotomy for OPCAB were r and omized to one of the two intravenous patient-controlled analgesia ( IV-PCA ) protocol s. MO-only patients received 1.5 mg MO bolus , and MK patients received 1.0 mg MO+5 mg ketamine/bolus , both with a 7 min lockout time . IV-PCA was initiated when the patient was sufficiently awake ( > or = 5/10 VAS ) and rated pain > or = 5/10 on a 0 - 10 VAS . Rescue intramuscular diclofenac 75 mg was available . Follow-up of respiratory , hemodynamic and pain statuses lasted 72 h. RESULTS Fifty-eight patients completed the 6-month study . Heart rate and blood pressures were identically stable in both groups . Respiratory rate and pulse oximetry were higher ( P < 0.05 ) in the MK than in the MO group . MO patients ( n = 28 ) used twice ( 2.0 + /-2.3 mg/patient/h ) the amount of morphine compared to MK patients ( n = 30 , 1.0 + /- 1.4 mg/patient/h , P < 0.05 ) . Thirty-six hours after starting PCA , 10 MO patients still required IV-PCA compared to 5 MK patients ( P < 0.05 ) . Diclofenac was used 70 % more in MO than in MK patients . MO patients suffered more postoperative nausea and vomiting . No patients had hallucinations . CONCLUSIONS The concomitant use of sub-anesthetic ketamine plus two-thirds the st and ard MO dose following thoracotomy , MIDCAB or OPCAB result ed in lower pain scores , reduced MO consumption and shorter postoperative IV-PCA dependence . These advantages were associated with cardiovascular stability and even better respiratory parameters |
10,719 | 31,752,903 | Conclusions Adding PA to the school day may enhance children ’s mathematics performance or has no negative effects on performance . | Background The benefits of physical activity ( PA ) on children ’s health and wellbeing are well established .
However , the benefits of PA on academic performance and particularly on mathematics performance warrant systematic analysis .
Mathematics is one of the core subjects in school education globally . | Objective : An emerging field of research indicates that physical activity can benefit cognitive functions and academic achievements in children . However , less is known about how academic achievements can benefit from specific types of motor activities ( e.g. , fine and gross ) integrated into learning activities . Thus , the aim of this study was to investigate whether fine or gross motor activity integrated into math lessons ( i.e. , motor-enrichment ) could improve children 's mathematical performance . Methods : A 6-week within school cluster-r and omized intervention study investigated the effects of motor-enriched mathematical teaching in Danish preadolescent children ( n = 165 , age = 7.5 ± 0.02 years ) . Three groups were included : a control group ( CON ) , which received non-motor enriched conventional mathematical teaching , a fine motor math group ( FMM ) and a gross motor math group ( GMM ) , which received mathematical teaching enriched with fine and gross motor activity , respectively . The children were tested before ( T0 ) , immediately after ( T1 ) and 8 weeks after the intervention ( T2 ) . A st and ardized mathematical test ( 50 tasks ) was used to evaluate mathematical performance . Furthermore , it was investigated whether motor-enriched math was accompanied by different effects in low and normal math performers . Additionally , the study investigated the potential contribution of cognitive functions and motor skills on mathematical performance . Results : All groups improved their mathematical performance from T0 to T1 . However , from T0 to T1 , the improvement was significantly greater in GMM compared to FMM ( 1.87 ± 0.71 correct answers ) ( p = 0.02 ) . At T2 no significant differences in mathematical performance were observed . A subgroup analysis revealed that normal math-performers benefitted from GMM compared to both CON 1.78 ± 0.73 correct answers ( p = 0.04 ) and FMM 2.14 ± 0.72 correct answers ( p = 0.008 ) . These effects were not observed in low math-performers . The effects were partly accounted for by visuo-spatial short-term memory and gross motor skills . Conclusion : The study demonstrates that motor enriched learning activities can improve mathematical performance . In normal math performers GMM led to larger improvements than FMM and CON . This was not the case for the low math performers . Future studies should further eluci date the neurophysiological mechanisms underlying the observed behavioral effects We compared changes in academic achievement across 3years between children in elementary schools receiving the Academic Achievement and Physical Activity Across the Curriculum intervention ( A+PAAC ) , in which classroom teachers were trained to deliver academic lessons using moderate-to-vigorous physical activity ( MVPA ) compared to a non-intervention control . Elementary schools in eastern Kansas ( n=17 ) were cluster r and omized to A+PAAC ( N=9 , target ≥100min/week ) or control ( N=8 ) . Academic achievement ( math , reading , spelling ) was assessed using the Wechsler Individual Achievement Test-Third Edition ( WIAT-III ) in a sample of children ( A+PAAC=316 , Control=268 ) in grade s 2 and 3 at baseline ( Fall 2011 ) and repeated each spring across 3years . On average 55min/week of A+PACC lessons were delivered each week across the intervention . Baseline WIAT-III scores ( math , reading , spelling ) were significantly higher in students in A+PAAC compared with control schools and improved in both groups across 3years . However , linear mixed modeling , accounting for baseline between group differences in WIAT-III scores , ethnicity , family income , and cardiovascular fitness , found no significant impact of A+PAAC on any of the academic achievement outcomes as determined by non-significant group by time interactions . A+PAAC neither diminished or improved academic achievement across 3-years in elementary school children compared with controls . Our target of 100min/week of active lessons was not achieved ; however , students attending A+PAAC schools received an additional 55min/week of MVPA which may be associated with both physical and mental health benefits , without a reduction in time devoted to academic instruction BACKGROUND Physically active learning that combines physical activity with core curriculum areas is emerging in school-based health interventions . This study investigates the effectiveness of learning an important numeracy skill of times tables ( TT ) while concurrently engaging in aerobic activity compared with a seated classroom approach . METHODS Grade -4 primary school students were r and omly allocated to physical activity ( P ) or classroom ( C ) groups and received the alternate condition in the following term . P group received moderate to vigorous exercise ( 20 min , 3 times per week , 6 wk ) while simultaneously learning selected TT . C group received similar learning , but seated . Changes in TT accuracy , general numeracy , aerobic fitness , and body mass index were assessed . Data were expressed as mean ( SEM ) and between-condition effect size ( ES ; 95 % confidence interval ) . RESULTS Participants [ N = 85 ; 55 % male , 9.8 ( 0.3 ) y , 36.4 % overweight/obese ] improved similarly on TT in both conditions [ C group : 2.2 % ( 1.1 % ) ; P group : 2.5 % ( 1.3 % ) ; ES = 0.03 ; -0.30 to 0.36 ; P = .86 ] . Improvement in general numeracy was significantly greater for P group than C group [ C group : 0.7 % ( 1.2 % ) ; P group : 5.3 % ( 1.4 % ) ; ES = 0.42 ; 0.08 to 0.75 ; P < .03 ] . An improvement in aerobic fitness for P group ( P < .01 ) was not significantly greater than C group [ C group : 0.8 ( 0.6 ) ; P group : 2.2 ( 0.5 ) mL·kg·min-1 ; ES = 0.32 ; -0.01 to 0.66 ; P = .06 ] . Body mass index was unchanged . CONCLUSION Combined movement with learning TT was effective . Physically active learning paradigms may contribute to meeting daily physical activity guidelines while supporting or even boosting learning OBJECTIVE To investigate the effect of a seven-month , school-based cluster-r and omized controlled trial on academic performance in 10-year-old children . METHODS In total , 1129 fifth- grade children from 57 elementary schools in Sogn og Fjordane County , Norway , were cluster-r and omized by school either to the intervention group or to the control group . The children in the 28 intervention schools participated in a physical activity intervention between November 2014 and June 2015 consisting of three components : 1 ) 90min/week of physically active educational lessons mainly carried out in the school playground ; 2 ) 5min/day of physical activity breaks during classroom lessons ; 3 ) 10min/day physical activity homework . Academic performance in numeracy , reading and English was measured using st and ardized Norwegian national tests . Physical activity was measured objective ly by accelerometry . RESULTS We found no effect of the intervention on academic performance in primary analyses ( st and ardized difference 0.01 - 0.06 , p>0.358 ) . Subgroup analyses , however , revealed a favorable intervention effect for those who performed the poorest at baseline ( lowest tertile ) for numeracy ( p=0.005 for the subgroup∗group interaction ) , compared to controls ( st and ardized difference 0.62 , 95 % CI 0.19 - 1.07 ) . CONCLUSIONS This large , rigorously conducted cluster RCT in 10-year-old children supports the notion that there is still inadequate evidence to conclude that increased physical activity in school enhances academic achievement in all children . Still , combining physical activity and learning seems a viable model to stimulate learning in those academically weakest schoolchildren A cluster-r and omized controlled trial was conducted to examine the effects of a 4-week program that integrated movements into cognitive tasks related to numerical skills . Participants ( N = 120 , Mage = 4.70 years , SD = 0.49 ; 57 girls ) were assigned to one of the following four conditions : performing integrated physical activity ( task relevant ) , performing nonintegrated physical activity ( task nonrelevant ) , observing integrated physical activity , or conventional sedentary teaching ( without performing or observing physical activity ) . Results showed that children who performed task-relevant integrated physical activity performed better than children in all other conditions . In addition , children who performed physical activity , either integrated or nonintegrated , reported higher scores for enjoyment of the instructional method than the two sedentary learning conditions . Implication s for educational theory and practice are discussed Background Physical activity is associated not only with health-related parameters , but also with cognitive and academic performance . However , no large scale school-based physical activity interventions have investigated effects on cognitive performance in adolescents . The aim of this study was to describe the effectiveness of a school-based physical activity intervention in enhancing cognitive performance in 12–14 years old adolescents . Methods A 20 week cluster r and omized controlled trial was conducted including seven intervention and seven control schools . A total of 632 students ( mean ( SD ) age : 12.9 ( 0.6 ) years ) completed the trial with baseline and follow-up data on primary or secondary outcomes ( 74 % of r and omized subjects ) . The intervention targeted physical activity during academic subjects , recess , school transportation and leisure-time . Cognitive performance was assessed using an executive functions test of inhibition ( flanker task ) with the primary outcomes being accuracy and reaction time on congruent and incongruent trials . Secondary outcomes included mathematics performance , physical activity levels , body-mass index , waist-circumference and cardiorespiratory fitness . Results No significant difference in change , comparing the intervention group to the control group , was observed on the primary outcomes ( p’s>0.05 ) or mathematics skills ( p>0.05 ) . An intervention effect was found for cardiorespiratory fitness in girls ( 21 meters ( 95 % CI : 4.4–38.6 ) and body-mass index in boys ( -0.22 kg/m2 ( 95 % CI : -0.39–0.05 ) . Contrary to our predictions , a significantly larger change in interference control for reaction time was found in favor of the control group ( 5.0 milliseconds ( 95 % CI : 0–9 ) . Baseline to mid-intervention changes in physical activity levels did not differ significantly between groups ( all p’s>0.05 ) . Conclusions No evidence was found for effectiveness of a 20-week multi-faceted school-based physical activity intervention for enhancing executive functioning or mathematics skills compared to a control group , but low implementation fidelity precludes interpretation of the causal relationship . Trial Registration www . Clinical Trials.gov OBJECTIVE This experiment tested the hypothesis that exercise would improve executive function . DESIGN Sedentary , overweight 7- to 11-year-old children ( N = 171 , 56 % girls , 61 % Black , M ± SD age = 9.3 ± 1.0 years , body mass index [ BMI ] = 26 ± 4.6 kg/m² , BMI z-score = 2.1 ± 0.4 ) were r and omized to 13 ± 1.6 weeks of an exercise program ( 20 or 40 min/day ) , or a control condition . MAIN OUTCOME MEASURES Blinded , st and ardized psychological evaluations ( Cognitive Assessment System and Woodcock-Johnson Tests of Achievement III ) assessed cognition and academic achievement . Functional MRI measured brain activity during executive function tasks . RESULTS Intent to treat analysis revealed dose-response benefits of exercise on executive function and mathematics achievement . Preliminary evidence of increased bilateral prefrontal cortex activity and reduced bilateral posterior parietal cortex activity attributable to exercise was also observed . CONCLUSION Consistent with results obtained in older adults , a specific improvement on executive function and brain activation changes attributable to exercise were observed . The cognitive and achievement results add evidence of dose-response and extend experimental evidence into childhood . This study provides information on an educational outcome . Besides its importance for maintaining weight and reducing health risks during a childhood obesity epidemic , physical activity may prove to be a simple , important method of enhancing aspects of children 's mental functioning that are central to cognitive development . This information may persuade educators to implement vigorous physical activity BACKGROUND This study examined associations of fitness and fatness with cognitive processes , academic achievement , and behavior , independent of demographic factors , at the baseline of an exercise trial . METHODS Overweight , sedentary but otherwise healthy 7 - 11 year olds ( N=170 ) participated in a study of health , cognition and achievement in the Augusta , GA area from 2003 - 2006 . Children underwent evaluations of fatness and fitness , psychological assessment s of cognition and academic achievement , and behavior ratings by parents and teachers . Partial correlations examined associations of fitness and fatness with cognitive and achievement scores and behavior ratings , controlling for demographic factors . RESULTS Fitness was associated with better cognition , achievement and behavior , and fatness with worse scores . Specifically , executive function , mathematics and reading achievement , and parent ratings of child behavior were related to fitness and fatness . Teacher ratings were related to fitness . CONCLUSION These results extend prior studies by providing reliable , st and ardized measures of cognitive processes , achievement , and behavior in relation to detailed measures of fitness and fatness . However , cross-sectional associations do not necessarily indicate that improving one factor , such as fatness or fitness , will result in improvements in factors that were associated with it . Thus , r and omized clinical trials are necessary to determine the effects of interventions 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 Purpose : The purpose of this study was to determine the acute dose – response relationship of classroom exercise breaks with executive function and math performance in 9- to 12-year-old children by comparing 5-min , 10-min , or 20-min classroom exercise breaks to 10 min of sedentary classroom activity . Method : This study used a within-subjects experimental design conducted in the spring of 2012 . Ninety-six 4th- and 5th- grade students in 5 classrooms in South Carolina were r and omized to receive each of 4 treatments : 5-min , 10-min , or 20-min exercise breaks or 10 min of a sedentary lesson led by research staff . Students completed the Trail-Making Test , an Operational Digit Recall test , and a math fluency test immediately before and after each condition . Planned linear contrasts were used to compare posttest scores between conditions using a repeated- measures mixed model , adjusted for gender , classroom , and the time-varying pretest scores . Potential effect modifiers were added as interaction terms . Results : Math scores were higher after the 10-min and 20-min exercise breaks compared with the sedentary condition ( d = 0.24 , p = .04 , and d = 0.27 , p = .02 , respectively ) , and an interaction was observed with gender , IQ , aerobic fitness , and lower engagement in some of the conditions . There were no improvements in executive function tasks . Conclusions : A 10-min and 20-min classroom exercise break moderately improved math performance in students compared with a seated classroom lesson BACKGROUND There is a paucity of research investigating the effects of innovative physical activity programs on physical health and academic performance in the Latino population . PURPOSE To examine the impact of Dance Dance Revolution [DDR]-based exercise on Latino children 's physical fitness and academic achievement . DESIGN A repeated- measures crossover design was used . In Year 1 , Grade -4 students were assigned to the intervention group and offered 30 minutes of exercise ( DDR , aerobic dance ) three times per week . Grade -3 and Grade -5 students made up the comparison group and were offered no structured exercise at school . In Year 2 , the Grade -4 students were again assigned to the intervention , whereas Grade -5 and Grade -6 students were in the comparison group . SETTING / PARTICIPANTS Assessment s were conducted with 208 Latino school children . MAIN OUTCOME MEASURES The baseline measures included time to complete a 1-mile run , BMI , and reading and math scores . Data were collected again 9 months later . Overall , data were collected in 2009 - 2011 and analyzed in 2012 . RESULTS Data yielded significant differences between the intervention and comparison groups in differences in 1-mile run and math scores in Year 1 and Year 2 . The results also revealed net differences in the intervention versus comparison group scores on the 1-mile run for Grade 3 ( p<0.01 ) . Additionally , children 's yearly pre-test and post-test BMI group changes differed ( χ(2)((2 ) ) = 6.6 , p<0.05 ) only for the first year of intervention . CONCLUSIONS The DDR-based exercise intervention improved children 's cardiorespiratory endurance and math scores over time . Professionals should consider integrating exergaming at schools to achieve the goals of promoting a physically active lifestyle and enhancing academic success among Latino children The global epidemic of obesity and physical inactivity may have detrimental implication s for young people ’s cognitive function and academic achievement . This prospect i ve study investigated whether childhood motor function predicts later academic achievement via physical activity , fitness , and obesity . The study sample included 8,061 children from the Northern Finl and Birth Cohort 1986 , which contains data about parent-reported motor function at age 8 y and self-reported physical activity , predicted cardiorespiratory fitness ( cycle ergometer test ) , obesity ( body weight and height ) , and academic achievement ( grade s ) at age 16 y. Structural equation models with unst and ardized ( B ) and st and ardized ( β ) coefficients were used to test whether , and to what extent , physical activity , cardiorespiratory fitness , and obesity at age 16 mediated the association between childhood motor function and adolescents ’ academic achievement . Physical activity was associated with a higher grade -point average , and obesity was associated with a lower grade -point average in adolescence . Furthermore , compromised motor function in childhood had a negative indirect effect on adolescents ’ academic achievement via physical inactivity ( B = –0.023 , 95 % confidence interval = –0.031 , –0.015 ) and obesity ( B = –0.025 , 95 % confidence interval = –0.039 , –0.011 ) , but not via cardiorespiratory fitness . These results suggest that physical activity and obesity may mediate the association between childhood motor function and adolescents ’ academic achievement . Compromised motor function in childhood may represent an important factor driving the effects of obesity and physical inactivity on academic underachievement OBJECTIVES : Using physical activity in the teaching of academic lessons is a new way of learning . The aim of this study was to investigate the effects of an innovative physically active academic intervention ( “ Fit & Vaardig op School ” [ F&V ] ) on academic achievement of children . METHODS : Using physical activity to teach math and spelling lessons was studied in a cluster-r and omized controlled trial . Participants were 499 children ( mean age 8.1 years ) from second- and third- grade classes of 12 elementary schools . At each school , a second- and third- grade class were r and omly assigned to the intervention or control group . The intervention group participated in F&V lessons for 2 years , 22 weeks per year , 3 times a week . The control group participated in regular classroom lessons . Children ’s academic achievement was measured before the intervention started and after the first and second intervention years . Academic achievement was measured by 2 mathematics tests ( speed and general math skills ) and 2 language tests ( reading and spelling ) . RESULTS : After 2 years , multilevel analysis showed that children in the intervention group had significantly greater gains in mathematics speed test ( P < .001 ; effect size [ ES ] 0.51 ) , general mathematics ( P < .001 ; ES 0.42 ) , and spelling ( P < .001 ; ES 0.45 ) scores . This equates to 4 months more learning gains in comparison with the control group . No differences were found on the reading test . CONCLUSIONS : Physically active academic lessons significantly improved mathematics and spelling performance of elementary school children and are therefore a promising new way of teaching Active learning combines academic content with physical activity ( PA ) to increase child PA and academic performance , but the impact of active learning is mixed . It may be that this is a moderated relationship in which active learning is beneficial for only some children . This paper examine the impact of baseline academic performance and gender as moderators for the effects of active learning on children 's academic performance . In the ASK- study , 1129 fifth- grade rs from 57 Norwegian elementary schools were r and omized by school to intervention or control in a physical activity intervention between November 2014 and June 2015 . Academic performance in numeracy , reading , and English was measured and a composite score was calculated . Children were split into low , middle and high academic performing tertiles . 3-way-interactions for group ( intervention , control)∗gender ( boys , girls)∗academic performance ( tertiles ) were investigated using mixed model regression . There was a significant , 3-way-interaction ( p=0.044 ) . Both boys ( ES=0.11 ) and girls ( ES=0.18 ) in the low performing tertile had a similar beneficial trend . In contrast , middle ( ES=0.03 ) and high performing boys ( ES=0.09 ) responded with small beneficial trends , while middle ( ES=-0.11 ) and high performing girls ( ES=-0.06 ) responded with negative trends . ASK was associated with a significant increase in academic performance for low performing children . It is likely that active learning benefited children most in need of adapted education but it may have a null or negative effect for those girls who are already performing well in the sedentary classroom . Differences in gendered responses are discussed as a possible explanation for these results . TRIAL REGISTRATION Clinical trials.gov registry , trial registration number : NCT02132494 Purpose The primary aim of this study was to test the effect of a school-based physical activity intervention on adolescents ’ performance in mathematics . A secondary aim was to explore potential mechanisms that might explain the intervention effect . Methods The Activity and Motivation in Physical EDucation intervention was evaluated using a two-arm cluster r and omized controlled trial in 14 secondary schools located in low socioeconomic areas of Western Sydney , Australia . Study participants ( n = 1173 ) were grade 8 students ( mean age = 12.94 yr , SD = 0.54 ) . The multicomponent intervention was design ed to help teachers maximize students ’ opportunities for moderate-to-vigorous physical activity ( MVPA ) during physical education ( PE ) and enhance students ’ motivation toward PE . Mathematics performance was assessed as part of national testing in grade 7 , which was the year before the trial began and then again in grade 9 . Potential mediators were : ( i ) proportion of PE lesson time that students spent in MVPA and leisure time MVPA ( % ) , measured using Actigraph GT3X+ accelerometers , and ( ii ) students ’ self-reported engagement ( behavioral , emotional , and cognitive ) during mathematics lessons . Mediators were assessed at baseline ( grade 8) and follow-up ( grade 9 , 14–15 months after baseline ) . Results The effect of the intervention on mathematics performance was small-to-medium ( & bgr ; = 0.16 , P < 0.001 ) . An intervention effect was observed for MVPA% in PE ( & bgr ; = 0.59 , P < 0.001 ) , but not for leisure time MVPA or any of the engagement mediators . There were no significant associations between changes in potential mediators and mathematics performance . Conclusions The Activity and Motivation in Physical EDucation intervention had a significant positive effect on mathematics performance in adolescents . However , findings should be interpreted with caution as the effect was small and not associated with changes in hypothesized mediators OBJECTIVES To assess the feasibility and efficacy of a 6-week pilot active break program ( ACTI-BREAK ) on academic achievement , classroom behaviour and physical activity . DESIGN Pilot cluster r and omised controlled trial . METHODS 374 children in Year 3 and 4 ( 74 % response ) were recruited from six schools across Melbourne , Australia . Schools were r and omised to the ACTI-BREAK intervention or usual teaching practice . The intervention involved teachers incorporating 3 × 5min active breaks into their classroom routine daily . Academic achievement was assessed using 1-min tests in reading and mathematics ; classroom behaviour at the individual and whole class level was observed by teachers ; and physical activity levels were assessed using accelerometers . Multilevel mixed effects linear regression models were conducted using intention to treat ( ITT ) and per protocol ( PP ) analyses . RESULTS Significant intervention effects were found for classroom behaviour at the individual level ( ITT B=16.17 ; 95 % CI : 6.58 , 25.76 ) ; effects were stronger for boys ( B=21.42 ; 95 % CI : 10.34 , 32.49 ) than girls ( B=12.23 ; 95 % CI : 1.52 , 22.92 ) . No effect was found for classroom behaviour at the whole class level , reading , math or physical activity . PP findings were similar . CONCLUSIONS Implementing active breaks during class time may improve classroom behaviour , particularly for boys . There was no evidence to suggest that implementing active breaks had any adverse effect on academic achievement or classroom behaviour , which may encourage classroom teachers to incorporate active breaks into their routine BACKGROUND To evaluate the impact of a primary school-based physical activity ( PA ) integration program delivered by teachers on objective ly measured PA and key educational outcomes . METHODS Ten classes from 8 Australian public schools were r and omly allocated to treatment conditions . Teachers from the intervention group were taught to embed movement-based learning in their students ' ( n = 142 ) daily mathematics program in 3 lessons per week for 6 weeks . The control group ( n = 98 ) continued its regular mathematics program . The primary outcome was accelerometer-determined PA across the school day . Linear mixed models were used to analyze treatment effects . RESULTS Significant intervention effects were found for PA across the school day ( adjusted mean difference 103 counts per minute [ CPM ] , 95 % confidence interval [ CI ] , 36.5 - 169.7 , P = .008 ) . Intervention effects were also found for PA ( 168 CPM , 95 % CI , 90.1 - 247.4 , P = .008 ) and moderate-to-vigorous PA ( 2.6 % , 95 % CI , 0.9 - 4.4 , P = .009 ) in mathematics lessons , sedentary time across the school day ( -3.5 % , 95 % CI , -7.0 to -0.13 , P = .044 ) and during mathematics ( -8.2 % , CI , -13.0 to -2.0 , P = .010 ) and on-task behavior ( 13.8 % , 95 % CI , 4.0 - 23.6 , P = .011)-but not for mathematics performance or attitude . CONCLUSION Integrating movement across the primary mathematics syllabus is feasible and efficacious |
10,720 | 31,900,793 | Conclusions SGLT2 inhibitors and GLP-1 agonists combination treatment improved glycemic control , reduced body weight , and decreased SBP without an increase in total adverse events or genital and urinary infections in patients with T2DM or obesity | Purpose To evaluate the efficacy and safety of combination therapy with sodium – glucose cotransporter 2 ( SGLT2 ) inhibitors and glucagon-like peptide-1 ( GLP-1 ) receptor agonists in the treatment of type 2 diabetes mellitus ( T2DM ) or obese adults . | Sodium‐glucose co‐transporter‐2 ( SGLT2 ) inhibitors and glucagon‐like peptide‐1 receptor agonists ( GLP‐1RAs ) are antihyperglycaemic agents with weight‐lowering effects . The efficacy and safety of the SGLT2 inhibitor canagliflozin as add‐on therapy in Japanese patients with type 2 diabetes mellitus ( T2DM ) and inadequate glycaemic control with a GLP‐1RA ( ≥12 weeks ) were evaluated in this phase IV study . Patients received canagliflozin 100 mg once daily for 52 weeks . Efficacy endpoints included change in glycated haemoglobin ( HbA1c ) , fasting plasma glucose ( FPG ) , body weight , systolic blood pressure ( SBP ) and HDL cholesterol from baseline to week 52 . Safety endpoints included adverse events ( AEs ) , hypoglycaemia and laboratory tests . Of the 71 patients treated with canagliflozin , 63 completed the study . At 52 weeks , HbA1c was significantly reduced from baseline ( −0.70 % ; paired t test , P < .001 ) . Significant changes were also observed in FPG ( −34.7 mg/dL ) , body weight ( −4.46 % ) , SBP ( −7.90 mm Hg ) , and HDL cholesterol ( 7.60 % ; all P < .001 ) . The incidence of AEs , adverse drug reactions and hypoglycaemia was 71.8 % , 32.4 % and 9.9 % , respectively . All hypoglycaemic events were mild . These findings suggest that the long‐term combination of canagliflozin with a GLP‐1RA is effective and well tolerated in Japanese patients with T2DM BACKGROUND Glucagon-like peptide-1 ( GLP-1 ) receptor agonists and sodium-glucose co-transporter-2 ( SGLT2 ) inhibitors improve glycaemic control and reduce bodyweight in patients with type 2 diabetes through different mechanisms . We assessed the safety and efficacy of the addition of the once-weekly GLP-1 receptor agonist dulaglutide to the ongoing treatment regimen in patients whose diabetes is inadequately controlled with SGLT2 inhibitors , with or without metformin . METHODS AWARD-10 was a phase 3b , double-blind , parallel-arm , placebo-controlled , 24-week study done at 40 clinical sites in Austria , Czech Republic , Germany , Hungary , Israel , Mexico , Spain , and the USA . Eligible adult patients ( ≥18 years ) with inadequately controlled type 2 diabetes ( HbA1c concentration ≥7·0 % [ 53 mmol/mol ] and ≤9·5 % [ 80 mmol/mol ] ) , a BMI of 45 kg/m2 or less , and taking stable doses ( > 3 months ) of an SGLT2 inhibitor ( with or without metformin ) were r and omly assigned ( 1:1:1 ) via an interactive web-response system to subcutaneous injections of either dulaglutide 1·5 mg , dulaglutide 0·75 mg , or placebo once per week for 24 weeks . Patients and investigators were masked to dulaglutide and placebo assignment , and those assessing outcomes were masked to study drug assignment . The primary objective was to test for the superiority of dulaglutide ( 1·5 mg or 0·75 mg ) versus placebo for change in HbA1c concentration from baseline at 24 weeks . All analyses were done in the intention-to-treat population , defined as all r and omly assigned patients who received at least one dose of study drug . This study is registered with Clinical Trials.gov , number NCT02597049 . FINDINGS Between Dec 7 , 2015 , and Feb 3 , 2017 , 424 patients were r and omly assigned to dulaglutide 1·5 mg ( n=142 ) , dulaglutide 0·75 mg ( n=142 ) , and placebo ( n=140 ) . One patient in the dulaglutide 0·75 mg group was excluded from the analysis because they did not receive any dose of the study drug . The reduction in HbA1c concentration at 24 weeks was larger in patients receiving dulaglutide ( least squares mean [ LSM ] for dulaglutide 1·5 mg -1·34 % [ SE 0·06 ] or -14·7 mmol/mol [ 0·6 ] ; dulaglutide 0·75 mg -1·21 % [ 0·06 ] or -13·2 mmol/mol [ 0·6 ] ) than in patients receiving placebo ( -0·54 % [ 0·06 ] or -5·9 mmol/mol [ 0·6 ] ; p<0·0001 for both groups vs placebo ) . The LSM differences were -0·79 % ( 95 % CI -0·97 to -0·61 ) or -8·6 mmol/mol ( -10·6 to -6·7 ) for dulaglutide 1·5 mg and -0·66 % ( -0·84 to -0·49 ) or -7·2 mmol/mol ( -9·2 to -5·4 ) for dulaglutide 0·75 mg ( p<0·0001 for both ) . Serious adverse events were reported for five ( 4 % ) patients in the dulaglutide 1·5 mg group , three ( 2 % ) patients in the dulaglutide 0·75 mg group , and five ( 4 % ) patients in the placebo group . Treatment-emergent adverse events were more common in patients treated with dulaglutide than in patients who received placebo , mainly because of an increased incidence of gastrointestinal adverse events . Nausea ( 21 [ 15 % ] patients in the dulaglutide 1·5 mg group vs seven [ 5 % ] in the dulaglutide 0·75 mg group vs five [ 4 % ] in the placebo group ) , diarrhoea ( eight [ 6 % ] vs 14 [ 10 % ] vs four [ 3 % ] ) , and vomiting ( five [ 4 % ] vs four [ 3 % ] vs one [ 1 % ] ) were more common with dulaglutide than with placebo . One episode of severe hypoglycaemia was reported in the dulaglutide 0·75 mg group . Two ( 1 % ) patients receiving dulaglutide 1·5 mg died , but these deaths were not considered to be related to study drug ; no deaths occurred in the other groups . INTERPRETATION Dulaglutide as add-on treatment to SGLT2 inhibitors ( with or without metformin ) result ed in significant and clinical ly relevant improvements in glycaemic control , with acceptable tolerability that is consistent with the established safety profile of dulaglutide . FUNDING Eli Lilly and Company ABSTRACT Review of : Neal B , Perkovic V , Mahaffey K , et al. Canagliflozin and cardiovascular and renal events in type 2 diabetes . N Engl J Med . 2017;377:644–657 . The report combines the data from two trials , CANVAS and CANVAS-Renal , which were design ed to evaluate the safety and effect of canagliflozin , an SGLT-2 inhibitor , on the appearance of cardiovascular and renal events in patients with type 2 diabetes . Enrollees were patients with type 2 diabetes of at least 30 years of age , with a glycated hemoglobin of > or equal to 7.0 % and < or equal to 10.5 % . Patients either had to have preexisting cardiovascular disease or to be at elevated risk for cardiovascular disease , and to have an estimated glomerular filtration rate ( eGFR ) of > 30 ml/min . Patients were r and omized to canagliflozin at doses of either 100 mg or 300 mg or matching placebo in CANVAS , and to canagliflozin 100 mg with a possible increase to 300 mg , or placebo , in CANVAS-Renal . Physicians were instructed to continue appropriate diabetic management and other therapies in accordance with the best practice s in their community . There was a significant 14 % reduction in the combined endpoint of cardiovascular events of death from cardiovascular causes , nonfatal myocardial infa rct ion , or nonfatal stroke in the canagliflozin treated patients . There was also a pattern of improvement in markers of renal disease , including the change in the level and nature of albuminuria , a 40 % decrease in the glomerular filtration rate , the need for renal replacement therapy , or death from renal causes . This study exp and s the scope of SGLT-2 inhibitor therapy to prevent cardiovascular disease in diabetic patients beyond those with preexisting cardiovascular disease studied in the previous empagliflozin study , raising the question as to whether SGLT-2 inhibitor therapy should be considered appropriate for most , if not all , type 2 diabetes patients , not only to control hyperglycemia but also to reduce cardiovascular and renal events BACKGROUND Despite a broad range of pharmacological options for the treatment of type 2 diabetes , optimum glycaemic control remains challenging for many patients and new therapies are necessary . Semaglutide is a glucagon-like peptide-1 ( GLP-1 ) analogue in phase 3 development for type 2 diabetes . We assessed the efficacy , safety , and tolerability of semaglutide monotherapy , compared with placebo , in treatment-naive patients with type 2 diabetes who had insufficient glycaemic control with diet and exercise alone . METHODS We did a double-blind , r and omised , parallel-group , international , placebo-controlled phase 3a trial ( SUSTAIN 1 ) at 72 sites in Canada , Italy , Japan , Mexico , Russia , South Africa , UK , and USA ( including hospitals , clinical research units , and private offices ) . Eligible participants were treatment-naive individuals aged 18 years or older with type 2 diabetes treated with only diet and exercise alone for at least 30 days before screening , with a baseline HbA1c of 7·0%-10·0 % ( 53 - 86 mmol/mol ) . We r and omly assigned participants ( 2:2:1:1 ) to either once-weekly subcutaneously injected semaglutide ( 0·5 mg or 1·0 mg ) , or volume-matched placebo ( 0·5 mg or 1·0 mg ) , for 30 weeks via prefilled PDS290 pen-injectors . Participants did their own injections and were encouraged to administer them on the same day of each week in the same area of their body ; the time of day and proximity of meal times was not specified . We did the r and omisation with an interactive voice or web response system . Investigators , participants , and the funder of the study remained masked throughout the trial . The primary endpoint was the change in mean HbA1c from baseline to week 30 , and the confirmatory secondary endpoint was the change in mean bodyweight from baseline to week 30 . We assessed efficacy and safety in the modified intention-to-treat population ( ie , all participants who were exposed to at least one dose of study drug ) ; both placebo groups were pooled for assessment . This trial was registered with Clinical Trials.gov , number NCT02054897 . FINDINGS Between February 3 , 2014 , and August 21 , 2014 , we r and omly assigned 388 participants to treatment ; 387 received at least one dose of study medication ( 128 0·5 mg semaglutide , 130 1·0 mg semaglutide , 129 placebo ) . 17 ( 13 % ) of those assigned to 0·5 mg semaglutide , 16 ( 12 % ) assigned to 1·0 mg semaglutide , and 14 ( 11 % ) assigned to placebo discontinued treatment ; the main reason for discontinuation was gastrointestinal adverse events such as nausea . Mean baseline HbA1c was 8·05 % ( SD 0·85 ) ; at week 30 , HbA1c significantly decreased by 1·45 % ( 95 % CI -1·65 to -1·26 ) with 0·5 mg semaglutide ( estimated treatment difference vs placebo -1·43 % , 95 % CI -1·71 to -1·15 ; p<0·0001 ) , significantly decreased by 1·55 % ( -1·74 to -1·36 ) with 1·0 mg semaglutide ( estimated treatment difference vs placebo -1·53 % , -1·81 to -1·25 ; p<0·0001 ) , and non-significantly decreased by 0·02 % ( -0·23 to 0·18 ) with placebo . Mean baseline bodyweight was 91·93 kg ( SD 23·83 ) ; at week 30 , bodyweight significantly decreased by 3·73 kg ( 95 % CI -4·54 to -2·91 ) with 0·5 mg semaglutide ( estimated treatment difference vs placebo -2·75 kg , 95 % CI -3·92 to -1·58 ; p<0·0001 ) , significantly decreased by 4·53 kg ( -5·34 to -3·72 ) with 1·0 mg semaglutide ( estimated treatment difference vs placebo -3·56 kg , -4·74 to -2·38 ; p<0·0001 ) , and non-significantly decreased by 0·98 kg ( -1·82 to -0·13 ) with placebo . No deaths were reported in any of the study groups and most reported adverse events were of mild or moderate severity . The most frequently reported adverse events in both semaglutide groups were gastrointestinal in nature : nausea was reported in 26 ( 20 % ) who received 0·5 mg semaglutide , 31 ( 24 % ) who received 1·0 mg semaglutide , and 10 ( 8 % ) who received placebo , and diarrhoea was reported in 16 ( 13 % ) who received 0·5 mg semaglutide , 14 ( 11 % ) who received 1·0 mg semaglutide , and three ( 2 % ) who received placebo . INTERPRETATION Semaglutide significantly improved HbA1c and bodyweight in patients with type 2 diabetes compared with placebo , and showed a similar safety profile to currently available GLP-1 receptor agonists , representing a potential treatment option for such patients . FUNDING Novo Nordisk A/S , Denmark BACKGROUND Patients with moderate to severe plaque psoriasis demonstrated positive responses to ixekizumab , an anti-interleukin-17A monoclonal antibody , in a phase-II , r and omized , placebo-controlled trial . OBJECTIVE We sought to evaluate long-term efficacy and safety of ixekizumab . METHODS After receiving 10 , 25 , 75 , or 150 mg of ixekizumab or placebo during r and omized , placebo-controlled trial , patients with less than 75 % improvement from baseline on the Psoriasis Area and Severity Index ( PASI ) score ( PASI75 ) entered open-label extension ( OLE ) ; patients with PASI75 or higher entered a treatment-free period ( weeks 20 - 32 ) , then entered OLE after meeting response criteria . During OLE , patients received 120 mg of subcutaneous ixekizumab every 4 weeks . RESULTS In all , 120 patients entered OLE ; 103 completed 52 weeks or more of treatment . Overall , 77 % of patients achieved PASI75 at week 52 ( nonresponder imputation ) . Patients who responded to treatment in the r and omized , placebo-controlled trial maintained a high-level response by week 52 of OLE ( PASI75 = 95 % ; 90 % improvement from baseline on the PASI score = 94 % ; 100 % improvement from baseline on the PASI score = 82 % ) . Irrespective of dose in the r and omized , placebo-controlled trial , each group had similar response rates at week 52 of OLE . The exposure-adjusted incidence rate for adverse events was 0.47 and for serious adverse events was 0.06 per patient-year during OLE . LIMITATIONS No control group , small sample sizes , and bias toward retention of patients with positive responses limit interpretation . CONCLUSION A high proportion of patients responded to ixekizumab therapy and maintained clinical responses over 1 year of treatment with no unexpected safety signals Aims : To determine the effects of empagliflozin on adiposity indices among patients with type 2 diabetes mellitus . Methods : Changes in weight , waist circumference , estimated total body fat , index of central obesity and visceral adiposity index were assessed using analysis of covariance and testing of treatment by strata for age , sex and baseline waist circumference in patients with type 2 diabetes mellitus r and omized to blinded treatment with empagliflozin versus placebo in clinical trials of 12 weeks ( cohort 1 ) or 24 weeks ( cohort 2 ) duration . Results : This study comprised 3300 patients ( cohort 1 , N = 823 ; cohort 2 , N = 2477 ) . Empagliflozin reduced weight , waist circumference and adiposity indices versus placebo in both cohorts . Adjusted mean ( 95 % confidence interval ) change from baseline in empagliflozin versus placebo was −1.7 kg ( −2.1 to −1.4 kg ) and −1.9 kg ( −2.1 to −1.7 kg ) for body weight ( p < 0.001 ) ; −1.3 cm ( −1.8 to −0.7 cm ) and −1.3 cm ( −1.7 to −1.0 cm ) for waist circumference ( p < 0.001 ) ; −0.2 % ( −0.7 % to 0.3 % ; p = 0.45 ) and −0.3 % ( −0.7 % to 0.0 % ; p = 0.08 ) for estimated total body fat ; −0.007 ( −0.011 to −0.004 ) and −0.008 ( −0.010 to −0.006 ) for index of central obesity ( p < 0.001 ) ; and −0.3 ( −0.5 to 0.0 ; p = 0.07 ) and −0.4 ( −0.7 to −0.1 ; p = 0.003 ) for visceral adiposity index in cohorts 1 and 2 , respectively . Adipose reductions were seen across most age , sex and waist circumference subgroups . Conclusion : Empagliflozin significantly reduced weight and adiposity indices with the potential to improve cardiometabolic risk among patients with type 2 diabetes mellitus Aims To explore the effects of dual therapy with dapagliflozin and exenatide on body weight , body composition , glycaemic variables and systolic blood pressure ( SBP ) in obese adults without diabetes . Material s and methods In this single‐centre , double‐blind trial , we r and omized 50 obese adults without diabetes ( aged 18–70 years ; body mass index 30–45 kg/m2 ) to oral dapagliflozin 10 mg once daily plus subcutaneous long‐acting exenatide 2 mg once weekly or placebo . MRI was used to assess change in body composition . Participants were instructed to follow a balanced diet and exercise moderately . Results Of 25 dapagliflozin/exenatide‐ and 25 placebo‐treated participants , 23 ( 92.0 % ) and 20 ( 80.0 % ) completed 24 weeks of treatment , respectively . At baseline , the mean participant age was 52 years , 61 % were female , the mean body weight was 104.6 kg , and 73.5 % of participants had prediabetes ( impaired fasting glucose or impaired glucose tolerance ) . After 24 weeks , for dapagliflozin/exenatide versus placebo : the difference in body weight change was −4.13 kg ( 95 % confidence interval −6.44 , −1.81 ; P < .001 ) , which was mostly attributable to adipose tissue reduction without lean tissue change ; 36.0 % versus 4.2 % of participants achieved ≥5 % body weight loss , respectively ; and prediabetes was less frequent with active treatment ( 34.8 % vs 85.0 % , respectively ; P < .01 ) . The difference in SBP change for dapagliflozin/exenatide versus placebo was −6.7 mm Hg . As expected , nausea and injection‐site reactions were more frequent with dapagliflozin/exenatide than with placebo . Only two and three participants , respectively , discontinued because of adverse events . Conclusions Compared with placebo , dapagliflozin/exenatide dual therapy reduced body weight , frequency of prediabetes and SBP over 24 weeks and was well tolerated in obese adults without diabetes Introduction Empagliflozin , a highly selective sodium-glucose cotransporter 2 ( SGLT2 ) inhibitor , improves glycaemic control in patients with type 2 diabetes mellitus ( T2DM ) by inducing urinary glucose excretion . Combination therapy with empagliflozin and glucagon-like peptide-1 ( GLP-1 ) receptor agonists had not previously been assessed , so we investigated the safety , tolerability and efficacy of empagliflozin as an add-on therapy to liraglutide , a GLP-1 receptor agonist . Methods This was a r and omised , double-blind , parallel-group phase 4 trial of empagliflozin ( 10 mg or 25 mg ) for 52 weeks as an add-on therapy to liraglutide ( 0.9 mg/day ) in Japanese patients with T2DM insufficiently controlled by liraglutide alone . Results 59.4 % ( 19/32 ) and 66.7 % ( 22/33 ) of patients in the empagliflozin 10 mg and 25 mg groups , respectively , reported at least one adverse event ( AE ) . 9.4 % ( 3/32 ) and 21.2 % ( 7/33 ) of patients , respectively , reported drug-related AEs ( primary endpoint ) . From baseline to week 52 , adjusted mean changes with empagliflozin 10 mg and 25 mg , respectively , were : − 0.55 ( st and ard error : 0.15 ) and − 0.77 (0.14)% for glycated haemoglobin ; − 32.5 ( 4.6 ) and − 36.0 ( 4.5 ) mg/dL for fasting plasma glucose ; − 2.6 ( 0.4 ) and −3.1 ( 0.3 ) kg for body weight ; − 6.7 ( 2.2 ) and − 8.4 ( 2.1 ) mmHg for systolic blood pressure ; and − 3.0 ( 1.2 ) and − 4.7 ( 1.1 ) mmHg for diastolic blood pressure . Conclusion Empagliflozin as an add-on to liraglutide for 52 weeks was well tolerated and led to clinical ly meaningful and sustained improvements in glycaemic control , body weight and blood pressure in Japanese patients with T2DM.Trial Registration Clinical Trials.gov with the identifier NCT02589626 . Funding Nippon Boehringer Ingelheim Co. BACKGROUND Glucagon-like peptide-1 ( GLP-1 ) receptor agonists and sodium-glucose co-transporter-2 ( SGLT2 ) inhibitors reduce glycaemia and weight , and improve cardiovascular risk factors via different mechanisms . We aim ed to compare the efficacy and safety of co-initiation of the GLP-1 receptor agonist exenatide and the SGLT2 inhibitor dapagliflozin with exenatide or dapagliflozin alone in patients with type 2 diabetes inadequately controlled by metformin . METHODS DURATION -8 was a 28 week , multicentre , double-blind , r and omised , active-controlled phase 3 trial done at 109 sites in six countries . Adults ( aged ≥18 years ) with type 2 diabetes and inadequate glycaemic control ( HbA1c 8 - 12 % [ 64 - 108 mmol/mol ] ) despite stable metformin monotherapy ( ≥1500 mg/day ) were r and omly assigned ( 1:1:1 ) , via an interactive voice and web-response system , to receive once-weekly exenatide 2 mg by subcutaneous injection plus once-daily dapagliflozin 10 mg oral tablets , exenatide with dapagliflozin-matched oral placebo , or dapagliflozin with exenatide-matched placebo injections . R and omisation was stratified by baseline HbA1c ( < 9·0 % vs ≥9·0 % [ < 75 mmol/mol vs ≥75 mmol/mol ] ) . The primary endpoint was change in HbA1c from baseline to week 28 . Secondary endpoints were the change from baseline in fasting plasma glucose at week 2 and week 28 , and 2 h postpr and ial glucose at week 28 ; the proportion of patients with an HbA1c less than 7·0 % ( < 53 mmol/mol ) at week 28 ; change in weight at week 28 ; the proportion of patients with weight loss of 5 % or more at week 28 ; and change in systolic blood pressure at week 28 . Analyses were by intention to treat . This trial is registered with Clinical Trials.gov , number NCT02229396 . FINDINGS Between Sept 4 , 2014 , and Oct 15 , 2015 , we r and omly assigned 695 patients to receive exenatide plus dapagliflozin ( n=231 ) , exenatide alone ( n=231 ; n=1 untreated ) , or dapagliflozin alone ( n=233 ) . The intention-to-treat population comprised 685 participants ( mean HbA1c 9·3 % [ SD 1·1 ] ; 78 mmol/mol [ 12 ] ) , of whom 611 ( 88 % ) completed the study . After 28 weeks , the change in baseline HbA1c was -2·0 % ( 95 % CI -2·1 to -1·8 ) in the exenatide plus dapagliflozin group , -1·6 % ( -1·8 to -1·4 ) in the exenatide group , and -1·4 % ( -1·6 to -1·2 ) in the dapagliflozin group . Exenatide plus dapagliflozin significantly reduced HbA1c from baseline to week 28 compared with exenatide alone ( -0·4 % [ 95 % CI -0·6 to -0·1 ] ; p=0·004 ) or dapagliflozin alone ( -0·6 % [ -0·8 to -0·3 ] ; p<0·001 ) . Exenatide plus dapagliflozin was significantly superior to either drug alone for all secondary efficacy endpoints , with greater reductions in fasting plasma and postpr and ial glucose , more patients with an HbA1c less than 7·0 % ( < 53 mmol/mol ) , greater weight loss , a greater proportion of patients with weight loss of 5 % or more , and greater reductions in systolic blood pressure ( all p≤0·025 ) . Adverse events were recorded in 131 ( 57 % ) of 231 patients in the exenatide plus dapagliflozin group , 124 ( 54 % ) of 230 patients in the exenatide group , and 121 ( 52 % ) of 233 patients in the dapagliflozin group . The most common adverse events ( ≥5 % of patients in any group ) were diarrhoea , injection-site nodules , nausea , and urinary tract infections . No episodes of major hypoglycaemia or minor hypoglycaemia were reported . INTERPRETATION Co-initiation of exenatide and dapagliflozin improved various glycaemic measures and cardiovascular risk factors in patients with type 2 diabetes inadequately controlled by metformin monotherapy . The dual treatment regimen was well tolerated , with the expected safety profile for this combination . Additional data from an ongoing study ( eg , AWARD-10 ; NCT02597049 ) will further inform the use of these drug classes in combination . FUNDING AstraZeneca |
10,721 | 21,958,602 | For most of the interventions considered , there was insufficient evidence to support or refute their effectiveness .
However , client reminders , reduction of structural barriers , and provision of provider assessment and feedback were recommended interventions to increase screening for at least two of three cancer sites studied .
Conclusion Using established guideline development method ologies and the AGREE II as our method ological frameworks , we developed an implementation guideline to advise on interventions to increase the rate of breast , cervical and colorectal cancer screening . | Background Appropriate screening may reduce the mortality and morbidity of colorectal , breast , and cervical cancers .
Several high- quality systematic review s and practice guidelines exist to inform the most effective screening options .
However , effective implementation strategies are warranted if the full benefits of screening are to be realized .
We developed an implementation guideline to answer the question : What interventions have been shown to increase the uptake of cancer screening by individuals , specifically for breast , cervical , and colorectal cancers ? | BACKGROUND Colorectal cancer ( CRC ) screening is underutilized despite evidence that screening reduces mortality . OBJECTIVE To assess the effect of an intervention targeting physicians and their patients on rates of CRC screening . DESIGN A r and omized clinical trial of community physicians and their patients . PARTICIPANTS Ninety-four community primary care physicians r and omly assigned to an intervention consisting of academic detailing and direct mailings to patients or a control group . Patients aged 50 to 79 years in the intervention group physicians received a letter from their physician , a brochure on CRC screening , and a packet of fecal occult blood test ( FOBT ) cards . MEASUREMENTS After 1 year we measured receipt of the following : ( 1 ) FOBT in the past 2 years , ( 2 ) flexible sigmoidoscopy ( SIG ) or colonoscopy ( COL ) in the previous 5 years , and ( 3 ) any CRC screening . We report the percent change from baseline in both groups . RESULTS 9,652 patients were enrolled for 2 years , and 3,732 patients were enrolled for 5 years . There was no increase in any CRC screening that occurred in the intervention group for patients enrolled for 2 years ( 12.7 increase vs 12.5 % , P=.51 ) . Similar results were seen for any CRC screening among patients enrolled for 5 years ( 9.7 % increase vs 8.6 % , P=.45 ) . The only outcome on which the intervention had an effect was on patient rates of screening SIG ( 7.4 % increase vs 4.4 % , P<.01 ) . CONCLUSION With the exception of an increase in rates of SIG in the intervention group , the intervention had no effect on rates of CRC screening . Future interventions should assess innovative approaches to increase rates of CRC screening OBJECTIVE First-degree relatives ( FDRs ) of people diagnosed with colorectal cancer ( CRC ) have a two- to threefold increased risk of developing the same disease . Tailored print interventions based on behavior change theories have demonstrated considerable promise in facilitating health-promoting behaviors . This study compared the impact of two mailed print interventions on CRC screening outcomes among FDRs . METHODS This r and omized trial compared effects of two mailed print interventions --one tailored and one nontailored -- on participation in CRC screening among FDRs of CRC survivors . Data collected via phone interviews from 140 FDRs at baseline , 1 week post-intervention , and 3 months post-intervention . RESULTS At 3 months , both the tailored and nontailored interventions yielded modest but statistically insignificant increases in adherence to any CRC screening test ( 14 % vs. 21 % , respectively ; p=0.30 ) . While there were no main effects for tailored versus nontailored interventions , there were significant interactions that showed that the tailored print intervention had significantly greater effects on forward stage movement for CRC screening depending on stage of adoption at baseline , race , and objective CRC risk . Receipt of the tailored intervention was 2.5 times more likely to move baseline precontemplators and contemplators forward in stage of adoption for colonoscopy ( 95 % CI : 1.10 - 5.68 ) and was three times more likely to move Caucasians forward in stage of adoption for FOBT ( 95 % CI : 1.00 - 9.07 ) . In addition , the tailored intervention was 7.7 times more likely to move people at average risk forward in stage of adoption for colonoscopy ( 95 % CI : 1.25 - 47.75 ) . CONCLUSION The tailored print intervention was more effective at moving Caucasians , those in precontemplation and contemplation at baseline , and those at average risk forward in their stage of adoption for CRC screening . PRACTICE IMPLICATION S Both tailored and nontailored print interventions showed moderate effects for increasing CRC screening participation . Tailored print interventions may be more effective for certain subgroups Background : Interventions to improve adherence to regular mammography screening have had conflicting results . Many studies have depended on women ’s self-report rather than clinical evidence of a mammography encounter . Methods : We tested the impact of two interventions on a population -based sample of NH women who were not receiving routine mammography to determine if adherence to screening could be improved . The interventions included a mailing of women ’s health information and a telephone counseling intervention based on the Transtheoretical Model . Participant eligibility and outcome measures were based on clinical events obtained from a population -based mammography registry . Results : Two hundred and fifty eight women completed all aspects of the intervention study . The women were r and omly assigned to one of two study groups : 51 % received the mail intervention and 49 % received the telephone intervention . Among women who received the telephone counseling intervention , 67 % percent reported being in either an action or maintenance stage at Call 1 , which increased to 84 % at Call 2 ( p<0.001 ) . Seventy-six percent of women identified barriers to screening mammography at Call 1 , which decreased to 44 % at Call 2 ( p<0.01 ) . The most frequently identified barrier was confusion over the guidelines for screening mammography . At the first assessment time interval , greater than 60 % of women were up-to- date for screening mammography in the group that received telephone counseling versus 48 % in the group that received health information by mail ( p = 0.04 ) . However , women ’s status as up-to- date fell for both groups between the first and second assessment time intervals . Conclusions : Tailored telephone counseling based on the Transtheoretical Model can improve adherence to screening mammography , though the duration of this effect is in question Abstract BACKGROUND : R and omized controlled trials have demonstrated that fecal occult blood testing ( FOBT ) reduces colorectal cancer ( CRC ) mortality . However , patient compliance with FOBT is low and this is one of the major barriers to CRC screening . OBJECTIVE : To determine whether intensive patient education increases FOBT card return rates . DESIGN : R and omized controlled trial . SETTING : Department of Veterans Affairs primary care clinic . PARTICIPANTS : Seven hundred eighty-eight patients who were referred for FOBT . INTERVENTIONS : Patients were r and omly allocated to receive either intensive ( n=396 ) or st and ard ( n=392 ) patient education . Patients in the intensive education group received a one-on-one educational session by primary care nurses on the importance of CRC screening , were instructed on how to properly collect stool specimens for FOBT , and were given a 2-page h and out on CRC screening . Patients in the st and ard education group only received the FOBT cards and written instructions from the manufacturer on how to properly collect stool specimens for FOBT . RESULTS : Patients in the intensive education group were more likely to return the FOBT cards ( 65.9 % vs 51.3 % ; P<.001 ) and called the clinic with additional questions less often ( 1.5 % vs 5.9 % ; P=.001 ) than the st and ard education group . The median time to return the FOBT cards was significantly shorter in the intensive education group ( 36 vs 143 days ; P<.001 by log-rank test ) . However , the proportion of patients who had a positive FOBT did not differ in the two groups ( 4.6 % vs 6.0 % ; P=.51 ) . CONCLUSIONS : Intensive patient education significantly improved patient compliance with FOBT . Future studies to evaluate additional educational strategies to further improve patient compliance with CRC screening are warranted Background Individuals with a sibling who has had colorectal cancer diagnosed before age 61 are at increased risk for colorectal cancer and may derive particular benefit from screening . Tailored interventions may increase participation in appropriate colorectal cancer screening . Purpose This study evaluated the efficacy of two tailored interventions and a generic print intervention . Methods Participant siblings ( N = 412 ) who were not up-to- date with colorectal cancer screening were r and omly assigned to receive either a generic print pamphlet , a tailored print pamphlet , or a tailored print pamphlet and tailored counseling call . Colorectal cancer screening 6 months after the baseline interview was the outcome measure . Results Results indicated that colorectal cancer screening adherence increased among intermediate risk siblings enrolled in all three intervention groups . Participants in both tailored intervention groups reported having colorectal cancer screening at significantly higher rates than participants in the generic print group . The increase in colorectal cancer screening in the tailored print and counseling call group was not significantly higher than that achieved by the tailored print alone . Decisional balance partially mediated treatment effects . Tailored behavioral interventions are effective methods for increasing screening adherence but telephone counseling did not add significantly to treatment effects Background : Low-income African American women face numerous barriers to mammography screening . We tested the efficacy of a combined interactive computer program and lay health advisor intervention to increase mammography screening . Methods : In this r and omized , single blind study , participants were 181 African American female health center patients of ages 41 to 75 years , at ≤250 % of poverty level , with no breast cancer history , and with no screening mammogram in the past 15 months . They were assigned to either ( a ) a low-dose comparison group consisting of a culturally appropriate mammography screening pamphlet or ( b ) interactive , tailored computer instruction at baseline and four monthly lay health advisor counseling sessions . Self-reported screening data were collected at baseline and 6 months and verified by medical record . Results : For intent-to-treat analysis of primary outcome ( medical record – verified mammography screening , available on all but two participants ) , the intervention group had increased screening to 51 % ( 45 of 89 ) compared with 18 % ( 16 of 90 ) for the comparison group at 6 months . When adjusted for employment status , disability , first-degree relatives with breast cancer , health insurance , and previous breast biopsies , the intervention group was three times more likely ( adjusted relative risk , 2.7 ; 95 % confidence interval , 1.8 - 3.7 ; P < 0.0001 ) to get screened than the low-dose comparison group . Similar results were found for self-reported mammography stage of screening adoption . Conclusions : The combined intervention was efficacious in improving mammography screening in low-income African American women , with an unadjusted effect size ( relative risk , 2.84 ) significantly higher ( P < 0.05 ) than that in previous studies of each intervention alone . Cancer Epidemiol Biomarkers Prev ; 19(1 ) ; Background . The American Cancer Society ( ACS ) is interested in facilitating colorectal cancer screening ( CRCS ) in primary care . Methods . Similar clinics were assigned r and omly to 1 of 3 CRCS arms : ( 1 ) usual care , ( 2 ) exam-room posters design ed by the ACS ; and ( 3 ) posters plus patient reminder calls from an ACS volunteer . Results . Compared to patients due for screening in Arm 1 , the odds ratio for getting CRCS in Arm 2 was 1.04 ( 95 % confidence interval [ CI ] , 0.81–1.34 ) , P value not significant ; in Arm 3 , it was 1.49 ( 95 % CI , 1.16–1.90 ) , P value < .001 . Conclusions . Exam-room posters plus patient reminder calls from the ACS can increase CRCS in primary care Background : Publicly-funded health centers serve disadvantaged population s who underuse colorectal cancer screening ( CRC ) . Because physicians play a key role in patient adherence to screening , provider interventions within health center practice s could improve the delivery/utilization of CRC screening . Methods : A 2-group study design was used with 4 pairs of health centers r and omized to the intervention or control condition . The provider intervention featured academic detailing of the small practice groups , followed by a strategic planning session with the entire health center staff using SWOT analysis . The outcome measure of provider endoscopy referral/fecal occult blood test dispensing and /or completion of CRC screening was determined by medical record audit ( n = 2224 ) . The intervention effect was evaluated using generalized estimating equations . Pre-post intervention patient surveys ( n = 281 ) were conducted . Results : Chart audits of the 1 year period before and after the intervention revealed a 16 % increase from baseline in CRC screening referral/dispensing/completion among intervention centers , compared with a 4 % increase among controls , odds ratio ( OR ) = 2.25 ( 1.67–3.04 ) P < 0.001 . Intervention versus control health center patient self-reports of lack of physician recommendation as a reason for not having CRC screening declined from baseline to follow-up ( P = 0.04 ) . Conclusions : Provider referrals/dispensing/completion of CRC screening within health centers was significantly improved and barriers reduced through a provider intervention combining continuing medical education with a team building strategic planning exercise BACKGROUND Few health promotion trials have evaluated strategies to increase regular mammography screening . We conducted a r and omized controlled trial of two theory-based interventions in a population -based , nationally representative sample of women veterans . METHODS Study c and i date s 52 years and older were r and omly sample d from the National Registry of Women Veterans and r and omly assigned to three groups . Groups 1 and 2 received interventions that varied in the extent of personalization ( tailored and targeted vs targeted-only , respectively ) ; group 3 was a survey-only control group . Postintervention follow-up surveys were mailed to all women after 1 and 2 years . Outcome measures were self-reported mammography coverage ( completion of one postintervention mammogram ) and compliance ( completion of two postintervention mammograms ) . In decreasingly conservative analyses ( intention-to-treat [ ITT ] , modified intention-to-treat [ MITT ] , and per- protocol [ PP ] ) , we examined crude coverage and compliance estimates and adjusted for covariates and variable follow-up time across study groups using Cox proportional hazards regression . For the PP analyses , we also used logistic regression . RESULTS None of the among-group differences in the crude incidence estimates for mammography coverage was statistically significant in ITT , MITT , or PP analyses . Crude estimates of compliance differed at statistically significant levels in the PP analyses and at levels approaching statistical significance in the ITT and MITT analyses . Absolute differences favoring the intervention over the control groups were 1%-3 % for ITT analysis , 1%-5 % for MITT analysis , and 2%-6 % for the PP analysis . Results from Cox modeling showed no statistically significant effect of the interventions on coverage or compliance in the ITT , MITT , or PP analyses , although hazard rate ratios ( HRRs ) for coverage were consistently slightly higher in the intervention groups than the control group ( range for HRRs = 1.05 - 1.09 ) . A PP analysis using logistic regression produced odds ratios ( ORs ) that were consistently higher than the corresponding hazard rate ratios for both coverage and compliance ( range for ORs = 1.15 - 1.29 ) . CONCLUSIONS In none of our primary analyses did the tailored and targeted intervention result in higher mammography rates than the targeted-only intervention , and there was limited support for either intervention being more effective than the baseline survey alone . We found that adjustment for variable follow-up time produced more conservative ( less favorable ) intervention effect estimates OBJECTIVES We compared the effectiveness of a telephone outreach approach versus a direct mail approach in improving rates of colorectal cancer ( CRC ) screening in a predominantly Black population . METHODS A r and omized trial was conducted between 2000 and 2003 that followed 456 participants in the New York metropolitan area who had not had recent CRC screening . The intervention group received tailored telephone outreach , and the control group received mailed printed material s. The primary outcome was medically documented CRC screening 6 months or less after r and omization . RESULTS CRC screening was documented in 61 of 226 ( 27.0 % ) intervention participants and in 14 of 230 ( 6.1 % ) controls ( prevalence rate difference=20.9 % ; 95 % CI = 14.34 , 27.46 ) . Compared with the control group , the intervention group was 4.4 times more likely to receive CRC screening within 6 months of r and omization . CONCLUSIONS Tailored telephone outreach can increase CRC screening in an urban minority population BACKGROUND Colorectal cancer ( CRC ) is one of the leading causes of cancer-related deaths in the United States . R and omized controlled trials have shown that annual screening fecal occult blood testing ( FOBT ) reduces CRC mortality and incidence . However , patient compliance with FOBT is low . OBJECTIVE To determine whether a mailed educational reminder increases FOBT card return rates and to examine predictors of FOBT compliance . DESIGN Blinded , r and omized , controlled trial at the Veteran Affairs Medical Center , San Diego , California . PATIENTS Seven hundred and seventy-five consecutive patients ≥50 years of age referred by their primary care physicians for FOBT.INTERVENTION Patients were r and omly assigned to the usual care group or the intervention group . Ten days after picking up the FOBT cards , a 1-page reminder with information related to CRC screening was mailed to the intervention group only . MEASUREMENTS The primary outcome was proportion of returned FOBT cards after 6 months . Patient demographic , clinical characteristics and prior FOBT completed were collected for multivariate regression analysis . RESULTS At 6 months after card distribution , 64.6 % of patients in the intervention group returned cards compared with 48.4 % in the control group ( P < 0.001 ) . Patients who received a mailed reminder ( OR 2.02 ; 95 % CI : 1.48–2.74 ) or have a prior history of returning the FOBT cards ( OR 1.87 ; 95 % CI : 1.29–2.70 ) were more likely to return the FOBT cards . Patients with current or recent illicit drug use were less likely to return the FOBT cards ( OR 0.26 ; 95 % CI : 0.13–0.50 ) . CONCLUSION A simple mailed educational reminder significantly increases compliance with FOBT for CRC screening BACKGROUND We tested an intervention based on social learning theory ( SLT ) to improve colorectal cancer ( CRC ) screening among Native Hawaiians , a group with low CRC screening rates . METHOD Sixteen Hawaiian civic clubs agreed to r and omization . Eight control clubs received a culturally targeted presentation , a free Fecal Occult Blood Test ( FOBT ) , and a reminder call . Eight experimental clubs also received culturally targeted education and free testing ; but , in line with SLT , education was delivered by a Native Hawaiian physician and Native Hawaiian CRC survivor , and members received an FOBT demo , were challenged to involve a family member in screening , and were telephoned multiple times to address change-related emotions and barriers . RESULTS One hundred twenty-one members age 50 and older from 16 clubs participated . At the club level , screening rates were modestly increased in four experimental clubs and six control clubs . Surprisingly , 64 % of participants reported being up to date with CRC screening at baseline . Only 13 individuals ( five in experimental arm and eight in the control arm ) were screened for the first time through this intervention , increasing the percent screened from 59 % to 67 % in the experimental group and from 69 % to 85 % in the control group . Although individuals in the experimental arm were more likely to rate the intervention as culturally appropriate , both arms realized similar and significant gains in CRC knowledge , attitudes , intent , and self-efficacy . CONCLUSIONS For Native Hawaiian individuals belonging to a network of civic clubs , an intervention based on SLT delivered by a Native Hawaiian physician and CRC survivor was less effective at further increasing compliance than was a culturally targeted educational session delivered by a non-Hawaiian nurse . That CRC screening compliance was high prior to our intervention suggests that we targeted a very health conscious segment of the Native Hawaiian population . Future work should focus on underserved segments of this indigenous group Background To determine the effectiveness of a single checklist reminder form to improve the delivery of preventive health services at adult health check-ups in a family practice setting . Methods A prospect i ve cluster r and omized controlled trial was conducted at four urban family practice clinics among 38 primary care physicians affiliated with the University of Toronto . Preventive Care Checklist Forms © were created to be used by family physicians at adult health check-ups over a five-month period . The sex-specific forms incorporate evidence -based recommendations on preventive health services and documentation space for routine procedures such as physical examination . The forms were used in two intervention clinics and two control clinics . Rates and relative risks ( RR ) of the performance of 13 preventive health maneuvers at baseline and post-intervention and the percentage of up-to- date preventive health services delivered per patient were compared between the two groups . Results R and omly-selected charts were review ed at baseline ( n = 509 ) and post-intervention ( n = 608 ) . Baseline rates for provision of preventive health services ranged from 3 % ( fecal occult blood testing ) to 93 % ( blood pressure measurement ) , similar to other setting s. The percentage of up-to- date preventive health services delivered per patient at the end of the intervention was 48.9 % in the control group and 71.7 % in the intervention group . This is an overall 22.8 % absolute increase ( p = 0.0001 ) , and 46.6 % relative increase in the delivery of preventive health services per patient in the intervention group compared to controls . Eight of thirteen preventive health services showed a statistically significant change ( p < 0.05 ) in favor of the intervention ( adjusted RR ( 95 % C.I. ) ) : counseling on brushing/flossing teeth ( 9.2 ( 4.3–19.6 ) ) , folic acid counseling ( 7.5 ( 2.7–20.8 ) ) , fecal occult blood testing ( 6.7 ( 1.9–24.1 ) ) , smoking cessation counseling ( 3.9 ( 2.2–7.2 ) ) , tetanus immunization ( 3.0 ( 1.7–5.2 ) ) , history of alcohol intake ( 1.33 ( 1.2–1.5 ) ) , history of smoking habits ( 1.28 ( 1.2–1.4 ) ) and blood pressure measurement ( 1.05 ( 1.00–1.10 ) ) . Conclusion This simple , low cost , clinical ly relevant intervention improves the delivery of preventive health services by prompting physicians of evidence -based recommendations in a checklist format that incorporates existing practice patterns . Periodic up date s of the Preventive Care Checklist Forms © will allow a feasible and easy-to-use tool for primary care physicians to provide evidence -based preventive health services to adults at routine health check-ups . The forms can also be incorporated into an electronic health record . The Preventive Care Checklist Forms © are accessible in English and French at the College of Family Physicians of Canada web site Background : Colon cancer screening ( CRCS ) tests are underused . Multiple CRCS options may confuse patients and lead to inaction . E-mail between patients and physicians may raise awareness about CRCS and allow physicians to answer questions about test options . Objectives : To develop and implement an electronic intervention , the InterNet LETter ( NetLET ) , to increase interest in and use of CRCS among patients with and without e-mail access at home or work . Research Methods : During 2004–2005 , 97 patients over 49 years old were recruited during a clinic visit . Patients with e-mail at home or work were assigned to the private access arm ; patients without e-mail but willing to use the public library system were assigned to the public access arm . Within each arm , patients were r and omized to the NetLET or control group . The NetLET consisted of a personalized e-mail from the physician reminding the patient to undergo CRCS and providing a link to a webpage with information about CRCS . Control groups were mailed a reminder letter from their physician . All were mailed a fecal occult blood test ( FOBT ) kit . Results : In the public access intervention group , only 1 of 11 patients viewed the NetLET . In the private access intervention group , 10 of 42 viewed it . Eleven of 42 ( 26 % ) private access intervention group participants , and 8 of 35 ( 23 % ) private access control group participants returned an FOBT . No public access intervention group patients , but 3 of 9 control group patients , returned an FOBT . Conclusions : We concluded that it was not feasible to implement the NetLET , but reasons for lack of success differed for the private and public access arms INTRODUCTION Although mammography is the most effective early detection breast cancer screening technology available , it is underutilized . This study was conducted to test the effectiveness of a loss-framed minimal intervention to increase mammography use . Loss-frame refers to a communication strategy in which messages are framed from the perspective of what a person has to lose by not taking a particular behavioral action . METHODS Participants were medically un- and underinsured women 50 - 64 years old who called one of two urban clinics r and omly selected based on demographic statistical equivalency . The women who participated telephoned to inquire about a mammogram during the 6-month study period . The group r and omly design ated as the experimental group received a loss-framed message conveyed by trained staff telephonically . Members of the comparison group received the " usual " communication , also conveyed telephonically . In the experimental group , 31 of 112 ( 27 % ) women who inquired received mammograms , whereas 157 of the 992 ( 16 % ) comparison group women who inquired received mammograms . RESULTS The odds of a mammogram , adjusted for race and breast cancer symptoms , significantly increased for the experimental ( odds ratio [ OR ] = 1.914 , chi2 = 7.48 , p = .0063 , 95 % confidence interval [ CI ] 1.20 - 3.05 ) versus comparison group . CONCLUSIONS A loss-framed , in-reach , minimal intervention approach holds promise as a mammography promotion strategy BACKGROUND A relatively simple procedure , the Pap test , is effective in detecting early changes in the cervix ; however , many at-risk women , even in developed countries , do not have regular Pap tests . METHODS A r and omized controlled trial of an interactive voice response ( IVR ) cervical screening brief advice involving 17,008 households is described . The IVR system automatically made calls to households and explained the nature of the call ; selected one eligible woman aged 18 - 69 years ; determined her screening status ; delivered a message appropriate to her screening status ; offered additional messages to counter common barriers ; offered additional information on cervical screening and cancer ; offered additional contact numbers ; and offered to arrange for someone to call back . Cervical screening rate data were obtained from the Australian Health Insurance Commission ( HIC ) for 6 months before and following the intervention . RESULTS The cervical screening rate was found to have increased by 0.43 % in intervention compared to the control postcodes , and the increase was greater for older women at 1.34 % . CONCLUSIONS The overall conclusion was that IVR technology was a feasible means to contact women to deliver brief interventions aim ed at increasing cervical screening rates and could economically target at-risk groups . The potential for linking IVR to central ized Pap test Registers to issue Pap test reminders should be explored Background : There are no effective breast cancer education programs targeting Samoan women . We tested the effectiveness of a theory-guided , culturally appropriate breast cancer education program ( the intervention ) design ed to increase mammography use among Samoan women . Methods : This community-based participatory cluster-r and omized controlled intervention trial used a parallel two-group design . The sample consisted of 776 women aged 42 and older who had not had a mammogram in the preceding 2 years . The primary outcome was self-reported mammogram use between pretest and posttest . Results : Overall , there was no statistically significant intervention effect , although the odds of self-reported mammogram use were higher in the intervention than the control group ( odds ratio ( OR ) , 1.26 ; 95 % confidence interval ( 95 % CI ) , 0.74 , 2.14 ; P = 0.39 ) . Exploratory subgroup analyses found that the intervention was effective only among women who were aware of mammograms but had never previously obtained one ( OR , 1.99 ; 95 % CI , 1.03 , 3.85 ; P = 0.04 ) . Low need for social support and lack of endorsement of culture-specific beliefs about breast cancer were associated with mammogram use in this group . In women unaware of mammography at pretest , high perceived susceptibility to breast cancer and endorsement of culture-specific beliefs were associated with mammogram use . For women who had previously obtained a mammogram , lower self-efficacy was associated with mammogram use . Intervention compared with control group women had significantly higher levels of knowledge of risk factors and lower endorsement of culture-specific beliefs at posttest . Conclusions : Results suggest that a multifaceted education intervention may improve mammogram usage for certain subgroups of Samoan women . ( Cancer Epidemiol Biomarkers Prev 2007;16(12):2594–604 ABSTRACT In this large r and omized trial among callers to the Cancer Information Service ( CIS ) , tailored print material s were tested for efficacy in promoting colorectal cancer ( CRC ) screening ( fecal occult blood test [ FOBT ] , flexible sigmoidoscopy , or colonoscopy ) . All participants completed baseline interviews at the end of their usual service calls to the CIS , as well as short-term ( 6-month ) and longer-term ( 14-month ) telephone follow-up interviews . The study sample ( n = 4,014 ) was restricted to English-speaking CIS callers 50 + years of age , who would be eligible for CRC screening at 14 months follow-up and did not call the CIS about CRC or CRC screening . Four experimental conditions were compared : a single untailored ( SU ) mailout of print material ( the control condition ) ; a single tailored ( ST ) mailout of print material ; four ( multiple ) tailored ( MT ) mailouts of print material s spanning 12 months , all of which were tailored to information obtained at baseline ; and four ( multiple ) retailored ( MRT ) mailouts also spanning 12 months , with retailoring of the print material s ( mailouts 2 , 3 , and 4 ) based on up date d information obtained from the 6-month follow-up interviews . Consistent with the main hypothesis of this trial , a significant linear trend across the SU , ST , MT , and MRT groups was found at 14 months ( 42 % , 44 % , 51 % , and 48 % , respectively , p = 0.05 ) . Only for MT was there a significant difference compared with SU ( p = 0.03 ) for the sample as a whole , while no differences were found for MT vs. MRT at 14 months . Significant moderator effects in the predicted direction were found among females , younger participants , and among those with a history of CRC screening , all of which involved the SU vs. MT MRT comparisons . Only among younger participants ( ages 50–59 ) was there a difference between SU vs. ST at 14 months . Given these results , we conclude from this trial the following : ( 1 ) the MRT intervention failed to show added benefit beyond the MT intervention , ( 2 ) the significant intervention effects involving the MT and MRT conditions can be explained by tailoring and /or the longitudinal nature of both interventions , and ( 3 ) the most compelling evidence in support of tailoring was found for the ST condition among younger participants , where a significant need for interventions exists at the national level . Directions for future research are discussed in light of the results summarized above OBJECTIVES Among patients unlikely to attend a scheduled colonoscopy , we examined the impact of peer coach versus educational brochure support and compared these with concurrent patients who did not receive support . METHODS From health system data , we identified 275 consecutive patients aged > 50 who kept < 75 % of visits to 4 primary care practice s and scheduled for a first colonoscopy from February 1 , 2005 to August 31 , 2006 . Using block r and omization , we assigned consenting patients to a phone call by a peer coach trained to address barriers to attendance or to a mailed colonoscopy brochure . Study data came from electronic medical records . Odds ratios of colonoscopy attendance were adjusted for demographic , clinical , and health care factors . RESULTS Colonoscopy attendance by the peer coach group ( N = 70 ) and brochure group ( N = 66 ) differed by 11 % ( 68.6 % vs 57.6 % , respectively ) . Compared with the brochure group , the peer coach group had over twofold greater adjusted odds ratio ( AOR ) of attendance ( 2.14 , 95 % confidence interval [ CI ] = 0.99–4.63 ) as did 49 patients who met the prespecified criteria for needing no support ( 2.68 , 95%CI = 1.05–6.82 ) but the AORs did not differ significantly for 41 patients who declined support ( 0.61 , 95%CI = 0.25–1.45 ) and 49 patients who could not be contacted ( 0.85 , 95%CI = 0.36–2.02 ) . Attendance was less likely for black versus white race ( AOR = 0.37 , 95%CI = 0.19–0.72 ) but more likely for patients with high versus low primary care visit adherence ( AOR = 2.30 , 95%CI = 1.04–5.07 ) . CONCLUSION For patients who often fail to keep appointments , peer coach support appears to promote colonoscopy attendance more than an educational brochure Objective : There is evidence that non-English speakers in the United States receive lower quality health care and preventive services than English speakers . We tested the hypothesis that Spanish-speaking women would respond differently to an intervention to increase up-to- date status for cancer screening . Study Design and Setting : A multisite r and omized controlled trial showed that scripted telephone support , provided by a Prevention Care Manager ( PCM ) , increased up-to- date rates for breast , cervical , and colorectal cancer screening . This subgroup analysis investigated the relative efficacy of the PCM among women who chose to communicate with the PCM in Spanish versus English . Results : Of 1,346 women in this analysis , 63 % were Spanish speakers . Whereas the PCM intervention increased cancer screening rates generally , Spanish-speaking women seemed to benefit disproportionately more than English-speaking women for cervical cancer screening ( unadjusted odds ratio , 1.77 ; 95 % confidence interval , 1.03 - 3.05 ) . In addition , in this exploratory analysis , there was a trend toward Spanish-speaking women receiving more benefit than English-speaking women from the intervention in increased breast and colorectal cancer screening rates . Conclusion : Spanish-speaking women seemed to benefit more than did English-speaking women from a bilingual telephone support intervention aim ed at increasing cancer screening rates . ( Cancer Epidemiol Biomarkers Prev 2007;16(10):2058–64 INTRODUCTION Mammography is underused by certain groups of women , in particular poor and minority women . We developed a lay health advisor ( LHA ) intervention based on behavioral theories and tested whether it improved mammography attendance in Robeson County , NC , a rural , low-income , triracial ( white , Native American , African American ) population . METHODS A total of 851 women who had not had a mammogram within the past year were r and omly assigned to the LHA intervention ( n = 433 ) or to a comparison arm ( n = 418 ) during 1998 - 2002 . Rates of mammography use after 12 - 14 months ( as verified by medical record review ) were compared using a chi-square test . Baseline and follow-up ( at 12 - 14 months ) surveys were used to obtain information on demographics , risk factors , and barriers , beliefs , and knowledge about mammography . Linear regression , Mantel-Haenszel statistics , and logistic regression were used to compare barriers , beliefs , and knowledge from baseline to follow-up and to identify baseline factors associated with mammography . RESULTS At follow-up , 42.5 % of the women in the LHA group and 27.3 % of those in the comparison group had had a mammogram in the previous 12 months ( relative risk = 1.56 , 95 % confidence interval [ CI ] = 1.29 to 1.87 ) . Compared with those in the comparison group , women in the LHA group displayed statistically significantly better belief scores ( difference = 0.46 points on a 0 - 10 scale , 95 % CI = 0.15 to 0.77 ) and reduced barriers at follow-up ( difference = -0.77 points , 95 % CI = -1.02 to -0.53 ) , after adjusting for baseline scores . CONCLUSIONS LHA interventions can improve mammography utilization . Future studies are needed to assess strategies to disseminate effective LHA interventions to underserved population Context Minority and low-income women have low screening rates for cancer . Contribution In this trial from 11 community and migrant health centers in New York City , 1413 women overdue for cancer screening were r and omly assigned to receive a telephone-based intervention ( delivered by 8 prevention care managers ) or usual care . The intervention included information about breast , cervical , and colorectal cancer and motivational and logistical support for obtaining screening . Within 18 months , the screening rates for all 3 forms of cancer increased more with telephone support than through usual care . Implication s Telephone support delivered by trained personnel can improve cancer screening rates among some minority , low-income women . The Editors Higher screening rates for breast , cervical , and colorectal cancer could reduce cancer mortality rates substantially ( 1 - 4 ) . Current cancer screening rates are particularly disappointing among ethnic minorities and individuals with low socioeconomic status ( 5 , 6 ) who often present with late-stage diagnoses ( 7 ) and have high mortality rates ( 8 , 9 ) . Interventions to increase cancer screening have shown limited sustainability and effect on health care disparities . A previous study showed that an office systems approach , which used a medical record flowsheet and practice teamwork , increased screening rates by 20 % to 33 % in small rural community practice s ( 10 ) ; however , a similar intervention was less effective in larger urban practice s ( 11 ) . An office intervention in low-income setting s in Florida increased mammography use and home fecal occult blood testing at 12 months ( 12 ) , but rates decreased substantially after research support ended ( 13 ) . Use of the telephone to support cancer screening is well documented ( 14 - 18 ) , but interventions have typically addressed a single form of cancer screening . In some setting s , telephone infrastructures to support childhood immunization ( 19 ) and patients with chronic illnesses ( 20 - 23 ) already exist . These infrastructures could add screening support for patients who are already enrolled , or they could exp and services to others while making minimal additional dem and s on primary care practice s ( 24 ) . This paper reports the results of a r and omized , controlled trial that tested the effect of central ized telephone care management on cancer screening rates among women 50 to 69 years of age who obtained care at community and migrant health centers in New York City . Methods Setting s Federally qualified community and migrant health centers provide comprehensive community-oriented primary care to over 12 million patients nationally ( 25 ) and are uniquely positioned to deliver cancer screenings to underserved and minority population s. We sought participation from 15 of the 21 community and migrant health centers in New York City because of their anticipated ability to provide sufficient patients for the study and their affiliations with tertiary care facilities that conduct mammography and colorectal screening and provide follow-up services for abnormal test results . Of these 15 sites , 2 were involved in competing research projects , 2 had few patients who were likely to be eligible and therefore served as pilot sites , and the remaining 11 participated . Clinical Directors Network , a practice -based research network in New York City , was responsible for recruiting clinicians , practice s , and women and for implementing the intervention and evaluation . The project was approved by the Committee for the Protection of Human Subjects at Dartmouth College , by the institutional review board at Clinical Directors Network , and by all relevant bodies responsible for review ing research at participating community and migrant health centers . Patients Recruitment Women were approached by research assistants during routine visits to the centers or were referred by a clinician . Research assistants explained the study and obtained written informed consent from women who agreed to participate . Women were compensated $ 15 for participating in an interview whether or not they met eligibility criteria . Eligibility Eligible women were 50 to 69 years of age , were overdue for at least 1 cancer screening according to their medical records , were patients of the center for at least 6 months , and had no plans to move or change health centers within 15 months . We excluded women whose primary language was not English , Spanish , or Haitian Creole and those who were acutely ill or currently receiving cancer treatment . After we obtained consent , a research assistant review ed patient medical records to confirm eligibility . Mammography and Papanicolaou tests that were performed within the past year were seen as evidence of breast and cervical cancer screening , respectively , whereas reports of home fecal occult blood testing within the past year , sigmoidoscopy within the past 5 years , or colonoscopy within the past 10 years were seen as evidence of colorectal cancer screening . Women whose charts indicated that they were up to date on all 3 cancer screenings were excluded . We also excluded women with unresolved abnormal screening results ( for example , positive results on home fecal occult blood testing ; mammography results that were categorized as American College of Radiology level 0 , 4 , or 5 ; and certain Papanicolaou test results ) and notified their physicians of these findings . Design Eligible , consenting women were grouped by center , duration of enrollment at their center ( 12 months or > 12 months ) , and the number of cancer screenings that they had received at recommended intervals ( 0 or 1 screening or 2 screenings ) . The New Yorkbased research assistant assigned women in each group to receive the intervention or usual care by using sealed r and omization forms that were produced by Dartmouth College staff with a computer-based r and om-number generator . Patients were informed of their group assignment individually by telephone . At time of consent , all women received the publication titled Put Prevention into Practice Personal Health Guide ( 26 ) , which contained information regarding recommended preventive services . Women who were assigned to the usual care group received a single telephone call during which trial staff answered questions about preventive care , informed women of their usual care status , advised them to obtain needed preventive care from their primary care clinician , and thanked them for their participation . Women who were assigned to the intervention group received a series of telephone support calls from a trained prevention care manager who was monitored to ensure quality and consistency . In much the same way that patient navigators guide women through the health care system during cancer treatment ( 27 ) , prevention care managers facilitated the screening process for each woman by addressing barriers that prevent or delay receipt of cancer screenings . Prevention care managers received 7 hours of training , including an overview of the U.S. Preventive Services Task Force guidelines ( 28 - 30 ) ; a review of barriers to breast , cervical , and colorectal cancer screenings ; and detailed explanations of the targeted screenings . Additional training included role-playing telephone calls during which the managers used the intervention scripts . Thereafter , logs were review ed in monthly meetings to ensure fidelity to the intervention . The 8 prevention care managers were women , and most were college graduates . Their assignments were determined by patient language needs . Each care manager focused most of her work on patients from 1 or 2 sites while supporting smaller numbers of patients from other sites ; contact with clinicians was limited . During the first call with a patient in the intervention group , the prevention care manager answered questions about the health guide and confirmed or up date d screening date s found in the woman 's medical record . She next determined how ready the woman was to act on each screening ( 31 ) and worked with the woman to prioritize overdue screenings . The prevention care manager then provided motivational support , responding to each participant 's specific barriers to screening by using a structured script that was developed through an earlier series of interviews with women ( 32 ) . Some participants had been advised during office visits with their clinicians to undergo screening ; those who had not received such recommendations were sent a written recommendation from their clinician . Women who reported that they had difficulty communicating with their physician were sent brightly colored patient activation cards that listed overdue screenings , which they could share with their clinician at their next appointment . Care managers also scheduled appointments , provided accurate information about screenings over the telephone and by mail , prompted women with appointment reminder calls and letters , provided directions to screening facilities , and helped women to find a means of transportation to appointments . During subsequent calls , which continued for 18 months or until the patient was up to date for all screenings , the prevention care manager asked about future appointments and screenings the patient had received since the last call . The manager then responded to new and ongoing barriers for remaining overdue screenings . Only clinicians , not care managers , were responsible for ordering screenings at all but 2 centers , which permitted care managers to mail home fecal occult blood test kits directly to women who were willing to perform this test . Evaluation Descriptive data on the centers were gathered from surveys that were completed by clinicians and clinical directors . Outcome data were based on review s of patient medical records , which were conducted at least 3 months after the intervention period to allow for the time lag between receipt of a service and the availability of documentation . Data included patient demographic characteristics , screening date s and results , chronic Abstract OBJECTIVE : To determine whether a multimedia computer program could effectively teach patients about fecal occult blood testing ( FOBT ) and increase screening rates . DESIGN : R and omized trial . SETTING : University-affiliated , community-based Internal Medicine outpatient practice . PARTICIPANTS : All English-speaking patients aged 50 years and older who were offered FOBT screening by their providers were invited to participate . Two hundred and four patients enrolled in the study . Ten patients were later determined to be ineligible . INTERVENTIONS : Patients were r and omized to either the educational multimedia computer program or usual nurse counseling about FOBT screening . Screening instructions were based on the material pre-printed on each test kit . Educational sessions were held in a private setting immediately after each patient ’ office visit . MEASUREMENTS AND MAIN RESULTS : A knowledge- assessment question naire was administered in a blinded fashion by telephone the following day . Successful screening was defined as return of the test kits within 30 d. Completion of the FOBT kits was similar in both groups : 62 % ( 58/93 ) in the computer group and 63 % ( 64/101 ) in the nurse group ( P=.89 ) . Mean knowledge scores were also similar , but there was a trend toward increased knowledge mastery in the computer group ( 56 % vs 41 % , P=.09 ) . CONCLUSIONS : A multimedia educational computer program was as effective as usual nurse counseling in educating patients and achieving adherence to FOBT screening . Future studies are needed to determine whether computer-assisted instruction can improve health outcomes Purpose : In 2004 only 68 % of women in Oklahoma over the age of 40 reported having a mammogram in the past 2 years , compared with 75 % nationally . Strategies to improve mammography rates have been numerous but have generally included single strategies , such as physician education , practice audit and feedback , and reminders ; flow sheets and results have been mixed . The purpose of this r and omized controlled trial was to determine the impact of a practice facilitator and “ best practice ” interventions on mammography rates in a practice -based research network . Methods : A total of 16 practice s participated ; 8 were assigned to intervention and 8 to usual care . Pre- and post-audits of mammography rates were conducted . Intervention practice s received feedback with benchmarking , academic detailing , and the assistance of a practice enhancement assistant to help with practice re design over a 9-month period . Results : The groups differed significantly for both the proportion of mammograms offered to eligible patients ( P = .043 ) and for the proportion of patients with current mammograms ( P < .015 ) . For the control group , 38 % of eligible women were offered a mammogram and 202 ( 35 % of those eligible ) actually did have documentation that a mammogram had been performed . Fifty-three percent of the eligible patients in the intervention group were offered a mammogram and 52 % of those eligible ( n = 332 ) did have documentation in the chart that the mammogram had been completed . Conclusion : The results suggest that these interventions can improve mammography rates in a range of practice setting s. These findings are consistent with other studies that have tested multicomponent interventions Objectives : To determine the impact of novel invitation strategies on population participation in faecal immunochemical test (FIT)-based colorectal cancer ( CRC ) screening . Setting A community screening programme in Adelaide , South Australia . Methods : In total , 2400 people aged 50–74 years were r and omly allocated to one of four CRC screening invitation strategies : ( a ) Control : st and ard invitation-to-screen letter explaining risk of CRC and the concept , value and method of screening ; ( b ) Risk : invitation with additional messages related to CRC risk ; ( c ) Advocacy : invitation with additional messages related to advocacy for screening from previous screening programme participants and ( d ) Advance Notification : first , a letter introducing Control letter messages followed by the st and ard invitation-to-screen . Invitations included an FIT kit . Programme participation rates were determined for each strategy relative to control . Associations between participation and sociodemographic variables were explored . Results : At 12 weeks after invitation , participation was : Control : 237/600 ( 39.5 % ) ; Risk : 242/600 ( 40.3 % ) ; Advocacy : 216/600 ( 36.0 % ) and Advance Notification : 290/600 ( 48.3 % ) . Participation was significantly greater than Control only in the Advance Notification group ( Relative risk [ RR ] 1.23 , 95 % confidence interval [ CI ] 1.06–1.43 ) . This effect was apparent as early as two weeks from date of offer ; Advance Notification : 151/600 ( 25.2 % ) versus Control : 109/600 ( 18.2 % , RR 1.38 , 95 % CI 1.11–1.73 ) . Conclusions : Advance notification significantly increased screening participation . The effect may be due to a population shift in readiness to undertake screening , and is consistent with the Transtheoretical Model of behaviour change . Risk or lay advocacy strategies did not improve screening participation . Organized screening programmes should consider using advance notification letters to improve programme participation PURPOSE We wanted to determine whether providing home fecal occult blood test ( FOBT ) kits to eligible patients during influenza inoculation ( flu shot ) clinics can contribute to higher colorectal cancer screening ( CRCS ) rates . METHODS The study was time r and omized . On 8 date s of an annual flu shot clinic at the San Francisco General Hospital , patients were offered flu shots as usual ( control group ) and on 9 other date s , patients were offered both flu shots and FOBT kits ( intervention group ) . RESULTS The study included 514 patients aged 50 to 79 years , with 246 in the control group and 268 in the intervention group . At the conclusion of flu season , FOBT screening rates increased by 4.4 percentage points from 52.9 % at baseline to 57.3 % ( P = .07 ) in the control group , and increased by 29.8 percentage points from 54.5 % to 84.3 % ( P < .001 ) in the intervention group , with the change among intervention participants 25.4 percentage points greater than among control participants ( P value for change difference < .001 ) . Among patients initially due for CRCS , 20.7 % in the control group and 68.0 % in the intervention group were up-to- date at the conclusion of the study ( P < .001 ) . In multivariate analyses , the odds ratio for becoming up-to- date with screening in the intervention group ( vs the control group ) was 11.3 ( 95 % CI , 5.8–22.0 ) . CONCLUSIONS Offering FOBT kits during flu shot clinics dramatically increased the CRCS rate for flu shot clinic attendees . Pairing home FOBT kits with annual flu shots may be a useful strategy to improve CRCS rates in other primary care or public health setting BACKGROUND Low public awareness is an important barrier for colorectal cancer screening participation . AIM To evaluate the impact of educational intervention on the health behavior process , patient knowledge and compliance with colorectal cancer screening in the average-risk population . METHODS 158 subjects ( aged 50 - 79 years ) were r and omly assigned either to watch a non-medical video or a colorectal cancer educational video . Before and after watching the experimental or control videotape , participants completed a five-item question naire that assessed their knowledge about risk factors for colorectal cancer , age of risk , warning symptoms , 5-year prognosis , and incidence . Subjective risk perception for developing colorectal cancer , barriers or benefits of screening , and intention to be screened were also investigated . Finally , subjects received a faecal occult blood test kit and were requested to use and return it within 2 weeks . RESULTS Participants in the video-based intervention group showed significant improvement in knowledge of colorectal cancer scores ( P<0.001 ) and decreased barrier scores . The intervention group returned significantly more faecal occult blood tests than controls ( 69.6 % vs. 54.4 % , P=0.035 ) . The intervention had a positive effect on modifying attitudes and intention to take part in screening . Additionally , the intervention was a predictor of compliance ( OR 2.0 ; 95 % CI=1.02 - 3.84 , P=0.044 ) . CONCLUSION Video-based intervention significantly reduced barriers to screening and improved participant awareness and compliance with colorectal cancer screening with faecal occult blood test BACKGROUND Screening mammography is recommended for early detection of breast cancer but screening rates remain suboptimal . METHODS A primary care portal for a large academic primary practice was developed for all preventive services . Another Web-based system ( PRECARES [ PREventive CAre REminder System ] ) was developed for appointment secretaries to manage proactive breast cancer screening . Female patients aged 40 to 75 years were r and omly assigned to a control group ( usual care ) and an intervention group . For the intervention group , 2 monthly letters inviting patients to undergo mammography were sent starting 3 months before they were due for annual screening , followed by a telephone call to nonresponding patients . A subgroup of women employees was further r and omized to receive a reminder by either US mail or e-mail . RESULTS Of the total eligible population of 6665 women identified as having consented to participate in research , 3339 were r and omly assigned to the control group and 3326 to the intervention group . The screening rate for annual mammography was 64.3 % for the intervention group and 55.3 % for the control group ( P < .001 ) . There were no significant differences between the 2 groups for any of the other adult preventive services . For the employee subgroup , the screening rate was 57.5 % for the control group , 68.1 % for the US mail group , and 72.2 % for the e-mail group ( intervention vs control , P < .001 ; e-mail vs US mail ; P = .24 ) . CONCLUSION The breast cancer screening rate improved significantly with the practice re design of having appointment secretaries proactively manage breast cancer screening needs Aims To assess the effect of the provider ( GPs versus hospital ) on the compliance in returning the faecal occult blood test . To analyse the characteristics of the GP associated with high compliance among his beneficiaries . Methods A question naire about screening attitudes was mailed to the 1192 GPs working in 13 districts of the Lazio region . We asked the GPs to participate in a r and omised trial , we sample d 130 GPs and about 1/10 of the GPs ’ 50–75 year old beneficiaries ( n = 3657 ) were invited to be screened at the GP office and 1/10 ( 3675 ) at the nearest gastroenterology centre . Results 58.5 % of the GPs completed the question naire and 22.7 % agreed to participate in the trial . The compliance in the GP arm was 50 % , in the hospital arm 16 % ( RR 3.4 ; 95 % CI : 3.13–3.70 ) . There was a high variability in the compliance obtained by the GPs . GPs with more than 25 patients visited/day and those incorrectly recommended screening of colorectal cancer obtained a lower compliance ( OR 0.74 , 95 % CI : 0.57–0.95 and OR 0.76 , 95 % CI : 0.59–0.97 , respectively ) . Conclusions The involvement of GPs in colorectal cancer screening can be very effective to enhance the compliance , but the effectiveness is dependent on their willingness to be involved Background : Previous research has found that wellness visits , recall and reminder systems , and st and ing orders are associated with higher rates of delivery of preventive services in primary care practice s. However , there is little information about how to help practice s implement these processes . Methods : A 6-month r and omized , controlled trial comparing a multicomponent quality improvement intervention to feedback and benchmarking . One clinician/nurse team from each of 24 practice s was r and omly assigned to one of 2 study arms . Intervention practice s received performance feedback , peer-to-peer education ( academic detailing ) , a practice facilitator , and computer ( information technology ) support . Implementation of the 3 targeted processes was determined by a blinded 3-clinician panel that review ed transcribed clinician interviews before and after intervention using performance definitions . Rates of delivery of selected preventive services were determined by chart audit . Results : Intervention practice s implemented more of the processes than control practice s overall ( P = .003 ) , for adults ( P = .05 ) , and for children ( P = .04 ) . They were also more likely to implement at least one of the processes for children ( P = .04 ) and to implement st and ing orders for either children or adults ( P = .02 ) . Mammography rates increased significantly . Neither clinician and practice characteristics nor clinician readiness to change predicted implementation . Conclusions : A multicomponent implementation strategy consisting of feedback , benchmarking , academic detailing , facilitation , and IT support increased implementation of evidence -based processes for delivering preventive services to a greater extent than performance feedback and benchmarking alone OBJECTIVE Despite the burden of colorectal cancer and improved health care outcomes with early detection and treatment , screening rates among eligible adults are low . We previously developed through a series of studies an interactive electronic tool , Colorectal Web , to promote colorectal cancer screening . METHOD From May 2002 to December 2003 , we conducted a r and omized controlled trial of Colorectal Web compared to a st and ard Web site on colorectal cancer screening in urban , suburban , and rural communities in Michigan with high colorectal cancer burden . Study participants were age 50 years and older , with no previous colorectal cancer screening . Major outcome was screened for colorectal cancer by 24 weeks post-intervention . RESULTS 174 eligible adults were r and omized and participated . Immediately post-intervention , Colorectal Web participants were significantly more likely to have a preferred colorectal cancer screening method , but this difference did not persist at subsequent follow-up . Eighty-nine participants had been screened for colorectal cancer by 24 weeks post-intervention . The probability of being screened for the Colorectal Web intervention study arm compared to the control is OR=3.23 ( 2.73 - 3.50 95 % Confidence Interval ) . CONCLUSION Colorectal Web is more effective than a st and ard colorectal cancer Web site at prompting previously unscreened individuals to choose a preferred colorectal cancer screening test and to be screened for colorectal cancer AIMS A r and omized trial investigated the impact of risk-tailored messages on mammography in diverse women in the Virginia Commonwealth University Health System 's gynecology clinics . METHODS From 2003 to 2005 , 899 patients > or = 40 years of age were r and omized to receive risk-tailored information or general information about breast health . Multiple logistic regression analyses summarize their breast health practice s at 18 months . RESULTS At baseline , 576 ( 64 % ) women reported having a mammogram in the past year . At 18-month follow-up , mammography rates were 72.6 % in the intervention group and 74.2 % in the control group ( N.S. ) . Women ( n = 123 ) who reported worrying about breast cancer " often " or " all the time " had significantly higher mammography rates with the intervention ( 85.0 % ) vs. the controls ( 63.5 % ) . No significant differences existed in clinical breast examination , self-examination , or mammography intentions between the two study arms . However , intervention women with lower education reported significantly fewer clinical breast examinations at follow-up . CONCLUSIONS The brief intervention with a risk-tailored message did not have a significant effect overall on screening at 18 months . However , among those who worried , mammography rates in the intervention group were higher . Individual characteristics , such as worry about breast cancer and education status , may impact interventions to improve breast cancer prevention practice BACKGROUND The purpose s of the study were to ( 1 ) assess the impact of direct-mail communications with and without phone intervention , and ( 2 ) examine the characteristics of women who were more likely to respond . METHODS Women were recruited from female family members of in patients admitted to one of the major teaching hospitals in Taiwan ( n = 424 ) , and were r and omly assigned into an intervention group , who received direct-mails and a phone follow-up , or a control group , who received placebo messages . RESULTS Logistic regression analysis showed that women in the intervention group ( ORadj . = 2.31 ) and contemplation stage ( ORadj . = 4.18 ) were more likely to receive a screening at the end of the program . Among women in the intervention group , contemplators were 5.58 times more likely to receive a screening before the phone intervention ( early adopters ) ; and 40 % of the screening adopters responded after the phone intervention ( late adopters ) . Late and early adopters were similar in their stage , age , and education . CONCLUSIONS Stage and intervention are both significant predictors of screening adoption . The study provides justification for programs to target women in contemplation stage . It also suggests that the boost of a later phone intervention may be consequential for encouraging more women with similar demographics to take action Women with inadequate health insurance have lower mammography rates than the general population . Finding successful strategies to enroll eligible women is an ongoing challenge for the National Breast and Cervical Cancer Early Detection Program . To test the effectiveness of a population -based strategy to increase mammography utilization among low-income underinsured women ages 40 to 64 years , a r and omized trial was conducted to assess the effect of two mailed interventions on mammography utilization through Sage , the National Breast and Cervical Cancer Early Detection Program in Minnesota . Women ( N = 145,467 ) ages 40 to 63 years [ mean ( SD ) , 49.7 ( 6.8 ) ] with estimated household incomes below $ 50,000 ( 47.9 % were < $ 35,000 ) from a commercial data base were r and omized to three groups : Mail , Mail Plus Incentive , or Control . Both the Mail and the Mail Plus Incentive groups received two simple mailings prompting them to call a toll-free number to access free mammography services . The Mail Plus Incentive intervention offered a small monetary incentive for a completed mammogram . After 1 year , both intervention groups had significantly higher Sage mammography rates than the Controls , and the Mail Plus Incentive group had a significantly higher rate than the Mail group . The Mail and Mail Plus Incentive interventions were estimated to produce increases in Sage screening rates of 0.23 % and 0.75 % , respectively , beyond the composite Control rate of 0.83 % . Direct mail is an effective strategy for increasing mammography use through Sage . Coupling direct mail with an incentive significantly enhances the intervention 's effectiveness . Direct mail should be considered as a strategy to increase mammography use among low-income , medically underserved women Objective : To compare the effectiveness and cost-effectiveness of three methods of inviting women with a long history of non-attendance to undergo cervical screening . Methods : R and omized controlled trial and cost-effectiveness analysis . In all , 1140 women were identified from routine NHS screening records as having no smear for at least 15 years and r and omly allocated to receive a telephone call from a nurse , a letter from a well-known celebrity ( Claire Rayner ) or letter from the local NHS Cervical Screening Commissioner . Uptake of screening was measured using routine data and attributed to interventions if occurring within three months . Uptake was compared with a control group . Costs of carrying out the interventions were noted from the perspective of the NHS and cost-effectiveness , as cost per additional attender , calculated . Results : Uptake following all interventions was low : telephone call ( 1.4 , 95 % confidence interval [ CI ] 0.38–3.6 % ) ; celebrity letter ( 1.8 , 95 % CI 0.57–4.0 % ) ; commissioner letter ( 4.6 , 95 % CI 2.5–7.7 % ) ; control group ( 1.8 , 95 % CI 0.57–4.0 % ) . There were no significant differences between groups . Telephone intervention was not possible in a quarter of women whose numbers were unlisted . Telephone intervention was the most expensive and least effective of the interventions . The commissioner letter yielded an additional attender within three months at an incremental cost of £ 23.21 compared with taking no action . Conclusions : Neither a telephone call from a nurse nor a letter from a celebrity to encourage attendance for cervical screening were effective or cost-effective in women with a prolonged history of non-participation in the screening programme . A letter from the local cervical screening programme commissioner result ed in a small , non-significant increase in uptake . The low cost and ease of implementation of this intervention supports further research into its use in routine practice Colorectal cancer ( CRC ) is the third most common cancer in the United States . Although CRC screening is recommended for individuals 50 years and older , screening completion rates are low . This can be attributed to provider and patient barriers . We developed an intervention to improve provider recommendation and patient screening among noncompliant male veterans in a 2-year r and omized controlled trial and examined the relationship between participation and study outcomes among patients and providers . Overall , providers who attended intervention sessions recommended CRC screening during 64 % of patient visits and providers who did not attend any intervention sessions recommended screening during 54 % of visits ( p < .01 ) . Patients of providers who attended intervention sessions also were more likely to be screened ( 42 % versus 29 % , p < .05 ) . The patient intervention did not have the desired impact . The subgroup of patients in the patient intervention was not more likely to complete CRC screening In this study we focus on women who have no registered cervical smear during the previous 5 years , their requirements for attendance , and promotive efforts performed . Of the 400 women r and omly selected to answer a telephone-based question naire about future attendance at cervical cancer screening ( CCS ) , 120 would consider having a cervical smear taken , and 50 of them wanted help to accomplish that . When meeting the women 's requirements , such as being assured friendly treatment and a suitable appointment time , the numbers of registered cervical smears were higher for the study group compared with a control group . Still , the most highly resistant women did not attend Organizational barriers play a key role in colorectal cancer ( CRC ) screening disparities in low-income minorities . This is a prospect i ve , r and omized trial to determine whether a patient navigator ( PN ) can help overcome the organizational barriers low-income minorities face in trying to obtain screening colonoscopy . Patients of average risk for CRC were referred by their primary care physician for screening colonoscopy . After the PN received the referral , patients were r and omly assigned to either receive navigation ( PN+ ) to screening colonoscopy or not receive navigation ( PN- ) . We hypothesized that a PN would increase patient compliance with screening colonoscopy . A total of 21 patients were enrolled in the pilot study ( PN+ = 13 , PN- = 8) ; 54 % of navigated patients completed screening colonoscopy versus 13 % of nonnavigated patients ( p = 0.058 ) . Eighty-six percent of navigated patients had an excellent or very good colon prep ; however , there was no difference in prep quality between groups ( p = 0.10 ) . One-hundred percent of navigated patients were very satisfied with navigation services . A PN improves compliance with screening colonoscopy in low-income minorities . Larger studies are needed to evaluate what features of navigation are most effective in facilitating completion of screening colonoscopy BACKGROUND Automated telephone outreach with speech recognition ( ATO-SR ) is used extensively by health plans . Whether ATO-SR can increase rates of colorectal cancer ( CRC ) screening is unknown . METHODS We r and omly allocated 40 000 health plan members to ATO-SR and 40 000 to usual care , of whom 10 432 and 10 506 in the intervention and usual care groups , respectively , had not been previously screened and were therefore eligible for analysis . The intervention was a single interactive outreach call using speech recognition to engage participants in conversation about the importance of CRC screening and options for and barriers to screening . The intervention directed participants to contact their primary care provider to schedule screening . The primary end point was any CRC screening in the year following intervention . Colonoscopy in the year following intervention was a secondary outcome . RESULTS The incidence of any CRC screening was 30.6 % in the intervention group and 30.4 % in the usual care group ( P = .76 ) . After adjustment for available covariates , there remained no intervention effect ( adjusted odds ratio [ OR ] , 1.01 ; 95 % confidence interval [ CI ] , 0.94 - 1.07 ) . A total of 21.4 % of members in the intervention group and 20.3 % in the usual care group underwent colonoscopy ( P = .04 ) . In multivariate analysis , there was a small intervention effect on colonoscopy ( OR , 1.08 ; 95 % CI , 1.00 - 1.16 ) . CONCLUSIONS This study showed that ATO-SR failed to improve rates of CRC screening . Future studies should examine approaches that combine efforts to target patients and their health care providers to overcome the barriers to CRC screening . Trial Registration clinical trials.gov Identifier : NCT00792285 Objective : Introduction . Mammography can reduce breast cancer mortality through routine screening . We tested an intervention to increase re-screening in a county program . Methods . The program requires enrollment before screening . We r and omized women who had previously been screened by the program to a telephone call reminder for re-enrollment or usual care ( postcard reminder ) . We followed re-enrollment and re-screening rates for both groups . Results . Compared with the control group ( n=610 ) , women in the intervention group ( n=599 ) had higher rates of initial re-enrollment at one month ( 10 % vs. 24 % , p<.001 ) and re-screening at two months ( 11 % vs. 19 % , p<.001 ) . These effects persisted over time ( five-month re-enrollment : 24 % vs. 35 % , p<.001 ; six-month re-screening : 23 % vs. 31 % , p=.004 ) . The intervention did not alter the odds of a woman 's being re-screened once re-enrolled . Conclusion . The increase in our re-screening rate after this simple intervention was as great or greater than the rates reported in other studies . A telephone reminder for women previously enrolled in a county breast screening program can increase re-enrollment and subsequent re-screening rates Colorectal cancer ( CRC ) is the second leading cause of cancer-related deaths in the United States . Racial disparities in CRC incidence and mortality have been well documented . In addition , lower rates of CRC screening among ethnic minorities have been reported . Therefore , we tested the effectiveness of a patient navigator ( PN ) in increasing compliance with CRC screening in a minority community health setting . Men and women aged 50 or older attending a primary care practice were enrolled if they had not had a fecal occult blood test within the past year , a sigmoidoscopy or barium enema within the past 3–5 years , or a colonoscopy within the past 10 years . Participants were r and omly assigned either to receive navigator services ( PN+ ) or not to receive navigator services ( PN− ) . There were no demographic differences between the two groups . Within 6 months of physician recommendation , 15.8 % in the PN+ group had complied with an endoscopic examination , compared with only 5 % in the PN− group ( P=.019 ) . The PN+ groups also demonstrated higher rates of fecal occult blood test completion ( 42.1 % vs. 25 % , P=.086 ) . Thus , a PN system successfully increases CRC screening rates among a predominantly minority population of low socioeconomic status BACKGROUND Few interventions to increase colorectal cancer screening have used a stage of change model to promote screening adoption . None have used computer-assisted tailored telephone counseling calls . This study 's purpose was to implement and evaluate stage-based computer-assisted tailored telephone counseling to promote colorectal cancer screening in a primary care population . METHODS This r and omized controlled trial used a two-stepped intervention that included a mailed booklet on colorectal cancer screening followed by computer-assisted telephone counseling that was based on the Pre caution Adoption Process Model . Chart audit was used to document completion of colonoscopy , sigmoidoscopy or fecal occult blood testing . RESULTS Record audits were completed on 2,474 ( 88 % ) of the 2,817 eligible participants . There was no significant difference in the frequency and nature of the screening tests completed in the study arms . In a sub- analysis , stages of adoption were evaluated pre- and post-telephone counseling . Over half those receiving counseling reported a change in stage towards screening adoption . CONCLUSION Overall , the intervention did not increase colorectal screening compared to control . Two possible reasons for the absence of a screening effect include : ( a ) the focus of the protocol on education for most patients rather than motivation , and ( b ) the requirement that patients interested in screening seek further information and a referral on their own from their providers . While those receiving telephone counseling improved their stage of adoption , we can not rule out selection bias . Stronger physician recommendation to speak with the counselors could improve call acceptance . Future colorectal screening should address these weaknesses Background : Many breast cancer outreach programs assume that dissemination of information through social networks and provision of social support will promote screening . The authors prospect ively examined the relationship between social network characteristics and adherence to screening guidelines . Method : Employed women age 40 years and older completed baseline and 2-year follow-up assessment s ( N = 1,475 ) as part of an intervention trial . The authors modeled screening adherence at follow-up as a function of social network characteristics at baseline . Results : Baseline adherence explained most of the variation in adherence at follow-up . For women age 40 to 51 years , having a mammogram at follow-up was predicted by encouragement by family and /or friends and subjective norms at baseline ( odds ratio = 2.20 and 1.18 , respectively ) . For women age 52 years and older , the perception that screening was normative was related to adherence at follow-up ( odds ratio = 1.46 ) . Conclusions : Previous mammography use is strongly predictive of future screening . Social network characteristics have a modest impact on screening . Outreach efforts should focus on those who have previously underutilized mammography OBJECTIVE The purpose of this intervention was to increase mammography adherence in women who had not had a mammogram in the last 15 months . METHODS A prospect i ve r and omized intervention trial used four groups : ( 1 ) usual care , ( 2 ) tailored telephone counseling , ( 3 ) tailored print , ( 4 ) tailored telephone counseling and print . Participants included a total of 1244 women from two sites-a general medicine clinic setting serving predominately low-income clientele and a Health Maintenance Organization ( HMO ) . Computer-tailored interventions addressed each woman 's perceived risk of breast cancer , benefits and /or barriers and self-efficacy related to mammography screening comparing delivery by telephone and mail . RESULTS Compared to usual care all intervention groups increased mammography adherence significantly ( odds ratio 1.60 - 1.91 ) when the entire sample was included . CONCLUSIONS All interventions groups demonstrated efficacy in increasing mammography adherence as compared to a usual care group . When the intervention analysis considered baseline stage , pre contemplators ( women who did not intend to get a mammogram ) did not significantly increase in mammography adherence as compared to usual care . PRACTICE IMPLICATION S Women who are in pre contemplation stage may need a more intensive intervention Context Many patients who might benefit from colorectal cancer screening do not get screening . Time pressure may prevent physicians from fully educating their patients about colorectal cancer screening . Contribution In this r and omized , controlled trial , an educational video about colorectal cancer screening mailed to patients before a primary care visit did not increase the rate of screening compared with usual care . Caution s The video focused on sigmoidoscopy rather than colonoscopy , and the study sample had a higher than average baseline rate of colorectal cancer screening . Colorectal cancer is a major cause of cancer death ( 1 ) . Evidence about screening test effectiveness ( 2 ) continues to mount , and guidelines from many organizations promote several screening options ( 3 - 7 ) . Rates of screening , however , remain lower than rates of other preventive services ( 8 - 10 ) . Barriers to screening are numerous . Physicians report inadequate time to educate patients and facilitate decision making ( 11 , 12 ) . Contributing factors include competing dem and s placed on clinicians ( 13 ) and the need to manage acute problems ( 12 , 14 ) . Prominent patient barriers include lack of knowledge about colorectal cancer and fears of cancer and screening tests ( 15 , 16 ) . Interventions to increase screening have generally focused on individual providers and clinical systems . Provider education programs , use of support staff , on-site sigmoidoscopy services , and reminder systems have all increased testing ( 11 , 16 - 23 ) . Patient-focused interventions have used education , reminders , and cost reduction to increase use of fecal occult blood testing ( 17 - 19 ) and sigmoidoscopy ( 20 , 21 ) . This study examined the effectiveness of an educational video design ed to increase colorectal cancer screening , particularly via sigmoidoscopy ; the video was mailed to patients ' homes before a scheduled periodic health examination . We studied the effectiveness of this patient education video for several reasons . First , the information that patients need for colorectal cancer screening is complex and voluminous because of the multiple screening options and the increased emphasis on informed decision making and informed consent ( 22 - 26 ) . Clinicians view time dem and s and competing medical needs as screening barriers ( 27 - 29 ) . The video contains considerable information , and thus clinicians can spend less time explaining the information to patients . Second , video assures st and ardized content that is not subject to providers ' individual opinions or weak communication skills . Video overcomes some weaknesses of mass media health messages : brevity , superficial rendering of complex issues , and lack of opportunity for review ( 30 ) . Third , the public is more oriented toward viewing than reading , and video is particularly attractive to population s with low literacy ( 31 , 32 ) . Last , to our knowledge no other study has evaluated the effect of a mailed video ( an aspect that solves in-clinic logistic problems ) independent of other systems changes ( 21 ) . Methods Study Overview We used a r and omized , controlled design to assess the effectiveness of a video intended to encourage discussion of colorectal cancer screening with the primary care provider and increase use of screening , particularly by sigmoidoscopy . St and ardized telephone interviews were conducted twice . Participants completed the baseline interview several weeks before their scheduled visit and were then r and omly assigned within age and sex strata to the experimental or the control group . Follow-up assessment was completed 4 to 6 months after the periodic examination . Study Sites Participants were recruited from 5 sites in central Massachusetts . Most were patients in internal medicine and family medicine clinics of an academic medical center ( university practice ) . Other sites were a suburban clinic of a staff-model health maintenance organization ( HMO ) ; 3 university-affiliated , community-based practice s ; a rural practice ; and 2 suburban practice s , which were combined for analyses because of small sample sizes and similar patient population s ( community practice s ) . The Committee for the Protection of Human Subjects of the University of Massachusetts Medical School and the Institutional Review Board of Fallon Community Health Plan review ed and approved the study . Participant Recruitment Eligible participants were patients 50 to 74 years of age who had an upcoming periodic health assessment and were eligible for sigmoidoscopy according to screening guidelines ( no sigmoidoscopy within 5 years or colonoscopy within 10 years ) . A computerized appointment system identified potentially eligible participants because appointments are coded by type , including appointments for physical examinations , and by appointment length ( 30 minutes ) . Records used to determine previous tests varied by site and included patient information systems , medical records , and a log of completed procedures . To assure sex and age representation ( men age 50 to 64 years , men age 65 to 74 years , women age 50 to 64 years , and women age 65 to 74 years ) , we determined that a sample size of 225 in each of the younger agesex groups and a sample size of 100 in each of the older agesex groups would assure 80 % power to detect significant differences ( at an level of 0.05 ) ranging from 7 % to 16 % depending on the outcome in the comparison group overall . Patients were enrolled from February 1999 through December 2000 . We sent 1883 eligible patients an invitation letter several weeks before their appointment . Of the 1788 who were contacted by telephone , 1575 ( 88 % ) consented to participate . Consenting persons were screened for additional eligibility criteria . Those excluded reported recent ( n= 339 ) or planned ( n= 26 ) tests ; did not undergo scheduled sigmoidoscopy in the past 10 months ( n= 3 ) ; reported a colorectal cancer diagnosis or related symptoms ( n= 30 ) ; canceled their periodic examination appointment ( n= 41 ) ; could not participate because of illness , death , disability , or dementia or because they were institutionalized ( n= 69 ) ; did not speak English ( n= 35 ) ; had a spouse enrolled in the study ( n= 17 ) ; had moved out of the area ( n= 12 ) ; or were older than 74 years of age ( n= 2 ) . The baseline sample consisted of 1001 persons . After the baseline interview was completed , we sorted consenting participants into the 4 sexage groups . A computer-generated r and om-number table determined assignment in each group . The project director , who was not located at any clinical site , allocated enrollees to the intervention or control group using the computer-generated assignment , tracked group assignment , and mailed intervention material s. The project director was the only individual with knowledge of or access to group or individual assignment . The interviewer was blinded to group assignment at both baseline ( conducted before r and omization ) and follow-up interviews . Subsequently , 63 patients were not eligible : 50 did not keep an index appointment , and 13 could not participate because of death , poor health , or decline in cognitive inability . Of the 938 persons eligible for follow-up ( 97.9 % ) , 926 were contacted by an interviewer who was blinded to group assignment , and 918 completed the follow-up interview . Intervention The objective of the video was to encourage patients to discuss colorectal cancer screening , particularly using sigmoidoscopy , with their physician at their upcoming appointment . This intervention builds on the promising literature about the effectiveness of video to improve health behavior ( 30 , 33 - 35 ) , increase patient knowledge ( 36 - 40 ) , reduce anxiety ( 41 , 42 ) , and provide role modeling ( 43 ) . The intervention consisted of a 15-minute video titled Say Yes to the Test . Development was guided by the PRECEDE/PROCEED model for health promotion planning ( 44 ) and the behavioral model of utilization ( 45 ) , incorporating elements of social cognitive theory ( 46 , 47 ) . We were also interested in testing a mailed outreach strategy . Showing videos in busy clinics is logistically difficult , presenting time , equipment , noise , space , and privacy problems . Friedman and colleagues ( 48 ) found that episodic technical difficulties hindered video education in the clinic setting . Mead and colleagues ( 49 ) reported that patient education material s ( video , pamphlets , posters ) placed in clinic waiting rooms did not increase use of preventive services . Of note , widespread ownership of video players and affordable per-unit cost make a mail-out approach feasible . The video , hosted by a nationally known actress who has had colorectal cancer , described screening by using graphics , footage of physicians discussing screening importance , and footage of a patient undergoing sigmoidoscopy . It addressed benefits and barriers to sigmoidoscopy , primarily with clips of several patients who had screening-detected colorectal cancer , and featured patients discussing sigmoidoscopy experiences ( 50 ) . Barriers included minimal knowledge of colorectal cancer , lack of screening information , low perceived risk , fear of cancer , and expectation of pain and embarrassment ( 16 , 20 , 51 - 60 ) . Videos were mailed to each participant 's home before the scheduled physical examination ; each package contained a letter , signed by the primary care physician , encouraging the participant to view the video . Participants in the control group received usual care with no special material s. Data Collection and Measures Fifteen- to 20-minute telephone surveys were conducted at baseline and 4 to 6 months after the primary care appointment . The timing of the follow-up survey allowed all recommended tests to be scheduled and completed . We developed survey items by using our previous work ( 50 , 61 ) and other studies ( 62 ) . The survey described all tests : For example , a fecal occult blood test was defined as a test taken at home , with cards mailed back . The follow-up survey also covered the intervention group 's experience with the video . Colorectal Cancer Screening PURPOSE An earlier r and omized controlled trial of prevention care management ( PCM ) found significant improvement in breast , cervical , and colorectal cancer-screening rates among women attending Community Health Centers but required substantial research support . This study evaluated the impact of a streamlined PCM delivered through a Medicaid managed care organization ( MMCO ) , an infrastructure with the potential to sustain this program for the long term . METHODS This r and omized trial was conducted within an MMCO serving New York City between May 2005 and December 2005 . A total of 1,316 women aged 40 to 69 years and not up to date for at least 1 targeted cancer-screening test were r and omized to either PCM or a comparison group . Women in the PCM group received up to 3 scripted telephone calls to identify barriers and provide support to obtain any needed breast , cervical , and colorectal cancer-screening tests . Women in the comparison group received a modified version of the MMCO ’s established mammography telephone outreach program , also in up to 3 calls . Women in both groups received a financial incentive on confirmation that they had received a mammogram . Screening status was assessed through MMCO administrative data . Groups were compared using odds ratios . RESULTS In an intent-to-treat comparison adjusted for baseline screening status , PCM women were 1.69 times more likely to be up-to- date for colorectal cancer-screening tests at follow-up than women in the comparison group ( 95 % confidence interval , 1.03–2.77 ) . Follow-up screening rates for cervical and breast cancer did not differ significantly between study groups on an intent-to-treat basis . CONCLUSIONS The abbreviated PCM telephone intervention was feasible to deliver through an MMCO and improved screening for 1 cancer . This approach has the potential to improve cancer-screening rates significantly in setting s that can provide telephone support to women known to be overdue METHOD The study was conducted over a four-year period , 1996 and 2000 . Participants were recruited using Computer Assisted Telephone Interviewing ( CATI ) software and r and om-digit dialing ( RDD ) . Study eligibility criteria included living in the King/Drew Medical Center service area in Los Angeles , having an operable telephone , being female > or = 40 years old and not having had a screening mammogram in the past year . Four-hundred-thirty respondents were r and omly assigned to the intervention and comparison groups . English and Spanish focus-group-tested tailored interventions were administered telephonically by trained interviewers . African Americans and Latinas constituted 83.0 % of the sample at assignment and 83.8 % at six-month follow-up , which is representative of the study area . RESULTS The main outcome variable of interest in this study was having a screening mammogram during the time interval between baseline and the six-month follow-up assessment . Multiple logistic regressions that revealed factors predicting the outcome variable included : 1 ) age ( p < or = 0.05 , OR=2.22 , CI 0.98 - 5.0 ) ; 2 ) study group ( p < or = 0.05 , OR=1.76 , CI 1.06 - 2.92 ) ; 3 ) prior mammograms ( p < or = 0.05 , O0R=2.51 , 1.39 - 4.56 ) ; and 4 ) and knowledge of the age when a woman should begin getting mammograms on a regular basis ( p < or = 0.05 , OR=0.55 , 0.33 - 0.92 ) . CONCLUSION Tailored telephone counseling increased the instances of screening mammograms by nearly 8 % in the intervention group at follow-up . The results of this study confirm previous findings regarding the impact of structural and behavioral factors related to screening mammography BACKGROUND This study compares the efficacy of three types of reminders in promoting annual repeat mammography screening . DESIGN RCT . SETTING AND PARTICIPANTS Study recruitment occurred in 2004 - 2005 . Participants were recruited through the North Carolina State Health Plan for Teachers and State Employees . All were aged 40 - 75 years and had a screening mammogram prior to study enrollment . A total of 3547 women completed baseline telephone interviews . INTERVENTION Prior to study recruitment , women were assigned r and omly to one of three reminder groups : ( 1 ) printed enhanced usual care reminders ( EUCRs ) ; ( 2 ) automated telephone reminders ( ATRs ) identical in content to EUCRs ; or ( 3 ) enhanced letter reminders that included additional information guided by behavioral theory . Interventions were delivered 2 - 3 months prior to women 's mammography due date s. MAIN OUTCOME MEASURES Repeat mammography adherence , defined as having a mammogram no sooner than 10 months and no later than 14 months after the enrollment mammogram . RESULTS Each intervention produced adherence proportions that ranged from 72 % to 76 % . Post-intervention adherence rates increased by an absolute 17.8 % from baseline . Women assigned to ATRs were significantly more likely to have had mammograms than women assigned to EUCRs ( p=0.014 ) . Comparisons of reminder efficacy did not vary across key subgroups . CONCLUSIONS Although all reminders were effective in promoting repeat mammography adherence , ATRs were the most effective and lowest in cost . Health organizations should consider using ATRs to maximize proportions of members who receive mammograms at annual intervals Background : The proportion of non-attenders in cervical cancer screening is high , and should be minimised . A targeted invitation to women not participating for the last 5 years in cervical screening was evaluated to determine whether it would decrease the number of these women . Increasing general practitioners ’ attention to the screening programme for cervical cancer was also evaluated to determine whether it would increase participation . Methods : A cluster r and omised controlled trial conducted in the county of Aarhus , Denmark . All women registered with a GP were r and omised . Regardless of group allocation , all women received a normal invitation . In the intervention arm , GPs were visited to facilitate quality enhancements of the screening programme , combined with a special targeted invitation to women aged 23–59 registered with the GP but not attending screening for the last 5 years . The main outcome was the proportion of non-attenders and the secondary outcome was coverage rate . Results : 117 129 women registered with 190 GPs were included in the study . 1737 non-attenders had a Papanicolaou smear during follow-up . The decline in non-attenders was 0.87 % ( 95 % CI 0.57 % to 1.16 % ) after 9 months in favour of the intervention . A difference of 0.94 % ( 95 % CI 0.21 % to 1.67 % ) in the change of coverage rate was observed at 6 months , which increased to 1.97 % ( 95 % CI 0.03 % to 3.91 % ) at 9 months in favour of the intervention . Conclusion : It is possible to decrease the proportion of non-attenders and increase the coverage rate in a screening programme for cervical cancer using a special targeted invitation to non-attenders combined with a visit to GPs . To further improve participation , other barriers must be identified and addressed |
10,722 | 28,760,795 | Interventions focused on discrete groups of older people with specific needs offering guidance or psychological support were more effective than those broadly targeting survival outcomes .
Advanced Practice Nursing roles , voluntary support roles and the involvement of geriatric teams provided some evidence of effectiveness .
Conclusions An array of workforce interventions focus on improving outcomes for older people with cancer but these are diverse and thinly spread across the cancer journey .
Higher quality and larger scale research that focuses on workforce features is now needed to guide developments in this field , and review findings indicate that interventions targeted at specific subgroups of older people with complex needs , and that involve input from advanced practice nurses , geriatric teams and trained volunteers appear most promising | Objectives To provide an overview of the evidence base on the effectiveness of workforce interventions for improving the outcomes for older people with cancer , as well as analysing key features of the workforce associated with those improvements . | OBJECTIVES The aim of this study was to assess the prevalence of potentially inappropriate medication ( PIM ) use upon admission and at discharge in a geriatric oncology unit after involving a clinical pharmacist . Although the few studies conducted in geriatric oncology units used the 2003 Beers criteria , this study used START and STOPP criteria , a more appropriate tool for European formularies . MATERIAL S AND METHODS Prospect i ve study in older ( ≥70years ) patients consecutively admitted to a geriatric oncology unit in a cancer center from July 2011 to April 2012 . Clinical pharmacist conducted a complete comprehensive medication review including non-prescription and complementary ( herbals ) medications . This information coupled with the patient 's medical history allows identifying PIMs using the STOPP and START criteria . The number of PIMs at admission and at discharge from the hospital was compared after clinical pharmacist intervention . RESULTS Ninety-one older patients with cancer ( mean age±SD=79±6years ) were included in the study . START criteria identified 41 PIMs for 31 persons ( 34 % ) at admission compared to 7 PIMs for 6 persons ( 7 % ) at discharge . STOPP criteria identified 50 PIMs at admission for 29 persons ( 32 % ) compared to 16 PIMs at discharge for 14 persons ( 16 % ) . Results showed significantly lower START scores at discharge than at admission ( p<0.001 ) ; similarly , STOPP criteria demonstrated fewer PIMs at discharge than at admission ( p<0.001 ) . CONCLUSION The use of START and STOPP criteria by a clinical pharmacist allows identifying PIMs and changing prescriptions for older patients with cancer in agreement with the oncologist and geriatrician of the team Background Depression is common among older cancer patients , but little is known about the optimal approach to caring for this population . This analysis evaluates the effectiveness of the Improving Mood-Promoting Access to Collaborative Treatment ( IMPACT ) program , a stepped care management program for depression in primary care patients who had an ICD-9 cancer diagnosis . Methods Two hundred fifteen cancer patients were identified from the 1,801 participants in the parent study . Subjects were 60 years or older with major depression ( 18 % ) , dysthymic disorder ( 33 % ) , or both ( 49 % ) , recruited from 18 primary care clinics belonging to 8 health-care organizations in 5 states . Patients were r and omly assigned to the IMPACT intervention ( n = 112 ) or usual care ( n = 103 ) . Intervention patients had access for up to 12 months to a depression care manager who was supervised by a psychiatrist and a primary care provider and who offered education , care management , support of antidepressant management , and brief , structured psychosocial interventions including behavioral activation and problem-solving treatment . Results At 6 and 12 months , 55 % and 39 % of intervention patients had a 50 % or greater reduction in depressive symptoms ( SCL-20 ) from baseline compared to 34 % and 20 % of usual care participants ( P = 0.003 and P = 0.029 ) . Intervention patients also experienced greater remission rates ( P = 0.031 ) , more depression-free days ( P < 0.001 ) , less functional impairment ( P = 0.011 ) , and greater quality of life ( P = 0.039 ) at 12 months than usual care participants . Conclusions The IMPACT collaborative care program appears to be feasible and effective for depression among older cancer patients in diverse primary care setting BACKGROUND Geriatric assessment has been suggested as a possibly useful approach in dealing with frail elderly cancer patients . METHODS This was a secondary subset analysis from a r and omized 2 x 2 factorial trial in 11 Department of Veterans Affairs medical centers . Hospitalized , frail patients at least 65 years old , after stabilization of their acute illness , were r and omized to receive care in a geriatric inpatient unit , a geriatric outpatient clinic , both , or neither . The interventions involved core teams that provided geriatric assessment and patient management . We identified 99 patients with a diagnosis of cancer by The International Classification of Diseases , 9th Revision ( ICD-9 ) codes , excluding all nonmelanoma skin cancers . Outcomes collected at discharge , 6 months , and 1 year after r and omization were survival , changes in health-related quality of life ( using the Medical Outcomes Study 36-Item Short-Form general health survey [ SF-36 ] ) , activities of daily living , physical performance , health service utilization , and costs . RESULTS There was no effect on mortality ( 1-year survival 59.6 % ) . The changes in the SF-36 scores from r and omization for emotional limitation , mental health and bodily pain ( also sustained at 1 year ) on the SF-36 were better for geriatric inpatient care cancer patients at discharge . There was no difference in SF-36 scores between geriatric outpatient and usual outpatient care . Days of hospitalization and overall costs were equivalent for the interventions and usual care over the 1-year study . CONCLUSIONS This study suggests that inpatient geriatric assessment and management may be an effective approach to the management of pain and psychological status in the elderly cancer inpatient at no greater length of hospitalization or extra cost than usual care Background Disadvantaged population s face many barriers to cancer care , including limited support in navigating through the complexities of the healthcare system . Family members play an integral role in caring for patients and provide valuable care coordination ; however , the effect of family navigators on adherence to cancer screening has not previously been evaluated . Training and evaluating trusted family members and other support persons may improve cancer outcomes for vulnerable patients . Methods Guided by principles of community based participatory research ( CBPR ) , “ Evaluating Coaches of Older Adults for Cancer Care and Healthy Behaviors ( COACH ) ” is a community-based r and omized controlled trial to assess the effectiveness of a trained participant- design ated coach ( support person or care giver ) in navigating cancer-screening for older African American adults , 50–74 years old . Participants are r and omly assigned as dyads ( participant + coach pair ) to receiving either printed educational material s only ( PEM — control group ) or educational material s plus coach training ( COACH — intervention group ) . We defined a coach as family member , friend , or other lay support person design ated by the older adult . The coach training is design ed as a one-time , 35- to 40-minute training consisting of : 1 ) a didactic session that covers the role of the coach , basic facts about colorectal , breast and cervical cancers ( including risk factors , signs and symptoms and screening modalities ) , engaging the healthcare provider in cancer screening , insurance coverage for screening , and related healthcare issues , 2 ) three video skits addressing misconceptions about and planning for cancer screening , and 3 ) an interactive role-play session with the trainer to reinforce and practice strategies for encouraging the participant to get screened . The primary study outcome is the difference in the proportion of participants completing at least one of the recommended screenings ( for breast , cervix or colorectal cancer ) between the control and intervention groups . Discussion Building on trusted patient contacts to encourage cancer screening , COACH is a highly sustainable intervention in a high-risk population . It has the potential to minimize the effect of mistrust of the medical establishment on screening behaviors by mobilizing participants ’ existing support networks . If effective , the intervention could have a high impact on health care disparities research across multiple diseases . Trial registration Clinical Trials.gov ( NCT01613430 ) . Registered June 5 , Background Delirium is a serious and common postoperative complication , especially in frail elderly patients . The aim of this study was to evaluate the effect of a geriatric liaison intervention in comparison with st and ard care on the incidence of postoperative delirium in frail elderly cancer patients treated with an elective surgical procedure for a solid tumour . Methods Patients over 65 years of age who were undergoing elective surgery for a solid tumour were recruited to a multicentre , prospect i ve , r and omized , controlled trial . The patients were r and omized to st and ard treatment versus a geriatric liaison intervention . The intervention consisted of a preoperative geriatric consultation , an individual treatment plan targeted at risk factors for delirium , daily visits by a geriatric nurse during the hospital stay and advice on managing any problems encountered . The primary outcome was the incidence of postoperative delirium . The secondary outcome measures were the severity of delirium , length of hospital stay , complications , mortality , care dependency , quality of life , return to an independent preoperative living situation and additional care at home . Results In total , the data of 260 patients were analysed . Delirium occurred in 31 patients ( 11.9 % ) , and there was no significant difference between the incidence of delirium in the intervention group and the usual-care group ( 9.4 % vs. 14.3 % , OR : 0.63 , 95 % CI : 0.29–1.35 ) . Conclusions Within this study , a geriatric liaison intervention based on frailty for the prevention of postoperative delirium in frail elderly cancer patients undergoing elective surgery for a solid tumour has not proven to be effective . Trial Registration Nederl and s Trial Register Trial ID NTR Objective We tested the effect of dietary advice dedicated to increase intake in older patients at risk for malnutrition during chemotherapy , versus usual care , on one-year mortality . Method We conducted a multicentre , open-label interventional , stratified ( centre ) , parallel r and omised controlled trial , with a 1∶1 ratio , with two-year follow-up . Patients were aged 70 years or older treated with chemotherapy for solid tumour and at risk of malnutrition ( MNA , Mini Nutritional Assessment 17–23.5 ) . Intervention consisted of diet counselling with the aim of achieving an energy intake of 30 kCal/kg body weight/d and 1.2 g protein/kg/d , by face-to-face discussion targeting the main nutritional symptoms , compared to usual care . Interviews were performed 6 times during the chemotherapy sessions for 3 to 6 months . The primary endpoint was 1-year mortality and secondary endpoints were 2-year mortality , toxicities and chemotherapy outcomes . Results Between April 2007 and March 2010 we r and omised 341 patients and 336 were analysed : mean ( st and ard deviation ) age of 78.0 y ( 4·9 ) , 51.2 % male , mean MNA 20.2 ( 2.1 ) . Distribution of cancer types was similar in the two groups ; the most frequent were colon ( 22.4 % ) , lymphoma ( 14.9 % ) , lung ( 10.4 % ) , and pancreas ( 17.0 % ) . Both groups increased their dietary intake , but to a larger extent with intervention ( p<0.01 ) . At the second visit , the energy target was achieved in 57 ( 40.4 % ) patients and the protein target in 66 ( 46.8 % ) with the intervention compared respectively to 13 ( 13.5 % ) and 20 ( 20.8 % ) in the controls . Death occurred during the first year in 143 patients ( 42.56 % ) , without difference according to the intervention ( p = 0.79 ) . No difference in nutritional status changes was found . Response to chemotherapy was also similar between the groups . Conclusion Early dietary counselling was efficient in increasing intake but had no beneficial effect on mortality or secondary outcomes . Cancer cachexia antianabolism may explain this lack of effect . Trial Registration Clinical Trials.gov OBJECTIVES To evaluate the effect of nurse case management on the treatment of older women with breast cancer . DESIGN R and omized prospect i ve trial . SETTING Sixty surgeons practicing at 13 community and two public hospitals in southeast Texas . PARTICIPANTS Three hundred thirty-five women ( 166 control and 169 intervention ) aged 65 and older newly diagnosed with breast cancer . INTERVENTION Women seeing surgeons r and omized to the intervention group received the services of a nurse case manager for 12 months after the diagnosis of breast cancer . MEASUREMENTS The primary outcome was the type and use of cancer-specific therapies received in the first 6 months after diagnosis . Secondary outcomes were patient satisfaction and arm function on the affected side 2 months after diagnosis . RESULTS More women in the intervention group received breast-conserving surgery ( 28.6 % vs 18.7 % ; P=.031 ) and radiation therapy ( 36.0 % vs 19.0 % ; P=.003 ) . Of women undergoing breast-conserving surgery , greater percentages in the case management group received adjuvant radiation ( 78.3 % vs 44.8 % ; P=.001 ) and axillary dissection ( 71.4 % vs 44.8 % ; P=.057 ) . Women in the case management group were also more likely to receive more breast reconstruction surgery ( 9.3 % vs 2.6 % , P=.054 ) , and women in the case management group with advanced cancer were more likely to receive chemotherapy ( 72.7 % vs 30.0 % , P=.057 ) . Two months after surgery , higher percentages of women in the case manager group had normal arm function ( 93 % vs 84 % ; P=.037 ) and were more likely to state that they had a real choice in their treatment ( 82.2 % vs 69.9 % , P=.020 ) . Women with indicators of poor social support were more likely to benefit from nurse case management . CONCLUSION Nurse case management results in more appropriate management of older women with breast cancer CONTEXT Changes in the healthcare system have result ed in shortened hospital stays , moving the focus of care from the hospital to the home . Patients are discharged post-operatively with ongoing needs , and whether they receive nursing care post-hospitalization can influence their recovery and survival . Little information is available about the factors that influence outcomes , including the survival of older cancer patients after cancer surgery . OBJECTIVE To compare the length of survival of older post-surgical cancer patients who received a specialized home care intervention provided by advanced practice nurses ( APNs ) with that of patients who received usual follow-up care in an ambulatory setting . We also assessed potential predictors of survival in terms of depressive symptoms , symptom distress , functional status , comorbidities , length of hospital stay , age of patient , and stage of disease . DESIGN A r and omized controlled intervention study . SETTING Discharged older cancer patients after surgery at a Comprehensive Cancer Center in southeastern Pennsylvania . PATIENTS Three hundred seventy-five patients aged 60 to 92 , newly diagnosed with solid cancers , were treated surgically between February 1993 and December 1995 . One hundred ninety patients were r and omized to the intervention groups and 185 to the usual care group . INTERVENTION The intervention was a st and ardized protocol that consisted of st and ard assessment and management post-surgical guidelines , doses of instructional content , and schedules of contacts . The intervention lasted 4 weeks and consisted of three home visits and five telephone contacts provided by APNs . Both the patients and their family caregivers received comprehensive clinical assessment s , monitoring , and teaching , including skills training . MAIN OUTCOME MEASURE Time from enrollment of patients into the study until death or last date known alive at the end of November 1996 . RESULTS During the 44-month follow-up period , 93 ( 24.8 % ) of 375 patients died . Forty-one ( 22 % ) of those who died were patients in the specialized home care intervention group , compared with 52 ( 28 % ) in the usual care group . Stage of disease at diagnosis differed between the two groups at baseline ( 38 % late stage patients in the intervention group compared with 26 % in the control group , P = .01 ) , so stratified analysis was performed . Overall , the specialized home care intervention group was found to have increased survival ( P = .002 using stratified log-rank test ) . Among early stage patients only , there was no difference in survival between the intervention and control groups . Among late stage patients , there was improved survival in the intervention group . For example , 2-year survival among late stage intervention group cases was 67 % compared with 40 % among control cases . When Cox 's proportional hazard model was used to adjust for significant baseline covariates , the relative hazard of death in the usual care group was 2.04 ( CI : 1.33 to 3.12 ; P = .001 ) after adjusting for stage of disease and surgical hospitalization length of stay . CONCLUSIONS This is the first empirical study of post-surgical cancer patients to link a specialized home care intervention by advanced practice nurses with improved survival . Additional research is needed to test home care interventions aim ed at maintaining quality of life outcomes and their effects on survival of post-surgical cancer patients A r and omized pre- and post-test control group design was conducted in 12 oncology wards to investigate the effectiveness of an intervention , existing of a communication skills training with web-enabled video feedback and a Question Prompt Sheet ( QPS ) , which aim ed to improve patient education to older cancer patients ( ≥65 years ) . The effects were studied by analyzing question naires and video recordings of patient education sessions preceding chemotherapy with 210 different patients . Patients ' recall of information was the primary outcome of the study . Recall was checked against the actual communication in the video-recordings . Moreover , communication skills were assessed by observing the extent to which nurses implemented 67 communication aspects , categorized in seven dimensions , using the QUOTE(chemo ) . Experimental nurses demonstrated a significant intervention effect on communicating realistic expectations . Within-group improvements were measured in the experimental group for tailored communication , affective communication and interpersonal communication . Although the use of a QPS significantly increased question asking , only limited results were found on older patients ' recall scores . The overall proportion recall of recommendations showed a marginally significant pre-/post-change in proportion recall in favour of the experimental group and there was a significant pre-/post-change in two out of six sub-categories . The results indicate that nurses ' communication skills can be improved by communication skills training . More research is needed to underst and the difficult relationship between patient-provider communication and recall of information PURPOSE / OBJECTIVES To test the feasibility and acceptability of an individualized representational intervention to improve symptom management ( IRIS ) in older breast cancer survivors and test the short-term effects of an IRIS on symptom distress . DESIGN Two small r and omized clinical trials and one pre-experimental study . SETTING Oncology clinic and community . SAMPLE 41 women with breast cancer ( aged 65 years and older ) in pilot study 1 , 20 in pilot study 2 , and 21 in pilot study 3 . METHODS In pilot study 1 , women were r and omized to the IRIS or usual care control . In pilot study 2 , women were r and omized to the IRIS or delayed IRIS ( wait list ) control . In pilot study 3 , all women received the IRIS by telephone . Measures were collected at baseline , postintervention , and follow-up ( up to four months ) . MAIN RESEARCH VARIABLES Feasibility , acceptability , symptom distress , symptom management behaviors , symptom management barriers , and quality of life . FINDINGS Across three pilot studies , 76 % of eligible women participated , 95 % completed the study , 88 % reported the study was helpful , and 91 % were satisfied with the study . Some measures of symptom distress decreased significantly after the IRIS , but quality of life was stable . Women in the IRIS group changed their symptom management behaviors more than controls . CONCLUSIONS Preliminary evidence supports the need for and feasibility of an IRIS . IMPLICATION S FOR NURSING Nurses may help older breast cancer survivors manage their numerous chronic symptoms more effectively by assessing women 's beliefs about their symptoms and their current symptom management strategies PURPOSE The primary goal of this study was to evaluate the feasibility and effectiveness of a structured , multidisciplinary intervention targeted to maintain the overall quality of life ( QOL ) , which is more comprehensive than psychosocial distress , of patients undergoing radiation therapy for advanced-stage cancer . PATIENTS AND METHODS Radiation therapy patients with advanced cancer and an estimated 5-year survival rate of 0 % to 50 % were r and omly assigned to either an eight-session structured multidisciplinary intervention arm or a st and ard care arm . The eight 90-minute sessions addressed the five domains of QOL including cognitive , physical , emotional , spiritual , and social functioning . The primary end point of maintaining overall QOL was assessed by a single-item linear analog scale ( Linear Analog Scale of Assessment or modified Spitzer Uniscale ) . QOL was assessed at baseline , week 4 ( end of multidisciplinary intervention ) , week 8 , and week 27 . RESULTS Of the 103 participants , overall QOL at week 4 was maintained by the patients in the intervention ( n = 49 ) , whereas QOL at week 4 significantly decreased for patients in the control group ( n = 54 ) . This change reflected a 3-point increase from baseline in the intervention group and a 9-point decrease from baseline in the control group ( P = .009 ) . Intervention participants maintained their QOL , and controls gradually returned to baseline by the end of the 6-month follow-up period . CONCLUSION Although intervention participants maintained and actually improved their QOL during radiation therapy , control participants experienced a significant decrease in their QOL . Thus , a structured multidisciplinary intervention can help maintain or even improve QOL in patients with advanced cancer who are undergoing cancer treatment The aim of this study was to evaluate the effect of an individual support ( IS ) intervention including intensified primary healthcare on the utilisation of specialist care among cancer patients , and to investigate if such an effect was modified by the patient 's age ( less than 70 years or 70 years and more ) . Newly diagnosed cancer patients ( n=416 ) were r and omised between the intervention and a control condition , and data were collected on the utilisation of specialist care within 3 months from inclusion . Intensified primary healthcare comprised extended information from the specialist clinics , and education and supervision in cancer care for general practitioners ( GPs ) and home-care nurses . The support given also included interventions design ed to diminish problems of weight loss and psychological distress . The intervention reduced the number of admissions ( NoA ) and the days of hospitalisation ( DoH ) after adjustment for weight loss and psychological distress , but only for older patients . Older patients r and omised to the intervention ( n=82 ) experienced 393 fewer DoH than the older control patients ( n=79 ) . In addition , the proportion of older patients in the IS group who utilised acute specialist care was smaller compared with older control patients group . The conclusion is that older cancer patients ' utilisation of specialist care may be reduced by intensified primary healthcare services BACKGROUND Patients experience reductions in quality of life ( QOL ) while receiving cancer treatment and several approaches have been proposed to address QOL issues . In this project , the QOL differences between older adult ( age 65 + ) and younger adult ( age 18 - 64 ) advanced cancer patients in response to a multidisciplinary intervention design ed to improve QOL were examined . METHODS This study was registered on Clinical Trials.gov , NCT01360814 . Newly diagnosed advanced cancer patients undergoing radiation therapy were r and omized to active QOL intervention or control groups . Those in the intervention group received six multidisciplinary 90-minute sessions design ed to address the five major domains of QOL . Outcomes measured at baseline and weeks 4 , 27 , and 52 included QOL ( Linear Analogue Self- Assessment ( LASA ) , Functional Assessment of Cancer Therapy-General ( FACT-G ) ) and mood ( Profile of Mood States ( POMS ) ) . Kruskall-Wallis methodology was used to compare scores between older and younger adult patients r and omized to the intervention . RESULTS Of 131 patients in the larger r and omized controlled study , we report data on 54 evaluable patients ( 16 older adults and 38 younger adults ) r and omized to the intervention . Older adult patients reported better overall QOL ( LASA 74.4 vs. 62.9 , p = 0.040 ) , higher social well-being ( FACT-G 91.1 vs. 83.3 , p = 0.045 ) , and fewer problems with anger ( POMS anger-hostility 95.0 vs. 86.4 , p = 0.028 ) . Long-term benefits for older patients were seen in the anger-hostility scale at week 27 ( 92.2 vs. 84.2 , p = 0.027 ) and week 52 ( 96.3 vs. 85.9 , p = 0.005 ) . CONCLUSIONS Older adult patients who received a multidisciplinary intervention to improve QOL while undergoing advanced cancer treatments benefited differently in some QOL domains , compared to younger adult patients . Future studies can provide further insight on how to tailor QOL interventions for these age groups OBJECTIVE To examine the potential impact of elderly age on response to participation in a structured , multidisciplinary quality -of-life ( QOL ) intervention for patients with advanced cancer undergoing radiation therapy . METHODS Study design was a r and omized stratified , two group , controlled clinical trial in the setting of a tertiary care comprehensive cancer center . Subjects with newly diagnosed cancer and an estimated 5-year survival rate of 0%-50 % who required radiation therapy were recruited and r and omly assigned to either an intervention group or a st and ard care group . The intervention consisted of eight 90-min sessions design ed to address the five QOL domains of cognitive , physical , emotional , spiritual , and social functioning . QOL was measured using Spitzer uniscale and linear analogue self- assessment ( LASA ) at baseline and weeks 4 , 8 , and 27 . RESULTS Of the 103 study participants , 33 were geriatric ( 65 years or older ) , of which 16 ( mean age 72.4 years ) received the intervention and 17 ( mean age 71.4 years ) were assigned to the st and ard medical care . The geriatric participants who completed the intervention had higher QOL scores at baseline , at week 4 and at week 8 , compared to the control participants . SIGNIFICANCE OF RESULTS Our results demonstrate that geriatric patients with advanced cancer undergoing radiation therapy will benefit from participation in a structured multidisciplinary QOL intervention . Therefore , geriatric individuals should not be excluded from participating in a cancer QOL intervention , and , in fact , elderly age may be an indicator of strong response to a QOL intervention . Future research should further explore this finding BACKGROUND Pain is a major concern for individuals with cancer , particularly older adults who make up the largest segment of individuals with cancer and who have some of the most unique pain challenges . One of the priorities of hospice is to provide a pain-free death , and while outcomes are better in hospice , patients still die with poorly controlled pain . OBJECTIVE This article reports on the results of a Translating Research into Practice intervention design ed to promote the adoption of evidence -based pain practice s for older adults with cancer in community-based hospices . SETTING This Institutional Human Subjects Review Board-approved study was a cluster r and omized controlled trial implemented in 16 Midwestern hospices . METHODS Retrospective medical records from newly admitted patients were used to determine the intervention effect . Additionally , survey and focus group data gathered from hospice staff at the completion of the intervention phase were analyzed . RESULTS Improvement on the Cancer Pain Practice Index , an overall composite outcome measure of evidence -based practice s for the experimental sites , was not significantly greater than control sites . Decrease in patient pain severity from baseline to post-intervention in the experimental group was greater ; however , the result was not statistically significant ( P = 0.1032 ) . CONCLUSIONS Findings indicate a number of factors that may impact implementation of multicomponent interventions , including unique characteristics and culture of the setting , the level of involvement with the change processes , competing priorities and confounding factors , and complexity of the innovation ( practice change ) . Our results suggest that future study is needed on specific factors to target when implementing a community-based hospice intervention , including determining and measuring intervention fidelity prospect ively This single-blind , prospect i ve , r and omized controlled trial was design ed to evaluate the effects of a culturally responsive health promotion program for elderly Korean ( CHP-K ) survivors of gastrointestinal ( GI ) cancers . The program consisted of 8 weeks of Qi exercise and face-to-face counseling on physical and psychological factors . A total of 63 Korean GI cancer survivors , aged ≥65 years , who had completed their active cancer treatment , were recruited from a cancer center in South Korea . Outcomes included the amount of exercise , body weight , BMI , the Patient Generated Subjective Global Assessment scale , the M.D. And erson Symptom Inventory , and self-efficacy and self-esteem scales . Repeated measures MANCOVA revealed a significant difference over time between the groups ( Wilks ' Lambda F1,62 = 5.361 , p = 0.007 ) . Univariate RM-ANCOVA for each outcome measure revealed statistically significant differences between groups . These results suggested that the participation in the CHP-K may have enhanced the health of elderly Korean GI cancer survivors PURPOSE / OBJECTIVES To describe relationships among perceived barriers to symptom management and quality of life and to test the mediating role of perceived communication difficulties on the relationships between other perceived barriers to symptom management and quality of life in older adult breast cancer survivors . DESIGN Cross-sectional descriptive-correlational design using baseline data from a r and omized , controlled trial that tested the efficacy and durability of the individualized representational intervention in reducing symptom distress and improving quality of life in older adult breast cancer survivors . SETTING The community , an oncology clinic , and a state tumor registry . SAMPLE 190 older adult breast cancer survivors ( X age = 70.4 years ) who were an average of 3.3 years after breast cancer diagnosis . METHODS Path analysis using Mplus , version 5.1 . MAIN RESEARCH VARIABLES Negative beliefs about symptom management ( Symptom Management Beliefs Question naire [ SMBQ ] ) , perceived negative attitudes from healthcare providers ( Communication Attitudes [ CommA ] ) , perceived communication difficulties ( CommD ) , and quality of life . FINDINGS Significant direct effects of SMBQ and CommA on CommD were found after controlling for age , number of health problems , and number of symptoms . CommD was a significant mediator of the effects of CommA on quality of life after controlling for the covariates . SMBQ had significant total effects on quality of life after adjusting for the covariates but was not mediated by CommD. CONCLUSIONS Patient-provider communication is an important factor in the quality of life of older adult breast cancer survivors . IMPLICATION S FOR NURSING Developing and testing nursing interventions focusing on enhancing both positive beliefs about symptom management and effective communication in old age is suggested . KNOWLEDGE TRANSLATION Older adults and healthcare providers must overcome stereotyped beliefs about aging that may affect self-care and health outcomes for this population . Older adults must be allowed to express their views and emotions about aging BACKGROUND And rogen deprivation therapy ( ADT ) can decrease the physical performance ( PP ) of older men with prostate cancer ( PC ) . METHODS We conducted a three-arm r and omized pilot study ( n=19 ) comparing a home-based walking and resistance intervention ( EXCAP ) and a technology-mediated walking and resistance intervention using Wii-Fit to a usual-care arm in men ≥70 years with PC receiving ADT . The intervention lasted for 6 weeks , with follow-up at 12 weeks . The primary pre-specified outcome was change in Short Physical Performance Battery ( SPPB ) score . Mixed effects regression models were used to assess change in outcomes over time . RESULTS Mean participant age was 70 years ( range : 67 - 93 ) . Eight patients were r and omized to the Wii-Fit arm , 6 to the EXCAP arm , and 5 to the usual-care arm . SPPB scores remained nearly constant in the usual-care arm ( β=-0.12 ; p=0.79 ) , while individuals in the EXCAP arm had on average a 1.2 point increase at each follow-up ( β=1.20 ; 95 % CI : 0.36 , 2.06 ) . The Wii-fit arm had a non-significant increase in SPPB score over time relative to usual-care ( β=0.32 ; 95 % CI -0.43 , 1.06 ; p=0.46 ) . Individuals in the EXCAP arm had an increase in steps per day over time compared to the usual-care arm ( p-value=0.006 ) ; the EXCAP arm had an increase of 2720 steps ( 95 % CI : 1313 , 4128 ) while the usual-care arm had an increase of 97 steps ( 95 % CI : -1140 , 1333 ) . Participants in the Wii-Fit arm had an increase of 1020 steps ( 95 % CI : -474 , 1238 , p=0.710 ) . Other outcomes ( i.e. , h and grip strength , lean muscle mass , and chest press repetitions ) were not statistically significant . CONCLUSIONS A home-based aerobic and resistance exercise program , EXCAP , shows promise for improving PP in older men with PC on ADT |
10,723 | 25,886,385 | We found positive average intervention effects for : body mass index ( BMI ) , physical activity , physical fitness , fruit and vegetable intake , tobacco use , and being bullied .
Intervention effects were generally small .
On average across studies , we found little evidence of effectiveness for z BMI ( BMI , st and ardized for age and gender ) , and no evidence for fat intake , alcohol use , drug use , mental health , violence and bullying others .
Conclusion This Cochrane review has found the WHO HPS framework is effective at improving some aspects of student health .
The effects are small but potentially important at a population level | Background Healthy children achieve better educational outcomes which , in turn , are associated with improved health later in life .
The World Health Organization ’s Health Promoting Schools ( HPS ) framework is a holistic approach to promoting health and educational attainment in school .
The effectiveness of this approach has not yet been rigorously review ed . | OBJECTIVE To evaluate the effect of the middle and junior high school Drug Abuse Resistance Education ( D.A.R.E. ) and D.A.R.E. Plus programs on drug use and violence . DESIGN R and omized controlled trial of 24 schools , with 3 conditions : D.A.R.E. only , D.A.R.E. Plus , and delayed program control . SETTING Schools and neighborhoods , primarily in Minneapolis-St Paul . PARTICIPANTS All seventh- grade students in 24 schools in the academic year 1999 - 2000 ( N = 6237 at baseline , 67.3 % were white , and there was 84.0 % retention at final follow-up ) . INTERVENTIONS The middle and junior high school D.A.R.E. curriculum in the 16 schools that received D.A.R.E. only and D.A.R.E. Plus . In the 8 schoolts that received D.A.R.E. Plus , additional components included a peer-led parental involvement classroom program called " On the VERGE , " youth-led extracurricular activities , community adult action teams , and postcard mailings to parents . The interventions were implemented during 2 school years , when the cohort was in the seventh and eighth grade s. MAIN OUTCOME MEASURES Self-reported tobacco , alcohol , and marijuana use ; multidrug use ; violence ; and victimization , assessed at the beginning and end of seventh grade and at the end of eighth grade . Growth curve analytic methods were used to assess changes over time by condition . RESULTS There were no significant differences between D.A.R.E. only and the controls ; significant differences among boys between D.A.R.E. Plus and controls for tobacco , alcohol , and multidrug use and victimization ; significant differences among boys between D.A.R.E. Plus and D.A.R.E. only in tobacco use and violence ; and no significant behavioral differences among girls . CONCLUSION D.A.R.E. Plus significantly enhanced the effectiveness of the D.A.R.E. curriculum among boys and was more effective than the delayed program controls , underscoring the potential for multiyear , multicomponent prevention programs and demonstrating sex differences in response to intervention programs Background Obesity has become a global public health problem , which also affects children . It has been proposed that the educational interventions during childhood could be a key strategy in the prevention of obesity . Objective To evaluate the efficacy of an intervention on food habits and physical activity in school children . Methods A 2-year cluster-r and omised prospect i ve study with two parallel arms was used to evaluate an intervention programme in children in their first year of primary schooling ( 5–6 years of age ) in schools in the city of Granollers . The intervention consisted of the promotion of healthy eating habits and physical activity by means of the educational methodology Investigation , Vision , Action and Change ( IVAC ) . At the beginning and at the end of the study ( 2006 and 2008 ) the weight and height of each child was measured in situ , while the families were given a self-report physical activity question naire and the Krece Plus quick test . Results Two years after the beginning of the study , the body mass index of the children in the control group was 0.89 kg/m2 higher than that of the intervention schools . The intervention reduced by 62 % the prevalence of overweight children . Similarly , the proportion of children that ate a second piece of fruit and took part in an after-school physical activity increased in the intervention group . In the control group , the weekly consumption of fish was reduced . Conclusions The educational intervention in healthy eating habits and physical activity in the school could contribute to lessen the current increase in child obesity Background Overweight and obesity in children in Mexico was among the countries with the highest prevalence 's in the world . Mexico currently has few innovative and comprehensive experiences to help curb the growth of this serious public health problem . Therefore , the aim of this study is to assess the effectiveness of a nutrition and physical activity strategy , called " Nutrition on the Go " ( " nutrición en movimiento " ) in maintaining the BMI values of school children in the State of Mexico . Methods A two-stage cluster trial was carried out . Sixty schools were selected in the State of Mexico , of which 30 were r and omly assigned to the intervention group ( IG ) and 30 to the control group ( CG ) . A total of 1020 fifth grade school children participated . The intervention strategy aim ed to decrease the energy content of school breakfasts and include fruits and vegetables , as well as increase physical activity and the consumption of water during the time spent at school . The strategy was implemented over a 6-month period . Results The estimated probability ( EP ) of obesity between baseline and the final stage for the IG decreased 1 % ( Initial EP = 11.8 % , 95%CI 9.0 , 15.2 , final EP = 10.8 , 95%CI 8.4 , 13 . ) For the CG , the probability increased 0.9 % ( baseline EP = 10.6 % ; 95%CI 8.1 , 13.7 ; final EP = 11.5 , 95%CI 9.0 , 14.6 ) . The interaction between the intervention and the stage is the average odd time corrected treatment effect , which is statistically significant ( p = 0.01 ) ( OR = 0.68 , 95%CI 0.52 , 091).This represents the interaction between intervention and stage , which is highly significant ( p = 0.01 ) ( OR = 0.68 ; 95%CI 0.52 , 091 ) . In addition , girls had a protective effect on obesity ( OR = 0.56 ; 95%CI 0.39 , 0.80 ) . Conclusions The intervention strategy is effective in maintaining the BMI of school children Abstract Objective : To assess if a school based intervention was effective in reducing risk factors for obesity . Design : Group r and omised controlled trial . Setting : 10 primary schools in Leeds . Participants : 634 children aged 7 - 11 years . Intervention : Teacher training , modification of school meals , and the development of school action plans targeting the curriculum , physical education , tuck shops , and playground activities . Main outcome measures : Body mass index , diet , physical activity , and psychological state . Results : Vegetable consumption by 24 hour recall was higher in children in the intervention group than the control group ( weighted mean difference 0.3 portions/day , 95 % confidence interval 0.2 to 0.4 ) , representing a difference equivalent to 50 % of baseline consumption . Fruit consumption was lower in obese children in the intervention group ( −1.0 , −1.8 to −0.2 ) than those in the control group . The three day diary showed higher consumption of high sugar foods ( 0.8 , 0.1 to 1.6 ) ) among overweight children in the intervention group than the control group . Sedentary behaviour was higher in overweight children in the intervention group ( 0.3 , 0.0 to 0.7 ) . Global self worth was higher in obese children in the intervention group ( 0.3 , 0.3 to 0.6 ) . There was no difference in body mass index , other psychological measures , or dieting behaviour between the groups . Focus groups indicated higher levels of self reported behaviour change , underst and ing , and knowledge among children who had received the intervention . Conclusion : Although it was successful in producing changes at school level , the programme had little effect on children 's behaviour other than a modest increase in consumption of vegetables . What is already known on this topic Obesity is increasing among school children and dem and s preventive strategies R and omised controlled trials of school based primary prevention programmes have all used a prescriptive approach What this study adds Behavioural changes were disappointing with this programme based on the health promoting schools philosophy , despite changes at school level The only positive outcome was a modest increase in vegetable consumption The discrepancy between changes achieved at the individual and school level raises issues regarding the problems inherent in such This study reports the effect of the Fruits and Vegetables Make the Marks intervention , a school-based fruit and vegetable intervention consisting of a home economics classroom component and parental involvement and encouraged participation in the Norwegian School Fruit Programme , all delivered during the school year of 2001 - 02 . Nine r and omly chosen schools received the intervention and 10 schools served as control schools . Participating pupils completed question naires at baseline ( September 2001 ) , at Follow-up 1 ( May-June 2002 ) and at Follow-up 2 ( May 2003 ) . A total of 369 pupils ( 69 % ; mean age , 11.3 years at baseline ) participated in all three surveys . No effect of the intervention was found for intake of fruit and vegetables eaten at school or all day , neither at Follow-up 1 nor at Follow-up 2 . On analysing the effects on potential mediators , significant differences between intervention and control groups were found for Awareness of the five-a-day recommendations only . The intervention programme was rated as very good by the teachers , and the pupils reported that they enjoyed it . However , the intervention failed to change fruit and vegetable intake , probably because it did not succeed in changing the pupils ' preferences for or the accessibility of fruit and vegetables -- the two strongest correlates of children 's fruit and vegetable intake OBJECTIVE To evaluate the effectiveness of a program to increase walking to and from school . DESIGN A cluster r and omised controlled trial . SETTING 24 primary public schools in inner west Sydney , Australia . PARTICIPANTS 1996 students aged 10 - 12 years and their parents . INTERVENTION A two-year multi-component program included classroom activities , development of school Travel Access Guides , parent newsletters and improving environments with local councils . MEASURES Two measures were used : a survey completed by students on how they travelled to and from school over five days , and a survey completed by their parents on how their child travelled to and from school in a usual week . RESULTS The percentage of students who walked to and from school increased in both the intervention and control schools . Data from parent surveys found that 28.8 % of students in the intervention group increased their walking , compared with 19 % in the control group ( a net increase of 9.8 % , p=0.05 ) . However this effect was not evident in the student data . CONCLUSION The study produced a mixed result , with a high variation in travel patterns from school to school . Intervention research should address the complexity of multiple factors influencing student travel to school with a focus on changing local environments and parents ' travel to work OBJECTIVE To assess the impact of a school-based nutrition education intervention aim ed at increasing the consumption of fruits and vegetables . DESIGN The intervention programme increased the provision of fruits and vegetables in schools and provided a range of point-of-purchase marketing material s , newsletters for children and parents , and teacher information . Curriculum material s at age 6 - 7 and 10 - 11 years were also developed and utilised . Evaluation was undertaken with groups of younger ( aged 6 - 7 years ) and older ( aged 10 - 11 years ) children . Methods included 3-day dietary records with interview and cognitive and attitudinal measures at baseline , with follow-up at 9 months , in intervention and control schools . SETTING The work was undertaken in primary schools in Dundee , Scotl and . SUBJECTS Subjects comprised 511 children in two intervention schools with a further 464 children from two schools acting as controls . RESULTS Children ( n=64 ) in the intervention schools had an average increase in fruit intake ( 133+/-1.9 to 183+/-17.0 g day(-1 ) ) that was significantly ( P<0.05 ) greater than the increase ( 100+/-11.7 to 107+/-14.2 g day(-1 ) ) estimated in children ( n=65 ) in control schools . No other changes in food or nutrient intake were detected . Increases in scores for variables relating to knowledge about fruits and vegetables and subjective norms were also greater in the intervention than in the control group , although taste preferences for fruits and vegetables were unchanged . CONCLUSIONS It is concluded that a whole school approach to increasing intakes of fruits and vegetables has a modest but significant effect on cognitive and attitudinal variables and on fruit intake This study demonstrates the effectiveness of the KiVa antibullying program using a large sample of 8,237 youth from Grade s 4 - 6 ( 10 - 12 years ) . Altogether , 78 schools were r and omly assigned to intervention ( 39 schools , 4,207 students ) and control conditions ( 39 schools , 4,030 students ) . Multilevel regression analyses revealed that after 9 months of implementation , the intervention had consistent beneficial effects on 7 of the 11 dependent variables , including self- and peer-reported victimization and self-reported bullying . The results indicate that the KiVa program is effective in reducing school bullying and victimization in Grade s 4 - 6 . Despite some evidence against school-based interventions , the results suggest that well-conceived school-based programs can reduce victimization OBJECTIVE To decrease the intake of sucrose , increase the intake of fibre and the consumption of fruit and vegetables among secondary -school pupils . DESIGN Intervention study among eighth grade pupils during one school year . Data were collected by question naires and from a subgroup of pupils by 48 h dietary recall at baseline in spring 2007 and after the intervention in 2008 . SETTING Twelve secondary schools were r and omly allocated to intervention ( IS ) and control schools ( CS ) within three cities . Intervention included nutrition education and improvement of the food environment focusing particularly on the quality of snacks at school . SUBJECTS A total of 659 pupils completed the question naires and the dietary recall was obtained from 287 pupils both at baseline and follow-up . RESULTS The frequency of consumption of rye bread increased ( P = 0.03 ) and that of sweets decreased ( P = 0.006 ) among girls in the IS . The intake of sucrose fell among IS pupils , from 12.8 % to 10.5 % of the total energy intake ( P = 0.01 ) . Intake of fruit ( g/MJ ) remained the same in IS , whereas it decreased in CS ( P = 0.04 ) . CONCLUSIONS Sugar intake can be lowered by improving the quality of snacks , but it is more difficult to increase fibre intake and fruit and vegetable consumption unless the content of school lunches can be modified . It is the responsibility of the adults working in schools to create a healthy environment and to make healthy choices easy for pupils BACKGROUND Childhood obesity is a major public health problem in the United States , particularly among American Indian communities . OBJECTIVE The objective was to evaluate the effectiveness of a school-based , multicomponent intervention for reducing percentage body fat in American Indian schoolchildren . DESIGN This study was a r and omized , controlled , school-based trial involving 1704 children in 41 schools and was conducted over 3 consecutive years , from 3rd to 5th grade s , in schools serving American Indian communities in Arizona , New Mexico , and South Dakota . The intervention had 4 components : 1 ) change in dietary intake , 2 ) increase in physical activity , 3 ) a classroom curriculum focused on healthy eating and lifestyle , and 4 ) a family-involvement program . The main outcome was percentage body fat ; other outcomes included dietary intake , physical activity , and knowledge , attitudes , and behaviors . RESULTS The intervention result ed in no significant reduction in percentage body fat . However , a significant reduction in the percentage of energy from fat was observed in the intervention schools . Total energy intake ( by 24-h dietary recall ) was significantly reduced in the intervention schools but energy intake ( by direct observation ) was not . Motion sensor data showed similar activity levels in both the intervention and control schools . Several components of knowledge , attitudes , and behaviors were also positively and significantly changed by the intervention . CONCLUSIONS These results document the feasibility of implementing a multicomponent program for obesity prevention in elementary schools serving American Indian communities . The program produced significant positive changes in fat intake and in food- and health-related knowledge and behaviors . More intense or longer interventions may be needed to significantly reduce adiposity in this population OBJECTIVE . Rising rates of skin cancer associated with early-life sun exposure make it important to improve adolescent sun-protection practice s. Our study objective was to determine if a multicomponent community-wide intervention could alter the decline in sun protection that begins in early adolescence . METHODS . A r and omized , controlled trial was conducted in 10 communities to assess the impact of the SunSafe in the Middle School Years program . The intervention sought to ( 1 ) educate and activate adults and peers to role model and actively promote sun-protection practice s and ( 2 ) create a pro – sun protection community environment . It targeted school personnel , athletic coaches , lifeguards , and clinicians and enlisted teens as peer advocates . Annual observations of cross-sectional sample s of teens at community beach/pool sites were used to assess the impact of 1 and 2 years of intervention exposure compared to grade -matched controls . The outcome was percent of body surface protected by sunscreen , clothing , or shade . RESULTS . Observers determined the sun protection level of 1927 adolescents entering 6th to 8th grade s. After 2 years of intervention exposure , adolescents at the beach/pool in intervention communities were significantly better protected than those in control communities . Over 2 years , the percent of body surface area protected declined by 23 % in the control arm but only 8 % in intervention arm . After intervention , the average percent of body surface protected at intervention sites ( 66.1 % ) was significantly greater than control sites ( 56.8 % ) . Teens in intervention communities reported sun-protection advice from more adult sources , were more likely to use sunscreen , and applied it more thoroughly than control-site teens . CONCLUSIONS . Our multicomponent model addressing adolescent sun protection shows the power of engaging teens and adults from across the community as role models and educators . This new ecological approach shows promise in changing adolescent sun protection behaviors and reducing skin cancer risks 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 BACKGROUND This study evaluated the effects of a school-based dietary intervention program to increase fruit and vegetable consumption among fourth- grade rs . METHODS Twenty-eight elementary schools were r and omized to an immediate intervention condition or to a delayed intervention control condition . Measures of diet and psychosocial variables were collected at base line and 1 and 2 years post-baseline . The intervention included classroom , parent , and cafeteria components . RESULTS Mean daily consumption of fruit and vegetables was higher for the intervention children compared with controls at Follow-up 1 ( X(t ) = 3.96 , X(c ) = 2.28 ) and at Follow-up 2 ( X(t ) = 3.20 , X(c ) = 2.21 ) . Macro- and micronutrient changes favoring the intervention children were also observed at both Follow-up 1 and Follow-up 2 . Mean daily consumption of fruit and vegetables was higher for intervention parents compared with controls at Follow-up 1 ( X(t ) = 4.23,X(c ) = 3.94 ) but not at Follow-up 2 . CONCLUSIONS Strong effects were found for the High 5 intervention on fruit and vegetable consumption , on macro- and micro-nutrients , and on psychosocial variables . Future work is needed to enhance the intervention effects on parents ' consumption and to test the effectiveness of the intervention when delivered by classroom teachers This article reports on the outcomes of the Teens Eating for Energy and Nutrition at School ( TEENS ) study , a 2-year intervention study conducted in 16 middle schools with a goal of increasing students ’ intakes of fruits , vegetables , and lower fat foods . Despite positive interim results for students r and omized to intervention schools , the positive effects of the intervention were not seen for the primary outcomes at the end of the 2nd year . Positive effects were seen only for a food choice score ( suggesting that the students usually choose lower versus higher fat foods ) and not for measures of food intake . Future studies may need to take a step back toward more controlled efficacy studies in working with this age-group . In addition , future work may consider the use of peer leaders , more intensive teacher training , ongoing formative assessment , and the testing of more powerful environmental change intervention strategies Few studies have tested schoolwide interventions to reduce sexual risk behavior , and none have demonstrated significant schoolwide effects . This study evaluates the schoolwide effects of Safer Choices , a multicomponent , behavioral theory – based HIV , STD , and pregnancy prevention program , on risk behavior , school climate , and psychosocial variables . Twenty urban high schools were r and omized , and cross-sectional sample s of classes were surveyed at baseline , the end of intervention ( 19 months after baseline ) , and 31 months after baseline . At 19 months , the program had a positive effect on the frequency of sex without a condom . At 31 months , students in Safer Choices schools reported having sexual intercourse without a condom with fewer partners . The program positively affected psychosocial variables and school climate for HIV/STD and pregnancy prevention . The program did not influence the prevalence of recent sexual intercourse . Schoolwide changes in condom use demonstrated that a school-based program can reduce the sexual risk behavior of adolescents Intensive h and washing promotion can reduce diarrheal and respiratory disease incidence . To determine whether less intensive , more scalable interventions can improve health , we evaluated a school-based h and washing program . We r and omized 87 Chinese schools to usual practice s : st and ard intervention ( h and washing program ) or exp and ed intervention ( h and washing program , soap for school sinks , and peer hygiene monitors ) . We compared student absence rates , adjusting for cluster design . In control schools , children experienced a median 2.0 episodes ( median 2.6 days ) of absence per 100 student-weeks . In st and ard intervention schools , there were a median 1.2 episodes ( P = 0.08 ) and 1.9 days ( P = 0.14 ) of absence per 100 student-weeks . Children in exp and ed intervention schools experienced a median 1.2 episodes ( P = 0.03 ) and 1.2 days ( P = 0.03 ) of absence per 100 student-weeks . Provision of a large-scale h and washing promotion program and soap was associated with significantly reduced absenteeism . Similar programs could improve the health of children worldwide This study tested the efficacy of two school-based programs for prevention of body weight/fat gain in comparison to a control group , in all participants and in overweight children . The Louisiana ( LA ) Health study utilized a longitudinal , cluster r and omized 3-arm controlled design , with 28 months of follow-up . Children ( N=2060 ; M age = 10.5 years , SD = 1.2 ) from rural communities in Grade s 4 to 6 participated in the study . 17 school clusters ( M = 123 children/cluster ) were r and omly assigned to one of three prevention arms : 1 ) Primary Prevention ( PP ) , an environmental modification program , 2 ) Primary + Secondary Prevention ( PP+SP ) , the environmental program with an added classroom and internet education component , or 3 ) Control ( C ) . Primary outcomes were changes in percent body fat and body mass index z scores . Secondary outcomes were changes in behaviors related to energy balance . Comparisons of PP , PP+SP , and C on changes in body fat and BMI z scores found no differences . PP and PP+SP study arms were combined to create an environmental modification arm ( EM ) . Relative to C , EM decreased body fat for boys ( −1.7 % ± 0.38 % versus −0.14 % ± 0.69 % ) and attenuated fat gain for girls ( 2.9 % ± 0.22 % versus 3.93 % ± 0.37 % ) , but st and ardized effect sizes were relatively small ( < 0.30 ) . In conclusion , this school-based environmental modification programs had modest beneficial effects on changes in percent body fat . Addition of a classroom/internet program to the environmental program did not enhance weight/fat gain prevention , but did impact physical activity and social support in overweight children BACKGROUND The prevalence of adolescent smoking has been increasing rapidly in China . Theory-based smoking prevention programmes in schools may be an effective approach in preventing smoking among Chinese adolescents . METHODS A school-level cluster r and omized controlled trial was conducted among 7th and 8th grade students ( N = 2343 ) in four junior high schools in southern China during 2004 - 06 . The theory-based , multi-level intervention was compared with the st and ard health curriculum . Outcome measures comprised changes in students ' smoking-related knowledge , attitudes and behaviour . RESULTS The mean knowledge scores from baseline to the 1- and 2-year follow-ups increased more in the intervention group than in the control group , whereas there was little change in attitude scores . At the 1-year follow-up ( the total sample ) , the interventions reduced the probability of baseline experimental smokers ' escalating to regular smoker [ 7.9 vs 18.3 % ; adjusted odds ratio ( OR ) 0.34 , 95 % confidence interval ( CI ) 0.12 - 0.97 , P = 0.043 ] , but did not reduce the probability of baseline non-smokers ' initiating smoking ( 7.9 vs 10.6 % ; adjusted OR 0.86 , 95 % CI 0.54 - 1.38 , P = 0.538 ) . At the 2-year follow-up ( only 7th grade students ) , similar proportions of baseline non-smokers initiated smoking in the intervention group and the control group ( 13.5 vs 13.1 % ) , while a possibly lower proportion of baseline experimental smokers escalated to regular smoking in the intervention group than the control group ( 22.6 vs 40.0 % ; adjusted OR 0.43 , 95 % CI 0.12 - 1.57 , P = 0.199 ) . CONCLUSIONS This multi-level intervention programme had a moderate effect on inhibiting the escalation from experimental to regular smoking among Chinese adolescents , but had little effect on the initiation of smoking . The programme improved adolescents ' smoking-related knowledge , but did not change their attitudes towards smoking OBJECTIVE To test the efficacy of 2 programs design ed to reduce high-risk behaviors among inner-city African American youth . DESIGN Cluster r and omized trial . SETTING Twelve metropolitan Chicago , Ill , schools and the communities they serve , 1994 through 1998 . PARTICIPANTS Students in grade s 5 through 8 and their parents and teachers . INTERVENTIONS The social development curriculum ( SDC ) consisted of 16 to 21 lessons per year focusing on social competence skills necessary to manage situations in which high-risk behaviors occur . The school/community intervention ( SCI ) consisted of SDC and school-wide climate and parent and community components . The control group received an attention-placebo health enhancement curriculum ( HEC ) of equal intensity to the SDC focusing on nutrition , physical activity , and general health care . MAIN OUTCOME MEASURES Student self-reports of violence , provocative behavior , school delinquency , substance use , and sexual behaviors ( intercourse and condom use ) . RESULTS For boys , the SDC and SCI significantly reduced the rate of increase in violent behavior ( by 35 % and 47 % compared with HEC , respectively ) , provoking behavior ( 41 % and 59 % ) , school delinquency ( 31 % and 66 % ) , drug use ( 32 % and 34 % ) , and recent sexual intercourse ( 44 % and 65 % ) , and improved the rate of increase in condom use ( 95 % and 165 % ) . The SCI was significantly more effective than the SDC for a combined behavioral measure ( 79 % improvement vs 51 % ) . There were no significant effects for girls . CONCLUSIONS Theoretically derived social-emotional programs that are culturally sensitive , developmentally appropriate , and offered in multiple grade s can reduce multiple risk behaviors for inner-city African American boys in grade s 5 through 8 . The lack of effects for girls deserves further research AIMS To determine the impact of a school-based harm minimization smoking intervention compared to traditional abstinence-based approaches . DESIGN , SETTING AND PARTICIPANTS A school-based cluster r and omized trial was conducted in Perth , Western Australia in 30 government high schools from 1999 to 2000 . Over 4000 students were recruited to participate and schools were assigned r and omly to either the harm minimization intervention or a st and ard abstinence-based programme . INTERVENTION The harm minimization intervention comprised eight 1-hour lessons over 2 years , quitting support from school nurses and enactment of policies to support programme components . Comparison schools implemented st and ard abstinence-based programmes and policies . MEASURES Cigarette smoking was categorized at two levels : regular smoking , defined as smoking on 4 or more days in the previous week ; and 30-day smoking as any smoking within the previous month . FINDINGS At immediate post-test ( 20 months post-baseline ) , after accounting for baseline differences , school-level clustering effects , socio-economic status , gender and family smoking , intervention students were less likely to smoke regularly [ OR = 0.51 , 95 % confidence interval ( CI ) = 0.36 , 0.71 ] or to have smoked within the previous 30 days ( OR = 0.69 , 95 % CI = 0.53 , 0.91 ) . CONCLUSION The school-based adolescent harm minimization intervention appears to have been more effective than the abstinence-based social influences programme at reducing regular smoking This study evaluated the effect of Students for Peace , a multi-component violence-prevention intervention , on reducing aggressive behaviors among students of eight middle schools r and omly assigned into intervention or control conditions . The intervention , based on Social Cognitive Theory , included the formation of a School Health Promotion Council , training of peer mediators and peer helpers , training of teachers in conflict resolution , a violence-prevention curriculum , and newsletters for parents . All students were evaluated in the spring of 1994 , 1995 and 1996 ( approximately 9000 students per evaluation ) . Sixth grade rs in 1994 were followed through seventh grade in 1995 or eighth grade in 1996 or both ( n = 2246 ) . Cohort and cross-sectional evaluations indicated little to no intervention effect in reducing aggressive behaviors , fights at school , injuries due to fighting , missing classes because of feeling unsafe at school or being threatened to be hurt . For all variables , the strongest predictors of violence in eighth grade were violence in sixth grade and low academic performance . Although ideal and frequently recommended , the holistic approach to prevention in schools in which teachers , administrators and staff model peaceful conflict resolution is difficult to implement , and , in this case , proved ineffective . The Students for Peace experience suggests that interventions begin prior to middle school , explore social environmental intervention strategies , and involve parents and community members OBJECTIVES A r and omized school based trial sought to increase fruit and vegetable consumption among children using a multicomponent approach . METHODS The intervention , conducted in 20 elementary schools in St. Paul , targeted a multiethnic group of children who were in the fourth grade in spring 1995 and the fifth grade in fall 1995 . The intervention consisted of behavioral curricula in classrooms , parental involvement , school food service changes , and industry support and involvement . Lunchroom observations and 24-hour food recalls measured food consumption . Parent telephone surveys and a health behavior question naire measured psychosocial factors . RESULTS The intervention increased lunchtime fruit consumption and combined fruit and vegetable consumption , lunchtime vegetable consumption among girls , and daily fruit consumption as well as the proportion of total daily calories attributable to fruits and vegetables . CONCLUSIONS Multicomponent school-based programs can increase fruit and vegetable consumption among children . Greater involvement of parents and more attention to increasing vegetable consumption , especially among boys , remain challenges in future intervention research Background Effective interventions to prevent overweight and obesity in children are urgently needed especially in inner-city neighbourhoods where prevalence of overweight and inactivity among primary school children is high . A school based intervention was developed aim ing at the reduction of overweight and inactivity in these children by addressing both behavioural and environmental determinants . Methods / design The main components of the intervention ( Lekker Fit ! ) are the re-establishment of a professional physical education teacher ; three ( instead of two ) PE classes per week ; additional sport and play activities outside school hours ; fitness testing ; classroom education on healthy nutrition , active living and healthy lifestyle choices ; and the involvement of parents . The effectiveness of the intervention is evaluated through a cluster r and omized controlled trial in 20 primary schools among grade s 3 through 8 ( 6–12 year olds ) . Primary outcome measures are BMI , waist circumference and fitness . Secondary outcome measures are assessed in a subgroup of grade 6–8 pupils ( 9–12 year olds ) through classroom question naires and constitute of nutrition and physical activity behaviours and behavioural determinants . Multilevel regression analyses are used to study differences in outcomes between children in the intervention schools and in control schools , taking clustering of children within schools into account . Discussion Hypotheses are that the intervention results in a lower prevalence of children being overweight and an improved mean fitness score , in comparison with a control group where the intervention is not implemented . The results of our study will contribute to the discussion on the role of physical education and physical activity in the school curriculum . Trial registration [ IS RCT N84383524 OBJECTIVES ICAPS ( Intervention Centred on Adolescents ' Physical activity and Sedentary behaviour ) is aim ed at preventing excessive weight gain and cardiovascular risk in adolescents by promoting physical activity ( PA ) with an emphasis on recreational and daily-life PA , with a lifelong perspective . DESIGN R and omized study design ed to last for four years . Study cohort constituted of 954 first-level students ( 91 % of eligible pupils ) , aged 11.7 + /- 0.6 y ( mean + /- SD ) from four pairs of schools r and omly selected in eastern France , after sociogeographical stratification . In each pair , intervention status was r and omised at school-level . The program , not limited to school setting s , involves multiple partners with three objectives : 1 ) changing attitudes through debates and access to attractive activities during breaks and after-school hours , 2 ) encouraging social support , 3 ) providing environmental conditions that enable PA . Adapted times and places , open participation , emphasis on fun , meeting with others and absence of competitive aspects are used to reduce usual barriers to PA . Accessibility and safety are permanent concerns . RESULTS Prevalence of overweight was 23.7 % . High participation rates were attained ( 50 % participated in at least one weekly activity ) . At six-month , the proportion of intervention adolescents not performing supervised PA out of academic PA was reduced by half ( 36 % to 17 % vs 42 % to 42 % in controls P < 10 - 4 ) ; the proportion of those spending > 3 h/day in sedentary occupations decreased ( 34 % to 28 % vs 27 % to 36 % ; P < 10 - 4 ) . CONCLUSION These data demonstrate the feasibility of implementing a multilevel PA intervention program in adolescents . Six-month results document increased PA and decreased sedentary behaviour Objective : To describe the effects of URMEL-ICE , a German school-based intervention for overweight prevention , on children ’s BMI and other measures of fat mass . Methods : A cluster-r and omised controlled design was used . The intervention which focused on physical activity , TV time and soft drink consumption was integrated into a second- grade curriculum and was implemented by classroom teachers themselves . It comprised 29 teaching lessons , 2 short exercise blocks per day and 6 family homework lessons . BMI was assessed as primary outcome measure , waist circumference and skinfold thickness as secondary outcomes . Data of 945 children were analysed . Results : Multivariate analyses adjusted for baseline values showed no statistically significant effect of the intervention on BMI , but on waist circumference ( –0.85 ; 95 % confidence interval ( 95 % CI ) –1.59 to –0.12 ) and subscapular skinfold thickness ( –0.64 ; 95 % CI –1.25 to –0.02 ) . After additional adjustment for individual time lag between baseline and follow-up , these effects were reduced to –0.60 ( 95 % CI –1.25 to 0.05 ) and –0.61 ( 95 % CI –1.26 to 0.04 ) and lost their statistical significance . Conclusion : This study contributes to the field of r and omised school-based studies on overweight prevention and shows that within a 1-year , integrated intervention no effect on BMI , but a tendency towards effects on fat mass can be achieved BACKGROUND Our objective was to evaluate the effects of environmental , policy , and social marketing interventions on physical activity and fat intake of middle school students on campus . DESIGN Twenty-four middle schools were r and omly assigned to intervention or control conditions . Baseline measures were collected in spring 1997 , and interventions were conducted during the 1997 - 1998 and 1998 - 1999 school years SETTING /PARTICIPATION : The schools had mean enrollments of 1109 , with 44.5 % nonwhite students . Over 2 years , physical activity interventions were design ed to increase physical activity in physical education classes and throughout the school day . Nutrition interventions were design ed to provide and market low-fat foods at all school food sources , including cafeteria breakfasts and lunches , a la carte sources , school stores , and bag lunches . School staff and students were engaged in policy change efforts , but there was no classroom health education . MAIN OUTCOMES MEASURES Primary outcomes were measured by direct observation and existing records . RESULTS R and omized regression models ( N = 24 schools ) revealed a significant intervention effect for physical activity for the total group ( p < 0.009 ) and boys ( p < 0.001 ) , but not girls ( p < 0.40 ) . The intervention was not effective for total fat ( p < 0.91 ) or saturated fat ( p < 0.79 ) . Survey data indicated that the interventions reduced reported body mass index for boys ( p < 0.05 ) . CONCLUSIONS Environmental and policy interventions were effective in increasing physical activity at school among boys but not girls . The interventions were not effective in reducing fat intake at school . School environmental and policy interventions have the potential to improve health behavior of the student population , but barriers to full implementation need to be better understood and overcome OBJECTIVE To evaluate the impact of a school-based diabetes mellitus prevention program on low-income fourth- grade Mexican American children . DESIGN A r and omized controlled trial with 13 intervention and 14 control schools . SETTING Elementary schools in inner-city neighborhoods in San Antonio , Tex . PARTICIPANTS Eighty percent of participants were Mexican American and 94 % were from economically disadvantaged households . Baseline and follow-up measures were collected from 1419 ( 713 intervention and 706 control ) and 1221 ( 619 intervention and 602 control ) fourth- grade children , respectively . INTERVENTION The Bienestar Health Program consists of a health class and physical education curriculum , a family program , a school cafeteria program , and an after-school health club . The objectives are to decrease dietary saturated fat intake , increase dietary fiber intake , and increase physical activity . MAIN OUTCOME MEASURES The primary end point was fasting capillary glucose level , and the secondary end points were percentage of body fat , physical fitness level , dietary fiber intake , and dietary saturated fat intake . Fasting capillary glucose level , bioelectric impedance , modified Harvard step test , three 24-hour dietary recalls , weight , and height were collected at baseline and 8 months later . RESULTS Children in the intervention arm attended an average of 32 Bienestar sessions . Mean fasting capillary glucose levels decreased in intervention schools and increased in control schools after adjusting for covariates ( -2.24 mg/dL [ 0.12 mmol/L ] ; 95 % confidence interval , -6.53 to 2.05 [ -0.36 to 0.11 mmol/L ] ; P = .03 ) . Fitness scores ( P = .04 ) and dietary fiber intake ( P = .009 ) significantly increased in intervention children and decreased in control children . Percentage of body fat ( P = .56 ) and dietary saturated fat intake ( P = .52 ) did not differ significantly between intervention and control children . CONCLUSION This intervention showed some positive results , but additional research is needed to examine long-term benefits , translation , and cost-effectiveness OBJECTIVE To determine whether an interactive curriculum that integrates dating violence prevention with lessons on healthy relationships , sexual health , and substance use reduces physical dating violence ( PDV ) . DESIGN Cluster r and omized trial with 2.5-year follow-up ; prespecified subgroup analyses by sex . SETTING Grade 9 health classes . PARTICIPANTS A total of 1722 students aged 14 - 15 from 20 public schools ( 52.8 % girls ) . Intervention A 21-lesson curriculum delivered during 28 hours by teachers with additional training in the dynamics of dating violence and healthy relationships . Dating violence prevention was integrated with core lessons about healthy relationships , sexual health , and substance use prevention using interactive exercises . Relationship skills to promote safer decision making with peers and dating partners were emphasized . Control schools targeted similar objectives without training or material s. MAIN OUTCOME MEASURES The primary outcome at 2.5 years was self-reported PDV during the previous year . Secondary outcomes were physical peer violence , substance use , and condom use . Analysis was by intention-to-treat . RESULTS The PDV was greater in control vs intervention students ( 9.8 % vs 7.4 % ; adjusted odds ratio , 2.42 ; 95 % confidence interval , 1.00 - 6.02 ; P = .05 ) . A significant group x sex interaction effect indicated that the intervention effect was greater in boys ( PDV : 7.1 % in controls vs 2.7 % in intervention students ) than in girls ( 12.1 % vs 11.9 % ) . Main effects for secondary outcomes were not statistically significant ; however , sex x group analyses showed a significant difference in condom use in sexually active boys who received the intervention ( 114 of 168 ; 67.9 % ) vs controls ( 65 of 111 [ 58.6 % ] ) ( P < .01 ) . The cost of training and material s averaged CA$16 per student . CONCLUSION The teaching of youths about healthy relationships as part of their required health curriculum reduced PDV and increased condom use 2.5 years later at a low per-student cost The aim of this study was to evaluate the impact of an intervention program on the patterns of physical activity in 8- to 10-year-old Mexican children from lower socioeconomic status . This study performed a r and omized controlled field trial in 498 children aged 8 - 10 years from 10 public schools of low socioeconomic status in Mexico City . Schools were r and omly assigned to intervention ( n = 5 ) or control ( n = 5 ) groups and followed up during 12 months . Physical and sedentary activities were assessed at the beginning of the program and after 6 and 12 months . At the end of follow-up , there was a significant increase in the performance of moderate physical activity ( MPA ) among children in intervention group who had not performed MPA at baseline any day of the week ( 40 % , P = 0.04 ) but not in the control group ( 8 % , P = not significant ) . The intervention group also showed a significant reduction in the proportion of children who spent more than 3 hours a day playing video games ( from 23 to 13 % , P = 0.01 ) , while control group did not show significant changes . Given these findings , we conclude that intervention was able to modify positively physical activity and reduce time spent on such sedentary activities as video games among those at highest risk studied children Abstract Objective : To determine whether being overweight in childhood increases adult obesity and risk of disease . Design : Prospect i ve cohort study . Setting : City of Newcastle upon Tyne . Participants : 932 members of thous and families 1947 birth cohort , of whom 412 attended for clinical examination age 50 . Main outcome measures : Blood pressure ; carotid artery intima-media thickness ; fibrinogen concentration ; total , low density lipoprotein , and high density lipoprotein cholesterol concentrations ; triglyceride concentration ; fasting insulin and 2 hour glucose concentrations ; body mass index ; and percentage body fat . Results : Body mass index at age 9 years was significantly correlated with body mass index age 50 ( r=0.24 , P<0.001 ) but not with percentage body fat age 50 ( r=0.10 , P=0.07 ) . After adult body mass index had been adjusted for , body mass index at age 9 showed a significant inverse association with measures of lipid and glucose metabolism in both sexes and with blood pressure in women . However , after adjustment for adult percentage fat instead of body mass index , only the inverse associations with triglycerides ( regression coefficient= −0.21 , P<0.01 ) and total cholesterol ( −0.17 , P<0.05 ) in women remained significant . Conclusions : Little tracking from childhood overweight to adulthood obesity was found when using a measure of fatness that was independent of build . Only children who were obese at 13 showed an increased risk of obesity as adults . No excess adult health risk from childhood or teenage overweight was found . Being thin in childhood offered no protection against adult fatness , and the thinnest children tended to have the highest adult risk at every level of adult obesity . What is already known on this topic Many studies have found that body mass index in childhood is significantly correlated with body mass index in adulthood Obese children have been found to have higher all cause mortality as adults What this study adds No excess health risk from childhood overweight was found Childhood body mass index was linked to adulthood body mass index but not percentage body fat Only children who were obese at 13 showed a significant increased risk of obesity as adults People who were thinnest as children and fattest as adults tended to have the highest adult Six schools were r and omly assigned to a multilevel bullying intervention or a control condition . Children in Grade s 3 - 6 ( N=1,023 ) completed pre- and posttest surveys of behaviors and beliefs and were rated by teachers . Observers coded playground behavior of a r and om sub sample ( n=544 ) . Hierarchical analyses of changes in playground behavior revealed declines in bullying and argumentative behavior among intervention-group children relative to control-group children , increases in agreeable interactions , and a trend toward reduced destructive byst and er behavior . Those in the intervention group reported enhanced byst and er responsibility , greater perceived adult responsiveness , and less acceptance of bullying/aggression than those in the control group . Self-reported aggression did not differ between the groups . Implication s for future research on the development and prevention of bullying are discussed This study examined the effects of the Positive Action ( PA ) programme in Chicago Public Schools on problem behaviours among a cohort of elementary school students from grade three through grade five . Using a matched-pair , r and omised control design with 14 elementary schools , approximately 510 fifth- grade rs self-reported lifetime substance use , serious violence-related behaviour , and current bullying and disruptive behaviours . Three-level ( i.e. students nested within schools within school pairs ) overdispersed Poisson models were used to examine programme effects on the number of items endorsed for each of the four outcomes . Findings indicated that students in the intervention endorsed 31 % fewer substance use behaviours ( incidence rate ratio [ IRR ] = 0.69 ) , 37 % fewer violence-related behaviours ( IRR = 0.63 ) and 41 % fewer bullying behaviours ( IRR = 0.59 ) , respectively , compared to students in the control schools . Reduction in reported disruptive behaviours was of a similar magnitude ( 27 % , IRR = 0.73 ) , but was not statistically significant . These results replicate findings of an earlier r and omised trial of the PA programme and extend evidence of its effectiveness to youth attending large urban school systems Study objective : The aim of this study was to determine the effect of a multilevel school based intervention on adolescents ’ emotional wellbeing and health risk behaviours . Design : School based cluster r and omised controlled trial . Students were surveyed using laptop computers , twice in the first year of intervention and annually thereafter for a further two years . Setting : Secondary schools . Participants : 2678 year 8 students ( 74 % ) participated in the first wave of data collection . Attrition across the waves was less than 3 % , 8 % , and 10 % respectively with no differential response rate between intervention and control groups at the subsequent waves ( 98 % v 96 % ; 92 % v 92 % , and 90 % v 89 % respectively ) . Main results : A comparatively consistent 3 % to 5 % risk difference was found between intervention and control students for any drinking , any and regular smoking , and friends ’ alcohol and tobacco use across the three waves of follow up . The largest effect was a reduction in the reporting of regular smoking by those in the intervention group ( OR 0.57 , 0.62 , and 0.72 at waves 2 , 3 , and 4 respectively ) . There was no significant effect of the intervention on depressive symptoms , and social and school relationships . Conclusions : While further research is required to determine fully the processes of change , this study shows that a focus on general cognitive skills and positive changes to the social environment of the school can have a substantial impact on important health risk behaviours Objective To assess the effectiveness of a school based physical activity programme during one school year on physical and psychological health in young schoolchildren . Design Cluster r and omised controlled trial . Setting 28 classes from 15 elementary schools in Switzerl and r and omly selected and assigned in a 4:3 ratio to an intervention ( n=16 ) or control arm ( n=12 ) after stratification for grade ( first and fifth grade ) , from August 2005 to June 2006 . Participants 540 children , of whom 502 consented and presented at baseline . Intervention Children in the intervention arm ( n=297 ) received a multi-component physical activity programme that included structuring the three existing physical education lessons each week and adding two additional lessons a week , daily short activity breaks , and physical activity homework . Children ( n=205 ) and parents in the control group were not informed of an intervention group . For most outcome measures , the assessors were blinded . Main outcome measures Primary outcome measures included body fat ( sum of four skinfolds ) , aerobic fitness ( shuttle run test ) , physical activity ( accelerometry ) , and quality of life ( question naires ) . Secondary outcome measures included body mass index and cardiovascular risk score ( average z score of waist circumference , mean blood pressure , blood glucose , inverted high density lipoprotein cholesterol , and triglycerides ) . Results 498 children completed the baseline and follow-up assessment s ( mean age 6.9 ( SD 0.3 ) years for first grade , 11.1 ( 0.5 ) years for fifth grade ) . After adjustment for grade , sex , baseline values , and clustering within classes , children in the intervention arm compared with controls showed more negative changes in the z score of the sum of four skinfolds ( −0.12 , 95 % confidence interval −0.21 to −0.03 ; P=0.009 ) . Likewise , their z scores for aerobic fitness increased more favourably ( 0.17 , 0.01 to 0.32 ; P=0.04 ) , as did those for moderate-vigorous physical activity in school ( 1.19 , 0.78 to 1.60 ; P<0.001 ) , all day moderate-vigorous physical activity ( 0.44 , 0.05 to 0.82 ; P=0.03 ) , and total physical activity in school ( 0.92 , 0.35 to 1.50 ; P=0.003 ) . Z scores for overall daily physical activity ( 0.21 , −0.21 to 0.63 ) and physical quality of life ( 0.42 , −1.23 to 2.06 ) as well as psychological quality of life ( 0.59 , −0.85 to 2.03 ) did not change significantly . Conclusions A school based multi-component physical activity intervention including compulsory elements improved physical activity and fitness and reduced adiposity in children . Trial registration Current Controlled Trials IS RCT N15360785 BACKGROUND . The prevalence and seriousness of childhood obesity has prompted calls for broad public health solutions that reach beyond clinic setting s. Schools are ideal setting s for population -based interventions to address obesity . OBJECTIVE . The purpose of this work was to examine the effects of a multicomponent , School Nutrition Policy Initiative on the prevention of overweight ( 85.0th to 94.9th percentile ) and obesity ( > 95.0th percentile ) among children in grade s 4 through 6 over a 2-year period . METHODS . Participants were 1349 students in grade s 4 through 6 from 10 schools in a US city in the Mid-Atlantic region with ≥50 % of students eligible for free or reduced-price meals . Schools were matched on school size and type of food service and r and omly assigned to intervention or control . Students were assessed at baseline and again after 2 years . The School Nutrition Policy Initiative included the following components : school self- assessment , nutrition education , nutrition policy , social marketing , and parent outreach . RESULTS . The incidences of overweight and obesity after 2 years were primary outcomes . The prevalence and remission of overweight and obesity , BMI z score , total energy and fat intake , fruit and vegetable consumption , body dissatisfaction , and hours of activity and inactivity were secondary outcomes . The intervention result ed in a 50 % reduction in the incidence of overweight . Significantly fewer children in the intervention schools ( 7.5 % ) than in the control schools ( 14.9 % ) became overweight after 2 years . The prevalence of overweight was lower in the intervention schools . No differences were observed in the incidence or prevalence of obesity or in the remission of overweight or obesity at 2 years . CONCLUSION . A multicomponent school-based intervention can be effective in preventing the development of overweight among children in grade s 4 through 6 in urban public schools with a high proportion of children eligible for free and reduced-priced school meals OBJECTIVE The present study aim ed to determine whether a multi-component school-based intervention can maintain children 's fruit and vegetable intake post eligibility for free school fruit and vegetables . DESIGN A r and om sample of fifty-four English primary schools was r and omised to receive the 10-month intervention Project Tomato , a multi-component theory-based intervention , or the control . Each group consisted of twenty-seven schools . SETTING Children 's intake of fruit and vegetables is below recommendations . The English School Fruit and Vegetable Scheme has a short-term impact on intake while children are eligible for the scheme . SUBJECTS Dietary measurements were collected from 658 Year 2 pupils aged 7 - 8 years at baseline and at follow-up 20 months later . RESULTS Following an intention to treat analysis , the intervention as delivered compared with the control had no impact on the intake of fruit and vegetables ( 2 g/d , 95 % CI -23 , 26 g/d ) or on the number of portions of fruit ( 0.0 portions , 95 % CI - 0.3 , 0.3 ) or vegetables ( 0.0 portions , 95 % CI - 0.2 , 0.3 ) consumed daily by children . Intake of fruit and vegetables at school and home dropped by ≈ 100 g/d and 50 g/d , respectively , between baseline and follow-up in both the intervention and control groups . CONCLUSIONS Implementation of the intervention was low , with associated lack of impact on fruit and vegetable consumption in children . Alternatives to the delivery of an intervention by teachers and parents are needed to improve the dietary intake of primary -school children OBJECTIVES We assessed the effectiveness of a 2-year multicomponent , school-based intervention design ed to reduce tobacco use rates among adolescents in an urban area of India . METHODS Students from 32 schools in Delhi and Chennai , India , were recruited and r and omly assigned to an intervention or control group . Baseline , intermediate , and outcome data were collected from 2 cohorts of 6th- and 8th- grade students in 2004 ; 14,063 students took part in the study and completed a survey in 2004 , 2005 , or 2006 . The intervention consisted of behavioral classroom curricula , school posters , a parental involvement component , and peer-led activism . The main outcome measures were self-reported use of cigarettes , bidis ( small h and -rolled , often flavored , cigarettes ) , and chewing tobacco and future intentions to smoke or use chewing tobacco . RESULTS Findings showed that students in the intervention group were significantly less likely than were students in the control group to exhibit increases in cigarette smoking or bidi smoking over the 2-year study period . They were also less likely to intend to smoke or chew tobacco in the future . CONCLUSIONS School-based programs similar to the intervention examined here should be considered as part of a multi strategy approach to reducing tobacco use among young people in India OBJECTIVE To evaluate the effects of a 2-year middle school physical activity and healthy food intervention , including an environmental and computer-tailored component on BMI and BMI z-score in boys and girls . RESEARCH METHODS AND PROCEDURES A r and om sample of 15 schools with seventh and eighth grade rs was r and omly assigned to three conditions : an intervention with parental support group , an intervention-alone group , and a control group . Weight and height were measured at the beginning and end of each school year to assess BMI and BMI z-score . A physical activity and healthy food program was implemented over 2 school years . RESULTS In girls , BMI and BMI z-score increased significantly less in the intervention with parental support group compared with the control group ( p < 0.05 ) or the intervention-alone group ( p = 0.05 ) . In boys , no significant positive intervention effects were found . DISCUSSION This was the first study evaluating the effectiveness of an intervention combining environmental changes with personal computer-tailored feedback on BMI and BMI z-score in middle school children . After 2 school years , BMI and BMI z-score changed in a more positive direction in girls as a result of the intervention with parental support OBJECTIVES To assess the outcome of oral health promotion in schoolchildren over a 3-year period in Yichang City , Hubei , China . METHODS In a cluster r and omized controlled trial , the concept of the World Health Organization Health Promoting Schools Project was applied to primary schoolchildren . Seven intervention schools and eight control schools were r and omly selected from one district by stratified cluster sampling . The study was conducted as a 3-year follow-up study . After 3 years , 661 children remained in the intervention group and 697 children in the control group . Data on dental caries , plaque accumulation , and sulcus bleeding were collected by clinical examination , while behavioural data were gathered by self-administered question naires . RESULTS The 3-year net mean DMFS increment score was 0.22 in the intervention schools and 0.35 in the control schools ( P < 0.013 ) . A statistically significant difference in mean plaque ( P < 0.013 ) and sulcus bleeding ( P < 0.005 ) increment scores after 3 years was found between the two groups . Statistically significant higher scores were observed in restorations received and sealants placed , and a lower score in untreated dental caries , in children from the intervention group than the control group after 3 years ( P < 0.01 ) . In addition , more children in the intervention schools adopted regular oral health behavioural practice s such as brushing their teeth at least twice a day , visiting the dentist within the past calendar year , and using fluoride toothpaste . CONCLUSION The study suggests that the school-based oral health promotion was an effective way to reduce new caries incidence , improve oral hygiene and establish positive oral health behavioural practice s in the targeted schoolchildren 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 This r and omized controlled trial evaluated the effectiveness of a multicomponent Health Promoting Schools ( HPS ) intervention program in improving self-reported smoking outcomes among a cohort of adolescents in 22 public secondary schools in the Hunter Region of New South Wales , Australia . Pre-test surveys were completed by students in the first 2 years of secondary school , with a 2-year post-test survey . Multivariate analyses examined intervention effect for the main outcome , post-test smoking behavior , controlling for pre-test smoking status , school and other confounders . The sample comprised the cohort of 1852 students who completed both surveys . The results demonstrated that the HPS program failed to improve smoking behavior over the 2 years ( equal increase of 10 % in both groups ) . The program was successful in improving smoking knowledge , but not attitudes , in intervention versus control group ( P < 0.001 ) . Independent predictors of post-test smoking included : pre-test smoking [ odds ratio ( OR ) = 5.44 ; 95 % confidence interval ( CI ) = 3.20 - 9.28 ] , being female ( OR = 0.55 ; CI = 0.35 - 0.87 ) , having more close friends who smoked ( OR = 1.42 ; CI = 1.33 - 1.52 ) , peer group having no clear opinion about smoking ( OR = 3.23 ; CI = 1.27 - 8.27 ) , having more positive and less negative attitudes towards smoking , and being less involved in school activities . We discuss method ological issues in multicomponent community-based interventions , and highlight the strengths and limitations of this study Objectives . Bicycle-related injury remains a major cause of death and injury hospitalization among Australian children . The study aim ed to assess the effectiveness of a whole-school intervention to increase the correct wearing of bicycle helmets by primary school children . Methods . A r and omized intervention trial was conducted in 27 Western Australian primary schools . A major component of the intervention was a peer-led classroom curriculum for 10–12 year old children . Helmet use by cyclists was observed as children were leaving school at baseline ( May 2000 ) and after the first year and second year of the intervention . A cohort of 10–11 year old children in study schools completed a self-administered question naire at the same three data collection points . Results . Over the 2 years of the study , observed helmet wearing rates declined by 13 % in the control group ( from 93 % at baseline to 80 % at post-test 2 ) and by 5 % in the intervention group ( from 89 % to 84 % ) ( F = 1.745 , p = 0.185 ) . Among the Grade 5/6 cohort students who were regular riders , the likelihood of reporting always wearing a helmet was 1.9 times higher at post-test 1 ( z = 2.51 , p = 0.012 ) and 1.7 times higher at post-test 2 ( z = 2.13 , p = 0.033 ) for the intervention group than the control group students who did not always wear a helmet at baseline . Conclusions . The data suggest that school-based activities can arrest the rate of decline in helmet use by children . Using peer teachers is a useful strategy to engage students in normative-based protective behaviours . The logistical challenges this strategy presents appear to be worth the outcomes BACKGROUND A growing awareness of health promotion and positive lifestyle change , coupled with the knowledge that cardiovascular risk has its origins in childhood , has led to the development of health promotion programs in the elementary school . While most school-based programs target specific behaviors or enlist singular intervention modalities , the Heart Smart cardiovascular school health promotion targeted the total school environment with a multidisciplinary approach to prompt the school 's varied institutions to implement changes in curriculum , school lunch , and physical education . METHODS Components of the Heart Smart environmental intervention included : ( a ) a school lunch program providing cardiovascular healthful food choices , reduced in fat by 30 % and in sodium and sugar by 50 % ; ( b ) a physical education program promoting personal fitness and aerobic conditioning ; and ( c ) cardiovascular risk factor screening , measuring fasting lipids and lipoproteins , anthropometrics , and blood pressure . Changes in cardiovascular risk factor status , school lunch selection s , and exercise performance were compared . RESULTS Screening participants showed greater improvement in health knowledge than non participants . School lunch choices were successfully altered , and children whose lunch choices were cardiovascular healthful evidence d the greatest cholesterol reduction . Improvements in run/walk performance were related in predicted directions to the overall cardiovascular risk profile . Increases in high-density lipoprotein cholesterol were observed at intervention schools . CONCLUSION Observations indicate a relationship between behavior change and physiologic changes achieved in a total school health promotion to reduce cardiovascular risk AIMS The goal of this group-r and omized trial was to test the effectiveness of an adapted alcohol use preventive intervention for urban , low-income and multi-ethnic setting s. DESIGN AND SETTING Sixty-one public schools in Chicago were recruited to participate , were grouped into neighborhood study units and assigned r and omly to intervention or ' delayed program ' control condition . PARTICIPANTS The study sample ( n = 5812 students ) was primarily African American , Hispanic and low-income . INTERVENTION Students , beginning in sixth grade ( age 12 years ) , received 3 years of intervention strategies ( curricula , family interventions , youth-led community service projects , community organizing ) . MEASUREMENTS Students participated in yearly classroom-based surveys to measure their alcohol use and related risk and protective factors . Additional evaluation components included a parent survey , a community leader survey and alcohol purchase attempts . FINDINGS Overall , the intervention , compared with a control condition receiving ' prevention as usual ' , was not effective in reducing alcohol use , drug use or any hypothesized mediating variables ( i.e. related risk and protective factors ) . There was a non-significant trend ( P = 0.066 ) that suggested the ability to purchase alcohol by young-appearing buyers was reduced in the intervention communities compared to the control communities , but this could be due to chance . Secondary outcome analyses to assess the effects of each intervention component indicated that the home-based programs were associated with reduced alcohol , marijuana and tobacco use combined ( P = 0.01 ) , with alcohol use alone approaching statistical significance ( P = 0.06 ) . CONCLUSIONS Study results indicate the importance of conducting evaluations of previously vali date d programs in context s that differ from the original study sample . Also , the findings highlight the need for further research with urban , low-income adolescents from different ethnic background s to identify effective methods to prevent and reduce alcohol use This paper describes an intervention to increase high school students ' fruit and vegetable consumption . Twelve schools were r and omized to intervention or control conditions . The cohort ( 2,213 students ; 56 % females , 84 % Caucasian ) were followed from 9th to 12th grade s. Interventions comprised a media campaign , classroom workshops , school meal modification , and parental support . Usual daily servings of fruit/vegetables increased 14 % in the intervention compared to the control group ( p > 0.001 ) the first three years . At follow-up , consumption within the control group also increased , result ing in no significant difference between groups . Intervention group knowledge scores and awareness indicators were significantly higher than those of the control group ( p < 0.0001 ) . Gimme 5 provided a first model to show that dietary habits of high school students can be influenced by positive media messages relative to that age group , increased exposure to a variety of tasty products , and minimal classroom activity OBJECTIVE To evaluate the effects of an antibullying school intervention in elementary schools . DESIGN Two-year follow-up r and omized intervention group-control group . SETTING Forty-seven elementary schools in the Netherl and s. PARTICIPANTS Three thous and eight hundred sixteen children aged 9 to 12 years . INTERVENTION During the first study year , an antibullying school program was implemented in the schools in the intervention group . MAIN OUTCOME MEASURES A question naire measuring bullying behavior , depression , psychosomatic complaints , delinquent behavior , and satisfaction with school life and peer relationships was filled out by the students at 3 times to obtain the following data : a baseline measurement , a first-effect measurement at the end of the first year , and a second-effect measurement at the end of the second year . RESULTS The number of bullied children decreased by 25 % in the intervention group compared with the control group ( relative risk , 0.75 ; 95 % confidence interval , 0.57 - 0.98 ) . The intervention group also showed a decline in the scale scores of victimization ( -1.06 vs 0.28 ; P < .01 ) and active bullying behaviors ( -0.47 vs 0.12 , P < .05 ) . Self-reported peer relationships also improved in the intervention schools ( 0.48 vs 0.11 ; P < .05 ) , and there was a trend for a decrease in reported depression in the intervention schools ( -0.33 vs -0.10 ; P < .10 ) . At follow-up , there were no differences between the intervention and control groups for the outcome measures . Schools had also lowered their antibullying activities during the second study year . CONCLUSIONS An antibullying school policy can reduce bullying behavior . To keep bullying at a consistently low level , schools must continue antibullying measures every year . Continued counseling may help schools in their efforts to establish a lasting antibullying policy To evaluate the effectiveness of an intensive h and hygiene campaign on reducing absenteeism caused by influenza-like illness ( ILI ) , diarrhea , conjunctivitis , and laboratory-confirmed influenza , we conducted a r and omized control trial in 60 elementary schools in Cairo , Egypt . Children in the intervention schools were required to wash h and s twice each day , and health messages were provided through entertainment activities . Data were collected on student absenteeism and reasons for illness . School nurses collected nasal swabs from students with ILI , which were tested by using a qualitative diagnostic test for influenza A and B. Compared with results for the control group , in the intervention group , overall absences caused by ILI , diarrhea , conjunctivitis , and laboratory-confirmed influenza were reduced by 40 % , 30 % , 67 % , and 50 % , respectively ( p<0.0001 for each illness ) . An intensive h and hygiene campaign was effective in reducing absenteeism caused by these illnesses Objective : The impact of a multicomponent intervention programme on the sexual health of adolescents was assessed in rural Tanzania . Design : A community-r and omized trial . Methods : Twenty communities were r and omly allocated to receive either a specially design ed programme of interventions ( intervention group ) or st and ard activities ( comparison group ) . The intervention had four components : community activities ; teacher-led , peer-assisted sexual health education in years 5–7 of primary school ; training and supervision of health workers to provide ‘ youth-friendly ’ sexual health services ; and peer condom social marketing . Impacts on HIV incidence , herpes simplex virus 2 ( HSV2 ) and other sexual health outcomes were evaluated over approximately 3 years in 9645 adolescents recruited in late 1998 before entering years 5 , 6 or 7 of primary school . Results : The intervention had a significant impact on knowledge and reported attitudes , reported sexually transmitted infection symptoms , and several behavioural outcomes . Only five HIV seroconversions occurred in boys , whereas in girls the adjusted rate ratio ( intervention versus comparison ) was 0.75 [ 95 % confidence interval ( CI ) 0.34 , 1.66 ] . Overall HSV2 prevalences at follow-up were 11.9 % in male and 21.1 % in female participants , with adjusted prevalence ratios of 0.92 ( CI 0.69 , 1.22 ) and 1.05 ( CI 0.83 , 1.32 ) , respectively . There was no consistent beneficial or adverse impact on other biological outcomes . The beneficial impact on knowledge and reported attitudes was confirmed by results of a school examination in a separate group of students in mid-2002 . Conclusion : The intervention substantially improved knowledge , reported attitudes and some reported sexual behaviours , especially in boys , but had no consistent impact on biological outcomes within the 3-year trial period This study evaluated the effects of a school-based intervention on growth trajectories of smoking , drinking , and antisocial behavior among early adolescents . Seven middle schools were r and omized to intervention or comparison conditions and students in two successive cohorts ( n = 1484 ) provided five waves of data from sixth to ninth grade . The Going Places Program , included classroom curricula , parent education , and school environment components . Latent growth curve analyses demonstrated significant treatment group effects , including reducing increases in friends who smoke , outcome expectations for smoking , and smoking progression , but had non-significant effects on drinking or antisocial behavior . The Going Places Program was effective in preventing increases in smoking progression , but its efficacy as a more cross-cutting problem behavior preventive intervention was not confirmed OBJECTIVES The purpose of this study was to evaluate the effect of a school-based intervention program to reduce overweight and improve fitness in primary school children . METHODS A cluster r and omized controlled design was used over one school year with schools as unit of r and omization . In total 20 schools and 2,622 children aged 6 - 12 years ( grade s 3 - 8 ) from multi-ethnic , low income inner-city neighbourhoods in Rotterdam , Netherl and s , participated . The intervention , named Lekker Fit ! ( Enjoy being fit ! ) was a multi-component intervention based on behavioural and ecological models . Main components of the intervention are the implementation of three physical education ( PE ) sessions a week by a professional PE teacher , additional sport and play activities outside school hours and an educational program . Main primary outcome measures were weight status , body mass index ( BMI ) , waist circumference and fitness ( 20 m shuttle run ) . RESULTS Significant positive intervention effects were found for percentage overweight children ( OR 0.53 ; 95 % CI 0.36 - 0.78 ) , waist circumference ( -1.29 cm ; 95 % CI -2.16 to -0.42 cm ) and 20 m shuttle run ( 0.57 laps ; 95 % CI 0.13 - 1.01 laps ) among pupils of grade s 3 - 5 ( 6 - 9-year olds ) . The prevalence of overweight in grade s 3 - 5 increased by 4.3 % in the control group and by 1.3 % in the intervention group . No significant effects were found for BMI or for grade s 6 - 8 ( 9 - 12-year olds ) . CONCLUSIONS Our results provide evidence for the effectiveness of the multi-component intervention Lekker Fit ! among pupils of grade s 3 - 5 and adds to the growing body of evidence that school-based programs with a focus on PA are most effective in reducing childhood obesity . [ IS RCT N84383524 ] BACKGROUND The positive of the Norwegian anti-bullying programme ( Olweus , 1992 ) stimulated other countries to tackle bully/victim problems . However , outcome studies found rather low levels of effect or even inconsistent results . AIMS The purpose of the present study was to evaluate behavioural effectiveness of a school-based anti-bullying approach within Flemish schools . In addition , specific attention was given to the relationship between outcome findings and external support . SAMPLE A total of 18 schools , comprising 1104 primary and secondary school children were recruited for this study . Students ranged in age from 10 to 16 years . METHOD For this study , an experimental pre-test/post-test design was used which included a control group . Three groups were established . The first group , Treatment with Support , involved students from schools that implemented a school-based anti-bullying intervention with additional support from the research group . The second group , Treatment without Support , also involved students from schools that implemented a school-based anti-bullying programme . However , in contrast with those falling under the first condition , this group of schools could not appeal to the research group for additional help . The last group involved students from schools that did not implement the anti-bullying programme and served as a Control condition . Repeated measures analyses of variance were carried out . RESULTS The findings regarding the effects of the school-based anti-bullying intervention programme on the extent of bullying and victimisation showed a mixed pattern of positive changes in primary schools and zero outcomes in secondary schools . The findings regarding the effects of external support revealed limited outcomes . CONCLUSIONS The outcomes of the evaluation study confirm that a school-based anti-bullying intervention strategy can be effective in reducing problems with bullying , especially within primary schools . It was argued that the developmental characteristics of secondary school students interfered with the programme outcomes . In addition , the findings revealed no extra effects of specific training sessions OBJECTIVES Project Northl and is an efficacy trial with the goal of preventing or reducing alcohol use among young adolescents by using a multilevel , communitywide approach . METHODS Conducted in 24 school districts and adjacent communities in northeastern Minnesota since 1991 , the intervention targets the class of 1998 ( sixth- grade students in 1991 ) and has been implemented for 3 school years ( 1991 to 1994 ) . The intervention consists of social-behavioral curricula in schools , peer leadership , parental involvement/education , and communitywide task force activities . Annual surveys of the class of 1998 measure alcohol use , tobacco use , and psychosocial factors . RESULTS At the end of 3 years , students in the intervention school districts report less onset and prevalence of alcohol use than students in the reference districts . The differences were particularly notable among those who were nonusers at baseline . CONCLUSIONS The results of Project Northl and suggest that multilevel , targeted prevention programs for young adolescents are effective in reducing alcohol use OBJECTIVE To evaluate the impact of a multi-component school-based physical activity intervention ( Fit-4-Fun ) on health-related fitness and objective ly measured physical activity in primary school children . METHODS Four Hunter primary schools were recruited in April , 2011 and r and omized by school into treatment or control conditions . Participants included 213 children ( mean age = 10.72 years ± 0.6 ; 52.2 % female ) with the treatment group ( n = 118 ) completing the 8-week Fit-4-Fun Program . Participants were assessed at baseline and 6-month follow-up , with a 91 % retention rate . Cardio-respiratory fitness ( CRF ) ( 20 m shuttle run ) was the primary outcome , and secondary outcomes included body composition ( BMI , BMI ( Z ) ) , muscular fitness ( 7-stage sit-up test , push-up test , basketball throw test , St and ing Jump ) , flexibility ( sit and reach ) and physical activity ( 7 days pedometry ) . RESULTS After 6-months , significant treatment effects were found for CRF ( adjusted mean difference , 1.14 levels , p < 0.001 ) , body composition ( BMI mean , -0.96 kg/m(2 ) , p < 0.001 and BMI z-score mean -0.47 z-scores , p < 0.001 ) , flexibility ( sit and reach mean , 1.52 cm , p = 0.0013 ) , muscular fitness ( sit-ups ) ( mean 0.62 stages , p = 0.003 ) and physical activity ( mean , 3253 steps/day , p < 0.001 ) . There were no group by time effects for the other muscular fitness measures . CONCLUSIONS A primary school-based intervention focusing on fitness education significantly improved health-related fitness and physical activity levels in children The objective of the present study was to evaluate the effects of the Pro Children intervention on schoolchildren 's fruit and vegetable ( FV ) intake after 1 and 2 years of follow-up . The intervention combined a FV curriculum with efforts to improve FV availability at schools and at home . Effects were examined in a group-r and omised trial among 1,472 10 - 11-year-old children from sixty-two schools in Norway , the Netherl and s and Spain . FV intake was assessed by means of vali date d self-administered question naires completed before the intervention ( September 2003 ) , immediately after the first year of the intervention ( May 2004 ) and 1 year later ( May 2005 ) . Data were analysed using multilevel linear regression analyses with age and sex as covariates . Significant intervention effects for FV intake were found at first follow-up in the total sample . The adjusted FV intake reported by the children from intervention schools was 20 % higher than FV intake reported by children from control schools . At 1 year later , a significant impact was only observed in Norway . Positive intervention effects on FV intake occurred both at school and outside school . We conclude that the Pro Children intervention is a promising means to promote European schoolchildren 's FV intakes , but mainly fruit intake , in the short term . As shown in Norway , where the intervention was best implemented , the intervention might also result in longer-term effects . Further strategies need to be developed that can improve implementation , have an impact on vegetable intake and can secure sustained effects Complex interventions are more than the sum of their parts , and interventions need to be better theorised to reflect this Many people think that st and ardisation and r and omised controlled trials go h and in h and . Having an intervention look the same as possible in different places is thought to be paramount . But this may be why some community interventions have had weak effects . We propose a radical departure from the way large scale interventions are typically conceptualised . This could liberate interventions to be responsive to local context and potentially more effective while still allowing meaningful evaluation in controlled design s. The key lies in looking past the simple elements of a system to embrace complex system functions and processes . The suitability of cluster r and omised trials for evaluating interventions directed at whole communities or organisations remains vexed.1 It need not be.2 Some health promotion advocates ( including the WHO European working group on health promotion evaluation ) believe r and omised controlled trials are inappropriate because of the perceived requirement for interventions in different sites to be st and ardised or look the same.1 3 4 They have ab and oned r and omised trials because they think context level adaptation , which is essential for interventions to work , is precluded by trial design s. An example of context level adaptation might be adjusting educational material s to suit various local learning styles and literacy levels . Lead thinkers in complex interventions , such as the UK 's Medical Research Council , also think that trials of complex interventions must “ consistently provide as close to the same intervention as possible ” by “ st and ardising the content and delivery of the intervention.”5 By contrast , however , they do not see this as a reason to reject r and omised controlled trials . These divergent views have led to problems on two fronts . Firstly , the field of health promotion is being turned away from r and omised OBJECTIVES We assessed the effectiveness of a 5-year trial of a comprehensive school-based program design ed to prevent substance use , violent behaviors , and sexual activity among elementary-school students . METHODS We used a matched-pair , cluster-r and omized , controlled design , with 10 intervention schools and 10 control schools . Fifth- grade rs ( N = 1714 ) self-reported on lifetime substance use , violence , and voluntary sexual activity . Teachers of participant students reported on student ( N = 1225 ) substance use and violence . RESULTS Two-level r and om-effects count models ( with students nested within schools ) indicated that student-reported substance use ( rate ratio [ RR ] = 0.41 ; 90 % confidence interval [ CI ] = 0.25 , 0.66 ) and violence ( RR = 0.42 ; 90 % CI = 0.24 , 0.73 ) were significantly lower for students attending intervention schools . A 2-level r and om-effects binary model indicated that sexual activity was lower ( odds ratio = 0.24 ; 90 % CI = 0.08 , 0.66 ) for intervention students . Teacher reports substantiated the effects seen for student-reported data . Dose-response analyses indicated that students exposed to the program for at least 3 years had significantly lower rates of all negative behaviors . CONCLUSIONS Risk-related behaviors were substantially reduced for students who participated in the program , providing evidence that a comprehensive school-based program can have a strong beneficial effect on student behavior PURPOSE To investigate the effectiveness of a universal intervention design ed to reduce depressive symptoms experienced by adolescents at high school . The results from annual assessment s during the 3-year intervention and a 2-year follow-up are reported . METHODS Twenty-five pairs of secondary schools matched on socio-economic status were r and omly assigned to either an intervention or a comparison group ( n = 5,633 year 8 students , mean age = 13.1 years , SD = .5 ) . The intervention used a comprehensive classroom curriculum program , enhancements to school climate , improvements in care pathways , and community forums . A range of measures completed by students and teachers was used to assess changes in depressive symptoms , risk and protective factors relevant to depression , and the quality of the school environment . RESULTS Changes in the levels of depressive symptoms and in the levels of risk and protective factors experienced by students in the two groups did not differ significantly over the 5 years of the study . Statistically significant differences in the ratings of school climate across this time were found only for teacher-rated assessment s. CONCLUSIONS There was little evidence that a multicomponent universal intervention delivered over a 3-year period reduced levels of depressive symptoms among participating students . Implementing universal interventions to improve student mental health is difficult in school setting s that commonly have a crowded agenda of educational and health-related programs . Successful implementation will require programs which are perceived by teachers and students as relevant to educational and learning goals , and which can be effectively delivered in conjunction with other school programs Background Community-based interventions are needed to reduce the burden of childhood obesity . Purpose To evaluate the impact of a multi-level promotora-based ( Community Health Advisor ) intervention to promote healthy eating and physical activity and prevent excess weight gain among Latino children . Methods Thirteen elementary schools were r and omized to one of four intervention conditions : individual/family level ( Family-only ) , school/community level ( Community-only ) , combined ( Family + Community ) , or a measurement-only condition . Participants were 808 Latino parents and their children enrolled in kindergarten through 2nd grade . Measures included parent and child body mass index ( BMI ) and a self-administered parent survey that assessed several parent and child behaviors . Results There were no significant intervention effects on children ’s BMI z-score . The family intervention changed several obesity-related child behaviors ( e.g. , fruit/vegetable consumption ) and these were mediated by changes in parenting variables ( e.g. , parent monitoring ) . Conclusion A promotora-based behavioral intervention was efficacious at changing parental factors and child obesity-related health behaviors |
10,724 | 18,983,627 | Providing an intervention is more effective than routine care .
Psychological interventions may improve discontinuation above GDR alone .
While some substitutive pharmacotherapies may have promise , current evidence is insufficient to support their use | AIMS To assess the effectiveness of current treatment approaches to assist benzodiazepine discontinuation . | Disturbed sleep is a common problem , particularly among elderly people , and is usually treated with hypnotics . The side effects of longterm administration of hypnotic drugs are well known , but despite this there remains a substantial population of chronic users . These people can be helped to reduce their dependence on hypnotics through psychological techniques . A group of longterm users treated in this manner were shown to reduce their intake of hypnotics significantly more than a group of users who did not receive any psychological treatment . Furthermore , the treated patients did not experience any deterioration in their sleep patterns , and their subjective refreshment from sleep improved significantly . For the patient with sleep problems , psychological techniques are preferable to the longterm use of hypnotics both as a weaning-off agent and as an alternative to drugs Chronic normal-dose benzodiazepine users requesting drug withdrawal were allocated to substitution with either the new anxiolytic alpidem ( n = 13 ) or placebo ( n = 12 ) . During the first 2 weeks of the tapering programme , the dose of benzodiazepine was kept constant ; for the next 2 weeks it was halved and half-dose alpidem ( 25 mg twice daily ) or placebo substituted ; for weeks 5 and 6 , the benzodiazepine was discontinued and full-dose alpidem or placebo given ; next alpidem or placebo were tapered to half-dose and then finally discontinued . Regular anxiety and tranquillizer withdrawal ratings were made . Nine of 12 patients given placebo withdrew successfully compared with four of 13 alpidem-treated patients . Anxiety and other symptom levels increased in the alpidem but not the placebo patients . It was concluded that alpidem is not helpful in helping patients withdrawing from a benzodiazepine withdrawal perhaps because of partial agonist properties . These actions may imply a lesser propensity to induce dependence on long-term use This study evaluated the specific effectiveness of cognitive-behavior therapy ( CBT ) combined with medication tapering for benzodiazepine discontinuation among generalized anxiety disorder ( GAD ) patients by using a nonspecific therapy control group . Sixty-one patients who had used benzodiazepines for more than 12 months were r and omly assigned to the experimental conditions . Nearly 75 % of patients in the CBT condition completely ceased benzodiazepine intake , as compared with 37 % in the control condition . Results of the 3- , 6- , and 12-month follow-ups confirmed the maintenance of complete cessation . Discontinuation rates remained twice as high in the CBT condition . The number of patients who no longer met GAD criteria was also greater in the CBT condition . The addition of specific CBT components thus seemed to facilitate benzodiazepine tapering among patients with GAD BACKGROUND Benzodiazepine withdrawal programmes have never been experimentally compared with a nonintervention control condition . AIMS To evaluate the efficacy and feasibility of tapering off long-term benzodiazepine use in general practice , and to evaluate the value of additional group cognitive-behavioural therapy ( CBT ) . METHOD A 3-month r and omised , 3-month controlled trial was conducted in which 180 people attempting to discontinue long-term benzodiazepine use were assigned to tapering off plus group CBT , tapering off alone or usual care . RESULTS Tapering off led to a significantly higher proportion of successful discontinuations than usual care ( 62 % nu . 21 % ) . Adding group CBT did not increase the success rate ( 58 % v. 62 % ) . Neither successful discontinuation nor intervention type affected psychological functioning . Both tapering strategies showed good feasibilityin general practice . CONCLUSIONS Tapering off is a feasible and effective way of discontinuing long-term benzodiazepine use in general practice . The addition of group CBT is of limited value BACKGROUND Many patients with depression take benzodiazepine drugs long term despite the absence of continuing therapeutic value . AIMS To evaluate a treatment programme involving gradual discontinuation with or without simultaneous selective serotonin reuptake inhibitor ( SSRI ) prescribing and to determine the long-term outcome after benzodiazepine withdrawal . METHOD Patients went through three phases - change to an equivalent dose of diazepam ; subsequent r and omisation to either 20 mg of paroxetine or placebo ; and gradual reduction of diazepam in depression-free patients - with a follow-up after 2 or 3 years . RESULTS A total of 230 patients were recruited and 75 % in the paroxetine group and 61 % in the placebo group were successfully treated after 6 weeks ( P:=0.067 ) . After 2 or 3 years 13 % of patients were still benzodiazepine free : 26 % of those who had successfully tapered off benzodiazepine and 6 % of the total group . CONCLUSIONS Transfer to diazepam followed by gradual withdrawal is an effective way of discontinuing chronic benzodiazepine use . The addition of SSRI treatment is of limited value Twenty four long-term benzodiazepine users were allocated r and omly to treatment with either buspirone ( mean dose 25 mg/day ) or placebo , prior to tapering off the benzodiazepine over 6 weeks . In both groups , six out of 12 patients successfully completed withdrawal . However , buspirone-treated patients tended to have lower anxiety levels than placebo-treated patients . The amount of previous benzodiazepine usage predicted outcome Recognizing the need to offer alternative methods of brief interventions , this study developed correspondence treatments for low-dependent problem drinkers and evaluated their impact . One hundred and twenty-one problem drinkers were recruited by media advertisements and were r and omly allocated to a full cognitive-behavioural treatment programme ( CBT ) or to a minimal intervention condition ( MI ) that gave information regarding alcohol misuse and instructions to record drinking++ . As predicted , CBT was more effective than MI in reducing alcohol consumption over the 4-month controlled trial period . CBT produced a 50 % fall in consumption , bringing the average intake of subjects within recommended maximum levels . Treatment gains at 6 months were well maintained to 12 months . High levels of consumer satisfaction , a high representation of women and a substantial participation from isolated rural areas attested to the feasibility of the correspondence programme as an alternative treatment . However , some drinking occasions still involved high intake for a significant subgroup of subjects , and this issue will be addressed in future programmes . The results supported the use of correspondence delivery as a means of promoting early engagement and equity of access between city and country areas This study investigated 2 methods of disseminating a cognitive-behavioral intervention for panic disorder ( PD ) . Thirty-six Ss who met diagnostic criteria for PD according to the Anxiety Disorders Interview Schedule-Revised were r and omly assigned to 1 of 3 conditions : bibliotherapy ( BT ) , group therapy ( GT ) , or a waiting-list control ( WL ) condition . Interventions lasted 8 weeks and were followed by a posttest , along with 3- and 6-month follow-up assessment s. Results indicated that both the BT and GT treatments were more effective than the WL condition in reducing frequency of panic attacks , severity of physical panic symptoms , catastrophic cognitions , agoraphobic avoidance , and depression and that the BT and GT treatments were more effective in increasing self-efficacy . Both interventions maintained their effects throughout the follow-up periods and produced clinical ly significant levels of change among the majority of treated Ss Abstract Recent uncontrolled research suggested that trazodone and sodium valproate may be helpful in benzodiazepine ( BZ ) discontinuation . We therefore undertook a double-blind study to assess whether trazodone and valproate , as compared to placebo , would attenuate withdrawal and facilitate discontinuation in BZ-dependent patients with a minimum of 1 year daily BZ use . Seventy-eight patients , taking a mean dose of 19 ± 17 mg/day of diazepam ( or its equivalent ) , were stabilized for several weeks on their BZ ( 16 diazepam , 25 lorazepam , 37 alprazolam ) and then for 1–2 weeks , pretreated with trazodone , sodium valproate or placebo before being tapered at 25 % per week . All treatments were continued for 5 weeks post-taper . BZ-free status was assessed after 5 and 12 weeks post-taper . Neither trazodone nor valproate had any significant effect on withdrawal severity . Peak physician withdrawal checklist change from baseline to peak severity was 16.4 for trazodone , 18.04 sodium valproate and 18.24 placebo ( F = 0.10 ; NS ) . Taper success rates were significantly effected by both active agents at the 5-week , but not 12-week , assessment . At 5 weeks post-taper , 79 % of sodium valproate and 67 % of trazodone , but only 31 % of placebo patients were BZ-free ( χ2 = 7.34 ; df 2 ; P < 0.03 ) . Major adverse events for trazodone were sedation and dry mouth , and for valproate , diarrhea , nausea and headaches A multicenter , double-blind , placebo-controlled study was conducted to determine the safety of concurrently using buspirone with alprazolam before and during a gradual tapering of the alprazolam dose . Thirty-six patients received placebo t.i.d . and 36 received buspirone 5 mg . t.i.d . Findings included significantly greater anxiety ( as measured by the Hamilton Rating Scale for Anxiety ) in the placebo group and significantly reduced manifestations of abstinence ( as measured by the Abstinence Rating Scale ) in the buspirone group . Buspirone and alprazolam may be used together safely , and buspirone may be started early in the alprazolam tapering process The present study examined a relapse prevention ( RP ) program delivered via bibliotherapy in the treatment of individuals with panic attacks . Compared with a wait list control group , individuals receiving RP exhibited significant reductions on measures of frequency of panic attacks , panic cognitions , anticipatory anxiety , avoidance , and depression . In addition , individuals in the RP group were more likely to attain a " clinical ly significant change " in status on both panic-free status and level of avoidance more frequently than individuals in the control group . When compared with treatment effects evaluated in two prior phases of the study , the obtained results appear to be the product of a synchronous effect of bibliotherapy and minimal phone contact during the 6-month follow-up period . The results reflect the importance of brief therapist contact in increasing motivation for active participation in bibliotherapy interventions This study aim ed to assess the efficacy of a minimal intervention focusing on hypnotic discontinuation and cognitive-behavioral treatment ( CBT ) for insomnia . Fifty-three adult chronic users of hypnotics were r and omly assigned to an 8-week hypnotic taper program , used alone or combined with a self-help CBT . Weekly hypnotic use decreased in both conditions , from a nearly nightly use at baseline to less than once a week at posttreatment . Nightly dosage ( in lorazepam equivalent ) decreased from 1.67 mg to 0.12 mg . Participants who received CBT improved their sleep efficiency by 8 % , whereas those who did not remained stable . Total wake time decreased by 52 min among CBT participants and increased by 13 min among those receiving the taper schedule alone . Total sleep time remained stable throughout withdrawal in both CBT and taper conditions . The present findings suggest that a systematic withdrawal schedule might be sufficient in helping chronic users stop their hypnotic medication . The addition of a self-help treatment focusing on insomnia , a readily available and cost-effective alternative to individual psychotherapy , produced greater sleep improvement AIMS To evaluate whether gradual benzodiazepine taper combined with cognitive-behavioural treatment is more effective than st and ard treatment for patients with dependence in out-patient clinics . DESIGN A r and omized , controlled clinical trial , using st and ard question naires and serum and urine tests . SETTING S Four public-sector out-patient clinics for alcohol and drug abusers in Helsinki . PARTICIPANTS Seventy-six patients with benzodiazepine dependence ( DSM-III-R ) . Patients taking high doses of the drug or with alcohol use disorders were included to obtain a subject group representative of usual clinical practice . INTERVENTION Subjects received gradual benzodiazepine taper combined with cognitive-behavioural therapy ( experimental group ) or st and ard withdrawal treatment not scheduled by the research ers ( control group ) . MEASUREMENTS The outcome was measured in terms of attaining a state of abstinence or by a decrease in the dosage during the study period of up to 12 months ' duration . FINDINGS No statistically significant differences in the outcomes were observed between the groups . A total of 13 % of the experimental group and 27 % of the control group were able to discontinue drug use . In addition 67 % of the experimental group and 57 % of the control group were able to decrease the dose . CONCLUSIONS The search continues for improved methods of helping patients with complicated benzodiazepine dependence Buspirone is a new antianxiety compound of a totally new type which may avoid the dependence problems of its predecessors . This study was design ed to evaluate any possible cross-tolerance to the benzodiazepines . Twenty-four out patients on long-term therapeutic dose benzodiazepine treatment , who wished to discontinue treatment , were allocated r and omly to placebo substitution or buspirone substitution and then withdrawal over a total of 10 weeks . Assessment s were made at weekly intervals . Of the 24 patients entered into the trial , 13 received buspirone and 11 placebo . Only five of the buspirone and six of the placebo patients successfully completed withdrawal . Some anxiolytic action of buspirone was detected , but it was insufficient to material ly assist the withdrawal . No evidence was found that buspirone was cross-tolerant to the benzodiazepines . It was concluded that buspirone does not help benzodiazepine withdrawal and does not suppress benzodiazepine withdrawal symptoms BACKGROUND Benzodiazepines are the most frequently used drug for the treatment of insomnia . Prolonged use of benzodiazepine therapy is not recommended . However , many patients , particularly older patients , have difficulties discontinuing therapy . Melatonin , a hormone that is produced at night by the pineal gl and , promotes normal sleep in humans and augments sleep induction by benzodiazepine therapy . OBJECTIVE To assess whether the administration of melatonin could facilitate the discontinuation of benzodiazepine therapy in patients with insomnia . METHODS Thirty-four subjects receiving benzodiazepine therapy were enrolled in the 2-period study . In period 1 , patients received ( double-blinded ) melatonin ( 2 mg in a controlled-release formulation ) or a placebo nightly for 6 weeks . They were encouraged to reduce their benzodiazepine dosage 50 % during week 2 , 75 % during weeks 3 and 4 , and to discontinue benzodiazepine therapy completely during weeks 5 and 6 . In period 2 , melatonin was administered ( single-blinded ) for 6 weeks to all subjects and attempts to discontinue benzodiazepine therapy were resumed . Benzodiazepine consumption and subjective sleep- quality scores were reported daily by all patients . All subjects were then allowed to continue melatonin therapy and follow-up re assessment s were performed 6 months later . RESULTS By the end of period 1 , 14 of 18 subjects who had received melatonin therapy , but only 4 of 16 in the placebo group , discontinued benzodiazepine therapy ( P = .006 ) . Sleep- quality scores were significantly higher in the melatonin therapy group ( P = .04 ) . Six additional subjects in the placebo group discontinued benzodiazepine therapy when given melatonin in period 2 . The 6-month follow-up assessment s revealed that of the 24 patients who discontinued benzodiazepine and received melatonin therapy , 19 maintained good sleep quality . CONCLUSION Controlled-release melatonin may effectively facilitate discontinuation of benzodiazepine therapy while maintaining good sleep quality OBJECTIVE To investigate the effectiveness of a minimal intervention in reducing the volume of prescription of benzodiazepines at the regional level . DESIGN Prospect i ve . METHOD Patients on compulsory health insurance who had received 180 or more daily doses of benzodiazepines in the course of one year received a letter from their general practitioner ( GP ) with information about the risks of chronic use , the advice to reduce or stop use , and an invitation to make an appointment to discuss the problem . This intervention took place in 19 GP practice s in East Groningen . A reminder was sent six months later to the patients who had not responded in 9 r and omly selected GP- practice s. Thirty-seven practice s in East Groningen and 91 practice s in Northwest Groningen served as controls . Outcome measures were : ( a ) the percentage of patients who stopped , and ( b ) the change in average benzodiazepine consumption . RESULTS During the period 6 - 12 months after the first letter in the intervention group ( n = 1343 ) , 11.3 % of the patients ( 95 % CI : 9.6 - 13.1 ) received no prescription whatsoever for benzodiazepines compared to 5.4 % ( 4.6 - 6.3 ) and 4.9 % ( 4.2 - 5.5 ) in East Groningen ( n = 2932 ) and in Northwest Groningen ( n = 4562 ) , respectively . The average decrease in prescription volume was 13 % ( -9.9 to -15.1 ) in the intervention group compared to 3 % ( -0.1 to -4.1 ) and 3 % ( -1.5 to -4 ) in the control groups . The reminder sent half a year later had no additional effect . CONCLUSION The informative letter from the GP to chronic users of benzodiazepines with the advice to stop or reduce this use was effective Cyamemazine is an anxiolytic antipsychotic , which reduces ethanol withdrawal symptoms . Here , we investigated if cyamemazine can be also effective as substitute drug to facilitate benzodiazepine withdrawal . A total of 168 patients treated with benzodiazepines for at least 3 months and with a < 18 score in the Hamilton Anxiety Rating Scale ( HARS ) were included in the study . Previous benzodiazepine treatment was withdrawn , and patients were r and omized to a 4-week treatment with cyamemazine ( 25 - 50 mg q.d . ) or bromazepam ( 3 - 6 mg q.d . ) , followed by 2 weeks of placebo . The primary efficacy variable was the maximal anxiety rebound as measured with the HARS during the 42 days of treatment . No statistically significant differences between treatment groups were found for the extent or incidence of rebound anxiety . Considering all dropout patients as withdrawal failures , after 6 months of follow-up , 56/84 patients in the cyamemazine group ( 66.7 % ) and 55/84 patients in the bromazepam group ( 65.5 % ) were successfully withdrawn . 28 patients in the cyamemazine group and 18 in the bromazepam group had an adverse event , including anxiety , insomnia , dry mouth and somnolence . No extra-pyramidal symptoms were reported . In conclusion , cyamemazine was comparable to bromazepam in ensuring successful benzodiazepine withdrawal and in controlling the acute benzodiazepine withdrawal syndrome . Cyamemazine may be useful to facilitate benzodiazepine withdrawal in those patients where bromazepam substitution is not appropriate BACKGROUND Discontinuation of benzodiazepine usage has never been evaluated in economic terms . This study aim ed to compare the relative costs and outcomes of tapering off long-term benzodiazepine use combined with group cognitive behavioural therapy ( TO+CBT ) , tapering off alone ( TOA ) and usual care . METHOD A r and omised controlled trial was conducted , incorporating a cost-effectiveness analysis from a societal as well as a pharmaceutical perspective . The cost of intervention treatment , prescribed drugs , healthcare services , productivity loss , and patients ' costs were measured using drug prescription data and cost diaries . Costs were indexed at 2001 prices . The principal outcome was the proportion of patients able to discontinue benzodiazepine use during the 18-month follow-up . A secondary outcome measure was quality of life ( Health Utility Index Mark III [ HUI-3 ] and the Medical Outcomes Study 36-item Short-Form Health Survey [ SF-36 ] ) . RESULTS A total of 180 patients were r and omised to one of TO+CBT ( n = 73 ) , TOA ( n = 73 ) or usual care ( n = 34 ) . Intervention treatment costs were an average of 172.99Euro per patient for TO+CBT and 69.50Euro per patient for TOA . Both treatment conditions significantly reduced benzodiazepine costs during follow-up compared with usual care . The incremental cost-effectiveness ratios ( ICERs ) showed that , for each incremental 1 % successful benzodiazepine discontinuation , TO+CBT cost 10.30 - 62.53Euro versus usual care , depending on the study perspective . However , TO+CBT was extendedly dominated or was dominated by TOA . This result ed in ICERs of 0.57Euro , 10.21Euro and 48.92Euro for TOA versus usual care from the limited pharmaceutical , comprehensive pharmaceutical and societal perspective , respectively . CONCLUSIONS TO+CBT and TOA both led to a reduction in benzodiazepine costs . However , it remains uncertain which healthcare utilisation has a causal relationship with long-term benzodiazepine consumption or its treatment . Although the ICERs indicated better cost effectiveness for TOA than for TO+CBT , the differences were relatively small . The addition of group CBT to tapering off had no clinical or economic advantages . Extrapolation of our data showed that the investment in TOA was paid back after 19 months when corrected for treatment gain with usual care OBJECTIVE The authors investigated whether cognitive behavioral treatment could facilitate discontinuation of alprazolam therapy and maintenance of drug abstinence among panic disorder patients treated with alprazolam doses sufficient to suppress spontaneous panic attacks . METHOD Twenty-one out patients who met DSM-III-R criteria for panic disorder with mild to severe agoraphobia were made panic-free with alprazolam ( mean dose = 2.2 mg/day ) and were then r and omly assigned to receive either supportive drug maintenance and slow , flexible drug taper or an identical medication treatment plus 12 weeks of concurrent , individual cognitive behavioral treatment . Taper in the combined treatment group was sequenced to conclude before cognitive behavioral treatment ended . RESULTS Twenty subjects completed the study . There was no significant difference between groups in the rate of alprazolam discontinuation ( 80 % and 90 % , respectively , in the alprazolam-only group and the combined treatment group ) . However , during the 6-month follow-up period , half of the subjects who discontinued alprazolam without cognitive behavior therapy , but none of those who were given cognitive behavior therapy , relapsed and resumed alprazolam treatment . CONCLUSIONS Cognitive behavioral treatment administered in parallel with alprazolam maintenance and taper was effective in preventing relapse after drug discontinuation . The results warrant further research on the thoughtful integration of these two therapeutic modalities BACKGROUND The possibility that treatment with tricyclic antidepressants , in the form of dothiepin , might attenuate benzodiazepine withdrawal symptoms was investigated in a double-blind trial . METHOD Eighty-seven non-depressed psychiatric out- patients with putative normal dose benzodiazepine dependence had their benzodiazepines reduced in stepwise amounts of 20 % of the original dose for eight weeks . The patients were r and omised to receive dothiepin ( with dosage increasing to 150 mg/day ) or placebo as an aid to withdrawal before benzodiazepine reduction and these drugs were taken for four further weeks before being stopped . RESULTS Fewer patients entered and completed the study than expected and a Type II error was possible in the results . Although there was some evidence of withdrawal symptoms being less marked in those patients allocated to dothiepin this was independent of any antidepressant effect as depression scores were lower in the placebo group in the early phase of withdrawal ( P < 0.01 ) . Of those completing the study , greater satisfaction ( P = 0.03 ) was recorded by those who had received dothiepin ; no other differences reached statistical significance . CONCLUSIONS Dothiepin ( and by implication other tricyclic antidepressants ) might have some value in reducing benzodiazepine withdrawal symptoms but does not aid drug withdrawal A double-blind study was performed to evaluate carbamazepine for the prophylaxis of benzodiazepine withdrawal syndrome in elderly patients --a controversial subject despite the extensive use of such drugs in old age . Thirty-six out patients aged > or = 60 yrs suffering from general anxiety disorders and benzodiazepine abuse underwent gradual discontinuation of benzodiazepine therapy in two groups , one treated with carbamazepine and one with placebo . The carbamazepine-treated group demonstrated a lower incidence of withdrawal symptoms rated according to the Physician Withdrawal Check List ( p < 0.01 ) , better results with the Hopkins Symptom Check List ( Covi cluster , p < 0.01 ) and a more markedly reduced score with the Hamilton Rating Scale for Anxiety ( p < 0.05 ) . Only 3 out of 18 patients in said group complained of side effects attributable to carbamazepine , which disappeared at lower dosages Thirty-one patients dependent on benzodiazepines were r and omly assigned to either slow withdrawal ( SW ) or abrupt withdrawal under propranolol cover ( PW ) . Of 16 patients in the SW group , 11 successfully withdrew from their drugs , while only 4 out of 15 in the PW group did so . Patients in the SW group had only mild withdrawal symptoms , while those in the PW group suffered more severe symptoms , which lasted around four weeks . In all , 81 % of the whole group suffered withdrawal symptoms of some kind . Patients in both groups were significantly less anxious at the end of the study than at baseline . Younger subjects and those who were more severely anxious at the start of the trial had more difficulty in withdrawing than older and less anxious patients OBJECTIVE The primary disadvantage of high-potency benzodiazepine treatment for panic disorder is the difficulty of discontinuing the treatment . During treatment discontinuation , new symptoms may emerge and anxiety may return , preventing many patients from successfully discontinuing their treatment . In this controlled , r and omized trial the authors investigated the efficacy of a cognitive-behavioral program for patients with panic disorder who were attempting to discontinue treatment with high-potency benzodiazepines . METHOD Out patients treated for panic disorder with alprazolam or clonazepam for a minimum of 6 months and expressing a desire to stop taking the medication ( N = 33 ) were r and omly assigned to one of two taper conditions : a slow taper condition alone or a slow taper condition in conjunction with 10 weeks of group cognitive-behavioral therapy . RESULTS The rate of successful discontinuation of benzodiazepine treatment was significantly higher for the patients receiving the cognitive-behavioral program ( 13 of 17 ; 76 % ) than for the patients receiving the slow taper program alone ( four of 16 ; 25 % ) . There was no difference in the likelihood of discontinuation success between the patients treated with alprazolam and those who received clonazepam . At the 3-month follow-up evaluation , 77 % of the patients in the cognitive-behavioral program who successfully discontinued benzodiazepine treatment remained benzodiazepine free . CONCLUSIONS These findings support the efficacy of cognitive-behavioral interventions in aiding benzodiazepine discontinuation for patients with panic disorder Summary In a double-blind outpatient trial , long-term users of therapeutic doses of benzodiazepines seeking treatment were r and omly assigned to either gradual tapering of their daily active dose ( N = 23 ) or abrupt cessation of benzodiazepine intake ( N = 19 ) . The latter was achieved by substitution of placebo tablets for active benzodiazepines . All subjects received cognitive-behavioural treatment preceded by a 2-week baseline period during which they took their benzodiazepine as usual . Both groups received on average about five therapy sessions involving : goal setting , daily self-monitoring , identification of anxiety-provoking situations , and development of cognitive and behavioural coping . Placebo subjects showed more prominent withdrawal symptomatology and supplemented more often with their own prescription . At the end of treatment , no significant differences were observed in rates of attrition ( 30 % for drug and 16 % for placebo subjects ) or in rates of abstinence ( 30 % for drug and 58 % for placebo ) . However , compared to drug subjects , those treated with placebo were significantly more successful in maintaining abstinence throughout the one-year follow-up period . It was argued that it may be advantageous to expose patients who are dependent on relatively low doses of benzodiazepines to some withdrawal distress during treatment . A relatively inexperienced therapist became as effective as a highly experienced therapist relatively quickly , thus indicating transferability of the treatment Minimal intervention strategies to decrease long-term benzodiazepine use have not yet been evaluated in large primary care based studies with a blinded control condition and a long follow-up period . The purpose of this study was to assess the effects of a letter with a discontinuation advice sent to long-term benzodiazepine users in family practice followed by an evaluation consultation offer . The experimental group consisted of 2425 long-term benzodiazepine users , 1707 of whom were addressed by a discontinuation letter and an evaluation consultation offer . The control group consisted of 1821 long-term users . Primary endpoints were the number of prescribed daily dosages ( PDD ) and the percentage of subjects without prescription ( quitters ) . At 21 months a reduction in benzodiazepine prescription of 26 % was observed in the experimental group , versus 9 % in the control group ( PDD difference=12.5 ; 95%-ci : 8.2 - 16.8 ) . In the experimental group 13 % and in the control group 5 % of the study completers were benzodiazepine prescription free through the full follow-up period ( RR=2.6 ; 95%-ci : 2.0 - 3.4 ) . The percentage of quitters at short-term ( 6 months ) was 24 % in the experimental group versus 12 % in the control group ( RR=2.1 ; 95%-ci : 1.8 - 2.4 ) . It is concluded that this intervention strategy steadily reduces long-term benzodiazepine use in family practice Eighty-four chronic phobic patients were r and omly assigned to self-exposure in vivo instructed by either a psychiatrist , a computer or a book ; mean therapy time per patient was respectively 3.1 , 3.2 and 0 hours . Seventy-one patients completed treatment . All three groups improved substantially and similarly to 6 months follow-up , with no significant difference between them ; self-exposure treatment was effective even without therapist contact . Among the three groups , initial expectation of help and positive attitude to the psychiatrist were equally high and related to subsequent rating of help received . All three groups rated the psychiatrist as more tolerant , reliable , and underst and ing than the computer or book , but these attitudes did not relate to outcome , were initially similar among all three groups , and changed minimally at 6 months follow-up The Internet can reach a large number of people at a low cost and offers the opportunity for 2-way communication . The present study was design ed to evaluate the effects of applied relaxation and problem solving in the treatment of recurrent headache when implemented via the Internet and E-mail . A group of 102 headache sufferers were r and omized to 2 conditions : a 6-week treatment condition or a waiting-list control . The dropout was proportionately large ( 56 % ) , and at the end of the study there were 20 participants in the treatment condition and 25 participants in the control condition . Results showed statistically significant reductions in headache for the treated participants . In 50 % of these , the reduction was clinical ly significant . The Internet has the potential to serve as a complement in the treatment of recurrent headache and deserves further study The objective of this study was to compare the efficacy of homeopathic drugs Homéogène 46 and Sédatif PC with a placebo as substitute for benzodiazepines in patients treated for at least 3 months with low doses ( less than 10 mg/d of diazepam equivalents ) . A double-blind r and omized trial was carried out in general practice . The treatment lasted one month . Several rating scales were used . The main outcome was success/failure defined according to the doctor 's clinical judgement and interruption of treatment . A total of 61 patients were r and omized , and 19 interrupted their treatment . Comparability between the groups was good . No statistically significant difference between homeopathic drugs and placebo was observed for the main outcome or for the secondary outcomes . The lack of statistical power due to accrual difficulties limits the conclusions of this trial which did not confirm the efficacy of homeopathic drugs in this indication SUMMARY Background and objectives : Discontinuation of benzodiazepines can be associated with the emergence of a withdrawal syndrome which compromises successful termination of treatment . The objective of the present study was to evaluate whether a six week administration of captodiamine during benzodiazepine discontinuation could prevent emergence of a benzodiazepine withdrawal syndrome and thus facilitate discontinuation of these drugs . Subjects and methods : A controlled , r and omised , double-blind trial of captodiamine versus placebo was conducted in 81 subjects presenting mild to moderate anxiety and treated for at least 6 months with a stable dose of benzodiazepine . Each subject was gradually weaned from benzodiazepines over a 14 day period using a tapering dose schedule and received captodiamine ( 150 mg/d ) or placebo for 45 days from the beginning of the weaning period . Outcome measures : The primary outcome criterion was the extent of withdrawal symptoms assessed using the Tyrer Benzodiazepine Withdrawal Symptom Question naire . Secondary outcome criteria were ; self-evaluation of tension , anxiety , drowsiness and slowing of physical and mental performance using visual analogue scales ; quality of sleep using the Spiegel question naire ; anxiety using the Hamilton Anxiety Rating Scale ; and cognitive function using a driving stimulation test . Results : Analysis of the primary study criterion revealed a statistically significant difference ( p < 0.0001 ) in the emergence of withdrawal symptoms between the two groups in favour of captodiamine at two , six and eight weeks following initiation of therapy . These results were supported by significant beneficial effects of captodiamine on the majority of secondary outcome measures . The switch to captodiamine was associated with an improvement in vigilance , which may be an advantage for the overall safety of the anxiolytic treatment , for example with regard to road safety . Discontinuation of captodiamine was not associated with the emergence of rebound anxiety . Conclusion : Captodiamine represents an interesting strategy for achieving benzodiazepine substitution with a low risk of dependence or impairment of cognitive function . Further clinical studies addressing the anxiolytic activity and safety of captodiamine in such subjects are merited BACKGROUND The long-term use of benzodiazepines is highly prevalent in developed societies and is not devoid of risks . Withdrawing patients from these drugs is often difficult . Tapering off benzodiazepines has been shown to be a good strategy for discontinuing their long-term use . AIM To establish the efficacy of an intervention programme for reducing the chronic use of benzodiazepines . DESIGN OF STUDY R and omised , two-arm , parallel , non-blinded controlled trial . SETTING Three urban healthcare centres covering a population of 50,000 inhabitants ( Mallorca , Spain ) . METHOD Adult patients ( n = 139 ) taking benzodiazepines daily for more than a year and visited by their family physician were r and omised into an intervention group ( n = 73 ) that received st and ardised advice and a tapering off schedule with biweekly follow-up visits , or into a control group ( n = 66 ) , that was managed following routine clinical practice . Both were followed for a year . RESULTS Patients achieved withdrawal or reduced their dose by at least 50 % after 6 and 12 months . Abstinence and withdrawal symptoms were also measured . Both groups were homogeneous for personal , clinical and psychological characteristics and for benzodiazepine use . Only two patients from each group were lost to follow-up . After 12 months , 33 ( 45.2 % ) patients in the intervention group and six ( 9.1 % ) in the control group had discontinued benzodiazepine use ; relative risk = 4.97 ( 95 % confidence interval [ CI ] = 2.2 to 11.1 ) , absolute risk reduction = 0.36 ( 95 % CI = 0.22 to 0.50 ) . For every three interventions , one patient achieved withdrawal . Sixteen ( 21.9 % ) subjects from the intervention group and 11 ( 16.7 % ) controls reduced their initial dose by more than 50 % . CONCLUSION St and ardised advice given by the family physician , together with a tapering off schedule , is effective for withdrawing patients from long-term benzodiazepine use and is feasible in primary care BACKGROUND Long-term use of hypnotics is not recommended because of risks of dependency and adverse effects on health . The usual clinical management of benzodiazepine dependency is gradual tapering , but when used alone this method is not highly effective in achieving long-term discontinuation . We compared the efficacy of tapering plus cognitive-behavioural therapy for insomnia with tapering alone in reducing the use of hypnotics by older adults with insomnia . METHODS People with chronic insomnia who had been taking a benzodiazepine every night for more than 3 months were recruited through media advertisements or were referred by their family doctors . They were r and omly assigned to undergo either cognitive-behavioural therapy plus gradual tapering of the drug ( combined treatment ) or gradual tapering only . The cognitive-behavioural therapy was provided by a psychologist in 8 weekly small-group sessions . The tapering was supervised by a physician , who met weekly with each participant over an 8-week period . The main outcome measure was benzodiazepine discontinuation , confirmed by blood screening performed at each of 3 measurement points ( immediately after completion of treatment and at 3- and 12-month follow-ups ) . RESULTS Of the 344 potential participants , 65 ( mean age 67.4 years ) met the inclusion criteria and entered the study . The 2 study groups ( 35 subjects in the combined treatment group and 30 in the tapering group ) were similar in terms of demographic characteristics , duration of insomnia and hypnotic dosage . Immediately after completion of treatment , a greater proportion of patients in the combined treatment group had withdrawn from benzodiazepine use completely ( 77 % [ 26/34 ] v. 38 % [ 11/29 ] ; odds ratio [ OR ] 5.3 , 95 % confidence interval [ CI ] 1.8 - 16.2 ; OR after adjustment for initial benzodiazepine daily dose 7.9 , 95 % CI 2.4 - 30.9 ) . At the 12-month follow-up , the favourable outcome persisted ( 70 % [ 23/33 ] v. 24 % [ 7/29 ] ; OR 7.2 , 95 % CI 2.4 - 23.7 ; adjusted OR 7.6 , 95 % CI 2.5 - 26.6 ) ; similar results were obtained at 3 months . INTERPRETATION A combination of cognitive-behavioural therapy and benzodiazepine tapering was superior to tapering alone in the management of patients with insomnia and chronic benzodiazepine use . The beneficial effects were sustained for up to 1 year . Applying this multidisciplinary approach in the community could help reduce benzodiazepine use by older people BACKGROUND It is recommended that long-term users of benzodiazepines in general practice be withdrawn from their medication where possible . AIM A study was undertaken to assess the effectiveness of minimal intervention delivered by general practitioners in helping chronic users of benzodiazepines to withdraw from their medication , and to determine the psychological sequelae on patients of such intervention . METHOD Patients taking benzodiazepines regularly for at least one year were recruited by their general practitioner and allocated either to a group receiving brief advice during one consultation supplemented by a self-help booklet or to a control group who received routine care . The patients completed the 12-item general health question naire and a benzodiazepine withdrawal symptom question naire at the outset of the study and at three and six months after this . RESULTS Eighteen per cent of patients in the intervention group ( 9/50 ) had a reduction in benzodiazepine prescribing recorded in the notes compared with 5 % of the 55 patients in the control group ( P < 0.05 ) . In the intervention group , 63 % of patients had a score of two or more on the general health question naire at baseline compared with 52 % at six months . Of the 20 intervention patients reporting benzodiazepine reduction , 60 % had a score of two or more at baseline compared with 40 % at six months . Intervention patients had significantly more qualitative , but not quantitative , withdrawal symptoms at six months compared with baseline . Consultation rates were not increased in the intervention group . CONCLUSION The study indicates that some chronic users can successfully reduce their intake of benzodiazepines with simple advice from the general practitioner and a self-help booklet . This type of intervention does not lead to psychological distress or increased consultation A double-blind placebo-controlled trial of 23 chronic benzodiazepine users showed that overall , buspirone did not appear to be helpful in alleviating benzodiazepine withdrawal symptoms . Buspirone ( 5 mg t.d.s . ) or placebo was administered for four weeks before , during and after diazepam withdrawal . Patients taking buspirone had a markedly higher dropout rate ( seven out of 11 ) than those taking placebo ( one out of 12 ) . Mean daily diazepam dosage at entry was significantly higher in the buspirone group , but overall initial diazepam dosage was not related to outcome . Higher subjectively rated anxiety at the start of withdrawal was significantly related to higher dropout rate , irrespective of treatment , and was greater ( although not significantly so ) in the buspirone group OBJECTIVE This study evaluated the effectiveness of a supervised benzodiazepine taper , singly and combined with cognitive behavior therapy , for benzodiazepine discontinuation in older adults with chronic insomnia . METHOD Seventy-six older adult out patients ( 38 women , 38 men ; mean age of 62.5 years ) with chronic insomnia and prolonged use ( mean duration of 19.3 years ) of benzodiazepine medication for sleep were r and omly assigned for a 10-week intervention consisting of a supervised benzodiazepine withdrawal program ( N=25 ) , cognitive behavior therapy for insomnia ( N=24 ) , or supervised withdrawal plus cognitive behavior therapy ( N=27 ) . Follow-up assessment s were conducted at 3 and 12 months . The main outcome measures were benzodiazepine use , sleep parameters , and anxiety and depressive symptoms . RESULTS All three interventions produced significant reductions in both the quantity ( 90 % reduction ) and frequency ( 80 % reduction ) of benzodiazepine use , and 63 % of the patients were drug-free within an average of 7 weeks . More patients who received medication taper plus cognitive behavior therapy ( 85 % ) were benzodiazepine-free after the initial intervention , compared to those who received medication taper alone ( 48 % ) and cognitive behavior therapy alone ( 54 % ) . The patients in the two groups that received cognitive behavior therapy perceived greater subjective sleep improvements than those who received medication taper alone . Polysomnographic data showed an increase in the amount of time spent in stages 3 and 4 sleep and REM sleep and a decrease in total sleep time across all three conditions from baseline to posttreatment . Initial benzodiazepine reductions were well maintained up to the 12-month follow-up , and sleep improvements became more noticeable over this period . No significant withdrawal symptoms or adverse events were associated with benzodiazepine tapering . CONCLUSIONS A structured , time-limited intervention is effective in assisting chronic users of benzodiazepine medication to discontinue or reduce their use of medication . The addition of cognitive behavior therapy alleviates insomnia , but sleep improvements may become noticeable only after several months of benzodiazepine abstinence Forty patients with a history of difficulty discontinuing long-term , daily benzodiazepine therapy were r and omly assigned , under double-blind conditions , to treatment with carbamazepine ( 200 to 800 mg/d ) or placebo . A gradual taper ( 25 % per week reduction ) off benzodiazepine therapy was then attempted . Five weeks after taper , significantly more patients who had received carbamazepine than placebo remained benzodiazepine free , this despite the fact that no statistically significant differences in withdrawal severity could be demonstrated . Patients receiving carbamazepine reported a larger reduction in withdrawal severity than patients receiving placebo , but only at a trend level , and only on the daily patient-rated withdrawal checklist . Eleven patients ( 28 % ) required antidepressant therapy for depression or panic when assessed at 12-weeks follow-up . The results of this pilot investigation suggest that carbamazepine might have promise as an adjunctive drug therapy for the benzodiazepine withdrawal syndrome , particularly in patients receiving benzodiazepines in daily dosages of 20 mg/d or greater of diazepam equivalents Chronic benzodiazepine ( BDZ ) users often have difficulty with BDZ withdrawal . To examine clinical effects of selective serotonin reuptake inhibitor ( SSRI ) on tapering BDZ use in non-depressive patients , 97 out patients with a history of BDZ use for at least 3 months were recruited at an internal medicine clinic of a university hospital . After the 4th edition of the Diagnostic and Statistical Manual ( DSM-IV ) clinical interviews for screening major depression , 66 out patients ( 68 % ) without the DSM-IV major depression were r and omly assigned to one of three groups : SSRI-assisted BDZ-reduction group ( 10 - 20 mg of paroxetine , n = 22 ) , simple BDZ-reduction group ( no paroxetine , n = 23 ) , and reference group ( no BDZ-reduction , n = 21 ) . A st and ardized 8-week program involving gradual BDZ discontinuation was performed in the two BDZ-reduction groups . The Hamilton Rating Scales for Depression ( HAM-D ) and Anxiety ( HAM-A ) and the BDZ Withdrawal Symptom Question naire were assessed during the intervention period . Those with major depression were excluded from the BDZ-reduction intervention and treated with a different protocol of medication . In total , 10 ( 45.5 % ) in the SSRI-assisted BDZ-reduction group ( n = 22 ) succeeded in becoming BDZ-free after completing the program , whereas only four ( 17.4 % ) in the simple BDZ-reduction group ( n = 23 ) succeeded . The assistance of the SSRI significantly predicted the success of becoming BDZ-free ( P = 0.023 ) , controlling for the effects of age , gender , period of BDZ use , and baseline HAM-D and HAM-A scores . The score changes on the three question naires were comparable ( all P > 0.05 ) among the three groups during the intervention period . The use of SSRI may have beneficial effects on BDZ withdrawal without the worsening of mood states in cases without major depression |
10,725 | 19,521,760 | Adherence to sun protection and screening recommendations is associated with a range of factors , including : female gender , sun-sensitive phenotype , greater perceived risk of skin cancer , greater perceived benefits of sun protection or screening , and doctor recommendation for screening .
The literature suggests that a large proportion of the general population engage in suboptimal levels of sun protection , although there is substantial variability in findings . | Primary prevention and early detection continue to be of paramount importance in addressing the public health threat of skin cancer .
The aim of this systematic review was to provide a comprehensive overview of the prevalence and correlates of skin cancer-related health behaviors in the general population . | BACKGROUND A representative sample of the British population was interviewed to identify the factors associated with sunburn and intention to tan , and the source from which people obtained their information about the risks of sun exposure . METHODS As part of its rolling Omnibus survey , the Office for National Statistics interviewed a r and omly selected representative sample of 1858 adults ( aged 16 or over ) in Great Britain in October 1996 . The analysis and interpretation of the result ing data form the basis of this study . RESULTS The response rate was just below 70 per cent . Forty-three per cent of men and 35 per cent of women reported sunburning in the 12 months to October 1996 . Factors associated with sunburn were : being male , having a skin that tans with difficulty and being younger . Concerning ' intention to tan ' , 34 per cent of men and 39 per cent of women admitted trying . There were associations with having a skin that tans easily , and , less strongly , with being younger . There was a clear association between trying to tan and severity of sunburn . Most people identified television as their main source of information about the dangers of sun exposure , and the majority had seen the sunburn forecasts on weather reports . Comparison with a previous Omnibus sunburn survey from 1993 shows little change in the proportion of the population becoming sunburnt , but some increase in the proportion of men intending to tan . CONCLUSIONS The data allow an insight into current sun-related behaviour and whether there has been a change since 1993 . Health promotion campaigns warning about the risk from the sun may have increased awareness , but have thus far failed to reduce the proportion becoming sunburnt . It is time to re-evaluate the thinking behind such programmes The feasibility of targeted screening for cutaneous malignant melanoma in the UK using a postal question naire and invitation to screening by a consultant dermatologist was investigated in a population based cross-sectional survey . A total of 1600 people aged 25–69 years , stratified by the social deprivation score of wards within one general practice , were r and omly selected from a population of 8000.1227 ( 77 % ) returned the question naire and 896 ( 56 % ) attended the screening clinic . Uptake was lower for men ( P < 0.001 ) , those aged under 50 ( P < 0.001 ) , people from deprived areas ( P < 0.001 ) and skin types III and IV ( men only , P < 0.001 ) . Twenty per cent of women and 10 % of men felt nervous about attending the clinic , but only 4 % were worried by the question naire . The level of agreement between the self- and dermatologist ’s assessment s of risk factors was best for hair colour ( Kappa = 0.67 , sensitivity 73 % and specificity 98 % ) . People tended to under-report their level of risk . Over 95 % knew about at least one major sign , but 54 % reported incorrect signs of melanoma . Targeted screening for melanoma in the UK will be hampered by difficulties in accurately identifying the target population . Strategies to improve skin self-awareness rather than screening should be developed and evaluated . © 2000 Cancer Research Sun exposure is the most important avoidable cause of skin cancers . We report characteristics of a representative sample ( N=2,324 ) of beachgoers in Southeastern New Engl and during the summer of 1995 . This sample was not employing adequate sun protection behaviors ( 83 % did not often avoid the sun during midday and only 45 % often used sunscreen ) . Important demographic and skin cancer risk factor differences in sun protective behaviors and stages of change for sun protection were found , especially differences based on age , gender , and degree of sun sensitivity . Consistent with previous research , increased age , female gender , and greater sun sensitivity were each independently associated with more sun protective behaviors . These findings underscore the need for interventions targeting high-risk population s , such as those receiving high-intensity sun exposures at the beach BACKGROUND Little information is available on the sun-related behavior of teenagers despite the considerable re sources spent to decrease sun exposure in this age group . OBJECTIVE Our purpose was to describe the sun exposure behavior of Australian adolescents and define characteristics that predict use of sun protection . METHODS Cross-sectional study of a r and om sample of 972 school students 13 to 15 years of age from three different locations in Australia ( two urban and one rural ) using a diary to document sun exposure and sun protection on two consecutive weekends . RESULTS More than 80 % of adolescent boys in each place and more than 60 % of adolescent girls in both of the large cities spent more than 2 hours outdoors during the peak ultraviolet ( UV ) periods on each weekend . Neither sunscreen nor hats were used for more than half the time spent in the sun ; however , shirts were worn most of the time . Students who wore hats were more likely to be boys ( odds ratios [ OR ] = 2.2 , 95 % confidence intervals [ CI ] 1.40 to 3.44 ) and live in the rural region ( OR = 4.6 , 95 % CI 2.36 to 9.04 ) . Students who used sunscreen tended to have skin that sunburned easily ( OR = 3.2 , 95 % CI 1.27 to 7.88 ) and score highly on the knowledge questions ( OR = 2.9 , 95 % CI 1.46 - 5.69 ) . This model was not a good predictor of behavior on a subsequent weekend , possibly because behavior was highly variable , with 35 % to 50 % of students changing their pattern of protection use from one weekend to the next . CONCLUSION Adolescents spend long periods on summer weekends in the sun and do not follow recommended sun protection guidelines . The high variability of sun-related behavior makes modeling and consequent development of education programs a difficult task BACKGROUND Adolescence has been identified as a critical period in the etiology of subsequent melanoma and nonmelanocytic skin cancer . This study examines the prevalence and predictors of solar protection use among adolescents . METHODS A total of 3,642 adolescents between the ages of 11 and 16 years were recruited from a r and om sample of 27 schools in an Australian state . The participants completed a vali date d survey that provided information on a range of demographic , knowledge , attitudinal , and behavioral factors . Sun protection practice s adopted during the preceding weekend were assessed using a vali date d self-report diary . A formula that quantifies protection status was then employed to categorize adolescents into those who were using adequate versus low levels of solar protection . RESULTS Overall 54 % of males and 44 % of females were classified as adequately protected during the preceding weekend . Logistic regression analyses identified the following as significant predictors of having an adequate level of sun protection -- gender ( males more likely to be protected ) , age ( 11 to 13 year olds more likely to be protected than 14 to 16 years olds ) , ownership of a broad-brimmed hat or cap , attitudes relating to the discomfort associated with wearing a hat , image to peers , " hassle " associated with the use of sun protective measures , school attended , and sun protective policies of the school . CONCLUSIONS Implication s of these findings for future preventive strategies are discussed and include improved targeting of sun protection programs to non-adopters , modification of attitudes relating to suntans and image to peers , reducing the level of perceived difficulty associated with utilizing sunscreen , and the potential role that schools may play in fostering sun protection This study investigated knowledge , behaviors , and health beliefs of Australian university students ( n=312 ) regarding skin cancers and evaluated the effects of videotaped presentations . Students ' knowledge and health beliefs were assessed , and they then viewed either an informational video , an emotionally involving video , or a control video . Knowledge and beliefs were assessed immediately and 10 weeks later . Postvideo skin protection intentions increased significantly from prevideo assessment among the two intervention groups compared to the controls . Maintenance of skin protection intentions was higher with the emotional video . Health belief variables , particularly perceived barriers , were significant predictors of knowledge , intention , and behavior . However , other variables such as skin type and previous experience with skin cancer were more important . Females had greater knowledge and stronger intentions to prevent skin cancer than males but reported fewer high-risk behaviors OBJECTIVE To describe the prevalence of sun exposure and protective behaviours during leisure time among Canadian adults 25 years of age or more . DESIGN A r and om-digit-dialling telephone household survey of 4023 people 15 years of age or more was completed ; 3449 adults 25 years of age or more responded to questions about sun exposure and protective behaviours from June to August 1996 . RESULTS Many of the adults ( 51 % ) reported getting 30 minutes to 2 hours of daily sun exposure , and 26 % reported getting more than 2 hours . Half ( 50 % ) reported having one or more sunburns during the study period ; 21 % said they actively spent time suntanning . Less than half reported taking adequate protective actions . Women , light-complexioned and adults 65 years or more were more likely than men , medium- or dark-complexioned adults and adults in younger groups to protect themselves . Nearly two-thirds ( 63 % ) of the adults said they forgot to take protective actions , 47 % felt it was inconvenient to do so , and 29 % were not concerned about sun exposure . DISCUSSION Canadian adults , especially younger men , are exposed to significant amounts of sun during summer leisure time , but they do not always protect themselves adequately . Interventions should emphasize and facilitate convenient , effective sun protection strategies In 1983 a classification scheme was proposed for patients with atypical naevi , according to their personal and family history of melanoma and atypical naevi . To assess the predictive value of these features we undertook prospect i ve surveillance of patients at high risk of primary melanoma . We followed up 116 patients each with 3 or more clinical ly atypical naevi for at least 5 years . Patients are examined and naevi are photographed every 3 - 6 months ; lesions showing disturbing change are excised for histopathology . Among 85 patients with no personal or family history of melanoma , 5 invasive ( level 2 or deeper ) melanomas developed during 583 person-years of follow up . The expected number of invasive melanomas in this population would be 0.054 ; the increased risk is significant ( p < 0.001 ; relative risk 92 [ 95 % CI 30 - 216 ] ) . There was a similarly increased risk of new melanoma also among 24 patients with atypical naevi plus a history of previous melanoma ( observed 2 , expected 0.022 , p < 0.001 ; relative risk 91 [ 11 - 328 ] ) . By comparison , no second melanoma developed among 25 patients with previous melanoma but a normal naevus pattern during 213 person-years of similarly intensive follow-up . The risk of melanoma was highest among 7 patients with atypical naevi and a family history of melanoma ( observed 6 , expected 0.009 , p < 0.001 ; relative risk 444 [ 121 - 1138 ] ) . The median thickness of surveillance-detected melanomas was 0.75 mm ( range 0.40 - 1.05 mm ) in this group . This study shows the value of clinical follow-up of high-risk patients to detect early thin melanomas This study explored the prevalence and predictors of solar protection behaviour in a community sample of beachgoers . A total of 670 participants was r and omly selected from six beaches in the Newcastle district . The solar protection behaviour of each participant was assessed by direct observation and interview . A sub sample was also asked to complete a written question naire to assess attitudes to solar protection use , knowledge of skin cancer and awareness of recommended solar protection behaviours . Forty-five per cent of the beachgoers in this sample were using a high level of solar protection , and a substantial proportion ( 16 per cent ) of the sample was not using any kind of solar protection . Sunscreen with SPF 15 + was applied to at least one body region by 69 per cent of the sample , 17 per cent of the sample were wearing a recommended hat , 15.1 per cent were using shade , and 3.4 per cent were wearing a recommended style of shirt at the time of observation . Chi-square analyses of the data for under-15-year-olds indicated that a significantly greater proportion of 0- to 9-year-olds were well protected compared to 11- to 14-year-olds , but there was no difference in use of protection by boys and girls under 15 years of age . Stepwise regression analysis of the adult sample ( 15 years and over ) showed that the predictors of overall level of solar protection were marital status and frequency of skin self-examination in the past 12 months . The practical implication s of these findings for future community-based skin cancer prevention programs are discussed Abstract Objective : Whole-body skin self-examination ( SSE ) with presentation of suspicious lesions to a physician may improve early detection of melanoma . The aim of this study was to establish the prevalence and determinants of SSE in a high-risk population in preparation for a community-based r and omised controlled trial of screening for melanoma . Methods : A telephone survey reached 3110 residents older than 30 years ( overall response rate of 66.9 % ) r and omly selected from 18 regional communities in Queensl and , Australia . Results : Overall , 804 ( 25.9 % ) participants reported whole-body SSE within the past 12 months and 1055 ( 33.9 % ) within the past three years . Whole-body SSE was associated in multivariate logistic regression analysis with younger age ( < 50 years ) ; higher education ; having received either a whole-body skin examination , recommendation or instruction on SSE by a primary care physician ; giving skin checks a high priority ; concern about skin cancer and a personal history of skin cancer . Conclusion : Overall , the prevalence of SSE in the present study is among the highest yet observed in Australia , with about one-third of the adult population reporting whole-body SSE in the past threeyears . People over 50 years , who are at relatively higher risk for skin cancer , currently perform SSE less frequently than younger people BACKGROUND Screening for melanoma by whole-body clinical skin examination or skin self-examination may improve early diagnosis of melanoma . As part of the first phase of a community-based r and omised controlled trial of screening for melanoma , this study examined the prevalence of skin screening intentions and associated factors in a population at high risk for skin cancer . METHODS A telephone survey stratified by gender reached 3,110 participants > or = 30 years representative for the population . RESULTS Overall , 45 % intended to have a clinical skin check , and 72 % intended to examine their own skin within the next 12 months . In multivariate analysis , a history of a clinical skin examination was most strongly related to intention to screen . Concern about skin cancer or a personal history of skin cancer and high susceptibility towards skin cancer were further important determinants of screening intention . Men were less likely than women to intend participation . CONCLUSIONS Given that skin screening is not recommended by health authorities in absence of scientific evidence of benefit , the intention to participate in screening for melanoma in this Australian sample was high . Except for the lower intention among men , screening intention appears to be highest in those at highest risk of melanoma Epidemiologic studies show that farmers are at increased risk of skin cancer , presumed to be secondary to the increased time they spend outdoors with exposure to the sun . We surveyed a r and om sample of farmers and their spouses 40 years of age or older from four rural counties in Michigan on their knowledge , attitudes , and behavior regarding protection of their skin from the sun and screening medical exams for skin cancer . Question naires were completed by 1,342 farmers and their spouses . This was a response rate of 63.5 % . Eighty to ninety percent knew the changes in the skin that could indicate cancer and required medical follow-up . Only 40 % of the men and 65 % of the women were likely to protect their skin when they went outdoors . Increasing age and personal history of skin cancer increased the likelihood of both men and women protecting their skin when they went outside . Additionally , higher-income women were likely to use sun protection . Despite the fact that 90 % of the respondents had had a physical examination in the last three years , less than one third reported ever having had their skin examined for cancer . Increasing age , income , and education increased the likelihood of having had such an exam . The majority of those who had had a skin exam had the exam for a particular skin problem , and not as part of a routine physical examination . Farmers and their spouses need to increase their use of sun protection when going outside . Additionally , health care providers need to routinely include examination of the skin for skin cancer and alert their patients that it is being performed Australian cancer councils recommend the practice of regular self screening of the skin or screening by another person for signs of melanoma and other skin cancers . They also recommend that medical practitioners screen adult patients annually . This study examined the prevalence and predictors of self screening ( or screening by another person ) and screening by a general practitioner in 1344 individuals from r and omly selected households . The results indicated that 48 % of the sample either regularly checked their own skin or had it checked by another person ( such as a spouse ) , and 17 % had been screened by a general practitioner in the preceding 12 months . Overall , this indicates that 50 % of the sample had their skin adequately screened as recommended . Individuals were less likely to have been screened if they were male ; of lower occupational status ; unemployed or too ill to work ; and had only a primary school education . Those who had only basic medical insurance were also less likely to have been screened . A higher prevalence of screening was reported in individuals at greater risk of developing melanoma , in those who perceived themselves as more susceptible to developing melanoma , and in those who believed that there were greater benefits associated with the early detection of melanoma . The implication s of these results for the development of effective public health education programmes , and for increasing the role of general practitioners in the education and screening of the public , are discussed BACKGROUND Some melanomas form on sun-exposed body sites , whereas others do not . We previously proposed that melanomas at different body sites arise through different pathways that have different associations with melanocytic nevi and solar keratoses . We tested this hypothesis in a case-case comparative study of melanoma patients in Queensl and , Australia . METHODS We r and omly selected patients from among three prespecified groups reported to the population -based Queensl and Cancer Registry : those with superficial spreading or nodular melanomas of the trunk ( n = 154 , the reference group ) , those with such melanomas of the head and neck ( n = 77 , the main comparison group ) , and those with lentigo maligna melanoma ( LMM ) ( n = 75 , the chronic sun-exposed group ) . Each participant completed a question naire , and a research nurse counted melanocytic nevi and solar keratoses . We calculated exposure odds ratios ( ORs ) and 95 % confidence intervals ( CIs ) to quantify the association between factors of interest and each melanoma group . RESULTS Patients with head and neck melanomas , compared with patients with melanomas of the trunk , were statistically significantly less likely to have more than 60 nevi ( OR = 0.34 , 95 % CI = 0.15 to 0.79 ) but were statistically significantly more likely to have more than 20 solar keratoses ( OR = 3.61 , 95 % CI = 1.42 to 9.17 ) and also tended to have a past history of excised solar skin lesions ( OR = 1.87 , 95 % CI = 0.89 to 3.92 ) . Patients with LMM were also less likely than patients with truncal melanomas to have more than 60 nevi ( OR = 0.32 , 95 % CI = 0.14 to 0.75 ) and tended toward more solar keratoses ( OR = 2.14 , 95 % CI = 0.88 to 5.16 ) . CONCLUSIONS Prevalences of nevi and solar keratoses differ markedly between patients with head and neck melanomas or LMM and patients with melanomas of the trunk . Cutaneous melanomas may arise through two pathways , one associated with melanocyte proliferation and the other with chronic exposure to sunlight A nationwide r and om sample of 15,169 Norwegian high school students completed a question naire about tanning habits , physical self-concept , attitudes , beliefs , and values . Although 90 % of the adolescents did use sunscreen , less than 25 % used an adequate sun-protection factor , and only 50 % applied the sunscreen an adequate number of times when sunbathing . Multiple regression analyses identified these predictors of sunbathing : opportunity to sunbathe , tender skin , heavy smoking , playing down the risk for skin cancer , valuing physical appearance , friends ' use of sunscreen ( girls only ) , a positive attitude toward having a tan , favorable physical self-concept , friends ' use of sunbeds , and friends ' sunbathing . Sunscreen use was also predicted by opportunity to sunbathe and skin type . Furthermore , the effects of perceived risk for skin cancer and peers ' use of sunscreen were particularly strong BACKGROUND Melanoma is a major public health problem for which early detection may reduce mortality . Since melanoma is generally asymptomatic , this requires skin examination . We sought to evaluate the extent to which the general public has their skin examined by themselves , their partners , or health care providers and the frequency of these examinations . METHODS R and om-digit-dial survey of adult Rhode Isl and ers . RESULTS Only 9 % performed a thorough skin examination ( TSE ) at least once every few months , although over half of the sample reported conducting skin self-examination " deliberately and systematic ally . " Participants were more likely to perform TSE if they were women and if their health care provider had asked them to examine their skin . Most participants reported that their health care provider never or rarely looked at the areas of their skin in which melanoma is most likely to arise . CONCLUSIONS The reported frequency of skin self-examination depends critically on the manner of inquiry . TSE by self or a partner is uncommon , and health care providers do not routinely examine the areas of the skin on which melanomas commonly arise Survival from cutaneous melanoma is mainly dependent on the thickness of the lesion at diagnosis . Skin screening may increase detection of thin lesions and hence improve survival . Within a community-based r and omized controlled trial of a population screening program for melanoma in Queensl and , Australia , 9 communities were r and omly assigned to the 3-year intervention and 9 communities to the control group . Skin screening prevalence was monitored by cross-sectional surveys at baseline , 1 , 2 and 3 years into the intervention and 2 years later . At baseline , prevalence of whole-body clinical skin examination was similar in intervention and control communities . In intervention communities , the prevalence of whole-body skin examinations increased to 29.2 % , an absolute difference of 18 % from baseline , with a peak of 34.8 % 2 years after baseline , and began to decline again at the end of the intervention period . The largest increases were seen in men and women > or = 50 years . Uptake of screening did not differ according to melanoma risk factors ; however , the decline in screening was less in participants who reported a number of melanoma risk factors . The prevalence of skin self-examination remained stable during the intervention program . No changes were observed in the control communities . These results indicate that the intervention program significantly increased the prevalence of whole-body clinical skin examinations in intervention communities . Once the intervention program ceased , and particularly after skin clinics ceased , levels of skin screening began to decline . The provision of specialized skin screening clinics may be needed to achieve sufficient screening rates should population based screening for skin cancer be considered BACKGROUND The prevalence of sunburn and tanning , and associated attitudes were investigated in a national sample of adults in Great Britain . METHODS A r and omly selected cross-sectional sample of 2025 adults aged 16 or over living in Engl and , Scotl and and Wales were interviewed in October 1993 in the Office of Population Censuses and Surveys Omnibus Survey . RESULTS The response rate was 77 per cent . Thirty-seven per cent reported at least one episode of sunburn in the past 12 months , the highest frequencies being found in young age groups , in those with skin that tans poorly ( p < 0.001 ) , and in those who specifically tried to tan in this period ( p < 0.001 ) . Sunbathing was the most frequent activity associated with most severe episodes of sunburn , and occurred most frequently at the beginning of the summer , 46 per cent of episodes occurring abroad . Thirty-three per cent had tried to tan in the past 12 months , the proportion being highest in younger age groups and women ( p < 0.001 ) . Among those with severe sunburn more men ( 34 per cent ) expected to burn when trying to tan than women ( 17 per cent ) . CONCLUSIONS The results provide background information with which to develop and evaluate primary prevention initiatives for skin cancer . These should take into account the strong association between sunburn and the desire to tan , particularly in young adults and men OBJECTIVE To determine the sunburn experience and factors associated with sunburn among white children aged 6 months to 11 years . METHODS Telephone interviews were conducted with parents and primary caretakers of children , selected by r and om , stratified sampling , in the contiguous United States in the summer of 1998 . Information was gathered on demographic characteristics of parents and children , and children 's sunburn experience during the past year , protection from sun exposure , and hours per week spent outdoors . The proportion of children experiencing sunburn in the past year was calculated . Multivariate logistic regression analyses were conducted to determine factors associated with sunburn . Information for 1052 white children was available for the analyses . RESULTS An estimated 42.6 % of U.S. white children experienced one or more sunburns within the past year ( 95 % CI 38.2 - 47.0 ) . Sunburn was less common among children who ever wore hats ( adjusted OR 0.59 , 95 % CI 0.40 - 0.87 ) and more common among children who did not always wear sunscreen ( OR for using sunscreen sometimes compared with always , 2.25 ; 95 % CI 1.31 - 3 . 86 ) . Sunburn was also more common among children with sun-sensitive skin and older children . CONCLUSIONS A large proportion of U.S. white children experience sunburns . Parents and children may benefit from education about protection from sun exposure BACKGROUND Thorough skin self-examination ( TSSE ) has substantial potential to reduce melanoma mortality by early detection . METHODS We interviewed 2,126 patients before a scheduled routine visit with a primary care physician , at which participation in a r and omized trial was offered as part of the Check-It-Out Project . We asked about skin examination behavior and related issues . RESULTS By our a priori definition of TSSE , 18 % of participants performed this activity , but other definitions led to widely varying estimates of 12 % to 38 % . Using a partner to assist in the examination was strongly associated with TSSE . That partner was generally the spouse , and wives were more likely to assist their husb and s in these examinations than the reverse . The availability of a wall mirror was a particularly important predictor of TSSE performance . Visual impairment also affected performance . CONCLUSIONS Estimates of TSSE performance vary substantially with the questions used to elicit this information . Partners , particularly spouses , appear to play a critical role in the conduct of TSSE , and wives appear more often and more effectively engaged in this process . Appropriate circumstances , such as availability of a wall mirror , are also important factors . These findings can be used to design interventions to increase TSSE performance with the ultimate aim of reducing melanoma mortality Two appearance-based interventions design ed to increase sun protection intentions and behaviors were evaluated . Sixty-eight college students in Experiment 1 and 76 beachgoers in Experiment 2 were r and omly assigned to receive or not receive a photoaging ( premature wrinkling and age spots ) information intervention and , separately , to receive or not receive a novel ultraviolet ( UV ) photo intervention that makes the negative-appearance consequences of UV exposure more salient . Both experiments indicated that the UV photo intervention significantly increased intentions to use sunscreen in the future . A follow-up conducted with the beach sample indicated that UV photo information also produced greater protective behaviors for incidental sun exposure and that the combination of UV photo and photoaging information result ed in substantially lower reported sunbathing BACKGROUND Because an estimated 50 % to 80 % of the skin 's lifetime sun damage is thought to occur in childhood and adolescence , it is during these critical periods that intense , intermittent sun exposure causing burning increases melanoma risk . METHODS A 1997 telephone survey of 503 households evaluated parental attitudes about their child having a tan , and ease of practicing sun protection , sun protection methods used , and sunburning on 5 successive summer weekends . RESULTS In a r and om sample of 1 child from each household , 13 % of children sunburned during the past week or weekend , and 9 % of their parents experienced a sunburn during the past weekend . Children 's sunburn was significantly associated with sunburn in the adult respondent , increasing age of the child , having fair skin , being white , and using sunscreens . Duration and peak hours of sun exposure were associated for children and parents . Sunscreen with a sun protection factor of at least 15 was the predominant form of sun protection used . Sunscreen use in children was significantly associated with longer duration of sun exposure , sunny weather conditions , younger age , fair skin , a history of sunburns before this study , a family history of skin cancer , and a higher family income . Feeling that a tan appeared healthy was associated with male gender of the adult and increasing age of the child . Complimenting the child on the appearance of a tan was associated with male gender of the adult , older children , children with skin type reported as olive or dark , and lower educational levels . CONCLUSION Although there has been a promising initial effort to alert parents to the need to protect their children from sunburns , many view a tan as healthy and do not effectively implement sun protection behaviors for their children , which results in sunburns . Sun protection that prevents sunburning could be achieved by more children seeking shade , wearing protective clothing , limiting exposure during peak hours , and effectively using sunscreen |
10,726 | 11,034,712 | Nortriptyline produced worse control in diabetes .
REVIEW ER 'S CONCLUSIONS The review provides evidence that antidepressants , significantly more frequently than either placebo or no treament , cause improvement in depression in patients with a wide range of physical diseases . | OBJECTIVES To determine whether antidepressants are clinical ly effective and acceptable for the treatment of depression in people who also have a physical illness . | We studied 11 patients with stable multiple sclerosis ( MS ) with major depression in terms of response to Sertraline at 100 mg q.d . in an open label trial . Patients were evaluated with self assessment measurements ( Carroll scale ) prior to and during treatment . Only one patient discontinued the drug during the three month treatment trial , and this was due to perceived lack of efficacy by the patient . The remainder of the patients completed at least three months of treatment and had significant improvement in depressive symptoms by self assessment measurements . No patients experienced side effects . Sertraline appears to be well tolerated and effective in treatment of major depression in MS . The Carroll scale is an easily administered means of assessing treatment response , and correlated highly with our clinical impressions In the double-blind study of 51 patients with duodenal ulcer the effect of doxepin and placebo was evaluated . Complete healing of the ulcer was found in 19 of 23 patients after 4 weeks of treatment with 50 mg doxepin ( 83 % ) and in 14 of 27 patients given placebo ( 52 % ) ( p less than 0.05 ) . Two patients in the placebo group developed complications necessitating surgical intervention . No serious side effects were registered in the doxepin group The reduction of pain by two antidepressants , clomipramine and mianserin , was , in this study on 253 patients with chronic idiopathic pain syndrome , found to be not better than a placebo when all patients were compared independently of the classification of pain . The improvement rate was around 40 % after 6 weeks of treatment when using a 50 % or better reduction in pain level . However , in patients who fulfilled a checklist definition of minor to major depression ( 30 % of the total patient material ) clomipramine was superior to mianserin and placebo with an improvement rate of 75 % after 6 weeks . Using pain curves over time as outcome measure in the various clinical pain categories it was found that both mianserin and clomipramine seemed superior to placebo in patients with tension headache , but in patients with low back pain syndrome placebo was superior to the two antidepressants . No difference among the three treatments was found in patients with burning mouth syndrome or in patients with abdominal pain . These differences underline the importance of study ing specific pain syndromes rather than composite groups of patients with idiopathic pain . The clinical significance of these pain curves needs further placebo controlled investigations Fluvoxamine belongs to the class of selective serotonin reuptake inhibitors ( SSRIs ) which have recently gained large popularity as antidepressant agents essentially because they lack the most troublesome adverse effects of older antidepressants ( i.e. tricyclic antidepressants ) such as anticholinergic effects and cardiotoxicity . Recent studies in the literature suggest that HIV-1 infected subjects are affected by depressive episodes with a relatively high frequency , often requiring an antidepressant treatment . Due to its favorable adverse effects profile , we used fluvoxamine as first line treatment for sixteen depressed HIV-1 infected subjects . They were administered the drug at a daily dosage of 100 mg in the evening . Fluvoxamine provided a good clinical efficacy for six of these patients , whereas the other ten had to discontinue the drug because of the presence of severe adverse effects such as acute total insomnia , gastro-intestinal disturbances together with anorexia , aggressive and impulsive behavior and excessive sedation . The observed fluvoxamine side-effects are not typical or specific for this particular patient group since they are also described in seronegative subjects taking fluvoxamine ; however , our findings seem to indicate that they become more frequent and more severe when the drug is administered to HIV-1 infected patients BACKGROUND No somatic treatment has been found to be effective for chronic fatigue syndrome ( CFS ) . Antidepressant therapy is commonly used . Fluoxetine is recommended in preference to tricyclic agents because it has fewer sedative and autonomic nervous system effects . However , there have been no r and omised , placebo-controlled , double-blind studies showing the effectiveness of antidepressant therapy in CFS . We have carried out such a study to assess the effect of fluoxetine in depressed and non-depressed CFS patients . METHODS In this r and omised , double-blind study , we recruited 44 patients to the depressed CFS group , and 52 to the non-depressed CFS group . In each group participants were r and omly assigned to receive either fluoxetine ( 20 mg once daily ) or placebo for 8 weeks . The effect of fluoxetine was assessed by question naires , self-observation lists , st and ard neuropsychological tests , and a motion-sensing device ( Actometer ) , which were applied on the day treatment started and on the last day . FINDINGS The two groups were well matched in terms of age , sex distribution , employment and marital status , and duration of CFS . There were no significant differences between the placebo and fluoxetine-treated groups in the change during the 8-week treatment period for any dimension of CFS . There was no change in subjective assessment s of fatigue , severity of depression , functional impairment , sleep disturbances , neuropsychological function , cognitions , or physical activity in the depressed or the non-depressed subgroup . INTERPRETATION Fluoxetine in a 20 mg daily dose does not have a beneficial effect on any characteristic of CFS . The lack of effect of fluoxetine on depressive symptoms in CFS suggests that processes underlying the presentation of depressive symptoms in CFS may differ from those in patients with major depressive disorder OBJECTIVE The authors present preliminary data from two treatment modalities of a r and omized clinical trial in which they compared 16-week interventions of interpersonal psychotherapy to supportive psychotherapy . METHOD HIV-positive patients who were not acutely medically ill and had scores of 15 or higher on the Hamilton Depression Rating Scale were r and omly assigned to one of four treatment modalities . They were assessed by the Hamilton scale and Beck Depression Inventory at 8 and 16 weeks . Most subjects who underwent either interpersonal psychotherapy ( N = 16 ) or supportive psychotherapy ( N = 16 ) were male , gay or bisexual , white , and college educated . RESULTS Results of last-observation-carried-forward and completer analyses showed that scores on the Hamilton scale and Beck Depression Inventory decreased significantly for both treatments . Differential improvement for interpersonal psychotherapy appeared by midtreatment ( week 8) and persisted at termination . CONCLUSIONS This is the first controlled study of individual psychotherapies for depressed HIV-positive patients . Results suggest that a specific antidepressant psychotherapy , interpersonal psychotherapy , has advantages over a supportive therapy The effectiveness of dothiepin ( a tricyclic anti-depressant ) at a dose of 75 mg given orally at night was compared with placebo for 4 weeks in alleviating pain in 60 patients with classical or definite active rheumatoid arthritis . Patients were classified as either ‘ depressed ’ or ‘ not depressed ’ . The week before , during and 2 weeks after the study , 600 mg ibuprofen was given orally three times daily to all patients . Compared with placebo , dothiepin produced a significant reduction in daytime pain by the end of the treatment period . The Hamilton rating scale in ‘ depressed ’ patients was significantly improved in patients given dothiepin . The Cassano – Castrogiovanni self-evaluation rating scale in both ‘ depressed ’ and ‘ not depressed ’ patients showed a tendency ( not significant ) to be improved following dothiepin treatment compared with placebo . These results suggest that patients with rheumatoid arthritis may experience an increase in pain symptoms due to an alteration of mood . Therapy with tricyclic anti-depressants , such as dothiepin , therefore , may determine an improvement of pain indexes besides having an anti-depressant effect In coronary artery disease the patients usually manifest both anxiety and depression disturbances . A controlled clinical study was conducted to test the efficacy of a new antidepressant agent , maprotiline , in the early stages of acute myocardial infa rct ion . The sample consisted of 126 patients , sixty-three receiving orally 25 mg of maprotiline twice daily and the remainder 5 mg of diazepam twice daily . Treatment lasted on an average two weeks ( ten days to eight weeks ) . The depressive and /or anxiety conditions were rated on the basis of a question naire administered before and after treatment . Depression improved markedly in patients receiving maprotiline , while the two drugs developed a comparable anxiolytic action . Tolerability was good . No clinical or ECG evidence of cardiotoxic signs was detected . The importance of a drug with these characteristics in the management of emotional disturbances in the early stages of coronary artery disease is emphasized OBJECTIVE The authors ' first objective was to ascertain whether imipramine is superior to placebo in treating axis I depressive disorders in the context of HIV illness . Supplementary questions were whether severity of immunodeficiency is associated with antidepressant response and whether patients with greater immunodeficiency can tolerate st and ard doses of imipramine . Second , the authors sought to determine whether imipramine treatment is associated with changes in immune status . METHOD A double-blind , r and omized placebo-controlled trial of imipramine was conducted in a university-affiliated research outpatient clinic . After 6 weeks of treatment , responders were maintained double-blind for another 6 weeks and nonresponders were removed from the study and treated openly . All patients were offered 26 weeks of treatment . Of the 97 patients who were r and omly assigned to placebo or imipramine , 80 completed the 6-week phase . Main outcome measures included the Clinical Global Impression , the Hamilton Depression Rating Scale , the Brief Symptom Inventory , and CD4 cell count . RESULTS Among study completers , 31 ( 39 % ) had AIDS . The response rate to imipramine was 74 % and the response rate to placebo was 26 % . There was no difference in depression response between patients with more or less severe immunodeficiency , nor was there a difference in medication dose or side effects . Neither type nor duration of treatment influenced CD4 cell count during the course of treatment . CONCLUSIONS Depressed patients with HIV illness respond to imipramine at the same rate as medically healthy depressed patients . Severity of immunosuppression is not associated with imipramine treatment outcome . There is no evidence that imipramine has negative effects on enumerative measures of immune status ECGs of 50 patients who completed a long-term nortriptyline ( NT ) study are presented at baseline , after 7 weeks on NT , and after 1 year . The ECGs of patients with preexisting cardiac disease were compared with non-cardiac patients . Significant ECG changes and increases in heart rate were observed by Week 7 and persisted at a mean of 55 weeks ( range : 24 - 111 ) in patients who were continued on NT . No significant difference was found in long-term ECG effects in patients with preexisting cardiac disease ; ECG changes reverted to baseline when placebo was substituted . Patients with known cardiac disease did not show significantly worse ECG changes on NT than non-cardiac patients Somatic symptoms often complicate the diagnosis and psychopharmacological treatment of depression in HIV illness . We treated 33 depressed HIV-positive men and women with medically symptomatic HIV or AIDS ( CDC stages 2B , 2C , 3B , or 3C ) in a 6 week open-label trial with sertraline , paroxetine , or fluoxetine , to assess their effectiveness and tolerability . We further assessed whether treatment of depression result ed in a reduction in both affective and somatic symptoms in this medically ill population . Twenty-four subjects ( 73 % ) completed the trial ( 7 on sertraline , 7 on paroxetine , 10 on fluoxetine ) , 20 ( 83 % ) of whom were clinical responders . Nine dropped out within 1 - 3 weeks of treatment because of adverse effects , mostly agitation , anxiety , and insomnia . Subjects who completed 6 weeks of SSRI treatment experienced significant reductions in both affective and somatic symptoms , many of the latter having been attributed to HIV rather than depression . These results suggest that , even in later stages of HIV illness , the contribution of depression to perceived somatic symptoms may be significant , and that these symptoms may improve with antidepressant treatment Sixty patients with chronic pain of the low back or cervical spine concomitant with clinical depression were studied in a 6-week , r and omized , double-blind comparison of doxepin and placebo . Significant improvements in the doxepin-treated group compared to placebo or to baseline values were seen on Hamilton depression scores , Global Assessment Scale scores , pain severity , percent of time pain felt , and effect of pain on activity , sleep , and muscle tension . Some improvements were observed after 1 week of treatment ; the most improvement occurred at 6 weeks , when the mean doxepin dosage was approximately 200 mg/day and plasma doxepin and nordoxepin averaged 80 ng/ml . No significant harmful effects were observed . Neither plasma beta-endorphin nor enkephalin-like activity demonstrated significant differences from baseline . These data indicate that doxepin is a valuable treatment for patients with chronic pain and depression Twenty-seven in patients participating in a stroke rehabilitation program were r and omized to receive either placebo or trazodone hydrochloride ( Desyrel ) beginning a mean ( + /- SEM ) of 44 + /- 4 days after stroke . The target dosage was 200 mg/d . Patients with either a clinical diagnosis of depression or abnormal Zung depression scores showed a consistent trend toward greater improvement in Barthel activities of daily living ( ADL ) scores with trazodone than with placebo . An abnormal dexamethasone suppression test result was associated with significant improvement in the Barthel ADL scores of patients receiving trazodone ( 38 + /- 6 vs 20 + /- 6 for placebo ) . Patients with stroke and evidence of depression are therefore likely to benefit from treatment with trazodone Patients with bilateral forebrain disease may commonly manifest the syndrome of pathologic laughing and weeping . We investigated the efficacy of low-dose amitriptyline in 12 patients in whom this syndrome was a consequence of multiple sclerosis . In a double-blind crossover study comparing amitriptyline with placebo , eight patients experienced dramatic and significant improvement with amitriptyline ( P = 0.02 ) . The mean dose of amitriptyline was 57.8 mg per day and did not exceed 75 mg per day in any patient . Concurrent measurements of depression showed no change during the study . We conclude that amitriptyline is effective in the treatment of this disturbance of affective expression , and that this effect is distinct from the antidepressant effect of the medication BACKGROUND Psychosocial factors have been implicated in the onset and exacerbation of psoriasis . OBJECTIVE We conducted a r and omized , placebo-controlled , double-blind study to investigate the effect of an antidepressant agent , moclobemide , on the course of psoriasis vulgaris . METHODS Sixty subjects were enrolled in the study . Patients were r and omly assigned to treatment groups . Patients received moclobemide 450 mg/day or placebo and a topical corticosteroid ointment ( diflucortolone valerate ) for 6 weeks . Patients were examined at the beginning of the study and at 2-week intervals . At each visit , the severity of psoriasis and psychologic status were evaluated with the Psoriasis Area Severity Index ( PASI ) , Beck Depression Inventory ( BDI ) , Hamilton Rating Scale for Anxiety ( HAM-A ) , Hamilton Rating Scale for Depression ( HRS-D-17 ) and State-Trait Anxiety Inventory including state ( STAI-1 ) and trait anxiety ( STAI-2 ) . RESULTS Treatment efficacy was able to be evaluated in 22 patients in the moclobemide-treated group and in 20 in the placebo-treated group . The improvement rates in PASI , BDI , STAI-1 , and HAM-A scores were significantly higher in the moclobemide treatment group . The level of state anxiety was diminished in the moclobemide group . Correlation was positive between improvement rates of the psoriatic lesions and state anxiety in all patients . CONCLUSION Our results suggest that an antidepressant drug is useful in the treatment of psoriasis Although antidepressant medications are commonly used to treat depression in Parkinson 's disease ( PD ) , little information is available regarding their safety and efficacy in this condition . Sertraline is a relatively selective serotonin reuptake inhibitor with some dopamine reuptake inhibitor activity . It has a favorable tolerability profile , especially in the elderly . We undertook an open-label pilot evaluation of the safety and efficacy of sertraline to treat depression in PD . A total of 15 patients with PD and depression participated in the study . Sertraline was introduced at a daily dose of 25 mg for 1 week and then increased to 50 mg/day . Patients underwent evaluation at baseline and at a final visit approximately 7 weeks later . Sertraline was generally well tolerated , but five patients experienced side effects , and two discontinued medication . Patients taking selegiline experienced more adverse effects . Beck Depression Inventory scores improved significantly ( mean + /- SE = 16.0 + /- 2.0 vs 11.7 + /- 1.9 , p = 0.03 ) , and Unified Parkinson 's Disease Rating Scale and energy-level scores were unchanged . These results suggest that sertraline may be a useful treatment for depression in PD . As substantial placebo effects can occur in studies of PD and depression , placebo-controlled , double-blind studies are warranted The aim of the present study was to confirm the efficacy of antidepressants in post-stroke depression and to identify the factors related to outcome . Subjects consisted of 20 in patients suffering from post-stroke in a rehabilitation hospital . The subjects were treated with various antidepressants , mainly imipramine , amitriptyline , and amoxapine . After 4 weeks of treatment , 13 showed some improvement ; significant improvement in 5 , moderate improvement in 5 , mild improvement in 3 by a clinical global impression . Whereas all the patients aged less than 65 yr were responders , only 3 of the 10 patients over 65 yr were responders . All of the male patients , but only half of the female patients , were responders . With regards to the presence of a spouse , 13 of the 16 patients with a spouse , but none of 4 patients without , showed a response . No significant correlation was found between the occurrence of each depressive symptom and outcome . Thus , the responders were younger and had better social support in comparison with the non-responders . This result implies that antidepressants are effective for post-stroke depression Twenty-four depressed patients with heart disease were treated for four weeks in a double-blind trial of imipramine , doxepin , or placebo to assess the effects of tricyclic antidepressants on ventricular function and rhythm . The tricyclic antidepressants had no effect on left ventricular ejection fraction at rest or during maximal exercise , as measured by radionuclide ventriculograms obtained before and after treatment . Premature ventricular contractions were reduced by imipramine but were not consistently changed by doxepin or placebo . Treatment with imipramine and doxepin , but not placebo , was associated with significant improvement ( P less than 0.001 ) in st and ard ratings of depression . Our findings underscore the need for a re appraisal of the cardiovascular risks of tricyclic antidepressants and suggest that in the absence of severe impairment of myocardial performance , depressed patients with preexisting heart disease can be effectively treated with these agents without an adverse effect on ventricular rhythm or hemodynamic function & NA ; The effect of the selective serotonin reuptake inhibitor paroxetine on diabetic neuropathy symptoms was examined in comparison to imipramine and placebo in a r and omised , double‐blind , cross‐over study . Paroxetine was given as a fixed dose of 40 mg/day , while the dose of imipramine was adjusted to yield optimal plasma levels of imipramine plus desipramine of 400–600 nM. Paroxetine significantly reduced the symptoms of neuropathy as measured by both observer‐ and self‐rating , but was somewhat less effective than imipramine . However , patients showing a weaker response to paroxetine than to imipramine had lower plasma concentrations of paroxetine than patients with similar response to the 2 drugs . On imipramine 5 patients dropped out because of intolerable side effects and 4 of 19 patients completing the study reported withdrawal symptoms after discontinuing imipramine . On paroxetine no patients dropped out due to side effects and no withdrawal symptoms were reported . Self‐rating showed no depressive symptoms at baseline , and no changes during the study . Neither paroxetine nor imipramine caused changes in objective measures of peripheral nerve function . In conclusion , 40 mg paroxetine/day significantly reduced the symptoms in peripheral diabetic neuropathy and it was suggested that by dose adjustment on the basis of drug level monitoring , paroxetine may become as effective as imipramine . Paroxetine was devoid of the often disturbing autonomic side effects limiting the use of imipramine in several patients Seventy consecutive patients presenting with a clinical diagnosis of chronic muscle contraction headache over a two-year period were evaluated for depression and anxiety scores , along with other possible aetiological factors in this form of headache . Fifty-five of these patients ( 33 from a hospital neurology clinic and 22 from a local general practice ) completed a double-blind study to evaluate flupenthixol 0.5 mg twice daily , diazepam 5 mg twice daily and placebo as prophylactic agents . Patients evaluated in the hospital neurology clinic had more frequent headaches of longer duration , higher analgesic consumption and higher depression , but no higher anxiety scores than those in general practice . Flupenthixol and diazepam were both significantly superior to placebo in reducing headaches and analgesic consumption . The trend was for flupenthixol to be superior to diazepam without reaching statistical significance . Flupenthixol was significantly better than diazepam and placebo in the reduction of Hamilton depression scores . This effect was independent of the effect on headache and analgesic reduction |
10,727 | 19,470,990 | Type 2 diabetes is an increasing epidemic in Asia , characterized by rapid rates of increase over short periods and onset at a relatively young age and low body mass index . | CONTEXT With increasing globalization and East-West exchanges , the increasing epidemic of type 2 diabetes in Asia has far-reaching public health and socioeconomic implication s. OBJECTIVE To review recent data in epidemiologic trends , risk factors , and complications of type 2 diabetes in Asia .
EVIDENCE SYNTHESIS The prevalence of diabetes in Asian population s has increased rapidly in recent decades .
In 2007 , more than 110 million individuals in Asia were living with diabetes , with a disproportionate burden among the young and middle aged .
Similarly , rates of overweight and obesity are increasing sharply , driven by economic development , nutrition transition , and increasingly sedentary lifestyles .
While young age of onset and long disease duration place Asian patients with diabetes at high risk for cardiorenal complications , cancer is emerging as an important cause of morbidity and mortality . | CONTEXT Type 2 diabetes is a common manifestation of hemochromatosis , a disease of iron overload . However , it is not clear whether higher iron stores predict the development of type 2 diabetes in a healthy population . OBJECTIVE To examine plasma ferritin concentration and the ratio of the concentrations of transferrin receptors to ferritin in relation to risk of type 2 diabetes . DESIGN , SETTING , AND PARTICIPANTS Prospect i ve nested case-control study within the Nurses ' Health Study cohort . Of the 32 826 women who provided blood sample s during 1989 - 1990 and were free of diagnosed diabetes , cardiovascular disease , and cancer , 698 developed diabetes during 10 years of follow-up . The controls ( n = 716 ) were matched to cases on age , race , and fasting status ; and on body mass index ( BMI ) for cases in the top BMI decile . MAIN OUTCOME MEASURE Incident cases of type 2 diabetes . RESULTS Among cases , the mean ( SD ) concentration of ferritin was significantly higher ( 109 [ 105 ] vs 71.5 [ 68.7 ] ng/mL for controls ; P<.001 for difference ) and the mean ( SD ) ratio of transferrin receptors to ferritin was significantly lower ( 102 [ 205 ] vs 141 [ 340 ] , respectively ; P = .01 ) . In conditional logistic regression stratified on the matching factors and controlled for BMI and other diabetes risk factors , the multivariate relative risks [ RRs ] of incident type 2 diabetes across increasing quintiles of ferritin were 1.00 , 1.09 ( 95 % confidence interval [ CI ] , 0.70 - 1.70 ) , 1.26 ( 95 % CI , 0.82 - 1.95 ) , 1.30 ( 95 % CI , 0.83 - 2.04 ) , and 2.68 ( 95 % CI , 1.75 - 4.11 ) ( P<.001 for trend ) . The RRs across increasing quintiles of transferrin receptors to ferritin ratio were 2.44 ( 95 % CI , 1.61 - 3.71 ) , 1.00 ( 95 % CI , 0.64 - 1.56 ) , 1.13 ( 95 % CI , 0.73 - 1.74 ) , 0.99 ( 95 % CI , 0.64 - 1.53 ) , and 1.00 ( P = .01 for trend ) . Further adjustment for an inflammatory marker ( C-reactive protein ) did not change the results appreciably . The associations persisted within strata defined by levels of BMI , menopausal status , alcohol consumption , and C-reactive protein . CONCLUSION Higher iron stores ( reflected by an elevated ferritin concentration and a lower ratio of transferrin receptors to ferritin ) are associated with an increased risk of type 2 diabetes in healthy women independent of known diabetes risk factors Diabetes mellitus is associated with tuberculosis . A cohort of 42,116 clients aged 65 years or more , enrolled at 18 Elderly Health Service centers in Hong Kong in 2000 , were followed up prospect ively through the territory-wide tuberculosis registry for development of tuberculosis from 3 months after enrollment to December 31 , 2005 , by use of their identity card numbers as unique identifier . The effects of diabetes mellitus and diabetic control on tuberculosis risk were assessed with adjustment for sociodemographic and other background variables . Diabetes mellitus was associated with a modest increase in the risk of active , culture-confirmed , and pulmonary ( with or without extrapulmonary involvement ) but not extrapulmonary ( with or without pulmonary involvement ) tuberculosis , with adjusted hazard ratios of 1.77 ( 95 % confidence interval : 1.41 , 2.24 ) , 1.91 ( 95 % confidence interval : 1.45 , 2.52 ) , 1.89 ( 95 % confidence interval : 1.48 , 2.42 ) , and 1.00 ( 95 % confidence interval : 0.54 , 1.86 ) , respectively . Diabetic subjects with hemoglobin A1c < 7 % at enrollment were not at increased risk . Among diabetic subjects , higher risks of active , culture-confirmed , and pulmonary but not extrapulmonary tuberculosis were observed with baseline hemoglobin A1c > or = 7 % ( vs. < 7 % ) , with adjusted hazard ratios of 3.11 ( 95 % confidence interval : 1.63 , 5.92 ) , 3.08 ( 95 % confidence interval : 1.44 , 6.57 ) , 3.63 ( 95 % confidence interval : 1.79 , 7.33 ) , and 0.77 ( 95 % confidence interval : 0.18 , 3.35 ) , respectively CONTEXT Diabetes is a serious and costly disease that is becoming increasingly common in many countries . The role of diabetes as a cancer risk factor remains unclear . OBJECTIVE To examine the relationship between fasting serum glucose and diabetes and risk of all cancers and specific cancers in men and women in Korea . DESIGN , SETTING , AND PARTICIPANTS Ten-year prospect i ve cohort study of 1,298,385 Koreans ( 829,770 men and 468,615 women ) aged 30 to 95 years who received health insurance from the National Health Insurance Corp and had a biennial medical evaluation in 1992 - 1995 ( with follow-up for up to 10 years ) . MAIN OUTCOME MEASURES Death from cancer and registry-documented incident cancer or hospital admission for cancer . RESULTS During the 10 years of follow-up , there were 20,566 cancer deaths in men and 5907 cancer deaths in women . Using Cox proportional hazards models and controlling for smoking and alcohol use , the stratum with the highest fasting serum glucose ( > or = 140 mg/dL [ > or = 7.8 mmol/L ] ) had higher death rates from all cancers combined ( hazard ratio [ HR ] , 1.29 ; 95 % confidence interval [ CI ] , 1.22 - 1.37 in men and HR , 1.23 ; 95 % CI , 1.09 - 1.39 in women ) compared with the stratum with the lowest level ( < 90 mg/dL [ < 5.0 mmol/L ] ) . By cancer site , the association was strongest for pancreatic cancer , comparing the highest and lowest strata in men ( HR , 1.91 ; 95 % CI , 1.52 - 2.41 ) and in women ( HR , 2.05 ; 95 % CI , 1.43 - 2.93 ) . Significant associations were also found for cancers of the esophagus , liver , and colon/rectum in men and of the liver and cervix in women , and there were significant trends with glucose level for cancers of the esophagus , colon/rectum , liver , pancreas , and bile duct in men and of the liver and pancreas in women . Of the 26,473 total cancer deaths in men and women , 848 were estimated as attributable to having a fasting serum glucose level of less than 90 mg/dL. For cancer incidence , the general patterns reflected those found for mortality . For persons with a diagnosis of diabetes or a fasting serum glucose level greater than 125 mg/dL ( 6.9 mmol/L ) , risks for cancer incidence and mortality were generally elevated compared with those without diabetes . CONCLUSION In Korea , elevated fasting serum glucose levels and a diagnosis of diabetes are independent risk factors for several major cancers , and the risk tends to increase with an increased level of fasting serum glucose Background — Abdominal adiposity is a growing clinical and public health problem . It is not known whether it is similarly associated with cardiovascular disease ( CVD ) and diabetes mellitus in different regions around the world , and thus whether measurement of waist circumference ( WC ) in addition to body mass index ( BMI ) is useful in primary care practice . Methods and Results — R and omly chosen primary care physicians in 63 countries recruited consecutive patients aged 18 to 80 years on 2 prespecified half days . WC and BMI were measured and the presence of CVD and diabetes mellitus recorded . Of the patients who consulted the primary care physicians , 97 % agreed to participate in the present study . Overall , 24 % of 69 409 men and 27 % of 98 750 women were obese ( BMI ≥30 kg/m2 ) . A further 40 % and 30 % of men and women , respectively , were overweight ( BMI 25 to 30 kg/m2 ) . Increased WC ( > 102 for men and > 88 cm for women ) was recorded in 29 % and 48 % , CVD in 16 % and 13 % , and diabetes mellitus in 13 % and 11 % of men and women , respectively . A statistically significant grade d increase existed in the frequency of CVD and diabetes mellitus with both BMI and WC , with a stronger relationship for WC than for BMI across regions for both genders . This relationship between WC , CVD , and particularly diabetes mellitus was seen even in lean patients ( BMI < 25 kg/m2 ) . Conclusions — Among men and women who consulted primary care physicians , BMI and particularly WC were both strongly linked to CVD and especially to diabetes mellitus . Strategies to address this global problem are required to prevent an epidemic of these major causes of morbidity and mortality BACKGROUND Increased abdominal adiposity has been linked to an increase in mortality in population s where many are overweight or obese ; it is unclear whether the same is true in relatively lean population s. METHODS We examined the association between waist-hip ratio and mortality in the Shanghai Women 's Health Study , a population -based , prospect i ve cohort study of Chinese women aged 40 to 70 years enrolled from December 28 , 1996 , through May 23 , 2000 , 95 % of whom had a body mass index ( calculated as weight in kilograms divided by height in meters squared ) of less than 30.0 . Included in this analysis were 72 773 nonsmoking women who had anthropometrics taken by trained interviewers at enrollment and who were followed up through December 31 , 2004 . Deaths were ascertained by biennial home visits and linkage with the vital statistics registry . RESULTS During a mean follow-up of 5.7 years , 1456 deaths occurred . The waist-hip ratio was positively and significantly associated with deaths from all causes , cardiovascular disease , and diabetes ( P<.01 for trend ) . A less significant positive association was found for death from cancer . After adjustment for body mass index and other potential confounders , the relative risks of total mortality were 1 ( reference group ) , 1.28 ( 95 % confidence interval [ CI ] , 1.04 - 1.58 ) , 1.40 ( 95 % CI , 1.14 - 1.72 ) , 1.54 ( 95 % CI , 1.26 - 1.88 ) , and 1.95 ( 95 % CI , 1.60 - 2.38 ) across the lowest to the highest waist-hip ratio quintiles . The positive association appeared to be more evident in women with a lower body mass index . The relative risks of total mortality comparing the extreme waist-hip ratio quintiles were 2.36 ( 95 % CI , 1.71 - 3.27 ) , 1.60 ( 95 % CI , 1.10 - 2.34 ) , and 1.46 ( 95 % CI , 0.97 - 2.20 ) for women with a body mass index of less than 22.3 , 22.3 to 25.1 , and 25.2 or greater , respectively . CONCLUSION Abdominal adiposity independently predicts mortality risk , particularly for nonobese women Prevention of type 2 diabetes by intensive lifestyle intervention design ed to achieve and maintain ideal body weight was assessed in subjects with impaired glucose tolerance ( IGT ) . Male subjects with IGT recruited from health-screening examinees were r and omly assigned in a 4:1 ratio to a st and ard intervention group ( control group ) and intensive intervention group ( intervention group ) . The final numbers of subjects were 356 and 102 , respectively . The subjects in the control group and in the intervention group were advised to maintain body mass index ( BMI ) of < 24.0 kg/m2 and of < 22.0 kg/m2 , respectively , by diet and exercise . In the intervention group , detailed instructions on lifestyle were repeated every 3 - 4 months during hospital visits . Diabetes was judged to have developed when two or more consecutive fasting plasma glucose ( FPG ) values exceeded 140 mg/dl . A 100 g oral glucose tolerance test was performed every 6 months to detect improvement of glucose tolerance . The subjects were seen in an ordinary outpatient clinic . The cumulative 4-year incidence of diabetes was 9.3 % in the control group , versus 3.0 % in the intervention group , and the reduction in risk of diabetes was 67.4 % ( P < 0.001 ) . Body weight decreased by 0.39 kg in the control group and by 2.18 kg in the intervention group ( P < 0.001 ) . The control group was subclassified according to increase and decrease in body weight . The incidence of diabetes was positively correlated with the changes in body weight , and the improvement in glucose tolerance was negatively correlated . Subjects with higher FPG at baseline developed diabetes at a higher rate than those with lower FPG . Higher 2h plasma glucose values and higher BMI values at baseline were also associated with a higher incidence of diabetes , but the differences were not significant . Subjects with a low insulinogenic index ( DeltaIRI/DeltaPG 30 min after an oral glucose load ) developed diabetes at a significantly higher rate than those with a normal insulinogenic index . Comparison of the BMI data and incidence of diabetes in five diabetes prevention studies by lifestyle intervention revealed a linear correlation between the incidence of diabetes and the BMI values , with the exception of the DaQing Study . However , the slope of the reduction in incidence of diabetes in the intensive intervention groups was steeper than expected simply on the basis of the reduction of BMI , suggesting that the effect of lifestyle intervention can not be solely ascribed to the body weight reduction . We conclude that lifestyle intervention aim ed at achieving ideal body weight in men with IGT is effective and can be conducted in an outpatient clinic setting To determine the prevalence of diabetes and hypertension , 6847 subjects of age 15 years or older , were investigated in a suburban population in Bangladesh . Fasting and post-pr and ial ( capillary ) blood glucose ( 2-hPG ) was estimated . According to WHO criteria the crude prevalence of impaired glucose tolerance ( IGT ) was 7.5 % and non-insulin-dependent diabetes mellitus ( NIDDM ) was 4.1 % . The age st and ardized ( 30 - 64 years ) prevalence of IGT was 7.7 % with 95 % confidence interval ( CI ) 6.96 - 8.44 and NIDDM was 4.5 % , CI 3.94 - 5.12 . Compared with the younger subjects the older subjects ( < 40 vs. > or = 40 years ) showed significant association with IGT ( chi2 , 65.9 ; P < 0.001 ) and NIDDM ( chi2 , 92.0 ; P < 0.001 ) . Higher BMI ( < or = 22.0 vs. > 22.1 ) was also significantly associated with IGT ( chi2 , 16.6 ; P < 0.001 ) and NIDDM ( chi2 , 83.9 ; P < 0.001 ) . The higher BMI had stronger association with NIDDM than with IGT . Lower height showed significant association only with NIDDM . The logistic regression analyses also showed that increased age , higher BMI and short stature were independent risks for NIDDM . The study showed an increased prevalence of IGT and NIDDM among the suburban population of Bangladesh and the excess risk was observed with increased age , higher BMI and short stature Few epidemiologic surveys have been performed to assess the prevalence of diabetes in representative sample s , and few data are available on the epidemiologic features of diabetes in Southeast Asia . We report the results of a 1990 study performed in the Hanoi area ( Vietnam ) on 4,912 subjects ( 95.0 % of the eligible population ) , aged 15 years or over , selected by a stratified r and om cluster procedure using the 1989 census list . A two-step design was used : 1 ) screening for diabetes by measuring capillary blood glucose ( CBG ) before dinner with a Glucometer II device ; and 2 ) for subjects with a CBG measurement of > or = 105 mg/dl , a diagnostic test on the following morning , using a 75-g oral glucose tolerance test and World Health Organization criteria ( 93.9 % of the positive screenees took this test ) . CBG values before dinner were unimodally distributed and skewed to the right , increasing with age in both sexes . Women had a significantly higher level of age-adjusted CBG than did men before dinner ( p < 0.0001 ) as well as when fasting ( p < 0.0001 ) and 2 hours after the oral glucose tolerance test ( p = 0.013 ) . The prevalence of diabetes was 1.2 % ( 95 % confidence interval ( CI ) 0.9 - 1.5 ) and of impaired glucose tolerance , 1.6 % ( 95 % CI 1.3 - 2.0 ) . Women had a significantly higher age-adjusted prevalence of diabetes than did men ( relative risk = 2.3 ; 95 % CI 1.3 - 4.1 ) . Of the 63 diabetic subjects , nine ( 14.3 % ) had been diagnosed before the study , only one was obviously insulin dependent , and only one was obese with a body mass index of > or = 27 kg/m2 . The subjects living in the urban areas had higher levels of fasting and 2-hour CBG and a higher diabetes prevalence than did the rural inhabitants ( relative risk = 1.3 ; 95 % CI 1.04 - 3.23 ) . Diabetes appears to be a rare disease in the Hanoi area ( 1.4 % for subjects aged 30 - 64 years , after age st and ardization using the Segi distribution ) , affecting women two times as often as men . Typical insulin-dependent ( type I ) or obese non-insulin-dependent ( type II ) diabetes mellitus patients are uncommon BACKGROUND Intensified multifactorial intervention - with tight glucose regulation and the use of renin-angiotensin system blockers , aspirin , and lipid-lowering agents - has been shown to reduce the risk of nonfatal cardiovascular disease among patients with type 2 diabetes mellitus and microalbuminuria . We evaluated whether this approach would have an effect on the rates of death from any cause and from cardiovascular causes . METHODS In the Steno-2 Study , we r and omly assigned 160 patients with type 2 diabetes and persistent microalbuminuria to receive either intensive therapy or conventional therapy ; the mean treatment period was 7.8 years . Patients were subsequently followed observationally for a mean of 5.5 years , until December 31 , 2006 . The primary end point at 13.3 years of follow-up was the time to death from any cause . RESULTS Twenty-four patients in the intensive-therapy group died , as compared with 40 in the conventional-therapy group ( hazard ratio , 0.54 ; 95 % confidence interval [ CI ] , 0.32 to 0.89 ; P=0.02 ) . Intensive therapy was associated with a lower risk of death from cardiovascular causes ( hazard ratio , 0.43 ; 95 % CI , 0.19 to 0.94 ; P=0.04 ) and of cardiovascular events ( hazard ratio , 0.41 ; 95 % CI , 0.25 to 0.67 ; P<0.001 ) . One patient in the intensive-therapy group had progression to end-stage renal disease , as compared with six patients in the conventional-therapy group ( P=0.04 ) . Fewer patients in the intensive-therapy group required retinal photocoagulation ( relative risk , 0.45 ; 95 % CI , 0.23 to 0.86 ; P=0.02 ) . Few major side effects were reported . CONCLUSIONS In at-risk patients with type 2 diabetes , intensive intervention with multiple drug combinations and behavior modification had sustained beneficial effects with respect to vascular complications and on rates of death from any cause and from cardiovascular causes . ( Clinical Trials.gov number , NCT00320008 . The epidemiology of new patients presenting to Sultanah Aminah Hospital Johor Bahru ( HSAJB ) with end-stage renal disease ( ESRD ) in 2003 and 2004 was analysed . Patients with ESRD were prospect ively registered in the renal replacement therapy ( RRT ) data base in the nephrology unit . The incidence of ESRD and the RRT provision rate in the district of Johor Bahru were calculated according to gender and race . There were 306 new patients in 2003 and 299 in 2004 . Diabetic nephropathy contributed 56.8 % new patients in 2003 and 57.9 % in 2004 . The mean age was 50.8 + 15.1 years in 2003 and 51.3 + 14.2 years in 2004 . Males accounted for 53.3 % in 2003 and 47.8 % in 2004 . Haemodialysis was the commonest form of RRT ( 60.5 % in 2003 , 69.9 % in 2004 ) , followed by continuous ambulatory peritoneal dialysis ( 30.1 % in 2003 , 19.4 % in 2004 ) and renal transplantation ( 5.5 % in 2003 , 2.3 % in 2004 ) . Ninety-one percent of patients in 2003 and 90 % in 2004 were alive at the end of the year they presented . The incidence of ESRD in the district of Johor Bahru was estimated as 136 per million population ( p.m.p . ) in 2003 and 151 p.m.p . in 2004 . In the two year period the incidence of ESRD was higher among females ( 154 p.m.p . ) than males ( 134 p.m.p . ) . Malays ( 194 p.m.p . ) had higher ESRD incidence compared to Chinese ( 126 p.m.p . ) and Indians ( 134 p.m.p . ) . RRT provision in Johor Bahru ( 92.7 % ) did not differ significantly with gender or race . The increasing number of patients presenting to HSAJB with ESRD especially those with diabetic nephropathy is a major concern . Prevention strategies at the primary care level may curb the burden of this chronic disease We described the characteristics in a referred cohort of type II diabetic patients in the Developing Education on Microalbuminuria for Awareness of renal and cardiovascular risk in Diabetes study evaluating the global prevalence and determinants of microalbuminuria ( MA ) . A cross-sectional study evaluating 32,208 type II diabetic patients without known albuminuria from 33 countries was performed . Overall , 8057 patients were excluded , either because of prior known proteinuria or non-diabetic nephropathy ( 3670 ) , or because of invalid urine collection s ( 4387 ) . One single r and om urinary albumin/creatinine ratio was obtained in 24,151 patients ( 75 % ) . The overall global prevalence of normo- , micro- , and macroalbuminuria was 51 , 39 , and 10 % , respectively . The Asian and Hispanic patients had the highest prevalence of a raised urinary albumin/creatinine ratio ( 55 % ) and Caucasians the lowest ( 40.6 ) , P<0.0001 . HbA1c , systolic blood pressure ( BP ) , ethnicity , retinopathy , duration of diabetes , kidney function , body height , and smoking were all independent risk factors of MA , P<0.0001 . Estimated glomerular filtration rate was below 60 ml/min/1.73 m(2 ) in 22 % of the 11,573 patients with available data . Systolic BP below 130 mmHg was found in 33 and 43 % had an HbA1c below 7 % . The frequency of patients receiving aspirin was 32 % , statins 29 % , and BP-lowering therapy 63 % . A high prevalence globally of MA and reduced kidney function , both conditions associated with enhanced renal and cardiovascular risk , was detected in type II diabetic patients without prior known nephropathy . Early detection , monitoring of vascular complications , and more aggressive multifactorial treatment aim ing at renal and vascular protection are urgently needed Objective : To study the inter-relationships between sleeping hours , working hours and obesity in subjects from a working population . Research design : A cross-sectional observation study under the ‘ Better Health for Better Hong Kong ’ Campaign , which is a territory-wide health awareness and promotion program . Subjects:4793 subjects ( 2353 ( 49.1 % ) men and 2440 ( 50.9 % ) women ) . Their mean age ( ±s.d . ) was 42.4±8.9 years ( range 17–83 years , median 43.0 years ) . Subjects were r and omly selected using computer-generated codes in accordance to the distribution of occupational groups in Hong Kong . Results : The mean daily sleeping time was 7.06±1.03 h ( women vs men : 7.14±1.08 h vs 6.98±0.96 h , P<0.001 ) . Increasing body mass index ( BMI ) was associated with reducing number of sleeping hours and increasing number of working hours reaching significance in the whole group as well as among male subjects . Those with short sleeping hour ( 6 h or less ) and long working hours ( > 9 h ) had the highest BMI and waist in both men and women . Based on multiple regression analysis with age , smoking , alcohol drinking , systolic and diastolic blood pressure , mean daily sleeping hours and working hours as independent variables , BMI was independently associated with age , systolic and diastolic blood pressure in women , whereas waist was associated with age , smoking and blood pressure . In men , blood pressure , sleeping hours and working hours were independently associated with BMI , whereas waist was independently associated with age , smoking , blood pressure , sleeping hours and working hours in men . Conclusion : Obesity is associated with reduced sleeping hours and long working hours in men among Hong Kong Chinese working population . Further studies are needed to investigate the underlying mechanisms of this relationship and its potential implication on prevention and management of obesity OBJECTIVE We conducted a prospect i ve study among Japanese Americans of diabetes incidence in relation to visceral and regional adiposity , fasting insulin and C-peptide , and a measure of insulin secretion , because little prospect i ve data exist on these associations . RESEARCH DESIGN AND METHODS Baseline variables included plasma glucose , C-peptide , and insulin measured after an overnight fast and 30 and 120 min after a 75-g oral glucose tolerance test ; abdominal , thoracic , and thigh fat areas by computed tomography ( CT ) ; BMI ( kg/m2 ) ; and insulin secretion ( incremental insulin response [ IIR ] ) . RESULTS Study subjects included 290 second-generation ( nisei ) and 230 third-generation ( sansei ) Japanese Americans without diabetes , of whom 65 and 13 , respectively , developed diabetes . Among nisei , significant predictors of diabetes risk for a 1 SD increase in continuous variables included intra-abdominal fat area ( IAFA ) ( odds ratio , 95 % CI ) ( 1.6 , 1.1 - 2.3 ) , fasting plasma C-peptide ( 1.4 , 1.1 - 1.8 ) , and the IIR ( 0.5 , 0.3 - 0.9 ) after adjusting for age , sex , impaired glucose tolerance , family diabetes history , and CT-measured fat areas other than intra-abdominal . Intra-abdominal fat area remained a significant predictor of diabetes incidence even after adjustment for BMI , total body fat area , and subcutaneous fat area , although no measure of regional or total adiposity was related to development of diabetes . Among sansei , all adiposity measures were related to diabetes incidence , but , in adjusted models , only IAFA remained significantly associated with higher risk ( 2.7 , 1.4 - 5.4 , BMI -adjusted ) . CONCLUSIONS Greater visceral adiposity precedes the development of type 2 diabetes in Japanese Americans and demonstrates an effect independent of fasting insulin , insulin secretion , glycemia , total and regional adiposity , and family history of diabetes OBJECTIVE To study the effect of birth weight on risk of type 2 diabetes in the schoolchildren in Taiwan . RESEARCH DESIGN AND METHODS From 1992 to 1997 , all schoolchildren aged 6 - 18 years were screened for diabetes in Taiwan Province . This cohort consisted of 1,966 patients with diabetes and 1,780 r and omly selected subjects with normal fasting glycemia ( NFG ) . Question naire interviewing was design ed to classify diabetes . The birth weight was obtained from the Taiwan 's Birth Registry . After merging the data , there were 978 subjects , including 429 with type 2 diabetes and 549 with of NFG enrolled in the present analyses . RESULTS The odds ratios ( 95 % CI ) for type 2 diabetes , after adjusting age , sex , BMI , family history of diabetes , and socioeconomic status , were 2.91 ( 1.25 - 6.76 ) for children with low birth weight ( < 2,500 g ) and 1.78 ( 1.04 - 3.06 ) for those with high birth weight ( > or = 4,000 g ) when compared with the referent group ( birth weight 3,000 - 3,499 g ) . The risk of diabetes was still 64 % higher in the high birth weight group [ odds ratio ( OR ) 1.64 ( 95 % CI 0.91 - 2.96 ) ] , even after adjustment for gestational diabetes mellitus ( GDM ) . Patients with type 2 diabetes who were born with high birth weight were more likely to have a higher BMI and diastolic blood pressure as well as a higher family history of diabetes compared with those with low birth weight . CONCLUSIONS A U-shaped relationship between birth weight and risk of type 2 diabetes was found in the schoolchildren aged 6 - 18 years in Taiwan . Schoolchildren with type 2 diabetes who were born with low birth weight had different metabolic phenotypes compared with those born with high birth weight 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 OBJECTIVE To determine the prevalence of diabetes and impaired glucose tolerance ( IGT ) in Yonchon County of South Korea and to investigate their associated factors . RESEARCH DESIGN AND METHODS We performed a population -based cross-sectional study with r and om cluster sampling of residents ≥30 years of age . Among the 3,804 residents sample d , a total of 2,520 participants had a st and ard 75-g oral glucose tolerance test and answered a detailed question naire . We also collected st and ard anthropometric data . RESULTS If the data for participants in the age range of 30–64 years were adjusted to the st and ard world population , the prevalence of diabetes was 7.2 % and the prevalence of IGT was 8.9 % . It was observed that the significant factors associated with diabetes were waist-to-hip circumference ratio , serum triglyceride levels , age , systolic blood pressure , family history of diabetes , and locality . CONCLUSIONS The prevalence of diabetes in Yonchon County was substantially higher than was previously suggested . The risk of diabetes increased with the increased central obesity and metabolic disturbances associated with insulin resistance Aims /hypothesisLifestyle modification helps in the primary prevention of diabetes in multiethnic American , Finnish and Chinese population s. In a prospect i ve community-based study , we tested whether the progression to diabetes could be influenced by interventions in native Asian Indians with IGT who were younger , leaner and more insulin resistant than the above population s. Methods We r and omised 531 ( 421 men 110 women ) subjects with IGT ( mean age 45.9±5.7 years , BMI 25.8±3.5 kg/m2 ) into four groups . Group 1 was the control , Group 2 was given advice on lifestyle modification ( LSM ) , Group 3 was treated with metformin ( MET ) and Group 4 was given LSM plus MET . The primary outcome measure was type 2 diabetes as diagnosed using World Health Organization criteria . Results The median follow-up period was 30 months , and the 3-year cumulative incidences of diabetes were 55.0 % , 39.3 % , 40.5 % and 39.5 % in Groups 1–4 , respectively . The relative risk reduction was 28.5 % with LSM ( 95 % CI 20.5–37.3 , p=0.018 ) , 26.4 % with MET ( 95 % CI 19.1–35.1 , p=0.029 ) and 28.2 % with LSM + MET ( 95 % CI 20.3–37.0 , p=0.022 ) , as compared with the control group . The number needed to treat to prevent one incident case of diabetes was 6.4 for LSM , 6.9 for MET and 6.5 for LSM + MET . Conclusions /interpretationProgression of IGT to diabetes is high in native Asian Indians . Both LSM and MET significantly reduced the incidence of diabetes in Asian Indians with IGT ; there was no added benefit from combining them Aims /hypothesisTo estimate the prevalence and incidence of diabetes mellitus and impaired glucose regulation ( IGR ) in a Chinese population aged 20–94 years . Subjects and methods A group of 5,628 r and omly selected adults , aged 20–94 years , living in the Huayang and Caoyang communities in Shanghai , China , were investigated between 1998 and 2001 . During 2002 - 04 , 2,666 subjects were followed up . All the participants underwent anthropometric measurements , blood biochemical analyses and a 75-g OGTT . Results Based on the 2000 census data of China , the age-st and ardised prevalences were 6.87 % for diabetes and 8.53 % for IGR at baseline . More than two in five cases with diabetes were undiagnosed . The age-adjusted prevalence of diabetes and IGR increased with age . The age-adjusted prevalences of hypertension , dyslipidaemia and overweight in males were significantly higher ( p < 0.001 ) than in females . The 3-year cumulative incidence rates of diabetes and IGR were 4.96 and 11.10 % , respectively . The relative risk of developing diabetes was significantly higher in subjects with IGR than in subjects with NGT ( p < 0.001 ) . Conclusions /interpretationThe prevalence and incidence rates for diabetes or IGR have increased dramatically over the last decades , especially in younger age groups . A large proportion of cases are undiagnosed . We strongly recommend that population -based diabetes screening programmes should be implemented and generalised for younger people Recognizing the problem posed by diabetes mellitus , the National Diabetes Commission was created by Republic Act 8191 in 1996 . The Commission identified the need for a Second National Diabetes Survey to have an up date d estimate of the magnitude of the disease in the country and to have the needed information for developing a diabetes prevention and control program . This paper reports the prevalence of diabetes mellitus and impaired glucose tolerance ( IGT ) in adults and the factors associated with the prevalence of these conditions . A cross-sectional population -based study assessed the occurrence of diabetes and impaired glucose tolerance among a r and om sample of 7044 adults , aged 20 - 65 years who were residents of urban and rural areas in Luzon . Blood glucose level was measured by OGTT using the current WHO criteria . The crude diabetes prevalence of 5.1 % represented a 54 % increase over the figure ( 3.3 % ) for a similar population in Luzon in 1982 . An increase was also noted in the magnitude of IGT which almost doubled from 4.1 % in 1982 to 8.1 % in the present survey . Only one in three diabetics reported that they had diabetes . The frequency of diabetes and IGT in urban and rural areas were about the same , although a substantial increase from the earlier survey was noted in rural areas . Women registered a higher prevalence for both conditions than men . Aside from age and gender , the other correlates of diabetes mellitus were hypertension , family history of diabetes , WHR , BMI , and physical inactivity . IGT had similar correlates as diabetes except physical inactivity . The present findings which are consistent with those of other studies underscore the role of lifestyle behaviors in diabetes and should be the target of intervention to prevent further increase in disease frequency This r and om multistage cross sectional population survey was undertaken to determine the prevalence of diabetes mellitus ( DM ) and impaired fasting glycemia/glucose ( IFG ) in subjects aged 25 years and above in India . The study was carried out in 108 centers ( 49 urban and 59 rural ) to reflect the size and heterogeneity of the Indian population . 41,270 ( 20,534 males and 20,736 females ) subjects were studied . 21,516 ( 10,865 males and 10,651 females ) were from urban areas and 19,754 ( 9669 males and 10,085 females ) from rural areas . Blood sample s were taken after a fast of 10 - 12h and the subjects were categorized as having IFG or DM using the 1997 American Diabetes Association criteria . The age and gender st and ardized prevalence rate for DM and IFG in the total Indian population was 3.3 and 3.6 % respectively ( P < 0.001 ) . The st and ardized prevalence of DM and IFG in urban areas was significantly higher than that for the rural population ( urban DM prevalence 4.6 % versus rural DM prevalence 1.9 % , P < 0.001 ; urban IFG prevalence 4.8 % versus rural IFG prevalence 2.5 % , P < 0.001 ) . There was no statistically significant difference in the prevalence between DM ( 4.6 % ) and IFG ( 4.8 % ) in the urban population . The rural prevalence of IFG ( 2.5 % ) was significantly ( P < 0.001 ) more than the rural prevalence of DM ( 1.9 % ) . Type 2 diabetes is a major health problem is India OBJECTIVE To examine the relationships between central obesity , insulin resistance index , plasma insulin , growth hormone ( GH ) , and cortisol concentrations in 90 young Chinese type 2 diabetic patients ( aged 33+/-5 years ) and 104 age- and sex-matched control subjects ( aged 32+/-9 years ) . RESEARCH DESIGN AND METHODS Young Chinese diabetic patients ( aged < 40 years ) were recruited from the Prince of Wales Hospital . Blood pressure , height , weight , and waist and hip circumferences were determined . Venous blood was sample d for measurements of fasting plasma glucose , HbA1c , lipids , creatinine , insulin , GH , and cortisol . A 24-h urine was assayed for urinary albumin excretion ( UAE ) . General and central obesity was represented by BMI and waist circumference , respectively . Insulin resistance index was estimated as a product of fasting plasma insulin and glucose concentrations . RESULTS Compared with control subjects , diabetic patients were more obese , hyperglycemic , and had worse lipid profile , higher blood pressures , UAE , insulin resistance index , plasma insulin , and cortisol concentrations ( all P < 0.001 ) but lower GH concentrations ( P < 0.05 ) . When analyzed as a whole group ( n = 194 ) , increasing quartiles of waist circumference were associated with increasing trends of insulin resistance index , plasma insulin , and cortisol concentrations ( all P < 0.01 ) but a decreasing trend of plasma GH concentration ( P < 0.05 ) . Using stepwise multiple regression analysis , waist circumference was only associated with sex variable ( being higher in men ) in the control subjects . In the diabetic group , 51 % of waist circumference was independently related to male sex and increased plasma insulin and cortisol concentrations as well as reduced plasma GH levels . CONCLUSIONS In young Chinese type 2 diabetic patients , hyperinsulinemia , hypercortisolemia , and reduced plasma GH levels were closely associated with central obesity . Based on these findings , we postulate that maladaptive hormonal responses to rapid changes in lifestyle may have led to obesity and type 2 diabetes in these young patients . Alternatively , lifestyle-related obesity may have given rise to these hormonal changes . More studies are required to delineate the nature of these relationships 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 The aim of the study was to determine the temporal changes in the prevalence of type 2 diabetes mellitus and its associated risk factors in a rural population of Bangladesh . A total of 4757 subjects age > /=20 years both male and female were enrolled r and omly in a cross-sectional study in 1999 . The same area and population was reinvestigated in 2004 following the same selection procedure , on a sample of 3981 individuals . Structural and economical changes were noted for the last 5 years in the locality . An increased prevalence of diabetes was found with 6.8 % in the present survey compared with 2.3 % in the earlier survey ( p<0.05 ) . Age , BMI and systolic blood pressure were found to be significant risk factors following both for FBG and for OGTT . WHR was found to be a significant risk factor for men only . A substantial agreement was observed between FBG and OGTT ( kappa 0.63 ) compared to the previous investigation in 1999 ( kappa 0.40 ) . Differences in the indices of obesity , that is BMI , WHR and waist girth , may in part explain the increased prevalence , which in turn may explain due to fast-exp and ed urbanization . The state of affairs warrants immediate measures necessary to prevent the epidemic particularly in the localities that are in the transition phase from rural to semi-urban facilities Although hepatitis C virus ( HCV ) infection is more common among adults with type 2 diabetes , it is uncertain whether HCV precedes the development of diabetes . Thus , we performed a prospect i ve ( case-cohort ) analysis to examine if persons who acquired type 2 diabetes were more likely to have had antecedent HCV infection when enrolled in a community-based cohort of men and women between the ages of 44 and 65 in the United States ( Atherosclerosis Risk in Communities Study [ ARIC ] ) . Among 1,084 adults free of diabetes at baseline , 548 developed diabetes over 9 years of follow-up evaluation . Incident cases of diabetes were identified by using fasting glucose and medical history and HCV antibodies were assessed at baseline . A priori , persons were categorized as low-risk or high-risk for diabetes based on their age and body mass index , factors that appeared to modify the type 2 diabetes-HCV infection incidence estimates . The overall prevalence of HCV in this population was 0.8 % . Among those at high risk for diabetes , persons with HCV infection were more than 11 times as likely as those without HCV infection to develop diabetes ( relative hazard , 11.58 ; 95 % confidence interval , 1.39 - 96.6 ) . Among those at low risk , no increased incidence of diabetes was detected among HCV-infected persons ( relative hazard , 0.48 ; 95 % confidence interval , 0.05 - 4.40 ) . In conclusion , pre-existing HCV infection may increase the risk for type 2 diabetes in persons with recognized diabetes risk factors . Additional larger prospect i ve evaluations are needed to confirm these preliminary findings BACKGROUND Type 2 diabetes affects approximately 8 percent of adults in the United States . Some risk factors -- elevated plasma glucose concentrations in the fasting state and after an oral glucose load , overweight , and a sedentary lifestyle -- are potentially reversible . We hypothesized that modifying these factors with a lifestyle-intervention program or the administration of metformin would prevent or delay the development of diabetes . METHODS We r and omly assigned 3234 nondiabetic persons with elevated fasting and post-load plasma glucose concentrations to placebo , metformin ( 850 mg twice daily ) , or a lifestyle-modification program with the goals of at least a 7 percent weight loss and at least 150 minutes of physical activity per week . The mean age of the participants was 51 years , and the mean body-mass index ( the weight in kilograms divided by the square of the height in meters ) was 34.0 ; 68 percent were women , and 45 percent were members of minority groups . RESULTS The average follow-up was 2.8 years . The incidence of diabetes was 11.0 , 7.8 , and 4.8 cases per 100 person-years in the placebo , metformin , and lifestyle groups , respectively . The lifestyle intervention reduced the incidence by 58 percent ( 95 percent confidence interval , 48 to 66 percent ) and metformin by 31 percent ( 95 percent confidence interval , 17 to 43 percent ) , as compared with placebo ; the lifestyle intervention was significantly more effective than metformin . To prevent one case of diabetes during a period of three years , 6.9 persons would have to participate in the lifestyle-intervention program , and 13.9 would have to receive metformin . CONCLUSIONS Lifestyle changes and treatment with metformin both reduced the incidence of diabetes in persons at high risk . The lifestyle intervention was more effective than metformin The results of several epidemiological studies of serum γ-glutamyltransferase ( GGT ) led us to hypothesise that associations of GGT within its normal range with type 2 diabetes may reflect detrimental effects of xenobiotics found in the environment , such as persistent organic pollutants ( POPs ) . Epidemiological observations showed that serum GGT activity within its normal range strongly predicted future type 2 diabetes ; the predictability of diabetes from obesity was low with GGT at the low end of the normal range ; and GGT showed a positive association with known markers of oxidative stress or inflammation . Experimental findings on cellular GGT suggest that serum GGT levels within the normal range may reflect oxidative stress related to the re- synthesis of intracellular glutathione ; however , this interpretation is not completely satisfying because , in its role of regenerating intracellular glutathione , GGT activity should be antioxidative . Alternatively , serum GGT activity may reflect amounts of glutathione conjugates formed during the metabolism of xenobiotics . Accordingly , we postulate a two-part hypothesis : that the association of serum GGT with type 2 diabetes reflects exposure to POPs , as these substances , which have a very long half-life , may influence diabetes risk by residing in adipose tissue as endocrine disruptors ; and that POPs or similar substances may interact with obesity to cause type 2 diabetes . Supporting this hypothesis , cross-sectional investigation of background exposure to POPs in the National Health and Nutrition Examination Survey showed relationships similar to those observed for GGT , including a powerful association with prevalent diabetes and no association between obesity and diabetes for very low POP concentrations . Our hypothesis can be tested in both prospect i ve studies and toxicological studies The incidence of colorectal cancer is highest in population s that consume an energy-dense diet , have low intakes of vegetables and fruit , or lead a sedentary lifestyle . These factors may influence colorectal carcinogenesis via insulin pathways . We examined whether diabetes mellitus was associated with colorectal cancer in Singapore Chinese , whose body type and lifestyle profiles are distinct from those of Western population s. Between April 1993 and December 1998 , 63,257 Singapore Chinese men and women aged 45 to 74 years were enrolled in a prospect i ve study of diet and cancer . Each subject provided dietary , medical , and lifestyle information through an in-person interview . As of December 31 , 2002 , 636 incident colorectal cancer cases had been diagnosed . A history of physician-diagnosed diabetes was statistically significantly associated with colorectal cancer risk in both men ( relative risk [ RR ] = 1.5 , 95 % confidence interval [ CI ] = 1.2 to 2.1 ) and women ( RR = 1.4 , 95 % CI = 1.0 to 1.9 ) . In stratified analyses , this association remained statistically significant among the subset of diabetics with high total calorie intake and low physical activity levels . Our results support the hypothesis that hyperinsulinemia may play a role in colorectal carcinogenesis , even in a relatively lean population Background To investigate the independent effects of smoking cessation on the risk for developing type 2 diabetes mellitus ( DM ) in the general population . Design An 8-year prospect i ve study . Methods This prospect i ve study started with baseline examinations in 1990 and 1992 , and continued with follow-up examinations every 2 years up to 1998 and 2000 . A total of 27635 nondiabetic men , aged 35–44 years were classified as 5701 nonsmokers , 7477 ex-smokers and 14457 sustained smokers , based on repeated self-reported question naires in 1992 , 1994 and 1996 . Baseline fasting serum glucose level and other risk factors were measured in 1990 and 1992 . The outcome was newly developed DM , defined as a fasting glucose level ≥7.0mmol/l in 1998 and 2000 ( averaged ) . Results Over the 8 years , 1170 men ( 4.2 % ) developed DM . When compared with nonsmokers , the fully adjusted risk ratio of ex-smokers and sustained smokers for diabetes was 1.22 [ 95 % confidence interval ( CI ) , 0.96–1.55 ] and 1.60 ( 95 % CI , 1.29–1.97 ) , respectively . Among the ex-smokers , the risk for diabetes differed according to the quit-smoking period . Compared with nonsmokers , the fully adjusted risk ratio for DM in men who quit smoking before 1992 , during 1992–1993 and during 1994–1995 was 0.95 ( 0.72–1.25 ) , 1.44 ( 0.96–2.15 ) and 2.13 ( 1.51–3.00 ) , respectively , after adjustment for age , baseline fasting serum glucose , weight change , baseline body mass index , family history of DM , alcohol consumption and exercise status . Conclusions Our results support cigarette smoking as an independent and modifiable risk factor for DM . Early smoking cessation could decrease the risk for developing DM to that of nonsmokers in the long term BACKGROUND Coronary heart disease ( CHD ) is expected to become one of the major health problems in developing countries such as Thail and where prevalence data are scarce . This study reports the prevalence of CHD , as indicated by electrocardiogram ( ECG ) Minnesota coding , and its risk factors in Thail and . METHODS In 1991 we conducted a cross-sectional ECG survey in a multistage r and om sample of the Thai population , aged > or = 30 . All major cardiovascular risk factors were measured . St and ard supine 12-lead ECG data were collected ; amplitudes and intervals were measured manually and entered into a computer . Abnormal tracings were verified by five cardiologists , and agreement among at least three of them was accepted as final . RESULTS The total sample included 3822 men and 4967 women aged > or = 30 years . The age-st and ardized prevalence rate of CHD was 9.9/1000 ( men 9.2/1000 , women 10.7/ 1000 ) . The age-st and ardized level of major cardiovascular risk factors among men and women respectively were : total cholesterol 4.8 mmol/l ( 187.3 mg/dl ) , 5.1 mmol/l ( 197.7 mg/dl ) ; hypercholesterolaemia ( > or = 6.2 mmol/l ) 12.2 % , 16.9 % ; systolic blood pressure ( mmHg ) 117.8 , 117.7 ; diastolic blood pressure ( mmHg ) 76.9 , 75.8 ; body mass index ( kg/m2 ) 21.7 , 22.8 ; fasting blood sugar 4.8 mmol/l ( 87.9 mg/dl ) , 5.0 mmol/l ( 90.3 mg/dl ) ; hypertension ( > or = 160/95 + /- on antihypertensive drugs ) 6.3 % , 8.1 % ; smoking 65.1 % , 8.5 % ; diabetes mellitus ( > or = 7.8 mmol/l ) 2.4 % , 3.7 % ; obesity ( > 25 kg/m2 ) 15.2 % , 27.2 % . CONCLUSIONS Most of the age-adjusted mean values and proportion of major cardiovascular disease risk factors as well as the prevalence of total CHD in the Thai population were much lower than the median of those values found in developing countries OBJECTIVE Microalbuminuria predicts mortality in non-insulin-dependent diabetes mellitus ( NIDDM ) , but its association with deterioration of renal function remains more controversial than in insulin-dependent diabetes mellitus ( IDDM ) . Using albumin-to-creatinine ratios ( ACRs ) in r and om spot urine sample s is a convenient method for evaluating albuminuria . We studied prospect ively the predictive values of albuminuria in NIDDM when assessed by this urine measurement . RESEARCH DESIGN AND METHODS Between 1991 and 1992 , we restudied the clinical and biochemical status of 403 Chinese NIDDM patients recruited in 1989 after a follow-up period of 26.6 ± 3.2 months ( mean ± SD ) . Spot urine ACR was measured on two occasions and microalbuminuria was defined as a mean ACR between 5.6 and 38 mg/mmol . RESULTS From the original cohort , 29 patients had died mostly because of cardiovascular events with or without renal failure . The overall relative risk of death in patients with abnormal albuminuria was 7.1 ( P < 0.001 ) ( microalbuminuria : 3.7 , P = 0.04 ; macroalbuminuria : 11 , P < 0.001 ) . On multivariate analysis , the independent predictive factors for mortality were plasma creatinine ( wald = 12.1 , P < 0.001 ) and glucose concentrations ( wald = 10.4 , P < 0.001 ) in the normo- and microalbuminuric patients ( n = 11 ) and age ( wald = 4.4 , P = 0.03 ) and plasma creatinine ( wald = 8.2 , P < 0.01 ) in the macroalbuminuric group ( n = 18 ) . In the survivors ( n = 374 ) , baseline spot urine ACR was independently associated with 2-year spot urine ACR in the normo- ( P < 0.001 ) , micro- ( P < 0.01 ) , and macroalbuminuric groups ( P = 0.01 ) . In addition , baseline spot urine ACR was independently related to 2-year plasma creatinine ( P = 0.01 ) in the macroalbuminuric group . The rates of change of the reciprocal of plasma creatinine ( Δ [Cr]−1 ) were −27.3 ± 62.5 , −43.4 ± 68.6 , and −108.8 ± 98.81·μmol−1·months−1 in the normo- , micro- , and macroalbuminuric groups , respectively ( P < 0.001 ) . The Δ [Cr]−1 was independently and inversely related to the baseline spot urine ACR ( P < 0.001 ) and 2-year systolic blood pressure ( P < 0.001 ) . CONCLUSIONS Abnormal albuminuria as indicated by a r and om spot urine ACR > 5.6 mg/mmol predicts increased mortality and is associated with the progression of albuminuria and deterioration of renal function in Chinese NIDDM patients There are no vali date d risk scores for predicting coronary heart disease ( CHD ) in Chinese patients with type 2 diabetes mellitus . This study aim ed to vali date the UKPDS risk engine and , if indicated , develop CHD risk scores . A total of 7,067 patients without CHD at baseline were analyzed . Data were r and omly assigned to a training data set and a test data set . Cox models were used to develop risk scores to predict total CHD in the training data set . Calibration was assessed using the Hosmer-Lemeshow test , and discrimination was examined using the area under the receiver-operating characteristic curve in the test data set . During a median follow-up of 5.40 years , 4.97 % of patients ( n = 351 ) developed incident CHD . The UKPDS CHD risk engine overestimated the risk of CHD with suboptimal discrimination , and a new total CHD risk score was developed . The developed total CHD risk score was 0.0267 x age ( years ) - 0.3536 x sex ( 1 if female ) + 0.4373 x current smoking status ( 1 if yes ) + 0.0403 x duration of diabetes ( years ) - 0.4808 x Log(10 ) ( estimated glomerular filtration rate [ ml/min/1.73 m(2 ) ] ) + 0.1232 x Log(10 ) ( 1 + spot urinary albumin-creatinine ratio [ mg/mmol ] ) + 0.2644 x non-high-density lipoprotein cholesterol ( mmol/L ) . The 5-year probability of CHD = 1 - 0.9616(EXP(0.9440 x [ RISK SCORE - 0.7082 ] ) ) . Predicted CHD probability was not significantly different from observed total CHD probability , and the adjusted area under the receiver-operating characteristic curve was 0.74 during 5 years of follow-up . In conclusion , the UKPDS CHD risk engine overestimated the risk of Chinese patients with type 2 diabetes mellitus and the newly developed total CHD risk score performed well in the test data set . External validations are required in other Chinese population AIMS To determine the prevalence of diabetes mellitus and pre-diabetes ( impaired fasting glucose and impaired glucose tolerance ) in adults in Sri Lanka . Projections for the year 2030 and factors associated with diabetes and pre-diabetes are also presented . METHODS This cross-sectional study was conducted between 2005 and 2006 . A nationally representative sample of 5000 adults aged > or= 18 years was selected by a multi-stage r and om cluster sampling technique . Fasting plasma glucose was tested in all participants and a 75-g oral glucose tolerance test was performed in non-diabetic subjects . Prevalence was estimated for those > 20 years of age . RESULTS Response rate was 91 % ( n = 4532 ) , males 40 % , age 46.1 + /- 15.1 years ( mean + /- st and ard deviation ) . The age-sex st and ardized prevalence ( 95 % confidence interval ) of diabetes for Sri Lankans aged > or= 20 years was 10.3 % ( 9.4 - 11.2 % ) [ males 9.8 % ( 8.4 - 11.2 % ) , females 10.9 % ( 9.7 - 12.1 % ) , P = 0.129 ) . Thirty-six per cent ( 31.9 - 40.1 % ) of all diabetic subjects were previously undiagnosed . Diabetes prevalence was higher in the urban population compared with rural [ 16.4 % ( 13.8 - 19.0 % ) vs. 8.7 % ( 7.8 - 9.6 % ) ; P < 0.001 ] . The prevalence of overall , urban and rural pre-diabetes was 11.5 % ( 10.5 - 12.5 % ) , 13.6 % ( 11.2 - 16.0 % ) and 11.0 % ( 10.0 - 12.0 % ) , respectively . Overall , 21.8 % ( 20.5 - 23.1 % ) had some form of dysglycaemia . The projected diabetes prevalence for the year 2030 is 13.9 % . Those with diabetes and pre-diabetes compared with normal glucose tolerance were older , physically inactive , frequently lived in urban areas and had a family history of diabetes . They had higher body mass index , waist circumference , waist-hip ratio , systolic/diastolic blood pressure , low-density lipoprotein cholesterol and triglycerides . Insulin was prescribed to 4.4 % ( 2.7 - 6.1 % ) of all diabetic subjects . CONCLUSIONS One in five adults in Sri Lanka has either diabetes or pre-diabetes and one-third of those with diabetes are undiagnosed BACKGROUND The Asia-Pacific region is thought to be severely affected by diabetes . However , reliable , st and ardised data on prevalence and characteristics of glucose intolerance in Asian population s remain sparse . We describe the results of two field surveys undertaken in Cambodia in 2004 . METHODS 2246 r and omly selected adults aged 25 years and older were examined in two communities , one rural ( Siemreap ) and one semi-urban ( Kampong Cham ) . The diagnosis of diabetes and impaired glucose tolerance was based on 2-h blood glucose estimation using criteria recommended by the latest report of a WHO Expert Group . Blood pressure , anthropometry , habitual diet , and other relevant characteristics were also recorded . FINDINGS Prevalence of diabetes was 5 % in Siemreap and 11 % in Kampong Cham . Prevalence of impaired glucose tolerance was 10 % in Siemreap and 15 % in Kampong Cham . About two-thirds of all cases of diabetes were undiagnosed before the survey . Prevalence of hypertension was 12 % at Siemreap and 25 % at Kampong Cham . People in Kampong Cham had higher estimates of central obesity than those in Siemreap . INTERPRETATION Diabetes and hypertension are not uncommon in Cambodia . A quarter of all adults in the chosen suburban community had some degree of glucose intolerance . Since Cambodian society is relatively poor , and lifestyle is fairly traditional by international st and ards , these findings are unexpected BACKGROUND Diabetes reduces life expectancy by 10 to 12 years , but whether death can be predicted in type 2 diabetes mellitus remains uncertain . METHODS A prospect i ve cohort of 7583 type 2 diabetic patients enrolled since 1995 were censored on July 30 , 2005 , or after 6 years of follow-up , whichever came first . A restricted cubic spline model was used to check data linearity and to develop linear-transforming formulas . Data were r and omly assigned to a training data set and to a test data set . A Cox model was used to develop risk scores in the test data set . Calibration and discrimination were assessed in the test data set . RESULTS A total of 619 patients died during a median follow-up period of 5.51 years , result ing in a mortality rate of 18.69 per 1000 person-years . Age , sex , peripheral arterial disease , cancer history , insulin use , blood hemoglobin levels , linear-transformed body mass index , r and om spot urinary albumin-creatinine ratio , and estimated glomerular filtration rate at enrollment were predictors of all-cause death . A risk score for all-cause mortality was developed using these predictors . The predicted and observed death rates in the test data set were similar ( P > .70 ) . The area under the receiver operating characteristic curve was 0.85 for 5 years of follow-up . Using the risk score in ranking cause-specific deaths , the area under the receiver operating characteristic curve was 0.95 for genitourinary death , 0.85 for circulatory death , 0.85 for respiratory death , and 0.71 for neoplasm death . CONCLUSIONS Death in type 2 diabetes mellitus can be predicted using a risk score consisting of commonly measured clinical and biochemical variables . Further validation is needed before clinical use BACKGROUND The risk of type 2 diabetes mellitus is increased in people who have low birth weights and who subsequently become obese as adults . Whether their obesity originates in childhood and , if so , at what age are unknown . Underst and ing the origin of obesity may be especially important in developing countries , where type 2 diabetes is rapidly increasing yet public health messages still focus on reducing childhood " undernutrition . " METHODS We evaluated glucose tolerance and plasma insulin concentrations in 1492 men and women 26 to 32 years of age who had been measured at birth and at intervals of three to six months throughout infancy , childhood , and adolescence in a prospect i ve , population -based study . RESULTS The prevalence of impaired glucose tolerance was 10.8 percent , and that of diabetes was 4.4 percent . Subjects with impaired glucose tolerance or diabetes typically had a low body-mass index up to the age of two years , followed by an early adiposity rebound ( the age after infancy when body mass starts to rise ) and an accelerated increase in body-mass index until adulthood . However , despite an increase in body-mass index between the ages of 2 and 12 years , none of these subjects were obese at the age of 12 years . The odds ratio for disease associated with an increase in the body-mass index of 1 SD from 2 to 12 years of age was 1.36 ( 95 percent confidence interval , 1.18 to 1.57 ; P<0.001 ) . CONCLUSIONS There is an association between thinness in infancy and the presence of impaired glucose tolerance or diabetes in young adulthood . Crossing into higher categories of body-mass index after the age of two years is also associated with these disorders |
10,728 | 24,102,196 | There is a sound evidence base for the efficacy of systemic therapy for children and adolescents ( and their families ) diagnosed with externalizing disorders | Systemic ( family ) therapy is a widely used psychotherapy approach .
However , most systematic efficacy review s have focused solely on " family-based treatment " rather than on the theoretic orientation " systemic therapy . " | The mechanisms through which multisystemic therapy ( MST ) decreased delinquent behavior were assessed in 2 sample s of juvenile offenders . Sample 1 included serious offenders who were predominantly rural , male , and African American . Sample 2 included substance-abusing offenders who were predominantly urban , male , and Caucasian . Therapist adherence to the MST protocol ( based on multiple respondents ) was associated with improved family relations ( family cohesion , family functioning , and parent monitoring ) and decreased delinquent peer affiliation , which , in turn , were associated with decreased delinquent behavior . Furthermore , changes in family relations and delinquent peer affiliation mediated the relationship between caregiver-rated adherence and reductions in delinquent behavior . The findings highlight the importance of identifying central change mechanisms in determining how complex treatments such as MST contribute to ultimate outcomes OBJECTIVE We used growth mixture modeling to examine heterogeneity in treatment response in a secondary analysis of 2 r and omized controlled trials testing multidimensional family therapy ( MDFT ) , an established evidence -based therapy for adolescent drug abuse and delinquency . METHOD The first study compared 2 evidence -based adolescent substance abuse treatments : individually focused cognitive-behavioral therapy and MDFT in a sample of 224 urban , low-income , ethnic minority youths ( average age = 15 years , 81 % male , 72 % African American ) . The second compared a cross-systems version of MDFT ( MDFT-detention to community ) with enhanced services as usual for 154 youths , also primarily urban and ethnic minority ( average age = 15 years , 83 % male , 61 % African American , 22 % Latino ) , who were incarcerated in detention facilities . RESULTS In both studies , the analyses supported the distinctiveness of 2 classes of substance use severity , characterized primarily by adolescents with higher and lower initial severity ; the higher severity class also had greater psychiatric comorbidity . In each study , the 2 treatments showed similar effects in the classes with lower severity/frequency of substance use and fewer comorbid diagnoses . Further , in both studies , MDFT was more effective for the classes with greater overall substance use severity and frequency and more comorbid diagnoses . CONCLUSIONS Results indicate that for youths with more severe drug use and greater psychiatric comorbidity , MDFT produced superior treatment outcomes A small r and omized trial investigated a new family-based intervention for Hispanic adolescents who met DSM-IV criteria for substance abuse disorder . The Culturally Informed and Flexible Family-Based Treatment for Adolescents ( CIFFTA ) is a tailored/adaptive intervention that includes a flexible treatment manual and multiple treatment components . The study used an " add on " design to isolate the effects on substance abuse , behavior problems , and parenting practice s attributable to the newly developed components . Twenty-eight Hispanic adolescents and their families were r and omized either to the experimental treatment or to traditional family therapy ( TFT ) and were assessed at baseline and 8-month follow-up . Despite the small sample , results revealed statistically significant time × treatment effects on both self-reported drug use ( marijuana + cocaine ) , F(1 , 22 ) = 10.59 , p < .01 , η² = .33 and adolescent reports of parenting practice s , F(1 , 22 ) = 9.01 , p < .01 , η² = .29 . Both sets of analyses favored CIFFTA participants . There was a significant time × treatment effect , F(1 , 22 ) = 6.72 , p = .02 , η² = .23 , favoring CIFFTA on parent report of parenting practice s using a composite that matched the variables used for adolescents , but only a nonsignificant trend , F(1 , 22 ) = 2.43 , p = .13 , η² = .10 , with a composite that used all parenting subscales . Parent reports of adolescent behavior problems did not show a significant time or time × treatment effect . These results show the promise of this adaptive treatment for substance abuse in Hispanic adolescents and suggest the need for a larger r and omized trial to fully investigate this treatment Evaluated the effectiveness of juvenile drug court for 161 juvenile offenders meeting diagnostic criteria for substance abuse or dependence and determined whether the integration of evidence -based practice s enhanced the outcomes of juvenile drug court . Over a 1-year period , a four-condition r and omized design evaluated outcomes for family court with usual community services , drug court with usual community services , drug court with multisystemic therapy , and drug court with multisystemic therapy enhanced with contingency management for adolescent substance use , criminal behavior , symptomatology , and days in out-of-home placement . In general , findings supported the view that drug court was more effective than family court services in decreasing rates of adolescent substance use and criminal behavior . Possibly due to the greatly increased surveillance of youths in drug court , however , these relative reductions in antisocial behavior did not translate to corresponding decreases in rearrest or incarceration . In addition , findings supported the view that the use of evidence -based treatments within the drug court context improved youth substance-related outcomes . Clinical and policy implication s of these findings are discussed OBJECTIVE A r and omized trial assessed the effectiveness of a 2-level strategy for implementing evidence -based mental health treatments for delinquent youth . METHOD A 2 x 2 design encompassing 14 rural Appalachian counties included 2 factors : ( a ) the r and om assignment of delinquent youth within each county to a multisystemic therapy ( MST ) program or usual services and ( b ) the r and om assignment of counties to the ARC ( for availability , responsiveness , and continuity ) organizational intervention for implementing effective community-based mental health services . The design created 4 treatment conditions ( MST plus ARC , MST only , ARC only , control ) . Outcome measures for 615 youth who were 69 % male , 91 % Caucasian , and aged 9 - 17 years included the Child Behavior Checklist and out-of-home placements . RESULTS A multilevel , mixed-effects , regression analysis of 6-month treatment outcomes found that youth total problem behavior in the MST plus ARC condition was at a non clinical level and significantly lower than in other conditions . Total problem behavior was equivalent and at non clinical levels in all conditions by the 18-month follow-up , but youth in the MST plus ARC condition entered out-of-home placements at a significantly lower rate ( 16 % ) than youth in the control condition ( 34 % ) . CONCLUSIONS Two-level strategies that combine an organizational intervention such as ARC and an evidence -based treatment such as MST are promising approaches to implementing effective community-based mental health services . More research is needed to underst and how such strategies can be used effectively in a variety of organizational context s and with other types of evidence -based treatments Runaway youth report a broader range and higher severity of substance-related , mental health and family problems relative to non-runaway youth . Most studies to date have collected self-report data on the family and social history ; virtually no research has examined treatment effectiveness with this population . This study is a treatment development project in which 124 runaway youth were r and omly assigned to ( 1 ) ecologically based family therapy ( EBFT ) or ( 2 ) service as usual ( SAU ) through a shelter . Youth completed an intake , posttreatment , 6 and 12 months follow-up assessment . Youth assigned to EBFT reported greater reductions in overall substance abuse compared to youth assigned to SAU while other problem areas improved in both conditions . Findings suggest that EBFT is an efficacious intervention for this relatively severe population of youth Due to the continuing prevalence of adolescent substance abuse , promising treatment models need to be developed and evaluated . Thus , the purpose of this study was to evaluate the efficacy of two promising models , Strengths Oriented Family Therapy ( SOFT ) and The Seven Challenges(R ) ( 7C ) . Adolescents who qualified for outpatient treatment and agreed to participate in our study were r and omly assigned to one of the two treatments and assessed at 3 and 6-months following baseline . Using a two-part , r and om-effects model , we examined the odds of achieving abstinence or full symptom remission between treatments and over time . For those not achieving full abstinence or full problem remission , we investigated whether frequency of use or symptom severity were reduced at follow-up . Participants in both SOFT and 7C demonstrated significant reductions in substance use and related problems , but treatments did not differ at 3 and 6 months following baseline . Overall , treatment services were delivered as planned . Both SOFT and 7C were efficacious with adolescents who abuse substances , as participants in both conditions were significantly more likely to be in symptom remission or abstinent at follow-up interviews versus at baseline . Replication studies are needed that address this study 's limitations Many family therapies for adolescent drug use include ecological interventions . The purpose of this r and omized clinical trial was to establish whether ecological interventions contribute to the impact of family therapy above and beyond the contributions of family process-only interventions . A family-based ecological approach , structural ecosystems therapy ( SET ) , was compared with family process-only condition ( FAM ) and community services control ( CS ) . One hundred ninety substance-abusing or dependent African American and Hispanic adolescents were r and omized to SET , FAM , or CS . Follow-up assessment s were conducted at 3 , 6 , 12 , and 18 months postr and omization . SET was significantly more efficacious than FAM and CS in reducing adolescent drug use . However , these improvements were limited to Hispanic adolescents . The study demonstrates the importance of investigating changes in adolescent drug use as a result of treatment condition across more than 1 racial/ethnic group This article examined the long-term effects of multisystemic therapy ( MST ) vs. individual therapy ( IT ) on the prevention of criminal behavior and violent offending among 176 juvenile offenders at high risk for committing additional serious crimes . Results from multiagent , multi method assessment batteries conducted before and after treatment showed that MST was more effective than IT in improving key family correlates of antisocial behavior and in ameliorating adjustment problems in individual family members . Moreover , results from a 4-year follow-up of rearrest data showed that MST was more effective than IT in preventing future criminal behavior , including violent offending . The implication s of such findings for the design of violence prevention programs are discussed OBJECTIVE Although several treatments for adolescent substance abuse have been identified as promising by review ers and federal agencies , treatment effects extending beyond 12 months have not been demonstrated in r and omized clinical trials . The primary purpose of this report was to examine the 4-year outcomes of an evidence -based treatment of substance-abusing juvenile offenders . METHOD Eighty of 118 substance-abusing juvenile offenders participated in a follow-up 4 years after taking part in a r and omized clinical trial comparing multisystemic therapy ( MST ) with usual community services . A multi method ( self-report , biological , and archival measures ) assessment battery was used to measure the criminal behavior , illicit drug use , and psychiatric symptoms of the participating young adults . RESULTS Analyses demonstrated significant long-term treatment effects for aggressive criminal activity ( 0.15 versus 0.57 convictions per year ) but not for property crimes . Findings for illicit drug use were mixed , with biological measures indicating significantly higher rates of marijuana abstinence for MST participants ( 55 % versus 28 % of young adults ) . Long-term treatment effects were not observed for psychiatric symptoms . CONCLUSIONS Findings provide some support for the long-term effectiveness of an evidence d-based family-oriented treatment of substance-abusing juvenile offenders . The clinical , research , and policy implication s of these findings are noted OBJECTIVE Although current evidence suggests that the positive effects of multisystemic therapy ( MST ) on serious crime reach as far as young adulthood , the longer term impact of MST on criminal and noncriminal outcomes in midlife has not been evaluated . In the present study , the authors examined a broad range of criminal and civil court outcomes for serious and violent juvenile offenders who participated on average 21.9 ( range = 18.3 - 23.8 ) years earlier in a clinical trial of MST ( C. M. Borduin et al. , 1995 ) . METHOD Participants were 176 individuals who were originally r and omized to MST or individual therapy ( IT ) during adolescence and averaged 3.9 arrests for felonies prior to treatment . Arrest , incarceration , and civil suit data were obtained in middle adulthood when participants were on average 37.3 years old . RESULTS Intent-to-treat analyses showed that felony recidivism rates were significantly lower for MST participants than for IT participants ( 34.8 % vs. 54.8 % , respectively ) and that the frequency of misdemeanor offending was 5.0 times lower for MST participants . In addition , the odds of involvement in family-related civil suits during adulthood were twice as high for IT participants as for MST participants . CONCLUSIONS The present study represents the longest follow-up to date of an MST clinical trial and demonstrates that the positive impact of an evidence -based youth treatment such as MST can last well into adulthood . Implication s of the authors ' findings for policymakers and service providers are discussed Hospitalization and out-of-home placement data for 113 youth participating in a r and omized trial comparing home-based multisystemic therapy ( MST ; n = 57 ) with hospitalization(n = 56 ) for psychiatric crisis stabilization were analyzed following the completion of MST treatment — approximately 4 months post approval for emergency psychiatric hospitalization . Analyses showed that MST prevented any hospitalization for 57 % of the participants in the MST condition and reduced the overall number of days hospitalized by 72 % . Importantly , the reduction in use and length of hospitalization was not offset by increased use of other placement options , as MST reduced days in other out-of-home placements by 49 % . The cost implication s for the viability of MST as an alternative to hospitalization for youth presenting psychiatric emergencies are discussed AIM To examine the efficacy of two adolescent drug abuse treatments : individual cognitive behavioral therapy ( CBT ) and multidimensional family therapy ( MDFT ) . DESIGN A 2 ( treatment condition ) x 4 ( time ) repeated- measures intent-to-treat r and omized design . Data were gathered at baseline , termination , 6 and 12 months post-termination . Analyses used latent growth curve modeling . SETTING Community-based drug abuse clinic in the northeastern United States . PARTICIPANTS A total of 224 youth , primarily male ( 81 % ) , African American ( 72 % ) , from low-income single-parent homes ( 58 % ) with an average age of 15 years were recruited into the study . All youth were drug users , with 75 % meeting DSM-IV criteria for cannabis dependence and 13 % meeting criteria for abuse . MEASUREMENTS Five outcomes were measured : ( i ) substance use problem severity ; ( ii ) 30-day frequency of cannabis use ; ( iii ) 30-day frequency of alcohol use ; ( iv ) 30-day frequency of other drug use ; and ( v ) 30-day abstinence . FINDINGS Both treatments produced significant decreases in cannabis consumption and slightly significant reductions in alcohol use , but there were no treatment differences in reducing frequency of cannabis and alcohol use . Significant treatment effects were found favoring MDFT on substance use problem severity , other drug use and minimal use ( zero or one occasion of use ) of all substances , and these effects continued to 12 months following treatment termination . CONCLUSION Both interventions are promising treatments . Consistent with previous controlled trials , MDFT is distinguished by the sustainability of treatment effects This study investigated the efficacy of brief strategic family therapy ( BSFT ) with Hispanic behavior problem and drug using youth , an underrepresented population in the family therapy research literature . One hundred twenty-six Hispanic families with a behavior problem adolescent were r and omly assigned to 1 of 2 conditions : BSFT or group treatment control ( GC ) . Results showed that , compared to GC cases , BSFT cases showed significantly greater pre- to post-intervention improvement in parent reports of adolescent conduct problems and delinquency , adolescent reports of marijuana use , and observer ratings and self reports of family functioning . These results extend prior findings on the efficacy of family interventions to a difficult to treat Hispanic adolescent sample R and om assignment was made of 182 clinical ly referred marijuana- and alcohol-abusing adolescents to one of three treatments : multidimensional family therapy ( MDFT ) , adolescent group therapy ( AGT ) , and multifamily educational intervention ( MEI ) . Each treatment represented a different theory base and treatment format . All treatments were based on a manual and were delivered on a once-a-week outpatient basis . The therapists were experienced community clinicians trained to model-specific competence prior to the study and then supervised throughout the clinical trial . A theory-based multimodal assessment strategy measured symptom changes and prosocial functioning at intake , termination , and 6 and 12 months following termination . Results indicate improvement among youths in all three treatments , with MDFT showing superior improvement overall . MDFT participants also demonstrated change at the 1-year follow-up period in the important prosocial factors of school/academic performance and family functioning as measured by behavioral ratings . Results support the efficacy of MDFT , a relatively short-term , multicomponent , multitarget , family-based intervention in significantly reducing adolescent drug abuse and facilitating adaptive and protective developmental processes Despite the serious and costly problems presented by juvenile sexual offenders , rigorous tests of promising interventions have rarely been conducted . This study presents a community-based effectiveness trial comparing multisystemic therapy ( MST ) adapted for juvenile sexual offenders with services that are typical of those provided to juvenile sexual offenders in the United States . Youth were r and omized to MST ( n = 67 ) or treatment as usual for juvenile sexual offenders ( TAU-JSO ; n = 60 ) . Outcomes through 12 months postrecruitment were assessed for problem sexual behavior , delinquency , substance use , mental health functioning , and out-of-home placements . Relative to youth who received TAU-JSO , youth in the MST condition evidence d significant reductions in sexual behavior problems , delinquency , substance use , externalizing symptoms , and out-of-home placements . The findings suggest that family- and community-based interventions , especially those with an established evidence -base in treating adolescent antisocial behavior , hold considerable promise in meeting the clinical needs of juvenile sexual offenders AIMS This paper provides a description of the rationale , study design , treatments and assessment procedures used in the Cannabis Youth Treatment ( CYT ) experiment . DESIGN CYT was design ed to ( a ) test the relative effectiveness , cost and benefit-cost of five promising treatment interventions under field conditions and ( b ) provide evidence based manual-guided models of these interventions to the treatment field . SETTING The study involved two community-based treatment programs and two major medical centers . PARTICIPANTS Participants were 600 adolescents recruited from the regular intake who were between the ages of 12 and 18 , had used marijuana in the past 90 days , and met one or more criteria of dependence or abuse . INTERVENTIONS Participants were r and omly assigned to one of five interventions : Motivational Enhancement Therapy ( MET ) , Cognitive Behavioral Therapy ( CBT ) , Family Support Network ( FSN ) , Adolescent Community Reinforcement Approach ( ACRA ) , or Multidimensional Family Therapy ( MDFT ) . MEASUREMENTS Self-report data were collected at intake , 3 , 6 , 9 and 12 months post discharge using the Global Appraisal of Individual Needs ( GAIN ) , as well as several supplemental self-reports , collateral reports , urine testing , and service logs . FINDINGS This paper reports on the study 's implementation including the psychometric properties of the measures ( alphas over 0.8 ) , validity of self-report ( kappa over 0.6 ) , high rates of treatment completion ( 81 % completed two or more months ) , and high rates of follow-up ( over 94 % per wave ) . CONCLUSIONS The feasibility of implementing the CYT manual-guided treatment and quality assurance model in community-based adolescent treatment programs is discussed BACKGROUND Treatments for aggression are based on the underlying causes and may combine pharmacological and environmental or psychotherapeutic measures . The aim of this study was to determine the effectiveness of family psychotherapy as a monotherapy for anger in female youth . METHODS Female youth from a r and omized sample ( 381 families ) were interviewed over the telephone . Those from 36 of the families complained of subjectively increased aggression owing to conflict at home . A total of 13 of these families were r and omly selected and took part in a family therapy programme for 6 months . The control group comprised 12 families . The responder rate was 92.6 % . Aggression and change in aggression were measured using the State-Trait Anger Expression Inventory ( STAXI ) . RESULTS In comparison with the control group , significant changes on all five scales of STAXI ( State-Anger , Trait-Anger , Anger-In , Anger-Out , Anger-Control ) were observed after 6 months in the treated subjects ( differences in change between the two groups were between 5.7 % and 28.6 % ) . CONCLUSION The results of this study show that ambulant family therapy appears to be a safe and effective method in the treatment of anger in aggressive female youth BACKGROUND Many girls bully others . They are conspicuous because of their risk-taking behavior , increased anger , problematic interpersonal relationships and poor quality of life . Our aim was to determine the efficacy of brief strategic family therapy ( BSFT ) for bullying-related behavior , anger reduction , improvement of interpersonal relationships , and improvement of health-related quality of life in girls who bully , and to find out whether their expressive aggression correlates with their distinctive psychological features . METHODS 40 bullying girls were recruited from the general population : 20 were r and omly selected for 3 months of BSFT . Follow-up took place 12 months after the therapy had ended . The results of treatment were examined using the Adolescents ' Risk-taking Behavior Scale ( ARBS ) , the State-Trait Anger Expression Inventory ( STAXI ) , the Inventory of Interpersonal Problems ( IIP-D ) , and the SF-36 Health Survey ( SF-36 ) . RESULTS In comparison with the control group ( CG ) ( according to the intent-to-treat principle ) , bullying behavior in the BSFT group was reduced ( BSFT-G from n = 20 to n = 6 ; CG from n = 20 to n = 18 , p = 0.05 ) and statistically significant changes in all risk-taking behaviors ( ARBS ) , on most STAXI , IIP-D , and SF-36 scales were observed after BSFT . The reduction in expressive aggression ( Anger-Out scale of the STAXI ) correlated with the reduction on several scales of the ARBS , IIP-D , and SF-36 . Follow-up a year later showed relatively stable events . CONCLUSIONS Our findings suggest that bullying girls suffer from psychological and social problems which may be reduced by the use of BSFT . Expressive aggression in girls appears to correlate with several types of risk-taking behavior and interpersonal problems , as well as with health-related quality of life OBJECTIVE To evaluate whether Multisystemic Therapy ( MST ) is more effective in reducing youth offending and out-of-home placement in a large , ethnically diverse , urban U.K. sample than an equally comprehensive management protocol ; and to determine whether MST leads to broader improvements in youth sociality and in mediators believed to be responsible for change in MST . METHOD 108 families were r and omized to either MST ( n=56 ) or the comprehensive and targeted usual services delivered by youth offending teams ( YOT , n = 52 ) . RESULTS Although young people receiving both MST and YOT interventions showed improvement in terms of reduced offending , the MST model of service-delivery reduced significantly further the likelihood of nonviolent offending during an 18-month follow-up period . Consistent with offending data , the results of youth-reported delinquency and parental reports of aggressive and delinquent behaviors show significantly greater reductions from pre-treatment to post-treatment levels in the MST group . In this study MST was observed to have some delayed impact on offending , the nature and causes of which will require further study . CONCLUSIONS The superiority of the MST condition in reducing offending and antisocial behavior suggests that MST adds value to current U.K. statutory evidence -based youth services . The provision of MST does not supplant existing services but is best used to facilitate the appropriate and cost-effective organization of statutory services for young persons and their families Abstract Oppositional , noncompliant behavior is a frequent referral problem of children seen in child treatment facilities and is the defining characteristic of Oppositional Disorder . The present study evaluated the comparative efficacy of two treatment modalities . Nineteen families were r and omly assigned to receive either social learning-based parent training ( SLPT ) or systems family therapy ( SFT ) . Dependent variables included a reliable , valid coding system that measures noncompliant child behavior and other aspects of parent-child interactions , as well as several parent self-report inventories . Results showed that SLPT was more effective than SFT in reducing the primary symptoms of Oppositional Disorder . No differences were noted on measures of parent adjustment . Results are discussed in terms of the relatively greater efficacy of SLPT for treatment of the primary symptoms of Oppositional Disorder . The efficacy of SFT on other aspects of child and family function in Oppositional Disorder , and for other childhood disorders is not ruled out Whereas biomedical products are required to be tested for safety with respect to vulnerable organ systems , psychosocial treatments are not required to be tested for safety with respect to vulnerable social systems such as the family . This article provides some evidence for the need to document the potential negative effects of psychosocial treatments on family-level outcomes . Three r and omized controlled trials are review ed in which independent ratings or self-reports of family functioning were measured . Each of the 3 studies compared the efficacy of a family and a nonfamily treatment . Totally unexpectedly , the nonfamily treatment in each of the 3 trials demonstrated significant declines in family functioning . The authors suggest that psychosocial treatments with vulnerable population s have the potential to produce negative side effects on families . Therefore , it is important to conduct further research to determine whether safety studies should be required for psychosocial treatments This r and omized clinical trial assessed the effectiveness of multisystemic therapy ( MST ) for 156 youths who met the diagnostic criteria for conduct disorder . Sweden 's 3 largest cities and 1 small town served as the recruiting area for the study . A mixed factorial design was used , with r and om allocation between MST and treatment as usual groups . Assessment s were conducted at intake and 7 months after referral . With an intention-to-treat approach , results from multiagent and multi method assessment batteries showed a general decrease in psychiatric problems and antisocial behaviors among participants across treatments . There were no significant differences in treatment effects between the 2 groups . The lack of treatment effect did not appear to be caused by site differences or variations in program maturity . MST treatment fidelity was lower than that of other studies , although not clearly related to treatment outcomes in this study . The results are discussed in terms of differences between Sweden and the United States . One difference is the way in which young offenders are processed ( a child welfare approach vs. a juvenile justice system approach ) . Sociodemographic differences ( e.g. , rates of poverty , crime , and substance abuse ) between the 2 countries may also have moderating effects on the rates of rehabilitation among young offenders . ( PsycINFO Data base Record ( c ) 2008 APA , all rights reserved ) The effectiveness and transportability of multisystemic therapy ( MST ) were examined in a study that included 118 juvenile offenders meeting DSM-III-R criteria for substance abuse or dependence and their families . Participants were r and omly assigned to receive MST versus usual community services . Outcome measures assessed drug use , criminal activity , and days in out-of-home placement at posttreatment ( T2 ) and at a 6-month posttreatment follow-up ( T3 ) ; also treatment adherence was examined from multiple perspectives ( i.e. , caregiver , youth , and therapist ) . MST reduced alcohol , marijuana , and other drug use at T2 and total days in out-of-home placement by 50 % at T3 . Reductions in criminal activity , however , were not as large as have been obtained previously for MST . Examination of treatment adherence measures suggests that the modest results of MST were due , at least in part , to difficulty in transporting this complex treatment model from the direct control of its developers . Increased emphasis on quality assurance mechanisms to enhance treatment fidelity may help overcome barriers to transportability A r and omized clinical trial evaluated the efficacy of multisystemic therapy ( MST ) versus usual community services ( UCS ) for 48 juvenile sexual offenders at high risk of committing additional serious crimes . Results from multiagent assessment batteries conducted before and after treatment showed that MST was more effective than UCS in improving key family , peer , and academic correlates of juvenile sexual offending and in ameliorating adjustment problems in individual family members . Moreover , results from an 8.9-year follow-up of rearrest and incarceration data ( obtained when participants were on average 22.9 years of age ) showed that MST participants had lower recidivism rates than did UCS participants for sexual ( 8 % vs. 46 % , respectively ) and nonsexual ( 29 % vs. 58 % , respectively ) crimes . In addition , MST participants had 70 % fewer arrests for all crimes and spent 80 % fewer days confined in detention facilities than did their counterparts who received UCS . The clinical and policy implication s of these findings are discussed This study examines the effectiveness of an evidence -based practice , multisystemic therapy ( MST ) , conducted in a real-world mental health setting with juvenile justice involved youth and their families . Importantly , this is the first r and omized clinical trial of MST with juvenile offenders in the United States conducted without direct oversight by the model developers . This study reports outcomes achieved for 93 youth r and omly assigned to MST or treatment as usual ( TAU ) services through 18-month follow-up posttreatment for offense data and 6-month follow-up posttreatment for ratings of the Child and Adolescent Functional Assessment Scale ( CAFAS ) . Outcomes include significant reduction in rearrest and improvement in 4 areas of functioning measured by the CAFAS for youth who received MST . Implication s for delivery of empirically supported treatments in real-world setting s are discussed BACKGROUND Multisystemic Treatment ( MST ) is an intensive home- and community based intervention for youths with serious behaviour problems . The aim of this study was to examine the effectiveness of MST compared to ' regular services ' ( RS ) two years after intake to treatment . In particular , our goals were to investigate whether MST was successful at preventing placement out of home , and to examine reductions in behaviour problems in multi-informant assessment s. METHOD Participants were 75 adolescents who were r and omly assigned to MST or Regular Child Welfare Services ( RS ) at 3 sites across Norway . Data were gathered from youths , caregivers and teachers . RESULTS MST was more effective than RS in reducing out of home placement and behavioural problems . DISCUSSION The sustainability of treatment effects was evident , supporting the MST approach to the treatment of serious behavioural problems in youth . Site differences and the moderating effects of age and gender are discussed The effects of multisystemic therapy ( MST ) in treating violent and chronic juvenile offenders and their families in the absence of ongoing treatment fidelity checks were examined . Across 2 public sector mental health sites , 155 youths and their families were r and omly assigned to MST versus usual juvenile justice services . Although MST improved adolescent symptomology at posttreatment and decreased incarceration by 47 % at a 1.7-year follow-up , findings for decreased criminal activity were not as favorable as observed on other recent trials of MST . Analyses of parent , adolescent , and therapist reports of MST treatment adherence , however , indicated that outcomes were substantially better in cases where treatment adherence ratings were high . These results highlight the importance of maintaining treatment fidelity when disseminating complex family-based services to community setting Multisystemic therapy ( MST ) delivered through a community mental health center was compared with usual services delivered by a Department of Youth Services in the treatment of 84 serious juvenile offenders and their multiproblem families . Offenders were assigned r and omly to treatment conditions . Pretreatment and posttreatment assessment batteries evaluating family relations , peer relations , symptomatology , social competence , and self-reported delinquency were completed by the youth and a parent , and archival records were search ed at 59 weeks postreferral to obtain data on rearrest and incarceration . In comparison with youths who received usual services , youths who received MST had fewer arrests and self-reported offenses and spent an average of 10 fewer weeks incarcerated . In addition , families in the MST condition reported increased family cohesion and decreased youth aggression in peer relations . The relative effectiveness of MST was neither moderated by demographic characteristics nor mediated by psychosocial variables BACKGROUND To meet the treatment needs of the growing number of adolescents who seek help for cannabis use problems , new or supplementary types of treatment are needed . We investigated whether multidimensional family therapy ( MDFT ) was more effective than cognitive behavioral therapy ( CBT ) in treatment-seeking adolescents with a DSM-IV cannabis use disorder in The Netherl and s. METHODS One hundred and nine adolescents participated in a r and omized controlled trial , with study assessment s at baseline and at 3 , 6 , 9 and 12 months following baseline . They were r and omly assigned to receive either outpatient MDFT or CBT , both with a planned treatment duration of 5 - 6 months . Main outcome measures were cannabis use , delinquent behavior , treatment response and recovery at one-year follow-up , and treatment intensity and retention . RESULTS MDFT was not found to be superior to CBT on any of the outcome measures . Adolescents in both treatments did show significant and clinical ly meaningful reductions in cannabis use and delinquency from baseline to one-year follow-up , with treatment effects in the moderate range . A substantial percentage of adolescents in both groups met the criteria for treatment response at month 12 . Treatment intensity and retention was significantly higher in MDFT than in CBT . Post hoc subgroup analyses suggested that high problem severity subgroups at baseline may benefit more from MDFT than from CBT . CONCLUSIONS The current study indicates that MDFT and CBT are equally effective in reducing cannabis use and delinquent behavior in adolescents with a cannabis use disorder in The Netherl and This article presents the main outcome findings from two inter-related r and omized trials conducted at four sites to evaluate the effectiveness and cost-effectiveness of five short-term outpatient interventions for adolescents with cannabis use disorders . Trial 1 compared five sessions of Motivational Enhancement Therapy plus Cognitive Behavioral Therapy ( MET/CBT ) with a 12-session regimen of MET and CBT ( MET/CBT12 ) and another that included family education and therapy components ( Family Support Network [ FSN ] ) . Trial II compared the five-session MET/CBT with the Adolescent Community Reinforcement Approach ( ACRA ) and Multidimensional Family Therapy ( MDFT ) . The 600 cannabis users were predominately white males , aged 15 - 16 . All five CYT interventions demonstrated significant pre-post treatment during the 12 months after r and om assignment to a treatment intervention in the two main outcomes : days of abstinence and the percent of adolescents in recovery ( no use or abuse/dependence problems and living in the community ) . Overall , the clinical outcomes were very similar across sites and conditions ; however , after controlling for initial severity , the most cost-effective interventions were MET/CBT5 and MET/CBT12 in Trial 1 and ACRA and MET/CBT5 in Trial 2 . It is possible that the similar results occurred because outcomes were driven more by general factors beyond the treatment approaches tested in this study ; or because of shared , general helping factors across therapies that help these teens attend to and decrease their connection to cannabis and alcohol OBJECTIVE This study examined the effects of an innovative treatment model that was design ed to reduce treatment dropout among substance abusing or dependent juvenile offenders . METHOD One hundred eighteen delinquents who met diagnostic criteria for substance abuse or dependence were r and omly assigned to receive either home-based multisystemic therapy ( N=58 ) or treatment that was provided by the usual community services ( N=60 ) . RESULTS In the multisystemic therapy condition , 98 % ( N=57 ) of the families completed a full course of treatment , which lasted an average of 130 days . In contrast , 78 % ( N=47 ) of the families assigned to treatment through the usual community services received no mental health or substance abuse treatment in the 5 months after referral . CONCLUSIONS The serious and long-st and ing problem of high dropout rates in the substance abuse field can be greatly attenuated by services that increase accessibility and place greater responsibility for engagement on service providers There is a dearth of research that examines the impact of family systems therapy on problems among sexually and /or physically abused youth . Given this void , differential outcome and predictors of substance use change were evaluated for abused , as compared with nonabused , runaway adolescents who were r and omly assigned to family therapy or treatment as usual . Abused adolescents reported lower family cohesion at baseline , although both abused and nonabused adolescents showed similar substance use reductions . Utilizing hierarchical linear modeling , we found that substance use changed with change in cohesion over time . These findings link change in family functioning to change in adolescent substance use , supporting fiamily systems theory . Findings suggest that a potent target of intervention involves focus on increasing positive communication interactions Comorbidity of substance abuse disorders ( SUD ) and psychiatric disorders is one of the most important areas of investigation in contemporary drug abuse treatment research . This study examined the impact of psychiatric comorbidity on the treatment of 182 adolescent drug abusers in a r and omized clinical trial comparing family and individual cognitive-behavioral therapy . Three distinct groups of adolescent substance abusers were compared : ( 1 ) Exclusive Substance Abusers ( SUD only ) ; ( 2 ) Externalizers ( SUD + externalizing disorder ) ; and ( 3 ) Mixed Substance Abusers ( SUD + externalizing and internalizing disorder ) . The purpose of this study was to determine whether adolescents in these comorbid groups differed in clinical presentation and treatment response . More severe comorbidity was associated with greater family dysfunction and being female and younger at intake . An examination of substance use trajectories over time indicated that the Mixed group initially responded to treatment but returned to intake levels of substance use by 1 year post-discharge The five manual-guided treatment models tested in the Cannabis Youth Treatment study funded by the Center for Substance Abuse Treatment are described . The five models include ( a ) a 6-week intervention consisting of two sessions of individual motivational enhancement therapy plus three sessions of group cognitive behavioral therapy ( MET/CBT5 ) ; ( b ) a 12-week intervention consisting of two sessions of motivational enhancement therapy plus 10 sessions of group cognitive behavioral therapy treatment ( MET/CBT12 ) ; ( c ) a 12-week intervention consisting of MET/CBT12 plus the family support network ( FSN ) , a multi-component intervention that includes parent education , family therapy and case management ; ( d ) a 12-week intervention based on the adolescent community reinforcement approach ( ACRA ) , an individual behavioral treatment approach design ed to help adolescents and their parents reshape their environment and learn new skills ; and ( e ) multi-dimensional family therapy ( MDFT ) , a multi-faceted , developmentally and context ually oriented family-based model targeting individual , family and social systems . For each model , we describe the treatment background and /or its empirical support , its theoretical underpinnings , its goals and proposed treatment mechanism and the structure and content of each treatment . Procedures used for maintaining treatment fidelity and monitoring quality assurance are also described . These interventions represent the first readily available , manual-guided interventions to be evaluated in a large r and omized field study for this population . Consequently , these manuals have the potential to advance treatment and research for adolescents with substance use disorders This r and omized clinical trial evaluated individual cognitive-behavioral therapy ( CBT ) , family therapy , combined individual and family therapy , and a group intervention for 114 substance-abusing adolescents . Outcomes were percentage of days marijuana was used and percentage of youths achieving minimal use . Each intervention demonstrated some efficacy , although differences occurred for outcome measured , speed of change , and maintenance of change . From pretreatment to 4 months , significantly fewer days of use were found for the family therapy alone and the combined interventions . Significantly more youths had achieved minimal use levels in the family and combined conditions and in CBT . From pretreatment to 7 months , reductions in percentage of days of use were significant for the combined and group interventions , and changes in minimal use levels were significant for the family , combined , and group interventions Structural family therapy , psychodynamic child therapy , and a recreational control condition were compared for 69 six-to-twelve-year-old Hispanic boys who presented with behavioral and emotional problems . The results suggest that the control condition was significantly less effective in retaining cases than the two treatment conditions , which were apparently equivalent in reducing behavioral and emotional problems as well as in improving psychodynamic ratings of child functioning . Structural family therapy was more effective than psychodynamic child therapy in protecting the integrity of the family at 1-year follow-up . Finally , the results did not support basic assumptions of structural family systems therapy regarding the mechanisms mediating symptom reduction This study investigated the economics of multisystemic therapy ( MST ) versus individual therapy ( IT ) using rearrest data from a 13.7-year follow-up ( Schaeffer & Borduin , 2005 ) of a r and omized clinical trial with serious juvenile offenders ( Borduin et al. , 1995 ) . Two types of benefits of MST were evaluated : The value to taxpayers was derived from measures of criminal justice system expenses ( e.g. , police and sheriff 's offices , court processing , jails , community supervision ) , and the value to crime victims was derived in terms of both tangible ( e.g. , property damage and loss , health care , police and fire services , lost productivity ) and intangible ( e.g. , pain , suffering , reduced quality of life ) losses . Results indicated that the reductions in criminality in the MST versus IT conditions were associated with substantial reductions in expenses to taxpayers and intangible losses to crime victims , with cumulative benefits ranging from $ 75,110 to $ 199,374 per MST participant . Stated differently , it was estimated that every dollar spent on MST provides $ 9.51 to $ 23.59 in savings to taxpayers and crime victims in the years ahead . The economic benefits of MST , as well as its clinical effectiveness , should be considered by policymakers and the public at large in the selection of interventions for serious juvenile offenders This article presents the results of a therapy- outcome study design ed to compare the relative effectiveness of conjoint family therapy ( CFT , therapy with the entire family present for most sessions ) and one-person family therapy ( OPFT , therapy with only one family member present for most sessions ) . The working hypothesis of the study was that it would be possible to achieve the goals of family therapy ( structural family change and symptom reduction ) by working primarily with one person . Results were presented on 37 Hispanic families r and omly assigned to one of the two treatment modalities ( i.e. , CFT or OPFT ) . Data were analyzed using a mixed- design ( repeated measures plus between-group independent variable ) analysis of variance with treatment ( OPFT vs. CFT ) as the between-group independent variable and time of assessment ( intake , termination , follow-up ) as the repeated measure . The results indicated that both conditions were highly effective in improving family functioning and that OPFT was slightly more effective in reducing identified patient symptomatology . Clinical and practical issues are discussed as well as the implication s of the findings for the current theory and practice of family therapy BACKGROUND MST is an intensive home- and community-based intervention for youths with serious antisocial behaviour and other serious clinical problems , which has been effective at reducing out-of-home placements and producing favourable long-term clinical outcomes in the US . The aims of the study were to determine the degree to which these outcomes would be replicated in Norway for youths with serious behaviour problems and to conduct a r and omised trial of MST by an independent team of investigators . METHOD Participants were 100 seriously antisocial youths in Norway who were r and omly assigned to Multisystemic Therapy ( MST ) or usual Child Welfare Services ( CS ) treatment conditions . Data were gathered from youths , parents , and teachers pre- and post-treatment . RESULTS MST was more effective than CS at reducing youth internalising and externalising behaviours and out-of-home placements , as well as increasing youth social competence and family satisfaction with treatment . DISCUSSION This is the first study of MST outside of the US and one of the first not conducted by the developers of MST . The findings replicate those obtained by MST 's developers and demonstrate the generalisability of short-term MST effects beyond the US In this study , the authors examined the long-term criminal activity of 176 youths who had participated in either multisystemic therapy ( MST ) or individual therapy ( IT ) in a r and omized clinical trial ( C. M. Borduin et al. , 1995 ) . Arrest and incarceration data were obtained on average 13.7 ( range = 10.2 - 15.9 ) years later when participants were on average 28.8 years old . Results show that MST participants had significantly lower recidivism rates at follow-up than did their counterparts who participated in IT ( 50 % vs. 81 % , respectively ) . Moreover , MST participants had 54 % fewer arrests and 57 % fewer days of confinement in adult detention facilities . This investigation represents the longest follow-up to date of a MST clinical trial and suggests that MST is relatively effective in reducing criminal activity among serious and violent juvenile offenders Two important theoretical assumptions of family therapy were examined : ( a ) Child behavior problems are associated with cross-generational coalitions , and ( b ) treatment of these coalitions using family therapy leads to decreases in individual symptomatology . Ss were 45 delinquent adolescents assigned to multisystemic therapy ( MST ) or individual therapy and 16 well-adjusted adolescents . Pretreatment and posttreatment assessment s included measures of observed family relations and self-reported symptoms . Cross-generational coalitions were more evident in families of delinquents vs. families of well-adjusted adolescents . In addition , changes in adolescent and paternal symptoms in the MST group were linked with changes in marital relations . Implication s for systemic conceptualizations of symptom maintenance and change are highlighted Secondary analyses of a r and omized clinical trial controlled for treatment condition effects and examined the impact of comorbid psychopathologies on the mental health , physical health , and criminal behavior of 80 substance abusing delinquents approximately 5 years later in emerging adulthood . Overall , emerging adults with a comorbid disorder during adolescence scored higher on psychopathology , criminal behavior , and health problems . Participants with both internalizing and externalizing disorders exhibited more negative outcomes than those with a comorbid externalizing disorder . For the entire sample , more internalizing diagnoses forecasted higher internalizing and aggression scores , more criminality , and poorer physical health . More externalizing disorders predicted higher internalizing , delinquency , and criminality scores , but was unrelated to physical health . More internalizing diagnoses for females but not males predicted greater criminality , and especially more aggressive crimes in emerging adulthood This article presents evidence for the effectiveness of a strategy for engaging adolescent drug users and their families in therapy . The intervention method is based on strategic , structural , and systems concepts . To overcome resistance , the identified pattern of interactions that interferes with entry into treatment is restructured . Subjects were 108 Hispanic families in which an adolescent was suspected of . or was observed , using drugs . Subjects were r and omly assigned to a strategic structuralsystems engagement ( experimental ) condition or to an engagement-as -usual ( control ) condition . Subjects in the experimental condition were engaged at a rate of 93 % compared with subjects in the control condition , who were engaged at a rate of 42 % . Seventy-seven percent of subjects in the experimental condition completed treatment compared wiih 25 " ! of subjects in the Abstract This r and omized clinical trial evaluated a family-based therapy ( Multidimensional Family Therapy , MDFT ; Liddle 2002a ) and a peer group therapy with 80 urban , low-income . and ethnically diverse young adolescents ( 11 to 15 years ) referred for substance abuse and behavioral problems . Both treatments were outpatient , relatively brief , manual-guided , equal in intervention dose , and delivered by community drug treatment therapists . Adolescents and their parents were assessed at intake to treatment , r and omly assigned to either MDFT or group therapy , and reassessed at six weeks after intake and at discharge . Results indicated that the family-based treatment ( MDFT . an intervention that targets teen and parent functioning within and across multiple systems on a variety of risk and protective factors ) was significantly more effective than peer group therapy in reducing risk and promoting protective processes in the individual , family , peer , and school domains . as well as in reducing substance use over the course of treatment . These results . which add to the body of previous findings about the clinical and cost effectiveness of MDFT , suppon the clinical effectiveness and dissemination potential of this family-based , multisystem and developmentally-oriented intervention This longitudinal study examined the relationships among the working alliance , treatment satisfaction , and posttreatment use among adolescents in treatment for substance abuse . Adolescents ( N = 600 ) from the Cannabis Youth Treatment study ( M. L. Dennis et al. , 2002 ) completed measures of working alliance and treatment satisfaction as well as substance use and substance-related problems at intake and 3 , 6 , 9 , 12 , and 30 months ' postintake . When controlling for initial substance use and substance-related problems , working alliance , but not treatment satisfaction , predicted use at 3 and 6 months ' postintake . Neither working alliance nor treatment satisfaction were predictive of longitudinal patterns of posttreatment use . Implication s for the assessment of working alliance and treatment satisfaction are discussed |
10,729 | 14,974,076 | REVIEW ER 'S CONCLUSIONS Although DBT and FSHT were better than no treatment when used in combination with an alarm , there was insufficient evidence to support their use without an alarm .
An alarm on its own was also better than DBT on its own , but there was some evidence that combining an alarm with DBT was better than an alarm on its own , suggesting that DBT may augment the effect of an alarm .
There was also some evidence that direct contact with a therapist might enhance the effects of an intervention | BACKGROUND Nocturnal enuresis ( bedwetting ) is a socially disruptive and stressful condition which affects around 15 - 20 % of five year olds , and up to 2 % of young adults .
OBJECTIVES To assess the effects of complex behavioural and educational interventions on nocturnal enuresis in children , and to compare them with other interventions . | Three variations in the mode of delivery of Dry Bed Training as a treatment for nocturnal enuresis were investigated . Twenty-three children , ranging in age from 4 to 14 , received dry bed training without the additional use of a urine alarm . Treatment variations included : ( a ) in-home training of parents and child , ( b ) office based training of parents and child , and ( c ) office based training of parents only . An additional 7 children served as a waiting list control during the first 8 weeks of the study . A wide variety of outcome measures showed improvement for the entire sample regardless of specific mode of delivery . Implication s for the treatment of enuresis using dry bed training and a number of critical method ological issues are discussed Abstract Bedwetting has been a major and unsolved problem for the severely retarded . To solve this problem , an intensive training program was design ed similar to a recently developed program for daytime toilet training of the retarded . Some distinctive features of the new procedure were frequent positive reinforcement for correct toileting , a negative reinforcer for accidents , positive practice in night time toileting , increased level of urination by forcing drinking , immediate detection of correct and incorrect toileting , and Positive Practice for accidents . Of twelve retarded adult bedwetters , the average bedwetter required only one night of intensive training . Several days of apparatus monitoring were used following the training but proved unnecessary for two-thirds of the trainees . Accidents were reduced by about 85 % during the first week after training , and almost entirely ( 95 % ) during the fifth week with no relapse during a 3 month follow-up . No reduction of accidents result ed when the same bedwetters were given a control procedure that provided no positive or negative reactions other than the sounding of an alarm upon bedwetting . The Dry-Bed procedure appears to be a very rapid solution to the problem of enuresis among the retarded and may be applicable to other difficult population s and also to normals Treatment of childhood enuresis requires a careful anamnesis , physical examination , urinalysis , and urine culture to determine if a subject is affected with functional or organic enuresis . Functional enuresis ( FE ) was present in the majority of our patients ( 168/204 ) . These 168 subjects , aged from 6 to 11 years , were r and omly divided into three therapy groups ( pharmacological therapy , behavioral therapy , and behavioral therapy with the aid of a personal computer ) . Our study shows that behavioral therapy gave better results in FE than did pharmacological therapy . We point out the usefulness of combining bladder retention training and behavioral therapy to improve the general maturity and autonomous behavior of the child , and the result ant positive effects on his personality Ten years after continence training , 14 severely and profoundly mentally h and icapped individuals were found to have substantially maintained their improvements in bladder control . Completely independent self-initiated toileting had not been maintained , but the level of prompting to toilet was considerably less than before training . Those who had received intensive individual training fared much better than those who had received less intensive group training . Intensive individual training was found to be cost effective and result ed in very substantial savings in career time Abstract Enuresis has been treated with moderate effectiveness by the urine-alarm method which requires many weeks of training . The present procedure used a urine-alarm apparatus but added such features as training in inhibiting urination , positive reinforcement for correct urinations , training in rapid awakening , increased fluid intake , increased social motivation to be nonenuretic , self-correction of accidents , and practice in toileting . After one all-night training session , the 24 enuretic children averaged only two bedwettings before achieving fourteen consecutive dry nights and had no major relapses . Little or no reduction in bedwetting occurred within the first two weeks for matched-control enuretics who were given the st and ard urine-alarm training . The results of a control-procedure showed that the new procedure did not involve Pavlovian conditioning . The new method appears to be a more rapid , effective and different type of treatment for enuresis OBJECTIVE This study evaluated the impact of child-focused information provision using a multimedia software package ' All About Nocturnal Enuresis ' and written leaflets containing the same information for bedwetting children . DESIGN A stratified cluster r and omized controlled trial with data on 270 children collected longitudinally . SETTING Fifteen school nurse-led community enuresis clinics in Leicestershire , UK . MAIN OUTCOME MEASURES The outcome measures were becoming and remaining dry and time to dry , non-attendance and dropout rates . The psychological measures completed by children were the impact of bedwetting and Coopersmith self-esteem scales . Parents completed the maternal tolerance scale . RESULTS No significant intervention effect was found for any of the outcome measures recorded during treatment , at discharge or six-months post discharge . CONCLUSIONS Multimedia educational programs and written leaflets are widely used to enable children to learn more about their health-related conditions . However , our result suggests that multimedia is no more effective than traditional material s at effecting health-related behavioural change Two experiments examined the significance of patient-therapist contact in the treatment of childhood nocturnal enuresis by behavioural methods . The first involving 45 enuretic children compared the effectiveness of the st and ard urine-alarm conditioning procedure when it is closely supervised as opposed to not supervised after the initial description of training . Results showed that adequate patient-therapist contact is necessary for the effective use of the st and ard conditioning treatment . One hundred and twenty children took part in the second experiment which compared st and ard conditioning with Dry-Bed Training ( DBT ) ( Azrin et al , 1974 ) administered under four different conditions — by the child 's parents at home , by a professional trainer at home , by a professional trainer in hospital and by the child 's parents without the adjunct of a conventional bed-buzzer device . DBT was superior to st and ard conditioning in terms of the proportion of bedwetters successfully treated and in terms of the speed of treatment . DBT was equally effective under all conditions of administration except where it did not have the adjunct of a machine , in which case it was only marginally better than no treatment at all Three treatments for enuresis were evaluated : ( a ) immediate detection with a urine-sensing alarm with additional operant training procedures , ( b ) delayed detection with staff activating the alarm and conducting the procedures in the morning , and ( c ) yoked-schedule awakenings when the awakening times were determined by the performance of a r and omly matched participant from the immediate-detection group . Twenty seven people with mental retardation ( most profoundly or severely h and icapped ) , whose ages ranged from 13 to 29 years , participated . Nine of the participants were noncompliant with the linen changing and practice walks to the bathroom and thus did not receive consistent treatment . All 7 of the compliant members of the immediate-detection group improved , 2 of the delayed-detection group worsened while 2 improved , and 6 of 7 yoked awakenings participants improved . Improvement negatively correlated with the frequency of baseline bed-wetting . Several method ological issues are raised concerning enuresis treatment To extend availability of a behavioral treatment package for enuresis , two outcome studies compared the effectiveness of live versus videotape delivery . In Study 1,40 primary entireties were r and omly assigned to live or film delivery . Outcome was superior for the live delivery . Overall , pretreatment measures of family and child psychosocial adjustment failed to predict treatment response . The results were replicated with 18 children , and an impact assessment suggested that film delivery result ed in higher confidence of children in their parents but lower confidence of parents in their children . Delivery of treatments by videotape may provide a way to identify nonspecific factors in psychological interventions Two studies examined the effectiveness of the body-worn alarm in out-patient treatment of childhood nocturnal enuresis . The first involved 40 children , previously untreated by conditioning methods , treated with either the body-worn alarm or the traditional pad and bell alarm . The second study compared the body-worn alarm with modified dry-bed training with 48 children previously resistant to treatment . Results of both studies indicated the body-worn alarm was as effective as other methods in terms of the proportion of children successfully treated and was superior with respect to rapidity of response and consumer appeal . Such findings indicate that the body-worn alarm could become the treatment of choice for nocturnal enuresis |
10,730 | 29,105,051 | Subgroup analysis including women older than 40 years of age yielded a HR of 0.65 ( 95 % CI 0.53 to 0.81 ; 2 studies , 5058 women , high- quality evidence ) .We found no data for the outcomes of acute toxicity , quality of life , or costs .
AUTHORS ' CONCLUSIONS It appears that local control rates are increased with the boost to the tumour bed , but we found no evidence of a benefit for other oncological outcomes .
Subgroup analysis including women older than 40 years of age yielded similarly significant results .
Objective percentage of breast retraction assessment appears similar between groups .
It appears that the cosmetic outcome is worse with the boost to the tumour bed , but only when measured by a panel , not when assessed by a physician | BACKGROUND Breast-conserving therapy , involving breast-conserving surgery followed by whole-breast irradiation and optionally a boost to the tumour bed , is a st and ard therapeutic option for women with early-stage breast cancer .
A boost to the tumour bed means that an extra dose of radiation is applied that covers the initial tumour site .
The rationale for a boost of radiotherapy to the tumour bed is that ( i ) local recurrence occurs mostly at the site of the primary tumour because remaining microscopic tumour cells are most likely situated there ; and ( ii ) radiation can eliminate these causative microscopic tumour cells .
The boost continues to be used in women at high risk of local recurrence , but is less widely accepted for women at lower risk .
Reasons for question ing the boost are twofold .
Firstly , the boost brings higher treatment costs .
Secondly , the potential adverse events are not negligible .
In this Cochrane Review , we investigated the effect of the tumour bed boost on local control and side effects .
OBJECTIVES To assess the effects of tumour bed boost radiotherapy after breast-conserving surgery and whole-breast irradiation for the treatment of breast cancer . | Background The initial quality assurance programme of the EORTC Radiotherapy Cooperative Group in trial 22881/10882 is described . The implication s of its results for quality assurance in future trials are discussed . Methods In the EORTC trial 22881/10882 patients with stage I or II breast cancer are treated with tumor excision , axillary dissection , 50 Gy whole breast irradiation and then r and omized to receive a boost dose of 15 Gy or no boost following complete tumor excision , or between 10 Gy or 25 Gy in case of incomplete excision . To avoid or diminish protocol deviations and to quantify inevitable variations an extensive initial quality assurance programme was conducted . The programme consisted of a dummy run procedure , an individual case review procedure , in vivo dosimetry studies and phantom dosimetry studies . Results This combination of quality assurance procedures allows a good estimation of patient to patient and inter-institutional variations , and early detection of ( potential ) systematic protocol deviations of 3 types : 1 . Deviations due to ambiguities in the protocol prescriptions . 2 . Deviations not known to the institution , such as mistakes in implementation of treatment planning algorithms result ing in a systematic overdosage or underdosage . 3 . Inability of an institution to cope with ( precise ) protocol prescriptions for technical or logistic reasons . Discussion The first 2 types of deviations may be corrected or avoided by direct discussion s and recommendations . With respect to the third type it is up to the trial coordinator to accept participation or not , depending upon the relative importance of the particular deviation(s ) for the trial end points . To be effective , such a quality assurance programme must be implemented as early as possible in the course of a clinical trial . ZusammenfassungHintergrundIm Anfang der EORTC-Studie 22881/10882 wurde ein ausführliches Qualitätssicherungsprogramm durchgeführt . Die Ergebnisse dieses Qualitätssicherungsprogramms werden beschrieben , und die Implikationen für Qualitätssicherungsmaßnahmen zukünftiger Studien werden diskutiert . Method enIn der EORTC-Studie 22881/10882 wurden Patientinnen mit Brustkrebs Stadium I und II wie folgt beh and elt : Exzision des Tumors und Dissektion in der Achsel , gefolgt von Bestrahlung der gesamten Brust mit 50 Gy . Danach wurden die Patientinnen r and omisiert , i m Falle vollständiger Exzision zwischen keinem Boost oder einem Boost von 15 Gy , i m Falle einer unvollständigen Exzision zwischen einem Boost von 10 Gy oder 25 Gy . Um Protokollverstöße zu vermeiden oder zu verringern und um unvermeidliche Variationen zu quantifizieren , wurde am Anfang der Studie ein Qualitätssicherungprogramm durchgeführt . Das Programm best and aus einem Probelauf , einer retrospektiven Analyse von individuellen Fällen und der Auswertung der Dosimetrie an Patientinnen und am Phantom . ErgebnisseDas Qualitätssicherungsprogramm ermöglicht sowohl eine Schätzung der Variation zwischen verschiedenen Patientinnen und Instituten als auch die frühzeitige Erkennung möglicher systematischer Protokollverstöße in drei Kategorien : 1 . Abweichungen wegen Ungenauigkeiten in den Protokollvorschriften , 2 . den Instituten unbekannte Abweichungen , wie zum Beispiel Über- oder Unterdosierung als Folge fehlerhafter Anwendung von Planungsalgorithmen und 3 . Schwierigkeiten in Instituten bei der Ausführung von Protokollvorschriften aus technischen oder logistischen Gründen . DiskussionDie ersten zwei Abweichungskategorien können durch direkte Diskussion und Empfehlungen korrigiert und für zukünftige Patientinnen vermieden werden . Bezogen auf die dritte Kategorie liegt es in der Verantwortlichkeit des Studienkoordinators , die Teilnahme von Instituten zu akzeptieren i m Hinblick auf den Einfluß , den zu erwartende Regelverletzungen auf die Ziele der Studie haben können . Um seine Aufgabe effektiv zu erfüllen , muß ein Qualitätssicherungsprogramm möglichst früh in den Ablauf einer Studie aufgenommen werden BACKGROUND After breast-conserving surgery , 90 % of local recurrences occur within the index quadrant despite the presence of multicentric cancers elsewhere in the breast . Thus , restriction of radiation therapy to the tumour bed during surgery might be adequate for selected patients . We compared targeted intraoperative radiotherapy with the conventional policy of whole breast external beam radiotherapy . METHODS Having safely piloted the new technique of single-dose targeted intraoperative radiotherapy with Intrabeam , we launched the TARGIT-A trial on March 24 , 2000 . In this prospect i ve , r and omised , non-inferiority trial , women aged 45 years or older with invasive ductal breast carcinoma undergoing breast-conserving surgery were enrolled from 28 centres in nine countries . Patients were r and omly assigned in a 1:1 ratio to receive targeted intraoperative radiotherapy or whole breast external beam radiotherapy , with blocks stratified by centre and by timing of delivery of targeted intraoperative radiotherapy . Neither patients nor investigators or their teams were masked to treatment assignment . Postoperative discovery of predefined factors ( eg , lobular carcinoma ) could trigger addition of external beam radiotherapy to targeted intraoperative radiotherapy ( in an expected 15 % of patients ) . The primary outcome was local recurrence in the conserved breast . The predefined non-inferiority margin was an absolute difference of 2.5 % in the primary endpoint . All r and omised patients were included in the intention-to-treat analysis . This trial is registered with Clinical Trials.gov , number NCT00983684 . FINDINGS 1113 patients were r and omly allocated to targeted intraoperative radiotherapy and 1119 were allocated to external beam radiotherapy . Of 996 patients who received the allocated treatment in the targeted intraoperative radiotherapy group , 854 ( 86 % ) received targeted intraoperative radiotherapy only and 142 ( 14 % ) received targeted intraoperative radiotherapy plus external beam radiotherapy . 1025 ( 92 % ) patients in the external beam radiotherapy group received the allocated treatment . At 4 years , there were six local recurrences in the intraoperative radiotherapy group and five in the external beam radiotherapy group . The Kaplan-Meier estimate of local recurrence in the conserved breast at 4 years was 1.20 % ( 95 % CI 0.53 - 2.71 ) in the targeted intraoperative radiotherapy and 0.95 % ( 0.39 - 2.31 ) in the external beam radiotherapy group ( difference between groups 0.25 % , -1.04 to 1.54 ; p=0.41 ) . The frequency of any complications and major toxicity was similar in the two groups ( for major toxicity , targeted intraoperative radiotherapy , 37 [ 3.3 % ] of 1113 vs external beam radiotherapy , 44 [ 3.9 % ] of 1119 ; p=0.44 ) . Radiotherapy toxicity ( Radiation Therapy Oncology Group grade 3 ) was lower in the targeted intraoperative radiotherapy group ( six patients [ 0.5 % ] ) than in the external beam radiotherapy group ( 23 patients [ 2.1 % ] ; p=0.002 ) . INTERPRETATION For selected patients with early breast cancer , a single dose of radiotherapy delivered at the time of surgery by use of targeted intraoperative radiotherapy should be considered as an alternative to external beam radiotherapy delivered over several weeks . FUNDING University College London Hospitals (UCLH)/UCL Comprehensive Biomedical Research Centre , UCLH Charities , National Institute for Health Research Health Technology Assessment programme , Ninewells Cancer Campaign , National Health and Medical Research Council , and German Federal Ministry of Education and Research ( BMBF ) The EORTC 22881 - 10882 trial in 5178 conservatively treated early breast cancer patients showed that a 16 Gy boost dose significantly improved local control , but increased the risk of breast fibrosis . To investigate predictors for the long-term risk of fibrosis , Cox regression models of the time to moderate or severe fibrosis were developed on a r and om set of 1797 patients with and 1827 patients without a boost , and vali date d in the remaining set . The median follow-up was 10.7 years . The risk of fibrosis significantly increased ( P<0.01 ) with increasing maximum whole breast irradiation ( WBI ) dose and with concomitant chemotherapy , but was independent of age . In the boost arm , the risk further increased ( P<0.01 ) if patients had post-operative breast oedema or haematoma , but it decreased ( P<0.01 ) if WBI was given with > 6 MV photons . The c-index was around 0.62 . Nomograms with these factors are proposed to forecast the long-term risk of moderate or severe fibrosis Two r and omized trials have recently shown a statistically significant improvement in local control when a boost is employed in the conservative treatment of early breast cancer . However , unresolved issues of cost effectiveness , potentially increased toxicity and the inability to automatically generalize these results to Australian and New Zeal and practice remain . In view of these unresolved controversies , the St George and Wollongong hospitals breast boost trial ( SGW trial ) will continue to recruit PURPOSE To determine whether the effect of an additional " boost " radiation after breast conservative therapy ( BCT ) on local control depends on age and evaluate the impact of a treatment policy with a threshold for age . PATIENTS AND METHODS We used data from EORTC 22881 - 10882 trial , with median follow-up of 77.4 months . Patients receiving BCT and 50Gy whole breast irradiation were r and omized to no boost and 16Gy boost ( N=5318 ) . RESULTS In univariate analysis , a boost reduced local failure by a factor of 2 ( P<0.0001 ) . Multivariate analysis showed local control increased with age ( P=0.0003 ) . There was no evidence that the relative effect of a boost on local control depends on age ( P=0.97 ) However in younger patients the 5-year local failure was higher , therefore the absolute reduction was greater . If the threshold-age for boost treatment were set at 40 years , 8.4 % of the study population would receive a boost , result ing in a 5-year local failure of 6.1 % in the study population . Changing the threshold-age to 60 years , 67 % of the study population would receive a boost and the 5-year local failure would be reduced to 4.4 % . CONCLUSIONS In younger patients a boost dose result ed in a greater absolute reduction of local failure . The relative risk reduction was however similar for all ages . Applying a treatment policy with a threshold-age of 60 would result in 0.6 % increase in local failure in the total study population , while sparing the boost to 1/3 of the patients Breast cancer multifocality was studied in mastectomy specimens by correlated specimen radiography and histologic techniques . The patients chosen for study were comparable to those eligible for breast‐conserving surgical therapy . Two study groups , one with 282 invasive cancers ( T1‐2 ) and the other with 32 intraductal cancers , were selected from a group of 399 consecutive cases by omitting patients who were clearly , or very probably , not c and i date s for breast‐conserving surgical therapy according to current trial criteria . Omitted patients included those with clinical ly and /or radiologically multifocal cancers and patients with tumor extension into the chest wall or skin ( 7 % ) . Also excluded were the socalled diffuse invasive cancers ( 8 % ) , the clinical ly and radiologically occult tumors ( 3 % ) , and the invasive cancers larger than 5 cm ( 3 % ) . Of the 282 invasive cancers , 105 ( 37 % ) showed no tumor foci in the mastectomy specimen around the reference mass . In 56 ( 20 % ) tumor foci were present within 2 cm , and in 121 ( 43 % ) tumor was found more than 2 cm from the reference tumor . In 75 ( 27 % ) the tumor foci beyond 2 cm were histologically noninvasive cancers , and in 46 cases ( 16 % ) they contained invasive cancers as well . A comparison between the group with reference tumors less than 2 cm and the group with reference tumors more than 2 cm in size showed no significant difference between the groups in terms of presence or absence of tumor foci or distance of tumor foci from the reference tumor . If the 264 invasive cancers in this series that were 4 cm or less in diameter had been removed with a margin of 3 to 4 cm , 7 % to 9 % of the patients would have had invasive cancer left in the remaining breast tissue , and 4 % to 9 % would have had foci of noninvasive cancer left in the remaining breast tissue . On the basis of the data on the distribution of tumor at different distances from the reference tumor , the current study estimates the expected rates of local recurrences after breast‐conserving surgical procedures relative to the extensiveness of the excision . The possible impact of postoperative local radiation therapy on the rates of expected local recurrence is discussed Background and Aims : To evaluate the effect of electron and high-dose-rate brachytherapy ( HDR BT ) boost on local tumor control ( LTC ) , side effects and cosmesis after breast-conserving surgery ( BCS ) in a prospect i ve r and omized study . Patients and Methods : 207 women with stage I – II breast cancer who underwent BCS were treated by 50 Gy irradiation to the whole breast and then r and omly assigned to receive either a boost to the tumor bed ( n = 104 ) or no further radiotherapy ( n = 103 ) . Boost treatments consisted of either 16 Gy electron irradiation ( n = 52 ) or 12–14,25 Gy HDR BT ( n = 52 ) . Breast cancer-related events , side effects , and cosmetic results were assessed . Results : At a median follow-up of 5.3 years , the crude rate of local recurrences was 6.7 % ( 7/104 ) with and 15.5 % ( 16/103 ) without boost . The 5-year probability of LTC , relapse-free survival ( RFS ) , and cancer-specific survival ( CSS ) was 92.7 % vs. 84.9 % ( p = 0.049 ) , 76.6 % vs. 66.2 % ( p = 0.044 ) , and 90.4 % vs. 82.1 % ( p = 0.053 ) , respectively . There was no significant difference in LTC between patients treated with electron or HDR BT boost ( 94.2 % vs. 91.4 % ; p = 0.74 ) . On multivariate analysis , patient age < 40 years ( RR : 4.53 ) , positive margin status ( RR : 4.17 ) , and high mitotic activity index ( RR : 3.60 ) were found to be significant risk factors for local recurrence . The incidence of grade 2–3 side effects was higher in the boost arm ( 17.3 % vs. 7.8 % ; p = 0.03 ) . However , the rate of excellent/good cosmetic results was similar for the two arms ( 85.6 % vs 91.3 % ; p = 0.14 ) . Cosmesis was rated as excellent/good in 88.5 % of patients treated with HDR BT and 82.7 % of patients with electron boost ( p = 0.29 ) . Conclusions : Boost dose significantly improves LTC and RFS in patients treated with BCS and radiotherapy . In spite of the higher incidence of late side effects in the boost arm , boost dose is strongly recommended for patients at high risk for local recurrence . Positive or close margin status , high mitotic activity index , and young patient age should be viewed as absolute indications for tumor bed boost . LTC and cosmesis are excellent and similar to patients boosted with either HDR BT or electrons . Hintergrund und Ziel : In einer prospektiv r and omisierten Studie werden die Effekte eines Elektronenboosts und eines High-Dose-Rate-Brachytherapie-(HDR-BT-)Boosts bezüglich lokaler Tumorkontrolle ( LTC ) , Nebenwirkungen und kosmetischer Ergebnisse nach brusterhaltender Operation ( BCS ) evaluiert . Patienten und Method ik : 207 Patientinnen mit Brustkarzinomen i m Stadium I – II wurden einer BCS zugeführt . Postoperativ erfolgte eine perkutane Radiatio der gesamten Brust bis 50 Gy . Daran schloss sich willkürlich entweder eine Boostbestrahlung des Tumorbetts ( n = 104 ) oder keine weitere Radiatio ( n = 103 ) an . Die Boostbestrahlung erfolgte perkutan mit 16 Gy Elektronen ( n = 52 ) oder in Form einer HDR-BT mit 12–14,25 By ( n = 52 ) . Untersucht wurden LTC , Nebenwirkungen und kosmetische Ergebnisse . Ergebnisse : Die mediane Nachbeobachtungszeit betrug 5,3 Jahre . Die Lokalrezidivrate lag mit Boostbestrahlung bei 6,7 % ( 7/104 ) , ohne Boost bei 15,5 % ( 16/103 ) . Die 5-Jahres-Überlebensrate für LTC , für die rezidivfreie Überlebenszeit ( RFS ) und für die krebsspezifische Überlebenszeit ( CSS ) betrugen 92,7 % vs. 84,9 % ( p = 0,049 ) , 76,6 % vs. 66,2 % ( p = 0,044 ) und 90,4 % vs. 82,1 % ( p = 0,053 ) . Bezüglich der LTC best and kein signifikanter Unterschied zwischen Patienten , die mit einem Elektronen- oder HDR-BT-Boost beh and elt wurden ( 94,2 % vs. 91,4 $ ; p = 0,74 ) . Die multivariate Analyse zeigte , dass Faktoren wie Patientenalter > 40 Jahre ( RR : 4,53 ) , positive Resektionsränder ( RR : 4,17 ) und ein hoher Mitoseaktivitätsindex ( RR : 3.60 ) das Risiko eines lokalen Rezidivs signifikant erhöhen . Die Inzidenz von Nebenwirkungen Grad 2–3 war i m Boost-Arm höher ( 17,3 % vs. 7,8 % ; p = 0,03 ) . Allerdings waren die sehr guten kosmetischen Ergebnisse in beiden Armen gleich ( 85,6 % bs . 91,3 % , p = 0,14 ) . Sehr gute kosmetische Ergebnisse wurden bei 88,5 % der Patientinnen mit HDR-BT-Boost und 82,7 % der Patientinnen mit Elektronenboost erreicht ( p = 0,29 ) . Schlussfolgerungen : Die Boost-Dosis verbessert signifikant LTC und RFS bei Patientinnen , die einer BCS und anschließender Radiatio zugeführt wurden . Obwohl eine höhere Inzidenz an Spätnebenwirkungen i m Boost-Arm gefunden wurde , wird eine Boost-Dosis für Patientinnen mit hohem Risiko für die Entwicklung eines Lokalrezidivs empfohlen . Unserer Meinung nach ist bei Faktoren wie positive Schnittränder , schmaler Sicherheitssaum , hoher Mitoseaktivitätsindex und niedriges Patientenalter , die absolute Indikation zur Boost-Bestrahlung des Tumorbetts gegeben . LTC und die kosmetischen Ergebnisse sind sehr gut und unterscheiden sich nicht in Bezug auf Elektronenboost oder HDR-BT-Boost PURPOSE To evaluate comprehensively the effect of a radiotherapy boost on breast cosmetic outcomes after 5 years in patients treated with breast-conserving surgery . METHODS The St. George and Wollongong trial ( NCT00138814 ) r and omized 688 patients with histologically proven Tis-2 , N 0 - 1 , M0 carcinoma to the control arm of 50 Gy in 25 fractions ( 342 patients ) and the boost arm of 45 Gy in 25 fractions to the whole breast followed by a 16 Gy in 8 fraction electron boost ( 346 patients ) . Five-year cosmetic outcomes were assessed by a panel subjectively in 385 patients and objective ly using pBRA ( relative breast retraction assessment ) . A subset of patients also had absolute BRA measurements . Clinician assessment and patient self- assessment of overall cosmetic and specific items as well as computer BCCT.core analysis were also performed . RESULTS The boost arm had improved cosmetic overall outcomes as scored by the panel and BCCT.core software with 79 % ( p = 0.016 ) and 81 % ( p = 0.004 ) excellent/good cosmesis respectively compared with 68 % in no-boost arm . The boost arm also had lower pBRA and BRA values with a mean difference of 0.60 and 1.82 mm , respectively , but was not statistically significant . There was a very high proportion of overall excellent/good cosmetic outcome in 95 % and 93 % in the boost and no-boost arms using patient self- assessment . However , no difference in overall and specific items scored by clinician assessment and patient self- assessment was found . CONCLUSION The results show the negative cosmetic effect of a 16-Gy boost is offset by a lower whole-breast dose of 45 Gy BACKGROUND AND PURPOSE To evaluate the impact of quality assurance on treatment compliance , we compared the outcome of the two individual case review s ( ICR ) conducted early and late during the accrual period of a large prospect i ve multi-centre trial . PATIENTS AND METHODS At the onset of the trial , medical files of five patients from each participating centre were evaluated for the compliance to the protocol for eligibility , surgery , pathology and radiotherapy and for the quality of reporting of the data on the case report forms . In nine major centres , this procedure was repeated near the end of the trial . RESULTS Both in the early and the late ICR , we found a very limited number of deviations from the guidelines for eligibility , staging , surgery , and pathology . Compliance to radiotherapy requirements was good with the exception of a too low minimal dose in 30 % and the lack of target volume delineation in the majority of the evaluated patients . The comparison of the late with the early ICR demonstrated an improvement of the quality of data reporting by 6 % and of target volume delineation from 33 to 53 % . CONCLUSIONS The initial ICR has lead to the identification of a number of parameters , which needed a clarification in the protocol . These items have been corrected and the individual institutions have been made aware of the necessary adaptations . The evaluation at the end of the trial period showed that there was an improvement but also showed that continuous monitoring is necessary , especially for institutions which have the most deviations in the first ICR BACKGROUND The EORTC 10801 trial compared breast-conserving therapy ( BCT ) with modified radical mastectomy ( MRM ) in patients with tumours 5 cm or smaller and axillary node negative or positive disease . Compared with BCT , MRM result ed in better local control , but did not affect overall survival or time to distant metastases . We report 20-year follow-up results . METHODS The EORTC 10801 trial was open for accrual between 1980 and 1986 in eight centres in the UK , the Netherl and s , Belgium , and South Africa . 448 patients were r and omised to BCT and 420 to MRM . R and omisation was done central ly , stratifying patients by institute , carcinoma stage ( I or II ) , and menopausal status . BCT comprised of lumpectomy and complete axillary clearance , followed by breast radiotherapy and a tumour-bed boost . The primary endpoint was time to distant metastasis . This analysis was done on all eligible patients , as they were r and omised . FINDINGS After a median follow-up of 22·1 years ( IQR 18·5 - 23·8 ) , 175 patients ( 42 % ) had distant metastases in the MRM group versus 207 ( 46 % ) in the BCT group . Furthermore , 506 patients ( 58 % ) died ( 232 [ 55 % ] in the MRM group and 274 [ 61 % ] in the BCT group ) . No significant difference was observed between BCT and MRM for time to distant metastases ( hazard ratio 1·13 , 95 % CI 0·92 - 1·38 ; p=0·23 ) or for time to death ( 1·11 , 0·94 - 1·33 ; 0·23 ) . Cumulative incidence of distant metastases at 20 years was 42·6 % ( 95 % CI 37·8 - 47·5 ) in the MRM group and 46·9 % ( 42·2 - 51·6 ) in the BCT group . 20-year overall survival was estimated to be 44·5 % ( 95 % CI 39·3 - 49·5 ) in the MRM group and 39·1 % ( 34·4 - 43·9 ) in the BCT group . There was no difference between the groups in time to distant metastases or overall survival by age ( time to distant metastases : < 50 years 1·09 [ 95 % CI 0·79 - 1·51 ] vs ≥50 years 1·16 [ 0·90 - 1·50 ] ; overall survival < 50 years 1·17 [ 0·86 - 1·59 ] vs ≥50 years 1·10 [ 0·89 - 1·37 ] ) . INTERPRETATION BCT , including radiotherapy , offered as st and ard care to patients with early breast cancer seems to be justified , since long-term follow-up in this trial showed similar survival to that after mastectomy . FUNDING European Organisation for Research and Treatment of Cancer ( EORTC ) PURPOSE To analyze the influence of different patient , tumor , and treatment parameters on the cosmetic outcome after breast-conserving therapy at 3-year follow-up . A subjective and an objective cosmetic scoring method was used and the results of both methods were compared . PATIENTS AND METHODS In EORTC trial 22881/10882 , 5569 early-stage breast cancer patients were treated with tumorectomy and axillary dissection , followed by tangential fields irradiation of the breast to a dose of 50 Gy in 5 weeks , at 2 Gy per fraction . A total of 5318 patients , having a microscopically complete tumorectomy , were r and omized between no further treatment and a boost of 16 Gy to the primary tumor bed . The cosmetic result at 3-year follow-up was assessed by a panel for 731 patients , and by digitizer measurements , measuring the displacement of the nipple , for 1141 patients . Univariate and multivariate analyses were used to evaluate the correlation between various patient , tumor , and treatment factors and cosmesis . RESULTS The factors associated with a worsened cosmesis according to the panel evaluation were : an inferior tumor location , a large excision volume , the presence of postoperative breast complications , and the radiotherapy boost . According to the digitizer measurements , a central /superior tumor location , a large excision volume , an increased pathological tumor size , an increased radiation dose inhomogeneity , and an increased bra cup size result ed in an increased asymmetry in nipple position . It appeared that the evaluation of the nipple position ( whether by panel or by digitizer ) is only moderately representative of the overall cosmetic outcome . CONCLUSION To achieve a good cosmesis , it is necessary to excise the tumor with a limited margin , to avoid postoperative complications , to assess the need for a boost in the individual patient , and to give the radiation dose as homogeneously as possible . As far as the method of evaluation is concerned , the panel evaluation is the most appropriate method for giving an overall impression of the cosmetic result after breast-conserving therapy ( BCT ) . The use of the digitizer is recommended for comparing the cosmetic outcome of two different approaches to BCT or for analyzing cosmetic changes over time BACKGROUND In breast cancer treated with breast-conserving radiotherapy , the influence of the boost dose on cosmetic outcome after long-term follow-up is unknown . PATIENTS AND METHODS We included 348 patients participating in the EORTC ' boost versus no boost ' mega trial with a minimum follow-up of 6 years . Digitalised pictures were analysed using specific software , enabling quantification of seven relative asymmetry features associated with different aspects of fibrosis . RESULTS After 3 years , we noted a statistically significantly poorer outcome for the boost patients for six features compared with those of the no boost patients . Up to 9 years of follow-up , results continued to worsen in the same magnitude for the both patient groups . We noted the following determinants for poorer outcome : ( i ) boost treatment , ( ii ) larger excision volumes , ( iii ) younger age , ( iv ) tumours located in the central lower quadrants of the breast and ( v ) a boost dose administered with photons . CONCLUSIONS A boost dose worsens the change in breast appearance in the first 3 years . Moreover , the development of fibrosis associated with whole-breast irradiation , as estimated with the relative asymmetry features , is an ongoing process until ( at least ) 9 years after irradiation BACKGROUND In 1976 , we initiated a r and omized trial to determine whether lumpectomy with or without radiation therapy was as effective as total mastectomy for the treatment of invasive breast cancer . METHODS A total of 1851 women for whom follow-up data were available and nodal status was known underwent r and omly assigned treatment consisting of total mastectomy , lumpectomy alone , or lumpectomy and breast irradiation . Kaplan-Meier and cumulative-incidence estimates of the outcome were obtained . RESULTS The cumulative incidence of recurrent tumor in the ipsilateral breast was 14.3 percent in the women who underwent lumpectomy and breast irradiation , as compared with 39.2 percent in the women who underwent lumpectomy without irradiation ( P<0.001 ) . No significant differences were observed among the three groups of women with respect to disease-free survival , distant-disease-free survival , or overall survival . The hazard ratio for death among the women who underwent lumpectomy alone , as compared with those who underwent total mastectomy , was 1.05 ( 95 percent confidence interval , 0.90 to 1.23 ; P=0.51 ) . The hazard ratio for death among the women who underwent lumpectomy followed by breast irradiation , as compared with those who underwent total mastectomy , was 0.97 ( 95 percent confidence interval , 0.83 to 1.14 ; P=0.74 ) . Among the lumpectomy-treated women whose surgical specimens had tumor-free margins , the hazard ratio for death among the women who underwent postoperative breast irradiation , as compared with those who did not , was 0.91 ( 95 percent confidence interval , 0.77 to 1.06 ; P=0.23 ) . Radiation therapy was associated with a marginally significant decrease in deaths due to breast cancer . This decrease was partially offset by an increase in deaths from other causes . CONCLUSIONS Lumpectomy followed by breast irradiation continues to be appropriate therapy for women with breast cancer , provided that the margins of resected specimens are free of tumor and an acceptable cosmetic result can be obtained PURPOSE To investigate the impact of the boost dose to the primary tumour bed in the framework of breast conserving therapy on local control , cosmetic results , fibrosis and overall survival for patients with early stage breast cancer . PATIENTS AND METHODS Five thous and five hundred and sixty-nine patients after lumpectomy followed by whole breast irradiation of 50 Gy were r and omised . After a microscopically complete lumpectomy ( 5318 patients ) , the boost doses were either 0 or 16 Gy , while after a microscopically incomplete ( 251 patients ) lumpectomy r and omisation was between 10 and 26 Gy . The results at a median follow-up of 10 years are presented . RESULTS At 10 years , the cumulative incidence of local recurrence was 10.2 % versus 6.2 % for the 0 Gy and the 16 Gy boost groups ( p < 0.0001 ) and 17.5 % versus 10.8 % for the 10 and 26 Gy boost groups , respectively ( p > 0.1 ) . There was no statistically significant interaction per age group but recurrences tended to occur earlier in younger patients . As younger patients had a higher cumulative risk of local relapse by year 10 , the magnitude of the absolute 10-year risk reduction achieved with the boost decreased with increasing age . Development of fibrosis was significantly dependent on the boost dose with a 10-year rate for severe fibrosis of 1.6 % after 0 Gy , 3.3 % after 10 Gy , 4.4 % after 16 Gy and 14.4 % after 26 Gy , respectively . CONCLUSION An increase of the dose with 16 Gy improved local control for patients after a complete lumpectomy only . The development of fibrosis was clearly dose dependent . With 10 years median follow-up , no impact of survival was observed PURPOSE To examine the cost-effectiveness of radiation therapy following conservative surgery for early-stage breast cancer . METHODS Using a Markov model , a cost-utility analysis was performed to compare a strategy of radiation therapy versus no radiation therapy in a hypothetical cohort of 60-year-old women following conservative surgery . Local recurrence , distant recurrence , and survival rates used in the model were derived from r and omized trial data . Utilities for the nonmetastatic health states were collected from actual patients . Direct medical costs were estimated using data from a single institution . Transportation and time costs were also estimated . Years of life , quality -adjusted life-years ( QALYs ) , costs , and incremental cost/QALY over a 10-year time horizon were calculated by the model for each strategy . RESULTS The addition of radiation therapy results in a cost increase of $ 9,800 per patient , no change in life expectancy , and an increase of 0.35 QALYs per patient , which leads to an incremental cost-effectiveness ratio of $ 28,000/QALY , which is well below $ 50,000/QALY , a commonly cited threshold for cost-effective care . Sensitivity analysis shows the ratio to be heavily influenced by the cost of radiation therapy and the quality -of-life benefit that results from decreased risk of local recurrence . CONCLUSION Radiation therapy following conservative surgery is cost-effective compared with other accepted medical interventions . This study illustrates the importance of considering an intervention 's effect on quality of life , as well as survival in defining cost-effectiveness PURPOSE To evaluate both qualitative and quantitative scoring methods for the cosmetic result after breast-conserving therapy ( BCT ) , and to compare the usefulness and reliability of these methods . METHODS AND MATERIAL S In EORTC trial 22881/10882 , stage I and II breast cancer patients were treated with tumorectomy and axillary dissection . A total of 5318 patients were r and omized between no boost and a boost of 16 Gy following whole-breast irradiation of 50 Gy . The cosmetic result was assessed for 731 patients in two ways . A panel scored the qualitative appearance of the breast using photographs taken after surgery and 3 years later . Digitizer measurements of the displacement of the nipple were also made using these photographs in order to calculate the breast retraction assessment ( BRA ) . The cosmetic results after 3-year follow-up were used to analyze the correlation between the panel evaluation and digitizer measurements . RESULTS For the panel evaluation the intraobserver agreement for the global cosmetic score as measured by the simple Kappa statistic was 0.42 , considered moderate agreement . The multiple Kappa statistic for interobserver agreement for the global cosmetic score was 0.28 , considered fair agreement . The specific cosmetic items scored by the panel were all significantly related to the global cosmetic score ; breast size and shape influenced the global score most . For the digitizer measurements , the st and ard deviation from the average value of 30.0 mm was 2.3 mm ( 7.7 % ) for the intraobserver variability and 2.6 mm ( 8.7 % ) for the interobserver variability . The two methods were significantly , though moderately , correlated ; some items scored by the panel were only correlated to the digitizer measurements if the tumor was not located in the inferior quadrant of the breast . CONCLUSIONS The intra- and interobserver variability of the digitizer evaluation of cosmesis was smaller than that of the panel evaluation . However , there are some treatment sequelae , such as disturbing scars and skin changes , that can not be evaluated by BRA measurements . Therefore , the methods of cosmetic evaluation used in a study must be chosen in a way that balances reliability and comprehensiveness The aims of this study were to evaluate the impact of cosmetic and functional outcomes after breast-conserving surgery ( BCS ) and radiation on quality of life ( QOL ) . In this exploratory analysis ; baseline , 5 and 10 years data of patient ’s assessment of breast cosmesis , arm swelling/pain , limitation of movement , loss of feeling in fingers and breast sensitivity/tenderness were dichotomized and their impact on QOL ( QLQ-C30 ) were assessed . Multivariable modelling was also performed to assess associations with QOL . The St. George and Wollongong r and omized trial r and omized 688 patients into the boost and no boost arms . 609 , 580 , and 428 patients had baseline , 5 and 10 years cosmetic data available , respectively . Similar numbers had the various functional assessment s in the corresponding period . By univariate analysis , cosmesis and a number of functional outcomes were highly associated with QOL . Adjusted multivariate modelling showed that cosmesis remained associated with QOL at 5 and 10 years . Breast sensitivity , arm pain , breast separation , age and any distant cancer event were also associated with QOL on multivariate modelling at 10 years . This study highlights the importance of maintaining favorable cosmetic and functional outcomes following BCS . In addition , the clinical ly and statistically significant relationship between functional outcomes and QOL shows the importance for clinicians and allied health professionals in identifying , discussing , managing , and limiting these effects in women with breast cancer in order to maintain QOL PURPOSE To investigate the long-term impact of pathologic characteristics and an extra boost dose of 16 Gy on local relapse , for stage I and II invasive breast cancer patients treated with breast conserving therapy ( BCT ) . PATIENTS AND METHODS In the European Organisation for Research and Treatment of Cancer boost versus no boost trial , after whole breast irradiation , patients with microscopically complete excision of invasive tumor , were r and omly assigned to receive or not an extra boost dose of 16 Gy . For a subset of 1,616 patients central pathology review was performed . RESULTS The 10-year cumulative risk of local breast cancer relapse as a first event was not significantly influenced if the margin was scored negative , close or positive for invasive tumor or ductal carcinoma in situ according to central pathology review ( log-rank P = .45 and P = .57 , respectively ) . In multivariate analysis , high- grade invasive ductal carcinoma was associated with an increased risk of local relapse ( P = .026 ; hazard ratio [ HR ] , 1.67 ) , as was age younger than 50 years ( P < .0001 ; HR , 2.38 ) . The boost dose of 16 Gy significantly reduced the local relapse rate ( P = .0006 ; HR , 0.47 ) . For patients younger than 50 years old and in patients with high grade invasive ductal carcinoma , the boost dose reduced the local relapse from 19.4 % to 11.4 % ( P = .0046 ; HR , 0.51 ) and from 18.9 % to 8.6 % ( P = .01 ; HR , 0.42 ) , respectively . CONCLUSION Young age and high- grade invasive ductal cancer were the most important risk factors for local relapse , while margin status had no significant influence . A boost dose of 16 Gy significantly reduced the negative effects of both young age and high- grade invasive cancer BACKGROUND Radiotherapy prevents local recurrence of breast cancer after breast-conserving surgery . We evaluated the effect of a supplementary dose of radiation to the tumor bed on the rates of local recurrence among patients who received radiotherapy after breast-conserving surgery for early breast cancer . METHODS After lumpectomy and axillary dissection , patients with stage I or II breast cancer received 50 Gy of radiation to the whole breast in 2-Gy fractions over a five-week period . Patients with a microscopically complete excision were r and omly assigned to receive either no further local treatment ( 2657 patients ) or an additional localized dose of 16 Gy , usually given in eight fractions by means of an external electron beam ( 2661 patients ) . RESULTS During a median follow-up period of 5.1 years , local recurrences were observed in 182 of the 2657 patients in the st and ard-treatment group and 109 of the 2661 patients in the additional-radiation group . The five-year actuarial rates of local recurrence were 7.3 percent ( 95 percent confidence interval , 6.8 to 7.6 percent ) and 4.3 percent ( 95 percent confidence interval , 3.8 to 4.7 percent ) , respectively ( P<0.001 ) , yielding a hazard ratio for local recurrence of 0.59 ( 99 percent confidence interval , 0.43 to 0.81 ) associated with an additional dose . Patients 40 years old or younger benefited most ; at five years , their rate of local recurrence was 19.5 percent with st and ard treatment and 10.2 percent with additional radiation ( hazard ratio , 0.46 [ 99 percent confidence interval , 0.23 to 0.89 ] ; P=0.002 ) . At five years in the age group 41 to 50 years old , no differences were found in rates of metastasis or overall survival ( which were 87 and 91 percent , respectively ) . CONCLUSIONS In patients with early breast cancer who undergo breast-conserving surgery and receive 50 Gy of radiation to the whole breast , an additional dose of 16 Gy of radiation to the tumor bed reduces the risk of local recurrence , especially in patients younger than 50 years of age PURPOSE To evaluate the influence of a radiotherapy boost on the cosmetic outcome after 3 years of follow-up in patients treated with breast-conserving therapy ( BCT ) . METHODS AND MATERIAL S In EORTC trial 22881/10882 , 5569 Stage I and II breast cancer patients were treated with tumorectomy and axillary dissection , followed by tangential irradiation of the breast to a dose of 50 Gy in 5 weeks , at 2 Gy per fraction . Patients having a microscopically complete tumor excision were r and omized between no boost and a boost of 16 Gy . The cosmetic outcome was evaluated by a panel , scoring photographs of 731 patients taken soon after surgery and 3 years later , and by digitizer measurements , measuring the displacement of the nipple of 3000 patients postoperatively and of 1141 patients 3 years later . RESULTS There was no difference in the cosmetic outcome between the two treatment arms after surgery , before the start of radiotherapy . At 3-year follow-up , both the panel evaluation and the digitizer measurements showed that the boost had a significant adverse effect on the cosmetic result . The panel evaluation at 3 years showed that 86 % of patients in the no-boost group had an excellent or good global result , compared to 71 % of patients in the boost group ( p = 0.0001 ) . The digitizer measurements at 3 years showed a relative breast retraction assessment ( pBRA ) of 7.6 pBRA in the no-boost group , compared to 8.3 pBRA in the boost group , indicating a worse cosmetic result in the boost group at follow-up ( p = 0.04 ) . CONCLUSIONS These results showed that a boost dose of 16 Gy had a negative , but limited , impact on the cosmetic outcome after 3 years BACKGROUND Since the introduction of breast-conserving treatment , various radiation doses after lumpectomy have been used . In a phase 3 r and omised controlled trial , we investigated the effect of a radiation boost of 16 Gy on overall survival , local control , and fibrosis for patients with stage I and II breast cancer who underwent breast-conserving treatment compared with patients who received no boost . Here , we present the 20-year follow-up results . METHODS Patients with microscopically complete excision for invasive disease followed by whole-breast irradiation of 50 Gy in 5 weeks were central ly r and omised ( 1:1 ) with a minimisation algorithm to receive 16 Gy boost or no boost , with minimisation for age , menopausal status , presence of extensive ductal carcinoma in situ , clinical tumour size , nodal status , and institution . Neither patients nor investigators were masked to treatment allocation . The primary endpoint was overall survival in the intention-to-treat population . The trial is registered with Clinical Trials.gov , number NCT02295033 . FINDINGS Between May 24 , 1989 , and June 25 , 1996 , 2657 patients were r and omly assigned to receive no radiation boost and 2661 patients r and omly assigned to receive a radiation boost . Median follow-up was 17.2 years ( IQR 13.0 - 19.0 ) . 20-year overall survival was 59.7 % ( 99 % CI 56.3 - 63.0 ) in the boost group versus 61.1 % ( 57.6 - 64.3 ) in the no boost group , hazard ratio ( HR ) 1.05 ( 99 % CI 0.92 - 1.19 , p=0.323 ) . Ipsilateral breast tumour recurrence was the first treatment failure for 354 patients ( 13 % ) in the no boost group versus 237 patients ( 9 % ) in the boost group , HR 0.65 ( 99 % CI 0.52 - 0.81 , p<0.0001 ) . The 20-year cumulative incidence of ipsilatelal breast tumour recurrence was 16.4 % ( 99 % CI 14.1 - 18.8 ) in the no boost group versus 12.0 % ( 9.8 - 14.4 ) in the boost group . Mastectomies as first salvage treatment for ipsilateral breast tumour recurrence occurred in 279 ( 79 % ) of 354 patients in the no boost group versus 178 ( 75 % ) of 237 in the boost group . The cumulative incidence of severe fibrosis at 20 years was 1.8 % ( 99 % CI 1.1 - 2.5 ) in the no boost group versus 5.2 % ( 99 % CI 3.9 - 6.4 ) in the boost group ( p<0.0001 ) . INTERPRETATION A radiation boost after whole-breast irradiation has no effect on long-term overall survival , but can improve local control , with the largest absolute benefit in young patients , although it increases the risk of moderate to severe fibrosis . The extra radiation dose can be avoided in most patients older than age 60 years . FUNDING Fonds Cancer , Belgium INTRODUCTION The nipple-areolar complex ( NAC ) has special histological properties with higher melanocyte concentration than breast skin . To date , there are no data describing the late effects on the NAC following breast-conserving therapy ( BCT ) . This study evaluated colour changes in the NAC in patients treated with breast-conserving surgery and adjuvant radiotherapy after 5 years . METHODS Digital photographs obtained at 5 years following breast irradiation from the St. George and Wollongong ( SGW ) trial ( NCT00138814 ) were evaluated by five experts using an iPad ® ( Apple Inc. , Cupertino , CA , USA ) application specifically created for this study . The SGW trial r and omised 688 patients with Tis-2 , N0 - 1 , M0 carcinoma to the control arm of 50 Gy in 25 fractions and boost arm of 45 Gy in 25 fractions and 16 Gy in 8 fractions electron boost . RESULTS A total of 141/372 ( 38 % ) patients had altered NAC ( 86 % lighter , 10 % darker ) . Patients with Celtic skin type had increased likelihood of having an altered NAC ( odds ratio ( OR ) , 1.75 ( CI 1.1 - 2.7 , P = 0.011 ) ) . On subgroup analysis , those with Celtic skin type receiving biologically equivalent dose ( BED ) Gy3 ≥ 80 Gy had OR of 3.03 ( 95 % CI 1.2 - 7.5 , P = 0.016 ) for having altered colour . There was a dose response with more profound changes seen in the NAC compared with irradiated breast skin if BED Gy3 ≥ 80 Gy with OR of 2.42 ( 95 % CI 1.1 - 5.6 , P = 0.036 ) . CONCLUSION In this Caucasian BCT population , over 30 % of patients developed lighter NAC and more commonly in women with Celtic skin type . The degree of this effect increased with higher radiation dose BACKGROUND AND PURPOSE The EORTC Trial 22881/10882 investigating the role of a boost dose in breast conserving therapy demonstrated a significantly better local control rate with the higher radiotherapy dose , especially in women younger than 50 years of age . This paper investigates the potential impact of the different boost techniques on local control and on fibrosis after breast conserving therapy . PATIENTS AND METHODS From 1989 to 1996 , 2661 patients were r and omised to receive a boost dose of 16Gy to the primary tumour bed after microscopically complete tumorectomy and 50Gy whole breast irradiation . The choice of the boost technique was left to the treating investigator . Treatment data were prospect ively recorded as well as the clinical outcome in terms of local control and fibrosis . Sixty-three percent of the patients received a boost dose with fast electrons , 28 % with photon beams and 9 % with interstitial brachytherapy . RESULTS At 5 years , local recurrences were seen in 74 of the 1635 patients who received an electron boost ( 4.8 % , CI 3.6 - 5.9 % ) , in 28 of the 753 patients who received a photon boost ( 4.0 % , CI 3.4 - 5.5 % ) and in 6 of the 225 patients after an interstitial boost ( 2.5 % , CI 0.3 - 4.6 % ) . The grade of fibrosis in the whole breast as well as at the primary tumour bed , as scored by the treating radiation oncologist , was similar in the three groups . CONCLUSIONS Although the three groups are of a rather unequal size , the results of the interstitial boost seem similar in terms of fibrosis and at least as good in terms of local control , despite a lower treatment volume and a longer overall treatment time The therapeutic use of ionizing radiations is predicated on sparing normal tissue effects while attempting to achieve lethal effects on tumor cells . From quite early in the history of radiation therapy , it was apparent that there were striking differences in effects in the panoply of normal tissues . Although there was early appreciation of some late effects in normal tissues , often not predicted by acute reactions , only in recent years has there been full documentation of the slow and progressive increase in severity of late damage . Pathophysiological mechanisms of acute and late radiation effects are better understood today ( 2 ) , but interactions of other modalities with radiation therapy require constant monitoring to recognize and mitigate untoward sequelae . The work of Stone ( 3 ) is a classic example of unanticipated late effects , which result ed from irradiation with ‘ fast neutrons . Acute reactions were moderate and tolerable , but the late sequelae were so marked that there was little interest in pursuing therapy with fast neutrons for nearly three decades . The Late Morbidity Scoring Criteria were developed as a joint effort between physicians with renewed interests in fast neutron therapy and Radiation Therapy Oncology Group ( RTOG ) staff . In the late 1970s the Neutron/Particle Committee was one of several modality committees of the RTOG . Recognizing the results of Stone , this committee , led by Lawrence Davis worked with RTOG staff to establish criteria and scoring for possible late effects from fast neutron radiation therapy . Investigators from the European Organization for Research and Treatment of Cancer ( EORTC ) , led by William Duncan of the Western General Hospital of Edinburgh , wished to have common toxicity criteria in anticipation of joint studies . RTOG Protocol 7929 , an international registry of patients treated with heavy particles , was started in 1980 . At the annual meetings of the international participants in particle studies , there were attempts to monitor interobserver variations in scoring effects in normal tissues and to seek consistency in reporting toxicity , but no publications document these efforts . The first prospect i ve trial to use the Late Morbidity Scoring Criteria was RTOG Protocol 8001 , a study of fast neutron therapy for malignant tumors arising in salivary gl and s. Although the RTOG began to use these criteria in reporting toxicity in patients enrolled in all studies from 198 1 ( beginning with RTOG Protocol 8 115 ) , the criteria only became a published part of protocol s in 1983 . At that time , statistical methods began to be used , which presented time-adjusted estimates of late effects , the rationale for which was described by Cox ( 1 ) . It is now considered st and ard to represent cumulative probabilities of late effects with methods similar to those for estimating local control and survival . The Acute Radiation Morbidity Scoring Criteria were developed in 1985 as complimentary to the Late Effects Scoring Criteria . The National Cancer Institute promulgated st and ard toxicity criteria in 1990 , but late effects were not considered . An abbreviated version of the RTOG/EORTC toxicity criteria was published by Winchester and Cox in 1992 as part of the St and ard for Breast Conservation Treatment . The current RTOG Acute Radiation Morbidity Scoring Criteria are presented in Table 1 . The RTOG/EORTC Late Radiation Morbidity Scoring Scheme is detailed in Table 2 . In both tables , 0 means an absence of radiation effects and 5 means the effects led to death . The Summary Background The international st and ard radiotherapy schedule for breast cancer treatment delivers a high total dose in 25 small daily doses ( fractions ) . However , a lower total dose delivered in fewer , larger fractions ( hypofractionation ) is hypothesised to be at least as safe and effective as the st and ard treatment . We tested two dose levels of a 13-fraction schedule against the st and ard regimen with the aim of measuring the sensitivity of normal and malignant tissues to fraction size . Methods Between 1998 and 2002 , 2236 women with early breast cancer ( pT1 - 3a pN0 - 1 M0 ) at 17 centres in the UK were r and omly assigned after primary surgery to receive 50 Gy in 25 fractions of 2·0 Gy versus 41·6 Gy or 39 Gy in 13 fractions of 3·2 Gy or 3·0 Gy over 5 weeks . Women were eligible if they were aged over 18 years , did not have an immediate surgical reconstruction , and were available for follow-up . R and omisation method was computer generated and was not blinded . The protocol -specified principal endpoints were local-regional tumour relapse , defined as reappearance of cancer at irradiated sites , late normal tissue effects , and quality of life . Analysis was by intention to treat . This study is registered as an International St and ard R and omised Controlled Trial , number IS RCT N59368779 . Findings 749 women were assigned to the 50 Gy group , 750 to the 41·6 Gy group , and 737 to the 39 Gy group . After a median follow up of 5·1 years ( IQR 4·4–6·0 ) the rate of local-regional tumour relapse at 5 years was 3·6 % ( 95 % CI 2·2–5·1 ) after 50 Gy , 3·5 % ( 95 % CI 2·1–4·3 ) after 41·6 Gy , and 5·2 % ( 95 % CI 3·5–6·9 ) after 39 Gy . The estimated absolute differences in 5-year local-regional relapse rates compared with 50 Gy were 0·2 % ( 95 % CI −1·3 % to 2·6 % ) after 41·6 Gy and 0·9 % ( 95 % CI −0·8 % to 3·7 % ) after 39 Gy . Photographic and patient self- assessment s suggested lower rates of late adverse effects after 39 Gy than with 50 Gy , with an HR for late change in breast appearance ( photographic ) of 0·69 ( 95 % CI 0·52–0·91 , p=0·01 ) . From a planned meta- analysis with the pilot trial , the adjusted estimates of α/β value for tumour control was 4·6 Gy ( 95 % CI 1·1–8·1 ) and for late change in breast appearance ( photographic ) was 3·4 Gy ( 95 % CI 2·3–4·5 ) . Interpretation The data are consistent with the hypothesis that breast cancer and the dose-limiting normal tissues respond similarly to change in radiotherapy fraction size . 41·6 Gy in 13 fractions was similar to the control regimen of 50 Gy in 25 fractions in terms of local-regional tumour control and late normal tissue effects , a result consistent with the result of START Trial B. A lower total dose in a smaller number of fractions could offer similar rates of tumour control and normal tissue damage as the international st and ard fractionation schedule of 50 Gy in 25 fractions 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 PURPOSE IBTR ! version 1.0 is a web-based tool that uses literature -derived relative risk ratios for seven clinicopathologic variables to predict ipsilateral breast tumor recurrence ( IBTR ) after breast-conserving therapy ( BCT ) . Preliminary testing demonstrated over-estimation in high-risk subgroups . This study uses two independent population -based data sets to create and vali date a modified nomogram , IBTR ! version 2.0 . METHODS Cox regression modeling was performed on 7,811 patients treated with BCT at the British Columbia Cancer Agency ( median follow-up , 9.4 years ) . Population -based hazard ratios were generated for the seven variables in the original nomogram . A modified nomogram was then tested against 664 patients from Massachusetts General Hospital ( median follow-up , 9.3 years ) . The mean predicted and observed 10-year estimates were compared for the entire cohort and for four groups predefined by nomogram-predicted risks : group 1 : less than 3 % ; group 2 : 3 % to 5 % ; group 3 : 5 % to 10 % ; and group 4 : more than 10 % . Results IBTR ! version 2.0 predicted an overall 10-year IBTR estimate of 4.0 % ( 95 % CI , 3.8 to 4.2 ) , while the observed estimate was 2.8 % ( 95 % CI , 1.6 to 4.7 ; P = .10 ) . The predicted and observed IBTR estimates were : group 1 ( n = 283 ) : 2.2 % versus 1.3 % , P = .40 ; group 2 ( n = 237 ) : 3.8 % versus 3.5 % , P = .80 ; group 3 ( n = 111 ) : 6.7 % versus 3.2 % , P = .05 ; and group 4 ( n = 33 ) : 12.5 % versus 8.7 % , P = .50 . CONCLUSION IBTR ! version 2.0 is accurate in the majority of patients with a low to moderate risk of in-breast recurrence . The nomogram still overestimates risk in a minority of patients with higher risk features . Validation in a larger prospect i ve data set is warranted |
10,731 | 30,045,912 | The BMJ Rapid Recommendations panel used a linked systematic review 1 triggered by three large r and omised trials published in September 2017 that suggested PFO closure might reduce the risk of ischaemic stroke more than alternatives.234 The panel felt that the studies , when considered in the context of the full body of evidence , might change current clinical practice .5 The linked systematic review finds that PFO closure prevents recurrent stroke relative to antiplatelet therapy , but possibly not relative to anticoagulants , and is associated with procedural complications and persistent atrial fibrillation.1 The review also presents evidence regarding the role of anticoagulants or antiplatelet therapy when PFO closure is not acceptable or is contraindicated . | null | null |
10,732 | 31,244,906 | Partner and family have similar diet , lifestyle , and micro- and macro-environments which could explain the similar increased risk of diabetes and non-communicable diseases .
Partner support has major role in prevention and control of diabetes distress , associated depression , and medication non-compliance which have an adverse impact in glycaemic outcomes .
Conclusion : The support of family and spouse/partner is beneficial to improve adherence to the lifestyle interventions and pharmacotherapy required to achieve optimum glycaemic control and avoid associated complications | Background and aims : Knowledge of therapeutic lifestyle interventions is one of the most important pillars of diabetes care ; however , its incorporation in real-world setting s is poor .
This review evaluates the role of partner and family support in diabetes management . | OBJECTIVE To compare glycemic control and secondary outcomes of a 4-month telephonic couples behavioral intervention to individual intervention , and to education , for adults with type 2 diabetes . RESEARCH DESIGN AND METHODS A r and omized trial with the following three arms : couples calls ( CC ) ( n = 104 ) ; individual calls ( IC ) ( n = 94 ) ; and diabetes education ( DE ) ( n = 82 ) . All arms had self-management education ( two calls ) . CC and IC had 10 additional behavior change calls . CC addressed collaboration and relationships/communication . Participants consisted of 280 couples , among whom one partner had type 2 diabetes and an A1C level ≥7.5 % . Blinded assessment s occurred at 4 , 8 , and 12 months . The primary outcome was change in A1C ; and secondary outcomes were BMI , waist circumference , blood pressure , depressive symptoms , diabetes self-efficacy , and diabetes distress . RESULTS Patients had a mean age of 56.8 years ; 61.6 % were male , and 30.4 % were minorities . The baseline mean A1C level was 9.1 % . Intention-to-treat analyses found significant A1C reductions for all ( 12 months : CC −0.47 % , IC −0.52 % , DE −0.57 % ) , with no differences between arms . Preplanned within-arm analyses were stratified by baseline A1C tertiles : lowest tertile ( 7.5–8.2 % ) , no change from baseline ; middle tertile ( 8.3–9.2 % ) , only CC led to significantly lower A1C level ; and highest tertile ( ≥9.3 % ) , significant improvement for all interventions . For BMI , CC showed significant improvement , and CC and DE led to decreased waist circumference . The IC group showed greater blood pressure improvement . Results for secondary psychosocial outcomes favored the CC group . CONCLUSIONS In adults with poorly controlled type 2 diabetes , a collaborative couples intervention result ed in significant , lasting improvement in A1C levels , obesity measures , and some psychosocial outcomes . For those with exceedingly high A1C levels , education alone was beneficial , but additional intervention is needed to achieve glycemic targets Background Many community-based self-management programs have been developed for older adults with type-2 diabetes mellitus ( T2DM ) , bolstered by evidence from r and omized controlled trials ( RCTs ) that T2DM can be prevented and managed through lifestyle modifications . However , the evidence for their effectiveness is contradictory and weakened by reliance on single-group design s and /or small sample s. Additionally , older adults with multiple chronic conditions ( MCC ) are often excluded because of recruiting and retention challenges . This paper presents a protocol for a two-armed , multisite , pragmatic , mixed- methods RCT examining the effectiveness and implementation of the Aging , Community and Health Research Unit-Community Partnership Program ( ACHRU-CPP ) , a new 6-month interprofessional , nurse-led program to promote self-management in older adults ( aged 65 years or older ) with T2DM and MCC and support their caregivers ( including family and friends ) . Methods / design The study will enroll 160 participants in two Canadian provinces , Ontario and Alberta . Participants will be r and omly assigned to the control ( usual care ) or program study arm . The program will be delivered by registered nurses ( RNs ) and registered dietitians ( RDs ) from participating diabetes education centers ( Ontario ) or primary care networks ( Alberta ) and program coordinators from partnering community-based organizations . The 6-month program includes three in-home visits , monthly group sessions , monthly team meetings for providers , and nurse-led care coordination . The primary outcome is the change in physical functioning as measured by the Physical Component Summary ( PCS-12 ) score from the short form-12v2 health survey ( SF-12 ) . Secondary client outcomes include changes in mental functioning , depressive symptoms , anxiety , and self-efficacy . Caregiver outcomes include health-related quality of life and depressive symptoms . The study includes a comparison of health care service costs for the intervention and control groups , and a subgroup analysis to determine which clients benefit the most from the program . Descriptive and qualitative data will be collected to examine implementation of the program and effects on interprofessional/team collaboration . Discussion This study will provide evidence of the effectiveness of a community-based self-management program for a complex target population . By study ing both implementation and effectiveness , we hope to improve the uptake of the program within the existing community-based structures , and reduce the research -to- practice gap . Trial registration Clinical Trials.gov , Identifier : NCT02158741 . Registered on 3 June 2014 Background : Non-adherence to oral antidiabetics drugs ( OADs ) has been a common problem and may contribute to poor glycemic control . Aim : To describe an experimental study protocol that aims at implementing and evaluating the effect of the “ action planning and coping planning ” interventions on medication adherence to OADs in patients with type 2 diabetes mellitus ( T2DM ) in follow-up at primary care services . Design : A r and omized controlled trial . Methods : Two groups ( intervention and control ) will be followed over a period of 105 days . The intervention group will receive a combination of the “ action planning ” and “ coping planning ” intervention strategies . There will be in-person meetings and phone calls to reinforce the intervention . The control group will receive the usual care from the health unit . Conclusions : It is hoped that this study will help health professionals to improve their approach with patients who have T2DM in relation to medication adherence AIMS Examine barriers for taking glucose-lowering oral medications , associated baseline characteristics , strategies used , and the adherence impact in the Treatment Options for Type 2 Diabetes in Adolescents and Youth ( TODAY ) study . METHODS We studied youth prescribed oral diabetes medications over two years ( N = 611 , 583 , and 525 at 6 , 12 , and 24 months ) . Clinicians documented barriers ( e.g. forgetting , routines , other concerns ) in the sub sample that reported missed doses ( N = 423 [ 69.2 % ] , 422 [ 72.4 % ] , and 414 [ 78.9 % ] at 6 , 12 , and 24 months , respectively ) . Adherence strategies were also assessed ( e.g. family , schedule , reminder device ) using st and ard questions . Logistic regression was used to analyze associations with medication adherence . RESULTS Those missing doses were not different from the total sample ( 61.5 % female , 13.9 ± 2.0 years , > 80 % racial/ethnic minorities ) . No baseline demographic or clinical predictors of barriers to medication adherence were identified . Among those for whom barriers were assessed , " forgetting " with no reason named ( 39.3 % ) and disruptions to mealtime , sleep , and schedule ( 21.9 % ) accounted for the largest proportion of responses . Family support was the primary adherence strategy identified by most youth ( ≥50 % ) , followed by pairing the medication regimen with daily routines ( > 40 % ) ; the latter strategy was associated with significantly higher adherence rates ( p = 0.009 ) . CONCLUSIONS Family supported medication adherence was common in this mid-adolescent cohort , but self-management strategies were also in evidence . Findings are similar to those reported among youth with other serious chronic diseases . Prospect i ve studies of multi-component family support and self-management interventions for improving medication adherence are warranted . TRIAL REGISTRATION Clinical Trials.gov NCT00081328 AIMS We evaluated a theoretically-derived family-oriented intervention aim ed to improve self-efficacy , self-management , glycemic control and quality of life in individuals living with Type 2 diabetes in Thail and . METHODS In a single-blinded r and omized controlled trial , 140 volunteer individuals with Type 2 diabetes , recruited from a diabetes clinic in rural Thail and , were r and omly allocated to intervention and control arms . Those in the intervention arm received routine care plus a family-oriented program that included education classes , group discussion s , a home visit , and a telephone follow-up while the control arm only received routine care . Improvement in outcomes over time ( baseline , Week 3 , and Week 13 following intervention ) was evaluated using Generalized Estimating Equations multivariable analyses . RESULTS Except for age , no between-group significant differences were observed in all other baseline characteristics . Diabetes self-efficacy , self-management , and quality of life improved in the intervention arm but no improvement was observed in the controls . In the risk-adjusted multivariable models , compared to the controls , the intervention arm had significantly better self-efficacy , self-management , outcome expectations , and diabetes knowledge ( p<0.001 , in each ) . Participation in the intervention increased the diabetes self-management score by 14.3 points ( β=14.3 , ( 95 % CI 10.7 - 17.9 ) , p<0.001 ) . Self-management was better in leaner patients and in females . No between-group differences were seen in quality of life or glycemic control , however , in the risk-adjusted multivariable models , higher self-management scores were associated with significantly decreased HbA1c levels ( p<0.001 ) and improved patient quality of life ( p<0.05 ) ( irrespective of group membership ) . CONCLUSIONS Our family-oriented program improved patients ' self-efficacy and self-management , which in turn could decrease HbA1c levels Objective Spousal clustering of diabetes merits attention . Whether old-age vulnerability or a shared family environment determines the concordance of diabetes is also uncertain . This study investigated the spousal concordance of diabetes and compared the risk of diabetes concordance between couples and noncouples by using nationally representative data . Methods A total of 22,572 individuals identified from the 2002–2013 National Health Insurance Research Data base of Taiwan constituted 5,643 couples and 5,643 noncouples through 1:1 dual propensity score matching ( PSM ) . Factors associated with concordance in both spouses with diabetes were analyzed at the individual level . The risk of diabetes concordance between couples and noncouples was compared at the couple level . Logistic regression was the main statistical method . Statistical data were analyzed using SAS 9.4 . C&RT and Apriori of data mining conducted in IBM SPSS Modeler 13 served as a supplement to statistics . Results High odds of the spousal concordance of diabetes were associated with old age , middle levels of urbanization , and high comorbidities ( all P < 0.05 ) . The dual PSM analysis revealed that the risk of diabetes concordance was significantly higher in couples ( 5.19 % ) than in noncouples ( 0.09 % ; OR = 61.743 , P < 0.0001 ) . Conclusions A high concordance rate of diabetes in couples may indicate the influences of assortative mating and shared environment . Diabetes in a spouse implicates its risk in the partner . Family-based diabetes care that emphasizes the screening of couples at risk of diabetes by using the identified risk factors is suggested in prospect i ve clinical practice interventions Background This paper presents the pilot study and protocol for a r and omised controlled trial to test the effectiveness of a psychological , family-based intervention to improve outcomes in those with poorly controlled type 2 diabetes . The intervention has been design ed to change the illness perceptions of patients with poorly controlled type 2 diabetes , and their family members . It is a complex psychological intervention , developed from the Self-Regulatory Model of Illness Behaviour . The important influence the family context can have in psychological interventions and diabetes management is also recognised , by the inclusion of patients ' family members . Methods / design We aim to recruit 122 patients with persistently poorly controlled diabetes . Patients are deemed to have persistent poor control when at least two out of their last three HbA1c readings are 8.0 % or over . Patients nominate a family member to participate with them , and this patient/family member dyad is r and omly allocated to either the intervention or control group . Participants in the control group receive their usual care . Participants in the intervention group participate , with their family members , in three intervention sessions . Sessions one and two are delivered in the participant 's home by a health psychologist . Session one takes place approximately one week after session two , with the third session , a follow-up telephone call , one week later . The intervention is based upon clarifying the illness perceptions of both the patient and the family member , examining how they influence self-management behaviours , improving the degree of similarity of patient and family member perceptions in a positive direction and developing personalized action plans to improve diabetes management . Discussion This study is the first of its kind to incorporate the evidence from illness perceptions research into developing and applying an intervention for people with poorly controlled diabetes and their families . This study also acknowledges the important role of family members in effective diabetes care . Trial registration IS RCT Objective To evaluate 8-year weight losses achieved with intensive lifestyle intervention ( ILI ) in the Look AHEAD ( Action for Health in Diabetes ) study . Design and Methods Look AHEAD assessed the effects of intentional weight loss on cardiovascular morbidity and mortality in 5,145 overweight/obese adults with type 2 diabetes , r and omly assigned to ILI or usual care ( i.e. , diabetes support and education [ DSE ] ) . The ILI provided comprehensive behavioral weight loss counseling over 8 years ; DSE participants received periodic group education only . Results All participants had the opportunity to complete 8 years of intervention before Look AHEAD was halted in September 2012 ; ≥88 % of both groups completed the 8-year outcomes assessment . ILI and DSE participants lost ( mean±SE ) 4.7±0.2 % and 2.1±0.2 % of initial weight , respectively ( p<0.001 ) at year 8 ; 50.3 % and 35.7 % , respectively , lost ≥5 % ( p<0.001 ) , and 26.9 % and 17.2 % , respectively , lost ≥10 % ( p<0.001 ) . Across the 8 years ILI participants , compared with DSE , reported greater practice of several key weight-control behaviors . These behaviors also distinguished ILI participants who lost ≥10 % and kept it off from those who lost but regained . Conclusions Look AHEAD ’s ILI produced clinical ly meaningful weight loss ( ≥5 % ) at year 8 in 50 % of patients with type 2 diabetes and can be used to manage other obesity-related co-morbid conditions . Trial Registration clinical trials.gov Identifier : A pilot study was conducted to assess the feasibility and potential efficacy of a couples focused diabetes intervention in which a collaborative problem-solving approach to diabetes self-care was promoted . Couples ( N = 44 ) , in which one partner had Type 2 diabetes and was in poor blood glucose control were r and omly assigned to one of three groups : a couples intervention , an individual intervention , or individual diabetes education . The intervention included goal - setting , dietary behavior change , and a focus on emotions . For those in the couples arm , this was done within the framework of promoting collaborative communication between the partners . All intervention contacts were over the telephone to increase reach . Results showed that both the individual and couples interventions yielded meaningful clinical improvements in medical outcomes . Diabetes education also result ed in improved blood glucose control . Despite the small number , mixed-model regression analyses found statistically significant treatment effects for total cholesterol . This pilot demonstrates the feasibility and potential efficacy of a telephone intervention for Type 2 diabetes patients and their partners . Information from implementing this pilot led to refinement and further development of the intervention , which is being assessed in a larger , more comprehensive trial Family context is thought to influence chronic disease management but few studies have longitudinally examined these relationships . Research on families and chronic illness has focused almost exclusively on European American families . In this prospect i ve study we tested a multidimensional model of family influence on disease management in type 2 diabetes in a bi-ethnic sample of European Americans and Latinos . Specifically , we tested how baseline family characteristics ( structure , world view , and emotion management ) predicted change in disease management over one year in 104 European American and 57 Latino patients with type 2 diabetes . We found that emotion management predicted change in disease management in both groups of patients as hypothesized , while family world view predicted change in both ethnic groups but in the predicted direction only for European Americans . Examining family context within ethnic groups is required to eluci date unique cultural patterns . Attending to culturally unique interpretations of constructs and measures is warranted . The import of family emotion management , specifically conflict resolution , in disease management deserves further study to support clinical intervention development . Examining multiple domains of family life and multidimensional health outcomes strengthens our capacity to develop theory about family context s and individual health BACKGROUND Type 2 diabetes is a chronic disorder that requires lifelong treatment . We aim ed to assess whether intensive weight management within routine primary care would achieve remission of type 2 diabetes . METHODS We did this open-label , cluster-r and omised trial ( DiRECT ) at 49 primary care practice s in Scotl and and the Tyneside region of Engl and . Practice s were r and omly assigned ( 1:1 ) , via a computer-generated list , to provide either a weight management programme ( intervention ) or best- practice care by guidelines ( control ) , with stratification for study site ( Tyneside or Scotl and ) and practice list size ( > 5700 or ≤5700 ) . Participants , carers , and research assistants who collected outcome data were aware of group allocation ; however , allocation was concealed from the study statistician . We recruited individuals aged 20 - 65 years who had been diagnosed with type 2 diabetes within the past 6 years , had a body-mass index of 27 - 45 kg/m2 , and were not receiving insulin . The intervention comprised withdrawal of antidiabetic and antihypertensive drugs , total diet replacement ( 825 - 853 kcal/day formula diet for 3 - 5 months ) , stepped food re introduction ( 2 - 8 weeks ) , and structured support for long-term weight loss maintenance . Co- primary outcomes were weight loss of 15 kg or more , and remission of diabetes , defined as glycated haemoglobin ( HbA1c ) of less than 6·5 % ( < 48 mmol/mol ) after at least 2 months off all antidiabetic medications , from baseline to 12 months . These outcomes were analysed hierarchically . This trial is registered with the IS RCT N registry , number 03267836 . FINDINGS Between July 25 , 2014 , and Aug 5 , 2017 , we recruited 306 individuals from 49 intervention ( n=23 ) and control ( n=26 ) general practice s ; 149 participants per group comprised the intention-to-treat population . At 12 months , we recorded weight loss of 15 kg or more in 36 ( 24 % ) participants in the intervention group and no participants in the control group ( p<0·0001 ) . Diabetes remission was achieved in 68 ( 46 % ) participants in the intervention group and six ( 4 % ) participants in the control group ( odds ratio 19·7 , 95 % CI 7·8 - 49·8 ; p<0·0001 ) . Remission varied with weight loss in the whole study population , with achievement in none of 76 participants who gained weight , six ( 7 % ) of 89 participants who maintained 0 - 5 kg weight loss , 19 ( 34 % ) of 56 participants with 5 - 10 kg loss , 16 ( 57 % ) of 28 participants with 10 - 15 kg loss , and 31 ( 86 % ) of 36 participants who lost 15 kg or more . Mean bodyweight fell by 10·0 kg ( SD 8·0 ) in the intervention group and 1·0 kg ( 3·7 ) in the control group ( adjusted difference -8·8 kg , 95 % CI -10·3 to -7·3 ; p<0·0001 ) . Quality of life , as measured by the EuroQol 5 Dimensions visual analogue scale , improved by 7·2 points ( SD 21·3 ) in the intervention group , and decreased by 2·9 points ( 15·5 ) in the control group ( adjusted difference 6·4 points , 95 % CI 2·5 - 10·3 ; p=0·0012 ) . Nine serious adverse events were reported by seven ( 4 % ) of 157 participants in the intervention group and two were reported by two ( 1 % ) participants in the control group . Two serious adverse events ( biliary colic and abdominal pain ) , occurring in the same participant , were deemed potentially related to the intervention . No serious adverse events led to withdrawal from the study . INTERPRETATION Our findings show that , at 12 months , almost half of participants achieved remission to a non-diabetic state and off antidiabetic drugs . Remission of type 2 diabetes is a practical target for primary care . FUNDING Diabetes UK |
10,733 | 25,503,775 | Follow-up of studies comparing different osteotomy techniques was too short to measure treatment failure , which implicates revision to a knee arthroplasty .
The conclusion of this up date did not change : Valgus high tibial osteotomy reduces pain and improves knee function in patients with medial compartmental osteoarthritis of the knee .
However , this conclusion is based on within-group comparisons , not on non-operative controls .
No evidence suggests differences between different osteotomy techniques .
No evidence shows whether an osteotomy is more effective than alternative surgical treatment such as unicompartmental knee replacement or non-operative treatment .
So far , the results of this up date d review do not justify a conclusion on benefit of specific high tibial osteotomy technique for knee osteoarthritis | BACKGROUND Patients with unicompartmental osteoarthritis of the knee can be treated with an osteotomy .
The goal of an osteotomy is to unload the diseased compartment of the knee .
This is the second up date of the original review published in The Cochrane Library , Issue 1 , 2005 .
OBJECTIVES To assess the benefits and harms of an osteotomy for treating patients with knee osteoarthritis , including the following main outcomes scores : treatment failure , pain and function scores , health-related quality of life , serious adverse events , mortality and reoperation rate . | We describe the results of 50 operations carried out on 46 patients with medial osteoarthritis of the knee of Ahlbäck grade 1 to 3 . Patients were r and omised either to a closed-wedge high tibial osteotomy ( HTO ) or an open-wedge procedure based on the hemicallotasis technique ( HCO ) . Their median age was 55 years ( 38 to 68 ) . The preoperative median hip-knee-ankle ( HKA ) angle was 171 degrees ( 164 to 176 ) in the HTO group and 173 degrees ( 165 to 179 ) in the HCO group . After six weeks , the median HKA angle was 185 degrees ( 176 to 194 ) in the HTO group and 184 degrees ( 181 to 188 ) in the HCO group . In the HTO group , seven patients were within the range of 182 degrees to 186 degrees compared with 21 in the HCO group ( p < 0.001 ) . One year later , ten HTO patients were within this range while the HKA angulation in the HCO group was unchanged . At two years the numbers were 11 and 18 , respectively . We evaluated the clinical results on the Hospital for Special Surgery , Lysholm and Wallgren-Tegner activity scores , and patients completed part of the Nottingham Health Profile question naire . An impartial observer at the two-year follow-up concluded that all scores had improved , but found no clinical differences between the groups Background : Arthrosis is particularly prevalent in the knee . Infiltration treatment for gonarthrosis is among the most widely used techniques in orthopaedic practice . Purpose : To compare the clinical response of hyaluronic acid ( HA ) and platelet-rich plasma ( PRP ) treatment in 2 groups of patients affected by gonarthrosis . Study Design : R and omized controlled trial ; Level of evidence , 1 . Methods : A total of 120 patients affected by clinical ly and radiographically documented gonarthrosis were included in this study . The gonarthrosis was grade d using the Kellgren-Lawrence radiographic classification scale . The 120 patients were r and omized into 2 study groups in a 1:1 ratio : 60 patients received 4 intra-articular injections of PRP ( specifically , autologous conditioned plasma [ ACP ] , 5.5 mL ) , and 60 patients received 4 intra-articular injections of HA ( 20 mg/2 mL ) . An unblinded physician performed infiltration once a week for 4 weeks into the knee affected by clinical ly relevant gonarthrosis ( in both groups ) . All patients were evaluated with the Western Ontario and McMaster ( WOMAC ) score before the infiltration and at 4 , 12 , and 24 weeks after the first injection . Results : Treatment with a local injection of ACP had a significant effect shortly after the final infiltration and a continuously improving sustained effect up to 24 weeks ( WOMAC score , 65.1 and 36.5 in the HA and ACP groups , respectively ; P < .001 ) , where the clinical outcomes were better compared with the results with HA . In the HA group , the worst results were obtained for grade III gonarthrosis , whereas the clinical results obtained in the ACP group did not show any statistically significant difference in terms of the grade of gonarthrosis . The mean WOMAC scores for grade III gonarthrosis were 74.85 in the HA group and 41.20 in the ACP group ( P < .001 ) . Conclusion : Treatment with ACP showed a significantly better clinical outcome than did treatment with HA , with sustained lower WOMAC scores . Treatment with HA did not seem to be effective in the patients with grade III gonarthrosis Background Bisphosphonates increase the callus size and strength in animal fracture studies . In a human non-r and omized pilot study of high tibial osteotomies in knee osteoarthritis , using the hemicallotasis ( HCO ) technique , bisphosphonates shortened the healing time by 12 days . In the present r and omized study , we wanted to determine whether a single infusion of zoledronic acid reduces the time to clinical osteotomy healing . Results from the same trial , showing improved pin fixation with zoledronate , have been published separately . Methods 46 consecutive patients ( aged 35–65 years ) were operated . At 4 weeks postoperatively , the patients were r and omized to an intravenous infusion of either zoledronic acid or sodium chloride . Dual-energy X-ray absorptiometry ( DEXA ) was performed 10 weeks postoperatively . Radiographs were taken at 10 weeks and every second week until there was radiographic and clinical healing . Healing was evaluated blind , with extraction of the external fixator as the endpoint . At 1.5 years , an additional radiograph was taken and the hip-knee-ankle ( HKA ) angle measured to evaluate whether correction had been retained . Results All osteotomies healed with no difference in healing time between the groups ( 77 ( SD 7 ) days ) . Bone mineral density and bone mineral content , as assessed with DEXA , were similar between the groups . Radiographically , both groups had retained the acquired correction at the 1.5-year follow-up . Interpretation In this r and omized comparison , a single infusion of zoledronic acid increased the pin fixation of the external frame but did not shorten the healing time . In both groups , the external fixator was extracted almost 2 weeks earlier than in previous studies . The early extraction did not cause a loss of correction in either group Background Obesity is an important risk factor for knee osteoarthritis ( OA ) , Weight loss can reduce the symptoms of knee OA . No prospect i ve studies assessing the impact of weight loss on knee cartilage structure and composition have been performed . Objectives To assess the impact of weight loss on knee cartilage thickness and composition . Methods 111 obese adults were recruited from either laparoscopic adjustable gastric b and ing or exercise and diet weight loss programmes from two tertiary centres . MRI was performed at baseline and 12-month follow-up to assess cartilage thickness . 78 eligible subjects also underwent delayed gadolinium-enhanced MRI of cartilage ( dGEMRIC ) , an estimate of proteoglycan content . The associations between cartilage outcomes ( cartilage thickness and dGEMRIC index ) and weight loss were adjusted for age , gender , body mass index ( BMI ) and presence of clinical knee OA . Results Mean age was 51.7±11.8 years and mean BMI was 36.6±5.8 kg/m2 ; 32 % had clinical knee OA . Mean weight loss was 9.3±11.9 % . Percentage weight loss was negatively associated with cartilage thickness loss in the medial femoral compartment in multiple regression analysis ( β=0.006 , r2=0.19 , p=0.029 ) . This association was not detected in the lateral compartment ( r2=0.12 , p=0.745 ) . Percentage weight loss was associated with an increase in medial dGEMRIC in multiple regression analysis ( β=3.9 , r2=0.26 ; p=0.008 ) but not the lateral compartment ( r2=0.14 , p=0.34 ) . For every 10 % weight loss there was a gain in the medial dGEMRIC index of 39 ms ( r2=0.28 ; p=0.014 ) . The lowest weight loss cut-off associated with reduced medial femoral cartilage thickness loss and improved medial dGEMRIC index was 7 % . Conclusions Weight loss is associated with improvements in the quality ( increased proteoglycan content ) and quantity ( reduced cartilage thickness losses ) of medial articular cartilage . This was not observed in the lateral compartment . This could ultimately lead to a reduced need for total joint replacements and is thus a finding with important public health implication OBJECTIVE Although knee malalignment is assumed to correlate with knee osteoarthritis ( OA ) , it is still unknown whether malalignment precedes the development of OA or whether it is a result of OA . The aim of this study was to assess the relationship between malalignment and the development of knee OA as well as progression of knee OA . METHODS A total of 1,501 participants in the Rotterdam study were r and omly selected . Knee OA at baseline and at followup ( mean followup 6.6 years ) was scored according to the Kellgren/Lawrence ( K/L ) grading system . Alignment was measured by the femorotibial angle on radiographs at baseline . Multivariable logistic regression for repeated measurements was used to analyze the association of malalignment with the development and progression of OA . RESULTS Of 2,664 knees , 1,012 ( 38 % ) were considered to have normal alignment , 693 ( 26 % ) had varus alignment , and 959 ( 36 % ) had valgus alignment . A comparison of valgus alignment and normal alignment showed that valgus alignment was associated with a borderline significant increase in development of knee OA ( odds ratio [ OR ] 1.54 , 95 % confidence interval [ 95 % CI ] 0.97 - 2.44 ) , and varus alignment was associated with a 2-fold increased risk ( OR 2.06 , 95 % CI 1.28 - 3.32 ) . Stratification for body mass index showed that this increased risk was especially seen in overweight and obese individuals but not in non-overweight persons . The risk of OA progression was also significantly increased in the group with varus alignment compared with the group with normal alignment ( OR 2.90 , 95 % CI 1.07 - 7.88 ) . CONCLUSION An increasing degree of varus alignment is associated not only with progression of knee OA but also with development of knee OA . However , this association seems particularly applicable to overweight and obese persons Medial opening-wedge has gained popularity in comparison to other techniques of high tibial osteotomy . This technique involves the creation of a gap in the tibia . Filling the gap with autologous iliac bone graft was recommended in the classic description , to prevent complications such as correction loss or delayed bone union . No previous reports have compared grafted and nongrafted osteotomies . This study hypothesized that the use of autologous bone graft in medial opening-wedge high tibial osteotomy ( MOWHTO ) less than 12.5 mm is unnecessary . A prospect i ve r and omized clinical trial was conducted . Forty-six opening-wedge high tibial osteotomies were carried out between April 2007 and December 2008 . All had fixation with a type of Puddu stainless steel plate and screws . Patients were r and omly divided by software analysis into two groups : group A had osteotomies that were filled with autologous bone graft and group B had osteotomies that were unfilled . Autologous iliac bone graft was harvested in both groups . Clinical and radiographic evaluations were performed twice monthly by blinded investigators . The rates of complications were compared between the groups . There was no difference in demographic data . Mean time to clinical bone union in group A was 12.4 weeks ( confidence interval [ CI ] 11.2 - 13.6 ) and in group B was 13.7 weeks ( CI 12.5 - 14.9 ) , but this difference was not significant ( P = 0.13 ) . Signals of correction loss occurred in one patient ( 4.35 % ) in group A , and in two patients ( 8.70 % ) in group B. All osteotomies had achieved bone union . It was concluded that time to bone union was not statistically different between the group with bone graft and the group without graft CONTEXT Knee osteoarthritis ( OA ) is a leading cause of disability in older persons . Few risk factors for disease progression or functional decline have been identified . Hip-knee-ankle alignment influences load distribution at the knee ; varus and valgus alignment increase medial and lateral load , respectively . OBJECTIVE To test the hypotheses that ( 1 ) varus alignment increases risk of medial knee OA progression during the subsequent 18 months , ( 2 ) valgus alignment increases risk of subsequent lateral knee OA progression , ( 3 ) greater severity of malalignment is associated with greater subsequent loss of joint space , and ( 4 ) greater burden of malalignment is associated with greater subsequent decline in physical function . DESIGN AND SETTING Prospect i ve longitudinal cohort study conducted March 1997 to March 2000 at an academic medical center in Chicago , Ill. PARTICIPANTS A total of 237 persons recruited from the community with primary knee OA , defined by presence of definite tibiofemoral osteophytes and at least some difficulty with knee-requiring activity ; 230 ( 97 % ) completed the study . MAIN OUTCOME MEASURES Progression of OA , defined as a 1- grade increase in severity of joint space narrowing on semiflexed , fluoroscopically confirmed knee radiographs ; change in narrowest joint space width ; and change in physical function between baseline and 18 months , compared by knee alignment at baseline . RESULTS Varus alignment at baseline was associated with a 4-fold increase in the odds of medial progression , adjusting for age , sex , and body mass index ( adjusted odds ratio [ OR ] , 4.09 ; 95 % confidence interval [ CI ] , 2.20 - 7.62 ) . Valgus alignment at baseline was associated with a nearly 5-fold increase in the odds of lateral progression ( adjusted OR , 4.89 ; 95 % CI , 2.13 - 11.20 ) . Severity of varus correlated with greater medial joint space loss during the subsequent 18 months ( R = 0.52 ; 95 % CI , 0.40 - 0.62 in dominant knees ) , and severity of valgus correlated with greater subsequent lateral joint space loss ( R = 0.35 ; 95 % CI , 0.21 - 0.47 in dominant knees ) . Having alignment of more than 5 degrees ( in either direction ) in both knees at baseline was associated with significantly greater functional deterioration during the 18 months than having alignment of 5 degrees or less in both knees , after adjusting for age , sex , body mass index , and pain . CONCLUSION This is , to our knowledge , the first demonstration that in primary knee OA varus alignment increases risk of medial OA progression , that valgus alignment increases risk of lateral OA progression , that burden of malalignment predicts decline in physical function , and that these effects can be detected after as little as 18 months of observation Objectives To compare the effects of an intermediate molecular weight ( MW ) intra-articular hyaluronic acid ( HA ) with a low MW product on knee osteoarthritis ( OA ) symptoms . Methods Patients with symptomatic knee OA were enrolled inar and omised , controlled , double-blind , parallel-group , non-inferiority trial with the possibility to shift to superiority . Patients were r and omised to GO-ON(MW 800–1500 kD , 25 mg/2.5 ml ) or Hyalgan(MW 500–730 kD , 20 mg/2 ml ) injected at 3-weekly intervals . The primary outcome was 6-month change in the WOMAC pain subscale ( 0–100 mm ) . Sample size was calculated on a non-inferiority margin of 9 mm , lower than the minimum perceptible clinical improvement . Secondary endpoints included OARSI-OMERACT responder rates Results The intention-to-treat ( ITT ) and per- protocol ( PP ) population s consisted of 217 and 209 patients and 171 and 172 patients in the GO-ON and Hyalgan groups , respectively . ITT WOMAC pain of 47.5±1.0(SE ) and 48.8±1.0 mm decreased by 22.9±1.4 mm with GO-ON and 18.4±1.5 mm with Hyalgan after 6 months . The primary analysis was conducted in the PP population followed by the ITT population .Mean ( 95 % CI ) differences in WOMAC pain change were 5.2 ( 0.9 to 9.6)mm and 4.5 ( 0.5 to 8.5)mm , respectively , favouring GO-ON , satisfying the cl aim for non-inferiority ( lower limit>−9 mm ) and for statistical superiority ( 95 % CI all>0 , p=0.021 ) . Ahigher proportion of OARSI/OMERACT responders was observed with GO-ONthan with Hyalgan ( 73.3 % vs58.4 % , p=0.001 ) . Both preparations were well tolerated . Conclusions Treatment with 3-weekly injections of intermediate MW HA may be superior to low MW HA on knee OA symptoms over 6 months , with similar safety In a r and omised clinical trial in 50 patients with symptomatic osteoarthritis of the medial compartment of the knee , the clinical results of high tibial osteotomy ( HTO ) according to the open wedge osteotomy ( OWO ) and closed wedge osteotomy ( CWO ) were compared . In both groups locked plate fixation was used . Clinical and radiological assessment s were performed preoperatively and after one year . Postoperative hip-knee-ankle ( HKA ) correction angles were monitored on st and ing leg X-rays . The effect of HTO on collateral laxity of the knee was measured with a specially design ed varus-valgus device . The WOMAC osteoarthritis index , the modified knee society score ( KS ) and visual analogue scales ( VAS ) were used to assess symptoms of osteoarthritis , function , pain and patient satisfaction . At one-year follow-up we found accurate corrections in both groups and the planned correction angles were achieved . No loss of correction was observed . Furthermore , the medial collateral laxity and the patellar height significantly decreased after OWO . Significant improvements of WOMAC and KS scores were found in both groups . All patients had significantly less pain and were very satisfied with the results . Surgery time was significantly longer in the CWO group , and complications were more frequent in this group . Both techniques led to good and comparable clinical results . The choice of whether to perform an open or a closed wedge osteotomy may be based on preoperative patellar height or concomitant collateral laxity We in vivo investigated the bone healing ability of a nanocomposite ( DBSint ® ) , constituted by biomimetic nano-structured Mg-hydroxyapatite ( SINTlife ® ) and human demineralized bone matrix . Thirty-one subjects undergoing high tibial osteotomy for genu varus were r and omly assigned to three groups : during surgery , DBSint ® was inserted into nine patients , SINTlife ® in thirteen patients and lyophilised bone chips , that is the routine surgery , in nine subjects . As outcome measures , clinical , radiographic and histomorphometry scores were calculated . The osseointegration was evaluated by imaging six weeks , three , six and twelve months after surgery . At six-week follow-up , DBSint ® showed a significantly higher osseointegration rate in comparison with lyophilised bone chips ( p = 0.008 ) . At the same follow-up , CT-guided bone biopsies were obtained and analysed by histomorphometry : a good osteogenetic potential was demonstrated with DBSint ® , as well as with SINTlife ® and controls . Unresorbed material was evident with DBSint ® and SINTlife ® , with a significantly higher percentage in SINTlife ® group . At 1-year follow-up , DBSint ® was demonstrated as effective and safe as SINTlife ® and lyophilized bone chips . More significant results could be obtained by continuing the clinical trial , by increasing the patient number and the study power . Eventually , the role of non-resorbed graft remnants is still unclear and requires further investigation In a prospect i ve clinical and roentgenographic analysis of 79 knees treated by a valgus closing wedge high tibial osteotomy , the average follow-up period was 5.8 years ( three to nine years ) ; 80 % of the patients had good or excellent results . Correction to a femorotibial angle between 6 degrees and 14 degrees of femorotibial valgus was associated with an optimal clinical result . Undercorrection to less than 5 degrees of femorotibial valgus was associated with a high ( 62.5 % ) failure rate . Patients whose distal femur had a femoral shaft-transcondylar ( FS-TC ) angle of less than 9 degrees have an increased incidence of undercorrection . A poor prognosis was noted in knees whose patellofemoral joint preoperatively had moderate or severe roentgenographic evidence of osteoarthritis ( OA ) when compared to the group whose patellofemoral compartment had no or mild roentgenographic evidence of OA . Accurate femorotibial realignment was essential for success . The slope of the distal femoral articular surface , the FS-TC angle , affects the degree of correction and should be considered in preoperative planning A prospect i ve , r and omised , controlled trial compared two different techniques of high tibial osteotomy with a lateral closing wedge or a medial opening wedge , stabilised by a Puddu plate . The clinical outcome and radiological results were examined at one year . The primary outcome measure was the achievement of an overcorrection of valgus of 4 degrees . Secondary outcome measures were the severity of pain ( visual analogue scale ) , knee function ( Hospital for Special Surgery score ) , and walking distance . Between January 2001 and April 2004 , 92 patients were r and omised to one or other of the techniques . At follow-up at one year the post-operative hip-knee-ankle angle was 3.4 degrees ( + /- 3.6 degrees SD ) valgus after a closing wedge and 1.3 degrees ( + /- 4.7 degrees SD ) of valgus after an opening wedge . The adjusted mean difference of 2.1 degrees was significant ( p = 0.02 ) . The deviation from 4 degrees of valgus alignment was 2.7 degrees ( + /- 2.4 degrees SD ) in the closing wedge and 4.0 degrees ( + /- 3.6 degrees sd ) in the opening-wedge groups . The adjusted mean difference of 1.67 degrees was also significant ( p = 0.01 ) . The severity of pain , knee score and walking ability improved in both groups , but the difference was not significant . Because of pain , the staples required removal in 11 ( 23 % ) patients in the closing-wedge group and a Puddu plate was removed in 27 ( 60 % ) patients in the opening-wedge group . This difference was significant ( p < 0.001 ) . We conclude that closing-wedge osteotomy achieves a more accurate correction with less morbidity , although both techniques had improved the function of the knee at one year after the procedure Most systematic review s rely substantially on the assessment of the method ological quality of the individual trials . The aim of this study was to obtain consensus among experts about a set of generic core items for quality assessment of r and omized clinical trials ( RCTs ) . The invited participants were experts in the field of quality assessment of RCTs . The initial item pool contained all items from existing criteria lists . Subsequently , we reduced the number of items by using the Delphi consensus technique . Each Delphi round comprised a question naire , an analysis , and a feedback report . The feedback report included staff team decisions made on the basis of the analysis and their justification . A total of 33 international experts agreed to participate , of whom 21 completed all question naires . The initial item pool of 206 items was reduced to 9 items in three Delphi rounds . The final criteria list ( the Delphi list ) was satisfactory to all participants . It is a starting point on the way to a minimum reference st and ard for RCTs on many different research topics . This list is not intended to replace , but rather to be used alongside , existing criteria lists The effect of electromagnetic field stimulation was investigated in a group of 40 consecutive patients treated with valgus tibial osteotomy for degenerative arthrosis of the knee . All patients were operated on by the same author and followed the same postoperative program . After surgery , patients were r and omly assigned to a control group ( dummy stimulators ) or to a stimulated one ( active stimulators ) . Four orthopedic surgeons , unaware of the experimental conditions , were asked to evaluate the roentgenograms taken 60 days postoperatively and to rate the osteotomy healing according to four categories ( the fourth category being the most advanced stage of healing ) . In the control group , 73.6 % of the patients were included in the first and second category . In the stimulated group , 72.2 % of the patients were included in the third and fourth category . On a homogeneous group of patients , electromagnetic field stimulation had positive effects on the healing of tibial osteotomies OBJECTIVE To investigate whether an exercise program , initially focusing on knee stabilization and subsequently on muscle strength and performance of daily activities is more effective than an exercise program focusing on muscle strength and performance of daily activities only , in reducing activity limitations in patients with knee osteoarthritis ( OA ) and instability of the knee joint . DESIGN A single-blind , r and omized , controlled trial involving 159 knee OA patients with self-reported and /or biomechanically assessed knee instability , r and omly assigned to two treatment groups . Both groups received a supervised exercise program for 12 weeks , consisting of muscle strengthening exercises and training of daily activities , but only in the experimental group specific knee joint stabilization training was provided . Outcome measures included activity limitations ( Western Ontario and McMaster Universities Osteoarthritis Index - WOMAC physical function , primary outcome ) , pain , global perceived effect and knee stability . RESULTS Both treatment groups demonstrated large ( ∼20 - 40 % ) and clinical ly relevant reductions in activity limitations , pain and knee instability , which were sustained 6 months post-treatment . No differences in effectiveness between experimental and control treatment were found on WOMAC physical function ( B ( 95 % confidence interval - CI ) = -0.01 ( -2.58 to 2.57 ) ) or secondary outcome measures , except for a higher global perceived effect in the experimental group ( P = 0.04 ) . CONCLUSIONS Both exercise programs were highly effective in reducing activity limitations and pain and restoring knee stability in knee OA patients with instability of the knee . In knee OA patients suffering from knee instability , specific knee joint stabilization training , in addition to muscle strengthening and functional exercises , does not seem to have any additional value . Dutch Trial Register ( NTR ) registration number : NTR1475 PURPOSE The purpose of this r and omized , prospect i ve study was to compare radiologic changes in the sagittal plane after closing-wedge and combined high tibial osteotomies ( HTOs ) performed in patients with medial knee arthrosis associated with a varus deformity and requiring a 10 degrees correction . METHODS The patellar height , determined by the Insall-Salvati index ( ISI ) , and tibial slope ( TS ) angle , measured by the Dejour-Bonnin method , were compared after 45 closing-wedge osteotomy ( CWO ) and 46 combined osteotomy ( CO ) procedures . CO is a relatively new technique effectively being the combination of closing-wedge and opening-wedge HTOs . It involves performing a proximal osteotomy parallel to the tibial plateau , followed by a distal osteotomy extending from the lateral part of the tibia to the line of the proximal osteotomy at the center of the tibial condyle . After closure of the lateral part of the osteotomy and consequent opening of the medial part , the removed lateral bone wedge is transferred to the gap on the medial side . RESULTS We found that at the end of the study , 12 months after the operation , CO result ed in significantly smaller changes in TS angle ( 4.7 % v 38.2 % ) and ISI ( 2.2 % v 5.7 % ) values than CWO . CONCLUSIONS The main conclusion of this study is that based on our radiologic findings , CO results in significantly smaller changes in TS angle and ISI values than CWO ; therefore , CO is better at preserving the normal or near normal condition of the knee than CWO . Altogether , when a 10 degrees correction is required during HTO , we recommend choosing CO instead of CWO . LEVEL OF EVIDENCE Level II , prospect i ve comparative study The aim of this study was to analyse gait improvement one year after high tibial osteotomy and unicompartmental knee arthroplasty in patients with strictly unilateral osteoarthrosis of the medial compartment of the knee . Thirty-six patients , 18 men and 18 women , received a unicompartmental Brigham knee prosthesis and 23 patients , 10 men and 13 women , were operated on with a high tibial osteotomy . Clinical and radiographical assessment s were supplemented by a functional test , measurements of thigh muscle torque with a Cybex II dynamometer and analysis on a force plate walkway with electrogoniometers . All patients were assessed prior to , and one year after surgery . Both groups showed overall clinical improvement , as assessed by the British Orthopaedic Association ( BOA ) score . Pain during walking decreased . The range of knee flexion remained unchanged . The ability to ascend and descend steps improved . The isokinetic thigh muscle torque remained unchanged . In the prosthetic group free walking speed increased from 1.03 to 1.09 m/s ( p < 0.001 ) . Step frequency and step length increased ( p < 0.001 ) . Single stance phase ratio increased from 0.96 to 0.99 ( p < 0.01 ) , indicating a more symmetrical gait . Double stance phase ( % gait cycle ) of both legs decreased ( p < 0.001 ) , indicating a faster transfer of weight during walking . In the osteotomy group , free walking speed did not increase . Step length of the uninvolved leg increased ( p < 0.01 ) . Double stance phase of the involved leg decreased ( p < 0.001 ) and double stance phase of the uninvolved leg decreased ( p < 0.01 ) . Both groups improved after surgery and there was no difference between the groups . ( ABSTRACT TRUNCATED AT 250 WORDS In a prospect i ve study , 32 knees in 32 patients were r and omized to either a cylinder plaster cast ( 17 knees ) or hinged cast-brace ( 15 knees ) after high tibial osteotomy for medial gonarthrosis . At 6 weeks , 3 months , and still 1 year after surgery , the range of motion was better in the cast-brace group . There was no difference in the other clinical results at 3 months and at 1 year after surgery , nor in changes of osseous correction or in the final knee alignment . All the patients in the cast-brace group were satisfied with early motion Purpose Since in vivo stability following high tibial osteotomy is unknown , surgeons customize the postoperative rehabilitation to the assumed implant stability , leaving us with numerous rehabilitation protocol s. The purpose of the study is to quantify the fixation stability of different open-wedge high tibial osteotomy implants . It is hypothesized that the higher fixation stability of a plate fixator justifies early weight bearing . Methods In this prospect i ve 30-subject clinical trial , fixation stability was determined over a 2-year period using radiostereometric analysis ( RSA ) . Patients were assigned to two angle-stable osteotomy plates : a spacer plate with 6 postoperative weeks of feather-touch weight bearing versus a plate fixator with 2 postoperative weeks of feather-touch weight bearing . Results Postoperative RSA data showed a significant higher lateral translation of the distal tibia and a significantly increased subsidence , varus and internal rotation of the tibial head in the spacer plate compared to the plate fixator group . Weight bearing following spacer plate fixation induced significant micromotion 6 weeks after surgery . Three months after surgery , bone healing was achieved regardless of the used implant . Conclusions Early weight bearing is appropriate for plate fixator fixation . The 6-week period of delayed weight bearing following spacer plate fixation is inadequate and should be prolonged presumably up to 8–10 weeks to avoid pseudarthrosis and /or recurrence of varus angulation . Level of evidence Level II , diagnostic study —investigating a diagnostic test Our aim was to compare the degree of patellar descent and alteration in angle of the inclination of the tibial plateau in lateral closing-wedge and medial opening-wedge high tibial osteotomy ( HTO ) in 51 consecutive patients with osteoarthritis of the medial compartment and varus malalignment . Patellar height was measured by the Insall-Salvati ( IS ) and the Blackburne-Peel ( BP ) ratios . The tibial inclination was determined by the Moore-Harvey ( MH ) method . Multivariate linear regression analysis was used to determine the influence of the type of HTO ( closing vs opening wedge ) on the post-operative patellar height or tibial inclination . The intra- and interobserver variability of these methods was determined before operation and at follow-up at one year . After an opening-wedge HTO the patellar height was significantly more decreased ( mean post-operative difference : IS = 0.15 ; 95 % confidence interval ( CI ) 0.06 to 0.23 ; BP = 0.11 ; 95 % CI 0.05 to 0.18 ) compared with a closing-wedge HTO . The angle of tibial inclination differed significantly ( mean post-operative difference MH = -6.40 degrees ; 95 % CI -8.74 to -4.02 ) between the two HTO techniques , increasing after opening-wedge HTO and decreasing after closing-wedge HTO . There was no clinical ly-relevant difference in the intra- and interobserver variability of measurements of patellar height either before or after HTO The purpose of this prospect i ve study was to determine whether or not abrasion arthroplasty promotes cartilage regeneration in osteoarthritic ( OA ) knees with eburnation . Patients with OA knees were divided into a group of 51 knees treated by osteotomy with abrasion arthroplasty ( Group A ) and another group of 37 knees treated by osteotomy alone ( Group B ) . Regeneration of cartilage was compared between the groups both arthroscopically and histologically . The Outerbridge classification was used for arthroscopic grading with Grade 0 being normal and Grade IV representing eburnation . On arthroscopic examination , around 12 months after surgery , Group A showed a significantly higher incidence of Grade II repair ( a smooth articular surface and small fissures ) and a lower incidence of Grade IV repair than Group B on both the femoral ( P < .001 ) and tibial ( P < .01 ) joint surfaces . Age was the only factor influencing the grade of tibial cartilage in Group A. Histological examination showed that 64 % of the regenerated tissue studied consisted of fibro-cartilage at around 12 months after surgery . There was no difference in the clinical outcome at 2 to 9 years postoperatively between Groups A and OBJECTIVE To compare the safety and efficacy of a single intra-articular ( IA ) injection of a new cross-linked hyaluronic acid product , Gel-200 , with phosphate buffered saline ( PBS , control ) in a multi-center r and omized controlled trial in patients with symptomatic osteoarthritis ( OA ) of the knee . DESIGN Patients were r and omized 2:1 to receive a single injection of Gel-200 or PBS , after joint aspiration . The primary measure of effectiveness was Western Ontario and McMaster Universities Osteoarthritis Index ( WOMAC ) pain subscores by 100-mm Visual Analog Scale ( VAS ) ; secondary outcomes included : total WOMAC , physical function , and stiffness subscores ; patient and physician global assessment s of disease activity , Outcome Measures in Rheumatology Clinical Trials and Osteoarthritis Research Society International ( OMERACT-OARSI ) strict responders , as well as safety of Gel-200 . RESULTS Of 379 patients r and omized , safety was evaluated in 377 and efficacy in 375 ( 98.9 % r and omized ) in the intent-to-treat population . Effectiveness of Gel-200 by WOMAC pain subscores was statistically significant at week 13 ( P=0.037 ) . Mean improvements from baseline in WOMAC pain subscores consistently favored Gel-200 at each visit . Effectiveness of Gel-200 treatment was statistically significant over weeks 3 - 13 by WOMAC total score , physical function , and physician global evaluations ( P<0.05 ) . The number of " strict " OMERACT-OARSI responders was statistically significant from weeks 6 to 13 ( P=0.022 ) . Adverse events were not significantly different between treatment groups , including serious adverse events considered related to study treatment . CONCLUSIONS This trial demonstrated that a single injection of Gel-200 was well tolerated and relieved pain associated with symptomatic OA of the knee over 13 weeks . TRIAL REGISTRATION NUMBER Clinical Trials.gov NTC 00449696 Purpose The purpose of our study was to compare clinical and radiological results of two groups of patients treated for medial compartment osteoarthritis of the knee with either conventional or computer-assisted open-wedge high tibial osteotomy ( HTO ) . Goals of surgical treatment were a correction of the mechanical axis between 2 ° and 6 ° of valgus and a modification of posterior tibial slope between −2 ° and + 2 ° . Methods Twenty-four patients ( 27 knees ) affected by varus knee deformity and operated with HTO were prospect ively followed-up . They were r and omly divided in two groups , A ( 11 patients , conventional treatment ) and B ( 13 patients , navigated treatment ) . The American Knee Society Score and the Modified Cincinnati Rating System Question naire were used for clinical assessment . All patients were radiologically evaluated with a comparative lower limb weight-bearing digital radiograph , a st and ard digital anteroposterior , a latero-lateral radiograph of the knee , and a Rosenberg view . Results Patients were followed-up at a mean of 39 months . Clinical evaluation showed no statistical difference ( n.s . ) between the two groups . Radiological results showed an 86 % reproducibility in achieving a mechanical axis of 182 ° –186 ° in group B compared to a 23 % in group A ( p = 0.0392 ) ; furthermore , in group B , we achieved a modification of posterior tibial slope between −2 ° and + 2 ° in 100 % of patients , while in group A , this goal was achieved only in 24 % of cases ( p = 0.0021 ) . Conclusion High tibial osteotomy with navigator is more accurate and reproducible in the correction of the deformity compared to st and ard technique . Level of evidence Therapeutic study , Level II Seventy-eight knee joints with varus malalignment were examined preoperatively using three-point measurement . Operation was performed with or without 5 degrees overcorrection of the varus deformity using r and om selection . The overcorrection group showed significantly better results than the normal-correction group OBJECTIVE To identify the demographic and operative factors that determine outcome in supracondylar femoral osteotomy for lateral compartment osteoarthritis of the knee . DESIGN Clinical and radiologic review of a nonr and omized , consecutive one-surgeon series . SETTING A university-affiliated , elective surgical referral centre . PATIENTS Forty-nine consecutive patients with unicompartmental osteoarthritis of the knee , involving the lateral compartment , and of sufficient severity that the alternative surgical procedure would be total knee replacement . INTERVENTION Supracondylar varus osteotomy stabilized with a blade plate . MAIN OUTCOME MEASURES Knee function measured by the Knee Society Score and time to conversion to total knee replacement . RESULTS A Knee Society Score greater than 80 was obtained in 81 % of patients , but in the function portion of the measurement only 30 % had a similar score . After discarding the patients who died , life-table analysis demonstrated the predicted survival before conversion to total knee replacement to be 87 % at 7 years . There was no correlation with patient age or sex , femorotibial angulation , amount of correction or time after the intervention . Removal of the fixation device improved the clinical result . CONCLUSION The role of supracondylar femoral osteotomy remains poorly defined , but the procedure can delay total knee replacement for considerable time in appropriate patients INTRODUCTION Valgus tibial osteotomy ( VTO ) is a well-known procedure for the treatment of medial compartment femoro-tibial osteoarthritis . Good and very good results have been reported with calcium phosphate wedges , which avoid the inconveniences of autologous grafts use . The hypothesis of this study is that with equivalent results in the treatment of osteoarthritis of the knee , the use of calcium phosphate wedges ( BMC aPh ) to fill the bone defect created by osteotomy would result in fewer specific complications and less pain associated with autologous grafts ( AUTO ) harvesting . PATIENTS AND METHODS This prospect i ve , controlled , r and omised study included one arm that received a macroporous , biphasic calcium phosphate wedge ( BMC aPh group ) and one arm that received an autologous tricortical graft ( AUTO group ) for filling . The same plate with locked screws was used for fixation in all cases . All patients underwent at least two years of clinical and radiographic post-operative follow-up . RESULTS Forty patients were included . Loss of correction occurred in six of the twenty-two patients in the BMC aPh group ( 27 % ) , result ing in three early surgical revisions , compared to one loss of correction in the AUTO group . Lateral cortical hinge tears were a risk factor for loss of correction for the entire cohort and in the BMC aPh group . ( relative risk 13.3 [ 1.9 - 92 ] . Moreover , union took significantly longer and pain lasted significantly longer in the BMC aPh group , although results were comparable at 6 months . DISCUSSION A significant number of undesirable events ( loss of correction ) occurred in this study , limiting the number of included patients . Nevertheless , the results show that although there was no difference in the two groups for overall complications , number of revisions all causes combined , or clinical results , filling with BMC aPh was less tolerated and increased the risk of loss of correction when local mechanical conditions of the knee were unfavourable ( lateral cortical hinge tears ) . Moreover , although it is not possible to draw a conclusion because of methodology bias in this study , early weight-bearing resumption on the knee also seemed to favour these complications . LEVEL OF EVIDENCE Level II . Prospect i ve r and omized study Abstract In a prospect i ve r and omised study , 65 high tibial osteotomies were performed in cases of varus osteoarthritis of the knee , and the incidence of thrombosis with and without the use of a tourniquet was studied . With an average incidence of thrombosis of 10.8 % , no statistically significant differences between these two groups were seen The clinical outcome of patients treated either by high tibial osteotomy or unicompartmental arthroplasty for medial unicompartmental osteoarthritis of the knee was compared in a prospect i ve r and omised study . In total , 32 patients received a high tibial osteotomy ( HTO ) and 28 patients a unicompartmental arthroplasty ( UKA ) . More intra- and postoperative complications were observed after HTO . Patients were assessed at an average of 2.5 ( 1.6 - 5 ) , 4.5 ( 3.6 - 7 ) , and 7.5 years ( 6.6 - 10 ) after the operation . Using the Knee Society Score , 71 % ( 15 ) of patients after osteotomy and 65 % ( 13 ) after replacement had a knee score of excellent or good 7 - 10 years postoperatively . The Kaplan-Meier survival analysis 7 - 10 years postoperatively showed a survivorship of 77 % for UKA and 60 % for HTO . Although the unicompartmental prosthesis used in this series has not shown promising results , we conclude that with the advanced design of unicompartmental prosthesis today , UKA offers better long-term success This prospect i ve cohort study compared opening wedge high tibial osteotomy with use of the Puddu plate and the Vitoss synthetic cancellous bone versus closing wedge high tibial osteotomy with use of the AO/ASIF L-plate , focusing on complications ( nonunions , infections , loss of correction , reoperations ) and patient satisfaction ( visual linear analog scale ) . During a 10-month period , we performed high tibial osteotomy for 40 patients experiencing medial knee osteoarthritis and a varus deformity . The average follow-up was 11 months . The complication rate in patients treated with the opening wedge technique was significantly higher regarding tibial nonunion , loss of correction , and material failure . Patients in the closing wedge group were more satisfied with the postoperative result . This study found that the Puddu plate , despite 6 weeks of non-weight bearing facilitating the osseous consolidation with Vitoss cement , was not able to maintain the correction during the time required for bone healing Valgus high tibial osteotomy for osteoarthritis of the medial compartment of the knee can be performed using medial opening- and lateral closing-wedge techniques . The latter have been thought to offer greater initial stability . We measured and compared the stability of opening- and closing-wedge osteotomies fixed by TomoFix plates using radiostereometry in a series of 42 patients in a prospect i ve , r and omised clinical trial . There were no differences between the opening- and closing-wedge groups in the time to regain knee function and full weight-bearing . Pain and knee function were significantly improved in both groups without any differences between them . All the osteotomies united within one year . Radiostereometry showed no clinical ly relevant movement of bone or differences between either group . Medial opening-wedge high tibial osteotomy secured by a TomoFix plate offers equal stability to a lateral closing-wedge technique . Both give excellent initial stability and provide significantly improved knee function and reduction in pain , although the opening-wedge technique was more likely to produce the intended correction 33 patients ( 22 men ) , median age 54 ( 40 - 68 ) years , with medial gonarthrosis grade s 1 - 3 , were treated by closed-wedge osteotomy ( high tibial osteotomy = HTO , n 16 ) or open-wedge osteotomy by hemicallotasis ( hemicallotasis osteotomy = HCO , n 19 ) . 2 patients were operated on bilaterally . The patients were studied by RSA ( radiostereometric analysis ) for measuring 3-D changes in the correction achieved . In the HTO group the RSA measurements were obtained at the time of plaster removal , 1 month later and 1 year after surgery . In the HCO group , the RSA measurements were performed at the time of removal of the external fixator , 1 month later and 1 year after surgery . After removal of the fixation , HTO was associated with increased medial/lateral and distal translation of the proximal segment , compared to HCO . In addition , the tibial plateau rotated more around the longitudinal axis of the tibia after HTO Purpose The aim of the study was to compare clinical and radiographic outcomes of opening-wedge high tibial osteotomy ( HTO ) augmented with either xenograft or tricalcium phosphate spacer for the management of medial compartment osteoarthritis ( OA ) with genu varum . Methods Between 2004 and 2007 , we prospect ively enrolled 52 patients with medial compartment knee OA who underwent opening-wedge HTO fixed with locking Puddu plate and xenograft ( n = 26 ) or non-locking Puddu plate and tricalcium phosphate spacer ( n = 26 ) . The alignment of the lower limb was assessed by measuring the hip-knee-ankle ( HKA ) angle . Clinical outcomes were assessed with the Knee Society Score , Western Ontario and McMaster Universities Osteoarthritis Index , SF-36 and European Quality of Life-5 Dimensions scale . All patients were followed up at six weeks and at three , six , 12 and 24 months post-operatively . Clinical outcomes were assessed preoperatively and at 24 months post-operatively . Results All clinical scores improved significantly in both groups after surgery , without any significant difference between the two groups . Immediately after surgery , the HKA angle went from 9.1 ± 5.2 ° in varus to 3.1 ± 4.8 ° in valgus ( P = 0.01 ) in the xenograft group , and from 8.5 ± 5.9 ° in varus to 3.4 ± 4.2 ° in valgus ( P = 0.01 ) in the tricalcium phosphate group . At the last follow-up , the tricalcium phosphate group showed a significant loss of correction ( P = 0.03 ) . Conclusions HTO performed with xenograft locking plate and tricalcium phosphate non-locking plate constructs showed good clinical outcomes . However , the xenograft locking plate construct is superior to the tricalcium phosphate spacer non-locking plate to prevent the loss of correction in the middle term Background and purpose Tibial osteotomy by the hemicallotasis technique ( HCO ) requires strong pin fixation . We compared pin fixation in HCO using a new self-drilling XCaliber pin ( Orthofix ) with optimized thread and tip design , with the commonly used st and ard pin ( Orthofix ) . Patients and methods 50 patients , mean age 51 ( 35–66 ) years , to be treated by HCO were r and omized to st and ard pins or XCaliber pins . In the metaphyseal bone , hydroxyapatite-coated ( HA-coated ) pins were used in both types of pins . In the diaphyseal bone , non-coated pins were used . The torque forces for insertion and extraction ( in Nm ) were measured . Results The insertion torque was higher for both the proximal and distal st and ard pins ( 2.1 Nm ( SD 0.9 ) and 7.0 Nm ( 1.3 ) , respectively ) than for the XCaliber pins ( 1.3 Nm ( 0.8 ) and 3.6 Nm ( 1.4 ) ) . The extraction torque force was higher for the proximal st and ard pins ( 4.3 Nm ( 3.1 ) ) than for the proximal XCaliber pins ( 1.5 Nm ( 1.7 ) ) ( p < 0.001 ) . The extraction torque for the distal st and ard pins was 1.9 Nm ( 2.0 ) and for the distal XCaliber pins it was 1.4 Nm ( 1.1 ) . Interpretation The commonly used st and ard pin gives stronger fixation during the treatment of HCO The aim of this prospect i ve follow-up study was to determine if gait measurements and /or clinical measurements could detect differences in treatment outcome between two surgical interventions in patients with knee osteoarthritis ( OA ) . The patients were followed for 5 years after surgery . Forty patients , 55 - 70 years of age , with unilateral knee OA were included . The patients were treated either with a high tibial osteotomy ( HTO ) ( n=18 ) or a unicompartmental knee arthroplasty ( UKA ) ( n=22 ) . Clinical outcome measures were the British Orthopaedic Association ( BOA ) score , pain during walking , passive range of knee motion ( PROM ) and patients ' subjective opinion . The gait variables were free walking speed , step frequency , step length and single and double-stance phase for each leg . The patients were examined before surgery and 3 months , 1 year and 5 years after surgery . The time-distance variables of gait could detect differences in treatment outcome , 3 months after surgery , while the clinical outcome measures , as given here , could not detect any differences between the two groups of patients . Measurements of free walking speed could be recommended for clinical evaluation , after surgical interventions , in patients with knee OA Between 1989 and 1992 we had 102 knees suitable for unicompartmental knee replacement ( UKR ) . They were r and omised to receive either a St Georg Sled UKR or a Kinematic modular total knee replacement ( TKR ) . The early results demonstrated that the UKR group had less complications and more rapid rehabilitation than the TKR group . At five years there were an equal number of failures in the two groups but the UKR group had more excellent results and a greater range of movement . The cases were review ed by a research nurse at 8 , 10 and 12 years after operation . We report the outcome at 15 years follow-up . A total of 43 patients ( 45 knees ) died with their prosthetic knees intact . Throughout the review period the Bristol knee scores of the UKR group have been better and at 15 years 15 ( 71.4 % ) of the surviving UKRs and 10 ( 52.6 % ) of the surviving TKRs had achieved an excellent score . The 15 years survivorship rate based on revision or failure for any reason was 24 ( 89.8 % ) for UKR and 19 ( 78.7 % ) for TKR . During the 15 years of the review four UKRs and six TKRs failed . The better early results with UKR are maintained at 15 years with no greater failure rate . The median Bristol knee score of the UKR group was 91.1 at five years and 92 at 15 years , suggesting little functional deterioration in either the prosthesis or the remainder of the joint . These results justify the increased use of UKR |
10,734 | 25,793,972 | This short-term follow-up is usually insufficient to observe any significant effect of the treatment on bone health ( such as the occurrence of fractures ) , limiting the findings .
There was low or moderate quality evidence that tibolone , raloxifene , estriol and ipriflavone help to preserve bone density and that MPA and tibolone may reduce vasomotor symptoms .
Larger uterine volume was an adverse effect associated with some add-back therapies ( MPA , tibolone and conjugated estrogens ) . | BACKGROUND Uterine fibroids ( also known as leiomyomas ) are the most common benign pelvic tumours among women .
They may be asymptomatic , or may be associated with pelvic symptoms such as bleeding and pain .
Medical treatment of this condition is limited and gonadotropin-releasing hormone ( GnRH ) analogues are the most effective agents .
Long-term treatment with such agents , however , is restricted due to their adverse effects .
The addition of other medications during treatment with GnRH analogues , a strategy known as add-back therapy , may limit these side effects .
There is concern , however , that add-back therapy may also limit the efficacy of the GnRH analogues and that it may not be able to completely prevent their adverse effects .
OBJECTIVES To assess the short-term ( within 12 months ) effectiveness and safety of add-back therapy for women using GnRH analogues for uterine fibroids associated with excessive uterine bleeding , pelvic pain , or urinary symptoms . | STUDY OBJECTIVE To compare uterine size reduction obtained with three monthly subcutaneous injections of 3.6 mg of goserelin versus a single subcutaneous injection of 10.8 mg . DESIGN Prospect i ve , r and omized clinical trial ( Canadian Task Force classification I ) . SETTING Department of Gynecology and Obstetrics at the Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo . PATIENTS Forty-five premenopausal women with uterine leiomyomas and uterine size greater than 600 cm(3 ) r and omized to one of two groups . INTERVENTION Group A : 23 women received three monthly subcutaneous 3.6-mg doses of goserelin . Group B : 22 women received a single subcutaneous injection of 10.8 mg of goserelin . Follicle-stimulating hormone ( FSH ) , estradiol , and hemoglobin levels were measured monthly . After 3 months , uterine size was determined by transvaginal and /or abdominal ultrasound . MEASUREMENTS AND MAIN RESULTS In group A , mean reduction of uterine size was 43 % ( 426 cm(3 ) ) at the end of treatment . In Group B , mean reduction of uterine size was 54 % ( 494 cm(3 ) ) . Serum levels of FSH and estradiol were in postmenopausal range during treatment . Hemoglobin level improvement was equivalent in both groups . CONCLUSION Use of single injection of 10.8 mg of goserelin promoted significantly greater reduction in uterine size than three monthly 3.6-mg injections in patients with voluminous uterine leiomyomas OBJECTIVE To characterize the relationship between self reported bleeding symptoms and uterine leiomyoma size and location . METHODS The leiomyoma status of a r and omly selected sample of women aged 35–49 in the Washington , DC , area was determined using abdominal and transvaginal ultrasound to measure size and location of leiomyomata found at screening . Women were asked about symptoms of heavy bleeding ( gushing-type bleeding , long menses , pad/ tampon use ) in a telephone interview . Using multivariable regression , we examined the relationships between leiomyoma characteristics and heavy bleeding symptoms among 910 premenopausal women . RESULTS Women with leiomyomata ( n = 596 ) were more likely to report gushing-type bleeding than women without leiomyomata ; risk increased with leiomyoma size . Adjusted relative risks with 95 % confidence intervals ( CI ) for women in each leiomyoma size category compared with the reference category ( women without leiomyomata ) were as follows : adjusted relative risk of 1.4 ( 95 % CI 1.1 , 1.9 ) for diffuse only , adjusted relative risk of 1.4 ( 95 % CI 1.1 , 1.8 ) for small leiomyomata ( less than 2 cm ) , adjusted relative risk of 1.6 ( 95 % CI 1.3 , 2.0 ) for medium leiomyomata ( 2–5 cm ) , and adjusted relative risk of 1.9 ( 95 % CI 1.5 , 2.5 ) for large leiomyomata ( greater than 5 cm ) . Reported use of eight or more pads/tampons on the heaviest days of menstrual bleeding increased with leiomyoma size , with a nearly 2.5-fold risk for women with large leiomyomata compared with women without leiomyomata ( adjusted relative risk of 2.4 ; 95 % CI 1.8 , 3.1 ) . Nonsubmucosal leiomyomata were associated with essentially the same increase in heavy bleeding as submuscosal leiomyomata of similar size . CONCLUSION Small leiomyomata were associated with increased risk of heavy bleeding , and risk increased with size . Contrary to published articles , nonsubmucosal leiomyomata were associated with heavy bleeding to the same extent as submucosal leiomyomata The purpose of this study was to evaluate efficacy and safety parameters in women with leiomyomata uteri treated with the GnRH agonist leuprolide acetate depot , 3.75 mg intramuscularly every 4 weeks for 24 weeks . One hundred twenty-eight patients were enrolled in a r and omized , double-blind , placebo-controlled multicenter study involving 13 investigative centers . Mean uterine volume decreased by 36 % at 12 weeks and 45 % at 24 weeks of leuprolide therapy . Patients treated with placebo had increases in mean uterine volume of 16 % at 12 weeks and 5 % at 24 weeks . Seventyseven percent of leuprolide-treated patients had a more than 25 % reduction in uterine volume , compared with 9 % of placebo-treated controls . Mean uterine volume returned to pre-treatment size 24 weeks after cessation of leuprolide treatment . The majority of patients had resolution or improvement of their fibroid-related symptoms after 24 weeks of leuprolide treatment . Of 38 leuprolide-treated patients presenting with menorrhagia , 37 ( 97 % ) had resolution of this symptom at the time of the final visit . Although 95 % of women treated with leuprolide acetate experienced some side effects related to hypoestrogenism , only five patients ( 8 % ) terminated treatment prematurely . We conclude that leuprolide acetate depot treatment of leiomyomata uteri is safe and causes significant but temporary reductions in uterine size and fibroid-related symptoms Fourteen premenopausal women with uterine leiomyomata were r and omized to receive a gonadotropin-releasing hormone agonist ( GnRH-a ) , leuprolide , either by daily subcutaneous ( SC ) injection ( 500 micrograms/day ) or by intranasal ( IN ) spray ( 1600 micrograms/day ) for 24 weeks . In the SC group , a significant reduction in uterine volume occurred from a pretreatment volume of 368 + /- 60 ( mean + /- st and ard error of the mean [ SEM ] ) cm3 to 202 + /- 61 cm3 at 12 weeks of therapy ( P less than 0.01 ) and to 172 + /- 49 cm3 at 24 weeks of therapy ( P less than 0.005 ) . In the IN group , no significant reduction in uterine volume occurred . In addition , there was a significant negative correlation between the serum estradiol concentration during treatment and the percent decrease in uterine volume ( r = -0.55 , P less than 0.05 ) . Four months after completing therapy , uterine volume increased to 296 + /- 104 cm3 in the SC group , which was not significantly different from pretreatment volume . These findings suggest that reduction in uterine volume depends on the degree of hypoestrogenism induced and that uterine volume increases soon after cessation of GnRH-a therapy BACKGROUND Our aim was to evaluate the long-term effectiveness and safety of GnRH agonist plus raloxifene administration in women with symptomatic uterine leiomyomas . METHODS Fifty pre-menopausal women with uterine leiomyomas were treated with leuprolide acetate depot at dose of 3.75 mg/28 days and raloxifene hydrochloride at 60 mg/day for 18 cycles . At admission and after each six cycles of treatment , bone mineral density ( BMD ) , uterine , leiomyoma and non-leiomyoma dimensions , serum bone metabolism markers , lipid , glucose and insulin levels were evaluated . Leiomyoma-related and climacteric-like symptoms were assessed using a daily diary . RESULTS Throughout the study , no significant change in BMD or in any bone metabolism markers was observed . A significant decrease in uterine , leiomyoma and non-leiomyoma sizes was detected in comparison with baseline already after 6 months . No other significant change was observed at the successive follow-up visits . No significant change in lipid and glucose profile was detected throughout the study . The treatments were well tolerated . All treatment withdrawals ( 16 % , eight out of 50 ) were due to lack of compliance , and none to drug-related adverse experiences . CONCLUSION GnRH agonist plus raloxifene administration is an effective and safe treatment for pre-menopausal women with uterine leiomyomas BACKGROUND Raloxifene hydrochloride is a synthetic non-steroidal drug used for the prevention and treatment of post-menopausal osteoporosis . Pre- clinical and clinical data have shown that raloxifene may have a beneficial effect on leiomyomas . The aim of this prospect i ve single-blind , r and omized , placebo-controlled clinical trial was to evaluate the effectiveness of the addition of raloxifene to GnRH analogues on uterine , leiomyoma , and non-leiomyoma sizes , and on the occurrence of leiomyoma-related symptoms . METHODS After r and omization using a computer-generated list , 100 pre-menopausal women with symptomatic uterine leiomyomas received either leuprolide acetate depot plus raloxifene 60 mg daily ( group A ) or leuprolide plus placebo tablet ( group B ) for six cycles of 28 days . At baseline and after treatment , uterine , leiomyoma and non-leiomyoma sizes , and leiomyoma-related symptoms were evaluated for each woman . Analysis was by intention-to-treat method . RESULTS After six cycles of treatment , a significant decrease in uterine , leiomyoma , and non-leiomyoma sizes was detected in both groups in comparison with baseline . At the same time , no significant difference in uterine and non-leiomyoma sizes was observed between the groups . Leiomyoma sizes were significantly ( P < 0.05 ) lower in group A than in group B. No difference was observed in leiomyoma-related symptoms between groups throughout the study period . CONCLUSIONS In women treated with GnRH analogue , the raloxifene administration induces a higher reduction of leiomyoma sizes Background . In articles and textbooks the prevalence of uterine leiomyomas is said to be 20–25 % in women over the age of 30 . The aim of this study was to investigate the rate of uterine leiomyoma , the thickness and the texture of the endometrium , and the size of the uterus in a r and om sample of asymptomatic women 25–40 years old OBJECTIVE Uterine leiomyoma , or fibroid tumors , are the leading indication for hysterectomy in the United States , but the proportion of women in whom fibroid tumors develop is not known . This study screened for fibroid tumors , independently of clinical symptoms , to estimate the age-specific proportion of black and white women in whom fibroid tumors develop . STUDY DESIGN R and omly selected members of an urban health plan who were 35 to 49 years old participated ( n = 1364 women ) . Medical records and self-report were used to assess fibroid status for those women who were no longer menstruating ( most of whom had had hysterectomies ) . Premenopausal women were screened by ultrasonography . We estimated the age-specific cumulative incidence of fibroid tumors for black and white women . RESULTS Thirty-five percent of premenopausal women had a previous diagnosis of fibroid tumors . Fifty-one percent of the premenopausal women who had no previous diagnosis had ultrasound evidence of fibroid tumors . The estimated cumulative incidence of tumors by age 50 was > 80 % for black women and nearly 70 % for white women . The difference between the age-specific cumulative incidence curves for black and white women was highly significant ( odds ratio , 2.9 ; 95 % CI , 2.5 - 3.4 ; P < .001 ) . CONCLUSION The results of this study suggest that most black and white women in the United States develop uterine fibroid tumors before menopause and that uterine fibroid tumors develop in black women at earlier ages than in white women OBJECTIVE To assess the efficacy of tibolone add-back therapy with Goserelin treatment of uterine fibroids . DESIGN R and omized placebo-controlled study . SETTING Gynecology department of an inner-city teaching hospital . PATIENT(S ) Seventy-five women of reproductive age with uterine fibroids . INTERVENTION(S ) All women were given monthly SC implants of 3.6 mg goserelin and were r and omized to take 3 months of placebo followed by 3 months of tibolone 2.5 mg daily ( delayed administration ) , tibolone 2.5 mg daily for 6 months , or placebo for 6 months . MAIN OUTCOME MEASURE(S ) Changes in bone mineral density ( BMD ) at the hip and spine , fibroid and uterine size , and patient symptomatology . RESULT ( S ) In the tibolone group , 2 % loss of BMD at the spine was observed compared with 5.5 % loss in the placebo group . For total hip , tibolone led to a 0.7 % gain in BMD compared with a loss of 1.7 % in the placebo group . Tibolone did not affect GnRH analogue-induced fibroid shrinkage . Vasomotor symptom scores in women taking tibolone were 2.2 and were significantly lower than those taking placebo or in the delayed administration groups ( mean scores 2.9 and 2.7 , respectively ) . CONCLUSION ( S ) Tibolone appears to be a safe and effective add-back therapy which can be given from the commencement of GnRH analogue treatment for fibroids A r and omized trial was carried out to investigate the effect of 12 months administration of the gonadotrophin-releasing hormone agonist ( GnRHa ) Zoladex in combination with either placebo or medroxyprogesterone acetate ( MPA ) from the third month . Bone density , markers of bone resorption , symptoms and uterine volume were monitored in 24 women with symptomatic fibroids or menstrual problems . A total of 21 women were recruited to act as controls for the assessment of bone parameters . Vasomotor side-effects were reduced significantly in the MPA-treated group . The reduction in uterine volume in women with fibroids was not impaired by the addition of MPA . The bone markers osteocalcin and alkaline phosphatase were assessed in plasma , and the cross-links pyridinoline and deoxypyridinoline measured in urine . Changes in these markers are reported which suggest increases in bone resorption during the period of observation . Bone mineral density ( BMD ) was assessed by dual energy X-ray absorptiometry at the spine and forearm . The net reduction in BMD at the spine in the treated groups was 4.30 + /- 0.59 % at 6 months and 7.50 + /- 0.78 % at 1 year , with no change in the control group . No change was seen in forearm BMD . No protective effect was observed when MPA was added . At 1 year after the completion of treatment , BMD remained significantly below baseline , and this has implication s for the prolonged use of GnRHa OBJECTIVE To evaluate the effects of long-term administration of GnRH agonist ( GnRH-a ) plus tibolone for uterine leiomyomatosis . DESIGN Prospect i ve open clinical trial . SETTING Department of Gynecology , Obstetrics and Pathophysiology of Human Reproduction , University of Naples " Federico II " , Naples , Italy . PATIENT(S ) Twenty-five subjects with symptomatic uterine leiomyomas . INTERVENTION(S ) Treatment for 2 years with leuprolide acetate ( 3.75 mg IM every 28 days ) and tibolone ( 2.5 mg/d per os ) . MAIN OUTCOME MEASURE(S ) Uterine and uterine leiomyoma sizes , endometrial thickness , lumbar spine bone mineral density ( BMD ) , bone metabolism , lipid profile , myoma-related symptoms at baseline and every 6 months . Hot flashes and vaginal bleeding episodes recorded in a daily symptom diary . RESULT ( S ) After 6 months of treatment , a significant reduction was observed in uterine and leiomyoma volumes and myoma-related symptoms compared with baseline values . No significant change was observed in bone turnover , lumbar BMD , or serum total cholesterol , low-density lipoprotein cholesterol , or triglyceride levels . High-density lipoprotein cholesterol values were significantly lower than baseline values after 6 months of treatment but not after 18 months of therapy . A low mean number of hot flashes per day was observed . CONCLUSION ( S ) Long-term administration of GnRH-a plus tibolone reduces hot flashes and prevents bone loss without changing the lipid profile OBJECTIVE To evaluate the effects of tibolone therapy in association with GnRH-a on uterine leiomyomata , on climacteric-like symptoms , on bone metabolism , and on the lipid profile . DESIGN A prospect i ve , r and omized , double-blind , placebo-controlled , clinical trial . SETTING Department of Gynecology and Obstetrics , University of Naples " Federico II , " Naples , Italy . PATIENT(S ) Fifty women with symptomatic uterine leiomyomata . INTERVENTION(S ) Six months of treatment with leuprolide acetate ( 3.75 mg every 28 days IM ) combined with daily placebo tablets ( group A ) or with 2.5-mg of tibolone per os ( group B ) . MAIN OUTCOME MEASURE(S ) Uterine and uterine leiomyomata sizes , lumbar spine bone mineral density , biochemical markers of bone metabolism , lipid profile , and myoma-related symptoms were measured at baseline and after 6 months of treatment . Daily symptom diary in which hot flushes and vaginal bleeding episodes were recorded . RESULT ( S ) No differences between the 2 groups in uterine and uterine leiomyomata size and myoma-related symptoms were detected . After 6 months of treatment , there were statistically significant changes from baseline in bone mineral density and in biochemical markers of bone metabolism in group A but not in group B. Vasomotor symptoms were significantly lower in group B than in group A. There was a statistically significant increase ( P<.01 ) in serum total cholesterol , high-density lipoprotein cholesterol , and triglycerides in group A after 6 months of treatment in comparison with baseline values . The difference in serum total cholesterol and triglyceride levels after 6 months of treatment in group B was not statistically significant in comparison with baseline values , but was statistically significant in comparison with group A values ( P<.01 ) . In group B , levels of high-density lipoprotein cholesterol were significantly lower after 6 months of therapy in comparison with baseline values and in comparison with group A values ( P<.01 ) . There were no statistically significant changes at baseline and after 6 months of treatment in the level of low-density lipoprotein cholesterol in either group . CONCLUSION ( S ) Administration of tibolone in association with GnRH-a reduces vasomotor symptoms and prevents bone loss , without compromising the therapeutic efficacy of GnRH-a alone The purpose of this study is to evaluate the efficacy of vitamin K2 and 1,25-dihydroxyvitamin D3 [ 1,25-(OH)2D3 ] in preventing bone loss induced by estrogen deficiency during therapy with the GnRH agonist ( GnRH-a ) leuprolide . One hundred ten women ( mean age , 46.2+/-0.5 yr ) , receiving leuprolide therapy for estrogen-dependent diseases ( such as endometriosis and uterine leiomyomas ) , were r and omly allocated into four groups ( group A , leuprolide only ; group B , leuprolide with vitamin K2 ; group C , leuprolide with 1,25-(OH)2D3 ; and group D , leuprolide with vitamin K2 and 1,25-(OH)2D3 ) . Bone mineral density of the lumbar spine was measured by dual-energy x-ray absorptiometry before and after 6 months of treatment . Bone formation and resorption markers were also measured before and after 6 months of treatment . There were no significant differences in the background parameters among the four groups . Bone mineral density was reduced in all four groups , but the percent changes varied slightly , at - 5.25 % ( group A ) , -3.72 % ( P < 0.05 vs. group A ) ( group B ) , -4.13 % ( group C ) , and -3.59 % ( P < 0.01 vs. group A ) ( group D ) , respectively . Bone formation markers were significantly increased in all four groups , and the percent changes of bone formation markers were highest in group B. Bone resorption markers also increased significantly in all four groups after treatment of 6 months . Group B tended to have the highest percent changes of bone resorption markers among the four groups , but these increases were not significantly different between any of the groups . Vitamin K2 , especially when combined with 1,25-(OH)2D3 , can partially prevent bone loss caused by estrogen deficiency . However , because this effect is attributable mainly to the activation of bone formation , it is not sufficient to eliminate bone loss induced by GnRH-a therapy Treatment of women with uterine myomas with GnRH agonists results in symptoms of hypoestrogenism which can be prevented by concurrent " add-back " estrogen administration . We took advantage of these induced endocrine changes to investigate their effects on cognitive functioning in young women with myomas . Nineteen women with uterine myomas were tested before treatment . They all received the GnRH agonist , leuprolide acetate depot ( LAD ) , every 4 weeks for 12 weeks and were then r and omized to receive LAD plus estrogen or LAD plus placebo every 4 weeks for 8 additional weeks . Levels of all sex hormones decreased after 12 weeks of LAD treatment ( P < 0.01 ) , and only estradiol ( E2 ) levels increased ( P < 0.01 ) following 8 weeks of subsequent treatment in the group that received LAD plus E2 . Scores on neuropsychological tests of verbal memory decreased from pretreatment to 12 weeks posttreatment with LAD ( P < 0.05 ) . These memory deficits were reversed in the group that received LAD plus E2 for 8 weeks coincident with an increase in plasma E2 , whereas memory scores remained depressed in the group that received LAD plus placebo . These findings are consistent with those from studies on surgically menopausal women and strongly suggest that estrogen serves to maintain verbal memory in women . These results provide support for the efficacy of add-back estrogen regimens in women treated with GnRH agonists and also imply that estrogen may be important for maintaining memory in the postmenopause OBJECTIVE Our purpose was to determine whether intermittent cyclic etidronate therapy blocks the decline in bone density associated with gonadotropin-releasing hormone agonist therapy . STUDY DESIGN Thirty-one premenopausal subjects who needed treatment with leuprolide ( Lupron ) 3.75 mg monthly for 6 months were r and omized to etidronate or placebo . Bone turnover was assessed by measurement of serum calcium , phosphorus , alkaline phosphatase , and fasting urinary calcium/creatinine ratios . Bone density was measured by dual energy x-ray absorptiometry . RESULTS Gonadotropin-releasing hormone treatment produced a significant decrease ( 4 % to 10 % ) in bone density at the anteroposterior and lateral spine in placebo-treated patients ( 11 ) . No significant change was demonstrated in etidronate-treated patients ( 15 ) . Significant increases in serum calcium , phosphorus , alkaline phosphatase , and urinary calcium/creatinine ratios were noted in the placebo group . No significant change in these parameters were evident in the etidronate group . CONCLUSION Etidronate blocks bone mineral density changes associated with gonadotropin-releasing hormone agonist therapy and normalizes serum and urine indicators of bone turnover The purpose of this study was to evaluate the efficacy of ipriflavone in preventing bone loss , decreasing in serum cholesterol and decreasing the rate of appearance of vasomotor symptoms , as well as the effects of ipriflavone on reduction of myoma volume by estrogen deficiency during treatment with the GnRH analog leuprolide . One hundred two women ( mean age , 44.3 + /- 0.53 yr ) receiving leuprolide therapy for uterine leiomyoma were r and omly allocated to two groups ( group A , leuprolide only ; group B , leuprolide with ipriflavone ) . Bone mineral density of the lumbar spine was measured by dual-energy x-ray absorptiometry before and after treatment for 6 months . Levels of serum total cholesterol ( TC ) , triglyceride ( TG ) , high-density lipoprotein cholesterol , and low-density lipoprotein cholesterol ( LDL-C ) were measured before treatment and after 3 and 6 months of treatment . Subjects were asked to report the appearance of vasomotor symptoms throughout treatment . Myoma node volumes were measured before treatment and after treatment for 6 months . Bone mineral density was reduced in both groups , with reduction rates of -5.26 % in group A and -3.70 % in group B ( P < 0.01 vs. group A ) . Changes in bone markers were not significant in either group . TC was significantly increased in both groups , and TG levels were increased significantly after 3 and 6 months of treatment in group A but not in group B. There was no significant difference between these two groups in amount of increase of either TC or TG . LDL-C levels were increased significantly after 3 and 6 months of treatment in both groups , and the differences between the groups ( 11.7 % in group A vs. 7.5 % in group B at 3 month and 22.6 % in group A vs. 8.4 % in group B at 6 month ) were significant . Severe vasomotor symptoms were reduced in group B. The rates of reduction of myoma volume were 49.8 % in group A and 52.9 % in group B ; this difference between groups was not significant . Ipriflavone efficaciously alleviated the adverse effects of estrogen deficiency such as bone loss and increase in LDL-C level , and the ability of leuprolide therapy to reduce myoma volume was not decreased by ipriflavone administration OBJECTIVE To evaluate whether administration of tibolone changes the effectiveness of GnRH analogue administered before laparoscopic myomectomy . DESIGN Prospect i ve , r and omized , open , placebo-controlled clinical trial . SETTING Department of Gynecology and Obstetrics , University of Naples Federico II , Naples , Italy . PATIENT(S ) 66 women with symptomatic uterine leiomyomas . INTERVENTION(S ) Treatment for 2 months with leuprolide acetate and iron tablets , plus tibolone ( group A ) or placebo tablets ( group B ) ; or with leuprolide acetate and iron tablets ( group C ) . MAIN OUTCOME MEASURE(S ) Laparoscopic myomectomy at the end of treatment . Operative time and blood loss during surgery were recorded . Uterine volume , volume and number of uterine leiomyomas , volume and echogenicity of the largest uterine leiomyomas , hematologic data , and myoma-related symptoms were evaluated at baseline and 1 week before and after surgery . RESULT ( S ) Uterine and leiomyomata volume and myoma-related symptoms were significantly reduced and hematologic variables improved significantly in groups A and B , compared with baseline values and with group C. Operative time and blood loss were significantly less in groups A and B than in group C. After surgery , hematologic variables were significantly worse in group C compared with groups A and B. During the study no significant difference was detected between groups A and B. CONCLUSIONS Administration of tibolone administration in patients treated with GnRH analogue before laparoscopic myomectomy does not change the effectiveness of the analogue administered alone The hypoestrogenic state induced by gonadotropin-releasing hormone agonists ( GnRHa ) has been shown to be effective in the treatment of uterine leiomyomas but to induce bone loss . Estriol has been described to be a weak and short-acting estrogen without an increased risk of endometrial proliferation and hyperplasia . The purpose of this study was to evaluate whether treatment of uterine leiomyomata with GnRHa plus oral estriol add-back therapy could prevent bone loss , without deteriorating the therapeutic effect of GnRHa . Twelve premenopausal women with symptomatic uterine leiomyomas were r and omized to receive either leuprolide acetate depot alone at a dose of 3.75 mg s.c . every month for 6 months ( non add-back group ; n = 6 ) , or GnRHa for 6 months plus oral estriol 4 mg/day for 4 months commencing with the third GnRHa injection ( add-back group ; n = 6 ) . In the add-back group , leiomyoma volume , as measured by transvaginal ultrasound , decreased to 59.1 % of baseline at 2 months of GnRHa therapy with no significant change in size during the remaining treatment period . In contrast , it decreased to 31.3 % of pretreatment size at the end of treatment in the non add-back group . The levels of bone metabolic markers such as CrossLaps , deoxypyridinoline , osteocalcin and bone-specific alkaline phosphatase , increased significantly throughout the treatment in the non add-back group , whereas they were suppressed by the add-back therapy . The bone mineral density of lumbar spine ( L2-L4 ) as measured by dual-energy X-ray absorptiometry decreased significantly by 7.5 % at the end of treatment in the non add-back group , but did not change significantly in the add-back group . In conclusion , GnRHa plus estriol add-back therapy might be considered for long-term treatment of uterine leiomyomata In this prospect i ve , r and omized , double-blind study , we evaluated the effects of tibolone therapy in association with preoperative gonadotropin releasing hormone agonist ( GnRHa ) therapy on the reduction of myoma volume . Twenty patients with myoma uteri were divided into two groups . Group I was given monthly triptoreline ( 3.75 mg every 28 days IM ) treatment for six months . As for group II , tibolone was added on to this treatment . For all of the patients , physical examinations , pelvic ultrasonography , and hormone analyses were carried out and the myoma volume was measured by ultrasonography . The patients were called every month and physical examination , ultrasonography and hormone analyses were repeated . Side-effects were recorded . The SPSS/PC 6.0 program was used for statistical analysis . Statistical significance was defined as a p < 0.05 . The results are expressed as means + /- SD . While the average volume of myoma was 72.97 + /- 68.5 cm3 in group I , 78.83 + /- 74.1 cm3 in group II before treatment ; it was reduced to 29.91 + /- 27.8 cm3 in group I at the end of six months of treatment . Reductions of 59.6 % in group I and 63.9 % in group II were determined , however the difference was not statistically significant ( p > 0.05 ) . At the beginning the level of serum estradiol was 65.4 + /- 22.3 pg/ml in group I which decreased to 37.2 + /- 4.2 pg/ml by the end of the first month . Amenorrhea occurred in six patients after the second injection and four patients after the third injection in group I. Whereas the level of estradiol was 60.9 + /- 19.5 pg/ml in group II at the beginning , it was reduced to 40.5 + /- 6.2 pg/ml by the end of the first month . Amenorrhea occurred in four patients after the second injection and four patients after the third injection in group II . In group I the patients had the problem of flushing ( 80 % ) , vaginal dryness ( 50 % ) , and night sweats ( 30 % ) . In group II these rates were 30 % , 20 % , and 20 % , respectively . Triptoreline is a GnRHa which has been found to be effective in reducing myoma volume , but this effect could not be deactivated with tibolone . However , a decrease was observed in the side-effects result ing from hypoestrogenism Gonadotropin-releasing hormone analogues ( GnRH-a ) are widely used for the preoperative treatment of uterine leiomyomas in premenopausal patients . They induce a pseudomenopausal hypoestrogenic state , result ing in decreased uterine and fibroid volumes , significantly improved pre and postoperative hemoglobin and hematocrit , and reduced intraoperative blood loss . After pretreatment with GnRH-a therapy , hysterectomy seems to be easier , the operating time is reduced , and a greater proportion of hysterectomies can be performed avoiding the abdominal approach ( 1 ) . The low estradiol levels induced by GnRH-a treatment may cause hypoestrogenism-related side effects , such as hot flushes and bone loss , that occur even during shortterm therapies ( 2 ) . Tibolone , a tissue-selective synthetic steroid [ (7a,17a)17-hydroxy-7-methyl-19-norpregn-5(10)-en-20-yn-3one ] with combined progestogenic , estrogenic , and and rogenic properties , is used as hormone replacement therapy and to prevent osteoporosis in postmenopausal women ( 3 ) . The compound itself does not bind with high affinity to any of the known steroid receptors ( 4 ) . Depending on the activity of the different enzymes during passage through the intestine and liver , tibolone can be converted by 3b-hydroxysteroid dehydrogenase into its D isomer or its 3b-derivative and /or by 3a-hydroxysteroid dehydrogenase into its 3a-reduced derivative ( 5 ) . In contrast to tibolone itself , these metabolic products show higher affinity binding to several steroid receptors ; D-tibolone binds to progesterone and and rogen receptors , and 3a-OH-tibolone and 3b-OH-tibolone bind to estrogen receptors ( 4 ) . Tibolone is reported to increase bone mass density and to have beneficial effects on hypoestrogenic symptoms . It does not cause uterine bleeding in most women and has no proliferative effects on the endometrium ( 6 ) . Tibolone has been shown to be a good add-back agent to GnRH-a , even in the short-term preoperative treatment of women with uterine fibroids ( 2 ) . It reduces the menopausal-like symptoms without influencing the therapeutic effects of GnRH-a ( 7 ) . The mechanism by which GnRH-a treatment causes uterine and fibroid volume shrinkage is still unclear . Decreased cell proliferation and increased apoptosis are among the hypotheses , but data are conflicting . Routine histological examinations of leiomyomas after GnRHa administration have failed to show changes in cell proliferation ( 8) . However , some authors reported reduced expression of Ki67 and /or proliferating cell nuclear antigen ( PCNA ) , which label proliferating cells ( 9,10 ) ; others found significant overexpression of PCNA antigen and significant elevation of Ki67 antigen after GnRH-a therapy ( 11 ) . The expression of the inhibitor of apoptosis Bcl-2 , which controls the survival and death of cells , has been From the Department of Obstetrical-Gynaecological and Urological Science and Reproductive Medicine ( M.D.F. , F.P. , M.P. , F.C. , A.D.L. ) and Department of Biomorphological and Functional Science ( S.S. , G.S. , G.M. ) , University ‘ ‘ Federico II ’ ’ of Naples , Napoli , Italy . Address correspondence and reprints requests to Prof. And rea Di Lieto , Via L. Giordano , 120 - 80127 Naples , Italy . E-mail : [email protected] International Journal of Gynecological Pathology 24:286–291 , Lippincott Williams & Wilkins , Baltimore 2005 International Society of Gynecological A group of 48 women with symptomatic leiomyomata were treated during 6 months with the short-acting Gn-RH superagonist analog buserelin . The first ( group C ) was followed up for an additional six months of no medication . The second ( group M ) was treated for 6 additional months with medroxyprogesterone acetate ( MPA ) at doses decreasing from 200 to 25 mg/day . Buserelin therapy significantly decreased uterine size ( P less than 0.001 ) in all patients , the average final volume being 48.5 % of the original ( from 262 + /- 147 ml to 127 + /- 85.4 ml ) . In group C there was a significant ( P less than 0.001 ) re-growth during the post-treatment observation period ( from 120 + /- 81.0 ml to 198 + /- 77.2 ml ) ; a significant ( P less than 0.01 ) re-growth was also observed in group M during MPA medication ( from 132 + /- 77.2 ml to 170 + /- 96.0 ml ) . The agonist had also a marked effect on fibroids : on average they decreased from 75.1 + /- 74.3 ml to 24.7 + /- 23.3 ml ( P less than 0.025 ) . In group C during the post-buserelin period of observation without treatment , there was a significant re-growth from 23.7 + /- 21.6 ml to 47.7 + /- 27.5 ml ( P less than 0.001 ) , whereas in group M treatment with MPA prevented any significant re-growth ( from 25.6 + /- 24.8 to 30.6 + /- 32.9 ml ; P greater than 0.3 ) OBJECTIVE To investigate the effects of tibolone co-administration with GnRH agonist treatment in terms of cognition , mood , and quality of life . DESIGN R and omized , controlled , single-blind , clinical trial . SETTING Department of gynecology and obstetrics at a university in Italy . PATIENT(S ) One hundred ten premenopausal women with symptomatic uterine leiomyomas . INTERVENTION(S ) Six months of treatment with leuprolide acetate depot ( 11.25 mg IM , every 3 mo ) associated with either tibolone ( 2.5 mg/d orally ; group A ) or placebo ( 1 tablet per d ; group B ) . MAIN OUTCOME MEASURE(S ) At baseline and after 6 months of treatment , uterine and leiomyoma sizes , leiomyoma-related symptoms , climacteric-like symptoms , cognition , mood , and quality of life . RESULT ( S ) At study entry , no difference was detected between groups in any parameters assessed . After treatment , the leiomyoma-related symptoms were significantly reduced in both groups , without any statistically significant differences between them . The Kupperman Index was statistically significantly higher in group B in comparison with baseline and group A. The cognition scores were statistically significantly different in comparison with baseline in group B , whereas no change was observed in group A. After treatment , mood and quality of life were statistically significantly improved in both groups , even though the improvement was significantly higher in group A than in group B. CONCLUSION ( S ) Tibolone administration reverses the deleterious effect on cognition that is caused by leuprolide acetate depot and improves mood and quality of life in patients who receive GnRH agonist for symptomatic uterine leiomyomas OBJECTIVE To assess whether tibolone can prevent the bone loss and symptomatic side effects normally associated with GnRH agonist ( GnRH-a ) use and whether tibolone modifies the effect of GnRH-a on endometriosis . DESIGN Prospect i ve , double-blind , placebo-controlled , group comparative study . SETTING Gynecological research unit in a London teaching hospital . PATIENTS Twenty-nine patients with endometriosis and two with fibroids . INTERVENTIONS Six months of treatment with 3.75 mg/mo IM triptorelin combined with daily tablets of either placebo or 2.5 mg tibolone . MAIN OUTCOME MEASURES Daily symptom diary for hot flushes and bleeding episodes , laparoscopic scoring of endometriosis , endocrine and biochemical changes , and bone mineral density scans . RESULTS Lumbar spine bone mineral density decreased significantly from baseline in the placebo group ( -5.1 % ) but not in the tibolone group ( -1.1 % ) . The frequency of hot flushes and sweating episodes was reduced significantly by tibolone . There was no difference between the two treatment groups with regard to the endometriosis scores . CONCLUSIONS The addition of tibolone to GnRH-a treatment reduces the bone loss and vasomotor symptoms that normally occur with GnRH-a , thus making long-term treatment with GnRH-a safer and more acceptable . It does not negate the therapeutic effect of GnRH-a on endometriosis The purpose of this study was to prospect ively compare the effectiveness of administering medroxyprogesterone acetate ( MPA ; 20 mg/day ) in either the first ( protocol A ) or last ( protocol B ) 12-week period along with a 6-month course of the GnRH analog ( GnRH-a ; leuprolide acetate ; 1 mg/day , sc ) on uterine and leiomyomata volumes and hormone ( estradiol , LH , and FSH ) and serum lipid ( total cholesterol , triglycerides , and high and low density lipoprotein ) levels . Sixteen women were r and omized into protocol A or B , received either MPA or placebo along with GnRH-a , respectively , and were then crossed over at 12 weeks to placebo or MPA , respectively , for the final 12-week interval of GnRH-a therapy . Total , myoma , and nonmyoma uterine volumes were determined by magnetic resonance imaging , and serum studies were performed at the beginning of the study and at 12 and 24 weeks . In both protocol s , LH and estradiol levels declined by 80 - 90 % ( P < 0.03 ) and 55 - 72 % ( P < 0.02 ) of the baseline , respectively , at 12 weeks and remained at this level at 24 weeks . There were no significant changes in the other laboratory tests between protocol s or longitudinally over time . Total uterine volume decreased to 73 % of the baseline at 12 weeks in protocol B ( P < 0.04 ) , but did not change in protocol A. After crossover at 12 weeks , the total uterine volume of women in protocol A decreased to 74 % of the baseline ( P < 0.02 ) at 24 weeks . Between- protocol comparisons demonstrated a greater decline in total uterine volume in protocol B than A at 12 weeks , but after cross-over , MPA addition was associated with a significant increase in total uterine volume ( protocol B ) compared to a decrease in protocol A at 24 weeks ( P < 0.005 ) . In contrast , although myoma volume declined in both protocol s , no significant changes in myoma volume were detected within or between groups over the treatment period . Nonmyoma volume changes in protocol s A and B roughly paralleled total uterine volume changes , with MPA coadministration showing a correlation with a reversal in the GnRH-a-associated decrease in nonmyomatous tissue volume . ( ABSTRACT TRUNCATED AT 400 WORDS Treatment of women with leiomyomata with gonadotrophin-releasing hormone agonists ( GnRHa ) for > 6 months is not recommended because of concerns regarding adverse sequelae of prolonged hypoestrogenism . It has been postulated that addition of low-dose sex steroids to GnRHa treatment , i.e. ' add-back ' therapy , may avert some of these adverse effects ( accelerated bone resorption , vasomotor flushes ) without altering the efficacy of GnRHa therapy . To evaluate the effects of long-term GnRHa therapy on uterine size , bleeding patterns , bone mass and lipids , 51 pre-menopausal women with leiomyomata were treated with the GnRHa leuprolide acetate depot , 3.75 mg every 4 weeks for 2 years . After 3 months of leuprolide therapy , the women were r and omized to receive either low-dose continuous oestropipate , 0.75 mg daily , plus cyclic norethindrone , 0.7 mg on days 1 - 14 each month ( the oestrogen-progestin add-back group ) or higher-dose norethindrone , 10 mg daily ( the progestin add-back group ) , for the remaining 21 months . Mean uterine volume decreased by 40 % in both treatment groups during the first 3 months on leuprolide treatment . There was no significant change in uterine size following oestrogen-progestin add-back . However , mean uterine volume in the progestin add-back group increased to 87 % of pre-treatment size by treatment month 12 and 95 % of pre-treatment size by treatment month 24 . Mean bone density of the lumbar spine as measured by dual X-ray absorptiometry decreased significantly by 2.6 % during the first 3 months in all patients , but did not change significantly following steroid add-back in both treatment groups during the final 21 treatment months . ( ABSTRACT TRUNCATED AT 250 WORDS OBJECTIVE To determine the effectiveness of leuprolide acetate ( LA ) followed by medroxyprogesterone acetate ( MPA ) in the treatment of abnormal uterine bleeding attributed to leiomyomata uteri . DESIGN R and omized , double-blinded , controlled clinical trial . SETTING Human volunteers in an academic research environment . PATIENTS Premenopausal women with abnormal uterine bleeding attributed to leiomyomata uteri . INTERVENTIONS Subjects received 6 months of LA after which they were r and omized to receive MPA or placebo . MAIN OUTCOME MEASURES Control of bleeding as assessed by menstrual calendar and self-report ; hematologic parameters ( hemoglobin and ferritin ) ; uterine size by ultrasonography . RESULTS More than three quarters of subjects became amenorrheic on LA . The proportion of subjects with improvement in the bleeding abnormality after therapy was not different in the group receiving MPA compared with placebo ; however , women who received MPA were less likely to be anemic after therapy than women receiving placebo . Among the women assigned to placebo , 55 % experienced an improvement in bleeding compared with pre-GnRH agonist therapy that persisted after discontinuation of LA . There was a high dropout rate ( 51 % ) , largely associated with failure of the regimens to control bleeding symptoms . CONCLUSIONS Approximately one half of women with abnormal bleeding attributed to leiomyomata uteri have sustained symptomatic improvement after 6 months of therapy with LA even when only placebo therapy is given , although MPA decreases the incidence of anemia . Leuprolide acetate with or without subsequent progestin may be useful as a component of nonsurgical management of these tumors , with monitoring of hematologic status . The interpretability of these data is limited by the high rate of therapy discontinuation in women with abnormal bleeding of the severity studied here Aim of the study is to compare the effects of preoperative therapy with tibolone plus gonadotropin-releasing hormone analogue ( GnRH-a ) in premenopausal women with those of GnRH-a alone on clinical response , uterine volume , immunohistochemical expression of platelet-derived growth factor ( PDGF ) , vascular endothelial growth factor ( VEGF ) and basic fibroblast growth factor ( bFGF ) and vascular features of myomas . Seventy women with symptomatic uterine fibromatosis were treated for four months with leuprorelin acetate alone or plus tibolone . Untreated patients were su bmi tted to uterine surgery directly . Uterine volume , hematological data , BMD , myoma-related symptoms and hot flushes were evaluated at the admission and before surgery . Immunohistochemical expression of PDGF , bFGF and VEGF , vascular changes and CD105 expression , as a marker of angiogenesis , were evaluated in myomas obtained after surgery . Uterine volume and myoma-related symptoms reduced and hematological variables increased in treated patients . BMD decreased in patients treated with GnRH-a alone . Hot flushes were less in GnRH-a plus tibolone group than in GnRH-a group . Immunohistochemical expression of PDGF , bFGF and VEGF , vascularization and angiogenesis reduced in treated patients in comparison with untreated ones . In conclusion , the administration of tibolone plus GnRH-a before uterine surgery does not change the clinical and immunohistochemical effects of GnRH-a alone From January 1987 to February 1988 patients affected by uterine fibroid were offered medical treatment with luteinizing hormone-releasing hormone analogs as an alternative to surgery . The aim was to compare results obtained with two different analog formulations . 42 patients were r and omly assigned to receive either intranasal buserelin , preceded by a short period of subcutaneous injections ( 500 micrograms thrice daily for 10 days ) or subcutaneous goserelin . Treatment was always started in the luteal phase . Response to therapy was evaluated through periodic clinic , endocrine and echotomographic controls . There were no significative differences in fibroid reduction between the two treatment groups . After 6 months of treatment , a fibroid reduction of more than 30 % of the initial volume was observed in 16 patients in the buserelin group and in 18 patients in the goserelin group . The fibroid regrowth observed in all patients during the follow-up period severely limits the usefulness of this medical approach to selected clinical cases Several studies have shown that treatment with a gonadotropin- releasing hormone ( GnRH ) analogue can reduce uterine volume in women with leiomyomata . However , no study to date has used a controlled population for comparison , nor has any study delineated the physiologic mechanism of volume reduction . We performed a double-blind , placebo-controlled study of a depot form of a GnRH analogue ( leuprolide ) given monthly for 24 weeks in 11 patients with symptomatic uterine leiomyomata . Patients initially treated with placebo were subsequently treated with active drug for 24 weeks . Magnetic resonance imaging was used to identify specifically the total uterine volume , total myoma volume , and total non-myoma volume . Treated patients had a significant reduction in total uterine and non-myoma volumes as compared with placebo patients ( P < .02 ) . Total myoma volume was also reduced , but only to a P=.06 level . Pre- versus post-therapy values for all 11 patients showed significant reduction in all three volumes ( P < .02 ) . Most symptoms were markedly improved . By 24 weeks post-therapy , all volumes had returned to baseline levels , although symptomatic improvement commonly persisted . The non-myoma volume was proportionally reduced to a greater extent than the myoma volume ( 42.7 versus 30.4 % ) , and we therefore could explain the reenlargement seen when treatment was discontinued . Side effects were well tolerated and there were no study dropouts . We conclude that temporary hypoestrogenism induced by GnRH analogues can produce significant though temporary reduction in uterine volumes , and that the non-myoma volume is responsible for much of the reduction and reenlargement . The treatment is well tolerated , and symptomatic benefits may well persist even with return of uterine volumes to pre-treatment size The LHRH analogues are used very much in gynecological practice , mostly for a long treatment periods . The menopausal side effects occur often and causes the patients to withdraw from treatment . The GnRh analogues are used for the treatment of endometriosis , uterine fibroids , for breast cancer , and pre and post operatively as hormonal therapy for endometrial cancer . 12 patients were given combined vaginal Ovestin and GnRh analogues ( Zoladex ) . Another 12 patients were taking GnRh analogues alone without Ovestin creme , and this group search ed as a control group . The group with the Ovestin had less side effects than the control group . This difference was statistically significant about the cervicovaginal symptoms ( p less than 0.01 ) . The treatment with vaginal estrogenes can better and improve the tolerance to therapy with GnRh analogues Objective : To evaluate the clinical features and the expression of transforming grwoth factor-β3 ( TGF-β3 ) and connective tissue growth factor ( CTGF ) in myometrium and uterine leiomyomas after preoperative treatment with gonadotropin-releasing hormone-analogs ( GnRH-a ) and tibolone . Methods : Twenty-three patients received 3.75 mg leuprolide acetate depot for 4 months . Twenty-two ptients received the same therapy plus 2.5 mg tibolone daily . Patients underwent uterine surgery after therapy . Twenty-two untreated patients underwent surgery directly . Hematologic tests , bone mineral density ( BMD ) measurement , and ultrasonographic evaluation of uterine volume were performed before and after treatment . Menorrhagia and pelvic pain were evaluated with a visual analog scale . Hot flushes were recorded in daily diaries . Immunohistochemical expression of TGF-β3 and CTGF in myometrium and myoma sample s was evaluated semiquantitatively . Results : After therapy , hemoglobin and iron levels similarly increased in both groups . BMD significantly decreased only in the GnRH-a group . Uterine volume similarly decreased in both groups . No patient had menorrhagia or pelvic pain at the end of therapy . The number of hot flushes increased after the first month in the GnRH-a group ; in the GnRH-a plus tibolone group , it remained constant and was lower . In untreated cases , TGF-β3 and CTGF smooth muscle cell immunoexpression was lower in myometrium than in leiomyomas . After medical treatment , growth factor immunoexpression remained unchanged in myometrial sample s and was reduced in leiomyomas . Endothelial cells showed strong immunopositivity , both in untreated and in treated cases . Conclusion : This study focuses on the effects of GnRH-a and tibolone on TGF-β3 and CTGF expression in myometrium and myomas and supports the hypothesis of a pathogenetic role of these growth factors in uterine fibromatosis |
10,735 | 28,759,701 | However , there was insufficient evidence to show a difference when looking at stimulated salivary flow rates .
There was insufficient ( very low- quality ) evidence to show that amifostine compromised the effects of cancer treatment when looking at survival measures .
There was low- quality evidence that amifostine is associated with increases in : vomiting ( RR 4.90 , 95 % CI 2.87 to 8.38 ; P < 0.00001 , 5 studies , 601 participants ) ; hypotension ( RR 9.20 , 95 % CI 2.84 to 29.83 ; P = 0.0002 , 3 studies , 376 participants ) ; nausea ( RR 2.60 , 95 % CI 1.81 to 3.74 ; P < 0.00001 , 4 studies , 556 participants ) ; and allergic response ( RR 7.51 , 95 % CI 1.40 to 40.39 ; P = 0.02 , 3 studies , 524 participants ) .We found insufficient evidence ( that was of very low quality ) to determine whether or not pilocarpine performed better or worse than a placebo or no treatment control for the outcomes : xerostomia , salivary flow rate , survival , and quality of life .
There was some low- quality evidence that pilocarpine was associated with an increase in sweating ( RR 2.98 , 95 % CI 1.43 to 6.22 ; P = 0.004 , 5 studies , 389 participants ) .We found insufficient evidence to determine whether or not palifermin performed better or worse than placebo for : xerostomia ( low quality ) ; survival ( moderate quality ) ; and any adverse effects .
There is some low- quality evidence to suggest that amifostine prevents the feeling of dry mouth in people receiving radiotherapy to the head and neck ( with or without chemotherapy ) in the short- ( end of radiotherapy ) to medium-term ( three months postradiotherapy ) .
However , it is less clear whether or not this effect is sustained to 12 months postradiotherapy .
There was insufficient evidence to show that any other intervention is beneficial | BACKGROUND Salivary gl and dysfunction is an ' umbrella ' term for the presence of either xerostomia ( subjective sensation of dryness ) , or salivary gl and hypofunction ( reduction in saliva production ) .
It is a predictable side effect of radiotherapy to the head and neck region , and is associated with a significant impairment of quality of life .
A wide range of pharmacological interventions , with varying mechanisms of action , have been used for the prevention of radiation-induced salivary gl and dysfunction .
OBJECTIVES To assess the effects of pharmacological interventions for the prevention of radiation-induced salivary gl and dysfunction . | PURPOSE To evaluate chronic xerostomia and tumor control 18 and 24 months after initial treatment with amifostine in a r and omized controlled trial of patients with head- and -neck cancer ; at 12 months after radiotherapy ( RT ) , amifostine had been shown to reduce xerostomia without changing tumor control . METHODS AND MATERIAL S Adults with head- and -neck cancer who underwent once-daily RT for 5 - 7 weeks ( total dose , 50 - 70 Gy ) received either open-label amifostine ( 200 mg/m2 i.v . ) 15 - 30 min before each fraction of radiation ( n = 150 ) or RT alone ( control ; n = 153 ) . RESULTS Amifostine administration was associated with a reduced incidence of Grade > or = 2 xerostomia over 2 years of follow-up ( p = 0.002 ) , an increase in the proportion of patients with meaningful ( > 0.1 g ) unstimulated saliva production at 24 months ( p = 0.011 ) , and reduced mouth dryness scores on a patient benefit question naire at 24 months ( p < 0.001 ) . Locoregional control rate , progression-free survival , and overall survival were not significantly different between the amifostine group and the control group . CONCLUSIONS Amifostine administration during head- and -neck RT reduces the severity and duration of xerostomia 2 years after treatment and does not seem to compromise locoregional control rates , progression-free survival , or overall survival A r and omized phase 2 study was performed to investigate the efficacy/toxicity of combining concomitant boost radiation and weekly carboplatin/paclitaxel with or without amifostine in patients with locally advanced squamous cell carcinoma of the head and neck ( SCCHN ) PURPOSE Promising results in a r and omized phase II trial with the hypoxic cytotoxin tirapazamine ( TPZ ) combined with cisplatin ( CIS ) and radiation led to this phase III trial . PATIENTS AND METHODS Patients with previously untreated stage III or IV ( excluding T1 - 2N1 and M1 ) squamous cell carcinoma of the oral cavity , oropharynx , hypopharynx , or larynx were r and omly assigned to receive definitive radiotherapy ( 70 Gy in 7 weeks ) concurrently with either CIS ( 100 mg/m(2 ) ) on day 1 of weeks 1 , 4 , and 7 or CIS ( 75 mg/m(2 ) ) plus TPZ ( 290 mg/m(2)/d ) on day 1 of weeks 1 , 4 , and 7 and TPZ alone ( 160 mg/m(2)/d ) on days 1 , 3 , and 5 of weeks 2 and 3 ( TPZ/CIS ) . The primary end point was overall survival ( OS ) . The planned sample size was 850 , estimated to result in 334 deaths , which would provide 90 % power to detect a difference in 2-year survival rates of 60 % v 70 % for CIS versus TPZ/CIS , respectively ( hazard ratio = 0.69 ) . RESULTS Eight hundred sixty-one patients were accrued from 89 sites in 16 countries . In an intent-to-treat analysis , the 2-year OS rates were 65.7 % for CIS and 66.2 % for TPZ/CIS ( TPZ/CIS -- CIS : 95 % CI , -5.9 % to 6.9 % ) . There were no significant differences in failure-free survival , time to locoregional failure , or quality of life as measured by Functional Assessment of Cancer Therapy-Head and Neck . CONCLUSIONS We found no evidence that the addition of TPZ to chemoradiotherapy , in patients with advanced head and neck cancer not selected for the presence of hypoxia , improves OS In a r and omized phase II trial in Germany , we investigated the clinical and economic impact of amifostine protection against the hematological and oral toxicities of carboplatin administered concurrently with st and ard fractions of radiotherapy . 28 patients with squamous cell carcinomas of the head and neck received adjunctive or primary radiotherapy ( 5 days per week with daily fractions of 2 Gy , up to a total dose of 60 Gy ) in conjunction with carboplatin ( 70 mg/m2 ) on days 1–5 and days 21–26 . All patients received radiation encompassing at least 75 % of the major salivary gl and s. Patients were r and omized to receive radiation and carboplatin ( RCT ) alone or RCT preceded by rapid infusion of amifostine ( 500 mg ) on days carboplatin was administered . The 14 patients who received amifostine , in comparison to 14 patients in the control arm , had significantly fewer episodes of grade 3 or 4 thrombocytopenia ( p = 0.001 ) , mucositis ( p = 0.001 ) , and xerostomia ( p = 0.001 ) . The patients receiving amifostine accrued significantly lower supportive care costs for re sources related to infection ( $ 241 vs. $ 1,275 , p < 0.01 ) , red blood cell and platelet support ( $ 286 vs. $ 1,276 p = 0.06 ) alimentation ( $ 343 vs. $ 894 , p = . 01 ) , and hospitalization ( $ 286 vs. $ 2,429 , p < 0.01 ) . Overall , including the costs of amifostine , mean per patient supportive care costs were $ 4,401 for the amifostine group and $ 5,873 ( p = .02 ) for the control group . Our results from a r and omized phase II trial indicate that selective cytoprotection with amifostine potentially offers clinical and economic benefits in patients with advanced head and neck cancer receiving radiochemotherapy . Additional economic studies alongside r and omized phase III trials and from other countries are needed The authors discuss the results of 3 studies of their group reflecting the possible role of amifostine in simultaneous radiochemotherapy ( RCT ) of advanced head and neck cancer . In a controlled phase II trial ( 1995 through 1996 ) , 39 patients were included in this pilot investigation . A control group ( n = 14 ) received simultaneous RCT of the head and neck region with an irradiation dose of 60 Gy and 2 cycles of carboplatin ( 700 mg/m(2 ) cumulative dose ) . Twenty-five patients received the same basic therapy and an additional 500-mg dose of amifostine before each chemotherapy . Amifostine was administered less than 45 minutes before the end of radiotherapy . The authors observed a dramatic reduction of typical radiotherapy-associated toxicities ( mucositis , xerostomia , loss of taste , dysphagia ) . The hematologic side effects ( leukocytopenia , anemia , thrombocytopenia ) also were decreased significantly . The overall survival rate and locoregional control of both groups were comparable after 12 months . In a controlled intensification trial ( 1997 through 1999 ) , the authors included 76 consecutive patients ( 69 men , 7 women ) with pharyngeal cancer ( oropharynx , n = 33 ; hypopharynx , n = 43 ) . The tumors were characterized as unresectable and locally advanced without distant metastasis . All patients received a conventional radiotherapy ( 2-Gy single dose , daily fractionation ) up to doses of 60 Gy and an additional 10 Gy as a boost in the tumor-infiltrated region . A dose of carboplatin , 70 mg/m(2 ) , was given to a group of 45 patients on days 1 through 5 and 29 through 33 of radiotherapy ( RCT arm ) . The result ing cumulative dose was 700 mg/m(2 ) . A group of 31 patients ( RCT intens arm ) received the same dose of carboplatin on days 1 through 5 , 22 through 26 , and 43 through 47 or 1 through 5 , 15 through 19 , 29 through 33 , and 43 through 47 of radiotherapy ( cumulative dose 1.05 to 1.40 mg/m(2 ) ) . All patients received 500 mg of amifostine before each carboplatin administration . If the tumor volume was less than 20 cm(3 ) , we observed an increased 1-year overall survival rate ( 91 % v 71 % ) and time to progression ( 17 months v 10 months ) . If the tumor volume was greater than 20 cm(3 ) , we observed comparable treatment results in both groups ( 1-year survival rate , 60 % v 61 % ; time to progression , 13 months v 12 months ) . In a long-term follow-up investigation ( 1999 through 2000 ) , 531 patients ( 89 women , 442 men ) were analyzed according to their toxicities during regular follow-up investigations at our outpatient facility . All patients were treated by surgery or radio(chemo)therapy because of an advanced head and neck cancer . A total of 218 of 531 patients received the antineoplastic therapy without cytoprotection . An additional 313 patients received their RCT combined with amifostine administration before administration of the radiosensitizer . A significant influence of cytoprotection was registered in the following toxicities : xerostomia , fibrosis , loss of taste , and dysphagia . No impact was seen on the development of interstitial lymph edema and esophageal stenosis . Amifostine could be integrated in simultaneous radiochemotherapy of advanced head and neck cancer patients . The authors favor the administration of amifostine before chemotherapeutics alone . Selective cytoprotection could decrease the main acute toxicities ( mucositis , xerostomia , dysphagia ) as well as late side effects ( xerostomia , loss of taste , fibrosis ) of this form of combined treatment . The enhanced therapeutic index may be changed into a prognostic benefit for selected patients with unresectable tumors , if the volume is smaller than 20 cm(3 ) A prospect i ve r and omized study is comparing intravenous ( IV ; arm A ) versus subcutaneous ( SC ; arm B ) administration of amifostine in patients receiving radiotherapy for head and neck cancer . Main eligibility criteria were newly diagnosed squamous cell head and neck cancer , inclusion of at least 75 % of both parotid gl and s within radiation fields that would receive at least 40 Gy , and no evidence of distant metastasis . Prophylactic use of pilocarpine and concomitant chemotherapy were prohibited . Intravenous administration of amifostine is 200 mg/m2/d in a short 3-minute infusion 15 to 30 minutes before each fraction of radiotherapy . Subcutaneous administration is 500 mg/d in two , slow 1.25-mL injections at two different sites 20 to 60 minutes before each radiotherapy fraction . Antiemetic treatment and blood pressure monitoring are required in both arms . As of April 25 , 2002 , 111 of the 292 required patients were included . Data are available for the first 54 patients . Acute toxicity included nausea/vomiting ( 12 % for arm A ; 13 % for arm B ) , hypotension ( 6 % in arm A ; 0 % in arm B ) , skin rash ( 15 % in arm A ; 16 % in arm B ) , and asthenia ( 4 % in arm A ; 0 % in arm B ) . Compliance with amifostine administration was 70 % in arm A ( IV ) and 80 % in arm B ( SC ) . The rate of acute xerostomia ( > or = grade 2 ) was 23 % in arm A and 19 % in arm B. These preliminary results indicate that tolerance is better with SC than IV administration , particularly because of the absence of hypotension . The absence of hypotension with SC administration facilitates patient monitoring and management in radiotherapy departments . More patients and data are required to assess the long-term efficacy of SC administration on acute and late xerostomia PURPOSE Salivary gl and impairment is a well-recognized side effect following high-dose radioiodine treatment ( HD-RIT ) . Since differentiated thyroid cancer has a good prognosis , reduction of long-term side effects is important . Therefore , the effect of amifostine was studied in HD-RIT . PATIENTS AND METHODS Parenchymal function was assessed by quantitative salivary gl and scintigraphy performed prospect ively in 50 patients with differentiated thyroid cancer before and 3 months after HD-RIT with either 3 GBq iodine ( (131)I ) ( n=21 ) or 6 GBq (131)I ( n=29 ) in a double-blind , placebo-controlled study . Twenty-five patients were treated with 500 mg/m2 amifostine intravenously before HD-RIT and 25 patients served as controls , who received physiologic saline solution . Xerostomia was grade d according to World Health Organization ( WHO ) criteria . RESULTS Before HD-RIT in 25 control patients , uptake of technetium-99 m (99mTc)-pertechnetate was 0.45%+/-0.16 % and 0.42%+/-0.16 % in parotid and subm and ibular gl and s , respectively . Three months after HD-RIT , parenchymal function was significantly ( P < .001 ) reduced by 40.2%+/-14.1 % and 39.9%+/-15.3 % in parotid and subm and ibular gl and s , respectively . Nine control patients developed grade I and two grade II xerostomia . In 25 amifostine-treated patients , uptake of 99mTc-pertechnetate was 0.46%+/-0.16 % and 0.43%+/-0.17 % in parotid and subm and ibular gl and s , respectively . Three months after HD-RIT , parenchymal function of salivary gl and s was not significantly altered ( P=.691 ) and xerostomia did not occur in any of these patients . CONCLUSION Parenchymal damage in salivary gl and s caused by HD-RIT can significantly be reduced by amifostine , which may improve the quality of life of patients with differentiated thyroid cancer Background . Salivary gl and hypofunction commonly develops during radiation therapy to the head and neck region . This study evaluated whether the sialogogue pilocarpine given during radiation therapy may reduce the severity of xerostomia and salivary dysfunction OBJECTIVE The purpose of the present study was to investigate the influence of parasympathomimetic pilocarpine and anticholinergic biperiden on salivation , pH value , and calcium , phosphate , and bicarbonate concentrations in saliva in patients irradiated for malignant tumors of the head and neck region . STUDY DESIGN Sixty-nine patients were r and omly assigned into 3 groups . Group A consisted of patients receiving pilocarpine , group B of those who were receiving biperiden during radiotherapy and pilocarpine for 6 weeks after its completion , and group C comprised patients receiving neither of the mentioned drugs . The quantity of secreted unstimulated saliva , its pH value , as well as calcium , phosphate , and bicarbonate concentrations in saliva were measured before the beginning of radiotherapy , after 30 Gy of irradiation , at completed irradiation , and 3 , 6 , and 12 months after completion of radiotherapy . RESULTS Saliva secretion was found to be the least affected in the group of patients receiving biperiden throughout the course of radiotherapy . One year after completion of therapy , the quantity of secreted saliva could only be measured in the patients receiving biperiden during radiotherapy ; it amounted to 16 % of the average initial quantity of saliva secreted before the beginning of irradiation . In all 3 groups of patients , mean pH value decreased during radiotherapy and started to increase again after completion of irradiation . In group B the decrease in pH value after radiotherapy was statistically significantly smaller than that in group C ( P = .01 ) . During and after irradiation , calcium concentration was increased in all 3 groups of patients . Phosphate concentration decreased during radiotherapy in all 3 groups . In group B it started to increase again 3 months after completion of radiotherapy . Bicarbonate concentration showed a slight increase during radiotherapy and started to decrease again after completion of irradiation . CONCLUSION The results of our study indicate that the inhibition of saliva secretion during radiotherapy and its stimulation after completion of treatment can contribute not only to some preservation of the quantity of saliva but also to at least partial preservation of its quality in terms of pH value and calcium , phosphate , and bicarbonate concentrations The aim of this study was to determine the impact of bethanechol administration concomitant to radiotherapy ( RT ) on oral mucositis , c and idiasis and taste loss . We performed a secondary analysis of a previously conducted prospect i ve r and omized trial which evaluated the effect of bethanechol on salivary gl and dysfunction before , during , and after RT for head and neck cancer ( HNC ) , in comparison to artificial saliva . Mucositis , c and idiasis and taste loss were analyzed in 36 patients . Mucositis was scored using the World Health Organization ( WHO ) method ; c and idiasis was diagnosed by means of clinical examination , whereas taste loss was assessed by the patients ' subjective report of absence of taste . No significant differences were observed between groups in relation to frequency and severity of mucositis or frequency of c and idiasis and taste loss . In conclusion , bethanechol does not appear to reduce the incidence of mucositis , c and idiasis , and taste loss when administered during RT BACKGROUND This prospect i ve r and omized study was undertaken to assess the effectiveness of oral pilocarpine chloratum ( Salagen ) during and after radiotherapy . PATIENTS AND METHODS Between October 1999 and December 2003 , 66 patients received 60 Gy of irradiation to their head and neck cancer . Half of the patients received 5 mg oral pilocarpine 3 times a day from the beginning of radiotherapy over a period of 12 weeks . The control group received similar doses of pilocarpine only in the second 6 weeks following irradiation . Patient saliva secretion was recorded , and a visual analog scale measuring overall and daily xerostomia , difficulty in sleeping , speaking , eating and wearing dentures was employed . RESULTS Pilocarpine , given concomitantly with radiotherapy , statistically improved the salivary flow and induced better patient comfort by the end of radiotherapy . Patient comfort and symptoms related to xerostomia greatly decreased compared to patients receiving pilocarpine after irradiation in the second 6-week period of therapy . The patients ' quality of life , saliva production and symptoms related to xerostomia showed significant progress by the end of the 12 weeks . CONCLUSION The results suggest that stimulated salivary gl and s suffer less decrease in saliva production during radiotherapy . The stimulated saliva flow reduced the side-effects of irradiation 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 PURPOSE To determine the prophylactic properties of amifostine against acute and late toxicities from radiochemotherapy in patients with head- and -neck cancer . METHODS AND MATERIAL S Fifty patients were r and omized to receive conventional radiotherapy ( RT ) ( 2-Gy fractions , 5 days weekly , to a total of 60 - 74 Gy , depending on the tumor localization and TNM classification ) and carboplatin ( 90 mg/m(2 ) infusion once per week before RT ) . Amifostine ( 300 mg/m(2 ) ) was administered in the study group only 15 - 30 min before RT for 6 - 7.5 weeks . The primary study end point was the grading of acute and late nonhematologic toxicities ( mucositis , dysphagia , xerostomia ) induced by radiochemotherapy . Secondary end points included treatment duration , hematologic toxicity , and clinical outcome . RESULTS The treatment duration was significantly shorter in the amifostine-treated group ( p = 0.013 ) , because treatment interruptions were more frequent in the control group . Acute toxicities ( mucositis and dysphagia ) were less severe in the amifostine-treated group . By Week 3 , all in the control group experienced Grade 2 mucositis compared with only 9 % in the amifostine-treated group ( p < 0.0001 ) . By Week 5 , 52.2 % of the patients in the control group experienced Grade 4 mucositis compared with 4.5 % in the amifostine-treated group ( p = 0.0006 ) . Similar results were obtained for dysphagia . At 3 months of follow-up , only 27 % of patients in the study group experienced Grade 2 xerostomia compared with 73.9 % in the control group ( p = 0.0001 ) . Eighteen months after cessation of therapy , the proportion of patients with Grade 2 xerostomia was 4.5 % vs. 30.4 % for each respective treatment group ( p = 0.047 ) . Cytoprotection with amifostine did not affect treatment outcome , with 90.9 % complete responses in the amifostine-treated group compared with 78.3 % in the control group ( p = 0.414 ) . CONCLUSION Amifostine was effective in reducing mucositis and dysphagia result ing from radiochemotherapy in patients with head- and -neck cancer . Furthermore , amifostine reduced the severity of late xerostomia , a side effect of RT with long-lasting consequences . Amifostine treatment did not affect the clinical outcome 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 assessed the prophylactic bethanechol use to prevent salivary gl and dysfunction during radiotherapy . A total of 97 head and neck cancer patients were allocated into two groups : Bethanechol or Placebo . Bethanechol group presented significantly improve of salivary parameters . Bethanechol was effective in decreasing the salivary gl and damage PURPOSE To determine if head and neck ( H/N ) cancer patients receiving daily amifostine during radiation therapy ( RT ) experienced clinical benefit ( improvement in their ability to carry out normal functions with reduced discomfort ) compared to nonamifostine treated patients . METHODS AND MATERIAL S This was an open-label , multi-institutional r and omized trial in 303 H/N cancer patients treated with RT + amifostine . Clinical benefit was measured using an 8-item vali date d Patient Benefit Question naire ( PBQ ) during and up to 11 months after RT . RESULTS 301 patients completed one or more PBQ assessment s. Amifostine patients had significantly better PBQ scores ( p < 0.05 ) than controls . The improvement in PBQ scores was most significant during chronic xerostomia . CONCLUSIONS Amifostine use results in improved Patient Benefit Question naire ( PBQ ) scores , which is indicative of improved oral toxicity related outcomes and improved clinical benefit . Less oral toxicity should lead to preservation of late dental and oral health , and improvements in activities such as diet , nutrition , and sleep PURPOSE Oral mucositis ( OM ) is a debilitating toxicity of chemoradiotherapy for head and neck cancer ( HNC ) . This r and omized , placebo-controlled , double-blind study evaluated the efficacy and safety of palifermin to reduce OM associated with definitive chemoradiotherapy for locally advanced HNC . PATIENTS AND METHODS Patients receiving conventionally fractionated radiotherapy ( 2.0 Gy/d , 5 days/wk to 70 Gy ) with cisplatin ( 100 mg/m(2 ) on days 1 , 22 , and 43 ) received palifermin ( 180 μg/kg ) or placebo before starting chemoradiotherapy and then once weekly for 7 weeks . The primary end point was the incidence of severe , observable , and functional OM ( WHO grade 3 to 4 ) . RESULTS The palifermin ( n = 94 ) and placebo ( n = 94 ) arms were well balanced . The incidence of severe OM was significantly lower for palifermin than for placebo ( 54 % v 69 % ; P = .041 ) . In the palifermin arm , median time to severe OM was delayed ( 47 v 35 days ) , median duration of severe OM was shortened ( 5 v 26 days ) , and the incidence of xerostomia grade ≥ 2 was lower ( 67 % v 80 % ) , favoring palifermin ; however , the differences were not significant after multiplicity adjustment . Opioid analgesic use , average mouth and throat soreness scores , and chemoradiotherapy compliance were not significantly different between treatment arms . Adverse events were similar between arms ( 98 % , palifermin ; 93 % , placebo ) . The most common study drug-related adverse events were rash , flushing , and dysgeusia . After median follow-up of 25.8 months , overall survival and progression-free survival were similar between treatment arms . CONCLUSION Although palifermin reduced severe functional OM , its role in the management of locally advanced HNC during chemoradiotherapy remains to be eluci date BACKGROUND The National Cancer Institute of Canada Clinical Trials Group undertook a multicenter , r and omized , double-blind controlled trial of an oral antimicrobial versus placebo to prevent and treat mucositis . We present the quality of life ( QOL ) analysis for this trial . METHODS One hundred thirty-eight patients were r and omly assigned . QOL data were collected every 2 weeks before , during , and after radiotherapy . The European Organization for Research and Treatment of Cancer Quality of Life question naire ( EORTC QLQ-C30 ) and a Trial Specific Checklist ( TSC ) were used . RESULTS The antimicrobial lozenge did not impact QOL . The principal acute side effect of radiotherapy is oral pain , affecting more than 90 % of patients . Role function is impacted during treatment , and patients experience fatigue . Appetite was reported to markedly increase during radiotherapy . There was a dramatic and persistent increase in dry mouth . CONCLUSIONS This study highlights the benefits of combining the EORTC QLQ-30 with an " oral " TSC in a r and omized controlled trial and provides valuable baseline data for their use with an objective mucositis scoring system PURPOSE Amifostine ( WR-2721 ) is an important cytoprotective agent . Although intravenous administration is the st and ard route , pharmacokinetic studies have shown acceptable plasma levels of the active metabolite of amifostine ( WR-1605 ) after subcutaneous administration . The subcutaneous route , due to its simplicity , presents multiple advantages over the intravenous route when amifostine is used during fractionated radiotherapy . PATIENTS AND METHODS Sixty patients with thoracic , 40 with head and neck , and 40 with pelvic tumors who were undergoing radical radiotherapy were enrolled onto a r and omized phase II trial to assess the feasibility , tolerance , and cytoprotective efficacy of amifostine administered subcutaneously . A flat dose of amifostine 500 mg , diluted in 2.5 mL of normal saline , was injected subcutaneously 20 minutes before each radiotherapy fraction . RESULTS The subcutaneous amifostine regimen was well tolerated by 85 % of patients . In approximately 5 % of patients , amifostine therapy was interrupted due to cumulative asthenia , and in 10 % , due to a fever/rash reaction . Hypotension was never noted , whereas nausea was frequent . A significant reduction of pharyngeal , esophageal , and rectal mucositis was noted in the amifostine arm ( P < .04 ) . The delays in radiotherapy because of grade 3 mucositis were significantly longer in the group of patients treated with radiotherapy alone ( P < .04 ) . Amifostine significantly reduced the incidence of acute perineal skin and bladder toxicity ( P < .0006 ) . CONCLUSION Subcutaneous administration of amifostine is well tolerated , effectively reduces radiotherapy 's early toxicity , and prevents delays in radiotherapy . The subcutaneous route is much simpler and saves time compared with the intravenous route of administration and can be safely and effectively applied in the daily , busy radiotherapy practice Objectives Salivary gl and impairment after high-dose radioiodine ( 131I ) treatment is well recognized . The aim of this study was to determine the protective effect of vitamin E on radiation-induced salivary gl and dysfunction in patients undergoing 131I treatment for differentiated thyroid cancer . Methods Thirty-six patients with differentiated thyroid carcinoma were enrolled in this study . They were r and omly divided into two groups before postsurgical ablation therapy with 3700–5550 MBq 131I : the control group , comprising 17 patients , and the vitamin E group , comprising 19 patients . All 19 patients in the experimental group received vitamin E at a dose of 800 IU/day for a duration of 1 week before to 4 weeks after 131I therapy and the 17 patients in the control group received a placebo for the same duration . Salivary gl and function was assessed using salivary gl and scintigraphy with intravenous injection of 370 MBq 99mTc-pertechnetate in two phases , one immediately before and the other 6 months after 131I ablative therapy . First-minute uptake ratio , maximum uptake ratio , maximum secretion percentage , and excretion fraction ( EF ) of each salivary gl and were measured and compared between the study phases for the two groups . Results There was no significant difference between preablative and postablative salivary scintigraphic indices in the experimental vitamin E group , whereas maximum secretion percentage and EF of the right subm and ibular gl and and EF of the left parotid gl and were significantly decreased in the control group . There was also a higher significant decrease in the EF of the left parotid gl and in the control group compared with the vitamin E group . Conclusion Vitamin E consumption may be associated with a significant protective effect against radiation-induced dysfunction in salivary gl and s following single-dose 131I therapy in patients with differentiated thyroid cancer PURPOSE Pilocarpine hydrochloride administered during head and neck irradiation was evaluated for its ability to relieve xerostomia and its adverse effects . MATERIAL AND METHOD A total of 60 head and neck cancer patients were enrolled in a r and omized , double blind , placebo-controlled trial . Each patient had both parotid gl and s treated with a radiation dose of at least 50 Gy . Patients received jelly containing pilocarpine or placebo 5.0 mg ( 1 cc . ) tid at meal times during radiation . Pilocarpine was administered beginning on the first day of radiation and continued until radiation was completed . Patients were evaluated for symptomatic relief by responding to question naires using a Visual Analogue Scale ( VAS ) . Question naires measured relief of oral dryness , oral discomfort , difficulty in chewing and swallowing , speaking , and sleeping . Evaluation was conducted preradiation as a baseline , weekly during radiation and monthly until 6 months after radiation was completed . RESULTS The baseline characteristics , disease and radiation technique including field arrangement and total dose , were not significantly different between the two groups . There was no statistically significant subjective difference in xerostomia , including oral dryness , oral discomfort , inability to chew and swallow , speak and sleep , during and postradiation between the two groups . The adverse effects were non-specific symptoms such as nausea , vomitting , dizziness , urinary frequency , palpitation , sweating and tearing . The adverse effects during radiation and postradiation were not significantly different between the two groups . CONCLUSION It was concluded that pilocarpine hydrochloride administered during head and neck irradiation produced subjectively insignificant benefit in relieving xerostomia with acceptable side effects 5568 Background : To evaluate the use of amifostine prophylactically in radiochemotherapy induced acute mucositis and xerostomia in patients with head and neck carcinoma . METHODS One hundred and seventy patients of head and neck carcinoma were r and omized to receive radiochemotherapy with or without amifostine . All the patients were suffering from locally advanced malignancy . A total of 66 - 72 gy was delivered conventionally with 40 mg/m2 weekly cisplatin . Amifostine 250 mg was infused 10 min . prior to RT for four days a week to the patients in study group . Parotid scintigraphy was done before starting the treatment and at 3,6,12 and 24 months after completion of treatment . Mucositis and xerostomia were evaluated using RTOG criteria . Disease control was assessed at each follow up for two years . RESULTS The control group experienced an earlier onset of mucositis than the study group . By the end of 2nd week 74/85 control patients experienced grade II mucositis while similar toxicity was observed in 64/85 in the study group ( p=0.05 ) . All the patients had grade 3 or 4 mucositis in the control group whereas such severity was seen in 75/85 patients in the control group ( p<0.001 ) . The post radiation recovery of mucositis was faster in study group . By the end of 5 weeks of completion of radiation therapy 73/85 and 64/85 had no mucositis in the study and control group respectively ( p<0.001 ) . At 3 months follow up xerostomia grade 2 or more was found in 42/85 in control group compared with 32/85 in study group ( p=0.017 ) . By the end of 12 months of treatment in study group 37/85 experienced grade 1 or no xerostomia as compared to 59/85 in the control groups ( p=0.002 ) . However , treatment result remained unaffected in the amifostine groups . There were 49/85 disease free patients in control group compared with 52/85 in the study group ( p=0.987 ) . CONCLUSIONS Amifostine was effective in reducing the severity and it delayed the onset of mucositis , a side effect with concurrent radiochemotherapy in head and neck carcinoma . It also decreased the severity of delayed xerostomia . Amifostine does not alter the response or the survival . No significant financial relationships to disclose PURPOSE To compare compliance with and efficacy of intravenous ( IV ) and subcutaneous ( SC ) amifostine for the treatment of patients undergoing radiotherapy for head and neck cancer . PATIENTS AND METHODS Patients with newly diagnosed squamous cell carcinoma of the head and neck , who were eligible for radiotherapy and who were not receiving concurrent chemotherapy , were r and omly assigned to receive either IV amifostine ( 200 mg/m(2 ) daily for 3 minutes , 15 to 30 minutes before irradiation ) or SC amifostine ( 500 mg ; two sites ; 20 to 60 minutes before irradiation ) . The primary end point was late xerostomia at 1 year as indicated by unstimulated and stimulated salivary flow rates , a patient benefit question naire score , and Radiation Therapy Oncology Group ( RTOG ) late toxicity grade . RESULTS Results for IV ( n = 143 ) versus SC ( n = 148 ) administration were as follows . There was no significant difference in compliance ( 69 % for IV v 71 % for SC ) in patients receiving a full dose of amifostine . Reasons for dose reduction were acute toxicity ( 25 % for IV v 27 % for SC ; P = .51 ) and logistics ( 18 % for IV v 9 % for SC administration ; P = .09 ) . Acute toxicity differed significantly in terms of grade 1 to 2 hypotension ( 19 % for IV v 8 % for SC ; P = .01 ) , grade 1 to 2 skin rash ( 9 % for IV v 21 % for SC ; P = .01 ) , and local pain ( 0 % for IV v 8 % for SC ; P = .003 ) . The incidence of grade 2 or greater xerostomia was significantly higher for patients who received amifostine via SC administration ( 37 % for IV v 62 % for SC ; P = .005 ) in the 127 patients ( n = 67 , IV ; n = 60 , SC ) evaluable at 1 year but not at 2 or 3 years ( 36 % for IV v 51 % for SC administration ; P = .19 ; 32 % for IV v 41 % for SC ; P = .63 ) . A generalized linear mixed-model analysis of all data revealed no significant difference in patient self- assessment of salivary function ( P = .25 ) , unstimulated or stimulated salivary flow rates ( P = .054 and .82 , respectively ) , or grade 2 or greater xerostomia ( P = .23 ) . CONCLUSION SC amifostine administration was not significantly superior to IV amifostine administration in terms of patient compliance or efficacy Abstract A r and omized study was conducted to evaluate the protective activity of amifostine ( A ) against the dose-limiting toxicities of radiochemotherapy ( RCT ) . Patients with head and neck cancer received radiotherapy ( 2 Gy/day 5 days a week up to 60 Gy ) with carboplatin 70 mg/m2 on days 1–5 and 21–25 inclusive . Patients either received RCT alone ( n=14 ) or RCT + A at a dose of 500 mg prior to treatment with carboplatin ( n=25 ) . There was a significant reduction in the incidence of grade 3/4 mucositis ( P<0.0001 ) , acute grade 2 xerostomia ( P<0.0001 ) and grade 3/4 thrombocytopenia ( P=0.012 ) in these patients who received A. The incidence of grade 2 late xerostomia at 12 months is 16.7 % and the incidence of loss of taste is 0 % in patients treated with A , as opposed to 54.5 % and 63.6 % in patients who received RCT alone . There were 18 ( 72 % ) complete responses ( CR ) and 6 ( 24 % ) partial responses ( PR ) in patients who received A , compared with 6 ( 43 % ) CR and 6 PR ( 43 % ) in patients treated with RCT alone . The disease-free survival at 12 months is 85.7 % in the RCT + A arm and 78.6 % in the RCT alone arm . The use of amifostine reduces the incidence and severity of acute and late toxicities associated with RCT whilst preserving antitumour activity To evaluate the ability of granulocyte-stimulating factor to decrease mucositis during postoperative radiotherapy for stage II – IV squamous head and neck cancer in a r and omized , double-blind , placebo-controlled trial . METHODS After undergoing complete resection , patients were r and omized to receive granulocyte-colony stimulating factor or placebo by daily subcutaneous injection during radiotherapy ( 63 Gy , 1.8 Gy/day ) . Patients undergoing prior radiotherapy or chemotherapy were excluded from the study . The primary outcome was the need for percutaneous endoscopic gas-trostomy placement . Severity of mucositis was a secondary outcome . RESULTS Forty-one patients were enrolled ( 132 planned ) . The study closed after slow accrual . Patient characteristics were as follows ( granulocyte-colony stimulating factor vs placebo ) : median age , 59 versus 54 years ; pT4 , 16 % versus 23 % ; pN2/3 , 68 % versus 59 % ; stage IV , 79 % versus 68 % . Forty patients were evaluable for planned outcomes . Patients in the granulocyte-colony stimulating factor arm showed trends toward lower rates of percutaneous endoscopic gastrostomy placement ( 0 % vs 14 % , P= 0.2 ) and severity of mucositis ( P = 0.13 ) , and had shorter mean radiotherapy duration ( 48.4 ± 4.32 days vs 51.6 ± 1.84 days , P = 0.005 ) . Overall survival was significantly greater in the granulocyte-colony stimulating factor arm ( hazard ratio , 0.37 ; P= 0.037 ) . DISCUSSION Granulocyte-colony stimulating factor during radiotherapy was feasible and led to significantly shorter radiotherapy duration and trends toward less percutaneous endoscopic gastrostomy placement and mucositis . The unanticipated improvement in survival outcomes warrants further hypothesis-driven investigation and validation Organ preservation in patients with head and neck cancer can be achieved using concomitant chemoradiation protocol s. Critical tissues can be spared using highly conformal radiation therapy techniques and /or radiation protectors . With three-dimensional conformal radiation therapy ( 3DCRT ) tight target definitions of the primary tumor and neck nodal levels are m and atory . In 2000 , a clinical trial for advanced-stage head and neck squamous cell carcinoma was initiated in Rotterdam , The Netherl and s. Patients are treated with paclitaxel administered concomitantly with 3DCRT and r and omized to receive subcutaneous ( SC ) amifostine or no amifostine . Those in the radioprotectant arm received amifostine 500 mg SC before each radiation therapy ( RT ) fraction . This article presents early findings on toxicity . Acute toxicity is evaluated according to Radiation Therapy Oncology Group criteria . Xerostomia was scored subjectively and by whole saliva measurements . Neck nodal levels were delineated in accordance with previously published computed tomography (CT)-based guidelines developed in Rotterdam . Forty-one patients are the subject of this report . In patients treated with amifostine , mucositis and dysphagia took longer to resolve than with conventional RT schedules . No difference in objective and subjective evaluation of xerostomia was seen between treatment arms . So far in this ongoing study , no advantage of SC amifostine has been detected . This might be because of the toxicity of the concomitant treatment itself , the dose of amifostine , the route of administration , or the insufficient sparing of critical structures by 3DCRT . These early findings and the ongoing development of better tissue-sparing techniques with more accurate CT-based target delineation protocol s and intensity-modulated radiation therapy ( IMRT ) are discussed 5536 Background : Amifostine ( A , Ethyol ) reduced radiotherapy (RT)-induced xerostomia without diminishing tumor control at 12 months in a prospect i ve , r and omized trial of patients receiving head and neck RT ( Brizel et al , J Clin Oncol 2000;18:3339 - 45 ) . The FDA approved A for protection against xerostomia based on that trial . We now evaluate follow-up data 12 - 24 months after RT to further assess both long-term radioprotective effects of A and tumor control . METHODS Adults with head and neck cancer who underwent once-daily fractionated RT for 5 - 7 weeks ( total dose 50 - 70 Gy ) received open-label intravenous A 200 mg/m2 15 - 30 minutes before each RT fraction ( n=150 ) or no treatment before RT ( control ; C ; n=153 ) . Xerostomia , disease progression , and survival were assessed at 12 , 18 , and 24 months . RESULTS Minimum followup for all survivors is now 2 years . A continued to result in diminished xerostomia during the second year of follow-up ( Table ) , based on incidence of RTOG Grade ≥2 xerostomia and proportion of patients with meaningful ( > 0.1 g ) unstimulated saliva production . Patients reported less mouth dryness ( P<.001 ) and greater mean benefit overall ( P=.053 ) with A vs C on a Patient Benefit Question naire . Locoregional tumor control , progression-free survival , and overall survival were similar between groups ( Table ) . CONCLUSIONS Amifostine provides radioprotection from xerostomia that continues for at least 2 years without evidence of change in tumor control . [ Figure : see text ] [ Table : see text ] OBJECTIVE To observe the therapeutic effect of shenqi fanghou recipe ( SFR ) in preventing and treating radiation injury in patients with head and neck tumor . METHODS One hundred and forty patients with head and neck tumor , including nasopharyngeal carcinoma , carcinoma of tonsil or tongue , were r and omly divided into 2 groups , 70 patients in the observed group were given modified SFR as adjuvant to radiotherapy , while 70 patients in the control group were treated with radiotherapy alone . The radiation reactions during radiotherapy and the condition of late stage radiation injury radiotherapy in patients in the 2 groups were observed . RESULTS The degree of oropharyngeal mucosa reaction , dryness in mouth and radiation dermatitis in cervical region in the observed group was milder than those in the control group , and the radiation injury induced late stage sequelae , such as the degree of mouth-opening was better and the cervical muscular sclerosis was better in the observed group than in the control group , showing significant difference ( P < 0.01 ) . CONCLUSION SFR has definite effect in preventing and treating radiation reaction and late stage radiation injury in patients with head and neck tumor PURPOSE To investigate the effect of concomitant administration of pilocarpine during radiotherapy for head- and -neck squamous cell carcinoma ( HNSCC ) on postradiotherapy xerostomia . METHODS AND MATERIAL S A prospect i ve , double blind , placebo-controlled r and omized trial including 170 patients with HNSCC was executed to study the protective effect of pilocarpine on radiotherapy-induced parotid gl and dysfunction . The primary objective endpoint was parotid flow rate complication probability ( PFCP ) scored 6 weeks , 6 months , and 12 months after radiotherapy . Secondary endpoints included Late Effects of Normal Tissue/Somatic Objective Management Analytic scale ( LENT SOMA ) and patient-rated xerostomia scores . For all parotid gl and s , dose-volume histograms were assessed because the dose distribution in the parotid gl and s is considered the most important prognostic factor with regard to radiation-induced salivary dysfunction . RESULTS Although no significant differences in PFCP were found for the two treatments arms , a significant ( p = 0.03 ) reduced loss of parotid flow 1 year after radiotherapy was observed in those patients who received pilocarpine and a mean parotid dose above 40 Gy . The LENT SOMA and patient-rated xerostomia scores showed similar trends toward less dryness-related complaints for the pilocarpine group . CONCLUSIONS Concomitant administration of pilocarpine during radiotherapy did not improve the PFCP or LENT SOMA and patient-rated xerostomia scores . In a subgroup of patients with a mean dose above 40 Gy , pilocarpine administration result ed in sparing of parotid gl and function . Therefore , pilocarpine could be provided to patients in whom sufficient sparing of the parotid is not achievable e20698 Background : The substitution of selenium effects in activation of the selenium dependent enzyme glutathione peroxidase which is important for scavenging free radicals . Until today only limited data are available about the clinical impact of selenium regarding the toxicities due to free radical producing therapies , e.g. irradiation or chemotherapy . METHODS 39 patients ( 8 female , 31 male ) with advanced head neck cancer were included to a r and omized phase II study . All patients had shown a reduced concentration of selenium in the blood and serum ( main inclusion criterium ) . The mean age was 63.52 ± 9.31 years . Tumour localizations : oral cancer 15 patients , oropharynx 19 patients , hypopharynx 5 patients , CUP 1 patient . Group A ( n=22 ) received 500 μg sodium selenite at the days of radiotherapy and 300 μg sodium selenite at holidays or weekend . Group B ( 17 ) was irradiated without any selenium substitution . Both groups were well balanced according age , gender , localization and stage of the tumour . We evaluated the RTOG grade of radiation-associated toxicities once per week . Following statistical methods were used : Mantel-Haenssel-χ2-test , Fisher 's exact Test . SPSS . RESULTS We observed the following serious toxicities ( group A versus group B ) : dysphagia 22.7 % vs. 35.3 % , loss of taste 22.7 % vs. 47.1 % , dry mouth 22.7 % vs. 23.5 % , and stomatitis 36.4 % vs. 23.5 % . A statistical trend ( Fisher 's exact test ) is only seen in the area of loss of taste ( p=0.172 ) . The analysis per week had only shown a significant reduction of dysphagia in the selenium group at the last week of irradiation ( p=0.04 ) . CONCLUSIONS The small r and omized trial has shown limited effects of selenium in the prevention of ageusia ( loss of taste ) and dysphagia due to radiotherapy because of head and neck cancer . A clinical relevant radioprotection was not observed . [ Table : see text ] BACKGROUND The principle of cytoprotection became a new supportive strategy in oncology during the last decade . Two principal ways of cytoprotection are well known in practice : the addition of external free thiols ( for example amifostine ) or the activation of internal detoxification-pathways ( for example the activation of glutathione peroxidase ) by administration of additional selenium . OWN EXPERIENCES We report about our experiences in both fields : At first we could show the significant possibilities of cytoprotection to reduce the acute hematological and non hematological toxicities of a simultaneous radiochemotherapy ( 2 cycles Carboplatin , 2 Gy single dose , 60 Gy total dose ) of head and neck cancer patients . After 1 year the survival of amifostine-protected patients was better compared to the control , the rate of severe late complications ( xerostomia Grade 3/4 ) was decreased from 57 % to 14 % . At second we report about the usage of selenium in the treatment of paravasats ( 10 patients ) and interstitial lymph edema ( 20 patients ) . In the acute intervention group 9/10 patients resolved from the paravasats without any necrosis . In the late intervention group 12/20 patients showed reduced edema . Nine of 15 patients with a supraglottic edema and subsequent dyspnoea resolved under treatment without any tracheostomy . CONCLUSION On the base of these data we have planned a phase-I/II study to investigate the chances of both cytoprotectants alone and in combination in order to get the most favorable supportive regimen for our basic type of radiochemotherapy OBJECTIVE To assess the effects of an antiseptic , non-alcohol based mouth-rinse containing chlorhexidine and cetylpyridinium chloride , in preventing the oral complications associated to radiation therapy in head- and -neck cancer patients . STUDY DESIGN This was a parallel , double blind , prospect i ve , r and omized clinical trial . Cancer patients were r and omly assigned to one of the two treatments ( test mouth-rinse or a placebo ) . Three visits were scheduled ( baseline , 14 and 28 days ) . Different outcome variables were evaluated : mucositis , plaque and gingival indices , stimulated saliva and salivary pH. RESULTS 70 patients were screened and 36 were included . The presence and the degree of mucositis significantly increased in both groups and no significant differences were detected between groups , although the median increase in the placebo group ( 1.81 ) at 2 weeks was higher than in the test group ( 1.20 ) . CONCLUSIONS Within the limitations of the small sample size , this study suggests that the use of the tested mouth-rinse may lead to some improvements in clinical parameters in patients irradiated for head- and -neck cancer Since differentiated thyroid cancer has an excellent prognosis , reduction of long-term side effects of high-dose radioiodine treatment ( HD-RIT ) , i.e. salivary gl and impairment is important . Thus , radioprotective effects of amifostine were studied . Salivary gl and function was quantified by scintigraphy both in rabbits and patients . Fifteen rabbits were studied prior to and up to 6 months after HD-RIT applying 2 GBq 131I . Ten animals received 200 mg/kg amifostine prior to HD-RIT , and five served as controls . Animals were examined histopathologically . Fifty patients with differentiated thyroid cancer were evaluated prospect ively prior to and 3 months after HD-RIT with either 3 or 6 GBq 131I in a double-blind , placebo-controlled study . Twenty-five patients were treated with 500 mg/m2 amifostine intravenously prior to HD-RIT , and 25 patients receiving physiological saline solution served as controls . Complete ablation of the thyroid was achieved in all rabbits four weeks after HD-RIT . In control rabbits 6 months after HD-RIT parenchymal function was reduced significantly ( p < 0.0001 ) by 75.3 + /- 5.3 % and 53.6 + /- 17.4 % in parotid and subm and ibular gl and s , respectively . In contrast , in amifostine-treated rabbits parenchymal function was not significantly reduced . Histopathologically , marked lipomatosis was observed in control animals but was negligible in amifostine-treated animals . In control patients , salivary gl and function was significantly ( p < 0.001 ) reduced by 40.2 + /- 14.1 % and 39.9 + /- 15.3 % in parotid and subm and ibular gl and s , respectively , three months after HD-RIT , and 11 patients developed xerostomia . In 25 amifostine-treated patients , salivary gl and function was not significantly reduced ( p = 0.691 ) , and xerostomia did not occur . Thus , parenchymal damage in salivary gl and s induced by high-dose radioiodine therapy can be reduced significantly by amifostine . This may improve quality of life of patients with differentiated thyroid cancer 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 PURPOSE To test the hypothesis that the use of oral pilocarpine during and after radiotherapy ( RT ) for head- and -neck cancer would reduce the symptoms of post-RT xerostomia . METHODS AND MATERIAL S One hundred thirty patients were r and omized in a double-blind method to receive either pilocarpine ( 5-mg tablets ) or placebo three times daily starting on Day 1 of RT and continuing for 1 month after treatment . The eligibility criteria included a planned dose of > 50 Gy as radical or postoperative RT for head- and -neck cancer , with at least 50 % of both parotid gl and s included in the treatment fields . The primary outcome measure was the severity of xerostomia as assessed by a patient-completed linear analog scale 3 months after RT . Secondary outcome measures included quality of life during therapy ( as assessed by the McMaster University Head- and -Neck Question naire ) and severity of mucositis during RT ( as assessed using Radiation Therapy Oncology Group scales ) . RESULTS No difference was observed between the pilocarpine-treated patients and the placebo group in the severity of xerostomia score as assessed by linear analog scale at baseline and 1 , 3 , and 6 months after treatment ( repeated measures analysis , p = 0.92 ) . No difference was apparent in the severity of mucositis during RT ; 56.3 % of patients receiving pilocarpine had Grade III/IV mucositis compared with 50.8 % treated with placebo . No difference in quality of life was noted between the treatment groups during or after RT . The question naire score at 3 months after RT was 5.0 ( SD 1.0 ) . in the pilocarpine group and 4.9 ( SD 0.9 ) in the placebo group . CONCLUSION We were unable to detect a beneficial effect of pilocarpine on RT-induced xerostomia when administered during RT for head- and -neck cancer OBJECTIVE To observe the effect of Chinese herbal medicine on the salivary gl and s of patients with head and neck cancer during radiotherapy ( RT ) . METHODS Fifty cases with head and neck cancer were r and omly divided into observation group treated with RT plus Chinese herbal medicine and control group treated with RT alone . The level of mouth dryness , the flow and secretion speed of salivary amylase were measured before and during the RT . RESULTS The severity of mouth dryness increased and the flow and secretion speed of salivary amylase declined during RT . The mouth dryness curve of patients in Chinese medicine group was significantly more flattened than that of the control group after RT . The flow and the secretion speed of salivary amylase of the observation group were significantly higher than those of the control group at 20 Gy , 40 Gy and 60 Gy . CONCLUSION Chinese herbal medicine used in this study was effective to relieve the severity of mouth dryness and to protect the salivary gl and s of patients with head and neck cancer during RT PURPOSE The cytoprotective agent amifostine has been shown to reduce the radiation-induced acute and chronic xerostomia in head and neck cancer patients . The purpose of this study was to evaluate whether or not amifostine also reduces the incidence of dental caries associated with the radiation-induced xerostomia . METHODS AND MATERIAL S The dental status before and 1 year after radiotherapy was retrospectively compared in 35 unselected patients treated as part of the prospect i ve r and omized and multicenter open-label Phase III study ( WR-38 ) at the University Hospitals of Heidelberg , Freiburg , and Erlangen . The WR-38 study compared radiotherapy in head and neck cancer with and without concomitant administration of amifostine . RESULTS Patient and treatment characteristics ( particularly the radiation dose and percentage of parotids included in the treatment volume ) were equally distributed between the patients who received ( n = 17 ) or did not receive ( n = 18 ) amifostine . Fifteen patients of the amifostine group showed no deterioration of the dental status 1 year after radiotherapy as compared to 7 patients who did not receive the cytoprotector ( p = 0 . 015 , two-tailed Fisher exact test ) . CONCLUSION Our data suggest a protective effect of amifostine on the dental health after radiotherapy of the head and neck . The dental status should be used as a primary endpoint in future studies on amifostine AIM To assess the utility of salivary gl and scintigraphy and salivary flow to quantify salivary function and to evaluate the usefulness of pilocarpine in the treatment of radiation-induced xerestomia in head and neck cancer patients . METHOD Thirty two patients with head and neck tumor treated with radiotherapy ( RDT ) were studied . Patients were classified into two groups : pilocarpine group ( P ) , that received prophylactic pilocarpine before RDT and during the first year after treatment . No pilocarpine group ( NP ) that received RDT without pilocarpine . Salivary gl and scintigraphy and salivary flow were performed before RDT and during one year after treatment . Parotid and submaxillary uptake and excretion were calculated . Salivary flow after stimulation during five minutes was also obtained . RESULTS Uptake and excretion in both salivary gl and s decreased after RDT . There were no statistical differences comparing P and NP groups ( p < 0.001 ) . However , in group P a trend to recovery was observed in parotid uptake values at 12 months after treatment , but it was not statistically significant . In both groups the salivary flow decreased after RDT and a good correlation ( r = 0.8 ) between salivary flow and submaxillary excretion and parotid excretion was found . CONCLUSIONS Salivary gl and scintigraphy and salivary flow could be useful to evaluate salivary gl and function in patients with head and neck irradiated tumors . Although better results on the salivary uptake at 12 months were noted , pilocarpine did not significantly improve salivary gl and function Radiation therapy is an important curative modality in the treatment of patients with head and neck cancer . However , radiation-induced changes in the oral cavity , such as xerostomia and mucositis , are among the most debilitating treatment sequelae experienced by patients undergoing radiation therapy , and attempts at ameliorating these side effects have been poor at best . Pilocarpine has been approved for post-radiation xerostomia , and the effect of its use during radiation therapy on salivary flow , xerostomia , mucositis , and quality of life ( QOL ) was assessed in a phase III study conducted by the Radiation Therapy Oncology Group ( RTOG 97 - 09 ) . In total , 245 evaluable patients were r and omized to pilocarpine or placebo . Selected patients were required to have > or = 50 % of the volume of the major salivary gl and s receive > or = 50Gy ; to agree to provide stimulated and unstimulated sample s of saliva ( measured in g ) before treatment , at the end of treatment , and 3 and 6 months after completion of radiation therapy ; and to complete the University of Washington Head and Neck Symptom Scale . Following the completion of radiation therapy , the average unstimulated salivary flow was statistically greater in the pilocarpine group , whereas no difference was noted following parotid stimulation . There was no effect on the amelioration of mucositis . The results of the QOL scales did not reveal any significant difference between the pilocarpine and placebo groups with regard to xerostomia and mucositis . The significant difference in unstimulated salivary flow supports the concomitant use of oral pilocarpine to decrease radiation-associated xerostomia . However , the absent correlation between improved salivary flow and QOL scores is of some concern ( though not a new finding ) and may be related to the existence of comorbidities and the lack of effect on mucositis PURPOSE Radiochemotherapy of head and neck cancer causes severe mucositis in most patients . We investigated whether palifermin reduces this debilitating sequela . METHODS We conducted a multicenter , double-blind , r and omized , placebo-controlled trial in 186 patients with stages II to IVB carcinoma of the oral cavity , oropharynx , hypopharynx , or larynx . Patients received 60 or 66 Gy after complete ( R0 ) or incomplete resection ( R1 ) , respectively , at 2 Gy/fraction and five fractions per week . Cisplatin 100 mg/m(2 ) was administered on days 1 and 22 ( and on day 43 with R1 ) . Patients were r and omly assigned to receive weekly palifermin 120 μg/kg or placebo from 3 days before and continuing throughout radiochemotherapy . Trained evaluators performed oral assessment s twice weekly . The primary end point was the incidence of severe oral mucositis ( WHO grade s 3 to 4 ) . Overall survival and time to locoregional progression were also assessed . Analysis was by intention to treat . RESULTS Severe oral mucositis was seen in 47 ( 51 % ) of 92 patients administered palifermin and 63 ( 67 % ) of 94 administered placebo ( P = .027 ) . Palifermin decreased the duration ( median , 4.5 v 22.0 days ) and prolonged the time to develop ( median , 45 v 32 days ) severe mucositis . Neither patient-reported mouth and throat soreness scores nor treatment breaks differed between treatment arms . After median follow-up of 32.8 months , 23 deaths ( 25 % ) had occurred in both treatment arms , and disease had recurred in 25 ( 27 % ) and 22 ( 24 % ) of palifermin- and placebo-treated patients , respectively . CONCLUSION Palifermin reduced the occurrence of severe oral mucositis in patients with head and neck cancer undergoing postoperative radiochemotherapy . Additional clinical exploration of palifermin with postoperative radiochemotherapy would be useful BACKGROUND Oral mucositis is a frequent and serious complication in patients receiving chemo-radiotherapy for head and neck squamous cell carcinoma . This study evaluated the effects of administering Lactobacillus brevis CD2 lozenges on the incidence and severity of mucositis and tolerance to chemo-radiotherapy . METHODS Two hundred patients suitable for chemo-radiotherapy were enrolled in a r and omised , double-blind study to receive daily treatment with lozenges containing either L. brevis CD2 or placebo . Anticancer therapy was RT 70 Grays/35 fractions over 7 weeks with weekly Inj . Cisplatin 40 mg/m(2 ) . The study treatment was given during , and for 1 week after completion of anticancer therapy . Primary end-points were the incidence of grade III and IV oral mucositis and the percentage of patients able to complete anticancer treatment . FINDINGS The efficacy analysis included the 188 patients who received ≥ 1 week of study treatment . Grade III and IV mucositis developed in 52 % of patients in the L. brevis CD2 arm and 77 % in the placebo arm ( P<0.001 ) . Anticancer treatment completion rates were 92 % in the L. brevis CD2 arm and 70 % in the placebo arm ( P=0.001 ) . A larger proportion of patients remained free of mucositis when treated with L. brevis CD2 ( 28 % ) compared to the placebo ( 7 % ) . INTERPRETATION L. brevis CD2 lozenges reduced the incidence of grade III and IV anticancer therapy-induced oral mucositis and were associated with a lower overall rate of mucositis and a higher rate of anticancer treatment completion BACKGROUND Xerostomia is one of the disturbing side-effects of radiotherapy to the head and neck region . Pilocarpine has been approved for the treatment of this condition in the chronic phase , but its use concurrent with radiation could also be beneficial for prevention or reduction of the subsequent radiation-induced xerostomia . We undertook to test this hypothesis in a clinical trial . METHODS At the start of radiotherapy , r and omization was performed to either pilocarpine 5 mg three times daily or placebo in a double-blind setting . The drug was started with irradiation and continued until 3 months after the end of radiotherapy . Xerostomia was evaluated 6 months after the end of radiation by a subjective visual analog scale question naire . Also the objective grade of xerostomia was recorded by two separate observers . RESULTS A total number of 60 patients were r and omized into the trial , but unfortunately only 39 patients were finally evaluated for xerostomia , 18 in the pilocarpine and 21 in the placebo group . Mean age was 42 years , and mean parotid dose was 58 Gy . Mean subjective xerostomia was 40.3 mm in the pilocarpine group and 57 mm in the placebo group ( P = 0.02 ) . Also mean objective xerostomia grade was 2.2 in the pilocarpine group and 2.6 in the placebo group ( P = 0.01 ) . Subjective and objective xerostomia results were positively correlated ( P = 0.01 ) . Age and the parotid dose did not have a significant effect on xerostomia . CONCLUSIONS Compared to placebo , pilocarpine used with radiotherapy could lead to a significant diminishment of subsequent radiation-induced xerostomia BACKGROUND Amifostine has reduced toxicities associated with radiation therapy and platinum-based chemotherapy . In a phase II r and omized trial , we investigated the ability of amifostine to reduce the toxicity of carboplatin plus radiotherapy ( RCT ) in patients with head and neck cancer . PATIENTS AND METHODS Thirty-nine patients with stage III or IV squamous cell carcinomas of the head and neck received RCT ( following surgery or as primary treatment ) . Radiotherapy was given five days per week with daily fractions of 2 Gy , up to a total dose of 60 Gy in conjunction with carboplatin 70 mg/m2 on days 1 through 5 and days 21 through 26 . Eligible patients were r and omised to receive RCT alone or preceded by a rapid infusion of amifostine ( 500 mg ) on the days when carboplatin was administered . RESULTS Patients receiving amifostine + RCT ( n = 25 ) had significantly reduced mucositis ( P = 0.0001 ) and xerostomia ( P = 0.0001 ) in comparison with patients receiving RCT alone ( n = 14 ) . Additionally , patients receiving amifostine + RCT had significantly less thrombocytopenia ( P = 0.001 ) and leukopenia ( P = 0.001 ) . At 12 months following therapy , 79 % of patients receiving amifostine + RCT had no evidence of disease compared with 64 % of those receiving RCT alone . CONCLUSIONS Amifostine reduces the RCT -induced toxicities in patients with head and neck cancer and has no negative impact on antitumour efficacy The availability of subcutaneously ( SC ) administered amifostine may present an advantage for radioprotectant therapy in head and neck cancer patients . In a r and omized phase II trial comparing SC amifostine versus no amifostine in 140 patients undergoing radiation therapy for head and neck , thoracic , or pelvic cancers , amifostine treatment was associated with reductions in mucosal toxicity and delays in radiation therapy among the 19 patients with head and neck cancer , as well as in the thoracic and pelvic cancer groups . A phase II trial of SC amifostine in head and neck cancer was performed in a patient population ( n = 54 ) similar to that studied in a phase III trial of intravenous amifostine to allow comparisons of outcomes . Acute xerostomia grade 2 occurred in 56 % with SC amifostine and 51 % with intravenous amifostine ( 78 % in the no-amifostine group in phase III trial ) , with median time to onset being 40 days and 45 days , respectively ( 30 days with no amifostine ) , and cumulative radiation dose to onset being 58 Gy and 60 Gy ( 42 Gy with no amifostine ) , respectively . Amifostine SC was well tolerated , with three quarters of patients receiving > or = 75 % of the planned dose . Nausea , vomiting , and hypotension were less severe with SC amifostine , but cutaneous toxicity was more frequent . The reduction in radiation therapy-induced acute xerostomia with SC amifostine is similar to that with intravenous amifostine in patients with head and neck cancer . If cutaneous toxicity is judged an acceptable risk , SC amifostine may represent a second , more convenient option for treating physicians The effects of bethanechol in the treatment of dry mouth were assessed in patients with xerostomia after radiation therapy to the head and neck . Bethanechol possesses muscarinic and nicotinic-cholinergic activity that likely accounts for its mode of action . Bethanechol ( 25 mg , three times daily ) was not associated with significant side effects . Statistically significant increases in whole resting saliva ( p = 0.003 ) and whole stimulated saliva ( p = 0.001 ) were seen . In patients with pretreatment stimulated saliva volumes greater than resting saliva volumes , a positive response to subsequent use of the sialagogue was seen There is controversy concerning the effect of pilocarpine in the reversal of radio-induced xerostomia ; however , the tests are usually performed at the end of radiotherapy . The present study evaluated the radioprotective effects of pilocarpine when ingested during radiation treatment . Eleven patients ( recently diagnosed with head and neck cancer who were not undergoing radiotherapy ) were divided into two groups : the control group ( saline solution intake n=6 ) and the pilocarpine-treated ( 5 mg pilocarpine three times daily , n=5 ) group , in a prospect i ve and double-blinded study . For five weeks , oral conditions , unstimulated salivary flow and stimulated saliva flow were collected weekly , with the first collection occurring prior to radiation therapy . As early as the second week , the control group exhibited oral complications and greater reduction in salivary flow rate . At the end of the study , the pilocarpine-treated group presented mean values of salivary flow greater than those of the control group . Pilocarpine intake applied simultaneously with radiotherapy demonstrated encouraging results with regard to lowering salivary flow reduction and incidence of xerostomia , as well as of oral complications AIM A large variety of adverse reactions are well known to frequently occur during chemotherapy and radiotherapy in oncology . Specific medications exist to target individual side effects . The aim of this study was to explore in a pilot trial whether supplementation with French maritime pine bark extract Pycnogenol could alleviate side effects and improve patient 's quality of life . METHODS Cancer patients who previously underwent surgery and who were in view of their pathology in relatively good condition , both physically and psychologically , were recruited for this study and divided into two groups . These patients received their first cycle of radiotherapy or chemotherapy , which lasted from 10 days up to 1 month . Then one group of patients received 150 mg Pycnogenol , the control group comparable placebo in a single-blinded fashion . The authors studied the occurrence of side effects and made attempts to judge their severity on a semi-quantitative visual analogue scale over a 2 months period starting after patients completed their first cycle of chemo- or radiotherapy , respectively . RESULTS Twenty five radiotherapy patients receiving Pycnogenol showed a decreased frequency of essentially all investigated side-effects as compared to 21 patients receiving placebo , though in many categories the difference was limited . The most apparent improvements of acute side effects related to decreased soreness and ulceration in the mouth and throat as well as less dryness of the mouth and the eyes . A decreased incidence of nausea /vomiting , diarrhoea , edema and weakness was noticed , which was reflected by semi-quantitative evaluation suggesting that severity was only half or even less pronounced than in the control group . Only one case of deep vein thrombosis occurred in the Pycnogenol group whereas 2 cases of superficial vein thromboses and one case of deep vein thrombosis occurred in the control group ( 2.9 % vs 10 % ) . Thirty four chemotherapy patients were supplemented with Pycnogenol and another 30 patients were in the control group . For all patients this was the first chemotherapy treatment period . The Pycnogenol group presented with a lowered incidence of all investigated side effects as compared to the control group , though in many cases to a limited extent . The most prominent improvements were found for nausea , vomiting , diarrhoea and weight loss . Semi-quantitative evaluation showed that here again symptom severity was half or less pronounced than in the control group . Various further symptoms improved such as cognitive impairment and also cardiotoxicity and neutropenia . Effects on anemia could not be investigated as several patients received erythrocyte transfusion . In the Pycnogenol group one case of superficial vein thrombosis was indentified while 3 cases of superficial vein thromboses and one deep vein thrombosis were detected in the control group ( 4 % vs 19 % ) . In both chemotherapy and radiotherapy patients Pycnogenol lowered the requirement for medication to address side effects . This was reflected by less days of hospitalisation the patients required . The authors did not investigate a possible interference with the anti-neoplastic efficacy of chemo- and radiotherapy . This possibility requires attention in future studies with Pycnogenol . From their previous clinical experience the authors suggest that alleviation of side effects described in this study results from Pycnogenol activities related to endothelial protection , and anti-inflammatory anti-edema activities . CONCLUSION The results of this pilot trial warrant further prospect i ve studies with larger number of patients to vali date benefits more specifically with regard to type of malignancy and treatment regimen Radiotherapy of head and neck malignancies is accompanied by oral discomforts , such as epithelitis , pain and functional impairment . This can lead to chronic sequalae with subjective distress such as loss of taste and xerostomia and pronounced decrease in quality of life . Thus , the need to reduce the mucosal damage following radiotherapy is obvious . Therefore , we investigated the possible ability of sucralfate , an aluminium hydroxide complex of sulphated sucrose used in the treatment of gastric ulcer , in preventing oral discomfort in patients treated with curative intent for malignancies in the head and neck region . The study was double-blind , placebo-controlled and r and omized and included 50 consecutive patients . The study demonstrated that the proportion of patients with severe mucosal reactions was significantly lower in the sucralfate group than in the placebo group BACKGROUND Amifostine has a potential role for salivary gl and protection in head and neck cancer patients who had radiotherapy . MATERIAL AND METHOD Sixty-seven head and neck cancer patients were r and omized to receive radiotherapy or radiotherapy plus Amifostine . The efficacy of the treatment was determined by a question naire evaluating dryness of mouth and the oral comfort , the RTOG/EORTC acute/late radiation morbidity scoring criteria , collection of the whole saliva and the 99mTc-pertecnetate scintigraphy of the salivary gl and s. RESULTS Amifostine significantly reduced the mean question naire scores from 6.49 to 3.73 , the incidence of grade > or = 2 mucositis from 75 % to 36 % and acute xerostomia from 82 % to 39 % . The salivary gl and function returned to normal at a rate of 36.3 % in the Amifostine group versus 9.1 % in the control group . CONCLUSION Amifostine is effective in reducing the incidence and severity of acute mucositis , acute and late xerostomia in head and neck cancer patients BACKGROUND AND PURPOSE Parenchymal impairment of salivary gl and s following high-dose radioiodine treatment is a well-known side effect in general caused by free radicals . Therefore , the radioprotective effect of the radical scavenger amifostine was evaluated prospect ively in patients receiving high-dose radioiodine treatment . PATIENTS AND METHODS Parenchymal function was assessed by quantitative salivary gl and scintigraphy performed in 50 patients with differentiated thyroid cancer prior to and 3 months after high-dose radioiodine treatment with either 3 GBq 131I ( n = 21 ) or 6 GBq 131I ( n = 29 ) in a double-blinded , placebo-controlled study . Twenty-five patients treated with 500 mg/m2 amifostine intravenously prior to high-dose radioiodine treatment were compared to 25 control patients receiving physiological saline solution . Xerostomia was grade d according to WHO- criteria . RESULTS In 25 control patients high-dose radioiodine treatment significantly ( p < 0.001 ) reduced parenchymal function of parotid and subm and ibular gl and s by 40.2 + /- 14.1 % and 39.9 + /- 15.3 % , respectively . Nine out of these 25 patients developed Grade I and 2 Grade II xerostomia . In contrast , in 25 amifostine-treated patients there was no significant ( p = 0.691 ) decrease in parenchymal function following high-dose radioiodine treatment , and xerostomia did not occur in any of them . CONCLUSION Parenchymal damage of salivary gl and s induced by high-dose radioiodine treatment can be significantly reduced by amifostine which may improve quality of life of patients with differentiated thyroid cancer PURPOSE The influence of parasympathicomimetic pilocarpine and anticholinergic biperiden on salivation in patients irradiated for malignant tumors of the head and neck region was assessed in a prospect ively design ed clinical study . METHODS AND MATERIAL S Sixty-nine patients , irradiated for head and neck cancer with salivary gl and s included in the irradiation fields , were r and omly assigned into three groups ( A , B , and C ) . Group A consisted of patients receiving pilocarpine , group B of those who were receiving biperiden during radiotherapy and pilocarpine for 6 weeks after its completion , while group C comprised patients not receiving any xerostomy prevention therapy during or after radiotherapy . The quantity of secreted unstimulated saliva was measured before the beginning of radiotherapy , after 30 Gy of irradiation , on completed irradiation , and 3 , 6 , and 12 months after completion of radiotherapy . RESULTS Saliva secretion has been found to be the least affected by irradiation treatment in the group of patients receiving biperiden throughout the course of radiotherapy . Six months after completed irradiation , the differences in the quantity of secreted saliva between groups C and B as well as between groups A and B were statistically significant ( P = 0.002 and 0.05 respectively ) . In patients receiving pilocarpine during radiotherapy , and those in the control group , further decrease in saliva secretion was observed . One year after completed therapy , the quantity of secreted saliva could only be measured in the patients receiving biperiden during radiotherapy : it amounted to 16 % of the average quantity of saliva secreted before the beginning of irradiation . CONCLUSION It seems that the inhibition of saliva production during irradiation treatment and the stimulation after completed radiotherapy may contribute to the preservation of salivary gl and function after therapy This controlled study assessed the incidence of oral c and idiasis , a xerostomia-related complication , in head and neck cancer patients receiving radiotherapy , with amifostine cytoprotection . Thirty-eight patients received 500 mg amifostine i.v . , prior to each radiotherapy fraction , while 16 patients received radiotherapy alone . Oral c and idiasis was diagnosed according to the criteria described before . Subjective xerostomia scales were completed by all patients . Mucositis was evaluated using the RTOG criteria . Oral c and idiasis was diagnosed in 11/38 amifostine patients and in 9/16 controls ( P = 0.07 ) . Severe xerostomia was reported by 4/38 amifostine patients and by 7/16 controls . Oral c and idiasis was reduced with amifostine cytoprotection . Oral c and idiasis is suggested as an objective , early , though indirect , endpoint for amifostine 's radioprotective effect on salivary gl and OBJECTIVE The efficacy of pilocarpine given during radiotherapy for head-neck cancer to reduce xerostomia was assessed . STUDY DESIGN 58 patients receiving 5000 cGy radiotherapy ( RT ) involving salivary gl and s bilaterally were selected at the Jewish General Hospital , Montreal , Canada . Patients were r and omly assigned to pilocarpine ( 5 mg , PILO , n=29 ) or placebo group ( PLA , n=29 ) . These drugs were taken 5 times daily during radiotherapy ( first study phase ) and 4 times daily for 5 weeks thereafter ( second study phase ) . Saliva was collected and estimated for not stimulated and stimulated patients using the SAXON method . RESULTS At the conclusion of the first phase , PILO patients reported a better global quality of life ( P=.02 ) and less oral discomfort ( P=.001 ) when compared to PLA . No significant difference was noted in the level of saliva , xerostomia , and other symptoms between patients in PILO and PLA . At the end of the second phase , a difference between groups was observed only for xerostomia and mucosal pain ; both were significantly higher in PILO when compared to PLA ( P < .05 ) . CONCLUSION Pilocarpine 5 mg given 5 times daily did not appear to improve the production of saliva and global quality of life assessment s , nor to decrease the symptoms of xerostomia 5 weeks after completion of RT in patients who were taking pilocarpine post-RT . There was a slight improvement in the quality of life and a decrease in the level of discomfort noted only after the first study phase . The limitations of this study are discussed This study presents an overview of costs of a chemoradiation protocol in head and neck cancer patients and an analysis of whether prevention of acute toxicity with amifostine results in a reduction to costs . Fifty-four patients treated with weekly paclitaxel concomitant with radiation were r and omised for treatment with subcutaneously administered amifostine ( 500 mg ) and analysed with respect to costs of treatment . Total costs for work-up , treatment and toxicity were calculated per treatment arm . No significant differences were found between treatment arms in preliminary results regarding response ( 98 % ) , toxicity and 2-year survival ( 77 % ) . Average costs for toxicity were Euro 3.789 , largely influenced by hospital admissions ( Euro 3.013 ) . Total costs for amifostine administration amounted to Euro 6.495 per patient . The average total costs of treatment were Euro 19.647 versus Euro 13.592 with or without amifostine , respectively . The applied ( subcutaneous ) dose of amifostine appeared to be insufficient for radioprotection and reduction of related costs in the concomitant chemoradiation scheme , whereas total costs increased remarkably . Although it would be accompanied by a further cost raise , applying a higher amifostine dose might reduce ( mucosal ) toxicity and therefore in the long run lower related costs for hospital admission and tube feeding Patients with head and neck cancers can develop salivary hypofunction after radiotherapy . The use of pilocarpine during radiotherapy treatment has been shown to be an effective treatment , although its usefulness is being discussed . The aim of this study was : ( 1 ) to determine the value of a semiquantitative scintigraphy method for measuring the uptake and excretory salivary function of patients with head and neck irradiated tumours ; and ( 2 ) to study the usefulness of pilocarpine as a salivary gl and protector during radiotherapy . We prospect ively studied 49 patients ( mean age 61 years , range 29 - 87 years ) with head and neck cancer in need of radiotherapy . Patients were divided into two groups consecutively : group P ( 26 patients ) received 5 mg of pilocarpine three times per day starting the day before radiation therapy , and group NP ( 23 patients ) received radiotherapy without pilocarpine and were used as the control group . Salivary gl and scintigraphy and a visual analogue scale ( VAS ) of mouth dryness were obtained from each patient before radiotherapy and during the first year after treatment . The most frequent finding after radiotherapy was a quick impairment in parotid and submaxillary excretion ( P<0.001 ) . There were no statistical differences comparing the pilocarpine group against the non-pilocarpine group . Parotid and submaxillary uptake significantly decreased after radiotherapy in both groups ( P<0.001 ) . However , a tendency to recover within the pilocarpine group was observed in both the parotids and the submaxillary gl and s at 12 months . No differences were found comparing the VAS results in both groups . Strikingly , VAS data did not correlate with salivary gl and dysfunction observed by means of scintigraphy . In conclusion , salivary scintigraphy is a useful technique to evaluate objective ly the salivary gl and function of patients with head and neck irradiated tumours as well as to test the response to pilocarpine . However , despite better results on the salivary uptake at 12 months , pilocarpine did not significantly improve salivary gl and function PURPOSE The oral complications associated with radiotherapy to the head and neck are a significant dose-limiting factor . The goals of this study were to determine whether oropharyngeal rinsing and ingestion of misoprostol protect mucous membranes from the acute effects of irradiation , and to evaluate the quality -of-life ( QOL ) outcomes of patients receiving misoprostol . We report the results of the QOL outcomes of patients in this study . METHODS AND MATERIAL S A total of 33 patients with resected or intact cancer of the oral cavity , oropharynx , supraglottic larynx , or hypopharynx were registered to receive postoperative radiotherapy plus misoprostol or primary radiotherapy plus misoprostol . All patients were scheduled to receive 60 - 70 Gy at 2 Gy/d within 6 - 7 weeks . QOL and function were evaluated . RESULTS A decrease in the QOL and function occurred in all areas covered by the question naire at the 6-week interval . This decrease was significant for eating , saliva , taste , and mucous . Of these significant factors , taste , saliva , and mucous consistency had not resolved by 12 weeks . CONCLUSION Increased underst and ing of the impact of treatment on QOL and symptoms will formulate the rational design of toxicity interventions and enhance the multidisciplinary care of head- and -neck patients Background Salivary gl and impairment following high-dose radioiodine treatment is a well-recognized side effect , in general caused by free radicals . Therefore , it seemed promising to evaluate the radioprotective effect of the radical scavenger amifostine in patients receiving high-dose radioiodine therapy . Patients and Method Quantitative salivary gl and scintigraphy using 100 to 120 MBq Tc-99m-pertechnetate was performed in 17 patients with differentiated thyroid cancer prior to and 3 months after radioiodine treatment with 6 GBq 1–131 . Eight patients were treated with 500 mg/m2 amifostine prior to high-dose radioiodine treatment and compared retrospectiveley with 9 control patients . Xerostomia was grade d according to WHO criteria . Results In 9 control patients high-dose radioiodine treatment significantly ( p < 0.01 ) reduced Tc-99m-pertechnetate uptake by 35.4 ±22.0 % and 31.7 ±21.1 % in parotid and subm and ibular gl and s , respectively . Of these 9 patients , 3 exhibited xerostomia Grade I ( WHO ) . In contrast , in 8 amifostine-treated patients , there was no significant ( p = 0.878 ) decrease in parenchymal function following high-dose radioiodine treatment , and xerostomia did not occur in any of them . Conclusion Parenchymal damage in salivary gl and s induced by high-dose radioiodine treatment can be reduced significantly by amifostine . This may help to increase patients ’ quality of life in differentiated thyroid cancer . ZusammenfassungHintergrundEine SchÄdigung der Speicheldrüsen mit konsekutiver Xerostomie ist eine bekannte , durch freie Radikale verursachte Nebenwirkung der hochdosierten Radiojodtherapie bei Patienten mit differenziertem Schilddrüsenkarzinom . Daher wurde der Effekt des RadikalfÄngers Amifostin nach hochdosierter Radiojodtherapie geprüft . Patienten und Method eIm Rahmen eines Heilversuchs wurde eine limitierte Anzahl von Patienten untersucht . Vor und drei Monate nach Gabe von 6 GBq 1–131 wurde eine quantitative Speicheldrüsenszintigraphie mit 100 bis 120 MBq Tc-99m-Pertechnetat an 17 Patienten mit differenzierten Schilddrüsenkarzinomen durchgeführt . Acht Patienten erhielten vor Radiojodtherapie 500 mg/m2 Amifostin und wurden mit einer historischen Kontrollgruppe aus neun Patienten verglichen . Eine Xerostomie wurde nach WHO-Kriterien beurteilt . ErgebnisseDie Patienten der Kontrollgruppe wiesen sowohl für die Gl and ulae parotides als auch für die Gl and ulae subm and ibulares eine signifikante Verminderung der Tc-99m-Pertechnetat-Aufnahme um 35,4 ±22,0 % bzw . 31,7 + 21 , 1 % ( Abbildungen 1 und 2 , Tabellen 1 und 2 ) als Zeichen einer ParenchymschÄdigung auf . Bei drei dieser neun Patienten f and sich eine Xerostomie Grad I ( WHO ) . I m Gegensatz dazu konnte bei den mit Amifostin beh and elten Patienten keine signifikante Verminderung der Parenchymfunktion festgestellt werden ( p = 0,878 ) . Dementsprechend wies keiner dieser Patienten eine Xerostomie auf . SchluΒfolgerungBei Patienten mit differenziertem Schilddrüsenkarzinom kann die durch hochdosierte Radiojodtherapie regelhaft verursachte ParenchymschÄdigung der Speicheldrüsen signifikant vermindert werden . Dies könnte die LebensqualitÄt dieser Patienten wesentlich verbessern BACKGROUND The primary objective was to investigate the validity and reliability of the Cancer Rehabilitation Evaluation System-Short Form ( the CARES-SF ) as a quality of life instrument in clinical trials [ 10 ] . PATIENTS AND METHODS A heterogeneous sample of 485 cancer patients completed the CARES-SF before treatment ( T1 ) , one month later ( T2 ) , and three months following T2 ( T3 ) . At T3 the patients completed the question naire either by mail , in a telephone interview , or in the clinic . A sub- sample of patients completed the CARES-SF a fourth time ( T4 ) one week following T3 , for purpose s of test-retest reliability estimation . RESULTS On average , the CARES-SF required 11 minutes for completion and could be completed by 90 % of the patients without assistance . However , 82 % of the patients reported difficulty with at least one item . Multitrait scaling analysis and factor analysis generally confirmed the hypothesized scale structure . Internal consistency reliability coefficients exceeded the 0.70 criterion for four of six multi-item scales . The test-retest reliability coefficients of the six scales were above 0.70 . No systematic differences were found in the psychometrics of the CARES-SF across administration conditions . In the mail condition the proportion of missing items was significantly higher , and patients reported having significantly more problems than in both the telephone and in-clinic condition . According to expectation , selective scales distinguished clearly between patients differing in disease stage , performance status , treatment modality and tumor response . Additionally , selective scales were responsive to changes in health status over time . CONCLUSION These results lend support to the reliability and validity of the CARES-SF in assessing the quality of life of patients with cancer . At the same time , efforts to refine the question naire are recommended OBJECTIVE The substitution of selenium activates the selenium-dependent enzyme glutathione peroxidase , which is important for scavenging free radicals . To date , only limited data are available about the clinical impact of selenium regarding the toxicities due to free radical producing therapies , e.g. irradiation or chemotherapy , and therefore the objective of this study was to investigate the clinical impact of selenium in such therapies . PATIENTS AND METHODS 39 patients ( 8 female , 31 male ) with advanced head and neck cancer were included in a r and omised phase II study . The mean age was 63.52+/-9.31 years . Tumour localizations : oral cavity 15 patients , oropharynx 19 patients , hypopharynx 5 patients , carcinoma of unknown primary 1 patient . Group A ( n=22 ) received 500 microg sodium selenite on the days of radiotherapy and 300 microg sodium selenite on days without radiotherapy . Group B ( 17 ) was irradiated without any selenium substitution . Both groups were well balanced according to age , gender , localization and stage of the tumour . The RTOG grade of radiation-associated toxicities was evaluated once per week . RESULTS The following serious toxicities were observed ( group A vs. group B ) : dysphagia 22.7 % vs. 35.3 % , loss of taste 22.7 % vs. 47.1 % , dry mouth 22.7 % vs. 23.5 % , and stomatitis 36.4 % vs. 23.5 % . A statistical trend ( Fisher 's exact test ) was only seen for the loss of taste ( p=0.172 ) . The weekly patient analysis ( Student 's t-test ) showed a significant reduction of dysphagia in the selenium group ( Group 1 ) at the last week of irradiation . CONCLUSION This small r and omised trial showed limited effects of selenium in the prevention of ageusia ( loss of taste ) and dysphagia due to radiotherapy of head and neck cancer The major salivary gl and s produce about 90 % of salivary secretions ; the minor salivary gl and s produce the remainder . St and ard conventional radiation therapy for advanced oropharyngeal tumors typically involves administering high radiation dose to the major salivary gl and s bilaterally . In most cases , this causes a marked reduction in oral saliva output . Xerostomia is the most prevalent late side effect of radiation for head and neck malignancies and is cited by patients as the major cause of decreased quality of life . The degree of xerostomia has been reported to depend on the radiation dose and salivary gl and volume irradiated . Several studies show dose volume response relationships in the salivary gl and s , suggesting the possibility of significant improvement in saliva production post radiation as well as quality of life if radiation techniques can spare the salivary gl and s. In recent years , conformal radiation techniques have evolved , which may allow radiation of tumor targets in the head and neck area while sparing substantial portions of salivary gl and s. It has been shown that in using these techniques , adequate irradiation of the targets while sparing major salivary gl and s is feasible . Early clinical experience showed substantial sparing of salivary flow following radiation and suggested an improvement of tumor control and of xerostomia over that achieved with st and ard radiation techniques . We hypothesize that the addition of a radioprotector may further improve salivary function over that obtained with intensity modulated radiation therapy alone . To test this hypothesis , we initiated a pilot clinical trial whose principal objective is to compare measurements of unstimulated and stimulated salivary flow rates 6 months after intensity modulated radiation therapy plus amifostine ( Ethyol ; MedImmune , Inc , Gaithersburg , MD ) ( study patients ) with those obtained in historical controls treated with intensity modulated radiation therapy alone During radiation therapy to the head and neck region , salivary gl and hypofunction commonly develops . The aim of our study was to evaluate whether the sialogogue pilocarpine given during radiation therapy may reduce the severity of xerostomia and salivary dysfunction . Our results showed the pilocarpine-treated group to have a lower frequency of oral symptoms during the treatment than the placebo-treated group . Although salivary flow decreased in all patients , the pilocarpine-treated group had smaller flow reductions . No drug effect was observed in the gl and s that were completely irradiated . Thus , pilocarpine appeared to stimulate salivary tissues outside the radiation field PURPOSE To retrospectively compare subjective postirradiation xerostomia scores of patients who received concomitant oral pilocarpine during radiotherapy for head and neck cancer and 3 months thereafter with those of similar cohorts who did not receive pilocarpine . METHODS AND MATERIAL S Subjective xerostomia was assessed using a visual analog scale xerostomia question naire that measured oral dryness , oral comfort , difficulty with sleep , speech , and eating . The concomitant pilocarpine group had both parotid gl and s in the initial field treated to at least 45 Gy and received 5 mg pilocarpine hydrochloride four times per day ( q.i.d . ) beginning on the first day of radiotherapy and continuing for 3 months after completion of radiation . The control cohort had also received at least 45 Gy to both parotid gl and s and had not received pilocarpine at the time of evaluation . Scores on the visual analog scale were averaged and compared using the Student 's t-test . RESULTS Seventeen patients who received concomitant pilocarpine during head and neck irradiation and 18 patients who had not been treated with pilocarpine were available for follow-up . The mean intervals between completion of radiation and evaluation of xerostomia were 17 months and 16 months , respectively . Only one of the pilocarpine-treated patients was still taking pilocarpine at the time of evaluation . For each of the individual components of xerostomia scored on the visual analog scale , as well as the composite of all components , the group that had received oral pilocarpine during radiation had significantly less xerostomia ( p < 0.01 for each ) . CONCLUSIONS The use of 5 mg oral pilocarpine q.i.d . during radiotherapy for head and neck cancer and 3 months thereafter was associated with significantly less subjective xerostomia than that reported by a similar cohort of patients who had not received pilocarpine . The continued use of pilocarpine does not appear to be necessary to maintain this benefit in most patients PURPOSE To determine whether prevention of hyposalivation after curative radiotherapy ( RT ) to the head and neck improves patients ' quality of life ( QOL ) . METHODS AND MATERIAL S Patients were to receive at least 50 Gy to 50 % of the volume of the major salivary gl and s , provide unstimulated and stimulated saliva sample s , and complete the University of Washington head- and -neck QOL tool before RT and 3 and 6 months after RT . Patients were r and omized to receive pilocarpine 5 mg or placebo q.i.d . RESULTS A total of 249 patients was r and omized between March 1998 and January 2000 . Of these , 214 were eligible for QOL analysis . Patients were evenly distributed between arms by race , gender , tobacco use , tumor site , T stage ( 50 % T2-T3 ) , and salivary function . A Karnofsky performance status of 90 % was more common in the pilocarpine arm . Twenty percent of the patients on the pilocarpine arm and 29 % of the patients on the placebo arm were taking nutritional supplements . The placebo arm patients had greater mouth pain and chewing difficulties . Compliance for the QOL tool at 3 and 6 months was 65 % and 50 % , respectively . Despite statistically significant ( p = 0.047 and p = 0.049 , respectively ) preservation of salivary function in the pilocarpine arm , patients on the pilocarpine arm reported difficulties with swallowing ( 75 % ) , activity ( 80 % ) , hyposalivation ( 64 % ) , and taste ( 81 % ) . No difference was noted between arms at 3 months in mucositis scores , with both arms demonstrating increased requirement for oral nutrients . CONCLUSION Objective prevention of hyposalivation did not affect patients ' assessment of salivary function or QOL because of the greater impact mucositis plays in QOL after RT OBJECTIVE To study the efficacy of coumarin/troxerutine for the protection of salivary gl and s and mucosa during irradiation . DESIGN Prospect i ve , r and omized , placebo-controlled , double-blind trial . SETTING University hospital , Germany . PATIENTS 48 patients who had radiotherapy to the head and neck . MAIN OUTCOME MEASURES Salivary gl and scintigraphy and acute side-effects of radiotherapy ( Radiation Therapy Oncology Group ( RTOG ) score ) . RESULTS 23 patients ( 11 experimental , 12 placebo ) completed the study . The global efficacy measure combining scintigraphy and RTOG score favoured the experimental arm ( P=0.07 ) . The RTOG score showed significantly fewer acute side-effects of radiation in the experimental arm ( P<0.05 ) . CONCLUSION The results suggest that coumarin/troxerutine have a favourable effect in the treatment of radiogenic sialadenitis and mucositis PURPOSE Radiotherapy for head and neck cancer causes acute and chronic xerostomia and acute mucositis . Amifositine and its active metabolite , WR-1065 , accumulate with high concentrations in the salivary gl and s. This r and omized trial evaluated whether amifostine could ameliorate these side effects without compromising the effectiveness of radiotherapy in these patients . PATIENTS AND METHODS Patients with previously untreated head and neck squamous cell carcinoma were eligible . Primary end points included the incidence of grade > or = 2 acute xerostomia , grade > or =3 acute mucositis , and grade > or = 2 late xerostomia and were based on the worst toxicity reported . Amifostine was administered ( 200 mg/m(2 ) intravenous ) daily 15 to 30 minutes before irradiation . Radiotherapy was given once daily ( 1.8 to 2.0 Gy ) to doses of 50 to 70 Gy . Whole saliva production was quantitated preradiotherapy and regularly during follow-up . Patients evaluated their symptoms through a question naire during and after treatment . Local-regional control was the primary antitumor efficacy end point . RESULTS Nausea , vomiting , hypotension , and allergic reactions were the most common side effects . Fifty-three percent of the patients receiving amifostine had at least one episode of nausea and /or vomiting , but it only occurred with 233 ( 5 % ) of 4,314 doses . Amifostine reduced grade > or = 2 acute xerostomia from 78 % to 51 % ( P<.0001 ) and chronic xerostomia grade > or = 2 from 57 % to 34 % ( P=.002 ) . Median saliva production was greater with amifostine ( 0.26 g v 0.10 g , P=.04 ) . Amifostine did not reduce mucositis . With and without amifostine , 2-year local-regional control , disease-free survival , and overall survival were 58 % versus 63 % , 53 % versus 57 % , and 71 % versus 66 % , respectively . CONCLUSION Amifostine reduced acute and chronic xerostomia . Antitumor treatment efficacy was preserved PURPOSE Clinical trials demonstrated the efficacy and safety of intravenous ( i.v . ) or subcutaneous ( s.c . ) amifostine for reducing xerostomia and mucositis after radiotherapy or radiochemotherapy for head- and -neck cancer . This r and omized , double-blinded , placebo-controlled , phase III study evaluated the efficacy and safety of i.v . amifostine during radiochemotherapy for head- and -neck cancer . METHODS AND MATERIAL S Patients from European and American study centers received i.v . amifostine 300 mg/m2 ( n = 67 ) or placebo ( n = 65 ) before carboplatin 70 mg/m2 and radiotherapy on Days 1 to 5 and 21 to 25 , and i.v . amifostine 200 mg/m2 or placebo before radiotherapy on other days . RESULTS Toxicity incidences were ( amifostine , placebo , p value ) : Grade 2 or higher acute xerostomia ( 39 % , 34 % , 0.715 ) , Grade 3 or higher acute mucositis ( 39 % , 22 % , 0.055 ) , Grade 2 or higher late xerostomia ( 37 % , 24 % , 0.235 ) , and Grade 3 or higher treatment-related adverse events ( 42 % , 20 % , 0.008 ) . One-year rates of locoregional failure , progression-free survival , and overall survival were not significantly different between treatments . CONCLUSIONS The used amifostine doses were not able to reduce the toxicity of simultaneous radiochemotherapy for head- and -neck cancer . The safety of amifostine and the lack of tumor protection were consistent with previous studies Abstract Ninety patients with salivary gl and or squamous cell tumours of the head and neck region presenting to two centres were included in a double blind controlled clinical trial of radiation plus razoxane versus radiation plus placebo . The patients were paired according to treatment centre , sex , tumour site and tumour stage , one member of a pair receiving razoxane and one placebo during radiotherapy . The dose of razoxane administered was 125 mg in the morning and 62.5 mg in the evening of each day of radiation . The treatments were assessed by comparing the tumour response of pairs of patients and the preferences for treatment type analyzed sequentially on the plan described by Bross . Of the 18 pairs eligible for analysis at the completion of the trial , one showed a preference for the treatment radiation plus razoxane , nine for the treatment radiation plus placebo , four showed no preference for either treatment and four had not been assessed . The conclusion drawn from the sequential analysis of the results is that razoxane , in the dose and schedule employed , has a deleterious effect on the response of head and neck tumours to radiation . Excluding a positive placebo action , the possibility of a radioprotective effect of razoxane is discussed and the importance of reconsidering the dose and timing of administration of the drug in future clinical studies is emphasized PURPOSE Radiotherapy ( RT ) for head and neck cancer typically involves the major salivary gl and s bilaterally and can cause acute and chronic xerostomia and mucositis . The degree of xerostomia has been reported to depend on the radiation dose and the salivary gl and volume irradiated . In this study , we evaluated the efficacy of the radioprotector amifostine to improve xerostomia and mucositis in head and neck cancer patients who received RT . PATIENTS AND METHODS A total of 53 patients with head and neck cancer entered this prospect i ve r and omized study . Patients were r and omly assigned to undergo RT or RT plus short intravenous ( i.v . ) infusion of amifostine 210 mg/m(2 ) before each RT fraction . RESULTS No statistically significant difference was seen between the 2 arms in terms of mucositis . Acute xerostomia occurred in 31 ( 93.9 % ) patients in the amifostine arm and all of the patients in the RT-alone arm ( p < 0.05 ) . Grade 3 acute xerostomia occurred in 13 ( 39.3 % ) patients in the amifostine arm , and in 9 ( 45 % ) patients in the RT-alone arm ( p=0.04 ) . Late xerostomia occurred in 19 ( 57.5 % ) patients in the amifostine arm , and in 14 ( 70 % ) patients in RT-alone arm ( p=0.03 ) . CONCLUSION The administration of amifostine in head and neck cancer patients receiving RT improved significantly acute and late xerostomia , while did not offer protection in the prevention of mucositis . Further prospect i ve studies are needed in order to better define the role of this agent BACKGROUND AND PURPOSE Amifostine has been shown to protect against xerostomia induced by radiotherapy for head and neck cancer , but its impact on the therapeutic index is unknown . This is the first report focusing on amifostine related adverse effects leading to discontinuation of amifostine treatment . PATIENTS AND METHODS Thirty-nine patients from two centers irradiated for head and neck cancer received i.v.-infusions of amifostine prior to each radiation fraction . In a phase III study , two daily amifostine doses , 200 mg/m(2 ) ( n = 21 ) and 340 mg/m(2 ) ( n = 18 ) , were compared for protection against radiation induced toxicity . Total radiation dose was 60 - 70Gy ( 2Gy per fraction ) , nine patients received concurrent chemotherapy with cisplatin/5-FU . amifostine was usually discontinued after > 1 episode of serious toxicity during subsequent treatment sessions . RESULTS In 16/39 patients ( 41 % ) amifostine was discontinued due to severe adverse effects , which led to discontinuation of the phase III study . In four of 16 patients radiotherapy was delayed due to amifostine related adverse effects for 1 - 3 days . Discontinuation occurred more often in patients receiving chemotherapy . The results led to a literature review for amifostine treatment during radiotherapy in head and neck cancer patients . Regarding our series and published series using an amifostine schedule comparable to ours , total discontinuation rate was 27 % ( 57/214 ) . Discontinuation was significantly influenced by chemotherapy ( P = 0.007 ) but not by amifostine dose ( P = 0.156 ) . CONCLUSION Daily i.v . administration of amifostine during radiotherapy in head and neck cancer is associated with a high rate of serious adverse effects leading to discontinuation of amifostine treatment and sometimes delay of radiotherapy The aim of this study was to verify whether the use of bethanechol during radiotherapy ( RT ) for head and neck cancer ( HNC ) prevents radiation-induced xerostomia and salivary flow reduction . Patients that would begin RT were r and omly allocated into bethanechol ( group 1 ) or artificial saliva ( group 2 ) . Whole resting saliva ( WRS ) and whole stimulated saliva ( WSS ) were collected from all the patients at the following four stages : baseline , during , immediately after , and at least two months after the end of RT . Xerostomia was assessed by a subjective visual analogue scale ( VAS ) , and by asking patients whether they felt dry mouth . Forty-three patients were r and omized into this trial . The use of bethanechol during RT for HNC cancer was associated with significantly higher WRS immediately after RT ( p=0.03 ) in comparison to a similar cohort of patients who had not received bethanechol The main objective of this study was to investigate whether nondaily intravenous administration of amifostine was as effective as daily intravenous administration with regard to the reduction of the incidence of Grade 2 or greater xerostomia in patients with head and neck cancer PURPOSE The aim of this study was to assess whether amifostine could minimize acute mucositis induced by a very accelerated irradiation regimen in patients with advanced head and neck squamous cell carcinoma ( HNSCC ) . METHODS AND MATERIAL S Between May 1996 and February 1998 , 26 patients with an inoperable nonmetastatic Stage IV HNSCC were entered in this study . The treatment consisted of very accelerated radiotherapy given 64 Gy in 3.5 weeks . The patients were r and omized to receive or not 150 mg/m(2 ) , amifostine ( Ethyol , U.S. Bioscience ) 15 - 30 min prior to each radiation session . RESULTS Of the 13 patients who received amifostine , definitive interruption of amifostine occurred in 5 cases ( 38 % ) , due to tolerance problems ( vomiting , liver enzyme elevation , generalized erythema ) . The distribution of Grade 4 mucositis ( WHO ) was 1 case versus 8 cases , with and without amifostine , respectively . The mean duration of " at least Grade 3 " mucositis ( WHO ) was 25.1 days versus 49.2 days with and without amifostine ( p = 0.03 ) . In the amifostine group , 11/13 of the patients required a feeding tube ( nasogastric tube or medical gastrostomy ) , because of acute mucositis , whereas in the control group a feeding tube was necessary in all cases . The mean duration of the use of this feeding tube was 1 month versus 2.5 months with and without amifostine respectively ( p < 0.01 ) . Local-regional control was not different between both arms with a median follow-up of 15 months . CONCLUSION Despite the limited number of patients , this pilot r and omized study suggests that amifostine was able to markedly reduce the severity and duration of mucositis induced by very accelerated radiotherapy . However , the tolerance of this twice daily amifostine schedule was relatively poor PURPOSE Acute mucositis is a dose-limiting toxicity of concurrent chemoradiotherapy regimens for locally advanced head and neck cancer . Palifermin ( a recombinant human keratinocyte growth factor ; DeltaN23-KGF ) stimulates the proliferation and differentiation of mucosal epithelium to reduce mucositis in patients receiving intensive therapy for hematologic cancers . This study assessed the efficacy and safety of palifermin in patients receiving concurrent chemoradiotherapy for advanced head and neck squamous cell carcinoma . PATIENTS AND METHODS In a phase II trial , st and ard radiotherapy was delivered in daily 2-Gy fractions to 70 Gy , or hyperfractionated radiotherapy was delivered in 1.25-Gy fractions twice daily to 72 Gy , over 7 weeks . Chemotherapy included cisplatin 20 mg/m(2 ) for 4 days and continuous-infusion fluorouracil 1,000 mg/m(2)/d for 4 days on weeks 1 and 5 of irradiation . Patients were r and omly assigned 2:1 to palifermin 60 microg/kg or placebo once weekly for 10 doses . A follow-up trial evaluated long-term survival . RESULTS Sixty-seven patients received palifermin and 32 received placebo . The median duration of grade > or= 2 mucositis was 6.5 and 8.1 weeks in the palifermin and placebo groups , respectively ( P = .157 ) . Palifermin appeared to reduce mucositis , dysphagia , and xerostomia during hyperfractionated radiotherapy ( n = 40 ) but not st and ard radiation therapy ( n = 59 ) . Adverse events were similar between treatment groups . Palifermin did not alter tumor response or survival . CONCLUSION Ten once-weekly doses of palifermin at 60 microg/kg were well tolerated . Most patients completed treatment , but palifermin did not reduce the morbidity of concurrent chemotherapy and radiotherapy . Future studies should evaluate higher palifermin doses with longer and more st and ardized assessment of acute mucositis |
10,736 | 31,773,969 | Conclusions : The development of an m-Health application could become a complementary monitoring tool during palliative care .
However , it seems important to question the impact of technique in the professional – patient relationship and avoid the pitfalls of st and ardizing palliative care and reducing the patient to a “ sick ” health technician . | Background : The major growth of mobile technologies in the recent years has led to the development of medical-monitoring applications , particularly on smartphones .
Aim : The aim of this study was to review the use of m-health in the monitoring of patients with chronic pathologies in order to consider what could be adapted for palliative care patients at home . | Purpose Poor medication adherence in adolescents with asthma results in poorly controlled disease and increased morbidity . The aim of the ADolescent Adherence Patient Tool ( ADAPT ) study is to develop an mHealth intervention to support self-management and to evaluate the effectiveness in improving medication adherence and asthma control . Intervention The ADAPT intervention consists of an interactive smartphone application ( app ) connected to a desktop application for health care providers , in this study , the community pharmacist . The app contains several functions to improve adherence as follows : 1 ) a question naire function to rate asthma symptoms and monitor these over time ; 2 ) short movie clips with medication and disease information ; 3 ) a medication reminder ; 4 ) a chat function with peers ; and 5 ) a chat function with the pharmacist . The pharmacist receives data from the patient ’s app through the desktop application , which enables the pharmacist to send information and feedback to the patient . Study design The ADAPT intervention is tested in a community pharmacy-based cluster r and omized controlled trial in the Netherl and s , aim ing to include 352 adolescents with asthma . The main outcome is adherence , measured by patient ’s self-report and refill adherence calculated from pharmacy dispensing records . In addition , asthma control , illness perceptions , medication beliefs , and asthma-related quality of life are measured . Conclusion This study will provide in-depth knowledge on the effectiveness of an mHealth intervention to support asthma self-management in adolescents . These insights will also be useful for adolescents with other chronic diseases OBJECTIVE To test the efficacy of a weight loss mobile app based on recommender systems and developed by experts in health promotion and computer science to target social support and self-monitoring of diet , physical activity ( PA ) , and weight ( Social POD app ) , compared to a commercially available diet and PA tracking app ( st and ard ) . MATERIAL S AND METHODS Overweight adults [ N=51 ] were recruited and r and omly assigned to either the experimental group [ n=26 ; theory-based podcasts (TBP)+Social POD app ] or the comparison group ( n=25 ; TBP+st and ard app ) . The Social POD app issued notifications to encourage users to self-monitor and send theory-based messages to support users who had not self-monitored in the previous 48h . Independent sample s t-test were used to examine group differences in kilograms lost and change in BMI . Analysis of covariance was used to analyze secondary outcomes while controlling for baseline values . RESULTS Participant attrition was 12 % ( n=3 experimental and n=3 comparison ) . Experimental group participants lost significantly more weight ( -5.3 kg , CI : -7.5 , -3.0 ) than comparison group ( -2.23 kg , CI : -3.6 , -1.0 ; d=0.8 , r=0.4 , p=0.02 ) and had a greater reduction in BMI ( p=0.02 ) . While there were significant differences in positive outcome expectations between groups ( p=0.04 ) other secondary outcomes ( e.g. , caloric intake and social support ) were not significant . DISCUSSION Use of the Social POD app result ed in significantly greater weight loss than use of a commercially available tracking app . This mobile health intervention has the potential to be widely disseminated to reduce the risk of chronic disease associated with overweight and obesity Background Chronic diseases , including diabetes mellitus , are the leading cause of mortality and disability in the United States . Current solutions focus primarily on diagnosis and pharmacological treatment , yet there is increasing evidence that patient-centered models of care are more successful in improving and addressing chronic disease outcomes . Objective The objective of this clinical trial is to evaluate the impact of a mobile health ( mHealth ) enabled nurse health coaching intervention on self-efficacy among adults with type-2 diabetes mellitus . Methods A r and omized controlled trial was conducted at an academic health system in Northern California . A total of 300 participants with type-2 diabetes were scheduled to be enrolled through three primary care clinics . Participants were r and omized to either usual care or intervention . All participants received training on use of the health system patient portal . Participants in the intervention arm received six scheduled health-coaching telephone calls with a registered nurse and were provided with an activity tracker and mobile application that integrated data into the electronic health record ( EHR ) to track their daily activity and health behavior decisions . All participants completed a baseline survey and follow-up surveys at 3 and 9 months . Primary and secondary outcomes include diabetes self-efficacy , hemoglobin A1c ( HbA1c ) , and quality of life measures . Results Data collection for this trial , funded by the Patient-Centered Outcomes Research Institute , will be completed by December 2017 . Results from the trial will be available mid-2018 . Conclusions This protocol details a patient-centered intervention using nurse health coaching , mHealth technologies , and integration of patient-generated data into the EHR . The aim of the intervention is to enhance self-efficacy and health outcomes by providing participants with a mechanism to track daily activity by offering coaching support to set reasonable and attainable health goals , and by creating a complete feedback loop by bringing patient-generated data into the EHR . Trial Registration Clinical Trials.gov NCT02672176 ; https:// clinical trials.gov/ct2/show/NCT02672176 ( Archived by WebCite at http://www.webcitation.org/6xEQXe1M5 Background The use of web-based monitoring for lung cancer patients is growing in interest because of promising recent results suggesting improvement in cancer and re source utilization outcomes . It remains an open question whether the overall survival ( OS ) in these patients could be improved by using a web-mediated follow-up rather than classical scheduled follow-up and imaging . Methods Advanced-stage lung cancer patients without evidence of disease progression after or during initial treatment were r and omly assigned in a multicenter phase III trial to compare a web-mediated follow-up algorithm ( experimental arm ) , based on weekly self-scored patient symptoms , with routine follow-up with CT scans scheduled every three to six months according to the disease stage ( control arm ) . In the experimental arm , an alert email was automatically sent to the oncologist when self-scored symptoms matched predefined criteria . The primary outcome was OS . Results From June 2014 to January 2016 , 133 patients were enrolled and 121 were retained in the intent-to-treat analysis ; 12 deemed ineligible after r and om assignment were not subsequently followed . Most of the patients ( 95.1 % ) had stage III or IV disease . The median follow-up was nine months . The median OS was 19.0 months ( 95 % confidence interval [ CI ] = 12.5 to noncalculable ) in the experimental and 12.0 months ( 95 % CI = 8.6 to 16.4 ) in the control arm ( one-sided P = .001 ) ( hazard ratio = 0.32 , 95 % CI = 0.15 to 0.67 , one-sided P = .002 ) . The performance status at first detected relapse was 0 to 1 for 75.9 % of the patients in the experimental arm and for 32.5 % of those in the control arm ( two-sided P < .001 ) . Optimal treatment was initiated in 72.4 % of the patients in the experimental arm and in 32.5 % of those in the control arm ( two-sided P < .001 ) . Conclusions A web-mediated follow-up algorithm based on self-reported symptoms improved OS due to early relapse detection and better performance status at relapse Background Chronic kidney disease ( CKD ) is a growing global problem affecting around 10 % of many countries ’ population s. Providing appropriate palliative care services ( PCS ) to those with advanced kidney disease is becoming paramount . Palliative/supportive care alongside usual CKD clinical treatment is gaining acceptance in nephrology services although the collaboration with and use of PCS is not consistent . Methods The goal of this study was to track and quantify the health service utilisation of people with CKD stages 3 - 5 over the last 12 months of life . Patients were recruited from a kidney health service ( Queensl and , Australia ) for this prospect i ve , longitudinal study . Data were collected for 12 months ( or until death , whichever was sooner ) during 2015 - 17 from administrative health sources . Emergency department presentations ( EDP ) and inpatient admissions ( IPA ) ( collectively referred to as critical events ) were review ed by two Nephrologists to gauge if the events were avoidable . Results Participants ( n = 19 ) with a median age of 78 years ( range 42 - 90 ) , were mostly male ( 63 % ) , 79 % had CKD stage 5 , and were heavy users of health services during the study period . Fifteen patients ( 79 % ) collectively recorded 44 EDP ; 61 % occurred after-hours , 91 % were triaged as imminently and potentially life-threatening and 73 % were admitted . Seventy-four IPA were collectively recorded across 16 patients ( 84 % ) ; 14 % occurred on weekends or public holidays . Median length of stay was 3 days ( range 1 - 29 ) . The median number of EDP and IPA per patient was 1 and 2 ( range 0 - 12 and 0 - 20 ) respectively . The most common trigger to both EDP ( 30 % ) and IPA ( 15 % ) was respiratory distress . By study end 37 % of patients died , 63 % were known to PCS and 11 % rejected a referral to a PCS . All critical events were deemed unavoidable . Conclusions Few patients avoided using acute health care services in a 12 month period , highlighting the high service needs of this cohort throughout the long , slow decline of CKD . Proactive end-of-life care earlier in the disease trajectory through integrating renal and palliative care teams may avoid acute presentations to hospital through better symptom management and planned care pathways OBJECTIVES This study evaluated the effectiveness ( changes in health behaviors , health status , and health service utilization ) of a self-management program for chronic disease design ed for use with a heterogeneous group of chronic disease patients . It also explored the differential effectiveness of the intervention for subjects with specific diseases and comorbidities . METHODS The study was a six-month r and omized , controlled trial at community-based sites comparing treatment subjects with wait-list control subjects . Participants were 952 patients 40 years of age or older with a physician-confirmed diagnosis of heart disease , lung disease , stroke , or arthritis . Health behaviors , health status , and health service utilization , as determined by mailed , self-administered question naires , were measured . RESULTS Treatment subjects , when compared with control subjects , demonstrated improvements at 6 months in weekly minutes of exercise , frequency of cognitive symptom management , communication with physicians , self-reported health , health distress , fatigue , disability , and social/role activities limitations . They also had fewer hospitalizations and days in the hospital . No differences were found in pain/physical discomfort , shortness of breath , or psychological well-being . CONCLUSIONS An intervention design ed specifically to meet the needs of a heterogeneous group of chronic disease patients , including those with comorbid conditions , was feasible and beneficial beyond usual care in terms of improved health behaviors and health status . It also result ed in fewer hospitalizations and days of hospitalization BACKGROUND Diabetes is a chronic disease , with high prevalence across many nations , which is characterized by elevated level of blood glucose and risk of acute and chronic complication . The Kingdom of Saudi Arabia ( KSA ) has one of the highest levels of diabetes prevalence globally . It is well-known that the treatment of diabetes is complex process and requires both lifestyle change and clear pharmacologic treatment plan . To avoid the complication from diabetes , the effective behavioural change and extensive education and self-management is one of the key approaches to alleviate such complications . However , this process is lengthy and expensive . The recent studies on the user of smart phone technologies for diabetes self-management have proven to be an effective tool in controlling hemoglobin ( HbA1c ) levels especially in type-2 diabetic ( T2D ) patients . However , to date no reported study addressed the effectiveness of this approach in the in Saudi patients . This study investigates the impact of using mobile health technologies for the self-management of diabetes in Saudi Arabia . METHODS In this study , an intelligent mobile diabetes management system ( SAED ) , tailored for T2D patients in KSA was developed . A pilot study of the SAED system was conducted in Saudi Arabia with 20 diabetic patients for 6 months duration . The patients were r and omly categorized into a control group who did not use the SAED system and an intervention group whom used the SAED system for their diabetes management during this period . At the end of the follow-up period , the HbA1c levels in the patients in both groups were measure together with a diabetes knowledge test was also conducted to test the diabetes awareness of the patients . RESULTS The results of SAED pilot study showed that the patients in the intervention group were able to significantly decrease their HbA1c levels compared to the control group . The SAED system also enhanced the diabetes awareness amongst the patients in the intervention group during the trial period . These outcomes confirm the global studies on the effectiveness of smart phone technologies in diabetes management . The significance of the study is that this was one of the first such studies conducted on Saudi patients and of their acceptance for such technology in their diabetes self-management treatment plans . CONCLUSIONS The pilot study of the SAED system showed that a mobile health technology can significantly improve the HbA1C levels among Saudi diabetic and improve their disease management plans . The SAED system can also be an effective and low-cost solution in improving the quality of life of diabetic patients in the Kingdom considering the high level of prevalence and the increasing economic burden of this disease AIM To verify the usefulness of a smartphone application ( App ) for facilitating self-care in patients with chronic hepatitis B ( CHB ) . BACKGROUND CHB is a global health problem , and patients with CHB need to routinely perform self-care . Health-related smartphone apps could help users self-manage their disease . METHODS Fifty-three CHB patients were assessed in this r and omized controlled before- and -after experimental study . The patients were r and omly and equally assigned to groups that did ( n=26 ) or did not ( n=27 ) use the smartphone app for 12weeks . The experimental and control groups were analyzed for differences in disease knowledge , self-efficacy , and self-care before and after use of the smartphone app . RESULTS After intervention , patients who used the app displayed significantly increased disease knowledge compared with the control group ( p=.015 ) . Self-efficacy and self-care also significantly increased in the experimental group ( p=0.006 and 0.001 , respectively ) . CONCLUSION The smartphone app can be useful for increasing self-care in CHB patients . ABBREVIATIONS App : application , CHB : chronic hepatitis B , CVI : content validity BACKGROUND & AIMS Mobile health technologies are advancing rapidly as smartphone use increases . Patients with inflammatory bowel disease ( IBD ) might be managed remotely through smartphone applications , but no tools are yet available . We tested the ability of an IBD monitoring tool , which can be used with mobile technologies , to assess disease activity in patients with Crohn 's disease ( CD ) or ulcerative colitis ( UC ) . METHODS We performed a prospect i ve observational study to develop and vali date a mobile health index for CD and UC , which monitors IBD disease activity using patient-reported outcomes . We collected data from disease-specific question naires completed by 110 patients with CD and 109 with UC who visited the University of California , Los Angeles , Center for IBD from May 2013 through January 2014 . Patient-reported outcomes were compared with clinical disease activity index scores to identify factors associated with disease activity . Index scores were vali date d in 301 patients with CD and 265 with UC who visited 3 tertiary IBD referral centers ( in California or Europe ) from April 2014 through March 2015 . RESULTS We assessed activity of CD based on liquid stool frequency , abdominal pain , patient well-being , and patient-assessed disease control , and activity of UC based on stool frequency , abdominal pain , rectal bleeding , and patient-assessed disease control . The indices identified clinical disease activity with area under the receiver operating characteristic curve values of 0.90 in patients with CD and 0.91 in patients with UC . They identified endoscopic activity with area under the receiver operating characteristic values of 0.63 in patients with CD and 0.82 in patients with UC . Both scoring systems responded to changes in disease activity ( P < .003 ) . The intraclass correlation coefficient for test-retest reliability was 0.94 for CD and for UC . CONCLUSIONS We developed and vali date d a scoring system to monitor disease activity in patients with CD and UC that can be used with mobile technologies . The indices identified clinical disease activity with area under the receiver operating characteristic curve values of 0.9 or higher in patients with CD or UC , and endoscopic activity in patients with UC but not CD BACKGROUND Continuity of care is widely regarded as an important marker of quality in the management of patients with long-term conditions . New services that integrate telemonitoring into care pathways have potential to change aspects of continuity in both positive and negative ways . AIMS A telemonitoring service for patients with chronic obstructive pulmonary disease ( COPD ) was introduced in Lothian , Scotl and , in 2009 . A qualitative study , nested within the TELESCOT COPD r and omised control trial , was undertaken to explore the views of patients and professionals on telemonitoring . The perceived impact of telemonitoring on continuity of care was investigated as part of the research . METHODS Semi-structured interviews were undertaken with 38 patients ( 47 % male , mean age 67.5 years ) . A maximum variation sample in relation to age , sex , socio-economic background , disease severity , and compliance with telemonitoring was recruited . Thirty-two stakeholders ( healthcare professionals and managers ) were interviewed . Transcribed coded data were analysed thematically using the framework approach . Interpretation was supported by multidisciplinary discussion . RESULTS Patients and healthcare professionals considered that relationship-based continuity of care was important in the delivery of telemonitoring services . Managers placed emphasis on improved continuity of clinical management as a means of reducing healthcare costs . However , professionals described many operational challenges arising from the ' bolting-on ' of telemonitoring provision to existing usual care provision which , they considered , result ed in the proliferation of additional managerial discontinuities . CONCLUSIONS Managers and healthcare professionals face major challenges in meeting dem and s for both relationship continuity and continuity of clinical management in the development of telemonitoring services OBJECTIVE To conduct an in-depth analysis of users ' experiences using an HIV self-management app . MATERIAL S AND METHODS We conducted four follow-up focus groups at the end of a 3-month r and omized feasibility trial . All focus group sessions were audio-recorded and transcribed . A thematic analysis was conducted to explore emerging themes . All of the themes were categorized into three factors of the PRECEDE component of the PRECEDE-PROCEED framework . For a finer granularity of analysis , the codes of each theme were broken into positive , negative , and neutral codes by study group . RESULTS 36 participants , including 24 from the intervention group and 12 from the control group , participated in the focus group sessions . A total of 14 themes organized by the PRECEDE factors were identified from focus group transcripts . Five themes related to predisposing factors were : 1 ) ease of app use ; 2 ) user-friendly functionality ; 3 ) self-efficacy for symptom management ; 4 ) design preference of illustrated strategies with videos ; and 5 ) user-control ( convenience vs. security ) . Four themes related to enabling factors were : 1 ) information needs of symptom management ; 2 ) symptom-tracking ; 3 ) fit in lifestyle/schedule/living conditions ; and 4 ) additional language s ( e.g. , Spanish ) . Five themes related to reinforcing factors were : 1 ) communication with healthcare providers ; 2 ) individual-tailored information visualization ; 3 ) social networking ; 4 ) individual-tailored information quality ; and 5 ) improvement in quality of life . DISCUSSION AND CONCLUSION Usability evaluation in a real-world setting enabled us to measure users ' actual experiences when interacting with the app during their everyday lives . Our work highlights the importance of using mobile technology for persons living with HIV , specifically those with low income/housing instability , and adds to the body of literature on the potential for implementation and dissemination of symptom self-management strategies through a mobile platform |
10,737 | 31,964,366 | Different invitation methods may be more effective for different groups of patients based on their ethnicity and gender .
This review also finds that uptake varies significantly by GP practice , which could be due either to unidentified practice -level factors or deprivation . | The NHS Health Check ( NHSHC ) is a risk assessment for those aged 40–74 without a pre-existing condition in Engl and , with the aim of preventing stroke , kidney disease , heart disease , type 2 diabetes and dementia .
Uptake has been lower than anticipated .
Ensuring that a high percentage of eligible patients receive a NHSHC is key to optimising the clinical and cost effectiveness of the programme .
The aim of this systematic review is to highlight interventions and invitation methods that increase the uptake of NHSHCs , and to identify whether the effectiveness of these interact with broader patient and context ual factors . | OBJECTIVE To test the efficacy of interventions based on the question -behavior effect in promoting the adoption of disease prevention behaviors . DESIGN In Study 1 , adults from the general public were r and omly allocated to complete a question naire about health checks ( question -behavior effect condition ) or not ( control ) and later received an invitation to attend for screening . In Study 2 , health care professionals were r and omly allocated to complete a question naire about influenza vaccination or not and later had the opportunity to receive a vaccination . MAIN OUTCOME MEASURES We objective ly assessed health check attendance ( Study 1 ) and influenza vaccination ( Study 2 ) . RESULTS In Study 1 , intention-to-treat analyses indicated that health check attendance was significantly higher in the question -behavior effect condition ( 68.3 % ) compared with the control condition ( 53.5 % ) . In Study 2 , intention-to-treat analyses indicated that influenza vaccination was significantly higher among participants in the question -behavior effect condition ( 42.0 % ) compared with the control condition ( 36.3 % ) , and this effect persisted after controlling for demographic variables . Explanatory analyses indicated that the effects in both studies were attributable to completing rather than merely receiving the question naire and were stronger for those with positive attitudes or intentions about the target behavior . CONCLUSION The question -behavior effect represents a simple , cost-effective means to increase disease prevention behaviors among the general public and health professionals . Implication s for promoting health behaviors are discussed Background The National Health Service Health Check ( NHS HC ) is a population level public health programme . It is a primary prevention initiative offering cardiovascular risk assessment and management for adults aged 40–74 years ( every five years ) . It was design ed to reduce the incidence of major vascular disease events by preventing or delaying the onset of diabetes , heart and kidney disease , stroke and vascular dementia . Effectiveness of the programme has been modelled on a national uptake of 75 % however in 2012/13 uptake , nationally , was 49 % . Ensuring a high percentage of those offered an NHS HC actually receive one is key to optimising the clinical and cost effectiveness of the programme . Methods A pragmatic quasi-r and omised controlled trial was conducted in four general practitioner practice s in Medway , Engl and with r and omisation of 3511 patients . The aim was to compare attendance at the NHS HC using the st and ard national invitation template letter ( control ) compared to an enhanced invitation letter using insights from behavioural science ( intervention ) . The intervention letter includes i ) simplification - reducing letter content for less effortful processing ii ) behavioural instruction - action focused language iii ) personal salience - appointment due rather than invited and iv ) addressing implementation intentions with a tear off slip to record the date , time and location of the appointment . Logistic Regression explored the association between control and intervention group and attendance at a health check . Results 29.3 % of patients who received the control letter and 33.5 % of those who received the intervention letter attended their NHS HC ( adjusted odds ratio 1.26 , 95 % confidence interval 1.09–1.47 , p < 0.01 ) . This was an absolute difference in uptake of 4.2 percentage points for those receiving the intervention letter . Conclusions An invitation letter applying behavioural insights was more effective than the existing national template letter at encouraging attendance at an NHS HC . Making small , no cost behaviourally informed changes to letter invitations can improve uptake of the NHS HC . Further research is required to replicate the effect with more robust methodology and powered for sub-group analysis including socio-economic status . Trial Registration Current Controlled Trials IS RCT N66757664 , date of registration 28/3/2014 Abstract Background Uptake of health checks for cardiovascular risk assessment in primary care in Engl and is lower than anticipated . The question -behavior effect ( QBE ) may offer a simple , scalable intervention to increase health check uptake . Purpose The present study aim ed to evaluate the effectiveness of enhanced invitation methods employing the QBE , with or without a financial incentive to return the question naire , at increasing uptake of health checks . Methods We conducted a three-arm r and omized trial including all patients at 18 general practice s in two London boroughs , who were invited for health checks from July 2013 to December 2014 . Participants were r and omized to three trial arms : ( i ) St and ard health check invitation letter only ; ( ii ) QBE question naire followed by st and ard invitation letter ; or ( iii ) QBE question naire with offer of a financial incentive to return the question naire , followed by st and ard invitation letter . In intention to treat analysis , the primary outcome of completion of health check within 6 months of invitation , was evaluated using a p value of .0167 for significance . Results 12,459 participants were r and omized . Health check uptake was evaluated for 12,052 ( 97 % ) with outcome data collected . Health check uptake within 6 months of invitation was : st and ard invitation , 590 / 4,095 ( 14.41 % ) ; QBE question naire , 630 / 3,988 ( 15.80 % ) ; QBE question naire and financial incentive , 629 / 3,969 ( 15.85 % ) . Difference following QBE question naire , 1.43 % ( 95 % confidence interval −0.12 to 2.97 % , p = .070 ) ; following QBE question naire and financial incentive , 1.52 % ( −0.03 to 3.07 % , p = .054 ) . Conclusions Uptake of health checks following a st and ard invitation was low and not significantly increased through enhanced invitation methods using the QBE Background NHS Health Check is a primary prevention programme offering cardiovascular disease ( CVD ) risk assessment to adults in Engl and aged 40–74 . Uptake remains a challenge and invitation method is a strong predictor of uptake . There is evidence of low uptake when using invitation letters . Telephone invitations might increase uptake , but are not widely used . We explored the potential to improve uptake through personalising letters to patient ’s CVD risk , and to compare this with generic letters and telephone invitations . Methods HEalth Check TRial ( HECTR ) was a three-arm r and omised controlled trial in nine general practice s in Staffordshire ( UK ) . Eligible patients were r and omised to be invited to a NHS Health Check using one of three methods : st and ard letter ( control ) ; telephone invitation ; letter personalised to the patient ’s CVD risk . The primary outcome was attendance/non-attendance . Data were collected on a range of patient- and practice -level factors ( e.g. , patient socio-demographics , CVD risk , practice size , Health Checks outside usual working hours ) . Multi-level logistic regression estimated the marginal effects to explore whether invitation method predicted attendance . Invitation costs were collated from practice s to estimate cost benefit . Results In total , 4614 patients were included in analysis ( mean age 50.2 ± 8.0 yr . ; 52.4 % female ) . Compared with patients invited by st and ard letter ( 30.9 % ) , uptake was significantly higher in those invited by telephone ( 47.6 % , P < .001 ) , but not personalised letter ( 31.3 % , p = .812 ) . In multi-level analysis , compared with the st and ard letter arm , likelihood of attendance was 18 percentage points higher in the telephone arm and 4 percentage points higher in the personalised letter arm . The effect of telephone calls appeared strongest in patients who were younger and had lower CVD risk . We estimated per 1000 patients invited , risk-personalised letters could result in 40 additional attended Health Checks ( at no extra cost ) and telephone invitations could result in 180 additional Health Checks at an additional cost of £ 240 . Conclusions Telephone invitations should be advocated to address the substantial deficit between current and required levels of NHS uptake , and could be targeted at younger and lower CVD risk adults . Risk-personalised letters should be explored further in a larger sample of high risk individuals . Trial registration Registration number : IS RCT N15840751 date of registration : 24/10/2017 Background The National Health Service ( NHS ) in Engl and introduced a population -wide programme for cardiovascular disease ( CVD ) prevention in 2009 , known as NHS Health Checks . This research aim ed to measure the cardiovascular risk management and cardiovascular risk factor outcomes of the health check programme during six years ’ follow-up . Methods and findings A controlled interrupted time series study was conducted . Participants were registered with general practice s in the Clinical Practice Research Data link ( CPRD ) in Engl and and received health checks between 1 April 2010 and 31 December 2013 . Control participants , who did not receive a health check , were matched for age , sex , and general practice . Outcomes were blood pressure , body mass index ( BMI ) , smoking , and total cholesterol ( TC ) and high-density lipoprotein cholesterol ( HDL ) . Analyses estimated the net effect of health check by year , allowing for the underlying trend in risk factor values and baseline differences between cases and controls , adjusting for age , sex , deprivation , and clustering by general practice . There were 127,891 health check participants and 322,910 matched controls . Compared with controls , health check participants had lower BMI ( cases mean 27.0 , SD 4.8 ; controls 27.3 , SD 5.6 , Kg/m2 ) , systolic blood pressure ( SBP ) ( cases 129.0 , SD 14.3 ; controls 129.3 , SD 15.0 , mm Hg ) , and smoking ( 21 % in health check participants versus 27 % in controls ) , but total and HDL cholesterol were similar . Health check participants were more likely to receive weight management advice ( adjusted hazard ratio [ HR ] 5.03 , 4.98 to 5.08 , P < 0.001 ) , smoking cessation interventions ( HR 3.20 , 3.13 to 3.27 , P < 0.001 ) , or statins ( HR 1.24 , 1.21 to 1.27 , P < 0.001 ) . There were net reductions in risk factor values up to six years after the check for BMI ( −0.30 , −0.39 to −0.20 Kg/m2 , P < 0.001 ) , SBP ( −1.43 , −1.70 to −1.16 mm Hg , P < 0.001 ) , and smoking ( 17 % in health check participants versus 25 % in controls ; odds ratio 0.90 , 0.87 to 0.94 , P < 0.001 ) . The main study limitation was that residual confounding may be present because r and omisation was not employed ; health check – associated measurement introduced differential recording that might cause bias . Conclusions Our results suggest that people who take up a health check generally have lower risk factor values than controls and are more likely to receive risk factor interventions . Risk factor values show net reductions up to six years following a health check in BMI , blood pressure , and smoking , which may be of public health importance The NHS Health Check ( NHS HC ) is a cardiovascular risk assessment to prevent cardiovascular disease . Public Health Engl and ( PHE ) wants to increase uptake . We explored the impact of behaviourally informed invitation letters and pre-notification and reminder SMS on uptake of NHS HCs . Patients at 28 General Practice s in the London Borough of Southwark who were eligible to receive an NHS HC between 1st November 2013 and 31st December 2014 were included . A double-blind r and omised controlled trial with a mixed 2 ( pre-notification SMS – yes or no ) × 4 ( letter – national template control , open-ended , time-limited , social norm ) × 2 ( reminder SMS – yes or no ) factorial design was used . The open-ended letter used simplification , behavioural instruction and a personalised planning prompt for patients to record the date and time of their NHS HC . The time-limited letter was similar but stated the NHS HC was due in a named forthcoming month . The social norms letter was similar to the open-ended letter but included a descriptive social norms message and testimonials from local residents and no planning prompt . The outcome measure was attendance at an NHS HC . Data for 12 , 244 invites were analysed . Uptake increased in almost all letter and SMS combinations compared to the control letter without SMS ( Uptake 18 % ) , with increases of up to 12 percentage points for the time-limited letter with pre-notification and reminder ( Uptake 30 % ; Adjusted Odds Ratio AOR 1.86 ; 95 % CI 1.45–2.83 ; p < 0.00 ) ; 10 percentage points for the open-ended letter with reminder ( Uptake 27 % ; AOR 1.68 ; 95 % CI 1.31–2.17 ; p < 0.00 ) and a 9 percentage point increase using the time-limited letter with reminder ( Uptake 27 % ; AOR 1.61 ; 95 % CI 1.25–2.10 ; p < 0.00 ) . The reminder SMS increased uptake for all intervention letters . The pre-notification did not add to this effect . This large r and omised controlled trial adds support to the evidence that small , low cost behaviourally informed changes to letter-based invitations can increase uptake of NHS HCs . It also provides novel evidence on the effect of SMS reminders and pre-notification on NHS HC attendance . Retrospectively Registered ( 24/01/2014 ) IS RCT N36027094 Background The NHS Health Check ( NHSHC ) is a national programme for the prevention of non-communicable diseases . Patients aged 40–74 without an existing cardiovascular-related condition should be invited quinquennially . Uptake is lower than anticipated . We assessed the impact on uptake of two new behaviourally-enhanced leaflets ( with the current national leaflet as a control ) , enclosed with the invitation letter : the first trial on the leaflet . Methods A double-blind three-armed r and omized controlled trial was conducted . The new leaflets were shorter ( two pages , instead of four ) ; one was loss-framed ( ‘ do n’t miss out ’ ) and the other was gain-framed ( ‘ make the most of life ’ ) . The participants were patients from 39 practice s in Lewisham and 17 practice s in NE Lincolnshire , who were allocated to interventions using a r and om-number generator and received one of the leaflets with their invitation letter from April – September 2018 . The outcome measure was uptake of an NHSHC by November 2018 . The trial was powered to detect a 2 % effect . Results Uptake was 17.6 % in the control condition ( n = 3677 ) , 17.4 % in the loss-framed condition ( n = 3664 ) , and 18.2 % in the gain-framed condition ( n = 3697 ) . Leaflet type was not a significant predictor of NHSHC uptake in a logistic regression that controlled for demographic variables , with GP practice as a r and om effect . Statistically significant predictors of uptake included location ( higher uptake in Lewisham ) , age ( increased age was associated with increased attendance ) and sex ( higher uptake in females ) . The Bayes Factor comparing the null to a hypothesis of differences between conditions was 416 , which is extreme evidence in favour of the null hypothesis . Conclusion There was no evidence for a meaningful effect of either a loss-framed or gain-framed behaviourally-informed leaflet type on uptake , which is surprising , given that behaviourally informed letters have improved uptake of NHSHCs . It is possible that people do not pay attention to leaflets that are enclosed with letters , or that the leaflet continues to support informed decision-making but this does not affect uptake . Trial registration Clinical trials.gov , NCT03524131 . Registered May 14 , 2018 . Retrospectively registered BACKGROUND Uptake of NHS Health Checks ( NHSHCs ) is sub-optimal . This study aim ed to increase their uptake using behaviourally informed invitation letters . METHOD Patients registered with 6 general practice s in Northamptonshire , Engl and who were eligible for an NHSHC between 10 February 2014 and 31 January 2015 were r and omized monthly , using a r and om number generator , to three trial arms : control ( st and ard invitation ) , sunk costs ( re sources already allocated ) and counterargument ( against common barriers to attendance ) . The outcome measure was uptake of NHSHC by 12 weeks after 31 January . RESULTS In total , 6331 patients were r and omized . After exclusions , due to in eligibility for the NHSHC , data were analysed for N = 6313 patients : N = 2123 control ; N = 2085 counterargument ; N = 2105 sunk costs . Overall , 2364 ( 37.45 % ) patients attended an NHSHC . Both intervention letters increased uptake compared to control , by 5.46 % using counterargument ( adjusted odds ratio ( AOR ) 1.32 , CI 1.162 - 1.51 , p < 0.001 ) and 4.33 % using sunk costs ( AOR 1.246 , CI 1.10 - 1.42 , p < 0.001 ) , with no significant difference between the two . CONCLUSION Behaviourally informed invitation letters , containing sunk costs or counterargument messages , can improve the uptake of NHSHCs . The trial was registered with the International St and ard R and omised Controlled Trial Registration Number Scheme ( IS RCT N57110614 ) |
10,738 | 25,860,499 | Unstable footwears were shown to immediately alter the stability in gait during daily-life activities .
The center of body pressure is moved posteriorly with a consequent posterior displacement of the upper part of body in order to regain an appropriate body balance , and these postural changes are associated with an overall increase in the activity of lumbar erector spine muscles , as well as certain lower limb muscles .
Current literature provides enough cues to conclude for a beneficial role of MBT shoes in the postural and proprioceptive recovery , but from the same literature can not be drown clear and appropriate guidance to determine more in detail their indication for specific pathological conditions or for particular phases of the musculoskeletal recovery process | The aim of this review is to collect and discuss the current best evidence published in literature about the effect of the Masai Barefoot Technology(MBT ) shoes on gait and muscle activation and try to draw conclusions on the possible benefits . | PURPOSE The purpose s of this study were to assess a ) the effectiveness of Masai Barefoot Technology ( MBT ) shoe in reducing knee pain in persons with knee osteoarthritis ( OA ) and ( b ) changes in balance , ankle and knee ROM , and ankle strength compared with a high-end walking shoe for 12 wk . METHODS The research design was a r and omized controlled trial ( 123 subjects , knee OA ) . Subjects were r and omized to a MBT ( N = 57 ) or a control shoe ( N = 66 ) . A Western Ontario and McMaster Universities ( WOMAC ) OA index , BMI , balance , active ROM , and ankle torque were quantified at week 0 , 3 , 6 , 9 , and 12 . Two- sample t-tests were done for between-group comparisons . RESULTS There was no significant difference between groups in total pain score . A significant reduction over the 12-wk period was found for both shoe conditions ( -42/500 or 25.6 % MBT , -46.2 or 27.1 % control ) . There was no significant group difference in pain during walking ( t = -1.09 , P = 0.28 ) . Pain during walking was significantly reduced by 5.2/100 mm in the MBT and 9.7/100 mm in the control group . Total pain showed a significant reduction for the MBT -27.4/500 ( -16.6 % ) and the control group -28.9/500 ( -17.0 % ) between baseline and week 3 . Between week 3 and 6 , there was a significant reduction for the MBT group only ( -27.2/500 or -20.0 % ) . There was a significant increase in the static balance between baseline and 12 wk in the MBT group only , although the difference between groups was not significant . DISCUSSION The results indicate that special shoe interventions can reduce pain in subjects with moderate knee OA Background Research es on the results of surgical treatment of thoracolumbar spine fractures are infrequent . The aim of this study was to determine midterm outcomes of surgical treatment of these fractures in a prospect i ve survey . Methods A case series study on pediatric patients with the diagnosis of thoracic and /or lumbar vertebral fractures was conducted over a ten-year period . Surgically treated patients were evaluated in the follow-up period , based on back pain , independent function , neurological status , and radiographic indices . Results There were 102 pediatric individuals , 61 boys and 41 girls , aged 3–17 years ( mean 12 years of age ) with thoracic and /or lumbar spinal fractures . Motor vehicle accident was the most common mechanism of injury ( 45.0 % ) . L1 was the most frequent level of fractured vertebra ( 24.4 % ) , and pelvic fracture was the most common associated orthopedic injury ( 21.5 % ) . Totally , 20 patients underwent surgery , but only fifteen ( 14 boys and one girl ) participated in follow-up ( mean 49 months ; range 12–81 months ) . Posterior spinal fusion and instrumentation was accomplished in 12 cases . Three patients were operated by anterior approach and fusion followed by posterior fusion and instrumentation because of delay in diagnosis . There were no major perioperative complications . Two cauda equina syndromes and two incomplete spinal cord injuries improved back to normal . Five cases ( 33.3 % ) reported occasional back pain , and all patients were functionally independent . Radiographic indices improved significantly . Conclusions Spinal fusion and instrumentation in pediatric patients with unstable thoracolumbar vertebral fractures with or without spinal cord injuries have favorable radiographic and functional outcomes BACKGROUND To compare kinematics , kinetics and muscle activity during st and ing and walking for healthy subjects using an unstable test shoe ( Masai Barefoot Technology , MBT ) and a stable control shoe . METHODS Eight subjects volunteered for this study . During quiet st and ing , center of pressure excursion and muscle activity were determined . During walking , lower extremity kinematics , kinetics , and muscle electromyographic ( EMG ) signals were determined . Data were collected for the two shoe conditions after a 2week accommodation period . Statistics included repeated measures ANOVAs ( alpha = 0.05 ) and post hoc tests where appropriate . FINDINGS During quiet st and ing , the center of pressure excursion was significantly and substantially greater in the unstable compared to the control shoe . Electromyographic intensity increased in the unstable test shoe for all tested muscles , but only significantly for the tibialis anterior . During locomotion , kinematics were similar in the two shoe conditions except for the initial plantar-dorsiflexion , which showed a significant more dorsiflexed position during the first half of stance in the unstable test shoe compared to the stable control shoe . The angular impulses did not show any significant differences between the two shoe conditions for all three joints but some trends towards a reduction for the knee and hip joint . There were no significant differences in electromyographic activities between the control and the unstable shoe . However , several muscles showed some trends . INTERPRETATION The unstable shoe produced changes and trends in kinematic , kinetic and electromyographic characteristics that seemed to be advantageous for the locomotor system . Further studies should investigate muscle strength , dynamic stability , pain reduction for arthritic knees and injury prevention for high performance athletes when using the unstable shoes Proprioceptive training has been shown to reduce the incidence of ankle sprains in different sports . It can also improve rehabilitation after anterior cruciate ligament ( ACL ) injuries whether treated operatively or nonoperatively . Since ACL injuries lead to long absence from sports and are one of the main causes of permanent sports disability , it is essential to try to prevent them . In a prospect i ve controlled study of 600 soccer players in 40 semiprofessional or amateur teams , we studied the possible preventive effect of a gradually increasing proprioceptive training on four different types of wobble-boards during three soccer seasons . Three hundred players were instructed to train 20 min per day with 5 different phases of increasing difficulty . The first phase consisted of balance training without any balance board ; phase 2 of training on a rectangular balance board ; phase 3 of training on a round board ; phase 4 of training on a combined round and rectangular board ; phase 5 of training on a so-called BABS board . A control group of 300 players from other , comparable teams trained “ normally ” and received no special balance training . Both groups were observed for three whole soccer seasons , and possible ACL lesions were diagnosed by clinical examination , KT-1000 measurements , magnetic resonance imaging or computed tomography , and arthroscopy . We found an incidence of 1.15 ACL injuries per team per year in the control group and 0.15 injuries per team per year in the proprioceptively trained group ( P<0.001 ) . Proprioceptive training can thus significantly reduce the incidence of ACL injuries in soccer players The incidence of Achilles tendinopathy is very high in young female gymnasts ( 17.5 % ) . According to literature , ecography screenings show the tendons thickening , but at the same time it does not reveal a direct link to the clinical picture . The neovessels are involved in the pathophysiological process of Achilles tendinopathy . For this reason , we wanted to verify there between perfusion tendon values and the type of sport activity . We performed a clinical observational study monitoring the oximetry of the Achilles tendon and the epidemiological data of 52 elite female ( artistic and rhythmic ) gymnasts versus 21 age-matched controls . Analyzing the main limb , we revealed statistically higher oximetry values in the artistic gymnasts group ( 69.5 % ) compared to the rhythmic gymnasts group ( 67.1 % ) ( t = 2.13 ; p = 0.01 ) and the sedentary group ( 66.2 % ) ( t = 2.70 ; p = 0.004 ) , but we did not find any differences between rhythmic gymnasts group and the sedentary group ( t = 0.68 ; p = 0.24 ) . The multiple logistic regression model highlighted that the oximetry value of the main limb is not influenced by age , knowledge of the main limb , years of general and gymnastic sports activity ( p > 0.05 ) . We discovered an increase of Achilles tendon perfusion in the main limb in the artistic gymnast group . We hypothesize that specific figures of artistic sports activity are responsible for muscle overload and gastrocnemius-soleus group and , at the same time , these figures cause hyperperfusion of the tendon . Prospect i ve longitudinal studies could explain if this could become a predictive sign of the next Achilles tendinopathy onset Objective : The objectives of this study were to assess the effect of unstable s and als on ( 1 ) low back pain ( LBP ) in golfers with undiagnosed moderate LBP , ( 2 ) static and dynamic balance , and ( 3 ) golf performance . Design : This was a 6-week prospect i ve study where subjects were r and omized to a control group and an intervention group . Setting : Baseline measurements were recorded in the Human Performance Laboratory . Participants : Forty male golfers with nonspecific moderate LBP . Intervention : The intervention group wore unstable shoes for 6 weeks , and the control group wore their regular golf shoes . Main Outcome Measures : Low back pain , timed balance , and golf performance were assessed at baseline and at 6 weeks . Changes were compared through independent sample s t tests . Results : ( 1 ) There was a significant difference between groups in the change of perceived LBP scores in the laboratory ( test group : −17.5/100 mm , control : −3.6/100 mm ) and in the comparison of the first week entries to the last week entries recorded in logbooks ( test group : −10.7/100 mm , control group : + 2.6/100 mm ) . ( 2 ) There was no significant change in the static or dynamic balance times . ( 3 ) There was no significant change in golf performance between the intervention and control groups . Conclusion : The results indicate that unstable s and als can be used to reduce moderate lower back pain in this population of golfers without negatively affecting performance BACKGROUND The age-associated loss of physical function engenders gait patterns which jeopardise the knee and hip to osteoarthritis . Masai Barefoot Technology ( MBT ) shoes have been shown to provide a facility to address specific needs for load modification in terms of musculoskeletal disease prevention in people with restricted proprioceptive or strength abilities . Therefore , a readjustment of lower extremity joint loading profiles in the elderly was hypothesised when using this type of footwear . AIM The aim of this study was to evaluate the effects of MBT shoes on gait kinematics and kinetics in both an elderly and young cohort during walking . DESIGN This was a cross-sectional study . SETTING A 3-dimensional motion analysis laboratory . POPULATION Eleven healthy elderly men and 11 healthy young men . METHODS A conventional sport shoe served as control situation to MBT . Subjects were advised to walk eight trials per shoe at a criterion speed of 1.5 ± 0.1 m·s(-1 ) in block-r and omised order . Peak joint angles , moments and powers at the ankle , knee and hip were calculated through an inverse dynamic model . Data were compared by a two-way repeated measure ANOVA ( α=0.05 ) . RESULTS MBT reduced external ankle joint moments and powers independent of age . At the hip , MBT footwear led to decreases in external hip flexion moments and concentric hip power output during early and late stance . Herein , no age-by-condition effects were present . Moreover , MBT reduced external knee flexion moments and concentric knee extensor powers at loading response , with the greater changes observed in the elderly . Additionally , a main effect of condition showing a general decrease in the MBT situation , but no interaction effect was noted for first peak external knee adduction moments . CONCLUSION These results suggest that MBT shoes diminish joint loads among age groups , whereas compared to young adults , the elderly , in particular , benefited from MBT footwear with regard to relief stress on the knee joint region . CLINICAL REHABILITATION IMPACT Based on these findings , the use of MBT shoes may attenuate the risk of developing knee and hip osteoarthritis in the elderly and may play an important role regarding pain avoidance and /or disability Abstract Purpose Economic crisis time gives to efficient procedures an important role in healthy system . Total hip replacement is a common bilateral orthopedic procedure , but there exists an important controversy to perform it in single or two stages . Our aim is to report our clinical and radiological short-term complications of bilateral uncemented total hip arthroplasty in a single time . Material s and methods We have retrospectively review ed the patients treated between 2000 and 2011 in our center by bilateral uncemented total hip replacement in a single time . We have review ed the medical history and analyzed by age , diagnosis and ASA parameters related to the procedure , hospital stay , transfusion requirements and clinical complications . Radiological evaluation was made with anteroposterior hip radiograph evaluation ( acetabular radiolucencies and stem migration ) . Functional assessment was carried out by the Merle D’Aubigné score . Results Seventeen patients with mean age of 47.4 ( 18–68 ) years were review ed with a mean follow-up of 44.3 ( 6–172 ) months . ASA distribution : 29.4 % grade I ; 52.9 % grade II and 17.6 % grade III . Merlé D’Aubigné score improved from 11.01 to 16.45 . Hospital stay was 6 days . Transfusion requirements were two hematic concentrates for each patient . Two external popliteal sciatic nerve neurapraxias fully recovered at follow-up . Radiological results showed one case of axial migration . Conclusions With proper patient selection and multidisciplinary team , the bilateral uncemented total hip arthroplasty in a single time has low complication rates . Our results could be used in the development of future r and omized controlled trials or prospect i ve cohort studies .Level of evidence IV BACKGROUND The Masai barefoot technology is used as a treatment option within the field of physical therapy to treat leg , back or foot problems . No information , however , is available on how Masai barefoot technology changes gait or muscle activity . METHODS Twelve healthy subjects underwent 3D gait analysis with simultaneously collecting surface electromyography data of the leg muscles when walking with regular shoes and with Masai barefoot technology-shoes . Before data collection , subjects were trained in Masai barefoot technology . A within-subjects study - design compared walking with regular shoes and Masai barefoot technology . FINDINGS With Masai barefoot technology , subjects walked slower with smaller steps . Movement pattern at the ankle showed major changes with increased dorsiflexion angle at initial contact followed by a continuous plantarflexion movement until terminal stance phase . With changed kinematics , alterations in the activity of tibialis anterior and gastrocnemius muscles could be observed . Smaller differences in movement and muscle activity were seen at knee and hip level . INTERPRETATION Masai barefoot technology has never been documented in detail concerning changes in movement pattern or muscle activity . This study showed that Masai barefoot technology changes movement patterns , especially at the ankle , and increases muscle activity . It may therefore be a useful training method for strengthening the muscle groups of the lower leg . Knee flexion and electromyographic characteristics around the knee joint are slightly increased and need to be considered in patients with knee problems . Our findings provide critical detailed information on changes compared to walking in regular shoes , but the clinical relevance of those changes remains to be determined The effects of two training programs on movement discrimination ability , at the ankle and knee , were assessed from the left and right lower limbs of forty-four football players . All players in three Under 18 Victorian Football League ( VFL ) squads were allocated to either wobble board training , jump l and ing training , or no-training conditions . Pre-tests to assess discrimination of extent for active movements made while st and ing were carried out on both ankles and knees of all subjects , using an automated device to accurately set the different movement stop points . Five distances were used , between 10.5 degrees and 14.5 degrees from horizontal for ankle inversion , and between 30.3 degrees and 31.7 degrees from vertical for knee flexion . From a series of 50 inversion movements and 50 knee flexion movements , matrices of absolute judgement by actual movement extent were produced . Non-parametric signal detection analysis was applied to the discrimination score . All subjects were retested after eight weeks . Improvement in discrimination of ankle movements into inversion from pre-test ( 0.65 ) to post test ( 0.70 ) for the wobble board trained group was significantly larger than the change in the jump-l and ing trained and the untrained groups ( Jump L and ing : Pretest : 0.64 to Post-test : 0.64 and Control ; Pretest : 0.63 to Post-test : 0.64 ) . Discrimination of knee flexion movements improved significantly from pre-test to post-test in all three groups . These data demonstrate that wobble board training can improve discrimination of discrete ankle inversion movements , an effect interpreted as enabling greater accuracy in the making of inversion movements in foot preparation prior to ground contact Background : Unstable shoes , which have recently become popular , cl aim to provide additional physiological and biomechanical advantages to people who wear them . Alterations in postural stability have been shown when using the shoe after training . However , the immediate effect on muscle activity when walking in unstable shoes for the first time has not been investigated . Objective : To evaluate muscle activity and temporal parameters of gait when wearing Masai Barefoot Technology shoes ® for the first time compared to the subject ’s own regular trainer shoes . Study Design : A pilot repeated- measures quasi control trial . Method : Electromyographic measurements of lower leg muscles ( soleus , medial gastrocnemius , lateral gastrocnemius , tibialis anterior , peroneus longus , rectus femoris , biceps femoris and gluteus medius ) were measured in 15 healthy participants using Masai Barefoot Technology shoes and trainer shoes over a 10-m walkway . Muscle activity of the third and sixth steps was used to study the difference in behaviour of the muscles under the two shoe conditions . Temporal parameters were captured with footswitches to highlight heel strike , heel lift and toe off . Paired sample s t-test was completed to compare mean muscle activity for Masai Barefoot Technology and trainer shoes . Results : Indicated that the use of Masai Barefoot Technology shoes increased the intensity of the magnitude of muscle activity . While this increase in the activity was not significant across the subjects , there were inter-individual differences in muscle activity . This variance between the participants demonstrates that some subjects do alter muscle behaviour while wearing such shoes . Conclusion : A more rigorous and specific assessment is required when advising patients to purchase the Masai Barefoot Technology shoe . Not all subjects respond positively to using unstable shoes , and the point in time when muscle behaviour can change is variable . Clinical relevance Use of Masai Barefoot Technology shoe in patient management should be monitored closely as the individual muscle changes and the point in time when changes occur vary between subjects , and evaluation of how a subject responds is not yet clear |
10,739 | 26,938,557 | A high AGE diet increased circulating tumour necrosis factor-alpha and AGEs in all population s. A high AGE diet increased 8-isoprostanes in healthy adults , and vascular cell adhesion molecule-1 ( VCAM-1 ) in patients with diabetes . | Dietary advanced glycation end-products ( AGEs ) form during heating and processing of food products and are widely prevalent in the modern Western diet .
Recent systematic review s indicate that consumption of dietary AGEs may promote inflammation , oxidative stress and insulin resistance .
Experimental evidence indicates that dietary AGEs may also induce renal damage , however , this outcome has not been considered in previous systematic review s. The purpose of this review was to examine the effect of consumption of a high AGE diet on biomarkers of chronic disease , including chronic kidney disease ( CKD ) , in human r and omized controlled trials ( RCTs ) . | Background —LDL modification by endogenous advanced glycation end products ( AGEs ) is thought to contribute to cardiovascular disease of diabetes . It remains unclear , however , whether exogenous ( diet-derived ) AGEs influence glycoxidation and endothelial cell toxicity of diabetic LDL . Methods and Results —Twenty-four diabetic subjects were r and omized to either a st and ard diet ( here called high-AGE , HAGE ) or a diet 5-fold lower in AGE ( LAGE diet ) for 6 weeks . LDL pooled from patients on HAGE diet ( Db-HAGE-LDL ) was more glycated than LDL from the LAGE diet group ( Db-LAGE-LDL ) ( 192 versus 92 AGE U/mg apolipoprotein B ) and more oxidized ( 5.7 versus 1.5 nmol malondialdehyde/mg lipoprotein ) . When added to human endothelial cells ( ECV 304 or human umbilical vein endothelial cells ) , Db-HAGE-LDL promoted marked ERK1/2 phosphorylation ( pERK1/2 ) ( 5.5- to 10-fold of control ) in a time- and dose-dependent manner compared with Db-LAGE-LDL or native LDL . In addition , Db-HAGE-LDL stimulated NF-κB activity significantly in ECV 304 and human umbilical vein endothelial cells ( 2.3-fold above baseline ) in a manner inhibitable by a MEK inhibitor PD98059 ( 10 μmol/L ) , the antioxidant N-acetyl-l-cysteine , NAC ( 30 mmol/L ) , and the NADPH oxidase inhibitor DPI ( 20 μmol/L ) . In contrast to Db-LAGE-LD and native LDL , Db-HAGE-LDL induced significant soluble vascular cell adhesion molecule-1 production ( 2.3-fold ) , which was blocked by PD98059 , NAC , and DPI . Conclusions —Exposure to daily dietary glycoxidants enhances LDL-induced vascular toxicity via redox-sensitive mitogen-activated protein kinase activation . This can be prevented by dietary AGE restriction 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 Reactive advanced glycation end products ( AGEs ) , known to promote diabetic tissue damage , occur endogenously as well as in heated foods and are orally absorbed . The relative contribution of diet-derived AGEs to diabetic nephropathy ( DN ) remains unclear . METHODS We tested a st and ard mouse food ( AIN-93 G ) found to be rich in AGEs ( H-AGE diet ) in parallel with a similar diet that contained six-fold lower AGE content ( L-AGE ) , but equal calories , macronutrients , and micronutrients . Non-obese diabetic mice ( NOD ) with type 1 diabetes ( T1D ) and db/db mice with type 2 diabetes ( T2D ) were r and omly assigned to each formula for either 4 or 11 months , during which time renal parameters and AGE levels were assessed . RESULTS Compared to the progressive DN and short survival seen in NOD mice exposed to long-term H-AGE feeding , L-AGE-fed NOD mice developed minimal glomerular pathology and a modest increase in urinary albumin : creatinine ratio ( p<0.005 ) , and a significantly extended survival ( p<0.0001 ) , consistent with lower serum ( p<0.025 ) and kidney AGEs ( p<0.01 ) . Also , in the 4-month study , and in contrast to the H-AGE-fed mice , L-AGE-fed NOD and db/db mice exhibited low levels of renal cortex TGF beta-1 ( p<0.05 ) , laminin B1 mRNA ( p<0.01 ) and alpha 1 IV collagen mRNA ( p<0.05 ) and protein , in concert with reduced serum and kidney AGEs ( p<0.05 , respectively ) . CONCLUSION Intake of high-level , food-derived AGEs is a major contributor to DN in T1D and T2D mice . Avoidance of dietary AGEs provides sustained protection against DN in mice ; providing the rationale for similar studies in human diabetic patients Dietary advanced glycosylation end products ( AGEs ) have been linked to insulin resistance in db/db(++ ) mice . To test whether dietary AGEs play a role in the progression of insulin resistance in normal mice fed high-fat diets , normal C57/BL6 mice were r and omly assigned to high-fat diets ( 35 % g fat ) , either high ( HAGE-HF group ; 995.4 units/mg AGE ) or low ( by 2.4-fold LAGE-HF group ; 329.6 units/mg AGE ) in AGE content for 6 months . Age-matched C57/BL6 and db/db(++ ) mice fed regular diet ( 5 % g fat , 117.4 units/mg AGE ) served as controls . After 6 months , 75 % of HAGE-HF mice were diabetic and exhibited higher body weight ( P < 0.001 ) , fasting glucose ( P < 0.001 ) , insulin ( P < 0.001 ) , and serum AGEs ( P < 0.01 ) than control mice , while none of the LAGE-HF mice were diabetic despite a similar rise in body weight and plasma lipids . The HAGE-HF group displayed markedly impaired glucose and insulin responses during glucose tolerance tests and euglycemic and hyperglycemic clamps and altered pancreatic islet structure and function compared with those of LAGE-HF mice , in which findings resembled those of control mice . The HAGE-HF group had more visceral fat ( by two- and fourfold ) and more AGE-modified fat ( by two- and fivefold ) than LAGE-HF and control mice , respectively . In the HAGE-HF group , plasma 8-isoprostane was higher ( P < 0.01 ) and adiponectin lower ( P < 0.001 ) than control mice , while in the LAGE-HF group , these were more modestly affected ( P < 0.05 ) . These results demonstrate that the development of insulin resistance and type 2 diabetes during prolonged high-fat feeding are linked to the excess AGEs/advanced lipoxidation end products inherent in fatty diets The augmented consumption of dietary advanced glycation end products ( dAGEs ) has been associated with increased oxidative stress and inflammation , however , there is insufficient information over the effect on insulin resistance . The objective of the present study is to investigate the effect of dAGEs restriction on tumor necrosis factor-α ( TNF-α ) , malondialdehyde , C-reactive protein ( CRP ) , and insulin resistance in DM2 patients . We carried out a r and omized 6 weeks prospect i ve study in two groups of patients : subjects with a st and ard diet ( n = 13 ) , vs low dAGEs ( n = 13 ) . At the beginning and the end of study , we collected anthropometric measurements , and values of circulating glucose , HbA1c , lipids , insulin , serum AGEs , CRP , TNF-α and malondialdehyde . Anthropometric measurements , glucose , and lipids were similar in both groups at base line and at the end of the study . Estimation of basal dAGEs was similar in both groups ; after 6 weeks it was unchanged in the st and ard group but in the low dAGEs group decreased by 44 % ( p<0.0002 ) . Changes in TNF-α levels were different under st and ard diet ( 12.5 ± 14.7 ) as compared with low dAGEs ( −18.36 ± 17.1 , p<0.00001 ) ; changes in malondialdehyde were different in the respective groups ( 2.0 ± 2.61 and −0.83 ± 2.0 , p<0.005 ) no changes were found for insulin levels or HOMA-IR . In conclusion , The dAGEs restriction decreased significantly TNF-α and malondialdehyde levels OBJECTIVE Increased oxidative stress ( OS ) and impaired anti-OS defenses are important in the development and persistence of insulin resistance ( IR ) . Several anti-inflammatory and cell-protective mechanisms , including advanced glycation end product ( AGE ) receptor-1 ( AGER1 ) and sirtuin ( silent mating-type information regulation 2 homolog ) 1 ( SIRT1 ) are suppressed in diabetes . Because basal OS in type 2 diabetic patients is influenced by the consumption of AGEs , we examined whether AGE consumption also affects IR and whether AGER1 and SIRT1 are involved . RESEARCH DESIGN AND METHODS The study r and omly assigned 36 subjects , 18 type 2 diabetic patients ( age 61 ± 4 years ) and 18 healthy subjects ( age 67 ± 1.4 years ) , to a st and ard diet ( > 20 AGE equivalents [Eq]/day ) or an isocaloric AGE-restricted diet ( < 10 AGE Eq/day ) for 4 months . Circulating metabolic and inflammatory markers were assessed . Expression and activities of AGER1 and SIRT1 were examined in patients ’ peripheral blood mononuclear cells ( PMNC ) and in AGE-stimulated , AGER1-transduced ( AGER1 + ) , or AGER1-silenced human monocyte-like THP-1 cells . RESULTS Insulin and homeostasis model assessment , leptin , tumor necrosis factor-α and nuclear factor-κB p65 acetylation , serum AGEs , and 8-isoprostanes decreased in AGE-restricted type 2 diabetic patients , whereas PMNC AGER1 and SIRT1 mRNA , and protein levels normalized and adiponectin markedly increased . AGEs suppressed AGER1 , SIRT-1 , and NAD+ levels in THP-1 cells . These effects were inhibited in AGER1 + but were enhanced in AGER1-silenced cells . CONCLUSIONS Food-derived pro-oxidant AGEs may contribute to IR in clinical type 2 diabetes and suppress protective mechanisms , AGER1 and SIRT1 . AGE restriction may preserve native defenses and insulin sensitivity by maintaining lower basal OS SIRT1 and PPARγ , host defenses regulating inflammation and metabolic functions , are suppressed under chronic high oxidant stress and inflammation ( OS/Infl ) conditions . In diabetes , dietary advanced glycation end products ( dAGEs ) cause OS/Infl and suppress SIRT1 . Herein , we ask whether dAGEs also suppress host defense in adults without diabetes . The relationships between dAGEs and basal SIRT1 mRNA , PPARγ protein levels in mononuclear cells ( MNC ) and circulating inflammatory/metabolic markers were examined in 67 healthy adults aged > 60 years and in 18 subjects , before and after r and om assignment to either a st and ard diet ( regular > 15 AGE Eq/day ) or an isocaloric AGE-restricted diet ( < 10 AGE Eq/day ) for 4 months . Also , the interactions of AGEs and anti-AGE receptor-1 ( AGER1 ) with SIRT1 and PPARγ were assessed in wild type ( WT ) and AGER1-transduced ( AGER1 + ) MNC-like THP-1 cells . We found that dAGE , but not caloric intake , correlated negatively with MNC SIRT1 mRNA levels and positively with circulating AGEs ( sAGEs ) , OS/infl , MNC TNFα and RAGE . Basal MNC PPARγ protein was also lower in consumers of regular vs. AGE-restricted diet . AGE restriction restored MNC SIRT1 and PPARγ , and significantly decreased sAGEs , 8-isoprostanes , VCAM-1 , MNC TNFα and RAGE . Model AGEs suppressed SIRT1 protein and activity , and PPARγ protein in WT , but not in AGER1 + cells in vitro . In conclusion , chronic consumption of high-AGE diets depletes defenses such as SIRT1 and PPARγ , independent of calories , predisposing to OS/Infl and chronic metabolic disease . Restricted entry of oral AGEs may offer a disease-prevention alternative for healthy adults OBJECTIVE High-heat cooking of food induces the formation of advanced glycation end products ( AGEs ) , which are thought to impair glucose metabolism in type 2 diabetic patients . High intake of fructose might additionally affect endogenous formation of AGEs . This parallel intervention study investigated whether the addition of fructose or cooking methods influencing the AGE content of food affect insulin sensitivity in overweight individuals . RESEARCH DESIGN AND METHODS Seventy-four overweight women were r and omized to follow either a high- or low-AGE diet for 4 weeks , together with consumption of either fructose or glucose drinks . Glucose and insulin concentrations — after fasting and 2 h after an oral glucose tolerance test — were measured before and after the intervention . Homeostasis model assessment of insulin resistance ( HOMA-IR ) and insulin sensitivity index were calculated . Dietary and urinary AGE concentrations were measured ( liquid chromatography t and em mass spectrometry ) to estimate AGE intake and excretion . RESULTS When adjusted for changes in anthropometric measures during the intervention , the low-AGE diet decreased urinary AGEs , fasting insulin concentrations , and HOMA-IR , compared with the high-AGE diet . Addition of fructose did not affect any outcomes . CONCLUSIONS Diets with high AGE content may increase the development of insulin resistance . AGEs can be reduced by modulation of cooking methods but is unaffected by moderate fructose intake In renal HEK-293 cells , the dietary Maillard reaction compounds casein-linked Nepsilon-carboxymethyllysine ( CML ) , CML , bread crust ( BC ) , and pronyl-glycine ( a key compound formed in association with the process-induced heat impact applied to bread dough ) all showed activation of p38-MAP kinase . Expression of the C-terminus truncated receptor for advanced glycation end products ( RAGE ) result ed in a reduction of HEK-293-MAP kinase activation . As these findings suggested a RAGE-mediated activating effect of CML , BC , and pronyl-glycine on kidney cellular signal transduction pathways , an in vivo study was performed . Male Wistar rats were subjected to a sham operation ( CTRL , n = 20 ) or to 5/6 nephrectomy ( NX , n = 20 ) . Both groups were r and omized into two subgroups and fed 20 g of a diet containing either 25 % by weight BC or wheat starch ( WS ) . GC-MS analyses of CML , carboxyethyllysine ( CEL ) , and pentosidine revealed increased levels of CML and CEL in the liver but decreased levels of CML in the kidneys of CTRL and NX rats fed the BC diet compared to those on the WS diet . However , urinary levels of CML were also elevated in the CTRL and NX rats on the BC diet , pointing to enhanced excretion of AGEs after BC administration . Although renal insufficiency in the NX rats was reflected by proteinuria , the renal h and ling of CML and , presumably , other AGEs was not impaired Diet is a major environmental source of proinflammatory AGEs ( heat-generated advanced glycation end products ) ; its impact in humans remains unclear . We explored the effects of two equivalent diets , one regular ( high AGE , H-AGE ) and the other with 5-fold lower AGE ( L-AGE ) content on inflammatory mediators of 24 diabetic subjects : 11 in a 2-week crossover and 13 in a 6-week study . After 2 weeks on H-AGE , serum AGEs increased by 64.5 % ( P = 0.02 ) and on L-AGE decreased by 30 % ( P = 0.02 ) . The mononuclear cell tumor necrosis factor-α/β-actin mRNA ratio was 1.4 ± 0.5 on H-AGE and 0.9 ± 0.5 on L-AGE ( P = 0.05 ) , whereas serum vascular adhesion molecule-1 was 1,108 ± 429 and 698 ± 347 ng/ml ( P = 0.01 ) on L- and H-AGE , respectively . After 6 weeks , peripheral blood mononuclear cell tumor necrosis factor-α rose by 86.3 % ( P = 0.006 ) and declined by 20 % ( P , not significant ) on H- or L-AGE diet , respectively ; C-reactive protein increased by 35 % on H-AGE and decreased by 20 % on L-AGE ( P = 0.014 ) , and vascular adhesion molecule-1 declined by 20 % on L-AGE ( P < 0.01 ) and increased by 4 % on H-AGE . Serum AGEs were increased by 28.2 % on H-AGE ( P = 0.06 ) and reduced by 40 % on L-AGE ( P = 0.02 ) , whereas AGE low density lipoprotein was increased by 32 % on H-AGE and reduced by 33 % on L-AGE diet ( P < 0.05 ) . Thus in diabetes , environmental ( dietary ) AGEs promote inflammatory mediators , leading to tissue injury . Restriction of dietary AGEs suppresses these effects When food is heated to high temperatures , the characteristic " browning " generates advanced glycation end products ( AGEs ) . AGEs are associated with an increased risk of cardiovascular disease , diabetes , and other adverse outcomes . Whether dietary AGEs are absorbed and are harmful to human health remains highly controversial . The objective of this study was to compare the effects of a diet high or low in AGEs on endothelial function , circulating AGEs , inflammatory mediators , and circulating receptors for AGEs in healthy adults . A r and omized , parallel-arm , controlled dietary intervention was conducted for 6 wk with 24 healthy adults , aged 50 - 69 y , that compared isocaloric , food-equivalent diets that were prepared at either high or mild temperatures . Peripheral arterial tonometry , serum and urine carboxymethyl-lysine ( CML ) , inflammatory mediators ( interleukin-6 , C-reactive protein , vascular adhesion molecule-1 , and tumor necrosis factor-α receptors I and II ) , soluble receptor for AGEs , and endogenous secretory receptor for AGEs were measured at baseline and after 6 wk of dietary intervention . In the low-AGE diet group , the following changed from baseline to 6 wk ( mean ± SE ) : serum CML from 763 ± 24 to 679 ± 29 ng/mL ( P = 0.03 ) and urine CML from 1.37 ± 1.47 to 0.77 ± 2.01 μg/mL creatinine ( P = 0.02 ) . There were no significant changes in serum and urinary CML concentrations from baseline to follow-up in the high-AGE diet group . A high- or low-AGE diet had no significant impact on peripheral arterial tonometry or any inflammatory mediators after 6 wk of dietary intervention . In healthy middle-aged to older adults , consumption of a diet high or low in AGEs for 6 wk had no impact on endothelial function and inflammatory mediators , 2 precursors of cardiovascular disease Obesity is highly prevalent in Western population s and is considered a risk factor for the development of renal impairment . Interventions that reduce the tissue burden of advanced glycation end-products ( AGEs ) have shown promise in stemming the progression of chronic disease . Here we tested if treatments that lower tissue AGE burden in patients and mice would improve obesity-related renal dysfunction . Overweight and obese individuals ( body mass index ( BMI ) 26 - 39 kg/m(2 ) ) were recruited to a r and omized , crossover clinical trial involving 2 weeks each on a low- and a high-AGE-containing diet . Renal function and an inflammatory profile ( monocyte chemoattractant protein-1 ( MCP-1 ) and macrophage migration inhibitory factor ( MIF ) ) were improved following the low-AGE diet . Mechanisms of advanced glycation-related renal damage were investigated in a mouse model of obesity using the AGE-lowering pharmaceutical , alagebrium , and mice in which the receptor for AGE ( RAGE ) was deleted . Obesity , result ing from a diet high in both fat and AGE , caused renal impairment ; however , treatment of the RAGE knockout mice with alagebrium improved urinary albumin excretion , creatinine clearance , the inflammatory profile , and renal oxidative stress . Alagebrium treatment , however , result ed in decreased weight gain and improved glycemic control compared with wild-type mice on a high-fat Western diet . Thus , targeted reduction of the advanced glycation pathway improved renal function in obesity The biological consequences of chronic consumption of Maillard reaction products ( MRPs ) on renal function in health and renal disease are still incompletely understood . We investigated the metabolic and renal effects of a diet with varying MRP content in healthy and subtotally nephrectomized rats . Male Wistar rats were subjected to sham operation ( control , C , n = 12 ) , or to 5/6 nephrectomy ( 5/6NX , n = 12 ) . Both groups were r and omized into subgroups and pair-fed with either a MRP-poor or -rich diet for six weeks . The diet was prepared by replacing 5 % or 25 % of wheat starch by bread crust ( BC ) . In spite of pair-feeding , the rats on the 25 % BC diet gained more body weight ( C : 183 + /- 6 g ; C + 5 % BC : 197 + /- 7 g ; C + 25 % BC : 229 + /- 6 g [ P < 0.05 ] ; 5/6NX : 165 + /- 10 g ; 5/6NX + 5 % BC : 202 + /- 3 g ; 5/6NX + 25 % BC : 209 + /- 8 g [ P < 0.05 ] ) and had a higher organ weight ( heart , liver , lung , kidney/remnant kidney ) . Bread crust-enriched diet induced proteinuria ( C : 15 + /- 5 mg/24 h ; C + 5 % BC : 19 + /- 4 ; C + 25 % BC : 26 + /- 3 [ P < 0.05 ] ; 5/6NX : 30 + /- 7 mg/24 h ; 5/6NX + 5 % BC : 47 + /- 9 ; 5/6NX + 25 % BC : 87 + /- 19 [ P < 0.01 ] ) and a rise in urinary transforming growth factor beta(1 ) excretion ( C : 0.4 + /- 0.1 ng/24 h ; C + 5 % BC : 0.6 + /- 0.1 ; C + 25 % BC : 1.2 + /- 0.3 ; 5/6NX : 0.5 + /- 0.1 ng/24 h ; 5/6NX + 5 % BC : 0.9 + /- 0.1 ; 5/6NX + 25 % BC : 1.6 + /- 0.2 [ P < 0.01 ] ) . Plasma creatinine or creatinine clearance were not affected significantly . In conclusion , our data suggests that long-term consumption of a diet rich in MRPs may lead to damage of the kidneys Diet-derived advanced glycation end products ( AGEs ) contribute significantly to accumulation of AGEs in renal insufficiency . To test whether modulation of dietary AGEs would impact on progression of chronic renal disease , 5/6 nephrectomy rats were r and omly placed on three diets that differed only in AGEs content ( low AGEs diet ( LAD ) , high AGEs diet ( HAD ) , and st and ard rodent diet ( SRD ) ) for 5 - 13 weeks . Compared with SRD- or HAD-fed rats , LAD-treated animals showed decreased proteinuria and retarded decline of creatinine clearance without alteration of blood pressure . Glomerular volume was reduced by 23 % compared with HAD-fed rats at week 13 ( P<0.001 ) . Renal fibrosis progressed with time in the remnant kidneys from HAD-fed rats . However , LAD-fed animals presented a better-preserved structure of the kidneys . LAD-fed rats demonstrated significantly decreased serum and renal AGEs concentration ( P<0.01 and P<0.01 ) . This was associated with marked decrease of intrarenal advanced oxidation protein products and thiobarbituric acid reactive substances , as well as increase of glutathione peroxidase activity . LAD treatment also downregulated expression of monocyte chemoattractant protein-1 and transforming growth factor-1 and ameliorated macrophage infiltration in the remnant kidney . These results demonstrated that restriction of dietary AGEs intake retards progression of renal fibrosis and dysfunction in the remnant kidney model Advanced glycation end products ( AGEs ) , known promoters of diabetic complications , form abundantly in heated foods and are ingested in bioreactive forms . To test whether dietary AGEs play a role in the progression of insulin resistance , C57/BL/KsJ db/db mice were r and omly placed for 20 weeks on a diet with either a low AGE content ( LAD ) or a 3.4-fold higher content of AGE ( high AGE diet [ HAD ] ) , including (epsilon)N-carboxymethyllysine ( CML ) and methylglyoxal ( MG ) . LAD-fed mice showed lower fasting plasma insulin levels throughout the study ( P = 0.01 ) . Body weight was reduced by approximately 13 % compared with HAD-fed mice ( P = 0.04 ) despite equal food intake . LAD-fed mice exhibited significantly improved responses to both glucose ( at 40 min , P = 0.003 ) and insulin ( at 60 min , P = 0.007 ) tolerance tests , which correlated with a twofold higher glucose uptake by adipose tissue ( P = 0.02 ) . Compared with the severe hypertrophy and morphological disorganization of islets from HAD-fed mice , LAD-fed mice presented a better-preserved structure of the islets . LAD-fed mice demonstrated significantly increased plasma HDL concentrations ( P < 0.0001 ) . Consistent with these observations , LAD-fed mice exhibited twofold lower serum CML and MG concentrations compared with HAD-fed mice ( P = 0.02 ) . These results demonstrate that reduced AGE intake leads to lower levels of circulating AGE and to improved insulin sensitivity in db/db mice BACKGROUND Inflammation is common in patients with chronic renal failure and has been associated with the increased risk for cardiovascular disease ( CVD ) in this condition . Advanced glycoxidation end products ( AGEs ) are among the factors implicated in the inflammatory state of chronic renal failure . METHODS In a cross-sectional study of 189 dialysis patients , we measured circulating levels of C-reactive protein ( CRP ) , tumor necrosis factor-alpha ( TNF-alpha ) , vascular adhesion molecule-1 ( VCAM-1 ) , vascular endothelial growth factor ( VEGF ) , and plasminogen activator inhibitor-1 ( PAI-1 ) to test for possible relationships between them and serum AGE levels . In addition , these parameters were measured in a subgroup of 18 patients with chronic renal failure r and omly assigned to a 4-week diet , either low ( L-AGE ) or high ( H-AGE ) in AGE content . AGEs were measured by means of a monoclonal antibody against epsilonN-carboxymethyllysine . RESULTS At baseline , serum AGE levels , as well as those for CRP , TNF-alpha , VCAM-1 , and VEGF , were markedly elevated , although no correlation was found between AGE levels and the other markers . Dietary AGE modulation result ed in a significant decrease in levels of serum AGEs , CRP , and PAI-1 in the L-AGE group ( approximately 35 % , 44 % , and 17 % , respectively ; P < 0.03 ) , whereas only serum AGE levels increased significantly in the H-AGE group . VCAM-1 and TNF-alpha levels , although similar at baseline , became significantly lower in patients on an L-AGE compared with H-AGE diet ( P < 0.05 ) at the end of the study . CONCLUSION Data from the interventional phase of the study suggest that AGEs have a role in the initiation of the inflammatory state of chronic renal failure , which eventually leads to increased CVD . This finding opens the possibility for using anti-AGE strategies in the prevention and treatment of CVD in patients with chronic renal failure BACKGROUND The modern Western lifestyle is characterized by the consumption of high-heat-treated foods because of their characteristic taste and flavor . However , it has been shown that treating food at high temperatures can generate potentially harmful compounds that promote inflammation and cardiovascular disease in subjects with diabetes . OBJECTIVE The aim of this study was to determine whether high-heat-treated foods also pose a risk for healthy subjects . DESIGN A r and omized , crossover , diet-controlled intervention trial with 62 volunteers was design ed to compare the potential metabolic effects of 2 diets , one that was based on mild steam cooking and another that was based on high-temperature cooking . These 2 diets differed mainly in their contents of Maillard reaction products ( MRPs ) . MRPs were assessed in the diet and in subjects ' feces , blood , and urine sample s , with N(epsilon)-carboxymethyllysine as an indicator of MRPs . Biological indicators of glucose and lipid metabolism as well as oxidative stress were analyzed in subjects after 1 mo on each diet . RESULTS In comparison with the steamed diet , 1 mo of consuming the high-heat-treated diet induced significantly lower insulin sensitivity and plasma concentrations of long-chain n-3 ( omega-3 ) fatty acids and vitamins C and E [ -17 % ( P < 0.002 ) , -13 % ( P < 0.0001 ) , and -8 % ( P < 0.01 ) , respectively ] . However , concentrations of plasma cholesterol and triglycerides increased [ + 5 % ( P < 0.01 ) and + 9 % ( P < 0.01 ) , respectively ] . CONCLUSIONS A diet that is based on high-heat-treated foods increases markers associated with an enhanced risk of type 2 diabetes and cardiovascular diseases in healthy people . Replacing high-heat-treatment techniques by mild cooking techniques may help to positively modulate biomarkers associated with an increased risk of diabetes mellitus and cardiovascular diseases |
10,740 | 27,098,454 | Multicomponent interventions ( SB and other behaviours ) delivered to children from 5 to 12 years old in a non-educational setting appear to favour BMI reduction . | Intervention studies have been undertaken to reduce sedentary behaviour ( SB ) and thereby potentially ameliorate unhealthy weight gain in children and adolescents . | The current review aim ed to systematic ally identify dietary , physical activity and sedentary behaviours in preschool children ( 4 - 6 years of age ) that are prospect ively related to overweight or obesity later in childhood . Prospect i ve studies published between January 1990 and June 2010 were selected from search es in PubMed , EMBASE , PsycINFO , CINAHL and Cochrane Library . Studies examining the prospect i ve association between at least one relevant behaviour measured during preschool period ( children aged 4 - 6 years at baseline ) in relation to at least one anthropometric measurement at follow-up ( age < 18 years ) were included . Harvest plots were used to summarize the results and draw conclusions from the evidence . Of the 8,718 retrieved papers , 23 papers reporting on 15 different study sample s were included in this review . Strong evidence was found for an inverse association between total physical activity and overweight . Moderate evidence was observed for a positive association between television viewing and overweight . Because of the heterogeneity in the assessed dietary behaviours , insufficient evidence was found for an association between dietary intake or specific dietary behaviours and overweight . These results suggest that interventions aim ing to prevent overweight among preschool children should focus on promotion of total physical activity and limitation of screen time and that further research is needed to establish whether and which dietary behaviours are important for obesity prevention in this age group . However , despite the lack of evidence for dietary behaviours from the present review , future interventions may already target specific dietary behaviours that are highly prevalent and for which there a clear rationale as well as preliminary evidence that these behaviours are associated with overweight Aims This study assessed the efficacy of a school-based healthy lifestyle intervention ( Sport for LIFE ) for increasing physical activity , decreasing sedentary behaviour , reducing screen time behaviour , encouraging healthy attitudes and behaviour to nutrition , and reducing body mass index ( BMI ) in 8–9-year-old primary school children from lower socioeconomic background s in Northern Irel and . Methods A non-r and omised controlled trial of 416 children from 24 schools took part . Schools were r and omly assigned to one of two groups , an intervention or control group with 12 schools in each group . The intervention group received a 12-week school-based programme based on social cognitive theory . At baseline and follow-up , groups completed question naires assessing physical activity , screen time behaviour and dietary patterns . On each occasion anthropometric assessment s of height and weight were taken . Physical activity and sedentary behaviour were measured by accelerometry . Results Significant effects were observed for vigorous , moderate and light activity for the intervention group at follow-up . Sedentary behaviour was significantly reduced for the intervention group but not for the control group . No significant effects of the intervention on BMI , screen time behaviour or attitudes to nutrition , with the exception of non-core foods , were shown . Conclusions The programme was effective in increasing physical activity and reducing sedentary behaviour , however no significant changes in screen time behaviour and attitude to nutrition , with the exception of non-core foods , were observed . Future research ideas are offered for tackling low levels of physical activity in children OBJECTIVE To test the feasibility , acceptability , and potential efficacy of after-school dance classes and a family-based intervention to reduce television viewing , thereby reducing weight gain , among African-American girls . DESIGN Twelve-week , 2-arm parallel group , r and omized controlled trial . SETTING Low-income neighborhoods . PARTICIPANTS Sixty-one 8 - 10-year-old African-American girls and their parents/guardians . INTERVENTIONS The treatment intervention consisted of after-school dance classes at 3 community centers , and a 5-lesson intervention , delivered in participants ' homes , and design ed to reduce television , videotape , and video game use . The active control intervention consisted of disseminating newsletters and delivering health education lectures . MAIN OUTCOME MEASURES Implementation and process measures , body mass index , waist circumference , physical activity measured by accelerometry , self-reported media use , and meals eaten with TV . RESULTS Recruitment and retention goals were exceeded . High rates of participation were achieved for assessment s and intervention activities , except where transportation was lacking . All interventions received high satisfaction ratings . At follow up , girls in the treatment group , as compared to the control group , exhibited trends toward lower body mass index ( adjusted difference = -.32 kg/m2 , 95 % confidence interval [ CI ] -.77 , .12 ; Cohen 's d = .38 st and ard deviation units ) and waist circumference ( adjusted difference = -.63 cm , 95 % CI -1.92 , .67 ; d = .25 ) ; increased after-school physical activity ( adjusted difference = 55.1 counts/minute , 95 % CI -115.6 , 225.8 ; d = .21 ) ; and reduced television , videotape , and video game use ( adjusted difference = -4.96 hours/week , 95 % CI -11.41 , 1.49 ; d = .40 ) . The treatment group reported significantly reduced household television viewing ( d = .73 , P = .007 ) and fewer dinners eaten while watching TV ( adjusted difference = -1.60 meals/week , 95 % CI -2.99 , -.21 ; d = .59 ; P = .03 ) . Treatment group girls also reported less concern about weight ( d = .60 ; P = .03 ) , and a trend toward improved school grade s ( d = .51 ; P = .07 ) . CONCLUSIONS This study confirmed the feasibility , acceptability , and potential efficacy of using dance classes and a family-based intervention to reduce television viewing , thereby reducing weight gain , in African-American girls Background : Population -based studies directed at promoting physical activity in youth have shown limited success in obesity prevention . Objective : To assess whether an intervention integrating environmental changes to induce sustained changes in physical activity , prevents overweight in adolescents . Design : Four-year r and omized trial started in 2002 in eight middle schools of Eastern France . The intervention , r and omized at school level , was design ed to promote physical activity by changing attitudes through debates and attractive activities , and by providing social support and environmental changes encouraging physical activity . Subjects : Nine hundred and fifty four 12-year-old six- grade rs . Measurements : Body mass index ( BMI ) , body composition , physical activity by question naire , plasma lipids and glucose , insulin resistance . Results : Intervention students had a lower increase in BMI ( P=0.01 ) and age- and gender-adjusted BMI ( P<0.02 ) over time than controls . The differences across groups of the age- and gender-adjusted BMI changes ( 95 % confidence interval ( CI ) ) were −0.29 ( −0.51 ; −0.07 ) kg/m2 at 3 years , −0.25 ( −0.51 ; 0.01 ) kg/m2 at 4 years . An interaction with baseline weight status was noted . The intervention had a significant effect throughout the study in initially non-overweight adolescents ( −0.36 ( −0.60;−0.11 ) kg/m2 for adjusted BMI at 4 years ) , corresponding to a lower increase in fat mass index ( P<0.001 ) . In initially overweight adolescents , the differences observed across groups at 2 years ( –0.40 ( −0.94 ; 0.13 ) kg/m2 for adjusted BMI ) did not persist over time . At 4 years , 4.2 % of the initially non-overweight adolescents were overweight in the intervention schools , 9.8 % in the controls ( odds ratio=0.41 ( 0.22 ; 0.75 ) ; P<0.01 ) . Independent of initial weight status , compared with controls , intervention adolescents had an increase in supervised physical activity ( P<0.0001 ) , a decrease of TV/video viewing ( P<0.01 ) and an increase of high-density cholesterol concentrations ( P<0.0001 ) . Conclusion : Enhancing physical activity with a multilevel program prevents excessive weight gain in non-overweight adolescents . Our study provides evidence that prevention of obesity in youth is feasible OBJECTIVE . The objective of this study was to determine whether a generalizable best- practice individualized behavioral intervention reduced BMI z score relative to st and ard dietetic care among overweight children . METHODS . The design consisted of an assessor-blinded , r and omized , controlled trial involving 134 overweight children ( 59 boys , 75 girls ; BMI ≥ 98th centile relative to United Kingdom 1990 reference data for children aged 5–11 years ) who were r and omly assigned to a best- practice behavioral program ( intervention ) or st and ard care ( control ) . The intervention used family-centered counseling and behavioral strategies to modify diet , physical activity , and sedentary behavior . BMI z score , weight , objective ly measured physical activity and sedentary behavior , fat distribution , quality of life , and height z score were recorded at baseline and at 6 and 12 months . RESULTS . The intervention had no significant effect relative to st and ard care on BMI z score from baseline to 6 months and 12 months . BMI z score decreased significantly in both groups from baseline to 6 and 12 months . For those who complied with treatment , there was a significantly smaller weight increase in those in the intervention group compared with control subjects from baseline to 6 months . There were significant between-group differences in favor of the intervention for changes in total physical activity , percentage of time spent in sedentary behavior , and light-intensity physical activity . CONCLUSIONS . A generalizable , best- practice individualized behavioral intervention had modest benefits on objective ly measured physical activity and sedentary behavior but no significant effect on BMI z score compared with st and ard care among overweight children . The modest magnitude of the benefits observed perhaps argues for a longer-term and more intense intervention , although such treatments may not be realistic for many health care systems OBJECTIVE The study presents the immediate post-intervention results of Kids and Adults Now - Defeat Obesity ! , a r and omized controlled trial to enhance healthy lifestyle behaviors in mother-preschooler ( 2 - 5 years old ) dyads in North Carolina ( 2007 - 2011 ) . The outcomes include change from baseline in the child 's diet , physical activity and weight , and in the mother 's parenting behaviors , diet , physical activity , and weight . METHOD The intervention targeted parenting through maternal emotion regulation , home environment , feeding practice s , and modeling of healthy behaviors . 400 mother-child dyads were r and omized . RESULTS Mothers in the intervention arm , compared to the control arm , reduced instrumental feeding ( -0.24 vs. 0.01 , p<0.001 ) and TV snacks ( -.069 vs. -0.24 , p=0.001 ) . There were also improvements in emotional feeding ( p=0.03 ) , mother 's sugary beverage ( p=0.03 ) and fruit/vegetable ( p=0.04 ) intake , and dinners eaten in front of TV ( p=0.01 ) ; these differences were not significant after adjustment for multiple comparisons . CONCLUSION KAN-DO , design ed to maximize the capacity of mothers as agents of change , improved several channels of maternal influence . There were no group differences in the primary outcomes , but differences were observed in the parenting and maternal outcomes and there were trends toward improvement in the preschoolers ' diets . Long-term follow-up will address whether these short-term trends ultimately improve weight status OBJECTIVE The purpose of the present study was to evaluate the effects of a school-based , 2-year , multi-component intervention on BMI , eating and physical activity behaviour in Fl and ers , Belgium , targeting children aged 3 - 6 years in communities of high and low socio-economic status ( SES ) . DESIGN Cluster-r and omized controlled trial . SETTING Thirty-one pre- primary and primary schools in three different intervention communities and three paired-matched ( on SES profile ) control communities in Fl and ers , Belgium . SUBJECTS BMI Z-scores at baseline and follow-up were calculated for 1102 children . Question naires with sociodemographic data and FFQ were available from 694 of these 1102 children . RESULTS No significant effects were found on BMI Z-scores for the total sample . However , there was a significant decrease in BMI Z-score of 0·11 in the low-SES intervention community compared with the low-SES control community , where the BMI Z-score increased by 0·04 ( F = 6·26 , P = 0·01 ) . No significant intervention effects could be found for eating behaviour , physical activity or screen-time . There were no significant interaction effects of age and gender of the children on the outcome variables . CONCLUSIONS Although no significant effects were found for BMI Z-scores in the total sample , this intervention had a promising effect in the low-SES community of reducing excess weight gain among young children Background : Treatment of childhood obesity is difficult , and successful management may differ in various areas with different cultural background s. The present study was conducted to assess the effect of lifestyle modification family-based intervention in young Iranian children . Methods : This field trial study was conducted in 2011 among 156 obese children in Tehran , Iran . They were r and omly assigned to intervention and control groups . At baseline , anthropometric measurements and biochemical analysis were performed . The second and third phases consisted of training sessions for parents of the intervention group . At the fourth phase , there was no training program . In all four phases , question naires on demographic characteristics , lifestyle and food frequency were completed by interviewing with mothers , and biochemical analysis was repeated at the end of the study . Results : During the second and third phases of the study , weight and height increased significantly in both groups , although weight increased more slowly , and waist and hip circumferences was decreased in the intervention group . Serum triglycerides and cholesterol decreased significantly in the intervention group ( P < 0.05 ) . Analysis of food group consumption showed that in the intervention group , not only consumption of milk , dairy and nuts group increased significantly but also the corresponding figure decreased for bread and cereals , sugar and confectionery ingredients ; moreover , the family 's oil and fat consumption decreased significantly ( P < 0.05 ) . Watching TV and playing on the computer decreased significantly in the intervention group ; however , walking time increased significantly in both groups ( P < 0.05 ) . Conclusions : The family-based lifestyle program had limited but desirable effects on anthropometric and metabolic outcomes of the obese children . We suggest that a longer period of intervention may have more favorable results Background Schools are the most frequent target for intervention programs aim ed at preventing child obesity ; however , the overall effectiveness of these programs has been limited . It has therefore been recommended that interventions target multiple ecological levels ( community , family , school and individual ) to have greater success in changing risk behaviors for obesity . This study examined the immediate and short-term , sustained effects of the Switch program , which targeted three behaviors ( decreasing children 's screen time , increasing fruit and vegetable consumption , and increasing physical activity ) at three ecological levels ( the family , school , and community ) . Methods Participants were 1,323 children and their parents from 10 schools in two states . Schools were matched and r and omly assigned to treatment and control . Measures of the key behaviors and body mass index were collected at baseline , immediately post-intervention , and 6 months post-intervention . Results The effect sizes of the differences between treatment and control groups ranged between small ( Cohen 's d = 0.15 for body mass index at 6 months post-intervention ) to large ( 1.38 ; parent report of screen time at 6 months post-intervention ) , controlling for baseline levels . There was a significant difference in parent-reported screen time at post-intervention in the experimental group , and this effect was maintained at 6 months post-intervention ( a difference of about 2 hours/week ) . The experimental group also showed a significant increase in parent-reported fruit and vegetable consumption while child-reported fruit and vegetable consumption was marginally significant . At the 6-month follow-up , parent-reported screen time was significantly lower , and parent and child-reported fruit and vegetable consumption was significantly increased . There were no significant effects on pedometer measures of physical activity or body mass index in the experimental group . The intervention effects were moderated by child sex ( for fruit and vegetable consumption , physical activity , and weight status ) , family involvement ( for fruit and vegetable consumption ) , and child body mass index ( for screen time ) . The perception of change among the experimental group was generally positive with 23 % to 62 % indicating positive changes in behaviors . Conclusion The results indicate that the Switch program yielded small-to-modest treatment effects for promoting children 's fruit and vegetable consumption and minimizing screen time . The Switch program offers promise for use in youth obesity prevention OBJECTIVE The aim of the present study was to evaluate the effects of a 1-year family-based healthy lifestyle intervention implemented through day-care centres on toddlers ' BMI Z-scores and reported activity- and dietary-related behaviours . DESIGN Pilot cluster-r and omized controlled trial . SETTING Seventy child-care centres in three different intervention communities and three paired-matched control communities in Fl and ers , Belgium . SUBJECTS A sample of 203 Belgian toddlers aged 9 - 24 months was included in the study . Objective ly assessed weight and height were used to calculate BMI Z-scores . A parental-report question naire was used to assess children 's lifestyle behaviours . RESULTS Positive intervention effects were found on BMI Z-score . No intervention effects were found for activity- and dietary-related behaviours targeted by the intervention . In both intervention and control groups , daily consumption of water , soft drinks , sweets and savoury snacks increased while daily consumption of fruit and vegetables decreased over 1 year . Daily physical activity remained stable but screen-time behaviour increased in both groups over time . CONCLUSIONS The study showed that a family-based healthy lifestyle intervention implemented through day-care centres can lead to healthier weight outcomes in toddlers . In both groups , an unhealthier lifestyle pattern was observed over 1 year which underlines the importance of the early childhood period as the focus of future behavioural interventions OBJECTIVE To determine whether a multicomponent health promotion intervention for Dutch adolescents ( defined as persons between 12 and 14 years of age ) would be successful in influencing body composition and dietary and physical activity behavior in both the short and long terms . DESIGN R and omized controlled trial . SETTING Ten intervention and 8 control prevocational secondary schools . PARTICIPANTS A total of 1108 adolescents ( mean age , 12.7 years ) . Intervention An interdisciplinary program with an adapted curriculum for 11 lessons in biology and physical education and environmental change options . MAIN OUTCOME MEASURES Body height and weight , waist circumference , 4 skinfold thickness measurements , and dietary and physical activity behavior data . RESULTS Multilevel analyses showed that the intervention remained effective in preventing unfavorable increases in important measures of body composition after 20-month follow-up in girls ( biceps skinfold and sum of 4 skinfolds ) and boys ( triceps , biceps , and subscapular skinfolds ) . Consumption of sugar-containing beverages was significantly lower in intervention schools both after intervention ( boys : -287 mL/d ; 95 % confidence interval [ CI ] , -527 to -47 ; girls : -249 ; -400 to -98 ) and at 12-month follow-up ( boys : -233 ; -371 to -95 ; girls : -271 ; -390 to -153 ) . For boys , screen-viewing behavior was significantly lower in the intervention group after 20 months ( -25 min/d ; 95 % CI , -50 to -0.3 ) . No significant intervention effects on consumption of snacks or active commuting to school were found . CONCLUSION The Dutch Obesity Intervention in Teenagers program result ed in beneficial effects on the sum of skinfold thickness measurements in girls and consumption of sugar-containing beverages in both boys and girls in both the short and long terms OBJECTIVE To test a 2-year community- and family-based obesity prevention program for low-income African American girls : Stanford GEMS ( Girls ' health Enrichment Multi-site Studies ) . DESIGN R and omized controlled trial with follow-up measures scheduled at 6 , 12 , 18 , and 24 months . SETTING Low-income areas of Oakl and , California . PARTICIPANTS African American girls aged 8 to 10 years ( N=261 ) and their parents or guardians . INTERVENTIONS Families were r and omized to one of two 2-year , culturally tailored interventions : ( 1 ) after-school hip-hop , African , and step dance classes and a home/family-based intervention to reduce screen media use or ( 2 ) information-based health education . MAIN OUTCOME MEASURE Changes in body mass index ( BMI ) . RESULTS Changes in BMI did not differ between groups ( adjusted mean difference [ 95 % confidence interval ] = 0.04 [ -0.18 to 0.27 ] per year ) . Among secondary outcomes , fasting total cholesterol level ( adjusted mean difference , -3.49 [ 95 % confidence interval , -5.28 to -1.70 ] mg/dL per year ) , low-density lipoprotein cholesterol level ( -3.02 [ -4.74 to -1.31 ] mg/dL per year ) , incidence of hyperinsulinemia ( relative risk , 0.35 [ 0.13 to 0.93 ] ) , and depressive symptoms ( -0.21 [ -0.42 to -0.001 ] per year ) decreased more among girls in the dance and screen time reduction intervention . In exploratory moderator analysis , the dance and screen time reduction intervention slowed BMI gain more than health education among girls who watched more television at baseline ( P = .02 ) and /or those whose parents or guardians were unmarried ( P = .01 ) . CONCLUSIONS A culturally tailored after-school dance and screen time reduction intervention for low-income , preadolescent African American girls did not significantly reduce BMI gain compared with health education but did produce potentially clinical ly important reductions in lipid levels , hyperinsulinemia , and depressive symptoms . There was also evidence for greater effectiveness in high-risk subgroups of girls 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 To assess the feasibility of a pediatric primary care based intervention to promote healthful behaviors among 0–6 month old infants and their mothers . We enrolled two intervention practice s ( 60 mother-infant pairs ) and one usual care control practice ( 24 pairs ) in a non-r and omized controlled trial . We completed visits and interviews with 80 ( 95 % ) pairs at birth and 6 months . The intervention included ( 1 ) brief focused negotiation by pediatricians , ( 2 ) motivational counseling by a health educator , and ( 3 ) group parenting workshops . We evaluated the intervention effects on infant feeding , sleep duration , TV viewing , and mothers ’ responsiveness to satiety cues . Maternal behavioral targets included postpartum diet , physical activity , TV and sleep . At 6 months , fewer intervention than control infants had been introduced to solid foods ( 57 % vs. 82 % ; P = 0.04 ) , and intervention infants viewed less TV ( mean 1.2 vs. 1.5 h/d ; P = 0.07 ) . Compared to control infants , intervention infants had larger increases in their nocturnal sleep duration from baseline to follow up ( mean increase 1.9 vs. 1.3 h/d ; P = 0.05 ) ; larger reductions in settling time ( mean reduction −0.70 vs. −0.10 h/d ; P = 0.02 ) ; and larger reductions in hours/day of nighttime wakefulness ( mean reduction −2.9 vs. −1.5 h/d ; P = 0.08 ) . There were no differences in breastfeeding , response to satiety cues , or maternal health behaviors . A program of brief focused negotiation by pediatricians , individual coaching by health educators using motivational interviewing , and group parenting workshops tended to improve infant feeding , sleep and media exposure , but had less impact on mothers ’ own health-related behaviors 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 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 Effective lifestyle interventions are needed to prevent noncommunicable diseases in low- and middle-income countries . We analyzed the effects of a school-based health promotion intervention on physical fitness after 28 months and explored if the effect varied with important school characteristics . We also assessed effects on screen time , physical activity and BMI . Methods and results We performed a cluster-r and omized pair matched trial in schools in urban Ecuador . The intervention included an individual and environmental component tailored to the local context and re sources . Primary outcomes were physical fitness ( EUROFIT battery ) , screen time ( question naires ) and physical activity ( accelerometers ) . Change in BMI was a secondary outcome . A total of 1440 grade 8 and 9 adolescents ( intervention : n = 700 , 48.6 % ) and 20 schools ( intervention : n = 10 , 50 % ) participated . Data of 1083 adolescents ( intervention : n = 550 , 50.8 % ) from 20 schools were analyzed . The intervention increased vertical jump ( mean effect 2.5 cm ; 95 % CI 0.8 - 4.2 ; P = 0.01 ) . Marginally insignificant , adolescents from the intervention group needed less time for speed shuttle run ( intervention effect = −0.8 s , 95 % CI −1.58 - 0.07 ; P = 0.05 ) . The proportion of students achieving over 60 minutes of moderate-to-vigorous physical activity/day decreased over time with the change in proportion significantly less in the intervention schools ( 6 vs. 18 percentage points , P < 0.01 ) . The intervention effect on speed shuttle run was significant in larger schools while the effect on vertical jump was larger in mixed gender school compared to small and female schools . The proportion of schools that met the recommendations for physical activity increased with 37 % in intervention schools with half-day schedule compared to the controls in the pair . No significant effects were found on screen time and BMI . Measurement of physical activity in a sub sample was a limitation . No adverse effects were reported . Conclusions A school-based intervention with an individual and environment component can improve physical fitness and can minimize the decline in physical activity levels from childhood into adolescence in urban Ecuador . Trial registration Clinical trials.gov identifier NCT01004367 This study tested the efficacy of two school-based programs for prevention of body weight/fat gain in comparison to a control group , in all participants and in overweight children . The Louisiana ( LA ) Health study utilized a longitudinal , cluster r and omized 3-arm controlled design , with 28 months of follow-up . Children ( N=2060 ; M age = 10.5 years , SD = 1.2 ) from rural communities in Grade s 4 to 6 participated in the study . 17 school clusters ( M = 123 children/cluster ) were r and omly assigned to one of three prevention arms : 1 ) Primary Prevention ( PP ) , an environmental modification program , 2 ) Primary + Secondary Prevention ( PP+SP ) , the environmental program with an added classroom and internet education component , or 3 ) Control ( C ) . Primary outcomes were changes in percent body fat and body mass index z scores . Secondary outcomes were changes in behaviors related to energy balance . Comparisons of PP , PP+SP , and C on changes in body fat and BMI z scores found no differences . PP and PP+SP study arms were combined to create an environmental modification arm ( EM ) . Relative to C , EM decreased body fat for boys ( −1.7 % ± 0.38 % versus −0.14 % ± 0.69 % ) and attenuated fat gain for girls ( 2.9 % ± 0.22 % versus 3.93 % ± 0.37 % ) , but st and ardized effect sizes were relatively small ( < 0.30 ) . In conclusion , this school-based environmental modification programs had modest beneficial effects on changes in percent body fat . Addition of a classroom/internet program to the environmental program did not enhance weight/fat gain prevention , but did impact physical activity and social support in overweight children Background Mexico has the highest adult overweight and obesity prevalence in the Americas ; 23.8 % of children < 5 years old are at risk for overweight and 9.7 % are already overweight or obese . Creciendo Sanos was a pilot intervention to prevent obesity among preschoolers in Instituto Mexicano del Seguro Social ( IMSS ) clinics . Methods We r and omized 4 IMSS primary care clinics to either 6 weekly educational sessions promoting healthful nutrition and physical activity or usual care . We recruited 306 parent-child pairs : 168 intervention , 138 usual care . Children were 2 - 5 years old with WHO body mass index ( BMI ) z-score 0 - 3 . We measured children ’s height and weight and parents reported children ’s diet and physical activity at baseline and 3 and 6-month follow-up . We analyzed behavioral and BMI outcomes with generalized mixed models incorporating multiple imputation for missing values . Results 93 ( 55 % ) intervention and 96 ( 70 % ) usual care families completed 3 and 6-month follow-up . At 3 months , intervention v. usual care children increased vegetables by 6.3 servings/week ( 95 % CI , 1.8 , 10.8 ) . In stratified analyses , intervention participants with high program adherence ( 5 - 6 sessions ) decreased snacks and screen time and increased vegetables v. usual care . No further effects on behavioral outcomes or BMI were observed . Transportation time and expenses were barriers to adherence . 90 % of parents who completed the post-intervention survey were satisfied with the program . Conclusions Although satisfaction was high among participants , barriers to participation and retention included transportation cost and time . In intention to treat analyses , we found intervention effects on vegetable intake , but not other behaviors or BMI .Trial registration Clinical Trials.gov NCT01539070.Comisión Nacional de Investigación Científica del IMSS : 2009 - 785 - 120 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 This paper reports the primary outcomes of the Healthy Opportunities for Physical Activity and Nutrition ( HOP'N ) after-school project , which was an effectiveness trial design ed to evaluate the prevention of childhood obesity through building the capacity of after-school staff to increase physical activity ( PA ) and fruit and vegetable ( FV ) opportunities . Methods We conducted a three-year , nested cross-sectional group r and omized controlled effectiveness trial . After a baseline assessment year ( 2005 - 2006 ) , schools and their after-school programs were r and omized to the HOP'N after-school program ( n = 4 ) or control ( n = 3 ) , and assessed for two subsequent years ( intervention year 1 , 2006 - 2007 ; intervention year 2 , 2007 - 2008 ) . Across the three years , 715 fourth grade students , and 246 third and fourth grade after-school program participants were included in the study . HOP'N included community government human service agency ( Cooperative Extension ) led community development efforts , a three-time yearly training of after-school staff , daily PA for 30 minutes following CATCH guidelines , a daily healthful snack , and a weekly nutrition and PA curriculum ( HOP'N Club ) . Child outcomes included change in age- and gender-specific body mass index z-scores ( BMI z ) across the school year and PA during after-school time measured by accelerometers . The success of HOP'N in changing after-school program opportunities was evaluated by observations over the school year of after-school program physical activity sessions and snack FV offerings . Data were analyzed in 2009 . Results The intervention had no impact on changes in BMI z. Overweight/obese children attending HOP'N after-school programs performed 5.92 minutes more moderate-to-vigorous PA per day after intervention , which eliminated a baseline year deficit of 9.65 minutes per day ( p < 0.05 ) compared to control site overweight/obese children . Active recreation program time at HOP'N sites was 23.40 minutes ( intervention year 1 , p = 0.01 ) and 14.20 minutes ( intervention year 2 , p = 0.10 ) greater than control sites . HOP'N sites and control sites did not differ in the number of FV offered as snacks . Conclusions The HOP'N program had a positive impact on overweight/obese children 's PA and after-school active recreation time . Trial registration NCT01015599 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 . Television viewing and physical inactivity increase the risk of obesity in youth . Thus , identifying new interventions that increase physical activity and reduce television viewing would be helpful in the prevention and treatment of pediatric obesity . This study evaluated the effects of open-loop feedback plus reinforcement versus open-loop feedback alone on physical activity , targeted sedentary behavior , body composition , and energy intake in youth . METHODS . Thirty overweight or obese 8- to 12-year-old children were r and omly assigned to an intervention ( n = 14 ) or control group ( n = 16 ) . Participants wore accelerometers every day for 8 weeks and attended biweekly meetings to download the activity monitors . For children in the open-loop feedback plus reinforcement ( intervention ) group , accumulating 400 counts of physical activity on pedometers earned 1 hour of television/VCR/DVD time , which was controlled by a Token TV electronic device . Open-loop feedback control subjects wore activity monitors but had free access to targeted sedentary behavior . RESULTS . Compared with controls , the open-loop feedback plus reinforcement group demonstrated significantly greater increases in daily physical activity counts ( + 65 % vs + 16 % ) and minutes per day of moderate-to-vigorous physical activity ( + 9.4 vs + 0.3 ) and greater reductions in minutes per day spent in television viewing ( −116.1 vs + 14.3 ) . The intervention group also showed more favorable changes in body composition , dietary fat intake , and energy intake from snacks compared with controls . Reductions in sedentary behavior were directly related to reductions in BMI , fat intake , snack intake , and snack intake while watching television . CONCLUSIONS . Providing feedback of physical activity in combination with reinforcing physical activity with sedentary behavior is a simple method of modifying the home environment that may play an important role in treating and preventing child obesity /index.php?title = Center_for_Consumer_Freedom . Accessed August 12 , 2008 . 9 . Pereira MA , Kartashov AI , Ebbeling CB , et al. Fast food habits , weight gain , and insulin resistance in a 15-year prospect i ve analysis of the CARDIA study . Lancet . 2005;365(9453):36 - 42 . 10 . Haber GB , Heaton KW , Murphy D , Burroughs LF . Depletion and disruption of dietary fibre : effects on satiety , plasma-glucose , and serum-insulin . Lancet . 1977 ; 2(8040):679 - 682 . 11 . PepsiCo . PepsiCo joins with America ’s YMCAs to help Americans live healthier lives . http://phx.corporate-ir.net/phoenix.zhtml?c=78265&p=irol-newsArticle & ID=828887&highlight . Accessed August 12 , 2008 . 12 . Lesser LI , Ebbeling CB , Goozner M , Wypij D , Ludwig DS . Relationship between funding source and conclusion among nutrition-related scientific articles . PLoS Med . 2007;4(1):e5 . 13 . American Dietetic Association . American Dietetic Association welcomes the Coca-Cola Co as an ADA partner . http://www.eatright.org/cps/rde/xchg/ada/hs .xsl/media_16174_ENU_HTML.htm . Accessed August 12 , 2008 . 14 . State Attorney General NY . Media center : executive summary . http://www .oag.state.ny.us/media_center/reports/nonprofit/full_text.html . Accessed September 3 , 2008 . 15 . Wootan MG ; Center for Science in the Public Interest . Study shows progress in getting soft drinks out of schools , still two-thirds of school beverage sales are sugary drinks . http://www.cspinet.com/new/200709171.html . Accessed September 3 , 2008 Background . Obesity has become the most common pediatric chronic disease in the modern era . Early prevention and treatment of childhood and adolescent obesity is m and ated . Surprisingly , however , only a minor fraction of obese children participate in weight reduction interventions , and the longer-term effects of these weight-reduction interventions among children have not been eluci date d. Objective . To examine prospect ively the short- and long-term effects of a 3-month , combined dietary-behavioral-physical activity intervention on anthropometric measures , body composition , dietary and leisure-time habits , fitness , and lipid profiles among obese children . Methods . In this r and omized prospect i ve study , 24 obese subjects completed the 3-month intervention and were compared with 22 obese , age- and gender-matched , control subjects . Results . At 3 months , there were significant differences in changes in body weight ( −2.8 ± 2.3 kg vs 1.2 ± 2.2 kg ) , BMI ( −1.7 ± 1.1 kg/m2 vs −0.2 ± 1.0 kg/m2 ) , body fat percentage ( from skinfold tests ; −3.3 ± 2.6 % vs 1.4 ± 4.7 % ) , serum total cholesterol level ( −24.6 ± 15.1 mg/dL vs 0.8 ± 18.7 mg/dL ) , low-density lipoprotein cholesterol level ( −23.3 ± 15.2 mg/dL vs −3.7 ± 17.3 mg/dL ) , and fitness ( 215 ± 107 seconds vs 50 ± 116 seconds ) in the intervention group versus the control group . After a 1-year follow-up period , there were significant differences between the intervention group ( n = 20 ) and the control group ( n = 20 ) in body weight ( 0.6 ± 6.0 kg vs 5.3 ± 2.7 kg ) , BMI ( −1.7 ± 2.3 kg/m2 vs 0.6 ± 0.9 kg/m2 ) , and body fat percentage . There was a significant increase in leisure-time physical activity among the intervention participants , compared with a decrease among the control subjects . Conclusions . Our data demonstrate the short- and longer-term beneficial effects of a combined dietary-behavioral-physical activity intervention among obese children . These results highlight the importance of multidisciplinary programs for the treatment of childhood obesity and emphasize their encouraging long-term effects OBJECTIVE : The goal of this study was to evaluate the impact of the Active Teen Leaders Avoiding Screen-time ( ATLAS ) intervention for adolescent boys , an obesity prevention intervention using smartphone technology . METHODS : ATLAS was a cluster r and omized controlled trial conducted in 14 secondary schools in low-income communities in New South Wales , Australia . Participants were 361 adolescent boys ( aged 12–14 years ) considered at risk of obesity . The 20-week intervention was guided by self-determination theory and social cognitive theory and involved : teacher professional development , provision of fitness equipment to schools , face-to-face physical activity sessions , lunchtime student mentoring sessions , research er-led seminars , a smartphone application and Web site , and parental strategies for reducing screen-time . Outcome measures included BMI and waist circumference , percent body fat , physical activity ( accelerometers ) , screen-time , sugar-sweetened beverage intake , muscular fitness , and resistance training skill competency . RESULTS : Overall , there were no significant intervention effects for BMI , waist circumference , percent body fat , or physical activity . Significant intervention effects were found for screen-time ( mean ± SE : –30 ± 10.08 min/d ; P = .03 ) , sugar-sweetened beverage consumption ( mean : –0.6 ± 0.26 glass/d ; P = .01 ) , muscular fitness ( mean : 0.9 ± 0.49 repetition ; P = .04 ) , and resistance training skills ( mean : 5.7 ± 0.67 units ; P < .001 ) . CONCLUSIONS : This school-based intervention targeting low-income adolescent boys did not result in significant effects on body composition , perhaps due to an insufficient activity dose . However , the intervention was successful in improving muscular fitness , movement skills , and key weight-related behaviors 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 : We evaluated the efficacy of family-based , behavioral weight control in the management of severe pediatric obesity . METHODS : Participants were 192 children 8.0 to 12.0 years of age ( mean ± SD : 10.2 ± 1.2 years ) . The average BMI percentile for age and gender was 99.18 ( SD : 0.72 ) . Families were assigned r and omly to the intervention or usual care . Assessment s were conducted at baseline , 6 months , 12 months , and 18 months . The primary outcome was percent overweight ( percent over the median BMI for age and gender ) . Changes in blood pressure , body composition , waist circumference , and health-related quality of life also were evaluated . Finally , we examined factors associated with changes in child percent overweight , particularly session attendance . RESULTS : Intervention was associated with significant decreases in child percent overweight , relative to usual care , at 6 months . Intent-to-treat analyses documented that intervention was associated with a 7.58 % decrease in child percent overweight at 6 months , compared with a 0.66 % decrease with usual care , but differences were not significant at 12 or 18 months . Small significant improvements in medical outcomes were observed at 6 and 12 months . Children who attended ≥75 % of intervention sessions maintained decreases in percent overweight through 18 months . Lower baseline percent overweight , better attendance , higher income , and greater parent BMI reduction were associated with significantly greater reductions in child percent overweight at 6 months among intervention participants . CONCLUSIONS : Intervention was associated with significant short-term reductions in obesity and improvements in medical parameters and conferred longer-term weight change benefits for children who attended ≥75 % of sessions BACKGROUND The objective of this study , focused on parents and children to reduce sedentary behavior , consumption of soft drinks and high-fat and salt containing snacks , and increase the consumption of fruits and vegetables , was to assess the effect of a six month intervention and an 18 month follow-up intervention on the body mass index , food consumption and physical activity of 2nd and 3rd grade elementary school children . METHODS This was a r and omized cluster controlled trial . School children were selected from 2nd and 3rd ( n = 532 ) grade . MEASUREMENTS BMI z-score for age and sex was calculated and classified according to the WHO ( 2006 ) . Abdominal obesity was defined as WC > 90th of NHANES III . RESULTS At six months of the study differences were observed in BMI , -0.82 ( p = 0.0001 ) . At 24 months , results such as an increase of z-score BMI and waist circumference , a decrease in abdominal obesity , eighth per cent remission and an incidence of 18 % of overweight and obesity were observed . Additionally , an increase ( p = 0.007 ) in vegetable intake and physical activity ( p = 0.0001 ) was also reported , along with a decrease in sedentary activities and the consumption of snacks high in fat and salt . CONCLUSIONS The results of this study indicate that with a comprehensive intervention there is a positive response to lifestyle changes and a reduction of abdominal obesity Objective To assess whether a physical activity intervention reduces body mass index in young children . Design Cluster r and omised controlled single blinded trial over 12 months . Setting Thirty six nurseries in Glasgow , Scotl and . Participants 545 children in their preschool year , mean age 4.2 years ( SD 0.2 ) at baseline . Intervention Enhanced physical activity programme in nursery ( three 30 minute sessions a week over 24 weeks ) plus home based health education aim ed at increasing physical activity through play and reducing sedentary behaviour . Main outcome measure Body mass index , expressed as a st and ard deviation score relative to UK 1990 reference data . Secondary measures were objective ly measured physical activity and sedentary behaviour ; fundamental movement skills ; and evaluation of the process . Results Group allocation had no significant effect on the primary outcome measure at six and 12 months or on measures of physical activity and sedentary behaviour by accelerometry . Children in the intervention group had significantly higher performance in movement skills tests than control children at six month follow-up ( P=0.0027 ; 95 % confidence interval 0.3 to 1.3 ) after adjustment for sex and baseline performance . Conclusions Physical activity can significantly improve motor skills but did not reduce body mass index in young children in this trial . Trial registration Current Controlled Trials IS RCT N36363490 Objective To test the effect of a multidimensional lifestyle intervention on aerobic fitness and adiposity in predominantly migrant preschool children . Design Cluster r and omised controlled single blinded trial ( Ballabeina study ) over one school year ; r and omisation was performed after stratification for linguistic region . Setting 40 preschool classes in areas with a high migrant population in the German and French speaking regions of Switzerl and . Participants 652 of the 727 preschool children had informed consent and were present for baseline measures ( mean age 5.1 years ( SD 0.7 ) , 72 % migrants of multicultural origins ) . No children withdrew , but 26 moved away . Intervention The multidimensional culturally tailored lifestyle intervention included a physical activity programme , lessons on nutrition , media use ( use of television and computers ) , and sleep and adaptation of the built environment of the preschool class . It lasted from August 2008 to June 2009 . Main outcome measures Primary outcomes were aerobic fitness ( 20 m shuttle run test ) and body mass index ( BMI ) . Secondary outcomes included motor agility , balance , percentage body fat , waist circumference , physical activity , eating habits , media use , sleep , psychological health , and cognitive abilities . Results Compared with controls , children in the intervention group had an increase in aerobic fitness at the end of the intervention ( adjusted mean difference : 0.32 stages ( 95 % confidence interval 0.07 to 0.57 ; P=0.01 ) but no difference in BMI ( −0.07 kg/m2 , −0.19 to 0.06 ; P=0.31 ) . Relative to controls , children in the intervention group had beneficial effects in motor agility ( −0.54 s , −0.90 to −0.17 ; P=0.004 ) , percentage body fat ( −1.1 % , −2.0 to −0.2 ; P=0.02 ) , and waist circumference ( −1.0 cm , −1.6 to −0.4 ; P=0.001 ) . There were also significant benefits in the intervention group in reported physical activity , media use , and eating habits , but not in the remaining secondary outcomes . Conclusions A multidimensional intervention increased aerobic fitness and reduced body fat but not BMI in predominantly migrant preschool children . Trial registration Clinical Trials NCT00674544 OBJECTIVE : To determine if an intervention for preschool-aged children in primary care is effective in reducing screen time , meals in front of the television , and BMI . METHODS : A r and omized controlled trial was conducted at a primary care pediatric group practice in Toronto , Canada . Three-year-old children and their parents were r and omly assigned to receive a short behavioral counseling intervention on strategies to decrease screen time . The primary outcome 1 year later was parent reported screen time . Secondary outcomes included television in the child ’s bedroom , number of meals in front of the television , and BMI . RESULTS : In the intention-to-treat analysis at 1 year , there were no significant differences in mean total weekday minutes of screen time ( 60 , interquartile range [ IQR ] : 35–120 vs 65 , IQR : 35–120 ; P = .68 ) or mean total weekend day minutes of screen time ( 80 , IQR : 45–130 vs 90 , IQR : 60–120 ; P = .33 ) between the intervention and control group . Adjusting for baseline BMI , there was a reduction in the number of weekday meals in front of the television ( 1.6 ± 1.0 vs 1.9 ± 1.2 ; P = .03 ) but no differences in BMI or number of televisions in the bedroom . CONCLUSIONS : This pragmatic trial was not effective in reducing screen time or BMI but was effective in reducing meals in front of the screen . Short interventions focused solely on reducing screen time implemented in the primary care practice setting may not be effective in this age group The preschool years offer an opportunity to interrupt the trajectory toward obesity in black children . The Hip-Hop to Health Jr. Obesity Prevention Effectiveness Trial was a group-r and omized controlled trial assessing the feasibility and effectiveness of a teacher-delivered weight control intervention for black preschool children . The 618 participating children were enrolled in 18 schools administered by the Chicago Public Schools . Children enrolled in the nine schools r and omized to the intervention group received a 14-week weight control intervention delivered by their classroom teachers . Children in the nine control schools received a general health intervention . Height and weight , physical activity , screen time , and diet data were collected at baseline and postintervention . At postintervention , children in the intervention schools engaged in more moderate-to-vigorous physical activity ( MVPA ) than children in the control schools ( difference between adjusted group means = 7.46 min/day , P = 0.02 ) . Also , children in the intervention group had less total screen time ( -27.8 min/day , P = 0.05 ) . There were no significant differences in BMI , BMI Z score , or dietary intake . It is feasible to adapt an obesity prevention program to be taught by classroom teachers . The intervention showed positive influences on physical activity and screen time , but not on diet . Measuring diet and physical activity in preschool children remains a challenge , and interventions delivered by classroom teachers require both intensive initial training and ongoing individualized supervision OBJECTIVE : To assess the effectiveness of a parent-focused intervention on infants ’ obesity-risk behaviors and BMI . METHODS : This cluster r and omized controlled trial recruited 542 parents and their infants ( mean age 3.8 months at baseline ) from 62 first-time parent groups . Parents were offered six 2-hour dietitian-delivered sessions over 15 months focusing on parental knowledge , skills , and social support around infant feeding , diet , physical activity , and television viewing . Control group parents received 6 newsletters on nonobesity-focused themes ; all parents received usual care from child health nurses . The primary outcomes of interest were child diet ( 3 × 24-hour diet recalls ) , child physical activity ( accelerometry ) , and child TV viewing ( parent report ) . Secondary outcomes included BMI z-scores ( measured ) . Data were collected when children were 4 , 9 , and 20 months of age . RESULTS : Unadjusted analyses showed that , compared with controls , intervention group children consumed fewer grams of noncore drinks ( mean difference = –4.45 ; 95 % confidence interval [ CI ] : –7.92 to –0.99 ; P = .01 ) and were less likely to consume any noncore drinks ( odds ratio = 0.48 ; 95 % CI : 0.24 to 0.95 ; P = .034 ) midintervention ( mean age 9 months ) . At intervention conclusion ( mean age 19.8 months ) , intervention group children consumed fewer grams of sweet snacks ( mean difference = –3.69 ; 95 % CI : –6.41 to –0.96 ; P = .008 ) and viewed fewer daily minutes of television ( mean difference = –15.97 : 95 % CI : –25.97 to –5.96 ; P = .002 ) . There was little statistical evidence of differences in fruit , vegetable , savory snack , or water consumption or in BMI z-scores or physical activity . CONCLUSIONS : This intervention result ed in reductions in sweet snack consumption and television viewing in 20-month-old children Objectives : To reduce gain in body mass index ( BMI ) in overweight/mildly obese children in the primary care setting . Design : R and omized controlled trial ( RCT ) nested within a baseline cross-sectional BMI survey . Setting : Twenty nine general practice s , Melbourne , Australia . Participants : ( 1 ) BMI survey : 2112 children visiting their general practitioner ( GP ) April – December 2002 ; ( 2 ) RCT : individually r and omized overweight/mildly obese ( BMI z-score < 3.0 ) children aged 5 years 0 months–9 years 11 months ( 82 intervention , 81 control).Intervention : Four st and ard GP consultations over 12 weeks , targeting change in nutrition , physical activity and sedentary behaviour , supported by purpose - design ed family material s . Main outcome measures : Primary : BMI at 9 and 15 months post-r and omization . Secondary : Parent-reported child nutrition , physical activity and health status ; child-reported health status , body satisfaction and appearance/self-worth . Results : Attrition was 10 % . The adjusted mean difference ( intervention – control ) in BMI was −0.2 kg/m2 ( 95 % CI : −0.6 to 0.1 ; P=0.25 ) at 9 months and −0.0 kg/m2 ( 95 % CI : −0.5 to 0.5 ; P=1.00 ) at 15 months . There was a relative improvement in nutrition scores in the intervention arm at both 9 and 15 months . There was weak evidence of an increase in daily physical activity in the intervention arm . Health status and body image were similar in the trial arms . Conclusions : This intervention did not result in a sustained BMI reduction , despite the improvement in parent-reported nutrition . Brief individualized solution-focused approaches may not be an effective approach to childhood overweight . Alternatively , this intervention may not have been intensive enough or the GP training may have been insufficient ; however , increasing either would have significant cost and re source implication s at a population level The purpose of the present study was to evaluate an intervention to prevent weight gain among households ( HHs ) in the community . Ninety HHs were r and omized to intervention or control group for 1 year . Intervention consisted of six face-to-face group sessions , placement of a television ( TV ) locking device on all home TVs , and home-based intervention activities . Measures were collected in person at baseline and 1 year . Weight , height , eating behaviors , physical activity ( PA ) , and TV viewing were measured among HH members ages ≥ 12 years . Follow-up rate at 1 year was 96 % . No significant intervention effects were observed for change in HH BMI -z score . Intervention HHs significantly reduced TV viewing , snacks/sweets intake , and dollars per person spent eating out , and increased ( adults only ) PA and self-weighing frequency compared with control HHs . A 1 year obesity prevention intervention targeting entire HHs was effective in reducing TV viewing , snack/sweets intake and eating out purchases . Innovative methods are needed to strengthen the home food environment intervention component . Longer intervention duration s also need to be evaluated BACKGROUND The primary care setting offers the opportunity to reach children and parents to encourage healthy lifestyle behaviours , and improve weight status among children . OBJECTIVE Test the feasibility of Helping H AND ( Healthy Activity and Nutrition Directions ) , an obesity intervention for 5- to 8-year-old children in primary care clinics . METHODS A r and omized controlled pilot study of Helping H AND , a 6-month intervention , targeted children with body mass index 85 - 99%tile and their parents . Intervention group attended monthly sessions and self-selected child behaviours and parenting practice s to change . Control group received regular paediatric care and was wait-listed for Helping H AND . Session completion , participant satisfaction , child anthropometrics , dietary intake , physical activity , TV viewing and behaviour-specific parenting practice s were measured pre and post intervention . RESULTS Forty parent-child dyads enrolled : 82.5 % were Hispanic , 80 % had a girl and 65 % reported income ≤ $ 30 , 000/year . There was 20 % attrition from Helping H AND ( attended < 4/6 sessions ) . Families self-selected 4.35 ( SD 1.75 ) behaviours to target during the 6-month programme and each of the seven behaviours was selected by 45 - 80 % of the families . There were no between group differences in the child 's body mass index z-score , dietary intake or physical activity post intervention . Intervention group viewed 14.9 ( SE 2.3 ) h/week of TV post intervention versus control group 23.3 ( SE 2.4 ) h/week ( P < 0.05 ) . CONCLUSION Helping H AND is feasible , due to low attrition , good programme attendance , and clinical ly relevant improvements in some child and parenting behaviours Low levels of physical activity coupled with high levels of television viewing have been linked with obesity in children . The objective of this study was to assess the efficacy of ' Switch Off-Get Active ' , a 16-week controlled health education intervention , in increasing physical activity and reducing screen time and BMI in primary school children . A secondary objective was to compare children with high and low screen time . Participants were 312 children aged 10.2+/-0.7 years , attending nine schools in areas of social disadvantage . The 10-lesson , teacher-led intervention , conducted in spring 2003 , emphasised self-monitoring , budgeting of time and selective viewing . Differences , adjusted for baseline values by ANCOVA , existed between intervention and control children at follow-up for self-reported physical activity ( intervention + 0.84 30 min blocks/day , 95%CI 0.11 - 1.57 , p<0.05 ) and self-efficacy for physical activity ( p<0.05 ) but not self-reported screen time ( intervention--0.41 blocks/day , 95%CI--0.93 - 0.12 , p=0.13 ) or BMI ( p=0.63 ) . Cross-sectional comparisons at baseline indicated lower physical activity , self-efficacy for physical activity and aerobic fitness and a higher BMI in children with high screen time . In conclusion , health education interventions can increase physical activity in primary school children but follow-ups of longer duration may be needed to demonstrate intervention effects on BMI OBJECTIVE To assess the effects of reducing television viewing and computer use on children 's body mass index ( BMI ) as a risk factor for the development of overweight in young children . DESIGN R and omized controlled clinical trial . SETTING University children 's hospital . PARTICIPANTS Seventy children aged 4 to 7 years whose BMI was at or above the 75th BMI percentile for age and sex . INTERVENTIONS Children were r and omized to an intervention to reduce their television viewing and computer use by 50 % vs a monitoring control group that did not reduce television viewing or computer use . MAIN OUTCOME MEASURES Age- and sex-st and ardized BMI ( z BMI ) , television viewing , energy intake , and physical activity were monitored every 6 months during 2 years . RESULTS Children r and omized to the intervention group showed greater reductions in targeted sedentary behavior ( P < .001 ) , z BMI ( P < .05 ) , and energy intake ( P < .05 ) compared with the monitoring control group . Socioeconomic status moderated z BMI change ( P = .01 ) , with the experimental intervention working better among families of low socioeconomic status . Changes in targeted sedentary behavior mediated changes in z BMI ( P < .05 ) . The change in television viewing was related to the change in energy intake ( P < .001 ) but not to the change in physical activity ( P = .37 ) . CONCLUSIONS Reducing television viewing and computer use may have an important role in preventing obesity and in lowering BMI in young children , and these changes may be related more to changes in energy intake than to changes in physical activity OBJECTIVE To evaluate the impact of a 12-month multicomponent school-based obesity prevention program , Nutrition and Enjoyable Activity for Teen Girls among adolescent girls . DESIGN Group r and omized controlled trial with 12-month follow-up . SETTING Twelve secondary schools in low-income communities in the Hunter and Central Coast regions of New South Wales , Australia . PARTICIPANTS Three hundred fifty-seven adolescent girls aged 12 to 14 years . INTERVENTION A multicomponent school-based intervention program tailored for adolescent girls . The intervention was based on social cognitive theory and included teacher professional development , enhanced school sport sessions , interactive seminars , nutrition workshops , lunch-time physical activity sessions , h and books and pedometers for self-monitoring , parent newsletters , and text messaging for social support . MAIN OUTCOME MEASURES Body mass index ( BMI , calculated as weight in kilograms divided by height in meters squared ) , BMI z score , body fat percentage , physical activity , screen time , dietary intake , and self-esteem . RESULTS After 12 months , changes in BMI ( adjusted mean difference , -0.19 ; 95 % CI , -0.70 to 0.33 ) , BMI z score ( mean , -0.08 ; 95 % CI , -0.20 to 0.04 ) , and body fat percentage ( mean , -1.09 ; 95 % CI , -2.88 to 0.70 ) were in favor of the intervention , but they were not statistically different from those in the control group . Changes in screen time were statistically significant ( mean , -30.67 min/d ; 95 % CI , -62.43 to -1.06 ) , but there were no group by time effects for physical activity , dietary behavior , or self-esteem . CONCLUSIONS A school-based intervention tailored for adolescent girls from schools located in low-income communities did not significantly reduce BMI gain . However , changes in body composition were of a magnitude similar to previous studies and may be associated with clinical ly important health outcomes . TRIAL REGISTRATION anzctr.org.au Identifier : 12610000330044 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 OBJECTIVE Hip-Hop to Health Jr. was a diet/physical activity intervention design ed to reduce gains in BMI ( kilograms per meter squared ) in preschool minority children . RESEARCH METHODS AND PROCEDURES Twelve predominantly Latino Head Start centers participated in a group-r and omized trial conducted between Fall 2001 and Winter 2003 . Six centers were r and omized to a culturally proficient 14-week ( three times weekly ) diet/physical activity intervention . Parents participated by completing weekly homework assignments . The children in the other six centers received a general health intervention that did not address either diet or physical activity . The primary outcome was change in BMI , and secondary outcomes were changes in dietary intake and physical activity . Measures were collected at baseline , post-intervention , and at Years 1 and 2 follow-up . RESULTS There were no significant differences between intervention and control schools in either primary or secondary outcomes at post-intervention , Year 1 , or Year 2 follow-ups . DISCUSSION When Hip-Hop to Health Jr. was conducted in predominantly black Head Start centers , it was effective in reducing subsequent increases in BMI in preschool children . In contrast , when the program was conducted in Latino centers , it was not effective . Although the intervention did not prevent excessive weight gain in Latino children , it was very well received . Future interventions with this population may require further cultural tailoring and a more robust parent intervention OBJECTIVE This study evaluates the post-treatment and short-term follow-up efficacy of , as well as participant satisfaction for , a 4-month behavioral weight control program for overweight adolescents initiated in a primary care setting and extended through telephone and mail contact . RESEARCH METHODS AND PROCEDURES 44 overweight adolescents were r and omly assigned to either a multiple component behavioral weight control intervention ( Healthy Habits [ HH ] ; n = 23 ) or a single session of physician weight counseling ( typical care [ TC ] ; n = 21 ) . Weight , height , dietary intake , physical activity , sedentary behavior , and problematic weight-related and eating behaviors and beliefs were assessed before treatment , after the 4-month treatment , and at 3-month follow-up . Participant satisfaction and behavioral skills use were measured . RESULTS HH adolescents evidence d better change in body mass index z scores to post-treatment than TC adolescents . Body mass index z scores changed similarly in the conditions from post-treatment through follow-up . Behavioral skills use was higher among HH than TC adolescents , and higher behavioral skills use was related to better weight outcome . Energy intake , percentage of calories from fat , physical activity , sedentary behavior , and problematic weight-related or eating behaviors/beliefs did not differ by condition or significantly change over time independent of condition . The behavioral intervention evidence d good feasibility and participant satisfaction . DISCUSSION A telephone- and mail-based behavioral intervention initiated in primary care result ed in better weight control efficacy relative to care typically provided to overweight adolescents . Innovative and efficacious weight control intervention delivery approaches could decrease provider and participant burden and improve dissemination to the increasing population of overweight youth OBJECTIVE The objective of this study was to test the hypothesis that community-based environmental change intervention prevents undesirable weight gain in children . METHOD The method used in this study was a two-year , non-r and omized , controlled trial ( 2003 - 2005 ) using community-based participatory methodology in three diverse cities in Massachusetts : one intervention and two socio-demographically-matched control communities ( pooled for analysis ) . Children ( n=1028 ) , with a mean age=7.61 + 1.04years participated . Interventions were made to improve energy balance by increasing physical activity options and availability of healthful foods ( Year 1 ) . To firmly secure sustainability , the study team supported policies and shifted intervention work to community members ( Year 2 ) . RESULTS Change in body mass index z-score ( BMI z ) was assessed by multiple regression , accounting for clustering within communities and adjusting for baseline covariates . Sex-specific overweight/obesity prevalence , incidence and remission were assessed . Over the two-year period , BMI z of children in the intervention community decreased by -0.06 [ p=0.005 , 95 % confidence interval : -0.08 to -0.04 ] compared to controls . Prevalence of overweight/obesity decreased in males ( OR=0.61 , p=0.01 ) and females ( OR=0.78 , p=0.01 ) and remission increased in males ( OR 3.18 , p=0.03 ) and females ( OR 1.93 , p=0.03 ) in intervention compared to controls . CONCLUSION Results demonstrate promise for preventing childhood obesity using a sustainable multi-level community-based model and reinforce the need for wide-reaching environmental and policy interventions OBJECTIVE To evaluate the short- and long-term results of FATaintPHAT , a Web-based computer-tailored intervention aim ing to increase physical activity , decrease sedentary behavior , and promote healthy eating to contribute to the prevention of excessive weight gain among adolescents . DESIGN Cluster r and omized trial with an intervention group and a no-intervention control group . SETTING Twenty schools in the Netherl and s. PARTICIPANTS A total of 883 students ( aged 12 - 13 years ) . INTERVENTION The FATaintPHAT ( VETisnietVET in Dutch ) Web-based computer-tailored intervention . OUTCOME MEASURES Self-reported behaviors ( diet , physical activity , sedentary behavior ) and pedometer counts were measured at baseline and at 4-month and 2-year follow-up ; body mass index ( BMI ) , waist circumference , and fitness were measured at baseline and at 2-year follow-up . Descriptive and multilevel regression analyses were conducted among the total study population and among students not meeting behavioral recommendations at baseline ( students at risk ) . RESULTS The complete case analyses showed that FATaintPHAT had no effect on BMI and waist circumference . However , the intervention was associated with lower odds ( 0.54 ) of drinking more than 400 mL of sugar-sweetened beverages per day and with lower snack intake ( β = -0.81 snacks/d ) and higher vegetable intake ( β = 19.3 g/d ) but also with a lower step count ( β = -10 856 steps/wk ) at 4-month follow-up . In addition , among students at risk , FATaintPHAT had a positive effect on fruit consumption ( β = 0.39 g/d ) at 4-month follow-up and on step count ( β = 14 228 steps/wk ) at 2-year follow-up but an inverse effect on the odds of sports participation ( odds ratio , 0.45 ) at 4-month follow-up . No effects were found for sedentary behavior . CONCLUSION The FATaintPHAT intervention was associated with positive short-term effects on diet but with no effects or unfavorable effects on physical activity and sedentary behavior BACKGROUND Interventions to prevent and control childhood obesity have shown mixed results in terms of short- and long-term changes . OBJECTIVES ' MOVE/me Muevo ' was a 2-year family- and recreation centre-based r and omized controlled trial to promote healthy eating and physical activity among 5- to 8-year-old children . It was hypothesized that children in the intervention group would demonstrate lower post-intervention body mass index ( BMI ) values and improved obesity-related behaviours compared with the control group children . METHODS Thirty recreation centres in San Diego County , California , were r and omized to an intervention or control condition . Five hundred forty-one families were enrolled and children 's BMI , diet , physical activity and other health indicators were tracked from baseline to 2 years post-baseline . Analyses followed an intent-to-treat approach using mixed-effects models . RESULTS No significant intervention effects were observed for the primary outcomes of child 's or parent 's BMI and child 's waist circumference . Moderator analyses , however , showed that girls ( but not boys ) in the intervention condition reduced their BMI . At the 2-year follow-up , intervention condition parents reported that their children were consuming fewer high-fat foods and sugary beverages . CONCLUSIONS Favourable implementation fidelity and high retention rates support the feasibility of this intervention in a large metropolitan area ; however , interventions of greater intensity may be needed to achieve effects on child 's BMI . Also , further research is needed to develop gender-specific intervention strategies so that both genders may benefit from such efforts 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 BACKGROUND Models are needed for implementing weight management interventions for adolescents through readily accessible venues . This study evaluated the feasibility and efficacy of a school nurse-delivered intervention in improving diet and activity and reducing body mass index ( BMI ) among overweight and obese adolescents . METHODS Six high schools were r and omized to either a 6-session school nurse-delivered counseling intervention utilizing cognitive-behavioral techniques or nurse contact with provision of information . Eighty-four overweight or obese adolescents in grade s 9 through 11 completed behavioral and physiological assessment s at baseline and 2- and 6-month follow-ups . RESULTS At 2 months , intervention participants ate breakfast on more days/week ( difference = 1.01 days ; 95 % CI : 0.11 , 1.92 ) , and had a lower intake of total sugar ( difference = -45.79 g ; 95 % CI : -88.34 , -3.24 ) and added sugar ( difference = -51.35 g ; 95 % CI : -92.45 , -10.26 ) compared to control participants . At 6 months , they were more likely to drink soda ≤ one time/day ( OR 4.10 ; 95 % CI : 1.19 , 16.93 ) and eat at fast food restaurants ≤ one time/week ( OR 4.62 ; 95 % CI : 1.10 , 23.76 ) compared to control participants . There were no significant differences in BMI , activity , or caloric intake . CONCLUSION A brief school nurse-delivered intervention was feasible , acceptable , and improved selected obesogenic behaviors , but not BMI PURPOSE The number of youth that meet activity guidelines is decreasing and easy access to reinforcing sedentary behaviors competes with increasing physical activity . In the laboratory , open-loop feedback that used pedometer activity counts to gain access to sedentary alternatives doubled physical activity . This study evaluated the influence of open-loop feedback and reinforcement on physical activity and television ( TV ) time in a small clinical trial . METHODS Children ( 8 - 12 yr old ) were r and omized to an open-loop feedback plus reinforcement intervention ( N = 11 ) or no feedback , no reinforcement control ( N = 7 ) . Subjects wore an accelerometer for 6 wk and attended meetings to download the accelerometer . Accumulating physical activity counts gave subjects in the open-loop group access to TV time , controlled by a TV Allowance device , with 400 counts = 1 h of TV . The control group had no feedback for activity and free access to TV . RESULTS The open-loop group had a 24 % increase in physical activity , which was greater ( P = 0.02 ) than the control group . TV time of the open-loop group was reduced by 18 % or 20 min x d(-1 ) whereas the control group increased by 13 min x d(-1 ) , but these were not significant changes . The change in time spent watching television was directly related to the change in BMI z-score ( r = 0.69 , P = 0.002 ) . CONCLUSION Open-loop feedback increases physical activity in children , thus helping children to achieve physical activity recommendations . Reductions in TV watching may reduce or minimize gains in body weight CONTEXT Few r and omized controlled trials ( RCTs ) of interventions for the treatment of childhood obesity have taken place outside the Western world . AIM To test whether a good practice intervention for the treatment of childhood obesity would have a greater impact on weight status and other outcomes than a control condition in Kuala Lumpur , Malaysia . METHODS Assessor-blinded RCT of a treatment intervention in 107 obese 7- to 11-year olds . The intervention was relatively low intensity ( 8 hours contact over 26 weeks , group based ) , aim ing to change child sedentary behavior , physical activity , and diet using behavior change counselling . Outcomes were measured at baseline and six months after the start of the intervention . Primary outcome was BMI z-score , other outcomes were weight change , health-related quality of life ( Peds QL ) , objective ly measured physical activity and sedentary behavior ( Actigraph accelerometry over 5 days ) . RESULTS The intervention had no significant effect on BMI z score relative to control . Weight gain was reduced significantly in the intervention group compared to the control group ( + 1.5 kg vs. + 3.5 kg , respectively , t-test p < 0.01 ) . Changes in health-related quality of life and objective ly measured physical activity and sedentary behavior favored the intervention group . CONCLUSIONS Treatment was associated with reduced rate of weight gain , and improvements in physical activity and quality of life . More substantial benefits may require longer term and more intensive interventions which aim for more substantive lifestyle changes OBJECTIVE Elevated television ( TV ) viewing and physical inactivity promote obesity in children . Thus , changes in physical activity and sedentary behavior seem critical to treating childhood obesity . PRESENT STUDY : Using a r and omized , 2-arm design , this pilot study tested the effects of contingent TV on physical activity and TV viewing in 10 obese children . TV viewing was contingent on pedaling a stationary cycle ergometer for experimental participants but was not contingent on pedaling for control participants . The study was conducted over 12 weeks , including a 2-week baseline period . RESULTS Multivariate analyses indicated that the intervention significantly increased pedaling and reduced TV-viewing time . During the treatment phase , the experimental group pedaled 64.4 minutes per week on average , compared with 8.3 minutes by controls . The experimental group watched 1.6 hours of TV per week on average , compared with 21.0 hours per week on average by controls during this phase . Secondary analyses indicated that the experimental group showed significantly greater reductions in total body fat and percent leg fat . Total pedaling time during intervention correlated with greater reductions in percent body fat ( r = -0.68 ) . CONCLUSIONS Contingencies in the home environment can be arranged to modify physical activity and TV viewing and may have a role in treating childhood obesity . Contingent TV may be one method to help achieve this goal BACKGROUND Television viewing has been associated with increased violence in play and higher rates of obesity . Although there are interventions to reduce television viewing by school-aged children , there are none for younger children . OBJECTIVE To develop and evaluate an intervention to reduce television viewing by preschool children . DESIGN R and omized controlled trial conducted in 16 preschool and /or day care centers in rural upstate New York . PATIENTS Children aged 2.6 through 5.5 years . INTERVENTION Children attending intervention centers received a 7-session program design ed to reduce television viewing as part of a health promotion curriculum , whereas children attending the control centers received a safety and injury prevention program . OUTCOME MEASUREMENTS Change in parent-reported child television/video viewing and measured growth variables . RESULTS Before the intervention , the intervention and control groups viewed 11.9 and 14.0 h/wk of television/videos , respectively . Afterward , children in the intervention group decreased their television/video viewing 3.1 h/wk , whereas children in the control group increased their viewing by 1.6 h/wk , for an adjusted difference between the groups of -4.7 h/wk ( 95 % confidence interval , -8.4 to -1.0 h/wk ; P = .02 ) . The percentage of children watching television/videos more than 2 h/d also decreased significantly from 33 % to 18 % among the intervention group , compared with an increase of 41 % to 47 % among the control group , for a difference of -21.5 % ( 95 % confidence interval , -42.5 % to -0.5 % ; P = .046 ) . There were no statistically significant differences in children 's growth between groups . CONCLUSIONS This study is the first to show that a preschool-based intervention can lead to reductions in young children 's television/video viewing . Further research is needed to determine the long-term effects associated with reductions in young children 's television viewing OBJECTIVES This pilot study evaluated the feasibility ( recruitment , retention , and acceptability ) and preliminary efficacy of a six-week home-based electronic time monitor intervention on New Zeal and children 's television watching in 2008 . METHODS Twenty-nine children aged 9 to 12 years who watched more than 20 h of television per week ( 62 % male , mean age 10.4 years ) were r and omised to either the intervention or the control group . The intervention group received an electronic TV time monitor for 6 weeks and advice to restrict TV watching to 1 h per day or less . The control group was given verbal advice to restrict TV watching . RESULTS Participant retention at 6 weeks was 93 % . Semi-structured interviews with intervention families confirmed moderate acceptability of TV time monitors and several perceived benefits including better awareness of household TV viewing and improved time planning . Drawbacks reported included disruption to parents ' TV watching and increased sibling conflict . Time spent watching television decreased by 4.2 h ( mean change [ SD ] : -254 [ 536 ] min ) per week in the intervention group compared with no change in the control group ( -3 [ 241 ] min ) , but the difference between groups was not statistically significant , p=0.77 . Both groups reported decreases in energy intake from snacks and total screen time and increases in physical activity measured by pedometer and between-group differences were not statistically significant . CONCLUSIONS Electronic TV time monitors are feasible to use for home-based TV watching interventions although acceptability varies between families . Preliminary findings from this pilot suggest that such devices have potential to decrease children 's TV watching but a larger trial is needed to confirm effectiveness . Future research should be family-orientated ; take account of other screen time activities ; and employ TV time monitors as just one of a range of strategies to decrease sedentary behaviour Background : Obese adolescents are at risk for type 2 diabetes mellitus ( T2DM ) . Obesity interventions delivered through media , such as the web and text messages [ short message service ( SMS ) ] may be beneficial when targeting obese adolescents . Methods : A r and omized controlled trial , Pace-Internet for Diabetes Prevention Intervention ( PACEi-DP ) , compared three forms of an obesity intervention to usual care ( UC ) : ( a ) website only ( W ) ; ( b ) website , monthly group sessions , and follow-up calls ( WG ) ; and ( c ) website and SMS ( WSMS ) . Participants were overweight or obese adolescents at risk for T2DM ( n = 101 ; age 12–16 years ; mean body mass index ( BMI ) percentile = 97.6 ; 74.3 % Hispanic ) . In addition to the website , WSMS participants received SMS supporting intervention goals and behavioral strategies and communicated via SMS with a case manager . WG participants had additional group activities related to weight loss and received follow-up calls from a health coach . UC participants were given printed material s and encouraged to attend three initial group sessions . Repeated measures mixed model regression analyses tested treatment effects for anthropometric , behavioral , and behavioral change strategy outcomes . Results : There were no treatment effects for BMI , adiposity , physical activity , or diet at 12 months . Treatment effects were observed for sedentary behavior , with the W arm having a greater decrease in sedentary behavior ( 4.9 to 2.8 h/day ) than the UC arm ( p = .006 ) . Conclusion : Although not sufficient to produce weight loss , the combination of web intervention and group sessions with telephone follow-up yielded improvements in sedentary behavior and in the use of behavior change strategies expected to lead to behavior change Objectives : To evaluate the effectiveness of an intervention to prevent excess weight gain , reduce time spent in screen behaviours , promote participation in and enjoyment of physical activity ( PA ) , and improve fundamental movement skills among children . Participants : In 2002 , 311 children ( 78 % response ; 49 % boys ) , average age 10 years 8 months , were recruited from three government schools in low socioeconomic areas of Melbourne , Australia . Design : Group-r and omized controlled trial . Children were r and omized by class to one of the four conditions : a behavioural modification group ( BM ; n=66 ) ; a fundamental movement skills group ( FMS ; n=74 ) ; a combined BM/FMS group ( BM/FMS ; n=93 ) ; and a control ( usual curriculum ) group ( n=62 ) . Data were collected at baseline , post intervention , 6- and 12-month follow-up periods . Results : BMI data were available for 295 children at baseline and 268 at 12-month follow-up . After adjusting for food intake and PA , there was a significant intervention effect from baseline to post intervention on age- and sex-adjusted BMI in the BM/FMS group compared with controls ( −1.88 kg m−2 , P<0.01 ) , which was maintained at 6- and 12-month follow-up periods ( −1.53 kg m−2 , P<0.05 ) . Children in the BM/FMS group were less likely than controls to be overweight/obese between baseline and post intervention ( adjusted odds ratio (AOR)=0.36 , P<0.05 ) ; also maintained at 12-month follow-up ( AOR=0.38 , P<0.05 ) . Compared with controls , FMS group children recorded higher levels and greater enjoyment of PA ; and BM children recorded higher levels of PA and TV viewing across all four time points . Gender moderated the intervention effects for participation in and enjoyment of PA , and fundamental movement skills . Conclusion : This programme represents a promising approach to preventing excess weight gain and promoting participation in and enjoyment of PA . Examination of the mediators of this intervention and further tailoring of the programme to suit both genders is required AIM Childhood overweight and obesity is a significant community health problem with severe long-term complications . This paper aims to evaluate a four-by-two-hour weekly group parent education programme targeting children who are overweight . METHODS A r and omised time series design with wait-list controls was conducted for overweight and obese children aged 3 - 10 years . RESULTS A statistically significant reduction in child body mass index and energy intake was found post treatment ; no differences were reported for child sedentary electronic media time , physical activity and waist circumference . Children 's baseline activity levels were found to be at or slightly above national recommended st and ards . No change occurred in primary parent body mass index or waist circumference after treatment . CONCLUSIONS A brief group education programme for parents was effective in reducing childhood overweight at 3 months follow-up OBJECTIVE To examine the effectiveness of a primary care-based obesity intervention over the first year ( 6 intervention contacts ) of a planned 2-year study . DESIGN Cluster r and omized controlled trial . SETTING Ten pediatric practice s , 5 intervention and 5 usual care . PARTICIPANTS Four hundred seventy-five children aged 2 to 6 years with body mass index ( BMI ) in the 95th percentile or higher or 85th to less than 95th percentile if at least 1 parent was overweight ; 445 ( 93 % ) had 1-year outcomes . INTERVENTION Intervention practice s received primary care restructuring , and families received motivational interviewing by clinicians and educational modules targeting television viewing and fast food and sugar-sweetened beverage intake . OUTCOME MEASURES Change in BMI and obesity-related behaviors from baseline to 1 year . RESULTS Compared with usual care , intervention participants had a smaller , nonsignificant change in BMI ( -0.21 ; 95 % confidence interval [ CI ] , -0.50 to 0.07 ; P = .15 ) , greater decreases in television viewing ( -0.36 h/d ; 95 % CI , -0.64 to -0.09 ; P = .01 ) , and slightly greater decreases in fast food ( -0.16 serving/wk ; 95 % CI , -0.33 to 0.01 ; P = .07 ) and sugar-sweetened beverage ( -0.22 serving/d ; 95 % CI , -0.52 to 0.08 ; P = .15 ) intake . In post hoc analyses , we observed significant effects on BMI among girls ( -0.38 ; 95 % CI , -0.73 to -0.03 ; P = .03 ) but not boys ( 0.04 ; 95 % CI , -0.55 to 0.63 ; P = .89 ) and among participants in households with annual incomes of $ 50 000 or less ( -0.93 ; 95 % CI , -1.60 to -0.25 ; P = .01 ) but not in higher-income households ( 0.02 ; 95 % CI , -0.30 to 0.33 ; P = .92 ) . CONCLUSION After 1 year , the High Five for Kids intervention was effective in reducing television viewing but did not significantly reduce BMI IMPORTANCE Racial/ethnic and socioeconomic disparities exist across risk factors for childhood obesity . OBJECTIVE To examine the effectiveness of a home-based intervention to improve household routines known to be associated with childhood obesity among a sample of low-income , racial/ethnic minority families with young children . DESIGN R and omized trial . SETTING The intervention was delivered in the families ' homes . PARTICIPANTS The study involved 121 families with children aged 2 to 5 years who had a television ( TV ) in the room where he or she slept ; 111 ( 92 % ) had 6-month outcome data ( 55 intervention and 56 control ) . The mean ( SD ) age of the children was 4.0 ( 1.1 ) years ; 45 % were overweight/obese . Fifty-two percent of the children were Hispanic , 34 % were black , and 14 % were white/other . Nearly 60 % of the families had household incomes of $ 20,000 or less . INTERVENTIONS The 6-month intervention promoted 4 household routines , family meals , adequate sleep , limiting TV time , and removing the TV from the child 's bedroom , using ( 1 ) motivational coaching at home and by phone , ( 2 ) mailed educational material s , and ( 3 ) text messages . Control subjects were mailed material s focused on child development . MAIN OUTCOMES AND MEASURES Change in parent report of frequency of family meals ( times/wk ) , child sleep duration ( hours/d ) , child weekday and weekend day TV viewing ( hours/d ) , and the presence of a TV in the room where the child slept from baseline to 6 months . A secondary outcome was change in age- and sex-adjusted body mass index ( calculated as weight in kilograms divided by height in meters squared ) . RESULTS Compared with control subjects , intervention participants had increased sleep duration ( 0.75 hours/d ; 95 % CI , 0.06 to 1.44 ; P = .03 ) , greater decreases in TV viewing on weekend days ( -1.06 hours/d ; 95 % CI , -1.97 to -0.15 ; P = .02 ) , and decreased body mass index ( -0.40 ; 95 % CI , -0.79 to 0.00 ; P = .05 ) . No significant intervention effect was found for the presence of a TV in the room where the child slept or family meal frequency . CONCLUSIONS AND RELEVANCE Our results suggest that promoting household routines , particularly increasing sleep duration and reducing TV viewing , may be an effective approach to reduce body mass index among low-income , racial/ethnic minority children . Longer-term studies are needed to determine maintenance of behavior change . TRIAL REGISTRATION clinical trials.gov Identifier : NCT01565161 BACKGROUND & AIMS R and omized controlled trials ( RCT ) have demonstrated the effectiveness of lifestyle interventions in obese children . However , the effectiveness of interventions for overweight , but no obese children has not been demonstrated yet by RCTs . METHODS A total of 66 overweight ( BMI > 90th < or = 97th percentile ) children ( mean age 11.5+/-1.6 years , 58 % females , mean BMI 23.4+/-1.5kg/m(2 ) ) were r and omized into a control group ( CG ) ( n=32 ; no intervention for a duration of 6 months ) or intervention group ( IG ) ( n=34 ; 6 months intervention " Obeldicks light " based on physical activity , nutrition education , and behaviour counselling ) . BMI , waist circumference , skinfold thickness , bioimpedance analyses , blood pressure , physical activity based on question naires , and three-day-weighed dietary records were determined at baseline ( T0 ) and 6 months ( T1 ) later . Degree of overweight was calculated as BMI -SDS . Comparisons were performed on an intention-to-treat approach . RESULTS The drop-out rate was 3 % in IG and 16 % in CG . At T1 , 94 % of the children in IG decreased their BMI -SDS and 24 % of them were normal weight . The changes between T0 and T1 in BMI -SDS differed significantly ( p<0.001 ) between IG and CG ( CG : + 0.05+/-0.19 BMI -SDS ; IG : -0.26+/-0.22 BMI -SDS ) . Similar findings were observed for blood pressure , waist circumference , skinfold thickness , and fat mass based on bioimpedance analyses . In the IG , energy , fat and sugar intake decreased significantly between T0 and T1 , while no significant changes were observed in the CG . CONCLUSIONS The lifestyle intervention was associated with an improvement of dietary patterns and was effective in reducing degree of overweight , fat mass , waist circumference , and blood pressure OBJECTIVES To assess the impact of a culturally proficient dietary/physical activity intervention on changes in body mass index ( BMI ) ( kg/m 2 ) . STUDY DESIGN R and omized controlled trial ( Hip-Hop to Health Jr. ) conducted between September 1999 and June 2002 in 12 Head Start preschool programs in Chicago , Illinois . RESULTS Intervention children had significantly smaller increases in BMI compared with control children at 1-year follow-up , 0.06 vs 0.59 kg/m 2 ; difference -0.53 kg/m 2 ( 95 % CI -0.91 to -0.14 ) , P = .01 ; and at 2-year follow-up , 0.54 vs 1.08 kg/m 2 ; difference -0.54 kg/m 2 ( 95 % CI -0.98 to -0.10 ) , P = .02 , with adjustment for baseline age and BMI . The only significant difference between intervention and control children in food intake/physical activity was the Year 1 difference in percent of calories from saturated fat , 11.6 % vs 12.8 % ( P = .002 ) . CONCLUSIONS Hip-Hop to Health Jr. was effective in reducing subsequent increases in BMI in preschool children . This represents a promising approach to prevention of overweight among minority children in the preschool years BACKGROUND Weight-related problems are prevalent in adolescent girls . PURPOSE To evaluate New Moves , a school-based program aim ed at preventing weight-related problems in adolescent girls . DESIGN School-based group-r and omized controlled design . SETTING / PARTICIPANTS 356 girls ( mean age=15.8±1.2 years ) from six intervention and six control high schools . More than 75 % of the girls were racial/ethnic minorities and 46 % were overweight or obese . Data were collected in 2007 - 2009 and analyzed in 2009 - 2010 . INTERVENTION An all-girls physical education class , supplemented with nutrition and self-empowerment components , individual sessions using motivational interviewing , lunch meetings , and parent outreach . MAIN OUTCOME MEASURES Percentage body fat , BMI , physical activity , sedentary activity , dietary intake , eating patterns , unhealthy weight control behaviors , and body/self-image . RESULTS New Moves did not lead to significant changes in the girls ' percentage body fat or BMI but improvements were seen for sedentary activity , eating patterns , unhealthy weight control behaviors , and body/self-image . For example , in comparison to control girls , at 9-month follow-up , intervention girls decreased their sedentary behaviors by approximately one 30-minute block a day ( p=0.050 ) ; girls increased their portion control behaviors ( p=0.014 ) ; the percentage of girls using unhealthy weight control behaviors decreased by 13.7 % ( p=0.021 ) ; and improvements were seen in body image ( p=0.045 ) and self-worth ( p=0.031 ) . Additionally , intervention girls reported more support by friends , teachers , and families for healthy eating and physical activity . CONCLUSIONS New Moves provides a model for addressing the broad spectrum of weight-related problems among adolescent girls . Further work is needed to enhance the effectiveness of interventions to improve weight status of youth |
10,741 | 25,807,422 | Results from pre clinical and clinical studies show that flavoxate significantly increases bladder volume capacity ( BVC ) , with greater results if compared to other drugs such as emepronium bromide and propantheline .
Moreover in clinical trials , both versus placebo or versus active comparators , flavoxate treatment was associated with a significant improvement in different low urinary tract symptoms , such as diurnal and night frequency , urgency and urinary incontinence , suprapubic pain , dysuria , hesitancy and burning .
In addition flavoxate was associated with an overall more favourable safety profile than competitors .
Several research es and a number of years of clinical practice have proven the efficacy and tolerability of flavoxate administration in the treatment of OAB and associated symptoms . | OBJECTIVE This non- systematic review discusses the available evidence on the use of flavoxate in the treatment of overactive bladder ( OAB ) .
RESULTS Flavoxate hydrochloride is an antispasmodic agent which exerts an inhibition of the phosphodiesterases , a moderate calcium antagonistic activity , and a local anesthetic effect . | To investigate the effect of flavoxate ( Urispadol ) treatment on patients with symptomatic benign prostatic hypertrophy ( BPH ) , with the main weight on the irritative symptoms , a r and omized , double-blind , parallel-group , placebo-controlled and multicenter investigation was carried out . Seventy patients entered the study , 37 were allocated to flavoxate treatment on a daily dose of 1,200 mg ( 400 mg t.i.d . ) for 12 weeks , and 33 patients were allocated to placebo treatment . In spite of a sufficient power , the study did not discriminate the two treatment groups in a statistically significant way ( p > 0.05 ) , when considering the main endpoints : the irritative symptom score and the global patient evaluation . Conservative treatment of micturition disorders accompanying BPH with flavoxate in doses of 1,200 mg/day can not be recommended for clinical use A detailed study and analysis of several hundred cases of motor urge incontinence in the female is presented and summarized . This includes the incidence , the history referring to a question naire with a new urge and stress score , the symptomatology , possible etiological factors , the cystometric manifestation and the responsiveness to several treatment modalities and medications . A comparison of flavoxate , emepronium , propantheline and a placebo for the treatment of urinary incontinence due to bladder instability is made , the results are discussed and recommendations are made Detrusor instability occurs in approximately 10 % of the adult population , producing troublesome symptoms . The pharmacotherapy currently available is usually only partially effective and can not be adequately evaluated except under " blind " conditions because of the significant component attributable to placebo effects . The results of the present study revealed no advantage result ing from treatment with flavoxate , as assessed both subjectively and objective ly . We suggest that this therapy does not appear to be beneficial in the medical management of detrusor instability Abstract : A drug utilization observation study collected data on a total of 1800 patients given flavoxate ( Spasuret ® 200 ) over 2 weeks for urge incontinence . Efficacy and tolerance parameters were determined . A subgroup of 618 patients without urinary tract infections or benign prostatic hyperplasia were treated with flavoxate only . The subgroup ( n= 618 ) showed a reduction of dysuria ( 37 % ) , nocturia ( 53 % ) , and both daytime ( 61 % ) and nighttime urge ( 69 % ) . Bladder volume at first urge sensation increased by 55.1 ± 58.8 ml ( 36 % ) , which was comparable to data from the entire group ( 1800 patients ) . In 89.2 % of all patients the residual urine volume was stable or decreased . Undesirable side effects occurred in 1.8 % of cases . Both groups showed better results with flavoxate four times daily ( 800 mg ) , compared to three times daily ( 600 mg ) . Flavoxate is effective and well tolerated and causes no additional problems due to residual urine or side effects OBJECTIVE To estimate the prevalence of and bother associated with overactive bladder ( OAB ) in adults aged ≥40 years in the United States , using current International Continence Society definitions . METHODS Internet-based panel members were selected r and omly to participate in EpiLUTS , a cross-sectional , population -representative survey . Participants used Likert scales to rate how often they experienced individual lower urinary tract symptoms during the previous 4 weeks and how much bother they experienced . Based on responses to questions regarding urgency and urgency urinary incontinence , OAB symptoms were categorized as occurring at least " sometimes " or at least " often . " Symptom bother was categorized as at least " somewhat " or at least " quite a bit . " RESULTS The response rate was 59.6 % , with a final sample of 9416 men and 10,584 women . Prevalence of OAB symptoms at least " sometimes " was 27.2 % and 43.1 % for men and women , respectively ; prevalence of OAB at least " often " was 15.8 % and 32.6 % , respectively . Among men with OAB symptoms at least " sometimes , " 60.0 % were bothered at least " somewhat " and 27.8 % were bothered at least " quite a bit . " Among women , bother rates were 67.6 % and 38.9 % , respectively . Among respondents with OAB at least " often , " 67.8 % and 38.2 % of men and 73.0 % and 47.1 % of women reported being bothered at least " somewhat " and at least " quite a bit , " respectively . We estimate that 29.8 million adults aged ≥40 years in the United States have bothersome OAB symptoms . CONCLUSIONS Bothersome OAB symptoms are highly prevalent among men and women aged ≥40 years in the United States Summary Two double-blind trials and one open study were carried out to assess the efficacy of the spasmolytic , flavoxate , in relieving the pain and discomfort associated with various urological conditions . In the first two studies , 24 patients with renal colic and 34 with cystitis or urethrotrigonitis were treated orally with either 0.2 g. flavoxate t.d.s . or placebo . In the open study , 25 patients with acute renal colic were given a single i/v injection of flavoxate ( 0–1 g.).Thirty-four ( 68 % ) of the 54 patients receiving flavoxate showed a good or moderate response in terms of symptom relief compared with only 8 ( 28 % ) of the patients on placebo . The results of cystometrography in 7 patients on flavoxate and 7 on placebo showed that the increase in bladder capacity and the reduction in pressure after flavoxate treatment were statistically significant but not so in the case of placebo . No side-effects or adverse reactions were noted in any of the patients treated This preliminary communication reports on a non-r and omized pilot type trial of 34 females with urgency after pelvic radiotherapy who were treated with flavoxate hydrochloride for 4 weeks . A dosage of 600 mg/day was given to 21 patients and 1200 mg/day to 13 patients . Clinical ly , both regimens achieved comparable results . Urodynamically ( first desire volume , bladder capacity and pressure at capacity ) treatment with 1200 mg/day was significantly superior to 600 mg/day . Both schedules were equally well tolerated by patients and no treatment interruption occurred . A r and omized double-blind trial comparing 600 and 1200 mg/day flavoxate hydrochloride is currently underway the results of which will be reported in due course 46 patients suffering from urgency/urge incontinency were treated with Mictonorm and Spasuret in a crossing-over study . In consideration of the placebo effect in this disease both agents were tested versus a non-verum . The application period was 4 weeks and the dosage was 45 mg/d Mictonorm and 300 mg/d Spasuret , respectively . Both with Mictonorm and with Spasuret a significant reduction of micturition frequency and an increase of the compliance could be observed , whereas the placebo was ineffective . A markedly growth of the maximal bladder capacity ( 16.9 % ) was obtained only by Mictonorm . Both agents keep likewise to an improvement of the symptoms or urgency/urge incontinency . Side effects could observed in a small size without a breaking-off of the treatment Flavoxate is a smooth muscle relaxant widely used to treat urgency and urge incontinence . It has been used in an unblinded , uncontrolled clinical trial in 14 urology departments in universities and major hospitals in the People 's Republic of China involving 361 patients with urgency/incontinence of various types . Patients were given 200 mg three times daily , orally , for 2 weeks , although 33 patients received a daily dosage of 1200 mg . Frequency , urgency , dysuria , nocturia and incontinence were assessed and scored clinical ly prior to and after treatment . Three departments also included urodynamic investigations , e.g. monitoring of the end-residual volume . Results from 336 evaluable patients indicate that 228 ( 67 % ) were completely cured of urgency/incontinence symptoms , 66 ( 20 % ) were improved and 42 ( 13 % ) patients were unchanged . Flavoxate was also effective in 77.4 % of patients refractory to previous anti-cholinergic treatment . Treatment did not increase the end-residual volume and adverse events occurred only in four ( 1.3 % ) patients , two ( 0.6 % ) of which discontinued the therapy . The 1200 mg dose produced a complete cure in 82 % of patients and improvement in the remaining 18 % , with no side-effects . In conclusion , flavoxate is an effective and well tolerated treatment for urgency/incontinence of various causes A double-blind , placebo-controlled trial of the antispasmodic flavoxate ( 600 mg . daily ) was carried out in 60 patients suffering from painful conditions of the lower urinary tract arising from inflammation and /or infection or from spasm following diagnostic or therapeutic procedures . Statistically significant improvement was noted in frequency and suprapubic pain , and marked relief was also afforded in dysuria , hesitancy and burning . Apart from dryness of the mouth , the incidence and type of side-effects reported were similar in both groups of patients and were probably not drug related . Fewer patients interrupted treatment with flavoxate because of inefficacy than in the placebo group , the difference being statistically significant A controlled double‐blind trial is reported of the para‐sympatholytic drug , flavoxate hydrochloride , and the new sympatho‐mimetic drug , clenbuterol , in the treatment of 39 women with motor urge incontinence . The clinical results and the urodynamic findings of urethrocystomanometry after therapy showed clenbuterol to be very effective with few side effects In nine separate clinical trials , 382 patients having symptoms of either prostatitis , acute cystitis , urethritis , and /or trigonitis were r and omly assigned to treatment with flavoxate or phenazopyridine . Over-all response was evaluated in 384 patients after five days of therapy . In patients having prostatitis , response was satisfactory in 66 per cent treated with flavoxate and 31 per cent treated with phenazopyridine . In all other patients , satisfactory responses were reported in 80 per cent on flavoxate compared with 56 per cent on phenazopyridine . Similarly , symptom-severity evaluations at two and five days of therapy showed most symptoms improved in more of the patients on flavoxate therapy than on phenazopyridine therapy . Although more adverse effects were reported in patients treated with phenazopyridine than with flavoxate , the difference between medications was not statistically significant Flavoxate hydrochloride at a daily dosage of 600 mg was compared to a daily dosage of 1200 mg for the treatment of unstable bladder . Twenty-seven patients were treated for 4 weeks in a double-blind , r and omized , parallel-group trial . Clinical ly , both schedules were equally successful . In urodynamic terms , however , particularly with respect to uninhibited detrusor contractions , 1200 mg/day was significantly superior to 600 mg/day . Tolerability was excellent for both regimens . The side-effect free treatment of urgency and urge incontinence is of paramount importance for a patient 's quality of life OBJECTIVE To determine the bother associated with overactive bladder ( OAB ) symptoms and its influence on health-related quality of life ( HRQL ) , anxiety , depression , and treatment seeking in adults in the United States . METHODS Data from U.S. respondents aged ≥ 40 years participating in the Epidemiology of Lower Urinary Tract Symptoms survey , a population -based , cross-sectional Internet survey , were analyzed to assess OAB prevalence , OAB-associated bother , and effect of OAB on HRQL , anxiety , depression , and healthcare use . Likert data were categorized as no/minimal OAB symptoms , OAB without bother , and OAB with bother at least " somewhat . " RESULTS Of 31 588 completed surveys , 20 000 participants ( 9416 men and 10 584 women ) were r and omly selected and matched to U.S. census demographics . Of the respondents with OAB at least " sometimes , " the women were more likely than the men to be bothered by OAB , with 68 % of the women and 60 % of the men bothered at least " somewhat . " Men and women with OAB with bother were more likely to report that their bladder condition caused at least some problems ; had worse scores on HRQL , anxiety , and depression assessment s ; and had the greatest number of healthcare visits annually compared with those with OAB without bother and those with no/minimal symptoms . The strongest correlation between bother and symptom frequency was seen for urinary urgency , followed by urgency urinary incontinence and nocturia . CONCLUSION OAB symptoms can be quite bothersome , especially for women , and can negatively affect HRQL , increase anxiety and depression , and increase healthcare usage . In the present study , the strongest predictor of OAB-associated bother was urinary urgency |
10,742 | 20,542,078 | After peaking at hard intensities , cerebral oxygen levels dropped during very hard intensities .
People who were aerobically trained attained higher levels of cortical oxygen , dHb , and tHb than untrained people during very hard intensities .
Among untrained people , a marked drop in oxygen levels and a small increase in dHb at very hard intensities accompanied declines in tHb , implying reduced blood flow .
In conclusion , prefrontal oxygenation measured with NIRS in healthy people showed a quadratic response to incremental exercise , rising between moderate and hard intensities , then falling at very hard intensities .
Training status influenced the responses .
While method ological improvements in measures of brain oxygen are forthcoming , these results extend the evidence relevant to existing models of central limitations to maximal exercise | We conducted a systematic review and meta-regression analysis to quantify effects of exercise on brain hemodynamics measured by near-infrared spectroscopy ( NIRS ) . | The effects of submaximal and maximal exercise on cerebral perfusion were assessed using a portable , recumbent cycle ergometer in nine unacclimatized subjects ascending to 5,260 m. At 150 m , mean ( SD ) cerebral oxygenation ( rSO2 % ) increased during submaximal exercise from 68.4 ( SD 2.1 ) to 70.9 ( SD 3.8 ) ( P < 0.0001 ) and at maximal oxygen uptake ( .VO2(max ) ) to 69.8 ( SD 3.1 ) ( P < 0.02 ) . In contrast , at each of the high altitudes studied , rSO2 was reduced during submaximal exercise from 66.2 ( SD 2.5 ) to 62.6 ( SD 2.1 ) at 3,610 m ( P < 0.0001 ) , 63.0 ( SD 2.1 ) to 58.9 ( SD 2.1 ) at 4,750 m ( P < 0.0001 ) , and 62.4 ( SD 3.6 ) to 61.2 ( SD 3.9 ) at 5,260 m ( P < 0.01 ) , and at .VO2(max ) to 61.2 ( SD 3.3 ) at 3,610 m ( P < 0.0001 ) , to 59.4 ( SD 2.6 ) at 4,750 m ( P < 0.0001 ) , and to 58.0 ( SD 3.0 ) at 5,260 m ( P < 0.0001 ) . Cerebrovascular resistance tended to fall during submaximal exercise ( P = not significant ) and rise at .VO2(max ) , following the changes in arterial oxygen saturation and end-tidal CO(2 ) . Cerebral oxygen delivery was maintained during submaximal exercise at 150 m with a nonsignificant fall at .VO2(max ) , but at high altitude peaked at 30 % of .VO2(max ) and then fell progressively at higher levels of exercise . The fall in rSO2 and oxygen delivery during exercise may limit exercise at altitude and is likely to contribute to the problems of acute mountain sickness and high-altitude cerebral edema We sought to describe cerebrovascular responses to incremental exercise and test the hypothesis that changes in cerebral oxygenation influence maximal performance . Eleven men cycled in three conditions : 1 ) sea level ( SL ) ; 2 ) acute hypoxia [ AH ; hypobaric chamber , inspired Po(2 ) ( Pi(O(2 ) ) ) 86 Torr ] ; and 3 ) chronic hypoxia [ CH ; 4,300 m , Pi(O(2 ) ) 86 Torr ] . At maximal work rate ( W(max ) ) , fraction of inspired oxygen ( Fi(O(2 ) ) ) was surreptitiously increased to 0.60 , while subjects were encouraged to continue pedaling . Changes in cerebral ( frontal lobe ) ( C(OX ) ) and muscle ( vastus lateralis ) oxygenation ( M(OX ) ) ( near infrared spectroscopy ) , middle cerebral artery blood flow velocity ( MCA V(mean ) ; transcranial Doppler ) , and end-tidal Pco(2 ) ( Pet(CO(2 ) ) ) were analyzed across % W(max ) ( significance at P < 0.05 ) . At SL , Pet(CO(2 ) ) , MCA V(mean ) , and C(OX ) fell as work rate rose from 75 to 100 % W(max ) . During AH , Pet(CO(2 ) ) and MCA V(mean ) declined from 50 to 100 % W(max ) , while C(OX ) fell from rest . With CH , Pet(CO(2 ) ) and C(OX ) dropped throughout exercise , while MCA V(mean ) fell only from 75 to 100 % W(max ) . M(OX ) fell from rest to 75 % W(max ) at SL and AH and throughout exercise in CH . The magnitude of fall in C(OX ) , but not M(OX ) , was different between conditions ( CH > AH > SL ) . Fi(O(2 ) ) 0.60 at W(max ) did not prolong exercise at SL , yet allowed subjects to continue for 96 + /- 61 s in AH and 162 + /- 90 s in CH . During Fi(O(2 ) ) 0.60 , C(OX ) rose and M(OX ) remained constant as work rate increased . Thus cerebral hypoxia appeared to impose a limit to maximal exercise during hypobaric hypoxia ( Pi(O(2 ) ) 86 Torr ) , since its reversal was associated with improved performance The combined effects of hyperventilation and arterial desaturation on cerebral oxygenation ( [ Formula : see text ] ) were determined using near-infrared spectroscopy . Eleven competitive oarsmen were evaluated during a 6-min maximal ergometer row . The study was r and omized in a double-blind fashion with an inspired O2 fraction of 0.21 or 0.30 in a crossover design . During exercise with an inspired O2 fraction of 0.21 , the arterial CO2 pressure ( 35 ± 1 mmHg ; mean ± SE ) and O2 pressure ( 77 ± 2 mmHg ) as well as the hemoglobin saturation ( 91.9 ± 0.7 % ) were reduced ( P < 0.05).[Formula : see text ] was reduced from 80 ± 2 to 63 ± 2 % ( P < 0.05 ) , and the near-infrared spectroscopy-determined concentration changes in deoxy- ( ΔHb ) and oxyhemoglobin ( ΔHbO2 ) of the vastus lateralis muscle increased 22 ± 3 μM and decreased 14 ± 3 μM , respectively ( P < 0.05 ) . Increasing the inspired O2fraction to 0.30 did not affect ventilation ( 174 ± 4 l/min ) , but arterial CO2 pressure ( 37 ± 2 mmHg ) , O2 pressure ( 165 ± 5 mmHg ) , and hemoglobin O2saturation ( 99 ± 0.1 % ) increased ( P < 0.05).[Formula : see text ] remained close to the resting level during exercise ( 79 ± 2 vs. 81 ± 2 % ) , and although the muscle ΔHb ( 18 ± 2 μM ) and ΔHbO2 ( -12 ± 3 μM ) were similar to those established without O2 supplementation , work capacity increased from 389 ± 11 to 413 ± 10 W ( P < 0.05 ) . These results indicate that an elevated inspiratory O2fraction increases exercise performance related to maintained cerebral oxygenation rather than to an effect on the working muscles Background —A classic , unresolved physiological question is whether central cardiorespiratory and /or local skeletal muscle circulatory factors limit maximal aerobic capacity ( & OV0312;o2max ) in humans . Severe heat stress drastically reduces & OV0312;o2max , but the mechanisms have never been studied . Methods and Results —To determine the main contributing factor that limits & OV0312;o2max with and without heat stress , we measured hemodynamics in 8 healthy males performing intense upright cycling exercise until exhaustion starting with either high or normal skin and core temperatures ( + 10 ° C and + 1 ° C ) . Heat stress reduced & OV0312;o2max , 2-legged & OV0312;o2 , and time to fatigue by 0.4±0.1 L/min ( 8 % ) , 0.5±0.2 L/min ( 11 % ) , and 2.2±0.4 minutes ( 28 % ) , respectively ( all P < 0.05 ) , despite heart rate and core temperature reaching similar peak values . However , before exhaustion in both heat stress and normal conditions , cardiac output , leg blood flow , mean arterial pressure , and systemic and leg O2 delivery declined significantly ( all 5 % to 11 % , P < 0.05 ) , yet arterial O2 content and leg vascular conductance remained unchanged . Despite increasing leg O2 extraction , leg & OV0312;o2 declined 5 % to 6 % before exhaustion in both heat stress and normal conditions , accompanied by enhanced muscle lactate accumulation and ATP and creatine phosphate hydrolysis . Conclusions —These results demonstrate that in trained humans , severe heat stress reduces & OV0312;o2max by accelerating the declines in cardiac output and mean arterial pressure that lead to decrements in exercising muscle blood flow , O2 delivery , and O2 uptake . Furthermore , the impaired systemic and skeletal muscle aerobic capacity that precedes fatigue with or without heat stress is largely related to the failure of the heart to maintain cardiac output and O2 delivery to locomotive muscle The present study tested the hypothesis that perceived exertion during prolonged exercise in hot environments is associated with changes in cerebral electrical activity rather than changes in the electromyogram ( EMG ) of the exercising muscles . Therefore , electroencephalogram ( EEG ) in three positions ( frontal , central , and occipital cortex ) , EMG , rating of perceived exertion ( RPE ) , and core temperature were measured in 14 subjects during submaximal exercise in normal ( 18 degrees C , control ) and hot ( 40 degrees C , hyperthermia ) environments . RPE increased from 11 + /- 1 units at 5 min to 20 + /- 0 units at exhaustion ( 50 + /- 3 min ) in the trial with progressive hyperthermia , whereas exercise in the control trial was maintained with a stable core temperature for 1 h without exhausting the subjects . Altered EEG activity was observed in all electrode positions , and stepwise forward-regression analysis identified core temperature and a frequency index of the EEG over the frontal cortex as the best predictors of RPE . In contrast , there were no significant correlations between RPE and any of the measured EMG parameters ( median spectral frequency , root mean square , or amplitude ) , and the EMG parameters were not different in hyperthermia compared with control . Thus hyperthermia does not seem to affect the activation pattern of the muscles . Rather , the linear correlation among core temperature , EEG frequency index , and RPE indicates that alterations in cerebral activity may be associated with the hyperthermia-induced development of fatigue during prolonged exercise in hot environments We have compared the effect of increasing optode separation ( range 0.7 - 5.5 cm ) on the sensitivity of near infrared spectroscopy ( NIRS ) to discrete reductions in scalp and cerebral oxygenation in 10 healthy men ( mean age 32 , range 26 - 39 yr ) using multichannel NIRS . During cerebral oligaemia ( a mean reduction in middle cerebral artery flow velocity of 47 % ) induced by a mean reduction in end-tidal PCO2 of 2.4 kPa , the decrease in oxyhaemoglobin detected by NIRS became significantly greater with increasing optode separation ( P < 0.0001 ) . In response to scalp hyperaemia induced by inflation and release of a pneumatic scalp tourniquet , increases in oxyhaemoglobin became significantly smaller with increasing optode separation ( P < 0.0002 ) . These results are consistent with theoretical models of the behaviour of NIR light in the adult head and support the concept of using multi-detector NIRS to separate intra- and extracranial NIR signal changes . However , the emitter-detector separation used by currently available cerebral oximeters is not large enough to provide optimal spatial resolution The basic parameters for physiological measurements provided by near-infrared spectroscopy are the local absorption and scattering coefficients . For the adult human head , they have been difficult to measure noninvasively because of the layered structure of the head . The results of measurements of absorption and reduced scattering coefficients through the forehead on 30 adult volunteers using a multidistance frequency domain method are reported . The optode separation distance ranged from 10 to 80 mm and measurements were recorded at 758 and 830 nm . The measured absorption and reduced scattering coefficients of the forehead were used to evaluate the hemoglobin content in the scalp and brain as well as cerebral oxygen saturation . We found that cerebral oxygenation was relatively narrowly distributed within the subject group ( the st and ard deviation was about 3 % for scalp and 6 % for brain , respectively ) , whereas hemoglobin concentrations had a relatively broader distribution . We found that as the optode distance increased , the absorption coefficients increased and the scattering coefficients decreased , retrieving the optical values of scalp and brain for shorter and longer optode distances , respectively . We present the transition curves of the absorption and reduced scattering coefficients as functions of the optode distance . In order to verify the values for each layer , a comparison between the experimental data and a prediction based on the two-layer model of the adult head was carried out . The thicknesses of scalp and skull for the two-layer model were obtained by magnetic resonance imaging of a subject 's head . The optical parameters obtained from the two-layer model agreed very well with those measured by the multidistance method During maximal exercise in humans , fatigue is preceded by reductions in systemic and skeletal muscle blood flow , O(2 ) delivery and uptake . Here , we examined whether the uptake of O(2 ) and substrates by the human brain is compromised and whether the fall in stroke volume of the heart underlying the decline in systemic O(2 ) delivery is related to declining venous return . We measured brain and central haemodynamics and oxygenation in healthy males ( n= 13 in 2 studies ) performing intense cycling exercise ( 360 + /- 10 W ; mean + /-s.e.m . ) to exhaustion starting with either high ( H ) or normal ( control , C ) body temperature . Time to exhaustion was shorter in H than in C ( 5.8 + /- 0.2 versus 7.5 + /- 0.4 min , P < 0.05 ) , despite heart rate reaching similar maximal values . During the first 90 s of both trials , frontal cortex tissue oxygenation and the arterial-internal jugular venous differences ( a-v diff ) for O(2 ) and glucose did not change , whereas middle cerebral artery mean flow velocity ( MCA V(mean ) ) and cardiac output increased by approximately 22 and approximately 115 % , respectively . Thereafter , brain extraction of O(2 ) , glucose and lactate increased by approximately 45 , approximately 55 and approximately 95 % , respectively , while frontal cortex tissue oxygenation , MCA V(mean ) and cardiac output declined approximately 40 , approximately 15 and approximately 10 % , respectively . At exhaustion in both trials , systemic VO(2 ) declined in parallel with a similar fall in stroke volume and central venous pressure ; yet the brain uptake of O(2 ) , glucose and lactate increased . In conclusion , the reduction in stroke volume , which underlies the fall in systemic O(2 ) delivery and uptake before exhaustion , is partly related to reductions in venous return to the heart . Furthermore , fatigue during maximal exercise , with or without heat stress , in healthy humans is associated with an enhanced rather than impaired brain uptake of O(2 ) and substrates The discharge frequency of human motoneurons declines during a sustained isometric maximal voluntary contraction ( MVC ) of elbow flexor muscles , but the cause is unresolved . We aim ed to determine whether motoneurons were inhibited during a sustained fatiguing contraction of the elbow flexor muscles and whether this inhibition was caused by the discharge of group III and IV muscle afferents . Subjects performed brief MVCs before and after a fatiguing 2 min MVC . During maximal efforts , electromyographic responses recorded from the elbow flexor muscles were evoked by stimulation of the corticospinal tracts at the cervicomedullary level [ cervicomedullary motor evoked potentials ( CMEPs ) ] and by supramaximal stimulation over the brachial plexus ( Mmax ) . This revealed a novel decrease in the size of the muscle response to corticospinal tract stimulation during fatigue . During the sustained MVCs , the size of CMEPs decreased to 81 ± 15 and 78 ± 15 % of the control value for brachioradialis and biceps brachii , respectively ( mean ± SEM ; n = 8) . This recovered within 15 sec after the fatiguing contraction . In a second set of studies , input from group III and IV muscle afferents was prolonged after the end of the fatiguing contraction by holding the muscle ischemic with a cuff inflated above arterial pressure . Despite the maintained discharge of group III and IV afferents , the CMEPs again recovered within 15 sec of the end of the sustained contraction . These results show a diminished output of spinal motoneurons to stimulation of corticospinal tracts during a fatiguing MVC ; however , the mechanisms responsible for this decline are not attributable to activity in group III and IV muscle afferents Cardiovascular fitness is thought to offset declines in cognitive performance , but little is known about the cortical mechanisms that underlie these changes in humans . Research using animal models shows that aerobic training increases cortical capillary supplies , the number of synaptic connections , and the development of new neurons . The end result is a brain that is more efficient , plastic , and adaptive , which translates into better performance in aging animals . Here , in two separate experiments , we demonstrate for the first time to our knowledge , in humans that increases in cardiovascular fitness results in increased functioning of key aspects of the attentional network of the brain during a cognitively challenging task . Specifically , highly fit ( Study 1 ) or aerobically trained ( Study 2 ) persons show greater task-related activity in regions of the prefrontal and parietal cortices that are involved in spatial selection and inhibitory functioning , when compared with low-fit ( Study 1 ) or nonaerobic control ( Study 2 ) participants . Additionally , in both studies there exist groupwise differences in activation of the anterior cingulate cortex , which is thought to monitor for conflict in the attentional system , and signal the need for adaptation in the attentional network . These data suggest that increased cardiovascular fitness can affect improvements in the plasticity of the aging human brain , and may serve to reduce both biological and cognitive senescence in humans In this study , we have preformed simultaneous near-infrared spectroscopy ( NIRS ) along with BOLD ( blood oxygen level dependent ) and ASL ( arterial spin labeling)-based fMRI during an event-related motor activity in human subjects in order to compare the temporal dynamics of the hemodynamic responses recorded in each method . These measurements have allowed us to examine the validity of the biophysical models underlying each modality and , as a result , gain greater insight into the hemodynamic responses to neuronal activation . Although prior studies have examined the relationships between these two method ologies through similar experiments , they have produced conflicting results in the literature for a variety of reasons . Here , by employing a short- duration , event-related motor task , we have been able to emphasize the subtle temporal differences between the hemodynamic parameters with a high contrast-to-noise ratio . As a result of this improved experimental design , we are able to report that the fMRI measured BOLD response is more correlated with the NIRS measure of deoxy-hemoglobin ( R = 0.98 ; P < 10(-20 ) ) than with oxy-hemoglobin ( R = 0.71 ) , or total hemoglobin ( R = 0.53 ) . This result was predicted from the theoretical grounds of the BOLD response and is in agreement with several previous works [ Toronov , V.A.W. , Choi , J.H. , Wolf , M. , Michalos , A. , Gratton , E. , Hueber , D. , 2001 . " Investigation of human brain hemodynamics by simultaneous near-infrared spectroscopy and functional magnetic resonance imaging . " Med . Phys . 28 ( 4 ) 521 - 527 . ; MacIntosh , B.J. , Klassen , L.M. , Menon , R.S. , 2003 . " Transient hemodynamics during a breath hold challenge in a two part functional imaging study with simultaneous near-infrared spectroscopy in adult humans " . NeuroImage 20 1246 - 1252 . ; Toronov , V.A.W. , Walker , S. , Gupta , R. , Choi , J.H. , Gratton , E. , Hueber , D. , Webb , A. , 2003 . " The roles of changes in deoxyhemoglobin concentration and regional cerebral blood volume in the fMRI BOLD signal " Neuroimage 19 ( 4 ) 1521 - 1531 ] . These data have also allowed us to examine more detailed measurement models of the fMRI signal and comment on the roles of the oxygen saturation and blood volume contributions to the BOLD response . In addition , we found high correlation between the NIRS measured total hemoglobin and ASL measured cerebral blood flow ( R = 0.91 ; P < 10(-10 ) ) and oxy-hemoglobin with flow ( R = 0.83 ; P < 10(-05 ) ) as predicted by the biophysical models . Finally , we note a significant amount of cross-modality , correlated , inter-subject variability in amplitude change and time-to-peak of the hemodynamic response . The observed co-variance in these parameters between subjects is in agreement with hemodynamic models and provides further support that fMRI and NIRS have similar vascular sensitivity The aim of the present study was to examine the effects of an exercise of moderate intensity ( 60 % of maximal aerobic power ) on specific information-processing mechanisms . 22 students completed 3 10-min . exercise bouts on a bicycle ergometer . Concomitantly , participants performed six manual choice-reaction tasks manipulating task variables ( Signal Intensity , Stimulus – Response Compatibility , and Time Uncertainty ) on two levels . Reaction tests , r and omly ordered , were administered at rest and during exercise . A significant underadditive interaction between Time Uncertainty and exercise was found for the highest quartiles of the distribution of reaction times . No other interaction effects were obtained for the other variables . These results reasonably support that moderate aerobic exercise showed selective rather than general influences on information processing Electrophysiological effects of aerobic fitness and maximal aerobic exercise were investigated by comparing P300 and N400 before and after a maximal cycling test . Event-related potentials ( ERPs ) were obtained from 20 students divided into two matched groups defined by their aerobic fitness level ( cyclists vs. sedentary subjects ) . The session of postexercise ERPs was performed immediately after body temperature and heart rate returned to preexercise values . At rest , no significant differences were observed in ERP parameters between cyclists and sedentary subjects . This finding argued against the hypothesis that ERP modifications may be directly assumed by aerobic fitness level . The postexercise session of ERPs showed a significant P300 amplitude increase and a significant P300 latency decrease in all subjects . Similarly , N400 effect increased significantly after the maximal exercise in all subjects . ERP changes were of the same magnitude in the two groups . The present study argues for a general arousing effect of maximal aerobic exercise , independently of the aerobic fitness level Critical power ( CP ) and the second ventilatory threshold ( VT2 ) are presumed to indicate the power corresponding to maximal lactate steady state ( MLSS ) . The aim of this study was to investigate the use of CP and VT2 as indicators of MLSS . Eleven male trained subjects [ mean ( SD ) age 23 ( 2.9 ) years ] performed an incremental test ( 25 W·min−1 ) to determine maximal oxygen uptake ( V̇O2max ) , maximal aerobic power ( MAP ) and the first and second ventilatory thresholds ( VT1 and VT2 ) associated with break points in minute ventilation ( V̇E ) , carbon dioxide production ( V̇CO2 ) , V̇E/V̇CO2 and V̇E/V̇O2 relationships . Exhaustion tests at 90 % , 95 % , 100 % and 110 % of V̇O2max and several 30-min constant work rates were performed in order to determine CP and MLSS , respectively . MAP and V̇O2max values were 344 ( 29 ) W and 53.4 ( 3.7 ) ml·min−1·kg−1 , respectively . CP [ 278 ( 22 ) W ; 85.4 (4.8)% V̇O2max ] and VT2 power output [ 286 ( 28 ) W ; 85.3 (5.6)% V̇O2max ] were not significantly different ( p=0.96 ) but were higher ( p<0.05 ) than the MLSS work rate [ 239 ( 21 ) W ; 74.3 (4.0)% V̇O2max ] and VT1 power output [ 159 ( 23 ) W ; 52.9 (6.9)% V̇O2max ] . MLSS work rate was significantly correlated ( p<0.05 ) with those noted at VT1 and VT2 ( r=0.74 and r=0.93 , respectively ) . VT2 overestimated MLSS by 10.9 (6.3)% V̇O2max which was significantly higher than VT1 [ + 21.4 (5.6)% V̇O2max ; p<0.01 ] . CP calculated from a given range of exhaustion times does not correspond to MLSS We examined the effects of hypoxia severity on peripheral versus central determinants of exercise performance . Eight cyclists performed constant-load exercise to exhaustion at various fractions of inspired O2 fraction ( FIO2 0.21/0.15/0.10 ) . At task failure ( pedal frequency < 70 % target ) arterial hypoxaemia was surreptitiously reversed via acute O2 supplementation ( FIO2 = 0.30 ) and subjects were encouraged to continue exercising . Peripheral fatigue was assessed via changes in potentiated quadriceps twitch force ( DeltaQ(tw , pot ) ) as measured pre- versus post-exercise in response to supramaximal femoral nerve stimulation . At task failure in normoxia ( haemoglobin saturation ( SpO2 ) approximately 94 % , 656 + /- 82 s ) and moderate hypoxia ( SpO2 ) approximately 82 % , 278 + /- 16 s ) , hyperoxygenation had no significant effect on prolonging endurance time . However , following task failure in severe hypoxia ( SpO2 ) approximately 67 % ; 125 + /- 6 s ) , hyperoxygenation elicited a significant prolongation of time to exhaustion ( 171 + /- 61 % ) . The magnitude of DeltaQ(tw , pot ) at exhaustion was not different among the three trials ( -35 % to -36 % , P = 0.8 ) . Furthermore , quadriceps integrated EMG , blood lactate , heart rate , and effort perceptions all rose significantly throughout exercise , and to a similar extent at exhaustion following hyperoxygenation at all levels of arterial oxygenation . Since hyperoxygenation prolonged exercise time only in severe hypoxia , we repeated this trial and assessed peripheral fatigue following task failure prior to hyperoxygenation ( 125 + /- 6 s ) . Although Q(tw , pot ) was reduced from pre-exercise baseline ( -23 % ; P < 0.01 ) , peripheral fatigue was substantially less ( P < 0.01 ) than that observed at task failure in normoxia and moderate hypoxia . We conclude that across the range of normoxia to severe hypoxia , the major determinants of central motor output and exercise performance switches from a predominantly peripheral origin of fatigue to a hypoxia-sensitive central component of fatigue , probably involving brain hypoxic effects on effort perception STUDY OBJECTIVES In patients with terminal lung disease who were exercising , we assessed whether improved arterial O2 saturation with an increased fraction of inspired oxygen ( FIO2 ) affects cerebral oxygenation . DESIGN R and omized , crossover . PATIENTS AND METHODS The cerebral changes in oxyhemoglobin ( DeltaHbO2 ) and changes in deoxyhemoglobin ( DeltaHb ) levels were evaluated using near-infrared spectrophotometry and the middle cerebral artery ( MCA ) mean velocity ( V(mean ) ) was determined by transcranial Doppler ultrasonography in 13 patients with terminal lung disease ( New York Heart Association class III-IV ) . Patients were allocated to an FIO2 of either 0.21 or 0.35 during incremental exercise with 15 min between trials . RESULTS Peak exercise intensity ( mean [ + /- SE ] , 26 + /- 4 W ) reduced the arterial O2 pressure ( at rest , 64 + /- 3 mm Hg ; during exercise , 56 + /- 3 mm Hg ) and the arterial oxygen saturation ( SaO2 ) [ at rest , 92 + /- 2 % ; 87 + /- 2 % ; p < 0.05 ] , while the arterial CO2 pressure was not significantly affected . The MCA V(mean ) increased from 49 + /- 5 to 63 + /- 7 cm/s ( p < 0.05 ) as did the DeltaHb , while the DeltaHbO2 remained unaffected by exercise . With an elevated FIO2 , the SaO2 level ( at rest , 95.8 + /- 0.7 % ; during exercise , 96.0 + /- 1.0 % ) and arterial O2 pressure ( at rest , 102 + /- 11 mm Hg ; during exercise , 100 + /- 8 mm Hg ) were not significantly affected by exercise , and the levels of blood oxygenation remained higher than the values established at normoxia ( p < 0.05 ) . The MCA V(mean ) increased to a level similar to that achieved during control exercise ( ie , to 70 + /- 11 cm/s ) . In contrast to control exercise , DeltaHb decreased while DeltaHbO2 increased during exercise with 35 % O2 ( p < 0.05 ) . CONCLUSION An O2-enriched atmosphere enabled patients with terminal lung disease to maintain arterial O2 saturation during exercise . An exercise-induced increase in cerebral perfusion was not affected by hyperoxia , whereby the enhanced availability of oxygenated hemoglobin increases cerebral oxygenation . The clinical implication of the study is that during physical activity patients with terminal lung disease are recommended to use an elevated FIO2 to protect cerebral oxygenation Investigators of brain electrocortical responses to exercise have interpreted increased activity , or frontal hemispheric asymmetry , in the alpha frequency b and as indicative of relaxation or a change in affect . However , few studies compared alpha activity with other frequencies and within or across hemispheres . To clarify the cumulative evidence in this area , we provide a quantitative review of the effects of exercise on brain electrocortical activity according to frequency b and s and recording sites . Fifty-eight effects from 18 studies and 282 participants were retrieved . The mean effect size was moderately large ( 0.54 SD , 95 % CI : 0.43 to 0.65 ) but heterogeneous . Compared to before exercise , alpha activity was greater immediately after and during exercise when expressed as absolute power but not as relative to power in other frequency b and s ; delta , theta , and beta activity also increased ( 0.38 to 0.75 SD ) . Effects did not differ significantly by recording sites . The cumulative evidence does not indicate that change in brain electrocortical activity after exercise is specific to alpha activity or hemispheric site Two experiments are reported that examine the possibility that exercise selectively influences different types of cognition . To our knowledge , these experiments represent the first attempt to study higher-cognitive processes during exercise . Theoretical thinking was guided by the transient hypofrontality hypothesis . In both experiments , athletes who exercised at a sustained , moderate pace were compared to sedentary controls on two neuropsychological tests , one that is generally regarded as heavily dependent on prefrontal cognition and one that is relatively insensitive to prefrontal operation . Results showed that during exercise performance on tests dem and ing prefrontal-dependent cognition was impaired , while at the same time , cognitive processes requiring little prefrontal activity were unaffected Aim : Beta‐blockers reduce exercise capacity by attenuated increase in cardiac output , but it remains unknown whether performance also relates to attenuated cerebral oxygenation We investigated changes of regional activation in the frontal cortices as assessed by changes of hemoglobin oxygenation during walking at 3 and 5 km/h and running at 9 km/h on a treadmill using a near-infrared spectroscopic ( NIRS ) imaging technique . During the acceleration periods immediately preceded reaching the steady walking or running speed , the levels of oxygenated hemoglobin ( oxyHb ) increased , but those of deoxygenated hemoglobin ( deoxyHb ) did not in the frontal cortices . The changes were greater at the higher locomotor speed in the bilateral prefrontal cortex and the premotor cortex , but there were less speed-associated changes in the sensorimotor cortices . The medial prefrontal activation was most prominent during the running task . These results indicate that the prefrontal and premotor cortices are involved in adapting to locomotor speed on the treadmill . These areas might predominantly participate in the control of running rather than walking Dynamic exercise enhances regional cerebral artery mean flow velocity . J. Appl . Physiol . 78(1 ) : 12 - 16 , 1995.--Anterior ( ACA ) and middle ( MCA ) cerebral artery mean flow velocities ( Vmean ) and pulsatility indexes were determined using transcranial Doppler in 14 subjects during dynamic exercise after assessment of the carbon dioxide reactivity for both arteries . Right h and contractions provoked an elevation in left MCA Vmean [ 19 % ( 12 - 28 ) ; P < 0.01 ] , whereas the pulsatility decreased in all four arteries ( P < 0.05 ) . During right foot movement , left ACA Vmean increased by 23 % ( 11 - 37 ; P < 0.01 ) with lesser ( approximately 10 % ; P < 0.05 ) increases in the other arteries , and pulsatility index decreased ( P < 0.05 ) . During cycling , ACA and MCA Vmean increased bilaterally by 23 % ( 10 - 49 ) and 18 % ( 5 - 32 ) , respectively ( P < 0.01 ) , and the pulsatility was also elevated ( P < 0.05 ) . Cerebral artery pulsatility did not demonstrate a focal response but depended did not demonstrate a focal response but depended on the muscle mass involved during exercise . The data demonstrate a significant increase in Vmean for the artery supplying the cortical projection of the exercising limb . Insignificant and marginally significant increases in Vmean may be related to sympathetically mediated vasoconstriction and /or coactivation of untargeted muscle groups The present study examined the regional differences of cortical oxygenation in the frontal lobe by near-infrared spectroscopy ( NIRS ) during incremental exercise tests and the precise location of NIRS was examined by brain magnetic resonance imaging ( MRI ) . Pulmonary gas exchange and NIRS measurement during incremental cycling ergometry tests were investigated in 14 men . In 7 of these subjects , the right middle cerebral artery mean velocity ( MCA Vmean ) was simultaneously measured by transcranial Doppler ( TCD ) . In the right medial of the frontal lobe cortex , Tissue Oxygenation Index ( TOI ) increased by 8.8 % with its peak value at respiratory compensation threshold ( RCT ) and Normalized Tissue Hemoglobin Index ( nTHI ) increased until endpoint by 16.2 % . During incremental exercise tests , the changing pattern of TOI was different according to the distribution of the probes . Volitional exhaustion by exercise induced the deteriorated TOI and MCA Vmean , whereas nTHI increased BACKGROUND In a recent study the indexes of cerebral oxygenation decreased during maximal exercise in nearly half of all patients with left ventricular dysfunction . Whether these levels decrease severely enough to influence mental status or level of consciousness was evaluated in the present study . METHODS AND RESULTS Forty-two patients with idiopathic dilated cardiomyopathy ( IDC ) and 29 healthy subjects underwent a symptom-limited maximal exercise test . The cerebral oxyhemoglobin ( O(2)Hb ) and tissue oxygenation index ( TOI ) were continuously monitored using near-infrared spectroscopy . The changes in O(2)Hb and TOI were also measured in 7 subjects : 2 who experienced episodes of reduced consciousness caused by sudden decreases in blood pressure during exercise recovery and 5 who exhibited sustained ventricular tachycardia during an electrophysiological study . The change in cerebral O(2)Hb during exercise in patients with IDC averaged 0.38+/-3.39 micromol/L , significantly lower than in the normal subjects ( 4.30+/-4.47 micromol/L , p<0.0001 ) . The cerebral O(2)Hb decreased during exercise in 18 of 42 patients with IDC . The change in cerebral TOI in the IDC patients during exercise was significantly less than that in the normal subjects ( -2.0+/-4.7 vs 2.1+/-5.8 % , p=0.002 ) . The mean decreases in cerebral O(2)Hb and TOI were -5.34 micromol/L and -9.7 % , respectively , in the patients with reduced consciousness during exercise recovery , and -2.52 micromol/L and -16.5 % , respectively , in those with ventricular tachycardia . CONCLUSION The indexes of cerebral oxygenation may drop severely enough during maximal exercise in some patients with severe IDC that consciousness is affected Near infrared spectroscopy ( NIRS ) may provide valuable insight into the determinants of exercise performance . We examined the effects of severe hypoxia on cerebral ( prefrontal lobe ) and muscle ( gastrocnemius ) oxygenation at rest and during a fatiguing task . After a 15-min rest , 15 healthy subjects ( age 25.3 + /- 0.9 yr ) performed a sustained contraction of the ankle extensors at 40 % of maximal voluntary force until exhaustion . The contraction was performed at two different fractions of inspired O2 fraction ( F(IO2 ) = 0.21/0.11 ) in r and omized and single-blind fashion . Cerebral and muscle oxy-(HbO2 ) deoxy-(HHb ) total-hemoglobin ( HbTot ) and tissue oxygenation index ( TOI ) were monitored continuously by NIRS . Arterial O2 saturation ( SpO2 ) was estimated by pulse oximetry throughout the protocol . Muscle TOI did not differ between normoxia and hypoxia after the 15-min rest , whereas SpO2 and cerebral TOI significantly dropped ( -6.5 + /- 0.9 % and -3.9 + /- 1.0 % , respectively , P<0.05 ) in hypoxia . The muscle NIRS changes during exercise were similar in normoxia and hypoxia , whereas the increased cerebral HbTot and HbO2 near exhaustion were markedly reduced in hypoxia . In conclusion , although F(IO2 ) had no significant effect on endurance time , NIRS patterns near exhaustion in hypoxia differed from normoxia |
10,743 | 19,191,776 | Recommendations for induction of labour for post-term gestation , PROM at term , and premature rupture of membranes near term with pulmonary maturity are supported by the evidence .
Induction for IUGR before term reduces intrauterine fetal death , but increases caesarean deliveries and neonatal deaths .
Evidence is insufficient to support induction for women with insulin-requiring diabetes , twin gestation , fetal macrosomia , oligohydramnios , cholestasis of pregnancy , maternal cardiac disease and fetal gastroschisis .
AUTHORS ' CONCLUSIONS Research is needed to determine risks and benefits of induction for many commonly advocated clinical indications | BACKGROUND Rates of labour induction are increasing .
OBJECTIVES To review the evidence supporting indications for induction . | OBJECTIVE : To compare induction of labor at gestational age 41 weeks with expectant management in regard to neonatal morbidity . Secondary aims were to assess the effect of these managements on mode of delivery and maternal complications . METHODS : Between September 2002 and July 2004 , postterm women with singleton cephalic presentation and no prelabor rupture of membranes were r and omly assigned to induction of labor at 289 days or antenatal fetal surveillance every third day until spontaneous labor . Main outcome measures were neonatal morbidity , operative delivery rates , and maternal complications . RESULTS : Five hundred eight women were r and omly assigned , 254 in each group . No differences of clinical importance were observed in women in whom labor was induced compared with women who were expectantly managed with regard to the following outcomes : neonates whose 5-minute Apgar score was less than 7 ( three neonates in the induction group compared with four in the monitoring group , P=.72 ) ; neonates whose umbilical cord pH was less than 7 ( three compared with two , P=.69 ) ; prevalence of cesarean delivery ( 28 compared with 33 , P=.50 ) ; or prevalence of operative vaginal delivery ( 32 compared with 27 , P=.49 ) . In the induction group more women had precipitate labors ( 33 compared with 12 , P<.01 ; number needed to treat was 13 ) , and the duration of second stage of labor was more often less than 15 minutes ( 94 compared with 56 , P<.01 ; number needed to treat was 7 ) . CONCLUSION : No differences were found between the induced and monitored groups regarding neonatal morbidity or mode of delivery , and the outcomes were generally good . CLINICAL TRIAL REGISTRATION : Clinical Trials.gov , www . clinical trials.gov , NCT00385229 LEVEL OF EVIDENCE : Background Around 80 % of intrauterine growth restricted ( IUGR ) infants are born at term . They have an increase in perinatal mortality and morbidity including behavioral problems , minor developmental delay and spastic cerebral palsy . Management is controversial , in particular the decision whether to induce labour or await spontaneous delivery with strict fetal and maternal surveillance . We propose a r and omised trial to compare effectiveness , costs and maternal quality of life for induction of labour versus expectant management in women with a suspected IUGR fetus at term . Methods / design The proposed trial is a multi-centre r and omised study in pregnant women who are suspected on clinical grounds of having an IUGR child at a gestational age between 36 + 0 and 41 + 0 weeks . After informed consent women will be r and omly allocated to either induction of labour or expectant management with maternal and fetal monitoring . R and omisation will be web-based . The primary outcome measure will be a composite neonatal morbidity and mortality . Secondary outcomes will be severe maternal morbidity , maternal quality of life and costs . Moreover , we aim to assess neurodevelopmental and neurobehavioral outcome at two years as assessed by a postal enquiry ( Child Behavioral Check List-CBCL and Ages and Stages Question naire-ASQ ) . Analysis will be by intention to treat . Quality of life analysis and a preference study will also be performed in the same study population . Health technology assessment with an economic analysis is part of this so called Digitat trial ( Disproportionate Intrauterine Growth Intervention Trial At Term ) . The study aims to include 325 patients per arm . Discussion This trial will provide evidence for which strategy is superior in terms of neonatal and maternal morbidity and mortality , costs and maternal quality of life aspects . This will be the first r and omised trial for IUGR at term . Trial registration Dutch Trial Register and IS RCT N-Register : IS RCT N10363217 Objectives : In low-risk pregnancies , the management of oligohydramnios is not clear . The aim of this study was to compare maternal and neonatal outcomes in cases of isolated oligohydramnios r and omised to either induction of labour or expectant management . Methods : 87 women pregnant beyond 40 completed weeks were asked to participate in the study . Fifty-four accepted and were r and omised at 288 days of pregnancy . Twenty-six were r and omised to expectant management and 28 to induction of labour . The primary maternal outcome was the mode of delivery and the primary neonatal outcomes were cord blood pH and Apgar score at delivery . Results : No significant differences were found for any important maternal or neonatal outcome . Conclusion : Based on these results , the decisions about management could be individualised . Even though the number of patients included was small , these results are well in concordance with others BACKGROUND As the interval between rupture of the fetal membranes at term and delivery increases , so may the risk of fetal and maternal infection . It is not known whether inducing labor will reduce this risk or whether one method of induction is better then another . METHODS We studied 5041 women with prelabor rupture of the membranes at term . The women were r and omly assigned to induction of labor with intravenous oxytocin ; induction of labor with vaginal prostagl and in E2 gel ; or expectant management for up to four days , with labor induced with either intravenous oxytocin or vaginal prostagl and in E2 gel if complications developed . The primary outcome was neonatal infection . Secondary outcomes were the need for cesarean section and women 's evaluations of their treatment . RESULTS The rates of neonatal infection and cesarean section were not significantly different among the study groups . The rates of neonatal infection were 2.0 percent for the induction-with-oxytocin group , 3.0 percent for the induction-with-prostagl and in group , 2.8 percent for the expectant-management ( oxytocin ) group , and 2.7 percent for the expectant-management ( prostagl and in ) group . The rates of cesarean section ranged from 9.6 to 10.9 percent . Clinical chorioamnionitis was less likely to develop in the women in the induction-with-oxytocin group than in those in the expectant-management ( oxytocin ) group ( 4.0 percent vs. 8.6 percent , P<0.001 ) , as was postpartum fever ( 1.9 percent vs. 3.6 percent , P=0.008 ) . Women in the induction groups were less likely to say they liked " nothing " about their treatment than those in the expectant-management groups . CONCLUSIONS In women with prelabor rupture of the membranes at term , induction of labor with oxytocin or prostagl and in E2 and expectant management result in similar rates of neonatal infection and cesarean section . Induction of labor with intravenous oxytocin results in a lower risk of maternal infection than does expectant management . Women view induction of labor more positively than expectant management Background Hypertensive disorders , i.e. pregnancy induced hypertension and preeclampsia , complicate 10 to15 % of all pregnancies at term and are a major cause of maternal and perinatal morbidity and mortality . The only causal treatment is delivery . In case of preterm pregnancies conservative management is advocated if the risks for mother and child remain acceptable . In contrast , there is no consensus on how to manage mild hypertensive disease in pregnancies at term . Induction of labour might prevent maternal and neonatal complications at the expense of increased instrumental vaginal delivery rates and caesarean section rates . Methods / Design Women with a pregnancy complicated by pregnancy induced hypertension or mild preeclampsia at a gestational age between 36 + 0 and 41 + 0 weeks will be asked to participate in a multi-centre r and omised controlled trial . Women will be r and omised to either induction of labour or expectant management for spontaneous delivery . The primary outcome of this study is severe maternal morbidity , which can be complicated by maternal mortality in rare cases . Secondary outcome measures are neonatal mortality and morbidity , caesarean and vaginal instrumental delivery rates , maternal quality of life and costs . Analysis will be by intention to treat . In total , 720 pregnant women have to be r and omised to show a reduction in severe maternal complications of hypertensive disease from 12 to 6 % . Discussion This trial will provide evidence as to whether or not induction of labour in women with pregnancy induced hypertension or mild preeclampsia ( nearly ) at term is an effective treatment to prevent severe maternal complications . Trial Registration The protocol is registered in the clinical trial register number IS RCT N08132825 Abstract Aim : To evaluate the efficacy and safety of oral misoprostol for labor induction in women with term premature rupture of membranes ( PROM ) and an unfavorable cervix . Methods : We r and omized 130 women with PROM of ≤4 h to either oral misoprostol , 50 μg , or a placebo given every 4 h for up to three doses . Intravenous oxytocin was initiated if active labor did not begin within 12 h. Results : Sixty-four women received oral misoprostol and 66 received placebo . The PROM-to-delivery interval was shorter with misoprostol than with placebo ( 13.7±5.8 vs. 20.3±6.8 h , respectively , P<0.05 ) . Misoprostol significantly reduced the need for oxytocin ( 28.1 vs. 72.7 % , P<0.001 ) and antibiotics ( 25 vs. 69.7 % , P<0.001 ) . No significant differences in cesarean section or hyperstimulation rate were noted . Conclusion : Oral misoprostol given to women with unfavorable cervix soon after term PROM significantly reduces the induction-to-delivery time and the need for oxytocin and antibiotics BACKGROUND Although delivery is widely used for preterm babies failing to thrive in utero , the effect of altering delivery timing has never been assessed in a r and omised controlled trial . We aim ed to compare the effect of delivering early with delaying birth for as long as possible . METHODS 548 pregnant women were recruited by 69 hospitals in 13 European countries . Participants had fetal compromise between 24 and 36 weeks , an umbilical-artery doppler waveform recorded , and clinical uncertainty about whether immediate delivery was indicated . Before birth , 588 babies were r and omly assigned to immediate delivery ( n=296 ) or delayed delivery until the obstetrician was no longer uncertain ( n=292 ) . The main outcome was death or disability at or beyond 2 years of age . Disability was defined as a Griffiths developmental quotient of 70 or less or the presence of motor or perceptual severe disability . Analysis was by intention-to-treat . This trial has been assigned the International St and ard R and omised Controlled Trial Number IS RCT N41358726 . FINDINGS Primary outcomes were available on 290 ( 98 % ) immediate and 283 ( 97 % ) deferred deliveries . Overall rate of death or severe disability at 2 years was 55 ( 19 % ) of 290 immediate births , and 44 ( 16 % ) of 283 delayed births . With adjustment for gestational age and umbilical-artery doppler category , the odds ratio ( 95 % CrI ) was 1.1 ( 0.7 - 1.8 ) . Most of the observed difference was in disability in babies younger than 31 weeks of gestation at r and omisation : 14 ( 13 % ) immediate versus five ( 5 % ) delayed deliveries . No important differences in the median Griffiths developmental quotient in survivors was seen . INTERPRETATION The lack of difference in mortality suggests that obstetricians are delivering sick preterm babies at about the correct moment to minimise mortality . However , they could be delivering too early to minimise brain damage . These results do not lend support to the idea that obstetricians can deliver before terminal hypoxaemia to improve brain development Clinical practice guidelines have improved in quality over the past 10 years by adhering to a few basic principles , such as conducting thorough systematic review s of relevant evidence and grading the recommendations and the quality of the underlying evidence . The large number of systems of measuring the quality of evidence and recommendations that have emerged are , however , confusing.1 The mission of the Grading of Recommendations , Assessment , Development , and Evaluation ( GRADE ) working group is to help resolve the confusion among the different systems of rating evidence and recommendations . The group has wide representation from many organisations including the Agency for Healthcare Research and Quality in the US , the National Institute for Clinical Excellence for Engl and and Wales , and the World Health Organization . Developing a new uniform rating system is challenging because all systems have limitations and because many organisations have invested a great deal of time and effort to develop their rating systems and are underst and ably reluctant to adopt a new system . The GRADE working group first published the results of its work in 2004 in the BMJ.2 A simpler , clinical ly oriented description will soon be published.3 GRADE has taken care to ensure its suggested system is simple to use and applicable to a wide variety of clinical recommendations that span the full spectrum of medical specialties and clinical care . The GRADE system classifies recommendations in 1 of 2 levels — strong and weak— and quality of evidence into 1 of 4 levels — high , moderate , low , and very low . Evidence based on r and omised controlled trials ( RCTs ) begins with a top rating on GRADE ’s 4 level quality of evidence classification ( table Objective To compare the effectiveness of immediate induction of labour with vaginal misoprostol versus expectant management for 24 hours followed by oxytocin induction in women with premature rupture of membranes at term ( term PROM ) OBJECTIVES To compare the effect of delivering early to pre-empt terminal hypoxaemia with delaying for as long as possible to increase maturity . DESIGN A r and omized controlled trial . SETTING 69 hospitals in 13 European countries . PARTICIPANTS Pregnant women with fetal compromise between 24 and 36 weeks , an umbilical artery Doppler waveform recorded and clinical uncertainty whether immediate delivery was indicated . METHODS The interventions were ' immediate delivery ' or ' delay until the obstetrician is no longer uncertain ' . The data monitoring and analysis were Bayesian . MAIN OUTCOME MEASURES ' Survival to hospital discharge ' and ' developmental quotient at two years of age ' , this latter to be reported later . RESULTS Of 548 women ( 588 babies ) recruited , outcomes were available on 547 mothers ( 587 babies ) . The median time-to-delivery intervals were 0.9 days in the immediate group and 4.9 days in the delay group . Total deaths prior to discharge were 29 ( 10 % ) in the immediate group versus 27 ( 9 % ) in the delay group ( odds ratio 1.1 , 95 % CI 0.61 - 1.8 ) . Total caesarean sections were 249 ( 91 % ) in the immediate group versus 217 ( 79 % ) in the delay group : ( OR 2.7 ; 95 % CI 1.6 - 4.5 ) . These odds ratios were similar for those r and omized at gestational ages above or below 30 weeks . INTERPRETATION The lack of difference in overall mortality suggests that clinicians participating in this trial were on average prepared to r and omize at about the correct equivocal threshold between delivery and delay . However , there was insufficient evidence to convince enthusiasts for either immediate or delayed delivery that they were wrong OBJECTIVE Our purpose was to compare induction of labor with preterm rupture of membranes between 34 and 37 weeks ' gestation with expectant management . STUDY DESIGN In this prospect i ve investigation 120 gravid women at > or = 34 weeks 0 days and < 36 weeks 6 days of gestation were r and omized to receive oxytocin induction ( n = 57 ) or observation ( n = 63 ) . RESULTS Estimated gestational age at rupture of membranes ( 34.3 + /- 1.4 weeks vs 34.5 + /- 1.4 weeks ) and ultrasonographically estimated fetal weight ( 2230 + /- 321 gm vs 2297 + /- 365 gm ) were equivalent between groups ( not significant ) . Chorioamnionitis occurred more often ( 16 % vs 2 % , p = 0.007 ) , and maternal hospital stay ( 5.2 + /- 6.8 days vs 2.6 + /- 1.6 days , p = 0.006 ) was significantly longer in the control group . Neonatal sepsis was also more common in the observation group ( n = 3 ) than among induction patients ( n = 0 ) , but the difference was not statistically significant . CONCLUSION Aggressive management of preterm premature rupture of the membranes at > or = 34 weeks 0 days of gestation by induction of labor is safe for the infant in our population and avoids maternal-neonatal infectious complications Ninety-nine patients with premature rupture of the membranes ( PROM ) before 36 weeks ' gestation and documented fetal pulmonary maturity were studied prospect ively . Fifty-two patients in labor were allowed to deliver . The remaining 47 were r and omly assigned to either prompt delivery ( N=26 ) or conservative management ( N=21 ) . The overall corrected perinatal survival was excellent ( 96 % ) . Only one death in the entire series clearly was due to prematurity . Expectant management prolonged gestation greater than one week in only four of 21 patients ( 19 % ) , and was associated with a significantly increased risk of maternal infections . There were no failed inductions of labor , and 22 of 24 induced patients ( 92 % ) delivered vaginally . Neonatal morbidity was similar in each group . These findings in an indigent , largely black population suggest that when pulmonary maturity is present , the maternal risks of conservative management may exceed the potential benefit to the fetus and newborn . The findings of this study may be specific to the population studied , and extrapolation to dissimilar population s may not be warranted . ( Obstet Gynecol 69:196 , 1987 Objective : The appropriate date of delivery in twin pregnancies is supposed to be earlier than that in singleton pregnancy . The aim of this study was to compare two strategies for managing twin pregnancies ( i.e. , immediate induction and expectant management ) . Methods : Seventeen patients underwent immediately induced labor by administration of oral prostagl and in E2 at 37 weeks , while 19 patients underwent expectant management . Results : The average gestational age at delivery in the induction group was 37.5 ± 0.4 weeks , significantly earlier than that in the expectant management group ( 39.0 ± 1.1 weeks ) . However , there were no significant differences in the average birth weight between the two groups ( 2,700 ± 330 g in the induction group vs. 2,672 ± 392 g in the expectant management group ) . The cesarean delivery rate in the induction group was 18 % , not significantly different from that in the expectant management group ( 32 % ) . The most common indication for cesarean section in the expectant management group was maternal infection , while there was no maternal infection in the induction group ( p = 0.08 ) . Conclusion : It may be acceptable do intervene in twin pregnancies earlier than in singleton pregnancies during term OBJECTIVE Our objective was to compare maternal and perinatal outcomes between two management schemes for women with preterm premature rupture of the membranes and documented fetal pulmonary maturity . STUDY DESIGN Of 164 women with preterm premature rupture of the membranes at 32 weeks to 36 weeks 6 days ' gestation , 93 eligible and consenting women were r and omly selected for either induction of labor ( n = 46 ) or expectant management ( n = 47 ) . Expectant management included hospitalization , assessment for fetal heart rate abnormalities , chorioamnionitis , and labor . Digital cervical examinations were prohibited until progressive labor occurred . Follow-up was also done for the 71 women who did not participate . RESULTS The women in the induction of labor and expectant management groups had similar demographic characteristics and gestational ages ( 34.1 vs 34.3 weeks ) . Expectant management was associated with prolonged latencies to labor , delivery , and maternal hospitalization ( p < 0.001 ) , as well as increased hospitalization of infants at 2 to 5 days after delivery ( p < 0.05 ) . These patients had increased chorioamnionitis and fetal heart rate abnormalities before labor ( p = 0.01 , 0.03 ) . Infants received more frequent ( p < 0.001 ) and prolonged antimicrobial therapy after expectant management ( p = 0.003 ) with no reduction in proven sepsis ( 6.8 % vs 4.4 % ) . These latter differences were influenced by the neonatologist 's concern over potential neonatal infection . CONCLUSIONS Among women with preterm premature rupture of the membranes at 32 to 36 weeks with mature surfactant profiles , immediate induction of labor reduces the duration of hospitalization and infection in both mothers and neonates BACKGROUND Elective preterm delivery of the fetus with gastroschisis may help to limit injury to the extruded fetal gut and thus promote faster recovery of neonatal gut function and earlier hospital discharge . This hypothesis has not previously been tested in a prospect i ve r and omized controlled trial . METHODS Between May 1995 and September 1999 , all women referred to a single tertiary center before 34 weeks ' gestation with a sonographically diagnosed fetal gastroschisis were invited to participate in a r and omized controlled trial . Eligible patients were r and omized to elective delivery at 36 weeks or to await the onset of spontaneous labor . The method of delivery was not prescribed by the trial . Primary outcome measures in the neonate were the time taken to tolerate full enteral feeding ( 150 mL/kg per day ) and duration of hospital stay . RESULTS Of 44 eligible women , 42 were r and omized , 21 to elective delivery and 21 to await spontaneous labor . There were 20 liveborn infants in each group . Four babies in the elective group and 4 in the spontaneous group delivered before 36 weeks ' gestation but were included in the analysis on an intention-to-treat basis . Mean gestational age at delivery was 35.8 weeks in the elective group and 36.7 weeks in the spontaneous group . Primary closure of the gastroschisis was achieved in a similar proportion ( 80%-85 % ) of infants in both groups . Two babies in the elective group died from short gut complications . In the survivors , there was a trend in favor of a shorter median time to achieve full enteral feeding ( 30.5 vs 37.5 days ) and a shorter median duration of hospital stay ( 47.5 vs 53 days ) in the elective group , but this was not statistically significant . These findings remained unaltered when the data were reanalyzed after ( a ) excluding infants with intestinal atresia or ( b ) excluding infants born before 36 weeks ' gestation . CONCLUSIONS Although limited by the small number of patients , this r and omized controlled trial demonstrates no significant benefit from elective preterm delivery of fetuses with gastroschisis Controversy continues over the mode of delivery in severe pre-eclampsia remote from term . The aim of this study was to assess prospect ively the mode of delivery in severe pre-eclampsia remote from term . The clinical data of 108 women who presented consecutively with severe pre-eclampsia over a 1-year period was used for the study material . Sixty-eight ( 63 % ) patients were delivered by elective caesarean section and 40 ( 37 % ) underwent induction of labour . Twenty-six had a vaginal delivery following induction , the others ( n = 14 ) had emergency caesarean section . No baby with a gestational age of ≤ 27 weeks survived after delivery . Perinatal mortality was highest for the babies delivered following induction of labour ( vaginal delivery vs. caesarean section after induction of labour , P = 0·0004 ; vaginal delivery vs. elective caesarean section , P = 0·002 ) . Severe pre-eclampsia remote from term is associated with a high caesarean section rate . In this study , carried out in a developing country , elective caesarean section contributed to a better perinatal outcome than vaginal delivery or emergency caesarean section following induction of labour OBJECTIVE Our purpose was to assess whether a program of expectant management of uncomplicated pregnancies in mothers with insulin-requiring gestational or pregestational class B reduces the incidence of cesarean birth . STUDY DESIGN Two hundred women with uncomplicated , insulin-requiring diabetes at 38 weeks ' gestation who were compliant with care and whose infants were judged appropriate for gestational age were r and omly assigned to ( 1 ) active induction of labor within 5 days or ( 2 ) expectant management . The expectant management group was monitored with weekly physical examination and twice-weekly nonstress tests and amniotic fluid volume estimation until delivery . RESULTS Expectant management increased the gestational age at delivery by 1 week . Approximately half ( 49 % ) of the mothers in the expectant management group required induction of labor for obstetric indications . The cesarean delivery rate was not significantly different in the expectant management group ( 31 % ) from the active induction group ( 25 % ) . The mean birth weight ( 3672 + /- 407 gm ) and percentage large for gestational age , as defined by birth weight > or = 90th percentile , of infants in the expectantly managed group ( 23 % ) was greater than those in the active induction group ( 3466 + /- 372 gm , p < 0.0001 , 10 % large for gestational age ) . This difference persisted after controlling for gestational age and maternal age and body weight ( p < 0.01 ) . CONCLUSION In women with uncomplicated insulin-requiring gestational or class B pregestational diabetes , expectant management of pregnancy after 38 weeks ' gestation did not reduce the incidence of cesarean delivery . Moreover , there was an increased prevalence of large-for-gestational-age infants ( 23 % vs 10 % ) and shoulder dystocia ( 3 % vs 0 % ) . Because of these risks , delivery should be contemplated at 38 weeks and , if not pursued , careful monitoring of fetal growth must be performed OBJECTIVE Our purpose was to determine whether aggressive or expectant management of severe preeclampsia at 28 to 32 weeks is more beneficial to maternal and neonatal outcome . STUDY DESIGN Ninety-five eligible patients were r and omly assigned to either aggressive ( n = 46 ) or expectant management ( n = 49 ) . Aggressive management patients were prepared for delivery , either by cesarean or induction , 48 hours after glucocorticoids were administered . Expectant management patients were managed with bed rest , oral antihypertensives , and intensive antenatal fetal testing . RESULTS At the time of r and omization there were no differences between the two groups in mean systolic blood pressure ( 170 + /- 9.7 vs 172 + /- 9.4 mm Hg ) , diastolic blood pressure ( 110 + /- 5.4 vs 112 + /- 4.2 mm Hg ) , proteinuria ( 3.0 + /- 2.3 vs 3.6 + /- 2.3 gm per 24 hours ) , and gestational age ( 30.4 + /- 1.6 vs 30.7 + /- 1.5 weeks ) for the aggressive and expectant management groups . The average latency period in the expectant management group was 15.4 days ( range 4 to 36 ) , and this period was not affected by the amount of proteinuria at r and omization . There was no eclampsia or perinatal death in either group . The two groups had similar incidences of abruptio placentae ( 4.1 % vs 4.3 % ) and similar days of postpartum hospital stay . The expectant management group had a significantly higher gestational age at delivery ( 32.9 + /- 1.5 vs 30.8 + /- 1.7 weeks , p < 0.0001 ) , higher birth weight , lower incidence of admission to the neonatal intensive care unit ( 76 % vs 100 % , p = 0.002 ) , lower mean days of hospitalization in the intensive care unit ( 20.2 + /- 14 vs 36.6 + /- 17.4 , p < 0.0001 ) , and lower incidence of neonatal complications . CONCLUSION Expectant management , with close monitoring of mother and fetus at a perinatal center , reduces neonatal complications and neonatal stay in the newborn intensive care unit Fifty-eight women with severe preeclampsia between 28 - 34 weeks ' gestation qualified for a r and omized controlled trial to establish whether elective delivery 48 hours after administration of betamethasone ( aggressive-management group ) or delivery later as indicated by maternal or fetal condition ( expectant-management group ) was more beneficial to maternal and fetal outcome . Twenty women who qualified were not r and omized because they developed maternal or fetal indications necessitating delivery within 48 hours ; these newborns developed most of the complications . Expectant management was not associated with an increase in maternal complications , but it significantly prolonged the gestational age ( mean 7.1 days ; P < .05 ) , reduced the number of neonates requiring ventilation ( P < .05 ) , and reduced the number of neonatal complications ( P < .05 ) OBJECTIVE To test the hypothesis that in pregnancies with a clinical ly suspected growth restricted foetus at term , induction of labour is as safe as expectant management , and does not lead to increased obstetrical interventions or perinatal morbidity . STUDY DESIGN In one obstetric centre , 33 women with a clinical ly suspected growth restricted foetus at term were r and omly allocated after stratification for parity to either induction or to expectant management . Obstetric and neonatal outcome variables were compared . RESULTS There was a lower gestational age at labour ( median 38(0 ) weeks versus 40(1 ) weeks ) with a corresponding tendency to lower birth weight ( mean 2428 g versus 2651 g ) , and a reduced need for ante partum medical surveillance , in the induction group . No significant differences in obstetrical interventions ( 25 % versus 24 % ) and neonatal morbidity rates ( 50 % versus 35 % ) were found . CONCLUSION A larger multicenter study with a sufficient power and long-term follow-up to decide the best policy for the term growth restricted foetus is feasible BACKGROUND Eclampsia has now emerged as one of the commonest cause of maternal mortality in Nigeria . There is need for research on best modality for delivery of eclamptics . METHODOLOGY The pilot study was conducted on 50 eclamptic patients at the Federal Medical Centre , Azare . The patients were r and omized for delivery either by caesarean section ( CS ) or induction of labour . The fetomaternal outcome of the two groups was compared . RESULTS 25 of the patients had CS and 25 had induction of labour with misoprostol . The mean decision delivery interval was 4.1 hours and 13.08 hours for the CS and misoprostol groups respectively . Misoprostol failure was recorded in 4 ( 16 % ) patients and they were subsequently delivered by CS . The duration of admission was longer in the CS group ( mean of 10.1 days ) compared to the misoprostol group ( mean of 6.08 days ) . There were more maternal complications and admissions of babies into the SCBU in the CS group . Maternal mortality in the two groups was similar ( 2 % each ) . CONCLUSION Misoprostol is cheap , available and safe for delivery of antepartum eclamptics . In the event of delay at caesarean section for antepartum eclamptics patients , misoprostol induction should be started . A multicenter study is called for Objective To determine maternal and neonatal outcomes in pregnancies complicated by preterm rupture of membranes ( PROM ) at 30–34 weeks ' gestation . Methods A r and omized controlled trial was conducted to study the benefits of expectant management in women hospitalized for PROM at 30–34 weeks ' gestation . During this investigation , no tocolytics , corticosteroids , or prophylactic antibiotics were used . Results Sixty-eight women with PROM were managed expectantly and 61 were delivered intentionally . The mean gestational age at study entry was 31.7 weeks in both the expectant management and intentional delivery groups ( P > .05 ) . The mean gestational ages at delivery were similar ( 32.0 and 31.7 weeks , respectively ) . Other indices of pregnancy outcome ( ie , birth weight , intraventricular hemorrhage , necrotizing enterocolitis , sepsis , respiratory distress syndrome , and perinatal death ) were not significantly improved by expectant management . However , there was a significant increase in the incidence of chorioamnionitis and antepartum hospitalization in the women managed expectantly . Conclusion There were no clinical ly significant neonatal advantages to expectant management of ruptured membranes at 30–34 weeks . Antepartum hospitalization was decreased by 2.5 days in those women r and omized to intentional delivery OBJECTIVE Conservative management of intrahepatic obstetric cholestasis is associated with a high stillbirth rate despite monitoring of fetal well-being with non-stress test and amniotic fluid volume assessment . Most cases of stillbirth are associated with meconium passage . We prospect ively evaluated the effect of a management protocol inclusive of surveillance for presence of meconium and induction of labor at 37 weeks . STUDY DESIGN Between January 1989 and December 1997 , all women with obstetric cholestasis underwent transcervical amnioscopy after 36 weeks for assessment of amniotic fluid color , in addition to st and ard monitoring of fetal well-being ( semi-weekly non-stress test and amniotic fluid volume determinations ) . Amniocentesis for fetal lung maturity and amniotic fluid color assessment was performed before 36 weeks in severe cases . Labor was induced at 37 weeks or earlier in the presence of non-reassuring fetal testing , meconium , or severe maternal symptoms unresponsive to therapy with mature fetal lungs . The obstetric outcome of the group with cholestasis was compared with that of the general obstetric population at our Institution during the study period . The rate of fetal death in the study group was compared with that of series published within the last 20 years , which used expectancy and conventional monitoring of fetal well-being . Statistical analysis utilized Fisher 's exact test , Chi-square , and Student 's t-test with P value < 0.05 or an odds ratio ( OR ) with 95 % confidence interval ( CI ) not inclusive of the unity considered significant . RESULTS Obstetric cholestasis was diagnosed in 206/20,815 pregnant women ( 1 % ) at a median gestational age of 34 weeks ( range 20 - 40 ) . Delivery was prompted by non-reassuring fetal testing in four cases ( 2 % ) . Meconium passage was documented in 33 cases ( 16 % ) , in 11 of which before onset of labor and in 10 before 37 weeks . The rate of meconium passage before 37 weeks ( 17.9 versus 2.9 % , OR=7.3 ; 95 % CI 3.3 , 16.0 ) was significantly higher in obstetric cholestasis than in the general obstetric population , whereas the cesarean section rate was similar in the two groups ( 15.1 versus 16.0 % , OR=0.9 ; 95 % CI 0.6 , 1.4 ) . The fetal death rate was significantly lower in the group managed with the current strategy than in the published series of obstetric cholestasis ( 0/218 versus 14/888 , P=0.045 ) . CONCLUSION In pregnancies complicated by obstetric cholestasis , a protocol inclusive of search for meconium and elective delivery at 37 weeks , in addition to st and ard monitoring of fetal well-being , can significantly reduce the stillbirth rate without increasing the cesarean delivery rate OBJECTIVES To compare the effects of induction/labor to delivery before labor in early onset , severe pre-eclampsia . METHODS Five-year prospect i ve case series . Delivery course and neonatal outcome were examined for 335 women with viable singletons . RESULTS Induction was successful in 45 % of attempts . Women exposed to labor had longer ( 5.5 days , P<0.0001 ) admissions to delivery periods and were more often delivered for maternal indications ( RR=2.87 , 95 % CI=1.98 - 4.16 ) . Their babies were born 1.6 weeks older ( P<0.0001 ) and 352 g heavier ( P<0.0001 ) than those delivered before labor . Babies exposed to labor needed intensive care less often ( RR=0.4 , 95 % CI=0.27 - 0.58 ) , had lower rates of severe hyaline membrane disease ( RR=0.26 , 95 % CI=0.11 - 0.59 ) and sepsis ( RR=0.56 , 95 % CI=0.33 - 0.93 ) , and were discharged earlier ( P<0.0001 ) . CONCLUSIONS Exposure to induction/labor in selected patients is not detrimental to neonatal outcome in early , severe pre-eclampsia Background Preterm prelabour rupture of the membranes ( PPROM ) is an important clinical problem and a dilemma for the gynaecologist . On the one h and , awaiting spontaneous labour increases the probability of infectious disease for both mother and child , whereas on the other h and induction of labour leads to preterm birth with an increase in neonatal morbidity ( e.g. , respiratory distress syndrome ( RDS ) ) and a possible rise in the number of instrumental deliveries . Methods / Design We aim to determine the effectiveness and cost-effectiveness of immediate delivery after PPROM in near term gestation compared to expectant management . Pregnant women with preterm prelabour rupture of the membranes at a gestational age from 34 + 0 weeks until 37 + 0 weeks will be included in a multicentre prospect i ve r and omised controlled trial . We will compare early delivery with expectant monitoring . The primary outcome of this study is neonatal sepsis . Secondary outcome measures are maternal morbidity ( chorioamnionitis , puerperal sepsis ) and neonatal disease , instrumental delivery rate , maternal quality of life , maternal preferences and costs . We anticipate that a reduction of neonatal infection from 7.5 % to 2.5 % after induction will outweigh an increase in RDS and additional costs due to admission of the child due to prematurity . Under these assumptions , we aim to r and omly allocate 520 women to two groups of 260 women each . Analysis will be by intention to treat . Additionally a cost-effectiveness analysis will be performed to evaluate if the cost related to early delivery will outweigh those of expectant management . Long term outcomes will be evaluated using modelling . Discussion This trial will provide evidence as to whether induction of labour after preterm prelabour rupture of membranes is an effective and cost-effective strategy to reduce the risk of neonatal sepsis . Controlled clinical trial registerIS RCT |
10,744 | 29,356,026 | Conclusions LEDs represent an emerging modality to alter skin biology and change the paradigm of managing skin conditions . | Objective In dermatology , patient and physician adoption of light‐emitting diode ( LED ) medical technology continues to grow as research indicates that LEDs may be used to treat skin conditions .
The goal of this systematic review is to critically analyze published r and omized controlled trials ( RCTs ) and provide evidence ‐based recommendations on the therapeutic uses of LEDs in dermatology based on published efficacy and safety data . | Purpose Many treatment modalities exist to counteract the effects of cutaneous aging . Ablative methods have been the mainstay for nonsurgical facial rejuvenation . In recent years , nonablative techniques have been developed with the aim of achieving facial rejuvenation without epidermal damage . Light-emitting diode ( LED ) photorejuvenation is a novel nonablative technique that induces collagen synthesis through biophotomodulatory pathways . Material s and methods A single-center , r and omized , single-blinded , placebo-controlled , split-faced clinical trial was design ed . Thirty-two patients were enrolled for a 12-week study . Patients were r and omized into one of four groups : Group A , treatment with KLOX-001 gel formulation and white LED ( placebo ) light ; Group B , treatment with a placebo/base gel ( no active chromophore ) formulation and KLOX LED light ; Group C , treatment with KLOX-001 gel formulation and KLOX LED light ; and Group D , treatment with the st and ard skin rejuvenating treatment ( 0.1 % retinol-based cream ) . Patients received treatment at weeks 0 , 1 , 2 , and 3 , and returned to the clinic at weeks 4 , 8 , and 12 for clinical assessment s performed by an independent , blinded committee of physicians using subjective clinician assessment scales . Tolerability , adverse outcomes , and patient satisfaction were also assessed . Results Analysis demonstrated that the KLOX LED light with KLOX placebo/base gel and the KLOX LED light + KLOX-001 gel formulation groups were superior to st and ard of care and KLOX-001 gel formulation with placebo light on subjective clinical assessment and multiple wrinkle scales , with statistically significant results obtained for brow positioning , perioral wrinkling , and total wrinkle score . Conclusion The study results show that KLOX LED light with KLOX-001 gel formulation and KLOX LED light with KLOX placebo/base gel are effective , safe , well-tolerated , and painless treatment modalities for skin rejuvenation Background : Cellulite of the upper lateral and posterior thighs and lower buttocks represents a common , physiological and unwanted condition whose etiologies and effective management are subjects of continued debate . Objective : The purpose of this controlled , double‐blinded study is to evaluate the efficacy and safety of a novel phosphatidylcholine‐based , cosmeceutical anti‐cellulite gel combined with a light‐emitting diode ( LED ) array at the wavelengths of red ( 660 nm ) and near‐infrared ( 950 nm ) , design ed to counter the possible mechanisms that purportedly accentuate the presence of thigh cellulite . Methods : Nine healthy female volunteers with Grade II – III thigh cellulite were r and omly treated twice daily with an active gel on one thigh and a placebo gel on the control thigh for 3 months . Twice weekly , each thigh was exposed for a 15‐minute treatment with LED light for a total of 24 treatments . At 0 , 6 , and 12 weeks of the study the following clinical determinants were obtained : st and ardized digital photography , height and weight measurements , st and ardized thigh circumference tape measurements , pinch testing , body mass index ( kg/m2 ) , body fat analysis ( Futrex‐5500/XL near‐infrared analyzer ) , and digital high‐resolution ultrasound imaging of the dermal – adiposal border . In selected patients , full‐thickness biopsies of the placebo and active‐treated sites were obtained . At 18 months , repeat st and ardized digital photography , height and weight measurements , and body mass index measurements were obtained . Results : At the end of 3 months , eight of nine thighs treated with the phosphatidylcholine‐based , anti‐cellulite gel and LED treatments were down grade d to a lower cellulite grade by clinical examination , digital photography , and pinch test assessment . Digital ultrasound at the dermal‐adiposal interface demonstrated not only a statistically significant reduction of immediate hypodermal depth , but also less echo‐like intrusions into the dermal layer . Three of six biopsies from thighs treated for 3 months with the active gel and LED treatments demonstrated less intrusion of subcutaneous fat into the papillary and reticular dermis . In nine placebo and LED‐treated thighs and one of the actively treated thighs , minimal clinical changes were observed or measured by the clinical determinants throughout the 3‐month study . At the month‐18 evaluation period for the eight responsive thighs , five thighs reverted back to their original cellulite grading , while three thighs continued to maintain their improved status . Patients experienced minimal and transient side effects that included puritus , erythema and swelling . Conclusions : The results of this small but well‐documented , r and omized , double‐blinded study affirms that eight of nine thighs with Grade II – III cellulite responded positively to a novel , combined 3‐month treatment program of a phosphatidylcholine‐based , anti‐cellulite gel and LED exposure , as determined by the clinical determinants obtained . Patients experienced minimal and transient side effects . At the month‐18 evaluation period ( 15 months after treatment ) , five responsive thighs reverted back to their original cellulite grading , indicating a need for maintenance treatment . Future studies are needed to verify these tentative positive observations Background Blue and red light have been reported to have beneficial effects on acne . However , there has been no double‐blind , r and omized study of acne treatment for combined blue and red light‐emitting diode ( LED ) devices , and the associated molecular mechanisms have rarely been investigated BACKGROUND The most common side effects of fractional laser skin treatment are erythema and edema . Low‐level light therapy and light‐emitting diode ( LED ) devices have been used to stimulate fibroblast activity and hasten wound healing . OBJECTIVE To determine whether LED treatment immediately after fractional laser skin resurfacing affects the severity and duration of postoperative eythema . MATERIAL S AND METHODS Twenty patients received treatment with a 590‐nm wavelength LED array to r and omly selected facial halves immediately after undergoing full‐face fractional laser skin resurfacing with a 1,550‐nm erbium‐doped fiber laser . Differences in erythema between LED‐treated and untreated facial halves were recorded at 24 , 48 , and 96 hours post‐treatment . RESULTS The LED‐treated facial halves were less erythematous in all 20 patients 24 hours postoperatively . The six patients who received the highest mean energy densities during fractional laser treatment continued to exhibit decreased erythema in the LED‐treated areas at 48 hours . At 96 hours post‐treatment , no discernible differences between facial halves were observed in any patient . CONCLUSIONS Photomodulation with a 590‐nm‐wavelength LED array can decrease the intensity and duration of postfractional laser treatment erythema . The authors have indicated no significant interest with commercial supporters Background : Blue light irradiation reduces the proliferation of keratinocytes and modulates T-cell immune response in vitro and has been shown to reduce the severity of psoriasis vulgaris ( Pv ) in two clinical trials . Objective : Evaluation of safety and efficacy of long-term UV-free blue light treatment at home for mild Pv . Methods : Forty-seven patients with mild Pv were r and omized for receiving high-intensity blue light treatment ( HI : 453 nm LED , 200 mW/cm2 , n = 24 ) and low-intensity treatment ( LI : 453 nm LED , 100 mW/cm2 , n = 23 ) of one Pv plaque for 12 weeks . A contralateral control plaque remained untreated . Results : Patient compliance and satisfaction were high . The primary endpoint , change from baseline ( CfB ) of the Local Psoriasis Severity Index , revealed a significant improvement of the target compared to the control plaques ( ΔCfB for the HI group : -0.92 ± 1.10 , p = 0.0005 ; for the LI group : -0.74 ± 1.18 , p = 0.0064 ) . Conclusion : UV-free blue light home treatment is safe and improves Pv plaques BACKGROUND Recently , a dem and for safe and effective treatment of acne has been increasing . Although visible light has attracted attention as a new option , the effect of red light alone has not yet been evaluated . OBJECTIVES The objective was to assess the efficacy of red light phototherapy with a portable device in acne vulgaris . METHODS Twenty-eight volunteers with mild to moderate acne were treated with portable red light – emitting devices in this split-face r and omized trial . The right or left side of the face was r and omized to treatment side and phototherapy was performed for 15 minutes twice a day for 8 weeks . Clinical photographs , lesion counts , and a visual analog scale ( VAS ) were used to assess each side of the face at baseline and Weeks 1 , 2 , 4 , and 8 , and a split-face comparison was performed . RESULTS The percent improvement in noninflammatory and inflammatory lesion counts of the treated side was significant compared to the control side ( p<.005 ) . VAS decreased from 3.9 to 1.9 on the treatment side and the difference between the treatment and control sides was significant at Week 8 ( p<.005 ) . CONCLUSIONS This study shows that red light phototherapy alone can be a new therapeutic option for acne vulgaris Abstract Introduction : Blue-light light-emitting diode ( LED ) therapy has become widely used for the treatment of inflammatory acne . In this study we evaluated the efficacy of a home use blue-light LED application in improving lesions and shortening their time to clearance . Methods : This was an IRB approved r and omized self-control study . For each patient ( n = 30 ) , 2 similar lesions , one of each side of the face were chosen for treatment with either a blue-light LED h and -held or sham device . Treatments ( n = 4 ) were conducted twice daily in the clinic and lesions were followed-up till resolution . Reduction in blemishes size and erythema and the overall improvement were evaluated by both the physician and the patients . Time to lesion resolution was recorded . Results : There was a significant difference in the response of lesions to the blue-light LED application as opposed to the placebo in terms of reduction in lesion size and lesion erythema as well as the improvement in the overall skin condition ( p < 0.025 ) . Signs of improvement were observed as early as post 2 treatments . Time to resolution was significantly shorter for the blue-light LED therapy . Conclusion : The results support the effectiveness of using blue-light LED therapy on a daily basis for better improvement and faster resolution of inflammatory acne lesions Abstract The treatment of acne vulgaris poses a challenge to the dermatologist , and the disease causes emotional anxiety for the patient . The treatment of acne vulgaris may be well-suited to home-use applications , where sufferers may be too embarrassed to seek medical treatment . This r and omized controlled study is design ed to quantify the effectiveness of using a blue light device in a therapy combined with proprietary creams , in the investigation of a self-treatment regimen . A total of 41 adults with mild-to-moderate facial inflammatory acne were recruited . The subjects were r and omly assigned to combination blue light therapy ( n = 26 ) or control ( n = 15 ) . Photography was used for qualitative assessment of lesion counts , at weeks 1 , 2 , 4 , 8 , and 12 . All subjects in the treatment cohort achieved a reduction in their inflammatory lesion counts after 12 weeks . The mean inflammatory lesion counts reduced by 50.02 % in the treatment cohort , and increased by 2.45 % in the control cohort . The reduction in inflammatory lesions was typically observable at week-3 , and maximal between weeks 8 and 12 . The treatment is free of pain and side-effects . The blue light device offers a valuable alternative to antibiotics and potentially irritating topical treatments . Blue light phototherapy , using a narrow-b and LED light source , appears to be a safe and effective additional therapy for mild to moderate acne Chronic wounds , especially in diabetic patients , represent a challenging health issue . Since st and ard treatment protocol s often do not provide satisfactory results , additional treatment methods —like phototherapy using low-level light therapy — are being investigated . The aim of our study was to evaluate the effect of phototherapy with light-emitting diodes on chronic wound treatment in diabetic and non-diabetic patients . Since a sufficient blood supply is m and atory for wound healing , the evaluation of microcirculation in the healthy skin at a wound ’s edge was the main outcome measure . Forty non-diabetic patients and 39 diabetics with lower limb chronic wounds who were referred to the University Medical Center Ljubljana between October 2012 and June 2014 were r and omized to the treated and control groups . The treated group received phototherapy with LED 2.4 J/cm2 ( wavelengths 625 , 660 , 850 nm ) three times a week for 8 weeks , and the control group received phototherapy with broadb and 580–900 nm and power density 0.72 J/cm2 . Microcirculation was measured using laser Doppler . A significant increase in blood flow was noted in the treated group of diabetic and non-diabetic patients ( p = 0.040 and p = 0.033 ) , while there was no difference in the control groups . Additional Falanga wound bed score evaluation showed a significant improvement in both treated groups as compared to the control group . According to our results , phototherapy with LED was shown to be an effective additional treatment method for chronic wounds in diabetic and non-diabetic patients Light-emitting diodes ( LEDs ) are considered to be effective in skin rejuvenation . We investigated the clinical efficacy of LED phototherapy for skin rejuvenation through the comparison with three different treatment parameters and a control , and also examined the LED-induced histological , ultrastructural , and biochemical changes . Seventy-six patients with facial wrinkles were treated with quasimonochromatic LED devices on the right half of their faces . All subjects were r and omly divided into four groups treated with either 830 nm alone , 633 nm alone , a combination of 830 and 633 nm , or a sham treatment light , twice a week for four weeks . Serial photography , profilometry , and objective measurements of the skin elasticity and melanin were performed during the treatment period with a three-month follow-up period . The subject 's and investigator 's assessment s were double-blinded . Skin specimens were evaluated for the histologic and ultrastructural changes , alteration in the status of matrix metalloproteinases ( MMPs ) and their tissue inhibitors ( TIMPs ) , and the changes in the mRNA levels of IL-1ss , TNF-alpha , ICAM-1 , IL-6 and connexin 43 ( Cx43 ) , by utilizing specific stains , TEM , immunohistochemistry , and real-time RT-PCR , respectively . In the results , objective ly measured data showed significant reductions of wrinkles ( maximum : 36 % ) and increases of skin elasticity ( maximum : 19 % ) compared to baseline on the treated face in the three treatment groups . Histologically , a marked increase in the amount of collagen and elastic fibers in all treatment groups was observed . Ultrastructural examination demonstrated highly activated fibroblasts , surrounded by abundant elastic and collagen fibers . Immunohistochemistry showed an increase of TIMP-1 and 2 . RT-PCR results showed the mRNA levels of IL-1ss , TNF-alpha , ICAM-1 , and Cx43 increased after LED phototherapy whereas that of IL-6 decreased . This therapy was well-tolerated by all patients with no adverse effects . We concluded that 830 and 633 nm LED phototherapy is an effective approach for skin rejuvenation OBJECTIVE To evaluate the efficacy and tolerance of a combined 445nm/630 nm light therapy mask for the treatment of mild-to-moderate acne vulgaris with and without topical 1 % salicylic acid with retinol versus 2.5 % benzoyl peroxide . DESIGN A 12-week evaluator-blinded , r and omized study . Subjects were r and omized to be treated with the 445nm/630 nm light therapy mask alone , benzoyl peroxide , or 445nm/630 nm light therapy mask with topical 1 % salicylic acid with retinol . PARTICIPANTS Healthy male and female subjects 12 to 35 years old with Fitzpatrick skin types I to VI and mild-to-moderate facial acne vulgaris . MEASUREMENTS The primary endpoint was the change in the number of inflammatory acne lesions after 12 weeks of treatment . Secondary endpoints included the change in noninflammatory acne lesions , change in total acne lesions , change in Investigator Global Acne Assessment s , and overall responder rate . RESULTS 445nm/630 nm light therapy mask-treated subjects showed a 24.4-percent improvement in inflammatory acne lesions ( p<0.01 ) versus 17.2 percent ( p<0.05 ) and 22.7 percent ( p<0.01 ) in benzoyl peroxide and 445nm/630 nm light therapy mask with topical 1 % salicylic acid with retinol , respectively , a 19.5-percent improvement in noninflammatory lesions ( p<0.001 ) versus 6.3 and 4.8 percent for benzoyl peroxide and 445nm/630 nm light therapy mask with topical 1 % salicylic acid with retinol , respectively . Subjects in the 445nm/630 nm light therapy mask group also achieved a 19.0-percent improvement in the Investigator Global Acne Assessment ( p<0.001 ) versus 4.7 percent in benzoyl peroxide and 13.9 percent in 445nm/630 nm light therapy mask with topical 1 % salicylic acid with retinol ( p<0.01 ) . Treatments were well-tolerated overall with trends toward less early irritation in the 445nm/630 nm light therapy mask group . CONCLUSION 445nm/630 nm light therapy mask appears to be a safe and effective therapy for mild-to-moderate acne Background : Previous laboratory research has shown that human lymphocytes pre‐irradiated with 1072 nm light are afforded some protection against subsequent ultraviolet light toxicity . Objective : To investigate the possibility that 1072 nm light can prevent or reverse skin ageing which itself is known to be accelerated by ultraviolet light . Methods : A r and omized , prospect i ve , double‐blind , placebo‐controlled , self‐reporting study was performed to assess the effect of one daily treatment episode for a period of between 6 and 8 weeks on wrinkles and fine lines around the eyes as well as the appearance of bags under the eyes . Results : Between 52 % and 57 % of volunteers were able to accurately identify an improvement in the fine lines and wrinkles of the treated areas of skin . Fewer volunteers , between 37 % and 46 % , observed an improvement in the bags under the treated eye or eyes , albeit with an emphatic statistical significance . Conclusion : Regular application of a non-thermal quantity of 1072 nm light around the eyes demonstrated efficacy as an anti-ageing agent Introduction : Non-ablative skin rejuvenation is becoming increasingly popular . Ellman RF produces an electric current that generates heat in the dermis producing a contraction of the collagen . LED is a non heating light emission system that induces fibroblast proliferation . Material s and methods : 30 Caucasian women , prototype I-IV , age from 35 to 65 with peri-orbital photo damage were r and omly divided in 3 groups . Group 1 received : 5 RF sessions , 1 every 10 days . Group 2 received 8 LED sessions , 1 every 5 days . Group 3 received RF and LED : 1 RF , 2 LED sessions every 5 days for 3 times ( 3 RF and 6 LED sessions ) . A score of satisfaction , considering skin texture , rhytidis reduction and firmness was obtained before the treatment , after each session and 2 months after the last session . Results : Two months after the last treatment in group 1:7 patients were satisfied and 3 were very satisfied ; in group 2 : 6 patients were satisfied and 4 were very satisfied , in group 3 : 4 patients were satisfied and 6 were very satisfied . LED was effective on improvement of skin texture and rhytidis reduction while slightly effective on firmness . RF was effective on skin texture and firmness while slightly effective on rhytidis reduction . LED and RF together were effective on all parameters . Conclusion : LED and RF seem to be safe and effective on skin rejuvenation especially when associated BACKGROUND AND AIMS Acne vulgaris is common in Asian population s. We compared three methods of phototherapy for the treatment of moderate to severe facial acne vulgaris in Chinese patients . METHODS Patients were r and omly assigned to receive photodynamic therapy ( PDT ) , intense pulsed light ( IPL ) or blue-red light-emitting diode ( LED ) phototherapy to the right side of the face until the inflammatory lesion count reduced by ≥ 90 % . Patients were examined at 1 and 3 months after the final treatment . RESULTS We enrolled 150 patients ( 92 males ; mean age , 28 years ) . At 1 month , ≥90 % clearance or moderate improvement occurred in 46/50 ( 92 % ) , 29/50 ( 58 % ) and 22/50 ( 44 % ) patients in the PDT , IPL and LED groups , respectively ( mean number of sessions required , PDT : 3 ± 1.52 ; IPL : 6 ± 2.15 ; LED : 9 ± 3.34 ) . Forty-six ( 92 % ) patients experienced mild to moderate pain , erythema and edema after PDT , which resolved within 5 - 7 days . Slight erythema and stinging were reported immediately after IPL and LED , resolving within 2 h. After 3 months , minimal papules and pustules were observed in 4 patients in the PDT group , 7 in the IPL group and 12 in the LED group , but no nodular pustules recurred . CONCLUSIONS Phototherapy is efficacious for moderate to severe facial acne vulgaris To determine the efficacy of Omnilux Revive facial treatment in skin rejuvenation , twenty-three volunteers received r and omised 20 min treatments three times a week for three weeks to one half of their face , with the untreated side acting as control . Regular assessment s were carried out , focusing on parameters of subject satisfaction , photographic assessment s , skin elasticity ( Cutometer ) and skin hydration ( Corneometer CM825 ) . Ninety-one percent of the volunteers reported visible changes to their skin . Blinded photographic evaluation reported a clinical response in 59 % of the subjects . Objective analysis failed to show statistically significant changes in skin hydration or elasticity . The Omnilux Revive LED lamp is a safe alternative non-ablative skin rejuvenation treatment OBJECTIVES This study evaluates the use of light-emitting diode ( LED ) photomodulation therapy to accelerate resolution of post-intense pulsed light ( IPL ) erythema . METHODS In this split-face study , 15 subjects were r and omized to receive LED treatment to one side of the face as determined by computer-generated r and omization numbers . All 15 subjects received a single IPL treatment for facial photodamage . Immediately after IPL treatment , one side of the face was treated for 35 s with the LED device . The other side was not treated . Subjects returned 24 h later for a second LED treatment on the same side of the face . Posttreatment erythema was rated on both sides of the face by the blinded investigator and by subjects immediately after IPL treatment , 24 h later , and 1 week later on a scale of 0 % ( no erythema ) to 100 % ( severe erythema ) . Patients commented on posttreatment discomfort immediately after IPL treatment . RESULTS Mean erythema scores on the first visit were significantly higher ( P = 0.0054 ) on the side not treated with LED ( 52.7 + /- 24.6 ) than on the LED-treated side ( 43.3 + /- 21.9 ) . Visit 2 data showed a similar trend ( P = 0.0281 ) . The subjects reported similar findings with mean erythema scores on the first visit on the LED-treated side ( 46.7 + /- 25.3 ) compared with the untreated side ( 60.0 + /- 23.3 ) ; the difference was significant ( P = 0.0382 ) . On the second visit , the mean erythema scores trended lower on the LED-treated side ( 24.3 + /- 22.1 ) than on the untreated side ( 27.9 + /- 25.8 ) , but the difference did not reach statistical significance ( P = 0.1365 ) . Erythema scores on both facial sides were 0 for all subjects 1 week after IPL treatment . Four patients commented that posttreatment discomfort was considerably less on the LED-treated side immediately after treatment . CONCLUSION LED photomodulation treatment may accelerate the resolution of erythema and reduce posttreatment discomfort in IPL-treated patients with photodamage BACKGROUND Low-level light therapy ( LLLT ) using light-emitting diodes ( LEDs ) is considered to be helpful for skin regeneration and anti-inflammation . OBJECTIVE To evaluate the efficacy and safety of 2 types of LLLTs using 660 nm – emitting red LEDs and 411 to 777 nm – emitting white LEDs in the treatment of facial wrinkles . MATERIAL S AND METHODS A prospect i ve , r and omized , double-blinded , comparative clinical trial involving 52 adult female subjects was performed . The faces of the subjects were irradiated daily with 5.17 J of red or white LEDs for 12 weeks . RESULTS In both groups treated with red and white LEDs , the wrinkle measurement from skin replica improved significantly from baseline at Week 12 . The red LED group showed slightly better improvement , but there were no statistical differences . In assessment s by blinded dermatologists , no significant differences were observed in both groups . In the global assessment of the subjects , the mean improvement score of the red LED group was higher than that of the white LED group . CONCLUSION Low-level light therapy using 660 nm LEDs or 411 to 777 nm LEDs significantly improved periocular wrinkles . Especially , 660 nm LEDs could be an effective and tolerable treatment option for wrinkles BACKGROUND AND OBJECTIVE Photodynamic therapy ( PDT ) is associated with erythema and edema . Photobiomodulation ( PBM ) therapy may stimulate the skin recovery process . We investigated the potential of PBM to reduce PDT-induced skin reactions . STUDY DESIGN AND METHODS Healthy volunteers ( n = 20 ) were r and omized to receive left- or right side PBM ( near-infrared 839/595 nm ) or placebo-PBM ( 595 nm ) on their buttocks . Corresponding test areas were exposed to st and ardized PDT reactions , using ablative fractional laser-assisted PDT ( AFXL-PDT ) with methyl-aminolevulinate ( MAL ) incubated for 30 , 90 , and 180 minutes before red-light illumination . Each buttock received PBM and placebo-PBM for five consecutive days , starting one day before PDT interventions . Follow-up visits were performed 4 and 11 days after PDT . Outcome measure included blinded , observer-assessed skin reactions , substantiated by objective ly measured erythema and pigment percentages and skin temperatures . RESULTS PDT interventions induced a st and ardized range of erythema and edema in all subjects . Skin reactions were clinical ly unaffected by PBM throughout the active treatment period and at all subsequent follow-up visits ( PBM vs. placebo-PBM , P = 1.000 ) . Clinical results were supported by similar erythema intensities and skin temperatures in PBM and placebo-PBM treated skin : median erythema 28.1 % versus 30.3 % ( AFXL-PDT with 30 minutes MAL-incubation ) , 36.1 % versus 35.2 % ( 90 minutes MAL-incubation ) and 39.4 % versus 40.9 % ( 180 minutes MAL-incubation ) ( Day 4 , P > 0.05 ) . No differences in clinical hyperpigmentation or pigment percentages were observed between corresponding test areas in any subject on the final 11-day follow-up . CONCLUSION Under the current study conditions , PDT-induced skin reactions were unaffected by PBM . Lasers Surg . Med . 49:810 - 818 , 2017 . © 2017 Wiley Periodicals , |
10,745 | 18,000,123 | Some task-restructuring interventions failed to alter the psychosocial work environment significantly , and so could not be expected to have a measurable effect on health .
Those that increased dem and and decreased control tended to have an adverse effect on health , while those that decreased dem and and increased control result ed in improved health , although some effects were minimal .
Increases in workplace support did not appear to mediate this relationship .
This systematic review suggests that task-restructuring interventions that increase dem and or decrease control adversely affect the health of employees , in line with observational research .
It lends support to policy initiatives such as the recently enforced EU directive on participation at work , which aims to increase job control and autonomy | OBJECTIVE To systematic ally review the health and psychosocial effects ( with reference to the dem and -control-support model ) of changes to the work environment brought about by task structure work reorganisation , and to determine whether those effects differ for different socioeconomic groups . | BACKGROUND Studies on the direct and buffering effects of social support have not examined psychiatric sickness absence and few studies have considered support both at home and at work . This study addresses prospect ively the effects of chronic stressors and social supports , at home and at work , on psychiatric sickness absence rates . METHODS Sociodemographic factors , health and social support were measured at baseline , and short and long spells of sickness absence were measured prospect ively over a 5-year period . The participants were a sub sample of 4202 male and female civil servants , aged 35 - 55 years at baseline , from an occupational cohort , the Whitehall II Study , who completed detailed social support questions . RESULTS Support from colleagues and supervisors at work is related to lower risk of short spells of psychiatric sickness absence , particularly for those also receiving high levels of negative aspects of close relationships from their closest person outside work . Negative aspects of close relationships from the closest person increase the risk of taking long spells of psychiatric sickness absence in men . High levels of material problems increase the risk of short spells of sickness absence . CONCLUSIONS Negative aspects of close relationships may have an aetiological role in non-psychotic psychiatric disorder . Social support at work appears to protect against short spells of psychiatric sickness absence . This potentially implies that levels of short spells of absence might be reduced by increasing support at work . Conversely , emotional support at home may influenced absence-related behaviour and encourage a person to take absence at a time of illness Study objectives : To investigate the association between job strain and components of the job strain model and coronary heart disease ( CHD ) risk . Design : Prospect i ve cohort study ( Whitehall II study ) . At the first phase of the study ( 1985–1988 ) , data on self reported psychosocial work characteristics were collected from all participants . Participants were followed up until the end of phase 5 ( 1997–2000 ) , with mean length of follow up of 11 years . Setting : London based office staff in 20 civil service departments . Participants : 6895 male and 3413 female civil servants aged 35–55 . Outcome measures : Incident vali date d CHD . Main results : People with concurrent low decision latitude and high dem and s ( job strain ) were at the highest risk for CHD . High job dem and s , and , less consistently , low decision latitude , predicted CHD incidence . The effect of job strain on CHD incidence was strongest among younger workers , but there was no effect modification by social support at work , or employment grade . Conclusions : Job strain , high job dem and s , and , to some extent , low decision latitude , are associated with an increased risk of CHD among British civil servants This cross-sectional study investigates the relationship between the psychosocial work environment and cardiovascular disease ( CVD ) prevalence in a r and omly selected , representative sample of 13,779 Swedish male and female workers . It was found that self-reported psychological job dem and s , work control , and co-worker social support combined greater then multiplicatively in relation to CVD prevalence . An age-adjusted prevalence ratio ( PR ) of 2.17 ( 95 % CI-1.32 , 3.56 ) was observed among workers with high dem and s , low control , and low social support compared to a low dem and , high control , and high social support reference group . PRs of approximately 2.00 were observed in this group after consecutively controlling for the effects of age together with 11 other potential confounding factors . The magnitude of the age-adjusted PRs was greatest for blue collar males . Due to the cross-sectional nature of the study design , causal inferences can not be made . The limitations of design and measurement are discussed in the context of the method ological weaknesses of the work stress field OBJECTIVES : The impact of work on the risk of future psychiatric disorder has been examined in few longitudinal studies . This was examined prospect ively in a large epidemiological study of civil servants . METHODS : In the Whitehall II study , a longitudinal , prospect i ve cohort study of 6895 male and 3413 female London based civil servants , work characteristics measured at baseline ( phase 1 : 1985 - 8 ) and first follow up ( phase 2 : 1989 ) were used to predict psychiatric disorder measured by a 30 item general health question naire ( GHQ ) at phase 2 and phase 3 follow up ( phase 3 : 1991 - 3 ) . Work characteristics and GHQ were measured at all three phases . RESULTS : Low social support at work and low decision authority , high job dem and s and effort-reward imbalance were associated with increased risk of psychiatric disorder as assessed by the GHQ at follow up adjusting for age , employment grade , and baseline GHQ score . CONCLUSIONS : Social support and control at work protect mental health while high job dem and s and effort-reward imbalance are risk factors for future psychiatric disorder . Intervention at the level of work design , organisation , and management might have positive effects on mental health in working population OBJECTIVES There is considerable evidence documenting the association between psychosocial risk factors and work disability due to musculoskeletal disorders , and this has prompted suggestions that psychosocial screening should be administered in the workplace in order to identify individuals at risk of prolonged absence . However , the predictive value of psychosocial risk factors on return-to-work is largely unknown . The present study aim ed to explore the predictive relationship between psychosocial risk factors and absence due to musculoskeletal disorders of the lower back and upper limbs . METHODS A prospect i ve study of 4637 workers from a large , multi-site company in the UK was conducted in which a wide range of established question naires were used to collect baseline psychosocial data . Respondents were then followed over the ensuing 15 months , and absence due to musculoskeletal disorders was recorded . RESULTS 219 workers took absence due to musculoskeletal disorders . Detrimental cut-off scores ( risks ) on the psychosocial instruments were established , and it was found that work-related psychosocial risk factors predicted the likelihood of a future spell of absence ( odds ratios ranging between 1.6 and 3.2 ) , but not the duration of that absence . CONCLUSIONS Although work-related psychosocial factors were associated with the occurrence of absence due to musculoskeletal disorders , these findings do not lend support to the use of routine occupational psychosocial screening in order to predict prolonged absence Objectives : To study the influence of change in self perceived psychosocial work characteristics on subsequent rates of sickness absence . Methods : Prospect i ve cohort study of British civil service employees . Job control , job dem and s , and work social supports were measured in 1985/88 and in 1991/93 . Analyses included 3817 British civil servants with sickness absence records at baseline ( 1985–89 ) and for two follow up periods , early ( 1994–95 ) and later follow up ( 1996–98 ) . Results : Change in work characteristics predicted subsequent incidence of long spells of sickness absence ( > 7 days ) in the early follow up period after adjustment for covariates including baseline work characteristics , health status , and sickness absence . Adjusted rate ratios were 1.23 ( 95 % CI 1.03 to 1.46 ) for decreased compared with stable decision latitude ; 1.17 ( 95 % CI 1.01 to 1.36 ) for increased compared with stable job dem and s and 0.79 ( 95 % CI 0.67 to 0.93 ) for increased compared with stable work social support . These associations were also seen in a sub- sample who did not change employment grade . In the later follow up period , associations between work change and long spells of sickness absence were similar for decision latitude , less pronounced for job dem and s , and no longer apparent for social supports . Changes in work characteristics were not associated with subsequent short spells of sickness absence ( ⩽7 days ) . Conclusions : Adverse changes in the psychosocial work environment may lead to increased rates of sickness absence . These findings suggest that workplace interventions to improve psychosocial working conditions may reduce levels of sickness absence Abstract Objective : To determine the association between adverse psychosocial characteristics at work and risk of coronary heart disease among male and female civil servants . Design : Prospect i ve cohort study ( Whitehall II study ) . At the baseline examination ( 1985 - 8 ) and twice during follow up a self report question naire provided information on psychosocial factors of the work environment and coronary heart disease . Independent assessment s of the work environment were obtained from personnel managers at baseline . Mean length of follow up was 5.3 years . Setting : London based office staff in 20 civil service departments . Subjects : 10 308 civil servants aged 35 - 55 were examined-6895 men ( 67 % ) and 3413 women ( 33 % ) . Main outcome measures : New cases of angina ( Rose question naire ) , severe pain across the chest , diagnosed ischaemic heart disease , and any coronary event . Results : Men and women with low job control , either self reported or independently assessed , had a higher risk of newly reported coronary heart disease during follow up . Job control assessed on two occasions three years apart , although intercorrelated , had cumulative effects on newly reported disease . Subjects with low job control on both occasions had an odds ratio for any subsequent coronary event of 1.93 ( 95 % confidence interval 1.34 to 2.77 ) compared with subjects with high job control at both occasions . This association could not be explained by employment grade , negative affectivity , or classic coronary risk factors . Job dem and s and social support at work were not related to the risk of coronary heart disease . Conclusions : Low control in the work environment is associated with an increased risk of future coronary heart disease among men and women employed in government offices . The cumulative effect of low job control assessed on two occasions indicates that giving employees more variety in tasks and a stronger say in decisions about work may decrease the risk of coronary heart disease . Key messages Low job control in the work environment contributes to the development of coronary heart disease among British male and female civil servants The risk of heart disease is associated with both objective low job control and perceived low job control . Increase in job control over time decreases the risk of coronary heart disease . This suggests that policies giving people a stronger say in decisions about their work or providing them with more variety in work tasks may contribute to better cardiovascular OBJECTIVE --To compare measures of job stress , job satisfaction , and mental health among general practitioners before and after the introduction of the new contract in April 1990 . DESIGN --Cross sectional postal question naire survey in July 1990 . Comparison of results with those obtained in previous survey in November 1987 . SETTING --General practice in United Kingdom . SUBJECTS--1500 general practitioners r and omly selected from general medical services lists , 917 of whom ( 61 % ) returned question naires usable for statistical analysis . MAIN OUTCOME MEASURES --Aspects of job causing stress , job satisfaction ( Warr , Cook , and Wall scale ) , and mental health ( Crown-Crisp experiential index ) . RESULTS --Compared with 1987 , in 1990 doctors experienced more stress from night calls ( mean score 3.83 in 1990 v 3.45 in 1987 ) , emergencies during surgery hours ( 3.72 v 3.48 ) , and interruption of family life by telephone ( 3.58 v 2.73 ; p less than 0.001 for all three variables ) . Scores for somatic anxiety and depression were higher in both men and women in 1990 ( men : somatic anxiety 3.12 v 2.36 ; depression 3.80 v 2.94 ; women : somatic anxiety 3.56 v 2.65 ; depression 4.02 v 3.37 ; p less than 0.001 ) . Job satisfaction had also decreased in 1990 ( 5.23 v 4.26 ; p less than 0.001 ) . CONCLUSIONS --Doctors experienced more stress , less job satisfaction , and poorer mental health in 1990 than in 1987 . These changes may have result ed from the introduction of the new contract OBJECTIVE --To identify sources of job stress associated with high levels of job dissatisfaction and negative mental wellbeing among general practitioners in Engl and . DESIGN --Multivariate analysis of large data base of general practitioners compiled from results of confidential question naire survey . Data obtained on independent variables of job stress , demographic factors , and personality . Dependent variables were mental health , job satisfaction , alcohol consumption , and smoking . SETTING --National sample of general practitioners studied by university department of organisational psychology . SUBJECTS -- One thous and eight hundred seventeen general practitioners selected at r and om by 20 family practitioner committees in Engl and . INTERVENTIONS --None . END POINT -- Determination of the combination of independent variables that were predictive of mental health and job satisfaction . MEASUREMENTS AND MAIN RESULTS --Women general practitioners both had job satisfaction and showed positive signs of mental wellbeing in contrast with other normative groups . Conversely , male doctors showed significantly higher anxiety scores than the norms , had less job satisfaction , and drank more alcohol than their women counterparts . Multivariate analysis disclosed four job stressors that were predictive of high levels of job dissatisfaction and lack of mental wellbeing ; these were dem and s of the job and patients ' expectations , interference with family life , constant interruptions at work and home , and practice administration . CONCLUSIONS --There may be substantial benefit in providing a counselling service for general practitioners and other health care workers who suffer psychological pressure from their work 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 The association between specific job characteristics and subsequent cardiovascular disease was tested using a large r and om sample of the male working Swedish population . The prospect i ve development of coronary heart disease ( CHD ) symptoms and signs was analyzed using a multivariate logistic regression technique . Additionally , a case-controlled study was used to analyze all cardiovascular-cerebrovascular ( CHD-CVD ) deaths during a six-year follow-up . The indicator of CHD symptoms and signs was vali date d in a six-year prospect i ve study of CHD deaths ( st and ardized mortality ratio 5.0 ; p less than or equal to .001 ) . A hectic and psychologically dem and ing job increases the risk of developing CHD symptoms and signs ( st and ardized odds ratio 1.29 , p less than 0.25 ) and premature CHD-CVD death ( relative risk 4.0 , p less than .01 ) . Low decision latitude-expressed as low intellectual discretion and low personal schedule freedom-is also associated with increased risk of cardiovascular disease . Low intellectual discretion predicts the development of CHD symptoms and signs ( SOR 1.44 , p less than .01 ) , while low personal schedule freedom among the majority of workers with the minimum statutory education increases the risk of CHD-CVD death ( RR 6.6 , p less than .0002 ) . The associations exist after controlling for age , education , smoking , and overweight A study was conducted in a Dutch hospital to evaluate the effects of the implementation of a Dutch form of Primary Nursing on nurses ' well-being in the work situation . The variables used as indicators of well-being at work were job satisfaction , experienced job significance , health complaints and absenteeism . The study included three measuring periods : one pre-intervention ( t1 ) and two post-intervention periods ( t2 , 8 months after t1 , and t3 , 14 months after t1 ) . Primary Nursing was implemented in group 1 ( consisting of two nursing units ) after t1 . At this time no changes were introduced into group 2 ( three nursing units ) but after t2 . Primary Nursing was also implemented in group 2 . The research variables were measured by means of question naires . The results of the study indicate that most of the expected effects of Primary Nursing did not occur . Some method ological and practical explanations for this outcome are given OBJECTIVES The effects of a stress reduction program on Japanese blue-collar workers were investigated using a controlled trial design . METHODS Two blue-collar worksites that showed higher depression scores ( Zung self-rating depression score ) were selected for the intervention group , after a survey of a large electric company in 1985 . Three blue-collar worksites were selected as a reference group whose workers were matched with the workers of the interventive worksites by mean age , worksite size and mean depression scores . A 1-year stress reduction program was conducted in the intervention group from 1986 to 1987 by worksite supervisors . Effects of the stress reduction program were assessed by comparing the initial depression scores , length of sick leave , and systolic and diastolic blood pressures with those after the follow-up . RESULTS The depression scores decreased during the follow-up in the intervention group , while the scores were almost the same in the reference group . An analysis of covariance with repeated measurements indicated a statistically significant intervention ( group x time interaction ) effect after control for gender and age ( P = 0.035 ) . Sick leave in the past year decreased in 1988 only in the intervention group ; generalized logit analysis with repeated measurements indicated a statistically significant intervention effect after control for gender and age ( P = 0.034 ) . No statistically significant intervention effects were observed on systolic and diastolic blood pressures or selected work stressors . CONCLUSIONS A stress reduction program directed towards worksite supervisors can be used to reduce depressive symptoms and sick leave among Japanese blue-collar workers This study was set up to test the effectiveness of primary nursing on the burnout level of psychiatric nurses . It was expected that , under certain conditions , such as a primary nursing care delivery with an adequate feedback system , the burnout level would decrease . In a quasi-experimental research design , a cohort of 161 psychiatric nurses was followed for 2.5 years . Results showed that although the burnout level did not change as a result of primary nursing , psychiatric nurses and the practical nurses seemed able to work according to the principles of primary nursing . Strong indications were found that the job turnover decreased as a result of the introduction of primary nursing . Because two main problems were encountered in this study , a high drop-out due to job turnover among nurses and the imitation of the intervention by the control group , several additional analyses were performed |
10,746 | 25,710,794 | Most of the studies assessed combination therapies which generally reported better results .
Studies assessing topical preparations , in particular topical corticosteroids , reported most adverse effects .
This review has found some evidence from individual studies to support existing therapies for vitiligo , but the usefulness of the findings is limited by the different design s and outcome measurements and lack of quality of life measures . | BACKGROUND Vitiligo is a chronic skin disorder characterised by patchy loss of skin colour .
Some people experience itching before the appearance of a new patch .
It affects people of any age or ethnicity , more than half of whom develop it before the age of 20 years .
There are two main types : generalised vitiligo , the common symmetrical form , and segmental , affecting only one side of the body .
Around 1 % of the world 's population has vitiligo , a disease causing white patches on the skin .
Several treatments are available .
Some can restore pigment but none can cure the disease .
OBJECTIVES To assess the effects of all therapeutic interventions used in the management of vitiligo . | BACKGROUND Oral minocycline has been recently shown to halt disease progression in active vitiligo . AIMS The present study was planned to compare the efficacy and tolerability of oral minocycline with oral mini pulse ( OMP ) corticosteroids in active vitiligo . METHODS A total of 50 patients with actively spreading vitiligo were r and omized to receive either minocycline 100 mg/day ( Group I-25 patients ) or OMP 2.5 mg dexamethasone on 2 consecutive days in a week ( Group II-25 patients ) for 6 months . These were followed-up at every 2 weeks interval . Mean vitiligo disease activity score ( VIDA ) and mean Vitiligo Area Scoring Index ( VASI ) were assessed in all patients in addition to the photographic comparison before and after treatment . RESULTS Both groups showed a significant decrease in VIDA from 4.0 to 1.64±0.86 ( P<0.001 ) in Group I and from 4.0 to 1.68±0.69 ( P<0.001 ) in Group II . However , the difference between the mean VIDA scores in the two groups was not statistically significant ( P=0.60 ) at the end of treatment period . The mean VASI declined from 1.71±1.45 to 1.52±1.43 Group I ( P=0.06 ) and from 1.39±1.31 to 1.17±1.34 in Group II ( P=0.05 ) . The difference between VASI in Group I and II was not significant at the end of 24 weeks of treatment ( P=0.11 ) . CONCLUSION Both dexamethasone OMP and oral minocycline are effective drugs for managing the arrest of disease activity in vitiligo Background Vitiligo is the most prevalent pigmentary disorder which occurs worldwide , with an incidence rate between 0.1 - 4 percent . It is anticipated that the discovery of biological pathways of vitiligo pathogenesis will provide novel therapeutic and prophylactic targets for future approaches to the treatment and prevention of vitiligo . The purpose s of this study were evaluating the efficacy of supplemental zinc on the treatment of vitiligo . Methods This r and omized clinical trial was conducted for a period of one year . Thirty five patients among 86 participants were eligible to entrance to the study . The patients in two equal r and omized groups took topical corticosteroid and combination of oral zinc sulfate-topical corticosteroid . Results The mean of responses in the corticosteroid group and the zinc sulfate-corticosteroid combination group were 21.43 % and 24.7 % , respectively . Conclusion Although , the response to corticosteroid plus zinc sulfate was more than corticosteroid , there was no statistically significant difference between them . It appeared that more robust long-term r and omized controlled trials on more patients , maybe with higher doses of zinc sulfate , are needed to fully establish the efficacy of oral zinc in management of vitiligo . Trial Registration BACKGROUND Vitiligo is an acquired skin disorder with great social impact . It can be successfully treated using cultured autologous melanocytes transplantation . OBJECTIVE To evaluate the effect of different modalities of narrow‐b and ultraviolet B ( NB‐UVB ) therapy on the outcome of cultured autologous melanocyte transplantation in treating vitiligo . METHODS Patients undergoing cultured autologous melanocyte transplantation were r and omly assigned to four different study groups . Group 1 underwent 20 sessions of NB‐UVB treatment before transplantation ; Group 2 underwent 30 sessions of NB‐UVB treatment after transplantation ; Group 3 underwent 20 sessions of NB‐UVB treatment before transplantation and 30 sessions after transplantation ; Group 4 underwent only transplantation . RESULTS Four hundred thirty‐seven patients were enrolled . Group 3 responded best , more than 90 % repigmentation was achieved in 81.3 % of patients , and 94.8 % patients experienced 50 % or greater repigmentation . Statistical analysis showed that there was a highly significant difference between the four groups ( χ2 = 35.56 , p < .001 ) . Homogeneous skin color was obtained on the repigmentation areas , and no scarring or other serious side effects were observed . CONCLUSIONS Cultured autologous melanocyte transplantation is an effective treatment for stable vitiligo . Combination of NB‐UVB therapy with melanocyte transplantation can accelerate repigmentation of transplanted vitiliginous areas , especially if NB‐UVB is given before and after transplantation Objective : Pseudocatalase/superoxide dismutase ( PSD ) is a topical gel considered having therapeutic effects in vitiligo . This study was design ed to evaluate the efficacy of this combination in vitiligo . Methods : This was a pilot r and omized , double-blind , placebo-controlled trial on 46 symmetrical vitiligo lesions of limbs in 23 patients referring to dermatology clinics , Isfahan , Iran in 2010 . Patients were received this formula or placebo gels for the right and left lesions . Lesion area and degree of pigmentation were assessed at baseline , 2 , 4 , and 6 months . Findings : There were no significant changes in lesion area and perifollicular pigmentation in each group ( P > 0.05 ) . Conclusion : The results indicated no significant therapeutic effect for PSD in vitiligo Background : Immunosuppressive agents are used widely in the treatment of vitiligo . Corticosteroids are used either alone or as adjuvant therapy by many practitioners . Cyclophosphamide and cycloporine‐A have also been used with variable success . Azathioprine may have the potential for the treatment of vitiligo alone or in combination with other modalities . Objective : To compare the efficacy of combined low‐dose azathioprine and oral PUVA therapy versus oral PUVA therapy alone for the treatment of vitiligo . Patients and methods : A total of 60 vitiligo patients were r and omized to receive either azathioprine ( 0.6–0.75 mg/kg ) and oral PUVA therapy ( group 1 ) or oral PUVA therapy alone ( group 2 ) . Patients were followed for 4 months . A graph transparency with squares of 2.5 × 2.5 mm was used to measure the rate of repigmentatiopn after 4 months of therapy . Results : Perifollicular repigmentation started after a mean of five sessions in group 1 , and eight sessions in group 2 . The mean total repigmentation rate after 4 months was 58.4 % for group 1 and 24.8 % for group 2 . No serious side effects were seen during or after treatment . Conclusion : Azathioprine may potentiate the repigmentary effects of PUVA therapy in vitiligo patients . A limitation of the study is the lack of vali date d measures for vitiligo assessment BACKGROUND Previous reports have shown the effectiveness of a basal layer cell suspension in the treatment of stable vitiligo ; however , there has been no mention in the literature until now of the optimal number of melanocytes required in an autologous noncultured epidermal suspension for transplantation to obtain early and acceptable results . METHODS In this r and omized prospect i ve study , we compared the efficacy of two different dilutions to determine the optimum density of melanocytes required for transplantation to achieve early and cosmetically acceptable results . We enrolled 20 patients with stable vitiligo with a body surface area involvement of < 10 % . RESULTS Fifty per cent of patients in Group A ( where the recipient area transplanted was approximately three times the size of the donor area , and the density of melanocytes transplanted per square millimeter was approximately 231.60+/- 27.03 ) showed marked ( > 75 % ) , 20 % moderate , 10 % mild , and 20 % minimal repigmentation ( or no response ) . In Group B ( where the recipient area was increased to five-fold the donor area ) , none of the patients showed marked , 10 % showed moderate , 20 % showed mild , and 70 % showed either minimal or no repigmentation . The density of melanocytes transplanted in this group was 154.90+/- 27.65/mm(2 ) . The extent of repigmentation was significantly greater ( P < 0.05 ) in Group A than in Group B , and the density of melanocytes in the suspension was also significantly greater ( P < 0.01 ) in Group A than in Group B. CONCLUSION We contend that the minimum number of melanocytes required to produce satisfactory repigmentation is probably in the range of 210 - 250/mm(2 ) Summary For effective treatment of vitiligo , it is as important to arrest the progression of the disease as it is to induce repigmentation . Recently , oxidative stress has been shown to play an important role in the pathogenesis of vitiligo . Ginkgo biloba extract has been shown to have antioxidant and immunomodulatory properties . In a double‐blind placebo‐controlled trial , we evaluated the efficacy of G. biloba extract in controlling the activity of the disease process in patients with limited and slow‐spreading vitiligo and in inducing repigmentation of vitiliginous areas . Fifty‐two patients were assigned to two treatment groups ( A and B ) in a double‐blind fashion , but only 47 patients could be evaluated , because one patient in group A and four patients in group B withdrew for reasons unrelated to the study . Patients in group A were given G. biloba extract 40 mg three times daily whereas patients in group B received placebo in similar doses . A statistically significant cessation of active progression of depigmentation was noted in patients treated with G. biloba ( P = 0.006 ) . Marked to complete repigmentation was seen in 10 patients in group A , whereas only two patients in group B showed similar repigmentation . The G. biloba extract was well tolerated . G. biloba extract seems to be a simple , safe and fairly effective therapy for arresting the progression of the disease BACKGROUND There is currently no quantitative tool for evaluating vitiligo treatment response using parametric methods . OBJECTIVE To develop and apply a simple clinical tool , the Vitiligo Area Scoring Index ( VASI ) , to model the response of vitiligo to narrowb and UV-B ( NB-UV-B ) phototherapy using parametric tests . DESIGN Prospect i ve , r and omized , controlled , bilateral left-right comparison trial . SETTING North American tertiary care , university-affiliated phototherapy center . PATIENTS Patients older than 18 years with stable vitiligo involving at least 5 % of their total body surface in a symmetric distribution . INTERVENTION Treatment with NB-UV-B was given 3 times a week to half of the body on all patients for either 60 treatments or 6 months . The contralateral side served as a no-treatment control . MAIN OUTCOME MEASURE Repigmentation was assessed using the VASI , which was based on a composite estimate of the overall area of vitiligo patches at baseline and the degree of macular repigmentation within these patches over time . The VASI was vali date d separately against physician and patient global assessment s. The overall reductions in VASI for NB-UV-B and control groups were modeled by multilevel regression with r and om effects and compared parametrically . RESULTS The VASI scoring correlated well with both patient and physician global assessment s ( P = .05 and P<.001 , respectively , using ordinal logistic regression ) . The extent of repigmentation after 6 months on the treated side was 42.9 % ( 95 % confidence interval , 26.7%-59.0 % ) vs 3.3 % ( 95 % confidence interval -19.3 % to 30.0 % ) on the untreated side ( P<.001 ) . A significant difference between control and NB-UV-B groups was apparent within the first 2 months of therapy . The legs , trunk , and arms were much more likely to repigment than the feet and h and s. CONCLUSIONS The VASI is a quantitative clinical tool that can be used to evaluate vitiligo parametrically . Patients treated with NB-UV-B can be expected to achieve approximately 42.9 % repigmentation of their vitiligo after 6 months of treatment , with the greatest response being achieved over the trunk and nonacral portions of the extremities OBJECTIVE To compare factors associated with halo nevi with nonsegmental vitiligo ( NSV ) vs NSV alone . DESIGN Prospect i ve observational study in 553 patients with a confirmed diagnosis of NSV attending a vitiligo clinic between January 1 , 2006 , and July 1 , 2010 . SETTING Vitiligo Clinic at the Department of Dermatology , University Hospital Center of Bordeaux , Bordeaux , France . PATIENTS The Vitiligo European Task Force question naire was informed for each patient attending the clinic with a confirmed diagnosis of NSV after the exclusion of other forms of vitiligo ( focal , mucosal , and not classifiable ) . Thyroid function and antithyroid antibodies were screened if not obtained in the previous year . MAIN OUTCOME MEASURES Extent of disease and markers of autoimmunity or autoinflammation . RESULTS Of the 553 patients , 130 had halo nevi-NSV and 423 had NSV . Family history of premature hair graying ( odds ratio , 1.74 ; P < .01 ) was positively associated with halo nevi-NSV by univariate analysis . Using multivariate analysis , age at onset younger than 18 years , phototype , total body area , localization on the trunk , involvement of h and s and feet , and total staging were found to be independent factors . Age at onset younger than 18 years ; phototypes I , II , and III ; trunk involvement ; and staging were positively associated with halo nevi-NSV , whereas this association was negative for total affected area and involvement of h and s and feet . CONCLUSIONS Halo nevi association in NSV affects age at onset and depigmentation pattern and has a stronger link with familial premature hair graying , suggesting that premature hair graying may involve , at least partly , an autoimmune pathway BACKGROUND Vitiligo is an acquired skin disorder that is characterized by well-defined , often symmetric white patches . Although current therapeutic modalities are directed toward increasing melanocyte melanin production , few treatment modalities address the immunologic nature of the disease . OBJECTIVE To determine whether excimer laser , a known therapeutic modality , in combination with tacrolimus , a topical immunomodulator , accelerate response time and /or improve the degree of response in patients with this disorder . METHODS Eight subjects diagnosed with vitiligo were recruited to participate in this institutional review board – approved double-blind , placebo-controlled study . Twenty-four symmetric vitiliginous patches ( elbows , knees ) from eight subjects received excimer laser treatment three times per week for 24 treatments or 10 weeks . Additionally , topical tacrolimus 0.1 % ointment ( Protopic ) and placebo ( Aquaphor ) were applied to r and omized patches ( left or right ) twice daily throughout the length of the trial . Vitiliginous patches were monitored with photographs at baseline , every 2 weeks , and 6 months after treatment . Biopsies were performed on subjects with significant results . RESULTS Twenty vitiliginous patches from six subjects qualified for evaluation . Fifty percent of patches treated with combination excimer laser and tacrolimus achieved a successful response ( 75 % repigmentation ) compared with 20 % for the placebo group . Subjects who responded successfully repigmented faster ( 19 % ) with combination therapy compared with excimer laser alone . Additionally , three subjects experienced transient hyperpigmentation in lesions treated with combination therapy . CONCLUSION Combining topical immunomodulators with known phototherapeutic modalities may represent a key advancement in the treatment of disease BACKGROUND Among surgical methods , punch skin grafting ( PSG ) and suction blister epidermal grafting ( SBEG ) are simple , inexpensive , and effective treatment methods for resistant lip vitiligo cases , but there is a lack of comparison between these procedures for lip vitiligo . OBJECTIVE The objective was to compare the outcome following PSG and SBEG in stable lip vitiligo . METHODS Eighteen patients with stable lip vitiligo were r and omly selected . Eight patients were included in PSG group and 10 patients in SBEG . All patients were kept on PUVA-SOL ( psoralen+ultraviolet A therapy of solar origin ) treatment after grafting . The results were evaluated after a follow-up period of 6 months . RESULTS At the end of 6 months of grafting in PSG group , two patients had a repigmentation of 50 % to 75 % , one had 75 % to 90 % , and three had 90 % to 100 % in the recipient site in lip . In SBEG group , one patient had repigmentation of 50 % to 75 % , three had 75 % to 90 % , and two had 90 % to 100 % . The color match was statistically significant in PSG when compared to SBEG . In the recipient site , cobblestone appearance was the predominant complication in PSG whereas hyperpigmentation and thickening of grafts were common in SBEG . In the donor site , superficial scarring and hypopigmentation were the common findings in PSG group whereas hyperpigmentation was the main problem in SBEG group . CONCLUSIONS Although both the procedures are effective in lip vitiligo , PSG gives a better color match than SBEG Background : Vitiligo is one of the autoimmune skin diseases that destroy the melanocytes of the skin . Moreover , its prevalence varies in different countries and regions . Objectives : The aim of this study was to compare the effect of Nigella sativa and fish oil on vitiligo lesions of the patients referred to a dermatology clinic . Material s and Methods : This r and omized , double blind clinical trial was conducted in the dermatology clinic of the Imam Khomeini Hospital Ahvaz , Iran , from June to December 2011 . We used a r and omized simple sampling . From 96 patients with vitiligo , 52 eligible patients were selected and allocated to two groups with equal size . The study medications were applied twice a day by patients on their lesions . After six months , the improvement rate of lesions was assessed by the Vitiligo Area Scoring Index ( VASI ) . Data were analyzed using SPSS v. 15 ; P value < 0.05 was considered as statistically significant . Results : After six months , a mean score of VASI decreased from 4.98 to 3.75 in patients applying topical Nigella sativa and from 4.98 to 4.62 in those using topical fish oil . Most of the percent improvement observed in upper extremities , trunk , head , and neck of those who received Nigella sativa and head , neck , trunk , and feet of those who received fish oil . No adverse effect was reported by the patients . Conclusions : Nigella sativa oil and fish oil were effective in reduction the size of patient ’s lesions ; however , Nigella sativa was more effective in comparison to the fish oil . Therefore , using Nigella sativa with the major drugs in the treatment of vitiligo is recommended Background A previous uncontrolled , open trial of levamisole in patients with limited and slowly spreading vitiligo had shown that new lesions did not develop in 94 % of patients after 2–4 months of treatment with the drug Vitiligo is an acquired cutaneous disorder of pigmentation , with an incidence of 0.5 % to 2 % worldwide . There are three major hypotheses for the pathogenesis of vitiligo that are not exclusive of each other : biochemical/cytotoxic , neural and autoimmune . Recent data provide strong evidence supporting an autoimmune pathogenesis of vitiligo . As vitiligo can have a major effect on quality of life , treatment can be considered and should preferably begin early when the disease is active . Current treatment modalities are directed towards stopping progression of the disease and achieving repigmentation . Therapies include corticosteroids , topical immunomodulators , photo(chemo)therapy , surgery , combination therapies and depigmentation of normally pigmented skin . Topical class 3 corticosteroids can be used for localized vitiligo . The use of topical immunomodulators ( TIMs ) in vitiligo seems to be equally effective as topical steroids , especially when used in the face and neck region . In photo(chemo)therapy , narrowb and ultraviolet-B therapy ( NB-UVB ) seems to be superior to psoralen ultraviolet-A therapy ( PUVA ) and broadb and UVB . In surgical techniques , split-thickness grafting and epidermal blister grafting were shown to be effective methods , although the non-cultured epidermal suspension technique has many advantages and seems to be a promising development . Depigmentation therapy can be considered if vitiligo affects more than 60 % to 80 % of the body . Complementary therapies such as Polypodium leucotomos show promising results in combination with UVB therapy . No causative treatment for vitiligo is currently available . More r and omized controlled trials on the treatment of vitiligo are necessary Background H and -held NB-UVB units are lightweight devices that may overcome the need to treat vitiligo in hospital-based phototherapy cabinets , allowing early treatment at home that may enhance the likelihood of successful repigmentation . The pilot Hi-Light trial examined the feasibility of conducting a large multi-centre r and omised controlled trial ( RCT ) on the use of such devices by exploring recruitment , adherence , acceptability , and patient education . Methods This was a feasibility , double-blind , multi-centre , parallel group r and omised placebo-controlled trial of h and -held NB-UVB phototherapy for the treatment of vitiligo at home . The overall duration of the trial was seven months ; three months recruitment and four months treatment . Participants were r and omly allocated to active or placebo groups ( 2:1 ratio ) . The primary outcome measure was the proportion of eligible participants who were willing to be r and omised . The secondary outcomes included proportion of participants expressing interest in the trial and fulfilling eligibility criteria , withdrawal rates and missing data , proportion of participants adhering to and satisfied with the treatment , and incidence of NB-UVB short-term adverse events . Results Eighty-three percent ( 45/54 ) of vitiligo patients who expressed interest in the trial were willing to be r and omised . Due to time and financial constraints , only 29/45 potential participants were booked to attend a baseline hospital visit . All 29 ( 100 % ) potential participants were confirmed as being eligible and were subsequently r and omised . Willingness to participate in the study for General Practice ( family physicians ) surgeries and hospitals were 40 % and 79 % , respectively ; 86 % ( 25/29 ) of patients adhered to the treatment and 65 % ( 7/11 ) of patients in the active group had some degree of repigmentation . Only one patient in the active group reported erythema grade 3 ( 3 % ) . Both devices ( Dermfix 1000 NB-UVB and Waldmann NB-UVB 109 ) were acceptable to participants . Conclusions H and -held NB-UVB devices need evaluation in a large , pragmatic RCT . This pilot trial has explored many of the uncertainties that need to be overcome before embarking on a full scale trial , including the development of a comprehensive training package and treatment protocol . The study has shown strong willingness of participants to be r and omised , very good treatment adherence and repigmentation rates , and provided evidence of feasibility for a definitive trial . Trial registration OBJECTIVE To assess the safety and efficacy of topical 0.1 % tacrolimus vs 0.05 % clobetasol propionate . DESIGN R and omized double-blind trial . SETTING Department of Dermatology , Hospital Central Dr Ignacio Morones Prieto , San Luis Potosí , México . PARTICIPANTS From 20 children with vitiligo , 2 symmetrical lesions of about the same size and evolution time were selected . They were devoid of any topical or systemic therapy for 2 months prior to inclusion . Interventions Treatment with topical tacrolimus and clobetasol for a 2-month period . MAIN OUTCOMES MEASURES The grade of repigmentation was evaluated by color slides at baseline and again at every 2-week visit . The slides were analyzed by 2 clinicians unrelated to the study and by a morphometric digitalized computer program . Characteristics of pigment , time of response , symptoms , telangiectasias , and atrophy were evaluated every 2 weeks . RESULTS Eighteen ( 90 % ) of the 20 patients experienced some repigmentation . The mean percentage of repigmentation was 49.3 % for clobetasol and 41.3 % for tacrolimus . Lesions in 3 patients using clobetasol presented atrophy , and 2 lesions incurred telangiectasias ; tacrolimus caused a burning sensation in 2 lesions . CONCLUSIONS Tacrolimus proved almost as effective as clobetasol propionate to restore skin color in lesions of vitiligo in children . Because it does not produce atrophy or other adverse effects , tacrolimus may be very useful for younger patients and for sensitive areas of the skin such as eyelids , and it should be considered in other skin disorders currently treated with topical steroids for prolonged periods BACKGROUND Vitiligo is an acquired pigment disorder characterized by areas of depigmented skin result ing from the loss of epidermal melanocytes . Recently , several investigations have documented the benefits of excimer phototherapy ( e.g. , using the 308-nm excimer laser or the 308-nm excimer lamp ) for the treatment of vitiligo . AIM To compare the effectiveness of the 308-nm excimer laser with the 308-nm excimer lamp in the treatment of vitiligo patients . METHODS This intervention study was design ed as a r and omized self-control trial . Fourteen subjects with 48 symmetrical vitiligo lesions were enrolled in this study . One lesion was treated with the 308-nm excimer laser , and its counterpart was treated with the 308-nm excimer lamp . Lesions were treated three times a week with the same dose on both sides for a total of 20 sessions . RESULTS All of the patients completed the study , and 48 lesions were treated . The two treatments exhibited similar results in terms of repigmentation . CONCLUSIONS The 308-nm excimer lamp and the 308-nm excimer laser exhibited similar efficacies in treating vitiligo BACKGROUND DATA Narrow b and ultraviolet B ( UVB ) is an effective and safe option for the treatment of vitiligo . However , a complete and long-lasting repigmention of vitiligo patches is difficult to achieve . Combined treatments with novel sources of phototherapy and topical agents represent possible new strategies . OBJECTIVE The purpose of this study was to compare the efficacy of combined tacrolimus and 308-nm excimer light ( MEL ) vs 308-nm MEL monotherapy in treating vitiligo in a controlled study . METHODS Fifty-three patients affected by vitiligo were enrolled in this open prospect i ve study . Patients were divided into three groups : Group I included 20 patients treated with MEL 308 nm twice weekly and oral vitamin E ; Group II included 20 patients treated with MEL 308 nm twice weekly combined with 0.1 % tacrolimus once a day and oral vitamin E ; and Group III included 13 patients treated only with oral vitamin E. Efficacy was assessed at the end of 12 weeks based on the percentage of repigmentation . RESULTS Fifty-two patients completed 12 weeks of treatment . Group I ( MEL + vitamin E ) showed a moderate repigmentation in 35 % of patients , good repigmentation in 30 % , excellent repigmentation in 25 % , and poor repigmentation in 10 % ; Group II ( MEL + tacrolimus 0.1%+ vitamin E ) presented moderate repigmentation in 25 % of patients , good repigmentation in 40 % , excellent repigmentation in 30 % , and poor repigmentation in 5 % ; Group III ( vitamin E ) showed moderate repigmentation in 16 % and 84 % did not show signs of repigmentation . CONCLUSIONS Our results demonstrate that the combination treatment of 0.1 % tacrolimus ointment plus 308-nm MEL and 308-nm MEL monotherapy are effective , safe , and well tolerated for the treatment of vitiligo compared to treatment with vitamin E. Furthermore , this study suggests that an association with topical immunomodulators could enhance the clinical response in vitiligo , especially in more resistant anatomical sites Background . Vitiligo is a pigmentary disorder characterized by depigmented macules due to absence of melanocytes . Increased levels of tumor necrosis factor alpha and interleukin-1 in the epidermis of lesions may play a role in keratinocyte apoptosis and less production of melanogenic cytokines . Tetracyclines reduce production of tumor necrosis factor alpha and interleukin-1 . Objective . To evaluate the effect of topical tetracycline on vitiligo patients on phototherapy . Methods . Thirty cases of generalized stable vitiligo were chosen r and omly and pigmentation of two assigned lesions on right and left sides ( same size and location ) was determined by vitiligo area severity index , and medication and placebo were r and omly assigned to be applied twice daily on either right or left side , respectively . Images were taken of the lesions at the end of the 4th , 8th , and 12th weeks and pigmentations were compared to baseline using aforementioned index . The patients also took narrow b and ultraviolet B two to three times a week . Results . Mean pigmentation , based on vitiligo area severity index , changed significantly from 90.1667 to 86.6667 ( P = 0.026 ) and on placebo side from 89.6667 to 86.8333 ( P = 0.026 ) . There was no significant difference between medication and placebo sides in terms of pigmentation ( P = 0.566 ) . Conclusions . No significant difference in improving repigmentation between medication and placebo sides was seen Narrow b and UVB is succeeding psoralen and UVA irradiation as the main treatment of vitiligo vulgaris in several European countries . Vitamin B12 and folic acid deficiency in some vitiligo patients has prompted research ers to investigate the efficacy of these vitamins in the treatment of vitiligo . In the present controlled study we investigated the value of narrow b and UVB phototherapy in the treatment of vitiligo and the possible additive effect of vitamin B12 and folic acid . Twenty-seven patients with long-term stable vitiligo were included and r and omized in a " UVB only " ( UVB ) or " UVB combined with vitamin B12 and folic acid " ( UVB+ ) group . Patients were irradiated thrice weekly for one year , whilst repigmentation was carefully monitored . In 92 % ( 25/27 ) of the patients up to 100 % repigmentation was seen . Repigmentation was notable in lesions on the face , neck and throat , lower arm , chest , back and lower legs , whilst repigmentation on the h and s , wrists , feet and ankles proved to be minimal . Maximum repigmentation rates did not differ significantly between the UVB group and the UVB+ group . Our study reconfirms that narrow b and UVB phototherapy is an effective treatment for vitiligo and shows that co-treatment with vitamin B12 and folic acid does not improve the outcome of treatment of vitiligo with narrow b and UVB phototherapy BACKGROUND Various surgical and non-surgical methods are available to treat vitiligo . Surgical techniques such as epidermal blister graft transplantation may be effective for the re-pigmentation of stable , but refractory vitiligo areas . Khellin has phototherapeutic properties that are similar to those of the psoralens , but with substantially lower phototoxic effects and DNA mutation effects . Its penetration into the hair follicles is enhanced by encapsulating it into liposomes . Subsequent activation of the khellin with UV light stimulates the melanocytes in the hair follicles . OBJECTIVE The first objective was to evaluate the additional value of combining blister roof transplantation ( BRT ) with khellin in liposomes and ultraviolet light ( KLUV ) in the treatment of recalcitrant vitiligo patches . The second objective was to assess patients ' satisfaction . MATERIAL S AND METHODS Nineteen patients with vitiligo lesions which did not respond to KLUV treatment for at least a year were treated with BRT followed by KLUV . The transplantation was performed by creating blisters with a suction device , preparing the target site with Erbium laser ablation and the actual transplantation . Locations where r and omly assigned . A blinded observer established the results . RESULTS Seventy-five percent of the patients were satisfied with the cosmetic result . All of the patients would recommend the treatment to other vitiligo patients . More than 75 % re-pigmentation of the vitiligo areas was noted in 47 % of the patients according to the blinded evaluation of photographs taken before and after the treatment OBJECTIVE To compare the efficacy and safety of using a combination of fluticasone propionate ( FP ) and UV-A with that of either drug used alone in the long-term treatment of vitiligo . DESIGN Prospect i ve , r and omized , controlled , left-right comparison study . Repigmentation was judged by a single dermatologist ( L.N.-K. ) and skin thickness was scored by a pathologist ( using biopsy sample s ) , a dermatologist ( L.N.-K. ) ( visually ) , and patients ( using a st and ard question naire ) . SETTING Netherl and s Institute for Pigmentary Disorders , Amsterdam . PATIENTS Patients with lesions on arms , legs , and trunk were treated on 2 symmetrical lesions for 9 months with FP alone and a combination of FP and UV-A ( FP group ) or with UV-A alone and a combination of FP and UV-A ( UV-A group ) . Fluticasone propionate cream was applied once daily at about bedtime , and UV-A ( 10 J/cm2 ) exposure was twice a week . Patients attended the clinic at 3-month intervals . RESULTS One hundred thirty-five patients were included , 96 of whom were evaluable after 9 months . Patients not reaching the end point withdrew because of insufficient repigmentation ( n = 23 ) , decreased motivation ( n = 11 ) , or protocol violations ( n = 5 ) . No patient ( irrespective of whether they withdrew ) experienced any adverse effects . The FP and UV-A groups were comparable with respect to sex , age , and location of lesions . On average , combination treatment was 3 times more effective than either UV-A or FP treatment alone . In the FP group , no atrophy was seen after 9 months with either treatment . In the UV-A group , a little atrophy was detected twice : as well during UV-A treatment alone as during combination treatment . CONCLUSIONS Combination treatment with FP and UV-A is much more effective in reaching complete repigmentation than are FP and UV-A used alone , but large inter-individual differences occur . Fluticasone propionate , UV-A , and a combination of FP and UV-A seem to be safe for long-term treatment of vitiligo OBJECTIVE To compare the efficacy of oral psoralen-UV-A ( PUVA ) with that of narrowb and -UV-B ( NB-UVB ) phototherapy in patients with nonsegmental vitiligo . DESIGN Double-blind r and omized study . SETTING Phototherapy unit in a university hospital . PATIENTS Fifty-six patients with nonsegmental vitiligo . Interventions Twice-weekly therapy with PUVA or NB-UVB . MAIN OUTCOME MEASURES The change in body surface area affected by vitiligo and the color match of repigmented skin compared with unaffected skin were assessed after 48 sessions of therapy , at the end of the therapy course , and 12 months after the end of therapy . RESULTS The results in the 25 patients each in the PUVA and NB-UVB groups who began therapy were analyzed . The median number of treatments was 47 in the PUVA-treated group and 97 in the NB-UVB-treated group ( P = .03 ) ; we suspect this difference was because of the differences in efficacy and adverse effects between the 2 modalities , such that patients in the NB-UVB group wanted a longer course of treatment . At the end of therapy , 16 ( 64 % ) of 25 patients in the NB-UVB group showed greater than 50 % improvement in body surface area affected compared with 9 ( 36 % ) of 25 patients in the PUVA group . The color match of the repigmented skin was excellent in all patients in the NB-UVB group but in only 11 ( 44 % ) of those in the PUVA group ( P<.001 ) . In patients who completed 48 sessions , the improvement in body surface area affected by vitiligo was greater with NB-UVB therapy than with PUVA therapy ( P = .007 ) . Twelve months after the cessation of therapy , the superiority of NB-UVB tended to be maintained . CONCLUSION In the treatment of nonsegmental vitiligo , NB-UVB therapy is superior to oral PUVA therapy BACKGROUND The potential of psoralen-narrowb and ultraviolet B ( NBUVB ) photochemotherapy has been investigated in vitiligo . The present study aims to evaluate the efficacy of psoralen-NBUVB ( P-NBUVB ) vs. NBUVB in vitiligo . METHODS In a r and omized study , 45 Indian patients ( age above 13 years ) with vitiligo involving more than 5 % body surface area were r and omly allocated to receive either NBUVB or P-NBUVB treatment . Both groups received NBUVB exposure thrice weekly , with a total of 60 sessions . The extent of repigmentation achieved was calculated on the basis of Vitiligo Area Severity Index ( VASI ) scoring . RESULTS Forty patients were available for analysis at the end of the study . The extent of repigmentation in the P-NBUVB group was statistically significantly greater in face and neck ( P = 0.006 , t-test ) and h and s ( P = 0.007 , t-test ) in comparison with the NBUVB group ( t-test ) . Percentage reduction in VASI scores was statistically significantly greater in the P-NBUVB group ( 29.2 % vs. 21.7 % , P = 0.043 , t-test ) . The response to P-NBUVB therapy started earlier than the response to NBUVB . After excluding sunlight as a confounding factor , treatment response was also significantly better in the P-NBUVB group ( P = 0.005 ) . CONCLUSION Addition of psoralen increased the extent of repigmentation due to NBUVB therapy in vitiligo . Further studies are required to determine the long-term efficacy and safety of P-NBUVB BACKGROUND A large variety of therapeutic agents are being used for the treatment of vitiligo , but treatment remains a challenge . Recently , monochromatic phototherapies such as 311-nm narrowb and ultraviolet B therapy and 308-nm xenon chloride excimer laser have been reported to be an effective and safe therapeutic option in children and adult patients with vitiligo . Single reports stipulate that the addition of topically applied calcipotriol to phototherapy increases its effectiveness . OBJECTIVE The purpose of the present pilot study was to determine if the addition of topical calcipotriol increases the efficacy of the 308-nm xenon chloride excimer in the treatment of vitiligo . METHODS Ten patients with vitiligo with essentially bilateral symmetrical lesions were enrolled in this prospect i ve right/left comparative , single-blinded trial conducted over a 15-month period . All patients received 308-nm XeCl excimer laser therapy three times weekly . Calcipotriol ointment ( Daivonex ) was applied to lesions on one side of the body twice daily . RESULTS After 24 treatments ( 8 weeks ) , nine patients were evaluated . Eight patients showed evidence of repigmentation on both body sides , with no significant difference between the body side treated with calcipotriol and excimer laser and the side treated with excimer laser alone . The mean repigmentation rate was 22.4 % ( 1 - 37 % ) . CONCLUSION The addition of calcipotriol ointment to 308-nm xenon chloride excimer laser phototherapy does not significantly enhance its efficacy . Small additive effects must be investigated in a larger trial BACKGROUND Small vitiliginous patches have been treated with epidermal grafts or their cell suspensions . In an attempt to overcome some of the shortcomings of cell suspension delivery , we have delivered melanocytes on a polymeric film . OBJECTIVES To evaluate the clinical effectiveness of a cultured graft consisting of autologous cultured melanocytes on a poly ( DL‐lactic acid ) ( PLA ) film in subjects with stable vitiligo . METHODS A prospect i ve open‐label , r and omized , multicenter clinical trial was conducted with 22 patients . Each subject was treated with cultured graft and polyurethane dressing ( control arm ) after epidermal ablation and followed for up to 9 months . The extent of repigmentation in the treated sites was compared with that control sites at days 90 , 180 , and 270 . RESULTS In the treatment arm , a minimum of 70 % repigmentation was observed in five subjects at day 90 ; nine at day 180 , and 10 at day 270 . In the control arm , only one subject showed repigmentation until day 270 . None of the test sites reported any recurrence of vitiliginous patches by the end of the study . CONCLUSIONS Cultured melanocytes delivered on PLA film were efficacious and safe when applied on patients with stable vitiligo Background Encouraging results of previous uncontrolled trials suggest that calcipotriol may potentiate the efficacy of psoralen plus ultraviolet ( UV ) A ( PUVA ) therapy in patients with vitiligo UNLABELLED Narrowb and ultraviolet B ( NB-UVB ) phototherapy , with a 308-nm xenon chloride excimer laser , and targeted UVB phototherapy have produced encouraging therapeutic results for vitiligo . However , very few studies employing broadb and UVB exist . Moreover , there has been no direct comparison study between broadb and UVB and NB-UVB for the treatment of vitiligo . The aims of this study were to compare the repigmenting efficacy of targeted broadb and UVB phototherapy with that of NB-UVB in an equi-erythemogenic manner . Twenty identical vitiliginous lesions from 10 patients were r and omly allocated to receive either targeted broadb and UVB or targeted NB-UVB phototherapy . UV fluences were started at 50 % of the minimal erythema dose detected within the vitiliginous patches , then increased gradually , in the same manner , to ensure equi-erythemogenic comparison . Treatments were carried out twice weekly for 12 weeks . The results show that grade 1 , i.e. 1 - 25 % repigmentation , to grade 2 , 26 - 50 % repigmentation , occurred in 6 of 10 subjects . Responses in terms of repigmentation , de-pigmentation , or lack thereof , were similar between lesions receiving broadb and and NB-UVB phototherapy . Onset of repigmentation occurred as early as 4 weeks of treatment in most subjects . Treatments were well tolerated , with only minimal erythema and hyperpigmentation . LIMITATIONS The study was carried out in a small number of patients with skin types III , IV and V. The irradiation device was a targeted UVB device and thus the results may not be applicable to other light sources , such as the excimer laser or total-body irradiation cabinets . In conclusion , targeted broadb and UVB produces similar clinical responses to targeted NB-UVB in the treatment of the non-segmental type of vitiligo Background : Limited data are available about the use of 308-nm monochromatic excimer light ( MEL ) and localized 311-nm narrow-b and ultraviolet B ( NB-UVB ) in the treatment of vitiligo . The aim of this study was to evaluate the efficacy of 308-nm MEL versus localized 311-nm NB-UVB in vitiligo patients . Methods : Eleven patients participated in this prospect i ve intrapatient placebo-controlled r and omized trial . In each patient , 3 lesions were selected and treated with NB-UVB , MEL and placebo during 24 sessions , respectively . Repigmentation was evaluated clinical ly and by objective surface measurement . Results : Twenty percent of the lesions treated with NB-UVB achieved repigmentation scores above 50 % . None of the lesions treated with MEL achieved a repigmentation higher than 50 % after 24 sessions . Conclusion : Localized 311-nm NB-UVB is effective in the treatment of vitiligo . It should be considered for localized vitiligo as it is easily accessible . In this study the efficacy of localized 311-nm NB-UVB was superior to 308-nm MEL Background Recently the beneficial effect of excimer laser treatment has been reported for patients with vitiligo . The influence of treatment frequency on this effect is not clear Background : Vitiligo is an acquired depigmenting disease with uncertain etiopathogenesis and the treatment modalities need to be consistently up date d. Aim : To evaluate a triple-combination treatment with oral α-lipoic acid ( ALA ) , betamethasone injection , and narrowb and ultraviolet B ( NB-UVB ) on vitiligo . Methods : Patients with non-segmental and progressive vitiligo lesions were r and omly assigned to two groups . The treatment group and the control group were respectively treated with oral ALA and placebo , in combination with betamethasone injection and NB-UVB . The effectiveness and adverse events were evaluated by investigators and patients before and after treatment . Results : Fifty non-segmental progressive vitiligo patients were enrolled in the study . The treatment period was 6 months . In treatment group , over 40 % patients achieved > 50 % improvement and ≥ 5 satisfaction score by 3-month therapy ( M3 ) . This percentage increased to 90 % at M6 . Treatment group achieved better efficacy than control group at M3 , while no difference was seen at M6 . Conclusion : The combined treatment with oral ALA , betamethasone injection , and NB-UVB was effective and safe on non-segmental progressive vitiligo . ALA could accelerate the initial response of repigmentation In this paper , we report on 366 East Indian patients with vitiligo who were treated for 2 to 3 years with either 8-methoxypsoralen ( 8-MOP ) , 4,5',8-trimethylpsoralen ( TMP ) , or psoralen and sunlight . These patients with amelanotic macules had 10 to 70 % skin involvement of 1 to 50 years duration . Male and female patients from ages 12 to 70 years were r and omly assigned to 8 treatment groups ; the study was conducted on a double-blind protocol . Patients in prone and supine positions were exposed to the sun for 45 - 60 minutes in gradually increasing doses between 11 a.m. and 2 p.m. thrice weekly and 2 hours after oral ingestion of the drug . The various drug dosage schedules investigated included 9 groups : 0.3 and 0.6 mg 8-MOP/kg ; 0.8 , 1.8 , and 3.6 mg TMP/kg ; a combination of 0.3 mg 8-MOP and 0.6 mg TMP/kg ; 0.6 and 1.2 mg psoralen/kg , and a placebo . For ethical reasons , the placebo group was terminated after 9 to 12 months of therapy . All patients were photographed before enrollment and at intervals of 6 , 12 , 18 , and 26 months during therapy . Of these patients treated for nearly 2 years , the faces of those 45 % receiving the combination dose of 8-MOP plus TMP or low-dose 8-MOP ( 0.3 mg/kg ) were fully repigmented , and nearly 60 % achieved 75 to 100 % repigmentation of the head and neck . The chest , abdomen , and back were repigmented nearly as well and better than the arms and legs . The patients receiving high-dose schedules of TMP and psoralen achieved better repigmentation response than those on lower dosage but still not as good as patients on 8-MOP or the combination group of 8-MOP plus TMP . ( ABSTRACT TRUNCATED AT 250 WORDS Background : Recently , narrow-b and ultraviolet B ( NB-UVB ) and topical immunomodulators have been successfully used in the treatment of vitiligo . Objective : To determine whether the combination of pimecrolimus with NB-UVB accelerates the response time and /or improves the degree of response in patients with vitiligo . Methods : Sixty-eight patients with vitiligo enrolled in this r and omized , double-blind , placebo-controlled study . The patients were r and omized into two groups and treated with NB-UVB plus either pimecrolimus or placebo for 3 months . Tri-weekly radiation was started at 280 mj/cm2 , with 15 % increments for each subsequent treatment until erythema was reported or a maximum of 800 mj/cm was achieved . At baseline and 6 and 12 weeks after commencement of therapy , vitiliginous patches were measured . Results : Fifty patients completed the 3-month study . No significant side effects except self-limited erythema and pruritus were observed . After 12 weeks of treatment , repigmentation of the facial lesions was higher in patients treated with combined pimecrolimus and NB-UVB compared with the placebo plus NB-UVB group ( 64.3 vs 25.1 % ) ( p < 0.05 % ) . There was no statistically significant difference in the repigmentation rate between the two groups on other body areas . Conclusion : On the face , NB-UVB works better if combined with pimecrolimus 1 % cream rather than used alone Minipunch grafting ( MPG ) and split-skin grafting ( SSG ) are common outpatient procedures for the surgical treatment of chronic stable vitiligo . However , there is a paucity of literature comparing the two procedures by the same group of investigators . Objective To compare the two techniques in patients with chronic stable localized vitiligo . Methods Sixty-four patients with stable vitiligo of 6 months duration were r and omized into two groups to be taken up for MPG or SSG in a representative patch followed by PUVAsol therapy for 3 months . They were evaluated 3 months postoperatively for the degree of repigmentation and side effects . Results In the MPG group , 644 grafts , 2.5 mm in size , were placed on a total vitiliginous area of 521.25 cm2 , whereas in the SSG group , 153 grafts covered a 1,489 cm2 recipient area . Three months postoperatively , in the first group , 15 cases ( 44.1 % ) showed very good to excellent ( > 75 % ) repigmentation compared with 25 cases ( 83.3 % ) in group 2 . Following MPG , 81 grafts ( 12.57 % ) were rejected . Cobblestoning was the main side effect , occurring in 13 cases ( 38.23 % ) , and a variegated appearance was observed in 7 ( 20.58 % ) patients . The complications noted after SSG were achromic fissuring in four ( 13.3 % ) cases , graft contracture in four grafts ( 2.61 % ) in three patients , and rejection of seven grafts ( 4.57 % ) in one case ; tire-pattern appearance in two patients ( 6.6 % ) ; milia formation in four ( 13.3 % ) patients ; and depigmentation of the grafts in two ( 6.6 % ) cases . In both groups , superficial scarring was noted at the donor site in all cases , whereas hypertrophic scarring occurred in 3 ( 10 % ) patients after SSG . Conclusion SSG carries a distinct advantage over MPG in producing excellent cosmetic matching over larger areas using fewer grafts , especially over the face and extremities BACKGROUND Among all the topical immunomodulators , vitiligo 's mainstay therapy includes topical corticosteroids . Many other non-immune theories have also been suggested for vitiligo 's pathogenesis , but the role of oxidative stress has gained more importance in recent years . OBJECTIVE To compare the effect of topical 0.05 % betamethasone vs. catalase/dismutase superoxide ( C/DSO ) . STUDY DESIGN R and omized , matched-paired , double-blind trial . SETTING Dermatology Section , University of Antioquia , Medellín , Colombia . SUBJECTS Patients ( aged > 18 years or between 12 and 18 years ) with parent 's informed consent , with stable or active bilateral vitiligo . INTERVENTION Topical 0.05 % betamethasone or C/DSO . METHODS Two lesions similar to each other in size were chosen . All assessment s were made by two blinded investigators , and photographs were subjected to morphometry analysis . MAIN OUTCOME Skin repigmentation by digital morphometry . RESULTS Twenty-five patients were enrolled in the study ( 21 women and 4 men ) . Mean age of participants was 40 years ( range : 12 - 74 years ) . One patient on C/DSO experienced a mild local erythematous papular rash that self-resolved . At 4 months of therapy , there was no statistical difference on the percentage of repigmentation between betamethasone and C/DSO ( 5.63 % + /- 27.9 vs. 3.22 % + /- 25.8 , respectively , P = 0.758 ) . After 10 months of therapy , the percentage of skin repigmentation increased to 18.5 + /- 93.14 % with betamethasone and to 12.4 + /- 59 % with C/DSO , but again , we found no statistical differences ( P = 0.79 ) . DISCUSSION AND CONCLUSIONS Few studies have described objective methods to evaluate repigmentation among vitiligo patients . Digital morphometry provides an objective assessment of repigmentation in vitiligo . Objective vitiligo repigmentation with topical C/DSO at 10 months is similar to topical 0.05 % betamethasone . Although a mild adverse effect was related to the use of C/DSO , such finding was not severe enough to discontinue treatment BACKGROUND Vitiligo is an acquired pigmentary disorder characterized by areas of depigmented skin result ing from loss of epidermal melanocytes . Recently , it has been shown that narrowb and ultraviolet B ( NB-UVB ) phototherapy may be more effective than psoralen and ultraviolet A ( PUVA ) photochemotherapy in treating vitiligo , and that 308-nm monochromatic excimer light ( MEL ) may present some advantages as compared to NB-UVB for the treatment of vitiligo . AIM The aim of this study was to compare the effectiveness of NB-UVB phototherapy and 308-nm MEL in vitiligo patients . METHODS The study was done in a r and omized , investigator-blinded and half-side comparison design . Twenty-one subjects with symmetrical vitiligo lesions were enrolled in this study . Vitiligo lesions on one body side were treated twice weekly for 6 months with 308-nm MEL , while NB-UVB phototherapy was used to treat lesions on the opposite side . RESULTS At the end of the study six lesions ( 37.5 % ) treated with 308-nm MEL and only one lesion ( 6 % ) treated with NB-UVB achieved an excellent repigmentation ( score 4 ) while four lesions ( 25 % ) treated with 308-nm MEL and five lesions ( 31 % ) treated with NB-UVB showed a good repigmentation ( score 3 ) . CONCLUSIONS It appears that 308-nm MEL is more effective than NB-UVB in treating vitiligo lesions and it induces repigmentation more rapidly AIM The aim of the present study was to evaluate the efficacy and safety of narrowb and UVB ( NB-UVB ) compared with tacrolimus ointment 0.1 % in patients with bilateral vitiligo . METHODS In this comparative study , four groups of patients were r and omized . Each group was composed by 12 patients with bilateral vitiligo ; in each group , every patient was irradiated with NB-UVB ( length : 311 nm ) twice a week for 9 months and applied tacrolimus ointment 0.1 % twice a day on the other area in the same period . Before starting therapy and after 3 , 6 and 9 months of therapy , a clinical and photographic evaluation of percentage of repigmentation was performed and Dermatology Life Quality Index Question naire was fulfilled . RESULTS A repigmentation at least partial occurred in 71 % of patients after 36 weeks of treatment with tacrolimus ointment 0.1 % ; in the whole sample , 14 patients ( 29 % ) showed no repigmentation at all , with 2 of them discontinuing the therapy because of side effects ( erythema and folliculitis-like manifestations ) . A homogeneous repigmentation at least partial occurred in 69 % of patients after 36 weeks of treatment with NB-UVB ; in the whole sample 15 patients ( 31 % ) showed no repigmentation at all , with 1 of them discontinuing the therapy because of side effects . CONCLUSION The present study confirmed that the efficacy of NB-UVB phototherapy in vitiligo is comparable to tacrolimus ointment 0.1 % therapy . On the basis of our study , we may suggest tacrolimus ointment 0.1 % as an alternative to NB-UVB therapy for treating vitiligo BACKGROUND / PURPOSE To study and compare the efficacy of combined 308-nm monochromatic excimer light ( MEL ) therapy with tacalcitol vs. that of MEL 308-nm therapy alone in treatment of vitiligo . METHODS Thirty-eight patients with vitiligo were enrolled in a single-blind , within patient controlled clinical trial . Symmetrical or nearby lesions were r and omly applied with either topical tacalcitol cream or vehicle . Each lesion was treated weekly with the 308-nm MEL , for a total of 12 sessions . Patients were examined at monthly intervals . The mean number of sessions and the cumulative dosage for initial repigmentation were calculated . RESULT Thirty-five patients were evaluated . Treatment with tacalcitol and MEL result ed in higher percentages for excellent repigmentation ( 25.7 % ) compared with vehicle and MEL ( 5.7 % ) ( P<0.05 ) . Percentages for total response were 71.4 % and 60 % , respectively ( P>0.05 ) . The mean+/-SEM cumulative dose and number of excimer light exposures for initial repigmentation were , respectively , 3.93+/-0.59 J/cm2 and 4.52+/-0.49 at the tacalcitol side , and , respectively , 4.99+/-0.68 J/cm2 and 5.3+/-0.52 at the vehicle side ( P<0.05 ) . CONCLUSION Our results have shown that concurrent topical tacalcitol potentiates the efficacy of the 308-nm MEL in the treatment of vitiligo , and that this combination achieves earlier pigmentation with a lower total dosage OBJECTIVE To compare the efficacy of combined tacrolimus and 308-nm excimer laser therapy vs 308-nm excimer laser monotherapy in treating vitiligo . DESIGN Comparative , prospect i ve , r and omized , intraindividual study . PATIENTS Fourteen patients , aged 12 to 63 years , with Fitzpatrick skin types II to IV . INTERVENTION For each patient , 4 to 10 target lesions were chosen . The treatment applied to each target lesion was r and omized by drawing lots . Each lesion was treated twice a week by the 308-nm excimer laser , for a total of 24 sessions . Initial fluences were 12 mcal/cm(2 ) ( 50 mJ/cm(2 ) ) less than the minimal erythemal dose in vitiliginous skin . Then , fluences were increased by 12 mcal/cm(2 ) every second session . Moreover , topical 0.1 % tacrolimus ointment was applied twice daily on target lesions receiving the combined tacrolimus and excimer laser treatment ( group A ) . Group B target lesions received only excimer laser monotherapy . For each treated lesion , the untreated lesion on the opposite side served as the control . Tolerance was evaluated by a visual analog scale , and secondary events were recorded at each session . MAIN OUTCOME MEASURE Treatment efficacy , which was blindly evaluated by 2 independent physicians by direct and polarized light photographs taken before and after treatment . RESULTS Forty-three lesions were treated ( 23 in group A and 20 in group B ) . All patients completed the study . Repigmentation was observed in all group A lesions ( 100 % ) and in 17 ( 85 % ) of the 20 group B lesions . Repigmentation was not observed in the untreated lesions ( control group ) . A repigmentation rate of 75 % or more was obtained in 16 ( 70 % ) of the 23 group A lesions and in 4 ( 20 % ) of the 20 group B lesions . In UV-sensitive areas ( the face , neck , trunk , and limbs , with the exception of bony prominences and extremities ) , 10 ( 77 % ) of 13 group A lesions had a repigmentation rate of 75 % or more vs 4 ( 57 % ) of 7 group B lesions . In classically UV-resistant areas , 6 ( 60 % ) of 10 group A lesions had a repigmentation rate of 75 % or more vs 0 of the 13 group B lesions . The mean number of sessions necessary for an improvement of repigmentation was 10 in group A and 12 in group B. Adverse effects have been limited , and tolerance was excellent . CONCLUSIONS The combination treatment of 0.1 % tacrolimus ointment plus the 308-nm excimer laser is superior to 308-nm excimer laser monotherapy for the treatment of UV-resistant vitiliginous lesions ( P<.002 ) . The efficacy and the good tolerance of the 308-nm excimer laser in monotherapy for treating localized vitiligo were also confirmed , but this treatment regimen should be proposed only for UV-sensitive areas Vitiligo is a common , idiopathic , acquired , depigmenting disease characterized by loss of normal melanin pigments in the skin . The most interesting treatment methods for extensive vitiligo involve psoralen plus ultraviolet A ( PUVA ) therapy and ultraviolet (UV)-B phototherapy , particularly narrow-b and UV-B. In this r and omized and comparative study , we investigated the safety and efficacy of narrow b and ultraviolet B as monotherapy and in combination with topical calcipotriol in the treatment of generalized vitiligo . Of the 40 vitiligo patients enrolled in the study , 15 were treated with the calcipotriol plus narrow-b and UV-B ( NBUVB ) and 25 with narrow b and UV-B alone . The patients were r and omized into two NBUVB treatment groups . The first group , consisting of 24 patients ( all male ) , received only NBUVB treatment ; the second group , consisting of 13 patients ( all male ) applied 0.05 % topical calcipotriol ointments twice daily . Both groups were irradiated with NBUVB ( 311 nm ) . In the NBUVB group , the percentage of the body surface affected was reduced from 27.21 + /- 10.41 % to 16.25 + /- 8.54 % after a mean of 30 treatment sessions . The mean repigmentation percentage was 41.6 + /- 19.4 % . In clinical evaluation ( moderate and marked/complete response was accepted as an effective treatment ) , 19 patients ( 19/24 ; 79.17 % ) had clinical ly good results . In the NBUVB plus calcipotriol group , the percentage of the body surface affected was reduced from 23.35 + /- 6.5 % to 13.23 + /- 7.05 % after a mean of 30 treatment sessions . The mean repigmentation percentage was 45.01 + /- 19.15 % . In clinical evaluation ( moderate and marked/complete response was accepted as an effective treatment ) , 10 patients ( 10/13 ; 76.92 % ) had clinical ly good results . Statistically significant intragroup reductions from the baseline percentage of the body surface affected were seen at the endpoint of treatment for the two treatment groups ( P < 0.001 ) . However , there was no statistically significant difference between the two treatment groups at the end of therapy with respect to the reduction of repigmentation rates ( P > 0.05 ) . The present study reconfirmed the efficacy of NBUVB phototherapy in vitiligo . It can be a therapeutic option considered in the management of patients with vitiligo . However , addition of topical calcipotriol to NBUVB did not show any advantage BACKGROUND The first choice treatment for vitiligo vulgaris is narrow-b and UVB ( NB-UVB ) , but no satisfactory treatment exists . OBJECTIVES To investigate if Polypodium leucotomos , an antioxidative and immunomodulatory plant extract , improves NB-UVB-induced repigmentation . METHODS Fifty patients with vitiligo vulgaris r and omly received 250 mg oral P. leucotomos or placebo three times daily , combined with NB-UVB twice weekly for 25 - 26 weeks . RESULTS Repigmentation was higher in the P. leucotomos group vs. placebo in the head and neck area ( 44 % vs. 27 % , P = 0.06 ) . Small repigmentation increases ( P = n.s . ) were observed for the trunk ( 6 % increased repigmentation ) , extremities ( 4 % ) , and h and s and feet ( 5 % ) in the P. leucotomos group vs. placebo . Patients attending more than 80 % of required NB-UVB sessions showed increased repigmentation in the head and neck area in the P. leucotomos group vs. placebo ( 50 % vs. 19 % , P < 0.002 ) ; no significant differences were seen in the other body areas . Patients with skin types 2 and 3 showed more repigmentation in the head and neck area in the P. leucotomos group vs. placebo ( 47 % vs. 21 % , P = 0.01 ) , and no significant differences were seen in the other body areas . No conclusions could be drawn on skin types 4 and 5 due to low patient numbers . CONCLUSION There is a clear trend towards an increase in repigmentation of vitiligo vulgaris affecting the head and neck area when NB-UVB phototherapy is combined with oral P. leucotomos . This effect may be more pronounced in light skin types BACKGROUND NB-UVB phototherapy is a very important modality in treating vitiligo but the treatment course usually exceeds 1 year . Skin ablation with mechanical dermabrasion with 5Fluorouracil ( 5FU ) was introduced to treat vitiligo in 1983 . This was modified replacing the mechanical dermabrasion by erbium-YAG ( ER : YAG ) laser ablation and result ed in better prognosis in periungual vitiligo . PURPOSE In the present study , we are exploring the effect of the use of ER : YAG laser skin ablation and application of 5FU on the outcome of short-term NB-UVB therapy for patients with non-segmental vitiligo ( NSV ) . METHODS This study included 50 adult patients with a total of 65-paired symmetrical NSV lesions in different body parts . One side was treated with ER : YAG laser ablation , followed by 5FU application before simultaneous NB-UVB therapy of both sides for a maximum period of 4 months . The outcome was then evaluated both qualitatively and quantitatively . RESULTS The overall response to therapy was better using the combination therapy . Fifty patients ( 78.1 % ) experienced a moderate-marked repigmentation response in the combination group compared with 23.4 % in the mono-therapy group . The response was significantly higher when using the combination therapy in different body parts ( P value is < 0.05 ) , except for feet lesions , which were better but not statistically significant ( P value=0.15 ) . Tolerable pain during ablation or at sites of 5FU application was reported in all cases . Transient hyperpigmentation occurred in 30 % of cases and 3.1 % of lesions healed by a transient slate blue color . Half of the treated periungual lesions showed a temporary tiny brownish spot on nail plates and Köebnerization was not detected in any patient . CONCLUSION We concluded that prior use of ER : YAG laser skin ablation , followed by 5FU application before NB-UVB phototherapy for vitiligo is a safe and tolerable technique that improves the outcome of short-term NB-UVB therapy and is expected to increase patient compliance BACKGROUND Vitiligo is a cosmetically disfiguring acquired depigmenting disorder caused by the loss of functional melanocytes from the epidermis . Various approaches that have been used for the treatment of vitiligo can be classified as medical and surgical therapies . Noncultured autologous melanocyte transplantation is a new and effective surgical treatment for stable vitiligo . OBJECTIVES To compare the repigmentation results in stable vitiligo of transplantation of autologous noncultured melanocytes suspended in normal saline with that of those suspended in the patient 's own serum . METHODS AND MATERIAL S Twenty‐five patients with 36 lesions of stable vitiligo were r and omized into two groups for noncultured melanocyte transplantation . Patients in Group A received melanocytes suspended in normal saline , and those in Group B received melanocytes suspended in their own serum . RESULTS Statistically significant difference in repigmentation results and reduction in Dermatology Life Quality Index ( DLQI ) score was observed between the two groups 16 weeks after surgery . Repigmentation results were excellent ( > 90 % ) and very good to excellent ( > 75 % ) in 44.4 % and 66.7 % of lesions , respectively , in Group A and 88.8 % and 94.4 % of lesions , respectively , in Group B. There was also a significant ( p=.002 ) decline in DLQI score in both groups , with the mean reduction being significantly greater in Group B than Group A ( p=.005 ) . CONCLUSION Results of noncultured melanocyte transplantation can be improved significantly more by suspending the melanocytes in the patients ' autologous serum than in normal saline . This could be an important innovation in the surgical management of patients with stable vitiligo . The authors have indicated no significant interest with commercial supporters BACKGROUND / PURPOSE Narrow-b and ultraviolet B ( NB-UVB ) is considered the most effective and safe initial treatment for moderate-to-severe vitiligo but phototoxicity and possible carcinogenicity are the reported side effects . Ultraviolet A1 ( UVA1 ) phototherapy has overlapping biological effects to NB-UVB and is relatively free of side effects associated with other phototherapy regimens . METHODS Forty patients with vitiligo were included in this prospect i ve , r and omized controlled comparative clinical trial . Twenty patients received NB-UVB and 20 received UVA1 three times weekly for 12 weeks . The UVA1 group was divided into two subgroups . Ten patients received moderate and 10 received low dose of UVA1 . Serum sample s were collected before and after 36 sessions to assess soluble interleukin 2 receptor level . Patients were clinical ly evaluated before therapy then monthly according to Vitiligo Area Scoring Index ( VASI ) and Vitiligo European Task Force ( VETF ) scores . In addition , extent of response was determined by a blinded dermatologist comparing before and after therapy photographs . Pattern of response and side effects were recorded . RESULTS NB-UVB was superior to UVA1 with a significant difference in blinded dermatological assessment ( P<0.001 ) , percentage change in VASI score ( P<0.001 ) and percentage change in VETF area score ( P=0.001 ) . No significant difference in side effects was observed between both groups . Comparing UVA1 subgroups , better response in moderate-dose group was found as regard to percentage change in VASI ( P<0.001 ) and percentage change in VETF area score ( P=0.001 ) , while no significant difference was found in blinded dermatological assessment ( P=0.121 ) . CONCLUSION NB-UVB phototherapy remains to be an effective and safe therapeutic option in vitiligo . Response to UVA1 in vitiligo seems to be dose dependent and seems to be of limited value in treatment of vitiligo as a monotherapy . Further studies combining it with other lines of therapy such as systemic steroids may prove beneficial Vitiligo is a progressive condition involving a loss of pigmentation in the skin ; it can be disfiguring and no effective treatment or cure exists . Although vitiligo 's medical effects have been studied extensively , little attention has been paid to its psychological impact or to the effects of psychological state on the illness itself . To address these issues , the present study examined the effect of cognitive behavioural therapy on coping with vitiligo and adaptation to the negative effects on body image , quality of life and self-esteem in adult patients . The study also examined whether any psychological gains acquired from psychological therapy would influence the progression of the condition itself . Two matched groups of vitiligo patients were compared , one of which received cognitive-behavioural therapy over a period of 8 weeks , while the other received no changes to their treatment status . All patients were assessed on self-esteem , body image and quality of life , prior to , immediately following and 5 months following the end of therapy . The progression of the condition was assessed by photographing patients prior to the start of counselling and 5 months following counselling . Results suggest that patients can benefit from cognitive behavioural therapy in terms of coping and living with vitiligo . There is also preliminary evidence to suggest that psychological therapy may have a positive effect on the progression of the condition itself . Implication s for incorporating psychological counselling into patient care and management are discussed BACKGROUND Punch grafting followed by PUVA is an established therapy for stable vitiligo , but punch grafting followed by topical corticosteroid has never been evaluated . OBJECTIVE The aim of this study was to evaluate the efficacy of topical corticosteroid in perigraft pigmentation and to compare it with perigraft pigmentation after PUVA in patients with stable vitiligo . METHODS Fifty patients with stable vitiligo of various clinical types were subjected to punch grafting . In a r and omized case study , these patients were divided into two groups : One group received post punch-grafting PUVA ( group I ) and the other group post punch-grafting topical application of fluocinolone acetonide 0.1 % ( group II ) . During the follow-up period of 6 months , six patients were lost to follow-up , and two patients were excluded from the study ; 42 patients were evaluated for pigment spread and side effects . RESULTS In group I , the average pigment spread was 6.38 mm , whereas in group II , it was 6.94 mm , showing a slightly higher pigment spread in group II , which was statistically not significant ( P = 0.301 ) . There was no difference in response to therapy in patients having segmental vitiligo as compared with nonsegmental vitiligo . Cobblestoning , depigmentation of the grafts , infection , and graft displacement were the important side effects seen in some patients in both the groups . CONCLUSION The study shows that the pigment spread with topical corticosteroid is comparable to that with PUVA . However , the studies with long-term follow-up are required to establish this . The advantages of topical corticosteroid are that its use is easy , less cumbersome , cheaper , and more cost effective than PUVA BACKGROUND / AIMS The combination of psoralens with different types of ultraviolet ( UVL ) sources in the treatment of vitiligo has led to different reports of success . The purpose of this trial is to compare in a r and om right-left comparison study the efficacy and side effects of oral 8-MOP plus UVA ( PUVA ) and oral 8-MOP plus UVB ( broadb and , 290 - 320 nm P-UVB ) in the treatment of vitiligo . METHODS The study included 24 cases of extensive vitiligo involving more than 30 % of the body surface area in a bilateral symmetrical distribution . Each patient received 0.7 mg/kg 8-MOP orally 2 h before the light session . The right side of the body was exposed to UVA ( 320 - 400 nm ) , while the left half was exposed to UVB ( 290 - 320 nm ) . The patients received 3 sessions/week for a total of 30 sessions . RESULTS Both PUVA and PUVB produced moderate ( 50 - 60 % ) improvement , with similar incidences of phototoxic reaction and skin thickening . However , the study revealed a significant difference in the number of sessions needed to improve produce erythema and perifollicular pigmentation as well as a moderate response , the response on the UVA side always being earlier . Furthermore , the amount of joules needed to achieve the same response was 10 times greater on the UVA side than on the UVB side . CONCLUSION The use of psoralen plus broadb and UVB is as effective as PUVA in the treatment of vitiligo . However , the long-term side effects of psoralen plus UVB are unknown BACKGROUND Low catalase levels and cellular vacuolation in the epidermis of patients with vitiligo support major oxidative stress in this compartment . There is now in vivo evidence for increased epidermal hydrogen peroxide ( H(2)O(2 ) ) accumulation in this patient group by utilizing noninvasive Fourier Transform Raman spectroscopy ( FT Raman ) . Epidermal H(2)O(2 ) can be removed with a topical application of narrow b and UVB activated pseudocatalase cream ( PC-KUS ) . ( Mn/EDTA-bicarbonate complex , patent No. EPO 58471 1 A ) , yielding initiation of repigmentation . Dead Sea climatotherapy is another successful treatment modality for vitiligo , but the mode of action has escaped definition so far . METHODS Epidermal hydrogen peroxide ( H(2)O(2 ) ) was assessed in vivo before and after 21 days treatment at the Dead Sea using noninvasive Fourier-Transform Raman spectroscopy . The effectiveness of repigmentation was followed in 59 patients with vitiligo by comparing Dead Sea climatotherapy alone with the combination of Dead Sea climatotherapy/pseudocatalase cream ( PC-KUS ) as well as Dead Sea climatotherapy/placebo cream . Clinical repigmentation was documented by st and ardized black/white photography using non-UV coated bulbs as flashlight and by color photography . RESULTS This study on 59 patients who had vitiligo for an average time of 17 years ( range 3 - 53 years ) confirmed in vivo H(2)O(2 ) accumulation in mM concentrations in the epidermis of untreated patients . Furthermore , we demonstrated a pseudocatalase activity after 15 min of Dead Sea bathing , but the decrease of epidermal H(2)O(2 ) levels was significantly less compared to narrowb and UVB activated pseudocatalase cream ( PC-KUS ) . Initiation of repigmentation was already observed between day 10 and day 16 after a combination of Dead Sea climatotherapy/pseudocatalase cream compared to conventional pseudocatalase monotherapy ( 8 - 14 weeks ) and Dead Sea climatotherapy alone ( 5 - 6 weeks ) . CONCLUSION The results of this study show a significantly faster initiation of repigmentation in vitiligo after a combination of short-term climatotherapy ( 21 days ) at the Dead Sea in combination with a pseudocatalase cream ( PC-KUS ) compared to either conventional climatotherapy at the Dead Sea alone or with placebo cream in combination with climatotherapy . This combined therapy is significantly faster in repigmentation than narrowb and UVB activated pseudocatalase cream ( PC-KUS ) treatment alone . The results of this study support the necessity of epidermal H2O2 removal as well as the influence of solar UV-light in the successful treatment of vitiligo BACKGROUND Only a few , small double-blind clinical trials have been reported for the treatment of vitiligo . Narrowb and -ultraviolet B ( NB-UVB ) is an established form of treatment for this condition . Tacrolimus ointment is assumed to have an effect in some patients . OBJECTIVES To assess the additive effect of tacrolimus ointment ( 0.1 % ) once daily in vitiligo patients treated with NB-UVB . METHODS In a r and omized double-blind trial , patients with stable symmetrical vitiligo were treated half-side with tacrolimus ointment ( 0.1 % ) and half-side with placebo ointment . Whole body NB-UVB was given twice or thrice weekly for at least 3 months . As a morphometric device , Visitrak(TM ) was used to measure the area of the vitiligo target lesions . RESULTS Of 40 patients , 27 had a better effect on the tacrolimus side . The degree of improvement was significantly better on the tacrolimus side ( P = 0.005 ) . The median reduction in the target lesion areas was 42.1 % on the tacrolimus side and 29 % on the placebo side . There was a correlation between the effect and the number of topical tacrolimus applications ( P = 0.044 ) , but there was no correlation with the number of UV treatments given ; neither any significance of gender , age , skin type , duration of disease , familial occurrence of vitiligo nor presence of other autoimmune disease or atopy was observed . We found a significant reduction in the patients ' subjective disease impact during the treatment period ( P < 0.001 ) . CONCLUSION According to this study , the combination of NB-UVB and tacrolimus ointment ( 0.1 % ) is more effective than UV treatment alone in patients with vitiligo . The effect is tacrolimus total dose-dependent BACKGROUND Mixed vitiligo ( MV ) , the association of segmental vitiligo ( SV ) and nonsegmental vitiligo , has been rarely reported . OBJECTIVE The aim of this study was to delineate the clinical spectrum of MV through a case series of patients with typical SV associated with patchy bilateral vitiligo . METHODS This was a cross-sectional evaluation in the setting of a prospect i ve observational study conducted in the vitiligo clinic of the department of dermatology in Bordeaux , France . RESULTS Nineteen patients with MV were identified . Four were male and 15 were female . Most patients had an onset of SV before the age of 18 years ( 18 of 19 ) . In all patients , SV preceded nonsegmental vitiligo with a delay ranging from 6 months to more than 24 months . LIMITATIONS This study was cross-sectional and based on a single-center experience . CONCLUSION MV is not yet part of a conventional classification . However , this entity may have been neglected until now and should be included in the classification of vitiligo in addition to SV and nonsegmental vitiligo . Moreover , MV may be essential to the underst and ing of the pathogenesis of vitiligo as a primary skin disorder BACKGROUND Segmental vitiligo is a small subset of vitiligo which responds very well to surgical therapy , but the role of medical treatment is not very well defined . AIM To compare the efficacy and safety of 0.1 % tacrolimus ointment versus 0.05 % fluticasone propionate cream in patients of segmental vitiligo . METHODS A r and omized control trial was conducted in a tertiary care hospital on 60 consecutive patients with segmental vitiligo . Patients with segmental vitiligo exclusively or along with focal vitiligo , untreated or had not taken any topical treatment in previous 1 month or systemic treatment in previous 2 months , from May 2005 to January 2007 , were block r and omized into two groups . Children < 5 years , pregnant and lactating women , and patients with known hypersensitivity to either drug and with associated multiple lesions of vitiligo were excluded . Group A ( n = 29 ) patients were treated with tacrolimus 0.1 % ointment twice daily and group B ( n = 31 ) patients were treated with 0.05 % of fluticasone cream once daily for 6 months . Response and side effects were recorded clinical ly and by photographic comparison . RESULTS Nineteen patients treated with tacrolimus and 21 patients treated with fluticasone completed the treatment with median repigmentation of 15 % and 5 % , respectively , at 6 months ( P = 0.38 ) . Transient side effects limited to the application site were observed . CONCLUSIONS Both tacrolimus and fluticasone propionate produce variable but overall unsatisfactory repigmentation in segmental vitiligo Objective To observe the clinical efficacy of Zengse Pill ( 퓶취 , ZSP ) on patients with vitiligo of qi-stagnancy and blood-stasis syndrome type ( V-QB ) , and to preliminarily explore its mechanism of action . Methods Sixty-five V-QB patients , with their diagnosis confirmed by clinical examination , were r and omized by digital table method into two groups , with 31 patients in the control group and 34 in the treatment group . Cobamamide ( 2 tablets ) was administered orally to all patients , and Psoralea tincture ( a self-formulated preparation ) was applied externally thrice a day . In addition , for patients in the treatment group , ZSP was given orally , at 5 pills per dose , 3 times every day . The therapeutic course for both groups was 3 months . Patients were re-examined every half-month , and changes in the skin lesions were observed and recorded . The levels of lymphocyte subsets , serum immune globulin , and complement C3 and C4 in patients were determined before and after the therapeutic course and compared with the corresponding indexes determined in 21 healthy subjects . Results The total effective rate in the treatment group was 82.4 % , which was markedly higher than that in the control group ( 54.8 % ) , showing a significant difference ( P<0.05 ) . After treatment , CD4 + percentage , CD4+/CD8 + ratio , and blood levels of C3 and C4 increased , while CD8 + percentage decreased in the treatment group ( P<0.05 or P<0.01 ) . All these indexes remained unchanged in the control group , and the respective comparisons between groups showed significant differences ( P<0.01 ) . Conclusion ZSP has a definite clinical effect on the treatment of V-QB but with no evident adverse reactions , and it can increase the CD4 + percentage , CD4+/CD8 + ratio , and the levels of serum C3 and C4 , thus regulating the immunity of the organism , which might be one of its mechanisms of action BACKGROUND Treatment of vitiligo is a challenge . Steroids are known to be effective but are associated with serious adverse effects . Many uncontrolled studies have shown calcipotriol to be a promising therapeutic modality in vitiligo . OBJECTIVE To conduct a r and omized trial to evaluate the effect of topical calcipotriol ointment ( 0.005 % ) and betamethasone dipropionate ( 0.05 % ) cream , given alone or in combination , in treatment of localized vitiligo . METHODS Forty-nine patients with vitiligo affecting 5 % of their skin were recruited . Patients were r and omized into three groups . Group I patients were treated with betamethasone dipropionate ( 0.05 % ) cream twice daily . Group II patients were treated with calcipotriol ointment ( 0.005 % ) twice daily , and group III with betamethasone dipropionate ( 0.05 % ) in the morning and calcipotriol ( 0.005 % ) in the evening . RESULTS Forty-five patients completed the study period of 3 months with 15 patients in each group . No patient achieved excellent ( > 75 % ) pigmentation . Marked ( 50 % to 75 % ) repigmentation was observed in 2 ( 13.3 % ) , 1 ( 6.7 % ) and 4 ( 26.7 % ) patients in groups I , II and III , respectively . Moderate ( 25 - 50 % ) repigmentation was observed in 7 ( 46.7 % ) , 5 ( 33.3 % ) and 7 ( 46.7 % ) patients in groups I , II and III , respectively . Patients with < 25 % pigmentation were termed as minimal pigmentation or no response . The mean time for initial pigmentation to appear was 9.04 + /- 2.0 weeks in group I , 10.18 + /- 1.6 weeks in group II and 5.17 + /- 2.4 weeks in group III ( P < 0.01 ) . The acquired pigmentation in the lesions was more stable in group III as compared with patients in groups II and I ( P < 0.01 ) . Side-effects in the form of atrophy and lesional burning sensations were more common in group I when compared with groups II and III ( P < 0.05 ) . CONCLUSION Combined therapy appeared to give a significantly faster onset of repigmentation along with better stability of the achieved pigmentation and with lesser number of side-effects Vitiligo is an acquired loss of pigmentation and its treatment remains very difficult up to date . Narrow b and ultraviolet B ( NB-UVB ) and topical immunomodulators are included among the most innovative approaches to vitiligo . We evaluated the efficacy and tolerability of NB-UVB , topical pimecrolimus and tacrolimus in the treatment of vitiligo . Adult patients with chronic and stable vitiligo refractory to conventional therapies were enrolled in an open parallel groups study . The patients were scheduled on the basis of a computer-generated r and omization into three groups : 13 patients received NB-UVB phototherapy 3 times a week , 15 patients were treated with pimecrolimus 1 % cream b.i.d . and 16 patients applied tacrolimus 0.1 % ointment b.i.d . All three treatment regimens were performed for 24 weeks . At baseline and every three weeks for the whole period of therapy the patients were examined through digital photographs and , at the end of the study , based on the percentage of repigmentation , treatment outcome was classified as " absent " ( 0 ) , " slight " ( < 25 % ) , mild ( 25 - 49 % ) , " moderate " ( 50 - 74 % ) , and " excellent " ( > 75 % ) . During the whole period of the study , possible side effects were recorded . The response to treatments varied according to the anatomical location of the lesions . No statistically significant differences in repigmentation for any anatomical site were recorded with the three treatments . The best results were obtained for lesions of the face with pimecrolimus cream and tacrolimus ointment and of the neck with NB-UVB . Statistically significant differences in repigmentation between photo-exposed and covered skin areas were recorded although the patients were asked to avoid direct UV exposition and to apply a very high protection sun screen on vitiligo lesions . All three treatments should be considered as a good option in the treatment of vitiligo . NB-UVB irradiation may represent the optimal choice in generalized vitiligo with topical immunomodulators in localized vitiligo BACKGROUND Several modalities of treatment have been tried in vitiligo with varied results ; however , Indian data on comparative studies of two or more therapies are limited . AIMS We compared different phototherapy methods with an oral steroid as an adjunct to determine the method with the best tolerability and efficacy . METHODS Eighty-six patients with progressive vitiligo were r and omly assigned to different study groups according to a continuous selection method over a period of one year . Group 1 was given OMP + PUVA , group 2 OMP + UVB ( NB ) , group 3 OMP + UVB ( BB ) and group 4 was given OMP alone . Each patient was followed up for six months and then released from treatment . Clinical evaluation was made at the end of three and six months . RESULTS In group 1 ( OMP + PUVA ) , marked improvement was seen in 18.51 % while moderate improvement was seen in 66.66 % of the patients . Marked improvement was seen in 37.03 % in group 2 ( OMP + NB-UVB ) while 44.44 % had moderate improvement . In group 3 ( OMP + BB UVB ) , 8.33 % showed marked improvement while moderate improvement was seen in 25 % of the patients . Marked and moderate improvement was seen in 5 and 10 % of group 4 ( OMP ) patients , respectively . CONCLUSIONS Our study compared four treatment modalities in vitiligo patients , out of which oral minipulse of steroids ( OMP ) only had an adjunct value and was not very effective by itself . Narrow b and UVB has a definite edge over broad b and UVB and should be preferred when both options are available . NB-UVB and PUVA showed comparable efficacy A LOW order autoimmune response result ing in inhibition of tyrosinase activity in the melanocyte has been suggested as a possible mechanism for the development of vitiligo . In fact antibodies specific against tyrosinase have been produced in experimental animals ( Lorincz , 1959 ) . If the autoimmune mechanism is operative , the use of steroids might be expected to be beneficial in the treatment of this disorder . The purpose of this communication is to report the results of the trial of the use of a combination of steroids and psoralens in the treatment of this disease Vitiligo is an acquired depigmenting disorder having disfiguring consequences . Many treatments have been attempted with varying reports of success . A parallel-group , assessor blinded , r and omized , controlled trial was design ed to compare the efficacy and adverse effects of narrowb and UVB ( NBUVB ) with oral psoralen UVA ( PUVA ) therapy in the treatment of vitiligo . Patients aged 13 - 70 years with vitiliginous lesions involving more than 5 % body surface area were eligible for the study . In total , 56 patients were r and omized in a 1:1 ratio to oral PUVA or NBUVB phototherapy groups . Patients were assessed for the percentage of repigmentation over the depigmented areas as the primary outcome measure at each visit during the first three months and then monthly within the next three months . The incidence of adverse effects was also noted during the study period as the secondary outcome measure . The median repigmentation achieved at the end of the six-month therapy course was 45 % in the NBUVB group and 40 % in the oral PUVA group . Focal vitiligo had the best response in both treatment groups . There were lesser adverse effects within the NBUVB ( 7.4 % ) than in the PUVA ( 57.2 % ) group . Two PUVA patients discontinued therapy due to severe dizziness . There was no significant difference in the mean degree of repigmentation ; however , NBUVB carried a greater response rate and might be superior to oral PUVA with better tolerance and color match with the surrounding normal skin , as well as fewer side effects in the treatment of vitiligo Both types of Ultraviolet ( UV ) , UVB ( 290 - 320 nm ) and UVA ( 320 - 400 nm ) , produce increased pigmentation or tanning . However , no evaluation of UVA alone in the treatment of vitiligo has been reported . Therefore , it was the purpose of this work to study the pigmentogenic effect of UVA ( 5 and 15 J/cm(2 ) ) in vitiligo . The study included 20 r and omly selected patients with vitiligo involving more than 30 % of the body surface area with a bilateral/symmetrical distribution . They were equally divided into two groups each of 10 patients . All patients received three weekly sessions of UVA , 15 J/cm(2 ) in group I and 5 J/cm(2 ) in group II , a total of 48 sessions over 16 weeks . Overall pigmentation of 60 % and above was recorded in 50 % and 10 % of patients in groups I and II , respectively . We conclude that broadb and UVA alone , without psoralens , and in appropriate doses may be of important therapeutic value in vitiligo OBJECTIVE To compare clinical efficacy difference between fire needle combined with narrow b and ultraviolet-B ( NB-UVB ) and NB-UVB therapy for vitiligo . METHODS Ninety-three cases of vitiligo were r and omly divided into an observation group ( n = 48 ) and a control group ( n = 45 ) . In the observation group , fire needle was applied to ashi points around the damaged skin and Zusanli ( ST 36 ) , meanwhile NB-UVB therapy irradiating the local area . The control group was treated by NB-UVB therapy . The clinical efficacy was evaluated after the treatment of 12 weeks . RESULTS The total effective rate was 79.2 % ( 38/48 ) in the observation group , which was superior to that 48.9 % ( 22/45 , P < 0.05 ) in the control group . CONCLUSION The fire needle combined with NB-UVB for vililigo achieves a more obvious efficacy than NB-UVB therapy Recently , topical immunomodulators have been successfully used in monotherapy or in combination with other therapeutic modalities in vitiligo . To determine whether combination pimecrolimus 1 % cream and microdermabrasion enhances response time and repigmentation rate in children with vitiligo . Sixty-five children diagnosed with vitiligo enrolled in this r and omized placebo-controlled study . Three vitiliginous patches were chosen in each patient . The first lesion was treated by pimecrolimus 1 % cream . On the second lesion after doing microdermabrasion on day 1 , pimecrolimus 1 % cream was applied . On the third lesion placebo was applied . The course of treatment was 10 days . Vitiliginous patches were measured at baseline , day 10 , and months 1 , 2 , and 3 . Sixty patients completed the 3-month study period . Clinical response ( pigmentation > 50 % ) was observed in 60.4 % of the patches treated by combined pimecrolimus plus microdermabrasion at the third month of follow-up , compared with 32.1 % and 1.7 % for pimecrolimus alone and placebo , respectively ( p = 0.000 ) . No significant side effect was observed . Microdermabrasion exerts an additive effect in enhancing the rate and degree of repigmentation by pimecrolimus . This new combined approach appears to be safe and effective in childhood vitiligo Background : Topical corticosteroids are used as first line of therapy for vitiligo , although side effects such as adrenal insufficiency are possible . Objectives : To establish the role of ACTH test before , during , and after treatment with high potency topical steroids ; to determine if adrenal insufficiency occurs secondary to the use of high potency topical steroids in patients with vitiligo and intact cutaneous barrier ; and also to determine response to treatment and side effects . Material s and Methods : Forty-four adults with non-segmental vitiligo affecting 20 % or less of the body surface area were included and r and omized to receive topical clobetasol propionate 0.05 % cream ( group 1 ) or placebo ( group 2 ) for 12 weeks , with a maximum dose of 50 g per week . The placebo group was crossed over after week 6 and started on clobetasol until completion of the study . Serum cortisol levels with the 1 μg ACTH test were determined at baseline and on weeks 6 and 12 . Results : No adrenal insufficiency was detected nor statistical significance was achieved when comparing cortisol levels between and within the groups at baseline and weeks 6 and 12 . Group 1 had a better response to therapy but with more side effects . Conclusions : Doses of 50 g or less per week of clobetasol during a period of 12 weeks are safe on adult vitiligo patients , although local side effects are possible . Repigmentation rates were incomplete with single steroid therapy , making combined therapy a better option BACKGROUND Although there are several treatment options available for patients with generalized vitiligo , their efficacy is still a matter of debate . Although shown to be effective , corticosteroids applied either systemically or topically carry the risk of significant side-effects in long-term therapy . We evaluated the effectiveness of intravenous methylprednisolone ( 8 mg/kg body weight ) administered on three consecutive days in patients with generalized vitiligo . MATERIAL S AND METHODS A total of 14 patients with progressive or static vitiligo were included in a prospect i ve , open , clinical study . RESULTS Eighty-five per cent of the patients presenting with progressive disease showed cessation of disease progression after the infusion therapy . Repigmentation was observed in 71 % of patients with progressive vitiligo . None of the six patients presenting with static disease showed any repigmentation in response to this form of treatment . The therapy was well tolerated in all but one patient who developed intermittent arterial hypertension during therapy . CONCLUSIONS High-dose glucocorticoid pulse therapy may represent a therapeutic option in patients with generalized progressive vitiligo , and should be further evaluated in a prospect i ve , r and omized , clinical trial BACKGROUND Vitiligo is a common pigmentary disorder with great cosmetic and psychological morbidity . No treatment available is a definitive cure . Systemic psoralen and ultraviolet A ( PUVA ) has been the mainstay of treatment . Narrow-b and ultraviolet B ( NB-UVB ) has been recently introduced . Although retrospective comparative study of systemic PUVA and NB-UVB has been published from our centre , no prospect i ve study has been reported to date . AIMS To investigate the position of NB-UVB vis-à-vis PUVA in terms of efficacy , time to repigment and adverse effects and to help decide if one therapy has an advantage over another in the treatment of vitiligo . SUBJECTS AND METHODS It was a r and omized , open , prospect i ve study of 50 patients divided equally in TMP PUVA and NB-UVB groups . The study period was from January 2004 to June 2005 . RESULTS The mean degree of repigmentation attained in the NB-UVB group was 52.24 % over a mean treatment period of 6.3 months , whereas in the PUVA group it was 44.7 % in a mean period of 5.6 months ( P=0.144 ) . After excluding the results of therapy-resistant sites , that is , h and s and feet , the mean degree of repigmentation in the NB-UVB group was 67.57 % , whereas in the PUVA group it was 54.2 % ( P=0.007 ) . CONCLUSIONS NB-UVB performed better in comparison to TMP PUVA in terms of mean total repigmentation when traditionally considered therapy-resistant sites were excluded BACKGROUND Surgical techniques have recently been introduced for patients with vitiligo . R and omized controlled trials have not been performed . AIM To compare the efficacy and side-effects of two surgical methods ( suction blister vs. thin split-thickness graft technique ) for the treatment of vitiligo . METHODS Three suction blisters , approximately 0.8 cm in diameter , made with a special tool attached to a vacuum extractor , which were converted to erosions by removal of the roofs of the bullae , and one round erosion of approximately the same diameter , made using a silver knife , were created . One roof of a blister and two cutaneous thin split-thickness grafts taken from the gluteal region were transferred onto recipient vitiliginous areas ; one was left alone . The results were evaluated by one non-blind and two blind observers bimonthly during the 3-month follow-up period . RESULTS Repigmentation rates were 25 - 65 % in the suction blister technique and 90 % in the thin split-thickness graft technique ( P < 0.001 ) . CONCLUSIONS The thin split-thickness graft technique is superior to the suction blister technique in treating vitiligo Narrowb and ultraviolet B phototherapy ( NB-UVB ) is the most widely and effective therapeutic option in vitiligo . Antioxidant supplementation has also been reported to be useful . The purpose of this study was to determine the efficacy of oral antioxidants with NB-UVB in the treatment of vitiligo . Twenty-four patients with stable vitiligo were recruited and divided r and omly into 2 groups . They were treated with NB-UVB plus oral vitamin E in group A and with NB-UVB only in group B. Improvement was recorded according to the extent of repigmentation in the existing lesions . Both plasma malondialdehyde ( MDA ; product of lipid peroxidation ) and reduced glutathione ( GSH ) were measured before and after treatment . Twenty patients completed the study . Marked to excellent repigmentation was noted in 72.7 % and 55.6 % of the patients in group A and group B , respectively . Of the patients , 70 % in group A and 85 % in group B experienced mild erythema . After treatment , there was a significant reduction in plasma MDA in group A than in group B , but the increase in plasma GSH was not significant . In conclusion , oral vitamin E may represent a valuable adjuvant therapy , preventing lipid peroxidation in the cellular membrane of melanocytes and increasing the effectiveness of NB-UVB BACKGROUND A few studies on the treatment of vitiligo with topical tacrolimus have been published and showed promising results . However , most of these trials were uncontrolled . OBJECTIVE This study aims to assess the response of vitiligo to once- or twice-daily treatment with 0.1 % tacrolimus in a controlled , r and omized , observer-blinded study . METHODS Seventeen patients with generalized vitiligo were enrolled in this study . In each patient , two lesions were selected and r and omized to treatment with either once- or twice-daily application of 0.1 % tacrolimus for a total period of 6 months . In 10 patients , a third patch was left untreated to serve as a control . RESULTS Fifteen patients with 40 target lesions completed the study . Twice-daily treatment induced excellent ( > 75 % ) repigmentation in two lesions , moderate ( > 25 - 50 % ) and poor ( 1 - 25 % ) repigmentation in four lesions each , and no response in five lesions . Once-daily treatment result ed in moderate repigmentation in two lesions and poor repigmentation in five lesions , whereas no effect was observed in the remaining eight lesions . One out of 10 control lesions developed moderate spontaneous repigmentation , the other nine remained unchanged . Besides the frequency of tacrolimus application , the treatment outcome was determined by the localization of the affected areas with the facial region showing the best response . CONCLUSIONS Tacrolimus ointment appears to be an effective treatment option for facial vitiligo . A guarded prognosis is advisable for vitiliginous lesions on other localizations . Treatment must be applied twice daily for optimum response BACKGROUND Replenishing melanocytes by autologous melanocytes selectively in vitiliginous macules is a novel and promising treatment . With expertise in culturing autologous melanocytes , it has now become possible to treat larger recipient areas with smaller skin sample s. To determine the relative efficacy of cultured versus non cultured melanocyte transfer in the management of stable vitiligo . METHODS The melanocytes were harvested as an autologous melanocyte rich cell suspension from a donor split thickness graft . Cultured or non cultured melanocytes were then transplanted to the recipient area that had been superficially dermabraded . 100 patches of vitiligo in patients reporting to this hospital were r and omly allocated into 2 groups to receive either of the interventions . RESULTS An excellent response was seen in 62.17 % cases with the autologous melanocyte rich cell suspension technique and in 52 % with the melanocyte culture technique . CONCLUSION Autologous melanocyte transplantation can be an effective form of surgical treatment in stable but recalcitrant lesions of vitiligo . Large areas of skin can be covered with a smaller donor skin using melanocyte culture technique ; however culture method is more time consuming , and a labour intensive process , requiring state of the art equipments with a sterile lab setup Forty-nine patients enrolled in a single-blinded , r and omized , comparing 308-nm excimer laser therapy together with topical 1 % pimecrolimus cream twice daily ( group A ) with excimer laser therapy twice per week ( group B ) . Of 48 patients evaluated after 30 weeks of treatment , 71 % of patients from group A achieved Grade 3 or 4 repigmentation compared with 50 % in group B. Significant difference was found between group A and B at the end of 30 weeks of treatment ( p = 0.001 ) OBJECTIVES To investigate the efficacy of epidermal noncultured cellular grafting in patients with vitiligo and the role of postinflammatory , spontaneous , or UV-induced pigmentation in obtaining repigmentation . DESIGN A prospect i ve , r and omized , double-blind , placebo-controlled study . SETTING Ambulatory patients in an institutional practice . Patients were followed up for 3 to 12 months . PATIENTS A total of 33 paired , symmetrically distributed leukodermic lesions , all resistant to therapy , were observed in 28 patients . Nineteen patients appeared to have a stable vitiligo ( group 1 ) , whereas there was doubt about the stability of the disease in 9 patients ( group 2 ) . INTERVENTION After laser ablation , a hyaluronic acid-enriched cellular graft was applied to 1 lesion while the paired lesion received placebo . Three weeks later all lesions were exposed to UV irradiation twice per week for approximately 2 months . MAIN OUTCOME MEASURES Primarily , the percentage of repigmentation was assessed after 3 , 6 , and 12 months using a digital image analysis system . The repigmentation pattern was also evaluated after 1 and 3 months . RESULTS A strongly significant difference between cellular grafts and placebo was observed after 3 , 6 , and 12 months ( P<.001 , P = .002 , and P = .002 , respectively ) . In group 1 , repigmentation of at least 70 % of the treated area was achieved in 55 % , 57 % , and 77 % of the actively treated lesions 3 , 6 , and 12 months after treatment , whereas in group 2 repigmentation of at least 70 % of the treated area was not observed at any time point . The repigmentation pattern was diffuse in 94 % of the responding patients . CONCLUSIONS After a strict preoperative selection for disease stability , transplantation result ed in repigmentation of at least 70 % of the treated area in most actively treated vitiligo lesions . Repigmentation was primarily caused by the transplanted melanocytes In order to evaluate the efficacy of L-phenylalanine ( L-Phe ) in combination with UVA therapy for vitiligo an open trial ( 149 patients , 18 months ) and a small double-blind trial ( 32 patients , 6 months ) were conducted . Oral L-Phe loading result ed in peak plasma levels of L-Phe after 30 - 60 min and a slight increase in the plasma tyrosine level . Response to L-Phe plus UVA irradiation was positive , and various grade s of repigmentation not exceeding 77 % in the open and 60 % in the blind trial were observed . An increased L-Phe dose result ed in increased L-Phe plasma levels but not in improved clinical results . The optimal L-Phe dose appears to be lower than 50 mg/kg/day . Although it is difficult to draw firm conclusions from the present investigation , we think that L-Phe may have a place in the treatment of vitiligo and its role merits further investigation Background : A large variety of therapeutic agents are being tried for the treatment of vitiligo , but psoralens continue to be mainstay of treatment although they are not uniformly effective . Recent advances in pathophysiology have established a perturbed calcium homeostasis in affected skin , and melanocytes were shown to express vitamin D3 receptors . Objective : The purpose of present study was to determine the efficacy of the combination of PUVAsol with topical calcipotriol in the treatment of vitiligo . Methods : Nineteen patients with essentially bilateral symmetrical lesions were enrolled in a r and omized , double-blind , right/left comparative study of 18 months duration . An oral dose of 0.6 mg/kg 8-methoxypsoralen was given 2 h before exposure to sunlight thrice weekly to all patients . The patients were advised to apply calcipotriol ( 50 μg/g ) on one side of the body and placebo ointment over the lesions on the other side twice daily . Results : At the end of 6 months , 12 patients ( 70 % ) showed marked to complete improvement on calcipotriol-treated sides as compared to 6 patients ( 35 % ) showing similar improvement on placebo-treated sides ( p < 0.05 ) . At the end of treatment , 13 patients ( 76 % ) showed marked improvement in calcipotriol-treated lesions whereas 9 patients ( 53 % ) showed moderate to marked improvement in placebo-treated lesions . The repigmentation of h and s and feet was much better with the combination of PUVAsol and calcipotriol . Conclusion : The combination of PUVA and calcipotriol is highly effective and works faster and may be used for shortening the therapy with PUVA in the treatment of vitiligo BACKGROUND Vitiligo is an acquired pigmentary disorder that affects between 1 % and 2 % of the general population . Phototherapy remains the cornerstone of treatment , with NB-UVB being the most frequently used . BB-UVA can be a plausible alternative for darker population ; skin photo type III and IV . PATIENTS AND METHODS The study was a prospect i ve , r and omized , controlled , and single-blinded clinical trial , conducted on 40 patients with bilateral symmetrical vitiligo . The patients were r and omly divided into two equal groups ; group ( A ) received a fixed dose of 15 J/cm(2 ) BB-UVA , while group ( B ) received NB-UVB . The study was conducted for a period of 16 weeks ( 48 sessions ) . RESULTS The final percentage of clinical improvement was significantly higher ( P = 0.047 ) within the BB-UVA group ( 63.82 % ± 27.42 ) , than within the NB-UVB group ( 44.32 % ± 29.78 ) . CONCLUSION BB-UVA can be considered as an alternative treatment line for vitiligo Objective : The purpose of this study is to compare the efficacy of three therapies in the treatment of non-segmental vitiligo : a combination of topical calcipotriol , narrowb and -ultraviolet B ( NB-UVB ) , and betamethasone therapies ; a combination of NB-UVB and topical calcipotriol ; and NB-UVB alone . Material and methods : Forty-five patients with non-segmental vitiligo presenting to our Dermatology clinic were recruited to participate in the study . Patients were r and omly divided into three groups . For each patient the size of the depigmented areas was assessed according to the rule of nines . The first group was treated with a combination of topical calcipotriol , NB-UVB , and betamethasone therapies . The second group was treated with a combination of NB-UVB and topical calcipotriol and third group was treated with NB-UVB alone . Since the patients ' vitiligo lesions had similar phototypes , all patients were started with 0.1 j/cm2 , regardless of their skin phototype . The dose of NB-UVB was increased 10 % in each session and no further increment was done after reaching 2.5 j/cm2 . Treatment effectiveness was evaluated according to the percentage improvement in repigmentation . The quality of life of the patients was measured by the Dermatology Life Quality Index ( DLQI ) . Results : The patients were aged from 13 to 55 years ( mean : 25.29 ) . The duration of disease ranged from 3 months to 20 years . Family history was positive for vitiligo in 10 patients ( 22.2 % ) . The percentage of recovery after treatment was 63.33 % ± 7.55 in group 1 , 60.67 % ± 5.75 in group 2 , and 46.67 % ± 7.98 in group 3 . There was no statistically significant difference between groups 1 and 2 , and groups 2 and 3 , but there was a statistically significant difference between groups 1 and 3 ( p = 0.0048 ) . Conclusions : In conclusion , NB-UVB-alone therapy and the combined therapies are effective treatment options in the treatment of vitiligo . Future studies with larger groups are warranted to confirm our results |
10,747 | 29,963,275 | Typical antipsychotic agents were associated with severer side-effects than alpha-2 adrenergic agonist agents .
In summary , alpha-2 adrenergic agonist agents were associated with the optimal weigh between efficacy and safety . | The efficacy of all pharmacotherapies for patients suffering from tics were unclear . | Background The treatment of children with attention deficit hyperactivity disorder ( ADHD ) and Tourette syndrome ( TS ) has been problematic because methylpheni date (MPH)—the most commonly used drug to treat ADHD — has been reported to worsen tics and because clonidine (CLON)—the most commonly prescribed alternative — has unproven efficacy . Methods The authors conducted a multicenter , r and omized , double-blind clinical trial in which 136 children with ADHD and a chronic tic disorder were r and omly administered CLON alone , MPH alone , combined CLON + MPH , or placebo ( 2 × 2 factorial design ) . Each subject participated for 16 weeks ( weeks 1–4 CLON/placebo dose titration , weeks 5–8 added MPH/placebo dose titration , weeks 9–16 maintenance therapy ) . Results Thirty-seven children were administered MPH alone , 34 were administered CLON alone , 33 were administered CLON + MPH , and 32 were administered placebo . For our primary outcome measure of ADHD ( Conners Abbreviated Symptom Question naire – Teacher ) , significant improvement occurred for subjects assigned to CLON ( p < 0.002 ) and those assigned to MPH ( p < 0.003 ) . Compared with placebo , the greatest benefit occurred with combined CLON + MPH ( p < 0.0001 ) . CLON appeared to be most helpful for impulsivity and hyperactivity ; MPH appeared to be most helpful for inattention . The proportion of individual subjects reporting a worsening of tics as an adverse effect was no higher in those treated with MPH ( 20 % ) than those being administered CLON alone ( 26 % ) or placebo ( 22 % ) . Compared with placebo , measured tic severity lessened in all active treatment groups in the following order : CLON + MPH , CLON alone , MPH alone . Sedation was common with CLON treatment ( 28 % reported moderate or severe sedation ) , but otherwise the drugs were tolerated well , including absence of any evident cardiac toxicity . Conclusions Methylpheni date and clonidine ( particularly in combination ) are effective for ADHD in children with comorbid tics . Prior recommendations to avoid methylpheni date in these children because of concerns of worsening tics are unsupported by this trial Objective : To test the hypothesis that atomoxetine does not significantly worsen tic severity relative to placebo in children and adolescents with attention deficit/hyperactivity disorder ( ADHD ) and comorbid tic disorders . Methods : Study subjects were 7 to 17 years old , met Diagnostic and Statistical Manual of Mental Disorders – IV criteria for ADHD , and had concurrent Tourette syndrome or chronic motor tic disorder . Patients were r and omly assigned to double-blind treatment with placebo ( n = 72 ) or atomoxetine ( 0.5 to 1.5 mg/kg/day , n = 76 ) for up to 18 weeks . Results : Atomoxetine treatment was associated with greater reduction of tic severity at endpoint relative to placebo , approaching significance on the Yale Global Tic Severity Scale total score ( –5.5 ± 6.9 vs –3.0 ± 8.7 , p = 0.063 ) and Tic Symptom Self-Report total score ( –4.7 ± 6.5 vs –2.9 ± 5.2 , p = 0.095 ) and achieving significance on the Clinical Global Impressions ( CGI ) tic/neurologic severity scale score ( –0.7 ± 1.2 vs –0.1 ± 1.0 , p = 0.002 ) . Atomoxetine patients also showed greater improvement on the ADHD Rating Scale total score ( –10.9 ± 10.9 vs –4.9 ± 10.3 , p < 0.001 ) and CGI severity of ADHD/psychiatric symptoms scale score ( –0.8 ± 1.1 vs –0.3 ± 1.0 , p = 0.015 ) . Discontinuation rates were not significantly different between treatment groups . Atomoxetine patients had greater increases in heart rate and decreases of body weight , and rates of treatment-emergent decreased appetite and nausea were higher . No other clinical ly relevant treatment differences were seen in any other vital sign , adverse event , or electrocardiographic or laboratory measures . Conclusions : Atomoxetine did not exacerbate tic symptoms . Rather , there was some evidence of reduction in tic severity with a significant reduction of attention deficit/hyperactivity disorder symptoms . Atomoxetine treatment appeared safe and well tolerated BACKGROUND Current pharmacological treatments for Tourette Syndrome ( TS ) , such as antipsychotic agents and α-2 agonists , are moderately effective in the treatment of tics , but have substantial side effects that limit their use . N-acetylcysteine ( NAC ) modulates glutamatergic systems , and has been used safely as an antioxidant agent with minimal side effects for decades . NAC has been increasingly studied for the treatment of other obsessive-compulsive spectrum disorders . We aim to examine the efficacy of NAC for the treatment of pediatric TS in a double-blind , placebo-controlled , add-on study . METHODS Thirty-one children and adolescents 8 - 17 years of age with TS were r and omly assigned to receive NAC or matching placebo for 12 weeks . Our primary outcome was change in severity of tics as measured by the Yale Global Tic Severity Scale ( YGTSS ) , Total tic score . Secondary measures assessed comorbid obsessive-compulsive disorder ( OCD ) , depression , anxiety , and attention-deficit/hyperactivity disorder ( ADHD ) . Linear mixed models in SAS were used to examine differences between NAC and placebo . RESULTS Of 31 r and omized subjects , 14 were assigned to placebo ( two females ; 11.5 + 2.8 years ) and 17 to active NAC ( five females ; 12.4 + 1.4 years ) treatment . No significant difference between NAC and placebo was found in reducing tic severity or any secondary outcomes . CONCLUSIONS We found no evidence for efficacy of NAC in treating tic symptoms . Our findings st and in contrast to studies suggesting benefits of NAC in the treatment of other obsessive-compulsive spectrum disorders in adults , including OCD and trichotillomania , but are similar to a recent placebo-controlled trial of pediatric trichotillomania that found no benefit of NAC Talipexole is a new dopamine autoagonist with putative preferential activity on presynaptic dopamine receptors . In a double-blind , placebo-controlled study , we tested the drug 's safety and efficacy in 13 adult men with Gilles de la Tourette 's syndrome . The drug was poorly tolerated because of clinical ly significant sedation and dizziness . Tics did not improve at tolerable doses . These findings suggest that talipexole has no role in the regular management of tic disorders BACKGROUND Tic disorders , in particular chronic tic disorder and Tourette syndrome , affect about 1 % of the population . The current treatment of choice is pharmacological or behavioural , addressing tics or the premonitory urges preceding tic onset . AIMS The current study reports an open trial evaluating the effectiveness of a cognitive psychophysiological treatment addressing Tourette-specific sensorimotor activation processes rather than the tic . METHOD Forty-nine people with Tourette syndrome and 36 people with chronic tics completed 10 weeks of individual cognitive psychophysiological therapy . Outcome measures included two tic severity scales and psychosocial measures . RESULTS Post-treatment both groups had significantly improved on the tic scales with strong effect sizes across tic locations and complex and simple tics , maintained at 6-month follow-up with further change in perfectionism and self-esteem . CONCLUSIONS The cognitive psychophysiological approach targeting underlying sensorimotor processes rather than tics in Tourette 's and chronic tic disorder reduced symptoms with a large effect size BACKGROUND Dopamine agonists could theoretically normalize the suspected central dopamine hypersensitivity in Tourette 's syndrome . METHODS There was a multicenter r and omized , placebo-controlled , double-blind clinical trial of pramipexole given for 6 weeks in 63 children and adolescents with Tourette 's syndrome . RESULTS There were no significant differences in the adjusted mean change in the Total Tic Score of the Yale Global Tic Severity Scale for patients treated with pramipexole ( -7.16 ) and placebo ( -7.17 ) . There were no significant treatment effects on change from baseline in the Global Severity score of the Yale Scale and parent- and investigator-scored Clinical Global Impression of Improvement . In patients with attention deficit hyperactivity disorder , there was improvement in DuPaul ADHD scale scores for patients receiving pramipexole compared with placebo . CONCLUSIONS There was no evidence that pramipexole has efficacy in suppressing tics . Pramipexole may decrease symptoms of associated attention deficit hyperactivity disorder Clonidine has been suggested to be effective in Gilles de la Tourette 's syndrome ( GTS ) , but no double‐blind study has ever evaluated its effects using objective measures . Thirty patients with GTS completed a 6‐month placebo‐controlled crossover study of the effectiveness of clonidine . Videotapes were obtained at each 3‐week visit and were evaluated r and omly at the end of the study for distribution , frequency , and severity of motor and vocal tics . Quantifiable psychometric examinations were performed as well . The use of clonidine did not significantly ( p < 0.05 ) reduce motor tics , vocalizations , or behavior . The effect of a low dose ( 0.0075 mg/kg/day ) was no different from that of a high dose ( 0.015 mg/kg/day ) ; children 's responses were no different from adults ' ; and those also receiving neuroleptic agents showed the same lack of efficacy as seen in patients on no other medication . Dosing schedule did not affect the objective ratings ; scores from clonidine given twice a day were equivalent to those for three times a day There are some uncontrolled studies about the efficacy and safety of both aripiprazole and risperidone for treating tic disorder . Moreover , the efficacy of these medications has never been compared . This is the first double blind r and omized clinical trial comparing the safety and efficacy of aripiprazole and risperidone for treating patients with tic disorder . Sixty children and adolescents with tic disorder were r and omly allocated into one of the two groups to receive either aripiprazole or risperidone for 2 months . The primary outcome measure was the score of Yale Global Tic Severity Scale . In addition , health related quality of life and adverse events were assessed . Both aripiprazole and risperidone decreased the Yale Global Tic Severity Scale score during this trial . Moreover , both medications increased the health related quality of life score . Both aripiprazole and risperidone were tolerated well . Aripiprazole [ 3.22 ( 1.9 ) mg/day ] decreased tic score as much as risperidone [ 0.6 ( 0.2 ) mg/day ] . Their adverse effects and their effects on health related quality of life were comparable . However , risperidone increased the patients ’ social functioning more than aripiprazole in short term This clinical guideline provides recommendations for the behavioural and psychosocial interventions ( BPI ) of children and adolescents with tic disorders prepared by a working group of the European Society for the Study of Tourette Syndrome ( ESSTS ) . A systematic literature search was conducted to obtain an up date on the efficacy of BPI for tics . Relevant studies were identified using computerised search es of the Medline and PsycINFO data bases and the Cochrane Library for the years 1950–2010 . The search identified no meta-analyses , yet twelve ( systematic ) review s and eight r and omised controlled trials provided evidence for the current review . Most evidence was found for habit reversal training ( HRT ) and the available but smaller evidence also supports the efficacy of exposure with response prevention ( ERP ) . Both interventions are considered first line behavioural treatments for tics for both children and adults and should be offered to a patient , taking into account his preference . Treatments that are considered second line or add-on behavioural treatments are contingency management , function based interventions and relaxation training . Neurofeedback is still experimental . Almost no research was identified that examined the efficacy of psychosocial interventions , e.g. , psychoeducation and group work . Based on clinical practice , this guideline recommends behavioural treatment as first line offer to patients in most cases . It should be embedded within a psychoeducational and supportive context and can be combined with drug treatment Objective : To evaluate the efficacy and safety of risperidone in children and adults with Tourette syndrome . Methods : This was an 8-week , r and omized , double-blind , placebo-controlled trial . The primary outcome measure was the Total Tic score of the Yale Global Tic Severity Scale ( YGTSS ) . Results : Thirty-four medication-free subjects ( 26 children and 8 adults ) ranging in age from 6 to 62 years ( mean = 19.7 ± 17.0 years ) participated . YGTSS Total Tic scores were similar at baseline ( 26.0 ± 5.1 for risperidone vs 27.4 ± 8.5 for placebo ) . After 8 weeks of treatment ( mean daily dose of 2.5 ± 0.85 ) , the 16 subjects on risperidone showed a 32 % reduction in tic severity from baseline , compared to a 7 % reduction for placebo patients ( n = 18 ) ( F[2,64 ] = 6.07 ; p = 0.004 ) . The 12 children r and omized to risperidone showed a 36 % reduction in tic symptoms compared to an 11 % decrease in the 14 children on placebo ( F[2,48 ] = 6.38 ; p = 0.004 ) . Two children on risperidone showed acute social phobia , which resolved with dose reduction in one subject but result ed in medication discontinuation in the other . A mean increase in body weight of 2.8 kg was observed in the risperidone group compared to no change in placebo ( F[2,64 ] = 10.68 ; p = 0.0001 ) . No extrapyramidal symptoms and no clinical ly significant alterations in cardiac conduction times or laboratory measures were observed . Conclusion : Risperidone appears to be safe and effective for short-term treatment of tics in children or adults with Tourette syndrome . Longer-term studies are needed to evaluate the durability of efficacy and safety over time We conducted a double-blind placebo-controlled crossover study to assess the efficacy of deprenyl for attention deficit hyperactivity disorder ( ADHD ) in children and adolescents with comorbid Tourette 's syndrome ( TS ) . Twenty-four subjects ( 21 boys , 3 girls ; mean age 12 years ) were enrolled at two sites ( University of Rochester and Baylor College of Medicine ) . The design included two 8-week treatment periods separated by a 6-week washout period . The primary outcome measures for ADHD and tic severity were total scores on the DuPaul Attention Deficit Hyperactivity Scale ( DADHS ) and the Yale Global Tic Severity Scale ( YGTSS ) . Fifteen subjects completed the study . The primary analysis revealed no statistically significant beneficial effect of deprenyl on the DADHS ( mean improvement 1.3 ; 95 % CI , minus 2.7 to 5.3 ; p equals 0.50 ) . Further post-hoc analyses revealed , however , that the effect of deprenyl in the first period was substantial ( p equals 0.02 ) . There was a marginally statistically significant beneficial effect of deprenyl on the YGTSS total score ( p equals 0.06 ) . Deprenyl may improve both ADHD and tics in children with TS and warrants further study . NEUROLOGY 1996;46 : 965 - 968 To investigate the effect of drugs acting on the endogenous opioid system , we studied 10 adults with Tourette 's syndrome who received propoxyphene hydrochloride ( 260 mg/day ) , naltrexone hydrochloride ( 50 mg/day ) , and placebo in a double‐blinded , r and omized clinical trial . Using a self‐report scale ( Tourette 's Syndrome Symptom List ) , subjects noted a significant ( p < 0.04 ) lessening of tics after treatment with naltrexone when compared with placebo . An improvement in performance on the Trail Making B test , a measure of attention and visuomotor sequencing and planning , occurred after receiving naltrexone when compared with placebo ( p < 0.08 ) or propoxyphene ( p < 0.02 ) . The Trail Making B test best discriminated the treatments ( p < 0.02 , analysis of variance ) . No other treatment effects were observed for several other measures of tic severity , attentional ability , or obsessive‐compulsive symptoms . Our findings indicate that pharmacological manipulation of the endogenous opioid system does influence symptoms of Tourette 's syndrome A double-blind , placebo-controlled trial was performed to determine the efficacy and tolerability of 8 weeks of treatment with risperidone in the management of 48 adolescent and adult patients with Tourette syndrome . Twenty-four patients were r and omly assigned to treatment with risperidone in doses of 0.5 to 6.0 mg/day , and 24 were assigned to placebo . The dosage of medication was increased in fixed increments during the first week of double-blind treatment and thereafter in a flexible dose regimen according to clinical response . Risperidone , at a median dose of 2.5 mg/day ( range , 1 to 6 mg/day ) , was found to be significantly ( p < 0.05 ) superior to placebo on the Global Severity Rating of the Tourette Syndrome Severity Scale . The proportion of patients who improved by at least one point on this seven-point scale was 60.8 % in the risperidone group and 26.1 % in the placebo group . Treatment with risperidone was accompanied by an improvement in global functioning in patients with average to above-average impairment at baseline as measured by the Global Assessment of Functioning scale . With respect to extrapyramidal symptom scores measured on the Extrapyramidal Symptom Rating Scale , hypokinesia and tremor increased in the risperidone group , but the effect on tremor was largely confined to subjects with higher baseline tremor scores . There were no significant differences in dystonic reactions , dyskinetic movements , subjective parkinsonism , or akathisia . Risperidone did not increase obsessive-compulsive symptoms . Fatigue and somnolence were the most common adverse events associated with risperidone Objective : To investigate the effectiveness of baclofen for the treatment of tics in children with Tourette syndrome ( TS ) . Background : Baclofen , which contains both γ-aminobutyric acid ( GABA ) and phenylethylamine moieties , was suggested in an open-label protocol to be an effective treatment for TS . This is a double-blind , placebo-controlled study to investigate this medication in children with TS . Methods : Subjects received , in a r and omized sequence , 4-week medication cycles of baclofen ( 20 mg three times daily ) and placebo with a 2-week intervening washout period between the cycles . Outcome measures included the Clinical Global Impression ( CGI ) scale , and the Yale Global Tic Severity Scale ( YGTSS ) , the latter including subscales for total tics and overall impairment . Measures were assessed at baseline and on days 28 , 42 , and 70 of the study . Results : Ten children ( seven boys and three girls , aged 8 to 14 ) with TS participated . Nine subjects completed the protocol ; one dropped out for psychosocial reasons . No major side effects were reported . The mean change in CGI score ( −0.9 ) after 4 weeks of baclofen treatment as compared with placebo treatment showed a significant improvement ( 95 % CI , −1.7 to −0.1 ; p = 0.04 ) . All subjects showed some amelioration in total YGTSS score during baclofen treatment . The mean change in total YGTSS score ( −14.7 ) approached significance ( 95 % CI , −30.3 to 0.9 ; p = 0.06 ) . Examination of differences between baclofen and placebo treatment groups expressed as a percent change from baseline showed that baclofen had a statistically significant effect on both outcome measures . Subscales of the YGTSS showed that the reduction in total tic scores was primarily due to a reduction in the impairment score rather than a decrease in tics . Conclusions : Children with TS may benefit from treatment with baclofen , although improvements may be related to factors other than tics . Larger studies directly comparing baclofen against other tic-suppressing agents are recommended The objective of this study was to investigate the effectiveness of levetiracetam for the treatment of tics in children with Tourette syndrome ( TS ) . Levetiracetam , an atypical anticonvulsant , has been suggested in open-label protocol s to be an effective tic-suppressing agent in individuals with TS . A double blind , r and omized , placebo-controlled , cross-over trial was performed to investigate this medication in children with moderate to moderately-severe tics . Subjects received , in a r and omized sequence , 4-weeks of levetiracetam ( maximum dose 30 mg/kg/day ) or placebo , with a 2-week intervening washout period between cycles . Primary outcome measures included two separate scales from the Yale Global Tic Severity Scale ; the Total Tic score and the Total overall score . Measures were assessed at baseline , prior to r and omization , on Day 28 ( end of Phase 1 ) , on Day 42 ( baseline for second phase ) and on Day 70 ( end of Phase 2 ) . Twenty-two subjects ( 21 boys and 1 girl ) with TS , mean age 12.2 + /- 2.3 years , range 8 to 16 years , participated . A mild reduction in tics occurred during both the levetiracetam and placebo treatment phases . There was no significant difference between treatments and no evidence of sequence or cross-over effects . In conclusion , Levetiracetam is not more beneficial than placebo in suppressing tics in children with TS ETHNOPHARMACOLOGICAL RELEVANCE Ningdong granula ( NDG ) is a traditional Chinese medicine ( TCM ) preparation for the treatment of Tourette 's syndrome ( TS ) . AIM OF THE STUDY To explore the effects of NDG on stereotyped behavior , homovanillic acid ( HVA ) in sera , dopamine ( DA ) and dopamine D2 receptor ( DRD2 ) in striatum in TS rats . MATERIAL S AND METHODS Sixty-four rats were r and omly divided into control group and three experimental groups . TS rat models were induced by intraperitoneal injection ( i.p . ) of Apomorphine ( Apo , 2 mg/kg ) in the experimental groups . After Apo i.p . , rats were intragastrically injected ( i.g . ) with NDG at 370 mg/kg ( NDG+Apo group ) , haloperidol ( Hal ) at 1.0 mg/kg ( Hal+Apo group ) , and normal saline ( 0.9 % ) at 10 ml/kg ( control group and Apo group ) , respectively , once a day for 12 weeks . The behaviors of the rats were observed and recorded each day . After 12 weeks , all rats were sacrificed and sera and striatum were collected . The levels of HVA in sera , DA in striatum were examined by ELISA , and the expression of DRD2 mRNA in striatum was measured by RT-PCR . RESULTS NDG could increase the HVA content in sera ( P<0.05 ) , meanwhile downregulate the expression of DRD2 mRNA in striatum ( P<0.05 ) , and inhibit the stereotyped behaviors induced by Apo ( P<0.01 ) in TS rats , the same effects with Hal . NDG could also reduce the DA content in striatum ( P<0.01 ) , while Hal could not . CONCLUSIONS NDG could effectively inhibit the stereotyped behaviors in TS rats , and the mechanisms may be related to the suppression of DA system by increasing the content of HVA in sera , decrease the content of DA and repressing the expression of DRD2 mRNA in striatum OBJECTIVE To determine the effects of methylpheni date ( MPH ) and dextroamphetamine ( DEX ) on tic severity in boys with attention-deficit/hyperactivity disorder ( ADHD ) comorbid with Tourette 's syndrome . METHOD A 9-week , placebo-controlled , double-blind crossover using a wide range of doses was completed by 20 subjects in three cohorts . RESULTS Relatively high doses of MPH and DEX in the first cohort produced significant increases in tic severity which were sustained on higher doses of DEX but which attenuated on MPH . Overall , 14 of 20 subjects continued stimulant treatment for 1 to 3 years , generally in combination with other psychotropics . Stimulant-associated adverse effects , including tic exacerbations , were reversible in all cases . CONCLUSION A substantial minority of comorbid subjects had consistent worsening of tics on stimulants , although the majority experienced improvement in ADHD symptoms with acceptable effects on tics . MPH was better tolerated than DEX Objective : To determine whether pergolide , a mixed D1/D2/D3 dopamine agonist , is efficacious and safe in the treatment of children with chronic tic disorders and Tourette syndrome . Background : Neuroleptics , which block dopamine transmission , are currently used to treat children with severe tics , but major side effects and limited efficacy reduce clinical utility . Prior open-label and crossover studies of pergolide suggest potential benefit . Methods : The authors enrolled 57 children and adolescents , ages 7 to 17 years , r and omizing them in a 2:1 ratio to either pergolide ( 0.15 to 0.45 mg per day ) or placebo . Tic symptoms had to be > 30 on the Yale Global Tic Severity Scale ( YGTSS ) . The primary outcome measure was change in tic severity assessed by YGTSS . Results : Compared to placebo treatment , pergolide treatment was associated with lower tic severity scores ( treatment effect 8.8 , pergolide vs placebo ; 95 % CI 0.1 to 17.6 ; p = 0.05 ) and attention-deficit hyperactivity disorder symptoms scores ( treatment effect 3.8 ; 95 % CI 0.7 to 6.8 ; p = 0.02 ) . No patient had a serious adverse event and pergolide was well tolerated . Conclusions : In this r and omized , placebo-controlled trial , pergolide appeared to be an efficacious and safe medication for tic reduction in children , and may also improve attention-deficit hyperactivity disorder symptoms CONTEXT Tourette disorder is a chronic and typically impairing childhood-onset neurologic condition . Antipsychotic medications , the first-line treatments for moderate to severe tics , are often associated with adverse effects . Behavioral interventions , although promising , have not been evaluated in large-scale controlled trials . OBJECTIVE To determine the efficacy of a comprehensive behavioral intervention for reducing tic severity in children and adolescents . DESIGN , SETTING , AND PARTICIPANTS R and omized , observer-blind , controlled trial of 126 children recruited from December 2004 through May 2007 and aged 9 through 17 years , with impairing Tourette or chronic tic disorder as a primary diagnosis , r and omly assigned to 8 sessions during 10 weeks of behavior therapy ( n = 61 ) or a control treatment consisting of supportive therapy and education ( n = 65 ) . Responders received 3 monthly booster treatment sessions and were reassessed at 3 and 6 months following treatment . INTERVENTION Comprehensive behavioral intervention . MAIN OUTCOME MEASURES Yale Global Tic Severity Scale ( range 0 - 50 , score > 15 indicating clinical ly significant tics ) and Clinical Global Impressions-Improvement Scale ( range 1 [ very much improved ] to 8 [ very much worse ] ) . RESULTS Behavioral intervention led to a significantly greater decrease on the Yale Global Tic Severity Scale ( 24.7 [ 95 % confidence interval { CI } , 23.1 - 26.3 ] to 17.1 [ 95 % CI , 15.1 - 19.1 ] ) from baseline to end point compared with the control treatment ( 24.6 [ 95 % CI , 23.2 - 26.0 ] to 21.1 [ 95 % CI , 19.2 - 23.0 ] ) ( P < .001 ; difference between groups , 4.1 ; 95 % CI , 2.0 - 6.2 ) ( effect size = 0.68 ) . Significantly more children receiving behavioral intervention compared with those in the control group were rated as being very much improved or much improved on the Clinical Global Impressions-Improvement scale ( 52.5 % vs 18.5 % , respectively ; P < .001 ; number needed to treat = 3 ) . Attrition was low ( 12/126 , or 9.5 % ) ; tic worsening was reported by 4 % of children ( 5/126 ) . Treatment gains were durable , with 87 % of available responders to behavior therapy exhibiting continued benefit 6 months following treatment . CONCLUSION A comprehensive behavioral intervention , compared with supportive therapy and education , result ed in greater improvement in symptom severity among children with Tourette and chronic tic disorder . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00218777 OBJECTIVE To examine the short-term efficacy and tolerability of aripiprazole for children and adolescents with Tourette 's disorder . METHOD This 10-week multicenter , double-blind , r and omized , placebo-controlled trial was conducted from August 2008 to April 2010 . Children and adolescents ( aged 6 - 18 years ) with a DSM-IV diagnosis of Tourette 's disorder and a Yale Global Tic Severity Scale total tic score of 22 or more were r and omly assigned ( 1:1 ratio ) to placebo or aripiprazole . The primary outcome measure was mean change from baseline in the total tic score on the Yale Global Tic Severity Scale ( last observation carried forward ) . Assessment s of safety and tolerability included spontaneously reported adverse events , extrapyramidal symptoms , serum prolactin level , metabolic variables , and other laboratory evaluations . RESULTS Of 61 subjects , 89 % completed the study . Patients who received aripiprazole demonstrated a significant reduction from baseline to end of study on the mean ( SD ) total tic score of the Yale Global Tic Severity Scale compared to those who received placebo ( -15.0 [ 8.4 ] and -9.6 [ 8.8 ] , respectively , P=.0196 ) . Response rate on the Tourette 's Syndrome Clinical Global Impression-Improvement was 66 % and 45 % in the aripiprazole and placebo groups , respectively . Mean decrease in the Tourette 's Syndrome Clinical Global Impression-Severity of Illness score was significantly different between the groups ( P=.0321 ) . In general , aripiprazole was well tolerated and there were no early discontinuations due to adverse events . The incidence of treatment-emergent adverse events between the groups was not significantly different ( P=.7550 ) . While aripiprazole decreased serum prolactin concentration ( P<.0001 ) , it increased mean body weight , body mass index , and waist circumference significantly ( P=.0055 , P=.0142 , and P=.0270 , respectively ) . CONCLUSIONS In comparison with placebo , aripiprazole was efficacious , generally tolerated and safe in the short-term treatment of children and adolescents with Tourette 's disorder . TRIAL REGISTRATION Clinical Trials.gov identifier : NCT00706589 To evaluate the efficacy of fluoxetine in the treatment of tics and obsessive-compulsive symptoms in patients with Tourette 's syndrome ( TS ) , 14 subjects ( 8 - 33 years old ) with TS participated in a 20-week , fixed-dose ( 20 mg daily ) , double-blind , placebo-controlled crossover trial of fluoxetine monotherapy . Five subjects met criteria for obsessive-compulsive disorder ( OCD ) , 6 additional subjects had obsessive-compulsive features , and 3 subjects had TS without obsessive-compulsive symptoms . There was no improvement in tics after 8 weeks of treatment with fluoxetine ( p = 0.58 ) . In contrast , fluoxetine treatment was associated with a significant reduction in obsessive-compulsive symptoms for the group of 6 subjects initially r and omized to fluoxetine ( p = 0.04 ) . Crossover analysis showed that fluoxetine had no marked effect on tics ( n = 10 , p = 0.30 , but produced a modest decrease in obsessive-compulsive symptoms ( n = 8 , p = 0.06 ) . Order effects and carry-over effects were not significant . Withdrawal to placebo was associated with a 55 % increase in obsessive-compulsive symptoms ( p = 0.05 ) , but there was no effect on tics . The most common side effect was transient behavioral activation , which occurred in about half of the subjects and was more common in children . Fluoxetine may be useful for the treatment of obsessive-compulsive symptoms in some patients with TS , but does not appear to be effective for tics Objective : To investigate the effects of topiramate on Tourette syndrome ( TS ) . Background : Dopamine-receptor-blocking drugs have been traditionally used to control tics in patients with TS , but these neuroleptics are associated with potentially limiting side effects . Methods : This is a r and omised , double-blind , placebo-controlled , parallel group study . To be included in the study , subjects required a DSM-IV diagnosis of TS , were 7–65 years of age , had moderate to severe symptoms ( Yale Global Tic Severity Scale ( YGTSS ) ⩾19 ) , were markedly impaired as determined by the Clinical Global Impression ( CGI ) scale severity score of ⩾4 and were taking no more than one drug each for tics or TS comorbidities . Results : There were 29 patients ( 26 males ) , mean age 16.5 ( SD 9.89 ) years , r and omised , and 20 ( 69 % ) completed the double-blind phase of the study . The primary endpoint was Total Tic Score , which improved by 14.29 ( 10.47 ) points from baseline to visit 5 ( day 70 ) with topiramate ( mean dose 118 mg ) compared with a 5.00 ( 9.88 ) point change in the placebo group ( p = 0.0259 ) . There were statistically significant improvements also in the other components of the YGTSS as well as improvements in various secondary measures , including the CGI and premonitory urge CGI . No differences were observed in the frequency of adverse events between the two treatment groups . Conclusion : This double-blind , placebo-controlled trial provides evidence that topiramate may have utility in the treatment of moderately severe TS OBJECTIVE To evaluate the efficacy and tolerability of ziprasidone in children and adolescents with Tourette 's syndrome and chronic tic disorders . METHOD Twenty-eight patients aged 7 to 17 years were r and omly assigned to ziprasidone or placebo for 56 days . Ziprasidone was initiated at a dose of 5 mg/day and flexibly titrated to a maximum of 40 mg/day . RESULTS Ziprasidone was significantly more effective than placebo in reducing the Global Severity ( p = .016 ) and Total Tic ( p = .008 ) scores on the Yale Global Tic Severity Scale . Compared with placebo , ziprasidone significantly reduced tic frequencies as determined by blind videotape tic counts ( p = .039 ) . The mean ( + /- SD ) daily dose of ziprasidone during the last 4 weeks of the trial was 28.2 + /- 9.6 mg . Mild transient somnolence was the most common adverse event . No clinical ly significant effects were observed on specific ratings of extrapyramidal symptoms , akathisia , or tardive dyskinesia . CONCLUSIONS In this limited sample , ziprasidone ( 5 - 40 mg/day ) appears to be effective and well tolerated in the treatment of Tourette 's syndrome . Ziprasidone may be associated with a lower risk of extrapyramidal side effects in children . However , additional studies are necessary to evaluate more fully its safety and efficacy in children with tic disorders This study evaluated the efficacy and safety of Lofexidine in treating children with tic disorders and attention deficit hyperactivity disorder ( ADHD ) . Subjects from a specialty tic disorders clinic were r and omly assigned to receive 8 weeks of treatment with lofexidine or placebo under double-blind conditions . Follow-up visits occurred every 2 weeks for safety monitoring and dose adjustment . Fourty-four medication-free subjects ( 41 boys and three girls ; mean age of 10.4 years ) with ADHD , combined type , and a tic disorder participated . After 8 weeks of treatment , lofexidine was associated with a mean improvement of 41 % in the total score on the teacher-rated ADHD Rating Scale compared to 7 % improvement for placebo . Eleven of 22 subjects who received lofexidine were blindly rated on the Clinical Global Scale-Improvement as either much improved or very much improved compared to none of 22 subjects who received placebo . The mean score on the parent-rated hyperactivity index improved by 29 % in the lofexidine group and 18 % in the placebo group , which was not a significant difference . On the Continuous Performance Test , commission errors decreased by 25 % and omission errors by 20 % in the lofexidine group , compared with increases of 33 % in commission errors and of 36 % in omission errors in the placebo group . Tic severity decreased by 27 % in the lofexidine group , compared to 0 % in the placebo group . One lofexidine subject with sedation withdrew at week 4 . Lofexidine was associated with insignificant decreases in blood pressure and pulse . Lofexidine appears to be a safe and effective treatment for children with tic disorders and ADHD BACKGROUND It has been hypothesized that glutamatergic transmission may be altered in Tourette syndrome . In this study , we explored the efficacy of a glutamate agonist ( D-serine ) and antagonist ( riluzole ) as tic-suppressing agents in children with Tourette syndrome . METHODS We performed a parallel three-arm , 8-week , double-blind , r and omized placebo-controlled treatment study in children with Tourette syndrome . Each child received 6 weeks of treatment with D-serine ( maximum dose 30 mg/kg/day ) , riluzole ( maximum dose 200 mg/day ) , or placebo , followed by a 2-week taper . The primary outcome measure was effective tic suppression as determined by the differences in the Yale Global Tic Severity Scale score ; specifically , the total tic score and the combined score ( total tic score + global impairment ) between treatment arms after 6 weeks of treatment . Mann-Whitney U tests were performed to analyze differences between each group and the placebo group . RESULTS Twenty-four patients ( males = 21 , ages 9 - 18 ) enrolled in the study ; one patient dropped out before completion . Combined Yale Global Tic Severity Scale score and total tic scores improved in all groups . The 6-week mean percent improvement of the riluzole ( n = 10 ) , D-serine ( n = 9 ) , and placebo ( n = 5 ) groups in the combined Yale Global Tic Severity Scale score were 43.7 , 39.5 , and 30.2 and for total tic scores were 38.0 , 25.0 , and 34.0 , respectively . There were no significant differences in Yale Global Tic Severity Scale score or total tic score , respectively , between the riluzole and placebo ( P = 0.35 , 0.85 ) or D-serine and placebo ( P = 0.50 , 0.69 ) groups . CONCLUSION Tics diminished by comparable percentages in the riluzole , D-serine , and placebo groups . These preliminary data suggest that D-serine and riluzole are not effective in tic suppression OBJECTIVE The pattern of dopamine antagonism by metoclopramide suggests benefits in the treatment of tic disorders . The purpose of this study was to examine the efficacy and safety of metoclopramide in the treatment of children and adolescents with tic disorders . METHOD Twenty-seven medication-free patients ( age 11.9 + /- 2.7 years ) with Tourette 's disorder or a chronic tic disorder participated in an 8-week double-blind , r and omized , placebo-controlled trial of metoclopramide . Metoclopramide was started at 5 mg daily and titrated as needed to a maximum dose of 40 mg daily . Tics were rated every 2 weeks , and adverse effects , including weight , cardiac , and laboratory measures , were monitored . RESULTS After 8 weeks of treatment , subjects receiving metoclopramide showed a 39 % reduction in their total tic score on the Yale Global Tic Severity Scale , while subjects receiving placebo showed only a 13 % reduction in tic severity ( p = .001 ) . Metoclopramide was well tolerated with no significant laboratory or cardiac changes noted other than an increase in serum prolactin . CONCLUSIONS The results of this small controlled study suggest that metoclopramide is an effective and well-tolerated treatment for children and adolescents with tic disorders . Further trials are needed to confirm its efficacy and safety in pediatric patients and adults OBJECTIVE To evaluate the efficacy and tolerability of risperidone in comparison with clonidine in the treatment of children and adolescents with Tourette 's syndrome ( TS ) . METHOD Following a 7- to 14-day single-blind , placebo lead-in , 21 subjects aged 7 to 17 years were r and omly assigned to 8 weeks of double-blind treatment with clonidine or risperidone . Research scales evaluated tics and comorbid obsessive-compulsive and attention-deficit/hyperactivity symptoms . RESULTS Risperidone and clonidine appeared equally effective in the treatment of tics in an intent-to-treat analysis , as rated by the Yale Global Tic Severity Scale ( YGTSS ) . Risperidone produced a mean reduction in the YGTSS of 21 % ; clonidine produced a 26 % reduction . Among subjects with comorbid obsessive-compulsive symptoms , 63 % of the risperidone group and 33 % of the clonidine group responded to treatment ( not significant ) . The most common adverse event seen with both treatments was sedation , which was mild to moderate in severity . Sedation subsequently resolved with continued administration of the medication or with a dose reduction . No clinical ly significant extrapyramidal symptoms were observed . CONCLUSIONS In this pilot study , risperidone demonstrated efficacy equivalent to clonidine in the treatment of tic symptoms in children and adolescents with TS . Further research is needed to clarify the role of atypical antipsychotics in TS and to delineate potential benefits for comorbid obsessive-compulsive and attention-deficit/hyperactivity symptoms OBJECTIVE This study evaluated the efficacy and safety of guanfacine in treating children with tic disorders and attention deficit hyperactivity disorder ( ADHD ) . METHOD Subjects from a specialty tic disorders clinic were r and omly assigned to receive 8 weeks of treatment with guanfacine or placebo under double-blind conditions . Follow-up visits occurred every 2 weeks for safety monitoring and dose adjustment . RESULTS Thirty-four medication-free subjects ( 31 boys and three girls with a mean age of 10.4 years ) with ADHD , combined type , and a tic disorder participated . After 8 weeks of treatment , guanfacine was associated with a mean improvement of 37 % in the total score on the teacher-rated ADHD Rating Scale , compared to 8 % improvement for placebo . Nine of 17 subjects who received guanfacine were blindly rated on the Clinical Global Improvement scale as either much improved or very much improved , compared with none of 17 subjects who received placebo . The mean score on the parent-rated hyperactivity index improved by 27 % in the guanfacine group and 21 % in the placebo group , not a significant difference . On the Continuous Performance Test , commission errors decreased by 22 % and omission errors by 17 % in the guanfacine group , compared with increases of 29 % in commission errors and of 31 % in omission errors in the placebo group . Tic severity decreased by 31 % in the guanfacine group , compared to 0 % in the placebo group . One guanfacine subject with sedation withdrew at week 4 . Guanfacine was associated with insignificant decreases in blood pressure and pulse . CONCLUSIONS Guanfacine appears to be a safe and effective treatment for children with tic disorders and ADHD BACKGROUND Pre clinical animal and open-trial clinical trials using nicotine gum and the transdermal nicotine patch found that treatment with nicotine potentiates the effects of neuroleptics in reducing the dyskinetic symptoms of Tourette 's disorder . We sought to verify and exp and these findings in a prospect i ve double-blind placebo-controlled trial . METHOD Seventy patients with DSM-IV Tourette 's disorder were treated with either transdermal nicotine ( 7 mg/24 hours ) or placebo patches in a 33-day , r and omized , double-blind study . Each patient received an individually based optimal dose of haloperidol for at least 2 weeks prior to r and om assignment to nicotine or placebo treatment . A new patch was worn each day for the first 5 days . On the sixth day , the dose of haloperidol was reduced by 50 % . Daily patch applications were then continued for an additional 2 weeks ( through day 19 ) , at which time the patch was discontinued , but the 50 % dose of haloperidol was continued for an additional 2 weeks ( through day 33 ) . Clinical and safety assessment s were made at each visit . RESULTS Patients who completed all 19 days of nicotine ( N = 27 ) or placebo ( N = 29 ) patch treatment were used in efficacy analyses . As documented by the Clinician- and Parent-rated Global Improvement scales , transdermal nicotine was superior to placebo in reducing the symptoms of Tourette 's disorder . The Yale Global Tic Severity Scale was less sensitive in detecting a placebo/drug difference than were the global improvement scores , suggesting that some of the improvement may not have been related to treatment-related changes in tic severity , but to the emotional and behavioral symptoms . The side effects of nausea and vomiting were significantly more common in the nicotine group ( 71 % [ N = 25 ] and 40 % [ N = 14 ] ) than in the placebo group ( 17 % [ N = 6 ] and 9 % [ N = 3 ] ) ( nausea , p = .0001 ; vomiting , p = .004 ) . CONCLUSION Transdermal nicotine was superior to placebo in reducing behavioral symptoms when patients were receiving an optimal dose of haloperidol , when the dose of haloperidol was reduced by 50 % , and when the patch had been discontinued for 2 weeks . These findings confirm earlier open-label findings and suggest that combining nicotinic receptor modulation and neuroleptics could be a therapeutic option for the treatment of Tourette 's disorder . While side effects limit chronic use of nicotine , it may be useful on a p.r.n . basis . Further clinical research is warranted to investigate the use of novel nicotinic receptor modulating agents with improved safety profiles over nicotine BACKGROUND The findings from case reports and patient question naire surveys have been interpreted as indicating that administration of stimulants is ill-advised for the treatment of attention-deficit hyperactivity disorder in children with tic disorder . METHODS Thirty-four prepubertal children with attention-deficit hyperactivity disorder and tic disorder received placebo and three dosages of methylpheni date hydrochloride ( 0.1 , 0.3 , and 0.5 mg/kg ) twice daily for 2 weeks each , under double-blind conditions . Treatment effects were assessed using direct observations of child behavior in a simulated ( clinic-based ) classroom and using rating scales completed by the parents , teachers , and physician . RESULTS Methylpheni date effectively suppressed hyperactive , disruptive , and aggressive behavior . There was no evidence that methylpheni date altered the severity of tic disorder , but it may have a weak effect on the frequency of motor ( increase ) and vocal ( decrease ) tics . CONCLUSION Methylpheni date appears to be a safe and effective treatment for attention-deficit hyperactivity disorder in the majority of children with comorbid tic disorder The objective of this study was to evaluate the neuropsychiatric effects of the alpha-2a adrenergic agonist guanfacine in children with Tourette syndrome ( TS ) . Twenty-four children with TS participated in a 4-week , double-blind , placebo-controlled study of guanfacine . Tic severity , neuropsychologic functioning , and parent ratings of behavior were evaluated pre- and post-treatment . The sample had mild tic severity and subtle neuropsychologic dysfunction pretreatment . Post-treatment , patients receiving guanfacine were rated by parents as significantly improved ( compared to placebo ) on one measure of executive function ( parent-rated metacognition ) . Improvement on tic severity , performance-based neuropsychologic measures , and all other parent ratings were not significantly better than placebo . At a moderate dose and short-term treatment duration , guanfacine did not provide significant neuropsychiatric benefits in this group of children with mild TS OBJECTIVE To compare the tic suppression , electrocardiogram ( ECG ) changes , weight gain , and side effect profiles of pimozide versus risperidone in children and adolescents with tic disorders . METHOD This was a r and omized , double-blind , crossover ( evaluable patient analysis ) study . Nineteen children aged 7 to 17 years with Tourette 's or chronic motor tic disorder were r and omized to 4 weeks of treatment with pimozide or risperidone , followed by the alternate treatment after a 2-week placebo washout . The primary efficacy outcome measure was change in tic severity assessed by the Yale Global Tic Severity Scale ( YGTSS ) . ECG results , weight gain , and side effects were also compared . RESULTS Compared to pimozide treatment , risperidone treatment was associated with significantly lower tic severity scores ( YGTSS : baseline 43.3 + /- 17.5 , pimozide 34.2 + /- 14.2 , risperidone 25.2 + /- 13.6 ; p = .05 ) . Weight gain during the 4-week treatment periods was greater for risperidone ( mean 1.9 kg ) than pimozide ( 1.0 kg ) . No patient suffered a serious adverse event , but 6 of 19 subjects failed to complete the protocol . Neither medication was associated with ECG changes . CONCLUSIONS In this study , risperidone appeared superior to pimozide for tic suppression but was associated with greater weight gain We studied the effects of chewing nicotine gum on tic frequency and severity in 10 patients with Tourette 's disorder ( TD ) on haloperidol , versus 9 untreated TD patients ; placebo gum was administered to 5 of these untreated patients . Videotapes of patients during a 2-hr period of 30 min baseline , 30 min gum chewing , and two 30-min postgum-chewing periods were utilized . For those TD patients on haloperidol , significant reductions occurred in tic frequency and severity during the gum-chewing and the two postgum-chewing periods . Nicotine gum alone caused a decrease in tic frequency only during gum-chewing and one postgum-chewing period , while placebo gum showed no effect . In this study , nicotine markedly potentiated haloperidol effects in treating TD , and showed lesser effects on TD when used alone This 8-week , r and omized , placebo-controlled , double-blind clinical study investigated the short-term effectiveness and safety of the traditional Chinese medicine , Ningdong ( ND ) granule in paediatric subjects ( aged 7 - 18 years ) with Tourette 's disorder ( TD ) . Subjects received either 1 g/kg per day ND granule ( n = 33 ) or placebo ( n = 31 ) and tics were measured at baseline and after 4 and 8 weeks of treatment . Body mass index , electrocardiogram and laboratory measures were recorded at baseline and at week 8 . After 8 weeks of treatment with ND granule , subjects exhibited a 41.39 % reduction in the total tic score while the placebo group showed a 10.79 % decrease . Regarding side-effects , two subjects reported loss of appetite and one experienced constipation in the ND granule group . There were no significant changes in laboratory and physical examinations . These results suggest that ND granule is both effective and safe , and may be a good c and i date for the treatment of patients with TD The results of this controlled study of the treatment of 57 patients with Gilles de la Tourette 's syndrome suggested that both haloperidol and pimozide were more effective than placebo , but that haloperidol was slightly more effective than pimozide . Adverse effects occurred more frequently with haloperidol vs placebo than with pimozide vs placebo , but the frequency was not significantly different for haloperidol compared with pimozide . Clinical ly significant cardiac effects did not occur at a maximum dosage of 0.3 mg/kg or 20 mg/d for pimozide and 10 mg/d for haloperidol . However , the QTc interval was prolonged during pimozide treatment compared with that during haloperidol treatment , although the values for both medications were not in an abnormal range BACKGROUND Tourette syndrome ( TS ) is a common tic disorder in children and adolescents . There is preliminary evidence that herbal medicine may possess the potential to treat tics . The purpose of this study was to formally evaluate the efficacy and safety of 5-Ling Granule ( 5-LGr ) , a proprietary polyherbal product , for the treatment of patients with TS in comparison with tiapride and placebo . METHODS In this multisite , double-blind , double-dummy , r and omized , placebo-controlled trial , 603 patients with TS aged 5 - 18 years were r and omly assigned to treatment with placebo ( n = 117 ) , tiapride ( n = 123 , 200 - 400 mg/day ) or 5-LGr ( n = 363 , 15 - 22.5 g/day ) for 8 weeks . The primary outcome was measured using the Yale Global Tic Severity Scale ( YGTSS ) and its subscales , total tic Score ( TTS ) and tic-related impairment . Incidence of adverse events was compared among the three groups . RESULTS While tics of all patients were reduced over time , 5-LGr and tiapride treatment produced significantly greater improvement on the YGTSS overall scale and subscale for TTS and impairment at endpoint than the placebo . Seventy-four percentage of patients in the 5-LGr arm and 68.3 % in the tiapride arm had clinical response and these rates of response were significantly higher than those on placebo ( 44.0 % , p < .001 ) . The incidence of overall adverse events was significantly fewer for patients on placebo and 5-LGr compared to tiapride ( 11.2 % and 13.8 % vs. 26.0 % , p = .002 ) ; in particular physical tiredness , dizziness and sleep disturbance . CONCLUSIONS The clinical efficacy of 5-LGr is comparable to tiapride in reducing tics . Its safety profile is better than tiapride . 5-LGr can be considered a safe and effective therapy for TS ( Trial registration : www . clinical trials.gov : NCT01501695 ) Objective : To determine whether pergolide , a mixed D1-D2-D3 dopamine agonist , is efficacious and safe in the treatment of children with Tourette ’s syndrome . Background : Neuroleptics , which block dopamine transmission , are currently used for treatment of children with severe tics , but major side effects and limited efficacy reduce clinical utility . Prior open-label reports of pergolide suggest potential benefit . Methods : The authors enrolled 24 children age 7 to 17 years with Tourette ’s disorder , chronic motor tic disorder , or chronic vocal tic disorder by Diagnostic and Statistical Manual of Mental Disorders ( 4th ed . ) criteria , plus severity criteria on the Yale Global Tic Severity Scale ( YGTSS ) of ≥20 , in a double-blind , placebo-controlled , crossover study . Children were r and omized to receive either placebo or up to 300 μg/day pergolide for the first 6-week treatment period , with a 2-week placebo washout , followed by crossover to the alternate treatment . The primary outcome measure was tic severity assessed by YGTSS . Results : Compared with placebo treatment , pergolide treatment was associated with significantly lower YGTSS scores ( 42.0 ± 20.4 versus 23.5 ± 18.7 ; F = 12.0 , df = 1 , 17 , p = 0.0011 ) . No patient had a serious adverse event and pergolide was well tolerated . Conclusions : In this r and omized , placebo-controlled , crossover trial , pergolide appeared to be a safe and efficacious treatment for Tourette ’s syndrome in children Summary Tiapride , a substituted benzamide derivative , possesses good clinical antidyskinetic properties due to its DA2-blocking activities . It has been shown to be clinical ly effective in the treatment of tic disease in children . In order to study tiapride 's antidyskinetic properties in the treatment of the tic syndrome in children , we conducted a simple , placebo-controlled study on 10 children followed by a double-blind crossover study on 17 children . Tiapride was shown to have a positive therapeutic effect on tics in children ; whereas it has no adverse effects on neuropsychologically measurable cognitive performances in children . Neurophysiological parameters such as the EEG frequency analysis and sensory evoked potentials were not affected by tiapride , nor was the neurosecretory , hypothalamic-hypophyseal regulation of the sex hormones , thyroid stimulating hormone , growth hormone , or thyroid hormone impaired . The hyperprolactinemia caused by tiapride 's dopaminergic properties was moderate and restricted to the duration of therapy BACKGROUND This study examined changes in attention-deficit hyperactivity ( ADHD ) behaviors and motor and vocal tics during long-term treatment with methylpheni date . METHODS Thirty-four prepubertal children with ADHD and chronic multiple tic disorder ( who had participated in an 8-week , double-blind , placebo-controlled methylpheni date evaluation ) were evaluated at 6-month intervals for 2 years as part of a prospect i ve , nonblind , follow-up study . Treatment effects were assessed using direct observations of child behavior in a simulated ( clinic-based ) classroom and behavior rating scales completed by parents and physician . Videotapes of the simulated classroom were scored by coders who were blind to treatment status . RESULTS There was no evidence ( group data ) that motor tics or vocal tics changed in frequency or severity during maintenance therapy compared with diagnostic or initial double-blind placebo evaluations . Behavioral improvements demonstrated during the acute drug trial were maintained during follow-up . There was no evidence ( group data ) of clinical ly significant adverse drug effects on cardiovascular function or growth at the end of 2 years of treatment . CONCLUSIONS Long-term treatment with methylpheni date seems to be safe and effective for the management of ADHD behaviors in many ( but not necessarily all ) children with mild to moderate tic disorder . Nevertheless , careful clinical monitoring is m and atory to rule out the possibility of drug-induced tic exacerbation in individual patients This double-blind , crossover , prospect i ve study compared the efficacy and safety of pimozide to placebo in 20 patients with Tourette 's syndrome ( TS ) . The study included a 2–week drug-free period , r and om assignment to pimozide or placebo for 6 weeks and crossover to the alternate medication for a second 6–week period . Multiple dependent measures of efficacy at endpoint by the clinician , patient and judges were all highly significant ( most p values = 0.0001 ) . Adverse reactions , commonly encountered with antipsychotic drugs , were related to dosage and generally could be managed by careful titration of dosage and use of antiparkinson drugs , except for an abnormal ECG in one patient . This study confirms previous reports in the literature that pimozide is an effective drug for the treatment of TS . Future controlled studies should be conducted to evaluate whether pimozide is more effective and has less adverse effects than haloperidol and other drugs Abstract We selected four patients with severe Gilles de la Tourette syndrome , high frequency of tics ( two to ten per minute ) , vocalizations , and lack of comorbidity . These patients ( aged 19–40 years ) underwent a 52-week double-blind cross-over study with olanzapine ( 5 and 10 mg daily ) vs. low-dose pimozide ( 2 and 4 mg daily ) . The reduction in rating scale scores for the syndrome was highly significant with 10 mg olanzapine vs. basal and vs. 2 mg pimozide , and was significant for 5 mg olanzapine vs. 4 mg pimozide . Only moderate sedation was reported by one patient during olanzapine treatment while three complained of minor motor side effects and sedation during pimozide treatment . At the end of the study all patients opted for olanzapine treatment The safety and effectiveness of clonidine hydrochloride ( 3 to 5 micrograms/kg per day ) were evaluated in 47 subjects with Gilles de la Tourette 's syndrome , aged 7 to 48 years . Twenty-four subjects were r and omly assigned to clonidine treatment and 23 to placebo . Forty subjects ( 21 given clonidine and 19 placebo ) successfully completed the 12-week , double-blind clinical trial . Clinical ratings of tic severity improved for both groups . The magnitude of response was greater in the group receiving clonidine . Clinician-rated measures of motor tic severity , the degree to which the tics are " noticeable to others , " motor tic counts from videotaped interviews , and parent-rated measures of impulsivity and hyperactivity were the most responsive to clonidine treatment . These results indicate that clonidine is more effective than placebo in reducing some of the tic and other behavioral symptoms associated with Gilles de la Tourette 's syndrome OBJECTIVE The safety and efficacy of mecamylamine as a monotherapy in children and adolescents with Tourette 's disorder ( TD ) was investigated in an 8-week multicenter , double-blind , placebo-controlled study . METHOD Eligible subjects included subjects with TD ( DSM-IV ) , with a naturalistic mix of comorbid diagnoses , nonsmokers , aged 8 to 17 years , whose behavioral and emotional symptoms ( according to parents ) were more disturbing than tics . After a washout period of all psychotropic medication , subjects were r and omly assigned to either mecamylamine ( n = 29 ) or placebo ( n = 32 ) . Mecamylamine doses ranged from 2.5 to 7.5 mg/day . Primary efficacy measures included the Tourette 's Disorder Scale-Clinician Rated ( TODS-CR ) and 21-point Clinical Global Improvement scale ; secondary efficacy measures included the Yale Global Tic Severity Scale and a rage-attack scale ( RAScal ) . RESULTS Of the 61 subjects who were r and omized , 50 ( 82 % ) completed at least 3 weeks on medication and 38 ( 62 % ) completed the full 8-week trial . Study withdrawals included 12/29 on mecamylamine and 11/32 on placebo . For the total sample , mecamylamine was no more effective than placebo on any of the outcome measures . However , an item analysis of the TODS-CR suggested that mecamylamine may have reduced sudden mood changes and depression in moderately to severely affected subjects . Except for a slight increase in heart rate during the 1st week in both the mecamylamine and the placebo groups , there where no significant mecamylamine-related changes in vital signs , electrocardiogram , complete blood cell count , or blood chemistry values . CONCLUSIONS Mecamylamine , in doses up to 7.5 mg/day , is well tolerated in children and adolescents , but as a monotherapy it does not appear to be an effective treatment for tics or for the total spectrum of symptoms associated with TD . However , further studies should be conducted to investigate its possible therapeutic effects in subjects with comorbid mood disorders and as an adjunct to neuroleptic medication OBJECTIVE The authors evaluated the relative efficacy and safety of pimozide and haloperidol in the treatment of Gilles de la Tourette 's syndrome in children and adolescents . METHOD A double-blind , 24-week , placebo-controlled double crossover study of equivalent dose formulations of haloperidol and pimozide was conducted with 22 subjects , aged 7 - 16 years , with Tourette 's disorder who were r and omly assigned to first one active drug treatment and then the other . Biweekly assessment and flexible dose titration mimicked clinical practice . The primary outcome variable was total score on the Tourette Syndrome Global Scale . Final outcome was determined after 6 weeks of each treatment ( placebo , pimozide , haloperidol ) , with a 2-week placebo baseline period and intervening 2-week placebo washout periods between treatments . RESULTS Pimozide proved significantly different from placebo in affecting the primary outcome variable , whereas haloperidol failed to have a significant effect . Haloperidol exhibited a threefold higher frequency of serious side effects and significantly greater extrapyramidal symptoms relative to pimozide . Haloperidol-associated treatment-limiting adverse events were experienced by 41 % of the patients . The therapeutic doses of pimozide and haloperidol were equivalent ( mean = 3.4 mg/day , SD = 1.6 , and mean = 3.5 mg/day , SD = 2.2 , respectively ) . CONCLUSIONS At equivalent doses , pimozide is superior to haloperidol for controlling symptoms of Tourette 's disorder in children and adolescents Objective To explore the clinical efficacy of integrative Chinese and Western medicine in treating Tourette syndrome ( TS ) . Methods Methods Ninety children with TS were r and omized into two groups by r and omizing : digital table method : the 60 patients in the treated group were treated by Ningdong Granule ( 宁动颗粒 , NDG ) plus haloperidol , and the 30 in the control group treated by haloperidol alone . The course for both groups was 6 months . Conditions of the patients were estimated before and after treatment with Yale Global Tic Severity Scale ( YGTSS ) , the short-term efficacy , adverse reaction of treatment were assessed at the end of treatment , and the long-term efficacy as well as the recurrent rate were evaluated half a year after the treatment was ended . Results Of the 60 patients in the treated group , the treatment on 36 was evaluated as remarkably effective , 21 as effective , and 3 as ineffective , the total effective rate being 95.0 % ( 57/60 ) , while of the 30 patients in the control group , the corresponding data were 9 , 13 , 8 and 73.3 % ( 22/30 ) , respectively , differences between groups in markedly effective rate and total effective rate were statistically significant ( χ2=7.20 , and χ2=6.85 , P<0.01 ) . The improvement on the condition of illness , motor tic and vocal tic , as well as the long-term efficacy of treatment were all better in the treated group than in the control group ( P<0.05 or P<0.01 ) . The incidence of adverse reaction and the recurrent rate in the treated group were 13.3 % ( 8/60 ) and 8.3 % ( 5/60 ) respectively , all were lower than those in the control group , 36.7 % ( 11/30 ) and 43.3 ( 13/30 ) , showing statistical significance s ( P<0.05 and P<0.01 ) . Conclusion Integrative medical treatment on TS was markedly effective in clinical practice with less adverse reaction and lower recurrent rate We compared the efficacy of clonidine and levetiracetam for treating tics in Tourette syndrome . Twelve subjects were enrolled ; 10 ( ages 8 - 27 years ) with moderate to moderately severe tics completed a 15-week r and omized , double-blind , flexible-dose crossover protocol . Initial medication doses were clonidine ( 0.05 mg , twice daily ) or levetiracetam ( 10 mg/kg/day , divided twice daily ) . Doses were adjusted weekly , based on telephone assessment . The primary outcome measure was baseline-to-posttreatment ( 6-week ) change in Total Tic Score of the Yale Global Tic Severity Scale . Secondary outcome measures included total Yale Global Tic Severity Scale and Clinical Global Impression scores and behavioral measures . The mean Total Tic Score improved significantly from baseline to posttreatment with clonidine ( 25.2 versus 21.8 ) compared with levetiracetam ( 22.7 versus 23.6 ) ( P = 0.013 ) . The mean total Yale Global Tic Severity Scale and Clinical Global Impression score did not change . For levetiracetam , no changes occurred in any scales . No significant change occurred in any secondary behavioral outcome measures for either group . The most commonly reported side effects were , for clonidine , sedation ( n = 5 ) , and for levetiracetam , irritability ( n = 4 ) . Treatment with clonidine , but not levetiracetam , result ed in a small reduction in Total Tic Score , with an effect size of 0.57 Objective To assess the effect and adverse reaction of Qufeng Zhidong Recipe ( 祛风止动方 , QZR ) in treating children ’s tic disorder ( TD ) . Methods With multicenter r and omized parallel open-controlled method adopted , the patients enrolled were assigned to two groups , 41 cases in the Chinese medicine ( CM ) group and 40 in the Western medicine ( WM ) group . They were treated by QZR and haloperidol plus trihexyphenidyl respectively for 12 weeks as one course . In total , two courses of treatment were given . The curative effect and adverse reactions were evaluated by scoring with Yale Global Tic Severity Scale ( YGTSS ) , Traditional Chinese Medicine Syndrome Scale ( TCMSS ) , and Treatment Emergent Symptom Scale ( TESS ) , as well as results of laboratory examinations . Results After one course of treatment , the markedly effective rate in the CM and the WM group was 14.6 % and 17.5 % , respectively , and the total effective rate 43.9 % and 47.5 % , respectively , which showed insignificant difference between groups ( P>0.05 ) . However , after two courses of treatment , markedly effective rate in them was 73.2 % and 7.5 % , and the total effective rate was 100.0 % and 57.5 % , both showing significant differences between groups ( P<0.05 ) . Besides , the adverse reactions occurred in the CM group was less than that in the WM group obviously . Conclusion QZR has definite curative effect with no apparent adverse reaction in treating TD , and it can obviously improve the symptoms and signs and up grade the quality of life and learning capacities in such patients BACKGROUND Currently , there is no consensus on the best therapeutic approach to chronic tic disorders and comorbid attention-deficit/hyperactivity disorder ( ADHD ) . To address this issue , we evaluated the tolerability and efficacy of the noradrenergic tricyclic antidepressant desipramine hydrochloride in the treatment of children and adolescents with chronic tic disorders and comorbid ADHD . METHODS Forty-one children and adolescents with chronic tic disorders , including Tourette disorder and comorbid ADHD , were studied in a 6-week , double-blind , placebo-controlled , parallel trial . Desipramine was titrated weekly up to 3.5 mg/kg per day . We rated ADHD and tic symptoms weekly and monitored adverse effects , laboratory findings , and cardiovascular parameters . RESULTS Treatment with desipramine ( mean total daily dose , 3.4 mg/kg per day ) was well tolerated without meaningful adverse effects . Desipramine significantly reduced core symptoms of ADHD ( ADHD Rating Scale ; 42 % decrease from baseline relative to placebo , P<.001 ) , with equal response in inattentive symptoms and hyperactive/impulsive symptoms ( P<.001 for both ) . The ADHD response rate was robust ( 71 % vs 0 % ; desipramine vs placebo , P<.001 ) . Likewise , desipramine significantly reduced tic symptoms ( Yale Global Tic Severity Scale ; 30 % decrease from baseline relative to placebo , P<.001 ) , with equal response in motor and phonic tic symptoms ( P<.01 for both ) . The tic response rate was substantial ( 58 % vs 5 % ; desipramine vs placebo , P<.001 ) . There were small but statistically significant differences between desipramine and placebo in heart rate and blood pressure . CONCLUSIONS Treatment with desipramine was well tolerated and was associated with robust clinical ly significant reductions in tic and ADHD symptoms in children and adolescents with chronic tic disorders and ADHD diagnoses OBJECTIVES Because psychostimulants can exacerbate preexisting motor/phonic tics in individuals with Tourette 's syndrome ( TS ) , a clinical trial was performed to examine the ability of clonidine and desipramine to modify attention-deficit hyperactivity disorder ( ADHD ) behaviors in children with TS + ADHD . METHODS A double-blind , placebo-controlled protocol was used in which each subject served as his or her own control and received , in a r and omly assigned fashion , 6-week medication cycles with clonidine ( 0.05 mg four times daily ) , desipramine ( 25 mg four times daily ) , and placebo . RESULTS Thirty-seven children with TS+ADHD between the ages 7 to 13 years and of normal intellect were recruited , and 34 ( 31 males , 3 females ) completed the entire protocol . Outcome measures for ADHD included Parent and Teacher Child Behavior Checklists ( CBCL ) , continuous performance tests , and neuropsychologic tests of executive function . Several markers for ADHD were shown to improve significantly ( P < .05 ) after treatment with desipramine ( parent linear analogue rating , parent CBCL " hyperactivity " subscale , and teacher CBCL subscales " nervous/overactive , " " anxious , " and " unpopular " ) . Improvement with desipramine was always superior to that noted with clonidine . Clinical improvement did not correlate with drug blood levels . On measures of tic severity , neither drug made tics worse . Desipramine showed a statistically significant improvement on a global linear analogue scale , but not on the Hopkins Motor/Vocal Tic Severity Scale , the Tourette Syndrome Severity Scale , or the Yale Global Tic Severity Scale . Clonidine did not significantly alter tic severity on any measure . CONCLUSION The results of this study suggest that desipramine may be a useful alternative for the treatment of symptoms of ADHD in children with TS OBJECTIVE The aim of the present study was to evaluate the efficacy of ondansetron , a selective 5-HT(3 ) antagonist , in the treatment of Tourette 's disorder . METHOD Participants ( N = 30 ) aged 12 to 46 years , diagnosed with DSM-IV Tourette 's disorder and resistant to previous haloperidol treatment , were enrolled in a 3-week , r and omized , double-blind , placebo-controlled outpatient study . Assessment s were conducted at baseline and once a week during the study period . Scales used included the Tourette 's Syndrome Global Scale ( TSGS ) , the Yale Global Tic Severity Scale ( YGTSS ) , and the Yale-Brown Obsessive Compulsive Scale . Ondansetron dose was 8 , 16 , and 24 mg/day in the first , second , and third weeks , respectively . RESULTS A significant positive effect of ondansetron on tic severity , as assessed by the TSGS , was noted ( baseline vs. endpoint : mean + /-SD = 29.62 + /-20.33 vs. 20.58 + /-12.82 , p = .002 vs. placebo ) . However , no significant effect was detected upon assessing ondansetron/ placebo effect on tic severity with the YGTSS ( baseline vs. endpoint : mean + /-SD = 24.04 + /-9.44 vs. 17.50 + /-9.48 , p = .15 vs. placebo ) . No change in obsessive-compulsive symptoms was noted in either group . Adverse effects included mild and transient abdominal pain . CONCLUSIONS Ondansetron may have antitic effects in patients with Tourette 's disorder . Large-scale , double-blind studies should further assess the antitic efficacy of ondansetron Objective : The aim of the present study was to evaluate the therapeutic effectiveness and safety of the clonidine adhesive patch in treating tic disorders . Method : A total of 437 patients , who met Chinese Classification of Mental Disorders – third edition diagnostic criteria for transient tic disorder ( 5 % ) , chronic motor or vocal tic disorder ( 40 % ) or Tourette disorder ( 55 % ) , aged 6–18years , were divided r and omly into an active treatment group and a clinical control group . Participants in the active treatment group were treated with a clonidine adhesive patch and participants in the clinical control group with a placebo adhesive patch for 4weeks . The dosage of the clonidine adhesive patch was 1.0 mg , 1.5 mg or 2.0 mg per week , depending on each participant 's bodyweight . Participants whose Yale Global Tic Severity Scale ( YGTSS ) score decreased < 30 % and Clinical Global Impression score was ≥4 by the end of week 3 were withdrawn from the trial . Results : After 4 weeks of treatment the active treatment group participants ’ YGTSS score was significantly lower than that of the clinical control group ( F=4.63 , p=0.03 ) . Further , the active treatment group had a significantly better therapeutic response than the clinical control group ( χ2=9.15 , p=0.003 ) . The response rate in the active treatment group was 68.85 % compared to 46.85 % in the clinical control group ( χ2=16.98 , p=0.0001 ) . The rate of adverse events was low ( active treatment group , 3.08 % ; clinical control group , 7.21 % ) and did not differ between the two groups . Conclusions : The clonidine adhesive patch is effective and safe for tic disorders |
10,748 | 30,656,475 | Similarly , there was no statistically significant difference demonstrated between the REP and REC groups in terms of ROM .
Conclusions Comparable results with good outcomes in terms of functional scores and ROM can be achieved with both REP and REC when treating TTIE , although the re-operation rate for both remains relatively high .
Given there is no apparent clear advantage between the two treatment groups , we would suggest that REC should be performed when a satisfactory fixation can be achieved as the longevity of REP in young patients with a TTIE is currently uncertain | Introduction The terrible triad injury of the elbow ( TTIE ) remains challenging to manage and has been associated with high complication rates and poor outcomes .
There is a trend towards performing radial head replacement ( REP ) in preference to radial head reconstruction ( REC ) as arthroplasty provides early stability and may allow mobilisation sooner , potentially result ing in a better functional outcome .
This systematic review compares the outcome of patients with TTIE treated with either REC or REP . | BACKGROUND Terrible triad injury ( TTI ) , one of the main patterns of complex elbow instability , is difficult to treat and yields conflicting surgical results . We analyzed prospect ively a series of patient affected by TTI and treated according to the current diagnostic and surgical protocol s to investigate whether their application allow to obtain more predictable outcomes . MATERIAL AND METHODS We analyzed 26 patients with a mean age of 52 years . Preoperative X-rays and CT were performed ; all patients were operated by the same elbow surgeon and underwent the same surgical and rehabilitation treatment . Final functional outcome was assessed by the Mayo Elbow Performance Score ( MEPS ) , Quick-Disability of the Arm Shoulder and H and -score ( Q-DASH ) and the modified-American Shoulder and Elbow Surgeons score ( m-Ases ) . A radiographic evaluation was also performed . RESULTS Mean follow-up was 31 months . At final evaluation , mean flexion , extension , supination and pronation were 137 ° , 10 ° , 77 ° and 79 ° , respectively ; mean MEPS , m-ASES and Q-DASH scores were respectively 96 , 91 and 8 points . Complications observed after first surgery were : elbow stiffness in 5 cases , mild posterolateral instability in 3 cases , chronic subluxation in 1 case . Radiographic evaluation showed secondary arthritis in 9 cases , symptomatic HO in 3 cases and late hardware displacement in 2 cases . Six out of 26 patient underwent reoperation with final satisfactory results . CONCLUSION The current diagnostic and therapeutic protocol s allow obtaining satisfactory clinical outcomes in majority of cases but a high number of major and minor unpredictable complications persist yet . In this series , low compliance , obesity , and extensive soft elbow tissue damage caused by high-energy trauma represented negative prognostic factors unrelated to surgery . On the other h and , the strict application of current algorithms by an expert elbow surgeon appears to improve clinical results by reducing the influence of other avoidable negative prognostic factors well known in current literature , such as the incomplete recognition of injuries , delayed treatment , inadequate treatment of bony and ligamentous injuries , prolonged immobilization and , last but not least , the surgeon 's inexperience . LEVEL OF EVIDENCE Level IV , Case series , Treatment study Complex fracture-dislocations of the elbow can often be either irreducible or unstable , with an inability to hold the reduction or with the delayed development of subluxation or dislocation . The aim of the present study was to evaluate the etiology of the instability , both osseous and ligamentous , and the results of stabilization with a combination of internal fixation , ligament repair , radial head arthroplasty and , when necessary , hinged external fixation . Figures 1 and 2 represent our formulated protocol and treatment algorithm for elbow fracture-dislocation in this series of thirty-two patients . Fig. 1 Constellation of the “ terrible triad ” injury and the anatomic structures encountered . LUCL = lateral ulnar collateral ligament , and MUCL = medial ulnar collateral ligament . The so-called terrible triad injury has a history of complicated outcomes as the surgeon attempts to maximize functional range-of-motion goals while maintaining stability1 - 3 . On the basis of previous evaluations of these specific injuries and the recent evolution of surgical protocol s , the restoration of congruency and stability coupled with progressive rehabilitation can reliably enhance the functional outcome 4 - 6 . Thirty-two consecutive patients with unstable elbow injuries who had been referred to three tertiary centers were prospect ively recruited for the present study between 2001 and 2005 . Six of these patients had been unsuccessfully managed at outside facilities and had been transferred to our care . The unsuccessful treatments had included attempted closed reduction ( four patients ) , radial head excision ( one patient ) , and open reduction and internal fixation of the proximal part of the ulna ( one patient ) . Fig. 2 Treatment algorithm proposed for the achievement of anatomic fixation and mechanical stability in patients with complex fracture-dislocations of the elbow . EUA = examination under anesthesia , MUCL = medial ulnar collateral ligament , LUCL = lateral ulnar collateral ligament , P/L = posterolateral stability , and ORIF = open reduction and internal fixation . All |
10,749 | 20,091,663 | In this study no beneficial effect of adenoidectomy was found .
The outcome was improvement in episodes of common colds . | BACKGROUND Adenoidectomy , surgical removal of the adenoids , is a common ENT operation worldwide in children with recurrent or chronic nasal symptoms .
A systematic review on the effectiveness of adenoidectomy in this specific group has not previously been performed .
OBJECTIVES To assess the effectiveness of adenoidectomy versus non-surgical management in children with recurrent or chronic nasal symptoms . | One hundred and fifty children aged between 2 and 9 years with bilateral SOM were allocated at r and om to three groups : Adeno-tonsillectomy ( 47 cases ) , adenoidectomy ( 47 cases ) and neither procedure ( 53 cases ) . A further 42 children were allocated to either adenoidectomy or no surgery . In all only one ear was treated at r and om by myringotomy and insertion of a ventilation tube . The unoperated ear was examined six weeks , six months , nine months , one , two and three years post-operatively for otoscopic clearance of the effusion , impedance change and improvement in mean hearing threshold . Thus the effects on middle ear status of adenoidectomy alone and in combination with tonsillectomy were assessed . There was a significant clearance of middle ear fluid , change from no peak to peak impedance measurement and hearing gain as a result of both procedures with a late trend favouring the combined operation . Neither pre-operative tonsils size nor the number of attacks of tonsillitis affect outcome . However there is a relationship between age and radiographic post-nasal space airway size with clearance of the effusion one year after surgery . These findings permit recommendation for adenoidectomy with improved expectation for resolution of SOM if cases are selected with reference to these two variables . They also suggest in which cases the operation should not be recommended . Despite the trends in outcome favouring combined operations , the extra morbidity associated with the addition of tonsillectomy does not at present justify recommendation for removal of the tonsils in addition to adenoidectomy for cases with SOM . Tonsillectomy in these children should be assessed on grounds of tonsillar pathology per se and not on the status of the middle ear CONTEXT Adenoidectomy and adenotonsillectomy are commonly performed in US children to reduce the occurrence of persistent or recurrent otitis media , but evidence supporting the efficacy of the operations is limited . OBJECTIVES To test the efficacy of adenoidectomy and adenotonsillectomy in children with persistent or recurrent otitis media who had not previously undergone tube placement and to compare the relative efficacy of adenoidectomy alone vs adenotonsillectomy in such children . DESIGN Two parallel r and omized clinical trials . SETTING AND PARTICIPANTS A total of 461 children aged 3 to 15 years were enrolled at Children 's Hospital of Pittsburgh , Pa , between April 1980 and April 1994 . Four hundred ten children were observed for up to 3 years . INTERVENTIONS Children without recurrent throat infection or tonsillar hypertrophy ( 304 enrolled ; 266 followed up ) were r and omized to either an adenoidectomy , adenotonsillectomy , or control group ; children who had such conditions ( 157 enrolled ; 144 followed up ) were r and omized to an adenotonsillectomy or control group . MAIN OUTCOME MEASURES Occurrence rate of episodes of acute otitis media by treatment group and estimated proportion of time with otitis media . RESULTS In both trials , most subjects were eligible because of recurrent acute otitis media , with or without persistent otitis media with effusion . A total of 47 children assigned to surgical treatment groups had no surgery . The efficacy of surgery in both trials was modest and limited mainly to the first follow-up year . The largest differences in that year were found in the 3-way trial between the adenotonsillectomy group and the control group : mean annual rate of episodes of acute otitis media , 1.4 vs 2.1 ( P<.001 ) ; and mean estimated percentage of time with otitis media , 18.6 % vs 29.9 % ( difference , 11.3 % ; 95 % confidence interval , 4.4%-18.2 % ; P=.002 ) . Perioperative and postoperative complications or other adverse events occurred not infrequently , especially among subjects undergoing adenotonsillectomy ( 14.6 % ) . CONCLUSIONS Our study showed limited and short-term efficacy of both adenoidectomy and adenotonsillectomy ; given the risks , morbidity , and costs of these procedures , these data suggest that neither operation should ordinarily be considered as a first surgical intervention in children whose only indication is recurrent acute otitis media The treatment of deafness secondary to glue ear by grommet insertion is compared to To investigate the mechanism whereby adenoidectomy influences the subsequent course of patients with chronic otitis media with effusion , we analyzed , on the basis of adenoid size , the outcomes of 476 children r and omly assigned to receive , after paracentesis and aspiration of the middle ear , either no treatment , tympanostomy tubes , adenoidectomy , or both . The two groups receiving adenoidectomy did significantly better than those who did not , and the effect was independent of adenoid size . This suggests that reduction of the adenoidal bacterial reservoir may be the mechanism whereby adenoidectomy is effective A prospect i ve study was conducted of the effects of adenoidectomy and adenotonsillectomy on established otitis media with effusion unresponsive to medical treatment . The operations were performed at r and om with a controlled no surgery group on a cohort of 103 children with the condition and the results assessed six weeks , three months , six months , nine months , and one year later . After adenoidectomy the rate of resolution of the condition increased from 39 % at six weeks to 72 % at one year ; and after adenotonsillectomy the rate increased from 59 % at six weeks to 62 % at one year . In the no surgery group the rate increased from 16 % at six weeks to 26 % at one year . Compared with the no surgery group the effect of adenoidectomy alone at one year was highly significant ( p less than 0.001 ) , and similarly the effect of adenotonsillectomy was significant ( p less than 0.01 ) . There was , however , no increased benefit from the addition of tonsillectomy compared with adenoidectomy alone . Thus there was resolution of 36 - 46 % of chronic effusions as a result of adenoidectomy OBJECTIVE --To measure the time to spontaneous resolution of severe chronic otitis media with effusion ( glue ear ) in children and study the effects of adenoidectomy , adenotonsillectomy , and ventilation tubes ( grommets ) . DESIGN --R and omised controlled study over 12 years . SETTING --Paediatric otorhinolaryngology clinics and in-patient unit . SUBJECTS--228 children aged 2 - 9 years with pronounced hearing loss from glue ear and persistent bilateral middle ear effusions confirmed on three occasions over three months . INTERVENTIONS --Children were r and omly allocated to adenotonsillectomy , adenoidectomy , or neither procedure . In all groups a Shepard type ventilation tube was inserted in one r and omly chosen ear . Follow up was annually for five years and then less often for up to seven years four months . For analysis the two operated groups were combined . MAIN OUTCOME MEASURES --Otoscopic clearance of fluid , change in tympanogram , and improvement in mean audiometric hearing threshold . RESULTS --Survival analysis showed appreciable otoscopic and tympanometric resolution of fluid with ventilation tubes alone and adenoidectomy alone compared with no surgery . Further improvement was seen after combination of both treatments . Mean audiometric hearing thresholds improved with fluid resolution . Resolution was delayed in younger children and in those whose parents smoked , irrespective of treatment . Whereas a single insertion of a Shepard tube resolved the glue for a mean ( SD ) period of 9.5 ( 5.2 ) months , the effect of adenoidectomy was sustained throughout follow up . CONCLUSIONS --Treatment of glue ear considerably shortened the time to fluid resolution , combined adenoidectomy and tube insertion being better than either procedure alone . Resolution was longer in younger children and those whose parent(s ) smoked , irrespective of treatment OBJECTIVE --To assess the effect of five different surgical treatments for glue ear ( secretory otitis media ) on improvement in hearing and , assuming one or more treatments to be effective , to identify the appropriate indications for surgery . DESIGN --R and omised controlled trial of children receiving ( a ) adenoidectomy , bilateral myringotomy , and insertion of a unilateral grommet ; ( b ) adenoidectomy , unilateral myringotomy , and insertion of a unilateral grommet ; ( c ) bilateral myringotomy and insertion of a unilateral grommet ; and ( d ) unilateral myringotomy and insertion of a grommet . Children were followed up at seven weeks , six months , 12 months , and 24 months by symptom history and clinical investigations . SETTING --Otolaryngology department in an urban hospital . PATIENTS --149 Children aged 4 - 9 years who were admitted for surgery for glue ear and who had no history of previous operations on tonsils , adenoids , or ears and no evidence of sensorineural deafness . Inadequate follow up information on levels of hearing and on middle ear function was obtained from 22 . MAIN OUTCOME MEASURES --Mean hearing loss ( dB ) of the three worst heard frequencies between 250 and 4000 Hz , results of impedance tympanometry , and parental views on their child 's progress . RESULTS --In the 127 children for whom adequate information was available ears in which a grommet had been inserted performed better in the short term ( for at least six months ) than those in which no grommet had been inserted , irrespective of any accompanying procedure . Most of the benefit had disappeared by 12 months . Adenoidectomy produced a slight improvement that was not significant , though was sustained for at least two years . The ears of children who had had an adenoidectomy with myringotomy and grommet insertion , however , continued to improve so that two years after surgery about 50 % had abnormal tympanometry compared with 83 % of those who had had only myringotomy and grommet insertion , and 93 % of the group that had had no treatment . Logistic regression analyses identified preoperative hearing level as the single best predictor of good outcome from surgery . Other variables contributed little additional predictive power . CONCLUSIONS --If the principal objective of surgery for glue ear is to restore hearing then our study shows that insertion of grommets is the treatment of choice . The addition of an adenoidectomy will increase the likelihood of restoration of normal function of the middle ear but will not improve hearing . When deciding appropriate indications for surgery , a balance has to be made between performing unnecessary operations and failing to treat patients who might benefit from surgical intervention . Preoperative audiometry scores might be the best predictor in helping to make this decision OBJECTIVES To test the effect of adenoidectomy in connection with tympanostomy compared with tympanostomy only in preventing otitis media in children younger than 2 years . DESIGN Prospect i ve trial with r and omized and nonr and omized arms . SETTING Primary care study clinics . PARTICIPANTS AND INTERVENTIONS The study participants were selected from 2497 children who had been enrolled in the Finnish Otitis Media Vaccine Trial at the age of 2 months . A total of 306 children , aged 1 to 2 years , who had experienced recurrent episodes of otitis media were r and omized into 2 treatment groups : tympanostomy with or without adenoidectomy . Of the 306 children , 137 were operated on according to r and om basis ( r and omized trial ) . The 169 children whose parents declined participation in the r and omized trial were operated on according to the parents ' preferences ( nonr and omized trial ) . All children were followed up until 2 years of age . The mean follow-up time was 7 months . MAIN OUTCOME MEASURE The rate of acute otitis media episodes . RESULTS The average reduction in the rate of all acute otitis media episodes in the adenoidectomy group was 19 % ( 95 % confidence interval [ CI ] , -14 % to 43 % ) among children enrolled in the r and omized trial and 25 % ( 95 % CI , -13 % to 50 % ) in the nonr and omized trial . The reduction in the r and omized trial was mainly due to reduction in the rate of pneumococcal otitis media ( 58 % , 95 % CI , 16%-79 % ) . CONCLUSION In children younger than 2 years , concurrent adenoidectomy during the insertion of tympanostomy tubes does not seem to have a major advantage over the insertion of tympanostomy tubes alone in preventing otitis media To study the effectiveness of adenoidectomy and tympanostomy tubes in the treatment of chronic otitis media with effusion , we r and omly assigned 578 4- to 8-year-old children to receive one of the following : Bilateral myringotomy and no additional treatment ( group 1 ) , tympanostomy tubes ( group 2 ) , adenoidectomy and myringotomy ( group 3 ) , or adenoidectomy and tympanostomy tubes ( group 4 ) . The 491 who accepted surgical treatment were evaluated at 6-week intervals for up to 2 years . Treatment effect was assessed by four main outcomes : Time with effusion , time with hearing loss , time to first recurrence of effusion , and number of surgical re-treatments . For the groups ( in order ) , the mean percent of time with any effusion in either ear was 49 , 35 , 30 , 26 ( p < .0001 ) ; the mean percent of time with hearing thresholds 20 dB or greater was 19 , 10 , 8 , and 7 ( p < .0001 ) in the better ear ; and 38 , 30 , 22 and 22 in the worse ear ( p < .0001 ) ; the median number of days to first recurrence was 54 , 222 , 92 , and 240 ( p < .0001 ) ; and the number of surgical re-treatments was 66 , 36 , 17 , and 17 ( p < .0001 ) . The most notable adverse sequela , purulent otorrhea , occurred in 22 % , 29 % , 11 % , and 24 % of the patients assigned to groups 1 through 4 , respectively ( p < .001 ) . In severely affected children who have chronic otitis media with effusion resistant to medical therapy , adenoidectomy is an effective treatment . Adenoidectomy plus bilateral myringotomy lowered posttreatment morbidity more than tympanostomy tubes alone and to the same degree as did adenoidectomy and tympanostomy tubes . Adenoidectomy appears to modify the underlying pathophysiology of chronic otitis media with effusion . This effect is independent of the preoperative size of the adenoid . Tympanostomy tube drainage and ventilation of the middle ear provide adequate palliation so long as the tubes remain in place and functioning . We recommend that adenoidectomy be considered in the initial surgical management of 4- to 8-year-old children with hearing loss due to chronic secretory otitis media that is refractory to medical management and , further , that the size of the adenoid not be used as a criterion for adenoidectomy . Concomitant bilateral myringotomy with suction aspiration of the middle ear contents also should be done , with or without placement of tympanostomy tubes at the discretion of the surgeon The object of this study was to compare the effect on the hearing of the insertion of a grommet , with or without adenoidectomy , against a non-surgically managed control ear in children with persistent hearing impairment due to otitis media with effusion . Seventy-eight children ( 44 boys , 34 girls , mean age 5.8 years ) with documented bilateral otitis media with effusion associated with a bilateral hearing impairment ( pure tone average air conduction thresholds over 0.5 , 1 and 2 kHz of > or = 25 dB HL ) over a three month period were admitted to a r and omized , controlled trial . Each child was r and omized to have or not to have an adenoidectomy . The ears in each child were then r and omly allocated to have a grommet ( tympanostomy tube ) inserted . The children 's hearing status was review ed six and 12 months post-operatively . During follow-up , should a child redevelop a persistent bilateral hearing impairment ( as defined above ) for three months they were managed with a hearing aid . Thus no child had repeat insertion of a grommet . Surgery of each type had an effect on the hearing and the presence of otitis media with effusion at six months post-operatively but not at 12 months when it was no different from natural resolution . If resolution of the otitis media with effusion is the outcome measure , then adenoidectomy alone is significantly better than no surgery but only in boys rather than in girls . Even in boys it only resolves about 60 per cent of effusions . However , when combined with a grommet ( one insertion ) adenoidectomy gives no greater resolution ( 89 per cent compared with 86 per cent ) . ( ABSTRACT TRUNCATED AT 250 WORDS Abstract Objective To evaluate the efficacy of adenoidectomy compared with long term chemoprophylaxis and placebo in the prevention of recurrent acute otitis media in children aged between 10 months and 2 years . Design R and omised , double blind , controlled trial . Setting Oulu University Hospital , a tertiary centre in Finl and . Participants 180 children aged 10 months to 2 years with recurrent acute otitis media . Intervention Adenoidectomy , sulfafurazole ( sulphisoxazole ) 50 mg/kg body weight , given once a day for six months or placebo . Follow up lasted for two years , during which time all symptoms and episodes of acute otitis media were recorded . Main outcome measures Intervention failure ( two episodes in two months or three in six months or persistent effusion ) during follow up , number of episodes of acute otitis media , number of visits to a doctor because of any infection , and antibiotic prescriptions Number of prescriptions , and days with symptoms of respiratory infection . Results Compared with placebo , interventions failed during both the first six months and the rest of the follow up period of 24 months similarly in the adenoidectomy and chemoprophylaxis groups ( at six months the differences in risk were 10 % ( 95 % confidence interval −9 % to 29 % ) and 18 % ( −2 % to 38 % ) , respectively ) . No significant differences were observed between the groups in the numbers of episodes of acute otitis media , visits to a doctor , antibiotic prescriptions , and days with symptoms of respiratory infection . Conclusions Adenoidectomy , as the first surgical treatment of children aged 10 to 24 months with recurrent acute otitis media , is not effective in preventing further episodes . It can not be recommended as the primary method of prophylaxis OBJECTIVE To compare the efficacy of three surgical treatment combinations - myringotomy and tympanostomy tube insertion ( M&T ) , adenoidectomy with M&T ( A-M&T ) , and adenoidectomy with myringotomy ( A-M ) - in reducing middle-ear disease in young children with chronic OME . METHODS Children 24 - 47 months of age , with a history of bilateral middle-ear effusion ( MEE ) for at least 3 months , unilateral for 6 months or longer or unilateral for 3 months after extrusion of a tympanostomy tube , unresponsive to recent antibiotic , were r and omly assigned to either M&T , A-M&T , or A-M. Treatment assignment was stratified by age ( 24 - 35 months , 36 - 47 months ) , nasal obstruction ( no , yes ) and previous history of M&T ( no , yes ) . Subjects were followed monthly and with any signs or symptoms of ear disease for up to 36 months . RESULTS Ninety-eight subjects were r and omly assigned to the three treatment groups . Fifty-six subjects ( 57 % ) were 24 - 35 months of age ; 63 % had nasal obstruction , and 36 % had previously undergone M&T. During the 36 months after entry , subjects were noted to have MEE for the following percentages of time : 18.6 % in the M&T group , 20.6 % in the A-M&T group , and 31.1 % in the A-M group ( M&T vs. A-M&T , p=0.87 ; M&T vs. A-M , p=0.01 ) . By 36 months , there were no differences in the number of further surgical procedures for ear disease needed among the groups . CONCLUSIONS Adenoidectomy with or without tube insertion provided no advantage to young children with chronic OME in regard to time with effusion compared to tube insertion alone . Fewer tympanostomy tubes were placed in children undergoing A-M as their initial procedure , but this should be balanced by the performance of the more invasive surgical procedure and their increased time with effusion Two hundred and twenty two children with bilateral secretory otitis media were allocated at r and om for adenoidectomy , adenotonsillectomy or for neither procedure . In all cases only a unilateral grommet was inserted . The contralateral unoperated ear was examined during a ten year period to show otoscopic clearance , change in tympanometric status and improvement in mean hearing threshold . Adenoidectomy or insertion of a grommet alone produces similar improvement but in combination are more effective than either procedure in isolation . The unoperated ear in cases not receiving either procedure reflects the natural history of the condition . It shows a steady improvement in all outcome measures as time passes To study the effectiveness of adenoidectomy and of the placement of tympanostomy tubes in the treatment of chronic otitis media with effusion , we r and omly assigned 578 children , aged four through eight years , to receive bilateral myringotomy and no additional treatment ( Group 1 ) , placement of tympanostomy tubes ( Group 2 ) , adenoidectomy ( Group 3 ) , or adenoidectomy and placement of tympanostomy tubes ( Group 4 ) . The 491 children who underwent one of these treatments were examined at six-week intervals for up to two years . The mean time spent with effusion of any type in either ear over the two-year follow-up in the four groups was 51 , 36 , 31 , and 27 weeks , respectively ( P less than 0.0001 ) , comparing Group 1 with each of the other groups . Hearing was equivalent in Groups 2 , 3 , and 4 , and was significantly better than in Group 1 . The most frequent sequela , purulent otorrhea , occurred one or more times in 22 , 29 , 11 , and 24 percent of the subjects in Groups 1 , 2 , 3 , and 4 , respectively ( P less than 0.001 ) . Adenoidectomy plus bilateral myringotomy lowered the overall post-treatment morbidity ( as measured by hearing acuity in the most severely affected ear [ P = 0.0174 ] and the number of surgical retreatments required [ P = 0.009 ] ) more than did tympanostomy tubes alone and to the same degree as did adenoidectomy and tympanostomy tubes . We conclude that adenoidectomy should be considered when surgical therapy is indicated in children four to eight years old who are severely affected by chronic otitis media with effusion One hundred children with glue ear , in whom surgical treatment was indicated , were r and omly allocated to 1 of 4 treatment groups . Children in 2 of the groups underwent adenoidectomy plus various combinations of ear operations while in the other 2 groups surgery was confined to the ears . The effect of adenoidectomy was assessed 6 weeks , 6 months and 1 year after surgery by means of audiometry , impedance tympanometry and parental opinion . Improvements in hearing were greater in those children who underwent an adenoidectomy than in those who did not ( 4.0 dB at 6 weeks ; 2.4 dB at 6 months ; 0.7 dB at 1 year ) . However , these differences are of little clinical significance and were only statistically significant ( P less than 0.05 ) 6 weeks after surgery . Middle ear function , measured by tympanometry , revealed a similar pattern of response to treatment . Despite this , 6 months after surgery a higher proportion of parents were satisfied with their child 's condition if an adenoidectomy had been performed . Possible explanations of this discrepancy between clinical and parental assessment s of outcome are discussed Seventy-eight preschool children considered to be suffering from long-st and ing secretory otitis media on the basis of a combination of impaired or abolished mobility of the tympanic membrane and conductive deafness , were examined consecutively . All children underwent bilateral paracentesis . Those children whose ears contained mucous secretion subsequently constituted a prospect i ve longitudinal study group . On the same occasion as the paracentesis was performed , 24 children with bilateral or unilateral mucous secretion in their ears underwent adenoidectomy . Thirty-five non-adenoidectomized children with mucous secretion in one or both ears served as controls . Both groups were followed up for 24 months . At the end of this period they were compared with respect to the state and mobility of the eardrum , a pure tone average audiogram and middle ear impedance . No difference was detected between the two groups . It is therefore concluded that the preventive and therapeutic effects of adenoidectomy on secretory otitis media are doubtful Adenoidectomy is a recommended treatment for otitis media with effusion ( OME ) . This work up- date s a previous report and includes a larger number of 155 cases . Surgery has been allocated at r and om with a control non-adenoidectomy group . The study is prospect i ve and allows for a wide variety of variables . These include age , sex , adenoid size , seasonal variation , observer accuracy , and spontaneous resolution . Adenoidectomy results in clearance of OME even one year following operation in 31 - 45 % of cases . Clearance is related to the duration of history of hearing loss though this may reflect on age effect . Tonsillectomy provides no additional benefit This r and om controlled study was undertaken to determine the extent to which nonsurgical treatment can control otitis media with effusion ( OME ) ; and if surgical treatment is indicated , and myringotomy , removal of middle ear liquid with insertion of aeration tubes is carried out , and whether removal of the adenoids produces any beneficial effect . A preparatory two-month nonsurgical treatment consisting of measures to improve the functional state of the nose was undertaken to eliminate from the study those children ( 42 % ) who would respond to medical treatment alone . The cure rate was similar in each of the operation groups with a greater relapse rate in the nonadenoidectomy groups who required 9 % more aeration tube insertions . An estimation from x-rays of the size of the adenoids , shows that the group cured without surgery has a tendency towards the smaller adenoids . The relapse rate in the nonadenoidectomy group was independent of the size of the adenoids , and the study failed to show that any benefit accrued through adenoidectomy . Accordingly , the removal of adenoids should cease to be indicated in cases of OME as a primary form of treatment Repeated tympanometric screening of a regionally defined population of 3-year-old children defined a group of 42 children with middle ear disease which had persisted for at least 6 months . These children were treated by either myringotomy with adenoidectomy or myringotomy without adenoidectomy decided by r and om allocation . Postoperative observation during 6 months failed to disclose any difference in middle ear status between the two groups 150 children aged between 2 and 9 years ( mean 5.25 years ) with chronic bilateral otitis media with effusion were r and omly allocated to three groups who , in addition to unilateral myringotomy and grommet insertion , would have an adenotonsillectomy , an adenoidectomy , or neither . The contralateral ear was assessed . Otoscopic , impedance , and audiometric findings were recorded preoperatively and at six and twelve months postoperatively . Subtraction of the no-surgery results indicates that at twelve months adenoidectomy produces otoscopic resolution of OME in 41.7 % and no-peak/peak conversion of impedance in 29.8 % . The hearing gain from adenoidectomy alone was similar to that result ing from insertion of a grommet alone , but the children having adenoidectomy required fewer reinsertions to maintain adequate subjective hearing thresholds in the treated ear ( 26 % versus 54 % ) . Tonsillectomy conferred no additional benefit . Without treatment there was a small but significant improvement in all indices at twelve months but not at six months postoperatively We studied the efficacy of adenoidectomy in 213 children who had received tympanostomy-tube placement because of persistent and /or recurrent otitis media and had again developed otitis media after tubal extrusion . Ninety-nine of the children were assigned r and omly to either an adenoidectomy group or a control group ; in a separate trial , 114 children whose parents withheld consent for r and omization were assigned according to parental preference . In both trials , control group outcomes appeared to have been biased favorably by the withdrawal of certain severely affected subjects from control status to receive adenoidectomy . Nonetheless , in both trials , adenoidectomy group outcomes were more favorable than control group outcomes during the first 2 follow-up years . Statistically significant differences were found mainly in the r and omized trial , where during the first and second years , respectively , adenoidectomy subjects had 47 % and 37 % less time with otitis media than control subjects and 28 % and 35 % fewer suppurative ( acute ) episodes than control subjects . We conclude that adenoidectomy is warranted on an individualized basis for children who develop recurrent otitis media after extrusion of tympanostomy tubes OBJECTIVE Nasopharyngeal adenoids may serve as a mechanical obstruction to the eustachian tube and contribute to the pathophysiology of otitis media ( OM ) . The purpose of this study was to determine whether abutment of adenoids laterally against the torus tubaris affects the outcome of patients requiring pressure equalization tubes ( PET ) for OM . STUDY DESIGN R and omized , controlled , prospect i ve clinical trial . METHOD Patients requiring PET for recurrent acute OM or OM with persistent effusion were r and omized into two groups : 1 ) PET placement and 2 ) PET placement and adenoidectomy , regardless of whether the adenoids were abutting or not abutting the torus tubaris . Patients were followed for a minimum of 1 year to determine rate of treatment failure , defined as recurrence of acute OM ( > 3 times/year ) , OM with effusion , or reinsertion of PET . RESULTS Of the 34 patients in the abutting group , 16 patients underwent only PET insertion , of whom 8 ( 50 % ) failed , whereas 18 patients had combined PET placement and adenoidectomy , of whom 3 ( 17 % ) failed . There was a statistical difference between these two groups ( P < 05 ) . Of the 29 patients in the nonabutting group , 24 patients underwent only PET insertion , of whom 9 ( 37.5 % ) failed , whereas 5 patients underwent combined PET placement and adenoidectomy , of whom 2 ( 40 % ) failed . There was no statistical difference between these two groups ( P = .92 ) . CONCLUSION This study demonstrates that the position of hypertrophied adenoids may alter the final otologic outcome of patients requiring PET insertion for OM . Patients with adenoids abutting the torus tubaris may benefit most from an adjuvant adenoidectomy Objective . To evaluate the efficacy of adenoidectomy in reducing the incidence of otitis media among children who are younger than 4 years and receive tympanostomy tubes . Methods . A r and omized trial was conducted at a tertiary center clinic . A total of 217 children who were aged 12 to 48 months and had recurrent acute otitis media ( > 3 episodes during the past 6 months ) or chronic otitis media with effusion , no obstructive symptoms as a result of adenoid enlargement , and no previous surgical intervention were enrolled in the study . Adenoidectomy in conjunction with the insertion of tympanostomy tubes or insertion of tympanostomy tubes without adenoidectomy was studied . The number of otitis media episodes during the follow-up period of 12 months was measured . Results . During the follow-up , the mean number of otitis media episodes was 1.7 among children who underwent adenoidectomy with concurrent insertion of tympanostomy tubes and 1.4 among children who received tympanostomy tubes only . The risk for recurrent otitis media ( ≥3 episodes ) could not be reduced by adenoidectomy ( odds ratio : 1.66 ; 95 % confidence interval : 0.80–3.46 ) . Conclusion . Adenoidectomy does not significantly reduce the incidence of acute otitis media in otitis prone children who are younger than 4 years and receive tympanostomy tubes A prospect i ve controlled study was made on the effect of adenoidectomy performed on 105 children . For various reasons , mainly severe long-st and ing nasal obstruction , 29 children were omitted from the study . The remaining 76 children were r and omly divided into two groups , one adenoidectomy , and one control . Both groups were slightly reduced in number due to drop out . Thus 36 adenoidectomized children were followed during one year and 35 children during two years . The corresponding numbers for the children in the control group were 37 and 33 . The incidence of common cold , purulent and serous otitis media and moderate nasal obstruction was compared in the two groups . A considerable reduction in the incidence of these variables was observed in both groups . The occurrence of moderate nasal obstruction was reduced more among the operated than among the unoperated children . The difference was only slightly significant during the first and not at all during the second year . Regarding the other variables , the differences were not significant , implying that adenoidectomy seems to have no effect on the incidence of common cold , serous and purulent otitis media |
10,750 | 26,110,757 | As the risk of adverse events , including mortality , may be increased by a fraction of inspired oxygen of 60 % or higher , and as robust evidence is lacking for a beneficial effect of a fraction of inspired oxygen of 60 % or higher on surgical site infection , our overall results suggest that evidence is insufficient to support the routine use of a high fraction of inspired oxygen during anaesthesia and surgery . | BACKGROUND Available evidence on the effects of a high fraction of inspired oxygen ( FIO2 ) of 60 % to 90 % compared with a routine fraction of inspired oxygen of 30 % to 40 % , during anaesthesia and surgery , on mortality and surgical site infection has been inconclusive .
Previous trials and meta-analyses have led to different conclusions on whether a high fraction of supplemental inspired oxygen during anaesthesia may decrease or increase mortality and surgical site infections in surgical patients .
OBJECTIVES To assess the benefits and harms of an FIO2 equal to or greater than 60 % compared with a control FIO2 at or below 40 % in the perioperative setting in terms of mortality , surgical site infection , respiratory insufficiency , serious adverse events and length of stay during the index admission for adult surgical patients .We looked at various outcomes , conducted subgroup and sensitivity analyses , examined the role of bias and applied trial sequential analysis ( TSA ) to examine the level of evidence supporting or refuting a high FIO2 during surgery , anaesthesia and recovery . | BACKGROUND Tissue oxygenation is a strong predictor of surgical site infection . Improving tissue oxygenation should thus reduce wound infection risk . Supplemental inspired oxygen can improve tissue oxygenation , but whether it reduces infection risk remains controversial . Low-dose dexamethasone is often given to reduce the risk of postoperative nausea and vomiting , but steroid-induced immunosuppression can increase infection risk . We therefore tested the hypotheses that supplemental perioperative oxygen reduces infection risk and that dexamethasone increases it . METHODS Using a factorial design , patients having colorectal resections expected to last ≥2 h were r and omly assigned to 30 % ( n=270 ) or 80 % ( n=285 ) inspired oxygen during and for 1 h after surgery , and to 4 mg intraoperative dexamethasone ( n=283 ) or placebo ( n=272 ) . Physicians blinded to group assignments evaluated wounds postoperatively , using US Centers for Disease Control criteria . RESULTS Subject and surgical characteristics were similar among study groups . Surgical site infection incidence was similar among groups : 30 % oxygen 15.6 % , 80 % oxygen 15.8 % ( P=1.00 ) ; dexamethasone 15.9 % , placebo 15.4 % , ( P=0.91 ) . CONCLUSIONS Supplemental oxygen did not reduce surgical site infection risk . The preponderance of clinical evidence suggests that administration of 80 % supplemental inspired oxygen does not reduce infection risk . We did not observe an increased risk of surgical site infection with the use of a single low dose of dexamethasone , indicating that it can be used for nausea and vomiting prophylaxis without promoting wound infections . CLINICAL TRIAL REGISTRATION Clinical Trials.gov number : NCT00273377 Background — Oxygen is commonly administered to patients with ST-elevation – myocardial infa rct ion despite previous studies suggesting a possible increase in myocardial injury as a result of coronary vasoconstriction and heightened oxidative stress . Methods and Results — We conducted a multicenter , prospect i ve , r and omized , controlled trial comparing oxygen ( 8 L/min ) with no supplemental oxygen in patients with ST-elevation – myocardial infa rct ion diagnosed on paramedic 12-lead ECG . Of 638 patients r and omized , 441 patients had confirmed ST-elevation – myocardial infa rct ion and underwent primary end-point analysis . The primary end point was myocardial infa rct size as assessed by cardiac enzymes , troponin I , and creatine kinase . Secondary end points included recurrent myocardial infa rct ion , cardiac arrhythmia , and myocardial infa rct size assessed by cardiac magnetic resonance imaging at 6 months . Mean peak troponin was similar in the oxygen and no oxygen groups ( 57.4 versus 48.0 & mgr;g/L ; ratio , 1.20 ; 95 % confidence interval , 0.92–1.56 ; P=0.18 ) . There was a significant increase in mean peak creatine kinase in the oxygen group compared with the no oxygen group ( 1948 versus 1543 U/L ; means ratio , 1.27 ; 95 % confidence interval , 1.04–1.52 ; P=0.01 ) . There was an increase in the rate of recurrent myocardial infa rct ion in the oxygen group compared with the no oxygen group ( 5.5 % versus 0.9 % ; P=0.006 ) and an increase in frequency of cardiac arrhythmia ( 40.4 % versus 31.4 % ; P=0.05 ) . At 6 months , the oxygen group had an increase in myocardial infa rct size on cardiac magnetic resonance ( n=139 ; 20.3 versus 13.1 g ; P=0.04 ) . Conclusion — Supplemental oxygen therapy in patients with ST-elevation – myocardial infa rct ion but without hypoxia may increase early myocardial injury and was associated with larger myocardial infa rct size assessed at 6 months . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT01272713 BACKGROUND Administration of supplemental oxygen in the perioperative period is controversial , as it may increase long-term mortality . Our aim was to assess the association between 80 % oxygen and occurrence of subsequent cancer in patients undergoing abdominal surgery in a post hoc analysis of the PROXI trial . METHODS The 1386 patients in the PROXI trial underwent elective or emergency laparotomy between 2006 and 2008 with r and omization to either 80 % or 30 % oxygen during and for 2 h after surgery . We retrieved follow-up status regarding vital status , new cancer diagnoses , and new histological cancer specimens . Data were analysed using the Cox proportional hazards model . RESULTS Follow-up was complete in 1377 patients ( 99 % ) after a median of 3.9 yr . The primary outcome of new cancer diagnosis or new malignant histological specimen occurred in 140 of 678 patients ( 21 % ) in the 80 % oxygen group vs 150 of 699 patients ( 21 % ) assigned to 30 % oxygen ; hazards ratio 1.06 [ 95 % confidence interval ( CI ) 0.84 , 1.34 ] , P=0.62 . Cancer-free survival was significantly shorter in the 80 % oxygen group ; hazards ratio 1.19 ( 95 % CI 1.01 , 1.42 ) , P=0.04 , as was the time between surgery and new cancer , median 335 vs. 434 days in the 30 % oxygen group . In patients with localized disease , non-significant differences in cancer and cancer-free survival were found with hazard ratios of 1.31 and 1.29 , respectively . CONCLUSIONS Although new cancers occurred at similar rate , the cancer-free survival was significantly shorter in the 80 % oxygen group , but this did not appear to explain the excess mortality in the 80 % oxygen group . CLINICAL TRIAL REGISTRATION Clinical Trials.gov ( NCT01723280 ) Background The role of supplemental oxygen therapy in the healing of colorectal anastomosis is still very much at an experimental stage . The aim of the present study , prospect i ve r and omized , was to assess the effect of administration of perioperative supplemental oxygen therapy on infraperitoneal anastomosis , where the risk of leakage is higher STUDY OBJECTIVE To assess the efficacy of intraoperative inspired oxygen fractions ( FIO(2 ) ) of 0.8 and 0.5 when compared with st and ard FIO(2 ) of 0.3 in the prevention of postoperative nausea and vomiting ( PONV ) . DESIGN Prospect i ve , r and omized , double-blinded , controlled study . SETTING General hospital , postanesthesia care unit ( PACU ) , and gynecology floor room . PATIENTS 120 ASA physical status I and II women , aged 21 to 76 years , undergoing elective gynecologic laparoscopic surgery . INTERVENTIONS Patients were r and omized to receive a gas mixture of 30 % oxygen in air ( FIO(2 ) = 0.3 , Group G30 ) , 50 % oxygen in air ( FIO(2 ) = 0.5 , Group G50 ) , or 80 % oxygen in air ( FIO(2 ) = 0.8 , Group G80 ) ; there were 36 patients in each group . A st and ardized sevoflurane general anesthesia , postoperative pain management , and antiemetic regimen were used . MEASUREMENTS Frequency of nausea , vomiting , and both was assessed for early ( 0 to two hrs ) and late PONV ( two to 24 hrs ) , along with use of rescue antiemetic , degree of nausea , and severity of pain . MAIN RESULTS There was no overall difference in the frequency of PONV at the early and late assessment periods among the three groups . G80 patients had significantly less vomiting than Group G30 at two hours , 3 % ( 1/36 ) vs. 22 % ( 8/36 ) , respectively , P = 0.028 . Nausea scores , rescue antiemetic use , pain scores , and opioid consumption did not differ among the groups . CONCLUSION High intraoperative FIO(2 ) of 0.8 and FIO(2 ) of 0.5 do not prevent PONV in patients without antiemetic prophylaxis . An intraoperative FIO(2 ) of 0.8 has a beneficial effect on early vomiting only BACKGROUND Perioperative supplemental oxygen has been proposed to decrease the incidence of surgical site infection ( SSI ) in colorectal surgery with controversial results . We have assessed the influence of hyperoxygenation on SSI by using the most homogeneous study population . METHODS We studied , in a prospect i ve r and omized study , 81 patients , who underwent elective open infraperitoneal anastomosis for rectal cancer . Patients were assigned r and omly to an oxygen/air mixture with a fraction of inspired oxygen ( FiO2 ) of 30 % ( n = 41 ) or 80 % ( n = 40 ) . Administration was commenced after induction of anesthesia and maintained for 6 hours after surgery . RESULTS The overall wound infection rate was 21 % : 11 patients ( 26.8 % ) had wound infections in the 30 % FiO2 group and 6 ( 15 % ) in the 80 % FiO2 group ( P < .05 ) . The risk of SSI was 41 % lower in the 80 % FiO2 group . CONCLUSION Supplemental 80 % FiO2 reduced postoperative SSI with few risks to the patient and little associated cost OBJECTIVE The purpose of this study was to investigate whether supplemental oxygen during and for 2 hours after cesarean delivery reduces the incidence of postcesarean infectious morbidity . STUDY DESIGN We conducted a r and omized , controlled trial from 2008 - 2010 . Women who underwent cesarean delivery were r and omly assigned to receive either 2 L of oxygen by nasal cannula during cesarean delivery only ( st and ard care ) or 10 L of oxygen by nonrebreather mask ( intervention group ) during and for 2 hours after cesarean delivery . Women who underwent scheduled or intrapartum cesarean delivery were eligible and were observed for 1 month after the procedure . The primary composite outcome was maternal infectious morbidity , which included endometritis and wound infection . RESULTS Five hundred eighty-five women were included in the final analysis . Infectious morbidity occurred in 8.8 % of patients in the st and ard care group and in 12.2 % of patients in the supplemental oxygen group . There was no significant difference in the rate of infectious morbidity between the st and ard care and intervention groups ( relative risk , 1.4 ; 95 % confidence interval , 0.9 - 2.3 ) . CONCLUSION Supplemental oxygen does not reduce the rate of postcesarean delivery infectious morbidity , including endometritis and wound infection BACKGROUND : There is a plausible pathophysiologic rationale for increased long-term cardiovascular morbidity and mortality in patients receiving significant exposure to nitrous oxide . However , this relationship has not been established clinical ly . The ENIGMA trial r and omized 2050 patients having noncardiac surgery lasting more than 2 hours to nitrous oxide – based or nitrous oxide – free anesthesia . We conducted a follow-up study of the ENIGMA patients to evaluate the risk of cardiovascular events in the longer term . METHODS : The trial case report forms and medical records of all study patients were review ed . The date and cause of death and occurrence of myocardial infa rct ion or stroke were recorded . A telephone interview was then conducted with all surviving patients . The primary endpoint of the study was survival . RESULTS : The median follow-up time was 3.5 ( range : 0 to 5.7 ) years . Three hundred eighty patients ( 19 % ) had died since the index surgery , 91 ( 4.5 % ) were recorded as having myocardial infa rct ion , and 44 ( 2.2 % ) had a stroke during the entire follow-up period . Nitrous oxide did not significantly increase the risk of death [ hazard ratio = 0.98 ( 95 % confidence interval , CI : 0.80 to 1.20 ; P = 0.82 ) ] . The adjusted odds ratio for myocardial infa rct ion in patients administered nitrous oxide was 1.59 ( 95 % CI : 1.01 to 2.51 ; P = 0.04 ) and for stroke was 1.01 ( 95 % CI : 0.55 to 1.87 ; P = 0.97 ) . CONCLUSIONS : The administration of nitrous oxide was associated with increased long-term risk of myocardial infa rct ion , but not of death or stroke in patients enrolled in the ENIGMA trial . The exact relationship between nitrous oxide administration and serious long-term adverse outcomes will require confirmation by an appropriately design ed large r and omized controlled trial Background The role of supplemental oxygen therapy in the healing of colorectal anastomosis is still very much at an experimental stage . The aim of the present study , prospect i ve r and omized , was to assess the effect of administration of perioperative supplemental oxygen therapy on infraperitoneal anastomosis , where the risk of leakage is higher . Methods We enrolled 72 patients between February , 2008 and February , 2011 , who underwent elective open infraperitoneal anastomosis for rectal cancer ( middle and low ) . Patients were assigned r and omly to an oxygen/air mixture with a fraction of inspired oxygen ( FiO2 ) of 30 % ( n = 37 ) or 80 % ( n = 35 ) . Administration was commenced after induction of anesthesia and maintained for 6 h after surgery . Results The overall anastomotic leak rate was 16.6 % ( 12 out of 72 ) ; 8 patients ( 21.6 % ) had an anastomotic dehiscence in the 30 % FiO2 group and 4 ( 11.4 % ) in the 80 % FiO2 group ( p < 0.05 ) . The risk of anastomotic leak was 46 % lower in the 80 % FiO2 group ( RR , 0.63 ; 95 % confidence interval , 0.42–0.98 ) vs. the 30 % FiO2 . Conclusion Therefore , supplemental 80 % FiO2 during and for 6 h after major rectal cancer surgery , reducing postoperative anastomotic dehiscence , should be considered part of ongoing quality improvement activities related to surgical care , with few risks to the patient and little associated cost BACKGROUND : A high perioperative inspiratory oxygen fraction ( 80 % ) has been recommended to prevent postoperative wound infections . However , the most recent and one of the largest trials , the PROXI trial , found no reduction in surgical site infection , and 30-day mortality was higher in patients given 80 % oxygen . In this follow-up study of the PROXI trial we assessed the association between long-term mortality and perioperative oxygen fraction in patients undergoing abdominal surgery . METHODS : From October 8 , 2006 , to October 6 , 2008 , 1386 patients underwent elective or emergency laparotomy and were r and omized to receive either 80 % or 30 % oxygen during and for 2 hours after surgery . The follow-up date was February 24 , 2010 . Survival was analyzed using Kaplan-Meier statistics and the Cox proportional hazards model . RESULTS : Vital status was obtained in 1382 of 1386 patients after a median follow-up of 2.3 years ( range 1.3 to 3.4 years ) . One hundred fifty-nine of 685 patients ( 23.2 % ) died in the 80 % oxygen group compared to 128 of 701 patients ( 18.3 % ) assigned to 30 % oxygen ( HR , 1.30 [ 95 % confidence interval , 1.03 to 1.64 ] , P = 0.03 ) . In patients undergoing cancer surgery , the HR was 1.45 ; 95 % confidence interval , 1.10 to 1.90 ; P = 0.009 ; and after noncancer surgery , the HR was 1.06 ; 95 % confidence interval , 0.69 to 1.65 ; P = 0.79 . CONCLUSIONS : Administration of 80 % oxygen in the perioperative period was associated with significantly increased long-term mortality and this appeared to be statistically significant in patients undergoing cancer surgery but not in noncancer patients Purpose Postoperative nausea and vomiting are among the most common and distressing side effects of general anesthesia . Supplemental intraoperative 80 % oxygen reduces postoperative nausea and vomiting following open and laparoscopic abdominal surgery . However , this benefit has not been observed in other patient population s. We undertook this study to evaluate the effect of 80 % supplemental intraoperative oxygen on the incidence of postoperative nausea and vomiting following ambulatory surgery for laparoscopic tubal ligation . Methods Following Research Ethics Board approval , 304 subjects were enrolled into one of two arms of a r and omized prospect i ve controlled study . The intervention group ( n = 147 ) breathed 80 % oxygen and the control group ( n = 145 ) breathed routine 30 % oxygen ( balance medical air ) while both groups were receiving a st and ardized general anesthetic . Nausea was assessed as : none , mild , moderate , or severe ; vomiting was any emetic episode or retching . Any assessment either greater than none ( nausea ) or greater than zero ( vomiting ) was considered positive . Results The incidence of postoperative nausea and vomiting up to 24 hr following surgery was 69 % in the 80 % oxygen intervention group and 65 % in the 30 % oxygen control group ( P = 0.62 ) . There were no differences in nausea alone , vomiting , or antiemetic use in the postoperative anesthetic care unit or at any time ( pre- or post-discharge ) up to 24 hr after surgery . Conclusions This trial of 304 women did not demonstrate that administering intraoperative supplemental 80 % oxygen during ambulatory surgery for laparoscopic tubal ligation prevented postoperative nausea or vomiting during the initial postoperative 24 hr compared with women who received routine 30 % oxygen . RésuméObjectifLes nausées et vomissements postopératoires sont parmi les effets secondaires les plus courants et pénibles de l’anesthésie générale . L’oxygène peropératoire supplémentaire à 80 % réduit les nausées et vomissements postopératoires après les chirurgies abdominales ouvertes et par laparoscopie . Toutefois , ce bienfait n’a pas été observé dans d’autres population s de patients . Nous avons entrepris cette étude afin d’évaluer l’effet d’oxygène peropératoire supplémentaire à 80 % sur l’incidence des nausées et vomissements postopératoires après une chirurgie ambulatoire de ligature tubaire par laparoscopie . MéthodeAprès avoir reçu l’approbation du Comité d’éthique de la recherche , 304 patientes ont été enrôlées dans deux groupes d’une étude prospect i ve r and omisée et contrôlée . Le groupe intervention ( n = 147 ) a respiré de l’oxygène à 80 % et le groupe témoin ( n = 145 ) a respiré de l’oxygène normal à 30 % ( air médical équilibré ) , et les deux groupes ont reçu un anesthésique général st and ardisé . Les nausées ont été évaluées selon l’échelle suivante : aucune , légères , modérées , ou graves ; tout épisode émétique ou haut-le-cœur a été considéré comme un vomissement . Toute évaluation rendant des résultats plus élevés que ‘ aucune ’ ( nausées ) ou ‘ zéro ’ ( vomissements ) a été considérée positive . RésultatsL’incidence des nausées et vomissements postopératoires jusqu’à 24 heures après la chirurgie était de 69 % dans le groupe intervention ( oxygène 80 % ) et de 65 % dans le groupe témoin ( oxygène 30 % ) ( P = 0,62 ) . Il n’y a pas eu de différence dans les nausées seules , les vomissements ou le recours à des antiémétiques dans l’unité de soins anesthésiques postopératoires ou en tout temps ( avant et après le congé de l’hôpital ) durant les premières 24 heures après la chirurgie . Conclusion Cette étude portant sur 304 femmes n’a pas démontré que l’administration peropératoire d’oxygène supplémentaire à 80 % pendant une chirurgie ambulatoire de ligature tubaire par laparoscopie a prévenu les nausées et vomissements postopératoires pendant les 24 premières heures par rapport à des patientes recevant de l’oxygène à 30 % utilisé normalement Supplemental oxygen maintained during and for 2 h after colon resection halves the incidence of nausea and vomiting . Whether supplemental oxygen restricted to the intraoperative period is sufficient remains unknown . Similarly , the relative efficacy of supplemental oxygen and ondansetron is unknown . We tested the hypothesis that intraoperative supplemental oxygen reduces the incidence of postoperative nausea and vomiting . Patients ( n = 240 ) undergoing gynecological laparoscopy were given a st and ardized isoflurane anesthetic . After induction , they were r and omly assigned to the following three groups : routine oxygen administration with 30 % oxygen , balance nitrogen ( 30 % Oxygen group ) , supplemental oxygen administration with 80 % oxygen , balance nitrogen ( 80 % Oxygen group ) , and Ondansetron 8 mg ( immediately after induction ) , combined with 30 % oxygen , balance nitrogen ( Ondansetron group ) . The overall incidence of nausea and /or vomiting during the initial 24 postoperative h was 44 % in the patients assigned to 30 % oxygen and 30 % in the Ondansetron group , but only 22 % in those given 80 % oxygen . The incidence was thus halved by supplemental oxygen and was significantly less than with 30 % oxygen . There were , however , no significant differences between the 30 % oxygen and ondansetron groups , or between the ondansetron and 80 % oxygen groups . We conclude that supplemental oxygen effectively prevents postoperative nausea and vomiting after gynecological laparoscopic surgery ; furthermore , ondansetron is no more effective than supplemental oxygen . IMPLICATION S Supplemental oxygen reduces the risk of postoperative nausea and vomiting ( PONV ) as well or better than 8 mg of ondansetron . Because oxygen is inexpensive and essentially risk-free , supplemental oxygen is a preferable method of reducing PONV OBJECTIVE To determine if an evidence -based practice bundle would result in a significantly lower rate of surgical site infections ( SSIs ) when compared with st and ard practice . DESIGN Single-institution , r and omized controlled trial with blinded assessment of main outcome . The trial opened in April 2007 and was closed in January 2010 . SETTING Veterans Administration teaching hospital . PATIENTS Patients who required elective transabdominal colorectal surgery were eligible . A total of 241 subjects were approached , 211 subjects were r and omly allocated to 1 of 2 interventions , and 197 were included in an intention-to-treat analysis . INTERVENTIONS Subjects received either a combination of 5 evidence d-based practice s ( extended arm ) or were treated according to our current practice ( st and ard arm ) . The interventions in the extended arm included ( 1 ) omission of mechanical bowel preparation ; ( 2 ) preoperative and intraoperative warming ; ( 3 ) supplemental oxygen during and immediately after surgery ; ( 4 ) intraoperative intravenous fluid restriction ; and ( 5 ) use of a surgical wound protector . MAIN OUTCOME MEASURE Overall SSI rate at 30 days assessed by blinded infection control coordinators using st and ardized definitions . RESULTS The overall rate of SSI was 45 % in the extended arm of the study and 24 % in the st and ard arm ( P = .003 ) . Most of the increased number of infections in the extended arm were superficial incisional SSIs ( 36 % extended arm vs 19 % st and ard arm ; P = .004 ) . Multivariate analysis suggested that allocation to the extended arm of the trial conferred a 2.49-fold risk ( 95 % confidence interval , 1.36 - 4.56 ; P = .003 ) independent of other factors traditionally associated with SSI . CONCLUSIONS An evidence -based intervention bundle did not reduce SSIs . The bundling of interventions , even when the constituent interventions have been individually tested , does not have a predictable effect on outcome . Formal testing of bundled approaches should occur prior to implementation CONTEXT Selective reporting of outcomes within published studies based on the nature or direction of their results has been widely suspected , but direct evidence of such bias is currently limited to case reports . OBJECTIVE To study empirically the extent and nature of outcome reporting bias in a cohort of r and omized trials . DESIGN Cohort study using protocol s and published reports of r and omized trials approved by the Scientific-Ethical Committees for Copenhagen and Frederiksberg , Denmark , in 1994 - 1995 . The number and characteristics of reported and unreported trial outcomes were recorded from protocol s , journal articles , and a survey of trialists . An outcome was considered incompletely reported if insufficient data were presented in the published articles for meta- analysis . Odds ratios relating the completeness of outcome reporting to statistical significance were calculated for each trial and then pooled to provide an overall estimate of bias . Protocol s and published articles were also compared to identify discrepancies in primary outcomes . MAIN OUTCOME MEASURES Completeness of reporting of efficacy and harm outcomes and of statistically significant vs nonsignificant outcomes ; consistency between primary outcomes defined in the most recent protocol s and those defined in published articles . RESULTS One hundred two trials with 122 published journal articles and 3736 outcomes were identified . Overall , 50 % of efficacy and 65 % of harm outcomes per trial were incompletely reported . Statistically significant outcomes had a higher odds of being fully reported compared with nonsignificant outcomes for both efficacy ( pooled odds ratio , 2.4 ; 95 % confidence interval [ CI ] , 1.4 - 4.0 ) and harm ( pooled odds ratio , 4.7 ; 95 % CI , 1.8 - 12.0 ) data . In comparing published articles with protocol s , 62 % of trials had at least 1 primary outcome that was changed , introduced , or omitted . Eighty-six percent of survey responders ( 42/49 ) denied the existence of unreported outcomes despite clear evidence to the contrary . CONCLUSIONS The reporting of trial outcomes is not only frequently incomplete but also biased and inconsistent with protocol s. Published articles , as well as review s that incorporate them , may therefore be unreliable and overestimate the benefits of an intervention . To ensure transparency , planned trials should be registered and protocol s should be made publicly available prior to trial completion AIM An association has been proposed between perioperative administration of 80 % oxygen and a lower incidence of wound infection after colorectal surgery . The present study was conducted to assess this hypothesis . METHODS Thirty-eight patients ( ASA classification 1 and 2 ) undergoing elective colorectal cancer surgery were allocated at r and om to 2 groups . Group 1 consisted of 19 patients who received an admixture of 80 % oxygen and 20 % nitrogen during anesthesia through an orotracheal tube and during the 2 first hours in the recovery room through a tight facemask with reservoir . Group 2 consisted of 19 patients who received an admixture of 70 % nitrous oxide and 30 % oxygen during anesthesia , followed by administration of 30 % oxygen delivered by a blender through a tight facemask with reservoir in the same manner than group 1 , during the first 2 hours in the recovery room . Wound infection was evaluated daily during hospital stay and after 7 days , 2 weeks , and 1 month . RESULTS The incidence of wound infection was 12.5 % in group 1 and 17.6 % in group 2 ( p=0.53 ) . CONCLUSIONS The results of this study showed no reduction in the incidence of wound infection following elective colorectal surgery in patients receiving 80 % oxygen during the perioperative period Supplemental 80 % oxygen administration halves the incidence of postoperative nausea and vomiting ( PONV ) in in patients . Whether it prevents PONV after ambulatory surgery is unknown . We tested the efficacy of supplemental 80 % oxygen in decreasing the incidence of PONV after ambulatory gynecologic laparoscopy . One hundred patients were given a st and ardized sevoflurane anesthetic . They were r and omly assigned to two groups : routine oxygen administration with 30 % oxygen , balance nitrogen ( Group A ) ; and supplemental oxygen with 80 % oxygen , balance nitrogen ( Group B ) . Oxygen was administered during surgery and up to 1 h after surgery . The incidence of nausea and vomiting and the need for rescue antiemetics did not differ between the groups in the postanesthesia care unit , in the Phase II unit , or during the 24-h follow-up . The overall incidence of nausea and vomiting during the first postoperative 24 h was 62 % in Group A and 55 % in Group B ( P = 0.486 ) . There were no differences in the recovery profiles and patient satisfaction between the groups . In this study , supplemental oxygen did not prevent PONV in patients undergoing ambulatory gynecologic laparoscopy Purpose One hundred percent O2 is used routinely for preoxy-genation and induction of anesthesia . The higher the O2 concentration the faster is the development of atelectasis , an important cause of impaired pulmonary gas exchange during general anesthesia ( GA ) . We evaluated the effect of ventilation with 0.4FiO2 in air , 0.4FiO2 in N2O and 100 % O2 following intubation on the development of impaired gas exchange . Methods Twenty-seven patients aged 18–40 yr , undergoing elective laparoscopic cholecystectomy were administered 100 % O2 for preoxygenation ( three minutes ) and ventilation by mask ( two minutes ) . Following intubation these patients were r and omly divided into three groups of nine each and ventilated either with 0.4FiO2 in air , 0.4FiO2 in N2O or 100 % O2 . Arterial blood gases were obtained before preoxygenation and 30 min following intubation for PaO2 analysis . Subsequently PaO2/FiO2 ratios were calculated . Results were analyzed with Student ’s t test and one-way ANOVA . P value of ≤ 0.05 was considered significant . Results Ventilation of the lungs with O2 in air ( FiO2 0.4 ) significantly improved the PaO2/FiO2 ratio from baseline , while 0.4FiO2 in N2O or 100 % O2 worsened the ratio ( 558 ± 47vs 472 ± 28 , 365 ± 34vs 472 ± 22 and 351 ± 23 vs 477 ± 28 respectively ; P < 0.05 ) . Conclusion Ventilation of lungs with O2 in air ( FiO2 0.4 ) improves gas exchange in young healthy patients during GA.RésuméObjectifCent pour cent d’O2 sont utilisés habituellement pour la préoxygénation et l’induction de l’anesthésie . Plus la concentration d’O2 est élevée , plus vite peut se développer l’atélectasie , une cause importante d’anomalie des échanges gazeux pulmonaires pendant l’anesthésie générale ( AG ) . Nous avons évalué l’effet de la ventilation avec uneFiO2 de 0,4 dans de l’air , FiO2 de 0,4 dans du N2O et 100 % d’O2 après l’intubation qu and apparaissent les anomalie des échanges gazeux . MéthodeVingt-sept patients de 18–40 ans , devant subir une cholé-cystectomie laparoscopique non urgente ont reçu 100 % d’O2 pour la préoxygénation , pendant trois minutes , et la ventilation au masque , pendant deux minutes . Après l’intubation , ces patients ont été répartis de façon aléatoire en trois groupes de neuf et ventilés avec 0,4FiO2 dans de l’air ou 0,4FiO2 dans du N2O ou 100 % d’O2 . La gazométrie du sang artériel a été obtenue pendant la préoxygénation et 30 min après l’intubation pour l’analyse de la PaO2 . Par la suite , les ratios PaO2/FiO2 ont été calculés . Les résultats ont été analysés selon le test t de Student et une analyse de variance à une voie . Une valeur de P ≤ 0,05 a été considérée comme significative . RésultatsLa ventilation pulmonaire avec de l’O2 dans de l’air ( FiO2 de 0,4 ) a sensiblement amélioré le ratio PaO2/FiO2 , comparativement aux données de base , t and is que 0,4FiO2 dans du N2O ou 100 % d’O2 l’ont altéré ( 558 ± 47vs 472 ± 28 , 365 ± 34 vs 472 ± 22 et 351 ± 23 vs 477 ± 28 respectivement ; P < 0,05 ) . Conclusion La ventilation pulmonaire avec de l’O2 dans de l’air ( FiO2 0,4 ) améliore les échanges gazeux chez les jeunes patients pendant l’AG Background : Benefits and limitations of supplementation with 80 % fraction of inspired oxygen for preventing surgical site infections have not yet been clearly defined . Some studies have reported benefits in colorectal surgery , whereas trials in abdominal and gynecologic surgery have reported either no effect or a deleterious effect . Methods : Controlled , r and omized , assessor-blind multicenter trial , the ISO2 study , comparing the effects of hyperoxygenation ( fraction of inspired oxygen , 80 % ) with those of 30 % oxygen on the frequency of surgical site infections in routine abdominal , gynecologic , and breast surgery on 434 patients . Patients not seen in consultation after discharge were contacted . Results : In total , 208 patients received 30 % perioperative oxygen and 226 received 80 % . There was no difference between the two groups for baseline , intraoperative , and postoperative characteristics , except for oxygen saturation at closure , higher in the 80 % group ( P = 0.01 ) . The frequency of 30-day surgical site infections was 7.2 % ( 15/208 ) in the 30 % group and 6.6 % ( 15/226 ) in the 80 % group ( relative risk , 0.92 ; 95 % CI [ 0.46–1.84 ] , P = 0.81 ) . Frequency of adverse events ( nausea and vomiting , sternal pain , cough , hypotension ) was similar in the two groups . Desaturation and bradycardia were more frequent in the 30 % group . In an up date d meta- analysis including the result of this trial and those of eight published r and omized trials , the overall relative risk was 0.97 ; 95 % CI ( 0.68–1.40 ) , I2 ( inconsistency degree ) = 73 % , ( P = 0.88 ) . Conclusions : The routine use of hyperoxygenation throughout abdominal , gynecologic , and breast surgery had no effect on the frequency of 30-day surgical site infections and was not accompanied by more frequent adverse effects CONTEXT Use of 80 % oxygen during surgery has been suggested to reduce the risk of surgical wound infections , but this effect has not been consistently identified . The effect of 80 % oxygen on pulmonary complications has not been well defined . OBJECTIVE To assess whether use of 80 % oxygen reduces the frequency of surgical site infection without increasing the frequency of pulmonary complications in patients undergoing abdominal surgery . DESIGN , SETTING , AND PATIENTS The PROXI trial , a patient- and observer-blinded r and omized clinical trial conducted in 14 Danish hospitals between October 2006 and October 2008 among 1400 patients undergoing acute or elective laparotomy . INTERVENTIONS Patients were r and omly assigned to receive either 80 % or 30 % oxygen during and for 2 hours after surgery . MAIN OUTCOME MEASURES Surgical site infection within 14 days , defined according to the Centers for Disease Control and Prevention . Secondary outcomes included atelectasis , pneumonia , respiratory failure , and mortality . RESULTS Surgical site infection occurred in 131 of 685 patients ( 19.1 % ) assigned to receive 80 % oxygen vs 141 of 701 ( 20.1 % ) assigned to receive 30 % oxygen ( odds ratio [ OR ] , 0.94 ; 95 % confidence interval [ CI ] , 0.72 - 1.22 ; P = .64 ) . Atelectasis occurred in 54 of 685 patients ( 7.9 % ) assigned to receive 80 % oxygen vs 50 of 701 ( 7.1 % ) assigned to receive 30 % oxygen ( OR , 1.11 ; 95 % CI , 0.75 - 1.66 ; P = .60 ) , pneumonia in 41 ( 6.0 % ) vs 44 ( 6.3 % ) ( OR , 0.95 ; 95 % CI , 0.61 - 1.48 ; P = .82 ) , respiratory failure in 38 ( 5.5 % ) vs 31 ( 4.4 % ) ( OR , 1.27 ; 95 % CI , 0.78 - 2.07 ; P = .34 ) , and mortality within 30 days in 30 ( 4.4 % ) vs 20 ( 2.9 % ) ( OR , 1.56 ; 95 % CI , 0.88 - 2.77 ; P = .13 ) . CONCLUSION Administration of 80 % oxygen compared with 30 % oxygen did not result in a difference in risk of surgical site infection after abdominal surgery . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00364741 This review summarizes the (patho)-physiological effects of ventilation with high FiO2 ( 0.8–1.0 ) , with a special focus on the most recent clinical evidence on its use for the management of circulatory shock and during medical emergencies . Hyperoxia is a cornerstone of the acute management of circulatory shock , a concept which is based on compelling experimental evidence that compensating the imbalance between O2 supply and requirements ( i.e. , the oxygen dept ) is crucial for survival , at least after trauma . On the other h and , “ oxygen toxicity ” due to the increased formation of reactive oxygen species limits its use , because it may cause serious deleterious side effects , especially in conditions of ischemia/reperfusion . While these effects are particularly pronounced during long-term administration , i.e. , beyond 12–24 h , several retrospective studies suggest that even hyperoxemia of shorter duration is also associated with increased mortality and morbidity . In fact , albeit the clinical evidence from prospect i ve studies is surprisingly scarce , a recent meta- analysis suggests that hyperoxia is associated with increased mortality at least in patients after cardiac arrest , stroke , and traumatic brain injury . Most of these data , however , originate from heterogenous , observational studies with inconsistent results , and therefore , there is a need for the results from the large scale , r and omized , controlled clinical trials on the use of hyperoxia , which can be anticipated within the next 2–3 years . Consequently , until then , “ conservative ” O2 therapy , i.e. , targeting an arterial hemoglobin O2 saturation of 88–95 % as suggested by the guidelines of the ARDS Network and the Surviving Sepsis Campaign , represents the treatment of choice to avoid exposure to both hypoxemia and excess hyperoxemia Objectives To compare st and ard high flow oxygen treatment with titrated oxygen treatment for patients with an acute exacerbation of chronic obstructive pulmonary disease in the prehospital setting . Design Cluster r and omised controlled parallel group trial . Setting Ambulance service in Hobart , Tasmania , Australia . Participants 405 patients with a presumed acute exacerbation of chronic obstructive pulmonary disease who were treated by paramedics , transported , and admitted to the Royal Hobart Hospital during the trial period ; 214 had a diagnosis of chronic obstructive pulmonary disease confirmed by lung function tests in the previous five years . Interventions High flow oxygen treatment compared with titrated oxygen treatment in the prehospital ( ambulance/paramedic ) setting . Main outcome measure Prehospital or in-hospital mortality . Results In an intention to treat analysis , the risk of death was significantly lower in the titrated oxygen arm compared with the high flow oxygen arm for all patients ( high flow oxygen n=226 ; titrated oxygen n=179 ) and for the subgroup of patients with confirmed chronic obstructive pulmonary disease ( high flow n=117 ; titrated n=97 ) . Overall mortality was 9 % ( 21 deaths ) in the high flow oxygen arm compared with 4 % ( 7 deaths ) in the titrated oxygen arm ; mortality in the subgroup with confirmed chronic obstructive pulmonary disease was 9 % ( 11 deaths ) in the high flow arm compared with 2 % ( 2 deaths ) in the titrated oxygen arm . Titrated oxygen treatment reduced mortality compared with high flow oxygen by 58 % for all patients ( relative risk 0.42 , 95 % confidence interval 0.20 to 0.89 ; P=0.02 ) and by 78 % for the patients with confirmed chronic obstructive pulmonary disease ( 0.22 , 0.05 to 0.91 ; P=0.04 ) . Patients with chronic obstructive pulmonary disease who received titrated oxygen according to the protocol were significantly less likely to have respiratory acidosis ( mean difference in pH 0.12 ( SE 0.05 ) ; P=0.01 ; n=28 ) or hypercapnia ( mean difference in arterial carbon dioxide pressure −33.6 ( 16.3 ) mm Hg ; P=0.02 ; n=29 ) than were patients who received high flow oxygen . Conclusions Titrated oxygen treatment significantly reduced mortality , hypercapnia , and respiratory acidosis compared with high flow oxygen in acute exacerbations of chronic obstructive pulmonary disease . These results provide strong evidence to recommend the routine use of titrated oxygen treatment in patients with breathlessness and a history or clinical likelihood of chronic obstructive pulmonary disease in the prehospital setting . Trial registration Australian New Zeal and Clinical Trials Register ACTRN12609000236291 BACKGROUND Supplemental intra-operative oxygen 80 % halves the incidence of nausea and vomiting after open and laparoscopic abdominal surgery , perhaps by ameliorating intestinal ischaemia associated with abdominal surgery . It is unlikely that thyroid surgery compromises intestinal perfusion . We therefore tested the hypothesis that supplemental perioperative oxygen does not reduce the risk of postoperative nausea and vomiting ( PONV ) after thyroidectomy . METHODS One hundred and fifty patients undergoing thyroidectomy were given sevoflurane anaesthesia . After induction , patients were r and omly assigned to the following treatments : ( i ) . 30 % oxygen , ( ii ) . 80 % oxygen , or ( iii ) . 30 % oxygen with droperidol 0.625 mg . RESULTS The overall incidence of nausea during the first 24 h after surgery was 48 % in the patients given oxygen 30 % , 46 % in those given oxygen 80 % , and 22 % in those given droperidol ( P=0.004 ) . There were no significant differences between the oxygen 30 % and 80 % groups in incidence or severity of PONV , the need for rescue antiemetics , or patient satisfaction . Droperidol significantly shortened the time to first meal . CONCLUSIONS Supplemental oxygen was ineffective in preventing nausea and vomiting after thyroidectomy , but droperidol reduced the incidence Background Subcutaneous tissue oxygen tension ( PsqO2 ) is a major predictor for wound healing and the occurrence of wound infections . Perioperative subcutaneous wound and tissue oxygen tension is significantly reduced in morbidly obese patients . Even during intraoperative supplemental oxygen administration , PsqO2 remains low . Tissue hypoxia is pronounced during surgery and might explain the substantial increase in infection risk in obese patients . It remains unknown whether long-term supplemental postoperative oxygen augments tissue oxygen tension . Consequently , we tested the hypothesis that 80 % inspired oxygen administration during 12–18 postoperative hours significantly increases PsqO2 compared to 30 % inspired oxygen fraction . Methods After IRB approval and informed consent , 42 patients undergoing laparoscopic bariatric surgery were r and omly assigned to receive either 80 % inspired oxygen via a PULMANEX Hi-Ox ™ Mask ( Viasys MedSystems , Wheeling , IL ) ( 10 L/min ) or 30 % oxygen via nasal cannula ( 2 L/min ) after surgery until the next morning . PsqO2 was measured with a temperature-corrected Clark-type electrode in the subcutaneous tissue of the upper arm and adjacent to the wound . Results Postoperative subcutaneous tissue oxygen tension was significantly increased in the Hi-Ox group : 58 ( 47.7 , 74.1 ) mmHg vs. 43 ( 38.7 , 55.2 ) mmHg , P = 0.002 . Also , wound tissue oxygen tension was improved during supplemental oxygen administration : 75.2 ( 69.8 , 95.5 ) mmHg vs. 52.4 ( 46.3 , 66.1 ) mmHg , P < 0.001 . ConclusionS ubcutaneous tissue oxygen tension was significantly increased by supplemental postoperative oxygen administration . Whether there is an effect on the incidence of wound infection in morbidly obese patients is matter of further research OBJECTIVE : Most postcesarean infections are caused by anaerobic bacteria . Oxidative killing , an important defense against surgical infections , depends on the oxygen level in contaminated tissue . Among patients undergoing colorectal surgery , perioperative supplemental oxygen decreased infection rates by 50 % . We tested the hypothesis that high-concentration inspired oxygen decreases the incidence of surgical site infection in women undergoing cesarean delivery . METHODS : Using a double blind technique , 143 women undergoing cesarean delivery under regional anesthesia after the onset of labor were r and omly assigned to receive low- or high-concentration inspired oxygen via nonrebreathing mask during the operation and for 2 hours after . Surgical site infection was defined clinical ly as administration of antibiotics for postpartum endometritis or wound infection during the initial hospital stay or within 14 days of surgery . Interim statistical analysis was performed after 25 % of the planned sample size ( 143 of 550 ) accrued using intention-to-treat principle . The stopping rule P value for futility was P>.11 with two planned interim analyses . RESULTS : Postcesarean infection occurred in 17 ( 25 % , 95 % confidence interval [ CI ] 15–35 % ) of 69 women assigned to high-concentration oxygen compared with 10 ( 14 % , 95 % CI 6–22 % ) of 74 women assigned to low-concentration inspired oxygen ( relative risk 1.8 , 95 % CI 0.9–3.7 , P=.13 ) . The P value exceeded the P value for futility , suggesting these differences were unlikely to reach statistical significance with continued recruitment . CONCLUSION : High-concentration perioperative oxygen delivered through a nonrebreathing mask did not decrease the risk of postcesarean surgical site infection . CLINICAL TRIAL REGISTRATION : Clinical Trials.gov , www . clinical trials.gov , NCT00670020 LEVEL OF EVIDENCE : BACKGROUND Postoperative nausea and vomiting ( PONV ) is one of the most frequent complications after general anaesthesia . Single-dose antiemetic prophylaxis has limited efficacy in high-risk patients . Adding a simple potential antiemetic approach , such as increasing the inspired oxygen fraction , to the antiemetic portfolio would preserve pharmacological interventions for treatment of symptoms in the postoperative period . However , the antiemetic effect of a high inspired oxygen fraction is still discussed controversially . The aim of the study was to evaluate whether an inspired oxygen fraction of 0.8 decreases PONV in patients receiving the 5-HT3-antagonist dolasetron . METHODS In a r and omized , placebo-controlled , double-blinded trial we studied 377 patients ( ASA I-III ) undergoing elective laparoscopic cholecystectomy . Induction of anaesthesia was st and ardized , including thiopental fentanyl and cis-atracurium . For all patients the individual risk for PONV was calculated using the Koivuranta score and all patients received 12.5 mg dolasetron i.v . before surgery . Patients were allocated r and omly to one of three groups : Group A ( n=125 ) received 80 % oxygen in air , Group B ( n=125 ) 40 % oxygen in air and Group C ( n=127 ) 40 % oxygen in nitrous oxide . Postoperative nausea , postoperative vomiting ( PV ) , or nausea , vomiting , or both ( PONV ) was assessed in the early ( 0 - 4 h ) and overall postoperative period ( 0 - 24 h ) by an anaesthesiologist unaware of patient allocation . RESULTS There was a significantly lower incidence of PONV and PV in Groups A ( PONV : 11.2 % ; PV : 3.2 % ) and B ( PONV : 10.4 % ; PV : 3.2 % ) compared with Group C ( PONV : 26.7 % ; PV : 13.3 % ) , but there were no significant differences between Groups A and B. CONCLUSIONS An inspired oxygen fraction of 0.8 does not further decrease PONV or vomiting in dolasetron-treated patients undergoing laparoscopic cholecystectomy . The lower incidence of PONV in Groups A and B compared with Group C is most likely caused by the omission of nitrous oxide OBJECTIVE To assess the influence of hyperoxygenation on surgical site infection by using the most homogeneous study population . DESIGN A r and omized , prospect i ve , controlled trial . SETTING Department of surgery in a government hospital . PATIENTS A total of 210 patients who underwent open surgery for acute appendicitis . In the study group , patients received 80 % oxygen during anesthesia , followed by high-flow oxygen for 2 hours in the recovery room . The control group received 30 % oxygen , as usual . INTERVENTION Open appendectomy via incision in the right lower quadrant of the abdomen . MAIN OUTCOME MEASURES Surgical site infection , mainly assessed by the ASEPSIS ( additional treatment , serous discharge , erythema , purulent discharge , separation of deep tissues , isolation of bacteria , and stay in hospital prolonged > 14 days ) system score . RESULTS Surgical site infections were recorded in 6 of 107 patients ( 5.6 % ) in the study group vs 14 of 103 patients ( 13.6 % ) in the control group ( P = .04 ) . Significant differences in the ASEPSIS score were also found . The mean hospital stay was longer in the control group ( 2.92 days ) compared with the study group ( 2.51 days ) ( P = .01 ) . CONCLUSION The use of supplemental oxygen is advantageous in operations for acute appendicitis by reducing surgical site infection rate and hospital stay . TRIAL REGISTRATION clinical trials.gov Identifier : NCT01002365 BACKGROUND AND OBJECTIVE it has been shown that supplemental oxygen reduces the incidence of postoperative nausea and vomiting ( PONV ) in patients undergoing colon surgery . Serotonin is a potent trigger of PONV . Theoretically , supplemental oxygen decreases gut ischaemia during surgery and in this way minimizes the release of serotonin . We investigated the release of serotonin during and after colorectal surgery with normal and supplemental oxygen administration . METHODS patients ( n = 53 ) undergoing colon surgery were r and omly assigned to one of two intraoperative ventilation regimens : group A ( n = 30 ) received 80 % oxygen and 20 % nitrogen mixed with desflurane and group B ( n = 23 ) received 30 % oxygen and 70 % nitrogen mixed with desflurane . To verify oxygenation status , we measured the arterial oxygen partial pressure ( pO2 ) by blood gas analysis and the intramuscular tissue oxygenation using a polarographic microoxygen sensor ( Licox , GMS , Mielkendorf , Germany ) . Serotonin levels in plasma and in platelets were measured using high-performance liquid chromatography ( HPLC ) before the beginning of surgery ( T0 ) , at the end of surgery ( T1 ) , and 2 h ( T2 ) , 8 h ( T3 ) and 24 h ( T4 ) postoperatively . PONV was assessed in the early ( 0 - 4 h ) and overall ( 0 - 24 h ) postoperative period by an anaesthesiologist unaware of patients ' treatment regime . RESULTS at T1 , T2 and T3 , serotonin levels were significantly ( T1 ' 80 % group ' 80 ± 68.2 vs. ' 30 % group ' 147 ± 130.5 ; T2 ' 80 % group ' 78.4 ± 61 vs. ' 30 % group ' 139 ± 103 ; T3 ' 80 % group ' 76.2 ± 49.5 vs. ' 30 % group ' 124 ± 73.7 ; P < 0.05 ) reduced in the ' 80 % oxygen group ' . Patients in the ' 80 % group ' showed a significantly higher pO2 and subcutaneous tissue oxygenation ( ptO2 ) . The overall incidence of PONV was significantly reduced in the ' 80 % oxygen group ' ( ' 80 % group ' 7 % vs. ' 30 % group ' 35 % ) . CONCLUSION an inspired oxygen fraction of 0.8 reduces serotonin levels significantly and decreases PONV significantly in patients undergoing colon surgery Background : Although a high fraction of inspired oxygen ( FIO2 ) could reduce surgical site infection , there is concern it could increase postoperative pulmonary complications , including hypoxemia . Intraoperative positive end-expiratory pressure can improve postoperative pulmonary function . A practical measure of postoperative pulmonary function and the degree of hypoxemia is supplemental oxygen requirement . We performed a double-blind r and omized 2 × 2 factorial study on the effects of intraoperative FIO2 0.3 versus more than 0.9 with and without positive end-expiratory pressure on the primary outcome of postoperative supplemental oxygen requirements in patients undergoing lower risk surgery . Methods : After Institutional Review Board approval and consent , 100 subjects were r and omized using computer-generated lists into four treatment groups ( intraoperative FIO2 0.3 vs. more than 0.9 , with and without 3–5 cm H2O positive end-expiratory pressure ) . Thirty minutes and 24 h after extubation , supplemental oxygen was discontinued . Arterial oxygen saturation by pulse oximetry was recorded 15 min later . If oxygen saturation decreased to less than 90 % , supplemental oxygen was added incrementally to maintain saturation more than 90 % . Results : Nearly all subjects required supplemental oxygen in the postanesthesia care unit . Nonparametric Wilcoxon rank sum test demonstrated no statistically significant difference between groups in supplemental oxygen requirements at 45 min and 24 h after tracheal extubation ( P = 0.56 and 0.98 , respectively ) . Conclusions : Use of intraoperative FIO2 more than 0.9 was not associated with increased oxygen requirement , suggesting it does not induce postoperative hypoxemia beyond anesthetic induction and surgery . Therefore , it may be reasonable to use high inspired oxygen in surgical patients with relatively normal pulmonary function BACKGROUND Nitrous oxide inactivates vitamin B12 and methionine synthase , thereby impairing DNA formation and , consequently , new cell formation . The gas also inhibits methionine production , which can reduce scar formation and depresses chemotactic migration by monocytes . Therefore , we assessed whether nitrous oxide increases the incidence of surgical wound infection . METHODS We recruited 418 patients aged 18 - 80 years , scheduled for colon resection that was expected to last more than 2 h , at three hospitals in Austria and Hungary . Patients were r and omly assigned 65 % intraoperative nitrous oxide ( n=208 ) or nitrogen ( n=206 ) , with remifentanil and isoflurane . The primary outcome was the incidence of clinical postoperative wound infection , analysed by intention to treat . FINDINGS 206 patients in the nitrous oxide group and 202 in the nitrogen group were included in the final analysis . Duration of surgery was longer in the nitrogen group ( 3.4 h [ 1.5 ] ) than in the nitrous oxide group ( 3.0 h [ SD 1.3 ] ) and arterial pressure ( 84 mm Hg [ 10 ] vs 81 mm Hg [ 9 ] ) , bispectral index values ( 53 [ 9 ] vs 44 [ 8 ] ) , and end-tidal isoflurane concentration ( 0.64 % [ 0.14 ] vs 0.56 % [ 0.13 ] ) were greater in patients given nitrogen than in those given nitrous oxide . Infection rate was 15 % ( 31/206 ) in patients given nitrous oxide and 20 % ( 40/202 ) in those given nitrogen ( p=0.205 ) . Additionally , the ASEPSIS wound healing score , wound collagen deposition , number of patients admitted to critical care unit , time to first food ingestion , duration of hospital stay , and mortality did not differ between treatment groups . INTERPRETATION Nitrous oxide does not increase the incidence of surgical wound infection OBJECTIVE Hyperglycemia has been found to occur in children placed on cardiopulmonary bypass . Our laboratory demonstrated that hyperoxia plays a role in this hyperglycemic response and also occurs in the absence of cardiopulmonary bypass . The purpose of this study was to eluci date potential mechanisms underlying the hyperoxic-induced hyperglycemia by examining glucagon , insulin , and epinephrine , which are important in glucose regulation and skeletal and cardiac glucose transporters ( GLUT1 and GLUT4 ) , which facilitate glucose entry . METHODS Three-day-old piglets were anesthetized , intubated , and ventilated to normoxia . Animals were then r and omly allocated to either 5 hours of normoxia ( n = 4 ) or hyperoxia ( n = 6 ) . Measurements of oxygen , blood glucose , plasma glucagon , insulin , and epinephrine levels were made . Total GLUT1 and GLUT4 content in cardiac and skeletal muscle was measured using Western blotting analysis . RESULTS A sustained hyperglycemic response ( P < .001 ) was seen throughout the 5-hour ventilatory period . A significant twofold elevation in glucagon levels ( P < .001 ) and a threefold elevation ( P < .003 ) in plasma insulin levels occurred , despite no significant changes in plasma epinephrine . Total GLUT1 and GLUT4 content were significantly reduced in skeletal muscle by 66 % and 59 % , respectively , while no significant changes occurred in cardiac muscle . CONCLUSION This study demonstrates that significant elevations in glucagon and insulin and reductions in total skeletal muscle GLUT1 and GLUT4 content all contribute to hyperoxia-induced hyperglycemia seen in newborns . To optimize postoperative recovery of newborns , consideration should be given to the levels of oxygen used to avoid the potential development of insulin resistance and subsequent decrease in glucose entry The effects on tissue oxygenation of postoperative adjuvant oxygen have been studied in a group of 20 patients undergoing below-knee ( BK ) amputation for vascular disease . Ten patients received no therapy , the remainder receiving 28 % oxygen for 48 hours following surgery . The results showed that the trancutaneous p02 in the amputation flaps fell significantly by some 20 mmHg ( p<0.01 ) following surgery and that this fall was prevented by the use of adjuvant oxygen . The fall was not observed in the non-amputated limbs . Tcp02 took almost two weeks to reach its pre-operative levels in the amputated limbs . The effect on stump healing of adjuvant oxygen therapy was investigated in a r and omized controlled trial in a series of 39 patients undergoing BK amputation . There were 22 patients in the control ( untreated ) group and 17 in the treated group ( adjuvant oxygen for 48 hours ) . In the treated group 14 patients healed primarily and three amputations failed . In the untreated group 14 limbs healed primarily , one secondarily and there were 7 failures . The pre-operative transcutaneous values in the stumps which failed ( 26 mmHg±14 ) was significantly lower ( p<0.005 ) than in those which healed ( 40 mmHg±9 ) . The mean pre-operative Tcp02 in the patients in whom healing occurred in the treated group ( 35 mmHg±10 ) was significantly lower ( p<0.001 ) than the mean pressure observed in the untreated group ( 44 mmHg±9 ) Background : Nitrous oxide is widely used in anesthesia , often administered at an inspired concentration around 70 % . Although nitrous oxide interferes with vitamin B12 , folate metabolism , and deoxyribonucleic acid synthesis and prevents the use of high inspired oxygen concentrations , the consequences of these effects are unclear . Methods : Patients having major surgery expected to last at least 2 h were r and omly assigned to nitrous oxide – free ( 80 % oxygen , 20 % nitrogen ) or nitrous oxide – based ( 70 % N2O , 30 % oxygen ) anesthesia . Patients and observers were blind to group identity . The primary endpoint was duration of hospital stay . Secondary endpoints included duration of intensive care stay and postoperative complications ; the latter included severe nausea and vomiting , and the following major complications : pneumonia , pneumothorax , pulmonary embolism , wound infection , myocardial infa rct ion , venous thromboembolism , stroke , awareness , and death within 30 days of surgery . Results : Of 3,187 eligible patients , 2,050 consenting patients were recruited . Patients in the nitrous oxide – free group had significantly lower rates of major complications ( odds ratio , 0.71 ; 95 % confidence interval , 0.56–0.89 ; P = 0.003 ) and severe nausea and vomiting ( odds ratio , 0.40 ; 95 % confidence interval , 0.31–0.51 ; P < 0.001 ) , but median duration of hospital stay did not differ substantially between groups ( 7.0 vs. 7.1 days ; P = 0.06 ) . Among patients admitted to the intensive care unit postoperatively , those in the nitrous oxide – free group were more likely to be discharged from the unit on any given day than those in the nitrous oxide group ( hazard ratio , 1.35 ; 95 % confidence interval , 1.05–1.73 ; P = 0.02 ) . Conclusions : Avoidance of nitrous oxide and the concomitant increase in inspired oxygen concentration decreases the incidence of complications after major surgery , but does not significantly affect the duration of hospital stay . The routine use of nitrous oxide in patients undergoing major surgery should be question ed Background : Postoperative nausea and vomiting ( PONV ) is a distressing problem after strabismus surgery . An inspired oxygen fraction has been reported to decrease PONV in patients after colon resection and to be more effective than ondansetron after gynecologic laparoscopy . Therefore , in a r and omized , prospect i ve , placebo-controlled study , the authors tested whether an inspired oxygen fraction of 0.8 decreases PONV in patients undergoing strabismus surgery and whether oxygen is more effective than ondansetron . Methods : With approval of the authors ’ institutional review board , 210 patients were r and omly assigned to receive one of three treatments : ( 1 ) 30 % inspired oxygen in air plus intravenous administration of saline , ( 2 ) 80 % inspired oxygen in air plus intravenous administration of saline , or ( 3 ) 30 % inspired oxygen in air plus 75 & mgr;g/kg ondansetron intravenously during induction . General anesthesia was st and ardized and included etomi date , alfentanil , and mivacurium for induction and sevoflurane for maintenance . PONV was evaluated 6 and 24 h postoperatively by an investigator unaware of treatment assignment . Results : Overall postoperative incidence of nausea and vomiting was 41 % for inspired oxygen fraction of 0.3 plus placebo , 38 % for inspired oxygen fraction of 0.8 plus placebo , and 28 % for inspired oxygen fraction of 0.3 plus ondansetron , respectively ( P = 0.279 ) . Therefore , there was no statistically significant difference of PONV incidence among groups . Conclusions : An inspired oxygen fraction of 0.8 during general anesthesia with sevoflurane does not decrease PONV in patients undergoing strabismus repair . Ondansetron also did not significantly decrease PONV in our study setting Background and objective Obesity aggravates the negative effects of general anaesthesia and surgery on the respiratory system , result ing in decreased functional residual capacity and expiratory reserve volume , and increased atelectasis and ventilation/perfusion ( Va/Q ) mismatch . High-inspired oxygen concentrations also promote atelectasis . This study compares the effects of perioperative inspired low-oxygen and high-oxygen concentrations on postoperative lung function and pulse oximetry values in moderately obese patients ( BMI 25–35 ) . Methods We prospect ively studied 142 overweight patients , BMI 25–35 , undergoing minor peripheral surgery ; they were r and omly allocated to receive either low-inspired or high-inspired oxygen concentrations during general anaesthesia . Premedication , general anaesthesia and respiratory patterns were st and ardized . Arterial oxygen saturation ( pulse oximetry ) was measured on air breathing . Inspiratory and expiratory lung functions were measured preoperatively ( baseline ) and at 10 min , 0.5 , 2 and 24 h after extubation with the patient supine , in a 30 ° head-up position . The two groups were compared using repeated-measure analysis of variance and t-test analysis . Results The low-inspired oxygen group had significantly better arterial saturation during the first 24 h ( P < 0.01 ) . Mid-expiratory flow 25 values indicating small airway collapse were significantly better in the low-oxygen group at all measurements ( P < 0.05 ) . Conclusion We conclude that postoperative lung function and arterial saturation is better preserved by a low-oxygen strategy , although it is not clear whether this has clinical relevance for the prevention of postoperative pulmonary complications OBJECTIVE : To evaluate whether supplemental perioperative oxygen decreases surgical site wound infections or endometritis . STUDY DESIGN : This was a prospect i ve , r and omized trial . Patients who were to undergo cesarean delivery were recruited and r and omly allocated to either 30 % or 80 % oxygen during the cesarean delivery and for 1 hour after surgery . The obstetricians and patients were blinded to the concentration of oxygen used . Patients were evaluated for wound infection or endometritis during their hospital stay and by 6 weeks postpartum . The primary end point was a composite of either surgical site infection or endometritis . RESULTS : Eight hundred thirty-one patients were recruited . Of these , 415 participants received 30 % oxygen perioperatively and 416 received 80 % oxygen . The groups were well matched for age , race , parity , diabetes , number of previous cesarean deliveries , and scheduled compared with unscheduled cesarean deliveries . An intention-to-treat analysis was used . There was no difference in the primary composite outcome ( 8.2 % in women who received 30 % oxygen compared with 8.2 % in women who received 80 % oxygen , P=.89 ) , no difference in surgical site infection in the two groups ( 5.5 % compared with 5.8 % , P=.98 ) , and no significant difference in endometritis in the two groups ( 2.7 % compared with 2.4 % , P=.66 ) , respectively . CONCLUSION : Women who received 80 % supplemental oxygen perioperatively did not have a lower rate of a surgical site infection or endometritis as compared with women who received 30 % supplemental oxygen concentration . CLINICAL TRIAL REGISTRATION : Clinical Trials.gov , www.clincaltrials.gov , NCT00876005 . LEVEL OF EVIDENCE : BACKGROUND Higher concentrations of fraction of inspired oxygen ( FIO2 ) have been shown to be associated with lower risk for surgical site infection in multiple studies outside the domain of orthopedic surgery . We evaluated the efficacy of high FIO2 administered during the perioperative period to reduce the rate of surgical site infection after open fixation of lower-extremity fractures at high risk of infection . METHODS We conducted a r and omized controlled , parallel design , double-blind study . Patients sustaining high-energy tibial plateau , tibial pilon , and calcaneus fractures treated in a staged fashion were selected for enrollment because these injuries are associated with high risk of infection . The study population included 222 patients with 235 fractures . Consenting patients were r and omized by r and om number sequence to either the treatment or the control group . Treatment group patients received 80 % FIO2 intraoperatively and for 2 hours afterward . Control group patients received 30 % FIO2 during the same period . Surgeons , patients , and personnel who performed wound assessment s were blinded to group assignment . The primary outcome measure was surgical site infection as defined by the Centers for Disease Control criteria for postoperative wound infection . RESULTS The overall rates of postoperative surgical site infection were 12 % ( 14 of 119 fractures ) in the treatment group and 16 % ( 19 of 116 fractures ) in the control group ( p = 0.31 ) . Multivariate analysis , accounting for risk factors for infection , yielded the closest to a statistically significant reduction in the odds of infection with treatment ( odds ratio , 0.54 ; p = 0.17 ) . No treatment-associated events were observed . CONCLUSION Use of a high concentration of FIO2 during the perioperative period is safe and shows a trend toward reduction of surgical site infection in patients undergoing open operative fixation of high-energy traumatic lower-extremity fractures . Further study in a larger patient population is indicated . LEVEL OF EVIDENCE Therapeutic study , level III Background Surgical wound infection ( SWI ) is a common complication after peripheral vascular surgery . Infections increase morbidity and costs of treatment . The aim of the present study was to test the hypothesis that supplemental postoperative oxygen decreases the incidence of SWI after lower limb revascularization . Methods This prospect i ve , r and omized , multicenter , single-blinded trial was conducted between May 2009 and February 2010 in six secondary referral hospitals in Finl and . We r and omly allocated 274 patients undergoing surgery for lower limb revascularization to the study group ( n = 137 ) or a control group ( n = 137 ) . The study group received supplemental inspired oxygen for the first 2 days after surgery . The main outcome was SWI . Patients were followed up for 30 days or until the SWI was healed . Logistic regression analysis was used to assess the independent effect of supplemental oxygen on the incidence of SWI . Results Altogether 63 ( 23 % ) patients developed SWI ; 47 ( 75 % ) of the infections were superficial . There were two vascular graft infections . SWI occurred in 25 patients ( 18.2 % ) in the study group and in 38 patients ( 27.7 % ) in the control group [ odds ratio ( OR ) 0.56 , 95 % confidence interval ( CI ) 0.30–1.04 ; P = 0.07 ] . In isolated groin incisions , 3 patients of 52 ( 5.8 % ) in the study group and 12 patients of 51 ( 23.5 % ) in the control group developed SWI ; OR = 0.20 , 95 % CI 0.04–0.95 ; P = 0.04 . Conclusions There was an indication that supplemental inspired oxygen tended to decrease the incidence of SWI after lower limb vascular surgery . In isolated groin incisions , the decrease of SWI incidence in the supplemental oxygen group was significant Background The role of supplemental oxygen therapy in the healing of esophagojejunal anastomosis is still very much in an experimental stage . The aim of the present prospect i ve , r and omized study was to assess the effect of administration of perioperative supplemental oxygen therapy on esophagojejunal anastomosis , where the risk of leakage is high . Methods We enrolled 171 patients between January 2009 and April 2012 who underwent elective open esophagojejunal anastomosis for gastric cancer . Patients were assigned r and omly to an oxygen/air mixture with a fraction of inspired oxygen ( FiO2 ) of 30 % ( n = 85 ) or 80 % ( n = 86 ) . Administration commenced after induction of anesthesia and was maintained for 6 h after surgery . Results The overall anastomotic leak rate was 14.6 % ( 25 of 171 ) : 17 patients ( 20 % ) had an anastomotic dehiscence in the 30 % FiO2 group and 8 ( 9.3 % ) in the 80 % FiO2 group ( P < 0.05 ) . The risk of anastomotic leak was 49 % lower in the 80 % FiO2 group ( relative risk 0.61 ; 95 % confidence interval 0.40–0.95 ) versus 30 % FiO2 . Conclusions Supplemental 80 % FiO2 provided during and for 6 h after major gastric cancer surgery to reduce postoperative anastomotic dehiscence should be considered part of ongoing quality improvement activities related to surgical care , with few risks to the patient and little associated cost OBJECTIVE To determine if supplemental perioperative oxygen will reduce surgical site infection ( SSI ) following cesarean delivery . METHODS This is a r and omized , controlled trial evaluating SSI following either 30 % or 80 % fraction of inspired oxygen ( FIO2 ) during and 2 hours after cesarean delivery . Anesthesia providers administered FIO2 via a high-flow oxygen blender . Subjects , surgeons , and wound evaluation teams were blinded . Serial wound evaluations were performed . Data were analyzed using logistic regression models , Fisher exact test , and t test . RESULTS In all , 179 women were r and omized , and 160 subjects were included in the analysis . There were 12/83 ( 14.5 % ) SSIs in the control group versus 10/77 ( 13.0 % ) in the investigational group ( p = 0.82 ) . Caucasian race , increased body mass index , and longer operative time were identified as significant risk factors for infection ( p = 0.026 , odds ratio 0.283 ; p = 0.05 , odds ratio = 1.058 ; p = 0.037 , odds ratio = 1.038 , respectively ) . CONCLUSION Perioperative oxygenation with 80 % Fio2 is not effective in reducing SSI following cesarean delivery OBJECTIVE To test the hypothesis that subcutaneous wound oxygen tension ( PsqO2 ) has a predictive relation to the development of wound infection in surgical patients . DESIGN A noninterventional , prospect i ve study . SETTING A university department of surgery . PATIENTS One hundred thirty operative general surgical patients at notable risk of infection as predicted by an anticipated Study on the Effect of Nosocomial Infection Control ( SENIC ) score of 1 or greater . OUTCOME MEASURES PsqO2 was measured perioperatively . Its relation to the subsequent incidence of surgical wound infection was then determined and compared with the SENIC score as a criterion st and ard . RESULTS Although the SENIC score and PsqO2 are inversely correlated , PsqO2 is the stronger predictor of infection . Low PsqO2 identified patients at risk and concentrated them in a cohort that was about half the size of that identified by the SENIC score . CONCLUSIONS Subcutaneous perfusion and oxygenation are important components of immunity to wound infections . The SENIC score identifies systemic physiological variables that are important to the development of wound infection . Nevertheless , PsqO2 is the more powerful predictor of wound infection . Moreover , PsqO2 can be manipulated by available clinical means , and thus may direct interventions to prevent infection CONTEXT Surgical site infection ( SSI ) in the general surgical population is a significant public health issue . The use of a high fractional inspired concentration of oxygen ( FIO2 ) during the perioperative period has been reported to be of benefit in selected patients , but its role as a routine intervention has not been investigated . OBJECTIVE To determine whether the routine use of high FIO2 during the perioperative period alters the incidence of SSI in a general surgical population . DESIGN , SETTING , AND PATIENTS Double-blind , r and omized controlled trial conducted between September 2001 and May 2003 at a large university hospital in metropolitan New York City of 165 patients undergoing major intra-abdominal surgical procedures under general anesthesia . INTERVENTIONS Patients were r and omly assigned to receive either 80 % oxygen ( FIO2 of 0.80 ) or 35 % oxygen ( FIO2 of 0.35 ) during surgery and for the first 2 hours after surgery . MAIN OUTCOME MEASURES Presence of clinical ly significant SSI in the first 14 days after surgery , as determined by clinical assessment , a management change , and at least 3 prospect ively defined objective criteria . RESULTS The study groups were closely matched in a large number of clinical variables . The overall incidence of SSI was 18.1 % . In an intention-to-treat analysis , the incidence of infection was significantly higher in the group receiving FIO2 of 0.80 than in the group with FIO2 of 0.35 ( 25.0 % vs 11.3 % ; P = .02 ) . FIO2 remained a significant predictor of SSI ( P = .03 ) in multivariate regression analysis . Patients who developed SSI had a significantly longer length of hospitalization after surgery ( mean [ SD ] , 13.3 [ 9.9 ] vs 6.0 [ 4.2 ] days ; P<.001 ) . CONCLUSIONS The routine use of high perioperative FIO2 in a general surgical population does not reduce the overall incidence of SSI and may have predominantly deleterious effects . General surgical patients should continue to receive oxygen with cardiorespiratory physiology as the principal determinant High intra‐operative oxygen concentration reportedly reduces postoperative nausea and vomiting ( PONV ) , but recent data are conflicting . Therefore , we tested whether the effectiveness of supplemental oxygen depends on the endpoint ( nausea vs. vomiting ) , observation interval ( early vs. late ) or surgical field ( abdominal vs. non‐abdominal ) . We r and omly assigned 560 adult patients undergoing various elective procedures with a PONV risk of at least 40 % to intra‐operative 80 % ( supplemental ) or 30 % oxygen ( control ) . Potential confounding factors were similar between groups . Incidences of nausea were similar in the groups during early ( 12 % ( supplemental ) vs. 10 % ( control ) , p = 0.43 ) and late intervals , 26%vs . 20 % , p = 0.09 , as were the incidences of vomiting ( early : 2%vs . 3 % , p = 0.40 ; late : 8%vs . 9 % , p = 0.75 ) . Supplemental oxygen was no more effective at reducing PONV in abdominal ( 40%vs . 31 % , p = 0.37 ) than in non‐abdominal surgery ( 25%vs . 21 % , p = 0.368 ) . Thus , supplemental oxygen was unable to reduce PONV independent of the endpoint , observational period or site of surgery BACKGROUND Destruction by oxidation , or oxidative killing , is the most important defense against surgical pathogens and depends on the partial pressure of oxygen in contaminated tissue . An easy method of improving oxygen tension in adequately perfused tissue is to increase the concentration of inspired oxygen . We therefore tested the hypothesis that the supplemental administration of oxygen during the perioperative period decreases the incidence of wound infection . METHODS We r and omly assigned 500 patients undergoing colorectal resection to receive 30 percent or 80 percent inspired oxygen during the operation and for two hours afterward . Anesthetic treatment was st and ardized , and all patients received prophylactic antibiotic therapy . With use of a double-blind protocol , wounds were evaluated daily until the patient was discharged and then at a clinic visit two weeks after surgery . We considered wounds with culture-positive pus to be infected . The timing of suture removal and the date of discharge were determined by the surgeon , who did not know the patient 's treatment-group assignment . RESULTS Arterial oxygen saturation was normal in both groups ; however , the arterial and subcutaneous partial pressure of oxygen was significantly higher in the patients given 80 percent oxygen than in those given 30 percent oxygen . Among the 250 patients who received 80 percent oxygen , 13 ( 5.2 percent ; 95 percent confidence interval , 2.4 to 8.0 percent ) had surgical-wound infections , as compared with 28 of the 250 patients given 30 percent oxygen ( 11.2 percent ; 95 percent confidence interval , 7.3 to 15.1 percent ; P=0.01 ) . The absolute difference between groups was 6.0 percent ( 95 percent confidence interval , 1.2 to 10.8 percent ) . The duration of hospitalization was similar in the two groups . CONCLUSIONS The perioperative administration of supplemental oxygen is a practical method of reducing the incidence of surgical-wound infections BACKGROUND Nitrous oxide is commonly used in general anaesthesia but concerns exist that it might increase perioperative cardiovascular risk . We aim ed to gather evidence to establish whether nitrous oxide affects perioperative cardiovascular risk . METHODS We did an international , r and omised , assessor-blinded trial in patients aged at least 45 years with known or suspected coronary artery disease having major non-cardiac surgery . Patients were r and omly assigned via automated telephone service , stratified by site , to receive a general anaesthetic with or without nitrous oxide . Attending anaesthetists were aware of patients ' group assignments , but patients and assessors were not . The primary outcome measure was a composite of death and cardiovascular complications ( non-fatal myocardial infa rct ion , stroke , pulmonary embolism , or cardiac arrest ) within 30 days of surgery . Our modified intention-to-treat population included all patients r and omly assigned to groups and undergoing induction of general anaesthesia for surgery . This trial is registered at Clinical Trials.gov , number NCT00430989 . FINDINGS Of 10,102 eligible patients , we enrolled 7112 patients between May 30 , 2008 , and Sept 28 , 2013 . 3543 were assigned to receive nitrous oxide and 3569 were assigned not to receive nitrous oxide . 3483 patients receiving nitrous oxide and 3509 not receiving nitrous oxide were assessed for the primary outcome . The primary outcome occurred in 283 ( 8 % ) patients receiving nitrous oxide and in 296 ( 8 % ) patients not receiving nitrous oxide ( relative risk 0·96 , 95 % CI 0·83–1·12 ; p=0·64 ) . Surgical site infection occurred in 321 ( 9 % ) patients assigned to nitrous oxide , and in 311 ( 9 % ) patients in the no-nitrous oxide group ( p=0·61 ) , and severe nausea and vomiting occurred in 506 patients ( 15 % ) assigned to nitrous oxide and 378 patients ( 11 % ) not assigned to nitrous oxide ( p<0·0001 ) . INTERPRETATION Our findings support the safety profile of nitrous oxide use in major non-cardiac surgery . Nitrous oxide did not increase the risk of death and cardiovascular complications or surgical-site infection , the emetogenic effect of nitrous oxide can be controlled with antiemetic prophylaxis , and a desired effect of reduced volatile agent use was shown . FUNDING Australian National Health and Medical Research Council ; Australian and New Zeal and College of Anaesthetists ; Heart and Stroke Foundation of Quebec , Heart and Stroke Foundation of Ontario , Canada ; General Research Fund of the Research Grant Council , Hong Kong Special Administrative Region , China BACKGROUND High concentrations of inspired oxygen are associated with pulmonary atelectasis but also provide recognized advantages . Consequently , the appropriate inspired oxygen concentration for general surgical use remains controversial . The authors tested the hypothesis that atelectasis and pulmonary dysfunction on the first postoperative day are comparable in patients given 30 % or 80 % perioperative oxygen . METHODS Thirty patients aged 18 - 65 yr were anesthetized with isoflurane and r and omly assigned to 30 % or 80 % oxygen during and for 2 h after colon resection . Chest radiographs and pulmonary function tests ( forced vital capacity and forced expiratory volume ) were obtained preoperatively and on the first postoperative day . Arterial blood gas measurements were obtained intraoperatively , after 2 h of recovery , and on the first postoperative day . Computed tomography scans of the chest were also obtained on the first postoperative day . RESULTS Postoperative pulmonary mechanical function was significantly reduced compared with preoperative values , but there was no difference between the groups at either time . Arterial gas partial pressures and the alveolar-arterial oxygen difference were also comparable in the two groups . All preoperative chest radiographs were normal . Postoperative radiographs showed atelectasis in 36 % of the patients in the 30%-oxygen group and in 44 % of those in the 80%-oxygen group . Relatively small amounts of pulmonary atelectasis ( expressed as a percentage of total lung volume ) were observed on the computed tomography scans , and the percentages ( mean + /- SD ) did not differ significantly in the patients given 30 % oxygen ( 2.5 % + /- 3.2 % ) or 80 % oxygen ( 3.0 % + /- 1.8 % ) . These data provided a 99 % chance of detecting a 2 % difference in atelectasis volume at an alpha level of 0.05 . CONCLUSIONS Lung volumes , the incidence and severity of atelectasis , and alveolar gas exchange were comparable in patients given 30 % and 80 % perioperative oxygen . The authors conclude that administration of 80 % oxygen in the perioperative period does not worsen lung function . Therefore , patients who may benefit from generous oxygen partial pressures should not be denied supplemental perioperative oxygen for fear of causing atelectasis BACKGROUND Increased long-term mortality was found in patients exposed to perioperative hyperoxia in the PROXI trial , where patients undergoing laparotomy were r and omised to 80 % versus 30 % oxygen during and after surgery . This post hoc follow-up study assessed the impact of perioperative hyperoxia on long-term risk of cardiovascular events . METHODS A total of 1386 patients undergoing either elective or emergency laparotomy were r and omised to 80 % versus 30 % oxygen during and two hours after surgery . At follow-up , the primary outcome of acute coronary syndrome was assessed . Secondary outcomes included myocardial infa rct ion , other heart disease , and acute coronary syndrome or death . Data were analysed in the Cox proportional hazards model . RESULTS The primary outcome , acute coronary syndrome , occurred in 2.5 % versus 1.3 % in the 80 % versus 30 % oxygen group ; HR 2.15 ( 95 % CI 0.96 - 4.84 ) . Patients in the 80 % oxygen group had significantly increased risk of myocardial infa rct ion ; HR 2.86 ( 95 % CI 1.10 - 7.44 ) , other heart disease ; HR 1.40 ( 95 % 1.06 - 1.83 ) , and acute coronary syndrome or death ; HR 1.22 ( 95 % CI 1.01 - 1.49 ) . CONCLUSIONS Perioperative hyperoxia may be associated with an increased long-term risk of myocardial infa rct ion and other heart disease |
10,751 | 27,157,143 | There was moderate quality evidence favouring buprenorphine maintenance over detoxification or psychological treatment on adverse events ( RR 0.19 , 95 % CI 0.06 to 0.57).The main weaknesses in the quality of the data was the use of open-label study design s. AUTHORS ' CONCLUSIONS There was low to moderate quality evidence supporting the use of maintenance agonist pharmacotherapy for pharmaceutical opioid dependence .
Methadone or buprenorphine appeared equally effective .
Maintenance treatment with buprenorphine appeared more effective than detoxification or psychological treatments . | BACKGROUND There are increasing concerns regarding pharmaceutical opioid harms including overdose and dependence , with an associated increase in treatment dem and .
People dependent on pharmaceutical opioids appear to differ in important ways from people who use heroin , yet most opioid agonist treatment research has been conducted in people who use heroin .
OBJECTIVES To assess the effects of maintenance agonist pharmacotherapy for the treatment of pharmaceutical opioid dependence . | Abstract Background Buprenorphine dependence is a relatively novel addiction . Aims To compare the treatment outcome in three groups over 12-weeks of treatment . Methods Two hundred and four intravenous (IV)-buprenorphine-dependent patients were r and omised into three groups . Subjects received 50 mg oral methadone tablet , or 5 mg sublingual buprenorphine tablet , or 50 mg oral naltrexone , and a weekly 30-minute clinical counselling session . Results The majority ( 80 % ) had a history of opium or heroin dependency before they were introduced to IV buprenorphine . The main source of buprenorphine for misusers was street sale ( 91 % ) . The mean duration of buprenorphine dependence was 1.9 years and the mean dose per day was 3.9 ampoules ( 1 ampoule contains 0.3 mg of buprenorphine in 1ml ) . Overall 59 % of the patients completed the 12-week study . Retention in the 50 mg methadone group was significantly better than the 5 mg dose buprenorphine group ( p=0.001 ) and the 50 mg dose naltrexone group ( p=0.000 ) . Retention in the 5 mg buprenorphine group was significantly better than the 50 mg naltrexone dose group ( p=0.000 ) . Conclusions These results support the efficacy and safety of oral methadone and sublingual buprenorphine tablets for injection buprenorphine-dependent patients BACKGROUND The partial opiate-receptor agonist buprenorphine has been suggested for treatment of heroin dependence , but there are few long-term and placebo-controlled studies of its effectiveness . We aim ed to assess the 1-year efficacy of buprenorphine in combination with intensive psychosocial therapy for treatment of heroin dependence . METHODS 40 individuals aged older than 20 years , who met DSM-IV criteria for opiate dependence for at least 1 year , but did not fulfil Swedish legal criteria for methadone maintenance treatment were r and omly allocated either to daily buprenorphine ( fixed dose 16 mg sublingually for 12 months ; supervised daily administration for a least 6 months , possible take-home doses thereafter ) or a tapered 6 day regimen of buprenorphine , thereafter followed by placebo . All patients participated in cognitive-behavioural group therapy to prevent relapse , received weekly individual counselling sessions , and su bmi tted thrice weekly supervised urine sample s for analysis to detect illicit drug use . Our primary endpoint was 1-year retention in treatment and analysis was by intention to treat . FINDINGS 1-year retention in treatment was 75 % and 0 % in the buprenorphine and placebo groups , respectively ( p=0.0001 ; risk ratio 58.7 [ 95 % CI 7.4 - 467.4 ] ) . Urine screens were about 75 % negative for illicit opiates , central stimulants , cannabinoids , and benzodiazepines in the patients remaining in treatment . INTERPRETATION The combination of buprenorphine and intensive psychosocial treatment is safe and highly efficacious , and should be added to the treatment options available for individuals who are dependent on heroin Most research examining buprenorphine has been conducted with heroin users . Few studies have examined buprenorphine pharmacotherapy for prescription opioid users . Data were from a r and omized controlled trial of behavioral treatment provided for 16weeks on a platform of buprenorphine pharmacotherapy and medication management . We compared heroin ( H , n=54 ) , prescription opioid ( PO , n=54 ) and combination heroin+prescription opioid ( POH , n=71 ) users to test the hypothesis that PO users will have better treatment outcomes compared with heroin users . The PO group provided more opioid-negative urine drug screens over the combined treatment period ( PO:70 % , POH:40 % , H:38 % , p<0.001 ) and at the end of the combined treatment period ( PO:65 % , POH:31 % , H:33 % , p<0.001 ) . Retention was lowest in the H group ( PO:80 % , POH:65 % , H:57 % , p=0.039 ) . There was no significant difference in buprenorphine dose between the groups . PO users appear to have better outcomes in buprenorphine pharmacotherapy compared to those reporting any heroin use , confirming that buprenorphine pharmacotherapy is effective in PO users AIMS To evaluate the safety and efficacy of buprenorphine implants ( BI ) versus placebo implants ( PI ) for the treatment of opioid dependence . A secondary aim compared BI to open-label sublingual buprenorphine/naloxone tablets ( BNX ) . DESIGN R and omized , double-blind , placebo-controlled trial . Subjects received either four buprenorphine implants ( 80 mg/implant ) ( n = 114 ) , four placebo implants ( n = 54 ) or open-label BNX ( 12 - 16 mg/day ) ( n = 119 ) . SETTING Twenty addiction treatment centers . PARTICIPANTS Adult out- patients ( ages 18 - 65 ) with DSM-IV-TR opioid dependence . MEASUREMENTS The primary efficacy end-point was the percentage of urine sample s negative for opioids collected from weeks 1 to 24 , examined as a cumulative distribution function ( CDF ) . FINDINGS The BI CDF was significantly different from placebo ( P < 0.0001 ) . Mean [ 95 % confidence interval ( CI ) ] proportions of urines negative for opioids were : BI = 31.2 % ( 25.3 , 37.1 ) and PI = 13.4 % ( 8.3 , 18.6 ) . BI subjects had a higher study completion rate relative to placebo ( 64 versus 26 % , P < 0.0001 ) , lower clinician-rated ( P < 0.0001 ) and patient-rated ( P < 0.0001 ) withdrawal , lower patient-ratings of craving ( P < 0.0001 ) and better subjects ' ( P = 0.031 ) and clinicians ' ( P = 0.022 ) global ratings of improvement . BI also result ed in significantly lower cocaine use ( P = 0.0016 ) . Minor implant-site reactions were comparable in the buprenorphine [ 27.2 % ( 31 of 114 ) ] and placebo groups [ 25.9 % ( 14 of 54 ) ] . BI were non-inferior to BNX on percentage of urines negative for opioids [ mean ( 95 % CI ) = 33.5 ( 27.3 , 39.6 ) ; 95 % CI for the difference of proportions = ( -10.7 , 6.2 ) ] . CONCLUSIONS Compared with placebo , buprenorphine implants result in significantly less frequent opioid use and are non-inferior to sublingual buprenorphine/naloxone tablets CONTEXT No r and omized trials have examined treatments for prescription opioid dependence , despite its increasing prevalence . OBJECTIVE To evaluate the efficacy of brief and extended buprenorphine hydrochloride-naloxone hydrochloride treatment , with different counseling intensities , for patients dependent on prescription opioids . DESIGN Multisite , r and omized clinical trial using a 2-phase adaptive treatment research design . Brief treatment ( phase 1 ) included 2-week buprenorphine-naloxone stabilization , 2-week taper , and 8-week postmedication follow-up . Patients with successful opioid use outcomes exited the study ; unsuccessful patients entered phase 2 : extended ( 12-week ) buprenorphine-naloxone treatment , 4-week taper , and 8-week postmedication follow-up . SETTING Ten US sites . Patients A total of 653 treatment-seeking out patients dependent on prescription opioids . INTERVENTIONS In both phases , patients were r and omized to st and ard medical management ( SMM ) or SMM plus opioid dependence counseling ; all received buprenorphine-naloxone . MAIN OUTCOME MEASURES Predefined " successful outcome " in each phase : composite measures indicating minimal or no opioid use based on urine test-confirmed self-reports . RESULTS During phase 1 , only 6.6 % ( 43 of 653 ) of patients had successful outcomes , with no difference between SMM and SMM plus opioid dependence counseling . In contrast , 49.2 % ( 177 of 360 ) attained successful outcomes in phase 2 during extended buprenorphine-naloxone treatment ( week 12 ) , with no difference between counseling conditions . Success rates 8 weeks after completing the buprenorphine-naloxone taper ( phase 2 , week 24 ) dropped to 8.6 % ( 31 of 360 ) , again with no counseling difference . In secondary analyses , successful phase 2 outcomes were more common while taking buprenorphine-naloxone than 8 weeks after taper ( 49.2 % [ 177 of 360 ] vs 8.6 % [ 31 of 360 ] , P < .001 ) . Chronic pain did not affect opioid use outcomes ; a history of ever using heroin was associated with lower phase 2 success rates while taking buprenorphine-naloxone . CONCLUSIONS Prescription opioid-dependent patients are most likely to reduce opioid use during buprenorphine-naloxone treatment ; if tapered off buprenorphine-naloxone , even after 12 weeks of treatment , the likelihood of an unsuccessful outcome is high , even in patients receiving counseling in addition to SMM CONTEXT Limitations of existing pharmacological treatments for opioid dependence include low adherence , medication diversion , and emergence of withdrawal symptoms . OBJECTIVE To determine the efficacy of buprenorphine implants that provide a low , steady level of buprenorphine over 6 months for the treatment of opioid dependence . DESIGN , SETTING , AND PARTICIPANTS A r and omized , placebo-controlled , 6-month trial conducted at 18 sites in the United States between April 2007 and June 2008 . One hundred sixty-three adults , aged 18 to 65 years , diagnosed with opioid dependence . One hundred eight were r and omized to receive buprenorphine implants and 55 to receive placebo implants . INTERVENTION After induction with sublingual buprenorphine-naloxone tablets , patients received either 4 buprenorphine implants ( 80 mg per implant ) or 4 placebo implants . A fifth implant was available if a threshold for rescue use of sublingual buprenorphine-naloxone treatment was exceeded . St and ardized individual drug counseling was provided to all patients . MAIN OUTCOME MEASURE The percentage of urine sample s negative for illicit opioids for weeks 1 through 16 and for weeks 17 through 24 . RESULTS The buprenorphine implant group had significantly more urine sample s negative for illicit opioids during weeks 1 through 16 ( P = .04 ) . Patients with buprenorphine implants had a mean percentage of urine sample s that tested negative for illicit opioids across weeks 1 through 16 of 40.4 % ( 95 % confidence interval [ CI ] , 34.2%-46.7 % ) and a median of 40.7 % ; whereas those in the placebo group had a mean of 28.3 % ( 95 % CI , 20.3%-36.3 % ) and a median of 20.8 % . A total of 71 of 108 patients ( 65.7 % ) who received buprenorphine implants completed the study vs 17 of 55 ( 30.9 % ) who received placebo implants ( P < .001 ) . Those who received buprenorphine implants also had fewer clinician-rated ( P < .001 ) and patient-rated ( P = .004 ) withdrawal symptoms , had lower patient ratings of craving ( P < .001 ) , and experienced a greater change on clinician global ratings of severity of opioid dependence ( P<.001 ) and on the clinician global ratings of improvement ( P < .001 ) than those who received placebo implants . Minor implant site reactions were the most common adverse events : 61 patients ( 56.5 % ) in the buprenorphine group and 29 ( 52.7 % ) in the placebo group . CONCLUSION Among persons with opioid dependence , the use of buprenorphine implants compared with placebo result ed in less opioid use over 16 weeks as assessed by urine sample s. TRIAL REGISTRATION clinical trials.gov Identifier : NCT00447564 CONTEXT The usual treatment for opioid-addicted youth is detoxification and counseling . Extended medication-assisted therapy may be more helpful . OBJECTIVE To evaluate the efficacy of continuing buprenorphine-naloxone for 12 weeks vs detoxification for opioid-addicted youth . DESIGN , SETTING , AND PATIENTS Clinical trial at 6 community programs from July 2003 to December 2006 including 152 patients aged 15 to 21 years who were r and omized to 12 weeks of buprenorphine-naloxone or a 14-day taper ( detox ) . INTERVENTIONS Patients in the 12-week buprenorphine-naloxone group were prescribed up to 24 mg per day for 9 weeks and then tapered to week 12 ; patients in the detox group were prescribed up to 14 mg per day and then tapered to day 14 . All were offered weekly individual and group counseling . MAIN OUTCOME MEASURE Opioid-positive urine test result at weeks 4 , 8 , and 12 . RESULTS The number of patients younger than 18 years was too small to analyze separately , but overall , patients in the detox group had higher proportions of opioid-positive urine test results at weeks 4 and 8 but not at week 12 ( chi(2)(2 ) = 4.93 , P = .09 ) . At week 4 , 59 detox patients had positive results ( 61 % ; 95 % confidence interval [ CI ] = 47%-75 % ) vs 58 12-week buprenorphine-naloxone patients ( 26 % ; 95 % CI = 14%-38 % ) . At week 8 , 53 detox patients had positive results ( 54 % ; 95 % CI = 38%-70 % ) vs 52 12-week buprenorphine-naloxone patients ( 23 % ; 95 % CI = 11%-35 % ) . At week 12 , 53 detox patients had positive results ( 51 % ; 95 % CI = 35%-67 % ) vs 49 12-week buprenorphine-naloxone patients ( 43 % ; 95 % CI = 29%-57 % ) . By week 12 , 16 of 78 detox patients ( 20.5 % ) remained in treatment vs 52 of 74 12-week buprenorphine-naloxone patients ( 70 % ; chi(2)(1 ) = 32.90 , P < .001 ) . During weeks 1 through 12 , patients in the 12-week buprenorphine-naloxone group reported less opioid use ( chi(2)(1 ) = 18.45 , P < .001 ) , less injecting ( chi(2)(1 ) = 6.00 , P = .01 ) , and less non study addiction treatment ( chi(2)(1 ) = 25.82 , P < .001 ) . High levels of opioid use occurred in both groups at follow-up . Four of 83 patients who tested negative for hepatitis C at baseline were positive for hepatitis C at week 12 . CONCLUSIONS Continuing treatment with buprenorphine-naloxone improved outcome compared with short-term detoxification . Further research is necessary to assess the efficacy and safety of longer-term treatment with buprenorphine for young individuals with opioid dependence . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00078130 This study evaluated the efficacy of a combination tablet formulation of buprenorphine containing 8 mg of buprenorphine and 2 mg of naloxone for every other day treatment and whether increasing the daily maintenance dose was essential for maintaining an efficacious alternate-day treatment . Twenty-six opioid-dependent out patients completing a 16-day baseline entered a double-blind , placebo-controlled , triple crossover trial . Twenty-one days of daily combination tablet administration were compared to two different 21-day periods of alternate-day buprenorphine administration where subjects received either 8 or 16 mg of the combination tablet every other day with placebo on the interposed day . Fifty-four percent ( 14/26 ) of subjects completed the study , but only two subjects dropped out during the 16-mg alternate-day condition . Rates of medication compliance , illicit opioid use and subject- and observer-rated measures of opioid effects did not distinguish daily from alternate-day treatments in subjects completing the study . However , pupillary diameter was significantly increased during 8-mg alternate-day compared to the 8-mg daily or 16-mg alternate-day treatment . These data replicate earlier findings describing the acceptability of alternate-day buprenorphine treatment using multiples of the daily maintenance dose and extend these findings by establishing the clinical efficacy of daily and alternate-day dosing regimens with the combination buprenorphine naloxone tablet . This study also suggests slightly improved outcomes during alternate-day treatment using multiples of the daily dose During a 12-week intervention , opioid dependent participants ( N = 120 ) maintained on thrice-a-week ( M , W , F ) buprenorphine plus therapist and computer-based counseling were r and omized to receive : ( a ) medication contingencies ( MC = thrice weekly dosing schedule vs. daily attendance and single-day 50 % dose reduction imposed upon su bmi ssion of an opioid and /or cocaine positive urine sample ) ; ( b ) voucher contingency ( VC = escalating schedule for opioid and /or cocaine negative sample s with reset for drug-positive sample s ) ; or ( c ) st and ard care ( SC ) , with no programmed consequences for urinalysis results . VC result ed in better 12-week retention ( 85 % ) compared to MC ( 58 % ; p = 0.009 ) , but neither differed from SC ( 76 % retained ) . After adjusting for baseline differences in employment , and compared to SC , the MC group achieved 1.5 more continuous weeks of combined opioid/cocaine abstinence ( p = 0.030 ) , while the VC group had 2 more total weeks of abstinence ( p = 0.048 ) . Drug use results suggest that both the interventions were efficacious , with effects primarily in opioid rather than cocaine test results . Findings should be interpreted in light of the greater attrition associated with medication-based contingencies versus the greater monetary costs of voucher-based contingencies AIMS To evaluate the safety and efficacy of an 8 mg/day sublingual dose of buprenorphine in the maintenance treatment of heroin addicts by comparison with a 1 mg/day dose over a 16-week treatment period . As a secondary objective , outcomes were determined concurrently for patients treated with two other dose levels . DESIGN Patients were r and omized to four dosage groups and treated double-blind . SETTING Twelve outpatient opiate maintenance treatment centers throughout the United States . PARTICIPANTS Two hundred and thirty-nine women and 497 men who met the DSM-III-R criteria for opioid dependence and were seeking treatment . INTERVENTION Patients received either 1 , 4 , 8 or 16 mg/day of buprenorphine and were treated in the usual clinical context , including a 1-hour weekly clinical counseling session . MEASUREMENT Retention in treatment , illicit opioid use as determined by urine toxicology , opioid craving and global ratings by patient and staff . Safety outcome measures were provided by clinical monitoring and by analysis of the reported adverse events . FINDINGS Outcomes in the 8 mg group were significantly better than in the 1 mg group in all four efficacy domains . No deaths occurred in either group . The 8 mg group did not show an increase in the frequency of adverse events . Most reported adverse effects were those commonly seen in patients treated with opioids . CONCLUSIONS The findings support the safety and efficacy of buprenorphine and suggest that an adequate dose of buprenorphine will be a useful addition to pharmacotherapy CONTEXT Despite evidence that methadone maintenance treatment ( MMT ) is effective for opioid dependence , it remains a controversial therapy because of its indefinite provision of a dependence-producing medication . OBJECTIVE To compare outcomes of patients with opioid dependence treated with MMT vs an alternative treatment , psychosocially enriched 180-day methadone-assisted detoxification . DESIGN R and omized controlled trial conducted from May 1995 to April 1999 . SETTING Research clinic in an established drug treatment service . PATIENTS Of 858 volunteers screened , 179 adults with diagnosed opioid dependence were r and omized into the study ; 154 completed 12 weeks of follow-up . INTERVENTIONS Patients were r and omized to MMT ( n = 91 ) , which required 2 hours of psychosocial therapy per week during the first 6 months ; or detoxification ( n = 88 ) , which required 3 hours of psychosocial therapy per week , 14 education sessions , and 1 hour of cocaine group therapy , if appropriate , for 6 months , and 6 months of ( nonmethadone ) aftercare services . MAIN OUTCOME MEASURES Treatment retention , heroin and cocaine abstinence ( by self-report and monthly urinalysis ) , human immunodeficiency virus ( HIV ) risk behaviors ( Risk of AIDS Behavior scale score ) , and function in 5 problem areas : employment , family , psychiatric , legal , and alcohol use ( Addiction Severity Index ) , compared by intervention group . RESULTS Methadone maintenance therapy result ed in greater treatment retention ( median , 438.5 vs 174.0 days ) and lower heroin use rates than did detoxification . Cocaine use was more closely related to study dropout in detoxification than in MMT . Methadone maintenance therapy result ed in a lower rate of drug-related ( mean [ SD ] at 12 months , 2.17 [ 3.88 ] vs 3.73 [ 6.86 ] ) but not sex-related HIV risk behaviors and in a lower severity score for legal status ( mean [ SD ] at 12 months , 0.05 [ 0.13 ] vs 0.13 [ 0.19 ] ) . There were no differences between groups in employment or family functioning or alcohol use . In both groups , monthly heroin use rates were 50 % or greater , but days of use per month dropped markedly from baseline . CONCLUSIONS Our results confirm the usefulness of MMT in reducing heroin use and HIV risk behaviors . Illicit opioid use continued in both groups , but frequency was reduced . Results do not provide support for diverting re sources from MMT into long-term detoxification Buprenorphine is a partial μ‐opiate agonist and κ‐opiate antagonist with established efficacy in the treatment of opiate dependence . Its efficacy for cocaine dependence is uncertain . This study evaluated buprenorphine for the treatment of concomitant cocaine and opiate dependence BACKGROUND There are approximately 12,000 opioid dependants in Norway . Methadone-assisted treatment was approved in Norway in 1998 , buprenorphine in 2000 . This study compares the efficacy of methadone ( n = 25 ) and buprenorphine ( n = 25 ) assisted maintenance treatment in a group of long-term ( > 10 years ) opioid dependant . MATERIAL AND METHODS After r and omisation patients received either 16 mg sublingual buprenorphine or individually adjusted methadone ( mean 106 mg , range 80 - 160 ) for 26 weeks , with a rehabilitation programme run in parallel . RESULTS After 180 days , patient retention was highest in the methadone group ( 85 % vs. 36 % , p < 0.0005 ) . Days in treatment were 167 vs. 114 ( 95 % CI for difference 53 days ( 26 - 80 ) , p < 0.001 ) . Positive urine test rates for opiates ( 20 % vs 24 % , p < 0.01 ) and cannabis ( 33 % vs 45 % , p < 0.001 ) were lower in the methadone group which also had lower self-reported risk behaviour and psychological distress . However , only those on buprenorphine reported significant improvement in physical health . For older , long-term opioid dependants with significant co-morbidity and unsuccessful medication-free treatment , high-dose methadone maintenance appears to be the treatment of choice . However , in cases where methadone is poorly tolerated , buprenorphine therapy may be a good alternative IMPORTANCE Although abuse of prescription opioids ( POs ) is a significant public health problem , few experimental studies have investigated the treatment needs of this growing population . OBJECTIVE To evaluate , following brief stabilization with a combination of buprenorphine hydrochloride and naloxone hydrochloride dihydrate , the relative efficacy of 1- , 2- , and 4-week buprenorphine tapering regimens and subsequent naltrexone hydrochloride therapy in PO-dependent out patients . DESIGN , SETTING , AND PARTICIPANTS A double-blind , 12-week r and omized clinical trial was conducted in an outpatient research clinic . Following a brief period of buprenorphine stabilization , 70 PO-dependent adults were r and omized to receive 1- , 2- , or 4-week tapers followed by naltrexone therapy . INTERVENTION During phase 1 ( weeks 1 - 5 after r and omization ) , participants visited the clinic daily ; during phase 2 ( weeks 6 - 12 ) , visits were reduced to thrice weekly . Participants received behavioral therapy and urine toxicology testing throughout the trial . MAIN OUTCOMES AND MEASURES The percentage of participants negative for illicit opioid use , retention , naltrexone ingestion , and favorable treatment response ( ie , retained in treatment , opioid abstinent , and receiving naltrexone at the end of the study ) . RESULTS Opioid abstinence at the end of phase 1 was greater in the 4-week compared with the 2- and 1-week taper conditions ( P = .02 ) , with 63 % ( n = 14 ) , 29 % ( n = 7 ) , and 29 % ( n = 7 ) of participants abstinent in the 4- , 2- , and 1-week conditions , respectively . Abstinence at the end of phase 2 was also greater in the 4-week compared with the 2- and 1-week conditions ( P = .03 ) , with 50 % ( n = 11 ) , 16 % ( n = 4 ) , and 20 % ( n = 5 ) of participants abstinent in the 4- , 2- , and 1-week conditions , respectively . There were more treatment responders in the 4-week condition ( P = .03 ) , with 50 % ( n = 11 ) , 17 % ( n = 4 ) , and 21 % ( n = 5 ) of participants in the 4- , 2- , and 1-week groups considered responders at the end of treatment , respectively . Retention and naltrexone ingestion also were superior in the 4-week vs briefer tapers ( both P = .04 ) . Experimental condition ( ie , taper duration ) was the strongest predictor of treatment response , followed by buprenorphine stabilization dose . CONCLUSIONS AND RELEVANCE This study represents a rigorous experimental evaluation of outpatient buprenorphine stabilization , brief taper , and naltrexone maintenance for treatment of PO dependence . Results suggest that a meaningful subset of PO-dependent out patients may respond positively to a 4-week taper plus naltrexone maintenance intervention Individuals who use heroin and illicit opioids are at high risk for infection with human immunodeficiency virus ( HIV ) and other blood-borne pathogens , as well as incarceration . The purpose of the r and omized trial reported here is to compare outcomes between participants who initiated methadone maintenance treatment ( MMT ) prior to release from incarceration , with those who were referred to treatment at the time of release . Participants who initiated MMT prior to release were significantly more likely to enter treatment postrelease ( P < .001 ) and for participants who did enter treatment , those who received MMT prerelease did so within fewer days ( P = .03 ) . They also reported less heroin use ( P = .008 ) , other opiate use ( P = .09 ) , and injection drug use ( P = .06 ) at 6 months . Initiating MMT in the weeks prior to release from incarceration is a feasible and effective way to improve MMT access postrelease and to decrease relapse to opioid use OBJECTIVE To investigate morbidity related to misuse of over-the-counter ( OTC ) codeine-ibuprofen analgesics . DESIGN AND SETTING Prospect i ve case series collected from Victorian hospital-based addiction medicine specialists between May 2005 and December 2008 . MAIN OUTCOME MEASURES Morbidity associated with codeine-ibuprofen misuse . RESULTS Twenty-seven patients with serious morbidity were included , mainly with gastrointestinal haemorrhage and opioid dependence . The patients were taking mean daily doses of 435 - 602 mg of codeine phosphate and 6800 - 9400 mg ibuprofen . Most patients had no previous history of substance use disorder . The main treatment was opioid substitution treatment with buprenorphine-naloxone or methadone . CONCLUSIONS Although codeine can be considered a relatively weak opioid analgesic , it is nevertheless addictive , and the significant morbidity and specific patient characteristics associated with overuse of codeine-ibuprofen analgesics support further awareness , investigation and monitoring of OTC codeine-ibuprofen analgesic use The authors r and omly assigned 95 male narcotic addicts to one of four treatment conditions : either methadone or LAAM maintenance and one of two drug-appropriate clinic attendance schedules . Although no differences were observed among treatment conditions on any of the outcome measures employed , the conclusion that the drugs and attendance regimens were equally efficacious and acceptable was made cautiously due to the relatively small sample size and to the observed trend ( p = . 10 ) in favor of methadone maintenance combined with the 3-day ( LAMM-appropriate ) attendance schedule . There was no evidence of untoward physical effects associated with any of the treatment approaches BACKGROUND Buprenorphine is a partial agonist at the mu-opioid receptor that has been proposed as an alternative to traditional full agonist maintenance therapy for the treatment of opioid addiction . We report on a clinical trial in which the relative safety and efficacy of long-term fixed-dose buprenorphine maintenance was examined in comparison to low- and high-dose methadone maintenance . METHODS Two hundred twenty-five treatment-seeking opioid addicts ( 46 women , 179 men ) were r and omly assigned to receive , in a double-blind manner , either 8 mg/d of buprenorphine , 30 mg/d of methadone , or 80 mg/d of methadone maintenance over a 1-year period . Objective and subjective measures of efficacy ( urine toxicology , retention , craving , and withdrawal symptoms ) were examined at the study midpoint and at termination , and safety data were tabulated over the entire 52-week study period . RESULTS Patients assigned to high-dose methadone maintenance performed significantly better on measures of retention , opioid use , and opioid craving than either the low-dose methadone or the buprenorphine group at both 26-week and 52-week time points . Performance on these measures was virtually identical between the latter two groups . No serious adverse health effects attributable to buprenorphine were noted . CONCLUSIONS Buprenorphine maintenance at 8 mg/d appears to be less than optimally efficacious under the conditions of the present study . Continued research is needed to reconcile these findings with the more positive results reported by other investigative groups . There are no apparent health risks associated with long-term buprenorphine maintenance at this dosage BACKGROUND Opioid dependence is a chronic , relapsing disorder with important public health implication s. METHODS In a 17-week r and omized study of 220 patients , we compared levomethadyl acetate ( 75 to 115 mg ) , buprenorphine ( 16 to 32 mg ) , and high-dose ( 60 to 100 mg ) and low-dose ( 20 mg ) methadone as treatments for opioid dependence . Levomethadyl acetate and buprenorphine were administered three times a week . Methadone was administered daily . Doses were individualized except in the group assigned to low-dose methadone . Patients with poor responses to treatment were switched to methadone . RESULTS There were 55 patients in each group ; 51 percent completed the trial . The mean ( + /-SE ) number of days that a patient remained in the study was significantly higher for those receiving levomethadyl acetate ( 89+/-6 ) , buprenorphine ( 96+/-4 ) , and high-dose methadone ( 105+/-4 ) than for those receiving low-dose methadone ( 70+/-4 , P<0.001 ) . Continued participation was also significantly more frequent among patients receiving high-dose methadone than among those receiving levomethadyl acetate ( P=0.02 ) . The percentage of patients with 12 or more consecutive opioid-negative urine specimens was 36 percent in the levomethadyl acetate group , 26 percent in the buprenorphine group , 28 percent in the high-dose methadone group , and 8 percent in the low-dose methadone group ( P=0.005 ) . At the time of their last report , patients reported on a scale of 0 to 100 that their drug problem had a mean severity of 35 with levomethadyl acetate , 34 with buprenorphine , 38 with high-dose methadone , and 53 with low-dose methadone ( P=0.002 ) . CONCLUSIONS As compared with low-dose methadone , levomethadyl acetate , buprenorphine , and high-dose methadone substantially reduce the use of illicit opioids AIMS To evaluate physical and mental health and compare treatment outcomes in opiate-dependent patients substituted either with heroin or methadone . DESIGN Twelve-month open-label r and omized controlled trial . SETTING Out-patient substitution clinics in seven German cities . PARTICIPANTS A total of 1015 opiate-dependent individuals . MEASUREMENTS Opiate Treatment Index-Health Scale Score ( OTI ) , Body Mass Index ( BMI ) , serology for infectious diseases such as hepatitis B , C and human immunodeficiency virus as well as tuberculosis , Karnofsky Performance Scale ( KPS ) , electrocardiogram ( ECG ) , echocardiogram , Symptom Checklist 90-R ( SCL-90-R ) , Global Assessment of Functioning ( GAF ) , Modular System for Quality of Life and study medication-related serious adverse events ( SAE ) . FINDINGS Improvements were found in both heroin and methadone substituted patients regarding OTI , BMI , KPS , SCL-90-R , and GAF , but they were more pronounced for the heroin group ( analysis of variance , all P = 0.000 ) . The frequency of pathological echocardiograms decreased in the heroin group and increased in the methadone group ( χ(2 ) test , < 0.05 ) . Markers for infectious diseases and frequencies of pathological ECGs did not differ between baseline and 12 months , or between treatment groups . Study medication-related serious adverse events , all of which were treated successfully , occurred 2.5 times more often in the heroin group . The majority of heroin-related SAEs ( 41 of 58 ) occurred within a few minutes of the injections . CONCLUSIONS The integration of severe injection drug users either in methadone or heroin-assisted maintenance treatment has positive effects on most physical and mental change-sensitive variables , with heroin showing superior results . Due to medication-related adverse events , patients should be observed for 15 minutes after a heroin injection Large-scale placebo controlled clinical trials assessing the efficacy of medications for the treatment of drug dependence have generally been limited to alcohol , cocaine and nicotine dependent population s. The purpose of the present study was to assess the early ( 1 - 2 week ) clinical effectiveness of buprenorphine versus placebo in an opioid dependent population . The study used a parallel-group design with a behavioral choice component to compare buprenorphine ( a mu-opioid partial agonist ) to placebo for the treatment of opioid dependence . Opioid dependent volunteer patients participated in a 14-day study to assess the effectiveness and patient acceptance of this new pharmacotherapy for the treatment of opioid dependence . Patients were r and omly assigned to placebo ( n = 60 ) or 2 mg ( n = 60 ) or 8 mg ( n = 30 ) daily sublingual buprenorphine . All doses were administered double-blind . On days 6 - 13 all patients could request a dose change , knowing that their new dose would be r and omly chosen from the remaining 2 alternatives . Compared to placebo , patients given buprenorphine ( independent of dose ) showed greater time on initial dose , requested fewer dose changes , used less illicit opioids ( assessed by urinalysis ) , and rated dose adequacy higher . These results demonstrate that a placebo controlled study with a behavioral choice component is an effective means of assessing the potential efficacy and acceptability of new pharmacotherapies for opioid dependence AIM The aim of this study is to define the efficacy of dihydrocodeine as an alternative to methadone in the maintenance treatment of opiate dependence . DESIGN A pragmatic open-label r and omized controlled study of patients recommended for opiate maintenance treatment to test equivalence of the two treatment options with follow-up continuing for up to 42 months after recruitment . SETTING Assessment at either Edinburgh 's Community Drug Problem Service or at two general practitioner practice s with specialist drug community psychiatric nurses , then with shared care follow-up . PARTICIPANTS Two hundred and thirty-five subjects ( 168 male , 67 female ) with opiate dependence syndrome were recruited . Subjects selected were suitable for opiate maintenance treatment . Routine treatment was offered throughout . INTERVENTION Patients were r and omized to receive either methadone mixture 1 mg/ml or dihydrocodeine , 30 mg or 60 mg tablets . MEASUREMENTS The primary outcome measure was retention in treatment . Eight secondary outcomes included total illicit opiate use , reported crime , physical health , mental health , injecting drug use , overdoses , selling drugs and being in education or work . Measures were compared over 42 months follow-up . FINDINGS There was no difference in groups for retention in treatment at follow-up and there was improvement in all secondary outcomes from baseline . No significant difference in outcomes was found between r and omized groups over time . Compliance with r and omized treatment differed by r and omized group and was affected by experiences in custody during follow-up . Those r and omized to dihydrocodeine were more likely to switch treatments . CONCLUSIONS These results , combined with existing clinical experience , provide evidence that dihydrocodeine is a viable alternative to methadone as a maintenance treatment for opiate dependence . Indirect comparisons with other studies show dihydrocodeine ( and methadone ) to be superior to placebo AIMS To compare levo-alpha-acetylmethadol ( LAAM ) and methadone maintenance ( MM ) on treatment retention , drug use during treatment and at follow-up , and abstinence . DESIGN A two-group experimental design with patients assigned r and omly ( 2:1 ) to receive fully subsidized LAAM or MM for 52 weeks . SETTING A community clinic providing maintenance treatment in Los Angeles , California . PARTICIPANTS A total of 315 treatment-seeking patients willing to be assigned r and omly to treatment condition ; 289 ( 91.7 % ) were interviewed at 52 weeks . INTERVENTION LAAM or MM , plus ancillary services available to all patients . Medication dose varied according to clinical judgement . MEASUREMENTS Treatment retention and status at 52-week follow-up , weekly clinical urinalysis , self-reported drug use and research urinalysis on sample s collected at follow-up . FINDINGS LAAM participants were more likely to complete the planned 52 weeks ( 57.4 % ) than MM participants ( 46.2 % ) and were less likely to be discharged for arrest/incarceration . LAAM produced fewer during treatment clinic opiate-positive sample s ( M = 48.8 ) than MM ( M = 62.3 ) . Further , 24.4 % on LAAM compared to 11.8 % on MM were able to sustain at least 12 weeks of abstinence during the last 24 weeks of treatment . Opiate use at follow-up was lowest ( 50.9 % ) among LAAM participants in maintenance treatment . No adverse events , cardiological or otherwise , were observed with LAAM administration . CONCLUSIONS LAAM is an effective medication for the treatment of opiate dependence in community clinics with numerous behavioral and clinical advantages . LAAM is more effective than MM in promoting retention and extended reduction in and abstinence from opiate use while in treatment OBJECTIVE To document trends in : ( i ) prescribing of morphine and oxycodone ; ( ii ) hospital separations for overdose ; ( iii ) presentations for treatment of problems associated with these drugs ; and ( iv ) oxycodone-related mortality data in Australia . DESIGN AND SETTING Cross-sectional study analysing prescriptions for morphine and oxycodone based on figures adjusted using Australian Bureau of Statistics estimated resident population and prospect ively collected data from : ( i ) the National Hospital Morbidity Data base on hospital separations primarily attributed to poisoning with opioids other than heroin ( " other opioids " ) ; ( ii ) the Alcohol and Other Drug Treatment National Minimum Data Set for treatment episodes where morphine or oxycodone were the primary or other drugs of concern ; ( iii ) the National Coronial Information System on deaths where oxycodone was the underlying cause of death or a contributory factor . MAIN OUTCOME MEASURES Population -adjusted numbers of ( i ) prescriptions for morphine and oxycodone by 10-year age group , ( ii ) hospital separations for " other opioid " poisoning , and ( iii ) treatment episodes related to morphine or oxycodone ; and ( iv ) number of oxycodone-related deaths . RESULTS Prescriptions for morphine declined , while those for oxycodone increased . Prescriptions for both were highest among older Australians . Hospital separations for " other opioid " poisoning doubled between the financial years 2005 - 06 and 2006 - 07 . Treatment episodes for morphine remained stable , while those for oxycodone increased . There were 465 oxycodone-related deaths recorded during 2001 - 2009 . CONCLUSIONS Oxycodone prescriptions in Australia have increased , particularly among older Australians . The increase may , in part , reflect appropriate prescribing for pain among an ageing population . However we are unable to differentiate non-medical use from appropriate prescribing from this data . In comparison to heroin , the morbidity and mortality associated with oxycodone is relatively low in Australia . There is a continued need for comprehensive training of general practitioners in assessing patients with chronic non-malignant pain and prescribing of opioids for these patients , to minimise the potential for harms associated with use of these medications AIM To assess the feasibility of a r and omized clinical trial of supervised injectable versus oral methadone maintenance and to assess medium-term treatment outcomes . DESIGN R and omized clinical trial of supervised injectable versus supervised oral methadone maintenance treatment ( MMT ) . Trial participants were dependent illicit opiate injectors allocated at intake to supervised injectable or oral methadone maintenance treatment . SETTING Specialist addictions treatment centre in South London . SUBJECTS Forty dependent illicit opiate injectors seeking methadone maintenance treatment . INTERVENTIONS Daily supervised injectable and oral methadone maintenance , delivered at the treatment centre . MAIN OUTCOME MEASURES Frequency of illicit heroin use and frequency of illicit drug injecting during 30 days before intake to treatment and prior to 6-month follow-up . SECONDARY OUTCOME MEASURES frequency of use of illicit methadone , crack cocaine , benzodiazepines and alcohol , physical and psychological health symptoms and acquisitive crime . RESULTS Injectable and oral MMT were both generally acceptable to the study participants : there was a high level of agreement to enter the r and omized trial , and subsequent retention in treatment was good . The average number of days of illicit heroin use reduced from 22.2 to 7.6 for the injectable MMT group and from 22.4 to 8.7 for the oral MMT group . The average number of days of illicit injecting reduced from 25.7 to 10.8 days for the injectable group and from 20.1 to 11.9 days for the oral group . Patients ' physical and psychological health symptoms and involvement in acquisitive crime also reduced in both groups . Treatment satisfaction ratings at follow-up were higher among patients in the injectable MMT group . The ratio for the actual medication costs between injectable and oral MMT was 6.8:1 , and for the direct operational costs was 4.7:1 . There was some evidence of a differential patient response with greater reductions in heroin use occurring among patients who were daily illicit injectors and had poorer psychological and physical health ( at entry ) who were allocated to injectable MMT . CONCLUSIONS Conduct of the trial has demonstrated that it is feasible to implement supervised injectable methadone maintenance treatment in the context of ( although separate from ) a specialist oral methadone maintenance service . Patients assigned to receive either supervised injectable or oral MMT had broadly equivalent , positive during-treatment outcomes at 6-month follow-up . Future studies should seek to identify patient characteristics which are linked to good outcome in injectable MMT . Practical evidence -based guidance to physicians about determining which patients are more suitable for injectable MMT is urgently needed BACKGROUND Buprenorphine/naloxone ( BUP ) and methadone ( MET ) are efficacious treatments for opioid dependence , although concerns about a link between BUP and drug-induced hepatitis have been raised . This study compares the effects of BUP and MET on liver health in opioid-dependent participants . METHODS This was a r and omized controlled trial of 1269 opioid-dependent participants seeking treatment at 8 federally licensed opioid treatment programs and followed for up to 32 weeks between May 2006 and August 2010 ; 731 participants met " evaluable " criteria defined as completing 24 weeks of medication and providing at least 4 blood sample s for transaminase testing . Participants were r and omly assigned to receive BUP or MET for 24 weeks . Shift table analysis determined how many evaluable participants moved between categories of low and elevated transaminase levels . Predictors of moving from low to high transaminase levels were identified . RESULTS Changes in transaminase levels did not differ by medication condition . Baseline infection with hepatitis C or B was the only significant predictor of moving from low to elevated transaminase levels ; 9 BUP and 15 MET participants showed extreme liver test elevations and were more likely than those without extreme elevations to have seroconverted to both hepatitis B and C during the study , or to use illicit drugs during the first 8 weeks of treatment . MET participants were retained longer in treatment than BUP participants . CONCLUSIONS This study demonstrated no evidence of liver damage during the initial 6 months of treatment in either condition . Physicians can prescribe either medication without major concern for liver injury Aims To test the effect of a 50‐mg day−1 dose of naltrexone in the maintenance treatment of intravenous‐buprenorphine dependence in comparison with a 50‐mg day−1 dose of methadone and also a 5‐mg day−1 dose of buprenorphine over a 24‐week treatment period Patients with opioid addiction who receive prescription opioids for treatment of nonmalignant chronic pain present a therapeutic challenge . Fifty-four participants with chronic pain and opioid addiction were r and omized to receive methadone or buprenorphine/naloxone . At the 6-month follow-up examination , 26 ( 48.1 % ) participants who remained in the study noted a 12.75 % reduction in pain ( P = 0.043 ) , and no participants in the methadone group compared to 5 in the buprenorphine group reported illicit opioid use ( P = 0.039 ) . Other differences between the two conditions were not found . Long-term , low-dose methadone or buprenorphine/naloxone treatment produced analgesia in participants with chronic pain and opioid addiction OBJECTIVE To assess the efficacy of buprenorphine for short-term maintenance/detoxification . DESIGN A r and omized , double-blind , parallel group study comparing buprenorphine , 8 mg/d , methadone , 60 mg/d , and methadone , 20 mg/d , in a 17-week maintenance phase followed by an 8-week detoxification phase . SETTING Outpatient facilities at the Addiction Research Center , Baltimore , Md. PATIENTS One hundred sixty-two volunteers seeking treatment for opioid dependence . INTERVENTION In addition to the medication , counseling using a relapse prevention model was offered but not required . PRIMARY OUTCOME MEASURES Retention time in treatment , urine sample s negative for opioids , and failure to maintain abstinence . RESULTS Throughout the maintenance phase , retention rates were significantly greater for buprenorphine ( 42 % ) than for methadone , 20 mg/d ( 20 % , P less than .04 ) ; the percentage of urine sample s negative for opioids was significantly greater for buprenorphine ( 53 % , P less than .001 ) and methadone , 60 mg/d ( 44 % , P less than .04 ) , than for methadone , 20 mg/d ( 29 % ) . Failure to maintain abstinence during the maintenance phase was significantly greater for methadone , 20 mg/d , than for buprenorphine ( P less than .03 ) . During the detoxification phase , no differences were observed between groups with respect to urine sample s negative for opioids . For the entire 25 weeks , retention rates for buprenorphine ( 30 % , P less than .01 ) and methadone , 60 mg/d ( 20 % , P less than .05 ) , were significantly greater than for methadone , 20 mg/d ( 6 % ) . All treatments were well tolerated , with similar profiles of self-reported adverse effects . The percentages of patients who received counseling did not differ between groups . CONCLUSIONS Buprenorphine was as effective as methadone , 60 mg/d , and both were superior to methadone , 20 mg/d , in reducing illicit opioid use and maintaining patients in treatment for 25 weeks AIMS To compare the effects of levo-alpha-acetylmethadol ( LAAM ) and methadone maintenance ( MM ) on treatment retention and abstinence from opiate use . DESIGN A two-group experimental design with patients r and omly assigned ( 2 : 1 LAAM : MM ) to receive LAAM ( three doses per week ) or methadone ( daily dosing ) . SETTING A community clinic in Los Angeles , California . PARTICIPANTS A total of 315 patients seeking LAAM or methadone maintenance . INTERVENTION LAAM or methadone maintenance , plus ancillary services available to all patients . LAAM and methadone dose levels varied according to clinical judgement . Electrocardiograms were administered to LAAM patients monthly . MEASUREMENTS Treatment status at 26-week follow-up and number of days retained in treatment , weekly clinical urine tests and 26-week research urine test . FINDINGS LAAM and methadone patients did not differ on treatment retention . LAAM patients were less likely to test positive for opiate use during treatment ( 40 % versus 60 % ) and at 26-week follow up ( 39.8 % versus 60.2 % ) . Benefits of LAAM were confined to patients ( n = 204 ) still in treatment at 26 weeks ( 33 % positive in patients receiving LAAM and 61 % in patients receiving methadone ) . No adverse events , cardiological or otherwise , were observed with LAAM administration . CONCLUSIONS LAAM is an effective medication for the treatment of opiate dependence with clinical advantages due not only to the reduction of opiate use but also to the alternate-day dosing schedule . LAAM may be more effective than methadone in promoting abstinence from opiate use among patients for whom LAAM is an acceptable alternative to methadone Objectives : Dependence on prescription opioids ( PO ) is a growing problem . Although most research with buprenorphine has focused on heroin-dependent population s , we hypothesize that individuals dependent on PO display characteristics that may predict different outcomes in treatment , particularly in short-term taper procedures in which comorbidities such as pain conditions may complicate taper . Methods : This secondary data analysis examined differences in outcomes between PO users ( n = 90 ) and heroin users ( n = 426 ) after a buprenorphine taper . Data were collected in a multisite r and omized clinical trial conducted by the National Drug Abuse Treatment Clinical Trials Network at 11 study sites across the United States . After a 4-week buprenorphine induction/stabilization phase , 516 opioid-dependent individuals were r and omized into 1 of 2 taper lengths ( 7 vs 28 days ) to assess the association between taper length and outcome . The primary outcome was measured by urine drug test for opioids at the end of the taper period . Craving , withdrawal , and buprenorphine dose were also examined . Results : After controlling for baseline demographic and drug use differences between the opioid use groups , results indicate that a higher percentage of the PO group ( 49 % ) provided an opioid-free urine drug specimen at the end of taper compared with the heroin group ( 36 % ; & khgr;21 = 6.592 , P < 0.010 ) . Conclusion Short-term taper is not recommended as a st and -alone treatment ; however , patients may taper from buprenorphine as part of a treatment plan . Despite greater comorbidity , PO users seem to have favorable taper outcomes compared with heroin users . Further studies are required to examine longer-term treatment outcomes IMPORTANCE Prescription opioid dependence is increasing and creates a significant public health burden , but primary care physicians lack evidence -based guidelines to decide between tapering doses followed by discontinuation of buprenorphine hydrochloride and naloxone hydrochloride therapy ( hereinafter referred to as buprenorphine therapy ) or ongoing maintenance therapy . OBJECTIVE To determine the efficacy of buprenorphine taper vs ongoing maintenance therapy in primary care-based treatment for prescription opioid dependence . DESIGN , SETTING , AND PARTICIPANTS We conducted a 14-week r and omized clinical trial that enrolled 113 patients with prescription opioid dependence from February 17 , 2009 , through February 1 , 2013 , in a single primary care site . INTERVENTIONS Patients were r and omized to buprenorphine taper ( taper condition ) or ongoing buprenorphine maintenance therapy ( maintenance condition ) . The buprenorphine taper was initiated after 6 weeks of stabilization , lasted for 3 weeks , and included medications for opioid withdrawal , after which patients were offered naltrexone treatment . The maintenance group received ongoing buprenorphine therapy . All patients received physician and nurse support and drug counseling . MAIN OUTCOMES AND MEASURES Illicit opioid use via results of urin analysis and patient report , treatment retention , and reinitiation of buprenorphine therapy ( taper group only ) . RESULTS During the trial , the mean percentage of urine sample s negative for opioids was lower for patients in the taper group ( 35.2 % [ 95 % CI , 26.2%-44.2 % ] ) compared with those in the maintenance group ( 53.2 % [ 95 % CI , 44.3%-62.0 % ] ) . Patients in the taper group reported more days per week of illicit opioid use than those in the maintenance group once they were no longer receiving buprenorphine ( mean use , 1.27 [ 95 % CI , 0.60 - 1.94 ] vs 0.47 [ 95 % CI , 0.19 - 0.74 ] days ) . Patients in the taper group had fewer maximum consecutive weeks of opioid abstinence compared with those in the maintenance group ( mean abstinence , 2.70 [ 95 % CI , 1.72 - 3.75 ] vs 5.20 [ 95 % CI , 4.16 - 6.20 ] weeks ) . Patients in the taper group were less likely to complete the trial ( 6 of 57 [ 11 % ] vs 37 of 56 [ 66 % ] ; P < .001 ) . Sixteen patients in the taper group reinitiated buprenorphine treatment after the taper owing to relapse . CONCLUSIONS AND RELEVANCE Tapering is less efficacious than ongoing maintenance treatment in patients with prescription opioid dependence who receive buprenorphine therapy in primary care . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00555425 BACKGROUND The optimal level of counseling and frequency of attendance for medication distribution has not been established for the primary care , office-based buprenorphine-naloxone treatment of opioid dependence . METHODS We conducted a 24-week r and omized , controlled clinical trial with 166 patients assigned to one of three treatments : st and ard medical management and either once-weekly or thrice-weekly medication dispensing or enhanced medical management and thrice-weekly medication dispensing . St and ard medical management was brief , manual-guided , medically focused counseling ; enhanced management was similar , but each session was extended . The primary outcomes were the self-reported frequency of illicit opioid use , the percentage of opioid-negative urine specimens , and the maximum number of consecutive weeks of abstinence from illicit opioids . RESULTS The three treatments had similar efficacies with respect to the mean percentage of opioid-negative urine specimens ( st and ard medical management and once-weekly medication dispensing , 44 percent ; st and ard medical management and thrice-weekly medication dispensing , 40 percent ; and enhanced medical management and thrice-weekly medication dispensing , 40 percent ; P=0.82 ) and the maximum number of consecutive weeks during which patients were abstinent from illicit opioids . All three treatments were associated with significant reductions from baseline in the frequency of illicit opioid use , but there were no significant differences among the treatments . The proportion of patients remaining in the study at 24 weeks did not differ significantly among the patients receiving st and ard medical management and once-weekly medication dispensing ( 48 percent ) or thrice-weekly medication dispensing ( 43 percent ) or enhanced medical management and thrice-weekly medication dispensing ( 39 percent ) ( P=0.64 ) . Adherence to buprenorphine-naloxone treatment varied ; increased adherence was associated with improved treatment outcomes . CONCLUSIONS Among patients receiving buprenorphine-naloxone in primary care for opioid dependence , the efficacy of brief weekly counseling and once-weekly medication dispensing did not differ significantly from that of extended weekly counseling and thrice-weekly dispensing . Strategies to improve buprenorphine-naloxone adherence are needed . ( Clinical Trials.gov number , NCT00023283 [ Clinical Trials.gov ] . ) BACKGROUND The evaluation of quality of life and self-perceived health represents an assessment of the impact of treatment on patient functioning and well-being . OBJECTIVE Our aim was to explore the impact of methadone maintenance treatment on quality of life and self-perceived health of opioid-dependent persons in Lithuania . METHODS A total of 102 opioid-dependent patients were recruited in the study . A prospect i ve follow-up study design was used . To assess quality of life , the WHOQOL-BREF 26-item version was used . The impact of methadone maintenance treatment on self-perceived health was assessed by Opiate Treatment Index ( OTI ) . RESULTS Following 6 months of methadone maintenance treatment , significant improvements in physical ( P=0.004 ) , psychological ( P=0.004 ) , and environmental ( P=0.048 ) components of quality of life were observed ; no statistically significant improvements were found in social component of quality of life . Study participants reported lower rates of medical morbidity associated with injection ( P<0.001 ) , cardiorespiratory ( P=0.034 ) , musculoskeletal ( P<0.001 ) , neurological ( P=0.013 ) , gastrointestinal ( P<0.001 ) , and general health ( P<0.001 ) . CONCLUSIONS Methadone maintenance treatment substantially reduces morbidity associated with opioid dependence and improves the quality of life of patients This article reports results for patients who completed the 16-week maintenance phase of a double-blind clinical trial comparing buprenorphine ( N = 43 ; average dose = 9.0 mg/day sublingually ) with methadone ( N = 43 ; average dose = 54 mg/day orally ) in the outpatient treatment of opioid dependence . In addition to pharmacotherapy , treatment during the clinical trial included individual counseling , weekly group therapy , and on-site medical services . Patients in both medication groups showed significant and substantial improvements over time in areas of psychosocial functioning , as assessed by the Addiction Severity Index , rates of urinalysis tests positive for opioids , and self-reports of opioid withdrawal symptoms , illicit opioid use , and cocaine use . Buprenorphine and methadone produced very similar outcomes on the wide array of outcome measures assessed , and improvements for both groups were large and occurred rapidly after treatment entry . A trend toward continued improvement in opioid-positive urines over time was noted for the buprenorphine but not the methadone group . These results provide further evidence of the efficacy of buprenorphine in the treatment of opioid dependence and provide a characterization of the time course of effects for buprenorphine and methadone . In addition , these results demonstrate the benefits of drug abuse treatment , both for drug and alcohol use and in other areas of psychosocial functioning BACKGROUND Important questions remain regarding the necessary duration and intensity for methadone treatment to be effective . METHODS As part of a clinical trial of tuberculosis chemoprophylaxis [ Batki , S.L. , Gruber , V.A. , Bradley , J.M. , Bradley , M. , Delucchi , K. , 2002 . A controlled trial of methadone treatment combined with directly observed isoniazid for tuberculosis prevention in injection drug users . Drug Alcohol Depend . 66 283 - 293 . doi:10.1016/S0376 - 8716(01)00208 - 3 ] , patients with opioid dependence were recruited from an outpatient 21-day methadone detoxification program and were r and omly assigned to one of three treatment conditions : ( 1 ) continuation in 21-day methadone detoxification ; ( 2 ) transfer to 6-month methadone maintenance with only minimal counseling ; or ( 3 ) transfer to 6-month methadone maintenance with st and ard twice monthly counseling and as-needed social work and psychiatric services . Both the 6-month maintenance treatments were followed by 1.5 months of detoxification . Urine drug tests and self-report measures were collected at baseline , months 1 - 6 , and month 8.5 . RESULTS Compared to 21-day methadone detoxification , 6-month methadone maintenance with either minimal or st and ard counseling result ed in fewer opiate positive urine tests and days of self-reported heroin and alcohol use . There was no change in cocaine use or other outcome measures . The increased counseling available in the st and ard counseling condition did not appear to reduce heroin use further than the minimal counseling condition , in contrast to the effect found for more structured counseling in long-term methadone maintenance ( McLellan et al. , 1993 ) . CONCLUSIONS Six months of methadone maintenance , even with minimal counseling , reduces heroin and alcohol use more than 21-day methadone detoxification This study compared the safety and efficacy of sublingual buprenorphine tablets with oral methadone in a population of opioid-dependent individuals in a double-blind , r and omized , 6-week trial using a flexible dosing procedure . Fifty-eight patients seeking treatment for opioid dependence were recruited in three outpatient facilities and r and omly assigned to substitution with buprenorphine or methadone . The retention rate was significantly better in the methadone maintained group ( 90 vs. 56 % ; P<0.001 ) . Subjects completing the study in both the treatment groups had similar proportions of opioid positive urine sample s ( buprenorphine 62 % ; methadone 59 % ) and positive urine specimens , as well as mean heroin craving scores decreased significantly over time ( P=0.035 and P<0.001 ) . The proportion of cocaine-positive toxicology results did not differ between groups . At week six mean stabilization doses were 10.5 mg per day for the sublingual buprenorphine tablet , and 69.8 mg per day for methadone , respectively . Patient performance during maintenance was similar in both the groups . The high attrition rate in the buprenorphine group during the induction phase might reflect inadequate induction doses . Thus , buprenorphine is a viable alternative for methadone in short-term maintenance treatment for heroin dependence if treatment induction is done with adequate dosages AIMS The aim of this study is to assess the prevalence of non-opioid drug use among opioid-addicted , buprenorphine injecting individuals in Georgia , during and after a 12-week course of buprenorphine-naloxone ( Suboxone ® ) or methadone . METHODS R and omized controlled trial with daily observed Suboxone ® or methadone and weekly counseling , urine tests and timeline followback ( TLFB ) in weeks 0 - 12 and 20 , and the Addiction Severity Index ( ASI ) at weeks 0 , 4 , 8 , 12 , 20 . RESULTS Of the 80 patients ( 40/group , 4 women ) , 68 ( 85 % ) completed the 12-weeks of study treatment and 66 ( 82.5 % ) completed the 20-week follow-up . At baseline , injecting more than one drug in the last 30 days was reported by 68.4 % of patients in the methadone and 72.5 % in the Suboxone ® groups . Drug use was markedly reduced in both treatment conditions but there were significant differences in the prevalence of specific drugs with more opioid ( 1.5 vs. 0.2 % ; p=0.03 ) , less amphetamine ( 0.2 vs. 2.8 % ; p<0.001 ) and less marijuana ( 1.7 vs. 10.2 % ; p<0.001 ) positive urine tests in the methadone vs. Suboxone ® groups . At the 20-week follow-up , TLFB results on the 34 that continued methadone or the 3 on Suboxone ® showed less opioid ( 5.6 vs. 27.6 % ; p<0.001 ) , illicit buprenorphine ( 2.7 vs. 13.8 % ; p=0.005 ) , benzodiazepine ( 13.5 vs. 34.5 % ; p<0.001 ) , and marijuana ( 2.8 vs. 20.7 % ; p<0.001 ) use than the 29 who did not continue opioid substitution therapy . CONCLUSIONS Despite small but significant differences in opioid and other drug use , both treatments were highly effective in reducing opioid and non-opioid drug use The efficacy of buprenorphine in opioid dependent patients ( n = 20 ) was compared to methadone maintained subjects ( n = 20 ) in a r and omized comparison trial . Sublingual application of buprenorphine as an alternative synthetical opioid is being compared to methadone during a 24 week study period . A trend ( p = 0.06 ) could be found in the retention rate of investigated patients being maintained on a mean dosage of 63 mg oral applicable methadone ( racemat of L- and D-methadone ) in comparison to the group on a mean dosage of 7.3 mg buprenorphine ( sublingual tablets ) . The dropout-rate of 11 subjects at the end of the study in the buprenorphine group was higher when compared to the dropout-rate of 5 in the methadone group . There was no significant difference between the two groups over the treatment period in respect to additional consumption of opiates , benzodiazepines and cocaine as evaluated through urine toxicology . The result in regard to compliance over the study period demonstrates that methadone appears to be the more successful oral opioid ( p = 0.04 ) . Nevertheless , efficacy of buprenorphine in maintenance could be demonstrated in the remaining subjects , and further studies with higher daily doses and a higher number of subjects have to be performed BACKGROUND Office-based treatment of opiate addiction with a sublingual-tablet formulation of buprenorphine and naloxone has been proposed , but its efficacy and safety have not been well studied . METHODS We conducted a multicenter , r and omized , placebo-controlled trial involving 326 opiate-addicted persons who were assigned to office-based treatment with sublingual tablets consisting of buprenorphine ( 16 mg ) in combination with naloxone ( 4 mg ) , buprenorphine alone ( 16 mg ) , or placebo given daily for four weeks . The primary outcome measures were the percentage of urine sample s negative for opiates and the subjects ' self-reported craving for opiates . Safety data were obtained on 461 opiate-addicted persons who participated in an open-label study of buprenorphine and naloxone ( at daily doses of up to 24 mg and 6 mg , respectively ) and another 11 persons who received this combination only during the trial . RESULTS The double-blind trial was terminated early because buprenorphine and naloxone in combination and buprenorphine alone were found to have greater efficacy than placebo . The proportion of urine sample s that were negative for opiates was greater in the combined-treatment and buprenorphine groups ( 17.8 percent and 20.7 percent , respectively ) than in the placebo group ( 5.8 percent , P<0.001 for both comparisons ) ; the active-treatment groups also reported less opiate craving ( P<0.001 for both comparisons with placebo ) . Rates of adverse events were similar in the active-treatment and placebo groups . During the open-label phase , the percentage of urine sample s negative for opiates ranged from 35.2 percent to 67.4 percent . Results from the open-label follow-up study indicated that the combined treatment was safe and well tolerated . CONCLUSIONS Buprenorphine and naloxone in combination and buprenorphine alone are safe and reduce the use of opiates and the craving for opiates among opiate-addicted persons who receive these medications in an office-based setting Two groups each of 10 patients enrolled in a 90-day outpatient detoxification program were classified on the basis of high ( 92.5 % of tests ) and low ( 7.5 % of tests ) rates of opiate-positive urine test results during two weeks of dosage stabilization . Pretreatment demographic variables did not differ between the two groups . Relapse to opiate use during the detoxification occurred in patients who were initially opiate free . By the end of the dose reduction period , opiate-positive rates were 60 % and 87 % of tests for the low and high opiate use groups , respectively . Sedative use and missed clinic days showed similar trends for both groups during the detoxification , although different patterns of drop-out from treatment were noted . Symptomatology increased during dose reduction for the low- but not for the high-frequency opiate group . In general , treatment outcome appeared equally poor for patients who showed low or high levels of illicit opiate drug use early in detoxification treatment Eight opioid-dependent individuals were maintained on daily sublingual buprenorphine ( 8 mg ) for 28 days and assigned r and omly to one of two outpatient detoxification schedules under double-blind , double-dummy conditions . The two detoxification schedules were buprenorphine gradual ( 36 days ; N = 3 ) or buprenorphine rapid ( 12 days ; N = 5 ) . Outcome variables were subject- and observer-ratings of opioid withdrawal , treatment retention and illicit-opioid use . Outcome measures were similar for the two groups during buprenorphine maintenance . Increases in subject-rated opioid withdrawal and illicit-opioid use , and a drop in treatment retention occurred during rapid detoxification . Stable subject-rated opioid withdrawal and treatment retention , and less illicit-opioid use occurred during gradual detoxification . These data suggest that gradual reduction in buprenorphine dose is likely to produce superior treatment outcomes than more rapid buprenorphine detoxification A three-centre , r and omised , double-blind study was design ed to compare the efficacy and safety of buprenorphine and methadone . This was the first European study to compare these agents and was based on a previous trial performed in the US . Opioid-dependent subjects were r and omised to receive either sublingual buprenorphine or oral methadone daily . Both objective and subjective measures of efficacy were monitored weekly , and safety parameters were regularly monitored over the entire six-week study . Urinalysis showed that the two treatments were similar with a slight increase in opioid-negative urines noted in both groups . The retention rate in the buprenorphine group was lower than in the methadone group , although it has been suggested that the buprenorphine dose may have been too low for some patients . None of the side effects noted were considered serious and all were attributable to chronic opioid dependence . Experience of two years substitution treatment in Fribourg suggests that initial induction onto buprenorphine allows for patients to be subgrouped before being given the most appropriate maintenance agent . Further investigation is required into the different dose-related effects of buprenorphine seen in particular subsets of addicts As a maintenance agent for opioid dependency , buprenorphine offers advantages such as a lower level of dependence and minimal withdrawal symptoms , due to its partial agonist properties at the µ-opioid receptor . Previous studies have shown 8 mg sublingual buprenorphine to be equivalent to 60 mg oral methadone in terms of retention rate and opioid-negative urine levels . In a 24-week , ongoing European study , 34 opioid-dependent subjects were assessed ; 16 receiving buprenorphine and 18 methadone . A free dosing schedule was used with no upper limit for methadone dosing but with a maximum buprenorphine dose of 8 mg . Screening prior to the study excluded subjects with polysubstance dependence , somatic disease and /or HIV infection . Primary outcome measures were abstinence from other drugs , for which subjects provided weekly urine sample s for analysis of opioids , cocaine and benzodiazepines , and retention in treatment . Patients in the buprenorphine group provided a greater proportion of negative urine sample s , in particular cocaine-negative sample s , compared with the methadone group , although this was not statistically significant . Retention in the buprenorphine group was significantly lower than in the methadone group , suggesting that the 8 mg buprenorphine limit may have biased the results in favour of methadone , and that this dose may have been too low for those subjects with high levels of dependence . However , buprenorphine is clearly effective in the more motivated subjects and further investigation in this subgroup is recommended IMPORTANCE Opioid-dependent patients often use the emergency department ( ED ) for medical care . OBJECTIVE To test the efficacy of 3 interventions for opioid dependence : ( 1 ) screening and referral to treatment ( referral ) ; ( 2 ) screening , brief intervention , and facilitated referral to community-based treatment services ( brief intervention ) ; and ( 3 ) screening , brief intervention , ED-initiated treatment with buprenorphine/naloxone , and referral to primary care for 10-week follow-up ( buprenorphine ) . DESIGN , SETTING , AND PARTICIPANTS A r and omized clinical trial involving 329 opioid-dependent patients who were treated at an urban teaching hospital ED from April 7 , 2009 , through June 25 , 2013 . INTERVENTIONS After screening , 104 patients were r and omized to the referral group , 111 to the brief intervention group , and 114 to the buprenorphine treatment group . MAIN OUTCOMES AND MEASURES Enrollment in and receiving addiction treatment 30 days after r and omization was the primary outcome . Self-reported days of illicit opioid use , urine testing for illicit opioids , human immunodeficiency virus ( HIV ) risk , and use of addiction treatment services were the secondary outcomes . RESULTS Seventy-eight percent of patients in the buprenorphine group ( 89 of 114 [ 95 % CI , 70%-85 % ] ) vs 37 % in the referral group ( 38 of 102 [ 95 % CI , 28%-47 % ] ) and 45 % in the brief intervention group ( 50 of 111 [ 95 % CI , 36%-54 % ] ) were engaged in addiction treatment on the 30th day after r and omization ( P < .001 ) . The buprenorphine group reduced the number of days of illicit opioid use per week from 5.4 days ( 95 % CI , 5.1 - 5.7 ) to 0.9 days ( 95 % CI , 0.5 - 1.3 ) vs a reduction from 5.4 days ( 95 % CI , 5.1 - 5.7 ) to 2.3 days ( 95 % CI , 1.7 - 3.0 ) in the referral group and from 5.6 days ( 95 % CI , 5.3 - 5.9 ) to 2.4 days ( 95 % CI , 1.8 - 3.0 ) in the brief intervention group ( P < .001 for both time and intervention effects ; P = .02 for the interaction effect ) . The rates of urine sample s that tested negative for opioids did not differ statistically across groups , with 53.8 % ( 95 % CI , 42%-65 % ) in the referral group , 42.9 % ( 95 % CI , 31%-55 % ) in the brief intervention group , and 57.6 % ( 95 % CI , 47%-68 % ) in the buprenorphine group ( P = .17 ) . There were no statistically significant differences in HIV risk across groups ( P = .66 ) . Eleven percent of patients in the buprenorphine group ( 95 % CI , 6%-19 % ) used inpatient addiction treatment services , whereas 37 % in the referral group ( 95 % CI , 27%-48 % ) and 35 % in the brief intervention group ( 95 % CI , 25%-37 % ) used inpatient addiction treatment services ( P < .001 ) . CONCLUSIONS AND RELEVANCE Among opioid-dependent patients , ED-initiated buprenorphine treatment vs brief intervention and referral significantly increased engagement in addiction treatment , reduced self-reported illicit opioid use , and decreased use of inpatient addiction treatment services but did not significantly decrease the rates of urine sample s that tested positive for opioids or of HIV risk . These findings require replication in other centers before widespread adoption . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00913770 |
10,752 | 25,347,444 | Thyroid screening could identify persons with sub clinical as well as undiagnosed overt thyroid dysfunction who could potentially benefit from treatment to reduce the risk for adverse health outcomes .
Does treating screen-detected overt or sub clinical thyroid dysfunction improve : a ) mortality and morbidity ? | An estimated 5 % of women and 3 % of men in the United States have sub clinical thyroid dysfunction ( 1 ) , and approximately 0.5 % of the population may have undiagnosed overt thyroid disease ( 2 , 3 ) .
Sub clinical thyroid dysfunction is defined as elevated or low results on a thyroid-stimulating hormone ( TSH ) test ( reference range , 0.45 to 4.50 mIU/L ) in the setting of normal thyroid hormone levels .
Overt thyroid disease is defined by the presence of abnormal thyroid hormone ( free thyroxine , with or without triiodothyronine ) levels ( 4 , 5 ) ( Table 1 ) .
In some studies , sub clinical hypothyroidism is associated with increased risk for coronary artery disease ( 6 , 7 ) ; congestive heart failure ( 8) ; and sub clinical hyperthyroidism with increased risk for all-cause and coronary heart disease mortality , atrial fibrillation ( 9 ) , and decreased bone density ( 5 ) .
Overt thyroid disease is associated with negative cardiovascular , musculoskeletal , dermatologic , gastrointestinal , and other effects , but clinical manifestations are highly variable and depend on the severity of thyroid abnormalities .
Nonetheless , prescribing rates for thyroid medication in the United States have increased dramatically , from an estimated 49.8 million in 2006 to 70.5 million in 2010 ( 10 ) .
Among community-dwelling persons who are older than 65 years with sub clinical hypothyroidism , the proportion receiving thyroid hormone has more than doubled , from 8.1 % to 20.0 % , between 1989 and 2005 ( 11 ) .
Before updating its 2004 recommendation , the USPSTF determined that in addition to sub clinical thyroid dysfunction , screening could also identify undiagnosed overt thyroid disease ( 2 , 3 ) ; therefore , the decision to screen should also consider the potential benefits and harms of identifying and treating undiagnosed overt disease .
Does screening for thyroid dysfunction reduce morbidity and mortality ?
2 .
What are the harms of screening ?
3 .
or b ) intermediate outcomes ?
4 .
What are the harms of treating thyroid dysfunction detected by screening ? | Background — American College of Cardiology/American Heart Association guidelines for the diagnosis and management of heart failure recommend investigating exacerbating conditions such as thyroid dysfunction , but without specifying the impact of different thyroid-stimulation hormone ( TSH ) levels . Limited prospect i ve data exist on the association between sub clinical thyroid dysfunction and heart failure events . Methods and Results — We performed a pooled analysis of individual participant data using all available prospect i ve cohorts with thyroid function tests and subsequent follow-up of heart failure events . Individual data on 25 390 participants with 216 248 person-years of follow-up were supplied from 6 prospect i ve cohorts in the United States and Europe . Euthyroidism was defined as TSH of 0.45 to 4.49 mIU/L , sub clinical hypothyroidism as TSH of 4.5 to 19.9 mIU/L , and sub clinical hyperthyroidism as TSH < 0.45 mIU/L , the last two with normal free thyroxine levels . Among 25 390 participants , 2068 ( 8.1 % ) had sub clinical hypothyroidism and 648 ( 2.6 % ) had sub clinical hyperthyroidism . In age- and sex-adjusted analyses , risks of heart failure events were increased with both higher and lower TSH levels ( P for quadratic pattern < 0.01 ) ; the hazard ratio was 1.01 ( 95 % confidence interval , 0.81–1.26 ) for TSH of 4.5 to 6.9 mIU/L , 1.65 ( 95 % confidence interval , 0.84–3.23 ) for TSH of 7.0 to 9.9 mIU/L , 1.86 ( 95 % confidence interval , 1.27–2.72 ) for TSH of 10.0 to 19.9 mIU/L ( P for trend < 0.01 ) and 1.31 ( 95 % confidence interval , 0.88–1.95 ) for TSH of 0.10 to 0.44 mIU/L and 1.94 ( 95 % confidence interval , 1.01–3.72 ) for TSH < 0.10 mIU/L ( P for trend=0.047 ) . Risks remained similar after adjustment for cardiovascular risk factors . Conclusion — Risks of heart failure events were increased with both higher and lower TSH levels , particularly for TSH ≥10 and < 0.10 PURPOSE The role of thyroxine replacement in sub clinical hypothyroidism remains unclear . We performed a 6-month r and omized , double-blind , placebo-controlled trial to evaluate the effects of thyroxine treatment for mild sub clinical hypothyroidism , defined as a serum thyroid-stimulating hormone level between 5 to 10 microU/mL with a normal serum free thyroxine level ( 0.8 - 16 ng/dL ) . SUBJECTS AND METHODS We r and omly assigned 40 women with mild sub clinical hypothyroidism who had presented to their family practitioners to either thyroxine treatment ( n = 23 ; 50 to 100 microg daily ) or placebo ( n = 17 ) . Health-related quality of life ( Hospital Anxiety and Depression scale , 30-item General Health Question naire ) , fasting lipid profiles , body weight , and resting energy expenditure were measured at baseline and 6 months . RESULTS The most common presenting symptoms were fatigue ( n = 33 [ 83 % ] ) and weight gain ( n = 32 [ 80 % ] ) . At presentation , 20 women ( 50 % ) had elevated anxiety scores and 22 ( 56 % ) had elevated scores on the General Health Question naire . Thirty-five women completed the study . There were no significant differences in the changes from baseline to 6 months between women in the thyroxine group and the placebo group for any of the metabolic , lipid , or anthropometric variables measured , expressed as the mean change in the thyroxine group minus the mean change in the placebo group : body mass index , -0.3 kg/m(2 ) ( 95 % confidence interval [ CI ] : -0.9 to 0.4 kg/m(2 ) ) ; resting energy expenditure , -0.2 kcal/kg/24 h ( 95 % CI : -1.3 to 1.0 kcal/kg/24 h ) ; and low-density lipoprotein cholesterol , -4 mg/dL ( 95 % CI : -23 to 15 mg/dL ) . There was a significant worsening in anxiety scores in the thyroxine group ( scores increased in 8 of 20 women and were unchanged in 2 of 20 ) compared with the placebo group ( scores increased in 1 of 14 women and were unchanged in 6 of 14 ; P = 0.03 ) . CONCLUSIONS ; We observed no clinical ly relevant benefits from 6 months of thyroxine treatment in women with mild sub clinical hypothyroidism Sub clinical hypothyroidism ( sHT ) is associated with dyslipidemia and enhanced cardiovascular risk . We assessed carotid artery intima-media thickness ( IMT , high-resolution ultrasonography ) and lipoprotein profile in 45 sHT patients ( aged 37 + /- 11 yr ) at baseline and after 6 months of r and omized , placebo-controlled L-T(4 ) replacement . In comparison with 32 age- and sex-matched controls , sHT patients had elevated total and low-density lipoprotein ( LDL ) cholesterol and ApoB levels ( P = 0.002 , P = 0.0007 , and P = 0.01 , respectively ) and higher mean-IMT values ( P < 0.0001 ) . In stepwise regression analysis , mean-IMT was positively related ( r(2 ) = 0.71 , P < 0.0001 ) to age , TSH , and LDL cholesterol . L-T(4 ) replacement significantly reduced both total and LDL cholesterol ( P < 0.0001 for both ) and mean-IMT ( by 11 % , P < 0.0001 ) . The decrement in IMT was directly related to the decrements of both total cholesterol and TSH ( P = 0.02 and P = 0.0001 , respectively ) . We conclude that early carotid artery wall alterations are present in sHT patients . Whether such IMT increase is related to an early atherosclerotic involvement of the arterial wall can not be clearly decided on the basis of the present results . However , the fact that L-T(4 ) replacement therapy was able to improve both the atherogenic lipoprotein profile and intima-media thickening suggests that lipid infiltration of arterial wall may represent a major mechanism underlying IMT increase in sub clinical hypothyroidism OBJECTIVE To evaluate the effects of physiologic doses of levothyroxine replacement on the lipoprotein profile in patients with sub clinical hypothyroidism ( SCH ) . METHODS In a prospect i ve , double-blind , placebo-controlled study , we enrolled 120 patients --mostly , but not exclusively , premenopausal women -- with SCH . Patients were r and omly assigned to either a levothyroxine-treated group ( n = 60 ) or a placebo ( control ) group ( n = 60 ) . Total cholesterol ( TC ) , low-density lipoprotein cholesterol ( LDL-C ) , high-density lipoprotein cholesterol ( HDL-C ) , and triglycerides ( TG ) were measured before and 52 weeks after assignment to either group . RESULTS In the levothyroxine-treated group , the lipoprotein mean values before and after the 52-week study were as follows : TC , 5.05 + /- 0.98 mmol/L versus 4.74 + /- 0.87 mmol/L ( P<.0001 ) ; LDL-C , 3.30 + /- 0.90 mmol/L versus 2.89 + /- 0.59 mmol/L ( P<.01 ) ; TG , 1.18 + /- 0.71 mmol/L versus 0.95 + /- 0.53 mmol/L ( P<.002 ) ; and HDL-C , 1.20 + /- 0.33 mmol/L versus 1.19 + /- 0.32 mmol/L ( P = .29 ) . In the control group , TC , HDL-C , and TG values remained unchanged after 52 weeks in comparison with baseline , but LDL-C mean values increased from 2.79 + /- 0.60 mmol/L to 3.11 + /- 0.77 mmol/L , a change that was statistically significant ( P<.001 ) . At the end of the study , the lipid profile changes between levothyroxine-treated and control groups were compared . Total cholesterol and LDL-C were significantly lower in the levothyroxine-receiving group ( P<.029 and P<.0001 , respectively ) in comparison with the control group . The difference did not reach statistical significance for TG and HDL-C values . CONCLUSION In premenopausal women , SCH has a negative effect on the lipoprotein profile and may translate into a sizable cardiovascular risk if left untreated BACKGROUND : Previous studies have suggested an association between sub clinical hypothyroidism and coronary artery disease that could be related to changes in serum lipids or endothelial dysfunction . METHODS : Thirty-two female sub clinical hypothyroidism patients were r and omly assigned to 12 months of L-thyroxine replacement or no treatment . Endothelial function was measured by the flow-mediated vasodilatation of the brachial artery , as well as mean carotid artery intima-media thickness , and lipid profiles were studied at baseline and after 12 months of follow-up . RESULTS : The mean ( ±SD ) serum thyroid-stimulating hormone levels in the L-thyroxine replacement and control groups were 6.09±1.32 and 6.27±1.39 µUI/ml , respectively . No relationship between carotid artery intima-media thickness or brachial flow-mediated vasodilatation and free T4 and serum thyroid-stimulating hormone was found . The median L-T4 dose was 44.23±18.13 µg/day . After 12 months , there was a significant decrease in the flow-mediated vasodilatation in the sub clinical hypothyroidism control group ( before : 17.33±7.88 to after : 13.1±4.75 % , p = 0.03 ) , but there were no significant differences in flow-mediated vasodilatation in the L-thyroxine treated group ( before : 16.81±7.0 to after : 18.52±7.44 % , p = 0.39 ) . We did not find any significant change in mean carotid intima-media thickness after 12 months of L-thyroxine treatment . CONCLUSION : Replacement therapy prevents a decline in flow-mediated vasodilatation with continuation of the sub clinical hypothyroidism state . Large prospect i ve multicenter placebo-controlled trials are necessary to investigate endothelial physiology further in sub clinical hypothyroidism patients and to define the role of L-thyroxine therapy in improving endothelial function in these patients The indications for treating patients with sub clinical hypothyroidism ( normal serum thyroxine and free thyroxine levels , but elevated serum thyrotrophin levels ) are poorly defined . In this study , 33 patients with sub clinical hypothyroidism were r and omly assigned in a double-blind manner to receive placebo or L-thyroxine therapy and were followed for 1 year with thyroid function tests , serum lipid measurements , basal metabolic rate and systolic time interval determinations , and a question naire on hypothyroid symptoms . The placebo group showed no changes in thyroid function or peripheral indices of thyroid hormone action . In the thyroxine-treated group , serum lipids and the mean systolic time interval did not change , but the systolic time intervals became normal in the 5 patients with the most abnormal baseline values . Symptoms improved in 8 of 14 patients receiving thyroxine and in 3 of 12 patients receiving placebo ( p less than 0.05 ) . L-Thyroxine therapy may be useful for patients with sub clinical hypothyroidism with abnormal myocardial contractility or symptoms consistent with mild hypothyroidism , or both Twenty women , who had been r and omly selected from women with sub clinical hypothyroidism identified in a population study were treated with l‐thyroxine and placebo in a double‐blind cross‐over design during 2·6 months . Three women did not complete the study , one because she moved to another part of the country , and two because of nervousness and sense of tachycardia . None of these ‘ drop‐outs ’ had any objective signs of overtreatment ; they had normal pulse rate and a serum T3 concentration within the reference interval . During l‐thyroxine treatment serum procollagen‐III‐peptide concentration increased in 13 women out of the 17 women completing the study and at the end of treatment the mean concentration was significantly raised ( P>0·001 ) . Serum concentrations of procollagen‐III‐peptide then correlated with those of free thyroxine ( P>0·01 ) , total thyroxine ( P>0·05 ) , and reverse triiodothyronine ( P>0·05 ) . The same comparison revealed little or no effect on the concentrations of serum creatine kinase activity , transcortin or sex‐hormone binding globulin . Heart rate‐corrected preejection period and symptom score decreased ( P>0·05 ) . Four women starting with l‐thyroxine showed a marked and prolonged ( 4–6 months ) rise in thyrotrophin concentration during the subsequent placebo period , but remained clinical ly euthyroid . Four women ( of 17 ) improved during therapy as judged by psychometric testing and their own rating . We could not by pretreatment observations identify these four women apart from serum free and total 3,5,3′‐triiodothyronine concentrations in the lower part of the health‐associated reference interval . Sub clinical hypothyroidism is common among middle‐aged and old women , and our findings indicate that approximately one woman in four with this ‘ sub clinical ’ condition will benefit from L‐thyroxine treatment Patients with sub clinical hypothyroidism ( SCH ) have impaired endothelial function probably related to dyslipidemia . The present study compares the effects of simvastatin versus levothyroxine ( LT-4 ) treatment on lipid profile and endothelial function in patients with SCH . Fifty-nine patients with newly diagnosed SCH were enrolled . Patients were r and omized into 3 groups to receive no treatment ( n = 19 ) , LT-4 ( n = 20 ) , or simvastatin ( n = 20 ) . We measured endothelium-dependent vasodilation ( EDV ) and endothelium-independent vasodilation ( EIV ) at baseline and after 8 months . Serum total cholesterol , triglycerides and LDL-cholesterol were significantly lower following simvastatin . EDV increased significantly in simvastatin treatment group ( 7.5 % ± 3.3 % vs 14.0 % ± 4.5 % ( P < 0.01 ) . The improvement of EDV correlated with the percent decrease of LDL-cholesterol ( ρ = 0.68 , P < 0.01 ) . Although LT-4 therapy caused a trend towards an increase in EDV compared to baseline , statistical significance was not achieved . EIV remained unchanged in all three groups . Simvastatin but not LT-4 treatment significantly improves EDV of the brachial artery and dyslipidemia in patients with SCH . Improvement in brachial artery endothelial function may be related in part to a hypolipidemic effect of simvastatin treatment We aim ed to analyze the natural course of sub clinical hypothyroidism , quantify the incidence rate of overt hypothyroidism , and evaluate the risk factors for the development of definitive thyroid failure in elderly patients . One hundred seven patients ( 93 women and 14 men ) over age 55 yr with sub clinical hypothyroidism and no previous history of thyroid disease were prospect ively studied . Subjects were followed up for 6 - 72 months ( mean , 31.7 months ) with repeated determinations of TSH and free T(4 ) . Twenty-eight patients ( 26.8 % ) developed overt hypothyroidism , and 40 ( 37.4 % ) showed normalization of their TSH values . The incidence rate of overt hypothyroidism was 9.91 cases per 100 patient-years in the whole population , and 1.76 , 19.67 , and 73.47 cases per 100 patient-years in subjects with initial TSH values between 5.0 - 9.9 , 10.0 - 14.9 , and 15.0 - 19.9 mU/liter , respectively . Kaplan-Meier analysis showed that the development of definitive thyroid hypofunction was significantly related to the presence of symptoms of hypothyroidism , goiter , positive thyroid antibodies ( P < 0.05 ) , and mainly low normal free T(4 ) ( P < 0.01 ) and high TSH ( P < 0.0001 ) concentrations at baseline . A stepwise multivariate Cox regression analysis showed that the only significant factor for progression to overt hypothyroidism was serum TSH concentration ( P < 0.0001 ) . In conclusion , TSH concentration is the most powerful predictor for the outcome of spontaneous sub clinical hypothyroidism in patients over age 55 yr . Subjects with mildly elevated TSH have a low incidence rate of overt hypothyroidism . We recommend follow-up with clinical and biochemical monitoring in these patients This study investigated whether symptoms and findings of hyperthyroidism exist in patients with sub clinical hyperthyroidism ( SCH ) and sought to determine whether hyperthyroidism treatment improves them . Twenty patients ( mean age : 36.10 + /- 1.41 years ) and 20 healthy controls [ mean age : 36.35 + /- 1.50 years ) were included in the study . The SCH duration of patients was at least 6 months . Bone mineral density ( BMD ) was measured in both patients and controls . The patients were r and omly divided into 2 groups of 10 patients each . Symptoms and findings of hyperthyroidism were evaluated and BMD , 24 hour ambulatory blood pressure , holter measurements and serum lipids were determined initially in both groups and 6 months after the attainment of euthyroidism in the treatment group ( Group 1 ) and after a 6 months follow-up in the observation group ( Group 2 ) . In the patient group , BMD showed a decrease of 1.3 % and 3.9 % in femur neck and L1 - 4 vertebra compared with controls , respectively . But there was no difference in BMD between patients and controls . Fatigue , nervousness , over sweating , tachycardia and tremor improved with treatment . The number of patients with fatigue , nervousness , over sweating and tachycardia increased in Group 2 after the observation . There was no difference between initial values and after a 6 month period from observation or on attainment of euthyroidism in the values of BMD , lipids , minimal and maximal heart rate , total number of ventricular and supraventricular beats and heart rate variability . As a result symptoms of hyperthyroidism were found to be increased in SCH but they partly decreased after antithyroid treatment . But no favourable effects of antithyroid treatment on BMD , heart rate and arrhythmia incidence were found in young , premenopausal patients with SCH during the 6 month period CONTEXT Sub clinical hypothyroidism ( SCH ) and cognitive dysfunction are both common in the elderly and have been linked . It is important to determine whether T4 replacement therapy in SCH confers cognitive benefit . OBJECTIVE Our objective was to determine whether administration of T4 replacement to achieve biochemical euthyroidism in subjects with SCH improves cognitive function . DESIGN AND SETTING We conducted a double-blind placebo-controlled r and omized controlled trial in the context of United Kingdom primary care . PATIENTS Ninety-four subjects aged 65 yr and over ( 57 females , 37 males ) with SCH were recruited from a population of 147 identified by screening . INTERVENTION T4 or placebo was given at an initial dosage of one tablet of either placebo or 25 microg T4 per day for 12 months . Thyroid function tests were performed at 8-weekly intervals with dosage adjusted in one-tablet increments to achieve TSH within the reference range for subjects in treatment arm . Fifty-two subjects received T4 ( 31 females , 21 males ; mean age 73.5 yr , range 65 - 94 yr ) ; 42 subjects received placebo ( 26 females , 16 males ; mean age 74.2 yr , 66 - 84 yr ) . MAIN OUTCOME MEASURES Mini-Mental State Examination , Middlesex Elderly Assessment of Mental State ( covering orientation , learning , memory , numeracy , perception , attention , and language skills ) , and Trail-Making A and B were administered . RESULTS Eighty-two percent and 84 % in the T4 group achieved euthyroidism at 6- and 12-month intervals , respectively . Cognitive function scores at baseline and 6 and 12 months were as follows : Mini-Mental State Examination T4 group , 28.26 , 28.9 , and 28.28 , and placebo group , 28.17 , 27.82 , and 28.25 [ not significant ( NS ) ] ; Middlesex Elderly Assessment of Mental State T4 group , 11.72 , 11.67 , and 11.78 , and placebo group , 11.21 , 11.47 , and 11.44 ( NS ) ; Trail-Making A T4 group , 45.72 , 47.65 , and 44.52 , and placebo group , 50.29 , 49.00 , and 46.97 ( NS ) ; and Trail-Making B T4 group , 110.57 , 106.61 , and 96.67 , and placebo group , 131.46 , 119.13 , and 108.38 ( NS ) . Linear mixed-model analysis demonstrated no significant changes in any of the measures of cognitive function over time and no between-group difference in cognitive scores at 6 and 12 months . CONCLUSIONS This RCT provides no evidence for treating elderly subjects with SCH with T4 replacement therapy to improve cognitive function CONTEXT Data regarding the association between sub clinical hypothyroidism and cardiovascular disease outcomes are conflicting among large prospect i ve cohort studies . This might reflect differences in participants ' age , sex , thyroid-stimulating hormone ( TSH ) levels , or preexisting cardiovascular disease . OBJECTIVE To assess the risks of coronary heart disease ( CHD ) and total mortality for adults with sub clinical hypothyroidism . DATA SOURCES AND STUDY SELECTION The data bases of MEDLINE and EMBASE ( 1950 to May 31 , 2010 ) were search ed without language restrictions for prospect i ve cohort studies with baseline thyroid function and subsequent CHD events , CHD mortality , and total mortality . The reference lists of retrieved articles also were search ed . DATA EXTRACTION Individual data on 55,287 participants with 542,494 person-years of follow-up between 1972 and 2007 were supplied from 11 prospect i ve cohorts in the United States , Europe , Australia , Brazil , and Japan . The risk of CHD events was examined in 25,977 participants from 7 cohorts with available data . Euthyroidism was defined as a TSH level of 0.50 to 4.49 mIU/L. Sub clinical hypothyroidism was defined as a TSH level of 4.5 to 19.9 mIU/L with normal thyroxine concentrations . RESULTS Among 55,287 adults , 3450 had sub clinical hypothyroidism ( 6.2 % ) and 51,837 had euthyroidism . During follow-up , 9664 participants died ( 2168 of CHD ) , and 4470 participants had CHD events ( among 7 studies ) . The risk of CHD events and CHD mortality increased with higher TSH concentrations . In age- and sex-adjusted analyses , the hazard ratio ( HR ) for CHD events was 1.00 ( 95 % confidence interval [ CI ] , 0.86 - 1.18 ) for a TSH level of 4.5 to 6.9 mIU/L ( 20.3 vs 20.3/1000 person-years for participants with euthyroidism ) , 1.17 ( 95 % CI , 0.96 - 1.43 ) for a TSH level of 7.0 to 9.9 mIU/L ( 23.8/1000 person-years ) , and 1.89 ( 95 % CI , 1.28 - 2.80 ) for a TSH level of 10 to 19.9 mIU/L ( n = 70 events/235 ; 38.4/1000 person-years ; P < .001 for trend ) . The corresponding HRs for CHD mortality were 1.09 ( 95 % CI , 0.91 - 1.30 ; 5.3 vs 4.9/1000 person-years for participants with euthyroidism ) , 1.42 ( 95 % CI , 1.03 - 1.95 ; 6.9/1000 person-years ) , and 1.58 ( 95 % CI , 1.10 - 2.27 , n = 28 deaths/333 ; 7.7/1000 person-years ; P = .005 for trend ) . Total mortality was not increased among participants with sub clinical hypothyroidism . Results were similar after further adjustment for traditional cardiovascular risk factors . Risks did not significantly differ by age , sex , or preexisting cardiovascular disease . CONCLUSIONS Sub clinical hypothyroidism is associated with an increased risk of CHD events and CHD mortality in those with higher TSH levels , particularly in those with a TSH concentration of 10 mIU/L or greater CONTEXT Sub clinical hypothyroidism ( SCH ) is defined as raised serum TSH levels with circulating thyroid hormones within the reference range . It is uncertain whether treatment of SCH with L-thyroxine improves cardiovascular ( CV ) risk factors and quality of life . OBJECTIVE The objective of the study was to assess CV risk factors and patient-reported outcomes after treatment . DESIGN This was a r and omized , double-blind , crossover study of L-thyroxine and placebo . SETTING The study was conducted with community-dwelling patients . PATIENTS One hundred patients [ mean age ( sd ) 53.8 ( 12 ) yr , 81 females ] with SCH [ mean TSH 6.6 ( 1.3 ) mIU/liter ] without previously treated thyroid or vascular disease . INTERVENTION Intervention consisted of 100 microg L-thyroxine or placebo daily for 12 wk each . MEASUREMENTS Primary parameters were total cholesterol ( TC ) and endothelial function [ brachial artery flow-mediated dilatation ( FMD ) ] , an early marker of atherosclerosis . Patient-reported outcomes were also assessed . RESULTS L-thyroxine treatment reduced TC ( vs. placebo ) from 231.6 to 220 mg/dl , P < 0.001 ; low-density lipoprotein cholesterol from 142.9 to 131.3 mg/dl , P < 0.05 ; waist to hip ratio from 0.83 to 0.81 , P < 0.006 ; and improved FMD from 4.2 to 5.9 % , P < 0.001 . Multivariate analysis showed that increased serum free T(4 ) level was the most significant variable predicting reduction in TC or improvement in FMD . Furthermore , the symptom of tiredness improved on L-thyroxine therapy , but other patient-reported outcomes were not significantly different after correction for multiple comparisons . CONCLUSION SCH treated by L-thyroxine leads to a significant improvement in CV risk factors and symptoms of tiredness . The CV risk factor reduction is related to the increased level of achieved free T(4 ) concentration Abstract Objectives : To determine whether thyroxine treatment is effective in patients with symptoms of hypothyroidism but with thyroid function tests within the reference range , and to investigate the effect of thyroxine treatment on psychological and physical wellbeing in healthy participants . Design : R and omised double blind placebo controlled crossover trial . Setting : Outpatient clinic in a general hospital . Participants : 25 patients with symptoms of hypothyroidism who had thyroid function tests within the reference range , and 19 controls . Methods : Participants were given thyroxine 100 µg or placebo to take once a day for 12 weeks . Washout period was six weeks . They were then given the other to take once a day for 12 weeks . All participants were assessed physiologically and psychologically at baseline and on completion of each phase . Main outcome measures : Thyroid function tests , measures of cognitive function and of psychological and physical wellbeing . Results : 22 patients and 19 healthy controls completed the study . At baseline , patients ' scores on 9 out of 15 psychological measures were impaired when compared with controls . Patients showed a significantly greater response to placebo than controls in 3 out of 15 psychological measures . Healthy participants had significantly lower scores for vitality when taking thyroxine compared to placebo ( mean ( SD ) 60 ( 17 ) v 73 ( 16 ) , P<0.01 ) . However , patients ' scores from psychological tests when taking thyroxine were no different from those when taking placebo except for a poorer performance on one visual reproduction test when taking thyroxine . Serum concentrations of free thyroxine increased and those of thyroid stimulating hormone decreased in patients and controls while they were taking thyroxine , confirming compliance with treatment . Although serum concentrations of free triiodothyronine increased in patients and controls taking thyroxine , the difference between the response to placebo and to thyroxine was significant only in the controls . Conclusions : Thyroxine was no more effective than placebo in improving cognitive function and psychological wellbeing in patients with symptoms of hypothyroidism but thyroid function tests within the reference range . Thyroxine did not improve cognitive function and psychological wellbeing in healthy participants . What is already known on this topic Recent anecdotal accounts suggest that patients with symptoms of hypothyroidism but who are biochemically euthyroid may benefit from thyroxine treatment No controlled trials in this area have been reported What this study adds This study suggests that thyroxine is no more effective than placebo in improving psychological and physical wellbeing in patients who show symptoms of being clinical ly hypothyroid but whose thyroid function tests are within the reference range Thyroxine replacement did not improve psychological and physical wellbeing in healthy This study evaluated the effect of physiological , TSH-guided , L-thyroxine treatment on serum lipids and clinical symptoms in patients with sub clinical hypothyroidism . Sixty-six women with proven sub clinical hypothyroidism ( TSH , 11.7 + /- 0.8 mIU/liter ) were r and omly assigned to receive L-thyroxine or placebo for 48 wk . Individual L-thyroxine replacement ( mean dose , 85.5 + /- 4.3 microg/d ) was performed based on blinded TSH monitoring , result ing in euthyroid TSH levels ( 3.1 + /- 0.3 mIU/liter ) . Lipid concentrations and clinical scores were measured before and after treatment . Sixty-three of 66 patients completed the study . In the L-thyroxine group ( n = 31 ) total cholesterol and low density lipoprotein cholesterol were significantly reduced [ -0.24 mmol/liter , 3.8 % ( P = 0.015 ) and -0.33 mmol/liter , 8.2 % ( P = 0.004 ) , respectively ] . Low density lipoprotein cholesterol decrease was more pronounced in patients with TSH levels greater than 12 mIU/liter or elevated low density lipoprotein cholesterol levels at baseline . A significant decrease in apolipoprotein B-100 concentrations was observed ( P = 0.037 ) , whereas high density lipoprotein cholesterol , triglycerides , apolipoprotein AI , and lipoprotein(a ) levels remained unchanged . Two clinical scores assessing symptoms and signs of hypothyroidism ( Billewicz and Zulewski scores ) improved significantly ( P = 0.02 ) . This is the first double blind study to show that physiological L-thyroxine replacement in patients with sub clinical hypothyroidism has a beneficial effect on low density lipoprotein cholesterol levels and clinical symptoms of hypothyroidism . An important risk reduction of cardiovascular mortality of 9 - 31 % can be estimated from the observed improvement in low density lipoprotein cholesterol The aim of this study was to evaluate the lipid profile of patients with different degrees of hypothyroidism and the effect of levothyroxine replacement in sub clinical hypothyroidism ( SH ) . Initially , a cross-sectional study was performed with 226 participants [ SH = 133 participants , manifest hypothyroidism ( MH ) = 23 participants , and euthyroidism ( EU ) = 70 participants ] . The mean levels of atherogenic lipid variables were greater in MH than in SH and were greater in SH than in EU , although the differences between SH and EU did not reach statistical significance . The SH subgroup with greater serum thyrotropin ( TSH ) levels and that with positive antithyroperoxidase antibodies ( TPO-Ab ) had greater levels of triglycerides and of the atherogenic index Apo B/Apo A. A positive correlation exists between serum TSH and total cholesterol ( rs = 0.167 ; P = 0.006 ) , triglycerides ( rs = 0.219 ; P < 0.001 ) , and ApoB levels ( rs = 0.205 ; P < 0.001 ) . Eleven patients who received levothyroxine ( L-T4 ) treatment and 15 patients who received placebo were reevaluated 1 year after TSH adjusted intervention . A fall in atherogenic variables was observed in the L-T4-treated group , with significance for total cholesterol ( -20.0 vs + 16.1 mg/dL in the placebo group ) and LDL-c ( -21.7 vs + 17.2 mg/dL ) . We concluded that SH leads to an intermediary lipid profile between euthyroid individuals and that found in manifest hypothyroidism and that a significant lipid profile improvement occurred 1 year after L-T4 replacement therapy OBJECTIVE : To determine if health-related quality of life ( HRQL ) in patients of middle age and older with elevated thyroid-stimulating hormone ( TSH ) and normal total thyroid hormone levels — sub clinical hypothyroidism — improves withl-thyroxine replacement therapy . DESIGN : R and omized , double-blind , placebo-controlled trial . SETTING : Outpatient clinic . PATIENTS : Thirty-seven patients with sub clinical hypothyroidism , most with symptoms consistent with hypothyroidism , over 55 years of age . INTERVEJVTIOJVS : Placebo or L-thyroxine replacement therapy to achieve normal TSH level . MEASUREMENTS AND MAIN RESULTS : Disease-specific and general HRQL , cognitive function , bone mineral density , lipid levels . The mean daily dose of L-thyroxine replacement in the active group was 68±21 µg . TSH decreased by 8.6 mIU/L ( 95 % confidence interval [ CI ] 4.1 to 13.1 ) and T4 increased by 27.9 nmol/L ( 95 % CI 14.8 to 41.2 ) . There was a statistically significant improvement in a composite psychometric memory score in treated versus control patients ; all other outcomes showed similar findings in the two groups . Although confidence intervals for most measures did not exclude an important improvement in HRQL with thyroid replacement , no measure of symptoms or HRQL either showed clinical ly important trends in favor of treatment , or approached conventional levels of statistical significance . CONCLUSIONS : In middle-aged and older patients with elevated TSH and normal T4 , it may not be harmful to follow biochemical and clinical status even in the presence of nonspecific symptoms potentially associated with hypothyroidism Although sub clinical hyperthyroidism ( SCH ) has been associated with increased risk of osteoporosis and cardiac arrhythmias , its treatment is still controversial . This study was design ed as a prospect i ve , r and omized , intervention , control- study with a 1-year follow-up in order to investigate whether normalization of serum TSH in SCH using methimazole has favorable bone and heart clinical effects . Fourteen patients with endogenous SCH ( not Graves ’ disease ) were enrolled , 7 ( 5 women/2 men ; group T ) were treated with methimazole ( 2.5–7.5 mg/day ) , and 7 ( 5 women/2 men ; group C ) were followed without treatment ; 10 healthy subjects were also included in the study as controls . Serum free-T3 ( FT3 ) , free-T4 ( FT4 ) and TSH , thyroid echography , bone stiffness index ( SI ) , as measured by heel ultrasonometry , and 24-h electrocardiography monitoring were obtained . SCH patients exhibited higher systolic and diastolic blood pressure than control subjects . They also had a significantly higher number of both ventricular premature beats ( VPB ) ( mean±SEM : 681 ±238 vs 6±2 beats/24 h ; p<0.02 ) and atrial premature beats ( APB ) ( mean±SEM : 495±331 vs 7±2 beats/24 h ; p<0.0001 ) , and a lower SI ( 66±5 vs 96±3 ; p<0.001 ) . Twelve months after normalization of TSH with the use of methimazole , the number of VPB decreased significantly ( 947±443 vs 214±109 beats/24 h ; p<0.05 ) while it remained unchanged in untreated SCH patients ( 414±163 vs 487±152 beats/24 h ; p = ns ) . An insignificant therapy effect was observed as far as APB were concerned ( 826±660 vs 144±75 beats/24 h ; p = ns ) , however their number increased significantly in the untreated group ( 463±49 vs 215±46 beats/ 24 h ; p<0.05 ) . The SI increased significantly as a result of therapy in group T ( 64.1 ±4.8 vs 70.0±5.3 ; p<0.02 ) and was further reduced in group C at the end of the study ( 69.1 ±7.3 vs 62.9±7.1 ; p<0.001 ) . No adverse effect was observed in group T. In conclusion , anti-thyroid therapy seems to have favorable bone and heart clinical effects in subjects with endogenous SCH Many studies have found clinical and metabolic alterations in sub clinical hypothyroidism , however , there are disagreements about the benefits of levothyroxine therapy . The objective of the present study was to analyze the effects of 6 months of treatment on the lipid profile of patients with sub clinical hypothyroidism . A r and omized double blind , placebo-controlled clinical assay was conducted . Sixty patients were enrolled in stratified r and om allocation by TSH levels that generated similar groups in average : free thyroxine levels , lipid levels , age , clinical score , and sedentary . At 6 months , 18 patients in the levothyroxine and 20 in the placebo group were reevaluated and a fall in all atherogenic lipid variables was observed with treatment . The TC and LDL-c variations ( -22.6+/-37.2 and -18.5+/-34.6 mg/dl , respectively ) in the group that received LT4 were statistically different ( p=0.023 and p=0.012 ) from those occurring in the placebo group ( + 7.3+/-37.1 and + 14.7+/-40.6 mg/dl ) . Baseline characteristics associated with better improvement in the levels of TC and LDL-c were the presence of TPO-Ab , TSH levels > 8.0 microUI/ml , Body Mass Index > or=25 kg/m2 , and the presence of menopause . We concluded that treatment with dose-adjusted levothyroxine reduced atherogenic lipid levels in some patients . Further studies to determine the effects of LT4 replacement in specific subgroups of SH patients are still necessary , especially in patients with TSH < 8.0 microUI/ml OBJECTIVE The association between established hypothyroidism and high cholesterol levels is well known . The aim of the present study was to investigate the effect of thyroxine ( T4 ) administration on cholesterol levels in hypercholesterolemic subjects with TSH levels within the normal range ( ' high-normal ' TSH compared with ' low-normal ' TSH ) . DESIGN AND METHODS We determined TSH levels in 110 consecutive patients referred for hypercholesterolemia ( serum cholesterol > 7.5 mmol/l ) . Those with ' high-normal ' TSH ( 2.0 - 4.0 microU/ml ) as well as those with ' low-normal ' TSH ( 0.40 - 1.99 microU/ml ) were r and omly assigned to receive either 25 or 50 microg T4 daily for two months . Thus , groups A and B ( low-normal TSH ) received 25 and 50 microg T4 respectively and groups C and D ( high-normal TSH ) received 25 and 50 microg T4 respectively . Serum T4 , tri-iodothyronine ( T3 ) , TSH , free thyroxine index , resin T3 uptake and thyroid autoantibodies ( ThAab ) as well as total cholesterol , high and low density lipoprotein cholesterol ( HDL , LDL ) , and triglycerides were determined before and at the end of the two-month treatment period . RESULTS TSH levels were reduced in all groups . The most striking effect was observed in group D ( TSH levels before : 2.77+/-0.55 , after : 1.41+/-0.85 microU/ml , P < 0.01 ) . Subjects in groups C and D had a higher probability of having positive ThAabs . A significant reduction in total cholesterol ( P < 0.01 ) and LDL ( P < 0.01 ) was observed after treatment only in group D. In those subjects in group D who were ThAab negative , there was no significant effect of thyroxine on cholesterol levels . CONCLUSIONS Subjects with high-normal TSH levels combined with ThAabs may , in fact , have sub clinical hypothyroidism presenting with elevated cholesterol levels . It is possible that these patients might benefit from thyroxine administration CONTEXT Despite the equivocal outcomes of r and omized controlled trials , general clinical opinion favors screening and treatment of elderly individuals with sub clinical thyroid disorders . OBJECTIVES To determine whether sub clinical thyroid dysfunction should be treated in old age and the long-term impact of thyroid dysfunction on performance and survival in old age . DESIGN , SETTING , AND PARTICIPANTS A prospect i ve , observational , population -based follow-up study within the Leiden 85-Plus Study of 87 % of a 2-year birth cohort ( 1912 - 1914 ) in the municipality of Leiden , the Netherl and s. A total of 599 participants were followed up from age 85 years through age 89 years ( mean [ SD ] follow-up , 3.7 [ 1.4 ] years ) . MAIN OUTCOME MEASURES Complete thyroid status at baseline ; disability in daily life , depressive symptoms , cognitive function , and mortality from age 85 years through 89 years . RESULTS Plasma levels of thyrotropin and free thyroxine were not associated with disability in daily life , depressive symptoms , and cognitive impairment at baseline or during follow-up . Increasing levels of thyrotropin were associated with a lower mortality rate that remained after adjustments were made for baseline disability and health status . The hazard ratio ( HR ) for mortality per SD increase of 2.71 mIU/L of thyrotropin was 0.77 ( 95 % confidence interval [ CI ] , 0.63 - 0.94 ; P = .009 ) . The HR for mortality per SD increase of 0.21 ng/dL ( 2.67 pmol/L ) of free thyroxine increased 1.16-fold ( 95 % CI , 1.04 - 1.30 ; P = .009 ) . CONCLUSIONS In the general population of the oldest old , elderly individuals with abnormally high levels of thyrotropin do not experience adverse effects and may have a prolonged life span . However , evidence for not treating elderly individuals can only come from a well- design ed , r and omized placebo-controlled clinical trial BACKGROUND Sub clinical hypothyroidism ( SCH ) has been associated with ischemic heart disease ( IHD ) ; however , it is unknown whether treatment of SCH with levothyroxine sodium will reduce the risk of IHD . The aim of this study was to investigate the association between levothyroxine treatment of SCH with IHD morbidity and mortality . METHODS We used the United Kingdom General Practitioner Research Data base to identify individuals with new SCH ( serum thyrotropin levels of 5.01 - 10.0 mIU/L and normal free thyroxine levels ) recorded during 2001 with outcomes analyzed until March 2009 . All analyses were performed separately for younger ( 40 - 70 years ) and older ( > 70 years ) individuals . Hazard ratios ( HRs ) for IHD events ( fatal and nonfatal ) were calculated after adjustment for conventional IHD risk factors , baseline serum thyrotropin levels , and initiation of levothyroxine treatment as a time-dependent covariate . RESULTS Sub clinical hypothyroidism was identified in 3093 younger and 1642 older individuals . For a median follow-up period of 7.6 years , 52.8 % and 49.9 % of younger and older patients with SCH were treated with levothyroxine , respectively . There were 68 incident IHD events in 1634 younger patients treated with levothyroxine ( 4.2 % ) vs 97 IHD events in 1459 untreated individuals ( 6.6 % ) ( multivariate-adjusted HR , 0.61 ; 95 % CI , 0.39 - 0.95 ) . In contrast , in the older group there were 104 events in 819 treated patients ( 12.7 % ) vs 88 events in 823 untreated individuals ( 10.7 % ) ( HR , 0.99 ; 95 % CI , 0.59 - 1.33 ) . CONCLUSIONS Treatment of SCH with levothyroxine was associated with fewer IHD events in younger individuals , but this was not evident in older people . An appropriately powered r and omized controlled trial of levothyroxine in SCH examining vascular outcomes is now warranted The relationship between sub clinical hypothyroidism ( SCH ) and an atherogenic lipoprotein profile is still controversial . We measured lipoproteins in 49 SCH patients by comparison with 33 euthyroid controls . Total cholesterol ( TC ) , triglyceride , high-density lipoprotein cholesterol , low-density lipoprotein cholesterol ( LDLc ) , apolipoprotein A(1 ) , apolipoprotein B , and lipoprotein ( a ) [ Lp(a ) ] were measured after an overnight fast . Patients were r and omly assigned to levothyroxine therapy or placebo and re-evaluated after 6 months of euthyroidism . SCH patients showed significantly higher TC ( P < 0.01 ) , LDLc ( P = 0.01 ) , and apolipoprotein B ( P = 0.001 ) levels than controls , positively correlated with baseline TSH levels ( P = 0.003 , P = 0.01 , and P = 0.03 , respectively ) . Elevated Lp(a ) levels were significantly more frequent in SCH ( P < 0.05 ) and associated with familial diabetes mellitus and /or coronary heart disease ( P < 0.01 ) . Levothyroxine treatment result ed in a significant decrease of both TC and LDLc concentrations ( P = 0.003 ) , in direct proportion to the respective baseline values ( P < 0.05 and P < 0.01 , respectively ) , whereas no change in Lp(a ) level was observed . No changes occurred in the placebo group . In conclusion , only serum LDLc levels are increased specifically and reversibly in association with SCH . Altered Lp(a ) values reflect a genetic influence rather than a reduced thyroid hormone action OBJECTIVE Sub clinical hypothyroidism affects 5 - 15 % of the general population , is especially prevalent in females , and may be associated with increased morbidity from cardiovascular disease , although it remains controversial . We recently reported a significant increase in the brachial-ankle pulse wave velocity ( baPWV ) , a parameter of arterial stiffening and an independent predictor of cardiovascular events , in sub clinical hypothyroidism without thyroiditis . The current study was performed to assess changes in baPWV in female sub clinical hypothyroidism with autoimmune chronic thyroiditis ( Hashimoto 's disease ) after restoration of normal thyroid function . METHODS In a r and omized placebo-controlled study , 95 female sub clinical hypothyroid patients were monitored for changes in baPWV before and after levothyroxine ( l-T(4 ) ) replacement therapy . Changes in baPWV were also measured in 42 age-matched normal female subjects . RESULTS The baseline baPWV values in patients with sub clinical hypothyroidism were significantly higher than in normal subjects . With attainment of euthyroidism , baPWV showed a significant decrease from 1776.7+/-86.0 to 1674.3+/-79.2 cm/s ( P=0.006 ) in patients treated with l-T(4 ) , but the changes in baPWV and TSH were not correlated . The change in baPWV was significantly and negatively correlated with age and baseline pulse pressure , but multiple regression analysis revealed that these parameters failed to be associated with the change in baPWV . CONCLUSIONS Sustained normalization of thyroid function during l-T(4 ) replacement therapy significantly decreases baPWV in female sub clinical hypothyroid patients with autoimmune chronic thyroiditis , suggesting the improvement of arterial stiffening and , consequently , possible prevention of cardiovascular disease Objective To assess the value of population screening for adult hypothyroidism . Setting Healthy people attending for a general health assessment . Methods A thyroid-stimulating hormone ( TSH ) measurement was performed on people attending for a general health assessment ( women aged 50–79 [ 35–49 with a family history of thyroid disease ] and men aged 65–79 ) . Those with TSH levels above 4.0 mU/L were invited to join a r and omized double-blind crossover trial of thyroxine and placebo , each given in r and om order for four months . On entry a second blood sample was collected for a TSH measurement after the end of the trial to determine whether this would help select individuals for thyroxine treatment . The daily thyroxine dose started at 50 µg and if necessary was increased to achieve a TSH level of 0.6–2.0 mU/L. Results There were 341 ( 8 % ) people with a TSH level above 4.0 mU/L , 110 met eligibility criteria ( 64 agreed to participate ) , and 56 ( 49 women , 7 men ) completed the trial . Among the 15 individuals with a repeat TSH measurement above 4.5 mU/L , 11 reported feeling better on thyroxine than placebo and none reported feeling better on placebo ( P = 0.001 ; four felt no different ) , indicating that in this group 73 % benefitted ( i.e. 11/15 ; 95 % CI 45–92 % ) . The main symptoms relieved were tiredness and loss of memory . There was no indication of harm . In the 41 individuals with a repeat serum TSH of 4.5 mU/L or less : 10 reported feeling better on thyroxine than placebo and 16 better on placebo ( P = 0.42 , 15 felt no different ) . Thus about 8 % of men and women in the specified age groups had a TSH above 4.0 mU/L , and of these about a quarter had a repeat TSH above 4.5 mU/L , of whom about half would benefit from thyroxine treatment . Conclusion The results indicate that screening for hypothyroidism would be worthwhile . Approximately 1 % of people screened would have a better quality of life . Pilot screening programmes for adult hypothyroidism are justified |
10,753 | 19,811,955 | Third trimester ultrasound seems a logical solution , but systematic review of evidence from r and omised trials has shown that third trimester ultrasound does not have a significant impact on perinatal mortality but may increase interventions such as caesarean delivery . | Foetal growth restriction is an important contributor to perinatal mortality , being responsible for up to 50 % of stillbirths .
Optimal prevention and accurate detection enabling timely intervention remain elusive , particularly in presumed low-risk pregnancy . | OBJECTIVE --To examine any associations between routine ultrasonography in utero and subsequent brain development as indicated by non-right h and edness at primary school age and neurological development during childhood . DESIGN --Follow up of 8 and 9 year old children of women who took part in two r and omised , controlled trials of routine ultrasonography during pregnancy . SETTING --Clinics of 60 general practitioners in Norway during 1979 - 81 . Maternal and child health centres . SUBJECTS--2161 ( 89 % ) of 2428 eligible singletons were followed up , partly through a question naire to their parents and partly through information from health centres . MAIN OUTCOME MEASURES --The dominant h and of the child was assessed by 10 questions . Deficits in attention , motor control , and perception were evaluated by five questions . Impaired neurological development during the first year of life was assessed by an abbreviated version of the Denver developmental screening test . RESULTS --The odds of non-right h and edness were higher among children who had been screened in utero than among control children ( odds ratio 1.32 ; 95 % confidence interval 1.02 to 1.71 ) . No clear differences were found between the groups with regard to deficits in attention , motor control , and perception or neurological development during the first year of life . CONCLUSION --Our data suggest a possible association between routine ultrasonography in utero and subsequent non-right h and edness , whereas no association with impaired neurological development was found . As the question on non-right h and edness was one of six initial hypotheses , the observed results may be due to chance . None the less , the results suggest that the hypothesis may have some merit and should be tested in future studies The objective of this study was to evaluate and characterise by study of newborn biometry a possible effect on birthweight which we observed previously in a r and omised controlled trial of multiple prenatal ultrasound examinations . A total of 2743 women with single pregnancies had been allocated at r and om to either a protocol of ultrasound imaging and continuous wave Doppler studies at 18 , 24 , 28 , 34 and 38 weeks gestation ( intensive group ) , or to a protocol of a single imaging examination at 18 weeks and further imaging scans only as clinical ly indicated ( regular group ) . When compared with those in the regular group , and adjusted for other confounding variables , normally formed babies of term gestational age in the intensive group tended to be shorter when measured at birth ( P = 0.123 ) and on day 2 - 3 of age ( P = 0.068 ) . There were statistically insignificant reductions in the circumferences of the chest , abdomen and mid-arm ; and in the skinfold thicknesses of the triceps , parascapular and subscapular regions . Principal component analysis showed a trend for a reduction for the skeletal component ( P = 0.085 ) but not for the soft tissue component ( P = 0.332 ) . Comparison of the neonatal biometry in the two groups is not conclusive , but the differential effects on the various growth parameters suggest that if multiple scans do indeed restrict fetal growth , the mechanism is more likely to be an effect on bone growth rather than a reduction in nutrient supply from the placenta Abstract Despite widespread application of ultrasound imaging and Doppler blood flow studies , the effects of their frequent and repeated use in pregnancy have not been evaluated in controlled trials . From 2834 women with single pregnancies at 16 - 20 weeks gestation , 1415 were selected at r and om to receive ultrasound imaging and continuous-wave Doppler flow studies at 18 , 24 , 28 , 34 , and 38 weeks gestation ( the intensive group ) and 1419 to receive single ultrasound imaging at 18 weeks ( the regular group ) . Outcome data was obtained from 99 % of women who entered the study . The only difference between the two groups was significantly higher intrauterine growth restriction in the intensive group , when expressed both as birthweight 342 : OBJECTIVE To evaluate the effect of introducing two biophysical ultrasound examinations in a low-risk antenatal population . METHODS Scans were performed at 30–32 weeks ' gestation and 36–37 weeks ' gestation . Scans assessed placental maturity , amniotic fluid volume , and estimated fetal weight . One thous and nine hundred ninety-eight low-risk patients were r and omized at 30 weeks ' gestation to a control group receiving st and ard antenatal care , or to the study group who also received an ultrasound scan . Outcome measures were frequency of small for date s ( less than 10th percentile at birth ) , intervention rates , and admissions to neonatal intensive care . RESULTS The proportion of infants assessed as small for date s at birth in the study group was 6.9 % ( 69 of 994 ) compared with 10.4 % ( 104 of 999 ) in the control group ( P = 008 ) . The rates of intervention in the study and control groups were 31.3 % ( 313 of 999 ) and 16.9 % ( 169 of 999 ) , respectively ( P < .001 ) . Twenty-eight ( 2.8 % ) neonates in the study group were admitted to the neonatal unit compared with 34 ( 3.4 % ) in the control group ( P = .532 ) . CONCLUSION Introduction of an ultrasound scan at 30–32 weeks ' and 36–37 weeks ' gestation may reduce the risk of a growth-restricted infant and increases antenatal interventions . Rates of admission to a neonatal unit are not significantly affected Summary : In this study 3 different methods of screening for birth‐weight < 10th percentile in pregnancy were evaluated both indivually and in combination ; 1,135 women with singleton pregnancies were studied . Measurements of symphysiofundal height by tape measure , and amniotic fluid index and fetal abdominal circumference by ultrasound imaging , were made at 18 , 24 , 28 , 34 and 38 weeks . At none of these gestational ages did amniotic fluid index perform well as a screening test for birth‐weight < 10th percentile . Combining the tests , using symphysiofundal height to select a group at high risk who then had a fetal abdominal circumference measurement , reduced the false positive rate but significantly decreased the percentage of infants diagnosed . The results of this study confirm that the most appropriate antenatal diagnostic test for birth‐weight < 10th percentile is ultrasound measurement of fetal abdominal circumference . Selecting pregnancies at risk by clinical measurement of symphysiofundal height will provide a lower false positive rate than a policy of performing ultrasound on all pregnancies during the third trimester , but will also reduce the sensitivity Most fetuses in developed countries are exposed in utero to diagnostic ultrasound examination . Many pregnant women express concern about whether the procedure harms the fetus . Since most routine ultrasound examinations are done at weeks 16 - 22 , when the fetal brain is developing rapidly , effects on neuronal migration are possible . We have sought an association between routine ultrasonography in utero and reading and writing skills among children in primary school . At the age of 8 or 9 years , children of women who had taken part in two r and omised , controlled trials of routine ultrasonography during pregnancy were followed-up . The women had attended the clinics of 60 general practitioners in central Norway during 1979 - 81 . The analysis of outcome was by intention to treat : 92 % of the " screened " group had been exposed to ultrasound screening at weeks 16 - 22 , and 95 % of controls had not been so exposed , but there was some overlap . 2428 singletons were eligible for follow-up , and the school performance of 2011 children ( 83 % ) was assessed by their teachers on a scale of 1 - 7 ; the teachers were unaware of ultrasound exposure status . A subgroup of 603 children underwent specific tests for dyslexia . There were no statistically significant differences between children screened with ultrasound and controls in the teacher-reported school performance ( scores for reading , spelling , arithmetic , or overall performance ) . Results from the dyslexia test sample showed no differences between screened children and controls in reading , spelling , and intelligence scores , or in discrepancy scores between intelligence and reading or spelling . The test results classified 21 of the 309 screened children ( 7 % [ 95 % confidence interval 3 - 10 % ] ) and 26 of the 294 controls ( 9 % [ 4 - 12 % ] ) as dyslexic . The risk of having poor skills in reading and writing was no greater for children whose mothers had been offered routine ultrasonography than for those whose mothers had not been offered the procedure BACKGROUND Despite the widespread use of prenatal ultrasound studies , there are no published data from r and omised controlled trials describing childhood outcomes that might be influenced by repeated ultrasound exposures . We previously undertook a r and omised controlled trial to assess the effects of multiple studies on pregnancy and childhood outcomes and reported that those pregnancies allocated to receive multiple examinations had an unexplained and significant increase in the proportion of growth restricted newborns . Our aim was to investigate the possible effects of multiple prenatal ultrasound scans on growth and development in childhood . Here , we provide follow-up data of the childrens ' development . METHODS Physical and developmental assessment s were done on children whose pregnant mothers had been allocated at r and om to a protocol of five studies of ultrasound imaging and umbilical artery Doppler flow velocity waveform between 18 and 38 weeks ' gestation ( intensive group n=1490 ) or a single imaging study at 18 weeks ' gestation ( regular group n=1477 ) . We used generalised logistic and linear regression models to assess the group differences in developmental and growth outcomes over time . Primary data analysis was done by intention-to-treat . FINDINGS Examinations were done at 1 , 2 , 3 , 5 , and 8 years of age on children born without congenital abnormalities and from singleton pregnancies ( intensive group n=1362 , regular group n=1352 ) . The follow-up rate at 1 year was 85 % ( 2310/2714 ) and at 8 years was 75 % ( 2042/2714 ) . By 1 year of age and thereafter , physical sizes were similar in the two groups . There were no significant differences indicating deleterious effects of multiple ultrasound studies at any age as measured by st and ard tests of childhood speech , language , behaviour , and neurological development . INTERPRETATION Exposure to multiple prenatal ultrasound examinations from 18 weeks ' gestation onwards might be associated with a small effect on fetal growth but is followed in childhood by growth and measures of developmental outcome similar to those in children who had received a single prenatal scan Summary : Poor fetal growth is an important cause of perinatal mortality and morbidity . Based on the hypothesis that early diagnosis of fetal growth problems leads to more appropriate management and therefore , improved outcome , a r and omized controlled trial of ultrasound measurement was performed on 1,528 women booked though a hospital antenatal clinic This compared a number of perinatal outcomes between the group who had a routine 2‐stage examination ( early dating and 34‐week scan ) and a group who had only a dating scan and then additional scans as generated by their clinical situations . No significant differences could be found between the groups when these perinatal outcomes were considered . These results mirror previously published r and omized controlled trials . Selection of women for third trimester ultrasound examination for suspected fetal growth problems should be based on careful clinical assessment and should not be routine In the hope of reducing perinatal risks associated with retardation of intrauterine growth a previously described two stage ultrasound screening schedule was evaluated by a controlled trial in 877 women with low risk single pregnancies . The two stages of ultrasound examination were an assessment of gestational age during early pregnancy followed by measurement of length from crown to rump and area of trunk at between 34 and 36 weeks ' gestation . The product of crown to rump length and trunk area was calculated . The sensitivity of this schedule in identifying in advance 94 % of babies who were small for date s at birth , with 90 % specificity , and the speed and simplicity of measurement confirmed the accuracy and feasibility of two stage ultrasonography as a screening procedure . The controlled trial did not , however , show any benefit from its routine application in these low risk pregnancies OBJECTIVE The objective of this r and omized clinical trial was to test the hypothesis that ultrasonographic screening would significantly alter perinatal outcome as a result of the antenatal detection of fetal congenital malformations . STUDY DESIGN Pregnant women without a specific indication for ultrasonography were r and omly assigned to have either two screening sonograms ( 15 to 22 weeks and 31 to 35 weeks ) or conventional obstetric care with ultrasonography used only as determined by the clinical judgment of the patient 's physician . The frequency of birth defect detection in the screened and control population s was compared , as was the impact of discovery on pregnancy outcome . RESULTS Major congenital malformations occurred in 2.3 % of the 15,281 fetuses and infants in this study . Antenatal ultrasonography detected 35 % of the anomalous fetuses in the screened group versus only 11 % in the control population ( relative detection rate 3.1 ; 95 % confidence interval 2.0 to 5.1 ) . Ultrasonography screening did not , however , significantly influence the management or outcome of pregnancies complicated by congenital malformations . Specifically , only 9 abortions were performed for anomalies among 7685 fetuses in the screened group whereas 4 pregnancies were terminated for fetal anomalies detected among 7596 control subjects . Ultrasonography screening also had no significant impact on survival rates among infants with potentially treatable , life-threatening anomalies despite the opportunity to take pre caution ary measures such as delivery in a tertiary center . CONCLUSIONS Ultrasonography screening in a low-risk pregnant population had no significant impact on the frequency of abortion for fetal anomalies . Survival rates for anomalous fetuses were also unaffected by screening |
10,754 | 29,547,670 | Because of the wide variety in characteristics of the physiotherapeutic exercise and control interventions , follow-up length and outcome measures , limited evidence was found on the effectiveness of physiotherapeutic exercise following THA .
The insufficient therapeutic validity and potentially high risk of bias in studies involving physiotherapeutic exercise interventions limit the ability to assess the effectiveness of these interventions following THA . | OBJECTIVE To assess the therapeutic validity and effectiveness of physiotherapeutic exercise interventions following total hip arthroplasty ( THA ) for osteoarthritis . | UNLABELLED Hip osteoarthritis ( OA ) is a degenerative disease , and total hip arthroplasty ( THA ) is one of the surgical procedures of choice to improve the OA patient 's quality of life . Without a rehabilitation program , THA patients will develop functional limitations . A r and omized double-blind trial was performed between July 2009 and October 2011 to compare in a short follow-up time two groups of patients who underwent THA for OA . The THA protocol ( THAP ) group received verbal instructions and physiotherapy exercise demonstrations , and the THA physiotherapy care protocol ( THAPCP ) group received the same verbal instructions and demonstrations associated with daily exercise practice guided by a physiotherapist . The outcomes that were assessed preoperatively and 15 d postoperatively in 106 patients were muscle strength force , goniometry , Medical Outcomes Study 36-Item Short Form Health Survey , and Merle d'Aubigné and Postel score . Higher muscle strength force scores and degrees in range of motion were found in the THAPCP group . Higher improvements were also observed for the THAPCP group compared with the THAP group in the Merle d'Aubigné and Postel score . At the end of the follow-up period , the intervention in the THAPCP group improved functional capacity , quality of life , mobility , muscle strength , goniometry , and pain . It appears to be a safe tool for accelerating recovery in THA patients . CLINICAL TRIAL REGISTRATION Clinical Trials.gov ; NCT01491048 Background In-hospital progressive resistance training ( PRT ) has been shown to be an effective method of rehabilitation following hip surgery . The aim of this study was to assess whether a home-based PRT program would be beneficial in improving patients ’ muscle strength and physical function compared to st and ard rehabilitation . Methods Subjects ( n = 49 ) either received home-based PRT rehabilitation ( n = 25 ) or st and ard rehabilitation ( n = 24 ) in a prospect i ve single blinded r and omized trial carried out over a two-year period . The primary outcome measure was the maximal voluntary contraction of the operated leg quadriceps ( MVCOLQ ) with secondary measures of outcome being the sit to st and score ( ST ) , timed up and go ( TUG ) , stair climb performance ( SCP ) , the 6 min walk test ( 6MWT ) , and lean mass of the operated leg ( LM ) . Results Twenty-six patients completed follow up at 1 year ( n = 13 per group ) for the final comparative analysis . All the outcome measures showed marked progressive improvements from the baseline measures at 9–12 months post op ( Estimated effect ( std error ) ; p value)- MVCOLQ 26.50 ( 8.71 ) N p = 0.001 ; ST 1.37 ( 0.33 ) p = 0.0001 ; TUG −1.44 ( 0.45 ) s p = 0.0001 ; SCP −3.41(0.80)s p = 0.0001 ; 6MWT 45.61 (6.10)m p = 0.0001 ; LM 20 (204)g p = 0.326 ) following surgery for both groups . Overall , there was no significant effect for participation in the exercise regime compared with st and ard care for all outcomes assessed . Conclusions Overall , this study demonstrated that there is no significant difference between the two groups for participation in the home-based PRT exercise programme when compared to st and ard care for all outcomes .Trial registration IS RCT N 1309951 . Registered February 2011 OBJECTIVE To examine the physical function , gait , and quality of life of patients after total hip replacement ( THR ) r and omly assigned to either a targeted home- or center-based exercise program . DESIGN R and omized controlled trial . SETTING Rehabilitation research center in Australia . PARTICIPANTS Twenty-three patients with unilateral THR were r and omly assigned to a supervised center-based exercise group ( n=11 ) or an unsupervised home-based exercise group ( n=12 ) . INTERVENTION The center-based group completed an 8-week targeted exercise program while under the direct supervision of a physiotherapist . After initial instruction , the home-based group completed the 8-week targeted exercise program at home without further supervision . MAIN OUTCOME MEASURES Quality of life , physical function , and spatiotemporal measures of gait . RESULTS No significant interaction ( group by time ) or main effects of grouping were found . Within each group , quality of life , and stair climbing improved significantly ( P<.05 ) as did Timed Up & Go test and 6-minute walk test performances ( P<.05 ) . Walking speed increased by 16 cm/s ( P<.01 ) , cadence by 8 steps/min ( P<.05 ) , step length by 4.7 cm ( P<.05 ) , and double-support time reduced by a factor of 16 % . Step length symmetry showed significant improvement ( P<.05 ) over time . Step length differential between the affected and unaffected limbs reduced from 4.0 to 2.7 cm . CONCLUSIONS The targeted strengthening program was effective for both the home- and center-based groups . No group differences were found in the majority of the outcome measures . This finding is important because it shows that THR patients can achieve significant improvements through a targeted strengthening program delivered at a center or at home Abstract Purpose : The purpose of this study was to investigate the effects of an exercise program focusing on hip external rotator muscle on physical recovery in the early post-operative period of total hip arthroplasty ( THA ) . Methods : Patients who underwent THA were r and omized to an exercise group ( n = 14 ) or a control group ( n = 14 ) . In exercise group , the hip external rotator exercise program was performed 5 times per week for four weeks . Outcome measures were hip pain , hip range of motion , muscle strength of lower extremity and Timed Up and Go ( TUG ) test . Results : Both the hip abductor strength ( effect size = 0.60 ) and TUG test ( effect size= −0.53 ) in the exercise group improved significantly after the intervention . Conclusions : The results of the present study demonstrated that exercise program focusing on hip external rotator muscle was an effective intervention , especially in improving both hip abductor strength and walking ability in the acute post-THA stage . Implication for Rehabilitation After THA , in order to safely progress patients back to their desired activity level , there is a need to develop rehabilitation strategies to expedite and promote the recovery during the acute postoperative period . Exercise program focusing on hip external rotator muscle may lead to significant improvement of hip abductor muscle strength and gait ability in the acute post-THA stage OBJECTIVES To better underst and how immobilization and surgery affect muscle size and function in the elderly and to identify effective training regimes . DESIGN A prospect i ve r and omized , controlled study . SETTING Bispebjerg University Hospital , Copenhagen , Denmark . PARTICIPANTS Thirty-six patients ( aged 60 - 86 ) scheduled for unilateral hip replacement due to primary hip osteoarthrosis . INTERVENTION Patients were r and omized to st and ard home-based rehabilitation ( 1 h/d x 12 weeks ) , unilateral neuromuscular electrical stimulation of the operated side ( 1 h/d x 12 weeks ) , or unilateral resistance training of the operated side ( 3/wk x 12 weeks ) . MEASUREMENTS Hospital length of stay ( LOS ) , quadriceps muscle cross-sectional area ( CSA ) , isokinetic muscle strength , and functional performance . Patients were tested presurgery and 5 and 12 weeks postsurgery . RESULTS Mean+/-st and ard error LOS was shorter for the resistance training group ( 10.0+/-2.4 days , P<.05 ) than for the st and ard rehabilitation group ( 16.0+/-7.2 days ) . Resistance training , but not electrical stimulation or st and ard rehabilitation , result ed in increased CSA ( 12 % , P<.05 ) and muscle strength ( 22 - 28 % , P<.05 ) . Functional muscle performance increased after resistance training ( 30 % , P<.001 ) and electrical stimulation ( 15 % , P<.05 ) but not after st and ard rehabilitation . CONCLUSION Postoperative resistance training effectively increased maximal muscle strength , muscle mass , and muscle function more than a st and ard rehabilitation regime . Furthermore , it markedly reduced LOS in elderly postoperative patients OBJECTIVE To examine if 2 weekly sessions of supervised progressive resistance training ( PRT ) in combination with 5 weekly sessions of unsupervised home-based exercise is more effective than 7 weekly sessions of unsupervised home-based exercise in improving leg-extension power of the operated leg 10 weeks after total hip replacement ( THR ) in patients with lower pre-operative function . METHOD A total of 73 patients scheduled for THR were r and omised ( 1:1 ) to intervention group ( IG , home based exercise 5 days/week and PRT 2 days/week ) or control group ( CG , home based exercise 7 days/week ) . The primary endpoint was change in leg extension power at 10 week follow up . Secondary outcomes were isometric hip muscle strength , sit-to-st and test , stair climb test , 20 m walking speed and patient-reported outcome ( HOOS ) . RESULTS Sixty-two completed the trial ( 85 % ) . Leg extension power increased from baseline to the 10 week follow up in both groups ; mean [ 95 % CI ] IG : 0.29 [ 0.13 ; 0.45 ] and CG : 0.26 [ 0.10 ; 0.42 ] W/kg , with no between-group difference ( primary outcome ) ( P = 0.79 ) . Maximal walking speed ( P = 0.008 ) and stair climb performance ( P = 0.04 ) improved more in the IG compared to CG , no other between-group differences existed . CONCLUSIONS In this trial , supervised PRT twice a week in addition to 5 weekly sessions of unsupervised exercise for 10 weeks was not superior to 7 weekly sessions of unsupervised home-based exercise for 10 weeks in improving the primary outcome , leg-extension power of the operated leg , at the primary endpoint 10 weeks after surgery in THR patients with lower pre-operative function . TRIAL REGISTRATION NCT01214954 Husby VS , Helgerud J , Bjørgen S , Husby OS , Benum P , Hoff J : Early postoperative maximal strength training improves work efficiency 6–12 months after osteoarthritis induced total hip arthroplasty in patients younger than 60 years . Objective : To assess physical outcome of early maximal strength training after total hip arthroplasty . Design : Six- and 12-mo follow-up of 24 ( 22 ) total hip arthroplasty patients r and omly assigned to 4 wks of maximal strength training and conventional rehabilitation and to conventional rehabilitation only was conducted . After the intervention period , all patients attended conventional rehabilitation . Outcome measures were hip abduction and leg press strength , gait patterns , work efficiency , maximal oxygen consumption , and health-related quality of life . Results : Work efficiency was significantly higher in the strength training and conventional rehabilitation group compared with the conventional rehabilitation – only group after 6 and 12 mos by 29 % and 30 % , respectively . Leg press for the healthy leg and rate of force development for the operated leg were significantly higher in the strength training and conventional rehabilitation group compared with the conventional rehabilitation – only group 12 mos postoperatively by 36 % and 74 % , respectively . Conclusions : This study demonstrates higher work efficiency after 6 and 12 mos and improved rate of force development after 12 mos in total hip arthroplasty patients who performed early maximal strength training combined with conventional rehabilitation after total hip arthroplasty surgery compared with total hip arthroplasty patients receiving conventional rehabilitation only . However , the study indicates that a prolonged maximal strength training program and aerobic endurance training are required to fully recover total hip arthroplasty patients Background Total Hip Arthroplasty ( THA ) is being used more commonly in younger higher dem and patients . The purpose of this r and omized pilot study was to explore a ) feasibility of comprehensive postoperative rehabilitation compared to usual care following primary THA in subjects < 65 years , b ) appropriate outcome measures including performance-based measures and c ) timing of assessment s. Methods 21 subjects who underwent primary THA were r and omized to receive a three-month out-patient rehabilitation program ( Intervention ) or usual postoperative care ( Control ) . Subjects were assessed preoperatively , six-weeks postoperatively ( Pre-intervention ) and four and 12 months postoperatively ( Post-intervention ) . Self-report measures were the Western Ontario McMaster Osteoarthritis Index ( WOMAC ) and R and 36-Item Health Survey ( R AND -36 ) . Performance-based measures included lower extremity strength , walking speed and endurance , and gait laboratory assessment . Results Ten Control and 11 Intervention subjects with an average age of 53.4 ( SD9.3 ) years were r and omized . All Intervention subjects completed the program without adverse effects . Although no statistically significantly results were reported , four months postoperatively , Intervention subjects had clinical ly important differences ( CID ) in strength compared with Control subjects . Walking endurance , WOMAC and R AND scores improved significantly with no CID noted between groups . Ten ( 48 % ) subjects reported a ceiling effect on the WOMAC ( 9 ( 43 % ) subjects on Pain ; 1 ( 5 % ) subject on Function ) . No group CID were noted in gait measures . Conclusions Our recommendations would be that performance-based strength measures should be considered for the primary outcome in this younger cohort . Because of the ceiling effects with WOMAC Pain , a different pain measure is indicated . Other more challenging functional performance-based tests should be considered such as a more prolonged endurance test . There is merit in one-year follow-up as strength improved after four months in both groups The influence of an upper-limb interval-training program after total hip arthroplasty ( THA ) in elderly patients was studied during a 1 yr follow-up on health status and walking ability . After surgery , 14 patients were r and omly assigned to the control group that started a 6 wk general rehabilitation program or the training group that combined it with an interval exercise program on an arm ergometer . A Western Ontario and McMaster Universities ( WOMAC ) Osteoarthritis Index was completed 1 mo before and 2 mo and 1 yr after surgery . A 6 min walking test was performed at 2 mo and 1 yr after surgery . The training group covered a significantly longer distance than the control group in the 6 min walk test and obtained significantly lower WOMAC scores both at 2 mo and 1 yr after surgery . However , both groups significantly improved in WOMAC and in their performance during the survey . Endurance-type upper-body aerobic training in a rehabilitation program might be important after THA UNLABELLED Husby VS , Helgerud J , Bjørgen S , Husby OS , Benum P , Hoff J. Early maximal strength training is an efficient treatment for patients operated with total hip arthroplasty . OBJECTIVE To compare muscle strength , work efficiency , gait patterns , and quality of life in patients undergoing total hip arthroplasty ( THA ) r and omly assigned to either maximal strength training or a conventional rehabilitation program . DESIGN A r and omized controlled study . SETTING Research laboratory , rehabilitation center , and physical therapy clinic . PARTICIPANTS Patients ( N=24 ) with osteoarthritis as the main reason for THA were r and omly assigned to perform maximal strength training ( n=12 ) or conventional rehabilitation ( n=12 ) . INTERVENTIONS The maximal strength training group ( STG ) performed maximal strength training in leg press and abduction with the operated leg only 5 times a week for 4 weeks in addition to the conventional rehabilitation program . The conventional rehabilitation group ( CRG ) received supervised physical therapy 3 to 5 times a week for 4 weeks . MAIN OUTCOME MEASURES 1-repetition maximum ( 1RM ) leg press strength , 1RM abduction strength , rate of force development ( RFD ) , work efficiency , gait patterns , and quality of life . RESULTS 1RM increased in the bilateral leg press ( P<.002 ) and in the operated leg separately ( P<.002 ) in the STG compared with the CRG . 1RM abduction strength in the operated leg ( P<.002 ) and the healthy leg ( P<.002 ) increased in the STG compared with the CRG . RFD increased in the STG compared with the CRG ( P(g)=.030 ) , followed by a trend towards increased peak force in the STG ( P(g)=.053 ) ( P(g ) = probability for differences between groups ) . Work efficiency tended to improve in the STG compared with the CRG ( P=.065 ) . No differences in gait patterns were revealed between the groups after the training intervention . CONCLUSIONS Early maximal strength training 1 week postoperatively is feasible and an efficient treatment to regain muscular strength for patients who have undergone THA , demonstrated by a significantly larger increase in muscular strength and a trend towards a better work efficiency in the STG compared with the CRG OBJECTIVE To investigate the influence of an arm-interval exercise program for the upper limbs on health status and walking ability in elderly patients after total hip arthroplasty . DESIGN A r and omized controlled investigation . After surgery , a control group started a general rehabilitation program , and a training group combined it with an arm-interval exercise program . SUBJECTS Fourteen patients ( age 75.1 + /- 4.8 years ) were r and omly assigned to the control group ( n = 7 ) and the training group ( n = 7 ) . METHODS A Western Ontario and MacMaster University ( WOMAC ) Osteoarthritis Index was completed and an incremental exercise test on an arm crank ergometer was also performed 1 month before ( T(-1 ) ) and 2 months after surgery ( T2 ) . Moreover , a 6-minute walk test was performed at T2 . RESULTS Both groups significantly improved all dimensions of WOMAC , except in WOMAC physical function subscale in the control group . The training group covered a significantly longer distance in the walking test than the control group and also presented significantly higher VO2 peak value at T2 . Correlation analyses indicate that VO2 peak value and the distance covered in the 6-minute walking test were significantly associated with functional status . After calculating the ratio distance covered/score at WOMAC physical function , we observed a significantly higher ratio value in the training group than in the control group . CONCLUSION Preliminary results indicate that the improvement in physical fitness and functional status of the training group seems to be associated with better health status Background and Aims : The effectiveness of partial weightbearing after hip surgery has been question ed as well as the need of intensive physiotherapy . Material and Methods : 36 patients ( average age 54.4 , 19 women ) operated with uncemented hip arthroplasty were r and omized either to unrestricted weightbearing ( UWB ) combined with intensive physiotherapy or to partial weightbearing ( PWB ) for 3 months combined with a short self-training program . The load during walking and the muscle strength ( MS ) in abduction was measured preoperative and subsequent up to 12 months . Results : The average peak load on the operated leg at one week was 39.0 kg for the UWB and 25.8 for the PWB group ( P = 0.009 ) while at three months 70.0 and 31.7 ( P = 0.001 ) respectively . At 6 and 12 months there were no differences between the groups . The muscle strength increased in both groups up to six months but there were no differences between the groups . Conclusions : Even though patients applied more load than the recommended 15 kg most patients were able to comply with partial weightbearing fairly well . The effect of intensive physiotherapy on the muscle strength after hip arthroplasty is question able Our objective was to investigate whether behavioral grade d activity ( BGA ) has particular benefit in specific subgroups of osteoarthritis ( OA ) patients . Two hundred participants with OA of hip or knee , or both ( clinical American College of Rheumatology , ACR , criteria ) participated in a r and omized clinical trial on the efficacy of BGA compared to treatment according to the Dutch physiotherapy guideline ( usual care ; UC ) . Changes in pain ( Visual Analog Scale , VAS ) , physical functioning ( Western Ontario and McMaster Universities Osteoarthritis Index , WOMAC , and McMaster Toronto Arthritis Question naire , MACTAR ) , and patient global assessment were compared for specific subgroups . Subgroups were assigned by the median split method and were analyzed using analysis of covariance . Beneficial effects of BGA were found for patients with a relatively low level of physical functioning ( p?0.03 ) . Furthermore , beneficial effects of BGA in patients with a low level of internal locus of control were marginally significant ( p = .05 ) . Patients with a relatively low level of physical functioning benefit more from BGA compared to UC . Compared to UC , BGA is the preferred treatment option in patients with a low level of physical functioning Organized physiotherapy starting two months after uncomplicated total hip replacements for primary arthrosis did not improve the rehabilitation . Six months after surgery there were no significant differences between 14 patients with and 16 patients without physiotherapy regarding improvement of passive hip motion , or hip or knee muscle strength of the operated limb . Neither were there any differences in walking ability or activities of daily living OBJECTIVES To recommend a consensus-derived set of performance-based tests of physical function for use in people diagnosed with hip or knee osteoarthritis ( OA ) or following joint replacement . METHODS An international , multidisciplinary expert advisory group was established to guide the study . Potential tests for consideration in the recommended set were identified via a survey of selected experts and through a systematic review of the measurement properties for performance-based tests . A multi-phase , consensus-based approach was used to prioritize and select performance-based tests by applying decision analysis methodology ( 1000Minds software ) via online decision surveys . The recommended tests were chosen based on available measurement-property evidence , feasibility of the tests , scoring methods and expert consensus . RESULTS Consensus incorporated the opinions of 138 experienced clinicians and research ers from 16 countries . The five tests recommended by the advisory group and endorsed by Osteoarthritis Research Society International ( OARSI ) were the 30-s chair-st and test , 40 m fast-paced walk test , a stair-climb test , timed up- and -go test and 6-min walk test . The first three were recommended as the minimal core set of performance-based tests for hip or knee OA . CONCLUSION The OARSI recommended set of performance-based tests of physical function represents the tests of typical activities relevant to individuals diagnosed with hip or knee OA and following joint replacements . These tests are complementary to patient-reported measures and are recommended as prospect i ve outcome measures in future OA research and to assist decision-making in clinical practice . Further research should be directed to exp and ing the measurement-property evidence of the recommended tests BACKGROUND AND PURPOSE Despite a successful surgical procedure , deficits in muscle strength and physical function are documented 1 - 2 years after total hip replacement ( THR ) . There is a lack of evidence concerning which rehabilitation strategy is the most effective after THR . The purpose of this pilot study was to investigate the feasibility of an early-initiated intensified , home-based training regime and to form the basis of future studies with regard to exercises , outcome measures and power calculations . METHODS The trial is a single-blinded , cluster-r and omized controlled trial performed at an orthopaedic physiotherapy department in a public hospital in Denmark . A consecutive sample of 46 patients undergoing primary THR surgery for osteoarthritis between September 2008 and January 2009 was included . Forty-four patients completed the trial ( 96 % follow-up ) . Participants were r and omly assigned to an intervention group ( IG , n = 23 ) receiving 12 weeks of intensified exercises ( e.g. rubber b and resistance ) or a control group ( CG , n = 21 ) receiving st and ard rehabilitation exercises without external resistance . The outcome measurements were maximal gait speed , isometric hip abductor muscle strength , one-legged stance , health-related quality of life ( EuroQol-5 Dimensions ) , patient satisfaction , and patient-evaluated function , stiffness and pain ( Western and Ontario McMasters University Osteoarthritis Index ) . RESULTS There were significant increases in both groups in all the measurements during the 12 weeks of exercises . All participants in the IG were satisfied or very satisfied with the exercises compared with 85 % in the CG ( P = 0.095 ) . In the IG , four participants ( 17.4 % ) had difficulties when performing the intensified exercises at home . Hip abduction strength was significantly weaker in the leg operated compared with the leg not operated on after the intervention in both groups ( P < 0.01 ) . CONCLUSION This pilot study indicates that the majority of THR patients tolerated early-initiated intensified exercises without additional pain and with high patient satisfaction . It seems that some of the patients need supervision to perform intensified exercises 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 . The aim of the study was to evaluate the subjective functional outcome of total hip arthroplasty ( THA ) in patients who underwent hydrotherapy ( HT ) 6 months after discharge . A prospect i ve r and omized study was performed on 70 elderly in patients with recent THA , who completed a rehabilitation program . After r and omization , 33 of them were treated in conventional gyms ( no-hydrotherapy group = NHTG ) and 31 received HT ( hydrotherapy group = HTG ) . Interviews with the Western-Ontario MacMasters Universities Osteoarthritis Index ( WOMAC ) were performed at admission , at discharge and 6 months later . Kruskal-Wallis , Mann-Whitney and Wilcoxon tests were applied for statistical analysis . Both groups improved . Pain , stiffness and function were all positively affected . Statistical analysis indicated that WOMAC sub-scales were significantly lower for all patients treated with HT . The benefits at discharge still remained after 6 months . We conclude that HT is recommended after THA in a geriatric population Objective : To evaluate the efficacy of an in-hospital programme based on task-oriented exercises associated with early full weight-bearing in patients with multiple comorbidities undergoing total hip replacement . Design : R and omized controlled trial . Setting : Specialised rehabilitation centre . Subjects : A total of 100 patients ( mean age of 69 ( 8) years ; 40 males , 60 females ) . Interventions : The experimental group underwent task-oriented exercises and was encouraged to ab and on any walking aids by the end of their in-hospital stay . The control group underwent open chain kinetic exercises , and was recommended to use partial weight-bearing and walking aids until three months after surgery . Both groups individually followed programmes of 90-minute sessions five times a week for three weeks . Outcome measures : Western Ontario and McMaster Universities Osteoarthritis Index , Pain Numerical Rating Scale , Functional Independence Measure , and Short-Form Health Survey . The participants were evaluated before , after training , and after a further 12 months . Results : There were no significant between-group differences at baseline . After training , a between-group difference of 12 points was found for the Western Ontario and McMaster Universities Osteoarthritis Index – functional subscale , indicating a clinical ly tangible treatment effect on disability . The Functional Independence Measure increased by 31 and 15 points in the experimental and control group , respectively . A linear mixed model revealed significant effects of time , group , and time by group interaction on disability , pain , activities of daily living , and most of the physical quality of life domains . Conclusion : Task-oriented exercises associated with early full weight-bearing improve disability , pain , activities of daily living , and quality of life after total hip replacement BACKGROUND Few guidelines are available whether early weight-bearing after an uncemented total hip arthroplasty ( THA ) can be recommended or not . Stability and ingrowth may be jeopardized by immediate loading of the implant while functional recovery may be promoted and periprosthetic demineralization reduced . PATIENTS AND METHODS We did a prospect i ve study of 20 patients who were operated on with a hydroxyapatite-coated ( HA ) , uncemented total hip arthroplasty with a tapered stem because of unilateral arthrosis , and r and omized the patients to the immediate ( I ) or late ( L ) weight-bearing ( after 3 months ) group . The shoe on the operated side was equipped with an auditory device signaling when the patient placed a load on the extremity . The clinical assessment was done with the Harris hip score at the time of the operation and after 12 and 24 months . Radiographs and dual-energy x-ray absorptiometry ( DEXA ) were evaluated for migration , femoral remodeling and bone mineral density ( BMD ) after 3 , 6 , 12 and 24 months . Tc-scintigraphy was done after 6 , 12 and 24 months . RESULTS Postoperatively , the Harris hip score showed no group difference . After 3 months , we noted a large reduction in BMD around the stem prosthesis . This was most marked in the proximal regions and the bone loss was significantly larger in zone 1 , 4 and 5 in the L group . Distally , the BMD normalized with time , but the loss of bone persisted in the proximal zones after 24 months . An initial increase in the scintigraphic uptake ratio in all zones in both groups declined with time , but it was still increased on the operated side after 24 months . Several radiographic signs of bone remodeling were seen , but the patterns were similar in both groups . INTERPRETATION We found no adverse effect of immediate weight bearing with this prosthesis OBJECTIVE The purpose of this systematic review was to determine the effectiveness of exercise for the management of soft tissue injuries of the hip , thigh , and knee . METHODS We conducted a systematic review and search ed MEDLINE , EMBASE , PsycINFO , the Cochrane Central Register of Controlled Trials , and CINAHL Plus with Full Text from January 1 , 1990 , to April 8 , 2015 , for r and omized controlled trials ( RCTs ) , cohort studies , and case-control studies evaluating the effect of exercise on pain intensity , self-rated recovery , functional recovery , health-related quality of life , psychological outcomes , and adverse events . R and om pairs of independent review ers screened titles and abstract s and assessed risk of bias using the Scottish Intercollegiate Guidelines Network criteria . Best evidence synthesis methodology was used . RESULTS We screened 9494 citations . Eight RCTs were critically appraised , and 3 had low risk of bias and were included in our synthesis . One RCT found statistically significant improvements in pain and function favoring clinic-based progressive combined exercises over a " wait and see " approach for patellofemoral pain syndrome . A second RCT suggests that supervised closed kinetic chain exercises may lead to greater symptom improvement than open chain exercises for patellofemoral pain syndrome . One RCT suggests that clinic-based group exercises may be more effective than multimodal physiotherapy in male athletes with persistent groin pain . CONCLUSION We found limited high- quality evidence to support the use of exercise for the management of soft tissue injuries of the lower extremity . The evidence suggests that clinic-based exercise programs may benefit patients with patellofemoral pain syndrome and persistent groin pain . Further high- quality research is needed BACKGROUND At present , there is an insufficient evidence base to evaluate the effectiveness of physiotherapy following total hip replacement ( THR ) . This study evaluated the effectiveness of a physiotherapy-supervised functional exercise programme between 12 and 18 weeks following THR . These time-points coincide with increased functional dem and in patients . DESIGN Adequately powered assessor-blinded r and omised controlled trial . SETTING Patients were recruited at a pre-operative assessment clinic and r and omised following surgery . PARTICIPANTS Sixty-three subjects were r and omised to either the usual care group ( control , n=31 ) or the functional exercise+usual care group ( n=32 ) . INTERVENTIONS Patients in the functional exercise group attended a physiotherapy-supervised functional exercise class twice weekly from 12 to 18 weeks following THR . Patients in the control group followed the usual care protocol with no exercise intervention . MAIN OUTCOME MEASUREMENT The main outcome measurement tool was the Western Ontario and McMaster Universities Osteoarthritis Index ( WOMAC ) question naire , and the secondary outcomes included walking speed , hip abduction dynamometry , Short Form 12 physical and mental health scores , and visual analogue pain scale score . RESULTS At 18 weeks post surgery , WOMAC function and walking speed improved significantly more in the functional exercise group [ mean difference -4.0 , 95 % confidence interval ( CI ) -7.0 to 1.0 ( P<0.01 ) ; mean difference 21.9 m , 95 % CI 0.60 to 43.3 ( P<0.04 ) ] than the control group , but there was no significant difference in hip abductor strength . CONCLUSION This study demonstrated that patients who undertake a physiotherapy-led functional exercise programme between 12 and 18 weeks after THR may gain significant functional improvement compared with patients receiving usual care . Clinical trial registration number NCT01683201 |
10,755 | 20,042,070 | Conclusions There is little evidence at the moment for the effectiveness of an increasingly used and commercialised instrument such as electronic multidimensional guidelines .
This conclusion implies a considerable risk towards inappropriate investments in ineffective implementation interventions and in suboptimal care | Background Electronic guideline -based decision support systems have been suggested to successfully deliver the knowledge embedded in clinical practice guidelines .
A number of studies have already shown positive findings for decision support systems such as drug-dosing systems and computer-generated reminder systems for preventive care services . | Abstract Objective : To evaluate the use of a computerised support system for decision making for implementing evidence based clinical guidelines for the management of asthma and angina in adults in primary care . Design : A before and after pragmatic cluster r and omised controlled trial utilising a two by two incomplete block design . Setting : 60 general practice s in north east Engl and . Participants : General practitioners and practice nurses in the study practice s and their patients aged 18 or over with angina or asthma . Main outcome measures : Adherence to the guidelines , based on review of case notes and patient reported generic and condition specific outcome measures . Results : The computerised decision support system had no significant effect on consultation rates , process of care measures ( including prescribing ) , or any patient reported outcomes for either condition . Levels of use of the software were low . Conclusions : No effect was found of computerised evidence based guidelines on the management of asthma or angina in adults in primary care . This was probably due to low levels of use of the software , despite the system being optimised as far as was technically possible . Even if the technical problems of producing a system that fully supports the management of chronic disease were solved , there remains the challenge of integrating the systems into clinical encounters where busy practitioners manage patients with complex , multiple conditions Background — Indirect evidence shows that alerting users with clinical decision support systems seems to change behavior more than requiring users to actively initiate the system . However , r and omized trials comparing these methods in a clinical setting are lacking . We studied the effect of both alerting and on-dem and decision support with respect to screening and treatment of dyslipidemia based on the guidelines of the Dutch College of General Practitioners . Methods and Results — In a clustered r and omized trial design , 38 Dutch general practice s ( 77 physicians ) and 87 886 of their patients ( 39 433 men 18 to 70 years of age and 48 453 women 18 to 75 years of age ) who used the ELIAS electronic health record participated . Each practice was assigned to receive alerts , on-dem and support , or no intervention . We measured the percentage of patients screened and treated after 12 months of follow-up . In the alerting group , 65 % of the patients requiring screening were screened ( relative risk versus control=1.76 ; 95 % confidence interval , 1.41 to 2.20 ) compared with 35 % of patients in the on-dem and group ( relative risk versus control=1.28 ; 95 % confidence interval , 0.98 to 1.68 ) and 25 % of patients in the control group . In the alerting group , 66 % of patients requiring treatment were treated ( relative risk versus control=1.40 ; 95 % confidence interval , 1.15 to 1.70 ) compared with 40 % of patients ( relative risk versus control=1.19 ; 95 % confidence interval , 0.94 to 1.50 ) in the on-dem and group and 36 % of patients in the control group . Conclusion — The alerting version of the clinical decision support systems significantly improved screening and treatment performance for dyslipidemia by general practitioners Abstract Objective : To underst and the factors influencing the adoption of a computerised clinical decision support system for two chronic diseases in general practice . Design : Practice based , longitudinal , qualitative interview study . Setting : Five general practice s in north east Engl and . Participants : 13 respondents ( two practice managers , three nurses , and eight general practitioners ) gave a total of 19 semistructured interviews . 40 people in practice s included in the r and omised controlled trial ( 34 doctors , three nurses ) and interview study ( three doctors , one previously interviewed ) gave feedback . Results : Negative comments about the decision support system significantly outweighed the positive or neutral comments . Three main areas of concern among clinicians emerged : timing of the guideline trigger , ease of use of the system , and helpfulness of the content . Respondents did not feel that the system fitted well within the general practice context . Experience of “ on-dem and ” information sources , which were generally more positively viewed , informed the comments about the system . Some general practitioners suggested that nurses might find the guideline content more clinical ly useful and might be more prepared to use a computerised decision support system , but lack of feedback from nurses who had experienced the system limited the ability to assess this . Conclusions : Significant barriers exist to the use of complex clinical decision support systems for chronic disease by general practitioners . Key issues include the relevance and accuracy of messages and the flexibility to respond to other factors influencing decision making in primary care . What is already known on this topic R and omised controlled trials of complex computerised decision support systems have found low rates of use and no effects on process and outcomes of care What this study adds Clinicians found a computerised decision support system for chronic disease in general practice to be difficult to use and unhelpful clinical ly It did not fit well into a general practice consultation and compared unfavourably with “ on-dem and ” information “ Active ” decision support can make clinicians aware of gaps between their own practice and “ best ” practice , but computer prompts need to be relevant and Abstract Objectives : To investigate the effect of a computer based clinical decision support system and a risk chart on absolute cardiovascular risk , blood pressure , and prescribing of cardiovascular drugs in hypertensive patients . Design : Cluster r and omised controlled trial . Setting : 27 general practice s in Avon . Participants : 614 patients aged between 60 and 79 years with high blood pressure . Interventions : Patients were r and omised to computer based clinical decision support system plus cardiovascular risk chart ; cardiovascular risk chart alone ; or usual care . Main outcome measures : Percentage of patients in each group with a five year cardiovascular risk≥10 % , systolic blood pressure , diastolic blood pressure , prescribing of cardiovascular drugs . Results : Patients in the computer based clinical decision support system and chart only groups were no more likely to have cardiovascular risk reduced to below 10 % than patients receiving usual care . Patients in the computer based clinical decision support group were more likely to have a cardiovascular risk≥10 % than chart only patients , odds ratio 2.3 ( 95 % confidence interval 1.1 to 4.8 ) . The chart only group had significantly lower systolic blood pressure compared with the usual care group ( difference in means−4.6 mm Hg ( 95 % confidence interval−8.4 to−0.8 ) . Reduction of diastolic blood pressure did not differ between the three groups . The chart only group were twice as likely to be prescribed two classes of cardiovascular drugs and over three times as likely to be prescribed three or more classes of drugs compared with the other groups . Conclusions : The computer based clinical decision support system did not confer any benefit in absolute risk reduction or blood pressure control and requires further development and evaluation before use in clinical care can be recommended . Use of chart guidelines are associated with a potentially important reduction in systolic blood pressure Computers are steadily being incorporated in clinical practice . We conducted a nonr and omised , controlled , prospect i ve trial of electronic messages design ed to enhance adherence to clinical practice guidelines . We studied 126 physicians and nurse practitioners who used electronic medical records when caring for 349 patients with HIV infection in a primary care practice . We analysed the response times of clinicians to the situations that triggered alerts and reminders , the number of ambulatory visits , and hospitalisation . The median response times to 303 alerts in the intervention group and 388 alerts in the control group were 11 and 52 days ( p < 0.0001 ) , respectively . The median response time to 432 reminders in the intervention group was 114 days and that for 360 reminders in the control group was over 500 days ( p < 0.0001 ) . There was no effect on visits to the primary care practice . There was , however , a significant increase in the rate of visits outside the primary care practice ( p = 0.02 ) , which is explained by the increased frequency of visits to ophthalmologists . There were no differences in admission rates ( p = 0.47 ) , in admissions for pneumocystosis ( p = 0.09 ) , in visits to the emergency ward ( p = 0.24 ) , or in survival ( p = 0.19 ) . We conclude that the electronic medical record was effective in helping clinicians adhere to practice guidelines The majority of general practitioners in the Netherl and s have replaced traditional paper-based patient records with computer-based records ; physicians enter patient data themselves in the computer during patient encounters ( 1 ) . The use of electronic patient records creates new opportunities to influence physician behavior through implementation of decision support systems ( 2 - 7 ) . In recent years , research ers have documented various computer-based decision support systems that have influenced physician behavior ( 8 - 17 ) . Other investigators , however , have reported that computer-based decision support has not affected patient care ( 18 ) . To resolve the issue , investigators have compared the results of studies that were conducted in different setting s , used different methods , and involved different population s ( 19 ) . Studies comparing different methods of providing computer-based decision support in r and omized trials are not available . In the Netherl and s , 3 % to 4 % of patient encounters with general practitioners in primary care result in the ordering of blood tests ( 20 ) . However , ordering of blood tests is not always appropriate ( 21 - 29 ) . Research ers argue that excessive ordering of tests causes physicians to pursue evaluation of false-positive results , which in turn leads to additional unnecessary diagnostic examinations ( 30 - 35 ) . Two methods have proven effective in reducing the number of tests ordered by Dutch general practitioners . The first method is based on restricting the number of tests that are listed on an order form . Zaat and colleagues ( 36 , 37 ) developed a restricted paper order form that replaced the existing form . The second method involves introduction of indication-oriented order forms that are based on clinical practice guidelines ( 38 - 40 ) . We hypothesized that an indication-oriented order form based on guidelines , which would provide an optimally restricted list of tests that are relevant for a specific indication , would be more effective in decreasing the number of tests ordered compared with an order form that provides an initially limited list of tests . We therefore conducted a r and omized trial to compare the effect of two versions of BloodLink , a computer-based clinical decision support system , on blood test ordering among Dutch general practitioners . Methods Participants In August and September 1995 , all 64 practice s ( 94 general practitioners ) in the region of Delft , the Netherl and s , were invited to participate in the study . Only practice s that had replaced their paper-based patient records with electronic records and were using the computer during patient encounters were eligible . A total of 46 practice s ( 62 general practitioners ) agreed to participate . R and omization To avoid contamination , we performed r and om allocation at the level of the practice ( 41 , 42 ) . The practice s were first stratified by type : solo practice s or group practice s ( two or more general practitioners in the same practice ) . Each practice was subsequently assigned by simple r and om allocation to use BloodLink-Restricted or BloodLink- Guideline for the full study period . A research er who was not involved in the study and was blinded to the identity of the practice s performed the r and omization by using a r and om-numbers table . After r and omization , 22 practice s involving 30 general practitioners were assigned to use BloodLink-Restricted and 24 practice s involving 32 general practitioners were assigned to use BloodLink- Guideline . Intervention We developed two versions of BloodLink , a computer-based decision support system . BloodLink-Restricted initially displays a reduced list of tests , whereas BloodLink- Guideline is based on the guidelines of the Dutch College of General Practitioners . Both versions of BloodLink are integrated with the computer-based patient record ( 43 ) . The option to use BloodLink was added to the screen that the general practitioner uses when entering data in the electronic patient record during patient encounters . The general practitioner can activate BloodLink to order blood tests as an alternative to using paper order forms . Because the total number of tests that can be ordered is too large to display on a computer screen , a set of tests is presented for selection . If the physician requires additional tests that are not currently displayed , he or she can type the first few letters of the names of the required tests , and the system will present all possible matches ( including those corresponding to possible typing errors of the general practitioner ) for selection . The number of tests that the general practitioners had at their disposal was the same both before and during the intervention ( 52 clinical chemistry tests and 46 microbiological tests ) . Options for specific instructions to the laboratory ( for example , urgent processing or fasting values ) are available . Once the physician has made his or her selection s , BloodLink prints a patient-specific test order form and instructions for the laboratory and up date s the patient record with the tests that have been ordered . The only difference between the two versions of BloodLink is the method used to present the initial set of tests to the general practitioner . BloodLink-Restricted is based on the idea of a restricted order form . It offers the general practitioner an initial set of 15 tests that have been shown to cover most of the clinical situations seen in primary care ( 36 ) . BloodLink-Restricted can be viewed as a general electronic order form that presents only 15 tests on the screen , together with a field labeled other tests that allows the physician to request any other blood test ( 43 ) . The 15 tests are alanine aminotransferase , aspartate aminotransferase , total bilirubin , cholesterol , creatinine , erythrocyte sedimentation rate , free thyroxine , -glutamyltransferase , glucose ( and fasting glucose ) , glycosylated hemoglobin , hemoglobin , mean corpuscular volume , PaulBunnell , potassium , and thyroid-stimulating hormone . At any time , the physician can customize tests for individual patients by adding or deleting tests . BloodLink- Guideline is based on the guidelines of the Dutch College of General Practitioners . By January 1996 , the Dutch College of General Practitioners had published 54 guidelines . Some guidelines focus on symptoms that are frequently seen in the primary care setting , such as acute diarrhea , acute sore throat , low back pain , alcohol abuse , fever in children , and sleeping disorders . Other guidelines focus on common diseases in primary care , such as diabetes , asthma , depression , dementia , and eczema . Finally , a set of guidelines covers preventive medicine . We review ed the most recent version of each guideline , available in January 1996 , and noted whether it contained a reference to a blood test ( 44 ) . We determined the clinical situation in which the test should be performed ( indication ) and the tests that should be performed in that situation ( advised tests ) . When general practitioners activate the system , BloodLink- Guideline first provides an overview of the available guidelines . The names of these guidelines are familiar to Dutch general practitioners . The general practitioner selects the appropriate guideline . A guideline may describe several different indications for requesting blood tests ; for example , the guideline for blood tests and liver disease mentions 10 different indications . After the indication has been identified , the system proposes the relevant tests . The general practitioner then decides whether to adhere to the protocol . At any time , the physician can customize tests for individual patients by adding or removing tests from the proposed list . Although new guidelines are published at regular intervals , the currently available guidelines cover only a limited set of indications for blood tests ( 44 ) . In the absence of national guidelines , local or regional guidelines may be used . The version of BloodLink- Guideline used during the clinical trial in the Delft region included three regional guidelines for anemia , AIDS , and clotting disorders , in addition to all national guidelines . Even with these additional guidelines , BloodLink- Guideline does not cover all possible indications for blood tests in primary care . To deal with these situations , the general practitioner can select the heading other indication and order any test . Protocol Before the study , the general practitioners were using two paper order forms : one for clinical chemistry and one for microbiology . After BloodLink was installed , one of the authors gave a brief orientation presentation to the participating practitioners . During a 3-month phase-in period , the general practitioners were allowed to use BloodLink in their practice s to become acquainted with the system . After this period , the general practitioners were asked whether they were willing to participate in the trial . The study period was March 1996 through February 1997 . Physicians always had the choice to use either the BloodLink software or the paper forms to order clinical chemistry and microbiology tests ; thus , paper order forms were still available during the entire intervention period . When the general practitioner ordered blood tests during a patient encounter , only one order form was generated regardless of whether the general practitioner used paper forms or BloodLink . The electronic patient record monitored use of BloodLink by the practitioners . To include the requests for blood tests that were made by using traditional paper forms , we retrieved from the regional laboratory all requests for blood tests . Outcomes We counted the number of order forms that the laboratory received from the general practitioners and the number of tests on each form . The main outcome measure was the average number of tests per order form ( including paper forms ) per practice ( summary variable ) . We defined the most frequently ordered tests as the tests that accounted for 80 % of the total number of tests ordered . For these tests , we OBJECTIVE To evaluate the implementation of clinical guidelines for hypertension in general practice by use of a computer-based clinical decision support system ( CDSS ) and a specific implementation strategy . Evaluation of patient outcome . DESIGN R and omised study with health centres as units . The intervention group had the CDSS installed and made ready for use , doctors and assistants were trained and received a user-manual , the doctors were offered telephone repetitions , a seminar in risk intervention and , at the same seminar , further demonstration of the CDSS . The doctors received baseline registration s with information of how they treated their own hypertensive patients , and use of the CDSS was checked repeatedly . SETTING General practice in Sør- and Nord-Trøndelag counties in Norway , 380,000 inhabitants . PARTICIPANTS Seventeen health centres with 24 doctors and 984 patients in the intervention group . Data from 879 patients used in the final analyses . Twelve health centres with 29 doctors and 1255 patients in the control group . Data from 1119 patients used in the final analyses . MAIN OUTCOME MEASURES After an intervention period of 18 months , group differences in level of systolic and diastolic blood pressure , serum cholesterol , body mass index , and risk score for myocardial infa rct ion were calculated , as well as group differences in fractions of smokers . RESULTS Significant group difference in favour of intervention group : diastolic blood pressure 1 mmHg ( 95 % CI -1.89 , -0.17 ) . However , a significant baseline difference in systolic blood pressure in favour of control group of 2.7 mmHg ( 95 % CI 1.0 , 4.5 ) had been reduced to 1.2 mmHg ( 95 % CI -0.6 , 3.0 ) after intervention . CONCLUSION Implementation of clinical guidelines in the treatment of hypertensive patients in general practice by means of a CDSS and several other procedures for implementation did not affect patient outcome in any clinical ly significant way CONTEXT As of 2005 , the International Committee of Medical Journal Editors required investigators to register their trials prior to participant enrollment as a precondition for publishing the trial 's findings in member journals . OBJECTIVE To assess the proportion of registered trials with results recently published in journals with high impact factors ; to compare the primary outcomes specified in trial registries with those reported in the published articles ; and to determine whether primary outcome reporting bias favored significant outcomes . DATA SOURCES AND STUDY SELECTION MEDLINE via PubMed was search ed for reports of r and omized controlled trials ( RCTs ) in 3 medical areas ( cardiology , rheumatology , and gastroenterology ) indexed in 2008 in the 10 general medical journals and specialty journals with the highest impact factors . DATA EXTRACTION For each included article , we obtained the trial registration information using a st and ardized data extraction form . RESULTS Of the 323 included trials , 147 ( 45.5 % ) were adequately registered ( ie , registered before the end of the trial , with the primary outcome clearly specified ) . Trial registration was lacking for 89 published reports ( 27.6 % ) , 45 trials ( 13.9 % ) were registered after the completion of the study , 39 ( 12 % ) were registered with no or an unclear description of the primary outcome , and 3 ( 0.9 % ) were registered after the completion of the study and had an unclear description of the primary outcome . Among articles with trials adequately registered , 31 % ( 46 of 147 ) showed some evidence of discrepancies between the outcomes registered and the outcomes published . The influence of these discrepancies could be assessed in only half of them and in these statistically significant results were favored in 82.6 % ( 19 of 23 ) . CONCLUSION Comparison of the primary outcomes of RCTs registered with their subsequent publication indicated that selective outcome reporting is prevalent Objectives : Having shown previously that an electronic prescription writer and decision support system improved pediatric prescribing behavior for otitis media in an academic clinic setting , we assessed whether point-of-care delivery of evidence could demonstrate similar effects for a wide range of other common pediatric conditions . Design : Cluster r and omized controlled trial . Setting : A teaching clinic/ clinical practice site and a primary care pediatric clinic serving a rural and semi-urban patient mix . Participants : A total of 36 providers at the teaching clinic/ practice site and eight providers at the private primary pediatric clinic . Intervention : An evidence -based message system that presented real-time evidence to providers based on prescribing practice s for acute otitis media , allergic rhinitis , sinusitis , constipation , pharyngitis , croup , urticaria , and bronchiolitis . Outcome measures : The proportion of prescriptions dispensed in accordance with evidence . Results : The proportion of prescriptions dispensed in accordance with evidence improved four percentage points , from 38 % at baseline to 42 % following the intervention . The control group improved by one percentage point , from 39 % at baseline to 40 % at trial 's conclusion . The adjusted difference between the intervention and control groups was 8 % ( 95 % confidence interval 1 % , 15 % ) . Intervention effectiveness did not decrease with time . Conclusion : For common pediatric outpatient conditions , a point-of-care evidence -based prescription writer and decision support system was associated with significant improvements in prescribing practice OBJECTIVE To test effects of a web-based decision support tool , the diabetes Disease Management Application ( DMA ) , developed to improve evidence -based management of type 2 diabetes . RESEARCH DESIGN AND METHODS We conducted a group r and omized controlled trial of 12 intervention and 14 control staff providers and 307 intervention and 291 control patients with type 2 diabetes in a hospital-based internal medicine clinic . Providers were r and omly assigned from May 1998 through April 1999 to have access to the DMA ( intervention ) or not to have access ( control ) . The DMA displays interactive patient-specific clinical data , treatment advice , and links to other web-based care re sources . We compared patients in the intervention and control groups for changes in processes and outcomes of care from the year preceding the study through the year of the study by intention-to-treat analysis . RESULTS The DMA was used for 42 % of scheduled patient visits . The number of HbA(1c ) tests obtained per year increased significantly in the intervention group ( + 0.3 tests/year ) compared with the control group ( -0.04 tests/year , P = 0.008 ) , as did the number of LDL cholesterol tests ( intervention , + 0.2 tests/year ; control , + 0.01 tests/year ; P = 0.02 ) and the proportions of patients undergoing at least one foot examination per year ( intervention , + 9.8 % ; control , -0.7 % ; P = 0.003 ) . Levels of HbA(1c ) decreased by 0.2 in the intervention group and increased by 0.1 in the control group ( P = 0.09 ) ; proportions of patients with LDL cholesterol levels < 130 mg/dl increased by 20.3 % in the intervention group and 10.5 % in the control group ( P = 0.5 ) . CONCLUSIONS Web-based patient-specific decision support has the potential to improve evidence -based parameters of diabetes care CONTEXT Prescribing practice s for otitis media are not consistent with current evidence -based recommendations . OBJECTIVE To determine whether point-of-care evidence delivery regarding the use and duration of antibiotics for otitis media decreases the duration of therapy from 10 days and decreases the frequency of prescriptions written . DESIGN R and omized , controlled trial . SETTING Primary care pediatric clinic affiliated with university training program . Intervention . A point-of-care evidence -based message system presenting real time evidence to providers based on their prescribing practice for otitis media . MAIN OUTCOME MEASURES Proportion of prescriptions for otitis media that were for < 10 days and frequency with which antibiotics were prescribed . RESULTS Intervention providers had a 34 % greater reduction in the proportion of time they prescribed antibiotics for < 10 days . Intervention providers were less likely to prescribe antibiotics than were control providers . CONCLUSIONS A point-of-care information system integrated into outpatient pediatric care can significantly influence provider behavior for a common condition BACKGROUND GPs are increasingly expected to meet the needs of patients concerned about their risk of inherited breast cancer , but may lack skills or confidence to use complex management guidelines . We developed an evidence -based , multifaceted intervention intended to promote confidence and skills in this area . OBJECTIVE To evaluate the effectiveness of the intervention in improving GP confidence in managing patients concerned about genetic risk of breast cancer . METHODS DESIGN Cluster r and omized controlled trial . SETTING General practice s in the Grampian region of Scotl and . SUBJECTS GPs and the patients they referred for genetic counselling for risk of breast cancer . MAIN OUTCOME MEASURES GPs ' self-reported confidence in four activities related to genetics ; rates of referral of patients at elevated genetic risk ; and referred patients ' underst and ing of cancer risk factors . RESULTS No statistically significant differences were observed between intervention and control arms in the primary or secondary outcomes . A possible effect of the intervention on the proportion of referred patients who were at elevated risk could not be discounted . Only a small proportion of intervention GPs attended the educational session , were aware or the software , or made use of it in practice . CONCLUSIONS No convincing evidence of the effectiveness of the intervention was found , probably reflecting barriers to its use in routine practice OBJECTIVE We developed AsthmaCritic , a non-inquisitive critiquing system integrated with the general practitioners ' electronic medical records . The system is based on the guidelines for asthma and chronic obstructive pulmonary disease ( COPD ) as issued by the Dutch College of General Practitioners . This paper assesses the effect of AsthmaCritic on monitoring and treatment of asthma and COPD by Dutch general practitioners in daily practice . METHODS A r and omized clinical trial in 32 practice s ( 40 Dutch general practitioners ) using electronic patient records . An intervention group was given the use of AsthmaCritic , a control group continued working in the usual manner . Both groups had the disposal of the asthma and COPD guidelines routinely distributed by the Dutch College of General Practitioners . We measured the average number of contacts , FEV 1 ( forced expiratory volume ) , and peak-flow measurements per asthma/ COPD patient per practice ; and , the average number of antihistamine , cromoglycate , deptropine , and oral bronchodilator prescriptions per asthma/ COPD patient per practice . RESULTS The number of contacts increased in the age group of 12 - 39 years . The number of FEV1 , peak-flow measurements , and the ratio of coded measurements increased , whereas the number of cromoglycate prescriptions decreased in the age group of 12 - 39 years . CONCLUSIONS Our study shows that the guideline -based critiquing system AsthmaCritic changed the manner in which the physicians monitored their patients and , to a lesser extent , their treatment behavior . In addition , the physicians changed their data -recording habits OBJECTIVES To evaluate the implementation of clinical guidelines for diabetes mellitus in general practice with a specific computer-based clinical decision support system ( CDSS ) as part of the intervention . METHODS R and omized study with health center as unit . General practice in Sør- and Nord-Trøndelag counties in Norway , 380,000 inhabitants . Seventeen health centers with 24 doctors and 499 patients with diabetes mellitus were in the intervention group and 12 health centers with 29 doctors and 535 patients were in the control group . Main outcome measures were group differences in fractions of patients without registration s ( process evaluation ) and mean group differences for the same variables ( patient outcome evaluation ) . RESULTS Statistically significant group differences were experienced for fractions of patients without registration of cigarette smoking ( intervention group , 82.6 % ; control group 94.5 % ) , body mass index ( 78.2 % vs. 93.0 % ) , and sufficient registration s for calculation of risk score for myocardial infa rct ion ( 91.1 % vs. 98.3 % ) ; all during 18 months . Large center variations were shown for all variables . The only statistically significant group difference was -2.3 mm Hg ( 95 % CI , -3.8 , -0.8 ) in diastolic blood pressure in favor of the intervention group . Statistically insignificant differences in favor of the intervention group were HbA1c , -0.1 % ( 95 % CI , -0.4 , 0.1 ) , systolic blood pressure , -1.2 mm Hg ( 95 % CI , -4.4 , 2.0 ) . Statistically insignificant differences in favor of the control group were fractions of smokers , + 3.0 % ( 95 % CI , -4.0 , 10.0 ) , body mass index , + 0.3 kg/m2 ( 95 % CI , -0.8 , 1.4 ) , risk score in female + 0.1 ( 95 % CI , -5.1 , 5.2 ) , and risk score in male + 2.6 ( 95 % CI , -14.2 , 19.5 ) . CONCLUSIONS Implementation of clinical guidelines for diabetes mellitus in general practice , by means of a CDSS and several procedures for implementation , did not result in a clinical ly significant change in doctors ' behavior or in patient outcome OBJECTIVE It is difficult to control drug-prescribing behaviour in general practice , despite the development and distribution of guidelines . The purpose of this study was to assess the effect on drug-prescribing behaviour of implementing prescribing guidelines by means of a reactive computer reminder system ( CRS ) . DESIGN Cluster-r and omised controlled trial with an incomplete block design in the south of the Netherl and s : 25 GPs ( 7 GP practice s ) received reminders about antibiotics and asthma/ COPD prescriptions , 28 GPs ( 7 GP practice s ) received reminders about cholesterol prescriptions . Prescription guidelines were integrated into the computerised GP information system . MEASUREMENTS Both performance indicators and prescription volumes were calculated as the main outcome measures . Next to individual volume measure , sum scores were constructed on the volume measures per drug group ( antibiotics , asthma/ COPD and cholesterol ) . RESULTS Variation between GPs turned out to be larger and more skewed than expected . No differences between groups were found for indicators and volumes related to recommendations advocating certain drugs . Although there was a tendency towards clinical ly relevant results for prescription volumes that were supposed to drop , the difference in sum score between the groups was not significant . For antibiotic prescriptions that were supposed to drop , the sum score for the intervention group was 28.2 ( 95 % CI : 20.8 - 44.5 ) prescriptions per 1000 patients per GP , while this was 39.7 ( 95 % CI : 29.7 - 64.1 ) for the control group ( p 0.2 ) . For prescriptions asthma/ COPD that were supposed to drop , the sum score for the intervention group was 1.1 ( 95 % CI : 0.6 - 2.6 ) prescriptions per 1000 patients per GP , while this was 2.2 ( 95 % CI : 1.4 - 4.3 ) for the control group ( p 0.1 ) . On three specific recommendations ( on quinolones for cystitis , corticosteroids for CPOD , and antibiotics for acute sore throat ) significant differences were found . CONCLUSIONS This study turned out to be underpowered due to high inter doctor variation in prescribing behaviour . Nevertheless , computerised reminders sometimes have a favourable effect on restricting certain drugs that are not or no longer indicated in general practice OBJECTIVE : To examine whether feedback and treatment advice for depression presented to primary care physicians ( PCPs ) via an electronic medical record ( EMR ) system can potentially improve clinical outcomes and care processes for patients with major depression . DESIGN : R and omized controlled trial . SETTING : Academically affiliated primary care practice in Pittsburgh , PA . PATIENTS : Two hundred primary care patients with major depression on the Primary Care Evaluation of Mental Disorders ( PRIME-MD ) and who met all protocol - eligibility criteria .INTERVENTION : PCPs were r and omly assigned to 1 of 3 levels of exposure to EMR feedback of guideline -based treatment advice for depression : “ active care ” ( AC ) , “ passive care ” ( PC ) , or “ usual care ” ( UC ) . MEASUREMENTS AND MAIN RESULTS : Patients ’ 3- and 6-month Hamilton Rating Scale for Depression ( HRS-D ) score and chart review of PCP reports of depression care in the 6 months following the depression diagnosis . Only 22 % of patients recovered from their depressive episode at 6 months ( HRS-D ≤7 ) . Patients ’ mean HRS-D score decreased regardless of their PCPs ’ guideline -exposure condition ( 20.4 to 14.2 from baseline to 6-month follow-up ; P<.001 ) . However , neither continuous ( HRS-D ≤7 : 22 % AC , 23 % PC , 22 % UC ; P=.8 ) nor categorical measures of recovery ( P=.2 ) differed by EMR exposure condition upon follow-up . Care processes for depression were also similar by PCP assignment despite exposure to repeated reminders of the depression diagnosis and treatment advice ( e.g. , depression mentioned in ≥3 contacts with usual PCP at 6 months : 31 % AC , 31 % PC , 18 % UC ; P=.09 and antidepressant medication suggested/prescribed or baseline regimen modified at 6 months : 59 % AC , 57 % PC , 52 % UC ; P=.3 ) . CONCLUSIONS : Screening for major depression , electronically informing PCPs of the diagnosis , and then exposing them to evidence -based treatment recommendations for depression via EMR has little differential impact on patients ’ 3- or 6-month clinical outcomes or on process measures consistent with high- quality depression care CONTEXT While clinical guidelines are considered an important mechanism to improve the quality of medical care , problems with implementation may limit their effectiveness . Few empirical data exist about the effect of computer-based systems for application of clinical guidelines on quality of care . OBJECTIVE To determine whether real-time presentation of clinical guidelines using an electronic medical record can increase compliance with guidelines . DESIGN Prospect i ve off-on-off , interrupted time series with intent-to-treat analysis . SETTING University hospital emergency department . SUBJECTS Patients were 280 health care workers ( 50 in the baseline control phase , 156 in the intervention phase , and 74 in the postintervention control phase ) who presented for initial treatment of occupational body fluid exposures , including 89 % ( 248/280 ) who sustained punctures and 81 % ( 208/257 ) who were exposed to blood . Physicians included resident physicians and attending physicians working in the emergency department during the study . INTERVENTIONS Implementation of a computer charting system that provides real-time information regarding history and recommendations for laboratory testing , treatment , and disposition based on rules derived from clinical guidelines . MAIN OUTCOME MEASURES Quality of care as determined by essential items documented in the medical record and in aftercare instructions , compliance with testing and treatment guidelines , and total charges and percentage of charges attributable to guideline -endorsed activities . RESULTS Mean percent documentation of 7 essential items regarding patient history in the medical record increased from 57 % during the baseline period to 98 % in the intervention phase ( 42 % increase ; 95 % confidence interval [ CI ] , 34%-49 % ) and 11 items in aftercare instruction increased from 31 % at baseline to 93 % during the intervention phase ( 62 % increase ; 95 % CI , 51%-74 % ) , but both decreased to baseline when the computer system was removed . Percent compliance with 4 laboratory testing guidelines increased from 63 % at baseline to 83 % during the intervention phase ( 20 % increase ; 95 % CI , 9%-31 % ) but decreased to 52 % when the computer system was removed . Compliance with 5 treatment guidelines increased from 83 % at baseline to 96 % during the intervention phase ( 13 % increase ; 95 % CI , 9%-17 % ) and decreased to 84 % following the intervention . Percentage of charges incurred for indicated laboratory tests and treatment increased from 44 % at baseline to 81 % during the intervention phase ( 37 % increase ; 95 % CI , 22%-52 % ) and decreased to 36 % following the intervention . Average total per-patient charges were $ 460 , $ 384 , and $ 373 in each phase , respectively . CONCLUSIONS Use of a computer-based system for clinical guidelines for management of patients with occupational exposure to body fluids improved documentation , compliance with guidelines , and percentage of charges spent on indicated activities , while decreasing overall charges . The parameters returned to baseline when the computer system was removed OBJECTIVE To compare the effects of computerized and paper-based versions of guidelines on recently qualified physicians ' consultation practice s. METHODS Two arm cluster r and omized controlled trial . Physicians were r and omized to receive computerized or textbook-based versions of the same guidelines for a 4-week study period . Physicians ' compliance with guideline recommendations about laboratory , radiological , physical and other examinations , procedures , nonpharmacologic and pharmacologic treatments , physiotherapy , and referrals were measured by case note review . RESULTS There were 139 recently qualified physicians working in 96 primary healthcare centers in Finl and who participated in the study . Data on 4,633 patient encounters were abstract ed , of which 3,484 were suitable for further analysis . Physicians ' compliance with guidelines was high ( over 80 % for use of laboratory , radiology , physical examinations , and referrals ) . There were no significant differences in physicians ' consultation practice s in any of the measured outcomes between the computerized and textbook group . CONCLUSION Guidelines are a useful source of information for recently qualified physicians working in primary care . However , the method of presentation of the guidelines ( electronic or paper ) does not have an effect on guideline use or their impact on decisions . Other factors should be considered when choosing the method of presentation of guidelines , such as information-seeking time , ease of use during the consultation , ability to up date , production costs , and the physician 's own preferences 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 BACKGROUND We conducted a cluster r and omized controlled trial to examine the effectiveness of computerized decision support ( CDS ) design ed to improve hypertension care and outcomes in a racially diverse sample of primary care patients . METHODS We r and omized 2,027 adult patients receiving hypertension care in 14 primary care practice s to either 18 months of their physicians receiving CDS for each hypertensive patient or to usual care without computerized support for the control group . We assessed prescribing of guideline -recommended drug therapy and levels of blood pressure control for patients in each group and examined if the effects of the intervention differed by patients ’ race/ethnicity using interaction terms . MEASUREMENTS AND MAIN RESULTS Rates of blood pressure control were 42 % at baseline and 46 % at the outcome visit with no significant differences between groups . After adjustment for patients ’ demographic and clinical characteristics , number of prior visits , and levels of baseline blood pressure control , there were no differences between intervention groups in the odds of outcome blood pressure control . The use of CDS to providers significantly improved Joint National Committee ( JNC ) guideline adherent medication prescribing compared to usual care ( 7 % versus 5 % , P < 0.001 ) ; the effects of the intervention remained after multivariable adjustment ( odds ratio [ OR ] 1.39 [ CI , 1.13–1.72 ] ) and the effects of the intervention did not differ by patients ’ race and ethnicity . CONCLUSIONS CDS improved appropriate medication prescribing with no improvement in disparities in care and overall blood pressure control . Future work focusing on improvement of these interventions and the study of other practical interventions to reduce disparities in hypertension-related outcomes is needed PRIMARY OBJECTIVE To investigate whether computer decision support software used in the management of patients with asthma improves clinical outcomes . RESEARCH DESIGN R and omized controlled trial with practice s each reporting on 30 patients with asthma over a 6 month period . METHODS AND PROCEDURES 447 patients were r and omly selected from practice asthma registers managed by 17 general practice s from throughout the UK . Intervention practice s used the software during consultations with these patients throughout the study while control practice s did not . MAIN OUTCOMES AND RESULTS Practice consultations , acute exacerbations of asthma , hospital contacts , symptoms on assessment and medication use . A smaller proportion of patients within the intervention group initiated practice consultations for their asthma : 34 ( 22 % ) vs 111 ( 34 % ) , odds ratio ( OR ) = 0.59 , 95 % confidence interval ( CI ) ( 0.37 - 0.95 ) ; and suffered acute asthma exacerbations : 12 ( 8 % ) vs 57 ( 17 % ) , OR = 0.43 , 95 % CI = 0.21 - 0.85 six months after the introduction of the computer decision support software . There were no discernable differences in reported symptoms , maintenance prescribing or use of hospital services between the two groups . CONCLUSION The use of computer decision support software that implements guidelines during patient consultations may improve clinical outcomes for patients with asthma OBJECTIVE Translation of evidence -based guidelines into clinical practice has been inconsistent . We performed a r and omized , controlled trial of guideline -based care suggestions delivered to physicians when writing orders on computer workstations . STUDY SETTING Inner-city academic general internal medicine practice . STUDY DESIGN R and omized , controlled trial of 246 physicians ( 25 percent faculty general internists , 75 percent internal medicine residents ) and 20 outpatient pharmacists . We enrolled 706 of their primary care patients with asthma or chronic obstructive pulmonary disease . Care suggestions concerning drugs and monitoring were delivered to a r and om half of the physicians and pharmacists when writing orders or filling prescriptions using computer workstations . A 2 x 2 factorial r and omization of practice sessions and pharmacists result ed in four groups of patients : physician intervention , pharmacist intervention , both interventions , and controls . DATA EXTRACTION / COLLECTION METHODS : Adherence to the guidelines and clinical activity was assessed using patients ' electronic medical records . Health-related quality of life , medication adherence , and satisfaction with care were assessed using telephone question naires . PRINCIPAL FINDINGS During their year in the study , patients made an average of five scheduled primary care visits . There were no differences between groups in adherence to the care suggestions , generic or condition-specific quality of life , satisfaction with physicians or pharmacists , medication compliance , emergency department visits , or hospitalizations . Physicians receiving the intervention had significantly higher total health care costs . Physician attitudes toward guidelines were mixed . CONCLUSIONS Care suggestions shown to physicians and pharmacists on computer workstations had no effect on the delivery or outcomes of care for patients with reactive airways disease STUDY OBJECTIVE To assess the effects of evidence -based treatment suggestions for hypertension made to physicians and pharmacists using a comprehensive electronic medical record system . DESIGN R and omized controlled trial with a 2 x 2 factorial design of physician and pharmacist interventions , which result ed in four groups of patients : physician intervention only , pharmacist intervention only , intervention by physician and pharmacist , and intervention by neither physician nor pharmacist ( control ) . SETTING Academic primary care internal medicine practice . SUBJECTS Seven hundred twelve patients with uncomplicated hypertension . MEASUREMENTS AND MAIN RESULTS Suggestions were displayed to physicians on computer workstations used to write outpatient orders and to pharmacists when filling prescriptions . The primary end point was generic health-related quality of life . Secondary end points were symptom profile and side effects from antihypertensive drugs , number of emergency department visits and hospitalizations , blood pressure measurements , patient satisfaction with physicians and pharmacists , drug therapy compliance , and health care charges . In the control group , implementation of care changes in accordance with treatment suggestions was observed in 26 % of patients . In the intervention groups , compliance with suggestions was poor , with treatment suggestions implemented in 25 % of patients for whom suggestions were displayed only to pharmacists , 29 % of those for whom suggestions were displayed only to physicians , and 35 % of the group for whom both physicians and pharmacists received suggestions ( p=0.13 ) . Intergroup differences were neither statistically significant nor clinical ly relevant for generic health-related quality of life , symptom and side-effect profiles , number of emergency department visits and hospitalizations , blood pressure measurements , charges , or drug therapy compliance . CONCLUSION Computer-based intervention using a sophisticated electronic physician order-entry system failed to improve compliance with treatment suggestions or outcomes of patients with uncomplicated hypertension |
10,756 | 20,697,521 | Topical corticosteroid agents were found to significantly reduce the severity of skin reactions ; however , the trials of corticosteroids evaluated various agents , and no clear indication about a preferred corticosteroid has emerged .
Biafine cream ( Ortho-McNeil Pharmaceuticals , Titusville , NJ , U.S.A. ) was found not to be superior to st and ard regimes in the prevention of radiation-induced skin reactions ( n = 6).In conclusion , the evidence is insufficient to support the use of a particular agent for the prevention and management of acute radiation-induced skin reactions . | Radiation therapy is a common treatment for cancer patients .
One of the most common side effects of radiation is acute skin reaction ( radiation dermatitis ) that ranges from a mild rash to severe ulceration .
Approximately 85 % of patients treated with radiation therapy will experience a moderate-to-severe skin reaction .
Acute radiation-induced skin reactions often lead to itching and pain , delays in treatment , and diminished aesthetic appearance- and subsequently to a decrease in quality of life .
Surveys have demonstrated that a wide variety of topical , oral , and intravenous agents are used to prevent or to treat radiation-induced skin reactions . | The aim of this study was to determine the effectiveness of granulocyte-macrophage colony-stimulating factor ( GM-CSF ) impregnated gauze in preventing or healing radiation-induced dermatitis . Sixty-one patients were irradiated for vulvar carcinoma . Thirty-seven applied steroid cream at irradiated areas throughout radiotherapy ( Group A ) and 24 patients applied additionally GM-CSF impregnated gauze ( 40 micrcog/cm2 of skin-irradiated area , twice per day ) in addition to the steroid cream , after 20 Gy of irradiation ( Group B ) . The score of skin reactions ( P=0.008 , chi2 test ) and the time interval of radiotherapy interruption ( P=0.037 , Mann-Whitney U test ) were statistically significantly reduced in Group B patients . Multivariate analysis of variance showed for this group not only a significant reduction in the Sum of Gross Dermatitis Scoring ( P<0.001 , adjusted for Duration of Dermatitis ) but also a significant reduction of the healing time ( P=0.02 , adjusted for Sum of Gross Dermatitis Scoring ) . The pain grading was less ( P=0.014 , chi2 test ) and pain reduction was noticed sooner after the application of GM-CSF impregnated gauze ( P=0.0017 , Mann-Whitney U test ) . Multivariate logistic regression analysis showed that the only significant effect on dermatitis score is due to Body Mass Index ( P=0.034 ) and the application of GM-CSF ( P=0.008 ) . GM-CSF impregnated gauze can be effective in preventing and healing radiation-induced dermatitis and in reducing the interruption intervals of radiotherapy for vulvar carcinomas PURPOSE The effectiveness of nonsteroid topical agents for the prevention of acute dermatitis during adjuvant radiotherapy for breast carcinoma has not been demonstrated . The goal of this study was to compare the effectiveness of calendula ( Pommade au Calendula par Digestion ; Boiron Ltd , Levallois-Perret , France ) with that of trolamine ( Biafine ; Genmedix Ltd , France ) , which is considered in many institutions to be the reference topical agent . PATIENTS AND METHODS Between July 1999 and June 2001 , 254 patients who had been operated on for breast cancer and who were to receive postoperative radiation therapy were r and omly allocated to application of either trolamine ( 128 patients ) or calendula ( 126 patients ) on the irradiated fields after each session . The primary end point was the occurrence of acute dermatitis of grade 2 or higher . Prognostic factors , including treatment modalities and patient characteristics , were also investigated . Secondary end points were the occurrence of pain , the quantity of topical agent used , and patient satisfaction . RESULTS The occurrence of acute dermatitis of grade 2 or higher was significantly lower ( 41 % v 63 % ; P < .001 ) with the use of calendula than with trolamine . Moreover , patients receiving calendula had less frequent interruption of radiotherapy and significantly reduced radiation-induced pain . Calendula was considered to be more difficult to apply , but self-assessed satisfaction was greater . Body mass index and adjuvant chemotherapy before radiotherapy after lumpectomy were significant prognostic factors for acute dermatitis . CONCLUSION Calendula is highly effective for the prevention of acute dermatitis of grade 2 or higher and should be proposed for patients undergoing postoperative irradiation for breast cancer Trial objectives were to assess effectiveness and tolerance of sterilized Avène thermal spring water anti burning gel ( ATSW gel ) in prevention of radiation dermatitis in adults irradiated ( 6 weeks ) for breast ( n=61 ) or head and neck ( n=8 ) cancer . Patients included in this open labelled , 2 parallel groups , multicentric study , were r and omly assigned to apply five times daily for ten weeks either the Avène spring water gel ( n=35 ) or trolamine cream ( n=34 ) . The median of emergence of the first objective radiation dermatitis signs was 31 days in the ATSW gel group and 29 days in the control group ( p=0,924 ) . The median incidence for pruritus in patients of the ETA gel group was 46 days versus 27 days ( p=0,028 ) and 44 days versus 24 days for pain ( p=0,426 ) . Global efficacy was < < very good > > in 46,7 % of patients of the ETA gel group versus 17,2 % ( p=0,029 ) and tolerance was < < very good > > in 65,5 % of the ETA gel group versus 40,7 % ( p=0,107 ) . No radionecrosis was observed . In conclusion , the efficacy of the Avène spring water gel was similar to the control product in prophylaxis of radiation dermatitis . Tolerance was better and the pruritus was significantly more delayed in patients who applied the Avène spring water gel than in controls ABSTRACT This study was design ed to assess the efficacy and tolerability of MAS065D ( Xclair ™ ) compared to a vehicle control in the management of radiation dermatitis in patients receiving radiotherapy for breast cancer . Twenty patients were r and omized blindly to use the two study substances , three times daily , on separate sections of irradiated skin throughout the duration of radiotherapy and for two weeks afterwards . Patients were monitored before therapy , weekly during therapy , and for 2 weeks after radiotherapy was completed . Skin appearance according to National Cancer Institute ( NCI ) toxicity criteria , erythema rating , transepidermal water loss ( TEWL ) , skin hydration , patients ' view of itch , pain , acceptance , and view of each cream and adverse events , were monitored ; at the final visit patients and investigators expressed their preference for one of the creams . MAS065D showed statistically significant superiority in the outcomes of NCI grading for radiation dermatitis and erythema . Patients ' and investigators ' preferences for one of the study substances were statistically in favor of MAS065D . Very few patients recorded nonzero itch and pain scales , so no significant differences emerged between the two groups . It was concluded that MAS065D can provide an effective option for managing radiation dermatitis although further studies are needed to assess its effect on pain and itch Purpose : The use of additional therapy with an oral enzyme preparation containing trypsin , chymotrypsin and papain has been suggested for the reduction of toxicity due to radiation therapy . This study was conducted to test the efficacy and tolerability of this enzyme combination in preventing or reducing the acute side effects of radiation therapy in patients with locally advanced cervical cancer . Methods : A prospect i ve , r and omised , open , clinical trial was carried out on 120 patients ( aged 24–85 years ) with locally advanced , biopsy-proven carcinomas of the uterine cervix ( stages IIa , IIb or IIIb ) . Patients received 50 Gy of external radiation therapy over a period of 5 weeks , followed by intra-cavitary brachytherapy ( 20–30 Gy ) . Patients assigned to the test group ( 60 patients ) received additional treatment with enzymes . Patients were evaluated at weekly intervals for acute radiation therapy-related side effects , according to the RTOG/EORTC grading criteria , and then after the end of radiation therapy for another 8 weeks . Occurrence of adverse events , if any , was also recorded . Results : The study revealed that the maximum extent of acute radiation side effects was reduced in the enzyme group : skin reactions ( mean : 0.97 vs 1.68 in the control group , P < 0.001 ) , vaginal mucosal reactions ( 0.55 vs 0.85 , P=0.10 ) , genitourinary symptoms ( 0.93 vs 1.38 , P < 0.001 ) and gastrointestinal reactions ( 1.12 vs 1.30 , P=0.12 ) . The sum-scores during treatment , expressed as area under the curve , were significantly less in the enzyme treated patients . In the follow-up visits all observed side effects of radiation therapy were of lower intensity in the enzyme group than in the control group . Conclusions : In patients with locally advanced cancer of the uterine cervix , oral enzyme therapy was found to be effective in significantly reducing radiation therapy-related side effects such as genitourinary symptoms , subcutaneous changes and reactions of the vaginal mucosa PURPOSE Silver-leaf nylon dressing ( SLND ) has been shown to have effective antimicrobial activity and to enhance healing in burns and skin grafts . The purpose of this study was to evaluate the value of SLND in preventing radiation dermatitis in patients undergoing radiotherapy to target volumes that included the perineum and concurrent chemotherapy . METHODS AND MATERIAL S Fifteen consecutive patients with either anal canal or gynecologic cancer were offered the SLND as a preventive intervention . The evaluation was based on st and ardized photographs taken at the end of treatment . A historical control group of 15 patients with the same neoplasms who received st and ard skin care was assessed in the same fashion . Ten observers unaware of the treatment intervention were enrolled in the evaluation of the skin changes . The Mann-Whitney U test was used to assess the statistical significance of the differences in the dermatitis scores between the two patient groups . RESULTS The mean dermatitis score for controls was 2.62 ( st and ard deviation , 0.48 ) . The mean score for the SLND group was significantly lower at 1.16 ( st and ard deviation , 0.40 ; p < 0.0001 ) . CONCLUSION The results of this study suggest that SLND is effective in reducing radiation dermatitis , apparently because of its antibacterial properties The aim of the study was to compare the effect of a gentian violet topical application with that of a moist dressing ( hydrocolloid ) on the rate and efficacy of radiotherapy-induced moist desquamation wound healing and the patients ' satisfaction level with each method . This prospect i ve r and omized clinical trial used a stratified sampling design . A sample of 39 patients with 60 wounds had their wounds assessed on alternate days in terms of several wound-healing parameters including wound size , wound pain , incidence of infection , and time required for healing . Patient satisfaction with each treatment was evaluated at the completion of the study . Gentian violet significantly decreased wound size and reduced wound pain . However , this treatment received significantly lower ratings for dressing comfort and dressing aesthetic acceptance . Nevertheless , the time required for healing was not statistically different in the two groups . These findings suggest that the lower score of dressing satisfaction level in the gentian violet group may result from the skin discoloration and drying effects of the treatment , which renders patients unable to move or stretch their skin . Although the aim is to have complete wound healing , this may not be realistic for many lesions such as radiotherapy-induced moist desquamation wounds . The best evidence on which to make decisions about individual care can now be based on patients ' own perception of quality BACKGROUND AND AIMS Radiation induced wet desquamation of skin in carcinoma breast patients is a painful condition . In this study topical beclomethasone dipropionate spray was used as prophylaxis with the purpose of reducing risk of the wet desquamation of skin in irradiated field . MATERIAL S AND METHODS Sixty patients of carcinoma breast were planned for postoperative loco regional radiotherapy ( 50 Gy in 25 fraction over five weeks ) were prospect ively r and omized into two groups ( 1 ) steroid group- patients were advised to use beclomethasone dipropionate spray in irradiated axilla from day one of radiotherapy , ( 2 ) control group- patients were not allowed to use any topical agent in irradiated area . Radiation induced skin reaction was noted in terms of erythema , dry desquamation and wet desquamation weekly till end of prescribed 50 Gy dose of the radiation therapy . STATISTICAL METHOD Chi-square test was used to see the statistical significance of the difference in wet desquamation between two arms of the study . Chi-square value and P-value was calculated for the difference of wet desquamation in two study arms . RESULT In steroid group 4/30 ( 13.33 % ) patients developed wet desquamation of the axillary skin at the end of the radiotherapy . For the control group , this figure was 11/30 ( 36.66 % ) . The difference in wet desquamation of the axillary skin in the two groups was statistically significant ( P-value = 0.0369 ) . CONCLUSION Topical steroid ( beclomethasone dipropionate spray ) for skin during radiotherapy significantly reduces the risk of wet desquamation of the skin To study the impact of amifostine as a cytoprotective agent against acute radiation dermatitis , we review ed 220 patient records . One hundred cancer patients , with tumors localised in the pelvis ( bladder , rectum , prostatic carcinomas , or gynecological cancer ) , who received radiotherapy and cytoprotective treatment with intravenous infusion of amifostine ( group A ) were included in this study . Retrospectively , we r and omly selected from a data base in our hospital 120 historical controls , who received only radiotherapy without cytoprotection ( group B ) . Mean gross dermatitis score ( MGDS ) was the mean value of recorded acute radiation dermatitis according to common toxicity criteria . In group A versus B patients , a significantly reduced severity of dermatitis ( P < 0.001 , Fisher 's exact test ) and significant reduction of MGDS as well as mean interruption treatment time ( P < 0.001 , Mann-Whitney U test ) was observed . The relative risk of the outcome of the two study groups was 0.23 ( 95 % CI : 0.15 to 0.34 ) . The significant dermato-cytoprotective effect of amifostine noticed in our retrospective analysis warrants further investigation with r and omised trials OBJECTIVE : The purpose of this study was to assess the prophylactic effect of pentoxifylline ( Ptx ) on complications related to radiation . STUDY DESIGN AND SETTING : Seventy-eight patients who had postoperative radiotherapy for squamous cell carcinoma of the head and neck were enrolled into a prospect i ve study . Patients were r and omly assigned to the Ptx group ( 40 patients ) and the control group ( 38 patients ) . Ptx was given to the patients at a dose of 400 mg 3 times a day orally to a total of 1200 mg . We noted radiotherapy complications in each group . RESULTS : Four patients were not able to tolerate this drug due to the development of gastrointestinal symptoms and dizziness . Late skin changes , fibrosis , and soft tissue necrosis were more severely in the control group than in the Ptx group ( P < 0.05 ) . We could find no positive effects on acute skin reactions and pain ( P > 0.05 ) . CONCLUSION : Our study suggests that Ptx has a prophylactic effect on the radiation complications . This can be explained by protective effect of Ptx against vascular pathology . ( Otolaryngol Head Neck Surg 2004;130:351–6 . Background and Purpose : In radiotherapy of the breast following breast-conserving surgery , the adverse reaction predominantly found is confined to the skin . After phase II studies , Thêta-Cream ® , containing CM Glucan , Hydroxyprolisilan C und Matrixyl as active substances , was said to have prophylactic properties of preventing acute radiation side effects in skin tissue . In a prospect i ve r and omized study , Thêta-cream ® was compared with st and ard skin care using Bepanthol ® lotion . Patients and Methods : 20 breast cancer patients were r and omly assigned to use Thêta-Cream ® or Bepanthol ® lotion during radiotherapy . At 0 , 30 , and 50 Gy , acute skin toxicity was scored with a modified RTOG scoring system . The patients ’ content with the skin care and the technical assistants ’ content with the skin marks were recorded . Results : For single aspects of toxicity and their sums in defined skin areas , no differences in median and range between study groups were found . The maximal toxicity anywhere in the breast averaged in a moderate erythema , mild elevation of skin temperature , no desquamation in both groups . Mild itchiness and sporadic efflorescences were more frequently seen with Thêta-Cream ® . According to a ranking of anonymized breast photos at 50 Gy by independent investigators , side effects were equal . Patients ’ content was high with both skin care regimens ( 1.25 on a scale from 0 to 10 ) . With Thêta-Cream ® a trend toward worse skin marks was noted . Adverse events exclusively occurred in Thêta-Cream ® users : suspected allergic reaction once , and the necessity for resimulation twice . Conclusion : In direct comparison with dexpanthenol-containing lotion , no advantage for Thêta-Cream ® was found . Higher costs and problems with skin marks prevent a general recommendation .Hintergrund und Ziel : Bei insgesamt guter Verträglichkeit der postoperativen Strahlentherapie an der Brust stehen Hautreaktionen i m Vordergrund der akuten Nebenwirkungen . Als Neuentwicklung mit prophylaktischer Wirkung wurde nach Phase-II-Studien Thêta-Creme ® angekündigt , die CM Glucan , Hydroxyprolisilan C und Matrixyl als aktive Substanzen enthält . Diese prospektive , r and omisierte Studie soll prüfen , ob Thêta-Creme ® einer St and ardpflege mit Bepanthol ® -Lotion überlegen ist . Patienten und Method ik:20 konsekutive Patientinnen mit Mammakarzinom ( Patientencharakteristika s. Tabelle 2 ) wurden postoperativ nach dem Zufallsprinzip einer Anwendung von Thêta-Creme ® oder Bepanthol ® -Lotion während der Strahlentherapie zugeordnet . Akuttoxizität an der Brusthaut wurde nach einer modifizierten RTOG-Systematik ( s. Tabelle 1 ) bei 0 , 30 und 50 Gy beurteilt . Die Meinung der Patientinnen zur Hautpflege und der MTRAs zur Güte der Hautmarkierungen wurde erfasst . Ergebnisse : An definierten Lokalisationen der Brust ( s. Abbildung 1 ) waren die Punktwerte für einzelne Aspekte ( Erythem , Überwärmung , Epitheliolyse , Juckreiz , Effloreszenzen ) sowie Summenwerte in Median und Spannweite in beiden Studienarmen gleich ( s. Abbildung 3 ) . Als maximale Ausprägung an beliebiger Lokalisation f and en sich bei 50 Gy in beiden Gruppen median eine mäßige Rötung , eine geringe Überwärmung , keine Epitheliolysen . Geringer Juckreiz und vereinzelte Effloreszenzen traten eher unter Thêta-Creme ® auf . Einschätzungen zur Rangfolge der Hauttoxizität anh and anonymisierter Brustphotos bei 50 Gy ergaben untersucherunabhängig keinen signifikanten Unterschied ( s. Abbildung 4 ) . Die Patientenzufriedenheit war in beiden Gruppen ausgesprochen hoch ( 1,25 auf einer visuellen Analogskala von 0 bis 10 ) . Der Erhalt der Hautmarkierungen wurde unter Thêta-Creme ® tendenziell ungünstiger beurteilt . Unerwünschte Ereignisse wurden ausschließlich unter Thêta-Creme ® beobachtet : einmal V.a . allergische Reaktion , zweimal Notwendigkeit der Resimulation . Schlussfolgerung : Im direkten Vergleich mit dexpanthenolhaltiger Lotion ist eine Überlegenheit von Thêta-Creme ® nicht erkennbar . Auch hohe Kosten und Probleme mit Hautmarkierungen sprechen gegen eine generelle Empfehlung PURPOSE This multicentered phase III trial was design ed to compare an emulsion containing trolamine against the usual supportive care within each participating institution for patients with head and neck cancer undergoing radiation therapy . PATIENTS AND METHODS Patients with biopsy-proven squamous cell carcinoma of the oral cavity , oropharynx , hypopharynx , or larynx were r and omly assigned to one of the following treatments : prophylactic trolamine emulsion , interventional trolamine emulsion , or declared institutional preference . The primary outcome was the reduction in grade 2 or higher skin toxicity , as per National Cancer Institute Common Toxicity Criteria version 2.0 . Secondary outcomes included patient-reported quality of life ( QOL ) . RESULTS From October 2000 to April 2002 , 547 patients from 51 institutions were entered onto the trial . The average age was 59 years . Patients were predominately male ( 79 % ) and most continued to use tobacco products ( 52 % ) . The rates of grade 2 or higher radiation dermatitis were 79 % , 77 % , and 79 % in the prophylactic , interventional , and institutional preference arms of the study , respectively . No significant differences in QOL were found . CONCLUSION The results of this trial demonstrate no advantage for the use of trolamine in reducing the incidence of grade 2 or higher radiation dermatitis or improving patient-reported QOL . The use of 15 different local st and ards of care highlights the need to continue research that will result in evidence -based recommendations to reduce the burden of radiation dermatitis PURPOSE To assess the efficacy of Biafine cream in preventing Grade 2 acute radiation dermatitis , according to the National Cancer Institute of Canada skin radiation toxicity criteria in patients undergoing concomitant adjuvant chemotherapy and radiotherapy to the breast . METHODS AND MATERIAL S Sixty patients participated in this study . Patients were treated with a lumpectomy followed by concomitant chemotherapy and radiotherapy to the breast . Biafine cream was applied daily , starting on the first day and ending 2 weeks post-radiotherapy . Patients underwent weekly skin assessment s throughout radiotherapy and at 2 and 4 weeks after treatment . Outcome measures were assessed using a Skin Assessment Question naire that was scored according to the National Cancer Institute of Canada skin radiation toxicity criteria and a self-administered question naire that evaluated skin symptoms . RESULTS The maximum skin toxicity observed during the course of treatment was as follows : less than Grade 2 toxicity , 15 % ( 9 patients ) ; Grade 2 , 83 % ( 50 patients ) ; Grade 3 , 2 % ( 1 patient ) ; Grade 4 , 0 % ( 0 patients ) . The majority of the radiation dermatitis was observed after 3 weeks of radiotherapy . CONCLUSION The majority of patients who underwent concomitant chemo- and radiotherapy for breast cancer developed Grade 2 radiation dermatitis with the use of Biafine cream . However , no treatment delays or interruptions were observed because of skin toxicity Summary Background Radiation dermatitis is a common side‐effect of radiation therapy , but there is no current consensus about its appropriate therapy . OBJECTIVE To observe the therapeutic effect of shenqi fanghou recipe ( SFR ) in preventing and treating radiation injury in patients with head and neck tumor . METHODS One hundred and forty patients with head and neck tumor , including nasopharyngeal carcinoma , carcinoma of tonsil or tongue , were r and omly divided into 2 groups , 70 patients in the observed group were given modified SFR as adjuvant to radiotherapy , while 70 patients in the control group were treated with radiotherapy alone . The radiation reactions during radiotherapy and the condition of late stage radiation injury radiotherapy in patients in the 2 groups were observed . RESULTS The degree of oropharyngeal mucosa reaction , dryness in mouth and radiation dermatitis in cervical region in the observed group was milder than those in the control group , and the radiation injury induced late stage sequelae , such as the degree of mouth-opening was better and the cervical muscular sclerosis was better in the observed group than in the control group , showing significant difference ( P < 0.01 ) . CONCLUSION SFR has definite effect in preventing and treating radiation reaction and late stage radiation injury in patients with head and neck tumor Na sucrose octasulfate ( Na SOS ) was tested for ability to relieve radiation-induced acute skin and mucosal reactions in patients with head and neck cancer . Sixty patients were included in this prospect i ve , double-blind , r and omized study . Skin and mucosal reactions were scored using several variables . No statistically significant difference was found between the results with Na SOS and those with placebo for any of the variables , with the exception of skin desquamation , which showed a significant difference in the placebo group . The most likely explanation for this is that the Na SOS gel itself left behind a flaky layer that was difficult to distinguish from radiation-induced flaking . In conclusion , we can not recommend Na SOS in the routine management of radiation-induced skin and mucosal reactions The aim of this study was to assess the effects of Belladonna 7cH and X-ray 15cH associated in the treatment of acute radiodermatitis . A r and omized double-blind placebo-controlled clinical trial involving 66 patients who had been operated on for breast cancer and were undergoing radiotherapy was conducted . The following parameters were assessed over ten weeks : breast skin colour , warmth , swelling and pigmentation . The efficacy of the treatment was assessed by the comparison of these parameters taken individually and by calculating an Index of Total Severity ( sum of the scores of the four parameters ) during radiotherapy , and during recovery , 15 and 30 d after the end of the radiotherapy . The differences of the scores of the Index of Total Severity during Radiotherapy were not statistically significant , but showed a trend towards a better activity of the homoeopathic medicine compared to placebo . Analysis of the data on Total Severity during recovery , showed a statistically significant benefit of the active medicines over placebo . The homeopathic medicines had particular effectiveness on the heat of the skin . The limited number of patients observed and the posology employed could have interfered with the significance of the results . Chemotherapy and hormonotherapy do not seem to affect the results BACKGROUND Mucositis and dermatitis are frequently encountered in patients treated with radiochemotherapy . Dead Sea products that contain minerals and other properties have proven effective in treating various skin diseases . OBJECTIVES To evaluate the effectiveness of Dead Sea products in reducing acute radiochemotherapy-induced side effects in patients with head and neck cancer . METHODS In this phase 2 study we compared the outcomes in 24 treated patients and 30 conventionally treated patients matched for age , tumor site , and type of treatment . The Dead Sea products comprised a mouthwash solution ( Lenom ) and a skin cream ( Solaris ) used three times daily for 1 week before , during , and up to 2 weeks after completion of radiotherapy . Mucositis and dermatitis were evaluated using common toxicity criteria . RESULTS Thirteen treated patients ( 54 % ) had grade 1 - 2 and none had 3 - 4 mucositis , while 17 controls ( 57 % ) had grade 1 - 2 and 4 ( 13 % ) had grade 3 - 4 mucositis . Thirteen treated patients ( 54 % ) had grade 1 - 2 dermatitis ; there was no instance of grade 3 - 4 dermatitis , while 11 patients in the control group ( 37 % ) had grade 1 - 2 and 5 ( 17 % ) had grade 3 - 4 dermatitis . More patients in the control arm needed a break than did patients in the treatment the control arm needed a break than did patients in the treatment arm ( P = 0.034 ) . CONCLUSIONS The two Dead Sea products tested decreased skin and mucosal toxicity in head and neck cancer patients receiving radiochemotherapy PURPOSE To determine if Biafine compared to Best Supportive Care ( BSC ) is effective in minimizing or preventing radiation-induced dermatitis in women undergoing breast irradiation . METHODS AND MATERIAL S Patients were r and omized between Biafine ( n = 83 ) vs. BSC ( n = 89 ) . The institutions identified preference for BSC at the time of r and omization . A no-treatment arm was allowed ( 16 % received no treatment ) . Patients were instructed to apply r and omized product three times a day , but not within 4 h of their daily RT session . Application began following their first radiation treatment and continued 2 weeks postradiation . Skin dermatitis was scored weekly utilizing the RTOG and ONS ( Oncology Nursing Society ) skin toxicity scales , a weekly patient satisfaction and quality -of-life question naire . RESULTS Using the RTOG toxicity scale there was no overall difference for maximum dermatitis during RT between Biafine and BSC ( p = 0.77 ) . There was no difference in maximum toxicity by arm or breast size . There was an interaction between breast size and toxicity , with large-breasted women exhibiting more toxicity . Large-breasted women receiving Biafine were more likely to have no toxicity 6 weeks post RT . CONCLUSION There was no overall difference between BSC and Biafine in the prevention , time to , or duration of radiation-induced dermatitis Background : Radiation treatment may induce acute skin reactions . There are several methods of managing them . Validity of these methods , however , is not sufficiently studied . We therefore investigated , whether moist skin care with 3 % urea lotion will reduce acute radiation skin toxicity . Patients and Methods : 88 patients with carcinomas of the head and neck undergoing radiotherapy with curative intent ( mean total dose 60 Gy , range : 50–74 Gy ) were evaluated weekly for acute skin reactions according to the RTOG-CTC score . In 63 patients , moist skin care with 3 % urea lotion was performed . The control group consisted of 25 patients receiving conventional dry skin care . The incidence of grade I , II , and III reactions and the radiation dose at occurrence of a particular reaction were determined and statistically analyzed using the log-rank test . The dose-time relations of individual skin reactions are described . Results : At some point of time during radiotherapy , all patients suffered from acute skin reactions grade I , > 90 % from grade II reactions . 50 % of patients receiving moist skin care experienced grade I reactions at 26 Gy as compared to 22 Gy in control patients ( p = 0.03 ) . Grade II reactions occurred at 51 Gy versus 34 Gy ( p = 0.006 ) . Further , 22 % of the patients treated with moist skin care suffered from acute skin toxicity grade III as compared to 56 % of the controls ( p = 0.0007 ) . Conclusion : Moist skin care with 3 % urea lotion delays the occurrence and reduces the grade of acute skin reactions in percutaneously irradiated patients with head and neck tumors . Hintergrund : Eine Strahlentherapie kann akute Hautreaktionen hervorrufen , die sich auf verschiedene Weise beh and eln lassen . Die einzelnen Beh and lungs method en wurden bislang jedoch nur unzureichend ausgewertet . Deshalb untersuchten wir , ob feuchte Hautpflege mit einer 3%igen Urea-Lotion akute Hautreaktionen bei einer Strahlentherapie vermindern kann . Patienten und Method ik : Bei 88 Patienten mit Plattenepithelkarzinomen i m Kopf-Hals-Bereich ( Tabelle 1 ) , die mit kurativer Intention bestrahlt wurden ( mittlere Gesamtdosis 60 Gy , 50–74 Gy ) , wurden wöchentlich akute Hautreaktionen nach dem RTOG-CTCScore bestimmt . 63 Patienten erhielten eine feuchte Hautpflege mit einer 3%igen Urea-Lotion . Die Kontrollgruppe best and aus 25 Patienten , welche eine konventionelle trockene Hautpflege erhielten . Die Inzidenz von Grad-I- , -II- und -III-Reaktionen und die Strahlendosis bei Auftreten der entsprechenden Reaktionen wurden bestimmt und mittels Log-Rank-Test analysiert ( Abbildung 2 ) . Zusätzlich erfolgte eine Darstellung der Korrelation von Dosis und Zeit für die einzelnen Hautreaktionen in den Patientengruppen mit unterschiedlicher Hautpflege ( Abbildung 1).Ergebnisse : Während der Strahlentherapie litten alle Patienten zu irgendeinem Zeitpunkt an einer akuten Hautreaktion Grad I und > 90 % an einer Grad-II-Reaktion . 50 % der Patienten mit feuchter Hautpflege zeigten bei einer Dosis von 26 Gy eine Hautreaktion Grad I , mit trockener Hautpflege bei einer Dosis von 22 Gy ( p = 0,03 ) . Grad-II-Reaktionen traten bei 51 Gy bzw . 34 Gy auf ( p = 0,006 ) . 22 % der Patienten mit feuchter Hautpflege litten unter einer akuten Hauttoxizität Grad III , verglichen mit 56 % der Patienten in der Kontrollgruppe ( p = 0,0007 ; Abbildung 2).Schlussfolgerung : Feuchte Hautpflege mit einer 3%igen Urea-Lotion verzögert das Auftreten und verringert das Ausmaß akuter Hautreaktionen während einer Strahlentherapie bei perkutan bestrahlten Patienten mit Tumoren i m Kopf-Hals-Bereich PURPOSE Postmastectomy irradiation provides an excellent model for irradiated skin care practice s because of the relatively uniform surface and radiation compared with other situations in which radiation-induced moist desquamation is common . We design ed a study to test the effect of prophylactic 3 M Cavilon No-Sting Barrier Film ( No-Sting ) on the rates of moist desquamation compared with sorbolene cream ( with 10 % glycerin ) . METHODS AND MATERIAL S The irradiated chest wall was divided into medial and lateral halves . Sixty-one women were r and omized to have No-Sting applied to either the medial or lateral half , with the alternate half treated with sorbolene . RESULTS For all patients , the skin toxicity , calculated as the area under the curve , mean No-Sting and sorbolene score was 8.1 vs. 9.2 , respectively ( p = 0.005 , Wilcoxon signed rank test ) . The total number of weeks of moist desquamation for the 61 patients was 40 vs. 45 , equating to a mean of 0.65 week vs. 0.74 week per patient in the No-Sting and sorbolene-treated areas , respectively . The rates of moist desquamation were 33 % vs. 46 % ( p = 0.096 , McNemar 's Exact test ) . For 58 fully assessable patients ( minimum of 7 weekly observations ) , the area under the curve and rates of moist desquamation were significantly different statistically ( p = 0.002 and 0.049 , respectively ) . No statistically significant differences were noted in the pain scores . The pruritus scores were significantly reduced in the No-Sting area ( area under the curve , p = 0.011 ) . CONCLUSION No-Sting reduces the duration and frequency of radiation-induced moist desquamation Objectives : This study evaluated for the first time in intraindividual comparison the conception of care with creme or powder . Acute skin reactions on the left and right side of the neck during symmetrically performed radiotherapy and subjective impairment were assessed . Patients and Methods : Twelve patients receiving radiotherapy of the head- and -neck region up to 50 , 60 , 66 and 72 Gy , respectively , were asked to treat one side of the neck with creme , the contralateral side with powder after r and om assignment . Objective and subjective assessment and photodocumentation were performed at therapy onset and weekly during therapy . The photodocumentation provides an impressive course of acute skin reactions under these care concepts . Results : Altogether we saw no relevant difference in favor of care with creme or powder according to objective as well as subjective assessment criteria ( Figures 2 and 3 ) . In this intraindividual comparison the results are independent from interindividual different sensitivity to radiotherapy , total dose or fractionation . Therefore the small patient number is a minor limitation for evidence . Our results are in accordance to trials comparing other care concepts . Conclusions : A relevant effect concerning onset and degree of acute skin reactions or differences in symptom relief could not be demonstrated . Both conceptions are to be regarded equal in terms of subjective symptom relief and in extent of acute skin reactions . The lack of differences may be explained by the fact that the underlying pathophysiological processes can not be influenced by topical agents . Hintergrund : In der vorliegenden Studie wurde erstmals i m intraindividuellen Vergleich die Wertigkeit der Anwendung von Creme versus Puderbeh and lung i m Bestrahlungsfeld bei Radatio i m Kopf-Hals-Bereich evaluiert . Dabei wurden akute Hautreaktionen der linken und rechten Halsseite unter symmetrischer Strahlentherapie sowie subjektive Beeinträchtigung beurteilt . Patienten und Method e : Zwölf Patienten mit Bestrahlungsbeh and lung der Kopf-Hals-Region bis 50 , 60 , 66 bzw . 72 Gy ( Tabelle 1 ) wurden nach zufälliger Auswahl angewiesen , jeweils eine Halsseite mit Creme zu beh and eln , die gegenseitige Halsseite mit Puder ( Abbildung 1 ) . Die Erhebung der objektiven und subjektiven Beurteilungskriterien sowie Fotodokumentation erfolgte zu Beginn und wöchentlich während der Therapie . Anh and der Fotodokumentation ist der Verlauf der akuten Hautreaktionen eindrücklich nachzuvollziehen ( Abbildungen 4 bis 11 ) . Ergebnisse : Insgesamt konnte kein relevanter Unterschied zugunsten der Pflege mit Creme oder Puder anh and objektiver wie subjektiver Bewertungskriterien gefunden werden ( Abbildungen 2 und 3 ) . Unsere Ergebnisse stimmen überein mit den Erfahrungen von Autoren , die and ere Pflegekonzepte verglichen ( Tabelle 2 ) . Schlussfolgerungen : Ein relevanter Effekt auf Ausmaß und Zeitpunkt des Auftretens akuter Hautreaktionen konnte nicht gezeigt werden . Ebenso best and kein Unterschied bezüglich subjektiver Beschwerden . I m intraindividuellen Vergleich sind die Ergebnisse unabhängig von interindividuell unterschiedlicher Strahlenempfindlichkeit , Gesamtdosis und Fraktionierung . Daher limitiert die niedrige Patientenzahl die Aussagekraft nur geringfügig . Beide Hautpflegekonzepte sind sowohl hinsichtlich des objektiv evaluierten Ausprägungs grade s der akuten Hautreaktion als auch der subjektiven Beeinträchtigung als gleichwertig anzusehen . Der fehlende Unterschied könnte darin begründet liegen , dass topische Agenzien nicht in der Lage sind , die zugrunde liegenden pathophysiologischen Prozesse zu beeinflussen The aim of the study was to see if topical aloe vera gel would be beneficial in reducing the identified skin side-effects of radiation therapy , including erythema , pain , itching , dry desquamation , and moist desquamation , when compared with aqueous cream . The secondary aim was to assess the effect of other factors known to predict severity of radiation skin reaction , ie , breast size , smoking habit , and one or more drainages of lymphocele after surgery , on other skin side effects . A Phase III study was conducted involving 225 patients with breast cancer after lumpectomy or partial mastectomy , who required a course of radiation therapy using tangential fields . Patients were r and omized to either topical aloe vera gel or topical aqueous cream to be applied 3 times per day throughout and for 2 weeks after completion of radiation treatment . Weekly skin assessment s were performed by nursing staff . Aqueous cream was significantly better than aloe vera gel in reducing dry desquamation and pain related to treatment . Subjects with D cup or larger size breasts experienced significantly more erythema , regardless of treatment arm . For subjects who had undergone lymphocele drainage , the aloe vera group experienced significantly more pain than the aqueous cream group . Within the aqueous cream arm , smokers were significantly more likely to experience itching within the treatment field than were nonsmokers . Within the aloe vera arm , subjects who had undergone one or more lymphocele drainages after surgery were significantly more likely to experience erythema and itching within the treatment field than those who did not have drainage . In this study , aloe vera gel did not significantly reduce radiation-induced skin side effects . Aqueous cream was useful in reducing dry desquamation and pain related to radiation therapy BACKGROUND The effect of washing the irradiated skin during radiotherapy for breast cancer is uncertain . The purpose of this study was to evaluate the impact of washing the breast skin with water and soap during radiotherapy on the intensity of acute skin toxicity . MATERIAL S AND METHODS Ninety-nine patients treated for breast cancer were prospect ively r and omized prior to receiving radiotherapy to the breast into two groups : ( 1 ) , no washing was allowed during radiotherapy ( 49 patients ) ; and ( 2 ) , washing was allowed with water and soap ( 50 patients ) . Acute toxicity was recorded according to the Radiation Therapy Oncology Group ( RTOG ) acute skin toxicity scale for each patient every week during radiotherapy and 1 month after the end of radiotherapy . Symptoms related to skin toxicity were scored by visual analogue scales at the same time intervals . Other data collected included sociodemographic data , characteristics related to the tumor and previous treatments , radiation technique , necessity for a second simulation due to loss of skin marks and treatment interruptions . RESULTS In the non-washing group , the following maximum acute toxicity scores were observed : grade 0 , 2 % ; grade 1 , 41 % ; grade 2 , 57 % ; grade s 3 and 4 , 0 % . For the washing group , the scores were : grade 0 , 0 % ; grade 1 , 64 % ; grade 2 , 34 % ; grade 3 , 2 % ; and grade 4 , 0 % . Moist desquamation was seen in 33 % of non-washing patients , but in only 14 % of washing patients . The median scores of pain , itching and burning of the treated skin were higher in the non-washing group , although this was not statistically significant . In a multivariate analysis using logistic regression , acute skin toxicity was associated with the patient 's weight , concomitant radiochemotherapy and hot spots on dosimetry , and there was a trend toward more acute skin toxicity in the non-washing group . CONCLUSION Washing the irradiated skin during the course of radiotherapy for breast cancer is not associated with increased skin toxicity and should not be discouraged PURPOSE Dermatitis is a frequent adverse effect of adjuvant breast radiotherapy . It is more likely in full-breasted women and when the radiation is distributed nonhomogeneously in the breast . Breast intensity-modulated radiation therapy ( IMRT ) is a technique that ensures a more homogeneous dose distribution . PATIENTS AND METHODS A multicenter , double-blind , r and omized clinical trial was performed to test if breast IMRT would reduce the rate of acute skin reaction ( notably moist desquamation ) , decrease pain , and improve quality of life compared with st and ard radiotherapy using wedges . Patients were assessed each week during and up to 6 weeks after radiotherapy . RESULTS A total of 358 patients were r and omly assigned between July 2003 and March 2005 in two Canadian centers , and 331 were included in the analysis . Breast IMRT significantly improved the dose distribution compared with st and ard radiation . This translated into a lower proportion of patients experiencing moist desquamation during or up to 6 weeks after their radiation treatment ; 31.2 % with IMRT compared with 47.8 % with st and ard treatment ( P = .002 ) . A multivariate analysis found the use of breast IMRT ( P = .003 ) and smaller breast size ( P < .001 ) were significantly associated with a decreased risk of moist desquamation . The use of IMRT did not correlate with pain and quality of life , but the presence of moist desquamation did significantly correlate with pain ( P = .002 ) and a reduced quality of life ( P = .003 ) . CONCLUSION Breast IMRT significantly reduced the occurrence of moist desquamation compared with a st and ard wedged technique . Moist desquamation was correlated with increased pain and reduction in the quality of life PURPOSE To determine whether zinc supplementation can accelerate the healing of mucositis and dermatitis after radiotherapy . METHODS AND MATERIAL S In this double-blind study , patients were placed into two r and omized groups ( experimental and control ) of 50 patients each . The groups were homogeneous with respect to medical history , tumor characteristics , and therapeutic details . The experimental group received a st and ard dose of a zinc supplement , and the control group was given a placebo . RESULTS Patients in the control group developed Grade 2 mucositis and dermatitis earlier and sooner than patients in the experimental group . There was also a significant difference in the development of Grade 3 mucositis and dermatitis between the two groups . Patients in the experimental group were found to have milder mucositis and dermatitis . Zinc supplementation did not show much benefit in those patients receiving concurrent chemotherapy or make a substantial impact on weight changes . CONCLUSIONS Zinc supplementation used in conjunction with radiotherapy could postpone the development of severe mucositis and dermatitis for patients with cancers of the head and neck . Zinc supplementation can also alleviate the degree of mucositis and dermatitis . The impact of zinc on tumor growth and patient survival is under further investigation Purpose : Based on in vitro and on clinical evidence of protection against acute side effects of radiation , a prospect i ve r and omized , open study was performed to determine the efficacy of an oral proteolytic enzyme preparation in patients with head and neck cancer receiving conventional fractionated radiation therapy . Methods : Patients with stage T3/T4 head and neck cancer were eligible . One hundred patients from two centres were entered into the study . 60Co gamma-radiation was delivered at a st and ard daily radiation dose of 2 Gy in 25–35 fractions over a period of 6–7 weeks . Two lateral parallel opposing fields were used with a portal area of 10 × 15 cm . Patients assigned to the test group arm additionally received enzyme tablets orally t.i.d . starting 3 days prior to radiation therapy , and continuing up to 5 days after completion of the course of radiation therapy . Patients in the control arm were not given any drug or placebo . Acute radiation side effects were described as mucositis , skin reaction , dysphagia , and were grade d at each visit during and after radiation therapy , following RTOG/EORTC criteria . Results : The severity ( maximum extent ) of acute radiation therapy side effects was significantly less in enzyme-treated patients than in control patients : mucositis ( mean : 1.3 vs 2.2 , P < 0.001 ) , skin reaction ( 1.2 vs 2.4 , P < 0.001 ) and dysphagia ( 1.4 vs 2.2 , P < 0.001 ) . The duration of these side effects as well as the sum scores of side effects were also less in the study arm . Conclusions : Combination of enzyme therapy with conventional fractionated radiation therapy was feasible and well-tolerated . There was significant protection against acute side effects of radiation therapy in the study arm . Not only was the severity of acute side effects less but the duration was shorter and the time to onset was also delayed . Prospect i ve r and omized double-blind studies would verify this role of an oral enzyme therapy as st and ard co-medication with radiation therapy to the head and neck region Purpose : Amifostine has been shown to be able to reduce acute radiation toxicity of administered daily prior to radiation during a course of a conventionally fractionated radiotherapy . A disadvantage is the necessity of daily intravenous injection . We have used amifostin in patients undergoing adjuvant radiochemotherapy for rectal cancer . Amifostine was administered only in the first and fifth week of radiotherapy together with 5-FU chemotherapy . The objective was to determine whether the intermittent use of amifostine may be effective in reducing acute radiation toxicity . Patients and Methods : From September 1997 through October 1998 , 30 patients with stage II/III rectal cancer underwent postoperative radiochemotherapy at our department . All patients had undergone curative ( R0 ) resection and received 50.4 Gy to the pelvis with a 3-field technique using a belly board followed by a boost of 5.4 Gy to the presacral space in conventional frationation with 1.8 Gy per fraction . 5-FU chemotherapy was administered as 120-hours continuous infusion in the first and fifth radiation week via a central venous catheter in a daily dosage of 1 000 mg/m2 . All patients were offered to participate in a phase-II study using additional amifostine . Fifteen patients participated and received 500 mg amifostine daily on chemotherapy days ( days 1 to 5 and 29 to 33 ) immediately prior to the daily radiation fraction . Fifteen patients did not participate and served as non-r and omized control . The study was approved by the ethical committee of the Martin-Luther-University and informed consent was obtained from all patients . Results : The distribution of patients ' characteristics and prognostic parameters was comparable in both groups . Side effects of amifostine were mild and included hypotension ( 53 % grade I , 7 % grade II ) and nausea ( 47 % grade I , 13 % grade II ) . Antiemetics were not routinely used . All patients completed radiochemotherapy plus amifostine without unplanned breaks or dose reductions . One patient developed a cerebral infa rct ion which was considered to be not related to the use of amifostine . As compared to the non-r and omized control group , patients with additional amifostine had less acute skin and bowel toxicity ( maximum erythema score 1.47±0.64 without vs. 0.87±0.52 with amifostine , p = 0.009 and maximum diarrhea score 1.07±1.03 vs 0.40±0.63 , p = 0.044 ) . Oral 5-FU-related mucositis and hematological toxicity were not significantly different . Conclusions : In this phase-II study , amifostine significantly reduced acute skin and bowel toxicity of adjuvant chemoradiation in patients with rectal cancer even if the drug was administered only intermittently and not during the whole course of radiotherapy . This finding might be important with regard to intense combined regimes and should be further investigated . Hintergrund : Amifostin ist in den letzten Jahren in mehreren Phase-II/III-Studien als Radioprotektor eingesetzt worden . Dabei zeigte sich eine Verringerung der Xerostomie bei Bestrahlungen i m Kopf-Hals-Bereich . Ein Effekt auf Mukositis wurde bisher nicht belegt . Wir haben Amifostin in einer Phase-II-Studie bei Patienten mit Rektumkarzinomen während der postoperativen Radiochemotherapie eingesetzt , aber das Präparat nur in den zwei Chemotherapiewochen gegeben . Es sollte geprüft werden , ob dieser intermittierende Applikationsmodus klinisch wirksam sein könnte . Patienten und Method ik : Zwischen September 1997 und Oktober 1998 wurden 15 Patienten mit postoperativer Radiochemotherapie wegen eines Rektumkarzinoms in die offene Phase-II-Studie eingebracht . Die Radiochemotherapie erfolgte nach den Empfehlungen der Deutschen Krebsgesellschaft ( 28 Fraktionen großvolumig mit 1,8 Gy in Drei-Felder-Technik , drei Fraktionen Boost auf Sakrum und Präsakralregion , zwei Kurse 5-FU mit 1000 mg/m2 pro Tag als 120-Stunden-Dauerinfusion in Woche 1 und 5 ) . Amifostin wurde nur an den Chemotherapietagen ( Tage 1 bis 5 und 29 bis 33 ) in einer Dosis von jeweils 500 mg direkt vor der täglichen Bestrahlungsfraktion intravenös appliziert . Die Zustimmung der Ethikkommission der Martin-Luther-Universität lag vor . Während des Studienzeitraums wurden weitere 15 Patienten mit Rektumkarzinom , die die Einschlusskriterien erfüllten , aber an der Studie nicht teilnehmen wollten , mit einer identischen Radiochemotherapie ohne Amifostin beh and elt ; diese dienten als nicht r and omisierte Kontrollgruppe . Ergebnisse : Alle Patienten beendeten die Therapie ohne Komplikationen oder ungeplante Unterbrechungen . Die Toxizität von Amifostin war mild ( Hypotension Grad I in 53 % und Grad II in 7 % , Nausea Grad I in 47 % und Grad II in 13 % ) . Patienten mit Amifostin hatten i m Vergleich zur nicht r and omisierten Kontrollgruppe signifikant weniger akute Nebenwirkungen an der Haut und am Darm ( maximaler Erythem-Score 1,47±0.64 ohne vs. 0,87±0,52 mit Amifostin , p = 0,009 und maximaler Diarrhö-Score 1,07±1,03 ohne vs. 0,40±0,63 mit Amifostin , p = 0,044 ) . Hämatologische Toxizität und orale 5-FU-Mukositis waren nicht signifikant verschieden . Schlussfolgerungen : In dieser Phase-II-Studie ergeben sich Hinweise für eine mögliche klinische Effektivität von Amifostin auch bei intermittierender Gabe während einer Radiochemotherapie bei Patienten mit Rektumkarzinom BACKGROUND Although acute radiation dermatitis ( ARD ) is a common side-effect of radiotherapy ( RT ) , currently there is no general consensus about its prevention or treatment of choice . AIMS The purpose of this study was to investigate whether prophylactic use of topical betamethasone 0.1 % can prevent ARD caused by chest wall irradiation . METHODS Fifty-one patients who underwent modified radical mastectomy for breast cancer and were going to receive RT , were r and omly assigned to receive topical betamethasone 0.1 % , petrolatum or none during RT . The frequency and severity of ARD ( measured using Radiation Therapy Oncology Group acute radiation morbidity scoring criteria ) were recorded at the end of each week during RT and two weeks after its completion . Clinical outcomes were analyzed by relevant statistical methods . RESULTS All patients developed some degree of ARD , the frequency and severity of which increased with time and reached the maximum at the end of the seventh week for all groups . Patients receiving betamethasone had less severe ARD than the other two groups throughout the course of the study , but this difference was significant only at the end of the third week ( p = 0.027 ) . No significant difference was observed between the petrolatum and control arms . CONCLUSION Prophylactic and ongoing use of topical betamethasone 0.1 % during chest wall RT for breast cancer delays occurrence of ARD but does not prevent it . Petrolatum has no effect on the prevention of ARD in these patients BACKGROUND AND PURPOSE Evidence on which to base decisions about the management of radiation skin reactions is lacking . The purpose of this study was to investigate whether sucralfate or aqueous cream reduced acute skin toxicity during radiotherapy to the head and neck , breast or anorectal area ( phase A ) , and to evaluate the effect of hydrogels and dry dressings on moist desquamation ( phase B ) . This paper presents the results of phase A. PATIENTS AND METHODS Three hundred and fifty seven patients were r and omised to apply aqueous cream , sucralfate cream or no cream to the irradiated area from day one of radical radiotherapy treatment . All patients were instructed to wash using unperfumed soap . Acute skin toxicity was measured using a modified radiation therapy oncology group ( RTOG ) score , reflectance spectrophotometry , patient diary card and dermatology life quality index ( DLQI ) . A cost minimisation approach was used to compare the costs of each skin care approach . RESULTS No consistent differences were found in the severity of skin reactions or levels of discomfort suffered by patients in each of the r and omised groups . Patients with a higher body mass index , who smoked , received concomitant chemotherapy , boost or bolus during treatment were more likely to develop skin reactions . CONCLUSIONS There is no evidence to support the prophylactic application of either of the creams tested for the prevention of radiation skin reactions . Our results show that it is possible to predict which patients are at greatest risk of skin reactions . We suggest that known risk factors should be incorporated into future study protocol OBJECTIVE Radiation dermatitis during therapy for breast malignancy can cause significant morbidity and delay treatment . RayGel ( reduced glutathione and anthocyanins ; Integrative Therapies , Portl and , OR ) appears to decrease this skin reaction , prompting us to undertake an objective evaluation of RayGel 's effectiveness . METHODS Patients undergoing whole breast external-beam irradiation were r and omized to treatment with placebo or RayGel . Patients and investigators/staff were blinded to treatment assignment . Skin reaction was documented by photograph and severity scale . RESULTS Thirty-two patients were enrolled . Thirty patients were r and omized to receive placebo ( n = 15 ) or RayGel ( n = 15 ) . Scores were calculated by percent of breast skin involved and grade of reaction . The group receiving RayGel had a lower average score , 93.7 , versus the placebo group , 123.3 . CONCLUSION RayGel provides skin protection during radiation therapy , superior to that observed with st and ard skin care and placebo . This formula may reduce discomfort associated with breast irradiation and thereby allow more consistent completion of radiation courses for the treatment of breast cancer OBJECTIVE The use of silver leaf dressing is common in the treatment of burn victims owing to its capacity to improve healing and inherent antimicrobial properties . The goal of this study was to investigate its effectiveness in the treatment of radiation-induced dermatitis in a patient population receiving radiotherapy with or without concurrent chemotherapy for various carcinomas of the head and neck compared with our current st and ard of care , silver sulfadiazine ( Flamazine ) . METHODS Twelve patients presenting with cancers of the head and neck region with Radiation Therapy Oncology Group ( RTOG ) grade 2 or more skin toxicity were offered topical treatment of silver sulfadiazine and silver leaf dressing . Each patient applied silver-leaf dressing on one side of the neck and silver sulfadiazine on the other . Three independent observers evaluated the patients based on st and ardized digital photography and regular follow-up by the treating physician . The sign test was used to evaluate whether the observed difference was statistically significant . RESULTS There was no improvement in RTOG grade skin toxicity . However , within the same grade , two of three observers agreed on some degree of improvement in the dermatitis with silver leaf dressing compared with silver sulfadiazine . As well , 67 % of patients reported improved pain control on the side treated with silver leaf dressing . Sign test analysis indicated that the use of silver-leaf dressing gave significantly superior results when compared with silver sulfadiazine ( p = .035 ) . CONCLUSION Silver leaf dressing does not appear to be superior to our st and ard treatment for radiation-induced dermatitis when the RTOG grading system is used . It does , however , seem to reduce the severity of reaction within the same grade , accelerate healing , and provide improved pain control over st and ard treatment . It shows promise regarding symptom control and merits further investigation PURPOSE We present the results of a r and omized controlled clinical trial that evaluated the effect of a hydrogel or dry dressing on the time to healing of moist desquamation after radiotherapy to the head- and -neck , breast , or anorectal areas . METHODS AND MATERIAL S A total of 357 patients were r and omized before radiotherapy to receive simple dry dressings ( Tricotex ) or a hydrogel ( Intrasite ) , with Tricotex as a secondary dressing . Patients were instructed to use their dressings from the onset of moist desquamation , if it occurred . RESULTS Of the 357 patients , 100 ( 28 % ) developed moist desquamation . The time to healing was significantly prolonged ( hazard ratio , 0.64 ; 95 % confidence interval , 0.42 - 0.99 ) , in patients assigned to gel dressings . No evidence was found that gel dressings had a significant impact on subjectively reported skin symptoms . CONCLUSION The results of this study have not supported the routine use of hydrogels in the care of patients with moist desquamation and suggests that the healing times are prolonged , without any improvement in patient comfort Our aim was to assess the efficacy of MAS065D , a non-steroidal water-in-oil cream , in preventing and limiting skin reactions caused by radiation therapy ( RT ) . 40 women treated with conservative breast cancer surgery followed by radiotherapy , were r and omised to receive MAS065D ( 22 pts ) or vehicle ( 18 pts ) . Radiotherapy was delivered in 20 fractions : 2.25 Gy to the whole breast plus a concomitant boost of 0.25 Gy to the tumour bed up to a total dose of 50 Gy . Evaluations of skin toxicity , erythema , and subjective symptoms were carried out weekly and 3 weeks after treatment completion . A statistically significant difference between vehicle and MAS065D groups was recorded regarding the maximum severity of skin toxicity ( p < 0.0001 ) , burning within the radiation field ( p = 0.039 ) and desquamation ( p = 0.02 ) , in favour of the latter . We conclude that MAS065D may be considered a safe and effective treatment in the prevention and minimization of skin reactions and associated symptoms OBJECTIVE To observe the effect of Lianbai liquid in prevention and treatment of acute radiation dermal injury . METHOD From May 2000 to December 2005 , 126 cancer patients were r and omly divided into a prevention group of 75 cases given externally topical application of Lianbai liquid since the first radiotherapy , and a control group I of 51 cases given only advice after radiotherapy ; while the other 92 cancer patients who had already had grade III acute radiation-induced dermal injury were r and omly divided into a treatment group of 54 cases treated by externally topical use of Lianbai liquid , and a control group II of 38 cases treated by topical use of norfloxacin . Clinical evaluation was carried out according to the CTC.V2.0 st and ard stipulated by NCI for classifying acute radiation dermal injury . RESULTS The incidence of skin reaction was 32.0 % in the prevention group and 92.2 % in the control group I , with an obvious difference between the two groups ( chi2=54.163 , P<0.01 ) . Mild radioactive reaction ( grade I and II ) was 28.0 % ( 21/75 ) in the prevention group and 70.6 % ( 36/51 ) in the control group I , with a remarkable difference between the two groups ( chi2=22.226 , P<0.01 ) . The effective rate for grade III dermal injury was 92.6 % ( 50/54 ) in the treatment group and 65.9 % ( 25/38 ) in the control group II , with a remarkable difference between the two groups ( chi2=6.018 , P=0.024 ) . The wound-healing time was 11.07+/-2.21 days in the treatment group and 18.08+/-1.76 days in the control group II , with a remarkable difference between the two groups ( u=16.932 , P<0.01 ) . CONCLUSION Lianbai liquid can effectively prevent the radiation dermatitis , and treat grade III acute radiation dermal injury with obvious curative effect We evaluated the effects of Biafine and Lipiderm ointments in preventing radiation dermatitis . The study population included 74 patients after conservative surgery for early breast carcinoma who were referred for adjuvant external beam irradiation . Patients were r and omized to receive Biafine or Lipiderm or no treatment . Both study preparations were applied twice daily , starting 10 days before onset of radiotherapy and continuing until 10 days after its completion . The skin treatment was up grade d , if clinical ly necessary , to steroids ( grade 3 ) , antibiotics ( grade 4 ) , or pause in therapy ( grade 5 ) . Success of treatment was evaluated according to the maximal level of skin treatment , the number of gaps in radiation therapy , the impression of the patients and the subjective skin reaction , and scores of the study nurse and radiotherapist . The three groups were comparable for all clinical features , except for a lower mean age of the Biafine group . Comparative analysis of the results showed no advantage for either preparation compared to the control arm other than maximal treatment level required for a skin reaction ( mean 1.7 and 1.6 vs. 2.2 ) , which did not reach statistical significance ( p=0.145 ) . Nevertheless , 86 % of the patients in both the Biafine and Lipiderm arms expressed satisfaction with the respective ointments . In conclusion , neither Biafine nor Lipiderm seems to have a radioprotective effect |
10,757 | 12,519,566 | REVIEW ER 'S CONCLUSIONS Nystatin can not be recommended for prophylaxis or treatment of C and ida infections in immunodepressed patients | BACKGROUND Nystatin is sometimes used prophylactically in patients with severe immunodeficiency or in the treatment of fungal infection in such patients , although the effect seems to be equivocal .
OBJECTIVES To study whether nystatin decreases morbidity and mortality when given prophylactically or therapeutically to patients with severe immunodeficiency . | OBJECTIVES : To evaluate the efficacy of low dose fluconazole treatment for the prevention of yeast colonization and infection in severely neutropenic patients . METHODS : An open r and omized trial , comparing fluconazole ( 100 mg per day ) with nystatin ( 800,000 IU per day ) , in a University Hospital setting . RESULTS : Antifungal prophylaxis was given during the period of neutropenia , defined as less than 500 polymorphonuclear cells (PMN)/mm3 ) . Thirty-six patients were r and omly assigned to fluconazole and 33 to nystatin treatment groups . New oropharyngeal colonizations were significantly reduced by fluconazole ( P=0.005 ) , and oropharyngeal infections occurred less frequently in the fluconazole group ( 3 % versus 16 % , P=0.07 ) . Stool colonization was identical between both groups . Systemic fungal infections were rare ; one fluconazole patient had pulmonary aspergillosis and one nystatin patient developped C and ida pseudotropicalis fungemia . Empiric amphotericin B was given with the same frequency in both groups . No side effects were associated with fluconazole . However , the administration of nystatin became impossible for three patients because of vomiting and lack of compliance . CONCLUSIONS : Fluconazole ( 100 mg per day ) is more effective than nystatin for the prevention of oropharyngeal yeast colonization . Comparison with results in the literature suggests that a 100-mg dose of fluconazole has similar effects to 200 or 400 mg per day Purpose The effectiveness of amphotericin B oral suspension versus nystatin oral suspension for the prevention of oral colonization by C and ida in hematopoietic cell transplant ( HCT ) patients was examined . Methods Prior to hematopoietic cell infusion , 40 patients receiving systemic fluconazole for prophylaxis were r and omized to receive either amphotericin B oral suspension or nystatin oral suspension , q.i.d . The study continued to day 21 or until the patient was discharge from the hospital or withdrawn from the study . Oral examinations were conducted twice weekly , and adverse events and compliance were recorded . Cultures were taken for quantitative counts and species identification . C and ida isolates were assessed for resistance to the oral antifungal agents . Blood was collected for assessment of amphotericin B levels . Results and discussion Ulcerative mucositis occurred in 84.6 % of patients undergoing HCT , and no correlation was observed between the severity of mucositis and the presence of oral C and ida and the severity of mucositis . Systemic and topical antifungal treatment result ed in a decrease in the number of colonized patients ( 54.8 % before treatment ; 23.1 % during treatment ) ; however , oral colonization was not eliminated . Tolerability of the oral rinse products was limited , with greater noncompliance in the amphotericin B than the nystatin group . Reports of altered taste appeared to be greater in the amphotericin B group . Minimal absorption of amphotericin B was seen following oral rinsing ( serum levels 0.12–0.50 μg/ml ) , and no consistent changes in organism susceptibility to polyenes were seen . The results suggest that topical antifungal rinses may further control oropharyngeal colonization by C and ida in patients on systemic antifungals receiving HCT , but the effect is limited by tolerability and reformulation and should be considered in order to increase compliance Fifty-six untreated patients with acute leukemia ( 38 acute myelogenous leukemia , 16 acute lymphoblastic leukemia , and 2 blast crisis of chronic granulocytic leukemia ) were r and omized on admission to one of three groups -- one to receive oral antic and idal prophylaxis through the period of remission induction chemotherapy with nystatin , another to receive natamycin , and the third to receive no antic and idal prophylaxis . Neither of the first two groups show any advantage over the last and it is concluded that provided gut sterilization regimes are not employed , prophylactic oral antic and idal treatment is of no value in these patients and should be reserved until there is clinical evidence of infection The goal of this prospect i ve r and omized single-center study was the comparison of safety and efficacy of high-dose oral/intravenous fluconazole ( 400 mg daily ) ( group A ) with oral nystatin plus miconazole inhalations ( group B ) in the prevention of fungal infections on a hemato-oncological isolation Ward . Of 157 patients admitted to the isolation ward during the study period only 90 ( 57 % ) were eligible for r and omization ; 22 ( 14 % ) had a fungal infection at admission . Of the 90 r and omized patients , 89 were evaluable , 43 in group A and 46 in group B. The age , sex , diagnosis , planned therapy and risk factors for fungal infections at admission as well as the duration of neutropenia were in the same proportions in both groups . Oral thrush and mucocutaneous c and idiasis were prevented in all patients of both groups , and 29 patients ( 32 % : 17 in group A , 12 in group B ) were discharged after successful prophylaxis ( NS ) . Empiric amphotericin B was given according to predetermined criteria to 45 patients ( 51 % : 23 group A , 22 group B ; NS ) . Fluconazole significantly delayed the time before the start of intravenous amphotericin B. It was begun after a median of 10 days ( 0–45 days , range ) of neutropenia below 0.5x109 granulocytes/l in group A and 7.5 days ( 0–26 , range ) in group B ( P<0.05 ) . The duration of successful prophylaxis was significantly longer in group A ( 26 days median ) than in group B ( 21 days , median ) ( P<0.05 ) . Systemic fungal infection was documented in 3 patients ( 1 group A , 2 group B ; NS ) . Colonisation with C and ida persisted for more than 14 days or occurred de novo after admission in 1 patient in group A and in 7 patients in group B ( NS ) . Oral nystatin had to be discontinued because of oral intolerance in 3 patients and fluconazol had to be stopped because of increased liver values in one patient . Compliance was worse ( P<0.01 ) in group B ; 82 % of the planned dose was given in group B compared to 99 % in group A. Both regimens successfully prevented oral fungal complications . Fluconazole was better tolerated and delayed the need for empiric amphotericin B. Neither approach cancelled the need for the empiric use of amphotericin B nor prevented fungal infections or colonization . Systemic fungal infections occur probably independently of oral or mucocutaneous c and idiasis The orointestinal yeast colonization of 46 children with newly diagnosed malignancies was studied prospect ively and longitudinally with quantitative cultures during remission induction chemotherapy . The initial colonization rate was 24 % ; only 28 % of the patients remained free of yeasts during their entire treatment although all of them continuously received oral polyenes as antifungal prophylaxis . A r and omized comparison of natamycin ( suspension , lozenges ) , nystatin ( suspension ) and amphotericin B ( suspension , lozenges ) failed due to serious problems with patient compliance . Natamycin was best accepted by the patients and natamycin lozenges were the most efficacious drug in the oral cavity . The effectivity of the suspensions of nystatin and amphotericin B was similar ; both were equally efficacious in the oral cavity and the gut . Assessment of faecal polyene concentrations by HPLC showed the highest results for amphotericin B ( mean 6808 microgram(-1 ) ) . Regularly performed C and ida serology ( indirect haemagglutination , indirect immunofluorescence and immunodiffusion precipitation ) revealed significant titre increases in 63 % of the patients . In six cases , the synopsis of clinical picture , culture and serology strongly suggested systemic yeast invasion Nystatin , one million units every four hours , was prospect ively studied as a prophylactic antifungal agent in 164 neutropenic patients who were not initially colonized by fungi : 104 received nystatin and 60 served as controls . Fungal colonization occurred in 68/104 ( 65 % ) nystatin recipients and in 43/60 ( 71 % ) controls . However , nystatin significantly reduced multiple body site colonization and persistent oropharyngeal colonization . Despite these alterations in colonization profile , 16/104 ( 15 % ) nystatin recipients developed disseminated fungal infections , as compared to 5/60 ( 8 % ) control patients ( 0.5 greater than p greater than 0.1 , N.S ) . Differences in the clinical course of colonized and non-colonized patients were observed . Eighteen of 111 ( 16 % ) colonized patients had afebrile clinical courses as compared to 16/53 ( 30 % ) non-colonized patients ( p less than 0.05 ) . Twenty-nine of 93 ( 31 % ) febrile episodes in colonized patients failed to respond to empiric antibiotic therapy as compared to 3/37 ( 8 % ) episodes in non-colonized patients ( p less than 0.01 ) . Disseminated fungal infections were diagnosed in 19/111 ( 17 % ) of colonized patients , as compared to 1/53 ( 2 % ) non-colonized patients ( p less than 0.02 ) . We conclude that colonized patients are more likely to develop febrile clinical courses , to fail to respond to empiric antibiotic therapy , and to develop disseminated fungal infection . Nystatin altered colonization patterns but did not prevent disseminated fungal infection The goal of reducing oral complications during chemotherapy and bone marrow transplantation has received attention at several centers . The current r and omized study of 86 adults with leukemia treated with chemotherapy or bone marrow transplantation assessed the potential role of chlorhexidine , nystatin , and saline solution rinses to reduce the findings of oral mucositis , gingivitis , and oral infection . The results of this study did not show a reduction in mucositis with the use of these rinses . However , potential bacterial and fungal pathogens were identified less frequently in the patients using chlorhexidine rinse A prospect i ve , r and omized , multicenter study addressed the safety and efficacy of fluconazole therapy in 143 liver transplant patients . Seventy-six patients received daily oral fluconazole ( 100 mg ) , and 67 received nystatin ( 4 X 10(6 ) U ) during the first 28 days after transplantation . C and ida colonization occurred in 25 % and 53 % of patients in the fluconazole and nystatin groups , respectively ( P = .04 ) , and 13 % and 34 % of patients in the respective groups had C and ida infections ( P = .022 ) . Of these patients , 10.5 % in the fluconazole group and 25.3 % in the nystatin group had superficial c and idal infections ( P = .024 ) . Invasive c and idiasis developed in 2 patients in the fluconazole group ( 2.6 % ) and 6 in the nystatin group ( 9.0 % ) ( P = .12 ) . There was no increased hepatotoxicity , cyclosporine interaction , or emergence of clinical ly relevant resistant C and ida strains attributable to fluconazole . Thus , oral fluconazole ( 100 mg ) is safe and reduces C and ida colonization and infection after liver transplantation A prospect i ve , r and omized study was conducted to determine if prophylactic antifungal agents prevented yeast colonization ( YC ) or yeast sepsis ( YS ) , or if they diminished mortality in 292 critically ill adult ( nontransplant/nonburned ) surgical and trauma patients admitted to the SICU for 48 hours or longer . Patients were r and omized to receive ( group I ) no therapy , ( group II ) clotrimazole 10 mg three times a day , ( group III ) ketoconazole 200 mg per day , or ( group IV ) nystatin 2 million units every 6 hours . For comparison patients were stratified by the criteria of Slotman and Burchard into high risk ( > or = 3 risk factors ) and low risk ( < 3 risk factors ) . Fifty patients ( 17 % ) had yeast colonization , nine ( 3.1 % ) had yeast sepsis , and 41 ( 14 % ) died . Stepwise logistic regression analysis of yeast colonization and sepsis using the variables APACHE II scores > 10 , need for ventilator support > 48 hours , and 14 risk factors ( Slotman and Burchard ) showed that treatment with three or more antibiotics , APACHE II > 10 , and ventilatory support > 48 hours were the only three variables that were significant predictors of yeast colonization and sepsis . There was no significant difference between the four groups with regard to YC ( 23 % , 18 % , 12 % , and 15 % , respectively ) , YS ( 3 % , 1 % , 2 % , and 7 % , respectively ) , or mortality ( 15 % , 14 % , 6 % , and 20 % , respectively ) . ( ABSTRACT TRUNCATED AT 250 WORDS OBJECTIVE To compare the efficacy , safety , and tolerance of fluconazole suspension versus nystatin in the treatment of oropharyngeal thrush in immunocompromised children . DESIGN Multicenter , r and omized , observer-masked trial . SETTING Thirty-two centers participated , including hospitals and ambulatory care clinics . PATIENTS We enrolled 182 immunocompromised infants and children , ages 5 months to 14 years , with signs of oral thrush and presence of yeasts on potassium hydroxide- or gram-stained preparations . Subjects were r and omly assigned to receive a single daily dose of fluconazole suspension , 2 to 3 mg/kg per day , or nystatin , 400,000 units four times daily for 14 days ; 159 patients , who had culture confirmation of thrush and received at least 7 days of study drug , were evaluated for efficacy ; all patients were evaluated for safety . RESULTS Clinical cure was demonstrated in 91 % of the subjects in the fluconazole group and 51 % of the subjects in the nystatin group ( p < 0.001 ) , and eradication of the organism cultured at entry occurred in 76 % and 11 % ( p < 0.001 ) , respectively . Gastrointestinal conditions developed in six patients who received fluconazole and in three who received nystatin ; two fluconazole recipients were subsequently withdrawn from the study . Laboratory abnormalities occurred with equal frequency in both groups . Clinical relapse rates were similar in both groups at 2 weeks ( 18 % and 24 % for fluconazole and nystatin , respectively ) and 1 month ( 28 % and 27 % , respectively ) after the completion of study drug . CONCLUSIONS Fluconazole suspension is more effective than nystatin in the treatment of thrush in immunocompromised children . Both regimens were well tolerated An open , prospect i ve , r and omized pilot study was performed to assess the efficacy and safety of oral fluconazole 3 mg/kg once daily compared with oral nystatin 50,000 units/kg/day in four divided doses in preventing c and ida infections in 50 children undergoing remission induction or consolidation therapy for cancer . In 21 of 25 fluconazole-treated and 20 of 25 nystatin-treated patients the overall outcome of prophylaxis was clearly successful . Mild and transient oropharyngeal c and idosis was observed in two and three patients in the fluconazole and nystatin groups respectively . One patient r and omized to fluconazole and two patients r and omized to nystatin required empirical treatment with amphotericin B and one patient assigned to fluconazole developed tissue-proven c and ida colitis . Initially non-colonized patients remained yeast-free throughout treatment with no differences between the two study arms . Initially colonized patients stayed colonized throughout treatment although at the end of the study , more patients r and omized to nystatin were still harbouring yeasts ( P = 0.05 ) . Almost exclusively , C and ida albicans ( 95 % ) was isolated . A change in species was observed in one patient in each arm of the study . C and ida krusei or C and ida glabrata were not encountered . Transient elevations of hepatic transaminases were more common in the fluconazole group , although not statistically significant ( 28 % vs 12 % , P = 0.15 ) . Reversible grade I gastrointestinal and skin symptoms were observed in four patients r and omized to fluconazole ( 16 vs 0 % , P < 0.05 ) . Fluconazole was as safe and effective as nystatin in controlling yeast colonization and in preventing superficial and invasive c and ida infections and the empirical use of amphotericin B in children and adolescents undergoing intensive chemotherapy for cancer A total of 167 human immunodeficiency virus (HIV)-infected patients with oropharyngeal c and idiasis were r and omly assigned to receive 14 days of therapy with liquid suspension fluconazole ( 100 mg once daily ) or liquid nystatin ( 500,000 U four times daily ) . At day 14 , 87 % of the fluconazole-treated patients were clinical ly cured , as opposed to 52 % in the nystatin-treated group ( P < .001 ) . Fluconazole eradicated C and ida organisms from the oral flora in 60 % , vs. a 6 % eradication rate with nystatin ( P < .001 ) . The fluconazole group had fewer relapses noted on day 28 ( 18 % , vs. 44 % in the nystatin group ; P < .001 ) . This relapse difference no longer existed by day 42 . Fluconazole oral suspension as a systemic therapy was more effective than liquid nystatin as a topical therapy in the treatment of oral c and idiasis in HIV-infected patients and provided a longer disease-free interval before relapse |
10,758 | 26,265,016 | This systematic review and meta- analysis provides evidence that breastfeeding protects against AOM until 2 years of age , but protection is greater for exclusive breastfeeding and breastfeeding of longer duration . | AIM To synthesis e the evidence on the association between duration and exclusivity of breastfeeding and the risk of acute otitis media ( AOM ) . | Using a cohort-based design and r and om enrollment , the relation of various risk factors to acute otitis media , respiratory infection and wheezy bronchitis was studied in 2512 children from the fetal period to the age of two years . The complex interrelations of the risk factors with each other were separated out by multivariate analysis , and the confounding effects of antenatal parameters were also st and ardized . Acute otitis media with effusion ( AOME ) , as demonstrated by myringotomy , was analyzed as a specific subgroup of acute otitis media ( AOM ) . Day care in local authority nursery was the major risk factor for both types of acute otitis media . The odds ratio ( OR ) for such children becoming ' otitis-prone ' ( greater than or equal to 3 episodes of AOME ) was 1.8 ( 95 % confidence interval , 1.4 - 2.2 ) . Short duration of breastfeeding involved another significant risk of recurrent respiratory infections and otitis media , the OR for AOME being 1.5 ( 1.1 - 2.0 ) and that for recurrent respiratory infection 1.3 ( 1.1 - 1.6 ) . Allergy and family day care were also significantly associated with infective parameters , but to a lesser extent . The risk factors for wheezy bronchitis were the same as for infections , indicating that wheezy bronchitis is closely related to infections A number of studies in developed countries suggest that breastfeeding protects against infections in infancy . However , the choice to breastfeed is often related to maternal characteristics , and many of these studies are limited in the extent to which they can take account of confounding influences . In a prospect i ve birth cohort study , we assessed the relationship between the duration of breastfeeding and the prevalence of lower respiratory tract infections , ear infections and gastrointestinal morbidity during the first year of life in 1764 infants . We considered the duration of all breastfeeding , including mixed feeding . Eighty-one per cent of the infants were breastfed initially , and 25 % were breastfed up to 6 months . There were grade d decreases in the prevalence of respiratory and gastrointestinal symptoms between birth and 6 months as breastfeeding duration increased ; these were robust to adjustment for a number of confounding factors . The adjusted relative risks ( 95 % confidence interval ) for infants breastfed for six or more months compared with infants who were never breastfed were 0.72 ( 0.58 - 0.89 ) , 0.43 ( 0.30 - 0.61 ) and 0.60 ( 0.39 - 0.92 ) for general respiratory morbidity , diarrhoea and vomiting , respectively . Duration of breastfeeding in the second half of infancy was less strongly related to diagnosed respiratory tract infections and gastrointestinal morbidity , although important benefits of breastfeeding were still seen . Our data provide strong support for a protective role of breastfeeding against respiratory and gastrointestinal infections in infancy . The grade d inverse associations with breastfeeding duration suggest that current efforts to promote breastfeeding and increase duration will have important effects in reducing morbidity in infancy A r and om sample of 2512 children was monitored to age 2 years to study the biologic effects of various risk variables on acute otitis media using a new dynamic modeling that controls both the confounding effects and time dependency . Dynamic modeling proved to be superior to conventional approaches , both the r and om and systematic error being much smaller and the effect estimates being biologically interpretable . The major risk factors were the existence of a previous episode of acute otitis media in general ( odds ratio , 2.03 ; 95 % confidence interval [ Cl ] , 1.81 to 2.25 ) or particularly during the preceding 3 months ( odds ratio , 3.74 ; 95 % Cl , 3.40 to 4.10 ) and attending a day nursery ( odds radio , 2.06 ; 95 % Cl , 1.81 to 2.34 ) . As the form of day care is the only modifiable risk variable of significant importance and previous episodes entail a risk of future ones , infants should be cared for at home , particularly after they have already experienced an episode of acute otitis media OBJECTIVE We followed a cohort ( N = 306 ) of infants at well-baby visits in two suburban pediatric practice s to assess the relation of exclusive breastfeeding , and other environmental exposures , to episodes of acute otitis media ( AOM ) and otitis media with effusion ( OME ) . METHODS Detailed prospect i ve information about the exclusiveness of breastfeeding , parental smoking , day care attendance , and family history was obtained at scheduled clinic visits . Tympanometric and otoscopic examinations were used in the diagnosis of otitis media ( OM ) . Nasopharyngeal cultures were performed at 1 - 6 months , and at 8 , 10 , 12 , 15 , 18 , and 24 months of age to detect colonization with middle-ear pathogens . RESULTS Between 6 and 12 months of age , cumulative incidence of first OM episodes increased from 25 % to 51 % in infants exclusively breastfed and from 54 % to 76 % in infants formula-fed from birth . Peak incidence of AOM and OME episodes was inversely related to rates of breastfeeding beyond 3 months of age . A twofold elevated risk of first episodes of AOM or OME was observed in exclusively formula-fed infants compared with infants exclusively breast-fed for 6 months . In the logistic regression analysis , formula-feeding was the most significant predictor of AOM and OME episodes , although age at colonization with middle-ear pathogens and day care ( outside the home ) were significant competing risk factors . A hazard health model suggested additionally that breastfeeding , even for short duration s ( 3 months ) , reduced onset of OM episodes in infancy . CONCLUSIONS Modifiable factors in the onset of AOM and OME episodes during the first 2 years of life include early age at colonization ( < /=3 months of age ) , day care outside the home , and not being breastfed OBJECTIVE This study was design ed to assess the relation of exclusive breast-feeding , independent of recognized risk factors , to acute and recurrent otitis media in the first 12 months of life . METHODS Records of 1220 infants who used a health maintenance organization and who were followed during their first year of life as part of the Tucson Children 's Respiratory Study were review ed . Detailed prospect i ve information about the duration and exclusiveness of breast-feeding was obtained , as was information relative to potential risk factors ( socioeconomic status , gender , number of siblings , use of day care , maternal smoking , and family history of allergy ) . Acute otitis media and recurrent otitis media , defined as three or more episodes of acute otitis media in a 6-month period or four episodes in 12 months , were the outcome variables . RESULTS Of the 1013 infants followed for their entire first year , 476 ( 47 % ) had at least one episode of otitis and 169 ( 17 % ) had recurrent otitis media . Infants exclusively breast-fed for 4 or more months had half the mean number of acute otitis media episodes as did those not breastfed at all and 40 % less than those infants whose diets were supplemented with other foods prior to 4 months . The recurrent otitis media rate in infants exclusively breast-fed for 6 months or more was 10 % and was 20.5 % in those infants who breast-fed for less than 4 months . This protection was independent of the risk factors considered . CONCLUSION These findings suggest that exclusive breast-feeding of 4 or more months protected infants from single and recurrent episodes of otitis media The authors compared parental reports with medical records for 157 children enrolled in a prospect i ve study of chronic otitis media with effusion between 1987 and 1991 . Parents completed a question naire about the child 's past health history , and the research nurse abstract ed history information from the clinic 's medical record . Previous insertion of a tympanostomy tube ( kappa = 0.96 ) and premature birth ( kappa = 0.68 ) were accurately reported , but there was a substantial proportion of missing data for age at first episode of otitis media , occurrence of otitis media the previous summer , and number of episodes in the previous 18 months . Data were significantly more likely to be missing for male children , children with siblings , and those with more episodes . Parents who reported six or more previous episodes for their child overestimated the number compared with the medical record ( 8.7 vs. 7.4 , respectively ; p = 0.01 ) , while those who reported fewer episodes underestimated the number ( 3.1 vs. 4.6 , respectively ; p = 0.01 ) . Episodes of otitis media during the 3 months between study visits were also accurately reported ( kappa = 0.94 ) . The accuracy and completeness of parental report of the child 's health history was influenced by the chronicity of otitis media , the duration of recall , and the seriousness of the event being recalled Risk factors for acute upper respiratory tract disease in childhood were evaluated in a population -based sample of the Atlanta metropolitan area . Mothers from 449 households containing 575 children less than 5 years of age were selected by r and om-digit dialing and question ed about upper respiratory tract infection and ear infection occurring in their children during the preceding 2 weeks . Household demographic and socioeconomic characteristics , maternal smoking history and child day-care attendance and breast-feeding information were also obtained . For children less than 5 years of age , the reported incidence of upper respiratory tract infection was 24 % , and of ear infection , 6 % . Controlling for the other variables measured , day-care attendance was associated with a significantly increased risk of both illnesses . For upper respiratory tract infection , increased risk was present for all children attending day care ( P = .02 , odds ratio = 1.6 ) , whereas for ear infection , risk could be demonstrated only for full-time attendees ( P = .005 , odds ratio = 3.8 ) . Maternal smoking was a second independent risk factor for a child 's having upper respiratory tract infection ( odds ratio = 1.7 , P = .01 ) . Thirty-one percent of all upper respiratory tract infection among day-care attendees and 66 % of all ear infections among full-time day-care attendees were attributable to day-care attendance . Given the proportion of children in day care , 9 % to 14 % of the total burden of upper respiratory tract disease in this population was day care related . ( ABSTRACT TRUNCATED AT 250 WORDS Acute otitis media is the most frequent diagnosis in children visiting physicians ’ offices . Risk factors for otitis media have been widely studied . Yet , the correlation between bacterial carriage and the development of otitis media is not entirely clear . Our aim was to study in a population -based prospect i ve cohort the risk factors for otitis media in the second year of life with special emphasis on the role of colonization with Streptococcus pneumoniae , Haemophilus influenzae and Moraxella catarrhalis . The study was embedded in the Generation R Study . Data on risk factors and doctor-diagnosed otitis media were obtained by midwives , hospital registries and postal question naires in the whole cohort ( n = 7,295 ) . Nasopharyngeal swabs were obtained at the age of 1.5 , 6 and 14 months in the focus cohort ( n = 1,079 ) . Of these children , 2,515 ( 47.2 % ) suffered at least one period of otitis media in their second year of life . The occurrence of otitis media during the follow-up period in the first 6 months of life and between 6 and 12 months of age was associated with the risk of otitis media in the second year of life ( aOR , 1.83 95 % CI 1.24–2.71 and aOR 2.72 , 95 % CI 2.18–3.38 , respectively ) . Having siblings was associated with an increased risk for otitis media in the second year of life ( aOR 1.42 , 95 % CI 1.13–1.79 ) . No associations were found between bacterial carriage in the first year of life and otitis media in the second year of life . In our study , otitis media in the first year of life is an independent risk factor for otitis media in the second year of life . Surprisingly , bacterial carriage in the first year of life did not add to this risk . Moreover , no association was observed between bacterial carriage in the first year of life and otitis in the second year of life OBJECTIVE Otitis media ( OM ) is an extremely common pediatric diagnosis . Several risk factors have been associated with OM , but the relationship between OM and race/ethnicity remains controversial . We sought to define the relationship between OM diagnosis and race/ethnicity in infants . METHODS By multivariable logistic regression , we evaluated the association between OM diagnosis and race/ethnicity in 11,349 non-low-birthweight infants who were participants in a prospect i ve cohort study of infant care practice s. RESULTS As in previous studies , breastfeeding was associated with a decreased risk of OM diagnosis while other factors were independently associated with a substantially increased risk of OM diagnosis : out-of-home daycare , multiple children living in the home , and mother 's multiparity . Daycare was associated with a " dose effect " in that the risk of OM diagnosis increased with an increasing number of children in the daycare . While the crude analysis suggested little relation of OM diagnosis and race/ethnicity , the association was confounded by several covariates including maternal marital status , number of children living in the home , breastfeeding status , and maternal age . After adjustment for relevant confounders , Black ( OR 0.74 ; 95 % CI 0.61 - 0.89 ) and Asian infants ( OR 0.77 ; 95 % CI 0.57 - 1.0 ] ) were less likely to be diagnosed with OM than White infants . CONCLUSIONS This large prospect i ve study confirms previous risk factors for OM and demonstrates a strong " dose effect " of the size of daycare centers on OM . The study also demonstrates that the association between race/ethnicity and OM diagnosis is confounded by social factors . After adjusting for such factors , Black and Asian infants are less likely to be diagnosed with OM than White infants . The reason for this racial disparity remains unknown The authors ' objective was to determine whether cumulative weekly breastfeeding duration by 13 weeks was associated with infant otitis media , respiratory and gastrointestinal illness , and total illness visits up to 12 months . The authors performed a secondary analysis of data from a r and omized clinical trial of low-income , primarily Hispanic and Black women enrolled from 2 medical center affiliated clinics . “ Breastfeeding sensitive ” ( BFS ) outpatient and emergency room ( ER ) visit data for the above illnesses were obtained for 255 mother/infant dyads . Outcome measures were unadjusted and adjusted rates of outpatient and ER visits with sick and BFS diagnoses . The authors found no significant associations between breastfeeding intensity and infant visits for otitis media , respiratory and gastrointestinal illness , or total illness visits . In this low-income , multiethnic sample , breastfeeding intensity was not associated with infant health service use , in contrast to other evidence -based reports . Low exclusive breastfeeding rates and lack of coverage for health visits may be reasons for this finding . J Hum Lact . 24(1):14 - 22 Objective To prospect ively investigate the effects of breastfeeding on the frequency and severity of infections in a well-defined infant population with adequate vaccination coverage and healthcare st and ards . Study design In a representative sample of 926 infants , successfully followed up for 12 months , feeding mode and all infectious episodes , including acute otitis media ( AOM ) , acute respiratory infection ( ARI ) , gastroenteritis , urinary tract infection , conjunctivitis and thrush , were recorded at 1 , 3 , 6 , 9 and 12 months of life . Results Infants exclusively breastfed for 6 months , as per WHO recommendations , presented with fewer infectious episodes than their partially breastfed or non-breastfed peers and this protective effect persisted after adjustment for potential confounders for ARI ( OR 0.58 , 95 % CI 0.36 to 0.92 ) , AOM ( OR 0.37 , 95 % CI 0.13 to 1.05 ) and thrush ( OR 0.14 , 95 % CI 0.02 to 1.02 ) . Prolonged exclusive breastfeeding was associated with fewer infectious episodes ( rs=−0.07 , p=0.019 ) and fewer admissions to hospital for infection ( rs=−0.06 , p=0.037 ) in the first year of life . Partial breastfeeding was not related to protective effect . Several confounding factors , including parental age and education , ethnicity , presence of other siblings , environmental tobacco smoke exposure and season of birth were demonstrated to have an effect on frequency of infections during infancy . Conclusions Findings from this large-scale prospect i ve study in a well-defined infant population with adequate healthcare st and ards suggest that exclusive breastfeeding contributes to protection against common infections during infancy regarding and lessens the frequency and severity of infectious episodes . Partial breastfeeding did not seem to provide this protective effect Otitis media ( OM ) is one of the most common diseases of childhood , and causes both direct and indirect costs to families and to society . This study calculated the costs arising from OM among 736 day care children whose infections were prospect ively monitored for up to 15 mo in 10 day care centres in the city of Oulu . The children in the survey had 1.5 attacks of acute OM per person year , made 2.1 visits to a physician ( cost $ US55 visit−1 ) and received 1.5 courses of antimicrobials ( cost $ 24 course−1 ) . Their parents were absent from work for 1.9 d per person year ( cost $ 85 d−1 ) . Either adenoidectomy ( $ 890 operation−1 ) or tympanostomy ( $ 740 ) was performed on 6 % of the children and the overall costs of surgery were $ 80 per person year at risk . In total , each single attack of acute OM cost $ 228 . The average annual costs per child younger than 2y were $ 1040 , those for children aged 2—3 y $ 283 and those for children older than 3 y $ 141 . The cumulative costs from age 6 mo to 7y were $ 2549 child−1 . When the attributable risk of OM at a day care centre is taken into account , in Finl and , a country with about 5 million inhabitants , OM gives rise to total annual costs of $ US138 million . OM leads to considerable expenses and even expensive preventive measures would be cost‐effective . □ Adenoidectomy , cost analysis , otitis media , During a 5-year prospect i ve study of nasopharyngeal ( NP ) colonization and acute otitis media ( AOM ) infections in children during the 7-valent pneumococcal conjugate vaccine ( PCV ) era ( July 2006-June 2011 ) we studied risk factors for NP colonization and AOM . NP sample s were collected at ages 6 , 9 , 12 , 15 , 18 , 24 , and 30 months during well-child visits . Additionally , NP and middle ear fluid ( MEF ) sample s were collected at onset of every AOM episode . From 1825 visits ( n = 464 children ) , 5301 NP and 570 MEF sample s were collected and analysed for potential otopathogens . Daycare attendance , NP colonization by Moraxella catarrhalis , and siblings aged < 5 years increased the risk of Streptococcus pneumoniae NP colonization . NP colonization with S. pneumoniae , M. catarrhalis , or Haemophilus influenzae and a family history of OM increased the risk of AOM . Risk factors that increase the risk of pneumococcal AOM will be important to reassess as we move into a new 13-valent PCV era , especially co-colonization with other potential otopathogens A r and om sample of 2,512 children with an estimated date of birth between July 1 , 1985 and June 30 , 1986 was monitored to age 2 years , and infection data based on a question naire and medical records were compared to evaluate the validity of question naire reports of a history of acute otitis media . The cumulative incidence of acute otitis media up to age 2 years in the question naire data was lower than in the record data ( 47.8 vs. 71.0 % , respectively ) , although the number of episodes per child per year , the incidence rate for recurrent episodes , was considerably higher in the question naire data ( 1.27 vs. 0.93 ) . The amount of acute otitis media was distinctly higher among the children of the nonrespondent parents . Finally , a tendency of question naire-based data sampling to damp the associations between various risk factors and acute otitis media is displayed . The results identify possible drawbacks which must be considered when interpreting question naire-based assessment s of acute otitis media in childhood BACKGROUND : Previous studies have shown that breastfeeding is associated with reductions in the risk of common infections among infants ; however , whether breastfeeding confers longer term protection is inconclusive . METHODS : We linked data from the 2005–2007 IFPS II ( Infant Feeding Practice s Study II ) and follow-up data collected when the children were 6 years old . Multivariable logistic regression was used , controlling for sociodemographic variables , to examine associations of initiation , duration , exclusivity of breastfeeding , timing of supplementing breastfeeding with formula , and breast milk intensity ( proportion of milk feedings that were breast milk from age 0–6 months ) with maternal reports of infection ( cold/upper respiratory tract , ear , throat , sinus , pneumonia/lung , and urinary ) and sick visits in the past year among 6-year-olds ( N = 1281 ) . RESULTS : The most common past-year infections were colds/upper respiratory tract ( 66 % ) , ear ( 25 % ) , and throat ( 24 % ) infections . No associations were found between breastfeeding and colds/upper respiratory tract , lung , or urinary tract infections . Prevalence of ear , throat , and sinus infections and number of sick visits differed according to breastfeeding duration , exclusivity , and timing of supplementing breastfeeding with formula ( P < .05 ) . Among children ever breastfed , children breastfed for ≥9 months had lower odds of past-year ear ( adjusted odds ratio [ aOR ] : 0.69 [ 95 % confidence interval ( 95 % CI ) : 0.48–0.98 ] ) , throat ( aOR : 0.68 [ 95 % CI : 0.47–0.98 ] ) , and sinus ( aOR : 0.47 [ 95 % CI : 0.30–0.72 ] ) infections compared with those breastfed > 0 to <3 months . High breast milk intensity ( > 66.6 % ) during the first 6 months was associated with lower odds of sinus infection compared with low breast milk intensity ( < 33.3 % ) ( aOR : 0.53 [ 95 % CI : 0.35–0.79 ] ) . CONCLUSIONS : This prospect i ve longitudinal study suggests that breastfeeding may protect against ear , throat , and sinus infections well beyond infancy |
10,759 | 29,901,487 | Results / Discussion : Based on survey results , the CPG focuses on OMs that have acceptable clinical utility and can be used to assess change over time in a patient 's balance , gait , transfers , and patient-stated goals .
Strong , level I evidence supports the use of the Berg Balance Scale to assess changes in static and dynamic sitting and st and ing balance and the Activities-specific Balance Confidence Scale to assess changes in balance confidence .
Strong to moderate evidence supports the use of the Functional Gait Assessment to assess changes in dynamic balance while walking , the 10 meter Walk Test to assess changes in gait speed , and the 6-Minute Walk Test to assess changes in walking distance .
Best practice evidence supports the use of the 5 Times Sit-to-St and to assess sit to st and ing transfers .
Evidence was insufficient to support use of a specific OM to assess patient-stated goals across adult neurologic conditions . | Background : Use of outcome measures ( OMs ) in adult neurologic physical therapy is essential for monitoring changes in a patient 's status over time , quantifying observations and patient-reported function , enhancing communication , and increasing the efficiency of patient care .
OMs also provide a mechanism to compare patient and organizational outcomes , examine intervention effectiveness , and generate new knowledge . | Background and Purpose — This study compared the psychometric properties of 3 clinical balance measures , the Berg Balance Scale ( BBS ) , the Balance subscale of the Fugl-Meyer test ( FM-B ) , and the Postural Assessment Scale for Stroke Patients ( PASS ) , in stroke patients with a broad range of neurological and functional impairment from the acute stage up to 180 days after onset . Methods — One hundred twenty-three stroke patients were followed up prospect ively with the 3 balance measures 14 , 30 , 90 , and 180 days after stroke onset ( DAS ) . Reliability ( interrater reliability and internal consistency ) and validity ( concurrent validity , convergent validity , and predictive validity ) of each measure were examined . A comparison of the responsiveness of each of the 3 measures was made on the basis of the entire group of patients and 3 separate groups classified by degree of neurological severity . Results — The FM-B and BBS showed a significant floor or ceiling effect at some DAS points , whereas the PASS did not show these effects . The BBS , FM-B , and PASS all had good reliability and validity for patients at different recovery stages after stroke . The results of effect size demonstrated fair to good responsiveness of all 3 measures within the first 90 DAS but , as expected , only a low level of responsiveness at 90 to 180 DAS . The PASS was more responsive to changes in severe stroke patients at the earliest period after stroke onset , 14 to 30 DAS . Conclusions — All 3 measures tested showed very acceptable levels of reliability , validity , and responsiveness for both clinicians and research ers . The PASS showed slightly better psychometric characteristics than the other 2 measures Objective The primary objective of this study was to develop a quantitative test to assess ambulation in multiple sclerosis ( MS ) patients that is more accurate and sensitive than the Timed 25-foot walk ( T25FW ) . For this purpose , we developed the Six Spot Step Test ( SSST ) , which besides speed includes co-ordination and balance , to be a lower limb counterpart to the 9-Hole Peg Test ( 9HPT ) . Background The T25FW , which is the ambulation test of the MS Functional Composite ( MSFC ) , reflects only the speed component of walking . The lack of sensitivity to other components of gait adds to the floor effect . Methods and patients In the SSST , the patient is instructed to walk as quickly as possible from one end to the other of a rectangular field measuring 1 × 5 m , while kicking five cylinder blocks out of five circles marked on the floor . Some 151 MS patients with the Exp and ed Disability Status Scale ( EDSS ) score 0 - 6.5 and 64 normal controls performed the SSST and the T25FW . In addition , 41 patients performed the tests twice . Results The range of the SSST ( 4.7 - 35.1 seconds ) was wider than that of the T25FW ( 3.5 - 22.6 seconds ) . Using control mean+ 2 SD as cut off , 107 patients had abnormal SSST , while 100 patients had abnormal T25FW . The T25FW ( mean ) increased 2.1 seconds over the EDSS range of 0 - 4.0 , while the SSST increased 4.9 seconds . The intra-class correlation between repeated tests ( r ) was 0.95 for the SSST and 0.96 for the T25FW . The correlation between the SSST and the T25FW was high ( r=0.92 ) . Conclusion The SSST seems to be superior to the T25FW in terms of dynamic range , floor effect and discriminatory power . The SSST is a relevant alternative for the T25FW as the ambulation component of the MSFC Background The COSMIN checklist is a tool for evaluating the method ological quality of studies on measurement properties of health-related patient-reported outcomes . The aim of this study is to determine the inter-rater agreement and reliability of each item score of the COSMIN checklist ( n = 114 ) . Methods 75 articles evaluating measurement properties were r and omly selected from the bibliographic data base compiled by the Patient-Reported Outcome Measurement Group , Oxford , UK . Raters were asked to assess the method ological quality of three articles , using the COSMIN checklist . In a one-way design , percentage agreement and intraclass kappa coefficients or quadratic-weighted kappa coefficients were calculated for each item . Results 88 raters participated . Of the 75 selected articles , 26 articles were rated by four to six participants , and 49 by two or three participants . Overall , percentage agreement was appropriate ( 68 % was above 80 % agreement ) , and the kappa coefficients for the COSMIN items were low ( 61 % was below 0.40 , 6 % was above 0.75 ) . Reasons for low inter-rater agreement were need for subjective judgement , and accustom to different st and ards , terminology and definitions . Conclusions Results indicated that raters often choose the same response option , but that it is difficult on item level to distinguish between articles . When using the COSMIN checklist in a systematic review , we recommend getting some training and experience , completing it by two independent raters , and reaching consensus on one final rating . Instructions for using the checklist are improved Background and Purpose — This study compared the validity , responsiveness , and interrater reliability of 3 mobility measures in stroke patients from the acute stage up to 180 days after stroke onset . The 3 measures were the Rivermead Mobility Index ( RMI ) , a modified RMI ( MRMI ) , and the Mobility Subscale of the Stroke Rehabilitation Assessment of Movement ( STREAM ) . Methods — The validity and responsiveness of the 3 mobility measures were prospect ively examined by monitoring 57 stroke patients with the measures and the Barthel Index at 14 , 30 , 90 , and 180 days after stroke onset . Two individual raters used the 3 measures to evaluate a different sample of 40 patients on 2 separate occasions to determine the interrater reliability . Results — The Spearman & rgr ; between STREAM and MRMI was ≥0.92 ; the intraclass correlation coefficient ( ICC , a measure of agreement ) between them was ≥0.89 , indicating high concurrent validity of both measures . RMI showed a moderate to high relationship and agreement with STREAM and MRMI ( & rgr;≥0.78 , ICC≥0.5 ) . Responsiveness of the 3 measures was high before 90 days after stroke onset ( st and ardized response mean ≥0.83 ) and low at 90 to 180 days after stroke onset ( 0.2≤st and ardized response mean≤0.4 ) . The score changes of the 3 measures at each stage were significant ( P ≤0.05 ) , except for RMI and MRMI at 90 to 180 days after stroke onset . The interrater agreement of the 3 measures was high ( ICC≥0.92 ) . Conclusions — All 3 measures examined showed acceptable levels of reliability , validity , and responsiveness in stroke patients . The psychometric characteristics of STREAM were slightly superior to those of the other 2 measures among our patients . We prefer and recommend STREAM for measuring mobility disability in stroke patients Background and Purpose — We compared the test-retest reliability , validity , and responsiveness of the Dynamic Gait Index , the 4-item Dynamic Gait Index , and the Functional Gait Assessment for assessment of walking in patients with stroke . Methods — Forty-five out patients participating in the validity and responsiveness study were tested using the 3 walking measures as well as the 10-m walk test , Barthel Index , and Postural Assessment Scale for Stroke Patients . We tested them during the first week , then again after 2 months and 5 months of therapy . Another 48 chronic patients completed the 3 measures twice , 1 week apart , in the test-retest reliability study . Results — Thirty-five participants completed 3 time-point assessment s. The Functional Gait Assessment showed the least floor and ceiling effects , indicating it has the best discriminative ability for patients with stroke with high walking function . We found the 3 measures were highly correlated with each other , indicating excellent concurrent validity , and all measures at the first week of therapy were moderately to highly correlated with the Barthel Index scores at 5 months , indicating good predictive validity . Responsiveness of the 3 measures was moderate during a 5-month period , and all showed good test-retest reliability . The minimal detectable changes between tests indicate acceptable r and om error . Conclusions — All 3 measures showed sufficient validity , responsiveness , and reliability for assessment of walking function in patients with stroke undergoing rehabilitation , but the Functional Gait Assessment is recommended for its psychometric properties Study design : The 10-m walk test ( 10MWT ) and the 6-min walk test ( 6MWT ) have been recommended for assessment of walking in spinal cord injury ( SCI ) patients . The study was design ed on test – retest analysis of the 10MWT and 6MWT . Objectives : The objective of this study was to assess validity/reliability of different methods of performing the tests . Setting : The study was set at an SCI unit of a rehabilitation hospital . Patients and methods : A total of 37 patients ; whose median age was 58.5 years ( interquartile range 40–66 , full range 19–77 ) ; median time since onset of SCI was 24 months ( interquartile range 16.25–70.5 , full range 6–109 ) . Non-traumatic etiology in 20 out of 37 patients ; level : 12C , 14 T and 11L ; American Spinal Injury Association Impairment Scale grade : 35D/2C . Assessment with the 10MWT ( with or without dynamic start ) and the 6MWT ( short or long track ) by two blinded raters to evaluate inter/intra-rater reliabilities . Results : The 10MWT was performed in a median of 19 s ( 25th–75th interquartile range 13–28 ) with the dynamic start and of 18.4 s ( 25th–75th interquartile range 12.6–29.9 ) with the static start ( P=0.092 ) . The correlation between the results of the two methods was between 0.98 and 0.99 . The inter- and intra-rater reliabilities were between 0.95 and 0.99 for both the methods . The 6MWT showed significant differences according to the track length : patients walked a median of 226.7 m ( 25th–75th interquartile range 123.2–319 ) on the longer track and of 187.6 m ( 25th–75th interquartile range 69.7–240.6 ) on the short one ( P<0.001 ) . The correlation between the results of the two methods was between 0.91 and 0.93 . The inter- and intra-rater reliabilities were between 0.98 and 0.99 . Conclusion : The 10MWT shows high inter/intra-rater reliability and shows comparable results with both dynamic and static start . The different testing conditions of the 6MWT ( track/turns ) results in significant differences that need st and ardization for use in future trials Background The minimal detectable change ( MDC ) is the smallest amount of difference in individual scores that represents true change ( beyond r and om measurement error ) . The MDCs of the Timed “ Up & Go ” Test ( TUG ) and the Dynamic Gait Index ( DGI ) in people with Parkinson disease ( PD ) are largely unknown , limiting the interpretability of the change scores of both measures . Objective The purpose of this study was to estimate the MDCs of the TUG and the DGI in people with PD . Design This investigation was a prospect i ve cohort study . Methods Seventy-two participants were recruited from special clinics for movement disorders at a university hospital . Their mean age was 67.5 years , and 61 % were men . All participants completed the TUG and the DGI assessment s twice , about 14 days apart . The MDC was calculated from the st and ard error of measurement . The percentage MDC ( MDC% ) was calculated as the MDC divided by the mean of all scores for the sample . Furthermore , the intraclass correlation coefficient was used to examine the reproducibility between testing sessions ( test-retest reliability ) . Results The respective MDC and MDC% of the TUG were 3.5 seconds and 29.8 , and those of the DGI were 2.9 points and 13.3 . The test-retest reliability values for the TUG and the DGI were high ; the intraclass correlation coefficients were .80 and .84 , respectively . Limitations The study sample was a convenience sample , and the participants had mild to moderately severe PD . Conclusions The results showed that the TUG and the DGI have generally acceptable r and om measurement error and test-retest reliability . These findings should help clinicians and research ers determine whether a change in an individual patient with PD is a true change OBJECTIVES To estimate the magnitude of small meaningful and substantial individual change in physical performance measures and evaluate their responsiveness . DESIGN Secondary data analyses using distribution- and anchor-based methods to determine meaningful change . SETTING Secondary analysis of data from an observational study and clinical trials of community-dwelling older people and subacute stroke survivors . PARTICIPANTS Older adults with mobility disabilities in a strength training trial ( n=100 ) , subacute stroke survivors in an intervention trial ( n=100 ) , and a prospect i ve cohort of community-dwelling older people ( n=492 ) . MEASUREMENTS Gait speed , Short Physical Performance Battery ( SPPB ) , 6-minute-walk distance ( 6MWD ) , and self-reported mobility . RESULTS Most small meaningful change estimates ranged from 0.04 to 0.06 m/s for gait speed , 0.27 to 0.55 points for SPPB , and 19 to 22 m for 6MWD . Most substantial change estimates ranged from 0.08 to 0.14 m/s for gait speed , 0.99 to 1.34 points for SPPB , and 47 to 49 m for 6MWD . Based on responsiveness indices , per-group sample sizes for clinical trials ranged from 13 to 42 for substantial change and 71 to 161 for small meaningful change . CONCLUSION Best initial estimates of small meaningful change are near 0.05 m/s for gait speed , 0.5 points for SPPB , and 20 m for 6MWD and of substantial change are near 0.10 m/s for gait speed , 1.0 point for SPPB , and 50 m for 6MWD . For clinical use , substantial change in these measures and small change in gait speed and 6MWD , but not SPPB , are detectable . For research use , these measures yield feasible sample sizes for detecting meaningful change Background and Purpose : Distinguishing between a clinical ly significant change and change due to measurement error can be difficult . The purpose of this study was to determine test-retest reliability and minimal detectable change for the Berg Balance Scale ( BBS ) , forward and backward functional reach , the Romberg Test and the Sharpened Romberg Test ( SRT ) with eyes open and closed , the Activities-specific Balance Confidence ( ABC ) Scale , the Six-Minute Walk Test ( 6MWT ) , comfortable and fast gait speed , the Timed “ Up & Go ” Test ( TUG ) , the Medical Outcomes Study 36-Item Short-Form Health Survey ( SF-36 ) , and the Unified Parkinson Disease Rating Scale ( UPDRS ) in people with parkinsonism . Subjects : Thirty-seven community-dwelling adults with parkinsonism ( mean age=71 years ) participated . The Hoehn and Yahr Scale median score of 2 was on the lower end of the scale ; however , the scores ranged from 1 to 4 . Methods : Subjects were tested twice by the same raters , with 1 week between tests . Test-retest reliability was calculated using intraclass correlation coefficients ( ICCs ) . Minimal detectable change was calculated using a 95 % confidence interval ( MDC95 ) . Results : The ICCs for test-retest reliability were above .90 for the BBS , ABC Scale , SRT with eyes closed , 6MWT , and comfortable and fast gait speeds . The MDC95 values for those functional tests were : BBS=5/56 , ABC Scale=13 % , SRT with eyes closed=19 seconds , 6MWT=82 m , comfortable gait speed=0.18 m/s , and fast gait speed=0.25 m/s . The ICCs for test-retest reliability of SF-36 scores were above .80 , with the exception of the social functioning subscale . The MDC95 values for the SF-36 ranged between 19 % and 45 % . The MDC95 values for the UPDRS Activities of Daily Living section , Motor Examination section , and total scores were 4/52 , 11/108 , and 13/176 , respectively . Discussion and Conclusion : Minimal detectable change values are useful to therapists in rehabilitation and wellness programs in determining whether change during or after intervention is clinical ly significant . High test-retest reliability of scores for the BBS , ABC Scale , SRT with eyes closed , 6MWT , and gait speed make them trustworthy functional assessment s in people with parkinsonism . The SF-36 and UPDRS provide quality -of-life and disease severity rating values in the ongoing assessment of people with parkinsonism Physiotherapists have traditionally relied on impairment measures such as range of motion and muscle strength to monitor patient progress . The impact of treatment on patients ' daily activities can be assessed with valid and reliable question naires , but the use of st and ardized question naires by physiotherapists appeared to be limited . A range of strategies were implemented that aim ed to increase physiotherapists ' use of st and ardized measures of functional activities . A simple r and om sample of 300 was drawn from a data base of physiotherapy providers to a transport accident scheme , and was surveyed in March and September 2003 , with response rates of 51 % and 55 % , respectively . There was a statistically significant ( P<.05 ) increase in reported use of seven question naires and a significant reduction in the perception of barriers that were targeted by the interventions The most frequently utilized tests were a pain rating scale and question naires for lumbar and cervical problems . Physiotherapists ' attitudes to outcome measurement were generally positive although there was a small but statistically significant ( P=.02 ) reduction in mean attitude score over the re-test period . Physiotherapists in the population sample d significantly increased their reported use of a range of st and ardized outcome measures over the re-test period . The trend towards greater objectivity in measuring the progress of rehabilitation can enable physiotherapists to develop improved treatment plans with the patients ' needs at the centre of the equation Purpose : To investigate the relative utility of Canadian Occupational Performance Measure ( COPM ) ( adapted for children ) and Goal Attainment Scaling ( GAS ) as outcome measures for paediatric rehabilitation . Methods : A two-group pre – post design investigated the impact of a 3-month programme . Forty-one children with spastic hemiplegic cerebral palsy ( mean 3.9 years ; GMPM level 1 ; 21 boys , 10 girls ) were r and omized to occupational therapy only and occupational therapy plus one Botulinum Toxin A injection . The latter was considered a ‘ proven ’ intervention for the purpose of this instrumentation study . Intervention impact was investigated using GAS and COPM . Instrument sensitivity , convergent validity , goal /problem profiles and administration were evaluated . Results : Both instruments were sensitive to within group change and detected significant between group change . Likert scale coding for GAS scores was more sensitive than the traditional weighted GAS or COPM . Different constructs were measured by each instrument . COPM was more time efficient in training , development and administration . Conclusion : Study aim , logistic and re source factors should guide the choice of COPM and /or GAS instruments as both are sensitive to change with a proven intervention and both evaluate different constructs 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 Goal attainment scaling ( GAS ) holds promise as an idiographic approach for measuring outcomes of psychosocial interventions in community setting s. GAS has been criticized for untested assumptions of scaling level ( i.e. , interval or ordinal ) , inter-individual equivalence and comparability , and reliability of coding across different behavioral observation methods . We tested assumptions of e quality between GAS descriptions for outcome measurement in a r and omized trial ( i.e. , measurability , equidistance , level of difficulty , comparability of behavior sample s collected from teachers vs. research ers and live vs. videotape ) . Results suggest GAS descriptions can be evaluated for equivalency , that teacher collected behavior sample s are representative , and that varied sources of behavior sample s can be reliably coded . GAS is a promising measurement approach . Recommendations are provided to ensure method ological quality OBJECTIVE To evaluate the internal and absolute reliability and construct validity of the Activities-Specific Balance Confidence ( ABC ) scale and a new Canadian French version ( ABC-CF ) of it among people with stroke . DESIGN Cross-sectional data from a r and omized controlled trial . SETTING Community . PARTICIPANTS Ninety-one people with a residual walking deficit between 57 and 386 days poststroke . INTERVENTIONS Not applicable . MAIN OUTCOME MEASURES The ABC and ABC-CF scales , Berg Balance Scale ( BBS ) , comfortable and maximum gait speeds , Timed Up & Go ( TUG ) test , 6-minute walk test ( 6MWT ) , Barthel Index , physical function scale of the Medical Outcomes Study 36-Item Short-Form Health Survey , Geriatric Depression Scale ( GDS ) , and the EQ-5D visual analog scale ( EQ VAS ) . RESULTS Internal consistency ( Cronbach alpha ) was .94 and .93 and the st and ard error of measurement was 5.05 and 5.13 for the ABC ( n=51 ) and the ABC-CF ( n=35 ) scales , respectively . Spearman rho values ranged from .30 to .60 for the ABC scale and from .45 to .68 on the ABC-CF scale for associations with scores on the BBS , comfortable and maximum gait speeds , TUG , 6MWT , Barthel Index , physical function scale , GDS , and EQ VAS . CONCLUSIONS Evidence of internal and absolute reliability and of construct validity of the ABC and the ABC-CF scales supports their use for cross-sectional measurements of balance self-efficacy among community-dwelling people in the first year poststroke OBJECTIVE To select a question naire and walking capacity test based on comparison of clinimetric properties and mutual association to be used as " core " qualifiers for physical functioning in patients with late-onset sequelae of poliomyelitis . DESIGN Repeated- measures at 3-week intervals . SUBJECTS An unselected sample of 57 patients with late-onset sequelae of poliomyelitis from a prospect i ve cohort study . METHODS Physical functioning scales from Short Form-36 ( SF36-PF ) , Western Ontario and McMaster Universities Osteoarthritis Index ( WOMAC-PF ) and Nottingham Health Profile ( NHP-PM ) . Timed-Up- and -Go test , 10-m walking at self-preferred and maximum speed , and 2-min walk test . RESULTS Test-retest reliability of SF36-PF and WOMAC-PF was good ( intraclass correlation coefficient ( ICC ) 0.92 and 0.89 , respectively ) , sufficient for NHP-PM ( ICC 0.74 ) and excellent for walking tests ( ICC 0.93 - 0.96 ) . The smallest detectable changes were 18.4 and 16.5 , respectively , for WOMAC-PF and SF36-PF , and 26.7 for NHP-PM . The smallest detectable change was best for the 2-min walk test ( 22.9 m ) . Correlation coefficients between question naires and walking tests ranged from 0.32 to 0.69 , with the highest correlation between the SF36-PF and 2-min walk test . CONCLUSION The SF36-PF and 2-min walk test are recommended as core qualifiers for physical functioning , the major increasing disability in late-onset sequelae of poliomyelitis , to assess perceived physical performance and walking capacity in research and clinical practice Background : St and ardized instruments for measuring patients ' activity limitations and participation restrictions have been advocated for use by rehabilitation professionals for many years . The available literature provides few recent reports of the use of these measures by physical therapists in the United States . Objective : The primary purpose of this study was to determine : ( 1 ) the extent of the use of st and ardized outcome measures and ( 2 ) perceptions regarding their benefits and barriers to their use . A secondary purpose was to examine factors associated with their use among physical therapists in clinical practice . Design : The study used an observational design . Methods : A survey question naire comprising items regarding the use and perceived benefits and barriers of st and ardized outcome measures was sent to 1,000 r and omly selected members of the American Physical Therapy Association ( APTA ) . Results : Forty-eight percent of participants used st and ardized outcome measures . The majority of participants ( > 90 % ) who used such measures believed that they enhanced communication with patients and helped direct the plan of care . The most frequently reported reasons for not using such measures included length of time for patients to complete them , length of time for clinicians to analyze the data , and difficulty for patients in completing them independently . Use of st and ardized outcome measures was related to specialty certification status , practice setting , and the age of the majority of patients treated . Limitations : The limitations included an unvali date d survey for data collection and a sample limited to APTA members . Conclusions : Despite more than a decade of development and testing of st and ardized outcome measures appropriate for various conditions and practice setting s , physical therapists have some distance to go in implementing their use routinely in most clinical setting s. Based on the perceived barriers , alterations in practice management strategies and the instruments themselves may be necessary to increase their use OBJECTIVE To evaluate psychometric properties of 16-item and 7-item Falls Efficacy Scale-International ( FES-I ) in people with multiple sclerosis ( MS ) . DESIGN Validation and prospect i ve cohort study . SETTING People with MS living in metropolitan areas . PARTICIPANTS Community-dwelling people with MS ( N=169 ; aged 21 - 73y ) who were referred to Multiple Sclerosis Australia for physiotherapy assessment . INTERVENTIONS Not applicable . MAIN OUTCOME MEASURES FES-I scores and a range of sociodemographic , physical , and neuropsychological measures . RESULTS The mean score for the 16-item FES-I was 34.9±11.2 , and the mean score for the 7-item FES-I was 14.7±4.7 . FES-I total scores were normally distributed : skewness of .35 ( SEM=.19 ) for the 16-item and .47 ( SEM .19 ) for the 7-item FES-I , indicating the absence of floor and ceiling effects . Internal reliability was excellent , with Cronbach 's alpha values of .94 ( 16-item ) and .86 ( 7-item ) . Rasch analyses indicated that the structure and measurement properties were better for the 7-item FES-I than for the 16-item FES-I. Construct validity of both scales was supported by sensitivity to group differences relating to demographic characteristics and fall-risk factors . CONCLUSIONS The findings indicate that both 16-item and 7-item versions of the FES-I provide valuable information about the fear of falling in people with MS . However , the 7-item version of FES-I has better psychometric properties in people with MS Objective : Within a sample of acute post-stroke patients , to compare the score on the Berg Balance Scale and the Static Balance Test for validity , inter-rater reliability , and the expenditure of time . Design : Prospect i ve , intra-individual , cross-sectional evaluation study . Setting : Acute stroke unit of a university hospital in Germany . Participants : A total of 53 patients with acute stroke who did not have other pathology affecting their balance . Main outcome measure : For intra-individual comparisons of the Berg Balance Scale and the Static Balance Test , Pearson correlation coefficients were calculated . For inter-rater reliability , Bl and Altman plots were drawn and the corresponding mean difference and limits of agreement were calculated . Results : The Static Balance Test took three to five minutes ; the Berg Balance Scale 20–30 minutes . There was a high correlation between the scores on the Berg Balance Scale and the Static Balance Test ( r = 0.91 ) . For the Berg Balance Scale , the mean difference between the two raters was 0.13 and the limits of agreement were small ( –0.25 ; 0.51 ) . For the Static Balance Test , the mean difference between the two raters was −0.02 and also the limits of agreement ( –0.06 ; 0.02 ) were even smaller than for the Berg Balance Scale . Both scales showed excellent inter-rater reliability . Conclusion : The Static Balance Test was compared with the Berg Balance Scale and turned out to be equally valid , more reliable , and takes much less time . For the moment , the scale can be recommended for the use in acute stroke care , especially for the daily routine therapy OBJECTIVES To determine whether a practice effect occurs across 2 trials of the six-minute walk test ( 6MWT ) among community-dwelling people within 1 year poststroke and to identify characteristics distinguishing people who show a practice effect from those who do not . DESIGN Secondary analysis of scores on 2 trials of the 6MWT administered approximately 30 minutes apart at baseline in a r and omized controlled trial . SETTING General community . PARTICIPANTS People ( N=91 ) living in the community with a residual walking deficit within the first year of a first or recurrent stroke . INTERVENTIONS Not applicable . MAIN OUTCOME MEASURE Distance walked on the 6MWT . RESULTS Mean 6MWT scores + /- SD for trials 1 and 2 were 196+/-119 m and 197+/-126 m , respectively ( n=83 ) . The mean difference in 6MWT performance across trials was 0+/-35 m ( 95 % confidence interval [ CI ] , -7 to 8 m ) . The Pearson correlation coefficient between 6MWT distances was .96 ( P<.001 ) , and the intraclass correlation coefficient was .98 ( 95 % CI , .97-.99 ) . The Bl and -Altman plot showed no clear pattern . Participants whose improvement was equal to or greater than the minimal detectable change of 29 m between trials ( 14 % ) did not significantly differ from those in the rest of the study sample ; however , they tended to be younger ( P=.05 ) and more likely to have a mild or moderate gait deficit ( P=.06 ) . CONCLUSIONS Findings do not support a practice effect across 2 trials of the 6MWT in individuals within 1 year poststroke . Thus , a practice walk does not appear necessary . Further research is recommended to evaluate the influence of young age , acute stroke , and mild-to-moderate gait deficit on practice effects OBJECTIVE To compare goal attainment scaling ( GAS ) and st and ardized measures in evaluation of person-centred outcomes in neurorehabilitation . DESIGN A prospect i ve cohort analysis from a tertiary inpatient neuro-rehabilitation service for younger adults with complex neurological disability . SUBJECTS/ PATIENTS Consecutive patients ( n = 164 ) admitted for rehabilitation following acquired brain injury ( any cause ) over 3 years . Mean age 44.8 ( st and ard deviation 14.4 ) years . DIAGNOSIS 66 % strokes , 18 % trauma , 16 % other . Male : female ratio 102:62 . METHODS GAS-rated achievement of 1 - 6 patient-selected goals was compared with the Functional Assessment Measure ( UK FIM+FAM ) , and Barthel Index ( BI ) , rated on admission and discharge . Personal goals were mapped retrospectively to the FIM+FAM and International Classification of Functioning , Disability and Health ( ICF ) . RESULTS Median ( interquartile range ; IQR ) GAS T-scores were 50.0 ( 44.2 - 51.8 ) and moderately correlated with changes in FIM+FAM and BI ( both rho 0.38 ( p < 0.001 ) ) . St and ardized response means were 2.2 , 1.6 and 1.4 for GAS , FIM+FAM and BI , respectively . Of 667 personal goals set , 495 ( 74 % ) were fully achieved . Although 413 ( 62 % ) goals were reflected by changes in FIM+FAM , over one-third of goals were set in other areas . CONCLUSION GAS appeared to be more responsive , and captured gains beyond the FIM+FAM , thus providing added value as an adjunct to outcome measurement in patients with complex disability OBJECTIVE Goal attainment scaling ( GAS ) is a measurement approach used extensively in mental health . It accommo date s multiple individual patient goals , yet retains mathematical properties allowing comparisons between patients . This study was carried out to investigate the feasibility and measurement properties of GAS in a geriatric care setting . DESIGN Prospect i ve descriptive study . SETTING The geriatric restorative care service and geriatric assessment unit at Camp Hill Hospital , a 350-bed tertiary care facility in Halifax , Canada . PATIENTS Fifteen patients aged 65 to 94 who were consecutively admitted to the two geriatric services ( mean age 79 years , mean length of stay 37 days , 9 females ) . INTERVENTION Goal Attainment follow-up guides were developed independently for each patient by two geriatricians after a comprehensive assessment of the patient . These guides were later compared to assess level of agreement in goal setting and scale development . A single goal attainment follow-up guide was then developed for each patient by consensus of the two geriatricians . At the end of the follow-up , the guides were scored independently for each patient by one of the geriatricians and by the patient 's primary care nurse . MAIN OUTCOME MEASURES GAS scores were determined on admission and discharge . Each patient also received admission and discharge ratings on the Barthel Index as well as a global rating of outcome ( on a subjective 10-point scale ) by a geriatrician who was blinded to the Goal Attainment follow-up score . RESULTS GAS proved feasible , requiring 15 - 20 minutes to scale an average of six goals per patient . GAS also appears reliable . Of 87 goals , 71 ( 82 % ) were identified independently by two geriatricians , and the remainder were determined by consensus . This is also a measure of content validity . The physician-nurse inter-rater reliability was 0.87 ( intraclass correlation ) . Concurrent validity was assessed by correlation with the Barthel Index ( r = 0.86 ) and the global clinical outcome rating ( r = 0.82 ) . Content validity was also assessed by comparing our goal areas with those identified in recent consensus reports on geriatric assessment . Of these 13 assessment areas , 12 appeared to be reasonably well covered while one assessment area ( sexual problems ) was not identified for any of the 15 patients . CONCLUSIONS GAS appears to be a feasible method of goal setting and outcome evaluation in geriatric care setting s , with promising reliability and validity BACKGROUND AND PURPOSE One must underst and the potentials and limitations of all tests used to evaluate interventions . The aim of the present study was to clarify the reproducibility , smallest percentage difference needed to be able to detect a genuine change and correlation regarding the 10-m and 30-m timed walks ( 10TW 30TW ) and the ' timed up and go ' ( TUG ) test in people with moderate multiple sclerosis ( MS ) . METHOD A repeated- measures design was used , with r and omization into two groups and different time intervals used for testing . The 10TW and 30TW were performed three times and TUG twice at each testing . Self-selected speed was used for 10TW and forced speed ( quickly but safely ) for 30TW and TUG . Forty-three people were tested on three occasions within one week . Each person was tested at approximately the same time of the day and by the same physiotherapist on each occasion . RESULTS The reproducibility was very high . For a single testing occasion , the intraclass correlation was 0.97 for the 10TW and 0.98 for the 30TW and TUG . The smallest percentage difference needed to be able to detect a genuine change in the entire study group was approximately -23 % or + 31 % for either the 1OTW or TUG . It was evident from the 30TW testing results that lower values applied to those with less ( -14 % to + 17 % ) rather than more ( -38 % or + 60 % ) disability . The correlation between all tests for the entire study group was 0.85 ( 0.76 - 0.91 ) . CONCLUSION It is sufficient to use only one attempt and to choose only one of the tests when evaluating people with moderate MS . In the case of the 30TW greater attention must be paid to the degree of disability when determining the smallest percentage difference needed to establish a genuine change , OBJECTIVES To use goal attainment scaling ( GAS ) to measure clinical ly important functional change in persons with multiple sclerosis ( MS ) and to assess its responsiveness compared with st and ard measures used to evaluate progress in rehabilitation . DESIGN Prospect i ve , observational cohort study . SETTING Tertiary inpatient rehabilitation unit in Victoria , Australia . PARTICIPANTS Consecutive sample of 24 persons with MS admitted for comprehensive rehabilitation program . The male-to-female ratio was 10:14 , and the mean age + /- st and ard deviation was 52.0+/-8.3 years ( range , 37 - 62y ) . Over half ( n=14 [ 58.3 % ] ) had secondary progressive MS . INTERVENTIONS Not applicable . MAIN OUTCOME MEASURES GAS scores were calculated for 5 to 10 priority goals set prospect ively by each patient in agreement with the multidisciplinary treating team and compared with st and ard outcome measures -the FIM instrument and Barthel Index-rated on admission and discharge from the program . Patients were categorized into responders and nonresponders based on an overall clinical global impression . RESULTS Of 203 selected goals , 167 were achieved at the predicted level . GAS recorded outcomes for 105 individualized goals not measured by the FIM and Barthel Index . Although all 3 measures showed statistically significant change from admission to discharge ( P<.001 ) , only GAS scores strongly correlated with the Clinical Global Impression scale ( rho=-.86 , P<.001 ) . GAS discharge scores differed significantly between the responder and nonresponder groups ( Mann-Whitney , z=-3.78 , P<.001 ) . Different measures of effect size gave different results , but GAS was consistently more responsive than either the FIM or Barthel Index . CONCLUSIONS This preliminary study suggests that GAS is a responsive and useful outcome measure for the rehabilitation of persons with MS , providing added value to st and ardized outcome measurement Background . Persons with spinal cord injury who are able to walk are at risk for falls . Objective . The objectives were to investigate if the Berg Balance Scale ( BBS ) can discriminate those with a propensity to fall ; to determine whether the BBS is associated with mobility measures , fear of falling , and muscle strength ; and to assess interobserver reliability . Methods . The measurement tools used were the BBS , the Spinal Cord Independence Measure , the Falls Efficacy Scale ( FES-I ) , the Walking Index for Spinal Cord Injury , the 10-m walk test , and the st and ard neurological classification including motor scores ( MS ) . Falls were recorded retrospectively for the previous month and prospect ively for the subsequent 4 months . To determine interobserver reliability , BBS performance was videotaped and analyzed by additional physical therapists . Associations between BBS and the number of falls , measures of mobility , FES-I , and MS were calculated using Spearman correlations . The interobserver reliability was quantified using Kendall ’s coefficient of concordance and intraclass correlation coefficients ( ICCs ) . Results . Forty-two participants were included of whom 26 sustained 1 or more falls . BBS performance correlated with measures of mobility , FES-I , and MS ( rs = -.83 to .93 ; P < .001 ) but not with the number of falls ( rs = -.17 ; P = .28 ) . The interobserver reliability was excellent , both for single items ( .84-.98 , P < .001 ) and for the total score ( ICC = .95 ; 95 % confidence interval = 0.910 - 0.975 ) . Conclusions . The BBS proved to be reliable and to relate well with other mobility measures , fear of falling , and muscle strength . However , it was unable discriminate between people who did fall and people who did not fall The Berg Balance Scale ( BBS ) was design ed to help determine change in functional st and ing balance over time . The purpose of this paper was to estimate the minimum detectable change score ( MDC ) using the st and ard error of measure ( SEM ) , thereby providing a means to decide if genuine change had occurred . Calculation of the agreement regarding the presence of change as determined by the MDC and clinicians ' perceptions was performed to give an indication of the validity of this criterion value . Forty-eight subjects who were receiving inpatient rehabilitation after stroke were assessed on consecutive days by two raters using the BBS . The MDC analysis suggests that a change of + /- 6 BBS points is necessary to be 90 % confident of genuine change . Only 25/45 subjects showed agreement between the statistically derived presence of change and clinicians ' perceptions of change . The lack of agreement may relate to the validity of the SEM/MDC methodology to determine the criterion BBS value , the heterogeneity of the subjects , or the use of clinician gestalt impressions of change Objective . This study examined test-retest agreement and measurement errors for the Rivermead Mobility Index ( RMI ) and the Mobility subscale of the Stroke Rehabilitation Assessment of Movement ( M-STREAM ) in patients with chronic stroke and mild to moderate disability . The authors aim ed to determine the level of agreement between test and retest as well as the extent to which a mobility score varies on test-retest measurements . Methods . Both mobility measures were tested on 50 chronic stroke patients twice , 7 days apart . Intraclass correlation coefficient ( ICC2,1 ) , a relative reliability index , was used to examine the level of agreement between test and retest . Absolute reliability indices , including the st and ard error of measurement and the smallest real differences , were used to determine the extent to which the mobility scores varied due to chance variation in measurement . Results . Test-retest agreements were excellent for both mobility measures . The st and ard errors of measurement of the RMI and the M-STREAM , representing the smallest change threshold that indicates a real improvement ( beyond measurement error ) for a group of individuals , were 0.8 and 1.5 , respectively . The smallest real differences of the RMI and the M-STREAM , exhibiting the smallest change threshold that indicates a real improvement for a single individual , were 2.2 and 4.2 , respectively . Conclusion . The RMI and the M-STREAM have high agreement between the test-retest measurements with acceptable measurement errors due to variation in measurement . The 2 measures can be used by clinicians and research ers to assess the mobility performance and monitor changes over time in stroke patients BACKGROUND The multiple sclerosis functional composite ( MSFC ) is a multidimensional , MS-specific outcome measure for use in clinical trials , comprising three tests : timed 25-foot walk ( T25FW ) , paced auditory serial addition ( PASAT ) , and 9-hole peg ( 9HP ) . OBJECTIVE To assess interrater and intrarater reliability and practice /fatigue effects in the MSFC . METHODS The MSFC was administered by two neurologists after a formal training session to 32 MS out patients . Patients were assessed four times by one examiner and twice by the other . The six tests were administered in a single day , with at least 20 min of rest between them . The examiners were blinded to the results of previous assessment s. Testing order was r and om . RESULTS Interrater reliability was excellent , with intraclass correlation coefficients ( ICC ) ranging from 0.93 for 9HP ( 95 % confidence interval [ CI ] 0.84 - 0.96 ) to 0.99 for T25FW ( 95 % CI 0.97 - 0.99 ) . For intrarater reliability , ICC ranged from 0.93 for PASAT ( 95 % CI 0.82 - 0.97 ) to 0.98 for T25FW ( 95 % CI 0.93 - 1.00 ) . We found no practice effect for T25FW after the first administration . However , performance improved with testing over the first three sessions for PASAT and over the first four sessions for 9HP . CONCLUSIONS The MSFC is characterised by excellent reliability . Practice effects for the three MSFC components differed , being negligible for T25FW and evident for PASAT and 9HP . To improve efficiency , we suggest one prebaseline administration of T25FW , three of PASAT and four of 9HP BACKGROUND The Multiple Sclerosis Walking Scale ( MSWS-12 ) was developed to measure the impact of multiple sclerosis on walking . Many other disabling neurological conditions affect patients ' ability to walk , and a generic measure of walking could provide valuable insights into patients ' perceptions in clinical trials and epidemiological studies as well as routine clinical practice . OBJECTIVE To evaluate the clinical usefulness and psychometric properties of the Walking Impact Scale ( Walk-12 ) , a modified version of the MSWS-12 , in patients with neurological conditions . DESIGN A prospect i ve , observational study of 120 consecutive patients admitted for rehabilitation . The Walk-12 was used to measure the impact of neurological disability on walking . Traditional psychometric methods ( data quality , scaling assumptions , targeting , reliability , validity and responsiveness ) were used to assess the Walk-12 . Transition questions were used on discharge to measure perception of change . Outcome was also measured using the timed walk test ( TWT ) , Barthel Index ( BI ) and Functional Independence Measure ( FIM ) . RESULTS For the total group , missing data were few , scaling assumptions were satisfied , and internal consistency was 0.94 . Correlations between the Walk-12 and TWT , BI and FIM motor score were moderate ( r=-0.58 , -0.26 , -0.31 ) . Responsiveness of the Walk-12 was high ( effect size=1.12 ) . Relationships between effect size and patients ' and physiotherapists ' opinion of change in walking demonstrated good concordance . Preliminary subgroup analyses indicate satisfactory psychometric properties across different neurological conditions ; however , sample numbers in these analyses are small . CONCLUSIONS In this sample of neurologically disabled patients the Walk-12 was clinical ly useful and satisfied st and ard psychometric criteria . This provides preliminary evidence that it may be suitable as a generic measure of walking ability Abstract Purpose : The reliability of the Modified Rivermead Mobility Index ( MRMI ) has not previously been investigated in the very early post-stroke phase . The aim of the study was to evaluate inter-rater and intra-rater reliability and internal consistency in patients , 1–14 d post-stroke . Method : A cohort study with repeated measures within 24 h , on 37 patients , 1–14 d post-stroke was conducted . Inter-rater ( two raters ) and intra-rater ( one rater ) reliability was analyzed using weighted kappa ( κ ) statistics and internal consistency with Cronbach ’s alpha and intra-class correlation ( ICC ) , 3.k . Results : Inter-rater and intra-rater reliability was excellent ( ICC coefficient 0.97 and 0.99 ) for MRMI summary score . Intra-rater exact agreement for separate items was between 77 % and 97 % ; κ between 0.81 and 0.96 . Inter-rater exact agreement for separate items was between 68 % and 92 % ; κ 0.59–0.87 . The internal consistency was high ( α 0.96 ; ICC 3.k 0.99 ) . Conclusion : The MRMI is a reliable measure of physical mobility in the early post-stroke phase BACKGROUND Mobility assessment in Multiple Sclerosis ( MS ) is crucial for trials and individual patient counseling . Up to now , st and ard tests as the Timed 25-Foot Walk ( T25FW ) are restricted by floor effects in mildly disabled patients . The 3-meter Timed T and em Walk ( TTW ) as a possibly more sensitive measure has not been investigated yet . OBJECTIVE To investigate sensitivity and specificity of the TTW and T25FW to detect mild clinical impairment in a large cohort of MS patients . METHODS We extracted T25FW , TTW and EDSS from our UMC patient data base ( 2009 - 2012 ) . After r and omization into an explorative ( n = 497 ) and validation ( n = 228 ) cohort , we calculated change rates and performed ROC analyses of gait tests and EDSS including Functional System Scores . RESULTS Between disability stages of EDSS 0 - 2.5 and EDSS 3.0 - 4.0 , the mean TTW difference was 4s ( T25FW = 0.9s ) . The accuracy to separate between EDSS groups was moderate but identical for both tests ( ROC-AUC T25FW = 0.79 , TTW = 0.80 , p = 0.4 ) . TTW had a higher sensitivity and specificity to differentiate between asymptomatic and symptomatic patients concerning FS motor/cerebellar scores ( ROC-AUC T25FW = 0.71 , TTW = 0.75 , p < 0.05 ) . All hypotheses could be vali date d in the second cohort . CONCLUSION A 3-m Timed T and em Walk is a st and ardized test that is easy to implement to detect impairment of the motor or cerebellar system in fully ambulatory MS patients . Based on the complex-task character , TTW is a potential new outcome measure for MS mobility in mildly disabled patients and can act as easily accessible and significant additional information in patient counseling Background Clinical intervention trials in people with Huntington disease ( HD ) have been limited by a lack of reliable and appropriate outcome measures . Objective The purpose of this study was to determine the reliability and minimal detectable change ( MDC ) of various outcome measures that are potentially suitable for evaluating physical functioning in individuals with HD . Design This was a multicenter , prospect i ve , observational study . Methods Participants with pre-manifest and manifest HD ( early , middle , and late stages ) were recruited from 8 international sites to complete a battery of physical performance and functional measures at 2 assessment s , separated by 1 week . Test-retest reliability ( using intraclass correlation coefficients ) and MDC values were calculated for all measures . Results Seventy-five individuals with HD ( mean age=52.12 years , SD=11.82 ) participated in the study . Test-retest reliability was very high ( > .90 ) for participants with manifest HD for the Six-Minute Walk Test ( 6MWT ) , 10-Meter Walk Test , Timed “ Up & Go ” Test ( TUG ) , Berg Balance Scale ( BBS ) , Physical Performance Test ( PPT ) , Barthel Index , Rivermead Mobility Index , and Tinetti Mobility Test ( TMT ) . Many MDC values suggested a relatively high degree of inherent variability , particularly in the middle stage of HD . Minimum detectable change values for participants with manifest HD that were relatively low across disease stages were found for the BBS ( 5 ) , PPT ( 5 ) , and TUG ( 2.98 ) . For individuals with pre-manifest HD ( n=11 ) , the 6MWT and Four Square Step Test had high reliability and low MDC values . Limitations The sample size for the pre-manifest HD group was small . Conclusions The BBS , PPT , and TUG appear most appropriate for clinical trials aim ed at improving physical functioning in people with manifest HD . Further research in people with pre-manifest HD is necessary |
10,760 | 30,961,435 | Conclusion Current evidence supports both efficacy and superiority of combination intranasal azelastine and fluticasone in reducing patient-reported symptom scores in patients with allergic rhinitis . | Objective Combination therapy with intranasal azelastine and fluticasone propionate is an option for treatment of allergic rhinitis .
This systematic review and meta- analysis examines existing literature to determine efficacy in treating allergic rhinitis compared to monotherapy . | BACKGROUND AND OBJECTIVE MP29 - 02 ( Dymista ) , a novel intranasal formulation of azelastine hydrochloride ( AZE ) and fluticasone propionate ( FP ) , is significantly better than first-line therapy for the treatment of moderate-to-severe seasonal allergic rhinitis ( SAR ) , and is well tolerated following 52 weeks of continuous use in chronic rhinitis . The aim of this study was to evaluate the long-term efficacy of MP29 - 02 versus FP in patients with chronic rhinitis . PATIENTS AND METHODS In total , 612 chronic rhinitis patients ( perennial allergic rhinitis [ PAR ] , n = 424 ; nonallergic rhinitis , n=188 ) aged 12 years or older were enrolled into this open-label , parallel-group study and r and omized to MP29 - 02 ( 1 spray/nostril bid ) or FP nasal spray ( 2 sprays/nostril qd ) for 52 weeks . Efficacy was assessed by change from baseline in PM reflective total nasal symptom score ( rTNSS ) , time to first achieve 100 % PM rTNSS reduction from baseline , and percentage of symptom-free days in the total and PAR population s posthoc . RESULTS MP29 - 02 reduced patients ' PM rTNSS from baseline significantly more than FP , from Day 1 up to and including week 28 ( -2.88 vs -2.53 ; P = .0048 ) , with treatment difference maintained for 52 weeks . Fluctuation in significance after week 28 might be explained , at least in part , by decreasing sample size , permitted according to ICH guidelines . By Day 1 almost twice as many MP29 - 02- patients were symptom free . After 1 month , 71.1 % of MP29 - 02 patients experienced 100 % rTNSS reduction ( 60.3 % for FP ) , and did on a median of 9 days faster ( P=.0024 ) . Over 52 weeks MP29 - 02 patients experienced 8.4 % more symptom-free days ( P = .0005 ) . These results were mirrored in the PAR sub population . CONCLUSION These results confirm MP29 - 02 's wide therapeutic spectrum and assert its consistent superiority over an intranasal corticosteroid The combination of intranasal antihistamines and intranasal corticosteroids results in superior relief of seasonal allergic rhinitis ( SAR ) symptoms compared with monotherapy . This study was design ed to evaluate the safety and efficacy of olopatadine hydrochloride nasal spray , 0.6 % ( OLO ) , administered in combination with fluticasone nasal spray , 50 micrograms ( FNS ) , relative to azelastine nasal spray , 0.1 % ( AZE ) , administered in combination with FNS in the treatment of SAR . This was a multicenter , double-blind , r and omized , parallel-group comparison of OLO + FNS versus AZE + FNS administered for 14 days to patients ≥12 years of age with histories of SAR . Efficacy assessment s recorded by patients in a daily diary included nasal symptom scores . Safety was evaluated based on adverse events ( AEs ) . Pretreatment values for reflective total nasal symptoms scores ( rTNSS ) were similar for both treatment groups . The mean ( SD ) 2-week average rTNSS was 4.28 ( 2.63 ) for OLO + FNS and 4.15 ( 2.63 ) for AZE + FNS ; these scores were not statistically different between treatment groups . No significant differences ( p > 0.05 ) between OLO + FNS and AZE + FNS were observed for the average 2-week percent changes from baseline in rTNSS or in the individual nasal symptoms ( nasal congestion , rhinorrhea , itchy nose , and sneezing ) . Compared with baseline , both groups had statistically significant improvement in rTNSS ( p < 0.05 ) . No serious AEs were reported in either group during the study period . Overall , 19 AEs were reported in the OLO + FNS group and 29 AEs were reported in the AZE + FNS group . OLO , when administered adjunctively with FNS , is effective , safe , and well-tolerated in patients with SAR BACKGROUND This study aim ed to assess the efficacy of MP-AzeFlu ( a novel intranasal formulation of azelastine hydrochloride and fluticasone propionate in a single spray ) in children with seasonal allergic rhinitis ( SAR ) and explore the importance of child symptom severity assessment in paediatric allergic rhinitis ( AR ) trials . METHODS A total of 348 children ( 4 - 11 years ) with moderate/severe SAR were r and omized into a double-blind , placebo-controlled , 14-day , parallel-group trial . Efficacy was assessed by changes from baseline in reflective total nasal symptom score ( rTNSS ) , reflective total ocular symptom score ( rTOSS ) and individual symptom scores over 14 days ( children 6 - 11 years ; n = 304 ) , recorded by either children or caregivers . To determine whether a by-proxy effect existed , efficacy outcomes were assessed according to degree of child/caregiver rating . Moreover , total Paediatric Rhinitis Quality of Life Question naire ( PRQLQ ) score was compared between the groups . RESULTS A statistically superior , clinical ly relevant efficacy signal of MP-AzeFlu versus placebo was apparent for PRQLQ overall score ( diff : -0.29 , 95 % CI -0.55 , -0.03 ; p = 0.027 ) , but not for rTNSS ( diff : -0.80 ; 95 % CI : -1.75 ; 0.15 ; p = 0.099 ) . However , as the extent of children 's self-rating increased , so too did the treatment difference between MP-AzeFlu and placebo ; MP-AzeFlu provided significantly better relief than placebo for rTNSS ( p = 0.002 ) , rTOSS ( p = 0.009 ) and each individual nasal and ocular symptom assessed ( except rhinorrhoea ; p = 0.064 ) when children mostly rated their own symptoms . CONCLUSIONS MP-AzeFlu is an effective treatment for AR in childhood . Caregivers are less able than children to accurately assess response to treatment with available tools . A simple paediatric-specific tool to assess efficacy in AR trials in children is needed BACKGROUND To our knowledge , there are no published studies that evaluated the efficacy of azelastine hydrochloride nasal spray in combination with an intranasal corticosteroid , although anecdotal reports of the use of these agents in combination are common . OBJECTIVE To determine if greater efficacy could be achieved with the intranasal antihistamine azelastine and the intranasal corticosteroid fluticasone propionate used concurrently compared with the efficacy of each agent alone . METHODS This r and omized , 2-week , multicenter , double-blind trial was conducted during the Texas mountain cedar season . After a 5-day placebo lead-in period , 151 patients with moderate to severe nasal symptoms were r and omized to treatment with the following : ( 1 ) azelastine nasal spray , 2 sprays per nostril twice daily ; ( 2 ) fluticasone nasal spray , 2 sprays per nostril once daily ; or ( 3 ) azelastine nasal spray , 2 sprays per nostril twice daily , plus fluticasone nasal spray , 2 sprays per nostril once daily . The primary efficacy variable was the change from baseline in the total nasal symptom score ( TNSS ) , consisting of sneezing , itchy nose , runny nose , and nasal congestion . RESULTS All 3 groups had statistically significant ( P < .001 ) improvements from their baseline TNSS after 2 weeks of treatment . The TNSS improved 27.1 % with fluticasone nasal spray , 24.8 % with azelastine nasal spray , and 37.9 % with the 2 agents in combination ( P < .05 vs either agent alone ) . All 3 treatments were well tolerated . CONCLUSIONS The significant improvement in the TNSS with combination therapy relative to the individual agents alone is in contrast to previously published studies that found no advantage with an oral antihistamine and an intranasal corticosteroid in combination . Azelastine nasal spray and fluticasone nasal spray in combination may provide a substantial therapeutic benefit for patients with seasonal allergic rhinitis compared with therapy with either agent alone Many patients with allergic rhinitis ( AR ) have uncontrolled symptoms despite available treatment options . This study was design ed to evaluate the efficacy and safety of MP29 - 02 ( a novel intranasal formulation of fluticasone propionate [ FP ] and azelastine [ AZ ] hydrochloride ) , compared with monotherapy with FP , AZ , and placebo sprays for the treatment of seasonal allergic rhinitis ( SAR ) . This 2-week r and omized , double-blind , placebo-controlled trial was conducted in 779 patients with moderate-to-severe SAR . Treatments were administered 1 spray/nostril twice daily in the same vehicle and delivery device . Daily doses of AZ and FP were 548 and 200 micrograms , respectively . The primary efficacy variable was the 12-hour reflective total nasal symptom score ( rTNSS ) , consisting of nasal congestion , sneezing , itchy nose , and runny nose . Secondary efficacy variables were ( 1 ) 12-hour reflective individual nasal symptom scores ; ( 2 ) onset of action ; ( 3 ) 12-hour reflective total ocular symptom score ( rTOSS ) , including itchy eyes , watery eyes , and red eyes ; and ( 4 ) the Rhinoconjunctivitis Quality of Life Question naire ( RQLQ ) overall score . MP29 - 02 significantly reduced the mean rTNSS from baseline by -5.54 points compared with FP ( -4.55 ; p = 0.038 ) , AZ ( -4.54 ; p = 0.032 ) , and placebo ( -3.03 ; p < 0.001 ) , improving the rTNSS by 39 % beyond the contribution of FP . All individual nasal symptoms contributed to the efficacy of MP29 - 02 . Onset of action was within 30 minutes . MP29 - 02 significantly improved rTOSS compared with placebo , provided a clinical ly important improvement in the overall RQLQ score , and was well tolerated . In this study , MP29 - 02 provided more complete symptom relief than two widely used first-line AR treatments and was well tolerated BACKGROUND Moderate-to-severe allergic rhinitis ( AR ) is a challenge to treat , with many patients using multiple therapies and achieving limited symptom control . More effective therapies must be developed and tested in well-controlled , r and omized , prospect i ve studies with a direct comparison to current st and ards . OBJECTIVES The aim of these studies was to investigate the efficacy of MP29 - 02 ( a novel formulation of azelastine and fluticasone propionate [ FP ] ) in patients with moderate-to-severe seasonal allergic rhinitis ( SAR ) and to compare its efficacy with 2 first-line therapies ( ie , intranasal azelastine and intranasal FP ) in this population . METHODS Three thous and three hundred ninety-eight patients ( ≥12 years old ) with moderate-to-severe SAR were enrolled into 3 multicenter , r and omized , double-blind , placebo- and active-controlled , parallel-group trials ( MP4002 [ NCT00651118 ] , MP4004 [ NCT00740792 ] , and MP4006 [ NCT00883168 ] ) . Each trial was conducted for 14 days during different allergy seasons . The primary efficacy variable was the sum of the morning and evening change from baseline in reflective total nasal symptom score ( range , 0 - 24 ) over the treatment period . Outcomes for the meta- analysis included efficacy according to disease severity and time to response in relevant responder criteria . RESULTS In the meta- analysis MP29 - 02 reduced the mean reflective total nasal symptom score from baseline ( -5.7 [ SD , 5.3 ] ) more than FP ( -5.1 [ SD , 4.9 ] , P < .001 ) , azelastine ( -4.4 [ SD , 4.8 ] , P < .001 ) , or placebo ( -3.0 [ SD , 4.2 ] , P < .001 ) . This benefit was observed from the first day of assessment , with improvement in each individual nasal symptom , even in the patients with the most severe disease . MP29 - 02 achieved response consistently days earlier and showed greater efficacy in patients with moderate-to-severe rhinitis than FP and azelastine . CONCLUSIONS MP29 - 02 represents a novel therapy that demonstrated superiority to 2 first-line therapies for AR . Patients with moderate-to-severe SAR achieved better control , and their symptoms were controlled earlier with MP29 - 02 than with recommended medications according to guidelines BACKGROUND A proof-of-concept study suggested that combination therapy with commercial azelastine hydrochloride nasal spray and fluticasone propionate nasal spray significantly improved nasal symptoms of seasonal allergic rhinitis compared with either agent alone . OBJECTIVE To compare an azelastine-fluticasone combination nasal spray administered in a single-delivery device with a commercially available azelastine nasal spray and fluticasone nasal spray . METHODS This 14-day , multicenter , r and omized , double-blind study was conducted during the Texas mountain cedar season . After a 5-day placebo lead-in , 610 patients with moderate-to-severe nasal symptoms were r and omized to treatment with ( 1 ) azelastine nasal spray , ( 2 ) fluticasone nasal spray , ( 3 ) combination azelastine and fluticasone nasal spray , or ( 4 ) placebo nasal spray . All treatments were given as 1 spray per nostril twice daily . The primary efficacy variable was the change from baseline in the total nasal symptom score ( TNSS ) , consisting of nasal congestion , runny nose , itchy nose , and sneezing . RESULTS All 3 active groups were statistically superior ( P < or= .02 ) to placebo , and the combination was statistically superior ( P < or= .003 ) to either agent alone . The TNSS improved by 28.4 % with combination azelastine-fluticasone , 20.4 % with fluticasone , 16.4 % with azelastine , and 11.2 % with placebo . All 3 treatments were well tolerated . CONCLUSIONS The combination azelastine-fluticasone nasal spray provided statistically significant improvement in the TNSS and additive clinical benefit compared with either agent alone in patients with moderate-to-severe seasonal allergic rhinitis . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00660517 |
10,761 | 31,390,997 | Conclusions Major prevention with antiplatelet agents ( cardiovascular events and access failure ) , might outweigh the risk of bleeding , and there seemed to be an overall net benefit . | Background The benefits and risks of antiplatelet therapy for patients with chronic kidney disease ( CKD ) remain controversial .
We undertook a systematic review and meta- analysis to investigate the effects of antiplatelet therapy on major clinical outcomes . | 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 BACKGROUND The potential benefit of dual antiplatelet therapy beyond 1 year after a myocardial infa rct ion has not been established . We investigated the efficacy and safety of ticagrelor , a P2Y12 receptor antagonist with established efficacy after an acute coronary syndrome , in this context . METHODS We r and omly assigned , in a double-blind 1:1:1 fashion , 21,162 patients who had had a myocardial infa rct ion 1 to 3 years earlier to ticagrelor at a dose of 90 mg twice daily , ticagrelor at a dose of 60 mg twice daily , or placebo . All the patients were to receive low-dose aspirin and were followed for a median of 33 months . The primary efficacy end point was the composite of cardiovascular death , myocardial infa rct ion , or stroke . The primary safety end point was Thrombolysis in Myocardial Infa rct ion ( TIMI ) major bleeding . RESULTS The two ticagrelor doses each reduced , as compared with placebo , the rate of the primary efficacy end point , with Kaplan-Meier rates at 3 years of 7.85 % in the group that received 90 mg of ticagrelor twice daily , 7.77 % in the group that received 60 mg of ticagrelor twice daily , and 9.04 % in the placebo group ( hazard ratio for 90 mg of ticagrelor vs. placebo , 0.85 ; 95 % confidence interval [ CI ] , 0.75 to 0.96 ; P=0.008 ; hazard ratio for 60 mg of ticagrelor vs. placebo , 0.84 ; 95 % CI , 0.74 to 0.95 ; P=0.004 ) . Rates of TIMI major bleeding were higher with ticagrelor ( 2.60 % with 90 mg and 2.30 % with 60 mg ) than with placebo ( 1.06 % ) ( P<0.001 for each dose vs. placebo ) ; the rates of intracranial hemorrhage or fatal bleeding in the three groups were 0.63 % , 0.71 % , and 0.60 % , respectively . CONCLUSIONS In patients with a myocardial infa rct ion more than 1 year previously , treatment with ticagrelor significantly reduced the risk of cardiovascular death , myocardial infa rct ion , or stroke and increased the risk of major bleeding . ( Funded by AstraZeneca ; PEGASUS-TIMI 54 Clinical Trials.gov number , NCT01225562 . ) 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 Blockade of the platelet glycoprotein IIb/IIIa receptor with abciximab ( a monoclonal-antibody Fab fragment directed against the receptor ) has been shown to diminish ischemic complications among patients undergoing high-risk coronary angioplasty or directional atherectomy but increases bleeding complications . The widespread applicability of this treatment is unknown , particularly in view of the observed risk of hemorrhage . METHODS In a prospect i ve , double-blind trial , we r and omly assigned patients undergoing urgent or elective percutaneous coronary revascularization at 69 centers to receive abciximab with st and ard-dose , weight-adjusted heparin ( initial bolus of 100 U per kilogram of body weight ) ; abciximab with low-dose , weight-adjusted heparin ( initial bolus of 70 U per kilogram ) ; or placebo with st and ard-dose , weight-adjusted heparin . The primary efficacy end point was death from any cause , myocardial infa rct ion , or urgent revascularization within 30 days of r and omization . RESULTS The trial was terminated at the first interim analysis , with 2792 of the planned 4800 patients enrolled . At 30 days , the composite event rate was 11.7 percent in the group assigned to placebo with st and ard-dose heparin ; 5.2 percent in the group assigned to abciximab with low-dose heparin ( hazard ratio , 0.43 ; 95 percent confidence interval , 0.30 to 0.60 ; P<0.001 ) ; and 5.4 percent in the group assigned to abciximab with st and ard-dose heparin ( hazard ratio , 0.45 ; 95 percent confidence interval , 0.32 to 0.63 ; P<0.001 ) . There were no significant differences among the groups in the risk of major bleeding , although minor bleeding was more frequent among patients receiving abciximab with st and ard-dose heparin . CONCLUSIONS Inhibition of the platelet glycoprotein IIb/IIIa receptor with abciximab , together with low-dose , weight-adjusted heparin , markedly reduces the risk of acute ischemic complications in patients undergoing percutaneous coronary revascularization , without increasing the risk of hemorrhage 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 BACKGROUND Aggregation of platelets is the pathophysiologic basis of the acute coronary syndromes . Eptifibatide , a synthetic cyclic heptapeptide , is a selective high-affinity inhibitor of the platelet glycoprotein IIb/IIIa receptor , which is involved in platelet aggregation . We tested the hypothesis that inhibition of platelet aggregation with eptifibatide would have an incremental benefit beyond that of heparin and aspirin in reducing the frequency of adverse outcomes in patients with acute coronary syndromes who did not have persistent ST-segment elevation . METHODS Patients who had presented with ischemic chest pain within the previous 24 hours and who had either electrocardiographic changes indicative of ischemia ( but not persistent ST-segment elevation ) or high serum concentrations of creatine kinase MB isoenzymes were enrolled in the study . They were r and omly assigned , in a double-blind manner , to receive a bolus and infusion of either eptifibatide or placebo , in addition to st and ard therapy , for up to 72 hours ( or up to 96 hours , if coronary intervention was performed near the end of the 72-hour period ) . The primary end point was a composite of death and nonfatal myocardial infa rct ion occurring up to 30 days after the index event . RESULTS A total of 10,948 patients were enrolled between November 1995 and January 1997 . As compared with the placebo group , the eptifibatide group had a 1.5 percent absolute reduction in the incidence of the primary end point ( 14.2 percent , vs. 15.7 percent in the placebo group ; P=0.04 ) . The benefit was apparent by 96 hours and persisted through 30 days . The effect was consistent in most major subgroups except for women ( odds ratios for death or nonfatal myocardial infa rct ion , 0.8 [ 95 percent confidence interval , 0.7 to 0.9 ] in men , and 1.1 [ 0.9 to 1.31 in women ) . Bleeding was more common in the eptifibatide group , although there was no increase in the incidence of hemorrhagic stroke . CONCLUSIONS Inhibition of platelet aggregation with eptifibatide reduced the incidence of the composite end point of death or nonfatal myocardial infa rct ion in patients with acute coronary syndromes who did not have persistent ST-segment elevation 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 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 : Chronic kidney disease ( CKD ) coexisting with type 2 diabetes mellitus ( DM ) leads to coronary artery disease . The present study compares clopidogrel and low-dose aspirin as prophylactic therapy against coronary events in patients with CKD with diabetes . Methods : Total 80 patients of CKD with type 2 DM were r and omized and allocated to clopidogrel and aspirin groups to receive the drug at a dose of 75 mg and 150 mg once daily respectively for 8 weeks as add-on therapy . Main outcome was change in blood pressure , metabolic parameters , renal function , inflammatory biomarkers , platelet aggregability and ( UKPDS ) United Kingdom Prospect i ve Diabetes Study risk scoring . Results : Significant decrease in blood pressure ( P < 0.01 ) , total cholesterol ( P = 0.02 ) , LDL ( P < 0.01 ) , triglyceride ( P < 0.01 ) and a better glycemic control ( P < 0.01 ) was found in clopidogrel group . Renal markers and electrolytes have been improved in clopidogrel group but in aspirin group there was deterioration ( 2.5 % ) of creatinine clearance . Clopidogrel group has shown a significant decrease in hsCRP ( P < 0.01 ) , UKPDS risk scoring ( P < 0.01 ) and better anti-aggregatory effect . Conclusions : Clopidogrel has prophylactic role in CKD with type 2 DM due to better control of metabolic parameters , renal function and inflammatory burden in comparison to aspirin Background The complications of vascular access are the most imperative etiology for hospitalization , morbidity and mortality in chronic hemodialysis . The most prevalent complication of central catheter is dysfunction due to thrombosis . Aspirin is an anti-aggregative platelet drug that may increase the patency of permanent catheters ( perm-cath ) . Objectives The aim of this study was to evaluate the role of Aspirin in perm-cath survival . Patients and Methods This study included a total of 185 ESRD cases according to the inclusion criteria for perm-cath insertion in hemodialysis . One hundred and eighty patients following perm-cath insertion had proper blood flow through perm-cath during hemodialysis . Patients were r and omly divided between intervention ( 80 mg/day Aspirin initiated a day following catheter insertion ) and control ( placebo ) groups . The average time that the perm-cath was functional was noted . Demographic characteristics included comorbidities and past history were also used to address probable influence on perm-cath function and patency . Results The mean survival time of the catheter in Aspirin group was significantly higher than the control group ( 5.3 ± 4.7 month versus 3.9 ± 2.7 month , P = 0.012 ) . No significant difference in major complications of Aspirin use ( such as GI bleeding ) was noted between two groups ( P = 0.52 ) . In terms of the patient ’s demographic characteristics , those of the female gender and a history of diabetes mellitus were found to have significant influence on median survival rate of the catheters ( P = 0.021 , 0.043 respectively ) . Conclusions These results suggest that Aspirin use following perm-cath insertion might be beneficial for catheter survival . This increased survival time might enable patient ’s use of AVF maturation for long term dialysis access Extended-release dipyridamole plus low-dose aspirin ( ERDP/ASA ) prolongs primary unassisted graft patency of newly created hemodialysis arteriovenous grafts , but the individual contributions of each component are unknown . Here , we analyzed whether use of aspirin at baseline associated with primary unassisted graft patency among participants in a r and omized trial that compared ERDP/ASA and placebo in newly created grafts . We used Cox proportional hazards regression , adjusting for prespecified baseline comorbidities and covariates . Of all participants , 43 % reported use of aspirin at baseline ; of these , 82 % remained on non study aspirin ( i.e. , excluding ERDP/ASA ) at 1 year . After 1 year of follow-up , the incidence of primary unassisted patency among participants using aspirin at baseline was 30 % ( 95 % CI : 24 to 35 % ) and among those not using aspirin was 23 % ( 95 % CI : 18 to 27 % ) . Use of aspirin at baseline associated with a dose-dependent prolongation of primary unassisted graft patency that approached statistical significance ( adjusted HR , 0.83 ; 95 % CI : 0.68 to 1.01 ; P=0.06 ) . Use of aspirin at baseline did not associate with prolongation of cumulative graft patency or participant survival . In conclusion , use of aspirin associates with a trend toward longer primary unassisted patency of newly placed hemodialysis grafts similar to that observed for ERDP/ASA BACKGROUND Dual-antiplatelet therapy with aspirin and a thienopyridine is a cornerstone of treatment to prevent thrombotic complications of acute coronary syndromes and percutaneous coronary intervention . METHODS To compare prasugrel , a new thienopyridine , with clopidogrel , we r and omly assigned 13,608 patients with moderate-to-high-risk acute coronary syndromes with scheduled percutaneous coronary intervention to receive prasugrel ( a 60-mg loading dose and a 10-mg daily maintenance dose ) or clopidogrel ( a 300-mg loading dose and a 75-mg daily maintenance dose ) , for 6 to 15 months . The primary efficacy end point was death from cardiovascular causes , nonfatal myocardial infa rct ion , or nonfatal stroke . The key safety end point was major bleeding . RESULTS The primary efficacy end point occurred in 12.1 % of patients receiving clopidogrel and 9.9 % of patients receiving prasugrel ( hazard ratio for prasugrel vs. clopidogrel , 0.81 ; 95 % confidence interval [ CI ] , 0.73 to 0.90 ; P<0.001 ) . We also found significant reductions in the prasugrel group in the rates of myocardial infa rct ion ( 9.7 % for clopidogrel vs. 7.4 % for prasugrel ; P<0.001 ) , urgent target-vessel revascularization ( 3.7 % vs. 2.5 % ; P<0.001 ) , and stent thrombosis ( 2.4 % vs. 1.1 % ; P<0.001 ) . Major bleeding was observed in 2.4 % of patients receiving prasugrel and in 1.8 % of patients receiving clopidogrel ( hazard ratio , 1.32 ; 95 % CI , 1.03 to 1.68 ; P=0.03 ) . Also greater in the prasugrel group was the rate of life-threatening bleeding ( 1.4 % vs. 0.9 % ; P=0.01 ) , including nonfatal bleeding ( 1.1 % vs. 0.9 % ; hazard ratio , 1.25 ; P=0.23 ) and fatal bleeding ( 0.4 % vs. 0.1 % ; P=0.002 ) . CONCLUSIONS In patients with acute coronary syndromes with scheduled percutaneous coronary intervention , prasugrel therapy was associated with significantly reduced rates of ischemic events , including stent thrombosis , but with an increased risk of major bleeding , including fatal bleeding . Overall mortality did not differ significantly between treatment groups . ( Clinical Trials.gov number , NCT00097591 [ Clinical Trials.gov ] . Although arterialovenous fistulae ( AVF ) is considered to be vital for chronic kidney disease ( CKD ) patients , but they may cause complications and problems . For instance they may fail soon after their creation . The most important cause of failure in these cases is intrafistula thrombus formation . Whereas anti-platelet drugs are not routinely used after fistulae creation , we conducted this study to determine the effect of these drugs ( aspirin and dipyridamol ) on the patency of AVFs . From Sep 2003 to Aug 2007 , all CKD patients who needed AVF for hemodilysis were included in our study . After fistulae creation , they were r and omly divided in 3 groups . The first group was received aspirin and the second one with dipyridamol and the third one was the control group that received placebo . Each group consisted of 130 patients . Exclusion criteria were bleeding tendency , active peptic ulcer disease , pregnancy , lactation , use of anticoagulant and or non steroidal anti-inflammatory drugs , hepatic insufficiency and history of significant side effects from aspirin or dipyridamol . The patency of AVF in the control , aspirin and dipyridamol groups were obtained 69.2 % , 70.8 % and 75.4 % respectively . Although the patency in the aspirin and the dipyridamol group were 1.6 % and 6.2 % more than the control group , but there was no statistically significant difference between them and placebo ( The p-value was 0.892 for the aspirin group and 0.332 for the dipyridamol group ) . Our study showed that neither the aspirin nor the dipyridamol can be effective on the patency of AVF after 72 h even within six months period 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 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 BACKGROUND Patients with chronic kidney disease are at increased risk for cardiovascular disease , but the efficacy and safety of simvastatin and aspirin are unknown in this patient group . METHODS Patients were r and omly assigned in a 2 x 2 factorial design to the administration of : ( 1 ) 20 mg of simvastatin daily versus matching placebo , and ( 2 ) 100 mg of modified-release aspirin daily versus matching placebo . RESULTS Overall , 448 patients with chronic kidney disease were r and omly assigned ( 242 predialysis patients with a creatinine level > or = 1.7 mg/dL [ > or = 150 micromol/L ] , 73 patients on dialysis therapy , and 133 patients with a functioning transplant ) . Compliance with study treatments was 80 % at 12 months . Allocation to treatment with 100 mg of aspirin daily was not associated with an excess of major bleeds ( aspirin , 4 of 225 patients [ 2 % ] versus placebo , 6 of 223 patients [ 3 % ] ; P = not significant [ NS ] ) , although there was a 3-fold excess of minor bleeds ( 34 of 225 [ 15 % ] versus 12 of 223 patients [ 5 % ] ; P = 0.001 ) . Among those with predialysis renal failure or a functioning transplant at baseline , aspirin did not increase the number of patients who progressed to dialysis therapy ( 7 of 187 [ 4 % ] versus 6 of 188 patients [ 3 % ] ; P = NS ) or experienced a greater than 20 % increase in creatinine level ( 63 of 187 patients [ 34 % ] versus 56 of 188 patients [ 30 % ] ; P = NS ) . After 12 months of follow-up , allocation to 20 mg of simvastatin daily reduced nonfasting total cholesterol levels by 18 % ( simvastatin , 163 mg/dL [ 4.22 mmol/L ] versus placebo , 196 mg/dL [ 5.08 mmol/L ] ; P < 0.0001 ) , directly measured low-density lipoprotein cholesterol levels by 24 % ( 89 mg/dL [ 2.31 mmol/L ] versus 114 mg/dL [ 2.96 mmol/L ] ; P < 0.0001 ) , and triglyceride levels by 13 % ( 166 mg/dL [ 1.87 mmol/L ] versus 186 mg/dL [ 2.10 mmol/L ] ; P < 0.01 ) , but there was no significant effect on high-density lipoprotein cholesterol levels ( 2 % increase ; P = NS ) . Allocation to simvastatin therapy was not associated with excess risk for abnormal liver function test results or elevated creatine kinase levels . CONCLUSION During a 1-year treatment period , simvastatin , 20 mg/d , produced a sustained reduction of approximately one quarter in low-density lipoprotein cholesterol levels , with no evidence of toxicity , and aspirin , 100 mg/d , did not substantially increase the risk for a major bleeding episode . Much larger trials are now needed to assess whether these treatments can prevent vascular events BACKGROUND The benefit of catheter-based reperfusion for acute myocardial infa rct ion ( MI ) is limited by a 5 % to 15 % incidence of in-hospital major ischemic events , usually caused by infa rct artery reocclusion , and a 20 % to 40 % need for repeat percutaneous or surgical revascularization . Platelets play a key role in the process of early infa rct artery reocclusion , but inhibition of aggregation via the glycoprotein IIb/IIIa receptor has not been prospect ively evaluated in the setting of acute MI . METHODS AND RESULTS Patients with acute MI of < 12 hours ' duration were r and omized , on a double-blind basis , to placebo or abciximab if they were deemed c and i date s for primary PTCA . The primary efficacy end point was death , reinfa rct ion , or any ( urgent or elective ) target vessel revascularization ( TVR ) at 6 months by intention-to-treat ( ITT ) analysis . Other key prespecified end points were early ( 7 and 30 days ) death , reinfa rct ion , or urgent TVR . The baseline clinical and angiographic variables of the 483 ( 242 placebo and 241 abciximab ) patients were balanced . There was no difference in the incidence of the primary 6-month end point ( ITT analysis ) in the 2 groups ( 28.1 % and 28.2 % , P=0.97 , of the placebo and abciximab patients , respectively ) . However , abciximab significantly reduced the incidence of death , reinfa rct ion , or urgent TVR at all time points assessed ( 9.9 % versus 3.3 % , P=0.003 , at 7 days ; 11.2 % versus 5.8 % , P=0.03 , at 30 days ; and 17.8 % versus 11.6 % , P=0.05 , at 6 months ) . Analysis by actual treatment with PTCA and study drug demonstrated a considerable effect of abciximab with respect to death or reinfa rct ion : 4.7 % versus 1.4 % , P=0.047 , at 7 days ; 5.8 % versus 3.2 % , P=0.20 , at 30 days ; and 12.0 % versus 6.9 % , P=0.07 , at 6 months . The need for unplanned , " bail-out " stenting was reduced by 42 % in the abciximab group ( 20.4 % versus 11.9 % , P=0.008 ) . Major bleeding occurred significantly more frequently in the abciximab group ( 16.6 % versus 9.5 % , P=0.02 ) , mostly at the arterial access site . There was no intracranial hemorrhage in either group . CONCLUSIONS Aggressive platelet inhibition with abciximab during primary PTCA for acute MI yielded a substantial reduction in the acute ( 30-day ) phase for death , reinfa rct ion , and urgent target vessel revascularization . However , the bleeding rates were excessive , and the 6-month primary end point , which included elective revascularization , was not favorably affected 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 BACKGROUND Renal function significantly impacts morbidity and mortality after a percutaneous coronary intervention . Platelet glycoprotein ( GP ) IIb/IIIa inhibitors reduce ischemic complications during percutaneous coronary intervention ; little is known of whether their safety and efficacy are influenced by renal function . In particular , whether outcome differences exist between agents that are renally excreted ( tirofiban ) or not ( abciximab ) in patients with mild renal impairment is not known . METHODS The TARGET trial r and omized 4623 patients to tirofiban or abciximab . In this analysis , patients were grouped in creatinine clearance quartiles ( < 70 , 70 - 90 , 90 - 114 , > 114 mL/min ) and analyzed for efficacy and bleeding risk . Univariate and multivariate analyses were performed to identify interactions between GP IIb/IIIa inhibitor used and creatinine clearance with respect to ischemic outcomes and bleeding . RESULTS Using unadjusted logistic regression tests for trend , 30-day death/myocardial infa rct ion/urgent target vessel revascularization was greater in patients with lower creatinine clearances ( 7.3 % , 8.5 % , 5.1 % , and 5.8 % , P = .005 ) , as were both major and minor bleeding . There was no interaction between assigned GP IIb/IIIa inhibitor , creatinine clearance and ischemic outcome , major bleeding or minor bleeding . CONCLUSIONS Both ischemic and bleeding complications are highest in the lowest creatinine clearance quartile of patients treated with GP IIb/IIIa inhibitors . Although tirofiban is renally cleared and abciximab is not , there was no interaction between these GP IIb/IIIa inhibitors and creatinine clearance regarding ischemic or bleeding events BACKGROUND Coronary stenting with use of heparin , aspirin , and ticlopidine for thromboprophylaxis is performed in more than 500,000 patients per year worldwide . We did a r and omised controlled trial to assess the role of platelet glycoprotein-IIb/IIIa blockade for use in elective stenting . METHODS At 63 hospitals in the USA and Canada , 2399 patients with ischaemic heart disease and suitable coronary-artery lesions were r and omly assigned stenting plus placebo ( n=809 ) , stenting plus abciximab , a IIb/IIIa inhibitor ( n=794 ) , or balloon angioplasty plus abciximab ( n=796 ) . The primary endpoint was a combination of death , myocardial infa rct ion , or need for urgent revascularisation in the first 30 days . All patients received heparin , aspirin , and st and ard pharmacological therapy . FINDINGS The primary endpoint occurred in 87 ( 10.8 % ) of 809 patients in the stent plus placebo group , 42 ( 5.3 % ) of 794 in the stent plus abciximab group ( hazard ratio 0.48 [ 95 % CI 0.33 - 0.69 ] p<0.001 ) , and 55 ( 6.9 % ) of 796 in the balloon plus abciximab group ( 0.63 [ 0.45 - 0.88 ] p=0.007 ) . The main outcomes that occurred less with abciximab were death and large myocardial infa rct ion--7.8 % in the placebo group , 3.0 % for stent plus abciximab ( p<0.001 ) , and 4.7 % for balloon angioplasty plus abciximab ( p=0.01 ) . Major bleeding complications occurred in 2.2 % of patients assigned stent plus placebo , 1.5 % assigned stent plus abciximab , and 1.4 % assigned balloon angioplasty plus abciximab ( p=0.38 ) . INTERPRETATION Platelet glycoprotein-IIb/IIIa blockade with abciximab substantially improves the safety of coronary-stenting procedures . Balloon angioplasty with abciximab is safer than stenting without abciximab BACKGROUND AND OBJECTIVES Sarpogrelate has been shown to reduce albuminuria in diabetic nephropathy . For examination of whether this is based on the same mechanisms as angiotensin II receptor blockers or thiazolidinedione , effects of sarpogrelate on atherosclerotic inflammatory molecules and their relations to albuminuria in patients who had diabetes and had already been treated with angiotensin II receptor blockers and with or without thiazolidinedione were examined . DESIGN , SETTING , PARTICIPANTS , & MEASUREMENTS Forty patients who had diabetes with nephropathy and arteriosclerosis obliterans and had already been treated with angiotensin II receptor blocker ( n = 40 ) were r and omly assigned to sarpogrelate ( 300 mg/d ; n = 20 ) or aspirin group ( 100 mg/d ; n = 20 ) . Plasma monocyte chemoattractant protein-1 and urinary albumin-to-creatinine ratio and monocyte chemoattractant protein-1 were measured at baseline and 16 wk after administration . RESULTS Only the sarpogrelate group showed increases in plasma adiponectin and decreases in both plasma and urinary monocyte chemoattractant protein-1 and albumin-to-creatinine ratio levels . Moreover , percentage change of monocyte chemoattractant protein-1 level correlated positively to that of albumin-to-creatinine ratio . Even when the sarpogrelate group was further divided into two groups with ( n = 9 ) or without thiazolidinedione ( n = 11 ) , changes in monocyte chemoattractant protein-1 or albumin-to-creatinine ratio did not differ . CONCLUSIONS Sarpogrelate can reduce albuminuria and plasma and urinary monocyte chemoattractant protein-1 levels while increasing plasma adiponectin in diabetic nephropathy . These effects seem to be mediated via mechanisms that are different from those of angiotensin II receptor blocker or thiazolidinedione 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 Cilostazol is an antiplatelet , antithrombotic agent with anti-inflammatory properties . To date , no clinical study has specifically evaluated the efficacy of cilostazol in patients with diabetic nephropathy ( DN ) . We hypothesized that cilostazol might delay renal deterioration in DN patients at high risk of progression . Between April 2008 and April 2010 , we screened 156 consecutive patients aged 35–80 years who were first diagnosed with type 2 diabetes after the age of 30 years . Of these , 90 patients with DN , as defined by morning spot urine microalbuminuria ( MAU ) > 20 mg/L or an albumin-to-creatinine ratio ( ACR ) > 30 μg/mg on at least two consecutive occasions within the prior 3 months , were enrolled into a 52-week r and omized , single-blinded , placebo-controlled trial of oral cilostazol 100 mg twice daily or placebo ( 45 subjects in each group ) . Morning spot urine sample s were collected to determine MAU and ACR . Fasting plasma levels of metabolic , endothelial variables , and inflammatory markers were examined . Following 52 weeks of treatment , urinary MAU and ACR were significantly reduced in the cilostazol group compared with the placebo group ( P = 0.024 and P = 0.02 , respectively ) . In regression analyses , changes in monocyte chemotactic protein-1 , E-selectin , and soluble vascular cell adhesion molecule-1 ( sVCAM-1 ) were significantly associated with changes in MAU and ACR . Net changes of E-selectin ( P < 0.001 ) and sVCAM-1 ( P < 0.05 ) were independent predictors of change in MAU and ACR , respectively . Our results suggest that cilostazol may effectively attenuate deterioration of albuminuria in patients with type 2 diabetes . This effect is likely mediated by an improvement of adhesion molecules BACKGROUND Platelet-mediated thrombosis has been implicated in the development of ischaemic complications of percutaneous coronary intervention . We investigated whether inhibition of the platelet glycoprotein IIb/IIIa integrin with eptifibatide ( Integrilin ) could prevent such complications . METHODS We undertook a double-blind , placebo-controlled trial at 82 centres in the USA , enrolling 4010 patients undergoing elective , urgent , or emergency coronary intervention . Patients were assigned one of three treatments : placebo ( n = 1328 ) , a bolus of 135 micrograms/kg eptifibatide followed by an infusion of 0.5 microgram kg-1 min-1 for 20 - 24 h ( n = 1349 ) , or 135 micrograms/kg eptifibatide bolus with a 0.75 microgram kg-1 min-1 infusion ( n = 1333 ) . The coronary procedure was started within 10 - 60 min of the start of study treatment . The primary endpoint was the 30-day composite occurrence of death , myocardial infa rct ion , unplanned surgical or repeat percutaneous revascularisation , or coronary stent implantation for abrupt closure ( by intention to treat ) . The primary safety endpoint was major bleeding . FINDINGS By 30 days , the composite endpoint had occurred in 151 ( 11.4 % ) patients in the placebo group compared with 124 ( 9.2 % ) in the 135/0.5 eptifibatide group ( p = 0.063 ) and 132 ( 9.9 % ) in the eptifibatide 135/0.75 group ( p = 0.22 ) . By treatment-received analysis , the 135/0.5 regimen produced a significant reduction in the composite endpoint ( 11.6 vs 9.1 % , p = 0.035 ) , but the 135/0.75 regimen produced a less substantial reduction ( 11.6 vs 10.0 % , p = 0.18 ) . Eptifibatide treatment did not increase rates of major bleeding or transfusion . INTERPRETATION In the 135/0.5 group , treatment with eptifibatide during coronary intervention reduced rates of early abrupt closure and ischaemic events at 30 days . Non-significant differences were seen with the 135/0.75 regimen . The doses studied thus appear to be at the low end of the efficacy-response curve . Further investigation to refine eptifibatide dosing during coronary intervention is warranted BACKGROUND The incidence of stroke in patients with acute coronary syndromes has not been clearly defined because few trials in this patient population have been large enough to provide stable estimates of stroke rates . METHODS AND RESULTS We studied the 10 948 patients with acute coronary syndromes without persistent ST-segment elevation who were r and omly assigned to placebo or the platelet glycoprotein IIb/IIIa receptor inhibitor eptifibatide in the Platelet Glycoprotein IIb/IIIa in Unstable Angina : Receptor Suppression Using Integrilin Therapy ( PURSUIT ) trial to determine stroke rates , stroke types , clinical outcomes in patients with stroke , and independent baseline clinical predictors for nonhemorrhagic stroke . Stroke occurred in 79 ( 0.7 % ) patients , with 66 ( 0.6 % ) nonhemorrhagic , 6 intracranial hemorrhages , 3 cerebral infa rct ions with hemorrhagic conversion , and 4 of uncertain cause . There were no differences in stroke rates between patients who received placebo and those assigned high-dose eptifibatide ( odds ratios and 95 % confidence intervals 0.82 [ 0.59 , 1.14 ] and 0.70 [ 0.49 , 0.99 ] , respectively ) . Of the 79 patients with stroke , 17 ( 22 % ) died within 30 days , and another 26 ( 32 % ) were disabled by hospital discharge or 30 days , whichever came first . Higher heart rate was the most important baseline clinical predictor of nonhemorrhagic stroke , followed by older age , prior anterior myocardial infa rct ion , prior stroke or transient ischemic attack , and diabetes mellitus . These factors were used to develop a simple scoring nomogram that can predict the risk of nonhemorrhagic stroke . CONCLUSIONS Stroke was an uncommon event in patients with acute coronary syndromes in the PURSUIT trial . These strokes are , however , associated with substantial morbidity and mortality rates . The majority of strokes were of nonhemorrhagic causes . Eptifibatide was not associated with an increase in intracranial hemorrhage , and no significant effect on nonhemorrhagic stroke was observed . We developed a useful nomogram for assigning baseline nonhemorrhagic stroke risk in this patient population 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 A r and omized double blind trial was performed to investigate the effect of the platelet aggregation inhibitor ticlopidine on the rate of decline in renal function in diabetic nephropathy . Twenty-two patients with insulin dependent diabetes complicated by nephropathy completed the trial--11 on ticlopidine , and 11 on placebo for one year . Ticlopidine effectively reduced platelet aggregation in vitro . Renal clearance of 51Cr-EDTA declined from 39 + /- 10 to 30 + /- 13 ml/min per 1.73 m2 body surface in the ticlopidine group and from 42 + /- 9 to 39 + /- 13 in the placebo group . The difference in decline between the two groups was not significant . In the ticlopidine group renal function expressed as the slope coefficient for 1/S-creatinine per month remained the same as before the trial . It is concluded that although there is much evidence to suggest a role of platelets in the development or progression of diabetic nephropathy treatment with ticlopidine could not prevent this process BACKGROUND Prasugrel led to a significant reduction in ischemic cardiovascular events among patients with acute coronary syndrome ( ACS ) undergoing percutaneous coronary intervention ( PCI ) with stent implantation compared to clopidogrel . Whether this benefit extends to patients undergoing PCI without stent implantation is unknown . METHODS In TRial to assess Improvement in Therapeutic Outcomes by optimizing platelet inhibitioN with prasugrel (TRITON)-Thrombolysis in Myocardial Infa rct ion ( TIMI ) 38 , patients ( n = 13 608 ) undergoing PCI for ACS were r and omized to aspirin plus clopidogrel or prasugrel . This postr and omization analysis of a prespecified subgroup was restricted to patients who underwent PCI without stent implantation ( n = 569 ) . RESULTS Patients who underwent PCI without stent implantation were older and had a higher incidence of hypertension , diabetes , prior myocardial infa rct ion ( MI ) , prior coronary artery bypass ( CABG ) surgery , and renal dysfunction than patients who underwent stent implantation . In the group that did not undergo stent implantation , baseline characteristics were similar between patients receiving clopidogrel and prasugrel . The composite of cardiovascular death , nonfatal MI , and nonfatal stroke occurred in 14.2 % of patients receiving prasugrel and 17.1 % of patients receiving clopidogrel ( HR 0.82 , P = .27 ) . There were significant reductions favoring prasugrel in the rates of urgent target vessel revascularization ( TVR ; HR 0.46 , P = .040 ) and any TVR ( HR 0.40 , P = .009 ) and a trend toward a reduction in the incidence of nonfatal MI ( HR 0.65 , P = .11 ) . CABG-related TIMI major bleeding was more frequent among patients receiving prasugrel . There were no significant interactions between treatment and PCI type . CONCLUSION Among ACS patients who underwent PCI without stent implantation , prasugrel therapy tended to reduce clinical ischemic events and to increase bleeding events to a similar magnitude as among patients who received stents OBJECTIVES This report presents information on the effects of aspirin on mortality , the occurrence of cardiovascular events , and the incidence of kidney disease in the patients enrolled in the Early Treatment Diabetic Retinopathy Study ( ETDRS ) . STUDY DESIGN This multicenter , r and omized clinical trial of aspirin vs placebo was sponsored by the National Eye Institute . PATIENTS Patients ( N = 3711 ) were enrolled in 22 clinical centers between April 1980 and July 1985 . Men and women between the ages of 18 and 70 years with a clinical diagnosis of diabetes mellitus were eligible . Approximately 30 % of all patients were considered to have type I diabetes mellitus , 31 % type II , and in 39 % type I or II could not be determined definitely . INTERVENTION Patients were r and omly assigned to aspirin or placebo ( two 325-mg tablets once per day ) . MAIN OUTCOME MEASURES Mortality from all causes was specified as the primary outcome measure for assessing the systemic effects of aspirin . Other outcome variables included cause-specific mortality and cardiovascular events . RESULTS The estimate of relative risk for total mortality for aspirin-treated patients compared with placebo-treated patients for the entire study period was 0.91 ( 99 % confidence interval , 0.75 to 1.11 ) . Larger differences were noted for the occurrence of fatal and nonfatal myocardial infa rct ion ; the estimate of relative risk was 0.83 for the entire follow-up period ( 99 % confidence interval , 0.66 to 1.04 ) . CONCLUSIONS The effects of aspirin on any of the cardiovascular events considered in the ETDRS were not substantially different from the effects observed in other studies that included mainly nondiabetic persons . Furthermore , there was no evidence of harmful effects of aspirin . Aspirin has been recommended previously for persons at risk for cardiovascular disease . The ETDRS results support application of this recommendation to those persons with diabetes at increased risk of cardiovascular disease 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 Patients with chronic kidney disease ( CKD ) are at high risk for developing cardiovascular events . However , limited evidence is available regarding the use of aspirin in CKD patients to decrease cardiovascular risk and to slow renal disease progression . Study Design Prospect i ve , multicenter , open-label r and omized controlled trial . Setting and Participants One hundred eleven patients with estimated glomerular filtration rate ( eGFR ) 15–60 ml/min/1.73 m2 without previous cardiovascular events . InterventionAspirin treatment ( 100 mg/day ) ( n = 50 ) or usual therapy ( n = 61 ) . Mean follow-up time was 64.8 ± 16.4 months . Outcomes The primary endpoint was composed of cardiovascular death , acute coronary syndrome ( nonfatal MI , coronary revascularization , or unstable angina pectoris ) , cerebrovascular disease , heart failure , or nonfatal peripheral arterial disease . Secondary endpoints were fatal and nonfatal coronary events , renal events ( defined as doubling of serum creatinine , ≥ 50 % decrease in eGFR , or renal replacement therapy ) , and bleeding episodes . Results During follow-up , 17 and 5 participants suffered from a primary endpoint in the control and aspirin groups , respectively . Aspirin did not significantly reduce primary composite endpoint ( HR , 0.396 ( 0.146–1.076 ) , p = 0.069 . Eight patients suffered from a fatal or nonfatal coronary event in the control group compared to no patients in the aspirin group . Aspirin significantly reduced the risk of coronary events ( log-rank , 5.997 ; p = 0.014 ) . Seventeen patients in the control group reached the renal outcome in comparison with 3 patients in the aspirin group . Aspirin treatment decreased renal disease progression in a model adjusted for age , baseline kidney function , and diabetes mellitus ( HR , 0.272 ; 95 % CI , 0.077–0.955 ; p = 0.043 ) but did not when adjusted for albuminuria . No differences were found in minor bleeding episodes between groups and no major bleeding was registered . Limitations Small sample size and open-label trial . Conclusions Long-term treatment with low-dose aspirin did not reduce the composite primary endpoint ; however , there were reductions in secondary endpoints with fewer coronary events and renal outcomes . Clinical Trials.gov Identifier : NCT01709994 |
10,762 | 23,543,524 | There was no evidence that Gingko biloba was effective in patients with a primary complaint of tinnitus .
The practical clinical significance of this is unclear .
The incidence of side effects was low .
The limited evidence does not demonstrate that Ginkgo biloba is effective for tinnitus when this is the primary complaint | BACKGROUND This is an up date of a Cochrane review first published in The Cochrane Library in Issue 2 , 2004 and previously up date d in 2007 and 2009.Tinnitus can be described as the perception of sound in the absence of external acoustic stimulation .
At present no specific therapy for tinnitus is acknowledged to be satisfactory in all patients .
There are a number of reports in the literature suggesting that Ginkgo biloba may be effective in the management of tinnitus .
However , there also appears to be a strong placebo effect in tinnitus management .
OBJECTIVES To assess the effect of Ginkgo biloba in patients who are troubled by tinnitus . | Although there is increasing awareness that depression can add significantly to the disability associated with chronic medical illness , it is not clear whether all of the impact of psychosocial factors upon medical disability are mediated by or moderated by depression . It has not been determined whether treating depression alone is an adequate strategy for addressing psychosocial magnification of medical disability . We analyzed data collected at initiation of a treatment trial from 92 subjects with chronic severe tinnitus to assess the role of coping , and 49 subject-spouse pairs to assess the role of marital interaction in tinnitus-related role dysfunction . Three multiple regression models were developed . After accounting for gender , tinnitus loudness , and depressive severity among the 92 subjects , greater role dysfunction was associated appraisal of tinnitus as salient , and less role dysfunction with coping through avoidance or seeking social support . Marital interaction was assessed from patient and spouse perspectives . In the patient-rated set , less marital cohesion was associated with greater tinnitus-related role dysfunction . In the spouse-rated set , more punishing responses to subject illness behavior were associated with greater tinnitus-related role dysfunction . In each case the disabling effect was greater in the face of high levels of subject depression . This study provides evidence for the oft-stated analogy between chronic tinnitus and chronic pain , and provides justification for a similar multimodal treatment strategy . Reducing depression is an important means to reduce medical disability but should be supplemented by clinical attention to appraisal of the illness , modes of coping with the illness , and spousal response to the illness Patients disabled by tinnitus show a high prevalence of major depression . Furthermore , tinnitus produces patterns of disability similar to those produced by major depression . To explore further this link between tinnitus and depression , and to investigate the efficacy of treating depression in the treatment of tinnitus , a single-blind , placebo-washout , nonr and omized pilot study of the tricyclic antidepressant nortriptyline ( hydrochloride ) was undertaken in disabled tinnitus patients who also met diagnostic criteria for major depression . Nineteen patients began the study , two responded to placebo , and two dropped out prior to completion . Fourteen considered their tinnitus improved , and 12 chose to continue taking nortriptyline after the study . Depression severity decreased , on the average , by 65 % ( p<.0001 ) . Tinnitus loudness measured by audiometric matching decreased by a mean of 10 dB or 50 % ( p<.02 ) . Self-reports of tinnitus loudness and severity , somatic and psychologic symptoms , and psychosocial dysfunction all showed significant improvement with treatment . These results suggest that what initially appears to be an irreversible otologic disability in these patients may be in large part a reversible psychiatric disability OBJECTIVE To determine whether the antidepressant , nortriptyline , is effective for treatment of depression , tinnitus-related disability , and tinnitus symptoms in patients with severe chronic tinnitus . DESIGN A 12-week , double-blind , r and omized controlled trial . SETTING A university otolaryngology clinic . PATIENTS Ninety-two subjects with severe chronic tinnitus : 38 with current major depression and 54 with depressive symptoms and significant tinnitus-related disability . INTERVENTION Nortriptyline ( maintained at 50 to 150 mg/mL for 6 weeks ) or placebo . MAIN OUTCOME MEASURES Hamilton Depression Rating Scale , Tinnitus Disability Measures , and Audiometric Measures . RESULTS Nortriptyline was superior to placebo by multivariate analysis of covariance for depression ( 10.6 vs 14.3 final Hamilton Depression score ) , for tinnitus-related disability ( 1.8 vs 2.4 final MPI Tinnitus Interference ) , and tinnitus loudness ( 13.6 vs 20.0 dB final loudness match [ in worst ear at tinnitus frequency ] ) . When major depression and depressive symptoms groups were considered separately , nortriptyline was superior to placebo on these same measures but differences did not achieve statistical significance . CONCLUSIONS The antidepressant nortriptyline decreases depression , functional disability , and tinnitus loudness associated with severe chronic tinnitus . What appears to be irreversible disability of otologic origin may , in part , be reversible disability of psychiatric origin |
10,763 | 27,545,342 | Finally , the results showed effectiveness of various combinations of psychosocial and pharmacological interventions .
We found high- quality evidence in a meta- analysis including four ( 1,540 participants ) of the 16 included studies that a combination of behavioural treatment and pharmacotherapy is effective in helping smokers with COPD to quit smoking .
Furthermore , we conclude that there is no convincing evidence for preferring any particular form of behavioural or pharmacological treatment | BACKGROUND Smoking cessation is the most important treatment for smokers with chronic obstructive pulmonary disease ( COPD ) , but little is known about the effectiveness of different smoking cessation interventions for this particular group of smokers .
OBJECTIVES To evaluate the effectiveness of behavioural or pharmacological smoking cessation interventions , or both , in smokers with COPD . | Background Tobacco consumption is a preventable risk factor for chronic disease and complicates the treatment of medical conditions . Therefore , the German health insurance company AOK NORDWEST has developed a collaborative smoking cessation intervention for individuals with cardiovascular disease , chronic obstructive pulmonary disease and heavy smokers , with the aim of reducing tobacco consumption . The objective of the study ENTER is to evaluate the effectiveness of the collaborative smoking cessation intervention and determine its cost-effectiveness . Methods / Design This study is a cluster-r and omized controlled trial conducted with 40 medical practice s that are being selected from different geographic regions in Germany . Participating medical practice s will be r and omly allocated to either the intervention or control group . Within the medical practice s , a total of 800 patients will be recruited for participation in the study and blinded to group assignment . Patients are included in the study if they are 18 years or older , insured by AOK , heavy smokers ( smoke at least 20 cigarettes per day ) and /or suffer from chronic obstructive pulmonary disease or cardiovascular disease . Exclusion criteria are patients who are nonsmokers , who have cognitive impairments or who are illiterate . Physicians from medical practice s in the intervention group will motivate patients to participate in a smoking cessation program offered by the health insurance , refer them to the program and ask about their program participation . Physicians from medical practice s in the control group will provide usual care . Data collection will take place on the date of study inclusion and after 6 and 12 months . The primary outcome is the amount of cigarettes consumed during the past 30 days , 12 months after the initial medical consultation . Secondary outcomes are abstinence from smoking , health-related quality of life and respiratory complaints . Moreover , a process evaluation and health economic analysis will be performed . Discussion The results of this study will help to determine whether the collaborative smoking cessation intervention is an effective and feasible way to promote smoking cessation in the primary care setting and provide evidence regarding its cost-effectiveness . Trial registration German Clinical Trials Register DRKS00006079 . Registered 4 June 2014 OBJECTIVES The prevalence of COPD in Greece is unknown . The aim of this study was to determine the prevalence and trends of COPD among adults in Greece . METHODS This study involved 888 r and omly identified adults ( 475 men and 413 women ) aged > 35 years , and smokers of at least 100 cigarettes , in a population -based , multiregional , cross-sectional descriptive design . The selected individuals reflected the urban/rural population distribution in Greece and , within each study region , the age group and gender of the community setting . The diagnosis of COPD was based on clinical and spirometric data including reversibility test ( DeltaFEV(1 ) < 15 % ) . RESULTS The overall prevalence of COPD in the population aged > 35 years with a smoking history of > 100 cigarettes per lifetime was 8.4 % . The gender-st and ardized COPD prevalence was 11.6 % for men and 4.8 % for women . The COPD prevalence by community setting was as follows : Athens , 6 % ; other urban areas , 10.1 % ; semiurban areas , 8.5 % ; and rural areas , 9.1 % . Smoking intensity and age were significantly associated with higher COPD prevalence in both men and women . CONCLUSIONS COPD is a substantial health problem in Greece , although prevalence rates are lower than expected when the high smoking rates are taken into account . The high proportion of the patients with mild COPD who were unaware of their illness highlights the need to increase public awareness of COPD Stopping smoking is the only known method to slow down the inevitable progression of COPD . Early detection of the disease in smokers at risk of COPD gives a unique opportunity to prevent the disease progression . The aim of the study was to evaluate the effects of smoking intervention in a group of subjects with newly diagnosed airflow limitation ( AL ) . Of 558 current smokers participating in population spirometric screening for COPD combined with smoking cessation advice , 297 were diagnosed to have AL ( FEV1/FVC < 0.7 ) . After one year 193 presented for follow-up visit . Thirty subjects ( 10.1 % ) quit smoking . Remaining 163 smokers were invited to smokers ' clinic . Attendees ( n = 70 ) , 40 males , and 30 females , mean age 56 years , were r and omized at visit 1 to treatment with nicotine patch ( n = 38 ) or bupropion SR ( n = 32 ) . Follow-up was scheduled at 2 weeks , at the end of treatment , 6 months and 12 months . After 12 months a phone call assessed the smoking status . Non smoking was vali date d with carbon monoxide measurements in exhaled air . Patients who did not attend the follow-up visits were considered smokers . The number of participants at follow-up decreased significantly : from 70 subjects at visit one to 57 after 2 weeks , 34 at end of treatment and 14 subjects at months . Almost all ( n = 69 ) were reached at 12 month by the phone . The vali date d quit rate after 12 months was 18.5 % ( 13/70 ) , 8 in group treated with nicotine patch and 5 in the group treated with bupropion SR ( NS ) . When total group of smokers with newly diagnosed COPD was considered 10 % quit smoking as result of minimal intervention with another 4.5 % after pharmacological treatment Introduction COPD is a leading cause of morbidity and mortality . Self-management interventions are considered important in order to limit the progression of the disease . Computer-tailored interventions could be an effective tool to facilitate self-management . Methods This r and omized controlled trial tested the effectiveness of a web-based , computer-tailored COPD self-management intervention on physical activity and smoking behavior . Participants were recruited from an online panel and through primary care practice s. Those at risk for or diagnosed with COPD , between 40 and 70 years of age , proficient in Dutch , with access to the Internet , and with basic computer skills ( n=1,325 ) , were r and omly assigned to either the intervention group ( n=662 ) or control group ( n=663 ) . The intervention group received the web-based self-management application , while the control group received no intervention . Participants were not blinded to group assignment . After 6 months , the effect of the intervention was assessed for the primary outcomes , smoking cessation and physical activity , by self-reported 7-day point prevalence abstinence and the International Physical Activity Question naire – Short Form . Results Of the 1,325 participants , 1,071 ( 80.8 % ) completed the 6-month follow-up question naire . No significant treatment effect was found on either outcome . The application however , was used by only 36 % of the participants in the experimental group . Conclusion A possible explanation for the nonsignificant effect on the primary outcomes , smoking cessation and physical activity , could be the low exposure to the application as engagement with the program has been shown to be crucial for the effectiveness of computer-tailored interventions . ( Netherl and s Trial Registry number : NTR3421 . UNLABELLED There are few data concerning changes in lung function and respiratory symptoms in smokers with chronic obstructive pulmonary disease ( COPD ) weeks to months after quitting smoking . We examined serial changes in spirometry and Clinical COPD Question naire ( CCQ ) scores ( measuring respiratory symptoms and health-related quality of life ) in COPD participants by smoking status during a smoking cessation trial . In this r and omized , double-blind trial , smokers with mild-to-moderate COPD were treated with varenicline 1 mg b.i.d . or placebo for 12 weeks and followed to Week 52 . Primary endpoints of abstinence were previously reported . Secondary endpoints were mean changes from baseline in post-bronchodilator forced expired volume in 1 s ( FEV(1 ) ) and CCQ scores . Change from baseline in post-bronchodilator FEV(1 ) was significantly improved in continuous abstainers ( 121.8 mL ) vs. continuous smokers ( 37.9 mL ) at Week 12 ( P = 0.0069 ) , but not at Weeks 24 or 52 . Mean change from baseline at Week 12 in CCQ Total Score was significantly better in continuous abstainers ( -1.04 ) vs. continuous smokers ( -0.53 ; P < 0.0001 ) : this improvement was sustained at Weeks 24 and 52 . In a 1-year cessation trial of smokers with COPD , continuous abstinence compared with continuous smoking significantly improved post-bronchodilator FEV(1 ) at Week 12 ( although the difference narrowed subsequently ) and CCQ Total Scores at Week 12 , with sustained improvement thereafter . ( TRIAL REGISTRY http://www . clinical trials.gov ; trial identifier : NCT00285012 ) Background Anxiety and depression are common co-morbidities in patients with chronic obstructive pulmonary disease ( COPD ) . Serious implication s can result from psychological difficulties in COPD including reduced survival , lower quality of life , and reduced physical and social functioning , increased use of health care re sources and are associated with unhealthy behaviours such as smoking . Cognitive behavioural therapy ( CBT ) is a psychological intervention which is recommended for the treatment of many mental health problems including anxiety and depression . Unfortunately access to trained CBT therapists is limited . The aim of this study is to test the hypothesis that CBT delivered by respiratory nurses is effective in the COPD population . In this paper the design of the Newcastle Chronic Obstructive Pulmonary Disease Cognitive Behavioural Therapy Study ( Newcastle COPD CBT Care Study ) is described . Methods / Design This is a prospect i ve open r and omised controlled trial comparing CBT with self-help leaflets . The primary outcome measure is the Hospital Anxiety & Depression Scale ( HADS ) – anxiety subscale . Secondary outcome measures include disease specific quality of life COPD Assessment Tool ( CAT ) , generic quality of life ( EQ5D ) and HADS-depression subscale . Patients will be followed up at three , six and 12 months following r and omisation . Discussion This is the first r and omised controlled trial to evaluate the use of cognitive behavioural therapy undertaken by respiratory nurses . Recruitment has commenced and should be complete by February 2014.Trial registration Current Controlled Trials , IS RCT Rationale : Adults with chronic lower respiratory disease differ in their barriers to smoking cessation but also suffer from tobacco‐related health concerns , which may motivate quit attempts . Few studies have examined differences in tobacco treatment response between smokers with and without chronic lower respiratory disease . Objective : We examined the effectiveness of a proactive outreach program for cessation among smokers with and without chronic lower respiratory disease . Methods : Subgroup analysis of the Veterans Victory over Tobacco Study , a pragmatic r and omized controlled trial that demonstrated the effectiveness of proactive outreach and the choice of tobacco treatments compared with usual care . Smokers identified via the electronic medical record were proactively offered phone‐based counseling and care coordination to receive medication from their Veterans Affairs providers or in‐person care . We compared the response among those with and without an International Classification of Diseases , 9th Revision diagnosis of a chronic lower respiratory disease ( chronic obstructive pulmonary disease , chronic bronchitis , emphysema , asthma ) . We used stratification by propensity scores to adjust for imbalanced covariates between groups with and without chronic lower respiratory disease within each treatment arm , using complete case analysis accounting for the stratified sampling by site . Results : The study participants were predominantly older , white , male smokers . Overall , 19.6 % had chronic lower respiratory disease . A total of 3,307 had outcome data with the following assignments to the intervention : proactive care : n = 1,272 without chronic lower respiratory disease , n = 301 with chronic lower respiratory disease ; usual care : n = 1,387 without chronic lower respiratory disease , n = 347 with chronic lower respiratory disease . A total of 1,888 had both complete baseline and outcome data and were included in the primary analysis . In unadjusted analyses ( n = 3,307 ) , among individuals with chronic lower respiratory disease , 13.1 % in the proactive group reported 6‐month prolonged abstinence compared with 8.7 % of those in the usual care group ( odds ratio , 1.57 ; 95 % confidence interval , 0.93‐2.65 ) . Among individuals without chronic lower respiratory disease , 13.1 % quit in the proactive group compared with 11.0 % in the usual care group ( odds ratio , 1.22 ; 95 % confidence interval , 0.95‐1.55 ) . In adjusted analyses ( n = 1,888 ) , the association between treatment arm and quit rate varied by the presence of chronic lower respiratory disease , with a stronger association between allocation to the proactive group and quit rate among those with chronic lower respiratory disease ( odds ratio , 3.45 ; 95 % confidence interval , 1.59‐7.47 ) than those without chronic lower respiratory disease ( odds ratio , 1.34 ; 95 % confidence interval , 0.95‐1.88 ; P for interaction with chronic lower respiratory disease = 0.03 ) . Conclusions : Smokers with chronic lower respiratory disease may be more likely to respond to a proactive outreach intervention for tobacco cessation treatment than those without chronic lower respiratory disease . Clinical trial registered with www . clinical trials.gov ( NCT 00608426 ) The Lung Health Study ( LHS ) , a multicenter r and omized clinical trial of treatment to prevent chronic obstructive pulmonary disease ( COPD ) , recruited , over a 28-month period , 5887 smokers aged 35 - 60 who had evidence of mild airflow obstruction on pulmonary function testing . The LHS participants were identified from a pool of over 73,000 age-eligible smokers who underwent the initial pulmonary function screening tests . Methods of recruitment in the 10 centers are here classified into five general strategies : worksites , public sites , mail/phone , media , and other . This paper deals with the results of each of these general methods and their effectiveness in producing participants eligible for the study . The most effective strategies proved to be mail/phone and media . Ongoing monitoring and a flexible approach to recruitment characterized the most successful clinics . Over the recruitment period , LHS clinics shifted their emphasis away from worksite and public site strategies and tended to focus on variations of the mail/phone strategy . Female screenees who passed first-screen eligibility criteria were more likely than males to refuse further participation Smoking cessation treatment is now integrated into many health-care systems and a major research effort is under way to improve current success rates . Until now results from r and omized clinical trials have been reported in many different ways , leading to problems of interpretation . We propose six st and ard criteria comprising the ' Russell St and ard ' ( RS ) . These criteria are applicable to trials of cessation aids where participants have a defined target quit date and there is face-to-face contact with research ers or clinic staff , as follows . ( 1 ) Follow-up for 6 months ( RS6 ) or 12 months ( RS12 ) from the target quit date or the end of a predefined ' grace period ' ; ( 2 ) self-report of smoking abstinence over the whole follow-up period allowing up to five cigarettes in total ; ( 3 ) biochemical verification of abstinence at least at the 6-month or 12-month follow-up point ; ( 4 ) use of an ' intention-to-treat ' approach in which data from all r and omized smokers are included in the analysis unless they have died or moved to an untraceable address ( participants who are included in the analysis are counted as smokers if their smoking status at the final follow-up can not be determined ) ; ( 5 ) following-up ' protocol violators ' and using their true smoking status in the analysis ; and ( 6 ) collecting follow-up data blind to smokers ' allocation to trial group . We believe that these criteria provide the best compromise between practicability and surrogacy for long-term cessation and will enable meaningful comparison between studies . There may be good reasons why other outcome criteria would also be reported , and studies that involve interventions with special groups or where there is no design ated target quit date or face to face contact would need to adapt these criteria accordingly Few studies have examined the effect of individual counseling for smoking cessation in China . The present study evaluated the efficacy of individual counseling in patients with chronic obstructive pulmonary disease ( COPD ) and asymptomatic smokers . This prospect i ve r and omized study evaluated 85 smokers with COPD and 105 asymptomatic smokers with normal lung function . The individuals were r and omly allocated to intervention and control groups . Subjects in the intervention group were provided with individual cognitive counseling based on face-to-face individual consultation , self-help material s and nine telephone follow-ups . Subjects in the control group were provided with simple smoking cessation advice . The smoking status for all subjects and the St. George ’s Respiratory Question naire ( SGRQ ) for COPD patients were assessed at baseline , week 4 and month 6 . The COPD patient exacerbations during the 6 months were recorded . In the total study population , individual counseling result ed in higher abstinence rates compared with those in the control : Intervention vs. control , 23.4 vs. 10.4 % ( P=0.007 ) , respectively . Similar results were observed in the smokers with COPD : Intervention vs. control , 40.5 vs. 18.6 % ( P=0.027 ) , respectively . However , for asymptomatic smokers , the effect of individual counseling was identified to be statistically insignificant : Intervention vs. control , 9.6 vs. 3.8 % ( P=0.230 ) , respectively . SGRQ scores and COPD exacerbations were significantly improved in patients who abstained from smoking compared with those in the patients who failed to stop smoking . Airway obstruction , quitting motivation and individual counseling were predictors associated with smoking cessation . Airway obstruction was the most significant predictor of smoking cessation ( odds ratio , 4.215 ; 95 % confidence interval , 2.215–7.865 ) . The results of the present study show that individual counseling is an effective method for smoking cessation , particularly in COPD patients . However , its efficacy in asymptomatic smokers requires confirmation in further studies BACKGROUND The design and results of the initial intervention program of the Lung Health Study are presented for 3,923 male and female participants . One of the major aims of this clinical trial was to achieve smoking cessation early in the study and to provide intensive follow-up procedures for maintaining abstinence . In addition , compliance with use of aerosolized inhalers ( either placebo or active bronchodilator ) would be necessary in order to achieve the trial goal of improved pulmonary function . RESULTS Eighty-eight percent of the special intervention participants attended the 4-month follow-up visit . Forty-six percent reported not smoking from quit day through the visit , and an additional 13 % had stopped smoking at the end of 4 months , although they had not achieved abstinence since quit day . The aerosol inhaler compliance was self-reported at 81 % at the 4-month visit . Validating the self-reports by weighing canisters reduced the " good " compliance rates to 66 % . CONCLUSIONS The intensive behavioral program was effective in achieving high initial rates of smoking cessation and inhaler compliance . Use of nicotine gum appeared to be an effective adjunct to the multicomponent behavioral program . Smoking status does appear to be related to inhaler compliance among both men and women participants OBJECTIVE To evaluate two counseling programs in general practice to help smokers with chronic obstructive pulmonary disease ( COPD ) to quit smoking . METHODS Cluster r and omized controlled trial including 68 general practice s ( 667 patients ) using a r and omly assigned intervention program with counseling and advice about nicotine replacement therapy ( and additional bupropion-SR in one of the programs ) or usual care . Usual care consisted of periodic regular check-ups and COPD information . The main outcome measure was biochemically verified point prevalence at 12 months . RESULTS The two intervention groups were treated as one in the analysis because they were equally effective . The intervention result ed in a significantly self-reported higher success rate ( 14.5 % ) compared to usual care ( 7.4 % ) ; odds ratio=2.1 , 95 % confidence interval=1.1 - 4.1 . Biochemically verified quit rates were 7.5 % ( intervention ) and 3.4 % ( usual care ) ; odds ratio=2.3 , 95 % confidence interval=0.9 - 6.0 . CONCLUSION The program doubled the cessation rates ( statistically nonsignificant ) . Too few participants used the additional bupropion-SR to prove its effectiveness . PRACTICE IMPLICATION S The protocol s can be used for COPD patients in general practice , but expectations should be modest . If quitting is unsuccessful , a stepped care approach should be considered Chronic obstructive pulmonary disease ( COPD ) is disabling , with symptoms such as chronic cough , phlegm , wheezing , shortness of breath and increased infections of the respiratory passage . The aim was to examine the effects of a structured educational intervention programme at a nurse-led primary health care clinic ( PHCC ) on quality of life ( QoL ) , knowledge about COPD and smoking cessation in patients with COPD . This study had an experimental design in which 52 patients with COPD from a Swedish primary care setting were r and omized into two groups ( intervention or control ) . Both groups received st and ard care but patients in the intervention group were also offered two visits to a nurse specialized in COPD care . The purpose of the visits was to increase the patients ' self-care ability and their knowledge about COPD . The study was approved by the local Research Ethics Committee . Data were collected using two question naires , one pertaining to knowledge about COPD and smoking habits and St. George 's Respiratory Question naire , addressing how QoL was affected by the patients ' respiratory symptoms . The intervention and control groups answered both question naires on their first and last visits to the PHCC . A statistically significant increase was noted in the intervention group on QoL , the number of patients who stopped smoking and patients ' knowledge about COPD at the follow-up , 3 - 5 months after intervention . However , a confounding factor may have been that one of the research ers ( Eva Osterlund Efr aims son ) , as a nurse in the PHCC , performed the intervention . This implies that patients were in a dependent relationship which may have affected the responses in a favourable direction . Our findings show that conventional care alone did not have an effect on patients ' QoL and smoking habits . Instead , the evidence suggests that a structured programme with self-care education is needed to motivate patients for life-style changes INTRODUCTION To determine the cost-effectiveness of a high-intensity smoking cessation program ( SmokeStop Therapy ; SST ) versus a medium-intensity treatment ( Minimal Intervention Strategy for Lung patients [ LMIS ] ) for chronic obstructive pulmonary disease out patients . METHODS The cost-effectiveness analysis was based on a r and omized controlled trial investigating the effectiveness of the SST compared with the LMIS with 12-month follow-up . The primary outcome measure was the cotinine-vali date d continuous abstinence rate based on intention to treat . A health care perspective was adopted , with outcomes assessed in terms of ( incremental ) additional quitters gained , exacerbations prevented , and hospital days prevented . Health care re source use , associated with smoking cessation , was collected at baseline and 12 months after the start of the interventions . Monte Carlo simulations were performed to evaluate the robustness of the results . RESULTS The average patient receiving SST generated € 581 in health care costs , including the costs of the smoking cessation program , versus € 595 in the LMIS . The SST is also associated with a lower average number of exacerbations ( 0.38 vs. 0.60 ) and hospital days ( 0.39 vs. 1 ) per patient and a higher number of quitters ( 20 vs. 9 ) at lower total costs . This leads to a dominance of the SST compared with the LMIS . CONCLUSIONS The high-intensive SST is more cost-effective than the medium-intensive LMIS after 1 year . This is associated with cost savings per additional quitter , prevented exacerbations , and hospital days at lower or equal costs OBJECTIVE To ascertain the differences in smoking characteristics between a group of smokers with COPD and another group of healthy smokers , both of which were identified in a population -based epidemiologic study . DESIGN AND PARTICIPANTS This is an epidemiologic , multicenter , population -based study conducted in seven areas of SPAIN : A total of 4,035 individuals , men and women aged 40 to 69 years , who were selected r and omly from a target population of 236,412 subjects , participated in the study . INTERVENTIONS Eligible subjects answered the European Commission for Steel and Coal question naire . Spirometry was performed followed by a bronchodilator test when bronchial obstruction was present . The Fagerström question naire was used for study of the degree of physical nicotine dependence , and the Prochazka model was followed for analysis of the smoking cessation phase . RESULTS Of 1,023 active smokers , 153 ( 15 % ) met the criteria for COPD . Smokers with COPD were more frequently men ( odds ratio [ OR ] , 2.18 ; 95 % confidence interval [ CI ] , 1.21 to 3.95 ) , were > or = 46 years of age ( OR , 1.97 ; 95 % CI , 1.18 to 3.31 ) , had a lower educational level ( OR , 1.96 ; 95 % CI , 1.23 to 3.14 ) , and had smoked > 30 pack-years ( OR , 3.70 ; 95 % CI , 2.42 to 5.65 ) . Smokers with COPD showed a higher dependence on nicotine than healthy smokers ( mean [ + /- SD ] Fagerström test score , 4.77 + /- 2.45 vs 3.15 + /- 2.38 , respectively ; p < 0.001 ) and higher concentrations of CO in exhaled air ( mean concentration , 19.7 + /- 16.3 vs 15.4 + /- 12.1 ppm , respectively ; p < 0.0001 ) . Thirty-four percent of smokers with COPD and 38.5 % of smokers without COPD had never tried to stop smoking . CONCLUSIONS Smokers with COPD have higher tobacco consumption , higher dependence on nicotine , and higher concentrations of CO in exhaled air , suggesting a different pattern of cigarette smoking . Cases of COPD among smokers predominate in men and in individuals with lower educational levels . A significant proportion of smokers have never tried to stop smoking ; thus , advice on cessation should be reinforced in both groups of smokers Background Smoking is the main preventable cause of morbidity and mortality in our region , it being the main causative agent of chronic obstructive pulmonary disease . There still is no consensus on the use of spirometry as a strategy for smoking cessation , given that there is insufficient scientific evidence from high quality studies to recommend the use of this technique . Methods / Design This is to be a r and omized , multicentre , open-label clinical trial . A total of 444 smokers over 40 years of age will be recruited by 39 general practitioners from 22 health centers . Primary objective of this study is to assess the effectiveness of spirometry together with information regarding the test for smoking cessation after 1 year in smokers over 40 years of age with a more than 10 pack-year history and no previous diagnosis of chronic obstructive pulmonary disease . Groups of 45 patients who smoke will be r and omly selected from the lists of the participating doctors . The names will be sent to the corresponding doctors who will contact c and i date patients and assess whether they meet the selection criteria . Patients who meet these criteria will be r and omly allocated to an intervention or control group . For patients in both groups , a nurse will conduct an interview and perform a spirometry test to measure forced vital capacity . Then , all patients will be referred for an appointment with their doctor for brief anti-smoking intervention , patients from the intervention group additionally being informed about the result of the spirometry test . After 1 year , smoking status will be assessed and , in those who report that they have quit smoking , abstinence will be confirmed by co-oximetry . Data will be analyzed on an intention-to-treat basis using the chi-squared test for outcomes and binary logistic regression if it is considered to be necessary to adjust for confounding variables . Discussion Performing a spirometry test and providing information on pulmonary function may increase awareness of the effect of smoking among smokers who are asymptomatic or have few symptoms and make them decide to quit . Specifically , in patients with chronic obstructive pulmonary disease it might increase levels of motivation to quit smoking in early stages of the disease . If this strategy were to be effective , it could be included in the health promotion activities offered in primary care . Trial registration Clinical Trials.gov Identifier : Background Chronic Obstructive Pulmonary Disease ( COPD ) is a major cause of morbidity and mortality . Effective self-management support interventions are needed to improve the health and functional status of people with COPD or at risk for COPD . Computer-tailored technology could be an effective way to provide this support . Methods / Design This paper presents the protocol of a r and omised controlled trial testing the effectiveness of a web-based , computer-tailored self-management intervention to change health behaviours of people with or at risk for COPD . An intervention group will be compared to a usual care control group , in which the intervention group will receive a web-based , computer-tailored self-management intervention . Participants will be recruited from an online panel and through general practice s. Outcomes will be measured at baseline and at 6 months . The primary outcomes will be smoking behaviour , measuring the 7-day point prevalence abstinence and physical activity , measured in minutes . Secondary outcomes will include dyspnoea score , quality of life , stages of change , intention to change behaviour and alternative smoking behaviour measures , including current smoking behaviour , 24-hour point prevalence abstinence , prolonged abstinence , continued abstinence and number of quit attempts . Discussion To the best of our knowledge , this will be the first r and omised controlled trial to test the effectiveness of a web-based , computer-tailored self-management intervention for people with or at risk for COPD . The results will be important to explore the possible benefits of computer-tailored interventions for the self-management of people with or at risk for COPD and potentially other chronic health conditions . Dutch trial BACKGROUND : A number of effective strategies have been developed to improve the quality of life in patients with COPD . However , few have been implemented in patients with COPD at all stages in a community setting . This study evaluated the efficacy of a complex COPD health management intervention in rural communities in China . METHODS : A r and omized controlled trial including 8,217 subjects with COPD was implemented from May 2008 to May 2012 in 14 community health-care centers . The control group of subjects received usual care , whereas the management group of subjects participated in a health management program that included assessing the subjects ' health status , giving regular health lectures , smoking cessation counseling , encouraging regular exercise , providing rehabilitative training and psychological counseling , and regular follow-up . As a primary outcome , we examined the changes in the BODE index . Secondary outcomes included depression and anxiety rates , current smoking rate , awareness of COPD , mortality , risk factors , respiratory medication use , hospital admissions , and emergency department visits . RESULTS : After 4 y , the mean cumulative value of the BODE index increased by 0.7 per subject in the control group and decreased by 0.4 per subject in the health management group ( difference of 1.1 , 95 % CI 0.2–2.0 , P < .001 ) . Health management reduced anxiety symptoms by 4.8 % , depression symptoms by 6.6 % , current smoking by 14.3 % , mortality due to all causes by 9.0 % , hospitalizations due to all causes by 16.1 % , and emergency department visits due to all causes by 18.1 % ( P < .05 for all ) . However , it increased immunomodulator use by 58.9 % , respiratory medication use by 14.1–21.9 % , and awareness scores for COPD by 57.2 % ( P < .05 for all ) . CONCLUSIONS : The health management program is an effective community-based strategy for the prevention and management of COPD in China , increasing awareness and knowledge among patients and practitioners and improving management within the limitations of access to pharmacotherapy Background The Swiss health ministry launched a national quality program ‘ QualiCCare ’ in 2011 to improve health care for patients with COPD .The aim of this study is to determine whether participation in the COPD quality initiative ( ‘ QualiCCare ’ ) improves adherence to recommended clinical processes and shows impact on patients ’ COPD care and on the impact of COPD on a person 's life . Methods CAROL is a cluster-r and omized controlled trial with r and omization on the general practioner ( GP ) level . Thirty GPs will be r and omly assigned to equally sized intervention group or control group . Each GP will approach consecutively and regardless of the reason for the current consultation , patients aged 45 years or older , with a smoking history of ≥ ten pack-years ( PY ) . Patients with confirmed ( by spirometric evaluation ) COPD will be included in the study . GPs in the intervention group will receive ‘ QualiCCare ’ education , which addresses knowledge , decision-making and behavioural aspects as well as delivery of care according to COPD quality indicators and evidence -based key elements . In the control group , no educational intervention will be applied and COPD patients will be treated as usual . The study period is one year . The primary outcome measure is an aggregated score of relevant clinical processes defining elements in the care of patients with COPD : smoking cessation counseling , influenza vaccination , motivation for physical activity , appropriate pharmacotherapy , patient education and collaborative care . Given a power of 90 % and a significance level alpha of 5 % , 15 GPs recruiting eight patients each will be necessary in both study arms . With an assumed dropout rate of 20 % , 288 patients will need to be included . Discussion It is important to develop and implement interventions that add value to COPD care considering quality and efficiency . Care pathways modifying the knowledge and behavior of physicians have the potential for improving care by transferring knowledge to clinical practice .Trial registration Clinical Trials.gov : Background Chronic obstructive pulmonary disease ( COPD ) is a progressive , debilitating disease associated with significant clinical burden and is estimated to affect 15 million individuals in the US . Although a large number of individuals are diagnosed with COPD , many individuals still remain undiagnosed due to the slow progression of the disorder and lack of recognition of early symptoms . Not only is there under-diagnosis but there is also evidence of sub-optimal evidence -based treatment of those who have COPD . Despite the development of international COPD guidelines , many primary care physicians who care for the majority of patients with COPD are not translating this evidence into effective clinical practice . Method / Design This paper describes the design and rationale for a r and omized , cluster design trial ( RCT ) aim ed at translating the COPD evidence -based guidelines into clinical care in primary care practice s. During Phase 1 , a needs assessment evaluated barriers and facilitators to implementation of COPD guidelines into clinical practice through focus groups of primary care patients and providers . Using formative evaluation and feedback from focus groups , three tools were developed . These include a computerized patient activation tool ( an interactive iPad with wireless data transfer to the spirometer ) ; a web-based COPD guideline tool to be used by primary care providers as a decision support tool ; and a COPD patient education toolkit to be used by the practice team . During phase II , an RCT will be performed with one year of intervention within 30 primary care practice s. The effectiveness of the material s developed in Phase I are being tested in Phase II regarding physician performance of COPD guideline implementation and the improvement in the clinical ly relevant outcomes ( appropriate diagnosis and management of COPD ) compared to usual care . We will also examine the use of a patient activation tool - ‘ MyLungAge ’ - to prompt patients at risk for or who have COPD to request spirometry confirmation and to request support for smoking cessation if a smoker . Discussion Using a multi-modal intervention of patient activation and a technology-supported health care provider team , we are testing the effectiveness of this intervention in activating patients and improving physician performance around COPD guideline implementation . Trial registration Clinical Trials.gov , This study aim ed to assess the efficacy of a rural community-based integrated intervention for early prevention and management of chronic obstructive pulmonary disease ( COPD ) in China . This 18-year cluster-r and omized controlled trial encompassing 15 villages included 1008 patients ( 454 men and 40 women in the intervention group [ mean age , 54 ± 10 years ] ; 482 men and 32 women in the control group [ mean age , 53 ± 10 years ] ) with confirmed COPD or at risk for COPD . Villages were r and omly assigned to the intervention or the control group , and study participants residing within the villages received treatment accordingly . Intervention group patients took part in a program that included systematic health education , smoking cessation counseling , and education on management of COPD . Control group patients received usual care . The groups were compared after 18 years regarding the incidence of COPD , decline in lung function , and mortality of COPD . COPD incidence was lower in the intervention group than in the control group ( 10 % vs 16 % , < 0.05 ) . A decline in lung function was also significantly delayed in the intervention group compared to the control group of COPD and high-risk patients . The intervention group showed significant improvement in smoking cessation compared with the control group , and smokers in the intervention group had lower smoking indices than in the control group ( 350 vs 450 , < 0.05 ) . The intervention group also had a significantly lower cumulative COPD -related death rate than the control group ( 37 % vs 47 % , < 0.05 ) . A rural community-based integrated intervention is effective in reducing the incidence of COPD among those at risk , delaying a decline in lung function in COPD patients and those at risk , and reducing mortality of COPD Background The use of spirometry for early detection of chronic obstructive pulmonary disease ( COPD ) is still an issue of debate , particularly because of a lack of convincing evidence that spirometry has an added positive effect on smoking cessation . We hypothesise that early detection of COPD and confrontation with spirometry for smoking cessation may be effective when applying an approach we have termed " confrontational counselling " ; a patient-centred approach which involves specific communication skills and elements of cognitive therapy . An important aspect is to confront the smoker with his/her airflow limitation during the counselling sessions . The primary objective of this study is to test the efficacy of confrontational counselling in comparison to regular health education and promotion for smoking cessation delivered by specialized respiratory nurses in current smokers with previously undiagnosed mild to moderate airflow limitation . Methods / Design The study design is a r and omized controlled trial comparing confrontational counselling delivered by a respiratory nurse combined with nortriptyline for smoking cessation ( experimental group ) , health education and promotion delivered by a respiratory nurse combined with nortriptyline for smoking cessation ( control group 1 ) , and " care as usual " delivered by the GP ( control group 2 ) . Early detection of smokers with mild to moderate airflow limitation is achieved by means of a telephone interview in combination with spirometry . Due to a comparable baseline risk of airflow limitation and motivation to quit smoking , and because of the st and ardization of number , duration , and scheduling of counselling sessions between the experimental group and control group 1 , the study enables to assess the " net " effect of confrontational counselling . The study has been ethically approved and registered . Discussion Ethical as well as method ological considerations of the study are discussed in this protocol . A significant and relevant effect of confrontational counselling would provide an argument in favour of early detection of current smokers with airflow limitation . Successful treatment of tobacco dependence in respiratory patients requires repeated intensive interventions . The results of this study may also show that respiratory nurses are able to deliver this treatment and that intensive smoking cessation counselling is more feasible . Trial registration : Netherl and s Trial Register ( IS RCT N 64481813 ) Introduction Limited tobacco dependence treatment re sources exist for smoking COPD patients not ready to quit . Smoking reduction may be a viable treatment approach if it prompts quit attempts and subsequent abstinence . This article describes the protocol of the REDUQ ( REDUce and Quit ) study , which examines whether smoking reduction counselling plus combination nicotine replacement therapy ( NRT ) is (cost-)effective in achieving long-term abstinence in smoking COPD patients not ready to quit . Methods / Design We conducted a two-centre , parallel-group , r and omised controlled trial with 18 months follow-up in smoking out patients with COPD . Patients not ready to quit within the next month but willing to reduce their smoking , were r and omised to receive either intensive smoking reduction counselling plus combination NRT or a single information meeting plus self-help manual . Outcomes were assessed at baseline , 6 , 12 and 18 months . The primary outcome is ≥ 1-year prolonged abstinence . Secondary outcomes are point prevalence abstinence , successful ( i.e. ≥ 50 % ) smoking reduction , and incidence of quit attempts reported at follow-up assessment s. Smoking status is biochemically verified by salivary cotinine and expired CO . Other variables include smoking-related cognitions , intention and motivation to reduce and quit smoking , withdrawal symptoms , health-related quality of life , symptoms of anxiety and depression , state of mindfulness , lung function , use of health care re sources , and costs . Discussion The outcomes of the REDUQ trial will advance knowledge on treatment of smoking COPD patients not ready to quit . If (cost-)effective , the smoking reduction intervention can be offered to this difficult-to-treat target group as a valuable adjunct to smoking cessation treatment Evans , J. A. , Morrison , I. M. , and Saunders , K. B. (1974).Thorax , 29 , 401 - 406 . A controlled trial of prednisone , in low dosage , in patients with chronic airways obstruction . Ten men with chronic airways obstruction took part in a double-blind controlled cross-over trial of 5 mg prednisone , daily for a week , versus placebo . All patients had breathlessness as their main complaint , and chronic cough with sputum for 2 to 30 years ; five had evidence of emphysema on the chest radiograph . None had a personal or family history of asthma . For the group , mean forced expiratory volume in one second was 1·11 1 . , and mean forced vital capacity was 2·28 1 . Six patients had abnormally high levels of arterial Pco2 ( 46 - 52 mmHg ) . When the ` placebo ' and ` prednisone ' measurements were compared there was no significant change in forced expiratory volumes , bronchodilator effect on forced expiratory volumes , or blood gas tensions . Inspiratory airways resistance measured by body plethysmography was significantly higher , or ` worse ' , on prednisone ( mean 4·2 cmH2O per 1/sec ) than on placebo ( mean 3·2 ) Objective To evaluate the impact of telling patients their estimated spirometric lung age as an incentive to quit smoking . Design R and omised controlled trial . Setting Five general practice s in Hertfordshire , Engl and . Participants 561 current smokers aged over 35 . Intervention All participants were offered spirometric assessment of lung function . Participants in intervention group received their results in terms of “ lung age ” ( the age of the average healthy individual who would perform similar to them on spirometry ) . Those in the control group received a raw figure for forced expiratory volume at one second ( FEV1 ) . Both groups were advised to quit and offered referral to local NHS smoking cessation services . Main outcome measures The primary outcome measure was verified cessation of smoking by salivary cotinine testing 12 months after recruitment . Secondary outcomes were reported changes in daily consumption of cigarettes and identification of new diagnoses of chronic obstructive lung disease . Results Follow-up was 89 % . Independently verified quit rates at 12 months in the intervention and control groups , respectively , were 13.6 % and 6.4 % ( difference 7.2 % , P=0.005 , 95 % confidence interval 2.2 % to 12.1 % ; number needed to treat 14 ) . People with worse spirometric lung age were no more likely to have quit than those with normal lung age in either group . Cost per successful quitter was estimated at £ 280 ( € 366 , $ 556 ) . A new diagnosis of obstructive lung disease was made in 17 % in the intervention group and 14 % in the control group ; a total of 16 % ( 89/561 ) of participants . Conclusion Telling smokers their lung age significantly improves the likelihood of them quitting smoking , but the mechanism by which this intervention achieves its effect is unclear . Trial registration National Research Register N0096173751 Background Chronic Obstructive Pulmonary Disease ( COPD ) is a leading cause of disability , hospitalization , and premature mortality . General practice is well placed to diagnose and manage COPD , but there is a significant gap between evidence and current practice , with a low level of awareness and implementation of clinical practice guidelines . Under-diagnosis of COPD is a world-wide problem , limiting the benefit that could potentially be achieved through early intervention strategies such as smoking cessation , dietary advice , and exercise . General practice is moving towards more structured chronic disease management , and the increasing involvement of practice nurses in delivering chronic care . Design A pragmatic cluster r and omised trial will test the hypothesis that intervention by a practice nurse-general practitioner ( GP ) team leads to improved health-related quality of life and greater adherence with clinical practice guidelines for patients with newly-diagnosed COPD , compared with usual care . Forty general practice s in greater metropolitan Sydney Australia will be recruited to identify patients at risk of COPD and invite them to attend a case finding appointment . Practice s will be r and omised to deliver either practice nurse-GP partnership care , or usual care , to patients newly-diagnosed with COPD .The active intervention will involve the practice nurse and GP working in partnership with the patient in developing and implementing a care plan involving ( as appropriate ) , smoking cessation , immunisation , pulmonary rehabilitation , medication review , assessment and correction of inhaler technique , nutritional advice , management of psycho-social issues , patient education , and management of co-morbidities . The primary outcome measure is health-related quality of life , assessed with the St George ’s Respiratory Question naire 12 months after diagnosis . Secondary outcome measures include vali date d disease-specific and general health related quality of life measures , smoking and immunisation status , medications , inhaler technique , and lung function . Outcomes will be assessed by project officers blinded to patients ’ r and omization groups . Discussion This study will use proven case-finding methods to identify patients with undiagnosed COPD in general practice , where improved care has the potential for substantial benefit in health and healthcare utilization . The study provides the capacity to trial a new model of team-based assessment and management of newly diagnosed COPD in Australian primary care . Trial registration The purpose of this study was to investigate the effects on activities of daily living , quality of life , and exercise tolerance of a comprehensive out-patient rehabilitation programme for patients with moderate-to-severe chronic obstructive pulmonary disease . In this r and omized and controlled trial , the main outcome measures were Activities of Daily Living ( ADL ) score , York Quality of Life Question naire ( YQLQ ) score , Chronic Respiratory Disease Question naire ( CRDQ ) score , 6 min walking distance ( 6MWD ) , forced expiratory volume in one second ( FEV1 ) , and forced vital capacity ( FVC ) . The rehabilitation programme included physical training , occupational therapy , education , and smoking cessation therapy , and lasted for 12 weeks . The patients were evaluated at entry , halfway through , and at the end of the programme . Follow-up was at 24 weeks . Forty seven patients were recruited , and 16 in each group completed the trial . There were significant differences in the improvements in ADL and CRDQ between the control and the treatment groups at 12 and 24 weeks , and at 24 weeks , respectively . At 6 , 12 and 24 weeks , improvements in the 6MWD were 21.6 versus 79.8 , 36.1 versus 113.1 and 21.4 versus 96.2 for control and treatment groups , respectively ( p<0.004 ) . A correlation matrix showed only ADL and 6MWD to be significantly correlated ; the matrix was also used to vali date the translated question naires . The programme required 124 staff-hours in total . An inexpensive , comprehensive out-patient rehabilitation programme can produce long-term improvement in activities of daily living , quality of life , and exercise tolerance in patients with moderate-to-severe chronic obstructive pulmonary disease 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 ) The study aim ed to estimate the cost-effectiveness of interdisciplinary community-based chronic obstructive pulmonary disease ( COPD ) management in patients with COPD . We conducted a cost-effectiveness analysis alongside a 2-yr r and omised controlled trial , in which 199 patients with less advanced airflow obstruction and impaired exercise capacity were assigned to the INTERCOM programme or usual care . The INTERCOM programme consisted of exercise training , education , nutritional therapy and smoking cessation counselling offered by community-based physiotherapists and dieticians and hospital-based respiratory nurses . All-cause re source use during 2 yrs was obtained by self-report and from hospital and pharmacy records . Health outcomes were the St George 's Respiratory Question naire ( SGRQ ) , exacerbations and quality -adjusted life years ( QALYs ) . The INTERCOM group had 30 % ( 95 % CI 3–56 % ) more patients with a clinical ly relevant improvement in SGRQ total score , 0.08 ( 95 % CI -0.01–0.18 ) more QALYs per patient , but a higher mean number of exacerbations , 0.84 ( 95 % CI -0.07–1.78 ) . Mean total 2-yr costs were € 2,751 ( 95 % CI -€632–€6,372 ) higher for INTERCOM than for usual care , which result ed in an incremental cost-effectiveness ratio of € 9,078 per additional patient with a relevant improvement in SGRQ or € 32,425 per QALY . INTERCOM significantly improved disease-specific quality of life , but did not affect exacerbation rate . The cost per QALY ratio was moderate , but within the range of that generally considered to be acceptable Background Adoption and maintenance of healthy behaviours is pivotal to chronic disease self-management as this influences disease progression and impact . This qualitative study investigated health behaviour changes adopted by participants with moderate or severe chronic obstructive pulmonary disease ( COPD ) recruited to a r and omised controlled study of telephone-delivered health-mentoring . Methods Community nurses trained as health-mentors used a patient-centred approach with COPD patients recruited in general practice to facilitate behaviour change , using a framework of health behaviours ; ‘ SNAPPS ’ Smoking , Nutrition , Alcohol , Physical activity , Psychosocial well-being , and Symptom management , through regular phone calls over 12 months . Semi-structured interviews in a purposive sample sought feedback on mentoring and behaviour changes adopted . Interviews were analysed using iterative thematic and interpretative content approaches by two investigators . Results Of 90 participants allocated to health-mentoring , 65 ( 72 % ) were invited for interview at 12-month follow up . The 44 interviewees , 75 % with moderate COPD , had a median of 13 mentor contacts over 12 months , range 5–20 . Interviewed participants ( n = 44 , 55 % male , 43 % current smokers , 75 % moderate COPD ) were representative of the total group with a mean age 65 years while 82 % had at least one additional co-morbid chronic condition . Telephone delivery was highly acceptable and enabled good rapport . Participants rated ‘ being listened to by a caring health professional ’ as very valuable . Three participant groups were identified by attitude to health behaviour change : 14 ( 32 % ) actively making changes ; 18 ( 41 % ) open to and making some changes and 12 ( 27 % ) more resistant to change . COPD severity or current smoking status was not related to group category . Mentoring increased awareness of COPD effects , helping develop and personalise behaviour change strategies , even by those not actively making changes . Physical activity was targeted by 43 ( 98 % ) participants and smoking by 14 ( 74 % ) current smokers with 21 % reporting quitting . Motivation to maintain changes was increased by mentor support . Conclusions Telephone delivery of health-mentoring is feasible and acceptable to people with COPD in primary care . Health behaviours targeted by this population , mostly with moderate disease , were mainly physical activity and smoking reduction or cessation . Health-mentoring increased motivation and assisted people to develop strategies for making and sustaining beneficial change . Trial registration STUDY OBJECTIVE --The aim was to measure experimentally the effects in middle aged men of stopping smoking . DESIGN --The study was a r and omised controlled trial . SETTING AND SUBJECTS -- The subjects were 1445 male smokers , initially aged 40 - 59 years , who were selected from the Whitehall study survey of 16,016 civil servants on the basis of a high risk of cardiorespiratory disease . MAIN RESULTS --During the next 20 years there were 620 deaths ( 231 from coronary heart disease ) , 96 cases of lung cancer , and 159 other cancers . Comparing the intervention with the normal care group , total mortality was 7 % lower , fatal coronary heart disease was 13 % lower , and lung cancer ( deaths+ registration s ) was 11 % lower . An excess rate for other cancers , reported previously , did not persist into the second decade of the trial . CONCLUSIONS --The results are consistent with observational studies , implying that smoking cessation by middle aged men substantially improves their changes of avoiding lung cancer or a fatal heart attack . Our estimate from the trial is that out of every 100 men who stopped smoking , between six and 10 were in consequence alive 20 years later Smoking causes chronic obstructive pulmonary disease ( COPD ) , but few controlled studies have tested anti-smoking treatments in COPD . With procedures likely to attract unmotivated persons we recruited 49 quite-ill , smoking COPD patients . During one or two daily home visits for 85 days , breath carbon monoxide ( CO ) and self-reports of daily smoking were obtained . Patients , given quit date s and nicotine gum ( 2-mg pieces , up to 30 per day ) , were assigned r and omly to three groups : Experimentals were reinforced with lottery tickets for CO < 10 ppm . Cigarette Self Report ( CSR ) patients were reinforced for reporting no smoking that day . Controls received non-contingent payments . Each group 's mean CO level fell at the quit date . Thereafter , reinforced patients maintained significantly lower CO levels than Controls . Although many more 24-h abstentions occurred in the intervention period than in baseline , few patients sustained abstinence ; the groups did not differ in that regard . Outcome was predicted by decisions to throw away cigarettes when intervention began , but not by motivation scales nor Fagerstrom dependence scores . Pay schedules apparently exaggerated self-reports of reduced smoking . Although results are statistically significant , there is still no proven , practical treatment for smoking in advanced COPD OBJECTIVE Within the framework of a r and omized , active treatment controlled trial , we used a mediation analysis to underst and the mechanisms by which an intervention that uses confrontation with spirometry for smoking cessation achieves its effects . METHODS Participants were 228 smokers from the general population with previously undetected chronic obstructive pulmonary disease ( COPD ) , who were detected with airflow limitation by means of spirometry . They received two equally intensive behavioural treatments by a respiratory nurse combined with nortriptyline for smoking cessation : confrontational counselling with spirometry versus conventional health education and promotion ( excluding confrontation with spirometry and COPD ) . RESULTS Cotinine vali date d abstinence rates from smoking at 5 weeks after the target quit date were 43.1 % in the confrontational counselling group versus 31.3 % in the control group ( OR=1.67 , 95%CI=0.97 - 2.87 ) . The effect of confrontational counselling on abstinence was independently mediated by the expectation of getting a serious smoking related disease in the future ( OR=1.76 , 95%CI=1.03 - 3.00 ) , self-exempting beliefs ( OR=0.42 , 95%CI=0.21 - 0.84 ) , and self-efficacy ( OR=1.38 , 95%CI=1.11 - 1.73 ) . CONCLUSION We conclude that confrontational counselling increases risk perceptions and self-efficacy , and decreases self-exempting beliefs ( risk denial ) in smokers with previously undetected COPD . These changes in mediators are associated with a higher likelihood of smoking cessation . PRACTICE IMPLICATION S Apart from the intensity , the content of smoking cessation counselling may be an important factor of success . A confrontational counselling approach as we applied may have the potential to alter smoking-related cognitions in such a way that smokers are more successful in quitting . Nurses can be trained to deliver this treatment OBJECTIVE To examine demographic , relationship , and smoking history factors related to expected positive and negative support for quitting smoking among chronically ill veterans . METHODS Data for this report comes from baseline data from a r and omized controlled trial of a support-based smoking cessation intervention for veterans with chronic diseases ( cancer , cardiovascular disease , hypertension , diabetes , and chronic obstructive pulmonary disease ) . We used separate multiple linear regression models to analyze relationships between positive and negative support and variables selected for model entry . RESULTS Veterans in our sample expected high positive and negative support for quitting . Veterans who were married/living as married , had some college education , were female , or named a female support person expected higher levels of positive support . Veterans who named a female or a nonsmoker as a support person expected higher levels of negative support . Males and non-Caucasians also reported higher levels of expected negative support . CONCLUSIONS Individual differences that influence perceptions of expected support are likely to influence intervention participation and engagement . Thus , underst and ing factors associated with expected positive and negative support is necessary to optimize future implementation of support-based cessation interventions through better treatment matching WHAT IS KNOWN AND OBJECTIVE Chronic obstructive pulmonary disease ( COPD ) , a preventable and treatable disease , has been described as ' 10 % medication and 90 % education ' . Extreme physician scarcity limits the implementation of quality healthcare delivery in India . We conducted this study to evaluate the effectiveness of clinical pharmacist intervention on health-related quality of life ( HRQoL ) in patients with COPD in an Indian tertiary care hospital . METHODS An open-labelled r and omized controlled study was conducted over a 3-year period , at Kasturba Medical College Hospital , Manipal , India , after obtaining institutional ethics clearance ( IEC 88/2012 ) . The study was registered with the Indian clinical trial registry ( CTRI/2014/08/004848 ) . Patients were r and omly assigned to two groups ( intervention group [ IG ] and control group [ CG ] ) by envelope method . St. George 's Respiratory Question naire ( SGRQ ) was used to assess the HRQoL. The pharmacist intervention laid emphasis on ( i ) importance of medication compliance , ( ii ) need for smoking cessation , ( iii ) simple exercise , ( iv ) proper use of inhaler devices and ( v ) need for timely follow-up by pulmonary medicine department . SGRQ assessment was repeated at 6 , 12 , 18 and 24 months . RESULTS Of 328 patients with COPD screened during the study period ( March 2012 to June 2013 ) , 260 ( 79 % ) were recruited . Of these , 202 ( 78 % ) patients completed follow-up ( 98 in CG and 104 in IG ) . Both groups were matched for baseline , sociodemographics and clinical characteristics . SGRQ scores and its subscales ( symptoms , activity and impact ) improved significantly after the pharmacist intervention in IG at follow-up ( P < 0·001 ) . WHAT IS NEW AND CONCLUSION Our r and omized controlled study shows that pharmacist intervention improved the HRQoL of patients with COPD in India . The generalizability of our results requires exploration even within other setting s in India . Nonetheless , our results provide support for a greater involvement of pharmacists in the care of patients with COPD BACKGROUND Smoking cessation is the primary disease modifying intervention for chronic obstructive pulmonary disease ( COPD ) . SETTING A Regional Respiratory Centre ( RRC ) out-patient department in Northern Irel and . METHODS A r and omised controlled trial ( RCT ) evaluated the effectiveness of brief advice alone or accompanied by individual nurse support or group support facilitated by nurses . Smoking status was biochemically vali date d and stage of change , nicotine addiction and dyspnoea were recorded at 2 , 3 , 6 , 9 and 12 months . PARTICIPANTS Ninety-one cigarette smokers with COPD were enrolled in the study ( mean age 61 years , 47 female ) . RESULTS After 12 months cessation rates were not significantly different between groups ( p=0.7 ) , but all groups had a significant reduction in their nicotine addiction ( p=0.03 - 0.006 ) . No changes in subjects ' motivation or dyspnoea were detected over the 12 months . CONCLUSION Patients with COPD were unable to stop smoking regardless of the type of support they received . Harm reduction may be a more appropriate goal than complete cessation for intractable smokers and nurses must evaluate their role in this arena Rationale Smoking cessation interventions in outpatient setting s have been demonstrated to be cost effective . Given this evidence , we aim ed to evaluate the effectiveness of varenicline tartrate plus Quitline-counselling compared with Quitline-counselling alone when initiated in the inpatient setting . Methods Adult patients ( 18–75 years ) admitted with a smoking-related illness to three hospitals , were r and omised to receive either 12-weeks of varenicline tartrate plus Quitline-counselling , ( n=196 ) or Quitline-counselling alone , ( n=196 ) , with 12-months follow-up . Results For the primary analysis population ( intention-to-treat ) , the proportion of subjects who remained continuously abstinent were significantly greater in the varenicline plus counselling arm ( 31.1 % , n=61 ) compared with counselling alone ( 21.4 % , n=42 ; RR 1.45 , 95 % CI 1.03 to 2.03 , p=0.03 ) . Conclusions The combined use of varenicline plus counselling when initiated in the inpatient setting has produced a sustained smoking cessation benefit at 12-months follow-up , indicating a successful opportunistic treatment for smokers admitted with smoking related illnesses . Trial registration http://www . clinical trials.gov/ Clinical Trials.gov identification number : NCT01141855 Seventy-four cigarette-smoking patients admitted with COPD to the Chest Unit of a 600-bed teaching hospital served as subjects for a r and omized trial of smoking cessation counseling . All patients were advised to quit smoking and smoking in the unit was not allowed . One-half of the patients were , in addition , provided with a self-help manual and three to eight 15- to 20-min counseling sessions on alternate days while in hospital . Self-reports of smoking status were obtained at 3 and 6 months , a sample of which were vali date d with serum COHb . The results were disappointing . Differences between the counseled group and the controls both in rates of cessation at 6 months ( 33.3 % vs 21.4 % ) and , for patients still smoking , reductions in amount smoked would have lacked practical significance even if statistical significance had been obtained . Some alternative treatment approaches are suggested for this group of patients OBJECTIVES In healthy smokers , antidepressants can double the odds of cessation . Because of its four times lower costs and comparable efficacy in healthy smokers , nortriptyline appears to be favourable compared to bupropion . We assessed which of both drugs was most effective and cost-effective in stopping smoking after 1 year compared with placebo among smokers at risk or with existing chronic obstructive pulmonary disease ( COPD ) . METHODS A total of 255 participants , aged 30 - 70 years , received smoking cessation counselling and were assigned bupropion , nortriptyline or placebo r and omly for 12 weeks . Prolonged abstinence from smoking was defined as a participant 's report of no cigarettes from week 4 to week 52 , vali date d by urinary cotinine . Costs were calculated using a societal perspective and uncertainty was assessed using the bootstrap method . RESULTS The prolonged abstinence rate was 20.9 % with bupropion , 20.0 % with nortriptyline and 13.5 % with placebo . The differences between bupropion and placebo [ relative risk ( RR ) = 1.6 ; 95 % confidence interval ( CI ) 0.8 - 3.0 ] and between nortriptyline and placebo ( RR = 1.5 ; 95 % CI 0.8 - 2.9 ) were not significant . Severity of airway obstruction did not influence abstinence significantly . Societal costs were 1368 euros ( 2.5th-97.5th percentile 193 - 5260 ) with bupropion , 1906 euros ( 2.5th-97.5th 120 - 17 761 ) with nortriptyline and 1212 euros ( 2.5th-97.5th 96 - 6602 ) with placebo . Were society willing to pay more than 2000 euros for a quitter , bupropion was most likely to be cost-effective . CONCLUSIONS Bupropion and nortriptyline seem to be equally effective , but bupropion appears to be more cost-effective when compared to placebo and nortriptyline . This impression holds using only health care costs . As the cost-effectiveness analyses concern some uncertainties , the results should be interpreted with care and future studies are needed to replicate the findings Introduction : Whether smoking-induced lung inflammation subsides after smoking cessation is currently a matter of debate . We used computed tomography ( CT ) to evaluate the effect of smoking cessation on lung density in patients with COPD . Material and methods : Thirty-six patients quit smoking out of 254 current smokers with COPD who were followed with annual CT and lung function tests ( LFT ) for 2–4 years as part of a r and omised placebo-controlled trial of the effect of inhaled budesonide on CT-lung density . Lung density was expressed as the 15th percentile density ( PD15 ) and relative area of emphysema below -910 HU ( RA-910 ) . From the time-trends in the budesonide and placebo groups the expected CT-lung densities at the first visit after smoking cessation were calculated by linear regression and compared to the observed densities . Results : Following smoking cessation RA-910 increased by 2.6 % ( p = 0.003 ) and PD15 decreased by −4.9 HU ( p = 0.0002 ) . Furthermore , changes were larger in the budesonide group than the placebo group ( PD15 : −7.1 vs −2.8 HU . RA-910 3.7 % vs 1.7 % ) . These differences were , however , not statistically significant . The LFT parameters ( FEV1 and diffusion capacity ) were not significantly influenced by smoking cessation . Conclusion : Inflammation partly masks the presence of emphysema on CT and smoking cessation results in a paradoxical fall in lung density , which resembles rapid progression of emphysema . This fall in density is probably due to an anti-inflammatory effect of smoking cessation Background . Smoking cessation is the most important therapeutic intervention in patients with chronic obstructive pulmonary diseases ( COPD ) and the health benefits are immediate and substantial . Major efforts have been made to develop methods with high smoking cessation rates . Objectives . To study whether a combination of spirometry and brief smoking cessation advice to smokers with COPD , annually for three years , increased their smoking cessation rate in comparison with groups of smokers with normal lung function . Method . Prospect i ve , r and omized study in primary care . Smoking cessation rates were compared between smokers with COPD followed-up yearly over a period of three years and smokers with normal lung function followed-up yearly for three years or followed-up only once after three years . Results . The point-prevalence abstinence rate and prolonged abstinence rate at 6 and 12 months increased yearly and in smokers with COPD at year 3 was 29 % , 28 % , and 25 % , respectively . The abstinence rates were significantly higher in smokers with COPD than in smokers with normal lung function . Smoking cessation rates among smokers with normal lung function did not increase with increasing number of follow-ups . Conclusion . Smokers diagnosed with COPD stopped smoking significantly more often than those with normal lung function Previous studies of lung function in relation to smoking cessation have not adequately quantified the long-term benefit of smoking cessation , nor established the predictive value of characteristics such as airway hyperresponsiveness . In a prospect i ve r and omized clinical trial at 10 North American medical centers , we studied 3 , 926 smokers with mild-to-moderate airway obstruction ( 3,818 with analyzable results ; mean age at entry , 48.5 yr ; 36 % women ) r and omized to one of two smoking cessation groups or to a nonintervention group . We measured lung function annually for 5 yr . Participants who stopped smoking experienced an improvement in FEV(1 ) in the year after quitting ( an average of 47 ml or 2 % ) . The subsequent rate of decline in FEV(1 ) among sustained quitters was half the rate among continuing smokers , 31 + /- 48 versus 62 + /- 55 ml ( mean + /- SD ) , comparable to that of never-smokers . Predictors of change in lung function included responsiveness to beta-agonist , baseline FEV(1 ) , methacholine reactivity , age , sex , race , and baseline smoking rate . Respiratory symptoms were not predictive of changes in lung function . Smokers with airflow obstruction benefit from quitting despite previous heavy smoking , advanced age , poor baseline lung function , or airway hyperresponsiveness BACKGROUND This study was undertaken to assess the safety and efficacy of a treatment involving brief counseling and the nicotine patch among hospital in patients and to identify variables associated with long-term smoking cessation following hospitalization . METHODS One hundred eighty-five patients were r and omly assigned to one of three smoking cessation interventions : ( 1 ) A Minimal Care ( MC ) condition , consisting of a brief physician-delivered motivational message to stop smoking , ( 2 ) a Counseling + Active Nicotine Patch ( CAP ) condition in which patients received the motivational message , a 6-week supply of nicotine patches , and extended bedside and telephone counseling , and ( 3 ) a Counseling + Placebo Patch ( CPP ) condition identical to the CAP condition except the supplied patches contained no nicotine . RESULTS At 6-month follow-up , abstinence rates for the three treatments were 4.9 , 6.5 , and 9.7 % for the MC , CPP , and CAP treatments , respectively . These differences were not statistically significant . Patients admitted for respiratory disease were more likely to quit than patients with any other diagnosis . The nicotine patch was well tolerated by hospital in patients . CONCLUSIONS The initiation of nicotine patch therapy during hospitalization appears to be safe when used among patients carrying a wide range of diagnoses . Our study provided no evidence of the superiority of nicotine patches versus placebo , but this does not preclude the possibility that future research using larger sample s might detect differences between patch groups . Hospital interventions for smoking cessation may be most effective among patients hospitalized for a smoking-related illness such as respiratory disease RATIONALE Underst and ing normal lung development and aging in health and disease , both in men and in women , is essential to interpreting any therapeutic intervention . OBJECTIVES We aim ed to describe lung function changes in healthy never-smoking males and females , from adolescence to old age , and to determine the effects of smoking and those derived from quitting . METHODS Prospect i ve cohort study within all participants of the Framingham Offspring cohort who had two or more valid spirometry measurements during follow-up ( n = 4,391 ; age range at baseline 13 to 71 yr ) , with a median follow-up time of 23 years . MEASUREMENTS AND MAIN RESULTS To best fit the curves describing FEV(1 ) changes with age to raw data , we used a generalized additive model with smooth terms and incorporating the subject-specific ( longitudinal ) r and om effects . We found that : ( 1 ) healthy never-smoker females achieve full lung growth earlier than males , and their rate of decline with age was slightly , but not significantly , lower ; ( 2 ) smoking increases the rate of lung function decline , both in males and in females ; ( 3 ) there is a range of susceptibility to the effects of smoking . The presence of respiratory symptoms at baseline and /or a respiratory diagnosis during follow-up appears to identify a group of susceptible smokers ; and ( 4 ) quitting smoking has a beneficial effect at any age , but it is more pronounced in earlier quitters . CONCLUSIONS Lung function changes from adolescence to old age differ in males and females , smoking has similar deleterious effects in both sexes , and quitting earlier is better BACKGROUND Hospital readmissions for acute exacerbations of COPD ( AE COPD s ) pose burdens to the health-care system and patients . A current gap in knowledge is whether a predischarge screening and educational tool administered to patients with COPD reduces readmissions and ED visits . METHODS A single-center , r and omized trial of admitted patients with AE COPD s was conducted at Henry Ford Hospital between February 2010 and April 2013 . One hundred seventy-two patients were r and omized to either the control ( st and ard care ) or the bundle group in which patients received smoking cessation counseling , screening for gastroesophageal reflux disease and depression or anxiety , st and ardized inhaler education , and a 48-h postdischarge telephone call . The primary end point was the difference in the composite risk of hospitalizations or ED visits for AE COPD between the two groups in the 30 days following discharge . A secondary end point was 90-day readmission rate . RESULTS Of the 172 patients , 18 of 79 in the control group ( 22.78 % ) and 18 of 93 in the bundle group ( 19.35 % ) were readmitted within 30 days . The risk of ED visits or hospitalizations within 30 days was not different between the groups ( risk difference , -3.43 % ; 95 % CI , -15.68 % to 8.82 % ; P = .58 ) . Overall , the time to readmission in 30 and 90 days was similar between groups ( log-rank test P = .71 and .88 , respectively ) . CONCLUSIONS A predischarge bundle intervention in AE COPD is not sufficient to reduce the 30-day risk of hospitalizations or ED visits . More re sources may be needed to generate a measurable effect on readmission rates . TRIAL REGISTRY Clinical Trials.gov ; No. : NCT02135744 ; URL : www . clinical trials.gov Background : The British Thoracic Society ( BTS ) guidelines have not been examined collectively for their impact on chronic obstructive pulmonary disease ( COPD ) . Whether intensive outpatient follow up of COPD patients after acute admission , using these guidelines , improved quality of life compared to the “ usual practice ” of primary care follow up was investigated . Methods : Altogether 103 patients with a new diagnosis of COPD were admitted and screened over a four year period . Seventy patients were excluded because of another dominant medical condition or a m and atory requirement for intervention . Patients were r and omised to regular primary care ( control group , n = 15 ) or chest clinic follow up ( intervention group , n = 10 ) . Spirometry , oxygen saturation , St George ’s Respiratory Question naire ( SGRQ ) , and Short Form 36 question naire were measured at baseline and six months . The intervention group was review ed at least four times in the six month period and received spirometry , ambulatory oxygen assessment , smoking cessation advice , nebuliser assessment , a steroid trial , advice about nutrition/exercise , and introduction to a patient support group . Results : There was no significant difference between baseline measurements in the two groups . There was a significant mean ( SD ) improvement in the SGRQ symptom score from baseline to six months in the intervention group [ 20.98 ( 20.36 ) ] compared with the controls [ 0.23 ( 12.55 ) ] ( p = 0.004 ) . At six months the SGRQ symptom score , impact score , and total score was significantly better in the intervention than the control group ( p = 0.01 , 0.02 , and 0.02 ) . Conclusion : Aggressive implementation of BTS guidelines after initial hospitalisation may improve respiratory health specific quality of life scores in patients with COPD . Larger studies are needed to confirm this finding OBJECTIVES The aims of this study were to identify prospect i ve determinants of smoking cessation in COPD patients , and to assess whether prospect i ve determinants vary between two different cessation interventions . METHODS Two hundred and twenty-five moderate to severe COPD patients were r and omly allocated to two smoking cessation interventions . One-year cotinine-vali date d continuous abstinence rates were 9 % for the minimal intervention strategy for lung patients ( LMIS ) and 19 % for the SmokeStopTherapy ( SST ) . The baseline characteristics that showed a significant univariate relationship with 1-year continuous abstinence ( p<.20 ) were included in the logistic regression model . This procedure was performed for each intervention separately . Variables that did not remain independent predictors were removed . RESULTS For the SST separately , no independent significant predictor remained . For the LMIS , attitude towards smoking cessation ( OR : 11.8 ; 95 % CI : 1.7 - 81.5 ; p=.013 ) and cotinine level ( OR : 2.1 ; 95 % CI : 1.08 - 3.93 ; p=.028 ) remained significant predictors . Within the LMIS , 31 % of the variance in continuous abstinence was explained by these variables ( p=.003 ) . CONCLUSION This study suggests that a moderately intensive intervention ( LMIS ) is primarily suitable for COPD patients with a positive attitude regarding smoking cessation . The more intensive SST can be an alternative for patients without such baseline characteristic . PRACTICE IMPLICATION S This stepped-care approach in smoking cessation counseling may be useful in clinical practice and will enable health care providers to match interventions to individual needs and increase efficiency The objective of the present study was to test whether confronting smokers with previously undetected chronic obstructive pulmonary disease ( COPD ) increases the rate of smoking cessation . In total , 296 smokers with no prior diagnosis of COPD were detected with mild-to-moderate airflow limitation by means of spirometry and r and omly allocated to : confrontational counselling by a nurse with nortriptyline for smoking cessation ( experimental group ) ; regular counselling by a nurse with nortriptyline ( control group 1 ) ; or “ care as usual ” for smoking cessation by the general practitioner ( control group 2 ) . Only the experimental group was confronted with their abnormal spirometry ( mean forced expiratory volume in one second ( FEV1 ) post-bronchodilator 80.5 % predicted , mean FEV1/forced vital capacity post-bronchodilator 62.5 % ) . There was no difference in cotinine-vali date d prolonged abstinence rate between the experimental group ( 11.2 % ) and control group 1 ( 11.6 % ) from week 5–52 ( odds ratio ( OR ) 0.96 , 95 % confidence interval ( CI ) 0.43–2.18 ) . The abstinence rate was approximately twice as high in the experimental group compared with control group 2 ( 5.9 % ) , but this difference was not statistically significant ( OR 2.02 , 95 % CI 0.63–6.46 ) . The present study did not provide evidence that the confrontational approach increases the rate of long-term abstinence from smoking compared with an equally intensive treatment in which smokers were not confronted with spirometry . The high failure rates ( ≥88 % ) highlight the need for treating tobacco addiction as a chronic relapsing disorder In this study a r and omised controlled trial was carried out to investigate the effectiveness of an education programme for patients with asthma or chronic obstructive pulmonary disease ( COPD ) . All asthma and COPD patients using medication and experiencing pulmonary symptoms were r and omly assigned to the intervention ( n=139 ) or usual-care group ( n=137 ) . The intervention consisted of taylor-made education conducted by a general practice assistant and focussing on a patients ' technical skills and coping with the disease . Measurements took place at baseline , and after 1 and 2 years of follow-up . After 1 and 2 years the inhalation technique was significantly better in the intervention group compared to the usual-care group . No significant differences were observed regarding disease symptoms , health related quality of life , compliance , smoking cessation , self-efficacy , and coping . The results only support the implementation of the intervention regarding the technical skills ( inhalation technique ) . However , given the importance of improvement of patients ' coping and the need for more efficient care , we recommend further exploration of the possibilities of a more structured and intensive education programme OBJECTIVE To evaluate a partnership model of care for patients with a diagnosis of chronic obstructive pulmonary disease ( COPD ) . DESIGN , SETTING AND PARTICIPANTS Cluster r and omised controlled trial with blinded outcome assessment of 44 general practice s in south-western Sydney comprising 451 people with a diagnosis of COPD , conducted between 2006 and 2009 . INTERVENTION Participants from intervention group practice s were visited at their home by a registered nurse with specific training in COPD care who worked with the general practitioner , the patient and other health professionals to develop and implement an individualised care plan based on best- practice guidelines . Participants from control group practice s received usual care . MAIN OUTCOME MEASURES The primary outcome was disease-related quality of life measured using the St George 's Respiratory Question naire ( SGRQ ) at 12-month follow-up . Other outcomes were overall quality of life , lung function , smoking status , immunisation status , patient knowledge of COPD , and health service use . RESULTS Of the 451 participants , 257 ( 57.8 % ) were confirmed as having COPD on post-bronchodilator spirometry . Follow-up was completed for 330 patients ( 73.2 % ) . At 12 months , there was no statistically significant difference in the mean SGRQ scores between intervention and control groups ( 38.7 v 37.6 ; difference , 1.1 ; 95 % CI , - 1.53 - 3.74 ; P = 0.41 ) or in measures of quality of life , lung function and smoking status . Compared with the control group , in the intervention group , attendance at pulmonary rehabilitation was more frequent ( 31.1 % v 9.6 % ; OR , 5.16 ; 95 % CI , 2.40 - 11.10 ; P = 0.002 ) and the mean COPD knowledge score was higher ( 10.5 v 9.8 ; difference , 0.70 ; CI , 0.10 - 1.21 ; P = 0.02 ) . CONCLUSION The nurse-GP partnership intervention did not have an impact on disease-related quality of life at 12-month follow-up . However , there was evidence of improved quality of care , in particular , in attendance at pulmonary rehabilitation and patient knowledge of COPD . TRIAL REGISTRATION Australian Clinical Trials Registry ACTRN012606000304538 In a controlled r and omised trial we analysed whether the use of the term " smoker 's lung " ( Danish : " rygerlunger " ) instead of chronic bronchitis when talking to patients with chronic obstructive lung disease ( COLD ) changed their smoking habits . Fifty-six smoking patients with COLD were allocated to either intervention ( n = 25 ) or control groups ( n = 31 ) . In the intervention group the lung disease was design ated smoker 's lung in all communication with patients about their illness and in the control group traditional terminology was used . All patients were given the same medical treatment and the same encouragement to stop smoking . One week after discharge 57 % had stopped smoking in the smoker 's lung group vs 26 % in the control group ( p = 0.028 ) , at three months 50 % vs 19 % ( p = 0.027 ) and at one year 40 % vs 20 % ( p = 0.148 ) . Referring directly to the cause of a self-inflicted illness may be an effective way of discouraging risk behaviour , at negligible cost The US Lung Health Study was a r and omized clinical trial carried out in 10 clinical centres in the United States of America and Canada that enrolled 5887 male and female smokers age 35 - 60 years with early chronic obstructive pulmonary disease ( COPD ) . Its purpose was to determine whether a programme incorporating smoking intervention and use of an inhaled bronchodilator ( ipratropium bromide ) can slow the rate of decline in the forced expiratory volume in one second ( FEV1 ) in middle aged smokers with early COPD . Participants were r and omized with equal probability into three groups : ( i ) smoking intervention plus bronchodilator ; ( ii ) smoking intervention plus placebo ; or ( iii ) no intervention . The primary outcome was rate of change and cumulative change in FEV1 over a 5 year period . The primary finding was that the use of the bronchodilator did not influence the long-term decline in FEV1 . However , the aggressive smoking intervention programme significantly reduced the age-related decline in FEV1 CONTEXT Prior cross-sectional studies have reported greater pain intensity among persistent smokers compared with nonsmokers or former smokers ; yet , few prospect i ve studies have examined how smoking abstinence affects pain intensity . OBJECTIVES To determine the impact of smoking cessation on subsequent pain intensity in smokers with chronic illness enrolled in a smoking cessation trial . METHODS We recruited veteran smokers with chronic illness ( heart disease , cancer , chronic obstructive pulmonary disease , diabetes , or hypertension ) for a r and omized controlled smoking cessation trial and prospect ively examined pain intensity and smoking status . Participants ( n = 380 ) were asked to rate their pain in the past week from 0 to 10 at baseline and the five-month follow-up . The primary outcome measure was self-reported pain intensity at the five-month follow-up survey . Self-reported smoking status was categorized as an abstainer if patients reported no cigarettes in the seven days before the follow-up survey . RESULTS In unadjusted analyses , abstainers reported significantly lower pain levels at the five-month follow-up compared with patients who continued to smoke ( parameter estimate = -1.07 ; 95 % CI = -1.77 , -0.36 ) . In multivariable modeling , abstaining from cigarettes was not associated with subsequent pain intensity at five-month follow-up ( parameter estimate = -0.27 ; 95 % CI = -0.79 , 0.25 ) . CONCLUSION Participants who were classified as abstainers did not report significantly different levels of pain intensity than patients who continued to smoke . Future studies should exp and on our findings and monitor pain intensity in smoking cessation trials . TRIAL REGISTRATION Clinical Trials.govNCT00448344 Introduction : Chronic obstructive pulmonary disease ( COPD ) is a major contributor to morbidity and mortality . Smoking is the leading cause of COPD . Results from r and omised trials regarding smoking cessation in hospitalised patients with COPD are few BACKGROUND Tobacco smoking is associated with chronic obstructive pulmonary disease ( COPD ) in more than 80 % of cases . Our aim was to investigate the effect of sustained-release bupropion ( amfebutamone ) ( SR ) in promoting abstinence from smoking in patients with COPD . METHODS In a double-blind , r and omised , placebo-controlled trial 404 individuals with mild or moderate COPD who smoked 15 or more cigarettes per day , were assigned bupropion SR ( 150 mg twice daily ) or placebo for 12 weeks . All patients received smoking cessation counselling . Study medication was taken for 1 week before patients attempted to stop smoking . The primary efficacy endpoint was the complete and continuous abstinence from smoking from the beginning of week 4 to the end of week 7 . Participants were followed up at month 6 . Analysis was by intention to treat . FINDINGS All patients were chronic smokers with a smoking history of about 51 pack-years . Continuous smoking abstinence rates from week 4 to 7 were significantly higher in participants receiving bupropion SR than in those receiving placebo ( 28 % [ 57/204 ] vs 16 % [ 32/200 ] , p=0.003 ) . Continuous abstinence rates from weeks 4 to 12 ( 18 % [ 36/204 ] vs 10 % [ 20/200 ] ) and weeks 4 to 26 ( 16 % [ 32/204 ] vs 9 % [ 18/200 ] ) were also higher in participants receiving bupropion SR than in those taking placebo ( p<0.05 ) . Furthermore , symptoms of tobacco craving and withdrawal were attenuated in those receiving bupropion SR . Seven individuals discontinued study medication because of adverse events . INTERPRETATION Bupropion SRis a well-tolerated and effective aid to smoking cessation in people with mild to moderate COPD Chronic obstructive pulmonary disease ( COPD ) represents one of the main causes of morbidity and mortality in the western world . Unfortunately , its therapy is largely palliative , the key aims of treatment being to reduce exacerbations , minimise symptoms , and improve patients ' ability to perform their usual daily activities . In the absence of true disease-modifying treatments , the concept of rehabilitation has become important . In addition , it has been shown that educational and self-management programmes may play a role in the general treatment of COPD patients . This study was promoted by the Italian Association of Hospital Pulmonologists ( AIPO ) with the aim to verify changes and improvements induced by an educational programme vali date d by AIPO in patients with COPD . Edu-Care is a 6-month , multicentre , r and omised , controlled , parallel-group study . In addition to treatment within the usual therapeutic schemes for COPD , patients were r and omised to either the ' Educational ' group , i.e. to receive a formal and structured educational programme , or the ' Normal General Advice ' group , i.e. to receive the usual general advice given by general practitioners on life-style and on the disease 's risk factors and treatment . A number of evaluations were performed : pulmonary function test , walking distance , quality of life , locus of control , register of number of exacerbations and hospital admissions . To date , of the 1,230 patients enrolled interim data are available from 1,003 patients . Males represent 85 % of the study population . Smoking habit is quite a common status ( 21 % ) . In the year prior to enrolment 34 % of patients had one exacerbation , 49 % 2 - 3 exacerbations , and 17 % more than 3 exacerbations . Seventy-two percent of patients were not hospitalised over the year prior to enroLlment , while 22 % were hospitalised once and 6 % had more than 2 hospitalisations . Edu-Care is the first large study aim ed to evaluate the efficacy of an educational programme for patients with COPD . AIPO wishes to make a contribution to this important field . This is the reason why Edu-Care includes a very large number of patients in numerous Italian centres throughout northern and southern Italy BACKGROUND Smoking is the most important risk factor for COPD and accelerates its progression . Despite the health implication s , a large proportion of patients with COPD continue to smoke , so finding effective smoking cessation interventions for this population is paramount . To our knowledge , this is the first r and omized clinical trial to compare the efficacy and safety of varenicline tartrate vs placebo in smokers with mild to moderate COPD . METHODS In a 27-center , double-blind , multinational study , 504 patients with mild to moderate COPD ( postbronchodilator FEV1/FVC , < 70 % ; FEV1 percent predicted normal value , ≥50 % ) and without known psychiatric disturbances were r and omized to receive varenicline ( n=250 ) or placebo ( n=254 ) for 12 weeks , with a 40-week nontreatment follow-up . The primary end point was carbon monoxide-confirmed continuous abstinence rate ( CAR ) for weeks 9 to 12 . A secondary end point was CAR for weeks 9 to 52 . RESULTS CAR for weeks 9 to 12 was significantly higher for patients in the varenicline group ( 42.3 % ) than for those in the placebo group ( 8.8 % ) ( OR , 8.40 ; 95 % CI , 4.99 - 14.14 ; P<.0001 ) . CAR in the patients treated with varenicline remained significantly higher than in those treated with placebo through weeks 9 to 52 ( 18.6 % vs 5.6 % ) ( OR , 4.04 ; 95 % CI , 2.13 - 7.67 ; P<.0001 ) . Nausea , abnormal dreams , upper-respiratory tract infection , and insomnia were the most commonly reported adverse events ( AEs ) for patients in the varenicline group . Serious AEs were infrequent in both treatment groups . Two patients in the varenicline group and one patient in the placebo group died during the study . Reports of psychiatric AEs were similar for both treatment groups . CONCLUSIONS Varenicline was more efficacious than placebo for smoking cessation in patients with mild to moderate COPD and demonstrated a safety profile consistent with that observed in previous trials . TRIAL REGISTRY Clinical Trials.gov ; No. : NCT00285012 ; URL : www . clinical trials.gov Objective To evaluate the effects of a community based integrated intervention for early prevention and management of chronic obstructive pulmonary disease ( COPD ) in China . Design Cluster r and omised controlled trial . Setting Eight healthcare units in two communities . Participants Of 1062 people aged 40 - 89 , 872 ( 101 with COPD and 771 without COPD ) who fulfilled the inclusion and exclusion criteria were allocated to the intervention or the usual care programmes . Intervention Participants r and omly assigned to integrated intervention ( systematic health education , intensive and individualised intervention , treatment , and rehabilitation ) or usual care . Main outcome measures Annual rate of decline in forced expiratory rate in one second ( FEV1 ) before use of bronchodilator . Results Annual rate of decline in FEV1 was significantly lower in the intervention community than the control community , with an adjusted difference of 19 ml/year ( 95 % confidence interval 3 to 36 ) and 0.9 % ( 0.1 % to 1.8 % ) of predicted values ( all P<0.05 ) , as well as a lower annual rate of decline in FEV1/FVC ( forced vital capacity ) ratio ( adjusted difference 0.6 % ( 0.1 % to 1.2 % ) P=0.029 ) . There were also higher rates of smoking cessation ( 21 % v 8 % , P<0.004 ) and lower cumulative death rates from all causes ( 1 % v 3 % , P<0.009 ) in the intervention community than in the control community during the four year follow-up . Improvements in knowledge of COPD and smoking hazards , outdoor air quality , environmental tobacco smoke , and working conditions were also achieved ( all P<0.05 ) . The difference in cumulative incidence rate of COPD ( both around 4 % ) and cumulative death rate from COPD ( 2 % v 11 % ) did not reach significance between the two communities . Conclusions A community based integrated intervention can have a significant impact on the prevention and management of COPD , mainly reflected in the annual rate of decline in FEV1 . Trial registration Chinese Clinical Trials Registration ( ChiCTR-TRC-00000532 ) Objective To investigate the long term effectiveness of integrated disease management delivered in primary care on quality of life in patients with chronic obstructive pulmonary disease ( COPD ) compared with usual care . Design 24 month , multicentre , pragmatic cluster r and omised controlled trial Setting 40 general practice s in the western part of the Netherl and s Participants Patients with COPD according to GOLD ( Global Initiative for COPD ) criteria . Exclusion criteria were terminal illness , cognitive impairment , alcohol or drug misuse , and inability to fill in Dutch question naires . Practice s were included if they were willing to create a multidisciplinary COPD team . Intervention General practitioners , practice nurses , and specialised physiotherapists in the intervention group received a two day training course on incorporating integrated disease management in practice , including early recognition of exacerbations and self management , smoking cessation , physiotherapeutic reactivation , optimal diagnosis , and drug adherence . Additionally , the course served as a network platform and collaborating healthcare providers design ed an individual practice plan to integrate integrated disease management into daily practice . The control group continued usual care ( based on international guidelines ) . Main outcome measures The primary outcome was difference in health status at 12 months , measured by the Clinical COPD Question naire ( CCQ ) ; quality of life , Medical Research Council dyspnoea , exacerbation related outcomes , self management , physical activity , and level of integrated care ( PACIC ) were also assessed as secondary outcomes . Results Of a total of 1086 patients from 40 clusters , 20 practice s ( 554 patients ) were r and omly assigned to the intervention group and 20 clusters ( 532 patients ) to the usual care group . No difference was seen between groups in the CCQ at 12 months ( mean difference –0.01 , 95 % confidence interval –0.10 to 0.08 ; P=0.8 ) . After 12 months , no differences were seen in secondary outcomes between groups , except for the PACIC domain “ follow-up/coordination ” ( indicating improved integration of care ) and proportion of physically active patients . Exacerbation rates as well as number of days in hospital did not differ between groups . After 24 months , no differences were seen in outcomes , except for the PACIC follow-up/coordination domain . Conclusion In this pragmatic study , an integrated disease management approach delivered in primary care showed no additional benefit compared with usual care , except improved level of integrated care and a self reported higher degree of daily activities . The contradictory findings to earlier positive studies could be explained by differences between interventions ( provider versus patient targeted ) , selective reporting of positive trials , or little room for improvement in the already well developed Dutch healthcare system . Trial registration Netherl and s Trial Register NTR2268 BACKGROUND Chronic obstructive pulmonary disease ( COPD ) is predominantly caused by cigarette smoking and is considered a worldwide preventable chronic illness . Smoking cessation is considered the primary intervention for disease management and nurses should play a major role in assisting patients to stop smoking . Currently there is a lack of professional consensus on how cessation interventions should be evaluated . The vast array of biochemical markers reported in the literature can be confusing and can make the comparisons of results difficult . OBJECTIVE To vali date self-report data on smoking with exhaled carbon monoxide in patients with chronic obstructive pulmonary disease over twelve months . DESIGN We performed a secondary analysis of a previously published r and omized controlled trial evaluating nursing interventions to assist respiratory patients to stop smoking . SETTING Northern Irel and 's Regional Respiratory Centre . PARTICIPANTS A total of 91 cigarette smokers attending secondary care for the treatment for COPD participated in the study . METHOD Self-reported smoking status and cigarettes smoked per day were compared to exhaled carbon monoxide readings at baseline , 2 , 3 , 6 , 9 and 12 months . The cut-off value of ≤10 ppm was used to identify non-smokers . The p-values are based on Pearson 's correlation coefficient and Kappa Coefficient as appropriate . RESULTS Findings suggest self-reported smoking status and cigarette consumption amongst patients with chronic obstructive pulmonary disease was highly consistent with exhaled carbon monoxide results ( p = 0.001 - 0.003 ) . CONCLUSION The majority of patients with chronic obstructive pulmonary disease reliably report their cigarette consumption AIMS To examine the influence of risk perception on intentions to quit smoking and post-treatment abstinence . DESIGN Prospect i ve and longitudinal . SETTING United States . PARTICIPANTS A total of 237 adult smokers ( mean age 56 years ) receiving medical care from home health-care nurses . Participants did not have to want to quit smoking to participate , but received cessation counseling within the context of their medical care . MEASUREMENTS Three measures of risk perception were given pre- and post-treatment : perceived vulnerability , optimistic bias and pre caution effectiveness . Smoking status was verified biochemically at end of treatment and at 2 , 6 and 12 months later . FINDINGS Principal components analysis supported the theoretical discriminability of the risk perception measures , and intercorrelations provided evidence for concurrent and predictive validity . Elevated risk perception was associated with a variety of socio-demographic and psychosocial characteristics . Optimistic bias was associated significantly with older age and ethnic minority status . Smokers in pre-contemplation had lower perceived vulnerability and pre caution effectiveness and greater optimistic bias than those in contemplation and preparation . Smokers in preparation had higher perceived vulnerability and lower optimistic bias than those in earlier stages . Change in perceived vulnerability predicted smoking cessation at follow-up . Optimistic bias predicted a lower likelihood of cessation and pre caution effectiveness predicted a greater likelihood of smoking cessation , but only among those with a smoking-related illness . CONCLUSIONS In patients receiving medical care from home health-care nurses , change in perceived vulnerability to smoking-related disease is predictive of smoking cessation . In those with smoking-related illnesses , optimistic bias predicts continued smoking while pre caution effectiveness predicts cessation Background : Spirometry for early detection of chronic obstructive pulmonary disease ( COPD ) and smoking cessation is criticised because of the potential negative effects of labelling with disease . Aim : To assess the effects of opinions of smokers with mild to moderate COPD on the effectiveness of spirometry for smoking cessation , the justification of early detection of airflow limitation in smokers and the impact of confrontation with COPD . Design : Qualitative study with data from a r and omised controlled trial . Setting : General population of Dutch and Belgian Limburg . Methods : Semistructured ethical exit interviews were conducted with 205 smokers who were motivated to quit smoking and had no prior diagnosis of COPD but were detected with airflows limitation by means of spirometry . They received either ( 1 ) counselling , including labelling with COPD , plus with nortriptyline for smoking cessation , ( 2 ) counselling excluding labelling with COPD , plus nortriptyline for smoking cessation or ( 3 ) care as usual for smoking cessation by the general practitioner , without labelling with COPD . Results : Of the participants , 177 ( 86 % ) agreed or completely agreed that it is justified to measure lung function in heavy smokers . These participants argued that measuring lung function raises consciousness of the negative effects of smoking , helps to prevent disease or increases motivation to stop smoking . Most of the 18 participants who disagreed argued that routinely measuring lung function in smokers would interfere with freedom of choice . Conclusions : Labelling with disease is probably a less important issue in the discussion about the pros and cons of early detection of COPD AIMS To assess the efficacy of nicotine replacement therapies ( NRT ) when the daily dose was adapted according to saliva cotinine concentrations . DESIGN R and omized , multi-centre , single-blind , controlled trial . SETTING Twenty-one smoking cessation clinics in France . PARTICIPANTS A total of 310 smokers with medical comorbidities , motivated to quit , smoking ≥ 10 cigarettes/day , for whom smoking cessation was m and atory . NRT was administered for 3 months . The st and ard care group received nicotine patches with monthly dose decreases ; buccal absorption NRT could be co-administered at the discretion of the investigator . In the dose adaptation group , the aim was a 100 ± 5 % nicotine substitution with respect to smoking state based on the determination of saliva cotinine concentrations . NRT daily doses were prescribed according to the previous week 's saliva cotinine concentrations in the dose adaptation group ; saliva cotinine concentrations were not provided in the st and ard care group . MEASUREMENTS Prolonged abstinence rate ( weeks 9 - 12 , main outcome measure ) , point-prevalence and continuous abstinence rate , saliva cotinine concentration , NRT daily dose , craving for cigarettes . FINDINGS The median daily prescribed NRT dose was 30 and 31 mg/day in the first study week and 17.25 and 35.5 mg/day during weeks 9 - 12 in the st and ard care group and dose adaptation group , respectively . Saliva cotinine remained stable in the dose adaptation group and decreased in the st and ard care group ( P < 0.01 ) by weeks 9 - 12 . The cotinine substitution rate was significantly lower in the st and ard care group than in the dose adaptation group . Despite differences in NRT doses and cotinine substitution rates , prolonged ( st and ard care group : 26.4 % , dose adaptation group : 30.3 % ) , continuous ( st and ard care group : 8 % , dose adaptation group : 12 % ) and point-prevalence abstinence rates were similar . CONCLUSIONS In smokers with medical comorbidities and highly motivated to quit , adaptation of the nicotine replacement therapy daily dose according to saliva cotinine does not appear to be substantially superior to st and ard nicotine replacement therapy use AIM This study aims to explore the experience of cigarette smokers with Chronic obstructive pulmonary disease ( COPD ) who have received smoking cessation support and describe their personal decision-making processes regarding their smoking behaviour . BACKGROUND Previous studies have demonstrated poor smoking cessation rates in people with COPD , despite this being the primary intervention for disease management . There is limited research exploring the reasons why this population continues to smoke . DESIGN Retrospective qualitative interviews were conducted and analysed using Giorgi 's ( 1985 ) process of analysis . METHOD Following a r and omised controlled trial to evaluate national smoking cessation guidelines , semi-structured interviews were conducted with a purposive sample ( n = 6 ) of those patients who were unable to stop smoking . RESULTS Six themes that typified patients ' decision-making were identified during six interviews ; too late to stop now , finding motivation , guilt about continued smoking , bargaining/contemplation , need to stop and reduced quality of life . CONCLUSION The reasons why smokers with COPD continue to smoke despite poor health and following support are complex . Cigarettes are regarded as friends , despite the knowledge that they are contributing to severe disability and poor quality of life . Owing to their inability to stop smoking , many patients avoid healthcare opportunities , further contributing to their poor health . RELEVANCE TO CLINICAL PRACTICE Smoking cessation is associated with ambivalence in this population . Health professionals need to underst and the volatility of patients ' decision-making and tailor advice and support to achieve more realistic goals such as reduced consumption Chronic obstructive pulmonary disease ( COPD ) is a common disease in industrialised countries and responsible for a considerable morbidity and mortality . Cigarette smoking is the most important aetiological factor . The EUROSCOP trial aims at investigating the hypothesis that airway inflammation plays an important pathogenic role in the development of chronic obstructive airway disease in smokers . In cigarette smokers with poorly reversible airflow obstruction , the effect over 3 yrs of an inhaled glucocorticosteroid , budesonide 400 micrograms b.i.d . , on the decline of lung function , measured as postbronchodilator forced expiratory volume in one second ( FEV1 ) , will be compared with that of placebo . The trial has been design ed to detect a difference in yearly decline of at least 30 ml.year-1 . The study is a parallel group , r and omised , double-blind , multicentre study . Patients will be recruited from 47 centres in 12 countries in Europe . It will start with a run-in consisting of two 3 month periods . During the first 3 months , the patients will be offered a smoking cessation programme . All patients who have not stopped smoking during this period will enter the second half of the run-in where compliance with the dosage regimen will be tested . After these two periods , patients will be r and omised to receive either inhaled budesonide , 400 micrograms b.i.d . , or placebo for a period of 3 yrs Introduction Up to half of all smokers develop clinical ly significant chronic obstructive pulmonary disease ( COPD ) . Gaps exist in the implementation and uptake of evidence -based guidelines for managing COPD in primary care . We describe the methodology of a cluster r and omised controlled trial ( c RCT ) evaluating the efficacy and cost-effectiveness of an interdisciplinary model of care aim ed at reducing the burden of smoking and COPD in Australian primary care setting s. Methods and analysis A c RCT is being undertaken to evaluate an interdisciplinary model of care ( RADICALS — Review of Airway Dysfunction and Interdisciplinary Community-based care of Adult Long-term Smokers ) . General practice clinics across Melbourne , Australia , are identified and r and omised to the intervention group ( RADICALS ) or usual care . Patients who are current or ex-smokers , of at least 10 pack years , including those with an existing diagnosis of COPD , are being recruited to identify 280 participants with a spirometry-confirmed diagnosis of COPD . H and held lung function devices are being used to facilitate case-finding . RADICALS includes individualised smoking cessation support , home-based pulmonary rehabilitation and home medicines review . Patients at control group sites receive usual care and Quitline referral , as appropriate . Follow-ups occur at 6 and 12 months from baseline to assess changes in quality of life , abstinence rates , health re source utilisation , symptom severity and lung function . The primary outcome is change in St George ’s Respiratory Question naire score of patients with COPD at 6 months from baseline . Ethics and dissemination This project has been approved by the Monash University Human Research Ethics Committee and La Trobe University Human Ethics Committee ( CF14/1018 – 2014000433 ) . Results of the study will be disseminated in peer- review ed journals and research conferences . If the intervention is successful , the RADICALS programme could potentially be integrated into general practice s across Australia and sustained over time . Trial registration number ACTRN12614001155684 ; Pre- results The aim of this study was to examine any dose response effect of 2 and 4 mg nicotine gum ( Nicorette ) as well as the effect of the treatment in relation to a control group . One hundred seventy-two cigarette smokers were r and omly allocated to group counselling and 2 mg- ( n = 62 ) or 4 mg- ( n = 54 ) nicotine chewing gum or to an " advice only " control group ( n = 56 ) . Six group meetings in a three month period were guided by physicians in groups of 10 - 12 members . The 4 mg gum was replaced by 2 mg after 4 weeks . The overall chemical verified success rate was significantly higher for the treatment group compared with the control group . The success rate for the gum group was 45.6 % after three months versus 7.1 % for the control group , 33.3 % versus 3.7 % after 12 months , and 27.2 % versus 5.7 % after 22 months , respectively ( p less than 0.001 ) . We could not demonstrate any significant dose response effect of 2 and 4 mg nicotine gum . The low dependent smokers had the best outcome . The subgroup of self-reported chronic bronchitis subjects had a significantly lower success rate than their healthy counterparts ( p less than 0.002 ) . Neither the p-nicotine level after smoking or chewing gum nor the difference between these two could predict the outcome . The gum p-nicotine after a week was only 37.1 % for 2 mg and 64.3 % for 4 mg of the corresponding smoking p-nicotine levels . Nicotine compensation was best for the high dependent smokers OBJECTIVE To evaluate the effect of health education on the symptoms , lung function and life quality in patients with stable chronic obstructive pulmonary diseases ( COPD ) . METHODS Eighty-two patients were assigned into 2 groups r and omly : The treatment group ( n = 43 ) accepted health education for 6 months and the control group ( n = 39 ) did not . Before and after the 6 months , we observed the number of smokers , Borg score , inhale treatment , times of acute episode , SGRQ score , lung function , and the therapeutic effect in the two groups . RESULTS Six months later , the ratio of smokers in the treatment group was 13.95 % , much lower than that in the control group ( 35.90 % , P = 0.021 ) ; the Borg score of the treatment group decreased from 4.86 + /- 1.21 to 3.38 + /- 0.94 ( P = 0.000 ) , but there was no difference in the control group ; the ratios of accepted inhale treatment in the treatment group and the control group were 100 % ( 43/43 ) and 20.51 % ( 8/39 ) respectively ( P = 0.000 ) , and the accuracy rates were 100 % ( 43/43 ) in the treatment group and 12 . 82 % ( 5/39 ) in the control group ( P = 0 . 000 ) ; the times of acute episode in the treatment group was 1.51 + /- 1.53 , much lower than that in the control group ( 4.46 + /- 5.17 , P = 0 . 000 ) ; the indexes of lung function before and after the 6 months between the two groups had no significant difference . The total score , the symptom section score , the activity section score , and the impact section score of SGRQ after the 6 months of health education were much lower than those of 6 months before , and those in the control group had no significant difference . CONCLUSION Six months of the health education can decrease the ratio of smokers and the times of acute episode , and to improve the life quality of patients with stable COPD OBJECTIVE To evaluate the effect of community intervention for COPD and chronic cor-pulmonale . METHODS The baseline survey of the study was carried out in 1992 . The total population was r and omly divided into intervention and control regions . From 1992 the comprehensive community intervention trial was conducted in the intervention region . The data of baseline study has been published elsewhere . The family inquiry was made in all baseline population , 50 percent of high risk population and 100 percent of COPD and cor pulmonale population were reexamined . RESULTS Of the 3,739 subjects who should be investigated 3,316 subjects were really investigated ( 88.7 % of responsive rate ) . Of 814 subjects r and omly abstract ed from 3,316 in intervention and control regions , the awareness rates of smoking harm to health were 95.0 % and 80.0 % , of how to prevent and treat COPD were 62.0 % and 35.7 % , of regular visit by doctors were 46.1 % and 27.0 % respectively . The rate of ex-smoker was 28.2 % in intervention region more than that of 23 % in control region ( P = 0.004 ) . Of 3,075 subjects undergone lung function test , FEV1 decrements per capita yearly were 32.0 ml and 37.9 ml ( P = 0.001 ) ; FVC decrement were 42.0 ml and 48.3 ml ( P = 0.012 ) in intervention and control regions . The prevalence increment in COPD were 5.6 % and 8.0 % ( P = 0.03 ) , cor-pulmonale were 3.5 % and 6.7 % ( P = 0.02 ) compared to baseline survey in both regions . The mortality of cor-pulmonale were 72.9 and 95 per 100,000 per year ( P = 0.0044 ) from 1995 to 1999 . CONCLUSION The rate of quiting smoke is significantly increased by intervention . The declination of lung function significantly decreases . The increment in prevalence of COPD and cor-pulmonale significantly decreases . The mortality of cor-pulmonale decreases significantly in intervention region . The results indicates that the comprehensive intervention in community is an important measurement for decreasing incidence of COPD and mortality of cor-pulmonale Background Low literacy skills are common and associated with a variety of poor health outcomes . This may be particularly important in patients with chronic illnesses such as chronic obstructive pulmonary disease ( COPD ) that require appropriate inhaler technique to maintain quality of life and avoid exacerbations . Objective To explore the impact of a literacy-sensitive self-management intervention on inhaler technique scores in COPD patients and to determine if effects differ by literacy . Design R and omized controlled trial . Participants Ninety-nine patients with COPD .Intervention Patients were r and omly assigned to a one-on-one self-management educational intervention or usual care . The intervention focused on inhaler technique , smoking cessation , and using a COPD action plan . Main Measures At baseline , an inhaler technique assessment , literacy assessment , health-related quality of life question naires , and pulmonary function tests were completed . Inhaler technique was re-evaluated after two to eight weeks . Key Results Mean age 63 , 65 % female , 69 % Caucasian , moderate COPD severity on average , 36 % with low literacy , moderately impaired health-related quality of life , and similar baseline metered dose inhaler technique scores . Patients in the intervention group had greater mean improvement from baseline in metered dose inhaler technique score compared to those in the usual care group ( difference in mean change 2.1 , 95 % CI 1.1 , 3.0 ) . The patients in the intervention group also had greater mean improvements in metered dose inhaler technique score than those in the usual care group whether they had low health literacy ( difference in mean change 2.8 , 95 % CI 0.6 , 4.9 ) or higher health literacy ( 1.8 , 95 % CI 0.7 , 2.9 ) . Conclusions A literacy-sensitive self-management intervention can lead to improvements in inhaler technique , with benefits for patients with both low and higher health literacy AIMS To evaluate the effectiveness of a 6-month , partnership-based self-management programme for patients with mild and moderate chronic obstructive pulmonary disease . BACKGROUND Self-management is a widely valued concept used to address contemporary issues of chronic health problems . Findings of self-management programmes for people with chronic obstructive pulmonary disease are inconclusive . DESIGN Pragmatic r and omized control trial . METHODS Patients , 45 - 65 years old , with mild and moderate chronic obstructive pulmonary disease were invited with a family member . Experimental group ( n = 48 ) participated in a 6-month , partnership-based self-management programme consisting of : ( a ) three to four conversations between nurse and patient-family member ; ( b ) 6 months of smoking cessation ; and ( c ) interdisciplinary team-patient-family member group meeting . Control group ( n = 52 ) received usual care . Data were collected at months zero , six and 12 . The trial lasted from June 2009-March 2013 . RESULTS Patients with mild and moderate chronic obstructive pulmonary disease who participated in the partnership-based self-management programme perceived less intrusiveness of the disease and its treatment than patients in the control group . Patients in the experimental group did not have better health-related quality of life , less anxiety or depression , increased physical activity , fewer exacerbations or better smoking status than patients in the control group . Patients in both groups found participation in the research useful and important . CONCLUSION The partnership-based self-management programme had benefits concerning perception of the intrusiveness of chronic obstructive pulmonary disease and its treatment on lifestyles , activities and interests for young patients with the disease in its early stages . High satisfaction in control group , low family attendance and the relatively short treatment period may explain the less than expected benefits of the programme |
10,764 | 28,382,827 | Conclusion : Preliminary evidence suggests inflammation should be considered within the context of cognitive behaviour therapy , although robust studies examining the relationship are sparse , and heterogeneity between studies and population s examined was high . | Objective : There is growing evidence confirming increased inflammation in a subset of adults with depression .
The impact of this relationship has mostly been considered in biologically based interventions ; however , it also has potential implication s for psychological therapies .
Cognitive behaviour therapy is the most commonly used psychological intervention for the treatment of depression with theories around its efficacy primarily based on psychological mechanisms .
However , cognitive behaviour therapy may have an effect on , and its efficacy influenced by , physiological processes associated with depression .
Accordingly , the purpose of this systematic review was to examine the relationship between cognitive behaviour therapy and inflammation . | Inflammation , part of the body 's innate immune response , can lead to " sickness behaviors , " as well as alterations in social and affective experiences . Elevated levels of pro-inflammatory cytokines have been associated with increased neural sensitivity to social rejection and social threat , but also decreased neural sensitivity to rewards . However , recent evidence suggests that inflammation may actually enhance sensitivity to certain social rewards , such as those that signal support and care . Despite a growing interest in how inflammation influences neural reactivity to positive and negative social experiences , no known studies have investigated these processes in the same participants , using a similar task . To examine this issue , 107 participants were r and omly assigned to receive either placebo or low-dose endotoxin , which safely triggers an inflammatory response . When levels of pro-inflammatory cytokines were at their peak , participants were scanned using fMRI while they received positive , negative , and neutral feedback from an " evaluator " ( actually a confederate ) about how they came across in an audio-recorded interview . In response to negative feedback ( vs. neutral ) , participants in the endotoxin condition showed heightened neural activity in a number of threat-related neural regions ( i.e. , bilateral amygdala , dorsal anterior cingulate cortex ) and a key mentalizing-related region ( i.e. , dorsomedial PFC ) , compared to placebo participants . Interestingly , when receiving positive feedback ( vs. neutral ) , endotoxin ( vs. placebo ) led to greater neural activity in the ventral striatum and ventromedial PFC , regions often implicated in processing reward , as well as greater activity in dorsomedial PFC . Together , these results reveal that individuals exposed to an inflammatory challenge are more " neurally sensitive " to both negative and positive social feedback , suggesting that inflammation may lead to a greater vigilance for both social threats and social rewards OBJECTIVE Sub clinical depression is one of the most frequent mental comorbidities in patients with diabetes and is associated with a poorer long-term prognosis . Since there is a lack of specific intervention concepts for this patient group , a self-management – oriented group program ( DIAMOS [ Diabetes Motivation Strengthening ] ) was newly developed and evaluated in a r and omized trial . RESEARCH DESIGN AND METHODS DIAMOS is composed of cognitive behavioral interventions aim ing at the reduction of diabetes distress . The active control group ( CG ) received diabetes education . The primary outcome was depressive symptoms . Secondary outcomes were diabetes distress , well-being , self-care behavior , diabetes acceptance , diabetes treatment satisfaction , HbA1c , and sub clinical inflammation . RESULTS Two hundred fourteen participants ( mean age 43.3 ± 13.3 years , female sex 56.5 % , type 2 diabetes 34.1 % , mean diabetes duration 14.2 ± 10.5 years , HbA1c 8.9 ± 1.8 % , BMI 28.7 ± 71 kg/m2 ) were r and omized . The 12-month follow-up revealed a significantly stronger reduction of depressive symptoms ( Center for Epidemiologic Studies Depression Scale score ) in the DIAMOS group compared with the CG ( Δ3.9 [ 95 % CI 0.6–7.3 ] , P = 0.021 ) . Of the secondary variables , the Patient Health Question naire-9 ( Δ1.7 [ 95 % CI 0.2–3.2 ] , P = 0.023 ) , Problem Areas in Diabetes scale ( Δ8.2 [ 95 % CI 3.1–13.3 ] , P = 0.002 ) , and Diabetes Distress Scale scores ( Δ0.3 [ 95 % CI 0.1–0.5 ] , P = 0.012 ) displayed significant treatment effects . Moreover , the risk of incident major depression in the DIAMOS group was significantly reduced ( odds ratio 0.63 [ 95 % CI 0.42–0.96 ] , P = 0.028 ) . Inflammatory variables were not substantially affected . CONCLUSIONS DIAMOS is more effective in lowering depressive symptoms and diabetes-related distress in diabetic patients with sub clinical depression . DIAMOS also has a preventive effect with respect to the incidence of major depression PURPOSE / OBJECTIVES To determine the dose effects of relaxation practice on immune responses and describe the types of relaxation techniques preferred and the extent of relaxation practice over 10 months . DESIGN Descriptive , prospect i ve , repeated measures . SETTING An interdisciplinary breast clinic at a university-affiliated comprehensive cancer center in the United States . SAMPLE 49 women with newly diagnosed breast cancer and undergoing adjuvant therapy who participated in a stress management intervention . METHODS Relaxation practice was assessed twice a month for 10 months with immune measurements ( e.g. , natural killer cell activity ; lymphocyte proliferation ; interferon [IFN]-γ ; interleukin [IL]-2 , -4 , -6 , and -10 ) at the beginning and end of 10-month practice . MAIN RESEARCH VARIABLES Relaxation practice ( representing the concepts of stress and adherence ) , relaxation technique , and immune response . FINDINGS After adjusting for covariates , the extent of relaxation practice significantly contributed to the variance of natural killer cell activity , lymphocyte proliferation , IL-4 , and IL-10 responses in a positive direction ; the higher the relaxation practice , the higher the immune responses . In comparison , IFN-γ , IL-2 , and IL-6 responses were not affected . The deep-breathing method was most preferred by participants , followed by progressive relaxation and imagination or visualization . The mean weekly frequency of relaxation practice was 5.29 ( SD = 3.35 ) , and the mean duration of relaxation practice was 19.16 ( SD = 10.81 ) minutes per session . CONCLUSIONS Persistent relaxation practice may have positive effects on multiple immune responses in a dose-dependent manner . IMPLICATION S FOR NURSING Allowing the choice of preferred techniques and emphasizing the importance of long-term adherence , a relaxation program may need to be routinely offered to women under high stress UNLABELLED Neuropsychiatric disorders ( e.g. , autism , schizophrenia ) are partially characterized by social cognitive deficits , including impairments in the ability to perceive others ' emotional states , which is an aspect of social cognition known as theory of mind ( ToM ) . There is also evidence that inflammation may be implicated in the etiology of these disorders , but experimental data linking inflammation to deficits in social cognition is sparse . Thus , we examined whether exposure to an experimental inflammatory challenge led to changes in ToM. One hundred and fifteen ( n=115 ) healthy participants were r and omly assigned to receive either endotoxin , which is an inflammatory challenge , or placebo . Participants completed a social cognition task , the Reading the Mind in the Eyes ( RME ) test , at baseline and at the peak of the inflammatory response for the endotoxin group . The RME test , a vali date d measure of ToM , evaluates how accurately participants can identify the emotional state of another person by looking only at their eyes . We found that endotoxin ( vs. placebo ) led to decreases in performance on the RME test from baseline to the peak of inflammatory response , indicating that acute inflammation can lead to decreases in the ability to accurately and reliably comprehend emotional information from others . Given that deficits in ToM are implicated in neuropsychiatric disorders , including those which may have an inflammatory basis , these results may have implication s for underst and ing the links between inflammation , social cognition , and neuropsychiatric disorders . CLINICAL TRIALS REGISTRATION Clinical Trials.gov NCT01671150 Although research has established links between feelings of social isolation and inflammation , the direction of these effects is unclear . Based on the role that proinflammatory cytokines play in initiating " sickness behavior , " which includes symptoms such as social withdrawal , it is possible that inflammatory processes heighten feelings of ' social disconnection . ' Here , we examined whether exposure to an inflammatory challenge increased self-reported feelings of social disconnection . In addition , because both inflammatory processes and feelings of social disconnection contribute to depressive symptoms , we also explored whether increases in feelings of social disconnection played a role in the link between inflammation and depressed mood . Participants were r and omly assigned to either receive endotoxin , an inflammatory challenge , or placebo . Proinflammatory cytokines ( IL-6 , TNF-alpha ) were collected at baseline and then hourly for 6h . Participants completed self-reports of sickness symptoms ( " fatigue " ) , social disconnection ( " I feel disconnected from others " ) , and depressed mood ( " unhappy " ) hourly . Results revealed that endotoxin led to significant increases ( from baseline ) in IL-6 and TNF-alpha levels as well as feelings of social disconnection and depressed mood . Moreover , controlling for increases in social disconnection eliminated the relationship between exposure to inflammatory challenge and depressed mood . This study demonstrates that inflammation can have social psychological consequences , which may play a role in cytokine-related depressive symptoms Major depressive disorder ( MDD ) is a debilitating disorder and its pathophysiology is associated with deregulation of the immune system . We investigated the changes in circulating levels of proinflammatory cytokines ( specifically IL-6 and TNF-α ) measured by the ELISA kit in two psychotherapeutic interventions for MDD : Narrative Cognitive Therapy ( NCT ) and Cognitive Behavioral Therapy ( CBT ) . This is a r and omized clinical trial including 97 individuals ( 18 to 29years-old ) with MDD . In CBT there was a significant difference in serum levels of IL-6 and TNF-α , therefore indicating that CBT was more effective than NCT on serum levels proinflammatory cytokines BACKGROUND Chronic threat and anxiety are associated with pro-inflammatory transcriptional profiles in circulating leukocytes , but the causal direction of that relationship has not been established . This study tested whether a cognitive-behavioral stress management ( CBSM ) intervention targeting negative affect and cognition might counteract anxiety-related transcriptional alterations in people confronting a major medical threat . METHODS One hundred ninety-nine women undergoing primary treatment of stage 0-III breast cancer were r and omized to a 10-week CBSM protocol or an active control condition . Seventy-nine provided peripheral blood leukocyte sample s for genome-wide transcriptional profiling and bioinformatic analyses at baseline , 6-month , and 12-month follow-ups . RESULTS Baseline negative affect was associated with > 50 % differential expression of 201 leukocyte transcripts , including upregulated expression of pro-inflammatory and metastasis-related genes . CBSM altered leukocyte expression of 91 genes by > 50 % at follow-up ( group × time interaction ) , including downregulation of pro-inflammatory and metastasis-related genes and upregulation of type I interferon response genes . Promoter-based bioinformatic analyses implicated decreased activity of NF-κB/Rel and GATA family transcription factors and increased activity of interferon response factors and the glucocorticoid receptor as potential mediators of CBSM-induced transcriptional alterations . CONCLUSIONS In early-stage breast cancer patients , a 10-week CBSM intervention can reverse anxiety-related upregulation of pro-inflammatory gene expression in circulating leukocytes . These findings clarify the molecular signaling pathways by which behavioral interventions can influence physical health and alter peripheral inflammatory processes that may reciprocally affect brain affective and cognitive processes Purpose There is ongoing controversy on the effectiveness of psychotherapy in inflammatory bowel disease ( IBD ) . In the few small studies , cognitive-behavioural therapy ( CBT ) has been shown to alleviate symptoms of anxiety or depression . However , there is little research on the impact of CBT on physical outcomes in IBD and no studies on long-term effectiveness of CBT . Methods The present two-arm pragmatic r and omised controlled trial aim ed to establish the impact of CBT on disease course after 24 months of observation . The study compared st and ard care plus CBT ( + CBT ) with st and ard care alone ( SC ) . CBT was delivered over 10 weeks , face-to-face ( F2F ) or online ( cCBT ) . The data were analysed using linear mixed-effects models . Results CBT did not significantly influence disease activity as measured by disease activity indices at 24 months ( Crohn ’s Disease Activity Index ( CDAI ) , p = 0.92 ; Simple Clinical Colitis Activity Index ( SCCAI ) , p = 0.88 ) or blood parameters ( C-reactive protein ( CRP ) , p < 0.62 ; haemoglobin ( Hb ) , p = 0.77 ; platelet , p = 0.64 ; white cell count ( WCC ) , p = 0.59 ) nor did CBT significantly affect mental health , coping or quality of life ( all p > 0.05 ) . Conclusions Therefore , we conclude that CBT does not influence the course of IBD over 24 months . Given the high rate of attrition , particularly in the CBT group , future trials should consider a personalised approach to psychotherapy , perhaps combining online and one-to-one therapist time OBJECTIVE To assess benefits of mindfulness meditation and cognitive behavioral therapy (CBT)-based intervention for opioid-treated chronic low back pain ( CLBP ) . DESIGN 26-week parallel-arm pilot r and omized controlled trial ( Intervention and Usual Care versus Usual Care alone ) . SETTING Outpatient . SUBJECTS Adults with CLBP , prescribed ≥30 mg/day of morphine-equivalent dose ( MED ) for at least 3 months . METHODS The intervention comprised eight weekly group sessions ( meditation and CLBP-specific CBT components ) and 30 minutes/day , 6 days/week of at-home practice . Outcome measures were collected at baseline , 8 , and 26 weeks : primary -pain severity ( Brief Pain Inventory ) and function/disability ( Oswestry Disability Index ) ; secondary -pain acceptance , opioid dose , pain sensitivity to thermal stimuli , and serum pain-sensitive biomarkers ( Interferon-γ ; Tumor Necrosis Factor-α ; Interleukins 1ß and 6 ; C-reactive Protein ) . RESULTS Thirty-five ( 21 experimental , 14 control ) participants were enrolled and completed the study . They were 51.8 ± 9.7 years old , 80 % female , with severe CLBP-related disability ( 66.7 ± 11.4 ) , moderate pain severity ( 5.8 ± 1.4 ) , and taking 148.3 ± 129.2 mg/day of MED . Results of the intention-to-treat analysis showed that , compared with controls , the meditation-CBT group reduced pain severity ratings during the study ( P = 0.045 ) , with between-group difference in score change reaching 1 point at 26 weeks ( 95 % Confidence Interval : 0.2,1.9 ; Cohen 's d = 0.86 ) , and decreased pain sensitivity to thermal stimuli ( P < 0.05 ) , without adverse events . Exploratory analyses suggested a relationship between the extent of meditation practice and the magnitude of intervention benefits . CONCLUSIONS Meditation-CBT intervention reduced pain severity and sensitivity to experimental thermal pain stimuli in patients with opioid-treated CLBP Few studies have addressed whether stress-associated physiological changes in caregivers are reversible by psychological interventions mitigating distress . We report on pro-inflammatory , sympathetic , and oxidative stress gene expression in response to stress management for caregivers of allogeneic hematopoietic stem cell transplant ( Allo-HSCT ) patients . Following r and omization by permuted block to either treatment as usual ( TAU , n = 11 ) or a stress management intervention ( PsychoEducation , Paced Respiration , and Relaxation , PEPRR , n = 13 ) , twenty-four caregivers were selected at the conclusion of a larger trial of 149 caregivers . PEPRR was provided one-on-one beginning around transplant . Genome-wide transcriptional profiling was conducted on peripheral blood mononuclear cells collected prior to r and omization and on completion of PEPRR 3 months post-transplant . Bioinformatics analysis of differentially expressed genes indicated reduced activity of transcription control pathways associated with inflammation ( NF-κB ) , sympathetic nervous system ( CREB ) , and oxidative stress ( NRF2 ) in caregivers receiving PEPRR compared to TAU aligning with reductions in stress , depression , and anxiety . This suggests that PEPRR may alter transcriptomic effects reported for distressed individuals Type 2 diabetes ( T2D ) is a growing national health problem affecting 35 % of adults ≥20 years of age in the United States . Recently , diabetes has been categorized as an inflammatory disease , sharing many of the adverse outcomes as those reported from cardiovascular disease . Medical nutrition therapy is recommended for the treatment of diabetes ; however , these recommendations have not been up date d to target the inflammatory component , which can be affected by diet and lifestyle . To assess the current state of evidence for which dietary programs contain the most anti-inflammatory and glycemic control properties for patients with T2D , we conducted an integrative review of the literature . A comprehensive search of the PubMed , CINAHL , Scopus , and Web of Science data bases from January 2000 to May 2012 yielded 786 articles . The final 16 studies met the selection criteria including r and omized control trials , quasiexperimental , or cross-sectional studies that compared varying diets and measured inflammatory markers . The Mediterranean and DASH diets along with several low-fat diets were associated with lower inflammatory markers . The Mediterranean diet demonstrated the most clinical ly significant reduction in glycosylated hemoglobin ( HbA1c ) . Information on best dietary guidelines for inflammation and glycemic control in individuals with T2D is lacking . Continued research is warranted CONTEXT Depression is common after coronary artery bypass graft ( CABG ) surgery , but little is known about its effect on post-CABG inflammation or infection or about the most effective treatment for post-CABG depression . OBJECTIVES ( 1 ) To determine ifpost-CABG depression is associated with increased infectious illness and ( 2 ) to test effects of cognitive behavioral therapy ( CBT ) on depressive symptoms , inflammatory biomarkers , and post-CABG infections in depressed post-CABG women . DESIGN R and omized , controlled trial . SETTING Two urban tertiary care centers . PATIENTS Fifteen clinical ly depressed women in the first month after CABG , along with a comparison group of 37 non-depressed postCABG women , were studied . Inclusion criteria were : < or = 75 years old , English-speaking , undergoing first-time CABG , available for 6 months offollow-up , and without malignancy or autoimmune disorders . INTERVENTION Eight weeks of individual home-based CBT . MAIN OUTCOME MEASURES ( 1 ) Depressive symptoms measured by the Beck Depression Inventory , ( 2 ) natural killer cell cytotoxicity ( NKCC ) measured by 51Cr-release assay , ( 3 ) infectious illness episodes measured by the Modified Health Review , ( 4 ) interleukin (IL)-6 and C reactive protein ( CRP ) measured by enzyme immunoabsorbent assay . RESULTS Clinical ly depressed post-CABG women exhibited decreased NKCC and a higher incidence of in-hospital fevers and infectious illness in the first 6 months after CABG . Among depressed women , CBT yielded moderate to large effects for improved NKCC ( D=0.67 ) and decreased IL-6 ( D=0.61 ) , CRP ( D=0.85 ) , and postoperative infectious illnesses ( D=0.93 ) . CBT holds promise for improving depression and immunity and reducing infection and inflammation after CABG Background Sleep disturbance is associated with activation of systemic and cellular inflammation , as well as pro-inflammatory transcriptional profiles in circulating leukocytes . Whether treatments that target insomnia-related complaints might reverse these markers of inflammation in older adults with insomnia is not known . Methods In this r and omized trial , 123 older adults with insomnia were r and omly assigned to cognitive behavioral therapy for insomnia ( CBT-I ) , tai chi chih ( TCC ) , or sleep seminar education active control condition ( SS ) for two hour sessions weekly over 4 months with follow-up at 7- and 16-months . We measured C-reactive protein ( CRP ) at baseline , month 4 and 16 , Toll-like receptor-4 (TLR-4)-activated monocyte production of proinflammatory cytokines at baseline , month 2 , 4 , 7 , and 16 , and genome-wide transcriptional profiling at baseline and month 4 . Results As compared to SS active control , CBT-I reduced levels of CRP ( month 4 , 16 , P’s<0.05 ) , monocyte production of proinflammatory cytokines ( month 2 only , P<0.05 ) , and pro-inflammatory gene expression ( month 4 , P<0.01 ) . TCC marginally reduced CRP ( month 4 , P=0.06 ) , and significantly reduced monocyte production of proinflammatory cytokines ( month 2 , 4 , 7 , 16 , all P’s<0.05 ) and proinflammatory gene expression ( month 4 , P<0.001 ) . In CBT and TCC , TELIS promoter-based bioinformatics analyses indicated reduced activity of nuclear factor (NF)-κB and AP1 . Conclusions Among older adults with insomnia , CBT-I reduced systemic inflammation , TCC reduced cellular inflammatory responses , and both treatments reduced expression of genes encoding proinflammatory mediators . The findings provide an evidence -based molecular framework to underst and the potential salutary effects of insomnia treatment on inflammation , with implication s for inflammatory disease risk BACKGROUND An appreciation of cognitive predictors of change in treatment outcome may help to better underst and differential treatment outcomes . The aim of this study was to examine how rumination and mindfulness impact on treatment outcome in two group-based interventions for non-melancholic depression : Cognitive Behaviour Therapy ( CBT ) and Mindfulness-Based Cognitive Therapy ( MBCT ) . METHOD Sixty-nine participants were r and omly allocated to either 8-weekly sessions of group CBT or MBCT . Complete data were obtained from 45 participants ( CBT = 26 , MBCT = 19 ) . Outcome was assessed at completion of group treatments . RESULTS Depression scores improved for participants in both group interventions , with no significant differences between the two treatment conditions . There were no significant differences between the interventions at post-treatment on mindfulness or rumination scores . Rumination scores significantly decreased from pre- to post-treatment for both conditions . In the MBCT condition , post-treatment rumination scores were significantly associated with post-treatment mindfulness scores . CONCLUSIONS Results suggest that decreases in rumination scores may be a common feature following both CBT and MBCT interventions . However , post-treatment rumination scores were associated with post-treatment mindfulness in the MBCT condition , suggesting a unique role for mindfulness in underst and ing treatment outcome for MBCT BACKGROUND Greater than 50 % of dialysis patients experience sleep disturbances . Cognitive-behavioral therapy ( CBT ) is effective for treating chronic insomnia , but its effectiveness has never been reported in peritoneal dialysis ( PD ) patients and its association with cytokines is unknown . We investigated the effectiveness of CBT in PD patients by assessing changes in sleep quality and inflammatory cytokines . STUDY DESIGN R and omized control study with parallel-group design . SETTING & PARTICIPANTS 24 PD patients with insomnia in a tertiary medical center without active medical and psychiatric illness were enrolled . INTERVENTION The intervention group ( N = 13 ) received CBT from a psychiatrist for 4 weeks and sleep hygiene education , whereas the control group ( N = 11 ) received only sleep hygiene education . OUTCOMES & MEASUREMENTS Primary outcomes were changes in the Pittsburgh Sleep Quality Index and Fatigue Severity Scale scores , and secondary outcomes were changes in serum interleukin 6 ( IL-6 ) , IL-1beta , IL-18 , and tumor necrosis factor alpha levels during the 4-week trial . RESULTS Median percentages of change in global Pittsburgh Sleep Quality Index scores were -14.3 ( interquartile range , -35.7 to - 6.3 ) and -1.7 ( interquartile range , -7.6 to 7.8 ) in the intervention and control groups , respectively ( P = 0.3 ) . Median percentages of change in global Fatigue Severity Scale scores were -12.1 ( interquartile range , -59.8 to -1.5 ) and -10.5 ( interquartile range , -14.3 to 30.4 ) in the intervention and control groups , respectively ( P = 0.04 ) . Serum IL-1beta level decreased in the intervention group , but increased in the control group ( P = 0.04 ) . There were no significant differences in changes in other cytokines . LIMITATIONS This study had a small number of participants and short observation period , and some participants concurrently used hypnotics . CONCLUSIONS CBT may be effective for improving the quality of sleep and decreasing fatigue and inflammatory cytokine levels . CBT can be an effective nonpharmacological therapy for PD patients with sleep disturbances OBJECTIVES Psychosocial factors , such as stress and vital exhaustion , are associated with an increased risk of cardiovascular events , and women report more psychosocial ill-being after an acute myocardial infa rct ion than men . We have earlier shown that a cognitive-behavioural intervention in women with ischaemic heart disease ( IHD ) improved psychosocial well-being . In the present study , we tested the hypothesis that the improvement in psychosocial well-being is associated with an improvement in biochemical indicators of cardiovascular risk . DESIGN R and omized-controlled trial in northern Sweden . SETTING Outpatient care . SUBJECTS Women with IHD were r and omized to either a 1-year cognitive-behavioural stress management programme or usual care . Of the 159 women who completed the study , 77 were in the intervention group , and 82 in the control group . INTERVENTIONS A 1-year cognitive-behavioural stress management programme versus conventional care . RESULTS Group assignment was not found to be a determinant of waist circumference , high sensitive C-reactive protein ( hs-CRP ) , fibrinogen , von Willebr and factor ( vWF ) , plasminogen activator inhibitor type 1 ( PAI-1 ) activity , tissue plasminogen activator ( tPA ) activity , tPA antigen , tPA-PAI-1 complex , leptin , or HOMA2 insulin resistance index ( HOMA2-IR ) at follow up . Changes in psychosocial variables were not associated with changes in any of the biological risk indicators . CONCLUSIONS Even if our cognitive-behavioural stress management programme had effects on proximal targets , such as stress behaviour and vital exhaustion , we found no improvement in intermediate biochemical targets related to the metabolic syndrome and IHD . Our results challenge the proposition that the relationship between psychological well-being and biological cardiovascular risk indicators is a direct cause-effect phenomenon Objective : This study examined the relationship between reduced anxiety level by therapeutic interventions and cell-mediated immunity ( CMI ) in patients with panic disorder . Methods : The subjects consisted of 42 patients with panic disorder and 42 normal gender- and age-matched controls . Among the patients , 21 were r and omly assigned to a combined treatment of cognitive-behavioral therapy and the benzodiazepine antianxiety agent ethyl loflazepate ( 2 mg daily ) , and 21 were assigned to the antianxiety agent only . The treatment lasted for 6 weeks . Cell-mediated immune function was measured by the lymphocyte proliferative response to phytohemagglutinin ( PHA ) and interleukin-2 ( IL-2 ) production . The anxiety level was assessed by the Hamilton Rating Scale for Anxiety and the anxiety subscale of the Symptom Checklist-90 Revised . Results : Prior to treatment , the panic disorder patients had significantly lower IL-2 production and blastogenic response to PHA than the normal controls . However , no significant differences in CMI were found between the pretreatment and posttreatment period in either the patient group receiving medication only or the combined treatment group , though after treatment , patients were significantly less anxious than before treatment in both intervention groups . The delta change ( posttreatment value minus pretreatment value ) in the self-reported anxiety level was significantly associated with the delta change in the blastogenic response in the combined treatment group . Conclusion : These findings suggest that panic disorder may be associated with decreased CMI , and the reduced level of self-reported anxiety in the patients who underwent combined therapeutic intervention is likely to increase the blastogenic response . Further studies are needed to evaluate the long-term effects of treatment on immune function OBJECTIVE Stress-related physiological activation may last longer for those who ruminate , or dwell , on past stressors . Correlational and quasi-experimental research has linked rumination to immune activity and elevated cortisol . This study 's aim was to experimentally test whether rumination ( relative to distraction ) can sustain stress-induced increases in inflammation and cortisol . Concentrations of poststressor cortisol and inflammatory markers were hypothesized to be greater for those who ruminated compared with those who were distracted . METHOD Thirty-four healthy young women completed a laboratory speech stressor and were then r and omly assigned to either ruminate on the stressor or engage in distraction for 5 minutes . Salivary cortisol and circulating plasma concentrations of C-reactive protein ( CRP ) , interleukin-6 ( IL-6 ) , and tumor necrosis factor-alpha ( TNF-α ) were assessed throughout the 2-hr visit . RESULTS As predicted , CRP and cortisol responses differed for the rumination and distraction groups . In the distraction group , participants ' CRP concentrations increased poststressor and then returned to prestressor levels by the end of the visit . In contrast , participants in the rumination condition demonstrated increases in CRP that did not return to prestressor levels by the end of the visit . Similarly , poststressor cortisol was higher for those who ruminated compared with those who were distracted . Plasma IL-6 and TNF-α concentrations increased over the visit , but did not differ by experimental group . CONCLUSIONS RESULTS suggest that ruminating on stressors may sustain CRP and cortisol responses , whereas distraction may diminish them . Findings have implication s for underst and ing potential risk and protective factors for stress-related activation Dementia caregiving is associated with elevations in depressive symptoms and increased risk for cardiovascular diseases ( CVD ) . This study evaluated the efficacy of the Pleasant Events Program ( PEP ) , a 6-week Behavioral Activation intervention design ed to reduce CVD risk and depressive symptoms in caregivers . One hundred dementia family caregivers were r and omized to either the 6-week PEP intervention ( N = 49 ) or a time-equivalent Information-Support ( IS ) control condition ( N = 51 ) . Assessment s were completed pre- and post-intervention and at 1-year follow-up . Biological assessment s included CVD risk markers Interleukin-6 ( IL-6 ) and D-dimer . Psychosocial outcomes included depressive symptoms , positive affect , and negative affect . Participants receiving the PEP intervention had significantly greater reductions in IL-6 ( p = .040 ) , depressive symptoms ( p = .039 ) , and negative affect ( p = .021 ) from pre- to post-treatment . For IL-6 , clinical ly significant improvement was observed in 20.0 % of PEP participants and 6.5 % of IS participants . For depressive symptoms , clinical ly significant improvement was found for 32.7 % of PEP vs 11.8 % of IS participants . Group differences in change from baseline to 1-year follow-up were non-significant for all outcomes . The PEP program decreased depression and improved a measure of physiological health in older dementia caregivers . Future research should examine the efficacy of PEP for improving other CVD biomarkers and seek to sustain the intervention 's effects BACKGROUND A diagnosis of breast cancer and treatment are psychologically stressful events , particularly over the first year after diagnosis . Women undergo many dem and ing and anxiety-arousing treatments such as surgery , radiation and chemotherapy . Psychosocial interventions that promote psychosocial adaptation to these challenges may modulate physiological processes ( neuroendocrine and immune ) that are relevant for health outcomes in breast cancer patients . METHODS Women with Stages 1 - 3 breast cancer recruited 4 - 8 weeks after surgery were r and omized to either a 10-week group-based cognitive behavioral stress management ( CBSM ) intervention or a 1-day psychoeducational control group and completed question naires and late afternoon blood sample s at study entry and 6 and 12 months after assignment to experimental condition . RESULTS Of 128 women initially providing psychosocial question naire and blood sample s at study entry , 97 provided complete data for anxiety measures and cortisol analysis at all time points , and immune assays were run on a subset of 85 of these women . Those assigned to a 10-week group-based CBSM intervention evidence d better psychosocial adaptation ( lower reported cancer-specific anxiety and interviewer-rated general anxiety symptoms ) and physiological adaptation ( lower cortisol , greater Th1 cytokine [ interleukin-2 and interferon-gamma ] production and IL-2:IL-4 ratio ) after their adjuvant treatment compared to those in the control group . Effects on psychosocial adaptation indicators and cortisol appeared to hold across the entire 12-month observation period . Th1 cytokine regulation changes held only over the initial 6-month period . CONCLUSIONS This intervention may have facilitated a " recovery or maintenance " of Th1 cytokine regulation during or after the adjuvant therapy period . Behavioral interventions that address dysregulated neuroendocrine function could play a clinical ly significant role in optimizing host immunologic resistance during a vulnerable period Eighty women undergoing multimodality treatment for large ( > 4 cm ) or locally advanced ( T3 , T4 , Tx , N2 ) , breast cancers participated in a r and omised controlled trial ( RCT ) to evaluate the immuno-modulatory effects of relaxation training and guided imagery . Patients underwent chemotherapy followed by surgery , radiotherapy , and hormone therapy . Those in the intervention group were taught relaxation and guided imagery . Patients kept diaries of the frequency of relaxation practice and imagery vividness . On 10 occasions during the 37 weeks following the diagnosis , blood was taken for immunological assays CD phenotyping : T cell subsets ( helper , cytotoxic ) , natural killer ( NK ) and lymphokine activated killer ( LAK ) cells , B lymphocytes and monocytes ; cytotoxicity : NK and LAK cell activities ; cytokines interleukin 1 beta ( 1beta ) , 2 , 4 and 6 and tumour necrosis factor alpha . Significant between-group differences were found in the number of CD25 + ( activated T cells ) and CD56 + ( LAK cell ) subsets . The number of CD3 + ( mature ) T cells was significantly higher following chemotherapy and radiotherapy , in patients r and omised to relaxation and guided imagery . Using a median split , women who rated their imagery ratings highly had elevated levels of NK cell activity at the end of chemotherapy and at follow-up . Significant correlations were obtained between imagery ratings and baseline corrected values for NK and LAK cell activity , and IL1beta . Relaxation frequency correlated with the number of CD4 + ( T helper ) cells , the CD4+:8 + ( helper : cytotoxic ) ratio , and IL1beta levels . Relaxation training and guided imagery beneficially altered putative anti-cancer host defences during and after multimodality therapy . Such changes , to the best of our knowledge , have not been previously documented in a RCT This research examined whether cognitive behavioral therapy and mindfulness interventions that target responses to chronic stress , pain , and depression reduce pain and improve the quality of everyday life for adults with rheumatoid arthritis ( RA ) . The 144 RA participants were clustered into groups of 6 - 10 participants and r and omly assigned to 1 of 3 treatments : cognitive behavioral therapy for pain ( P ) ; mindfulness meditation and emotion regulation therapy ( M ) ; or education-only group ( E ) , which served as an attention placebo control . The authors took a multi method approach , employing daily diaries and laboratory assessment of pain and mitogen-stimulated levels of interleukin-6 ( IL-6 ) , a proinflammatory cytokine . Participants receiving P showed the greatest Pre to Post improvement in self-reported pain control and reductions in the IL-6 ; both P and M groups showed more improvement in coping efficacy than did the E group . The relative value of the treatments varied as a function of depression history . RA patients with recurrent depression benefited most from M across several measures , including negative and positive affect and physicians ' ratings of joint tenderness , indicating that the emotion regulation aspects of that treatment were most beneficial to those with chronic depressive features Objective Although early trauma ( trauma in childhood ) has been linked to adult inflammation and adult disease of inflammatory origin , it remains unknown whether this relationship is due to long-term consequences of early life stress or other familial factors . Methods We examined 482 male middle-aged twins ( 241 pairs ) born between 1946 and 1956 from the Vietnam Era Twin Registry . Childhood traumatic experiences , before the age of 18 years , were measured retrospectively with the Early Trauma Inventory and included physical , sexual , emotional abuse and general trauma . Lifetime major depressive disorder and posttraumatic stress disorder were assessed with the Structured Clinical Interview for DSM-IV . Traditional risk factors for cardiovascular disease were also assessed . Plasma C-reactive protein and interleukin 6 were measured to determine levels of inflammation . Mixed-effects regression models with a r and om intercept for pair were used to separate between– and within – twin pair effects . Results When twins were analyzed as individuals , increasing levels of early trauma were positively related to C-reactive protein ( p = .03 ) but not to interleukin 6 ( p = .12 ) . When estimating within- and between-pair effects , only the between-pair association of early trauma with the inflammatory markers remained significant . Conclusions The link between early trauma and inflammation is largely explained by familial factors shared by the twins because levels of inflammation were highest when both twins were exposed to trauma . Exposure to early trauma may be a marker for an unhealthy familial environment . Clarification of familial factors associated with early stress and adult inflammation will be important to uncover correlates of stress and disease STUDY OBJECTIVES To investigate the comparative efficacy of cognitive behavioral therapy ( CBT ) , Tai Chi Chih ( TCC ) , and sleep seminar education control ( SS ) on the primary outcome of insomnia diagnosis , and secondary outcomes of sleep quality , fatigue , depressive symptoms , and inflammation in older adults with insomnia . DESIGN R and omized controlled , comparative efficacy trial . SETTING Los Angeles community . PATIENTS 123 older adults with chronic and primary insomnia . INTERVENTIONS R and om assignment to CBT , TCC , or SS for 2-hour group sessions weekly over 4 months with follow-up at 7 and 16 months . MEASUREMENTS Insomnia diagnosis , patient-reported outcomes , polysomnography ( PSG ) , and high-sensitivity C-reactive protein ( CRP ) levels . RESULTS CBT performed better than TCC and SS in remission of clinical insomnia as ascertained by a clinician ( P < 0.01 ) , and also showed greater and more sustained improvement in sleep quality , sleep parameters , fatigue , and depressive symptoms than TCC and SS ( all P values < 0.01 ) . As compared to SS , CBT was associated with a reduced risk of high CRP levels ( > 3.0 mg/L ) at 16 months ( odds ratio [ OR ] , 0.26 [ 95 % CI , 0.07 - 0.97 ] P < 0.05 ) . Remission of insomnia was associated with lower levels of CRP ( P < 0.05 ) at 16 months . TCC was associated with improvements in sleep quality , fatigue , and depressive symptoms as compared to SS ( all P 's < 0.05 ) , but not insomnia remission . PSG measures did not change . CONCLUSIONS Treatment of late-life insomnia is better achieved and sustained by cognitive behavioral therapies . Insomnia treatment and remission reduces a marker of inflammatory risk , which has implication s for cardiovascular morbidity and diabetes observed with sleep disturbance in epidemiologic surveys Sleep disturbance is common in dialysis patients and is associated with the development of enhanced inflammatory responses . Cognitive-behavioral therapy is effective for sleep disturbance and reduces inflammation experienced by peritoneal dialysis patients ; however , this has not been studied in hemodialysis patients . To determine whether alleviation of sleep disturbance in hemodialysis patients also leads to less inflammation , we conducted a r and omized controlled interventional study of 72 sleep-disturbed hemodialysis patients . Within this patient cohort , 37 received tri-weekly cognitive-behavioral therapy lasting 6 weeks and the remaining 35 , who received sleep hygiene education , served as controls . The adjusted post-trial primary outcome scores of the Pittsburgh Sleep Quality Index , the Fatigue Severity Scale , the Beck Depression Inventory , and the Beck Anxiety Inventory were all significantly improved from baseline by therapy compared with the control group . The post-trial secondary outcomes of high-sensitive C-reactive protein , IL-18 , and oxidized low-density lipoprotein levels significantly declined with cognitive-behavioral therapy in comparison with the control group . Thus , our results suggest that cognitive-behavioral therapy is effective for correcting disorganized sleep patterns , and for reducing inflammation and oxidative stress in hemodialysis patients PURPOSE Cross-sectional studies suggest that clinical insomnia is associated with immune downregulation . However , there is a definite need for experimental studies on this question . The goal of this r and omized controlled study was to assess the effect of an 8-week cognitive-behavioral therapy ( CBT ) for chronic insomnia on immune functioning of breast cancer survivors . Previous analyses of this study showed that CBT was associated with improved sleep and quality of life , and reduced psychological distress . PATIENTS AND METHODS Fifty-seven women with chronic insomnia secondary to breast cancer were r and omly assigned to CBT ( n = 27 ) or to a waiting-list control condition ( WLC ; n = 30 ) . Peripheral-blood sample s were taken at baseline and post-treatment ( and postwaiting for WLC patients ) , as well as at 3- , 6- , and 12-month follow-up for immune measures , including enumeration of blood cell counts ( ie , WBCs , monocytes , lymphocytes , CD3 + , CD4 + , CD8 + , and CD16+/CD56 + ) and cytokine production ( ie , interleukin-1-beta [ IL-1beta ] and interferon gamma [ IFN-gamma ] ) . RESULTS Patients treated with CBT had higher secretion of IFN-gamma and lower increase of lymphocytes at post-treatment compared with control patients . Pooled data from both treated groups indicated significantly increased levels of IFN-gamma and IL-1beta from pre- to post-treatment . In addition , significant changes in WBCs , lymphocytes , and IFN-gamma were found at follow-up compared with post-treatment . CONCLUSION This study provides some support to the hypothesis of a causal relationship between clinical insomnia and immune functioning . Future studies are needed to investigate the clinical impact of such immune alterations OBJECTIVE Recent work suggests effective emotion regulation may protect against risk of developing coronary heart disease ( CHD ) , but the mechanisms remain unknown . Strategies for regulating emotions vary in how effectively they mitigate potentially toxic effects of stressful life experiences , and therefore may be differentially associated with CHD risk . In this study , we examined the emotion regulation strategies of re appraisal and suppression in relation to inflammation , a biological state associated with both stress and CHD . We hypothesized that suppression would be associated with elevated inflammation and re appraisal would be associated with lower levels of inflammation . METHODS We studied adult offspring ( n = 379 ; mean age = 42.2 years ) of Collaborative Perinatal Project participants , a national cohort of pregnant women enrolled in 1959 - 1966 . Vali date d measures of two emotion regulation strategies were examined : re appraisal and suppression . Inflammation was measured as plasma C-reactive protein ( CRP ) levels . We fit multiple linear regression models predicting CRP while controlling for demographic , socioeconomic , and health factors , including depressive symptoms , measured across the life course . RESULTS A 1 st and ard deviation increase in re appraisal was associated with significantly lower CRP ( b = -0.18 , SE = 0.06 , p < .01 ) controlling for demographics . This relation was somewhat attenuated in life course models , with adulthood body mass index partially explaining the association . A 1 st and ard deviation increase in suppression was associated with significantly higher CRP ( b = 0.21 , SE = 0.05 , p < .001 ) , and this association was not substantively attenuated with further covariate adjustment . CONCLUSION Adaptive emotion regulation was associated with lower levels of inflammation and maladaptive emotion regulation was associated with higher levels of inflammation . If these associations are confirmed by prospect i ve and experimental studies , such evidence may provide insight into novel targets for interventions to promote health and reduce cardiovascular risk |
10,765 | 32,128,633 | Overall , early RRT initiation did not provide a survival benefit , but a possible benefit of fewer MV days was detected .
Early RRT might also provide the benefit of shorter MV or RRT support in the surgical population and in AKI patients with high plasma NGAL .
Depending on the conventional indication for RRT initiation , the watchful waiting strategy is safe on the basis of all primary and secondary outcomes | The optimal timing of renal replacement therapy ( RRT ) initiation is debatable .
Many articles in this field enrolled trials not based on acute kidney injury .
The safety of the watchful waiting strategy has not been fully discussed , and late RRT initiation criteria vary across studies .
The effect of early RRT initiation in the AKI population with high plasma neutrophil gelatinase-associated lipocalin ( NGAL ) has not been examined yet . | The incidence and consequences of fluid overload in the surgical ICU ( SICU ) have not been well defined , but may influence length of stay , days requiring mechanical ventilation , and mortality . Forty-eight consecutive patients admitted to our SICU were prospect ively monitored for acute changes in weight and its impact on clinical management and outcome . When defined as a gain greater than 10 % from their preoperative or premorbid weight ( or an approximately 20 % increase in total body water ) , 40 % of patients had fluid overload . Patients were divided into three groups : those who had gained less than or equal to 10 % , those with a weight gain between 11 % and 20 % , and those with greater than 20 % increase in weight . Significant differences were found with respect to vasopressor dependence , colloid administration , and mortality . When indexed by initial Acute Physiology and Chronic Health Evaluation ( APACHE II ) mortality prediction scores , all groups had similar degrees of illness . On average , presumably due to volume limitations , patients were inadequately nourished during 85 % of their SICU stay . Our results suggest that the morbidity of fluid overload can be significant , and warrants a fresh look at the methods of intraoperative fluid resuscitation Background Continuous renal replacement therapy ( CRRT ) is essential in the management of critically ill patients with acute kidney injury ( AKI ) . However , the optimal timing for initiating CRRT remains controversial , especially in elderly patients . Therefore , we investigated the outcomes of early CRRT initiation in elderly patients with AKI . Methods A total of 607 patients ≥65 years of age who started CRRT due to AKI between August 2009 and December 2013 were prospect ively enrolled . They were divided into two groups based on the median 6-hour urine output immediately before CRRT initiation . Propensity score matching was used to compare the overall survival rate , CRRT duration , and hospitalization duration . Results The median age of both groups was 73.0 years , and 60 % of the patients were male . The most common cause of AKI was sepsis . In the early CRRT group , the mean arterial pressure was higher , but the prothrombin time and total bilirubin , aspartate aminotransferase , and alanine aminotransferase levels were lower . The overall cumulative survival rate was higher in the early CRRT group ( log-rank P < 0.01 ) . Late CRRT initiation was associated with a higher mortality rate than early initiation after adjusting for age , sex , the Charlson comorbidity index , systolic arterial pressure , prothrombin time , the total bilirubin , aspartate aminotransferase , and alanine aminotransferase levels , cumulative fluid balance and diuretic use ( hazard ratio , 1.35 ; 95 % confidence interval 1.06 , 1.71 , P = 0.02 ) . Following propensity score matching , patient survival was significantly better in the early CRRT group than in the late CRRT group ( P < 0.01 ) . The total duration of hospitalization from the start of CRRT was shorter among the survivors when CRRT was started earlier ( 26.7 versus 39.1 days , P = 0.04 ) . Conclusion A better prognosis can be expected if CRRT is applied early in the course of AKI in critically ill , elderly patients Whether earlier initiation of RRT in critically ill patients with AKI can improve outcomes remains debated . We examined follow-up data from a large clinical trial to prospect ively investigate the long-term outcomes associated with the timing of RRT initiation in such patients . We extended the follow-up of patients in the Early Versus Delayed Initiation of RRT in Critically Ill Patients with AKI ( ELAIN ) Trial from 90 days to 1 year after r and omization for 230 ( 99.6 % ) patients . The primary outcome was a composite of major adverse kidney events ( persistent renal dysfunction , dialysis dependence , and mortality ) at 1 year . Secondary outcomes included inflammatory markers . Overall , 72 of 111 ( 64.9 % ) and 106 of 119 ( 89.1 % ) patients met the primary outcome in the early ( stage 2 AKI ) and delayed ( stage 3 AKI ) initiation groups , respectively ( odds ratio [ OR ] with early initiation , 0.23 ; 95 % confidence interval [ 95 % CI ] , 0.11 to 0.45 ; P < 0.001 ) . The early initiation group had a 1-year all-cause mortality rate ( 56 of 111 [ 50.2 % ] ) significantly lower than that of the delayed initiation group ( 83 of 119 [ 69.8 % ] ; absolute difference , -19.6 % ; 95 % CI , -32.0 % to -7.2 % ; P<0.01 ) . After 1 year , 16 of 55 ( 29.1 % ) and 23 of 36 ( 63.9 % ) surviving patients in the early and delayed groups , respectively , failed to recover renal function ( absolute difference , -34.8 % ; 95 % CI , -54.6 % to -15.0 % ; P=0.001 ) . In conclusion , early initiation of RRT in these critically ill patients with AKI significantly reduced the occurrence of major adverse kidney events , reduced mortality , and enhanced renal recovery at 1 year Background The timing of initiation of renal replacement therapy ( RRT ) in severe acute kidney injury ( AKI ) remains controversial , with early initiation result ing in unnecessary therapy for some patients while expectant therapy may delay RRT for other patients . The furosemide stress test ( FST ) has been shown to predict the need for RRT and therefore could be used to exclude low-risk patients from enrollment in trials of RRT timing . We conducted this multicenter pilot study to determine whether FST could be used to screen patients at high risk for RRT and to determine the feasibility of incorporating FST into a trial of early initiation of RRT . Methods FST was performed using intravenous furosemide ( 1 mg/kg in furosemide-naive patients or 1.5 mg/kg in previous furosemide users ) . FST-nonresponsive patients ( urine output less than 200 mL in 2 h ) were then r and omized to early ( initiation within 6 h ) or st and ard ( initiation by urgent indication ) RRT . Results FST was completed in all patients ( 100 % ) . Only 6/44 ( 13.6 % ) FST-responsive patients ultimately received RRT while 47/60 ( 78.3 % ) nonresponders r and omized to st and ard RRT either received RRT or died ( P < 0.001 ) . Among 118 FST-nonresponsive patients , 98.3 % in the early RRT arm and 75 % in the st and ard RRT arm received RRT . The adherence to the protocol was 94.8 % and 100 % in the early and st and ard RRT group , respectively . We observed no differences in 28-day mortality ( 62.1 versus 58.3 % , P = 0.68 ) , 7-day fluid balance , or RRT dependence at day 28 . However , hypophosphatemia occurred more frequently in the early RRT arm ( P = 0.002 ) . Conclusion The furosemide stress test appears to be feasible and effective in identifying patients for r and omization to different RRT initiation times . Our findings should guide implementation of large-scale r and omized controlled trials for the timing of RRT initiation . Trial registration clinical trials.gov , NCT02730117 . Registered 6 April 2016 In patients with severe acute kidney injury ( AKI ) but no urgent indication for renal replacement therapy ( RRT ) , the optimal time to initiate RRT remains controversial . While starting RRT preemptively may have benefits , this may expose patients to unnecessary RRT . To study this , we conducted a 12-center open-label pilot trial of critically ill adults with volume replete severe AKI . Patients were r and omized to accelerated ( 12 h or less from eligibility ) or st and ard RRT initiation . Outcomes were adherence to protocol -defined time windows for RRT initiation ( primary ) , proportion of eligible patients enrolled , follow-up to 90 days , and safety in 101 fully eligible patients ( 57 with sepsis ) with a mean age of 63 years . Median serum creatinine and urine output at enrollment were 268 micromoles/l and 356 ml per 24 h , respectively . In the accelerated arm , all patients commenced RRT and 45/48 did so within 12 h from eligibility ( median 7.4 h ) . In the st and ard arm , 33 patients started RRT at a median of 31.6 h from eligibility , of which 19 did not receive RRT ( 6 died and 13 recovered kidney function ) . Clinical outcomes were available for all patients at 90 days following enrollment , with mortality 38 % in the accelerated and 37 % in the st and ard arm . Two surviving patients , both r and omized to st and ard RRT initiation , were still RRT dependent at day 90 . No safety signal was evident in either arm . Our findings can inform the design of a large-scale effectiveness r and omized control trial 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 Abstract Acute kidney injury ( AKI ) is associated with increased morbidity and mortality and is frequently encountered in coronary care units ( CCUs ) . Its clinical presentation differs considerably from that of prerenal or intrinsic AKI . We used the biomarkers calprotectin and neutrophil gelatinase-associated lipocalin ( NGAL ) and compared their utility in predicting and differentiating intrinsic AKI.This was a prospect i ve observational study conducted in a CCU of a tertiary care university hospital . Patients who exhibited any comorbidity and a kidney stressor were enrolled . Urinary sample s of the enrolled patients collected between September 2012 and August 2013 were tested for calprotectin and NGAL . The definition of AKI was based on Kidney Disease Improving Global Outcomes classification . All prospect i ve demographic , clinical , and laboratory data were evaluated as predictors of AKI.A total of 147 adult patients with a mean age of 67 years were investigated . AKI was diagnosed in 71 ( 50.3 % ) patients , whereas intrinsic AKI was diagnosed in 43 ( 60.5 % ) of them . Multivariate logistic regression analysis revealed urinary calprotectin and serum albumin as independent risk factors for intrinsic AKI . For predicting intrinsic AKI , both urinary NGAL and calprotectin displayed excellent areas under the receiver operating characteristic curve ( AUROC ) ( 0.918 and 0.946 , respectively ) . A combination of these markers revealed an AUROC of 0.946.Our result revealed that calprotectin and NGAL had considerable discriminative powers for predicting intrinsic AKI in CCU patients . Accordingly , careful inspection for medication , choice of therapy , and early intervention in patients exhibiting increased biomarker levels might improve the outcomes of kidney injury Introduction Abdominal surgery is probably associated with more likelihood to cause acute kidney injury ( AKI ) . The aim of this study was to evaluate whether early or late start of renal replacement therapy ( RRT ) defined by simplified RIFLE ( sRIFLE ) classification in AKI patients after major abdominal surgery will affect outcome . Methods A multicenter prospect i ve observational study based on the NSARF ( N ational Taiwan University S urgical ICU A ssociated R enal F ailure ) Study Group data base . 98 patients ( 41 female , mean age 66.4 ± 13.9 years ) who underwent acute RRT according to local indications for post-major abdominal surgery AKI between 1 January , 2002 and 31 December , 2005 were enrolled The demographic data , comorbid diseases , types of surgery and RRT , as well as the indications for RRT were documented . The patients were divided into early dialysis ( sRIFLE-0 or Risk ) and late dialysis ( LD , sRIFLE -Injury or Failure ) groups . Then we measured and recorded patients ' outcome including in-hospital mortality and RRT wean-off until 30 June , 2006 . Results The in-hospital mortality was compared as endpoint . Fifty-seven patients ( 58.2 % ) died during hospitalization . LD ( hazard ratio ( HR ) 1.846 ; P = 0.027 ) , old age ( HR 2.090 ; P = 0.010 ) , cardiac failure ( HR 4.620 ; P < 0.001 ) , pre-RRT SOFA score ( HR 1.152 ; P < 0.001 ) were independent indicators for in-hospital mortality . Conclusions The findings of this study support earlier initiation of acute RRT , and also underscore the importance of predicting prognoses of major abdominal surgical patients with AKI by using RIFLE classification Objective : The impact of continuous venovenous hemofiltration on sepsis-induced multiple organ failure severity is controversial . We sought to assess the effect of early application of hemofiltration on the degree of organ dysfunction and plasma cytokine levels in patients with severe sepsis or septic shock . Design : Prospect i ve , r and omized , open , multicenter study setting , 12 French intensive care units . Patients : A total of 80 patients were enrolled within 24 hours of development of the first organ failure related to a new septic insult . Interventions : Patients were r and omized to group 1 ( HF ) , who received hemofiltration ( 25 mL/kg/hr ) for a 96-hour period , or group 2 ( C ) who were managed conventionally . Measurements and Main Results : The primary end point was the number , severity , and duration of organ failures during 14 days , as evaluated by the Sepsis-Related Organ Failure Assessment score , on an intention-to-treat analysis . Strict guidelines were provided to perform continuous hemofiltration under the same conditions and bearing the same objectives in all centers . Because of inclusion stagnation , the trial was discontinued after an interim analysis by which time 76 patients had been r and omized . The number and severity of organ failures were significantly higher in the HF group ( p < 0.05 ) . No modifications in plasma cytokine levels could be detected . Conclusion : These data suggest that early application of st and ard continuous venovenous hemofiltration is deleterious in severe sepsis and septic shock . This study does not rule out an effect of high-volume hemofiltration ( > 35 mL/kg/hr ) on the course of sepsis Objectives : To explore the relationship between timing of continuous renal replacement therapy commencement and clinical outcomes in critically ill patients with acute kidney injury . The primary outcomes were all-cause mortality at 28 and 90 days . Design : Nested observational cohort study using data from the R and omized Evaluation of Normal Versus Augmented Level Replacement Therapy Study . Setting : Twenty-three ICUs in Australia and New Zeal and . Patients : Four hundred thirty-nine critically ill patients with acute kidney injury Risk , Injury , Failure , Loss , End-stage kidney disease-injury ( RIFLE-I ) criteria . Interventions : None . Measurements and Main Results : The time between RIFLE-I acute kidney injury and r and omization in the R and omized Evaluation of Normal Versus Augmented Level Replacement Therapy Study ( proxy for continuous renal replacement therapy commencement ) was the variable of interest . All baseline variables in the R and omized Evaluation of Normal Versus Augmented Level Replacement Therapy Study were assessed . Multivariable Cox , logistic , and linear regression models were used to assess the independent relationship of time of onset of RIFLE-I acute kidney injury and r and omization and patient outcomes . The median time between RIFLE-I acute kidney injury and continuous renal replacement therapy commencement was 17.6 hours ( interquartile range , 7.1–46 hr ) . Based on four groups of continuous renal replacement therapy commencement ( [ group 1 ; reference ] : < 7.1 , [ group 2 ] : ≥ 7.1 to < 17.6 , [ group 3 ] : ≥ 17.6 to < 46.0 , [ group 4 ] : ≥ 46.0 hr ) , earlier commencement of continuous renal replacement therapy was not associated with a significantly lower risk of death at 28 days ( hazard ratio for group 2 : 1.06 , 95 % CI : 0.62–1.81 ; p = 0.83 ; hazard ratio for group 3 : 1.23 , 95 % CI : 0.71–2.12 ; p = 0.46 ; hazard ratio for group 4 : 1.33 , 95 % CI : 0.77–2.31 ; p = 0.31 ) . Similar findings were observed for death at 90 days . Conclusions : In a subgroup of participants of the R and omized Evaluation of Normal Versus Augmented Level Replacement Therapy Study , earlier commencement of continuous renal replacement therapy relative to RIFLE-I acute kidney injury was not significantly associated with improved survival . Additional studies with larger sample sizes and broader commencement times are warranted Fluid accumulation is associated with adverse outcomes in critically ill patients . Here , we sought to determine if fluid accumulation is associated with mortality and non-recovery of kidney function in critically ill adults with acute kidney injury . Fluid overload was defined as more than a 10 % increase in body weight relative to baseline , measured in 618 patients enrolled in a prospect i ve multicenter observational study . Patients with fluid overload experienced significantly higher mortality within 60 days of enrollment . Among dialyzed patients , survivors had significantly lower fluid accumulation when dialysis was initiated compared to non-survivors after adjustments for dialysis modality and severity score . The adjusted odds ratio for death associated with fluid overload at dialysis initiation was 2.07 . In non-dialyzed patients , survivors had significantly less fluid accumulation at the peak of their serum creatinine . Fluid overload at the time of diagnosis of acute kidney injury was not associated with recovery of kidney function . However , patients with fluid overload when their serum creatinine reached its peak were significantly less likely to recover kidney function . Our study shows that in patients with acute kidney injury , fluid overload was independently associated with mortality . Whether the fluid overload was the result of a more severe renal failure or it contributed to its cause will require clinical trials in which the role of fluid administration to such patients is directly tested BACKGROUND The timing of renal-replacement therapy in critically ill patients who have acute kidney injury but no potentially life-threatening complication directly related to renal failure is a subject of debate . METHODS In this multicenter r and omized trial , we assigned patients with severe acute kidney injury ( Kidney Disease : Improving Global Outcomes [ KDIGO ] classification , stage 3 [ stages range from 1 to 3 , with higher stages indicating more severe kidney injury ] ) who required mechanical ventilation , catecholamine infusion , or both and did not have a potentially life-threatening complication directly related to renal failure to either an early or a delayed strategy of renal-replacement therapy . With the early strategy , renal-replacement therapy was started immediately after r and omization . With the delayed strategy , renal-replacement therapy was initiated if at least one of the following criteria was met : severe hyperkalemia , metabolic acidosis , pulmonary edema , blood urea nitrogen level higher than 112 mg per deciliter , or oliguria for more than 72 hours after r and omization . The primary outcome was overall survival at day 60 . RESULTS A total of 620 patients underwent r and omization . The Kaplan-Meier estimates of mortality at day 60 did not differ significantly between the early and delayed strategies ; 150 deaths occurred among 311 patients in the early- strategy group ( 48.5 % ; 95 % confidence interval [ CI ] , 42.6 to 53.8 ) , and 153 deaths occurred among 308 patients in the delayed- strategy group ( 49.7 % , 95 % CI , 43.8 to 55.0 ; P=0.79 ) . A total of 151 patients ( 49 % ) in the delayed- strategy group did not receive renal-replacement therapy . The rate of catheter-related bloodstream infections was higher in the early- strategy group than in the delayed- strategy group ( 10 % vs. 5 % , P=0.03 ) . Diuresis , a marker of improved kidney function , occurred earlier in the delayed- strategy group ( P<0.001 ) . CONCLUSIONS In a trial involving critically ill patients with severe acute kidney injury , we found no significant difference with regard to mortality between an early and a delayed strategy for the initiation of renal-replacement therapy . A delayed strategy averted the need for renal-replacement therapy in an appreciable number of patients . ( Funded by the French Ministry of Health ; Clinical Trials.gov number , NCT01932190 . ) BACKGROUND Optimum timing of the initiation of dialysis therapy in acute kidney injury is not clear . STUDY DESIGN Prospect i ve , open label , 2-arm , r and omized , controlled trial . SETTING & PARTICIPANTS 208 adults with acute kidney injury with progressively worsening azotemia at the artificial kidney dialysis unit of a tertiary-care referral center in western India . INTERVENTION Earlier-start dialysis was initiated when serum urea nitrogen and /or creatinine levels increased to 70 and 7 mg/dL , respectively , whereas the usual-start dialysis patients ( control group ) received dialysis when clinical ly indicated as judged by treating nephrologists . OUTCOMES Primary outcome was in-hospital mortality and dialysis dependence at 3 months . Secondary outcome in patients receiving dialysis was time to recovery of kidney function , computed from time of enrollment to the last dialysis session . RESULTS Of 585 screened patients , 102 were assigned to earlier-start dialysis , and 106 to usual-start dialysis . Baseline characteristics were similar between r and omized groups . 93 ( 91.1 % ) and 88 ( 83.1 % ) participants received dialysis in the intervention and control groups , respectively . Mean serum urea nitrogen and serum creatinine levels at dialysis therapy initiation were 71.7 ± 21.7 ( SD ) and 7.4 ± 5.3 mg/dL , respectively , in the intervention group versus 100.9 ± 32.6 and 10.41 ± 3.3 mg/dL in the control group . Data on primary outcome were available for all patients . In-hospital mortality was 20.5 % and 12.2 % in the intervention and control groups , respectively ( relative risk , 1.67 ; 95 % CI , 0.88 - 3.17 ; P = 0.2 ) . 4.9 % and 4.7 % of patients in the intervention and control groups , respectively , were dialysis dependent at 3 months ( relative risk , 1.04 ; 95 % CI , 0.29 - 3.7 ; P = 0.9 ) . LIMITATIONS Study was not double blind , event rate ( ie , mortality ) was less than predicted , wide CIs preclude definitive findings . CONCLUSIONS Our data do not support the earlier initiation of dialysis therapy in community-acquired acute kidney injury 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 Among critically ill patients , acute kidney injury ( AKI ) is a relatively common complication that is associated with an increased risk for death and other complications . To date , no treatment has been developed to prevent or attenuate established AKI . Dialysis often is required , but the optimal timing of initiation of dialysis is unknown . Data from the Program to Improve Care in Acute Renal Disease ( PICARD ) , a multicenter observational study of AKI , were analyzed . Among 243 patients who did not have chronic kidney disease and who required dialysis for severe AKI , we examined the risk for death within 60 d from the diagnosis of AKI by the blood urea nitrogen ( BUN ) concentration at the start of dialysis ( BUN < or = 76 mg/dl in the low degree of azotemia group [ n = 122 ] versus BUN > 76 mg/dl in the high degree of azotemia group [ n = 121 ] ) . St and ard Kaplan-Meier product limit estimates , proportional hazards ( Cox ) regression methods , and a propensity score approach were used to account for selection effects . Crude survival rates were slightly lower for patients who started dialysis at higher BUN concentrations , despite a lesser burden of organ system failure . Adjusted for age , hepatic failure , sepsis , thrombocytopenia , and serum creatinine and stratified by site and initial dialysis modality , the relative risk for death that was associated with initiation of dialysis at a higher BUN was 1.85 ( 95 % confidence interval 1.16 to 2.96 ) . Further adjustment for the propensity score did not material ly alter the association ( relative risk 1.97 ; 95 % confidence interval 1.21 to 3.20 ) . Among critically ill patients with AKI , initiation of dialysis at higher BUN concentrations was associated with an increased risk for death . Although the results could reflect residual confounding by severity of illness , they provide a rationale for prospect i ve testing of alternative dialysis initiation strategies in critically ill patients with severe AKI Clinicians have access to limited tools that predict which patients with early AKI will progress to more severe stages . In early AKI , urine output after a furosemide stress test ( FST ) , which involves intravenous administration of furosemide ( 1.0 or 1.5 mg/kg ) , can predict the development of stage 3 AKI . We measured several AKI biomarkers in our previously published cohort of 77 patients with early AKI who received an FST and evaluated the ability of FST urine output and biomarkers to predict the development of stage 3 AKI ( n=25 [ 32.5 % ] ) , receipt of RRT ( n=11 [ 14.2 % ] ) , or inpatient mortality ( n=16 [ 20.7 % ] ) . With an area under the curve (AUC)±SEM of 0.87±0.09 ( P<0.0001 ) , 2-hour urine output after FST was significantly better than each urinary biomarker tested in predicting progression to stage 3 ( P<0.05 ) . FST urine output was the only biomarker to significantly predict RRT ( 0.86±0.08 ; P=0.001 ) . Regardless of the end point , combining FST urine output with individual biomarkers using logistic regression did not significantly improve risk stratification ( ΔAUC , P>0.10 for all ) . When FST urine output was assessed in patients with increased biomarker levels , the AUC for progression to stage 3 improved to 0.90±0.06 and the AUC for receipt of RRT improved to 0.91±0.08 . Overall , in the setting of early AKI , FST urine output outperformed biochemical biomarkers for prediction of progressive AKI , need for RRT , and inpatient mortality . Using a FST in patients with increased biomarker levels improves risk stratification , although further research is needed Objective To study the effects of the initiation time of continuous venovenous hemofiltration and of the ultrafiltrate rate in patients with circulatory and respiratory insufficiency developing early oliguric acute renal failure . The primary end points were mortality at 28 days and recovery of renal function . Design A r and omized , controlled , two-center study . Setting The closed-format multidisciplinary intensive care units of a university hospital ( 30 beds ) and a teaching hospital ( 18 beds ) . Patients and Interventions A total of 106 ventilated severely ill patients who were oliguric despite massive fluid resuscitation , inotropic support , and high-dose intravenous diuretics were r and omized into three groups . Thirty-five patients were treated with early high-volume hemofiltration ( 72–96 L per 24 hrs ) , 35 patients with early low-volume hemofiltration ( 24–36 L per 24 hrs ) , and 36 patients with late low-volume hemofiltration ( 24–36 L per 24 hrs ) . Results Median ultrafiltrate rate was 48.2 ( 42.3–58.7 ) mL·kg−1·hr−1 in early high-volume hemofiltration , 20.1 ( 17.5–22.0 ) mL·kg−1·hr−1 in early low-volume hemofiltration , and 19.0 ( 16.6–21.1 ) mL·kg−1·hr−1 in late low-volume hemofiltration . Survival at day 28 was 74.3 % in early high-volume hemofiltration , 68.8 % in early low-volume hemofiltration , and 75.0 % in late low-volume hemofiltration ( p = .80 ) . On average , hemofiltration started 7 hrs after inclusion in the early groups and 42 hrs after inclusion in the late group . All hospital survivors had recovery of renal function at hospital discharge , except for one patient in the early low-volume hemofiltration group . Median duration of renal failure in hospital survivors was 4.3 ( 1.4–7.8 ) days in early high-volume hemofiltration , 3.2 ( 2.4–5.4 ) days in early low-volume hemofiltration , and 5.6 ( 3.1–8.5 ) days in late low-volume hemofiltration ( p = .25 ) . Conclusions In the present study of critically ill patients with oliguric acute renal failure , survival at 28 days and recovery of renal function were not improved using high ultrafiltrate volumes or early initiation of hemofiltration Purpose Current reports on acute kidney injury ( AKI ) in the intensive care unit ( ICU ) show wide variation in occurrence rate and are limited by study biases such as use of incomplete AKI definition , selected cohorts , or retrospective design . Our aim was to prospect ively investigate the occurrence and outcomes of AKI in ICU patients . Methods The Acute Kidney Injury – Epidemiologic Prospect i ve Investigation ( AKI-EPI ) study was an international cross-sectional study performed in 97 centers on patients during the first week of ICU admission . We measured AKI by Kidney Disease : Improving Global Outcomes ( KDIGO ) criteria , and outcomes at hospital discharge . Results A total of 1032 ICU patients out of 1802 [ 57.3 % ; 95 % confidence interval ( CI ) 55.0–59.6 ] had AKI . Increasing AKI severity was associated with hospital mortality when adjusted for other variables ; odds ratio of stage 1 = 1.679 ( 95 % CI 0.890–3.169 ; p = 0.109 ) , stage 2 = 2.945 ( 95 % CI 1.382–6.276 ; p = 0.005 ) , and stage 3 = 6.884 ( 95 % CI 3.876–12.228 ; p < 0.001 ) . Risk-adjusted rates of AKI and mortality were similar across the world . Patients developing AKI had worse kidney function at hospital discharge with estimated glomerular filtration rate less than 60 mL/min/1.73 m2 in 47.7 % ( 95 % CI 43.6–51.7 ) versus 14.8 % ( 95 % CI 11.9–18.2 ) in those without AKI , p < 0.001 . Conclusions This is the first multinational cross-sectional study on the epidemiology of AKI in ICU patients using the complete KDIGO criteria . We found that AKI occurred in more than half of ICU patients . Increasing AKI severity was associated with increased mortality , and AKI patients had worse renal function at the time of hospital discharge . Adjusted risks for AKI and mortality were similar across different continents and regions OBJECTIVES Acute kidney injury after cardiac surgery ( CS-AKI ) is strongly associated with in-hospital mortality and morbidity . We aim ed to investigate whether ' early ' or ' late ' initiation of renal replacement therapy ( RRT ) in patients with CS-AKI is associated with a survival benefit or more favourable outcomes . METHODS All patients who had undergone cardiac surgery at ' Ospedali Riuniti ' of Ancona from July 2011 to February 2013 were prospect ively enrolled and divided into two treatment groups : the ' early ' approach was used during the first 10 months , and the ' late ' approach during the next 10 months . ' Early ' RRT was started after 6 h of urine output less than 0.5 ml/kg/h , whereas in the ' late ' group , therapy started on the basis of persistent ( > 12 h ) oliguria . A total of 1658 patients were enrolled in the trial . The primary outcome was operative mortality , and the secondary outcomes were length of intensive care unit and hospital stay . RESULTS The total number of patients treated with RRT was 59 ( 3.6 % ) : 46 ( 5.5 % ) in the ' early ' group and 13 ( 1.6 % ) in the ' late ' group ( P < 0.0001 ) . Although RRT was significantly less utilized in the ' late ' group , no significant difference in the primary and secondary outcomes was found , but a trend towards a better outcome in the ' late ' group was observed . Furthermore , we found a significant difference in mortality between the two approaches in the subgroups of patients with preoperative renal dysfunction and in patients suffering from CS-AKI with a clear advantage of the late strategy . CONCLUSIONS Our results do not support the use of early RRT in CS-AKI . CLINICAL TRIAL REGISTRATION This trial is registered in the clinical trial.gov registry : NCT01961999 IMPORTANCE Optimal timing of initiation of renal replacement therapy ( RRT ) for severe acute kidney injury ( AKI ) but without life-threatening indications is still unknown . OBJECTIVE To determine whether early initiation of RRT in patients who are critically ill with AKI reduces 90-day all-cause mortality . DESIGN , SETTING , AND PARTICIPANTS Single-center r and omized clinical trial of 231 critically ill patients with AKI Kidney Disease : Improving Global Outcomes ( KDIGO ) stage 2 ( ≥2 times baseline or urinary output < 0.5 mL/kg/h for ≥12 hours ) and plasma neutrophil gelatinase-associated lipocalin level higher than 150 ng/mL enrolled between August 2013 and June 2015 from a university hospital in Germany . INTERVENTIONS Early ( within 8 hours of diagnosis of KDIGO stage 2 ; n = 112 ) or delayed ( within 12 hours of stage 3 AKI or no initiation ; n = 119 ) initiation of RRT . MAIN OUTCOMES AND MEASURES The primary end point was mortality at 90 days after r and omization . Secondary end points included 28- and 60-day mortality , clinical evidence of organ dysfunction , recovery of renal function , requirement of RRT after day 90 , duration of renal support , and intensive care unit ( ICU ) and hospital length of stay . RESULTS Among 231 patients ( mean age , 67 years ; men , 146 [ 63.2 % ] ) , all patients in the early group ( n = 112 ) and 108 of 119 patients ( 90.8 % ) in the delayed group received RRT . All patients completed follow-up at 90 days . Median time ( Q1 , Q3 ) from meeting full eligibility criteria to RRT initiation was significantly shorter in the early group ( 6.0 hours [ Q1 , Q3 : 4.0 , 7.0 ] ) than in the delayed group ( 25.5 h [ Q1 , Q3 : 18.8 , 40.3 ] ; difference , -21.0 [ 95 % CI , -24.0 to -18.0 ] ; P < .001 ) . Early initiation of RRT significantly reduced 90-day mortality ( 44 of 112 patients [ 39.3 % ] ) compared with delayed initiation of RRT ( 65 of 119 patients [ 54.7 % ] ; hazard ratio [ HR ] , 0.66 [ 95 % CI , 0.45 to 0.97 ] ; difference , -15.4 % [ 95 % CI , -28.1 % to -2.6 % ] ; P = .03 ) . More patients in the early group recovered renal function by day 90 ( 60 of 112 patients [ 53.6 % ] in the early group vs 46 of 119 patients [ 38.7 % ] in the delayed group ; odds ratio [ OR ] , 0.55 [ 95 % CI , 0.32 to 0 . 93 ] ; difference , 14.9 % [ 95 % CI , 2.2 % to 27.6 % ] ; P = .02 ) . Duration of RRT and length of hospital stay were significantly shorter in the early group than in the delayed group ( RRT : 9 days [ Q1 , Q3 : 4 , 44 ] in the early group vs 25 days [ Q1 , Q3 : 7 , > 90 ] in the delayed group ; P = .04 ; HR , 0.69 [ 95 % CI , 0.48 to 1.00 ] ; difference , -18 days [ 95 % CI , -41 to 4 ] ; hospital stay : 51 days [ Q1 , Q3 : 31 , 74 ] in the early group vs 82 days [ Q1 , Q3 : 67 , > 90 ] in the delayed group ; P < .001 ; HR , 0.34 [ 95 % CI , 0.22 to 0.52 ] ; difference , -37 days [ 95 % CI , -∞ to -19.5 ] ) , but there was no significant effect on requirement of RRT after day 90 , organ dysfunction , and length of ICU stay . CONCLUSIONS AND RELEVANCE Among critically ill patients with AKI , early RRT compared with delayed initiation of RRT reduced mortality over the first 90 days . Further multicenter trials of this intervention are warranted . TRIAL REGISTRATION German Clinical Trial Registry Identifier : DRKS00004367 Aim To study the demographics and outcome of acute kidney injury ( AKI ) at Groote Schuur Hospital , Cape Town , South Africa . Methods and findings A prospect i ve observational study of AKI fulfilling the Kidney Disease : Improving Global Outcomes definition , from 8 July 2012 to 8 July 2013 . Ethics approval was granted by the University of Cape Town Human Research Ethics Committee . Consent was waived because patient data was de-identified and patient management was not adversely affected by the study . A clerking sheet was used for data collection . Patients were reassessed after 3 months . Main outcomes were renal recovery and 3 month mortality . Descriptive statistics and multivariate logistic regression were carried out for risk factors . Over this period there were 10,750 hospital admissions and 366 patients with AKI giving an incidence of 3.4 % . Median age was 44 years ( IQR 14–82 ) and 214 ( 58.5 % ) were male , with 152 ( 41.5 % ) female . Most , 265 ( 72.4 % ) , had community acquired AKI . Common underlying comorbidities were hypertension ( n = 152 , 41.5 % ) , diabetes mellitus ( n = 65 , 17.8 % ) Human immunodeficiency virus ( HIV ) ( n = 75 , 20.6 % ) , heart disease ( n = 58 , 16.1 % ) , and chronic kidney disease ( n = 37 , 10.1 % ) . Renal biopsies were performed in 36 ( 9.8 % ) patients . In total , 202 ( 55.2 % ) patients were in the intensive care unit , and of the whole study population 204 ( 55.7 % ) were dialysed . Those admitted to ICU who required dialysis amounted to 145 ( 39.6 % ) . The overall 3 month mortality was 38.8 % . Among the 145 patients dialysed in ICU , there were 71 deaths ( 49 % ) at 3 month follow up . Of the 119 patients with follow up serum creatinine , 95 ( 79.8 % ) had full renal recovery , and 4 ( 3.4 % ) had end-stage renal disease . On multivariate analysis , mechanical ventilation was associated with 3 month mortality ( OR 2.46 , p-value 0.019 , 95 % CI 1.41–4.03 ) . Sepsis had a borderline significant association ( OR 1.83 , P-value 0.066 , 95%CI 1.02–3.27 ) , as did prolonged time to dialysis ( OR 1.93 , p-value 0.08 , 095 % CI 0.93–4.03 ) . HIV status did not affect outcome . The main study limitations were the large numbers of patients with AKI stage 3 , reflecting the fact that the institution is a tertiary referral centre and that patients with earlier stages of AKI tended not to be referred . Another study limitation was the low number of patients who were available for follow up for 3 month serum creatinine . Conclusions The incidence of AKI in the population studied is 3.4 % of hospital admissions and carries a high mortality risk , most significant in mechanically ventilated patients . Sepsis and late dialysis initiation may carry a risk of mortality , but HIV infection did not affect outcome . Follow up of patients at least 3 months after an episode of AKI is essential to detect and appropriately manage those with incomplete renal recovery . In this study 36 patients underwent a kidney biopsy , and in many of these the results guided patient management . This study demonstrates finally that it remains imperative that clinicians actively pursue underlying causes of acute decline in renal function , including urine analysis , renal ultrasonography and if indicated and safe , a renal biopsy RATIONALE Post-cardiac surgery shock is associated with high morbidity and mortality . By removing toxins and proinflammatory mediators and correcting metabolic acidosis , high-volume hemofiltration ( HVHF ) might halt the vicious circle leading to death by improving myocardial performance and reducing vasopressor dependence . OBJECTIVES To determine whether early HVHF decreases all-cause mortality 30 days after r and omization . METHODS This prospect i ve , multicenter r and omized controlled trial included patients with severe shock requiring high-dose catecholamines 3 - 24 hours post-cardiac surgery who were r and omized to early HVHF ( 80 ml/kg/h for 48 h ) , followed by st and ard-volume continuous venovenous hemodiafiltration ( CVVHDF ) until resolution of shock and recovery of renal function , or conservative st and ard care , with delayed CVVHDF only for persistent , severe acute kidney injury . MEASUREMENTS AND MAIN RESULTS On Day 30 , 40 of 112 ( 36 % ) HVHF and 40 of 112 ( 36 % ) control subjects ( odds ratio , 1.00 ; 95 % confidence interval , 0.64 - 1.56 ; P = 1.00 ) had died ; only 57 % of the control subjects had received renal-replacement therapy . Between-group survivors ' Day-60 , Day-90 , intensive care unit , and in-hospital mortality rates , Day-30 ventilator-free days , and renal function recovery were comparable . HVHF patients experienced faster correction of metabolic acidosis and tended to be more rapidly weaned off catecholamines but had more frequent hypophosphatemia , metabolic alkalosis , and thrombocytopenia . CONCLUSIONS For patients with post-cardiac surgery shock requiring high-dose catecholamines , the early HVHF onset for 48 hours , followed by st and ard volume until resolution of shock and recovery of renal function , did not lower Day-30 mortality and did not impact other important patient-centered outcomes compared with a conservative strategy with delayed CVVHDF initiation only for patients with persistent , severe acute kidney injury . Clinical trial registered with www . clinical trials.gov ( NCT 01077349 ) BACKGROUND Preoperative creatinine values higher than 2.5 mg/dL are associated with markedly increased risk for both mortality and morbidity in patients undergoing coronary artery bypass surgery . We aim ed to determine the effects of prophylactic perioperative hemodialysis on operative outcome in patients with nondialysis-dependent moderate renal dysfunction . METHODS Forty-four adult patients with creatinine levels greater than 2.5 mg/dL but not requiring dialysis underwent coronary artery bypass surgery with cardiopulmonary bypass . The patients were r and omly divided into two groups . In group 1 ( dialysis group , 21 patients ) , perioperative prophylactic hemodialysis was performed in all patients . Group 2 ( 23 patients ) was taken as a control group and hemodialysis was performed only if postoperative acute renal failure was diagnosed . RESULTS The hospital mortality was 4.8 % ( 1 patient ) in the dialysis group , and 30.4 % ( 7 patients ) in the control group ( p = 0.048 ) . Postoperative acute renal failure requiring hemodialysis was seen in 1 patient ( 4.8 % ) in the dialysis group and in 8 patients ( 34.8 % ) in the control group ( p = 0.023 ) . Thirty-three postoperative complications were observed in the control group for an early morbidity of 52.2 % ( 12 patients ) and 13 complications occurred in 8 patients in the dialysis group ( 38.1 % ) . The average length of the intensive care unit and postoperative hospital stay were shorter in the dialysis group than in the control group ( p = 0.005 and p = 0.023 , respectively ) . CONCLUSIONS Preoperative creatinine levels higher than 2.5 mg/dL , increase the risk of mortality and the development of acute renal failure and prolong the length of hospital stay after on-pump coronary artery bypass surgery . Perioperative prophylactic hemodialysis decreases both operative mortality and morbidity in these high-risk patients Purpose : The optimal time and the parameter utilized for decision to initiate renal replacement therapy ( RRT ) in acute kidney injury ( AKI ) are still controversial . Recently , high levels of plasma NGAL ( pNGAL ) has been strongly correlated with poor AKI outcome . This is a feasibility study conducted to test whether early RRT initiation guided by pNGAL could improve AKI outcome . Material and methods : The study comprised of triage trial and interventional trial running subsequently . As a guide for triage to RRT , we measured pNGAL at the enrollment time . Forty patients with pNGAL ≥ 400 ng/mL ( high pNGAL group ) were r and omized to ‘ early ’ or ‘ st and ard ’ group . Patients with pNGAL < 400 ng/mL ( n = 20 ) were defined as low pNGAL group . Results : The triggering pNGAL selected AKI patients with more severity of illness and worse clinical outcome . However , in high pNGAL group , early RRT did not result in different 28‐day mortality from the st and ard group . The median numbers of day free from mechanical ventilation were significantly higher in the early RRT group . Conclusions : Our finding suggested that it was feasible to use pNGAL to triage severe AKI patients . However , early initiation of RRT in this high risk group did not affect the 28‐day mortality . Highlights : The first feasibility study using plasma NGAL triaged severe AKI patients for early initiation of renal replacement therapy . High plasma NGAL at the cut‐off point 400 ng/mL had shown the association with the worse AKI outcomes .Early RRT strategy has shown comparable 28 day‐mortality to st and ard RRT strategy in this feasibility study The study was conducted in 35 cases of acute tubular necrosis of varied aetiology . Cases were divided in 2 groups , Group A--17 cases treated conservatively and Group B--18 cases managed by early haemodialysis . Criteria for early haemodialysis were blood urea < 120 mg% and serum creatinine < 7 mg% . Before starting therapy both the groups had comparable biochemical and renal parameters ( p > 0.05 ) . Overall mortality was lower in Group B as compared to Group A ( 22.2 % Vs 29.4 ) . Complication events such as uraemic encephalopathy , pulmonary oedema , haematemesis and malena , thrombophlebitis and vomiting were significantly lower in Group B ( p < 0.05 ) . Hospital stay was also significantly lower ( p < 0.05 ) in Group B ( 18 + /- 2.5 days Vs 28 + /- 3 days ) , this can reduce the cost of treatment also Sepsis is the most common cause of acute kidney injury ( AKI ) in critical illness , but there is limited information on septic AKI . A prospect i ve , observational study of critically ill patients with septic and nonseptic AKI was performed from September 2000 to December 2001 at 54 hospitals in 23 countries . A total of 1753 patients were enrolled . Sepsis was considered the cause in 833 ( 47.5 % ) ; the predominant sources of sepsis were chest and abdominal ( 54.3 % ) . Septic AKI was associated with greater aberrations in hemodynamics and laboratory parameters , greater severity of illness , and higher need for mechanical ventilation and vasoactive therapy . There was no difference in enrollment kidney function or in the proportion who received renal replacement therapy ( RRT ; 72 versus 71 % ; P = 0.83 ) . Oliguria was more common in septic AKI ( 67 versus 57 % ; P < 0.001 ) . Septic AKI had a higher in-hospital case-fatality rate compared with nonseptic AKI ( 70.2 versus 51.8 % ; P < 0.001 ) . After adjustment for covariates , septic AKI remained associated with higher odds for death ( 1.48 ; 95 % confidence interval 1.17 to 1.89 ; P = 0.001 ) . Median ( IQR ) duration of hospital stay for survivors ( 37 [ 19 to 59 ] versus 21 [ 12 to 42 ] d ; P < 0.0001 ) was longer for septic AKI . There was a trend to lower serum creatinine ( 106 [ 73 to 158 ] versus 121 [ 88 to 184 ] mumol/L ; P = 0.01 ) and RRT dependence ( 9 versus 14 % ; P = 0.052 ) at hospital discharge for septic AKI . Patients with septic AKI were sicker and had a higher burden of illness and greater abnormalities in acute physiology . Patients with septic AKI had an increased risk for death and longer duration of hospitalization yet showed trends toward greater renal recovery and independence from RRT BACKGROUND AND OBJECTIVES No data on the development of conventional indications for RRT ( refractory acidosis , hyperkalemia , uremia , oliguria/anuria , and volume overload ) related to timing of RRT exist . The prevalence of conventional indications among critically ill patients on RRT for AKI was evaluated , and patients manifesting indications versus patients without indications were compared in terms of crude and adjusted 90-day mortality . DESIGN , SETTING , PARTICIPANTS , & MEASUREMENTS In this sub study of the Finnish Acute Kidney Injury study conducted in 2011 and 2012 in 17 intensive care units with 2901 patients , patients were classified as pre-emptive ( no conventional indications ) and classic ( one or more indications ) RRT recipients . Patients with classic RRT were divided into classic-urgent ( RRT initiated ≤ 12 hours from manifesting indications ) and classic-delayed ( RRT > 12 hours from first indication ) . Additionally , 2450 patients treated without RRT were matched to patients with pre-emptive RRT . RESULTS Of 239 patients treated with RRT , 134 ( 56.1 % ; 95 % confidence interval [ 95 % CI ] , 49.8 % to 62.4 % ) fulfilled at least one conventional indication before commencing RRT . Crude 90-day mortality of 134 patients with classic RRT was 48.5 % ( 95 % CI , 40.0 % to 57.0 % ) , and it was 29.5 % ( 95 % CI , 20.8 % to 38.2 % ) for the 105 patients with pre-emptive RRT . Classic RRT was associated with a higher risk for mortality ( adjusted odds ratio , 2.05 ; 95 % CI , 1.03 to 4.09 ) . Forty-four patients with classic-delayed RRT showed higher crude mortality ( 68.2 % ; 95 % CI , 54.4 % to 82.0 % ) compared with patients with classic-urgent RRT , and this association persisted after adjustment for known confounders ( odds ratio , 3.85 ; 95 % CI , 1.48 to 10.22 ) . Crude 90-day mortality of 67 1:1 matched patients with pre-emptive RRT was 26.9 % ( 95 % CI , 6.3 % to 37.5 % ) , and it was 49.3 % ( 95 % CI , 37.3 % to 61.2 % ; P=0.01 ) for their non-RRT matches . CONCLUSIONS Patients on RRT after one or more conventional indications had both higher crude and adjusted 90-day mortality compared with patients without conventional indications . These findings require confirmation in an adequately powered , multicenter , r and omized controlled trial PURPOSE The aim of this study is to evaluate the relationship between timing of renal replacement therapy ( RRT ) in severe acute kidney injury and clinical outcomes . METHODS This was a prospect i ve multicenter observational study conducted at 54 intensive care units ( ICUs ) in 23 countries enrolling 1238 patients . RESULTS Timing of RRT was stratified into " early " and " late " by median urea and creatinine at the time RRT was started . Timing was also categorized temporally from ICU admission into early ( < 2 days ) , delayed ( 2 - 5 days ) , and late ( > 5 days ) . Renal replacement therapy timing by serum urea showed no significant difference in crude ( 63.4 % for urea < or=24.2 mmol/L vs 61.4 % for urea > 24.2 mmol/L ; odds ratio [ OR ] , 0.92 ; 95 % confidence interval [ CI ] , 0.73 - 1.15 ; P = .48 ) or covariate-adjusted mortality ( OR , 1.25 ; 95 % CI , 0.91 - 1.70 ; P = .16 ) . When stratified by creatinine , late RRT was associated with lower crude ( 53.4 % for creatinine > 309 micromol/L vs 71.4 % for creatinine < or=309 micromol/L ; OR , 0.46 ; 95 % CI , 0.36 - 0.58 ; P < .0001 ) and covariate-adjusted mortality ( OR , 0.51 ; 95 % CI , 0.37 - 0.69 ; P < .001 ) . However , for timing relative to ICU admission , late RRT was associated with greater crude ( 72.8 % vs 62.3 % vs 59 % , P < .001 ) and covariate-adjusted mortality ( OR , 1.95 ; 95 % CI , 1.30 - 2.92 ; P = .001 ) . Overall , late RRT was associated with a longer duration of RRT and stay in hospital and greater dialysis dependence . CONCLUSION Timing of RRT , a potentially modifiable factor , might exert an important influence on patient survival . However , this largely depended on its definition . Late RRT ( days from admission ) was associated with a longer duration of RRT , longer hospital stay , and higher dialysis dependence AIM Optimal timing for acute renal replacement therapy ( ARRT ) initiation in critically ill patients with acute kidney injury ( AKI ) is unclear . We aim ed to evaluate outcomes in patients who initiated ARRT for traditional indications versus those who met Acute Kidney Injury Network ( AKIN ) criteria without traditional indications . METHODS This was a single-centre prospect i ve cohort study of medical and surgical intensive care patients with AKI . Traditional indications for ARRT initiation included : serum potassium ≥6.0 mmol/L , serum urea ≥30 mmol/L , arterial pH < 7.25 , serum bicarbonate < 10 mmol/L , acute pulmonary oedema , acute uraemic encephalopathy or pericarditis . In absence of these indications , ARRT was commenced if patients had ( i ) AKIN Stage 3 or ( ii ) AKIN Stage 1 or 2 with ' compelling ' conditions . Primary outcomes were intensive care unit ( ICU ) and in-hospital mortality . RESULTS ARRT was initiated in 140 patients : traditional indications in 56 ( 40 % ) ; AKIN Stage 3 without traditional indications in 38 ( 27 % ) ; and AKIN Stage 1 or 2 with ' compelling ' conditions in 46 ( 33 % ) patients . Traditional indications at ARRT initiation was associated with increased in-hospital mortality ( adjusted odds ratio ( 95 % confidence interval ) , 6.48 ( 1.54 , 27.29 ) ) . In absence of traditional indications , earlier ARRT initiation , as defined by those with AKIN Stage 1 or 2 , did not decrease ICU deaths ( 30.0 % vs 18.8 % , P = 0.30 ) or in-hospital mortality ( 50.0 % vs 34.2 % , P = 0.15 ) compared with those who were started on ARRT for AKIN Stage 3 . CONCLUSIONS Presence of traditional indications at ARRT initiation was associated with greater mortality . Initiating dialysis at earlier AKIN stage did not improve survival in patients without traditional indications BACKGROUND Acute kidney injury is the most frequent complication in patients with septic shock and is an independent risk factor for death . Although renal‐replacement therapy is the st and ard of care for severe acute kidney injury , the ideal time for initiation remains controversial . METHODS In a multicenter , r and omized , controlled trial , we assigned patients with early‐stage septic shock who had severe acute kidney injury at the failure stage of the risk , injury , failure , loss , and end‐stage kidney disease ( RIFLE ) classification system but without life‐threatening complications related to acute kidney injury to receive renal‐replacement therapy either within 12 hours after documentation of failure‐stage acute kidney injury ( early strategy ) or after a delay of 48 hours if renal recovery had not occurred ( delayed strategy ) . The failure stage of the RIFLE classification system is characterized by a serum creatinine level 3 times the baseline level ( or ≥4 mg per deciliter with a rapid increase of ≥0.5 mg per deciliter ) , urine output less than 0.3 ml per kilogram of body weight per hour for 24 hours or longer , or anuria for at least 12 hours . The primary outcome was death at 90 days . RESULTS The trial was stopped early for futility after the second planned interim analysis . A total of 488 patients underwent r and omization ; there were no significant between‐group differences in the characteristics at baseline . Among the 477 patients for whom follow‐up data at 90 days were available , 58 % of the patients in the early‐ strategy group ( 138 of 239 patients ) and 54 % in the delayed‐ strategy group ( 128 of 238 patients ) had died ( P=0.38 ) . In the delayed‐ strategy group , 38 % ( 93 patients ) did not receive renal‐replacement therapy . Criteria for emergency renal‐replacement therapy were met in 17 % of the patients in the delayed‐ strategy group ( 41 patients ) . CONCLUSIONS Among patients with septic shock who had severe acute kidney injury , there was no significant difference in overall mortality at 90 days between patients who were assigned to an early strategy for the initiation of renal‐replacement therapy and those who were assigned to a delayed strategy . ( Funded by the French Ministry of Health ; IDEAL‐ICU Clinical Trials.gov number , NCT01682590 . & NA ; Acute kidney injury ( AKI ) affects many ICU patients and is responsible for increased morbidity and mortality . Although lifesaving in many situations , renal replacement therapy ( RRT ) may be associated with complications , and the appropriate timing of its initiation is still the subject of intense debate . An early initiation strategy can prevent some metabolic complications , whereas a delayed one may allow for renal function recovery in some patients without need for this costly and potentially dangerous technique . For years , most of the knowledge on this issue stemmed from observational studies or small r and omized controlled trials . Recent r and omized controlled trials have indicated that a watchful waiting strategy ( in the absence of life‐threatening conditions such as severe hyperkalemia or pulmonary edema ) during severe AKI allowed many patients to escape RRT and did not seem to adversely affect survival compared with a strategy of immediate RRT . In addition , data suggest that a delayed strategy may reduce the rate of complications ( such as catheter infection ) and favor renal function recovery . Ongoing studies will have to both confirm these conclusions and clarify to what extent the delay in initiating RRT can be prolonged . Pending those results , the bulk of evidence suggests that , in the absence of potential severe complications of AKI , delaying RRT is a valid and safe strategy that may also allow for considerable cost savings |
10,766 | 28,667,204 | In the face of these results , administering or withholding steroids both appear reasonable courses of action | OBJECTIVES This review investigates the impact of corticosteroids on donation rates and transplant outcomes in light of findings from r and omised controlled trials ( RCTs ) and to highlight the sources of uncertainty in this unresolved donor management issue . | Objective To investigate the adrenocortical function in brain-dead patients , potential organ donors . Design Prospect i ve study . Setting Intensive care units in two teaching hospitals . Patients A total of 37 patients ( 28 men , nine women ) with severe brain injury , having a mean age of 42 ± 18 yrs , were included in the study . Group A consisted of 20 brain-injured patients who did not deteriorate to brain death . Group B included 17 brain-injured patients who were brain dead ; of these , ten patients developed brain death during ICU stay and seven patients were admitted to the ICU after clinical brain death . Interventions In all patients ( group A and group B ) , a morning blood sample was obtained at admission to the ICU to determine baseline plasma cortisol . Subsequently , 1 & mgr;g of corticotropin ( adrenocorticotropic hormone , Synacthen ) was administered intravenously , and a blood sample was taken 30 mins after the injection . In group B patients who became brain dead while being treated in the ICU ( n = 10 ) , the same procedure was repeated the morning after the confirmation of brain death . Patients having a cortisol level of at least 18 & mgr;g/dL after the administration of adrenocorticotropic hormone were defined as responders . Measurements and Main Results After the occurrence of brain death , group B patients had significantly lower values for baseline ( 8.5 ± 6.2 vs. 17.0 ± 6.6 & mgr;g/dL , p < .001 ) and stimulated ( 16.9 ± 6.3 vs. 23.9 ± 5.7 & mgr;g/dL , p = .001 ) plasma cortisol compared with group A patients . Thirteen group B patients ( 76 % ) and two group A patients ( 10 % ) were nonresponders to adrenocorticotropic hormone ( p < .001 ) . In group B patients , baseline and stimulated cortisol concentrations were significantly related ( r = .71 , p = .001 ) , whereas there was no correlation between baseline cortisol and the increment in cortisol ( r = −.37 , p = .15 ) . Mean hormonal data of the ten brain-dead patients studied at admission in the ICU and after the occurrence of brain death were the following : baseline plasma cortisol ( 23.5 ± 11.4 vs. 6.8 ± 4.2 & mgr;g/dL , p = .003 ) and stimulated serum cortisol ( 28.8 ± 9.9 vs. 16.3 ± 4.3 & mgr;g/dL , p = .008 ) . Conclusions Adrenal cortisol secretion after dynamic stimulation is deficient in a substantial proportion of brain-dead potential organ donors 34 cadaveric donor grafts were r and omized in a blind study of the effect of pretreatment of 5 g each of methylprednisolone and cyclophosphamide on kidney graft outcome . There was no difference in overall survival or functioning after 3 , 6 or 12 months between grafts from pretreated ( 33 kidneys ) or control ( 29 kidneys ) cadaveric donors . In addition , this pretreatment protocol did not modify the recipient immune response against B-lymphocyte alloantigens which developed in unsuccessful transplants . Our data , thus , neither confirm the high rate of kidney graft survival attributed to cadaveric donor treatment nor the supposition that treatment is effective in suppressing recipient antidonor B-lymphocyte antibodies BACKGROUND Posttransplantation acute renal failure ( ARF ) occurs in roughly 25 % of recipients of organs from deceased donors . Inflammation in the donor organ is associated with risk for ARF . OBJECTIVE To determine whether administering corticosteroids to deceased organ donors reduces the incidence and duration of ARF in organ recipients more than placebo . DESIGN Parallel , blocked r and omized trial , performed between February 2006 and November 2008 , with computer-generated r and omization and central ized allocation . Investigators were masked to group assignment . ( Controlled-trials.com registration number : IS RCT N78828338 ) SETTING : 3 renal transplantation centers in Austria and Hungary . PATIENTS 306 deceased heart-beating donors and 455 renal transplant recipients . INTERVENTIONS Organ donors were administered an intravenous infusion of either 1000 mg of methylprednisolone ( 136 donors ) or placebo ( 0.9 % saline ) ( 133 donors ) at least 3 hours before organ harvesting . MEASUREMENTS Incidence of ARF , defined as more than 1 dialysis session in the first week after transplantation , was the primary end point . Secondary and other end points included duration of ARF and trajectories of serum creatinine level . The suppression of immune response and inflammation by the intervention was assessed in the donor organ on a genome-wide basis . RESULTS 52 of 238 recipients ( 22 % ) of kidneys from steroid-treated donors and 54 of 217 recipients ( 25 % ) of kidneys from placebo-treated donors had ARF ( difference , 3 percentage points [ 95 % CI , -11 to 5 percentage points ] ) . One graft was lost on day 1 in each group , and 1 recipient in the placebo group died of cardiac arrest on day 2 . The median duration of ARF was 5 days ( interquartile range , 2 days ) in the steroid group and 4 days ( interquartile range , 2 days ) in the placebo group ( P = 0.31 ) . The groups had similar trajectories of serum creatinine level in the first week ( P = 0.72 ) . Genomic analysis showed suppressed inflammation and immune response in kidney biopsies from deceased donors who received corticosteroids . LIMITATION Donors and recipients were mainly white , and all were from 3 transplantation centers in central Europe , which may limit generalizability . CONCLUSION Systemic suppression of inflammation in deceased donors by corticosteroids did not reduce the incidence or duration of posttransplantation ARF in allograft recipients . PRIMARY FUNDING SOURCE Austrian Science Fund and Austrian Academy of Science OBJECTIVE To test the reliability and validity of specific instructions to classify blinding , when unclearly reported in r and omized trials , as " probably done " or " probably not done . " STUDY DESIGN AND SETTING We assessed blinding of patients , health care providers , data collectors , outcome adjudicators , and data analysts in 233 r and omized trials in duplicate and independently using detailed instructions . The response options were " definitely yes , " " probably yes , " " probably no , " and " definitely no. " We contacted authors for data verification ( 46 % response ) . For each of the five questions , we assessed reliability by calculating the agreement between the two review ers and validity by calculating the agreement between review ers ' consensus and verified data . RESULTS The percentage with unclear blinding status varied between 48.5 % ( patients ) and 84.1 % ( data analysts ) . Reliability was moderate for blinding of outcome adjudicators ( κ=0.52 ) and data analysts ( κ=0.42 ) and substantial for blinding of patients ( κ=0.71 ) , providers ( κ=0.68 ) , and data collectors ( κ=0.65 ) . The raw agreement between the consensus record and the author-verified record varied from 84.1 % ( blinding of data analysts ) to 100 % ( blinding of health care providers ) . CONCLUSION With the possible exception of blinding of data analysts , use of " probably yes " and " probably no " instead of " unclear " may enhance the assessment of blinding in trials AIMS The aim of this study was to assess the haemodynamic effects of tri-iodothyronine ( T3 ) and methylprednisolone in potential heart donors . METHODS AND RESULTS In a prospect i ve r and omized double-blind trial , 80 potential cardiac donors were allocated to receive T3 ( 0.8 microg kg(-1 ) bolus ; 0.113 microg kg(-1 ) h(-1 ) infusion ) ( n = 20 ) , methylprednisolone ( 1000 mg bolus ) ( n = 19 ) , both drugs ( n = 20 ) , or placebo ( n = 21 ) following initial haemodynamic assessment . After hormone or placebo administration , cardiac output-guided optimization was initiated , using vasopressin as a pressor and weaning norepinephrine and inotropes . Treatment was administered for 5.9 + /- 1.3 h until retrieval or end- assessment . Cardiac index increased significantly ( P < 0.001 ) but administration of T3 and methylprednisolone alone or in combination did not affect this change or the heart retrieval rate . Thirty-five per cent ( 14/40 ) of initially marginal or dysfunctional hearts were suitable for transplant at end- assessment . At end- assessment , 50 % of donor hearts fulfilled criteria for transplant suitability . CONCLUSION Cardiac output-directed donor optimization improves donor circulatory status and has potential to increase the retrieval rate of donor hearts . Tri-iodothyronine and methylprednisolone therapy do not appear to acutely affect cardiovascular function or yield 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 Introduction Circulatory failure during brain death organ donor resuscitation is a problem that compromises recovery of organs . Combined administration of steroid , thyroxine and vasopressin has been proposed to optimize the management of brain deceased donors before recovery of organs . However the single administration of hydrocortisone has not been rigorously evaluated in any trial . Methods In this prospect i ve multicenter cluster study , 259 subjects were included . Administration of low-dose steroids composed the steroid group ( n = 102 ) . Results Although there were more patients in the steroid group who received norepinephrine before brain death ( 80 % vs. 66 % : P = 0.03 ) , mean dose of vasopressor administered after brain death was significantly lower than in the control group ( 1.18 ± 0.92 mg/H vs. 1.49 ± 1.29 mg/H : P = 0.03 ) , duration of vasopressor support use was shorter ( 874 min vs. 1160 min : P < 0.0001 ) and norepinephrine weaning before aortic clamping was more frequent ( 33.8 % vs. 9.5 % : P < 0.0001 ) . Using a survival approach , probability of norepinephrine weaning was significantly different between the two groups ( P < 0.0001 ) with a probability of weaning 4.67 times higher in the steroid group than in the control group ( 95 % CI : 2.30 – 9.49 ) . Conclusions Despite no observed benefits of the steroid administration on primary function recovery of transplanted grafts , administration of glucocorticoids should be a part of the resuscitation management of deceased donors with hemodynamic instability BACKGROUND Lung transplantation activity is frustrated by donor lung availability . We sought to examine the effect of active donor management and hormone administration on pulmonary function and yield in cadaveric heart-beating potential lung donors . METHODS We studied 182 potential lung donors ( arterial oxygen tension [PaO2]/fractional inspired oxygen [ FIO2 ] ratio > or = 230 ) . From this group , 60 patients ( 120 lungs ) were allocated , within a r and omized trial , to receive methylprednisolone ( 1 g ) , triiodothyronine ( 0.8 microg/kg bolus and 0.113 microg/kg/h infusion ) , both methylprednisolone and triiodothyronine , or placebo as soon as feasible after consent and initial assessment . Trial donors underwent protocol -guided optimization of ventilation and hemodynamics , lung water assessment , and bronchoscopy . Function was assessed by PaO2/FIO2 ratio , extravascular lung water index ( EVLWI ) , and pulmonary vascular resistance ( PVR ) . A nontrial group of 122 donors ( 244 lungs ) received similar management without bronchoscopy , pulmonary artery flotation catheter monitoring , or lung water assessment . RESULTS Within the trial , management commenced within a median of 2 hours ( interquartile range , 0.5 to 3.5 hours ) of consent and continued for an average of 6.9 + /- 1.2 hours . The PaO2/FIO2 ratio deteriorated ( p = 0.028 ) from 397 + /- 78 ( 95 % CL , 376 to 417 ) to 359 + /- 126 ( 95 % CL , 328 to 390 ) and EVLWI from 9.7 + /- 4.5 mL/kg ( 95 % CL , 8.6 to 10.9 mL/kg ) to 10.8 + /- 5.2 mL/kg ( 95 % CL , 9.4 to 12.2 mL/kg ; p = 0.009 ) . PVR remained unchanged ( p = 0.28 ) . At end management , 48 of 120 trial lungs ( 40 % ) were transplanted versus 66 of 244 nontrial lungs ( 27 % ; p = 0.016 ) . Neither methylprednisolone and triiodothyronine nor T3 increased lung yield or affected PaO2/FIO2 or EVLWI ; however , methylprednisolone attenuated the increase in EVLWI ( p = 0.009 ) . CONCLUSIONS Early active management of lung donors increases yield . Steroid administration reduces progressive lung water accumulation OBJECTIVES The measurement of extravascular lung water could aid the assessment and guide the management of potential lung donors following brain death . We therefore sought to vali date a single indicator thermodilution extravascular lung water index ( EVLWI-T ) measurement using gravimetry and to assess the impact and clinical correlates of elevated EVLWI-T in potential lung donors and transplant recipients . METHODS In a prospect i ve study , we measured serial EVLWI-T and haemodynamic and oxygenation data in 60 potential lung donors . To vali date the EVLWI-T measurement , we measured in vivo thermodilution EVLWI ( EVLWI-T ) and gravimetric ex vivo EVLWI ( EVLWI-G ) in donor lungs rejected for transplant using the Holcroft and Trunkey modification of Pearce 's method . We assessed the clinical correlates of elevated lung water and measured interleukin-8 and hepatocyte growth factor in bronchoalveolar lavage ( BAL ) fluid . RESULTS The mean EVLWI-T ( n = 60 ) was 9.7 ( 4.5 ) ml kg(-1 ) , being > 7 - 10 ml kg(-1 ) in 23/60 and > 10 ml kg(-1 ) in 16/60 potential donors . Donor lungs with EVLWI > 10 ml kg(-1 ) were more likely to be receiving norepinephrine ( P = 0.04 ) , have higher pulmonary capillary wedge pressures ( P = 0.008 ) , be unsuitable for transplantation ( P = 0.007 ) and , if transplanted , have worse survival ( P = 0.04 ) . Lungs su bmi tted to gravimetric analysis [ n = 20 in 11 donors ( 9 double and 2 single ) ] had EVWLI-T of 10.8 ( 2.7 ) and EVLWI-G was 10.1 ( 2.5 ) . There was a strong correlation between EVLW-T and EVLW-G ( r = 0.7 ; P = 0.014 ) , but EVLWI-T over-predicted the EVLWI-G by ≈ 1 ml kg(-1 ) ( EVLW-T = 1.05 × EVLW-G ) . Cytokine levels in BAL fluid were elevated . CONCLUSIONS Elevated lung water is found in > 50 % of potential lung donors , predicts lung suitability for transplant and may adversely affect recipient outcome . Although EVLWI-T intrinsically overestimates gravimetric lung water , its measurement may aid the assessment of organ suitability . Lung water accumulation and the proinflammatory response may both be targets for modifying therapy Objective : To investigate potential beneficial effects of donor treatment with methylprednisolone on organ function and outcome after liver transplantation . Summary Background Data : It is proven experimentally and clinical ly that the brain death of the donor leads to increased levels of inflammatory cytokines and is followed by an intensified ischemia/reperfusion injury after organ transplantation . In experiments , donor treatment with steroids successfully diminished these effects and led to better organ function after transplantation . Methods : To investigate whether methylprednisolone treatment of the deceased donor is applicable to attenuate brain death-associated damage in clinical liver transplantation we conducted a prospect i ve r and omized treatment-versus-control study in 100 deceased donors . Donor treatment ( n = 50 ) consisted of 250 mg methylprednisolone at the time of consent for organ donation and a subsequent infusion of 100 mg/h until recovery of organs . A liver biopsy was taken immediately after laparotomy and blood sample s were obtained after brain death diagnosis and before organ recovery . Cytokines were assessed by real-time reverse transcriptase-polymerase chain reaction . Soluble serum cytokines were measured by cytometric bead array system . Results : After methylprednisolone treatment , steroid plasma levels were significantly higher ( P < 0.05 ) , and a significant decrease in soluble interleukins , monocyte chemotactic protein-1 , interleukin-2 , interleukin-6 , tumor necrosis factor-&agr ; , and inducible protein-10 was observed . Methylprednisolone treatment result ed in a significant downregulation of intercellular adhesion molecule-1 , tumor necrosis factor-&agr ; , major histocompatibility complex class II , Fas-lig and , inducible protein-10 , and CD68 intragraft mRNA expression . Significantly ameliorated ischemia/reperfusion injury in the posttransplant course was accompanied by a decreased incidence of acute rejection . Conclusions : Our present study verifies the protective effect of methylprednisolone treatment in deceased donor liver transplantation , suggesting it as a potential therapeutical approach Fifty cadaveric kidney donors were r and omly allocated to two groups . Group 1 received 5 grams of intravenously administered methylprednisolone two to four hours prior to organ harvesting after the pronouncement of brain death . Group 2 , which served as the control group , received no pretreatment . Of 100 kidneys harvested , 16 were discarded for various reasons , and 84 were transplanted and were available for evaluation , 40 from the pretreatment group and 44 from the control group . The transplant centers using these kidneys were unaware of the status of the kidney they received , that is , whether it was from a pretreated or a control group . The two groups of kidneys , pretreated and control , did not differ according to the length of warm or cold ischemia time or presence of preformed cytotoxic antibodies . The difference in graft failure between the two groups at three months was insignificant , even when the two groups were compared according to the method of preservation used Objective : Brain death induces dramatic changes in hemodynamics . Ischemic injury and inflammation result ing from inadequate resuscitation might influence organ yield for transplantation . Using functional hemodynamic monitoring in brain-dead organ donors , we test the hypothesis that donor preload ( fluid ) responsiveness is associated with increased inflammatory response and lower organ yield for transplantation . Design : Prospect i ve , observational , pilot study . Setting : A large intensive care unit of a university hospital in the United States . Patients : Twenty-one brain-dead organ donors between July 2006 and April 2007 . Interventions : None . Measurements and Main Results : Following declaration of brain death , we collected data on donor demographics , mechanism of brain death , and number of organs procured and transplanted . Functional hemodynamics were monitored using pulse contour analysis technique . Plasma tumor necrosis factor , interleukin-6 , and interleukin-10 concentrations were measured at study enrollment , after 4 hrs , and immediately before organ procurement for transplantation . Preload responsiveness ( pulse pressure variation > 13 % ) was observed in 48 % of donors ( mean ± sd pulse pressure variation , 19.2 % ± 4.8 % ) . Plasma interleukin-6 and tumor necrosis factor concentrations at study enrollment were greater in preload responsive donors : mean concentrations of interleukin-6 in preload responsive vs. unresponsive donors were 5420 ± 9102 vs. 378 ± 631 pg/mL ( p = .009 ) , and mean concentrations of tumor necrosis factor were 60.5 ± 103.6 vs. 15.7 ± 10.1 pg/mL ( p = .048 ) . Preload responsive compared with unresponsive donors had significantly increased interleukin-6 ( p = .013 ) and tumor necrosis factor ( p = .044 ) concentrations over time . Fewer organs were transplanted from preload responsive donors : mean organs transplanted from preload responsive vs. unresponsive donors were 1.8 ± 0.9 vs. 3.7 ± 2.5 ( p = .034 ) . In multivariable regression , older donor age ( p = .028 ) and increased plasma interleukin-6 concentration ( p = .035 ) were significantly associated with lower number of organs transplanted . Conclusions : Preload responsiveness is common in brain-dead organ donors and is associated with higher inflammatory response and lower organ yield . A controlled trial of preload optimization is warranted in brain-dead donors 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 SUMMARY In a r and omized study we have been unable to demonstrate any beneficial effect of cadaver donor pretreatment with 5 g of methylprednisolone and 7 g of cyclophosphamide on graft function or survival in 22 recipients of pretreated kidneys compared with 30 recipients of nonpretreated kidneys Background & Aims Brain death-associated inflammatory response contributes to increased risk of impaired early liver allograft function , which might be counterbalanced by steroid pretreatment of the organ donor . The aim of this r and omized controlled trial was to eluci date whether steroid pretreatment of liver donors improves early liver allograft function , prevents rejection and prolongs survival . Methods A placebo-controlled blinded r and omized clinical trial was performed in three different centers in Austria and Hungary between 2006 and 2008 . Ninety deceased organ donors received either 1000 mg of methylprednisolone or placebo 6 h before recovery of organs . The primary end point was the concentration slope of transaminases within the first week . The secondary end point included survival and biopsy-confirmed acute rejection ( BCAR ) within 3 years after transplantation . Results Of the 90 r and omized donors , 83 recipients were eligible for study . The trajectories of ALT and AST were not different between treatments ( p = 0.40 and p = 0.13 , respectively ) . Eight subjects died in the steroid and 13 in the placebo group within 3 years after engraftment ( RR = 0.63 95 % CI [ 0.29 , 1.36 ] , p = 0.31 ) . Eleven recipients experienced biopsy-confirmed rejection ( BCAR ) in the steroid and 11 in the placebo group ( RR = 1.02 95 % CI [ 0.50 , 2.10 ] , p = 1.00 ) . No effect modification could be identified in the predefined strata of donor age , sex , cold ischemic time , and cause of donor death . Conclusions Steroid pretreatment of organ donors did not improve outcomes after liver transplantation |
10,767 | 29,243,086 | The majority of studies failed to demonstrate an association between observed aspiration and oxygen desaturation .
Current evidence does not support the use of pulse oximetry to detect aspiration | Pulse oximetry is a commonly used means to measure peripheral capillary oxyhemoglobin saturation ( SpO2 ) .
Potential use of pulse oximetry to detect aspiration is attractive to clinicians , as it is readily available , quick , and noninvasive .
However , research regarding validity has been mixed .
This systematic review examining evidence on the use of pulse oximetry to detect a decrease in SpO2 indicating aspiration during swallowing is undertaken to further inform clinical practice in dysphagia assessment . | Abstract . Objective : Pulse oximetry ( SpO2 ) is a st and ard monitoring device in intensive care units ( ICUs ) , currently used to guide therapeutic interventions . Few studies have evaluated the accuracy of SpO2 in critically ill patients . Our objective was to compare pulse oximetry with arterial oxygen saturation ( SaO2 ) in such patients , and to examine the effect of several factors on this relationship . Design : Observational prospect i ve study . Setting : A 26-bed medical ICU in a university hospital . Patients : One hundred two consecutive patients admitted to the ICU in whom one or serial arterial blood gas analyses ( ABGs ) were performed and a reliable pulse oximeter signal was present . Interventions : For each ABG , we collected SaO2 , SpO2 , the type of pulse oximeter , the mode of ventilation and requirement for vasoactive drugs . Measurements and results : Three hundred twenty-three data points were collected . The mean difference between SpO2 and SaO2 was –0.02 % and st and ard deviation of the differences was 2.1 % . From one sample to another , the fluctuations in SpO2 to arterial saturation difference indicated that SaO2 could not be reliably predicted from SpO2 after a single ABG . Subgroup analysis showed that the accuracy of SpO2 appeared to be influenced by the type of oximeter , the presence of hypoxemia and the requirement for vasoactive drugs . Finally , high SpO2 thresholds were necessary to detect significant hypoxemia with good sensitivity . Conclusion : Large SpO2 to SaO2 differences may occur in critically ill patients with poor reproducibility of SpO2 . A SpO2 above 94 % appears necessary to ensure a SaO2 of 90 % Bolus manipulation is a primary treatment strategy in the management of oral-pharyngeal dysphagia . The use of thickening agents to alter bolus rheology is particularly commonplace ; however , the precise effects of these alterations on swallowing remain uncertain . The purpose of our study , a prospect i ve , double-blind clinical trial ( Level 1b ) , was to investigate the effects of viscosity on aspiration . One hundred patients with dysphagia were prospect ively evaluated with fluoroscopic swallow studies performed across three st and ardized and r and omized conditions : thin liquid barium ( THIN ) , liquid barium thickened with a starch-based agent ( STARCH ) , and liquid barium thickened with a gum-based agent ( GUM ) . Outcome measures included the prevalence of aspiration and score on the Penetration-Aspiration Scale . A total of 23 out of 100 patients exhibited 56 episodes of aspiration . Twenty patients aspirated on THIN , 15 on STARCH , and 11 on GUM bolus conditions ( P<0.05 , thin vs gum ) . There were 28 instances of aspiration on THIN , 16 on STARCH , and 12 on GUM . Mean Penetration-Aspiration Scale score ± st and ard deviation was 2.11 ± 2.22 for THIN , 1.76 ± 1.88 for STARCH , and 1.42 ± 1.47 for GUM conditions , respectively ( P<0.001 , THIN vs GUM ) . A clinical ly significant reduction in the incidence of penetration and aspiration was observed for gum-thickened barium compared with thin liquid barium BACKGROUND AND PURPOSE The aim of the present study was to examine the value of pulse oximetry in the diagnosis of aspiration by comparing it with the gold st and ard , videofluoroscopy , by use of a prospect i ve , controlled , single-blind study design . METHODS Pulse oximetry was performed simultaneously with videofluoroscopy in 54 consecutive dysphagic stroke patients . Oxygen saturation measurements were taken before the video-fluoroscopic examination ( baseline ) , on swallowing and continuously for 2 minutes after swallowing , and 10 minutes later . RESULTS Pulse oximetry reliably predicted aspiration or lack of it in 81.5 % of cases . The predictive value of the test was low in patients aged > or = 65 years and possibly those with chronic lung disease . One smoker also had a false-negative pulse oximetry result , ie , normal oxygen saturation despite radiological evidence of aspiration . CONCLUSIONS Pulse oximetry is a reliable method of diagnosis of aspiration in most dysphagic patients . However , careful interpretation of pulse oximetry data is necessary in older subjects , possibly those with chronic pulmonary disease , and smokers . The method is noninvasive , simple , and quick , and can be used routinely in the clinical assessment of dysphagic patients Increasing bolus viscosity of thin liquids is a basic therapeutic strategy to protect patients with oropharyngeal dysphagia ( OD ) from aspiration . However , conventional starch thickeners increase post‐deglutitive residue OBJECTIVE To examine the reliability of pulse oximetry for identifying aspiration by comparing it with the videofluoroscopic swallowing study ( VFSS ) . DESIGN Nonr and omized , prospect i ve , double-blind study . SETTING VFSS laboratory in a teaching hospital . PARTICIPANTS Sixty patients from among 130 patients with clinical ly diagnosed dysphagia between September and December 2002 . INTERVENTIONS Not applicable . MAIN OUTCOME MEASURES Simultaneously monitoring the arterial oxygen saturation ( Sp o 2 ) by pulse oximetry while patients were performing VFSS . A decrease in Sp o 2 exceeding 3 % was considered as significant desaturation . Bolus or portion of bolus passing through the vocal cords and entering the subglottic space was defined as aspiration on VFSS . The results of pulse oximetry and VFSS were compared . RESULTS No significant correlation existed between desaturation measured by pulse oximetry and aspiration on VFSS ( chi 2 test , P = .87 ) . The positive predictive rate of pulse oximetry in detecting aspiration on VFSS was 39.1 % , and the negative predictive rate was 59.4 % . CONCLUSIONS Aspiration occurring on VFSS can not be predicted based on decrease in Sp o 2 in pulse oximetry . The application of pulse oximetry to detect aspiration during regular meals requires further investigation |
10,768 | 29,502,328 | Conclusion This meta- analysis adds further evidence to the clinical ly significant larger increase in peak oxygen uptake following aerobic interval training vs. aerobic continuous training in patients with coronary artery disease and chronic heart failure . | Background In a previous meta- analysis including nine trials comparing aerobic interval training with aerobic continuous training in patients with coronary artery disease , we found a significant difference in peak oxygen uptake favoring aerobic interval training .
Objective The objective of this study was to ( 1 ) up date the original meta- analysis focussing on peak oxygen uptake and ( 2 ) evaluate the effect on secondary outcomes . | OBJECTIVES Peak oxygen uptake ( VO2 peak ) increases more after high intensity interval training compared to isocaloric moderate exercise in patients with coronary heart disease ( CHD ) . We assessed the impact of exercise intensity during high intensity intervals on the increase in VO2 peak . DESIGN / METHODS We included 112 patients with coronary heart disease who had participated in r and omized trials of interval training consisting of four times four minutes intervals at 85 - 95 % of heart rate maximum ( HRmax ) for 12 weeks . Exercise intensity was calculated for each patient using HR during the two last minutes of each interval , expressed as percentage of HRmax . We used a univariate general linear model with VO2 peak increase as the dependent variable and percentage of HRmax , age , number of exercise sessions , and baseline VO2 peak as covariates . Exercise intensity was also divided into three categories ; < 88 % , 88 - 92 % , and > 92 % of HRmax , and these categories were used as a fixed factor in the model . RESULTS VO2 peak increased by 3.9 ( SD 3.1 ) mL kg(-1)min(-1 ) , equal to 11.9 % after 23.4 exercise sessions . Percentage of HRmax had a significant effect on increase in VO2 peak , both as a continuous ( p=0.019 ) and categorical variable ( p=0.020 ) . The estimated marginal means and 95 % confidence intervals of the increase in VO2 peak for the three intensity categories were 3.1 ( 2.0 , 4.2 ) , 3.6 ( 2.8 , 4.4 ) , and 5.2 ( 4.1 , 6.3 ) for the < 88 % , the 88 - 92 % , and the > 92 % category , respectively . CONCLUSIONS Even within the high intensity training zone , exercise intensity was an important determinant for improving VO2 peak in patients with coronary heart disease The oxygen uptake efficiency slope ( OUES ) is a submaximal index incorporating cardiovascular , peripheral , and pulmonary factors that determine the ventilatory response to exercise . The purpose of this study was to evaluate the effects of continuous exercise training and interval exercise training on the OUES in patients with coronary artery disease . Thirty-five patients ( 59.3±1.8 years old ; 28 men , 7 women ) with coronary artery disease were r and omly divided into two groups : continuous exercise training ( n=18 ) and interval exercise training ( n=17 ) . All patients performed grade d exercise tests with respiratory gas analysis before and 3 months after the exercise-training program to determine ventilatory anaerobic threshold ( VAT ) , respiratory compensation point , and peak oxygen consumption ( peak VO2 ) . The OUES was assessed based on data from the second minute of exercise until exhaustion by calculating the slope of the linear relation between oxygen uptake and the logarithm of total ventilation . After the interventions , both groups showed increased aerobic fitness ( P<0.05 ) . In addition , both the continuous exercise and interval exercise training groups demonstrated an increase in OUES ( P<0.05 ) . Significant associations were observed in both groups : 1 ) continuous exercise training ( OUES and peak VO2 r=0.57 ; OUES and VO2 VAT r=0.57 ) ; 2 ) interval exercise training ( OUES and peak VO2 r=0.80 ; OUES and VO2 VAT r=0.67 ) . Continuous and interval exercise training result ed in a similar increase in OUES among patients with coronary artery disease . These findings suggest that improvements in OUES among CAD patients after aerobic exercise training may be dependent on peripheral and central mechanisms 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 Background Heart rate recovery ( HRR1 ) immediately after exercise reflects parasympathetic activity , which is markedly attenuated in chronic heart failure ( CHF ) patients . The aim of our study was to examine both continuous and interval exercise training effects on HRR1 in these patients . Design The population study consisted of 29 stable CHF patients that participated at a rehabilitation program of 36 sessions , three times per week . Of the 29 patients , 24 completed the program . Patients were r and omly assigned to interval { n = 10 [ 100 % peak work rate ( WRp ) for 30 s , alternating with rest for 30 s ] } and to continuous training [ n = 14 ( 50%WRp ) ] . Methods All patients performed a symptom-limited cardiopulmonary exercise test on a cycle ergometer before and after the completion of the program . Measurements included peak oxygen uptake ( VO2p ) , anaerobic threshold ( AT ) , WRp , first degree slope of VO2 during the first minute of recovery ( VO2/t-slope ) , chronotropic response [ % chronotropic reserve ( CR ) = ( peak HR - resting HR ) × 100/(220 - age - resting HR ) ] , HRR1 ( HR difference from peak exercise to one minute after ) . Results After the completion of the rehabilitation program there was a significant increase of WRp , VO2p , AT and VO2/t-slope ( by 30 % , P=0.01 ; 6 % , P=0.01 ; 10 % , P=0.02 ; and 27 % , P=0.03 respectively for continuous training and by 21 % , P≤0.05 ; 8 % , P=0.01 ; 6 % , P = NS ; and 48 % , P=0.02 respectively for interval training ) . However , only patients exercised under the continuous training regime had a significant increase in HRR1 ( 15.0±9.0 to 24.0±12bpm ; P=0.02 ) and CR ( 57±19 to 72±21 % , P=0.02 ) , in contrast with those assigned to interval training ( HRR1 : 21 ± 11 to 21 ± 8 bpm ; P = NS and CR : 57 ± 18 to 59 ± 21 % , P = NS ) . Conclusions Both continuous and interval exercise training program improves exercise capacity in CHF patients . However , continuous rather than interval exercise training improves early HRR1 , a marker of parasympathetic activity , suggesting a greater contribution to the autonomic nervous system Objective . To study the effect of aerobic treadmill exercise training with different intensity on left ventricular ( LV ) function in patients with stable coronary artery disease , using Strain Rate- and Tissue Doppler Imaging . Design . Seventeen patients were r and omly assigned to either moderate ( 50–60 % of peak oxygen uptake ( VO2peak ) ) or high intensity exercise ( 80–90 % of VO2peak ) for 10 weeks . Results . The increase of VO2peak was significantly higher ( p=0.01 ) in the high intensity group ( 17 vs. 8 % ) . Mean LV early diastolic strain rate increased in the high , but not in the moderate , intensity group . For systolic strain rate or mitral annular velocities there were no change after training in either group . Conclusions . Aerobic treadmill exercise improves early diastolic relaxation in patients with stable coronary artery disease , measured by the mean LV early diastolic strain rate BACKGROUND Peak oxygen uptake ( Vo(2peak ) ) strongly predicts mortality in cardiac patients . We compared the effects of aerobic interval training ( AIT ) versus moderate continuous training ( MCT ) on Vo(2peak ) and quality of life after coronary artery bypass grafting ( CABG ) . METHODS Fifty-nine CABG patients were r and omized to either AIT at 90 % of maximum heart rate or MCT at 70 % of maximum heart rate , 5 d/wk , for 4 weeks at a rehabilitation center . Primary outcome was Vo(2peak ) , at baseline , after rehabilitation ( 4 weeks ) , and after 6 months of home-based exercise ( 6 months ) . RESULTS Vo(2peak ) increased between baseline and 4 weeks in AIT ( 27.1 + /- 4.5 vs 30.4 + /- 5.5 mL.kg(-1).min(-1 ) , P < .001 ) and MCT ( 26.2 + /- 5.2 vs 28.5 + /- 5.6 mL.kg(-1).min(-1 ) , P < .001 ; group difference , not significant ) . Aerobic interval training increased Vo(2peak ) between 4 weeks and 6 months ( 30.4 + /- 5.5 vs 32.2 + /- 7.0 mL.kg(-1).min(-1 ) , P < .001 ) , with no significant change in MCT ( 28.5 + /- 5.6 vs 29.5 + /- 5.7 mL.kg(-1).min(-1 ) ) . Quality of life improved in both groups from baseline to 4 weeks , remaining improved at 6 months . There were no changes in echocardiographic systolic and diastolic left ventricular function . Adiponectin increased between 4 weeks and 6 months in both groups ( group differences , not significant ) . CONCLUSIONS Four weeks of intense training increased Vo(2peak ) significantly after both AIT and MCT . Six months later , the AIT group had a significantly higher Vo(2peak ) than MCT . The results indicate that AIT and MCT increase Vo(2peak ) similarly in the short term , but with better long-term effect of AIT after CABG We found that interval training provides an effective means to improve the cardiovascular fitness and health status of highly functional patients with coronary artery disease . We also revealed that interval training improves anaerobic tolerance to a greater extent than the traditional exercise training model without increasing the risk to the patient . This research supports the implementation of interval training for highly functional patients with coronary artery disease Introduction : Several established tools are available to assess study quality and reporting of r and omized controlled trials ; however , these tools were design ed with clinical intervention trials in mind . In exercise training intervention trials some of the traditional study quality criteria , such as participant or research er blinding , are extremely difficult to implement . Methods : We developed the Tool for the assEssment of Study qualiTy and reporting in EXercise ( TESTEX ) – a study quality and reporting assessment tool , design ed specifically for use in exercise training studies . Our tool is a 15-point scale ( 5 points for study quality and 10 points for reporting ) and addresses previously unmentioned quality assessment criteria specific to exercise training studies . Results : There were no systematic differences between the summated TESTEX scores of each observer [ H(2 ) = 0.392 , P = 0.822 ] . There was a significant association between the summated TESTEX scores of the three observers , with almost perfect agreement between observers 1 and 2 [ intra-class correlation coefficient ( ICC ) = 0.93 , 95 % confidence interval ( CI ) 0.82–0.97 , P < 0.001 ] , observers 1 and 3 ( ICC = 0.96 , 95 % CI 0.89–0.98 , P < 0.001 ) and observers 2 and 3 ( ICC = 0.91 , 95 % CI 0.75–0.96 , P < 0.001 ) . Conclusions : The TESTEX scale is a new , reliable tool , specific to exercise scientists , that facilitates a comprehensive review of exercise training trials Background : Small studies have suggested that high-intensity interval training ( HIIT ) is superior to moderate continuous training ( MCT ) in reversing cardiac remodeling and increasing aerobic capacity in patients with heart failure with reduced ejection fraction . The present multicenter trial compared 12 weeks of supervised interventions of HIIT , MCT , or a recommendation of regular exercise ( RRE ) . Methods : Two hundred sixty-one patients with left ventricular ejection fraction ⩽35 % and New York Heart Association class II to III were r and omly assigned to HIIT at 90 % to 95 % of maximal heart rate , MCT at 60 % to 70 % of maximal heart rate , or RRE . Thereafter , patients were encouraged to continue exercising on their own . Clinical assessment s were performed at baseline , after the intervention , and at follow-up after 52 weeks . Primary end point was a between-group comparison of change in left ventricular end-diastolic diameter from baseline to 12 weeks . Results : Groups did not differ in age ( median , 60 years ) , sex ( 19 % women ) , ischemic pathogenesis ( 59 % ) , or medication . Change in left ventricular end-diastolic diameter from baseline to 12 weeks was not different between HIIT and MCT ( P=0.45 ) ; left ventricular end-diastolic diameter changes compared with RRE were −2.8 mm ( −5.2 to −0.4 mm ; P=0.02 ) in HIIT and −1.2 mm ( −3.6 to 1.2 mm ; P=0.34 ) in MCT . There was also no difference between HIIT and MCT in peak oxygen uptake ( P=0.70 ) , but both were superior to RRE . However , none of these changes was maintained at follow-up after 52 weeks . Serious adverse events were not statistically different during supervised intervention or at follow-up at 52 weeks ( HIIT , 39 % ; MCT , 25 % ; RRE , 34 % ; P=0.16 ) . Training records showed that 51 % of patients exercised below prescribed target during supervised HIIT and 80 % above target in MCT . Conclusions : HIIT was not superior to MCT in changing left ventricular remodeling or aerobic capacity , and its feasibility remains unresolved in patients with heart failure . Clinical Trial Registration : URL : http://www . clinical trials.gov . Unique identifier : NCT00917046 Objective : It is unclear which exercise training protocol yields superior heart rate recovery ( HRR ) improvement in heart failure ( HF ) patients . Whether baseline HRR normality plays a role in the improvement is unknown . We hypothesized that an exercise training protocol and baseline HRR normality would be factors in altering HRR in HF patients . Methods : In this prospect i ve , r and omized , controlled and 3 group parallel study , 41 stable HF patients were r and omly assigned to 3-times-weekly training sessions for 12 weeks , consisting of i ) 30 minutes of interval training ( IT ) ( n=17 , 63.7±8.8 years old ) versus ii ) 30 minutes of continuous training ( CT ) ( n=13 , 59.6±6.8 years old ) versus iii ) no training ( CON ) ( n=11 , 60.6±9.9 years old ) . Each patient had cardiopulmonary exercise testing before and after the training program . Maximum heart rates attained during the test and heart rates at 1 and 2 min ( HRR1 and HRR2 ) during the recovery phase were recorded . Paired sample s t-test or Wilcoxon signed-rank test was used for comparisons before and after training . One-way ANOVA or Kruskal-Wallis variance analysis was used for comparisons among groups . Results : HRR1 was unchanged after training . HRR2 improved in the IT group after training , and post-training HRR2 values were significantly faster in the IT group than in controls . Both HRR1 and HRR2 was significantly faster , irrespective of exercise protocol in patients with abnormal baseline values after training . Conclusion : HRR1 did not improve after training . HRR2 improved only in the IT group . Both HRRs in patients with abnormal baseline values improved after both exercise protocol s. IT might be superior to CT in improving HRR2 . Baseline HRR might play a role in its response to exercise Objective Peak oxygen uptake ( VO2peak ) is a strong predictor of survival in cardiac patients . The aims of this study were to compare the effects of high interval training ( HIT ) to moderate continuous training ( MCT ) on VO2peak and to identify the safety of HIT in acute myocardial infa rct ion patients with drug-eluting stent . Design Twenty-eight acute myocardial infa rct ion patients with drug-eluting stent were r and omized to either HIT at 85%–95 % of heart rate reserve or MCT at 70%–85 % of heart rate reserve , 3 days a week for 6 wks at a cardiac rehabilitation clinic . Primary outcome was VO2peak at baseline and after cardiac rehabilitation . Results Both HIT and MCT groups showed significant increases in VO2peak and heart rate recovery after 6 wks of training . The 22.16 % improvement in VO2peak in the HIT group was significantly greater than the 8.48 % improvement in the MCT group ( P = 0.021 ) . There were no cardiovascular events related to both HIT and MCT . Conclusions HIT is more effective than MCT for improving VO2peak in acute myocardial infa rct ion patients with drug-eluting stent . These findings may have important implication s for more effective exercise training in cardiac rehabilitation program The aim of the present study was to investigate effects of aerobic interval training ( AIT ) versus moderate continuous training ( MCT ) on coronary atherosclerosis in patients with significant coronary artery disease on optimal medical treatment . Thirty-six patients were r and omized to AIT ( intervals at ≈ 90 % of peak heart rate ) or MCT ( continuous exercise at ≈ 70 % of peak heart rate ) 3 times a week for 12 weeks after intracoronary stent implantation . Grayscale and radiofrequency intravascular ultrasounds ( IVUS ) were performed at baseline and follow-up . The primary end point was the change in plaque burden , and the secondary end points were change in necrotic core and plaque vulnerability . Separate lesions were classified using radiofrequency IVUS criteria . We demonstrated that necrotic core was reduced in both groups in defined coronary segments ( AIT -3.2 % , MCT -2.7 % , p < 0.05 ) and in separate lesions ( median change -2.3 % and -0.15 mm(3 ) , p < 0.05 ) . Plaque burden was reduced by 10.7 % in separate lesions independent of intervention group ( p = 0.06 ) . No significant differences in IVUS parameters were found between exercise groups . A minority of separate lesions were transformed in terms of plaque vulnerability during follow-up with large individual differences between and within patients . In conclusion , changes in coronary artery plaque structure or morphology did not differ between patients who underwent AIT or MCT . The combination of regular aerobic exercise and optimal medical treatment for 12 weeks induced a moderate regression of necrotic core and plaque burden in IVUS-defined coronary lesions Background . We tested the hypothesis that high intensity interval training ( HIIT ) would be more effective than moderate intensity continuous training ( MIT ) to improve newly emerged markers of cardiorespiratory fitness in coronary heart disease ( CHD ) patients , as the relationship between ventilation and carbon dioxide production ( VE/VCO2 slope ) , oxygen uptake efficiency slope ( OUES ) , and oxygen pulse ( O2P ) . Methods . Seventy-one patients with optimized treatment were r and omly assigned into HIIT ( n = 23 , age = 56 ± 12 years ) , MIT ( n = 24 , age = 62 ± 12 years ) , or nonexercise control group ( CG ) ( n = 24 , age = 64 ± 12 years ) . MIT performed 30 min of continuous aerobic exercise at 70–75 % of maximal heart rate ( HRmax ) , and HIIT performed 30 min sessions split in 2 min alternate bouts at 60%/90 % HRmax ( 3 times/week for 16 weeks ) . Results . No differences among groups ( before versus after ) were found for VE/VCO2 slope or OUES ( P > 0.05 ) . After training the O2P slope increased in HIIT ( 22 % , P < 0.05 ) but not in MIT ( 2 % , P > 0.05 ) , while decreased in CG ( −20 % , P < 0.05 ) becoming lower versus HIIT ( P = 0.03 ) . Conclusion . HIIT was more effective than MIT for improving O2P slope in CHD patients , while VE/VCO2 slope and OUES were similarly improved by aerobic training regimens versus controls BACKGROUND Exercise prescription in cardiac patients is based on heart rate ( HR ) response to exercise . How to prescribe long-term exercise training outside medically-supervised setting s also considering changes in individual physical capacity over time is unknown . In this study we hypothesized that in patients with chronic heart failure ( CHF ) the session-rate of perceived exertion ( RPE ) , a subjective-based training methodology , provides autonomic and functional capacity changes superimposable to those observed with HR-based Training Impulses ( TRIMPi ) method . METHODS Twenty patients with stable CHF were r and omized to either aerobic continuous training ( ACT ) or aerobic interval training ( AIT ) for 12 weeks . For each TRIMPi-guided exercise session , the session-RPE was recorded . By this method , internal training load ( TL ) is quantified by multiplying the RPE of the whole training session , using the Borg CR10-scale , by its duration . Heart rate variability ( HRV ) , and baroreflex sensitivity ( BRS ) were assessed at baseline and at 3 weeks intervals . RESULTS Significant correlations were found between TRIMPi and individual session-RPE , for both ACT and AIT ( r=0.63 to 0.81 ) , ( P<0.05 ) . The same occurred when ACT and AIT groups were pooled together ( r=0.72 ; P<0.01 ) . R-R interval , HRV and BRS were significantly and very highly correlated with weekly RPE-session ( r(2 ) ranged from 0.77 to 0.97 ; P<0.001 ) . A significant relationship between session-RPE and performance at the 6MWT was also found . CONCLUSIONS Session-RPE is an easy-to-use , inexpensive and valid method for exercise prescription and health maintenance , consistent with objective physiological indices of training , that could be used for long-term physical activity in patients with CHF OBJECTIVES The health benefits of high-intensity interval training in cardiac rehabilitation warrant further research . We compared the effectiveness of low-volume high-intensity interval training vs continuous aerobic exercise training in chronic heart failure . DESIGN / SETTING S Unblinded , two arm parallel design with r and om assignment to exercise interventions in out-patient hospital rehabilitation gym . METHODS Patients with signs of chronic heart failure and ejection fraction < 45 % , ( mean age : 59.1 years ( st and ard deviation ( SD ) 8.6 ) ; 3 women ) completed 6 months of exercise using continuous aerobic exercise training ( n = 9 ) or high-intensity interval training ( n = 8) . Cardiorespiratory fitness was determined during cycle ergometry using respiratory gas exchange analysis . Functional capacity was assessed via sit-to-st and and gait speed . Quality of life was assessed using the MOS Short-Form 36 and Minnesota living with heart failure question naires . Cardiac autonomic regulation was assessed using Heart Rate Variability . RESULTS Analysis of Covariance revealed significant time effects but no group × time interactions for exercise and functional capacity outcomes . Peak oxygen uptake ( VO2peak ) improved by a mean of 14.9 % ( SD 16.3 % ) from baseline and by 22 % ( SD 28.3 ) at ventilatory threshold in both groups . Sit-to-st and ( 11.9 ( SD 11 % ) ) and gait speed ( 16.0 ( SD 19 % ) ) improved similarly in both groups . No changes in quality of life or heart rate variability were noted . Training adaptations in high-intensity interval training were achieved despite a significantly reduced time commitment and total work volume compared to continuous aerobic exercise training . CONCLUSION Low-volume high-intensity interval training is a feasible and well tolerated training modality in cardiac rehabilitation setting s , but is not more effective than continuous aerobic exercise training PURPOSE Isocaloric interval exercise training programs have been shown to elicit improvements in numerous physiological indices in patients with CAD . Low-volume high-intensity interval exercise training ( HIT ) is effective in healthy population s ; however , its effectiveness in cardiac rehabilitation has not been established . This study compared the effects of 12-wk of HIT and higher-volume moderate-intensity endurance exercise ( END ) on brachial artery flow-mediated dilation ( FMD ) and cardiorespiratory fitness ( VO2 peak ) in patients with CAD . METHODS Twenty-two patients with documented CAD were r and omized into HIT ( n = 11 ) or END ( n = 11 ) based on pretraining FMD . Both groups attended two supervised sessions per week for 12 wk . END performed 30 - 50 min of continuous cycling at 58 % peak power output ( PPO ) , whereas HIT performed ten 1-min intervals at 89 % PPO separated by 1-min intervals at 10 % PPO per session . RESULTS Relative FMD was increased posttraining ( END , 4.4 % ± 2.6 % vs 5.9 % ± 3.6 % ; HIT , 4.6 % ± 3.6 % vs 6.1 % ± 3.4 % , P ≤ 0.001 pre- vs posttraining ) with no differences between groups . A training effect was also observed for relative VO2 peak ( END , 18.7 ± 5.7 vs 22.3 ± 6.1 mL · kg(-1 ) · min(-1 ) ; HIT , 19.8 ± 3.7 vs 24.5 ± 4.5 mL · kg(-1 ) · min(-1 ) , P < 0.001 for pre- vs posttraining ) , with no group differences . CONCLUSIONS Low-volume HIT provides an alternative to the current , more time-intensive prescription for cardiac rehabilitation . HIT elicited similar improvements in fitness and FMD as END , despite differences in exercise duration and intensity In patients with chronic heart failure ( CHF ) blood pressure ( BP ) control , represents a relevant target of management . This study evaluated the effect of different intensities exercise training on 24-h ambulatory BP profile and insulin resistance in patients with CHF . Thirty-six CHF patients with left ventricular ejection fraction < 40 % , were r and omized to high-intensity interval training ( HIT ) or moderate continuous training ( MIT ) for 12 weeks . HIT consisted in treadmill exercise at ~75–80 % of heart rate reserve ( HRR ) , alternated with active pauses at 45–50 % of HRR . MIT consisted in continuous treadmill at ~45–60 % of HRR . Peak VO2 and anaerobic threshold increased significantly with both HIT and MIT , without significant differences between the two training programs . 24-h , systolic and diastolic BP decreased with both HIT and MIT . The same occurred for day-time and night-time systolic and diastolic BP . The decrease in day-time diastolic BP was slightly but significantly greater in HIT . Both HIT and MIT induced a significant decrease in fasting glucose and insulin , whereas HOMA-IR decreased significantly only after HIT . In patients with CHF exercise training reduces BP throughout the day , without substantial differences between moderate and more vigorous exercise intensity , with a small exception for day-time diastolic BP . HIT was more effective in improving insulin resistance The authors compared the effects of continuous ( CON ) and intermittent ( INT ) exercise training programs on functional capacity , quality of life ( QOL ) , and cardiac function in 23 congestive heart failure patients . Patients were r and omized to CON exercise training ( n=13 ; aged 66±7 years ; peak oxygen consumption [ VO(2 ) ] , 12.4±2.5 mL/kg/min ; weight , 83±12 kg ; left ventricular ejection fraction [ LVEF ] , 29.5%±7.2 % ) or INT exercise training ( n=10 ; aged 59±11 years ; VO(2 ) , 12.2±6.5 mL/kg/min ; weight , 87±24 kg ; LVEF 27%±7.9 % ) . These groups completed 16 weeks of stationary cycling at 70 % VO(2 ) thrice weekly for 30 minutes continuously or 60 minutes ( 60 seconds work:60 seconds rest ) intermittently ; both groups completed the same absolute volume of work . Three QOL question naire responses , VO(2 ) , LVEF , and regional tissue Doppler were quantified . After exercise training , VO(2 ) increased by 13 % in the CON group ( P=.12 ) and significantly by 21 % in the INT group ( P=.03 ) , although not significantly between the groups ( P=.72 ) . In the CON group , Minnesota Living With Heart Failure score improved at 16 weeks ( P=.02 ) , while in the INT group , Hare-Davis scores improved ( P=.02 ) . Cardiac volumes , resting and peak LVEF , contractile reserve , and tissue velocities were all unchanged from baseline . Intermittent exercise may improve functional capacity to a greater extent than continuous exercise . QOL changes were variable between groups Background High-intensity interval training has recently emerged as superior to continuous endurance training in cardiac rehabilitation upon other training regimes . Individually tailored continuous endurance training and pyramid training could induce comparable effects on peak work capacity as high intensity interval training . Design A prospect i ve , r and omized study . Methods Effects of the following isocaloric cycle ergometer protocol s on peak work capacity have been assessed in patients with coronary artery disease ( n = 60 ) during 6 weeks of outpatient cardiac rehabilitation , i.e. 18 supervised sessions of exercise training : ( 1 ) continuous endurance training ( n = 20 ) : 33 min at 65–85 % peak heart rate ; ( 2 ) high intensity interval training ( n = 20 ) : 4 × 4 min intervals at 85–95 % peak heart rate , each followed by 3 min of active recovery at 60–70 % peak heart rate ; ( 3 ) pyramid training ( n = 20 ) : 3 × 8 min of stepwise load increase and subsequent decrease from 65–95–65 % peak heart rate , supplemented by 2 min recovery at 60–70 % peak heart rate between pyramids . All protocol s were preceded by 5 min of warm-up and followed by 5 min cool-down at 60–70 % peak heart rate . Results Attendance during exercise sessions was 99.2 % . There were significant increases in peak work capacity of comparable magnitude in all three training groups ( begin vs. end : continuous endurance training : 136.0 ± 49.6 W vs. 163.4 ± 60.8 W ( 21.1 ± 8.5 % ) ; high-intensity interval training : 141.0 ± 60.4 W vs. 171.1 ± 69.8 W ( 22.8 ± 6.6 % ) ; pyramid training : 128.7 ± 50.6 W vs. 158.5 ± 57.9 W ( 24.8 ± 10.8 % ) ; within groups all p < 0.001 ; between groups , p = not significant ) . Conclusion Endurance training protocol s assessed in this study all led to significant increases in peak work capacity of comparable magnitude . Our findings suggest that these protocol s can be used interchangeably , which will lead to further individualization of exercise prescription and may therefore result in improved adherence to lifelong behavioural changes Background — A well-developed coronary collateral circulation provides a potential source of blood supply in coronary artery disease . However , the prognostic importance and functional relevance of coronary collaterals is controversial with the association between exercise training and collateral growth still unclear . Methods and Results — This prospect i ve , open-label study r and omly assigned 60 patients with significant coronary artery disease ( fractional flow reserve ⩽0.75 ) to high-intensity exercise ( group A , 20 patients ) or moderate-intensity exercise ( group B , 20 patients ) for 4 weeks or to a control group ( group C , 20 patients ) . The primary end point was the change of the coronary collateral flow index ( CFI ) after 4 weeks . Analysis was based on the intention to treat . After 4 weeks , baseline CFI increased significantly by 39.4 % in group A ( from 0.142±0.07 at beginning to 0.198±0.09 at 4 weeks ) in comparison with 41.3 % in group B ( from 0.143±0.06 to 0.202±0.09 ) , whereas CFI in the control group remained unchanged ( 0.7 % , from 0.149±0.09 to 0.150±0.08 ) . High-intensity exercise did not lead to a greater CFI than moderate-intensity training . After 4 weeks , exercise capacity , VO2 peak and ischemic threshold increased significantly in group A and group B in comparison with group C with no difference between group A and group B. Conclusions — A significant improvement in CFI was demonstrated in response to moderate- and high-intensity exercise performed for 10 hours per week . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT01209637 We conducted a three-week r and omized trial comparing the improvement of functional capacity by exercise training in chronic heart failure by the steady-state ( EF 27.3 % , n = 20 ) and the interval modus ( EF 29.3 % , n = 20 ) with a control group ( EF = 26.6 % , n = 10 ) . Minimal EF was 10 % , the lowest maximal oxygen consumption was 9.3 ml/kg/min and the lowest cardiac output was 1.9 l/min ; 9 patients had been evaluated for HTX . VO2 at the anaerobic threshold and at maximal exercise increased in the continuous exercise group by 1.4 or 1.6 ml/kg/min , respectively , corresponding to an increase of 13.7 % ( p < 0.05 ) and 9.3 % ( p < 0.05 ) . In the interval training group the increase was 1.3 and 1.5 ml/kg/min corresponding to 14 % ( p < 0.05 ) and 8.1 % ( p < 0.05 ) . Continuous short-term exercise had no impact to central hemodynamics as pulmonary artery pressure ( PA ) , capillary wedge pressure ( pc ) , cardiac index ( CI ) or stroke volume index ( SVI ) , whereas after interval training a significant increase at maximal exercise could be seen in CI ( p < 0.05 ) and SVI ( p < 0.01 ) with a concomitant drop in systemic peripheral resistance ( p < 0.05 ) compared to the steady-state modus . Interval training was further characterized by a higher short-term but lower mean work load with a significantly smaller increase in lactate . Quality of life was improved according to the SF-36 question naire in both training groups but the psychologic sum factor was three times as high , increasing to 24.2 % in the steady-state exercise group . It can be concluded that clinical ly stable patients with heart failure and even those already having been evaluated for cardiac transplantation profit from short-term physical training . Both training modalities seem equally suited to improve functional capacity . However interval training leads to more pronounced improvement in hemodynamics compared to the steady-state exercise , whereas the later had a greater impact on psychological well-being and quality of life . Patients with heart failure and severe peripheral deconditioning tolerate higher workloads with more peripheral stress by an interval training modus . Long-term training modalities need to be established to further improve and stabilize functional status BACKGROUND Abnormal ventilatory/hemodynamic responses to exercise contribute to functional impairment in patients with heart failure ( HF ) . This study investigates how interval and continuous exercise regimens influence functional capacity by modulating ventilatory efficiency and hemodynamic function in HF patients . METHODS Forty-five HF patients were r and omized to perform either aerobic interval training ( AIT ; 3-minute intervals at 40 % and 80 % VO(2peak ) ) or moderate continuous training ( MCT ; sustained 60 % VO()for 30 min/day , 3 days/week for 12 weeks , or to a control group that received general healthcare ( GHC ) . A noninvasive bio-reactance device was adopted to measure cardiac hemodynamics , whereas a near-infrared spectroscopy was employed to assess perfusion/O2 extraction in frontal cerebral lobe ( ∆[THb]FC/∆[HHb]FC ) and vastus lateralis ( ∆[THb]VL/∆[HHb]VL ) , respectively . RESULTS Following the 12-week intervention , the AIT group exhibited higher oxygen uptake efficiency slope ( OUES ) and lower VE-VCO2 slope than the MCT and GHC groups . Furthermore , AIT , but not MCT , boosted cardiac output ( CO ) and increased ∆[THb]FC , ∆[THb]VL , and ∆[HHb]VL during exercise . In multivariate analyses , CO was the dominant predictor of VO(2peak ) . ∆[THb]FC and ∆[THb]VL , which modulated the correlation between CO and OUES , were significantly correlated with OUES . Simultaneously , ∆[THb]VL was the only factor significantly associated with VE-VCO2 slope . Additionally , AIT reduced plasma brain natriuretic peptide , myeloperoxidase , and interleukin-6 levels and increased the Short Form-36 physical/mental component scores and decreased the Minnesota Living with Heart Failure question naire score . CONCLUSIONS AIT effectively improves oxygen uptake efficiency by enhancing cerebral/muscular hemodynamics and suppresses oxidative stress/inflammation associated with cardiac dysfunction , and also promotes generic/disease-specific qualities of life in patients with HF Heart failure with preserved ejection fraction ( HFpEF ) is a major cause of morbidity and mortality . Exercise training is an established adjuvant therapy in heart failure ; however , the effects of high-intensity interval training ( HIIT ) in HFpEF are unknown . We compared the effects of HIIT vs. moderate-intensity aerobic continuous training ( MI-ACT ) on peak oxygen uptake ( V̇o₂peak ) , left ventricular diastolic dysfunction , and endothelial function in patients with HFpEF . Nineteen patients with HFpEF ( age 70 ± 8.3 yr ) were r and omized to either HIIT ( 4 × 4 min at 85 - 90 % peak heart rate , with 3 min active recovery ) or MI-ACT ( 30 min at 70 % peak heart rate ) . Fifteen patients completed exercise training ( HIIT : n = 9 ; MI-ACT : n = 6 ) . Patients trained 3 days/wk for 4 wk . Before and after training patients underwent a treadmill test for V̇o₂peak determination , 2D-echocardiography for assessment of left ventricular diastolic dysfunction , and brachial artery flow-mediated dilation ( FMD ) for assessment of endothelial function . HIIT improved V̇o₂peak ( pre = 19.2 ± 5.2 ml·kg(-1)·min(-1 ) ; post = 21.0 ± 5.2 ml·kg(-1)·min(-1 ) ; P = 0.04 ) and left ventricular diastolic dysfunction grade ( pre = 2.1 ± 0.3 ; post = 1.3 ± 0.7 ; P = 0.02 ) , but FMD was unchanged ( pre = 6.9 ± 3.7 % ; post = 7.0 ± 4.2 % ) . No changes were observed following MI-ACT . A trend for reduced left atrial volume index was observed following HIIT compared with MI-ACT ( -3.3 ± 6.6 vs. + 5.8 ± 10.7 ml/m(2 ) ; P = 0.06 ) . In HFpEF patients 4 wk of HIIT significantly improved V̇o₂peak and left ventricular diastolic dysfunction . HIIT may provide a more robust stimulus than MI-ACT for early exercise training adaptations in HFpEF Background Increased aerobic exercise capacity appears to reduce both all-cause mortality and cardiovascular disease mortality . Physical exercise to improve peak oxygen uptake ( VO2peak ) is thus strongly recommended , however evidence regarding the most efficient training intensity for patients with coronary artery disease ( CAD ) is still lacking . The purpose of this r and omized study was therefore to assess the effects of high intensity aerobic interval exercise compared to moderate intensity exercise , representing the same total training load , for increasing VO2peak in stable CAD- patients . Methods Twenty-one stable CAD- patients were r and omized to supervised treadmill walking at either high intensity ( 80–90 % of VO2peak ) or moderate intensity ( 50–60 % of VO2peak ) three times a week for 10 weeks . Results After training VO2peak increased by 17.9 % ( P = 0.012 ) in the high intensity group and 7.9 % ( P = 0.038 ) in the moderate intensity group . The training-induced adaptation was significantly higher in the high intensity group ( P = 0.011 ) . Conclusions High intensity aerobic interval exercise is superior to moderate exercise for increasing VO2peak in stable CAD- patients . As VO2peak seems to reflect a continuum between health and cardiovascular disease and death , the present data may be useful in design ing effective training programmes for improved health in the future OBJECTIVE To test whether greater exercise is associated with progressively lower mortality after a cardiac event . PATIENTS AND METHODS We used Cox proportional hazard analyses to examine mortality vs estimated energy expended by running or walking measured as metabolic equivalents ( 3.5 mL O2/kg per min per day or metabolic equivalent of task-h/d [ MET-h/d ] ) in 2377 self-identified heart attack survivors , where 1 MET-h/d is the energy equivalent of running 1 km/d . Mortality surveillance via the National Death Index included January 1991 through December 2008 . RESULTS A total of 526 deaths occurred during an average prospect i ve follow-up of 10.4 years , 376 ( 71.5 % ) of which were related to cardiovascular disease ( CVD ) ( International Statistical Classification of Diseases , 10th Revision codes I00-I99 ) . CVD-related mortality compared with the lowest exercise group decreased by 21 % for 1.07 to 1.8 MET-h/d of running or walking ( P=.11 ) , 24 % for 1.8 to 3.6 MET-h/d ( P=.04 ) , 50 % for 3.6 to 5.4 MET-h/d ( P=.001 ) , and 63 % for 5.4 to 7.2 MET-h/d ( P<.001 ) but decreased only 12 % for ≥7.2 MET-h/d ( P=.68 ) . These data represent a 15 % average risk reduction per MET-h/d for CVD-related mortality through 7.2 MET-h/d ( P<.001 ) and a 2.6-fold risk increase above 7.2 MET-h/d ( P=.009 ) . Relative to the risk reduction at 7.2 MET-h/d , the risk for ≥7.2 MET-h/d increased 3.2-fold ( P=.006 ) for all ischemic heart disease (IHD)-related mortalities but was not significantly increased for non-IHD-CVD , arrhythmia-related CVD , or non-CVD-related mortalities . CONCLUSION Running or walking decreases CVD mortality risk progressively at most levels of exercise in patients after a cardiac event , but the benefit of exercise on CVD mortality and IHD deaths is attenuated at the highest levels of exercise ( running : above 7.1 km/d or walking briskly : 10.7 km/d ) PURPOSE : We tested the hypothesis that higher-intensity interval training ( HIIT ) could be deployed into a st and ard cardiac rehabilitation ( CR ) setting and would result in a greater increase in cardiorespiratory fitness ( ie , peak oxygen uptake , ) versus moderate-intensity continuous training ( MCT ) . METHODS : Thirty-nine patients participating in a st and ard phase 2 CR program were r and omized to HIIT or MCT ; 15 patients and 13 patients in the HIIT and MCT groups , respectively , completed CR and baseline and followup cardiopulmonary exercise testing . RESULTS : No patients in either study group experienced an event that required hospitalization during or within 3 hours after exercise . The changes in resting heart rate and blood pressure at followup testing were similar for both HIIT and MCT . at ventilatory-derived anaerobic threshold increased more ( P < .05 ) with HIIT ( 3.0 ± 2.8 mL·kg·−1min−1 ) versus MCT ( 0.7 ± 2.2 mL·kg·−1min−1 ) . During followup testing , submaximal heart rate at the end of stage 2 of the exercise test was significantly lower within both the HIIT and MCT groups , with no difference noted between groups . Peak V˙o2 improved more after CR in patients in HIIT versus MCT ( 3.6 ± 3.1 mL·kg.−1·min−1 vs 1.7 ± 1.7 mL·kg.−1·min−1 ; P < .05 ) . CONCLUSIONS : Among patients with stable coronary heart disease on evidence -based therapy , HIIT was successfully integrated into a st and ard CR setting and , when compared to MCT , result ed in greater improvement in peak exercise capacity and submaximal endurance Objective : To study the effects of three individualized exercise training prescriptions using either a percentage of maximal heart rate ( HR ) , maximal 6-minute walk test ( 6MWT ) HR , or maximal 200-metre fast walk test ( 200-mFWT ) HR , on walking performance and exercise capacity in coronary artery disease ( CAD ) patients . Design : Controlled clinical study . Participants : Twenty-seven out patients enrolled in a rehabilitation programme after an acute coronary syndrome . Setting : Cardiac rehabilitation unit . Interventions : Three groups : ( A ) : moderate intensity continuous exercise ( MICE ) at 70 % of the maximal HR of the grade d maximal exercise test ( n = 10 ) ; ( B ) : MICE at the maximal 6MWT HR ( n = 8) ; ( C ) : high intensity interval training ( HIIT ) based on the 6MWT and the 200-mFWT maximal HR ( n = 9 ) . Group B and C performed walk tests every 2 weeks , to readjust training HR ( THR ) if needed . Measures : 6MWT and 200-mFWT performances , peak VO2 and peak power ( Pmax ) . Results : 6MWT and 200-mFWT performances improved significantly and similarly in all groups ( P < 0.05 ) . Peak VO2 improved significantly in all groups ( P < 0.05 ) , this improvement being higher in group C ( HIIT ) versus A ( P < 0.05 ) . Group B was closer to the recommended THR during exercise sessions compared to group A. Conclusion : This pilot study showed that using the 6MWT and 200-mFWT HR to individualize MICE or HIIT prescription is feasible in CAD patients , and could lead them closer to THR objective , to similar improvements in walking performance , and greater peak VO2 increase for HIIT . Future r and omised studies should investigate long-term effects of programmes prescribed from walk tests HR , especially for HIIT modality Background Aerobic interval training ( AIT ) and aerobic continuous training ( ACT ) both improve physical fitness ( peak VO2 ) in coronary artery disease patients . However , little is known about the long-term effects of AIT and ACT on peak VO2 and exercise adherence . Design This study is a r and omized clinical multicenter trial . Methods In total , 163 patients were assessed after 12 weeks of AIT or ACT and 12 months after their enrollment . Physical fitness and physical activity measures served as the primary outcomes , and peripheral endothelial function , cardiovascular risk factors and quality of life ( QoL ) served as the secondary outcomes . Results Twenty-six patients dropped out during the intervention ; 11 were lost during the follow-up period . Dropouts ( n = 37 ) consisted of more women ( p = 0.001 ) compared to completers ( n = 163 ) . Physical fitness ( VO2 , heart rate and workload at peak and at thresholds ) and physical activity ( steps , active energy expenditure [ kcal ] , physical activity duration [ minutes ] ) were preserved at the 1-year follow-up ( p-time > 0.05 ) after both AIT and ACT ( p-interaction > 0.05 ) . Forty percent of patients showed increased peak VO2 , 52 % showed increased active energy expenditure and 91.2 % met the recommended levels of 150 minutes/week of moderate physical activity ( p-group > 0.05 ) . Further , peripheral endothelial function , QoL and cardiovascular risk factors , except systolic blood pressure ( p-time < 0.05 ) , remained stable ( p-time > 0.05 ) after both AIT and ACT ( p-interaction > 0.05 ) . Conclusion The short-term improvements of center-based AIT and ACT on physical fitness , physical activity , peripheral endothelial function , cardiovascular risk factors and QoL are sustained after a 1-year follow-up period . The majority of patients ( > 90 % ) met the recommended physical activity levels of 150 minutes/week |
10,769 | 28,259,168 | Conclusions There is an agreement across methods of four tasks that need to be completed when design ing individual-level interventions : identifying barriers , selecting intervention components , using theory , and engaging end-users . | Background Systematic review s consistently indicate that interventions to change healthcare professional ( HCP ) behaviour are haphazardly design ed and poorly specified .
Clarity about methods for design ing and specifying interventions is needed .
The objective of this review was to identify published methods for design ing interventions to change HCP behaviour . | Background Parasitological confirmation is now recommended for all cases of suspected malaria . The roll-out of rapid diagnostic tests ( RDTs ) is hoped to enable this goal in low re source setting s through point of care testing . However , simply making RDTs available has not led to high uptake of the tests or adherence to results by clinicians , with malaria continuing to be overdiagnosed in many setting s. We undertook to design an evidence -based intervention package that would be sufficient to support the introduction of RDTs at dispensaries in Tanzania , to be evaluated through the Targeting Artemisinin Combination Therapy ( TACT ) cluster r and omised controlled trial . Methods We describe five steps in our intervention design : formative research , review of existing evidence and theory , a workshop to define the intervention approach and content and results of formative research , engagement with behaviour change theory and literature , detailed design of intervention material s and piloting and pretesting of intervention material s. This involved fieldwork with a total of 19 health workers and 212 community members in northeast Tanzania . Results The formative research suggested that RDTs were a potential source of conflict in the health worker-patient interaction , but that health workers used various techniques to resolve this , including provision of antimalarial drugs for RDT-negative patients . Our review s showed that evidence was mixed regarding the effectiveness of different methods and theories to support change in prescribing practice . Our design process is presented , drawing from this collective evidence . We describe the final TACT intervention package ( including interactive small group workshops , feedback text messages , motivational text messages and patient information leaflets and posters ) in terms of its programme theory and implementation theory . Conclusions Our study suggests that evidence -based design of complex interventions is possible . The use of formative research to underst and malaria overdiagnosis in context was central to the design of the intervention as well as empirical research to test material s and methods prior to implementation . The TACT interventions may be appropriate for other setting s where clinicians face similar challenges with malaria diagnostics . Trial registration NCT01292707 Background We describe a simple approach we used to identify barriers and tailor an intervention to improve pharmacological management of hypertension and hypercholesterolaemia . We also report the results of a post hoc exercise and survey we carried out to evaluate our approach for identifying barriers and tailoring interventions . Methods We used structured reflection , search ed for other relevant trials , surveyed general practitioners and talked with physicians during pilot testing of the intervention . The post hoc exercise was carried out as focus groups of international research ers in the field of quality improvement in health care . The post hoc survey was done by telephone interviews with physicians allocated to the experimental group of a r and omised trial of our multifaceted intervention . Results A wide range of barriers was identified and several interventions were suggested through structured reflection . The survey led to some adjustments . Study ing other trials and pilot testing did not lead to changes in the design of the intervention . Neither the post hoc focus groups nor the post hoc survey revealed important barriers or interventions that we had not considered or included in our tailored intervention . Conclusions A simple approach to identifying barriers to change appears to have been adequate and efficient . However , we do not know for certain what we would have gained by using more comprehensive methods and we do not know whether the result ing intervention would have been more effective if we had used other methods . The effectiveness of our multifaceted intervention is under evaluation in a r and omised controlled trial A study was conducted to estimate the accuracy and reliability of review ers when screening records for relevant trials for a systematic review . A sensitive search of ten electronic bibliographic data bases yielded 22 571 records of potentially relevant trials . Records were allocated to four review ers such that two review ers examined each record and so that identification of trials by each review er could be compared with those identified by each of the other review ers . Agreement between review ers was assessed using Cohen 's kappa statistic . Ascertainment intersection methods were used to estimate the likely number of trials missed by review ers . Full copies of reports were obtained and assessed independently by two research ers for eligibility for the review . Eligible reports formed the ' gold st and ard ' against which an assessment was made about the accuracy of screening by review ers . After screening , 301 of 22 571 records were identified by at least one review er as potentially relevant . Agreement was ' almost perfect ' ( kappa>0.8 ) within two pairs , ' substantial ' ( kappa>0.6 ) within three pairs and ' moderate ' ( kappa>0.4 ) within one pair . Of the 301 records selected , 273 complete reports were available . When pairs of review ers agreed on the potential relevance of records , 81 per cent were eligible ( range 69 to 91 per cent ) . If review ers disagreed , 22 per cent were eligible ( range 12 to 45 per cent ) . Single review ers missed on average 8 per cent of eligible reports ( range 0 to 24 per cent ) , whereas pairs of review ers did not miss any ( range 0 to 1 per cent ) . The use of two review ers to screen records increased the number of r and omized trials identified by an average of 9 per cent ( range 0 to 32 per cent ) . Review ers can reliably identify potentially relevant records when screening thous and s of records for eligibility . Two review ers should screen records for eligibility , whenever possible , in order to maximize ascertainment of relevant trials |
10,770 | 27,432,053 | Some evidence was found to indicate that patients with resistant mechanical symptoms who initially fail nonoperative management may benefit from meniscal debridement No studies compared meniscal repair with meniscectomy or nonoperative management .
Initial evidence suggested that meniscal transplant might be favorable in certain patient groups . | Background : Arthroscopic surgery of the knee is one of the most frequently performed orthopaedic procedures .
One-third of these procedures are performed for meniscal injuries .
It is essential that this commonly performed surgery be supported by robust evidence . | OBJECTIVE Our purpose was to measure the agreement , reliability , construct validity , and feasibility of a measurement tool to assess systematic review s ( AMSTAR ) . STUDY DESIGN AND SETTING We r and omly selected 30 systematic review s from a data base . Each was assessed by two review ers using : ( 1 ) the enhanced quality assessment question naire ( Overview of Quality Assessment Question naire [ OQAQ ] ) ; ( 2 ) Sacks ' instrument ; and ( 3 ) our newly developed measurement tool ( AMSTAR ) . We report on reliability ( interobserver kappas of the 11 AMSTAR items ) , intraclass correlation coefficients ( ICCs ) of the sum scores , construct validity ( ICCs of the sum scores of AMSTAR compared with those of other instruments ) , and completion times . RESULTS The interrater agreement of the individual items of AMSTAR was substantial with a mean kappa of 0.70 ( 95 % confidence interval [ CI ] : 0.57 , 0.83 ) ( range : 0.38 - 1.0 ) . Kappas recorded for the other instruments were 0.63 ( 95 % CI : 0.38 , 0.78 ) for enhanced OQAQ and 0.40 ( 95 % CI : 0.29 , 0.50 ) for the Sacks ' instrument . The ICC of the total score for AMSTAR was 0.84 ( 95 % CI : 0.65 , 0.92 ) compared with 0.91 ( 95 % CI : 0.82 , 0.96 ) for OQAQ and 0.86 ( 95 % CI : 0.71 , 0.94 ) for the Sacks ' instrument . AMSTAR proved easy to apply , each review taking about 15 minutes to complete . CONCLUSIONS AMSTAR has good agreement , reliability , construct validity , and feasibility . These findings need confirmation by a broader range of assessors and a more diverse range of review Background Techniques for repairing the meniscus include both open and arthroscopic techniques using sutures and bioabsorbable implants . The purpose of this study was to compare the effectiveness of inside-out suturing and bioabsorbable arrows for repair of vertical meniscal lesions . Study Design R and omized controlled clinical trial ; Level of evidence , 1 . Methods One hundred consecutive patients were r and omly assigned to arrows ( n = 51 ) or sutures ( n = 49 ) . Sixty-five percent of patients ( 31 sutures , 34 arrows ) underwent a concomitant anterior cruciate ligament reconstruction . A blinded research associate conducted assessment s at 6 weeks and 3 , 6 , 12 , and 24 months postoperatively . The primary outcome was retear rate . Secondary outcomes included the Western Ontario Meniscal Evaluation Tool , Anterior Cruciate Ligament Quality of Life Outcome Measure , and side-to-side comparisons of flexion and extension . Results At baseline , groups were similar in age , gender , time from injury to surgery , and length and location of tear . Mean follow-up was 28.0 ± 8.4 months . There were 22 failed meniscal repairs ( 11 in each group ) , which did not represent a significant difference in the rate of failure between groups ( P = .92 ) . The mean quality of life scores and side-to-side differences in extension and flexion measurements were not significantly different between groups . Two patients from the arrow group crossed over into the suture group at the time of surgery because of technical difficulties with the device , and in 3 instances , a single suture was needed to keep the tear reduced while arrows were introduced . Two patients required reoperation for removal of a prominent , subcutaneous arrow , and 1 patient in the suture group suffered a transient peroneal nerve palsy during revision suturing . Conclusion At intermediate follow-up , there were no statistically significant differences in measured outcomes between meniscal suturing and arrows . Longer term follow-up is necessary to identify differences between these 2 treatments , particularly to estimate the incidence of articular surface damage in patients whose meniscal tear was repaired using arrows Abstract This study examined the effect of four different methods for treating intrasubstance meniscal lesions . Forty patients ( 21 men , ¶19 women ; age 30.4 years , range 16–50 ) with an isolated and symptomatic painful horizontal grade 2 meniscal lesion on the medial side ( documented with MRI ) were included . Patients were r and omly assigned by the birth date to one of four treatment groups : group A , conservative therapy ( n = 12 ) ; group B , arthroscopic suture repair with access channels ( n = 10 ) ; group C , arthroscopic minimal central resection , intrameniscal fibrin clot and suture repair ( n = 7 ) ; and group D , arthroscopic partial meniscectomy ¶(n = 11 ) . The average length of follow-up was 26.5 months ( range 12–38 months ) . Follow-up evaluation consisted of clinical examination with the findings recorded according to the IKDC protocol , radiographs , and control MRI . Group A had 75 % normal or nearly normal final evaluation at follow-up , group B 90 % , group C 43 % , and group D 100 % normal or nearly normal at follow-up . These short-term results indicate that intrasubstance meniscal lesions can be treated best by performing partial meniscectomy . To preserve the important function of the meniscus , arthroscopic suture repair with access channels might give even better medium- to long-term results . Conservative treatment is often not satisfactory . Additionally , our findings show that MRI examinations are not superior to accurate clinical examinations Background : It is still debated whether a degenerative horizontal tear of the medial meniscus should be treated with surgery . Hypothesis : The clinical outcomes of arthroscopic meniscectomy will be better than those of nonoperative treatment for a degenerative horizontal tear of the medial meniscus . Study Design : R and omized controlled trial ; Level of evidence , 1 . Methods : A total of 102 patients with knee pain and a degenerative horizontal tear of the posterior horn of the medial meniscus on magnetic resonance imaging were included in this study between January 2007 and July 2009 . The study included 81 female and 21 male patients with an average age of 53.8 years ( range , 43 - 62 years ) . Fifty patients underwent arthroscopic meniscectomy ( meniscectomy group ) , and 52 patients underwent nonoperative treatment with strengthening exercises ( nonoperative group ) . Functional outcomes were compared using a visual analog scale ( VAS ) for pain , Lysholm knee score , Tegner activity scale , and patient subjective knee pain and satisfaction . Radiological evaluations were performed using the Kellgren-Lawrence classification to evaluate osteoarthritic changes . Results : In terms of clinical outcomes , meniscectomy did not provide better functional improvement than nonoperative treatment . At the final follow-up , the average VAS scores were 1.8 ( range , 1 - 5 ) in the meniscectomy group and 1.7 ( range , 1 - 4 ) in the nonoperative group ( P = .675 ) . The average Lysholm knee scores at 2-year follow-up were 83.2 ( range , 52 - 100 ) and 84.3 ( range , 58 - 100 ) in the meniscectomy and nonoperative groups , respectively ( P = .237 ) . In addition , the average Tegner activity scale and subjective satisfaction scores were not significantly different between the 2 groups . Although most patients initially had intense knee pain with mechanical symptoms , both groups reported a relief in knee pain , improved knee function , and a high level of satisfaction with treatment ( P < .05 for all values ) . Two patients in the meniscectomy group and 3 in the nonoperative group with Kellgren-Lawrence grade 1 progressed to grade 2 at the 2-year follow-up . Conclusion : There were no significant differences between arthroscopic meniscectomy and nonoperative management with strengthening exercises in terms of relief in knee pain , improved knee function , or increased satisfaction in patients after 2 years of follow-up 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 . ) Purpose The aim of this prospect i ve r and omized intervention study was to evaluate the outcome at a 2 and 5 year follow-up whether combined arthroscopic surgery followed by exercise therapy was superior to the same exercise therapy alone when treating non-traumatic , degenerative medial meniscal tears . Methods Ninety-six middle-aged patients with MRI-verified degenerative medial meniscus tear and radiographic osteoarthritis grade ≤1 ( Ahlbäck ) participated in the study . Radiographic examination was done before r and omization and after 5 years . The patients were r and omly assigned to either arthroscopic treatment followed by exercise therapy for 2 months or to the same exercise therapy alone . At the start of the study and at the follow-ups at 24 and 60 months the patients answered three question naires KOOS , Lysholm Knee Scoring Scale and Tegner Activity Scale and made pain ratings on the Visual Analogue Scale ( VAS ) . Results Both groups showed highly significant clinical improvements from baseline to the follow-ups at 24 and 60 months on all subscales of KOOS , Lysholm Knee Scoring Scale and VAS ( p < 0.0001 ) . No group differences were found at any of the testing occasions . One third of the patients that were treated with exercise therapy alone did not feel better after the treatment but were improved after arthroscopic surgery . According to radiographic findings two patients from each group had a slight progression of their osteoarthritis after 5 years . Conclusion The findings indicate that arthroscopic surgery followed by exercise therapy was not superior to the same exercise therapy alone for this type of patients . Consequently , exercise therapy can be recommended as initial treatment . However , one third of the patients from the exercise group still had disabling knee symptoms after exercise therapy but improved to the same level as the rest of the patients after arthroscopic surgery with partial meniscectomy . Level of evidence Abstract In a prospect ively r and omized study including 68 patients , the results of inside-out horizontal meniscus suturing were compared to meniscus repair using the meniscus arrow . 96 % of the patients underwent re-arthroscopy after 3–4 months . Only lesions in the red/red or red/white areas were included . Patients were treated with a hinged brace for 9 weeks . 30 patients had an isolated bucket-h and le lesion . In 19 cases the repair was done in conjunction with an ACL reconstruction and in 19 cases the repair was performed in an ACL-insufficient knee . The two groups were comparable . Operating time in the arrow group was one half that of the suture group . Of 65 re-arthroscopies , 91 % of the patients had healed or partially healed in the arrow group compared to 75 % in the suture group ( P = 0.11 ) . In only 50 % of the non-healed cases was this clinical ly suspected prior to control arthroscopy . The difference between healing in ACL-reconstructed and ACL-insufficient knees was not significant . Two patients in the suture group had a deep infection . There were no serious neurovascular injuries . Five patients in the suture group and two patients in the arrow group had symptoms in the saphenous nerve area . All patients had some synovial irritation at control arthroscopy but no severe reactions to suture or arrows were seen . Short-term results with meniscus arrows , based on healing and evaluated by second-look arthroscopy , seem promising BACKGROUND Magnetic resonance imaging ( MRI ) of the knee is often performed in patients who have knee symptoms of unclear cause . When meniscal tears are found , it is commonly assumed that the symptoms are attributable to them . However , there is a paucity of data regarding the prevalence of meniscal damage in the general population and the association of meniscal tears with knee symptoms and with radiographic evidence of osteoarthritis . METHODS We studied persons from Framingham , Massachusetts , who were drawn from census-tract data and r and om-digit telephone dialing . Subjects were 50 to 90 years of age and ambulatory ; selection was not made on the basis of knee or other joint problems . We assessed the integrity of the menisci in the right knee on 1.5-tesla MRI scans obtained from 991 subjects ( 57 % of whom were women ) . Symptoms involving the right knee were evaluated by question naire . RESULTS The prevalence of a meniscal tear or of meniscal destruction in the right knee as detected on MRI ranged from 19 % ( 95 % confidence interval [ CI ] , 15 to 24 ) among women 50 to 59 years of age to 56 % ( 95 % CI , 46 to 66 ) among men 70 to 90 years of age ; prevalences were not material ly lower when subjects who had had previous knee surgery were excluded . Among persons with radiographic evidence of osteoarthritis ( Kellgren-Lawrence grade 2 or higher , on a scale of 0 to 4 , with higher numbers indicating more definite signs of osteoarthritis ) , the prevalence of a meniscal tear was 63 % among those with knee pain , aching , or stiffness on most days and 60 % among those without these symptoms . The corresponding prevalences among persons without radiographic evidence of osteoarthritis were 32 % and 23 % . Sixty-one percent of the subjects who had meniscal tears in their knees had not had any pain , aching , or stiffness during the previous month . CONCLUSIONS Incidental meniscal findings on MRI of the knee are common in the general population and increase with increasing age Summary Two hundred patients were r and omly selected for either a partial or a total meniscectomy for a meniscal tear during open operation . They were followed for a median of 7.8 years after operation . After partial meniscectomy , posterior horn tears had the worst outcome , but this was only apparent when more than two-thirds of the meniscus had been removed . The amount of meniscal tissue excised was inversely related to the function of the knee , except with bucket-h and le tears treated by partial meniscectomy . Patients with bucket-h and le , anterior and posterior horn tears had similar functional results after total meniscectomy . Preservation of the peripheral rim of the meniscus following partial meniscectomy produces the best functional results .RésuméDeux cents patients atteints de lésion méniscale ont été répartis en cours d'opération , de façon r and omisée , entre méniscectomie partielle et méniscectomie totale . Ces patients ont été revus , au dernier examen , de 6.3 à 9.8 ans après l'intervention ( à 7.8 ans en moyenne ) . Après méniscectomie partielle c'étaient les lésions de la corne postérieure qui avaient les moins bons résultats fonctionnels , mais les différences de résultat selon les types de lésion n'étaient observées que lorsque plus d'un tiers de la surface méniscale avait été réséquée . La quantité de tissu méniscal enlevé était inversement proportionnelle à la qualité de la fonction du genou , sauf dans les déchirures en anse de seau traitées par méniscectomie partielle . Ces lésions étaient celles où la plus forte proportion de tissu méniscal avait été réséquée , mais do nt les résultats fonctionnels étaient meilleurs que ceux des lésions de la corne postérieure . Les patients présentant des anses de seau , des lésions de la corne antérieure ou de la corne postérieure , avaient des résultats fonctionnels similaires après méniscectomie totale . La conservation de la périphérie du ménisque après méniscectomie partielle est le facteur essentiel d'un bon résultat fonctionnel post-opératoire OBJECTIVES Virtually all early cases of knee osteoarthritis have degenerative medial meniscus lesions accompanying the chondral defects on MRI . It is difficult to determine if the symptoms are caused by the unstable meniscus or by osteoarthritis , hence unclear guidance towards treatment . We , therefore , aim ed to determine the clinical improvement following arthroscopic meniscectomy compared to intraarticular administration of corticosteroids for degenerative ruptures of the medial meniscus in the presence of early stage medial compartment knee osteoarthritis . PATIENTS AND METHODS We included 120 consecutive cases of nontraumatic symptomatic knees which had degenerative lesions of the medial compartment ( cartilage and meniscus ) on MRI 's . They were r and omized to receive either intraarticular steroid injection or arthroscopic debridement . We also analyzed the correlation between BMI , age , gender , MRI , intraoperative aspect of the meniscus and cartilage and clinical improvement using the Oxford Knee Score up to one year . At one month there was significant improvement of the scores for all the examined cases . Also at one month , the arthroscopic group performed better in terms of symptom improvement . This was maintained for 79 % of the knees in the arthroscopic group and 61 % in the intraarticular steroid injection respectively , out of those available for follow up at one year . RESULTS At one month , symptoms reappeared for 12 patients in the steroid group and 7 in the arthroscopy respectively . Gender and age did not correlate with treatment , whereas extrusion of the meniscus , bone marrow edema , duration of the clinical symptoms , obesity and a low preoperative score were negative prognostic factors . CONCLUSIONS Degenerative medial meniscal tears , in the presence of osteoarthritis , can only marginally benefit from arthroscopic debridement over intraarticular steroid injections in short term follow up . When considering individual cases , factors become more predictive when analyzed in group Arthroscopy of the knee is one of the most commonly performed orthopaedic procedures worldwide . Large-volume outcome data have not previously been available for English NHS patients . Prospect ively collected admissions data , routinely collected on every English NHS patient , were analysed to determine the rates of complications within 30 days ( including re-operation and re-admission ) , 90-day symptomatic venous thromboembolism and all-cause mortality . There were 301,701 operations performed between 2005 and 2010 - -an annual incidence of 9.9 per 10,000 English population . Of these , 16,552 ( 6 % ) underwent ligament reconstruction and 106,793 ( 35 % ) underwent meniscal surgery . The 30-day re-admission rate was 0.64 % ( 1662 ) and 30-day wound complication rate was 0.26 % ( 677 ) . The overall 30-day re-operation rate was 0.40 % ( 1033 ) and the 90-day pulmonary embolism rate was 0.08 % ( 230 ) , of which six patients died . 90-day mortality was 0.02 % ( 47 ) . Age < 40 years , male gender and ligament reconstruction were significantly associated with an increased rate of 30-day re-admission and unplanned re-operation . In addition , a significant increase in 30-day admission rates were seen with Charlson comorbidity scores of 1 ( p = 0.037 ) and ≥ 2 ( p < 0.001 ) compared with scores of 0 , and medium volume units compared with high volume units ( p < 0.001 ) . Complications following arthroscopy of the knee are rare . It is a safe procedure , which in the majority of cases is performed as day case surgery . These data can be used for quality benchmarking , in terms of consent , consultant re-validation and individual unit performance BACKGROUND Many patients report symptomatic relief after undergoing arthroscopy of the knee for osteoarthritis , but it is unclear how the procedure achieves this result . We conducted a r and omized , placebo-controlled trial to evaluate the efficacy of arthroscopy for osteoarthritis of the knee . METHODS A total of 180 patients with osteoarthritis of the knee were r and omly assigned to receive arthroscopic débridement , arthroscopic lavage , or placebo surgery . Patients in the placebo group received skin incisions and underwent a simulated débridement without insertion of the arthroscope . Patients and assessors of outcome were blinded to the treatment-group assignment . Outcomes were assessed at multiple points over a 24-month period with the use of five self-reported scores -- three on scales for pain and two on scales for function-- and one objective test of walking and stair climbing . A total of 165 patients completed the trial . RESULTS At no point did either of the intervention groups report less pain or better function than the placebo group . For example , mean ( + /-SD ) scores on the Knee-Specific Pain Scale ( range , 0 to 100 , with higher scores indicating more severe pain ) were similar in the placebo , lavage , and débridement groups : 48.9+/-21.9 , 54.8+/-19.8 , and 51.7+/-22.4 , respectively , at one year ( P=0.14 for the comparison between placebo and lavage ; P=0.51 for the comparison between placebo and débridement ) and 51.6+/-23.7 , 53.7+/-23.7 , and 51.4+/-23.2 , respectively , at two years ( P=0.64 and P=0.96 , respectively ) . Furthermore , the 95 percent confidence intervals for the differences between the placebo group and the intervention groups exclude any clinical ly meaningful difference . CONCLUSIONS In this controlled trial involving patients with osteoarthritis of the knee , the outcomes after arthroscopic lavage or arthroscopic débridement were no better than those after a placebo procedure BACKGROUND Whether arthroscopic partial meniscectomy for symptomatic patients with a meniscal tear and knee osteoarthritis results in better functional outcomes than nonoperative therapy is uncertain . METHODS We conducted a multicenter , r and omized , controlled trial involving symptomatic patients 45 years of age or older with a meniscal tear and evidence of mild-to-moderate osteoarthritis on imaging . We r and omly assigned 351 patients to surgery and postoperative physical therapy or to a st and ardized physical-therapy regimen ( with the option to cross over to surgery at the discretion of the patient and surgeon ) . The patients were evaluated at 6 and 12 months . The primary outcome was the difference between the groups with respect to the change in the Western Ontario and McMaster Universities Osteoarthritis Index ( WOMAC ) physical-function score ( ranging from 0 to 100 , with higher scores indicating more severe symptoms ) 6 months after r and omization . RESULTS In the intention-to-treat analysis , the mean improvement in the WOMAC score after 6 months was 20.9 points ( 95 % confidence interval [ CI ] , 17.9 to 23.9 ) in the surgical group and 18.5 ( 95 % CI , 15.6 to 21.5 ) in the physical-therapy group ( mean difference , 2.4 points ; 95 % CI , -1.8 to 6.5 ) . At 6 months , 51 active participants in the study who were assigned to physical therapy alone ( 30 % ) had undergone surgery , and 9 patients assigned to surgery ( 6 % ) had not undergone surgery . The results at 12 months were similar to those at 6 months . The frequency of adverse events did not differ significantly between the groups . CONCLUSIONS In the intention-to-treat analysis , we did not find significant differences between the study groups in functional improvement 6 months after r and omization ; however , 30 % of the patients who were assigned to physical therapy alone underwent surgery within 6 months . ( Funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases ; METEOR Clinical Trials.gov number , NCT00597012 . ) |
10,771 | 25,569,206 | Well conducted ecological and cohort studies in multiple setting s are the most appropriate approach for quantifying and monitoring overdiagnosis in cancer screening programs . | OBJECTIVE To determine the optimal method for quantifying and monitoring overdiagnosis in cancer screening over time . | BACKGROUND Cancer screening has been effective in detecting tumors early before symptoms appear . However , the effectiveness of the regular fecal occult blood test ( FOBT ) in colorectal cancer in the long term has not been quantified . METHODS We applied the statistical method developed by Wu and Rosner using data from the Minnesota Colon Cancer Control Study ( MCCCS ) . All initially asymptomatic participants were classified into four mutually exclusive groups : true-early-detection , no-early-detection , over-diagnosis , and symptom-free life ; human lifetime was treated as a r and om variable and is subject to competing risks . All participants in the screening program will eventually fall into one of the four outcomes above . Predictive inferences on the percentages of the four outcomes for both genders were made using the Minnesota study data . RESULTS Depending on gender , screening frequency and age at the initial screening , for all participants the probability of " symptom-free-life " varies between 95.3 % and 96.6 % ; the probability of " true-early-detection " is 1.9 - 3.8 % ; the probability of no-early-detection is 0.3 - 2.0 % ; the probability of over-diagnosis is 0.16 - 0.3 % . Among those with colorectal cancer detected by regular FOBT , the probability of over-diagnosis is lower than expected and is between 6 % and 9 % , with 95 % CI ( 2.5 % , 21.3 % ) for females and ( 1.9 % , 44.7 % ) for males . The probability of true-early-detection increases as screening interval decreases . The probability of no-early-detection decreases as screening interval decreases . CONCLUSION The probability of over-diagnosis among the screen-detected cases is not as high as previously thought . We hope this outcome can provide valuable information on the effectiveness of the FOBT in colorectal cancer detection in the long term Objectives To estimate the absolute numbers of breast cancer deaths prevented and the absolute numbers of tumours overdiagnosed in mammographic screening for breast cancer at ages 50–69 years . Setting The Swedish Two-County r and omized trial of mammographic screening for breast cancer , and the UK Breast Screening Programme in Engl and , ages 50–69 years . Methods We estimated the absolute numbers of deaths avoided and additional cases diagnosed in the study group ( active study population ) of the Swedish Two-County Trial , by comparison with the control group ( passive study population ) . We estimated the same quantities for the mortality and incidence rates in Engl and ( 1974–2004 and 1974–2003 , respectively ) . We used Poisson regression for statistical inference . Results A substantial and significant reduction in breast cancer mortality was associated with screening in both the Two-County Trial ( P < 0.001 ) and the screening programme in Engl and ( P < 0.001 ) . The absolute benefits were estimated as 8.8 and 5.7 breast cancer deaths prevented per 1000 women screened for 20 years starting at age 50 from the Two-County Trial and screening programme in Engl and , respectively . The corresponding estimated numbers of cases overdiagnosed per 1000 women screened for 20 years were , respectively , 4.3 and 2.3 per 1000 . Conclusions The benefit of mammographic screening in terms of lives saved is greater in absolute terms than the harm in terms of overdiagnosis . Between 2 and 2.5 lives are saved for every overdiagnosed case Introduction Overdiagnosis of breast cancer due to mammography screening , defined as thediagnosis of screen-detected cancers that would not have presented clinical ly in awomen 's lifetime in the absence of screening , has emerged as a highly contentiousissue , as harm caused may question the benefit of mammographic screening . Most studies included women over 50 years old and little information is available foryounger women . Methods We estimated the overdiagnosis of breast cancer due to screening in women aged 40to 49 years using data from a r and omised trial of annual mammographic screeningstarting at age 40 conducted in the UK . A six-state Markov model was constructedto estimate the sensitivity of mammography for invasive and insitu breast cancer and the screen-detectable mean sojourn time fornon-progressive in situ , progressive in situ , and invasivebreast cancer . Then , a 10-state simulation model of cancer progression , screening , and death , was developed to estimate overdiagnosis attributable to screening . Results The sensitivity of mammography for invasive and in situ breast cancerswas 90 % ( 95 % CI , 72 to 99 ) and 82 % ( 43 to 99 ) , respectively . The screen-detectablemean sojourn time of pre clinical non-progressive and progressive in situ cancers was 1.3 ( 0.4 to 3.4 ) and 0.11 ( 0.05 to 0.19 ) years , respectively , and 0.8 years ( 0.6 to 1.2 ) for pre clinical invasive breast cancer . The proportion ofscreen-detected in situ cancers that were non-progressive was 55 % ( 25 to77 ) for the first and 40 % ( 22 to 60 ) for subsequent screens . In our main analysis , overdiagnosis was estimated as 0.7 % of screen-detected cancers . A sensitivity analysis , covering a wide range of alternative scenarios , yielded a range of 0.5%to 2.9 % . Conclusion Although a high proportion of screen-detected in situ cancers werenon-progressive , a majority of these would have presented clinical ly in theabsence of screening . The extent of overdiagnosis due to screening in women aged40 to 49 was small . Results also suggest annual screening is most suitable forwomen aged 40 to 49 in the United Kingdom due to short cancer sojourn times Background : Published lead time estimates in breast cancer screening vary from 1 to 7 years and the percentages of overdiagnosis vary from 0 to 75 % . The differences are usually explained as r and om variations . We study how much can be explained by using different definitions and methods . Methods : We estimated the clinical ly relevant lead time based on the observed incidence reduction after attending the last screening round in the Norwegian mammography screening programme . We compared this estimate with estimates based on models that do not take overdiagnosis into account ( model-based lead times ) , for varying levels of overdiagnosis . Finally , we calculated overdiagnosis adjusted for clinical and model-based lead times and compared results . Results : Clinical lead time was about one year based on the reduction in incidence in women previously offered screening . When overdiagnosed tumours were included , the estimates increased to 4–9 years , depending on the age at which screening begins and the level of overdiagnosis . Including all breast cancers detected in women long after the end of the screening programme dilutes the level of overdiagnosis by a factor of 2–3 . Conclusion : When overdiagnosis is not taken into account , lead time is substantially overestimated . Overdiagnosis adjusted for model-based lead time is a function tending to zero , with no simple interpretation . Furthermore , the estimates are not in general comparable , because they depend on both the duration of screening and duration of follow-up . In contrast , overdiagnosis adjusted for clinical ly relevant tumours is a point estimate ( and interpreted as percentage ) , which we find is the most reasonable method BACKGROUND No r and omized controlled trial of prostate cancer screening has been reported and none is likely to be completed in the near future . In the absence of direct evidence , the decision to screen must therefore be based on estimates of benefits and risks . The main risk of screening is overdetection -- the detection of cancer that , if left untreated , would not cause death . In this study the authors estimate the level of overdetection that might result from annual screening of men aged 50 - 70 . METHODS The annual rate of lethal screen-detectable cancer ( detectable cancer that would prove fatal before age 85 if left untreated ) was calculated from the observed prostate cancer mortality rate in Quebec ; the annual rate of all cases of screen-detectable prostate cancer was calculated from 2 recent screening studies . RESULTS The annual rate of lethal screen-detectable prostate cancer was estimated to be 1.3 per 1000 men . The annual rate of all cases of screen-detectable prostate cancer was estimated to be 8.0 per 1000 men . The estimated case-fatality rate among men up to 85 years of age was 16 % ( 1.3/8.0 ) ( sensitivity analysis 13 % to 22 % ) . INTERPRETATION Of every 100 men with screen-detected prostate cancer , only 16 on average ( 13 to 22 ) could have their lives extended by surgery , since the prostate cancer would not cause death before age 85 in the remaining 84 ( 78 to 87 ) It is currently not known whether most lung cancers detected by computerized tomography ( CT ) screening are aggressive and likely to be fatal if left untreated , or if a sizable fraction are indolent and unlikely to cause death during the natural lifetime of the individual . We developed a longitudinal biologically-based model of the relationship between individual smoking histories and the probability for lung cancer incidence , CT screen detection , lung cancer mortality , and other-cause mortality . The longitudinal model relates these different outcomes to an underlying lung cancer disease pathway and an effective other-cause mortality pathway , which are both influenced by the individual smoking history . The longitudinal analysis provides additional information over that available if these outcomes were analyzed separately , including testing if the number of CT detected and histologically-confirmed lung cancers is consistent with the expected number of lung cancers " in the pipeline " . We assume indolent nodules undergo Gompertz growth and are detectable by CT , but do not grow large enough to contribute significantly to symptom-based lung cancer incidence or mortality . Likelihood-based model calibration was done jointly to data from 6878 heavy smokers without asbestos exposure in the control ( placebo ) arm of the Carotene and Retinol Efficacy Trial ( CARET ) ; and to 3,642 heavy smokers with comparable smoking histories in the Pittsburgh Lung Screening Study ( PLuSS ) , a single-arm prospect i ve trial of low-dose spiral CT screening for diagnosis of lung cancer . Model calibration was checked using data from two other single-arm prospect i ve CT screening trials , the New York University Lung Cancer Biomarker Center ( NYU ) ( n=1,021 ) , and Moffitt Cancer Center ( Moffitt ) cohorts ( n=677 ) . In the PLuSS cohort , we estimate that at the end of year 2 , after the baseline and first annual CT exam , that 33.0 ( 26.9 , 36.9)% of diagnosed lung cancers among females and 7.0 (4.9,11.7)% among males were overdiagnosed due to being indolent cancers . At the end of the PLuSS study , with maximum follow-up of 5.8 years , we estimate that due to early detection by CT and limited follow-up , an additional 2.2 (2.0,2.4)% of all diagnosed cancers among females and 7.1 (6.7,8.0)% among males would not have been diagnosed in the absence of CT screening . We also find a higher apparent cure rate for lung cancer among CARET females than males , consistent with the larger indolent fraction of CT detected and histologically confirmed lung cancers among PLuSS females . This suggests that there are significant gender differences in the aggressiveness of lung cancer . Females may have an inherently higher proportion of indolent lung cancers than males , or aggressive lung cancers may be brought into check by the immune system more frequently among females than males OBJECTIVES To estimate overdiagnosis ( detection of latent carcinomas ) as a consequence of screening for prostate cancer . DESIGN Based on actual screen ( first or repeat ) detected and interval prostate cancer rates observed in the Florence screening pilot study , a scenario was simulated where males aged 60 years ( or 65 ) had six biennal screens and were followed up for four years . Overdiagnosis was determined as the proportional excess of cancers detected by screening with respect to that expected in its absence . SETTING City of Florence , Italy , from 1992 through 1995 . POPULATION 2,740 resident males , aged 60 to 74 years . RESULTS Overdiagnosis was estimated to be 51 % ( 95 % confidence limits : 44%-55 % ) or 93 % ( 85%-101 % ) for age 60 or 65 at entry . Comparison with other screening experiences obtaining higher detection rates suggests that a more aggressive screening approach could be associated with overdiagnosis estimates as big as 200%-250 % . CONCLUSIONS Screening for prostate cancer is associated with a relevant risk of overdioagnosis . As latent carcinomas can not be presently identified , this would lead to overtreatment in most overdiagnosed cases . The negative consequences of overdiagnosis ( knowledge of having a cancer ) and of overtreatment ( impotence , incontinence , perioperatory death ) may be extremely serious . In absence of any scientific evidence of screening benefits ( if any ) screening should not be recommended as a current practice , but should be limited to prospect i ve controlled studies design ed to assess its cost-effectiveness As with wide-spread use of prostate cancer ( Pca ) screening with prostate-specific antigen testing , overdetection has increasingly gained attention . The authors aim ed to estimate absolute risk of overdetection ( RO ) in Pca screening with various interscreening intervals and ages at start of screening . We estimated age-specific pre clinical incidence rates ( per 100,000 person-years ) for progressive cancer ( from 128 for age group 55 - 58 years to 774 for age group 67 - 71 years ) and nonprogressive cancer ( from 40 for age group 55 - 58 years to 66 for age group 67 - 71 years ) , the mean sojourn time ( 7.72 years ) and the sensitivity ( 42.8 % at first screen and 59.8 % at the second screen ) by using a multistep epidemiological model with data from the Finnish r and omized controlled trial . The overall number of screens for overdetection ( NSO ) was 29 ( 95 % confidence interval ( CI ) : 18 , 48 ) for screenees aged 55 - 67 years , equivalent to 3.4 ( 95 % CI : 2.1 , 5.7 ) overdetected Pcas per 100 screenees . The NSO decreased from 63 ( 95 % CI : 37 , 109 ) at the first screen to 29 ( 95 % CI : 18 , 48 ) at the third screen and from 43 ( 95 % CI : 36 , 52 ) for age 55 years to 25 ( 95 % CI : 8 , 75 ) at age 67 years at the first screen . In conclusion , around 3.4 cases for every 100 screened men would be overdetected during three screen rounds ( ~ 13 years of follow-up ) in the Finnish r and omized controlled trial . Elucidating the absolute RO under various scenarios makes contribution for evaluating the benefit and harm of Pca screening IMPORTANCE Screening for lung cancer has the potential to reduce mortality , but in addition to detecting aggressive tumors , screening will also detect indolent tumors that otherwise may not cause clinical symptoms . These overdiagnosis cases represent an important potential harm of screening because they incur additional cost , anxiety , and morbidity associated with cancer treatment . OBJECTIVE To estimate overdiagnosis in the National Lung Screening Trial ( NLST ) . DESIGN , SETTING , AND PARTICIPANTS We used data from the NLST , a r and omized trial comparing screening using low-dose computed tomography ( LDCT ) vs chest radiography ( CXR ) among 53 452 persons at high risk for lung cancer observed for 6.4 years , to estimate the excess number of lung cancers in the LDCT arm of the NLST compared with the CXR arm . MAIN OUTCOMES AND MEASURES We calculated 2 measures of overdiagnosis : the probability that a lung cancer detected by screening with LDCT is an overdiagnosis ( PS ) , defined as the excess lung cancers detected by LDCT divided by all lung cancers detected by screening in the LDCT arm ; and the number of cases that were considered overdiagnosis relative to the number of persons needed to screen to prevent 1 death from lung cancer . RESULTS During follow-up , 1089 lung cancers were reported in the LDCT arm and 969 in the CXR arm of the NLST . The probability is 18.5 % ( 95 % CI , 5.4%-30.6 % ) that any lung cancer detected by screening with LDCT was an overdiagnosis , 22.5 % ( 95 % CI , 9.7%-34.3 % ) that a non-small cell lung cancer detected by LDCT was an overdiagnosis , and 78.9 % ( 95 % CI , 62.2%-93.5 % ) that a bronchioalveolar lung cancer detected by LDCT was an overdiagnosis . The number of cases of overdiagnosis found among the 320 participants who would need to be screened in the NLST to prevent 1 death from lung cancer was 1.38 . CONCLUSIONS AND RELEVANCE More than 18 % of all lung cancers detected by LDCT in the NLST seem to be indolent , and overdiagnosis should be considered when describing the risks of LDCT screening for lung cancer |
10,772 | 14,583,990 | REVIEW ER 'S CONCLUSIONS This review recommends the use of both verbal and written health information when communicating about care issues with patients and /or significant others on discharge from hospital to home .
The combination of verbal and written health information enables the provision of st and ardised care information to patients and /or significant others , which appears to improve knowledge and satisfaction . | BACKGROUND It is becoming commonplace for patients to be discharged earlier from acute hospital setting s to their own homes and be required to manage various aspects of their own care .
This has increased the need for detailed information to be given to patients and /or significant others to enable them to effectively manage care at home .
It has been suggested that providing written health information can assist in this self management .
OBJECTIVES To determine the effectiveness of providing written health information in addition to verbal information for patients and /or significant others being discharged from acute hospital setting s to home . | OBJECTIVES to investigate the effectiveness of a pharmacy discharge plan in elderly hospitalized patients . DESIGN r and omized controlled trial . SUBJECTS AND SETTING S we r and omized patients aged 75 years and older on four or more medicines who had been discharged from three acute general and one long-stay hospital to a pharmacy intervention or usual care . INTERVENTIONS the hospital pharmacist developed discharge plans which gave details of medication and support required by the patient . A copy was given to the patient and to all relevant professionals and carers . This was followed by a domiciliary assessment by a community pharmacist . In the control group , patients were discharged from hospital following st and ard procedures that included a discharge letter to the general practitioner listing current medications . OUTCOMES the primary outcome was re-admission to hospital within 6 months . Secondary outcomes included the number of deaths , attendance at hospital outpatient clinics and general practice and proportion of days in hospital over the follow-up period , together with patients ' general well-being , satisfaction with the service and knowledge of and adherence to prescribed medication . RESULTS we recruited 362 patients , of whom 181 were r and omized to each group . We collected hospital and general practice data on at least 91 and 72 % of patients respectively at each follow-up point and interviewed between 43 and 90 % of the study subjects . There were no significant differences between the groups in the proportion of patients re-admitted to hospital between baseline and 3 months or 3 and 6 months . There were no significant differences in any of the secondary outcomes . CONCLUSIONS we found no evidence to suggest that the co-ordinated hospital and community pharmacy care discharge plans in elderly patients in this study influence outcomes This pilot study 's objective was to determine the effectiveness of postpartum education received by midwifery clients at the University of New Mexico Hospital . The authors of the study r and omized 100 women following delivery to two groups . Group one , n = 55 , received written postpartum instructions only . Group two , n = 45 , received oral instructions by the certified nurse-midwife in addition to the written instructions . Both groups answered a written question naire after the teaching . Analyses were carried out on 100 posttest scores . Mean test scores for group one was 17.9 out of a possible score of 20 . Mean score for group two was 18.3 . No significant difference was detected between these two mean scores . A 95 % confidence interval for the difference between mean scores was -1.9 to 1.1 ( P > .05 ) . Reliability of instrument was established via the Kuder-Richardson formula 21 . This conservative estimate of internal consistency yielded r = .50 . The authors found that oral instructions by the certified nurse-midwife did not significantly increase the knowledge of primiparas as evidence d by posttest results . However , results must be interpreted cautiously for three reasons : low reliability of the instrument , the small difference between groups , and the sample size . The need to determine how best to approach postpartum education is imperative in this era of early hospital discharge . A certified nurse-midwife 's time may be better spent focusing on individual concerns rather than on a set teaching agenda . Alternative opportunities such as postpartum home visits need to be explored as a means of providing support and guidance to new mothers For this study a r and omized clinical trial was design ed to test the effects of an early home recovery information intervention on physical functioning , psychological distress , and symptom frequency 1 month following coronary artery bypass graft surgery ( CABG ) . Recovery outcomes were compared between two groups : those receiving an audiotape of information on expected physical sensations and their management ( Cardiac Home Information Program [ CHIP ] ) in addition to the usual care , and those receiving the usual cardiac discharge information protocol . A nonprobability sample of 180 patients ( 84 women and 96 men ; mean age = 62 years ) was equally distributed between the two study groups . When controlling for age , comorbidity , and cardiac functional status , the results showed positive effects on physical functioning in women and psychological distress , vigor and fatigue in men . Consistent with other studies , women had worse physical functioning and more symptom frequency than men . These findings indicate that the CHIP intervention is an effective method to prepare CABG patients for home recovery To determine whether st and ardized instructions enhance communication of discharge information , we provided 197 parents of children in whom otitis media was diagnosed with one of three types of instruction at the time of discharge from a pediatric emergency department : ( 1 ) instruction by individual housestaff and medical students after consultation with an attending physician ( control group ) ; ( 2 ) st and ardized verbal instructions given by housestaff and students trained in their use ( verbal group ) ; or ( 3 ) the same instructions given to the verbal group , together with a type-written copy of the information to take home ( verbal + written group ) . Prior to leaving the emergency department and , again , by phone , 1 and 3 days later , parents were question ed concerning the prescribed medication 's name , dose , frequency , and duration of administration ( medication data ) , three signs of improvement , and eight signs indicating the need for medical advice ( worrisome signs ) . The mean percentage of correct responses per parent in each group was computed for each information category . Both at exit interview and at follow-up , parents receiving either form of st and ardized instructions showed significantly greater knowledge of information related to their child 's illness than did controls . Information regarding medication data was more likely to be communicated to parents in all groups than were signs of improvement or worrisome signs . The addition of written instructions to st and ardized verbal instructions did not improve parental recall of discharge information Abstract Objective : To examine the consistency of survey estimates of patient satisfaction with interpersonal aspects of hospital experience . Design : Interview and postal surveys , evidence from three independent population surveys being compared . Setting : Scotl and and Lothian . Subjects : R and omly selected members of the general adult population who had received hospital care in the past 12 months . Main outcome measures : Percentages of respondents dissatisfied with aspects of patient care . Results : For items covering respect for privacy , treatment with dignity , sensitivity to feelings , treatment as an individual , and clear explanation of care there was good agreement among the surveys despite differences in wording . But for items to do with being encouraged and given time to ask questions and being listened to by doctors there was substantial disagreement . Conclusions : Evidence regarding levels of patient dissatisfaction from national or local surveys should be calibrated against evidence from other surveys to improve reliability . Some important aspects of patient satisfaction seem to have been reliably estimated by surveys of all Scottish NHS users commissioned by the management executive , but certain questions may have underestimated the extent of dissatisfaction , possibly as a result of choice of wording . Key messages High levels of satisfaction with regard to personal treatment by hospital staff , involvement in decisions , and communication with doctors have been reported in successive interview surveys in Scotl and Levels of satisfaction with doctor-patient com- munication and involvement in decisions are sensi- tive to changes in wording Asking patients if they agree with a negative description of their hospital experience tends to produce greater apparent satisfaction than asking if they agree with a positive To evaluate the influence of a modular , multidisciplinary , pediatric burn discharge book on burn-care-related knowledge and satisfaction of caregivers , we studied children less than 17 years of age admitted with an acute thermal injury to the pediatric burn unit of a large , tertiary care hospital in Winnipeg , Canada over a 32 month period . Demographic characteristics of the population are similar to published profiles of other pediatric burn units with the exception that North American Indian ( NAI ) families were disproportionately admitted , with 59 out of the 123 ( 48 % ) admissions from a geographic area that has less than 15 % NAIs . We r and omly assigned the families to receive discharge instructions with the book ( intervention group ) or routine discharge teaching without the book ( comparison group ) . Knowledge levels of burn care and satisfaction with discharge teaching of caregivers were evaluated with a question naire administered in single-blind fashion at the first outpatient follow-up visit . Sixty-two families received the book and 61 families received st and ard discharge teaching . Bivariate analysis showed greater knowledge in the intervention group , with an average score ( range , 0.0 to 1.0 ) of 0.79 + /- 0.15 versus 0.73 + /- 0.15 in the comparison group ( p < 0.05 ) . We did not observe this positive effect of the book when we analyzed NAI families separately : 28 families instructed with the book scored 0.68 + /- 0.14 versus 0.63 + /- 0.13 in 31 families provided with routine teaching ( p = 0.18 ) . Stepwise multiple-regression analysis found that the influence of the book was limited to families with children who sustained scald burns ( p < 0.05 ) . Factors negatively related to the knowledge levels of caregivers ( p < 0.05 ) were being of NAI origin and being NAI with no safety devices in the home . A positive correlation ( p < 0.05 ) was found with having English as the first language , having a child with more extensive burns , having a younger age of the child with burns , and having fewer children in the home . In conclusion , we found that the discharge book improved the burn-care-related knowledge of caregivers . However , other factors , particularly ethnic and language background , were of greater influence PURPOSE The purpose of this study was to test a strategy for improving patient 's retention of discharge teaching . METHODOLOGY A pretest-posttest experimental design was used . Forty postpartum women were r and omly assigned to a group . All subjects received infant feeding instruction until they reached criterion on the Infant Feeding Question naire . The experimental group received additional instruction on the same material ( overlearning ) . The two groups were compared 2 weeks later on the same question naire . Mean scores were compared by a t-test , demographic variables were correlated to outcomes , and effect of race or culture was analyzed by ANOVA . FINDINGS The pretest showed no significant difference between the groups . Posttest scores were significantly higher for the experimental group . The mother 's education was the only demographic variable that was correlated to the results . CONCLUSION Mothers who receive overlearning beyond the mastery level retain significantly more of the material This study examines the contribution of hospital discharge planning in meeting the needs of patients for care after their return home . A r and om sample of 919 admissions ( age 60 and over ) to five hospitals was studied to obtain information on characteristics of discharge planning during the patients ' hospital stay . Specifically , information was obtained on the involvement of a design ated professional for managing and coordinating the discharge plan , and the extent to which the planning was interdisciplinary . Patient interviews conducted two weeks after discharge provided information on needs for care related to : ( 1 ) treatment , ( 2 ) activity limitations , and ( 3 ) other self-sufficiency limitations . Patients were asked about their need for care in these three areas and about whether or not these needs were being met . Overall , 97 percent reported one or more needs for care and 33 percent reported that at least one of these needs was not being met . Findings show that the involvement of a discharge planning case manager is related to a significant reduction in unmet treatment needs , but not to reductions in activity limitation , other self-sufficiency needs , or overall needs . No significant effects of interdisciplinary planning were identified . These findings suggest that treatment-related benefits result when a case manager has specific responsibility for the discharge planning of elderly patients returning home after hospitalization . These results provide insights into what is being achieved through current discharge planning practice s. The meeting of specific patient needs through enhanced discharge planning may save future costs by reducing the rates of complications and hospital readmissions in an era of prospect i ve payment , thus potentially off setting the increased costs involved in planning and coordinating postdischarge care for older adults Objectives : To assess the impact of information packs on patients with stroke and their carers , and to pilot some of the methodology for a trial of a Family Support Organiser ( FSO ) . Subjects : Seventy-one patients admitted to Oxford hospitals with acute stroke during February – July 1995 , and 49 informal carers of these patients . Design : R and omized controlled trial . Intervention group received an information pack containing various Stroke Association publications one month after their stroke , or at discharge from hospital , whichever was sooner . Control group received nothing . Follow-up was by interview at the place of residence of the patients six months after their stroke . Measures : Outcome measures assessed knowledge about stroke ; satisfaction with information received ; patient behaviour in terms of access to community services and benefits ; and health status and quality of life . Results : Patients and carers in the intervention group tended to know more about stroke , but these differences were not significant once adjusted for age . Patients in the intervention group ( but not carers ) tended to be more satisfied with the information that they had received , but the differences were not significant . There were no differences with regard to any aspects of quality of life in patients in the intervention group , though carers in the intervention group were found to have significantly better mental health ( p = 0.04 ) . Conclusions : While the study was too small to generate firm conclusions , information leaflets may lead to improved knowledge about stroke several months after they have been distributed . This finding is worth following up with larger studies . The stroke knowledge question naire that was piloted in this trial seems to be able to detect differences between groups BACKGROUND Discharge planning is becoming an important part of the management of childhood asthma in hospital . Readmission to hospital , although often inevitable , might represent a failure of the opportunity for intervention presented by a brief period of supervised care in hospital . AIM To examine the impact of a structured , nurse-led discharge package for children admitted to hospital with acute asthma on readmission to hospital , reattendance at the accident and emergency ( A&E ) department , and general practitioner consultations for asthma . METHODS A structured nurse-led discharge package , consisting of a 20 minute patient education programme and self management plan for children with asthma was developed on the wards of a busy children ’s hospital . A r and omised controlled trial was conducted involving 160 children aged 2–16 years admitted for asthma over a 12 month period . Readmission and A&E reattendance ’s over the six months after discharge from hospital were obtained from the hospital computerised information system and general practitioner consultations from practice records . RESULTS Children in the intervention group were significantly less likely to be readmitted to hospital in the next six months than those in the control group ( 12 of 80 v30 of 80 patients ) , and significantly less likely to attend the A&E department ( 6 of 80 v 31 of 80 ) . Significantly fewer children in the intervention group had visits to their general practitioner for problematic asthma ( 31 of 78v 72 of 77 for whom data were available ) . CONCLUSION By delivering the simplest form of education and support during a child ’s stay in hospital , readmissions over a six month period were reduced . The programme was design ed to be suitable for administration by nursing staff on the children ’s wards after a brief period of training AIMS To investigate how seamless pharmaceutical care could be delivered . METHODS Elderly patients discharged from hospital , to their own home , were r and omized into control and study groups . Control and study group patients received the normal discharge information . The study group were also counselled about their medicines and informed about their pharmaceutical care plan . Copies of the plan were given to the study patients . All patients received a domiciliary visit between 7 and 10 days after discharge . Their current medication was compared with that on discharge and contact was made with the General Practitioner as appropriate . RESULTS Twenty-eight study and 25 control patients with a mean ( s.d . ) age of 77.5 ( 7.3 ) and 77.6 ( 6.1 ) years completed the study . A pharmaceutical domiciliary visit was necessary for 21 ( 75 % ) and 24 ( 96 % ) of the study and control patients respectively . Compliance was better ( P < 0.01 ) in the study group . Unintentional changes to the medication of 31 ( 14 study and 17 control ) patients were found during the visit and after contact with the prescriber all but one prescription was restored to that on discharge . CONCLUSIONS At present it is difficult to ensure seamless pharmaceutical care . A pharmaceutical domiciliary visit may be useful to ensure seamless therapeutic care and thus avoid unnecessary healthcare events and costs after a patient is discharged home BACKGROUND Medication adherence by older adults who are discharged from the emergency department ( ED ) is an essential attribute of effective treatment . Research ers have demonstrated that delivery of well-structured instructions increases the knowledge of discharge regimens and increases adherence among ED population s. OBJECTIVES This study compared the level of medication knowledge of elderly ED patients receiving instruction by one of two teaching methods : the usual preprinted discharge instructions with h and written medication information and individualized computer-generated discharge instructions design ed within a geragogy framework . METHOD The geragogy intervention included large-print , easily readable , specific information ordered within the elderly memory schema . This schema consists of purpose , administration , and emergency information in that order . The Knowledge of Medication Subtest by Horn and Swain ( 1977 ) was administered by telephone 48 to 72 hours after discharge . Sixty patients ( 38 women , 22 men ) with a mean age of 76 years were r and omly assigned to groups and completed the study at three rural ED sites . RESULTS Subjects in the geragogy-based intervention group demonstrated significantly more knowledge of medications than did subjects experiencing the usual discharge teaching method ( t = 2.19 , p = .016 ) . CONCLUSIONS These findings suggest that a medication teaching intervention geared to the special needs of the elderly can be effective in increasing medication knowledge A widely recognized problem in the mental health services delivery system is that of patients ' early discontinuance of therapy . But less attention has been given to the high rate of nonattendance at initial appointments in outpatient mental health setting s. The purpose of the study discussed in this article was to determine if particular predischarge interventions had an effect on whether psychiatric patients attended their initial aftercare appointments at a Veterans Administration mental health clinic . Two groups of patients were given predischarge interventions and one was not ( a control group ) . Results showed a trend of greater attendance at initial aftercare appointments by those who received a predischarge intervention ; however , the differences were not statistically significant . Suggestions for clinicians and research ers are provided The purpose of this intervention study was to evaluate educational protocol s to see which would be more effective in increasing medication compliance rates within an elderly population . Forty-two patients were r and omized into four groups . Group 1 received a st and ard education protocol ; group 2 received the st and ard education and 30 minutes of verbal instruction ; group 3 received the st and ard education and a medication schedule ; and group 4 received the st and ard education , a medication schedule , and 30 minutes of verbal instruction . The intervention was given on the day of hospital discharge . Home visits were made 2 weeks , 1 and 2 months post-hospital discharge . Results of the visits revealed that groups 1 and 2 had higher rates of errors with medications than groups 3 and 4 . In conclusion , the groups with a medication schedule had higher compliance rates . Considering the sample size of 42 , this study can act as a pilot study to justify further research in the effects of a medication schedule on compliance Prescription information leaflets ( PILs ) for penicillins , diuretics and benzodiazepines were evaluated in a small Hampshire town . A second town , in which no leaflets were distributed , acted as a control . Knowledge about these medicines was greater amongst the 252 patients who received leaflets compared with 247 controls . Significantly more patients who received leaflets knew the potential side-effects of their treatment and , with the exception of those taking penicillins , were more satisfied with the information they received . These findings add further support for the routine use of PILs in general practice OBJECTIVE To evaluate the effect of cartoon illustrations on patient comprehension of and compliance with ED release instructions . METHODS A prospect i ve , r and omized , controlled study of consecutive patients who presented to the ED of a community teaching hospital with lacerations necessitating wound repair during a three-month study period . At ED release , the patients were r and omly assigned to receive wound care instructions with or without cartoon illustrations . Three days later , the patients were followed up by telephone . A blinded investigator asked a series of questions design ed to test the patient 's recall of , underst and ing of , and compliance with wound care instructions . RESULTS A total of 234 patients were successfully contacted by telephone ; 105 ( 45 % ) had been given ED release instructions with cartoons , 129 ( 55 % ) , without cartoons . There was no significant difference in age , gender , level of education , or satisfaction with the ED visit between the two groups . The patients given cartoon instructions were more likely to have read the instructions ( 98 % vs 79 % , p < 0.001 ) , were more likely to answer all wound care questions correctly ( 46 % vs 6 % , p < 0.001 ) , and were more compliant with daily wound care ( 77 % vs 54 % , p < 0.01 ) . Subset analysis of those patients who had less than a high school education ( n = 57 ) demonstrated even larger differences between the two treatment groups in terms of comprehension of and compliance with ED release instructions . CONCLUSION Cartoon illustrations are an effective strategy for conveying information and may improve patient compliance with ED release instructions |
10,773 | 23,690,511 | Descent rates were similar among studies comparing laparoscopic and open surgeries .
Reported harms of hormonal treatments were mild and transient .
Adverse effects specifically associated with surgical repair were rare .
Hormonal treatment is marginally effective relative to placebo but is successful in some children and with minimal harms , suggesting that it may be an appropriate trial of care for some patients .
Surgical options are effective , with high rates of testicular descent ( moderate strength of evidence for FS procedures , high for primary orchiopexy ) .
Comparable outcomes occur with laparoscopic and open approaches | BACKGROUND AND OBJECTIVE : Controversy remains concerning the optimal treatment approach for cryptorchidism .
The objective of this study was to assess effectiveness of hormone therapy or surgery for cryptorchidism . | A double-blind , placebo-controlled study of the efficacy of LH-RH nasal spray in treatment of cryptorchidism involving 252 prepuberal boys with 301 undescended testes , showed a success rate of 9 % ( 14 testes ) for LH-RH and 8 % ( 10 testes ) for placebo . Including a subsequent open study and a second course of LH-RH as required , the rate for LH-RH rose to 18 % ( 48 testes ) . The follow-up period saw late descent in another 5 % ( 14 testes ) , in a few cases coinciding with the onset of puberty . Retrospective evaluation revealed a previous scrotal position of the testes for 43 % of the boys with success of treatment and even for 17 % of the boys with failure of treatment . In many of these cases surgery revealed an anatomical anomaly that might have caused testicular ascent . Hormonal evaluation revealed no abnormalities in cryptorchid boys compared with control subjects , nor was there a divergence in values before and after treatment . The lower the pretreatment testicular position , the better the rate of success OBJECTIVE To compare orchiopexy by laparoscopy versus traditional surgical technique in patients with an undescended palpable testicle in the inguinal canal . MATERIAL S AND METHODS A prospect i ve , comparative , observational , longitudinal , and double-blind research was done between August 2006 and March 2009 in the Centro de Especialidades Médicas del Estado de Veracruz , " Dr. Rafael Lucio " ; 63 patients underwent surgery , age 1 - 10 years , all with the diagnosis of palpable undescended testicle in the inguinal canal ; in 33 patients , the traditional surgical technique and in 30 patients laparoscopy were done . A visual analogue scale ( VAS ) was used to evaluate post-surgery pain . A testicle ultrasound was practice d before surgery and at 6 months after it . RESULTS The majority of patients were 1 - 4 years old with a median age of 2.3 years ; 51 cases were unilateral and 12 cases were bilateral ; 37 testicles were descended with the open traditional surgical technique and 38 through laparoscopy ( 75 testicles ) ; 44 on the right side and 31 on the left side ; there was a hernia associated with 37 undescended testicles , 23 with open surgical technique , and 14 by laparoscopy , without relapsing in any patient . The median surgery time with the open surgical technique was 38 minutes and by laparoscopy , it was 45 minutes . The gobernaculum testis was sectioned by laparoscopy in 23 descended testicles to facilitate the procedure , in the remaining 11 it was not necessary ; whereas in the open technique , all the gobernaculum testis were sectioned . In 80 % of cases , the laparoscopy caused less pain when compared with the other technique . All patients regardless of the technique used left hospital during the first 24 hours . All have had follow-up for more than 6 months with a median of 18 months , with satisfactory results in relation to size and location of the testicle , with a good ultrasound correlation , and not finding any statistical differences between surgical techniques . There were no accidents with any of the techniques , and 1 patient with the open technique had an important hematoma ; hemophilia was later diagnosed in the patient . The esthetical aspect was better with laparoscopy , but the cost was 15 % more expensive with the open technique . CONCLUSIONS Both techniques had satisfactory results without any significant differences to make us choose one over the other . It is the surgeons ' decision based on experience and training on laparoscopy to choose any of the techniques INTRODUCTION Infertility is the primary concern for boys with uni- or bilateral undescended testes . An early and seemingly successful orchiopexy does not improve fertility in a substantial number of cryptorchid males . We confirmed that LH-RH analogue ( LH-RHa ) treatment induces an increase in and maturation of the germ cells ; however , it was uncertain if treatment would improve the chance of fertility later in life . MATERIAL S AND METHODS Thirty unilateral cryptorchid boys , with an average age of 3 years at the time of surgery , were included in the study . Testicular biopsy showed that they had impaired testicular maturation and were therefore at high risk for infertility . Fifteen of the 30 unilateral cryptorchid boys were treated with 10 microg LH-RHa ( Buserelin ) nasal spray , administered on alternate days for a period of 6 months , following orchiopexy . The control group consisted of 15 cryptorchid boys who had been treated by Schoemakers type of orchiopexy , alone . After puberty , the ejaculates of both groups were analyzed . RESULTS All males in the untreated group were severely oligospermic , with 20 % being azoospermic . In contrast , 86 % of the treated ex-cryptorchid males had a sperm concentration within the normal range ; this was significantly different from the sperm concentration found in the untreated group ( p=0.000008 ) . CONCLUSION For the first time , we demonstrate that infertility in cryptorchidism can be successfully corrected when suitably treated with a LH-RHa . Sperm parameters normalized following therapy in the majority of cryptorchid males who , untreated , would have remained infertile . This innovative hormonal treatment will have a profound effect on the current recommended surgical treatment of boys with undescended testes Two courses of LHRH nasal spray ( 400 micrograms three times a day for 28 days ) , partly administered in a double-blind placebo-controlled study , result ed in the descent of 48 of 281 testes ( 18 % ) in 237 prepuberal boys . Logistic regression analysis confirmed the clinical observation that pretreatment testicular position was the major factor influencing treatment results : the lower the pretreatment testicular position , the better the result . Of the unsuccessfully treated boys , 170 with 196 undescended testes subsequently underwent orchiopexy revealing anatomic anomalies that accounted for failure of hormonal treatment in 80 % of the cases . Most frequent finding amounted to an underdeveloped processus vaginalis , extending no further than the level of the pubic bone , often associated with major epididymal deformities and a lack of obliteration of the processus vaginalis ( 107 of 196 operations ) . Obstruction of the scrotal entrance due to abnormal Scarpa 's fascia or abnormal gubernacular remnant was found in 35 and testicular absence in 15 cases . LHRH nasal spray might be effective when the testis can be manipulated to at least the scrotal entrance before treatment , but in view of our surgical findings , LHRH nasal spray will not replace orchiopexy This r and omized double-blind placebo-controlled study was initiated to analyze the behavior of epididymis , processus vaginalis and testicular descent in cryptorchid boys treated with a low dose ( 20 μg ) of a luteinizing hormone-releasing hormone analogue ( Buserelin ) , administered daily , as a nasal spray , for a short period ( 28 days ) . Fifty-nine true cryptorchid boys were r and omly assigned to 3 groups : buserelin , treatment [ 22 ] , surgical treatment [ 18 ] or placebo control group [ 19 ] . The 3 groups of patients were similar before treatment in regard to testicular position , chronological and bone age , height and weight , luteinizing hormone , follicle-stimulating hormone , testosterone , penile size and the volume of the contralateral descended testis . None of the patients had retractile testes . Buserelin significantly induced testicular descent compared to the boys treated with a placebo ( P<0.01 ) . A normal epididymis was found more often in boys with successful descent ( P<0.003 ) . A closed processus vaginalis was also more frequently observed in the group treated with buserelin than in surgically treated one ( P<0.05 ) . In conclusion , buserelin was capable of inducing testicular descent besides provoking further development of the epididymis and closing the processus vaginalis The effect of intranasal , synthetic LH-RH ( Hoe 471 ) on undescended testes was investigated in : I. a double blind study comprising 50 patients given either placebo or 0.6 mg LH-RH daily and II . an open study comprising 50 patients with a daily dosage of 1.2 mg LH-RH . In both studies LH-RH was given for 4 weeks . Since some patients had bilateral undescended testes , 116 testes were treated in total . Patients ' ages varied between 11/2 and 101/2 years , with a mean of 5 years . Clinical examination before , during and at end of treatment was performed by both the authors independently . In the placebo group , one testicular descent was seen , indicating difficulty in diagnosis . A therapeutic result , i.e. a significant move from the pretreatment location towards the bottom of the scrotum was seen in 60 % of the testes , complete descent being seen in about 40 % . In a follow-up study 6 months after treatment , in 23 cases with complete descent from a pretreatment inguinal position , relapse was seen in 5 patients ( 2 were located at scrotal neck , 3 at the pretreatment position i.e. inguinal ) . The best results were seen on testes located not too far from the scrotal neck , with the higher dosage of LH-RH and in patients less than 6 years of age . No significant hormonal changes ( testosterone-,LH-or FSH-levels in peripheral blood ) were seen during the study . Side effects were negligible Purpose We prospect ively evaluated the surgical outcomes of single scrotal incision orchiopexy in children with a palpable undescended testis compared with the traditional two incision orchiopexy . Material s and Methods A total of 398 orchiopexies ( 292 children ) were included and r and omly assigned to the single scrotal incision orchiopexy group ( Group I , 147 children , 201 testes ) or the traditional inguinal incision orchiopexy group ( Group II , 145 children , 197 testes ) . The final number of patients enrolled ( excluding those lost to follow-up ) was 107 children ( 146 testes ) in group I and 105 children ( 141 testes ) in group II . Success was defined as no complications , postoperative intrascrotal location of the testis , and no conversion to the traditional inguinal approach . Surgical outcomes and complications were compared between the two groups . Testicular location , complications , and subjective satisfaction rate were assessed at the follow-up evaluation at least 12 months postoperatively . Results The overall success rate in group I was 92.5 % in 135 of 146 testes ; the remaining 9 testes required conversion to traditional two incision orchiopexy . In group II , orchiopexy was successful in 136 of 141 testes ( 96.5 % ) . The operation time and hospital stay were significantly shorter in group I ( 40.5±25.9 minutes , 2.1±0.8 days ) than in group II ( 62.3±35.6 minutes , 2.5±0.7 days ) , respectively ( p<0.001 , p=0.03 ) . Postoperative complications were found in two cases ( hematoma , wound dehiscence ) in group I and in one case ( wound dehiscence ) in group II ; all cases with complications recovered with conservative care . The subjective rate of satisfaction with the cosmetic result was 96.6 % in group I and 96.5 % in group II ( p=0.97 ) . Conclusions We conclude that single scrotal incision orchiopexy is a simple technique that is associated with a shorter operation time and hospital stay than the traditional method and that is more feasible cosmetically Fifty unilaterally cryptorchid boys aged 3 to 8 years were r and omly and blindly allocated to treatment with luteinizing hormone releasing hormone or placebo intranasally . In the treated group , no significant descent of the undescended testis was found , whereas a minor downward movement of the scrotal testis occurred ( P less than 0.001 ) , probably as a result of decreased retraction by the cremaster muscle . Basal serum testosterone concentrations and testicular volume increased after treatment ( P less than 0.01 and P less than 0.001 , respectively ) . The response to an acute LHRH test , 100 micrograms/m2 body surface IV , before and after treatment , showed an increase in the luteinizing hormone peak value and a decrease in the follicle-stimulating hormone response in a significant number of patients ( P less than 0.001 ) . In the individual patient , there was a positive correlation between the increase in basal serum testosterone concentration and the degree of downward movement of the undescended testis ( P less than 0.05 ) PURPOSE Laparoscopic assessment of pelvic anatomy has gained wide popularity over the years . Today surgical treatment of impalpable testis is nearly always preceded by diagnostic laparoscopy . The actual role of such a procedure remains undefined . We performed a prospect i ve r and omized clinical trial in patients with impalpable testis to evaluate the clinical usefulness of laparoscopy before surgical exploration . MATERIAL S AND METHODS We studied pediatric , age matched patients with impalpable testis who were r and omized to group 1 - 30 who underwent open surgery only and group 2 - 31 who underwent laparoscopy and open surgery . Anatomical findings , operative procedures , operative time and cost , number of recurrences and testicular volume at followup were then compared in the 2 groups . RESULTS There were no statistically significant differences in the 2 groups for any of the considered parameters except operative cost and time , which were significantly higher in the laparoscopy group . CONCLUSIONS Preoperative laparoscopy does not provide any significant advantage over open surgery for treating impalpable testis In a double‐blind placebo‐controlled study in 49 boys with cryptorchidism the effect of intranasal synthetic LHRH was studied . After 8 weeks improvement in testicular location was found in 13 testes ( 37 % ) , but this improvement was considered sufficient of only six testes . Placebo result ed in an improved location in 18 % of the testes . The mean change in testicular position ( expressed in cm ) after LHRH therapy was slightly greater than after placebo but only in the squatting position did this difference reach significance . Aggressive behaviour was reported in 23 % of the children treated with LHRH . A second LHRH course did not result in significant improvement in any of the patients . At follow‐up reascent was frequently seen . The final results in unilateral cryptorchidism are poorer than those in bilateral cryptorchidism . LHRH therapy leads to higher plasma LH levels and a lower FSH in response to an intravenous LHRH test . In 15 boys plasma testosterone levels rose above 0.4 nmol/1 . We conclude that intranasal LHRH application has a limited value for the treatment of cryptorchidism but may be suitable as a diagnostic test OBJECTIVE To assess the outcome of laparoscopic orchiopexy and the two-stage Fowler Stephens technique for managing patients with impalpable testis in terms of safety , feasibility and efficacy . PATIENTS AND METHODS This study included 78 patients who presented with 88 non-palpable testes to the outpatient clinic of Sohag university hospital in 2005 - 2009 , and underwent laparoscopy by the same surgeon . Intra-abdominal testes were managed by laparoscopic orchiopexy if low , two-stage Fowler-Stephens technique if high , and orchiectomy if atrophic . Children were evaluated postoperatively to check the location and size of the testicle and to exclude any other complication . RESULTS Median age at presentation was 16 months ( range 11 - 42 months ) . Four testes were absent while inguinal exploration was necessary for six testes with the vas entering the internal ring . Of the 78 intra-abdominal testes , 45 were identified as high ( Fowler-Stephens in 43 ; orchiectomy in two atrophic testes ) and 33 as low ( orchiopexy ) . Follow up was 3 - 55 months ( mean 34 months ) . Twelve patients ( 12 testes ) were lost to follow up ( 7 Fowler-Stephens ; 5 orchiopexy ) . On follow up , the testes were normal sized and well positioned in the scrotum in 28/28 and 32/36 testes in the orchiopexy and Fowler-Stephens groups with an overall success rate of 100 % and 88.8 % , respectively . Two testes showed testicular displacement and two showed testicular atrophy in patients of the Fowler-Stephens group . CONCLUSION Laparoscopy provides a safe and accurate modality for diagnosing and managing patients with non-palpable testes , with excellent outcomes In a double-blind , placebo-controlled study , 252 prepubertal boys with 301 undescended testes were treated with luteinising-hormone-releasing-hormone ( LHRH ) , 1.2 mg/day intranasally . After the 8-week double-blind period 10 placebo-treated ( 8 % ) and 14 LHRH-treated ( 9 % ) testes had completely descended . After a second LHRH course , involving all the subjects in an open study , 48 testes ( 18 % ) had descended completely . The lowest success rate ( 7 % ) occurred in the youngest age group ( 1 - 2 years ) . Of the successfully treated testes , 75 % could be manipulated at least to the scrotal entrance before treatment . In comparison with age-matched controls , the cryptorchid boys ' responses to LHRH and human chorionic gonadotropin before treatment did not suggest a deficient hypothalamo-pituitary-gonadal axis or deficient Leydig cell function . After treatment there was no evidence of stimulation of the hypothalamo-pituitary-gonadal axis ; serum testosterone did not increase . Surgery was required in 170 patients ( 196 testes ) revealing various anatomical anomalies INTRODUCTION Orchidopexy is one of the most common pediatric surgeries . In general , the operation for truly undescended testis ( UDT ) includes opening of the external oblique fascia . The most common location of the testis in UDT is adjacent to the external inguinal canal ( superficial inguinal type ) . Using a new method we performed orchidopexy without opening the fascia . In this clinical trial we compared the outcome after a classic procedure with that obtained using our method . METHODS AND PATIENTS This clinical controlled trial was undertaken in the Al Zahra hospital between 2008 and 2010 . Patients were r and omized into either into the closed technique group ( group A , n=52 ) or the open group ( group B , n=52 ) . The incidence of short-term and long-term complications was recorded with a specific question naire at the time of surgery and at follow-up visits . Data were analyzed with the SPSS 15.0 software using chi-square and t-tests . RESULTS 104 patients were included in this study . The incidence of short-term complications ( surgical site hematoma , surgical wound infection , scrotal hematoma ) and long-term complications ( testicular atrophy ) did not differ significantly between the 2 groups . Procedure duration in group A was significantly shorter than in group B ( p=0.001 ) . Medial thigh sensory loss was more common in group B ( p=0.05 ) . CONCLUSION When investigating the surgical management of undescended testes , our study found differences in medial thigh sensory loss rate and procedure duration between the open and closed techniques . Operative treatment of UDT without opening the external oblique fascia is highly recommended We have conducted a modified double-blind study on the effect of human chorionic gonadotropin ( hCG ) , gonadotropin releasing hormone ( GnRH ) and placebo on bilateral and unilateral maldescended testes . One hundred and fifty-five boys with bilateral and 88 boys with unilateral cryptorchidism fulfilled the inclusion criteria and completed the treatment protocol . The boys were between 1 and 13 years of age . hCG was administered as intramuscular injections twice weekly for 3 weeks . GnRH and placebo were given intranasally . hCG was superior to GnRH and placebo in the treatment of bilateral maldescended testes ( p = 0.0009 ) . Both testes descended in 25 % of the boys following treatment with hCG , and improvement in the position of the testes was obtained in a further 25 % of the cases . hCG administration result ed in complete testicular descent in 14 % of boys with unilateral cryptorchidism compared with 3 and 0 % after placebo and GnRH , respectively ( p = 0.07 ) . The testis had moved to a more distal position in 46 % of the boys treated with hCG . There was no significant difference between the treatment groups with regard to age or initial position of the testes . We conclude that a success rate of 25 % justifies the use of hCG in the treatment of maldescended testes , whereas the study did not support a general use of GnRH administered intranasally AIMS Treatment of patients with abdominal non-palpable testis ( NPT ) is still controversial among pediatric urologists . This is a prospect i ve r and omized comparative study between open and laparoscopic orchiopexy for management of abdominal testis . The aim of this study was to evaluate the success rate and morbidity of both approaches . METHODS Eighty-two patients with a mean age of 5.3 years were evaluated by laparoscopy for 87 NPT . Patients with viable abdominal testes were r and omly treated with either open or laparoscopic orchiopexy procedures . RESULTS On laparoscopy , 75 viable abdominal testes were found . According to location : 41 ( 47.1 % ) testes were high abdominal , 27 ( 31 % ) testes were low abdominal and 7 ( 8 % ) testes were peeping from the internal ring . Laparoscopic first stage Fowler-Stephens orchiopexy was done initially for those with high abdominal testes . For further management , all patients were divided r and omly into open ( 36 cases ) and laparoscopic ( 39 cases ) groups where primary ( with spermatic vessel preservation ) or second stage Fowler-Stephens orchiopexy was done . Statistical analysis was done using Student 's t-test . Laparoscopic procedures showed significant less morbidity than the open counterparts . Follow up ranged from 9 to 31 months and included evaluation of testicular site and size . All testes were located satisfactorily inside the scrotum . Five cases of testicular atrophy were encountered ( three and two testes with open and laparoscopic second stage Fowler-Stephens orchiopexy respectively ) after 1 year follow up . CONCLUSION Results of open versus laparoscopic orchiopexy procedures ( primary or staged ) are fairly comparable . However , laparoscopy provides significantly less morbidity In a double-blind , placebo-controlled multicentre study , the effect of luteinizing-hormone-releasing-hormone ( LHRH ) in 141 boys was analysed after 4-week treatment period with 0.4 mg LHRH nasal spray or placebo nasal spray three times daily . Data from 123 boys was analysed , with 62 boys in the treatment group and 61 in the placebo group . Full response i.e. the testis at the bottom of the scrotum on both sides in boys with bilaterally undescended testes , was found in six patients , one of them in the placebo group [ Therapeutic gain of LHRH with 95 % CI : 8.1 % ( 0.1 - 16.6 % , P = 0.12 ) ] . Only in these boys could surgery be avoided . Considering the number of testes ( and not the number of boys ) a significant effect was found on at least one testis in 25 % of boys with bilaterally undescended testes [ Therapeutic gain with 95 % CI : 24.0 % ( 13.2 - 34.8 % , P = 0.001 ) ] . In unilateral undescended testes , the LHRH treatment showed no effect ( P = 1.00 ) . The inclusion of retractile testes did not affect our results . In our opinion LHRH has a limited place in treatment of the non-descended testis We conducted a r and omized , double-blind study comparing intranasal gonadotropin-releasing hormone ( 1.2 mg per day for 28 days ) with parenteral human chorionic gonadotropin ( 3300 IU per week for four weeks ) in the treatment of cryptorchidism in 33 boys one to five years old ( 29 with unilateral and 4 with bilateral cryptorchidism ) . Testicular descent into the scrotum occurred in 3 of the 16 patients ( 19 percent ) treated with gonadotropin-releasing hormone and in 1 of the 17 ( 6 percent ) treated with human chorionic gonadotropin ( P = 0.23 ) . The mean luteinizing hormone and testosterone levels were similar in both groups before treatment . During treatment , the testosterone levels were significantly increased in both groups , but higher levels occurred in the group treated with human chorionic gonadotropin ( P less than 0.05 ) . In a parallel ( but uncontrolled ) study of five boys with retractile testes ( defined as a nonscrotal testis that could be manipulated into the bottom of the scrotum ) who were originally excluded from the main protocol but were treated with the same regimen of human chorionic gonadotropin , descent into the scrotum occurred in all patients . We conclude that hormonal therapy with either gonadotropin-releasing hormone or human chorionic gonadotropin is , in most cases , ineffective in promoting testicular descent of true cryptorchid testes . However , short-term treatment with human chorionic gonadotropin is very effective in producing descent of retractile testes . These results suggest that the wide discrepancies in apparent efficacy in previous trials of hormonal therapy of cryptorchidism may have been due to inclusion in those studies of various proportions of patients with retractile testes The oligospermia observed after unilateral torsion of the spermatic cord could reflect immunological damage to the opposite testis . An alternative explanation , that there may be a pre‐existing defect in spermatogenesis , was tested in 20 post‐pubertal males with acute torsion . In a prospect i ve study the contralateral testis was biopsied at operation and the histological appearances were related to subsequent testicular function as assessed by seminal analysis 3 months later . Thirteen patients had biopsy evidence of partial maturation arrest in spermatogenesis which was either mild ( 6 ) , moderate ( 4 ) or severe ( 3 ) , and ten of these were oligospermic ( < 20 × 106/ml ) . By contrast all seven patients with normal histology had a sperm concentration gt ; 25 × 106/ml . Histological grading of spermatogenesis by the Johnsen technique gave a higher score in patients with a normal biopsy ( median 9·01 , semi‐quartile range 8·96–9·21 ) than in those with abnormal histology ( median 8·28 , semi‐quartile range 7·98–8·45 , P < 0·001 ) and correlated with the log of the sperm concentration 3 months later ( r = 0·79 , P < 0·001 ) . There was minimal anti‐sperm and no anti‐testis antibody formation following torsion . Serum FSH levels were raised in 6 of 10 oligospermic patients , while all those with a normal sperm count had FSH concentrations within the normal range . Thus many patients who develop testicular torsion have an underlying defect in spermatogenesis , which correlates closely with poor postoperative exocrine function Objective : We aim ed to compare the three techniques of dartos pouch orchiopexy , suture fixation to the scrotal wall and narrowing of the neck of pouch with or without suture fixation , in regard to the postoperative ascensus of testes . Material s and Methods : We operated on 150 unilateral palpable undescended testis with the scrotal pouch orchiopexy technique . In this prospect i ve study , patients were r and omly divided into three groups : Testes were fixed to the scrotal wall in the first group , they were placed into the scrotal pouch without fixation but the neck of the dartos pouch was narrowed around the vas deferens and the vessels in the second group and testes were fixed to the scrotum with a suture and the dartos fascial opening was narrowed concomitantly in the third group . Results : Patients were followed between 6 and 48 months ( 28.0 - 11.4 ) . Only four testes of the first group ( 8.0 % ) were replaced upward after the operation where all the other two groups ' testes were in their places . Conclusion : We believe that only narrowing of the dartos fascia around the vas deferens and vessels without fixation to the scotum prevents ascending of the testis upward after orchiopexy operations . We think this technique decrease the risk of supposed damage to the testicular tissue due to suture material OBJECTIVE To compare the effects of medical therapy on boys with cryptorchidism , a prospect i ve study was carried out in five groups of patients over a 30-month period . MATERIAL AND METHODS A total of 439 boys with undescended testicles were enrolled ; their ages ranged between 6 months and 13 years ( median 4.2 years ) . Of these , 327 had true unilateral and 112 bilateral undescended testicles . In 115 patients surgery was performed directly either because the condition was associated with inguinal hernia or because the child had undergone previous inguinal surgery ; hormonal treatment was attempted in the remaining 324 patients . Human chorionic gonadotrophin ( hCG ) was administered to 113 patients ( 34.8 % ) , luteinizing hormone-releasing hormone ( LH-RH ) to 85 ( 26.2 % ) , a combination of LH-RH and hCG to 64 ( 19.7 % ) , human menopausal gonadotrophin ( hMG ) to 35 ( 10.8 % ) and a combination of hMG and hCG to 27 ( 8.3 % ) . RESULTS Overall , testicular descent was achieved in 27.7 % ( 90/324 ) of patients : specifically , in 38.2 % ( 36/94 ) of boys with bilateral undescended testicles ( both testes in 22/36 , one testis only in 14/36 ) but in only 23.4 % ( 54/230 ) of those with unilateral undescended testicles ( p = 0.007 ) . The correlation between the type of therapy and testicular descent can be summarized as follows : hCG , 39/113 ( 34.5 % ) ; LH-RH , 25/85 ( 29.4 % ) ; hCG+LH-RH , 19/64 ( 29.6 % ) ; hCG+hMG , 7/27 ( 25.9 % ) ; hMG alone , 0/35 ( 0 % ) . CONCLUSIONS In our experience , pharmacological treatment seems to yield better results in cases of bilateral than unilateral cryptorchidism . hCG seems to be equally effective as LH-RH for the treatment of cryptorchidism in approximately 30 % of cases ; the combination of these two drugs does not seems to increase the success rate . The use of hMG alone is ineffective . We believe that hormonal treatment can lead to acceptable results in boys with cryptorchidism , without relevant adverse effects The objectives of the study were to determine whether a low dose of a luteinizing hormone-releasing hormone analogue ( buserelin ) has an effect on testicular descent , if buserelin affects germ cell maturation and epididymal development , the incidence of retractile testes in the controlled trials , and if the subsequent administration of human chorionic gonadotropin has any effect on the groups treated . The study was double blind , placebo controlled in which patients with cryptorchidism were assigned r and omly into 3 groups : buserelin treatment ( 22 ) , surgical treatment ( 18 ) or placebo control group ( 19 ) . The 3 groups of patients were similar before treatment in regard to testicular position , chronological and bone age , height and weight , luteinizing hormone , follicle-stimulating hormone , testosterone , penile size and the volume of the contralateral testis . Buserelin ( 20 micrograms ) . administered daily in a nasal spray significantly induced testicular descent compared to the group treated with a placebo ( p less than 0.01 ) . A normal epididymis was found more often in boys with successful descent ( p less than 0.003 ) . Boys treated with buserelin had the highest number and the best maturation index of the germ cells ; human chorionic gonadotropin influenced the descent in both groups but it was more efficacious when it was administered after treatment with buserelin , although it had no additional effect on germ cell maturation . None of the boys had retractile testes . Buserelin was capable of inducing testicular descent in addition to increasing simultaneously the number of germ cells and provoking further development of the epididymis Background : Hormonal treatment of cryptorchidism has been used since the 30s , but controversies persist on its efficacy . It is also unclear whether there are differences with the use of different hormonal trials . Aims : To evaluate the efficacy of four hormonal treatments on testicular descent in a homogeneous group of cryptorchid boys . Patients : 155 patients ( age 10–48 months ) with unilateral inguinal palpable testis were studied . Methods : The patients were subdivided into four groups according to hormonal treatment : group 1 = hCG [ 500 IU/week ( if the chronological age was < 2 years ) or 1,000 IU/week ( if the chronological age was > 2 years ) for 6 weeks ] ; group 2 = hCG + hMG ( hCG as in group 1 + hMG 75 IU/week for 6 weeks ) ; group 3 = GnRH ( 1,200 µg/daily for 28 days ) ; group 4 = GnRH + hCG ( 1,200 µg/daily for 28 days + 1,500 IU/week for 3 weeks , respectively ) . The results were evaluated at the end of the treatment period and 6 months later to exclude temporarily positive results . Results : At the end of the hormonal therapy , scrotal testicular descent was present in 30 of 155 boys ( success rate 19.3 % ) . Seven testes relapsed during follow-up ( 23.3 % ) . The long-term success rate was 14.8 % ( 23/155 testes ) . No significant differences were observed in success rates as well as in relapse rates among the four groups . Conclusions : Hormonal therapy induced permanent testicular descent in a minority of young cryptorchid boys with inguinal palpable testis . Similar results were obtained with four different trials A r and omized study of two protocol s of human chorionic gonadotropin ( hCG ) treatment was performed in 183 prepubertal boys between 7 months and 12 years of age : protocol I , in which the boys were given 7 injections of 1,500 IU every other day , and protocol II consisting of 4 injections of 100 IU/kg at 4- to 5-day intervals . In both protocol s , by the end of the test , testosterone had risen significantly to values within the normal adult male range . However , the amplitude of the rise was slightly but significantly lower using protocol II ( 4.08 + /- 2.07 ng/ml ) than protocol I ( 5.16 + /- 2.73 ng/ml ) . It would thus appear that repetition of the hCG injection at intervals of less than 4 days is unnecessary , and that a total stimulation period of 2 - 3 weeks is sufficient . Although not correlated with testosterone levels , the success rates for treatment were similar in both protocol s and comparable to rates reported in the literature |
10,774 | 25,584,423 | Effective or promising trials include physical activity interventions in South Asian men in Norway and South Asian school-children in the UK .
A home-based , family-orientated diet and physical activity intervention improved obesity outcomes in South Asian adults in the UK , when adjusted for baseline differences .
Meta-analyses of interventions in children showed no significant difference between intervention and control for body mass index or waist circumference .
Conclusions : Meta- analysis of a limited number of controlled trials found an unclear picture of the effects of interventions on body mass index for South Asian children .
Meta-analyses of a limited number of controlled trials showed significant improvement in weight for adults but no significant differences in body mass index and waist circumference .
One high quality study in South Asian children found that a school-based physical activity intervention that was delivered within the normal school day which was culturally sensitive , was effective .
There is also evidence of culturally appropriate approaches to , and characteristics of , effective interventions in adults which we believe could be transferred and used to develop effective interventions in children | Background and Aims : The metabolic risks associated with obesity are greater for South Asian population s compared with White or other ethnic groups , and levels of obesity in childhood are known to track into adulthood .
Tackling obesity in South Asians is therefore a high priority .
The rationale for this systematic review is the suggestion that there may be differential effectiveness in diet and physical activity interventions in South Asian population s compared with other ethnicities .
The research territory of the present review is an emergent , rather than mature , field of enquiry , but is urgently needed .
Thus the aim of this systematic review and meta- analysis was to assess the effectiveness of diet and physical activity interventions to prevent or treat obesity in South Asians living in or outside of South Asia and to describe the characteristics of effective interventions . | The aim was to explore the relationships between degree of participation in a culturally adapted lifestyle intervention and stages of change for healthy eating and weight loss among Pakistani immigrant women in Norway . The intervention lasted 7 months and included 198 women , r and omized into control and intervention groups . The odds of losing weight from baseline to follow-up , and being in action stages of change ( compared to pre-action stages ) with regard to intake of amount and type of fat , sugar and white flour at follow-up , increased significantly with number of group sessions attended . Those in action stage of reducing intake of fat and increasing intake of vegetables , as well as of reducing weight , were significantly more likely than others to have experienced weight loss at follow-up . Participation in the culturally adapted intervention was related to increase in intentions to change dietary behaviours and to weight loss This study explored a community-based after-school program ’s effect on obesity in minority children . Study participants included 178 third through fifth grade rs ( 47 % Latino , 25 % Asian , and 18 % African-American ) enrolled in America SCORES Bay Area . Outcomes were attendance , change in fitness ( 20-meter shuttle test ) , and body mass index ( BMI ) z-score over eight months . At baseline , 52 percent of children were overweight or obese . Children attended SCORES > 4 days/week and fitness significantly improved ( p < 0.01 ) . BMI z-score decreased by 0.04 ( p = 0.10 ) overall , and by 0.05 ( p = 0.08 ) among obese children , but increased among African-American children . These results suggest that SCORES increases fitness and may improve BMI in some minority children . Effect modification by race may relate to differential growth patterns or engagement in SCORES . These findings suggest community-based programs could effectively address obesity . A r and omized trial of the SCORES program is warranted to rigorously examine this type of after-school program ’s impact on child health Background South Asian migrants are at particularly high risk of type 2 diabetes . Previous studies have shown that intensive lifestyle interventions may prevent the onset of diabetes . Such interventions have not been culturally adapted and evaluated among South Asians in industrialized countries . Therefore , we have set up a r and omized controlled trial to study the effectiveness of a targeted lifestyle intervention for the risk of type 2 diabetes and cardiovascular risk factors among 18 to 60-year-old Hindustani Surinamese ( South Asians ) in The Hague , the Netherl and s. Here we present the study design and describe the characteristics of those recruited . Methods Between May 18 , 2009 and October 11 , 2010 , we screened 2307 Hindustani Surinamese ( 18–60 years old ) living in The Hague . We sent invitations to participate to those who had an impaired fasting glucose of 5.6 - 6.9 mmol/l , an impaired glucose tolerance of 7.8 - 11.0 mmol/L , a glycated hemoglobin level of 6.0 % or more and /or a value of 2.39 or more for the homeostasis model assessment of estimated insulin resistance . In total , 536 people ( 56.1 % of those eligible ) participated . People with a higher level of education and a family history of type 2 diabetes were more likely to participate . The control and intervention groups were similar with regard to important background characteristics . The intervention group will receive a culturally targeted intervention consisting of dietary counseling using motivational interviewing and a supervised physical activity program . The control group will receive generic lifestyle advice . To determine the effectiveness , a physical examination ( anthropometrics , cardiorespiratory test , lipid profile , and measures of oral glucose tolerance , glycated hemoglobin , and insulin ) and interview ( physical activity , diet , quality of life , and intermediate outcomes ) were carried out at baseline and will be repeated at 1 year and 2 years . The process and the costs will be evaluated . Discussion This trial will provide insight into the feasibility and effectiveness of a targeted , intensive , lifestyle intervention for the risk of type 2 diabetes and cardiovascular risk factors among 18 to 60-year-old South Asians . Trial registration Dutch Trial Register : OBJECTIVE The present study was design ed to assess the impact of intensive and repetitive nutrition education and lifestyle interventions on insulin resistance , β-cell function , disposition index ( DI ) , and sub clinical inflammation in Asian Indian adolescents ( 15 - 17 years ) residing in North India . METHOD In this prospect i ve study , two matched schools were r and omly allocated to the intervention ( n = 56 ; 31 boys and 25 girls ) or control group ( n = 50 ; 30 boys and 20 girls ) . The intervention consisted of seven components : ( 1 ) Dissemination of health-related information through lectures and focused group discussion s , ( 2 ) planning of activities such as quizzes , ( 3 ) individual counseling of students , ( 4 ) promotion of physical activity , ( 5 ) change in the canteen menu to healthier alternatives , ( 6 ) conducting health camps involving parents and teachers , and ( 7 ) training of student volunteers for sustainability of the program in school . Impact of intervention was studied on surrogate markers of insulin resistance , β-cell function , disposition index , and sub clinical inflammation . RESULTS At 6 months follow-up , significantly higher ( P = 0.037 ) mean value of homeostasis model assessment denoting β-cell function ( HOMA-βCF ) was seen in the intervention group compared to the control group , whereas high sensitivity C-reactive protein ( hs-CRP ) was significantly lowered ( P < 0.001 ) . The increase ( 30.3 ± 73.4 ; P < 0.037 ) observed in the DI in adolescents in the intervention group was significantly higher compared to the control group . The Pearson 's coefficient of correlation in the intervention group showed that the Δ-decrease in mean waist circumference was significantly correlated ( r = 0.267 , P < 0.05 ) with Δ-decrease in homeostasis model assessment of insulin resistance ( HOMA-IR ) . CONCLUSION The intervention model developed by us could be used for amelioration of insulin resistance with potential of preventing type 2 diabetes mellitus in Asian Indian adolescents 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 OBJECTIVE Pakistani women in Oslo have high risk of overweight and type 2 diabetes . The objective is to present the effect of an intervention study on Pakistani women 's intentions to change dietary behaviour and changes made in dietary intake . DESIGN The intervention group received culturally adapted lifestyle education , including diet and physical activity . The question naire , applied before and after the 7-month intervention , included FFQ and questions on intentions to change . SETTING Oslo , Norway . SUBJECTS A total of 198 Pakistani women , aged 25 - 63 years , r and omised into control and intervention groups . RESULTS There was a shift in distribution of intentions to change the intake of selected foods in the intervention group after the intervention , result ing in significant differences between the groups . The daily intake of vegetables , fruits and fruit juice had increased ( P = 0.043 ) , and the intake of red meats ( P = 0.001 ) , full fat milk/yoghurt ( P = 0.027 ) and sugar-rich drinks ( P < or= 0.007 ) was reduced in the intervention group . The differences between intervention and control after the intervention were significant for sugar-rich drinks ( P < or= 0.022 ) . More women in the intervention group used olive and rapeseed oil and fewer used ' vegetable ' oil after than before intervention ( P < 0.011 ) . Differences between intervention and control were significant ( P = 0.001 ) for rapeseed oil . Comparing those who attended at least 60 % of the group sessions with the control group result ed in minor changes in these estimates . CONCLUSIONS Culturally adapted education has the potential to change Norwegian-Pakistani women;s intentions to make their diet healthier , and also to induce some beneficial , however modest , self-reported changes in diet Objectives To describe the design and baseline population characteristics of an adapted lifestyle intervention trial aim ed at reducing weight and increasing physical activity in people of Indian and Pakistani origin at high risk of developing type 2 diabetes . Design Cluster , r and omised controlled trial . Setting Community-based in Edinburgh and Glasgow , Scotl and , UK . Participants 156 families , comprising 171 people with impaired glycaemia , and waist sizes ≥90 cm ( men ) and ≥80 cm ( women ) , plus 124 family volunteers . Interventions Families were r and omised into either an intensive intervention of 15 dietitian visits providing lifestyle advice , or a light ( control ) intervention of four visits , over a period of 3 years . Outcome measures The primary outcome is a change in mean weight between baseline and 3 years . Secondary outcomes are changes in waist , hip , body mass index , plasma blood glucose and physical activity . The cost of the intervention will be measured . Qualitative work will seek to underst and factors that motivated participation and retention in the trial and families ’ experience of adhering to the interventions . Results Between July 2007 and October 2009 , 171 people with impaired glycaemia , along with 124 family volunteers , were r and omised . In total , 95 % ( 171/196 ) of eligible participants agreed to proceed to the 3-year trial . Only 13 of the 156 families contained more than one recruit with impaired glycaemia . We have recruited sufficient participants to undertake an adequately powered trial to detect a mean difference in weight of 2.5 kg between the intensive and light intervention groups at the 5 % significance level . Over half the families include family volunteers . The main participants have a mean age of 52 years and 64 % are women . Conclusions Prevention of Diabetes & Obesity in South Asians ( PODOSA ) is one of the first community-based , r and omised lifestyle intervention trials in a UK South Asian population . The main trial results will be su bmi tted for publication during 2013 . Trial registration Current controlled trials IS RCT N25729565 ( http://www.controlled-trials.com/is rct n/ ) Introduction Interventions that make extensive use of theory tend to have larger effects on behaviour . The Intervention Mapping ( IM ) framework incorporates theory into intervention design , implementation and evaluation , and was applied to the development of a community-based childhood obesity prevention intervention for a multi-ethnic population . Methods IM was applied as follows : 1 ) Needs assessment of the community and culture ; consideration of evidence -base , policy and practice ; 2 ) Identification of desired outcomes and change objectives following identification of barriers to behaviour change mapped alongside psychological determinants ( e.g. knowledge , self-efficacy , intention ) ; 3 ) Selection of theory-based methods and practical applications to address barriers to behaviour change ( e.g. , strategies for responsive feeding ) ; 4 ) Design of the intervention by developing evidence -based interactive activities and re sources ( e.g. , visual aids to show babies stomach size ) . The activities were integrated into an existing parenting programme ; 5 ) Adoption and implementation : parenting practitioners were trained by healthcare professionals to deliver the programme within Children Centres . Results HAPPY ( Healthy and Active Parenting Programme for Early Years ) is aim ed at overweight and obese pregnant women ( BMI > 25 ) ; consists of 12 × 2.5 hr . sessions ( 6 ante-natal from 24 weeks ; 6 postnatal up to 9 months ) ; it addresses mother ’s diet and physical activity , breast or bottle feeding , infant diet and parental feeding practice s , and infant physical activity . Conclusion We have demonstrated that IM is a feasible and helpful method for providing an evidence based and theoretical structure to a complex health behaviour change intervention . The next stage will be to assess the impact of the intervention on behaviour change and clinical factors associated with childhood obesity . The HAPPY programme is currently being tested as part of a r and omised controlled feasibility trial 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 Orlistat has been shown to increase adiponectin and reduce progression to type 2 diabetes in obese Caucasians . Some effects of orlistat are thought to be independent of weight loss by altering gut flora and the production of endotoxin lipopolysaccharide ( LPS ) . We studied the effect of dietary treatment with and without orlistat in South Asian individuals with impaired glucose tolerance ( IGT ) on adiponectin and inflammatory markers including LPS . METHODS South Asian individuals were r and omised to either dietary treatment with orlistat or dietary treatment alone . At the end of 12 months , a comparison was made between the two groups for differences in anthropomorphic measurements and serum markers . RESULTS Three hundred and five individuals underwent oral glucose tolerance test of whom 40 had IGT . Complete baseline and 1-year data was available for 31 patients . After 1 year , patients in the orlistat group demonstrated a greater but insignificant decrease in weight ( 4.5 + /- 0.1 kg ) , and a significant increase in adiponectin ( 6.73 + /- 3.2 microg/ml ) and decrease in LPS ( 4.55 + /- 1.98 EU/ml ) compared with- the diet-alone group . In the orlistat group the reduction in LPS was correlated with the increase in adiponectin ( p < 0.005 ) . CONCLUSION The increase in adiponectin levels in the orlistat group would suggest that orlistat may reduce the progression to type 2 diabetes in South Asian individuals by raising serum adiponectin . The finding that LPS levels are also reduced by orlistat and that this reduction correlates with the increase in adiponectin raises the possibility that the increase in adiponectin may be mediated via an effect on LPS levels Aims /hypothesisLifestyle modification helps in the primary prevention of diabetes in multiethnic American , Finnish and Chinese population s. In a prospect i ve community-based study , we tested whether the progression to diabetes could be influenced by interventions in native Asian Indians with IGT who were younger , leaner and more insulin resistant than the above population s. Methods We r and omised 531 ( 421 men 110 women ) subjects with IGT ( mean age 45.9±5.7 years , BMI 25.8±3.5 kg/m2 ) into four groups . Group 1 was the control , Group 2 was given advice on lifestyle modification ( LSM ) , Group 3 was treated with metformin ( MET ) and Group 4 was given LSM plus MET . The primary outcome measure was type 2 diabetes as diagnosed using World Health Organization criteria . Results The median follow-up period was 30 months , and the 3-year cumulative incidences of diabetes were 55.0 % , 39.3 % , 40.5 % and 39.5 % in Groups 1–4 , respectively . The relative risk reduction was 28.5 % with LSM ( 95 % CI 20.5–37.3 , p=0.018 ) , 26.4 % with MET ( 95 % CI 19.1–35.1 , p=0.029 ) and 28.2 % with LSM + MET ( 95 % CI 20.3–37.0 , p=0.022 ) , as compared with the control group . The number needed to treat to prevent one incident case of diabetes was 6.4 for LSM , 6.9 for MET and 6.5 for LSM + MET . Conclusions /interpretationProgression of IGT to diabetes is high in native Asian Indians . Both LSM and MET significantly reduced the incidence of diabetes in Asian Indians with IGT ; there was no added benefit from combining them The objective of the present study was to explore whether a culturally adapted lifestyle education programme would improve the risk factor profile for type 2 diabetes ( T2D ) and the metabolic syndrome ( MetS ) among Pakistani immigrant women in Oslo , Norway . The r and omised controlled trial ( the InnvaDiab study ) , lasting 7 ± 1 months , comprised six educational sessions about blood glucose , physical activity and diet . Participants ( age 25 - 62 years ) were r and omised into either a control ( n 97 ) or an intervention ( n 101 ) group . Primary outcome variables were fasting and 2 h blood glucose , and secondary outcome variables were fasting levels of insulin , C-peptide , lipids , glycated Hb , BMI , waist circumference and blood pressure , measured 1 - 3 weeks before and after the intervention . During the intervention period , the mean fasting blood glucose decreased by 0·16 ( 95 % CI -0·27 , -0·05 ) mmol/l in the intervention group , and remained unchanged in the control group ( difference between the groups , P=0·022 ) . Glucose concentration 2 h after the oral glucose tolerance test decreased by 0·53 ( 95 % CI -0·84 , -0·21 ) mmol/l in the intervention group , but not significantly more than in the control group . A larger reduction in fasting insulin was observed in the intervention group than in the control group ( between-group difference , P= 0·036 ) . Among the individuals who attended four or more of the educational sessions ( n 59 ) , we found a more pronounced decrease in serum TAG ( -0·1 ( 95 % CI -0·24 , 0·07 ) mmol/l ) and BMI ( -0·48 ( 95 % CI -0·78 , -0·18 ) kg/m² ) compared with the control group . During the intervention period , there was a significant increase in participants having the MetS in the control group ( from 41 to 57 % ) , which was not seen in the intervention group ( from 44 to 42 % ) . Participation in a culturally adapted education programme may improve risk factors for T2D and prevent the development of the MetS in Pakistani immigrant women Objective To assess feasibility and acceptability of a multifaceted , culturally appropriate intervention for preventing obesity in South Asian children , and to obtain data to inform sample size for a definitive trial . Design Phase II feasibility study of a complex intervention . Setting 8 primary schools in inner city Birmingham , UK , within population s that are predominantly South Asian . Participants 1090 children aged 6–8 years took part in the intervention . 571 ( 85.9 % from South Asian background ) underwent baseline measures . 85.5 % ( n=488 ) were followed up 2 years later . Interventions The 1-year intervention consisted of school-based and family-based activities , targeting dietary and physical activity behaviours . The intervention was modified and refined throughout the period of delivery . Main outcome measures Acceptability and feasibility of the intervention and of measurements required to assess outcomes in a definitive trial . The difference in body mass index ( BMI ) z-score between arms was used to inform sample size calculations for a definitive trial . Results Some intervention components ( increasing school physical activity opportunities , family cooking skills workshops , signposting of local leisure facilities and attending day event at a football club ) were feasible and acceptable . Other components were acceptable , but not feasible . Promoting walking groups was neither acceptable nor feasible . At follow-up , children in the intervention compared with the control group were less likely to be obese ( OR 0.41 ; 0.19 to 0.89 ) , and had lower adjusted BMI z-score ( −0.15 kg/m2 ; 95 % CI −0.27 to −0.03 ) . Conclusions The feasibility study informed components for an intervention programme . The favourable direction of outcome for weight status in the intervention group supports the need for a definitive trial . A cluster r and omised controlled trial is now underway to assess the clinical and cost-effectiveness of the intervention . Trial registration number IS RCT N51016370 BACKGROUND Delivery of high- quality , evidence -based health care to deprived sectors of the community is a major goal for society . We investigated the effectiveness of a culturally sensitive , enhanced care package in UK general practice s for improvement of cardiovascular risk factors in patients of south Asian origin with type 2 diabetes . METHODS In this cluster r and omised controlled trial , 21 inner-city practice s in the UK were assigned by simple r and omisation to intervention ( enhanced care including additional time with practice nurse and support from a link worker and diabetes-specialist nurse [ nine practice s ; n=868 ] ) or control ( st and ard care [ 12 practice s ; n=618 ] ) groups . All adult patients of south Asian origin with type 2 diabetes were eligible . Prescribing algorithms with clearly defined targets were provided for all practice s. Primary outcomes were changes in blood pressure , total cholesterol , and glycaemic control ( haemoglobin A1c ) after 2 years . Analysis was by intention to treat . This trial is registered , number IS RCT N 38297969 . FINDINGS We recorded significant differences between treatment groups in diastolic blood pressure ( 1.91 [ 95 % CI -2.88 to -0.94 ] mm Hg , p=0.0001 ) and mean arterial pressure ( 1.36 [ -2.49 to -0.23 ] mm Hg , p=0.0180 ) , after adjustment for confounders and clustering . We noted no significant differences between groups for total cholesterol ( 0.03 [ -0.04 to 0.11 ] mmol/L ) , systolic blood pressure ( -0.33 [ -2.41 to 1.75 ] mm Hg ) , or HbA1c ( -0.15 % [ -0.33 to 0.03 ] ) . Economic analysis suggests that the nurse-led intervention was not cost effective ( incremental cost-effectiveness ratio pound28 933 per QALY gained ) . Across the whole study population over the 2 years of the trial , systolic blood pressure , diastolic blood pressure , and cholesterol decreased significantly by 4.9 ( 95 % CI 4.0 - 5.9 ) mm Hg , 3.8 ( 3.2 - 4.4 ) mm Hg , and 0.45 ( 0.40 - 0.51 ) mmol/L , respectively , and we recorded a small and non-significant increase for haemoglobin A1c ( 0.04 % [ -0.04 to 0.13 ] ) , p=0.290 ) . INTERPRETATION We recorded additional , although small , benefits from our culturally tailored care package that were greater than the secular changes achieved in the UK in recent years . Stricter targets in general practice and further measures to motivate patients are needed to achieve best possible health-care outcomes in south Asian patients with diabetes 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 Disseminating and implementing evidence -based , cardiovascular disease ( CVD ) prevention lifestyle interventions in community setting s and in ethnic minority population s is a challenge . We describe the design and methods for the South Asian Heart Lifestyle Intervention ( SAHELI ) study , a pilot study design ed to determine the feasibility and initial efficacy of a culturally-targeted , community-based lifestyle intervention to improve physical activity and diet behaviors among medically underserved South Asians ( SAs ) . Participants with at least one CVD risk factor will be r and omized to either a lifestyle intervention or a control group . Participants in both groups will be screened in a community setting and receive a primary care referral after r and omization . Intervention participants will receive 6weeks of group classes , followed by 12weeks of individual telephone support where they will be encouraged to initiate and maintain a healthy lifestyle goal . Control participants will receive their screening results and monthly mailings on CVD prevention . Primary outcomes will be changes in moderate/vigorous physical activity and saturated fat intake between baseline , 3- , and 6-month follow-up . Secondary outcomes will be changes in weight , clinical risk factors , primary care visits , self-efficacy , and social support . This study will be one of the first to pilot-test a lifestyle intervention for SAs , one of the fastest growing racial/ethnic groups in the U.S. and one with disparate CVD risk . Results of this pilot study will provide preliminary data about the efficacy of a lifestyle intervention on CVD risk in SAs and inform community-engaged CVD prevention efforts in an increasingly diverse U.S. population BACKGROUND This study evaluated a school-based obesity intervention for elementary school children ( N = 835 ) where health professionals assisted teachers with the integration of healthy messages into the school curriculum . METHODS Schools were r and omized into a professional-facilitated intervention ( PFI ; N = 4 ) or a self-help ( SH ; N = 3 ) condition . Changes in weight-based outcomes were assessed in students enrolled in the second grade from all 7 schools ( overall : N = 835 students ; PFI : N = 509 students , SH : N = 326 students ) . Students were between ages 7 and 9 and from diverse ethnic background s ( Asian = 25.3 % , Black = 23.3 % , Hispanic = 23.1 % , White = 28.3 % ) . The sample included 321 overweight/obese ( BMI ≥ 85th percentile ) , 477 normal-weight ( BMI ≥ 5th percentile and < 85th percentile ) , and 37 underweight ( BMI < 5th percentile ) students . RESULTS After 2 years , children who were overweight/obese in the PFI condition significantly reduced their st and ardized BMI ( z BMI ) compared to children in the SH condition ( Wald χ(2 ) = 28.7 , p < .001 ) . End-of-year grade s decreased for overweight/obese students in both conditions ; however , students in the PFI exhibited a smaller decrease in grade s compared to the SH condition ( Wald χ(2 ) = 80.3 , p < .001 ) . CONCLUSION The results indicate that an obesity prevention program where health professionals assist teachers by integrating healthy messages into existing curriculum was effective in reducing z BMI compared to the SH condition BACKGROUND Khush Dil was set up in Edinburgh in 2002 to manage cardiovascular risk factors in South Asians . We assessed its impact in an in-service evaluation . METHODS Between June 2002 and July 2004 , 304 South Asians attended health visitor led screening clinics . Measurements included self-report , anthropometry , blood pressure and blood tests . A total 140 subjects attended follow-up screening ( henceforth returnees ) . The outcomes relate to them . RESULTS In most respects , including ethnicity , family history , medical history and motivational stage , returnees were similar to the non-returnees , but were a little older and were more likely to be women . Between baseline and return visits , returnees reported an increased motivational status ( those in the action stage of change increased from 12 to 28 % ) and increased physical activity ( e.g. 45 % of women reported improvement at follow-up ) . Returnees had reduced their risk factor profiles at follow-up in a range of risk factors , e.g. reduction in cholesterol ( 0.19 mmol/l ; 95 % CL , 0.1 - 0.37 ) , in diastolic and systolic blood pressures ( 3.15 and 3.7 mmHg , respectively ) and in weight ( 0.61 kg ; 95 % CL , 0.22 - 1.02 ) . CONCLUSIONS The Khush Dil Project had an impact as indicated by self-report , physical measures and laboratory tests . Such initiatives now need evaluation for cost-effectiveness . Cluster r and omized controlled trials warrant consideration Background Effective strategies to combat childhood obesity are challenging , especially among South Asian girls . We conducted a pilot cluster trial of a school-based physical activity programme among preadolescent girls to determine the feasibility ( recruitment , retention and implementation ) of the programme and influence on blood pressure ( BP ) and body mass index ( BMI ) . Methods This two-arm parallel cluster intervention trial was conducted in four similar all-girls public sector schools in Karachi over a 20-week period . All girls aged 9–11 years were included . Intervention was a physical activity programme of 30 min duration four times a week . Primary outcome was to assess the feasibility of the physical activity programme defined as recruitment and retention > 70 % and treatment fidelity of > 80 % of physical activity programme . Secondary outcomes were changes in systolic BP ( SBP ) , diastolic BP ( DBP ) and BMI from baseline to follow-up . Results A total of 360 participants were invited to participate , 280 girls met eligibility criteria , and were recruited ; 131 ( 77 % ) in the intervention group and 146 ( 87 % ) in control group . At follow-up , the overall retention of participants was 222 ( 79.2 % ) ; 105 ( 80.1 % ) in the intervention group and 117 ( 78.5 % ) in the control group . The difference in mean change from baseline to follow-up in SBP , DBP and BMI score was 1.9 mm Hg , 0.7 mm Hg and 0.55 kg/m2 between intervention and control arms , respectively . Conclusions A school-based physical activity programme in a public sector girls school of urban Pakistan is feasible . There was a favourable trend in BP and BMI at follow-up . ( Clinical trial ID NCT 00533819 ) |
10,775 | 24,729,894 | There was no significant association between mammographic density and rate of dairy consumption , amount of sunlight exposure , and daily physical activity . | Background .
Mammographic density is a risk factor , for breast cancer and its association with various factors is under investigation ; we carried out a study to assess its relationship with daily dairy intake , sun exposure , and physical activities . | Background : A better underst and ing of factors that affect breast density , one of the strongest breast cancer risk indicators , may provide important clues about breast cancer etiology and prevention . This study evaluates the association of vitamin D and calcium , from food and /or supplements , to breast density in premenopausal and postmenopausal women separately . Methods : A total of 777 premenopausal and 783 post-menopausal women recruited at two radiology clinics in Quebec City , Canada , in 2001 to 2002 , completed a food frequency question naire to assess vitamin D and calcium . Breast density from screening mammograms was assessed using a computer-assisted method . Associations between vitamin D or calcium and breast density were evaluated using linear regression models . Adjusted means in breast density were assessed according to the combined daily intakes of the two nutrients using generalized linear models . Results : In premenopausal women , total intakes of vitamin D and calcium were inversely related to breast density ( β = −1.4 ; P = 0.004 for vitamin D ; β = −0.8 ; P = 0.0004 for calcium ) . In multivariate linear regression , simultaneous increments in daily total intakes of 400 IU vitamin D and 1,000 mg calcium were associated with an 8.5 % ( 95 % confidence interval , 1.8 - 15.1 ) lower mean breast density . The negative association between dietary vitamin D intake and breast density tended to be stronger at higher levels of calcium intake and vice versa . Among postmenopausal women , intakes of vitamin D and calcium were not associated with breast density . Conclusion : These findings show that higher intakes of vitamin D and calcium from food and supplements are related to lower levels of breast density among premenopausal women . They suggest that increasing intakes of vitamin D and calcium may represent a safe and inexpensive strategy for breast cancer prevention Background : Because of its nutrients and anabolic hormones , cow 's milk may promote height growth , which in turn has been related to breast cancer risk . We prospect ively investigated associations between dairy intakes and height growth . Methods : A cohort of 5,101 girls from throughout the United States completed annual surveys ( 1996 - 2001 , 2003 ) , providing height , weight , and past-year diet . At baseline , all were premenarchal , ages 9 years and above , with no serious medical conditions . We studied three outcomes : annual height growth , peak growth velocity , and adult height . Multivariate models estimated the effects of milk , cheese , yogurt , and energy on subsequent growth , adjusted for race/ethnicity , age , prior height , and body mass index . Other models studied fats and proteins . Results : Premenarchal girls who drank > 3 servings per day of milk grew 0.11 in . ( P = 0.02 ) more the following year than girls consuming < 1 serving per day . Yogurt ( + 0.13 in./cup ; P = 0.02 ) , but not cheese or total calories , predicted height growth . In a separate model , dairy protein ( + 0.034 in./10 g ; P < 0.001 ) predicted height growth . Larger peak velocities were seen among girls reporting , at baseline , more milk ( > 3 glasses per day versus < 1 ; + 0.14 in . , P = 0.01 ) , more yogurt ( + 0.17 in./cup , P = 0.02 ) , and , in a separate model , more dairy protein ( + 0.039 in./10 g ; P = 0.003 ) . Baseline milk and dairy protein predicted taller adults . Dairy protein was more important than dairy fat , for all outcomes . Nondairy animal protein and vegetable protein were never significant , nor were nondairy animal fat and vegetable fat . Conclusion : Of the foods/nutrients studied , dairy protein had the strongest association with height growth . These findings suggest that a factor in the nonlipid phase of milk , but not protein itself , has growth-promoting action in girls . ( Cancer Epidemiol Biomarkers Prev 2009;18(6):1881–7 Mammographic density is a strong risk factor for breast cancer ; however the mechanism that underlies this association is unclear . We hypothesized that measures of energy balance early in life and in adulthood may be associated with mammographic density . We conducted a cross-sectional analysis of 1,398 women in the Nurses ’ Health Study to examine associations between physical activity , childhood and current body fatness , weight gain from age 18 years to present and mammographic density . Percent mammographic density was measured from digitized mammograms by a computer-assisted method . Demographic and lifestyle data were obtained from prospect ively collected question naires . For all analyses , subjects were stratified into three groups : premenopausal women , postmenopausal women not currently taking hormones , and postmenopausal women currently taking hormones . Childhood body fatness was inversely associated with mammographic density . The correlations ranged from −0.15 to −0.19 in the three strata of women ( P ≤ 0.001 ) . The difference in mean percent mammographic density between the leanest and heaviest body types ranged from 6.2 to 9.9 % . Similarly , adult body fatness was inversely associated with percent mammographic density . The correlations ranged from −0.41 to −0.48 in the three strata of women ( P < 0.0001 ) . The difference in mean percent mammographic density between the leanest and heaviest body types ranged from 22.3 to 35.1 % . Weight gain from age 18 was also inversely associated with mammographic density . There was no association between recent physical activity and mammographic density . These findings indicate that childhood and adult body fatness and weight change from age 18 are inversely associated with mammographic density Objective To examine the effects of various anthropometric determinants on mammographic patterns at postmenopausal ages , accounting for reproductive differences . Methods Mammograms from 900 post-menopausal women classified into high- ( P2/DY ) versus low-density ( N1/P1 ) groups using the Wolfe criteria were associated with changes in body figure , reported and measured height and weight , body mass index , hip , waist and chest circumferences , chest/hip ratio , waist/hip ratio ( WHR ) , breast size , and leg length . Reproductive factors included ages at menarche , first pregnancy and menopause , years since menopause , parity , and breast feeding duration . The study was nested within a large cross-sectional survey of a population -based breast cancer screening program in Northern Greece . Results Increasing chest circumference ( p = 0.002 ) , change in body build during adulthood to a heavier profile ( p = 0.04 ) , and heavy somatotype at age 18 ( p = 0.007 ) were the anthropometric determinants significantly associated with low-density mammographic patterns . Conclusions Chest circumference as a measure of upper body fat adiposity appears to be a stronger determinant of mammographic patterns than body fat distribution ( measured as WHR ) . A heavy body build in adulthood is associated with decreased mammographic density . Further studies are necessary to confirm our results , ideally prospect i ve cohorts , looking at the effect of anthropometric determinants on mammographic pattern changes over time and breast cancer risk Physical activity has been associated with a reduced risk of breast cancer . However , little is known about the association between recreational physical activity and mammographic density . We examined the association between recreational physical activity and mammographic density using mammograms from 375 white and African American women without breast cancer who served as controls in the Los Angeles component of the Women 's Contraceptive and Reproductive Experiences Study . We used data from 5 time periods of activity in the statistical analysis : from menarche to mammogram screening , the first 3 and 10 years after menarche , the most recent 10 years and the 3 years prior to mammogram screening . Lifetime history of recreational physical activity was obtained through interviews using a structured question naire . We used multiple linear regression to estimate least-squared mean values of absolute and percent mammographic density within categories of physical activity . Overall , we found no statistically significant evidence that physical activity reduced absolute or percent mammographic density . We observed a modest positive association between lifetime physical activity and percent mammographic density ( p for trend = 0.04 ) among younger women , and between recent physical activity and percent density among both younger ( < 50 years , p for trend = 0.09 ) and older ( > or = 50 years , p for trend = 0.06 ) women , but these associations diminished after additionally adjusting for body mass index ( BMI ) ( all p > or = 0.10 ) . However , among women younger than 50 years , we found some evidence for a protective effect of " strenuous " physical activity in the first 3 years after menarche , with a nonstatistically significant inverse association with both absolute ( p for trend = 0.07 ) and percent ( p for trend = 0.08 ) mammographic density after adjustment for BMI . Our results suggest that physical activity is not a strong predictor of mammographic density To examine the effects of dietary fat intake on breast cancer risk , we are conducting a r and omized trial of dietary intervention in women with extensive areas of radiologically dense breast tissue on mammography , a risk factor for breast cancer . Early results show that after 2 years on a low-fat , high-carbohydrate diet there is a significant reduction in area of density , particularly in women going through menopause . In women who went through menopause during the 2-year follow-up , the mean decreases in area of density and percentage of density in the intervention group were 11.0 cm2 and 11.0 % , respectively , whereas the control group decreased 4.5 cm2 and 5.2 % . The purpose of this analysis was to determine whether changes in intake of specific macronutrients could account for the observed reduction in breast density in these women . Differences between 2-year and baseline values of macronutrients ( averaged over 3 nonconsecutive days of food intake ) were calculated . We examined the effect of dietary variables , adjusted for changes in total calorie intake and weight and for family history of breast cancer , on changes in area of density and percentage of density using linear regression . Reduction in total or saturated fat intake or cholesterol intake was significantly associated with decreased dense area ( p < or = .004 ) . The most significant dietary variable associated with reduction in percentage of density was reduction in dietary cholesterol intake ( P = 0.001 ) , although reducing saturated fat intake was of borderline significance ( P = 0.05 ) . The effect of the membership in the intervention and control groups on change in area of density or percentage of density was reduced by models that included changes in intake of any fat , or cholesterol , or carbohydrates . The observation of an effect of diet at menopause on breast density , a marker of increased risk of breast cancer , may be an indication that exposures at this time have an enhanced effect on subsequent risk Background : The Alberta Physical Activity and Breast Cancer Prevention ( ALPHA ) Trial examined the influence of aerobic exercise on biological factors that are associated with breast cancer risk . Mammographic density , a secondary outcome , is reported here . Methods : The ALPHA Trial was a parallel group r and omized controlled trial conducted between May 2003 and July 2007 . Postmenopausal , sedentary women ages 50 to 74 years ( n = 320 ) were evenly r and omized to aerobic exercise ( 45 minutes , 5 days per week ) or control ( usual life-style ) for 1 year . Dense fibrogl and ular tissue and nondense fatty tissue were measured from mammograms at baseline and 1 year using computer-assisted thresholding software for area measurements and a new technique that relies on the calibration of mammography units with a tissue-equivalent phantom for volumetric measurements . Results : Nondense volume decreased in the exercise group relative to the control group ( difference between groups = −38.5 cm3 ; 95 % confidence interval , −61.6 to 15.4 ; P = 0.001 ) . Changes in total body fat accounted for this decrease . Changes in dense area and dense volume , measures that have previously been associated with breast cancer risk , were not significantly different between the groups ( P ≥ 0.26 ) . Conclusions : Achieving changes in mammographic measures may require more exercise or a study population with higher baseline levels of sex hormones or a wider range of mammographic density . The data from this study , however , suggest that the protective effect of exercise on breast cancer risk may operate through a mechanism other than mammographic density . Cancer Epidemiol Biomarkers Prev ; 19(4 ) ; 1112–21 . © 2010 AACR Purpose Few studies have investigated the association between breast density and breast cancer by a family history of breast cancer , menopausal status , and postmenopausal hormone use ( PMH ) . We investigated if associations of breast density and breast cancer differ according to the status of these risk factors . Methods This study included 1,481 incident breast cancer cases diagnosed within the Nurses ’ Health Study I and II cohorts and 2,779 matched controls . Breast density was measured from digitized film images with computerized techniques . Information on breast cancer risk factors was obtained prospect ively from the biennial question naires before the date of the cancer diagnosis for cancer cases and their matched controls . The data were analyzed with logistic regression . Results Breast cancer risk increased with increasing percent breast density in all strata ( p for trend in all subsets < 0.0001 ) . The density-related risk of breast cancer was similar in women with and without a family history ( OR = 4.00 [ 95 % CI 2.01–7.94 ] vs. 3.71 [ 95 % CI 2.79–4.94 ] for density ≥50 % vs. < 10 % , p for interaction = 0.53 ) . The magnitude of the association between density and breast cancer risk , however , appeared to be stronger in premenopausal women than in postmenopausal women without PMH history ( OR = 5.49 [ 95 % CI 2.44–12.39 ] vs. 3.02 [ 95 % CI 1.62–5.63 ] for density ≥50 % vs. < 10 % , p-heterogeneity = 0.17 ) and appeared to be stronger in postmenopausal women currently using hormones compared with postmenopausal women who never used PMH ( OR = 4.50 [ 95 % CI 2.99–6.78 ] vs. 3.02 , p-heterogeneity = 0.20 ) or with past hormone use ( OR = 4.50 vs. 3.71 [ 95 % CI 1.90–7.23 ] , p-heterogeneity = 0.23 ) . Conclusions Findings on associations by menopausal status/hormone use are suggestive and should be examined in additional larger studies OBJECTIVE To study daily intake of calcium , phosphorus and vitamin D , to determine the biochemical findings of rickets and the effect of sunlight exposure and vitamin D supplementation in school girls with hypovitaminosis D. METHODS A cross-sectional study was conducted on school girls aged 11 - 15 years selected r and omly from various areas of Tehran , Iran . Dietary information and amount of sunlight exposure were estimated by a 7 day recalling method using self-reported question naire . Hypovitaminosis D defined as low serum 25-hydroxyvitamin D concentration with two or more others abnormal biochemical findings . Girls with hypovitaminoses D were r and omly divided into two groups . The faces and h and s of girls in group 1 were exposed to sunlight for one hour per day for twenty days , while those in group 2 were administered vitamin D capsules , 50,000 IU per day for the same period . RESULTS four-hundred fourteen girls evaluated , mean daily calcium intake , sunlight exposure and vitamin D acquirement were 360 mg , 10 minutes and 119 IU , respectively . Mean serum 25-hydroxyvitamin D concentration was 30 ng/ml among all girls whereas in 15 ( 3.63 % ) of 414 girls was 7.8 ng/ml . Abnormal biochemical findings in these girls included hypocalcemia ( n=4 ) , hypophosphatemia ( n=5 ) , raised serum alkaline phosphatase ( n=13 ) , and parathyroid hormone ( n=15 ) . After intervention , mean serum 25-hydroxyvitamin D concentration in sunlight exposure ( n=8 ) and vitamin D ( n=7 ) supplementation increased to 14.4+/-4 ng/ml and 23+/-4 ng/ml respectively . There was a significant difference between the two groups ( p<0.05 ) . CONCLUSION Vitamin D deficiency developed in rapid growth period of girls without clear clinical rickets in sunny temperate climate city in Iran which vitamin D supplementation improved biochemical findings better than sunlight exposure Background : Evidence accumulates that physical inactivity is one of the few modifiable risk factors for breast cancer . The mechanism through which physical inactivity affects breast cancer risk is not clear . The study aim was to investigate the association between physical activity and breast density because mammographic density is strongly associated with breast cancer risk . Methods : We did a cross-sectional study in 620 women , of ages 49 to 68 years and participants of the Dutch Prospect -European Prospect i ve Investigation into Cancer and Nutrition cohort . A self-administered question naire was used to obtain information on duration and intensity of physical activity ( recreational , household , and occupational ) during the year preceding study recruitment . A total activity index ( inactive , moderately inactive , moderately active , and active ) was estimated by combining all activity types . Percent and absolute breast density were determined on screening mammograms using a computer-aided method . Multivariate linear regression was used to examine the association between physical activity and breast density . Results : Mean percent density was 35.3 % [ 95 % confidence interval ( 95 % CI ) , 31.8 - 38.8 ] for the inactive category compared with 36.1 % ( 95 % CI , 33.0 - 39.2 ) for the active category . Mean absolute density values for the inactive and active category were 45.8 cm2 ( 95 % CI , 40.9 - 50.7 ) and 42.6 cm2 ( 95 % CI , 38.3 - 47.0 ) , respectively . Subgroup analysis for postmenopausal women showed similar results , as did separate analyses for recreational and household activity . Conclusions : The result does not support a relation between current physical activity and mammographic density in postmenopausal women . ( Cancer Epidemiol Biomarkers Prev 2006;15(3):456–60 |
10,776 | 27,862,801 | Despite medical advances , individuals with diabetes have a 50 % greater long-term mortality compared with those without . | AIMS To conduct a systematic review and meta- analysis with the aim of providing robust estimates of the association between diabetes and long-term ( ≥1 year ) mortality after acute myocardial infa rct ion ( AMI ) . | CONTEXT The worldwide epidemic of diabetes mellitus is increasing the burden of cardiovascular disease , the leading cause of death among persons with diabetes . The independent effect of diabetes on mortality following acute coronary syndromes ( ACS ) is uncertain . OBJECTIVE To evaluate the influence of diabetes on mortality following ACS using a large data base spanning the full spectrum of ACS . DESIGN , SETTING , AND PATIENTS A subgroup analysis of patients with diabetes enrolled in r and omized clinical trials that evaluated ACS therapies . Patients with ACS in 11 independent Thrombolysis in Myocardial Infa rct ion ( TIMI ) Study Group clinical trials from 1997 to 2006 were pooled , including 62,036 patients ( 46,577 with ST-segment elevation myocardial infa rct ion [ STEMI ] and 15,459 with unstable angina/non-STEMI [ UA/NSTEMI ] ) , of whom 10 613 ( 17.1 % ) had diabetes . A multivariable model was constructed to adjust for baseline characteristics , aspects of ACS presentation , and treatments for the ACS event . MAIN OUTCOME MEASURES Mortality at 30 days and 1 year following ACS among patients with diabetes vs patients without diabetes . RESULTS Mortality at 30 days was significantly higher among patients with diabetes than without diabetes presenting with UA/NSTEMI ( 2.1 % vs 1.1 % , P < .001 ) and STEMI ( 8.5 % vs 5.4 % , P < .001 ) . After adjusting for baseline characteristics and features and management of the ACS event , diabetes was independently associated with higher 30-day mortality after UA/NSTEMI ( odds ratio [ OR ] , 1.78 ; 95 % confidence interval [ CI ] , 1.24 - 2.56 ) or STEMI ( OR , 1.40 ; 95 % CI , 1.24 - 1.57 ) . Diabetes at presentation with ACS was associated with significantly higher mortality 1 year after UA/NSTEMI ( hazard ratio [ HR ] , 1.65 ; 95 % CI , 1.30 - 2.10 ) or STEMI ( HR , 1.22 ; 95 % CI , 1.08 - 1.38 ) . By 1 year following ACS , patients with diabetes presenting with UA/NSTEMI had a risk of death that approached patients without diabetes presenting with STEMI ( 7.2 % vs 8.1 % ) . CONCLUSION Despite modern therapies for ACS , diabetes confers a significant adverse prognosis , which highlights the importance of aggressive strategies to manage this high-risk population with unstable ischemic heart disease OBJECTIVE Diabetes has been shown to be associated with worse survival and repeat target vessel revascularization ( TVR ) after primary angioplasty . The aim of the current study was to evaluate the impact of diabetes on long-term outcome in patients undergoing primary angioplasty treated with bare metal stents ( BMS ) and drug-eluting stents ( DES ) . RESEARCH DESIGN AND METHODS Our population is represented by 6,298 ST-segment elevation myocardial infa rct ion ( STEMI ) patients undergoing primary angioplasty included in the DESERT data base from 11 r and omized trials comparing DES with BMS . RESULTS Diabetes was observed in 972 patients ( 15.4 % ) who were older ( P < 0.001 ) , more likely to be female ( P < 0.001 ) , with higher prevalence of hypertension ( P < 0.001 ) , hypercholesterolemia ( P < 0.001 ) , and longer ischemia time ( P < 0.001 ) , and without any difference in angiographic and procedural characteristics . At long-term follow-up ( 1,201 ± 441 days ) , diabetes was associated with higher rates of death ( 19.1 % vs. 7.4 % ; P < 0.0001 ) , reinfa rct ion ( 10.4 % vs. 7.5 % ; P < 0.001 ) , stent thrombosis ( 7.6 % vs. 4.8 % ; P = 0.002 ) with similar temporal distribution — acute , subacute , late , and very late — between diabetic and control patients , and TVR ( 18.6 % vs. 15.1 % ; P = 0.006 ) . These results were confirmed in patients receiving BMS or DES , except for TVR , there being no difference observed between diabetic and nondiabetic patients treated with DES . The impact of diabetes on outcome was confirmed after correction for baseline confounding factors ( mortality , P < 0.001 ; repeat myocardial infa rct ion , P = 0.006 ; stent thrombosis , P = 0.007 ; TVR , P = 0.027 ) . CONCLUSIONS This study shows that among STEMI patients undergoing primary angioplasty , diabetes is associated with worse long-term mortality , reinfa rct ion , and stent thrombosis in patients receiving DES and BMS . DES implantation , however , does mitigate the known deleterious effect of diabetes on TVR after BMS OBJECTIVES To compare the use of evidence -based pharmacological and invasive treatments and 12-month mortality rates between patients with and without diabetes who present with acute myocardial infa rct ion ( MI ) , and to explore the relationship between these treatments and late clinical outcomes . DESIGN AND SETTING Prospect i ve , nationwide multicentre registry : the Acute Coronary Syndrome Prospect i ve Audit ( ACACIA ) . PATIENTS Patients presenting to 24 metropolitan and 15 non-metropolitan hospitals with acute coronary syndrome ( ACS ) and a final discharge diagnosis of acute MI between November 2005 and July 2007 . MAIN OUTCOME MEASURE All-cause mortality at 12 months . RESULTS Nearly a quarter of 1744 patients with a final diagnosis of acute MI had a history of diabetes on presentation . Patients with diabetes were older , with a greater prevalence of comorbidities than non-diabetic patients , and were less likely to be treated at discharge with evidence -based medications ( aspirin , clopidogrel , a statin and /or a beta-blocker ) or to receive early invasive procedures . After adjusting for baseline characteristics and therapeutic interventions , diabetes at presentation was independently associated with a higher mortality at 12 months after MI ( hazard ratio , 1.79 ; 95 % CI , 1.18 - 2.72 ; P=0.007 ) . Early invasive management and discharge prescription of guideline -recommended medications were associated with a significantly reduced hazard of mortality at 12 months . CONCLUSION Patients with diabetes have a higher risk than non-diabetic patients of late mortality following an acute MI , yet receive fewer guideline -recommended medications and early invasive procedures . Increased application of proven pharmacotherapies and an early invasive management strategy in patients with diabetes presenting with ACS might improve their outcomes . STUDY PROTOCOL NUMBER ( SANOFI-AVENTIS ) : PML-0051 OBJECTIVE —Elevation of blood glucose is a common metabolic disorder among patients with acute myocardial infa rct ion ( AMI ) and is associated with adverse prognosis . However , few data are available concerning the long-term prognostic value of elevated fasting glucose during the acute phase of infa rct ion . RESEARCH DESIGN AND METHODS —We prospect ively studied the relationship between fasting glucose and long-term mortality in patients with AMI . Fasting glucose was determined after an ≥8 h fast within 24 h of admission . The median duration of follow-up was 24 months ( range 6–48 ) . All multivariable Cox models were adjusted for the Global Registry of Acute Coronary Events ( GRACE ) risk score . RESULTS —In nondiabetic patients ( n = 1,101 ) , compared with patients with normal fasting glucose ( < 100 mg/dl ) , the adjusted hazard ratio for mortality progressively increased with higher tertiles of elevated fasting glucose ( first tertile 1.5 [ 95 % CI 0.8–2.9 ] , P = 0.19 ; second tertile 3.2 [ 1.9–5.5 ] , P < 0.0001 ; third tertile 5.7 [ 3.5–9.3 ] , P < 0.0001 ) . The c statistic of the model containing the GRACE risk score increased when fasting glucose data were added ( 0.8 ± 0.02–0.85 ± 0.02 , P = 0.004 ) . Fasting glucose remained an independent predictor of mortality after further adjustment for ejection fraction . Elevated fasting glucose did not predict mortality in patients with diabetes ( n = 462 ) . CONCLUSIONS —Fasting glucose is a simple robust tool for predicting long-term mortality in nondiabetic patients with AMI . Fasting glucose provides incremental prognostic information when added to the GRACE risk score and left ventricular ejection fraction . Fasting glucose is not a useful prognostic marker in patients with diabetes OBJECTIVE This analysis was undertaken to determine the composite incidence of cumulative adverse events ( death , reinfa rct ion , disabling stroke , and target vessel revascularization ) at the end of the first year after acute myocardial infa rct ion , in diabetic patients who underwent coronary stenting or primary coronary balloon angioplasty . METHODS From the STENT PAMI trial , we analyzed the 6-month angiographic and 1-year clinical outcomes of 135 diabetic ( 112 , noninsulin dependent ) patients who underwent the r and omization process of the trial and compared them with 758 nondiabetic patients . RESULTS Coronary stenting did not significantly reduce the primary composite clinical end point when compared with PTCA ( 20 vs. 30 % , p=0.2 ) . A significant benefit from stenting was observed in patients with noninsulin dependent diabetes , with a trend toward a lesser need for new revascularization procedures ( 10 vs. 21 % , p<.001 ) , with a significant reduction in the primary composite clinical end point at 1 year ( 12 vs. 28 % , p=. 04 ) . At 6 months , the restenosis rate were significantly reduced only in nondiabetic patients ( 18 vs. 33 % , p<. 001 ) . Diabetic patients had the same restenosis rate ( 38 % ) either with stenting or balloon PTCA . CONCLUSIONS Coronary Stenting in diabetics noninsulin dependent offered a significant reduction in the composite incidence of major clinical adverse events compared with balloon PTCA BACKGROUND It has been shown that , among patients with ST-segment elevation myocardial infa rct ion ( STEMI ) , diabetes is associated with a significantly higher mortality . The aim of this study was to investigate in a large cohort of patients the impact of diabetes on mortality in a large cohort of patients with STEMI treated with primary angioplasty . METHODS Our population is represented by consecutive patients with STEMI treated by primary angioplasty and enrolled in the POLISH registry in 2003 . All clinical , angiographic , and follow-up data were prospect ively collected . Diagnosis of diabetes was based on history of diabetes at admission . RESULTS Among 7193 patients , 877 ( 12.2 % ) had diabetes at admission . Diabetes was associated with more advanced age ( p<0.0001 ) , higher prevalence of female gender ( p<0.0001 ) , hyperlipidemia ( p<0.0001 ) , shock at presentation ( p<0.0001 ) , renal failure ( p<0.0001 ) , previous myocardial infa rct ion ( p<0.0001 ) , more often treated after 6h from symptom onset ( p<0.0001 ) . Diabetes was associated with more extensive coronary artery disease ( p<0.0001 ) , less often treated with stenting ( p<0.0001 ) . Diabetes was significantly associated with impaired epicardial reperfusion ( TIMI 0 - 2 : OR [ 95 % CI]=1.81 [ 1.5 - 2.18 ] , p<0.0001 ) , that persisted after correction for baseline confounding factors ( OR [ 95 % CI]=1.33 [ 1.075 - 1.64 ] , p=0.009 ) . At a mean follow-up of 524+/-194 days , diabetes was associated with higher mortality ( unadjusted cumulative mortality : 23.5 % vs. 12.6 % , unadjusted HR=1.95 [ 1.66 - 2.3 ] , p<0.0001 ) , that persisted after correction for confounding factors ( adjusted cumulative mortality : 13.3 % vs. 10.7 % , adjusted HR=1.23 [ 1.04 - 1.46 ] , p=0.013 ) . CONCLUSIONS This study shows that among STEMI treated by primary angioplasty diabetes is independently associated with impaired epicardial reperfusion and higher mortality Background The results of R and omized Controlled Trials ( RCTs ) on time-to-event outcomes that are usually reported are median time to events and Cox Hazard Ratio . These do not constitute the sufficient statistics required for meta- analysis or cost-effectiveness analysis , and their use in secondary analyses requires strong assumptions that may not have been adequately tested . In order to enhance the quality of secondary data analyses , we propose a method which derives from the published Kaplan Meier survival curves a close approximation to the original individual patient time-to-event data from which they were generated . Methods We develop an algorithm that maps from digitised curves back to KM data by finding numerical solutions to the inverted KM equations , using where available information on number of events and numbers at risk . The reproducibility and accuracy of survival probabilities , median survival times and hazard ratios based on reconstructed KM data was assessed by comparing published statistics ( survival probabilities , medians and hazard ratios ) with statistics based on repeated reconstructions by multiple observers . Results The validation exercise established there was no material systematic error and that there was a high degree of reproducibility for all statistics . Accuracy was excellent for survival probabilities and medians , for hazard ratios reasonable accuracy can only be obtained if at least numbers at risk or total number of events are reported . Conclusion The algorithm is a reliable tool for meta- analysis and cost-effectiveness analyses of RCTs reporting time-to-event data . It is recommended that all RCTs should report information on numbers at risk and total number of events alongside KM curves OBJECTIVE To determine the effect of diabetes on long-term survival after acute myocardial infa rct ion and to compare its effect with that of a previous myocardial infa rct ion . RESEARCH DESIGN AND METHODS In a prospect i ve cohort study , we followed 1,935 patients hospitalized with a confirmed acute myocardial infa rct ion at 45 U.S. medical centers between 1989 and 1993 , as part of the Determinants of Myocardial Infa rct ion Onset Study . Trained interviewers performed chart review s and face-to-face interviews with all patients . We analyzed survival using Cox proportional hazards regression to control for potentially confounding factors . RESULTS Of the 1,935 patients , 320 ( 17 % ) died during a mean follow-up of 3.7 years . A total of 399 patients ( 21 % ) had previously diagnosed diabetes . Diabetes was associated with markedly higher total mortality in unadjusted ( hazard ratio [ HR ] 2.4 ; 95 % CI 1.9 - 3.0 ) and adjusted ( 1.7 ; 1.3 - 2.1 ) analyses . The magnitude of the effect of diabetes was identical to that of a previous myocardial infa rct ion . The effect of diabetes was not significantly modified by age , smoking , household income , use of thrombolytic therapy , type of hypoglycemic treatment , or duration of diabetes , but the risk associated with diabetes was higher among women than men ( adjusted HRs 2.7 vs. 1.3 , P = 0.01 ) . CONCLUSIONS Diabetes is associated with markedly increased mortality after acute myocardial infa rct ion , particularly in women . The increase in risk is of the same magnitude as a previous myocardial infa rct ion and provides further support for aggressive treatment of coronary risk factors among diabetic patients The effect of diabetes on survival after myocardial infa rct ion ( MI ) was examined in a prospect i ve population -based study of individuals hospitalized with MI in a bi-ethnic community of Mexican-Americans and non-Hispanic whites . Among Mexican-Americans , 54 % ( 331 of 610 ) had diabetes compared with 33 % ( 192 of 589 ) of non-Hispanic whites ( P < 0.001 ) . Among those with diabetes , the prevalence of a history of a cardiac event before the index admission was significantly higher ( odds ratio = 1.4 , 95 % confidence interval [ CI ] 1.1–1.8 ) than among nondiabetic subjects . During the index hospitalization , diabetic subjects received cardiac catheterization less frequently than did nondiabetic subjects ( 45.1 vs. 51.5 % , P = 0.03 ) . Diabetic subjects had lower estimated ejection fractions , and the number of coronary arteries with significant obstruction ( > 75 % ) was higher ( P < 0.001 ) . The peak creatine phosphokinase and creatine phosphokinase myocardial isoenzyme ( CK-MB ) levels were similar in diabetic and nondiabetic subjects . Despite a similar infa rct size , diabetic subjects had a higher incidence of congestive heart failure ( relative ratio = 2.2 , 95 % CI 1.7–2.8 ) , more adverse indexes of short-term and long-term prognosis , and a longer average hospital stay ( 12.1 vs. 8.9 days , P < 0.01 ) . After adjustment for age , sex , and ethnicity , the cumulative risk for total mortality , over 44 months of follow-up , was 37.4 % among diabetic compared with 23.3 % among nondiabetic subjects ( P < 0.001 ) . Diabetic subjects had a higher 28-day case-fatality rate post-MI as well as higher long-term mortality . In conclusion , diabetic subjects have similar size infa rcts compared with nondiabetic subjects , but they have a more complicated hospital course and higher total mortality post-MI . Diabetes had a similar adverse effect on post-MI mortality in both Mexican-Americans and non-Hispanic whites Objective To evaluate the effectiveness of a structured group education programme on biomedical , psychosocial , and lifestyle measures in people with newly diagnosed type 2 diabetes . Design Multicentre cluster r and omised controlled trial in primary care with r and omisation at practice level . Setting 207 general practice s in 13 primary care sites in the United Kingdom . Participants 824 adults ( 55 % men , mean age 59.5 years ) . Intervention A structured group education programme for six hours delivered in the community by two trained healthcare professional educators compared with usual care . Main outcome measures Haemoglobin A1c levels , blood pressure , weight , blood lipid levels , smoking status , physical activity , quality of life , beliefs about illness , depression , and emotional impact of diabetes at baseline and up to 12 months . Main results Haemoglobin A1c levels at 12 months had decreased by 1.49 % in the intervention group compared with 1.21 % in the control group . After adjusting for baseline and cluster , the difference was not significant : 0.05 % ( 95 % confidence interval −0.10 % to 0.20 % ) . The intervention group showed a greater weight loss : −2.98 kg ( 95 % confidence interval −3.54 to −2.41 ) compared with 1.86 kg ( −2.44 to −1.28 ) , P=0.027 at 12 months . The odds of not smoking were 3.56 ( 95 % confidence interval 1.11 to 11.45 ) , P=0.033 higher in the intervention group at 12 months . The intervention group showed significantly greater changes in illness belief scores ( P=0.001 ) ; directions of change were positive indicating greater underst and ing of diabetes . The intervention group had a lower depression score at 12 months : mean difference was −0.50 ( 95 % confidence interval −0.96 to −0.04 ) ; P=0.032 . A positive association was found between change in perceived personal responsibility and weight loss at 12 months ( β=0.12 ; P=0.008 ) . Conclusion A structured group education programme for patients with newly diagnosed type 2 diabetes result ed in greater improvements in weight loss and smoking cessation and positive improvements in beliefs about illness but no difference in haemoglobin A1c levels up to 12 months after diagnosis . Trial registration Current Controlled Trials IS RCT N17844016 We sought to determine the benefits of stent implantation and abciximab in patients with diabetes mellitus and acute myocardial infa rct ion ( AMI ) who underwent primary angioplasty . In a 2-by-2 factorial design , 2,082 patients with AMI were r and omly assigned to balloon angioplasty versus stenting , with or without abciximab . Diabetes was present in 346 patients ( 16.6 % ) . The primary end point was the composite incidence of death , disabling stroke , reinfa rct ion , and ischemic target vessel revascularization ( TVR ) . The primary end point at 1 year occurred significantly more frequently in diabetic than nondiabetic patients ( 21.9 % vs 16.8 % , p < 0.02 ) , driven by increased rates of death ( 6.1 % vs 3.9 % , p = 0.04 ) and TVR ( 16.4 % vs 12.7 % , p = 0.07 ) . Among patients with diabetes , TVR at 1 year was significantly reduced with routine stenting compared with balloon angioplasty ( 10.3 % vs 22.4 % , p = 0.004 ) , with no differences in death , reinfa rct ion , or stroke . Angiographic restenosis was also greatly reduced in diabetics r and omized to stenting ( 21.1 % vs 47.6 % , p = 0.009 ) . No beneficial effects were apparent with abciximab in diabetic patients at 1 year . Despite the improved outcomes with stenting in patients with diabetes , 1-year mortality remained increased in diabetic patients who received stents compared with nondiabetics ( 8.2 % vs 3.6 % , p = 0.005 ) . Thus , routine stent implantation in diabetic patients with AMI significantly reduces restenosis and enhances survival free from TVR , independent of abciximab use , although survival remains reduced compared with survival in nondiabetic patients regardless of reperfusion modality OBJECTIVES This study was design ed to assess outcome in patients with diabetes who received thrombolytic therapy and to determine whether differences in angiographic characteristics may account for the worse outcome observed in diabetic patients . BACKGROUND Patients with diabetes are known to have a worse outcome after acute myocardial infa rct ion than that of patients without diabetes . METHODS Clinical and angiographic characteristics of the 148 patients with diabetes and the 923 patients without diabetes in the Thrombolysis and Angioplasty in Myocardial Infa rct ion ( TAMI ) trials were examined and analyzed . RESULTS Patients with diabetes tended to be older ( median age 59 vs. 56 years ) and to have a higher incidence of hypertension and hyperlipidemia and a lower incidence of cigarette smoking . Patients with diabetes had significantly more severe anatomic disease ( 66 % vs. 46 % had multivessel disease , p < 0.0001 ) , similar global left ventricular ejection fraction ( 49 % vs. 51 % ) and worse noninfa rct zone ventricular function ( -0.13 vs. 0.32 SD/chord , p = 0.02 ) than that of nondiabetic patients . Angiographic patency rates at 90 min after thrombolytic therapy were similar in patients with and without diabetes ( initial 90-min patency 71 % vs. 70 % ) . Diabetic patients had nearly twice the in-hospital mortality rate ( 11 % vs. 6 % , p < 0.02 ) and a higher incidence of pulmonary edema ( 11 % vs. 4 % , p = 0.001 ) . Diabetic women had an especially high in-hospital mortality rate ( 21 % ) . No retinal hemorrhages were observed . Although diabetes as an unadjusted variable was predictive of in-hospital ( p < 0.02 ) and long-term ( p = 0.003 ) mortality , after adjustment for baseline clinical and angiographic characteristics , diabetes was not found to have an independent influence on mortality . CONCLUSIONS Patients with diabetes after myocardial infa rct ion have a worse outcome than that of patients without diabetes despite similar rates of infa rct vessel patency . However , diabetes was not found to be an independent risk factor for increased mortality . These findings suggest that diabetes itself is not a major risk factor for poor early outcome after thrombolytic therapy for myocardial infa rct ion ; rather , the secondary effects such as more extensive coronary artery disease account for the worse outcome OBJECTIVES We studied the outcome of diabetics enrolled in the Global Use of Strategies to Open Occluded Coronary Arteries ( GUSTO ) V trial to assess whether the combination of half-dose reteplase and abciximab provides any propitious benefits over st and ard fibrinolytic therapy in diabetic patients . BACKGROUND Diabetics with acute ST-segment elevation myocardial infa rct ion ( MI ) have a worse outcome compared with nondiabetics . Higher-risk patients are usually more likely to benefit from advances in medical therapy . METHODS We analyzed diabetic patients enrolled in the GUSTO V trial to assess the outcome of those r and omized to the combination of half-dose reteplase and abciximab versus those r and omized to reteplase . We also evaluated whether any differences existed in presentation and outcome of MI among the diabetics versus the nondiabetics enrolled in the study . RESULTS The trial enrolled 13782 nondiabetics and 2633 diabetics . Compared to nondiabetics , diabetics had a significantly higher mortality at 30 days ( 8.5 % vs. 5.1 % , p < 0.001 ) and at 1 year ( 12.7 % vs. 7.5 % , p < 0.001 ) . Among the diabetic subset , no significant difference existed in the incidence of 30-day ( 8.8 % vs. 8.2 % , p = 0.52 ) or 1-year mortality ( 13.0 % vs. 12.4 % , p = 0.62 ) among patients r and omized to reteplase compared to those receiving combination of abciximab and reteplase . The incidence of reinfa rct ion ( 2.5 % vs. 4.3 % , p = 0.013 ) , recurrent ischemia ( 11.8 % vs. 14.9 % , p = 0.017 ) , and urgent revascularization ( 10.9 % vs. 13.3 % , p = 0.055 ) at seven days was lower in diabetics treated with the combination therapy . CONCLUSIONS Compared to nondiabetics , diabetics continue to have a worse outcome with MI . Although combination therapy did not provide a survival benefit , nonfatal ischemic outcomes , including reinfa rct ion , recurrent ischemia , and urgent revascularization , were substantially reduced Little is known about the effect of diabetes mellitus on long-term clinical outcome after primary percutaneous coronary intervention ( pPCI ) compared with fibrinolysis in patients who have acute ST-elevation myocardial infa rct ion . We analyzed 3-year clinical outcome in diabetic patients and nondiabetic patients who had been r and omized to fibrinolysis or pPCI in the DANAMI-2 trial to compare long-term clinical outcome . The primary end point was a composite of death , clinical reinfa rct ion , or disabling stroke . Median follow-up was 3.8 years . Among 1,572 consecutive patients who had ST-elevation myocardial infa rct ion and were r and omized to pPCI or fibrinolysis , 173 ( 11.0 % ) had diabetes mellitus ; 60 of these patients received metformin treatment and were excluded . After 3 years no difference was found between diabetic patients who underwent pPCI versus fibrinolysis ( combined event p=0.37 , reinfa rct ion p=0.06 in favor of fibrinolysis ) , whereas pPCI was superior to fibrinolysis in nondiabetic patients ( combined event p=0.002 , clinical reinfa rct ion p<0.001 ) . Three-year incidence of clinical reinfa rct ion analyzed with Cox 's regression showed that pPCI compared with fibrinolysis increased the relative risk of clinical reinfa rct ion in diabetic patients ( relative risk 2.57 , 95 % confidence interval 1.48 to 4.46 , p < 0.001 ) but decreased the risk in nondiabetic patients ( relative risk 0.52 , 95 % confidence interval 0.36 to 0.74 , p<0.001 ) . In conclusion , from the DANAMI-2 trial we hypothesize that diabetes may abolish the beneficial effect of pPCI on long-term risk of clinical reinfa rct ion BACKGROUND High admission blood glucose levels after acute myocardial infa rct ion ( AMI ) are common and associated with an increased risk of death in subjects with and without known diabetes . Recent data indicate a high prevalence of abnormal glucose metabolism in patients with unknown diabetes at the time of AMI . We investigated the predictive value of admission blood glucose levels after AMI for long-term prognosis in patients with and without previously diagnosed diabetes mellitus , particularly in those with unknown diabetes but with blood glucose levels in the diabetic range . METHODS In a retrospective study with prospect i ve follow-up , 846 patients ( 737 without and 109 with known diabetes ) were eligible for follow-up during a median of 50 months ( range , 0 - 93 months ) . RESULTS During follow-up , 208 nondiabetic patients ( 28.2 % ) and 47 diabetic patients ( 43.1 % ) died ( P = .002 ) . An increase of 18 mg/dL ( 1 mmol/L ) in glucose level was associated with a 4 % increase of mortality risk in nondiabetic patients and 5 % in diabetic patients ( both P<.05 ) . Of the 737 previously nondiabetic subjects , 101 had admission blood glucose levels of 200 mg/dL ( 11.1 mmol/L ) or more , and mortality in these patients was comparable to that in patients who had established diabetes ( 42.6 % vs 43.1 % ) . CONCLUSIONS Admission blood glucose level after AMI is an independent predictor of long-term mortality in patients with and without known diabetes . Subjects with unknown diabetes and admission glucose levels of 200 mg/dL ( 11.1 mmol/L ) or more after AMI have mortality rates comparable to those of subjects with established diabetes . Admission blood glucose level may serve to identify subjects at high long-term mortality risk , in particular among those with unknown diabetes Hypertension ( HT ) and diabetes mellitus ( DM ) lead to structural and functional cardiac impairment and worsen the prognosis after myocardial infa rct ion ( MI ) . However , the prognosis of male or female patients with the coexistence of HT and DM after MI has not been clearly demonstrated . The study sample comprised 4317 consecutive patients with an acute MI from a prospect i ve nationwide survey conducted in 1992 , 1994 and 1996 in all 25 coronary care units operating in Israel . The in-hospital , 30-day and 1-year outcome of diabetic hypertensive patients ( n=546 ) was compared with that of diabetic normotensive patients ( n=547 ) and with that of nondiabetic hypertensive patients ( n=1192 ) and nondiabetic normotensive subjects ( n=2032 ) . The crude in-hospital , 30-day and 1-year mortality rates of diabetic hypertensive patients ( 11.7 , 16.5 and 27.6 % , respectively ) were significantly higher than those of the diabetic normotensive patients ( 9.5 , 15.4 and 22.9 % , respectively ) and nondiabetic hypertensive patients ( 7.1 , 11.6 and 17.6 % , respectively ) . Kaplan – Meier survival curves showed increased mortality rates during the 1-year follow-up in diabetic hypertensive patients . Adjusted risk for 1-year mortality was increased in diabetic patients . However , the risk was similar in diabetic hypertensive and normotensive patients ( hazard ratio ( HR ) 1.55 , 95 % confidence interval ( CI ) 1.25–1.93 , and 1.62 , 95 % CI 1.29–2.04 , respectively ) . Adjusted Kaplan – Meier survival curves of diabetic hypertensive patients converged with those of the diabetic normotensives . The existence of DM increases the 1-year mortality after MI by about 60 % . However , controlled hypertension did not worsen the outcome of diabetic male or female patients after MI OBJECTIVE Mortality in diabetic patients with acute myocardial infa rct ion ( MI ) is high . The significance of the pretreatment coronary status in type 2 diabetic patients with acute MI , as well as the effect of mechanical revascularization using percutaneous transluminal coronary angioplasty ( PTCA ) , has not been established . RESEARCH DESIGN AND METHODS All patients with type 2 diabetes and acute MI ( n = 54 ) were prospect ively enrolled into a study of immediate coronary angiography to guide PTCA of the occluded infa rct vessel . Hospital and long-term course were assessed and compared with an unselected control group of nondiabetic patients ( n = 358 ) who were enrolled in the same study . RESULTS Angiography showed that sites of occlusion and acute coronary flow were similar in both groups . Multivessel disease and shock were more common in type 2 diabetic versus nondiabetic patients : 69 vs. 51 % and 21 vs. 10 % ( P < 0.02 ) , respectively . Direct PTCA was successful in > 90 % in both groups . Mortality after 30 days was 13 % in type 2 diabetic patients versus 5 % in patients without diabetes ( P < 0.04 ) . Left ventricular ( LV ) ejection fraction before discharge was lower in diabetic patients ( 48 + /- 17 vs. 55 + /- 15 % , P < 0.05 ) . Mortality 1 year after discharge was 11 vs. 4 % in diabetic versus nondiabetic patients ( P < 0.02 ) . Multivariate analysis identified type 2 diabetes as an independent risk factor for acute , but not for late , mortality . CONCLUSIONS Direct PTCA is safe and effective in type 2 diabetic patients with acute MI . Mortality after 30 days in unselected diabetic patients is < 15 % with this approach . Advanced disease and shock contribute to an increased mortality in type 2 diabetic patients with acute MI versus nondiabetic patients Several studies have highlighted the prognostic role of preprocedural Thrombolysis In Myocardial Infa rct ion ( TIMI ) flow in the infa rct -related artery ( IRA ) in patients with ST-segment elevation myocardial infa rct ion ( STEMI ) . However , the impact of preprocedural IRA occlusion in patients with diabetes with STEMI has been insufficiently studied . The aim of this study was to evaluate the effects of baseline IRA occlusion and diabetic status in patients with STEMI who underwent primary percutaneous coronary intervention by using data from a pooled analysis of r and omized trials comparing intracoronary with intravenous abciximab bolus administration . A total of 3,046 patients with STEMI who underwent primary percutaneous coronary intervention were included . Diabetes was present in 578 patients ( 19 % ) . The primary outcome was mortality after a median follow-up period of 375 days . Secondary end points were reinfa rct ion and stent thrombosis . In patients without diabetes , IRA occlusion versus no occlusion was not associated with increased rates of mortality ( 4.3 % vs 2.7 % , p = 0.051 ) and reinfa rct ion ( 3.3 % vs 2.5 % , p = 0.33 ) . Patients with diabetes with IRA occlusion compared with those without occlusion showed higher rates of mortality ( 10.6 % vs 4.6 % , p = 0.01 ) and reinfa rct ion ( 5.6 % vs 2.1 % , p = 0.03 ) . Baseline IRA occlusion increased the rate of stent thrombosis in the nondiabetic ( 2.1 % vs 1.0 % , p = 0.04 ) and diabetic ( 3.2 % vs 0.8 % , p = 0.05 ) cohorts . Interaction analysis demonstrated that the risk for death and reinfa rct ion was significantly increased when diabetes and IRA occlusion occurred concomitantly . In conclusion , patients with STEMI with diabetes and baseline IRA occlusion had disproportionately higher rates of death and reinfa rct ion . Preprocedural IRA occlusion increased the risk for stent thrombosis , irrespective of diabetic status Objective — There is an excess mortality after myocardial infa rct ion in diabetics , but also documented significant differences in the characteristics of MI and in management between diabetics and non-diabetics . The aim of this prospect i ve study in a large unselected patient cohort in a single French region was to determine if baseline characteristics , management , or in-hospital and one-year mortality differed in diabetic and non-diabetic patients with myocardial infa rct ion . Methods and results — Data were prospect ively collected in consecutive patients with myocardial infa rct ion admitted to all hospitals in three departments in the Rhône-Alpes region between September 1 , 1993 and January 31,1995 . Among the 2,297 patients , 410 patients ( 17.8 % ) were diabetic . Although diabetics were older than non-diabetics ( 70.3 vs. 67.8 years ; p < 0.0004 ) , and less likely to receive thrombolysis ( 31 % vs. 36 % ; p = 0.043 ) , in-hospital mortality was not significantly higher ( 17.3 % vs. 14.7 % ) than in non-diabetics . In multivariate analysis , diabetes was a significant predictor of one-year mortality ( relative risk : 1.41 ; 95 % CI = 1.10 – 1.79 ; p = 0.0063 ) but not of in-hospital mortality ( relative risk : 1.2 ; 95 % CI = 0.9 – 1.7 ; p = 0.25 ) . Multivariate predictors of in-hospital and one-year mortality in diabetics were age and Killip class at admission . Conclusions — In this large unselected French cohort , diabetes mellitus was a significant predictor of one-year but not of in-hospital mortality after myocardial infa rct ion in a French region . This negative effect of diabetes on mortality was not related to differences in baseline characteristics , or in initial or post-discharge management between diabetics and non-diabetics |
10,777 | 21,205,241 | Longitudinal studies have demonstrated detectable progression of lesion load over short time periods , and weak correlations with cognition .
Stronger correlations with cognition have been found with diffusion tensor imaging , which is more sensitive to white matter tract structure , supporting a role for disconnection in the pathogenesis of cognitive impairment .
Brain volume also consistently correlates with cognition in asymptomatic small vessel disease , sporadic small vessel disease , and Cerebral Autosomal Dominant Arteriopathy with Subcortical Infa rcts and Leukoencephalopathy .
The greater sensitivity of diffusion tensor imaging parameters and brain volume to change , and the stronger correlation of these parameters with cognition , suggest that they may be more powerful surrogates . | Cerebral small vessel disease is an important cause of vascular cognitive impairment and dementia .
On brain imaging , discrete lacunar infa rcts and /or more diffuse regions of white matter hyperintensities or leucoaraiosis are seen .
Magnetic resonance imaging plays a crucial role in diagnosis , and advanced magnetic resonance imaging techniques are providing new information on disease mechanisms and offering potential as surrogate disease markers .
In this systematic review , we describe the use of both conventional and advanced magnetic resonance imaging techniques in patient groups with the full spectrum of clinical small vessel disease , from normal population s with WMH to patients groups with lacunar stroke and dementia | Cerebral autosomal dominant arteriopathy with subcortical infa rcts and leucoencephalopathy ( CADASIL ) is a hereditary arteriopathy caused by mutations of the Notch3 gene . The risk factors for cerebral microhaemorrhages ( CM ) , their relationship to other MRI lesions in the disease and their potential clinical impact have not been previously defined . Our purpose was to examine the frequency , number and location of microhaemorrhages in a multicentre cohort study , defining predisposing factors and associated radiographic markers in CADASIL patients . We collected clinical data from 147 consecutive patients enrolled in an ongoing prospect i ve cohort study . Degree of neurological disability and cognitive impairment were assessed by st and ardized scales . T(1)-weighted , FLAIR and T2 * -weighted gradient-echo ( GE ) MRI sequences were performed . Volume and location of lacunar infa rcts and white matter hyperintensity ( WMH ) were assessed . Number and location of CM were recorded . CM were present in 35 % patients , most commonly occurring in the thalamus , brainstem and basal ganglia . The location of CM qualitatively differed from areas of lacunar infa rct ion and WMH . There was a significant association between the presence of CM and a history of hypertension ( P = 0.005 ) , systolic blood pressure ( SBP ) ( P = 0.014 ) , haemoglobin A1c ( HbA1c ) ( P = 0.004 ) and the volume of lacunar infa rcts ( P = 0.010 ) and WMHs ( P = 0.046 ) . The number of CM was independently associated with SBP ( P = 0.005 ) , the diagnosis of hypertension ( P = 0.0004 ) , volume of WMH ( P = 0.0005 ) and lacunar infa rcts ( P = 0.004 ) . In contrast , no association was found between blood pressure or HbA1c and the load of WMH or lacunar infa rcts . The presence of CM was independently associated with increased modified Rankin scores . CM are independently associated with blood pressure and HbA1c as well as with lacunar infa rct and WMH volume in CADASIL . Both the vascular risk factors and regional distribution of CM appear distinct from those associated with other MRI markers , suggesting a distinct pathological process . These lesions have a potential clinical impact in CADASIL . These findings further suggest that modulation of blood pressure and glucose levels might influence the course of the disease Background —The prevalence of white matter hyperintensities ( WMHs ) detected on cerebral MRI is associated with hypertension , but it is not known whether blood pressure lowering can arrest their progression . We report here the results of an MRI sub study of PROGRESS ( Perindopril Protection Against Recurrent Stroke Study ) , a r and omized trial of blood pressure lowering in subjects with cerebrovascular disease . Methods and Results —The sub study comprised 192 participants who had a cerebral MRI both at baseline and after a mean follow-up time of 36 months ( SD=6.0 months ) . At the first MRI , WMHs were grade d with a visual rating scale from A ( no WMH ) to D ( severe WMH ) . Participants were assigned to a combination of perindopril plus indapamide ( or their placebos ; 58 % ) or to single therapy with perindopril ( or placebo ) . At the time of the second MRI , the blood pressure reduction in the active arm compared with the placebo arm was 11.2 mm Hg for systolic blood pressure and 4.3 mm Hg for diastolic blood pressure . Twenty-four subjects ( 12.5 % ) developed new WMHs at follow-up . The risk of new WMH was reduced by 43 % ( 95 % CI −7 % to 89 % ) in the active treatment group compared with the placebo group ( P=0.17 ) . The mean total volume of new WMHs was significantly reduced in the active treatment group ( 0.4 mm3 [ SE=0.8 ] ) compared with the placebo group ( 2.0 mm3 [ SE=0.7 ] ; P=0.012 ) . This difference was greatest for patients with severe WMH at entry , 0.0 mm3 ( SE=0 ) in the active treatment group versus 7.6 mm3 ( SE=1.0 ) in the placebo group ( P<0.0001 ) . Conclusions —These results indicate that an active blood pressure – lowering regimen stopped or delayed the progression of WMHs in patients with cerebrovascular disease Cerebral white matter lesions ( WMLs ) have been associated with cognitive dysfunction . Whether periventricular or subcortical WMLs relate differently to cognitive function is still uncertain . In addition , it is unclear whether WMLs are related to specific cognitive domains such as memory or psychomotor speed . We examined the relationship between periventricular and subcortical WMLs and cognitive functioning in 1,077 elderly subjects r and omly sample d from the general population . Quantification of WMLs was assessed by means of an extensive rating scale on 1.5‐T magnetic resonance imaging scans . Cognitive function was assessed by using multiple neuropsychological tests from which we constructed compound scores for psychomotor speed , memory performance , and global cognitive function . When analyzed separately , both periventricular and subcortical WMLs were related to all neuropsychological measures . When periventricular WMLs were analyzed conditional on subcortical WMLs and vice versa , the relationship between periventricular WMLs and global cognitive function remained unaltered whereas the relationship with subcortical WMLs disappeared . Subjects with most severe periventricular WMLs performed nearly 1 SD below average on tasks involving psychomotor speed , and more than 0.5 SD below average for global cognitive function . Tasks that involve speed of cognitive processes appear to be more affected by WMLs than memory tasks . Ann Neurol 2000;47:145–151 Background and Purpose We investigated the hypothesis that patients with one or more asymptomatic lacunar infa rcts and those with only one symptomatic lacunar infa rct represent two clinical ly distinct lacunar infa rct entities . Methods In a prospect i ve series of 100 lacunar infa rct patients , univariate and multivariate logistic regression analysis was performed on clinical features , vascular risk factors , and leukoaraiosis between patients with and without asymptomatic lacunar infa rcts . Results Patients with asymptomatic lacunar infa rcts had hypertension significantly more often ( 71 % versus 43 % ; [ crude ] odds ratio , 3.31 ; 95 % confidence intervals , 1.16 - 9.43 ; p<0.05 ) and had leukoaraiosis significantly more often ( 71 % versus 19 % ; [ crude ] odds ratio , 10.67 ; 95 % confidence intervals , 3.81 - 32.10 ; p < 0.001 ) than those with only a symptomatic lacunar infa rct . After multivariate logistic regression analysis , only leukoaraiosis was significantly associated with the presence of asymptomatic lacunar infa rcts . The asymptomatic lacunar infa rcts differed in location , involved vascular territory , and volume from the symptomatic infa rcts . Conclusions Two distinct lacunar infa rct entities might be broadly distinguished during life : lacunar infa rct patients with a single , symptomatic lacunar infa rct , and patients with multiple lacunar infa rcts and a high frequency of hypertension and leukoaraiosis , in which the underlying small-vessel vasculopathy might be different Background and Purpose — Gradient-echo T2 * -weighted MRI is uniquely sensitive to detect silent , old hemosiderin deposits , but the clinical significance of such “ microbleeds ” remains to be determined . Therefore , we investigated the incidence and the number of microbleeds among different stroke subtypes and the correlation with stroke recurrence and the severity of leukoaraiosis . Methods — This study consisted of 213 patients ( 73.5±9.1 years old , 104 men and 109 women ) , who were classified according to stroke subtypes into atherothrombotic infa rct ion ( 24 patients ) , cardioembolic infa rct ion ( 23 patients ) , lacunar infa rct ion ( 66 patients ) , intracerebral hemorrhage ( 35 patients ) , and control ( 65 patients ) groups . Gradient-echo T2 * -weighted MRI was performed with a 1.5 T system , and asymptomatic microbleeds were located and counted . Results — The incidence and the number of microbleeds were significantly greater in patients with intracerebral hemorrhage ( 71.4 % and 9.1±13.8 , respectively ) and lacunar infa rct ion ( 62.1 % and 7.4±16.1 ) compared with patients with cardioembolic infa rct ion ( 30.4 % and 2.5±5.6 ) , atherothrombotic infa rct ion ( 20.8 % and 0.63±1.53 ) , and controls ( 7.7 % and 0.09±0.34 ) . There was a correlation between the number of microbleeds and the severity of periventricular hyperintensity ( r = 0.626 , P < 0.0001 ) . There was also a correlation between the number of microbleeds and the number of intracerebral hemorrhages ( r = 0.689 , P < 0.0001 ) or lacunar infa rct ions ( r = 0.514 , P < 0.0001 ) . The locations of microbleeds were subcortical white matter ( 31.8 % ) , thalamus ( 24.8 % ) , basal ganglia ( 19.8 % ) , brain stem ( 12.0 % ) , and cerebellum ( 11.7 % ) . Conclusions — The findings suggest that microbleeds on T2 * -weighted MRI are an indicator of advanced small artery disease of the brain with an increased risk for bleeding . This result should be taken into consideration when treating patients with stroke , and further studies are required Patients with cerebral small vessel disease ( SVD ) can present as isolated lacunar infa rct ion or with diffuse white matter changes , with the imaging appearance of leukoaraiosis . Endothelial dysfunction , which can lead to breakdown of the blood-brain barrier , impaired cerebral autoregulation and prothrombotic changes , is believed to be important in mediating disease . Circulating levels of intercellular adhesion molecule 1 ( ICAM1 ) , thrombomodulin ( TM ) , tissue factor ( TF ) and tissue factor pathway inhibitor ( TFPI ) are markers of endothelial activation and damage , and may provide insights into disease pathogenesis or differences between phenotypes . We therefore measured these markers in a prospect i ve series of patients with lacunar stroke . One hundred and ten white Caucasian patients with previous lacunar stroke and 50 community control subjects were studied . Markers of endothelial function were measured on venous blood sample s. Patients were classified on brain imaging into two groups : isolated lacunar infa rct ion ( n = 47 ) and ischaemic leukoaraiosis , defined as a clinical lacunar stroke and leukoaraiosis on brain imaging ( n = 63 ) . The number of lacunes and severity of leukoaraiosis were also scored on MRI . ICAM1 , TM and TFPI were elevated in cerebral SVD subjects compared with controls ( P < or= 0.006 ) . The ischaemic leukoaraiosis group had a different endothelial marker profile , with lower levels of TFPI ( P = 0.01 ) and a higher TF/TFPI ratio ( P = 0.01 ) compared with the isolated lacunar infa rct ion group . TM levels were associated with the number of lacunes ( P = 0.008 ) and the leukoaraiosis score ( P = 0.03 ) , but TF levels and the TF/TFPI ratio were associated only with the extent of leukoaraiosis ( P < or= 0.02 ) . These results suggest that there is evidence of chronic endothelial dysfunction in cerebral SVD , and endothelial prothrombotic changes may be important in mediating the ischaemic leukoaraiosis phenotype . Therapies which help to stabilize the endothelium may have a role in this group of patients Background and Purpose — Most previous studies addressed the cognitive impact of lacunar infa rcts using radiologic correlations that are known to correlate poorly with neuropathological data . Moreover , absence of systematic bilateral assessment of vascular lesions and masking effects of Alzheimer disease pathology and macrovascular lesions may explain discrepancies among previous reports . To define the relative contribution of silent lacunes to cognitive decline , we performed a detailed analysis of lacunar and microvascular pathology in both cortical and subcortical areas of 72 elderly individuals without significant neurofibrillary tangle pathology or macrovascular lesions . Methods — Cognitive status was assessed prospect ively using the Clinical Dementia Rating ( CDR ) scale ; neuropathological evaluation included Aβ-protein deposition staging and bilateral assessment of microvascular ischemic pathology and lacunes ; statistical analysis included multivariate models controlling for age , amyloid deposits , and microvascular pathology . Results — Thalamic and basal ganglia lacunes were negatively associated with CDR scores ; cortical microinfa rcts , periventricular and diffuse white matter demyelination also significantly affected cognition . In a multivariate model , cortical microinfa rcts and thalamic and basal ganglia lacunes explained 22 % of CDR variability ; amyloid deposits and microvascular pathology explained 12 % , and the assessment of thalamic and basal ganglia lacunes added an extra 17 % . Deep white matter lacunes were not related to cognitive status in univariate and multivariate models . Conclusions — In agreement with the recently proposed concept of subcortical ischemic vascular dementia , our autopsy series provides important evidence that gray matter lacunes are independent predictors of cognitive decline in elderly individuals without concomitant dementing processes such as Alzheimer disease BACKGROUND Silent brain infa rcts are frequently seen on magnetic resonance imaging ( MRI ) in healthy elderly people and may be associated with dementia and cognitive decline . METHODS We studied the association between silent brain infa rcts and the risk of dementia and cognitive decline in 1015 participants of the prospect i ve , population -based Rotterdam Scan Study , who were 60 to 90 years of age and free of dementia and stroke at base line . Participants underwent neuropsychological testing and cerebral MRI at base line in 1995 to 1996 and again in 1999 to 2000 and were monitored for dementia throughout the study period . We performed Cox proportional-hazards and multiple linear-regression analyses , adjusted for age , sex , and level of education and for the presence or absence of subcortical atrophy and white-matter lesions . RESULTS During 3697 person-years of follow-up ( mean per person , 3.6 years ) , dementia developed in 30 of the 1015 participants . The presence of silent brain infa rcts at base line more than doubled the risk of dementia ( hazard ratio , 2.26 ; 95 percent confidence interval , 1.09 to 4.70 ) . The presence of silent brain infa rcts on the base-line MRI was associated with worse performance on neuropsychological tests and a steeper decline in global cognitive function . Silent thalamic infa rcts were associated with a decline in memory performance , and nonthalamic infa rcts with a decline in psychomotor speed . When participants with silent brain infa rcts at base line were subdivided into those with and those without additional infa rcts at follow-up , the decline in cognitive function was restricted to those with additional silent infa rcts . CONCLUSIONS Elderly people with silent brain infa rcts have an increased risk of dementia and a steeper decline in cognitive function than those without such lesions Background : Cerebral small vessel disease is a common cause of vascular dementia . Both discrete lacunar infa rcts and more diffuse ischaemic changes , seen as confluent high signal ( leukoaraiosis ) on T2 weighted magnetic resonance imaging ( MRI ) , occur . However , there is a weak correlation between T2 lesion load and cognitive impairment . Diffusion tensor MRI ( DTI ) is a new technique that may provide a better index of white matter damage . Objectives : To determine whether DTI measures are correlated more strongly with cognitive performance than lesion load on T2 weighted images , and whether these correlations are independent of conventional MRI parameters . Methods : 36 patients with ischaemic leukoaraiosis ( leukoaraiosis plus a previous lacunar stroke ) and 19 healthy volunteers underwent DTI , conventional MRI , and neuropsychological assessment . Results : On DTI , diffusivity was increased both within lesions and in normal appearing white matter . Mean diffusivity of normal appearing white matter correlated with full scale IQ ( r = −0.46 , p = 0.009 ) and tests of executive function . These correlations remained significant after controlling for age , sex , brain volume , and T1/T2 lesion volumes . No significant correlation was identified between T2 lesion load and IQ or neuropsychological scores . Of conventional measures , brain volume correlated best with cognitive function . Conclusions : Diffusion tensor measurements correlate better with cognition than conventional MRI measures . They may be useful in monitoring disease progression and as a surrogate marker for treatment trials . The findings support the role of white matter damage and disruption of white matter connections in the pathogenesis of cognitive impairment in cerebral small vessel disease Background and Purpose — Cerebral autosomal dominant arteriopathy with subcortical infa rcts and leukoencephalopathy ( CADASIL ) is a cerebral small vessel disease caused by mutations in the NOTCH3 gene . MRI is sensitive in detecting pre clinical involvement and changes over time . However , little is known about correlations between MRI metrics and clinical measures on a longitudinal scale . In this study , we assessed the role of quantitative MRI ( T2-lesion volume and diffusion tensor imaging [DTI]–derived metrics ) in monitoring and predicting disease progression . Methods — Sixty-two CADASIL subjects were followed prospect ively over a period of 26.3±1.2 months . Dual-echo scans , DTI scans , and clinical scales were obtained at baseline and at follow-up . T2-lesion volumes were determined quantitatively , and histograms of mean diffusivity ( MD ) were produced . Results — At follow-up , T2-lesion volumes and MD histogram metrics had changed significantly ( all P<0.01 ) . Lesion volumes and average MD correlated with clinical scores at baseline . Changes of average MD correlated with changes of the Rankin score , the National Institutes of Health Stroke Scale score , and the structured interview for the diagnosis of Alzheimer dementia and multiinfa rct dementia score ( all P<0.01 ) . On multivariate analysis , average MD and systolic blood pressure at baseline were predictors of changes of average MD during follow-up . Moreover , average MD was the main predictor of clinical progression . Sample size estimates showed that the number of individuals required to detect a treatment effect in an interventional trial may be reduced when using MD histograms as an end point . Conclusions — This study establishes correlations between changes of DTI histogram metrics and clinical measures over time . DTI histograms may be used as an adjunct outcome measure in future therapeutic trials . Moreover , DTI histogram metrics predict disease progression in CADASIL Background and Purpose — We obtained magnetization transfer imaging ( MTI ) scans from individuals with cerebral autosomal-dominant arteriopathy with subcortical infa rcts and leukoencephalopathy ( CADASIL ) ( 1 ) to investigate the presence , extent , and nature of pathology in white and gray matter outside proton density (PD)-visible lesions ; ( 2 ) to quantify the degree of tissue damage occurring in lesions seen on PD-weighted scans ; and ( 3 ) to correlate MTI-derived measures of disease burden with age , physical disability , and cognitive performance . Methods — Dual-echo , T1-weighted , and MTI scans of the brain were obtained from 33 individuals with CADASIL and 12 control subjects . Magnetization transfer ratio ( MTR ) values from PD-visible lesions , normal-appearing white matter ( NAWM ) , and normal-appearing gray matter ( NAGM ) were measured . Histograms of MTR from the whole brain and normal-appearing brain tissue were also produced . Results — All MTR values from NAWM and NAGM regions studied were significantly lower for individuals with CADASIL than for control subjects , with the exception of those obtained from the NAWM of the infratentorial structures and the NAGM of the occipital cortex . The average MTR from PD lesions in individuals with CADASIL was significantly lower than that from all the NAWM regions . Average MTR and peak location from whole-brain and normal-appearing brain tissue histograms were significantly lower for individuals with CADASIL than for control subjects . MTR values from NAWM were strongly correlated with the extent of macroscopic lesions and their average MTR . Apart from NAGM , average MTR from all other tissues studied significantly decreased with increasing age , physical disability , and cognitive impairment . Conclusions — PD lesions of individuals with CADASIL have variable degrees of tissue damage . Brain tissue outside PD abnormalities is also damaged . This study suggests that the extent and the severity of the brain tissue damage are critical factors in determining clinical status in CADASIL Objective : To investigate the influence of deep white matter hyperintensities ( DWMH ) and periventricular white matter hyperintensities ( PVWMH ) on progression of cognitive decline in non-demented elderly people . Methods : All data come from the nested MRI sub- study of the PROspect i ve Study of Pravastatin in the Elderly at Risk ( PROSPER ) . We performed a 3 year follow up study on 554 subjects of the PROSPER study using both repeated magnetic resonance imaging and cognitive testing . Cognitive decline and its dependency on WMH severity was assessed using linear regression models adjusted for sex , age , education , treatment group , and test version when applicable . Results : We found that the volume of PVWMH at baseline was longitudinally associated with reduced mental processing speed ( p = 0.0075 ) . In addition , we found that the progression in PVWMH volume paralleled the decline in mental processing speed ( p = 0.024 ) . In contrast , neither presence nor progression of DWMH was associated with change in performance on any of the cognitive tests . Conclusion : PVWMH should not be considered benign but probably underlie impairment in cognitive processing speed To precise the severity of dilated Virchow-Robin spaces ( VRS ) in CADASIL patients and to determine their correlation with clinical presentation and other abnormalities on cerebral Magnetic Resonance Imaging ( MRI ) . Dilated VRS were previously associated with aging , hypertension , dementia , epilepsy or migraine . We already reported increased frequency of enlarged VRS in CADASIL patients when compared with family members without the affected haplotype . We analysed clinical and MRI data from 50 CADASIL patients collected prospect ively in our center . The presence of dilated VRS was assessed in the subcortical white matter of temporal lobes , the centrum semi-ovale and the basal ganglia . Their severity in each region was evaluated according to the scale proposed by Heier . We compared the clinical data , the severity of white matter abnormalities and the presence of microbleeds in patients with and without dilated VRS . Seventy-eight percent of patients in our series had dilated VRS , mostly located in the lentiform nuclei ( 94 % ) and subcortical white matter of the temporal lobes ( 66 % ) . The severity of these lesions was variable but not correlated neither to the extent of white matter abnormalities nor to the clinical presentation in our patients . Only the age was found to be related to the extent of dilated VRS . Dilated VRS are frequent in CADASIL and mostly located in the temporal white matter and basal ganglia . The dilation of perivascular spaces does not seem to be directly related to the occurrence of ischemic or hemorrhagic lesions in CADASIL . In contrast , the relation with age suggests that either aging , progression of vascular wall alterations during the course of the disease , or both of these processes can favour the extension of VRS in CADASIL Cerebral white matter lesions are a common finding on MRI in elderly persons . We studied the prevalence of white matter lesions and their relation with classic cardiovascular risk factors , thrombogenic factors , and cognitive function in an age- and gender-stratified r and om sample from the general population that consisted of 111 subjects 65 to 84 years of age . Overall , 27 % of subjects had white matter lesions . The prevalence and severity of lesions increased with age . A history of stroke or myocardial infa rct ion , factor VIIc activity , and fibrinogen level were each significantly and independently associated with the presence of white matter lesions . Significant relations with blood pressure level , hypertension , and plasma cholesterol were present only for subjects aged 65 to 74 years . White matter lesions tended to be associated with lower scores on tests of cognitive function and were significantly associated with subjective mental decline . This study suggests that classic cardiovascular risk factors , as well as thrombogenic factors , are associated with white matter lesions in subjects over 65 years of age in the general population , and that these lesions may be related to cognitive function Objective : To investigate the location and severity of MRI signal abnormalities in cerebral autosomal dominant arteriopathy with subcortical infa rcts and leukoencephalopathy ( CADASIL ) . Background : One hallmark of this arteriopathy due to mutations of Notch 3 gene is the presence of MRI signal abnormalities in both symptomatic and asymptomatic patients . Methods : MRIs of 75 patients ( 43 with symptoms ) were review ed by a neuroradiologist masked to their clinical status . After assessing the presence of MRI lesions on T1- and T2-weighted images ( T1-WI , T2-WI ) in different subcortical regions , the severity of hyperintensities on T2-WI was scored using a global rating scale and a regional semiquantitative scale in the periventricular white matter ( PV ) , deep white matter ( WM ) , basal ganglia ( BG ) , and infratentorial areas ( IT ) . Results : Sixty-eight patients ( 90 % ) had hyperintensities on T2-WI located in the white matter , more frequent in PV ( 96 % ) and WM ( 85 % ) than in the superficial white matter ( 25 % ) . Hyperintensities also occurred in BG ( 60 % ) and brainstem(45 % ) . Forty-seven patients ( 62 % ) presented with hypointensities on T1-WI . In one-third of the affected inviduals , white matter hyperintensities occurred in the absence of small deep infa rcts on T1-WI . The frequency and severity scores calculated for PV , WM , BG , or IT hyperintensities increase dramatically with age . These scores were higher in symptomatic compared with asymptomatic gene carriers . Dementia , Rankin score > 1 , or both occurred only in the presence of diffuse white matter signal abnormalities . Conclusion : Our results suggest that different subcortical areas have different vulnerabilities to ischemia in CADASIL . The age effect we observed may show an accumulation of lesions with aging during the course of the disease . A prospect i ve study is needed to investigate if the rating of MRI lesions is of prognostic value in CADASIL Background Retrospective studies suggested that cerebral microbleeds ( MB ) on magnetic resonance images ( MRI ) increase risk of intracerebral haemorrhage ( ICH ) . Objective To compare the benefit of anti-thrombotic agents in stroke prevention ( absolute risk reduction 2.49 –6 % ) versus risk of ICH in ischaemic stroke patients with MB . Material s and methods We prospect ively studied patients admitted consecutively for acute ischaemic stroke between 1999 and 2004 . MB on MRI were documented . Primary end points were subsequent ICH , recurrent cerebral infa rct ( CI ) and mortality . Results A total of 908 patients were recruited . MB were identified in 252 ( 27.8 % ) patients . Mean follow-up period was 26.6 ± 15.4 months . Risk of subsequent ICH increased significantly with quantity of MB : 0.6 % ( no MB ) , 1.9 % ( 1 MB ) , 4.6 % ( 2–4 MB ) and 7.6 % ( ≥ 5 MB ) ( p < 0.001 ) . There was also a significant increase in mortality from ICH : 0.6 % , 0.9 % , 1.5 % and 3.8 % respectively ( p = 0.054 ) . Rate of recurrent CI was 9.6 % , 5.6 % , 21.5 % and 15.2 % respectively ( p = 0.226 ) . Mortality from CI and myocardial infa rct ion did not increased with quantity of MB . Survival analyses showed that age , presence of MB , mixed cortical-subcortical distribution of MB were independent predictors of subsequent ICH . Conclusion Risk and mortality of ICH increased with quantity of MB . As tendency to recurrent CI exceed that of ICH , anti-thrombotic agents are still warranted . However , in patients with ≥ 5 MB , the high risk and mortality of ICH seem to outweigh the modest benefit of antithrombotic agents . Extra pre caution s should be taken to minimize risk of ICH . Further studies in patients on Coumadin and assessment of functional outcome are warranted to support these preliminary findings Objective : Cerebral autosomal dominant arteriopathy with subcortical infa rcts and leukoencephalopathy ( CADASIL ) is a hereditary arteriopathy caused by mutations of the Notch3 gene . The disease is characterized by T2-hyperintense lesions ( subcortical white matter lesions ) , T1-hypointense lesions ( lacunar lesions ) , and T2 * -weighted gradient-echo ( GE ) lesions ( cerebral microhemorrhages [ CMs ] ) visualized on clinical MRI sequences and is considered as a model of “ pure ” subcortical ischemic vascular dementia . Although numerous studies have investigated the impact of white matter lesions in patients with CADASIL , the clinical importance of lacunar lesions remains unknown . Our purpose was to examine the influence of the visible MRI markers in the disease , including the load of lacunar lesions on cognitive impairment and disability in CADASIL . Methods : We collected clinical data from 147 consecutive patients enrolled in an ongoing two-center prospect i ve cohort study . Degree of disability was assessed by modified Rankin scale and Barthel index . Degree of cognitive impairment was assessed by Mattis Dementia Rating Scale and Mini-Mental Status Examination . T1-weighted , fluid-attenuated inversion recovery , and GE images were obtained on a 1.5-T MRI . Volume and location of lacunar lesions , white matter hyperintensities ( WMHs ) , and CMs were assessed . Results : There was a significant independent association between age , volume of lacunar lesions , and global cognitive function scales when analyzed in a multivariable model . In contrast , WMHs and CMs had no independent influence on cognitive function . Disability in this cohort was associated with volume of lacunar lesions , CMs , systolic blood pressure , and age but not with WMHs . Conclusions : Among the lesions observed on conventional MRI in cerebral autosomal dominant arteriopathy with subcortical infa rcts and leukoencephalopathy ( CADASIL ) , the overall lacunar lesion burden seems to have the most important impact on cognitive function and disability . These findings suggest that preventive strategies to decrease the risk of lacunar lesions as observed on MRI may reduce disease-related impairment in CADASIL . These results suggest that lacunar lesions may also play a key role in disability and cognitive impairment in more common forms of small-vessel disease Serial quantitative magnetic resonance imaging ( MRI ) allows the detection of subtle volumetric changes in brain volume . We used serial volumetry and voxel-based difference image analysis to quantify and characterize longitudinal changes in the hippocampus , cerebellum , and neocortex in younger and middle-age individuals . Paired volumetric MRI brain scans 3.5 years apart were performed on 90 healthy subjects 14 to 77 years old . Quantitative assessment of registered images included hippocampal volumetry , cerebellar volumetry , and automatically determined regional brain volumes . Longitudinal volume changes in three age epochs ( < 35 , 35 - 54 , > 54 years ) were compared and neocortical changes beyond regions of interest were visualized using filtered difference images . Cross-sectional analysis revealed a significant association between age and reduction in all brain volumes except hippocampal volume . Changes in normalized hippocampal and white matter volume were significantly different among the three groups . Individual analysis revealed 5 subjects with significant longitudinal volume changes lying outside the normative range . Difference image analysis showed global involutional changes in the > 54 age group . Our findings suggest that cross-sectional observations in intracranial volume , cerebellar volume , and gray matter volume are likely to reflect uniform rates of volume loss or secular changes . Accelerated brain atrophy was seen from the age of 35 - 54 and increased rates of hippocampal atrophy from the age of 54 . Our findings emphasize the importance of controlling for age effects when study ing pathological brain changes over a wide age range The purpose of this study was to prospect ively compare high-spatial-resolution accelerated three-dimensional ( 3D ) T2 * -weighted gradient-recalled-echo ( GRE ) magnetic resonance ( MR ) images with conventional two-dimensional ( 2D ) T2 * -weighted GRE MR images for the depiction of cerebral microbleeds . After obtaining institutional review board approval and informed consent , 200 elderly participants ( age range , 69.7 - 96.7 years ; 108 [ 54 % ] women ) were imaged at 1.5 T by using both sequences . Presence , number , and location of microbleeds were recorded for both sequences , and differences were tested by using McNemar and signed rank tests . Cerebral microbleeds were detected in significantly more participants on 3D T2 * -weighted GRE images ( 35.5 % ) than on 2D T2 * -weighted GRE images ( 21.0 % ; P < .001 ) . Furthermore , in persons with microbleeds visualized on both image sets , significantly more microbleeds ( P < .001 ) were seen on 3D images than on 2D images . For both sequences , the proportion of participants with a microbleed in a lobar ( cortical gray and subcortical white matter ) , deep , or infratentorial location was similar . In conclusion , accelerated 3D T2 * -weighted GRE images depict more microbleeds than do conventional 2D T2 * -weighted GRE images |
10,778 | 28,081,889 | Conclusions Approximately 41 % of children with abdominal pain‐related functional gastrointestinal disorders improve on placebo .
Several trial characteristics are correlated significantly with the proportion of patients with no pain on placebo and with the magnitude of the placebo response on Faces Pain Scales . | Objective To investigate the magnitude and determinants of the placebo response in studies with pediatric abdominal pain‐related functional gastrointestinal disorders . | Several studies with probiotics have shown promising results in the treatment of IBS . One of the probiotics used was saccharomyces boulardii . This is a r and omized double blind placebo controlled clinical trial of S. boulardii in diarrhoea predominant IBS and was carried out in the hospital of Bangab and hu Sheikh Mujib Medical University ( BSMMU ) , Dhaka , Bangladesh from June 2004 to July 2005 . Thirty five ( 35 ) patients were included in each of the control and study groups . The study group was treated with S. boulardii 250 mg twice daily orally for one month . Patients were evaluated before therapy , at the end of therapy and 30 days after end of therapy by a scoring system which included symptoms as well as personal and professional life . No significant difference between the two groups was found in any of the parameters evaluated on any of the observation days . S. boulardii treatment for 30 days in diarrhoea predominant IBS patients did not result in any improvement in this study Background : Functional abdominal pain ( FAP ) is one of the most common diseases , and large percentages of children suffer from it . Objectives : The purpose of the study was to evaluate the effect of Lactobacillus reuteri in treatment of children with functional abdominal pain . Patients and Methods : This study was a r and omized double-blind placebo-controlled trial . Children aged 4 to 16 years with chronic functional abdominal pain ( based on Rome III criteria ) were enrolled in the study . They were r and omly divided into two groups , one receiving probiotic and the other placebo . Results : Forty children received probiotic and forty others placebo . There were no significant differences in age , weight , sex , location of pain , associated symptoms , frequency and intensity of pain between the groups . The severity and frequency of abdominal pain in the first month compared to baseline was significantly less and at the end of the second month , there was no significant difference between both groups compared to the end of the first month . Conclusions : This study showed that the severity of pain was significantly reduced in both groups . There was no significant difference in pain scores between them . The effect of probiotic and placebo can probably be attributed to psychological effect of the drugs BACKGROUND Antidepressants are effective in adults with pain-related functional gastrointestinal disorders . We investigated the effectiveness of citalopram in the treatment of childhood functional abdominal pain ( FAP ) . METHODS Children with FAP , based on the Rome III criteria ( n = 115 , aged 6 - 18 years ) , were r and omized to receive either citalopram 20 mg/day or placebo for 4 weeks . Treatment response was defined as ≥ 2 point reduction in the 6-point Faces pain rating scale or ' no pain ' . Depression , anxiety , somatization , and physician-rated global severity and improvement were also evaluated . Patients were followed up for 8 weeks after medication period . KEY RESULTS Eighty-six patients completed the medication ( 43 in each group ) . Response rate in the citalopram and placebo groups based on per- protocol ( intention-to-treat ) analysis was 55.8 % ( 40.6 % ) and 39.5 % ( 30.3 % ) at week 4 ( p = 0.097 [ 0.169 ] ) and 72.0 % ( 52.5 % ) and 53.4 % ( 41.0 % ) at week 12 ( p = 0.059 [ 0.148 ] ) , respectively . In per- protocol analysis , more reduction was observed in pain ( F = 3.84 , p = 0.024 ) and global severity scores ( F = 4.12 , p = 0.021 ) in the citalopram group compared with the placebo group over the study period . Such differences were not present in the intention-to-treat analysis . No difference was found between the two groups regarding change in depression , anxiety , or somatization score over the study . CONCLUSIONS & INFERENCES Overall , we found a trend toward the effectiveness of citalopram in the treatment of children with FAP . Trials with longer treatment duration in larger sample s of patients are required in this regard Background : Irritable bowel syndrome ( IBS ) is a common gastrointestinal disorder in children . Recently , probiotics have been suggested as a treatment option for gastrointestinal disorders . The most effective species and the most appropriate doses are still unknown . Objective : The aim of this study was to assess the effects of Lactobacillus GG ( LGG ) for treating IBS in pediatric patients . Methods : In a controlled , double blind , r and omized trial , patients with IBS diagnosed by Rome III criteria from August 2012 to September 2012 at Dr. Sheikh Hospital , Mashhad University of Medical Sciences , Iran , were assigned to one of two groups , i.e. , intervention and control groups . For four weeks , the intervention group received a probiotic in capsule form that contained LGG at a concentration of 1 × 1010 cfu/ml bacteria . For the same period , the control group received a placebo capsule that had the same shape and color but only contained inulin , which also was present in the LGG capsules . The primary outcome was any change in the severity of the patients ’ pain , and we used a five-point Likert scale to evaluate the severity of their pain . Secondary outcomes were ghanges of the functional scale , stool patterns , and associated problems . Results : Fifty-two patients participated in the study , and 26 patients were assigned r and omly to each of the two groups . The severity of the patients ’ pain decreased significantly in the intervention group after one , two , three , and four weeks of treatment , as indicated by P-values of 0.01 , 0.00 , 0.00 , and 0.00 , respectively . Also , there was significant improvement in the functional scale after two weeks of treatment ( P-value ≤ 0.00 ) . Conclusion : Lactobacillus GG at a concentration of 1 × 1010 cfu/ml for a period of four weeks can lessen the severity of the patients ’ pain and improve the functional scale in patients with irritable bowel syndrome . Probiotics can have therapeutic effects for IBS patients Abstract The objective of this study was to assess the impact of parent attention and distraction on symptom complaints by children with and without chronic functional abdominal pain . The water load symptom provocation task was used to induce visceral discomfort in pediatric patients with abdominal pain ( N = 104 ) and well children ( N = 119 ) , ages 8–16 years . Parents were r and omly assigned and trained to interact with their children according to one of three conditions : Attention , Distraction , or No Instruction . Children 's symptom complaints and parents ' responses were audiotaped and coded . Children completed a self‐report measure of gastrointestinal ( GI ) symptoms before and after interacting with their parents . Parents ' and children 's perceptions of their interaction were assessed . Compared to the No Instruction condition , symptom complaints by pain patients and well children nearly doubled in the Attention condition and were reduced by half in the Distraction condition . The effect of attention on symptom complaints was greater for female pain patients than for male patients or well children . Findings for self‐report GI symptoms were similar to those for audiotaped symptom complaints . Both pain patients and well children in the Distraction condition rated parents as making them feel better compared to ratings for the Attention condition . Parents of pain patients rated distraction as having greater potential negative impact on their children than attention . Parents ' responses to children 's symptom complaints can significantly increase or decrease those complaints . Girls with functional abdominal pain are particularly vulnerable to the symptom‐reinforcing effects of parental attention AIM The management of functional abdominal pain ( FAP ) in children and adolescents is challenging for health care professionals , and there are only limited or inconclusive studies of pharmacologic or behavioral therapy in childhood FAP . The objective of this r and omized placebo-controlled clinical trial was to determine the potential efficacy and safety of cyproheptadine in the treatment of pediatric FAP . METHODS Between January 2006 and March 2007 , 29 clinical ly referred children and adolescents with FAP ( aged 4.5 to 12 years ) completed a 2-week , double-blinded r and omized placebo-controlled trial of cyprohetadine . Primary outcome measure was the self-reported change of frequency and duration of abdominal pain by using a 6-point scale , and the parents ' impression or assessment of the children 's improvement . RESULTS By week 1 and 2 of the intervention , the intensity and frequency of abdominal pain among the patients treated with cyproheptadine , were rated as complete resolved and very much improved or improved for 3 ( 20 % ) , 10 ( 66.6 % ) , respectively . However , in the placebo-receiver children , these scales had no change in 7 ( 50 % ) , rated as improved or very much improved in 5 ( 35.7 % ) , and become worse in 2 ( 14.3 % ) . The patients ' self-reported and the parents ' impression in the cyproheptadine group were significantly better than it in the placebo group ( P=0.003 ) . CONCLUSION Among children with functional abdominal pain , cyproheptadine is enough effective to improve the intensity and frequency of abdominal pain in a short-term period BACKGROUND Analgesics for children with acute abdominal pain are often withheld for fear that they might mask physical examination findings and thus might be unsafe . This viewpoint has been challenged recently . OBJECTIVE To evaluate the effects of buccal oxycodone on pain relief , physical examination findings , diagnostic accuracy , and final clinical outcomes in children with acute abdominal pain . DESIGN Prospect i ve , r and omized , double-blind , and placebo-controlled trial between December 2001 and November 2003 . SETTING University teaching hospital in Finl and . Patients A total of 104 children aged 4 to 15 years with abdominal pain of less than 7 days ' duration were screened , and 63 children with pain scores of 5 or higher on a 10-cm visual analog scale were eligible for the trial . Intervention Children were r and omized to receive buccally either 0.1 mg/kg(-1 ) of oxycodone hydrochloride ( n = 32 ) or the same volume of normal saline ( n = 31 ) . The same surgeon described the physical findings and indicated a provisional diagnosis and a provisional disposition before the children received the study medication and at 1 hour and 3.5 hours after initial dosing . Pain scores were recorded at baseline and every 30 minutes for 3.5 hours after the first study drug administration . MAIN OUTCOME MEASURES Pain intensity difference , presence or absence of abdominal guarding , and diagnostic accuracy . RESULTS The demographic characteristics , initial pain scores , and physical signs and symptoms were similar between the 2 groups . Both study drugs were associated with decreasing pain scores . The summed pain intensity difference over 7 observations was significantly greater in the oxycodone group , 22 + /- 18 cm , than in the placebo group , 9 + /- 12 cm ( mean difference 13 cm , with a 95 % confidence interval of 2 - 24 cm ; P = .04 ) . The diagnostic accuracy increased from 72 % to 88 % in the oxycodone group and remained at 84 % in the placebo group after study drug administration . Laparotomy was performed in 17 patients in the oxycodone group and in 14 patients in the placebo group . Four patients without appendicitis underwent exploratory laparotomy in each group . One patient in the placebo group was initially diagnosed as having nonspecific abdominal pain , but at 14 hours , she was operated on for appendiceal perforation . CONCLUSIONS Early administration of buccal oxycodone provides a significant pain relief to children with acute abdominal pain , without adversely altering the clinical signs or obscuring the surgical diagnosis Aim : We evaluated the effectiveness of a synbiotic in the treatment of childhood functional abdominal pain ( FAP ) . Background : Probiotics are effective in the treatment of functional gastrointestinal disorders in adult patients , but there is lack of information in children . Patients and methods : Children with FAP , based on the Rome III criteria ( n = 115 , aged 6 - 18 years ) , were r and omized to receive either synbiotic ( Bacillus coagulans , Unique IS-2 , 150 million spore plus FOS , 100 mg ) twice daily or placebo for four weeks . Treatment response was defined as ≥ 2-point reduction in the 6-point self-rated pain scale or “ no pain ” . Physician-rated global severity and improvement were also evaluated . Patients were followed for a total of 12 weeks . Results : Eighty-eight patients completed the trial ( 45 with synbiotic ) . Response rate was higher with synbiotic than placebo after medication ( 60 % vs. 39.5 % , P = 0.044 ) , but was not different between the two groups at week 12 ( 64.4 % vs. 53.4 % , P = 0.204 ) . Difference between the two groups regarding the physician-rated global severity over the study period was not statistically significant ( z = -1.87 , P = 0.062 ) . There was no significant difference between the two groups in physician-rated global improvement ( week 4 , P = 0.437 ; week 12 , P = 0.111 ) . Receiving synbiotic ( OR 2.608 , 95 % CI : 1.01 - 6.68 ) and baseline pain score ( OR 2.21 , 95 % CI : 1.19 - 4.10 ) were predictors of treatment response after medication . Conclusion : The synbiotic containing Bacillus coagulans and FOS seems to be effective in the treatment of childhood FAP . Further trials are recommended in this regard BACKGROUND & AIMS There are no prospect i ve , multicenter , double-blind , placebo-controlled , r and omized pharmacologic trials for the treatment of pain-predominant functional gastrointestinal disorders in children . The aim of this study was to evaluate the efficacy of amitriptyline in children with pain-predominant functional gastrointestinal disorders . METHODS In this multicenter placebo-controlled trial , children with irritable bowel syndrome , functional abdominal pain , or functional dyspepsia were r and omized to 4 weeks of placebo or amitriptyline ( 10 mg/d , weight < 35 kg ; 20 mg/d , weight > 35 kg ) . Assessment of gastrointestinal symptoms , psychological traits , and daily activities occurred before and after intervention . Pain was assessed daily with self-report diaries . The primary outcome was overall response to treatment ( child 's assessment of pain relief and sense of improvement ) . Secondary outcomes were effect on psychosocial traits and daily functioning . RESULTS Ninety children were enrolled , and 83 completed the study ( placebo , 40 children [ 30 girls ] ; drug , 43 children [ 35 girls ] ) . A total of 63 % of patients reported feeling better and 5 % feeling worse in the amitriptyline arm compared with 57.5 % feeling better and 2.5 % feeling worse in the placebo arm ( P = .63 ) . Pain relief was excellent in 7 % and good in 38 % of children receiving placebo compared with excellent in 15 % and good in 35 % of children treated with amitriptyline ( P = .85 ) . Logistic regression analysis of those reporting excellent or good response versus fair , poor , or failed response showed no difference between amitriptyline and placebo ( P = .83 ) . Children who had more severe pain at baseline in both groups ( P = .0065 ) had worse outcome . Amitriptyline reduced anxiety scores ( P < .0001 ) . CONCLUSIONS Both amitriptyline and placebo were associated with excellent therapeutic response . There was no significant difference between amitriptyline and placebo after 4 weeks of treatment . Patients with mild to moderate intensity of pain responded better to treatment Background Gas-related symptoms represent very common complaints in children . The reduction of gas production can be considered as a valuable target in controlling symptoms . α-galactosidase has been shown to reduce gas production and related symptoms in adults . To evaluate the efficacy and tolerability of α-galactosidase in the treatment of gas-related symptoms in pediatric patients . Methods Single center , r and omized , double-blind , placebo-controlled , parallel group study performed in tertiary care setting . Fifty-two pediatric patients ( 32 female , age range 4–17 ) with chronic or recurrent gas-related symptoms were r and omized to receive placebo ( n = 25 ) or α-galactosidase ( n = 27 ) . Both treatments were given as drops or tablets , according to body weight for 2 weeks . The primary endpoint was the reduction in global distress measured by the Faces Pain Scale-Revised ( FPS-R ) at the end of treatment compared to baseline . Secondary endpoints were the reduction in severity and frequency of gas-related symptoms as recorded by parents and /or children . Results α-galactosidase significantly reduced global distress ( p = 0.02 ) compared to placebo . The digestive enzyme decreased the number of days with moderate to severe bloating ( p = 0.03 ) and the proportion of patients with flatulence ( p = 0.02 ) . No significant differences were found for abdominal spasms and abdominal distension . No adverse events were reported during treatment . Conclusions Although larger and longer trials are needed to confirm this result , α-galactosidase seems to be a safe , well tolerated and effective treatment for gas-related symptoms in the pediatric population .Trial registration Clinical Trials.gov , Background : Still there is no consensus on the best treatment for abdominal pain-related functional Gastrointestinal Disorders ( FGIDs ) . Objectives : The purpose of this study was to compare the effects of a synbiotic Lactol ( Bacillus coagulans + fructooligosaccharide ( FOS ) ) , peppermint oil ( Colpermin ) and placebo ( folic acid ) on abdominal pain-related FGIDs except for abdominal migraine . Patients and Methods : This placebo-controlled study was conducted on 120 children aged 4 - 13 years to compare the efficacy of pH-dependent peppermint oil ( Colpermin ) versus synbiotic Lactol ( Bacillus coagulans + fructooligosaccharids ( FOS ) ) in decreasing duration , severity and frequency of functional abdominal pain . The patients were r and omly allocated into three equal groups ( n = 40 in each group ) and each group received Colpermin or Lactol or placebo . Results : Eighty-eight out of 120 enrolled patients completed a one-month protocol and analyses were performed on 88 patients ’ data . Analyses showed that improvement in pain duration , frequency and severity in the Colpermin group was better than the placebo group ( P = 0.0001 , P = 0.0001 and P = 0.001 , respectively ) . Moreover , pain duration and frequency were decreased in the Lactol group more than the placebo ( P = 0.012 and P = 0.0001 , respectively ) , but changes in pain severity were not significant ( P = 0.373 ) . Colpermin was superior to Lactol in decreasing pain duration and severity ( P = 0.040 and P = 0.013 , respectively ) . No known side effects or intolerance were seen with Colpermin or Lactol . Conclusions : The pH-dependent peppermint oil capsule and Lactol tablet ( Bacillus coagulans+ FOS ) as synbiotics seem to be superior to placebo in decreasing the severity , duration and frequency of pain in abdominal pain-related functional GI disorders Identifying patients who are potential placebo responders has major implication s for clinical practice and trial design . Catechol-O-methyltransferase ( COMT ) , an important enzyme in dopamine catabolism plays a key role in processes associated with the placebo effect such as reward , pain , memory and learning . We hypothesized that the COMT functional val158met polymorphism , was a predictor of placebo effects and tested our hypothesis in a subset of 104 patients from a previously reported r and omized controlled trial in irritable bowel syndrome ( IBS ) . The three treatment arms from this study were : no-treatment ( “ waitlist ” ) , placebo treatment alone ( “ limited ” ) and , placebo treatment “ augmented ” with a supportive patient-health care provider interaction . The primary outcome measure was change from baseline in IBS-Symptom Severity Scale ( IBS-SSS ) after three weeks of treatment . In a regression model , the number of methionine alleles in COMT val158met was linearly related to placebo response as measured by changes in IBS-SSS ( p = .035 ) . The strongest placebo response occurred in met/met homozygotes treated in the augmented placebo arm . A smaller met/met associated effect was observed with limited placebo treatment and there was no effect in the waitlist control . These data support our hypothesis that the COMT val158met polymorphism is a potential biomarker of placebo response Rationale A visuospatial episodic memory impairment has recently been identified in irritable bowel syndrome . Increased tryptophan metabolism along the kynurenine pathway has also been reported in irritable bowel syndrome , which may play a role in altered cognitive performance as peripheral kynurenine can cross the blood brain barrier and lead to the production of neuroactive metabolites , which modulate glutamatergic and cholinergic signalling , key neurotransmitter systems involved in cognitive function . Objectives Utilising the acute tryptophan depletion ( ATD ) protocol , the aim of this study was to examine if manipulating peripheral levels of tryptophan regulates cognitive performance in irritable bowel syndrome and also to determine for the first time if the ATD protocol alters kynurenine supply to the central nervous system . Methods In this double-blind , placebo-controlled , crossover design study , nine female patients with irritable bowel syndrome and 14 matched female healthy controls participant completed a range of tests from the CANTAB ® following ATD and placebo . Plasma tryptophan and kynurenine , self-report measures of gastrointestinal symptoms , mood and arousal were determined pre- and post-treatment on each study day . Results Following placebo ( p = 0.016 ) but not ATD ( p > 0.05 ) , patients with irritable bowel syndrome exhibited impaired visuospatial memory performance ( Paired Associates Learning ( PAL ) test ) . In addition , ATD significantly decreased ( p < 0.001 ) and placebo significantly increased ( p < 0.001 ) plasma kynurenine levels in both groups . Conclusions Manipulating peripheral tryptophan and kynurenine levels using ATD modulates hippocampal-mediated cognitive performance in irritable bowel syndrome but not healthy controls . These data may have important implication s for reducing cognitive impairment in irritable bowel syndrome In a r and omized , double-blind controlled trial , 42 children with irritable bowel syndrome ( IBS ) were given pH-dependent , enteric-coated peppermint oil capsules or placebo . After 2 weeks , 75 % of those receiving peppermint oil had reduced severity of pain associated with IBS . Peppermint oil may be used as a therapeutic agent during the symptomatic phase of IBS Objective To evaluate the efficacy and safety of Drotaverine hydrochroride in children with recurrent abdominal pain . Design Double blind , r and omized placebo-controlled trial . Setting Pediatric Gastroenterology clinic of a teaching hospital . Participants 132 children ( age 4 - 12 y ) with recurrent abdominal pain ( Apley Criteria ) r and omized to receivedrotaverine ( n=66 ) or placebo ( n=66 ) orally . InterventionChildren between 4 - 6 years of age received 10 mL syrup orally ( 20 mg drotaverine hydrochloride or placebo ) thrice daily for 4 weeks while children > 6 years of age received one tablet orally ( 40 mg drotaverine hydrochloride or placebo ) thrice daily for 4 weeks . Outcome Measures Primary : Number of episodes of pain during 4 weeks of use of drug/placebo and number of pain-free days . Secondary : Number of school days missed during the study period , parental satisfaction ( on a Likert scale ) , and occurrence of solicited adverse effects . Results Reduction in number of episodes of abdominal pain [ mean ( SD ) number of episodes 10.3 ( 14 ) vs 21.6 ( 32.4 ) ; P=0.01 ] and lesser school absence [ mean ( SD ) number of school days missed 0.25 ( 0.85 ) vs 0.71 ( 1.59 ) ; P=0.05 ] was noticed in children receiving drotaverine in comparison to those who received placebo . The number of pain-free days , were comparable in two groups [ 17.4 ( 8.2 ) vs 15.6 ( 8.7 ) ; P=0.23 ] . Significant improvement in parental satisfaction score was noticed on Likert scale by estimation of mood , activity , alertness , comfort and fluid intake . Frequency of adverse events during follow-up period was comparable between children receiving drotaverine or placebo ( 46.9 % vs 46.7 % ; P=0.98 ) Conclusion Drotaverine hydrochloride is an effective and safe pharmaceutical agent in the management of recurrent abdominal pain in children Background & Aims We sought to determine the efficacy of psyllium fiber treatment on abdominal pain and stool patterns in children with irritable bowel syndrome ( IBS ) . We evaluated effects on breath hydrogen and methane production , gut permeability , and microbiome composition . We also investigated whether psychological characteristics of children or parents affected the response to treatment . Methods We performed a r and omized , double‐blind trial of 103 children ( mean age , 13 ± 3 y ) with IBS seen at primary or tertiary care setting s. After 2 weeks on their habitual diet , children began an 8‐day diet excluding carbohydrates thought to cause symptoms of IBS . Children with ≥75 % improvement in abdominal pain were excluded ( n = 17 ) . Children were assigned r and omly to groups given psyllium ( n = 37 ) or placebo ( maltodextrin , n = 47 ) for 6 weeks . Two‐week pain and stool diaries were compared at baseline and during the final 2 weeks of treatment . We assessed breath hydrogen and methane production , intestinal permeability , and the composition of the microbiome before and after administration of psyllium or placebo . Psychological characteristics of children were measured at baseline . Results Children in the psyllium group had a greater reduction in the mean number of pain episodes than children in the placebo group ( mean reduction of 8.2 ± 1.2 after receiving psyllium vs mean reduction of 4.1 ± 1.3 after receiving placebo ; P = .03 ) ; the level of pain intensity did not differ between the groups . Psychological characteristics were not associated with response . At the end of the study period , the percentage of stools that were normal ( Bristol scale scores , 3–5 ) , breath hydrogen or methane production , intestinal permeability , and microbiome composition were similar between groups . Conclusions Psyllium fiber reduced the number of abdominal pain episodes in children with IBS , independent of psychological factors . Psyllium did not alter breath hydrogen or methane production , gut permeability , or microbiome composition . Clinical Trials.gov no : NCT00526903 BACKGROUND In functional gastrointestinal disorders , patient recall of symptoms drives diagnostic decisions and evaluation of treatment response , and research conclusions about potential treatments . In pediatrics , parent report also impacts assessment and care . Hence , identifying methods for accurately capturing patient and parent report of irritable bowel syndrome ( IBS ) symptoms is important . This study evaluated correspondence between retrospective question naire ( parent and child report ) and prospect i ve diary data for children and adolescents with IBS . METHODS Participants included 50 children/adolescents with IBS per Rome III criteria . Children completed a 2-week pain and stool diary . Children and parents subsequently completed a 2-week recall question naire , reporting number of pain days , maximum pain , days without bowel movement , and days with diarrhea during the diary interval . Intraclass correlation coefficients and Bl and -Altman plots assessed agreement . KEY RESULTS For pain and days without bowel movement , overall agreement between child recall question naire and child diary was strong , although under conditions likely to facilitate agreement and with individual variation observed . Parent recall and child diary were less concordant , and agreement about diarrhea was poor for parent and child . Age did not significantly correlate with agreement . CONCLUSIONS & INFERENCES Child question naire with short recall interval may be a reasonable approximation for diary data , although this varies by individual and replication/investigation of lengthier recall are needed . Relying on parent question naire does not appear a suitable proxy , and recall of stool form by both parent and child appears more problematic . These results combined with existing literature support use of diary data whenever possible OBJECTIVE To determine whether oral administration of the probiotic Lactobacillus GG under r and omized , double-blinded , placebo-controlled conditions would improve symptoms of irritable bowel syndrome ( IBS ) in children . STUDY DESIGN Fifty children fulfilling the Rome II criteria for IBS were given Lactobacillus GG or placebo for 6 weeks . Response to therapy was recorded and collected on a weekly basis using the Gastrointestinal Symptom Rating Scale ( GSRS ) . RESULTS Lactobacillus GG was not superior to placebo in relieving abdominal pain ( 40.0 % response rate in the placebo group vs 44.0 % in the Lactobacillus GG group ; P=.774 ) . There was no difference in the other gastrointestinal symptoms , except for a lower incidence of perceived abdominal distention ( P=.02 favoring Lactobacillus GG ) . CONCLUSIONS Lactobacillus GG was not superior to placebo in the treatment of abdominal pain in children with IBS but may help relieve such symptoms as perceived abdominal distention Recurrent abdominal pain ( RAP ) affects 10 % to 18 % of school-age children and is caused by obvious organic pathology in fewer than 10 % of cases . Two recent studies do not support previous beliefs that most RAP is psychogenic . Studies have shown disorders of bowel motility in children with RAP similar to those of adult irritable bowel syndrome ( IBS ) ; controlled trials of additional dietary fiber in adult IBS have shown beneficial results . We did a r and omized , double-blind , placebo-controlled study in 52 children with RAP and demonstrated a clinical ly and statistically significant decrease in pain attacks ( at least 50 % fewer ) in almost twice as many children who were given additional fiber as placebo . Compliance was excellent in both groups and side effects were few . Although the cause of RAP is poorly understood , it is hypothesized that the beneficial effect of added fiber is due to its effect on shortening transit time , as in IBS A consecutive series of 31 children ( median age 12 years ) suffering from migraine with ( n=21 ) or without ( n=10 ) aura underwent endoscopic oesophageal , gastric and duodenal biopsy in order to determine whether the complaints were of gastro-intestinal origin . Of these 31 children , 13 ( 41.9 % ) showed oesophagitis , 16 ( 51.6 % ) gastritis of corpus , 12 ( 38.7 % ) antral gastritis and 27 ( 87.1 % ) duodenitis . Thus , 29 of the 31 children studied had an underlying inflammatory lesion explaining their complaints . Helicobacter pylori colonization was found in 7 of the children : one hadH. pylori associated antral and corporal gastritis and 6H . pylori associated antral gastritis only . Gastritis of corpus withoutH. pylori was present in all these 6 children . Our data do not support thatH. pylori is a primary pathogen of inflammatory changes seen in children studied , neither do they establish an association betweenH. pylori , antral gastritis and migraine . However , our data strongly suggest that there is a gastro-intestinal origin of these patients ' complaints . Conclusion Our findings provide further evidence that recurrent abdominal pain is an early expression of migraine and strongly support a causal link between recurrent abdominal pain and migraine Background Controlled trials considering the effect of Helicobacter pylori ( H. pylori ) eradication on gastrointestinal symptoms in children are scant . We aim ed to study the connection between recurrent abdominal pain and dyspepsia and H. pylori infection in children . Study This was a double blind r and omised controlled trial . Twenty children with recurrent abdominal pain ( RAP ) being H. pylori positive as measured with the 13C urea breath test ( UBT ) were r and omized either to receive omeprazole , amoxycillin and clarithromycin ( n = 10 ) , or omeprazole and 2 placebos ( n = 10 ) for 1 week after gastroscopy . Symptoms were registered prior to the treatment and at follow up visits 2 , 6 , 24 , and 52 weeks after stopping the treatment . Control UBT was performed on all patients 6 weeks post-treatment and again at the 52 week follow-up visit , when also re-endoscopy with biopsies was done to all participants . Results All infected children had histologic gastritis . Bacterial eradication was achieved in 8/10 in the triple treatment group and in none in the placebo group . There was no change in symptom index in either group at 2 weeks post treatment . At 52 weeks a similar reduction in symptom index was observed in both groups irrespective of the healing of gastritis , which was more commonly achieved along the eradication . Conclusions Bacterial eradication and healing of gastric inflammation does not lead to symptomatic relief of chronic abdominal pain in children To determine the benefit of using an H2-receptor antagonist in children with abdominal pain and dyspepsia , 25 such children were enrolled in a double-blind , placebo-controlled trial of famotidine . Global and quantitative pain assessment s were done before and after each treatment period . The quantitative assessment was calculated based on the abdominal pain score that was the sum of three components . Based on the global evaluation , there was a clear benefit of famotidine over placebo ( 68 % vs 12 % ) . Using the quantitative assessment , however , the mean improvement of the score using famotidine versus placebo was not statistically significant ( 3.37+/-3.53 vs 1.66+/-2.7 ) . There was a significant improvement in this score during the first treatment period regardless of medication used ( period effect : P = 0.05 ) . A subset of patients with peptic symptoms demonstrated a significant drug effect that outweighed the period effect ( drug effect : P = 0.01 ; period effect : P = 0.02 ) . We conclude that famotidine subjectively improves the symptoms of children with recurrent abdominal pain but not objective ly using the derived score . However , famotidine is significantly more effective than placebo among children with peptic symptoms . The use of this simple scoring scale may facilitate selecting those children who will benefit from H2-receptor antagonist therapy AIM To assess the effects of partially hydrolyzed guar gum ( PHGG ) diet supplement in pediatric chronic abdominal pain ( CAP ) and irritable bowel syndrome ( IBS ) . METHODS A r and omized , double-blind pilot study was performed in sixty children ( 8 - 16 years ) with functional bowel disorders , such as CAP or IBS , diagnosed according to Rome III criteria . All patients underwent ultrasound , blood and stool examinations to rule out any organic disease . Patients were allocated to receive PHGG at dosage of 5 g/d ( n = 30 ) or placebo ( fruit-juice n = 30 ) for 4 wk . The evaluation of the efficacy of fiber supplement included IBS symptom severity score ( Birmingham IBS Question naire ) , severity of abdominal pain ( Wong-Baker Face Pain Rating Score ) and bowel habit ( Bristol Stool Scale ) . Symptom scores were completed at 2 , 4 , and 8 wk . The change from baseline in the symptom severity scale at the end of treatment and at 4 wk follow-up after treatment was the primary endpoint . The secondary endpoint was to evaluate compliance to supplementation with the PHGG in the pediatric population . Differences within groups during the treatment period and follow-up were evaluated by the Wilcoxon signed-rank test . RESULTS The results of the study were assessed considering some variables , such as frequency and intensity of symptoms with modifications of the bowel habit . Both groups were balanced for baseline characteristics and all patients completed the study . Group A ( PHGG group ) presented a higher level of efficacy compared to group B ( control group ) , ( 43 % vs 5 % , P = 0.025 ) in reducing clinical symptoms with modification of Birmingham IBS score ( median 0 ± 1 vs 4 ± 1 , P = 0.025 ) , in intensity of CAP assessed with the Wong-Baker Face Pain Rating Score and in normalization of bowel habit evaluated with the Bristol Stool Scale ( 40 % vs 13.3 % , P = 0.025 ) . In IBS subgroups , statistical analysis shown a tendency toward normalization of bowel movements , but there was no difference in the prevalence of improvement in two bowel habit subsets . PHGG was therefore better tolerated without any adverse effects . CONCLUSION Although the cause of pediatric functional gastrointestinal disorders is not known , the results show that complementary therapy with PHGG may have beneficial effects on symptom control OBJECTIVES To determine the efficacy of amitriptyline ( AMI ) in treating irritable bowel syndrome ( IBS ) in adolescents . STUDY DESIGN Adolescents 12 to 18 years with newly diagnosed IBS were surveyed with a symptom checklist , pain rating scale , visual analog scale , and IBS quality of life ( QOL ) question naire . Subjects were r and omized in a double-blinded fashion to receive AMI or placebo , and again completed surveys at 2 , 6 , 10 , and 13 weeks . RESULTS Thirty-three patients ( 24 female ) were enrolled . Patients receiving AMI were more likely to experience improvement from baseline in overall QOL at 6 , 10 , and 13 weeks ( P = .019 , .004 , and .013 ) . Patients receiving AMI were also more likely to experience a reduction in IBS-associated diarrhea at 6 and 10 weeks ( P = .029 for both ) , a reduction in periumbilical pain at 10 weeks ( P = .018 ) , and a reduction in right lower quadrant pain at 6 , 10 , and 13 weeks ( P = .014 , .039 , and .004 ) . CONCLUSION AMI significantly improves overall QOL in adolescents with IBS and should be a therapeutic option for adolescents with this disorder AIM To assess the efficacy of glucomannan ( GNN ) as the sole treatment for abdominal pain-related functional gastrointestinal disorders ( FGIDs ) . METHODS We conducted a double-blind , placebo-controlled , r and omized trial . Patients were recruited among children referred to the Department of Paediatrics , Medical University of Warsaw . Included in the study were children aged 7 - 17 years with abdominal pain-related FGIDs classified according to the Rome III diagnostic criteria . The children were r and omly assigned to receive GNN , a polysaccharide of 1,4-D-glucose and D-mannose , a soluble fiber from the Japanese Konjac plant , at a dosage of 2.52 g/d ( 1 sachet of 1.26 g 2 times a day ) , or a comparable placebo ( maltodextrin ) at the same dosage . The content of each sachet was dissolved in approximately 125 mL of fluid and was consumed twice daily for 4 wk . RESULTS Of the 89 eligible children , 84 ( 94 % ) completed the study . " No pain " and " treatment success " ( defined as no pain or a decrease ≥ 2/6 points on the FACES Pain Scale Revised ) were similar in the GNN ( n = 41 ) and placebo ( n = 43 ) groups [ no pain ( 12/41 vs 6/43 , respectively ; RR = 2.1 , 95%CI : 0.87 - 5.07 ) as well as treatment success ( 23/41 vs 20/43 ; RR = 1.2 , 95%CI : 0.79 - 1.83 ) ] . No significant differences between the groups were observed in the secondary outcomes , such as abdominal cramps , abdominal bloating/gassiness , episodes of nausea or vomiting , or a changed in stool consistency . GNN demonstrated no significant influence on the number of children requiring rescue therapy , school absenteeism , or daily activities . CONCLUSION In our setting , GNN , as dosed in this study , was no more effective than the placebo in achieving therapeutic success in the management of FGIDs in children AIM Functional abdominal pain ( FAP ) is a frequent condition affecting 10 - 20 % of children and can be considered within the classification of functional gastrointestinal disorders ( FGID ) . The objective of this study was to determine the effect of daily supplementation with the probiotic Lactobacillus reuteri DSM 17938 in children with FAP . METHODS The children ( aged 6 - 16 years ) were screened for FAP as defined in the Rome III criteria and 60 patients were recruited in this double-blind , r and omised , placebo-controlled trial . The children were r and omly allocated to receive either L. reuteri ( 2 × 10(8 ) CFU/day ) or identical placebo for 4 weeks followed by a 4-week follow-up period without supplementation . Frequency and intensity of pain was self-recorded by the subjects . RESULTS The L. reuteri-supplemented children had significantly lower pain intensity compared with the placebo controls . CONCLUSIONS Supplementation with L. reuteri reduced perceived abdominal pain intensity , which may encourage clinicians to use this probiotic in children with FAP OBJECTIVES The characterization and prediction of placebo response in clinical trials of youth with anxiety disorders have received little attention , despite the critical effects of placebo response rate on the success or failure of clinical trials . With this in mind , we sought to examine the factors that predict or influence placebo response in r and omized controlled trials of youth with anxiety disorders . METHODS Prospect i ve , r and omized , parallel-group controlled trials of psychopharmacologic interventions in pediatric patients with anxiety disorders were identified using a search of PubMed / Medline ( 1966 - 2015 ) . Weighted least squares regression models and z-tests were utilized to examine the impact of continuous and categorical variables , respectively , on placebo response . These variables included demographic ( e.g. , age , percent white , percent female ) , clinical ( e.g. , baseline symptom severity ) , and trial characteristics ( sample size , duration , funding ) . Finally , the relationship between the class of comparator medication and placebo response rate was examined using a multiple comparison for proportions test . RESULTS The analyses of data from 14 trials involving 2230 patients and 9 medications reveal that higher placebo response rates were associated with a greater number of study sites ( p = 0.013 ) and fewer patients per site ( p < 0.008 ) , while placebo dropout rates increased with more recent publication ( p = 0.01 ) and were positively associated with the number of study visits ( p < 0.02 ) . Lower placebo response rates were associated with federally funded studies ( z = -4.61 , p < 0.001 ) , studies conducted in the United States ( z = 1.81 , p < 0.035 ) , and with an increased likelihood of detecting a significant effect on the primary outcome ( z = 4.58 , p < 0.0001 ) . Additionally , studies , in which the majority of patients ( > 60 % ) had a diagnosis of social anxiety disorder , exhibited lower placebo response rates ( p < 0.001 ) . Finally , for trials , effect size has decreased over time ( p = 0.004 ) . CONCLUSIONS Important trial-specific factors affect placebo response and placebo dropout in youth with anxiety disorders and have pragmatic implication s for the conduct and design of clinical trials and raise the possibility that limiting the number of sites while maximizing the number of patients per site could enhance the ability to detect medication-placebo differences AIM To study the effectiveness of melatonin vs placebo in children with functional dyspepsia ( FD ) . METHODS The study was conducted as a double blind , r and omized , placebo controlled crossover trial . Subjects were aged 8 - 17 years and diagnosed with FD based on Rome III criteria . All subjects had failed to respond to 4 wk of acid suppression . Subjects receive a continuous two weeks of placebo and a continuous two weeks of melatonin in an order blinded to the participant and the study team . A Global Clinical Score was obtained to assess changes in abdominal pain . Pain was self-reported to be worse ( grade 1 ) , no change ( grade 2 ) , moderate improvement ( grade 3 ) , good ( grade 4 ; minimal pain and not interfering with daily activities ) , or excellent ( grade 5 ; no pain ) , respectively . A positive clinical response was defined as a grade 3 or greater response . Subjects wore an actigraph to assess sleep during a one week baseline period and during each treatment period . Subjects ' sleep latency and total sleep time were recorded throughout the duration of the study . RESULTS Fourteen subjects were enrolled and 12 completed the study . One withdrew prior to starting both melatonin and placebo and the other before starting melatonin . A positive clinical response ( grade 3 - 5 ) was achieved in 42 % of subjects on melatonin vs 50 % of subjects on placebo ( NS ) . Effect size was calculated and revealed a Cohen 's D of 0.343 which demonstrates a medium effect favoring placebo . A grade 4 or grade 5 response was seen in 4 patients on melatonin and 5 patients on placebo . Baseline sleep parameters were in the healthy range with the longest sleep latency being just over 20 min ( mean 7.46 ± 8.53 min ) and the shortest sleep duration just over 7 h ( mean 10.09 ± 2.72 h ) . The mean latency did not differ between periods of treatment with melatonin as compared to placebo ( 4.48 ± 6.45 min vs 3.58 ± 4.24 min ; NS ) . The mean sleep duration did not differ between periods of treatment with melatonin as compared to placebo ( 9.90 ± 3.53 h vs 9.41 ± 2.70 h ; NS ) . CONCLUSION Melatonin does not appear to have efficacy in relieving pain in unselected pediatric FD . Future studies should consider FD subtypes , pathophysiologic mechanisms , and baseline sleep disturbances Objective : The aim of the study was to investigate whether recurrent abdominal pain ( RAP ) in Blastocystis hominis – positive children can be treated successfully with trimethoprim-sulfamethoxazole ( TMP/SMX ) . Methods : From October 2004 to December 2008 , all of the patients referred to the Division of Gastroenterology and Nutrition of the University Children 's Hospital Zurich because of RAP and detection of B hominis in stool sample s as the only pathological finding after a st and ard workup were offered to participate in the study . Patients were r and omly assigned into 2 groups . TMP/SMX or placebo was given for 7 days in a double-blind , placebo-controlled manner . Pain index ( PI ) was measured with a visual analogue scale . Two weeks after completion of treatment , 3 stool sample s were collected and patients were followed clinical ly . If B hominis was still present , metronidazole was given for 7 days . Results : Forty patients were included ; 37 finished the study ( TMP/SMX n = 20 , placebo n = 17 ) . Mean PI declined from 7.1 to 3.6 for all of the patients , with a decrease from 6.9 to 4.1 in the TMP/SMX and 7.4 to 3.0 in the placebo group , irrespective of detection of B hominis after treatment . There was no statistically significant difference in PI reduction between the 2 groups . Metronidazole treatment led to a further PI decline from 3.7 to 1.9 . Eradication rates were 35 % ( TMP/SMX ) and 44 % ( metronidazole ) , compared with spontaneous clearance of 29 % in the placebo group . Conclusions : There is no advantage for TPM/SMX over placebo in the treatment of RAP in B hominis – positive children Goals : We assessed the efficacy of a probiotic mixture of Bifidobacterium infantis M-63 , breve M-16V , and longum BB536 in improving abdominal pain ( AP ) and quality of life ( QoL ) in children with irritable bowel syndrome ( IBS ) and functional dyspepsia ( FD ) . Background : AP-associated functional gastrointestinal disorders , particularly IBS and FD , are common in pediatrics , and no well-established treatment is currently available . Although probiotics have shown promising results in adults , data in children are heterogeneous . Study : Forty-eight children with IBS ( median age , 11.2 y ; range , 8 to 17.9 y ) and 25 with FD ( age , 11.6 y ; range , 8 to 16.6 y ) were r and omized to receive either a mixture of 3 Bifidobacteria or a placebo for 6 weeks . After a 2-week “ washout ” period , each patient was switched to the other group and followed up for further 6 weeks . At baseline and follow-up , patients completed a symptom diary and a QoL question naire . AP resolution represented the primary outcome parameter . Results : In IBS , but not in FD , Bifidobacteria determined a complete resolution of AP in a significantly higher proportion of children , when compared with placebo ( P=0.006 ) , and significantly improved AP frequency ( P=0.02 ) . The proportion of IBS children with an improvement in QoL was significantly higher after probiotics than after placebo ( 48 % vs. 17 % , P=0.001 ) , but this finding was not confirmed in FD . Conclusions : In children with IBS a mixture of Bifidobacterium infantis M-63 , breve M-16V , and longum BB536 is associated with improvement in AP and QoL. These findings were not confirmed in FD subjects . Trial identifier : NCT02566876 ( http://www . clinical trial.gov ) Introduction : The therapeutic effect of domperidone on abdominal pain-predominant functional gastrointestinal diseases ( AP-FGIDs ) was assessed on children in 5–12 year age group at the Gastroenterology Research Laboratory of Faculty of Medicine , University of Kelaniya , Sri Lanka . Methods : Children fulfilling Rome III criteria for AP-FGIDs were recruited from the out-patient clinic of the University Paediatric Unit , North Colombo Teaching Hospital , Ragama , Sri Lanka , after obtaining parental consent . They were r and omized in to 8 weeks of placebo or Domperidone ( Motillium 10 mg , 3 times per day , before meals ) groups , using computer generated r and om numbers . Placebo was a specially prepared dummy tablet without any active ingredients , had the same colour , size , shape and taste of domperidone tablet and were packaged similarly . Primary outcomes defined were cure ( abdominal pain less than 25 mm on the visual analogue scale and no impact on daily activities ) and improvement ( pain relief and sense of improvement recorded on global assessment scale ) . Secondary outcomes were significant improvement in symptoms , gastric motility , quality of life ( QoL ) and family impact . Both patients and investigators who assessed primary and secondary outcomes before and after intervention were blind to inventions administered . Symptom severity was recorded on a vali date d 100 mm visual analogue scale . Translated and vali date d PedQL Generic Score Scale version 4.0 and Family Impact Module were used . Gastric motility was assessed using a vali date d ultrasound method . Results : One hundred children were enrolled and 89 completed the trial [ Placebo 42 ( 22 girls ) , Domperidone 47(33 girls ) ] . While comparing primary outcomes , domperidone group had significant improvement [ 37 ( 78.7 % ) vs. 25 ( 59.5 % ) in placebo group , p = 0.04 ] , while no such difference was observed in cure . When assessing secondary outcomes , domperidone group reported significant reduction in abdominal pain severity ( 70.84 % vs. 48.18 % p = 0.03 ) and improvement in motility index ( 29.3 % vs. 8.6 % p = 0.04 ) after intervention . No such difference was seen in improvement of QoL and family impact ( p > 0.05 ) . Conclusions : Domperidone has a favorable therapeutic effect on improvement AP-FGIDs in children aged 5–12 years . It causes significant reduction in abdominal pain and improvement in motility of the gastric antrum . However , it has no significant effect on improvement of QoL and family impact Background and Objectives : Chronic abdominal pain ( CAP ) in children may be a precursor to irritable bowel syndrome ( IBS ) in adults . The prevalence of abnormal lactulose breath tests ( LBT ) suggesting small intestinal bacterial overgrowth ( SIBO ) has been reported as 91 % in children with CAP and 35 % in healthy controls . In addition , patients with IBS with SIBO who responded to nonabsorbable antibiotic treatment with normalization of LBT reported 75 % global improvement in symptoms . The aim of the study was to test whether treatment with a nonabsorbable antibiotic may reduce symptoms in children with CAP . Methods : Seventy-five children ages 8 to 18 years with CAP based on Rome II criteria were enrolled . Subjects underwent baseline LBT and completed symptom-based question naires . They were then r and omized in a 2:1 , double-blind fashion to receive a 10-day course of 550 mg of rifaximin or placebo 3 times per day ( t.i.d . ) . LBT and question naires were repeated 2 weeks after treatment . Results : Forty-nine children received rifaximin and 26 received placebo . There were no differences in demographics between groups . Ninety-four percent who received rifaximin and 92 % who received placebo had abnormal baseline LBT , suggesting SIBO ( not significant [ NS ] ) . There was no significant difference in symptom improvement between groups ; however , only 20 % of children treated with rifaximin achieved a normalized repeat LBT , demonstrating successful treatment of SIBO . Conclusions : Similar to adults with IBS , the prevalence of abnormal LBT suggesting SIBO in children with CAP is high ; however , treatment with 10 days of rifaximin has low efficacy in normalizing LBT in this group . Additional studies are needed to determine whether a treatment approach with higher efficacy would lead to improvement in children with CAP OBJECTIVE : Our aim was to determine whether Lactobacillus rhamnosus GG ( LGG ) relieves symptoms in children with recurrent abdominal pain . PATIENTS AND METHODS : A total of 141 children with irritable bowel syndrome ( IBS ) or functional pain were enrolled in 9 primary care sites and a referral center . Children entered a r and omized , double-blind , placebo-controlled trial and received LGG or placebo for 8 weeks and entered follow-up for 8 weeks . The primary outcome was overall pain at the end of the intervention period . At entry and at the end of the trial , children underwent a double-sugar intestinal permeability test . RESULTS : Compared with baseline , LGG , but not placebo , caused a significant reduction of both frequency ( P < .01 ) and severity ( P < .01 ) of abdominal pain . These differences still were significant at the end of follow-up ( P < .02 and P < .001 , respectively ) . At week 12 , treatment success was achieved in 48 children in the LGG group compared with 37 children in the placebo group ( P < .03 ) ; this difference still was present at the end of follow-up ( P < .03 ) . At entry , 59 % of the children had abnormal results from the intestinal permeability test ; LGG , but not placebo , determined a significant decrease in the number of patients with abnormal results from the intestinal permeability testing ( P < .03 ) . These effects mainly were in children with IBS . CONCLUSIONS : LGG significantly reduces the frequency and severity of abdominal pain in children with IBS ; this effect is sustained and may be secondary to improvement of the gut barrier |
10,779 | 19,493,679 | The surgical time was longer than the open procedure .
This procedure meets the tumor control and staging requirements .
It has shown similar results to the traditional procedure in terms of patient recovery , although the available evidence is not method ologically appropriate and does not justify its oncological safety | OBJECTIVES To assess the feasibility , effectiveness and morbidity associated with Endoscopic Axillary Dissection . | Nonpalpable , mammographically detected breast cancers are on the increase . The percentage of patients with histologically involved nodes is therefore decreasing . Axillary clearance aims at reducing the probability of later clinical involvement of the axilla and at establishing a sound basis for adjuvant treatment planning . Minimally invasive techniques have been applied to a growing number of surgical procedures now including exploration of the axilla . The technique used and results achieved in a series of 50 consecutive patients treated by liposuction and axilloscopy by one single surgeon , including all the patients from the very first attempt , are presented here . Patients were excluded with palpable lymph nodes or a primary tumor in the direct vicinity of the axilla that could be injured by the liposuction canula . The average number of lymph nodes removed was 13.4 . Thirty-four percent of patients had involved nodes . The mean number of involved nodes in these patients was 3.1 . After a median follow-up time of only 15 months no axillary recurrences or trocar site metastases have been found in the first 40 patients . Using a self- assessment question naire , the patients rate this technique as excellent . There was no lymphedema . The cosmetic result is certainly better than after conventional axillary clearance . Great experience of laparoscopic surgery and an excellent knowledge of the axillary anatomy are prerequisites for the practice of axilloscopic treatment of the axilla . The working space within the axilla is small and a number of structures need absolutely to be preserved . A longer follow-up period than the one so far achieved in this series or any other in the literature to date is necessary before this technique can be generally recommended STUDY OBJECTIVE To compare endoscopic and classic axillary lymphadenectomy staging of breast cancer with respect to operation-induced changes such as seroma formation , pain , neurologic sensations , lymphedema , infection , and reduction of shoulder-arm mobility . DESIGN Prospect i ve , r and omized study ( Canadian Task Force classification I ) . SETTING University-affiliated hospital . PATIENTS Eighty consecutive women with histopathologically confirmed invasive breast cancer who had clinical ly and sonographically negative axillary lymph nodes ( < 1 cm ) . INTERVENTION Classic and endoscopic lymphadenectomies . MEASUREMENTS AND MAIN RESULTS We attempted to obtain 10 axillary lymph nodes/patient . After 1 , 3 , 5 , 7 , 9 , 42 , and 84 days , clinical and ultrasonographic examinations were conducted to evaluate operation-induced changes . Short-term results showed that , with endoscopic technique , a representative number of axillary lymph nodes was removed , with reduced axillary infiltration and seroma induction , as well as less impaired shoulder-arm mobility . During the first month , postoperative infection , lymphedema , and neurologic complaints were comparable in both groups , with more stretching pain in the classic group and predominantly paresthesia in the endoscopic group . After 3 months no differences in postoperative complications were detected . CONCLUSIONS Endoscopic axillary lymphadenectomy avoids short-term reduction of shoulder-arm mobility . Long-term studies are necessary to prove if this technique is as safe as the classic procedure with regard to local axillary recurrence . If so , endoscopy could become the method of choice for staging breast cancer in women with clinical ly negative lymph nodes Quadrantectomy with axillary-node dissection is the treatment of choice for early-stage breast cancers . The minimally invasive approach to axillary dissection has the theoretical prerequisite to be oncologically correct , while ensuring a better cosmetic result and causing less psychological distress . A prospect i ve , r and omised study was carried out to assess the feasibility and the preliminary results of video-assisted axillary-node dissection . Quadrantectomy and video-assisted axillary-node dissection ( study group = 10 patients ) was compared with st and ard quadrantectomy and axillary-node dissection ( control group = 12 patients operated on during the same period of time ) . The early outcomes were analysed , taking into account the following parameters : patient 's age , ASA group , staging , operating time , number of nodes harvested , postoperative pain , postoperative course ( complications , lymphatic drainage , upper-limb mobility ) , hospital stay and cosmetic results at 6 months . Follow-up was 43 - 70 months in the study group and 43 - 64 months in the control group BACKGROUND Electrocautery has been postulated as a factor in the risk of seroma formation after mastectomy . METHODS Eighty consecutive mastectomies in 74 patients were r and omly assigned to dissection of the mastectomy flaps with either scalpel ( n = 38 ) or electrocautery ( n = 42 ) . Total volume of fluid output through drains and aspirated from seromas was recorded . Other factors investigated included the type of drain utilized , estimated blood loss , and complications . RESULTS Seromas developed in 16 wounds in the electrocautery group compared with 5 in the scalpel group ( 38 % and 13 % , respectively ; P = 0.01 ) . Other factors with an independent risk for seroma included use of Jackson-Pratt drains compared with Blake drains ( P = 0.006 ) , and lower estimated blood loss ( P = 0.006 ) . No differences in characteristics of patients or in other complications were noted . CONCLUSIONS Use of electrocautery to create skin flaps in mastectomy reduced blood loss but increased the rate of seroma formation OBJECTIVE To describe the technique of endoscopic exploration of the axilla . To compare this technique to open surgical treatment by comparing the following variables : operative time , peri-operative complications , duration of hospital stay , node 's histology and morphologic aspects and esthetic results . MATERIAL S St and ard instruments for traditional operative laparoscopy plus a lipo-aspirator ( 0.8 Bar ) . PATIENTS Forty patients , 20 ( group A ) undergoing open surgery and 20 ( group B ) undergoing axilloscopy . All patients with early invasive breast cancer are eligible for conservative operative treatment . METHOD R and omized study . The technique is described and preliminary results are presented . RESULTS The operative time for axilloscopy is approximately double that for open surgery . A comparable number of lymph nodes is collected by axilloscopy and open surgery . The nodes collected by axilloscopy are more likely to be fractured . What is the clinical consequence ? Two loco-regional relapses are observed in the endoscopic group . DISCUSSION Axillary sampling by endoscopic procedure gives the same pathologic information than surgical axillary sampling . Anatomo-pathologic aspects of nodes and possibilities of relapses were two drawbacks of this procedure . CONCLUSION Operative time is increased for axilloscopy compared with open surgery . The techniques yield comparable anatomo-pathologic results . It is still unknown whether this endoscopic technique is as effective as traditional surgery or if the frequency or severity of lymphedema is decreased by the endoscopic approach Background We prospect ively compared the sensory morbidity and lymphedema experienced after sentinel node biopsy ( SLNB ) and axillary dissection ( ALND ) over a 12-month period by using a vali date d instrument . Methods Patients undergoing breast-conserving therapy completed the Breast Sensation Assessment Scale ( BSAS ) at baseline and 3 , 6 , and 12 months after surgery . Repeated- measures analysis of variance was used to compare ALND and SLNB over the 12-month period . Upper- and lower-arm circumference measurements at baseline and 12 months were used to assess lymphedema . Results SLNB was associated with substantial sensory morbidity , although significantly less than ALND , over time on all four subscales and the summary score . A statistically significant improvement in sensory morbidity occurred for both groups in the first 3 months , with no further change thereafter . For both types of axillary surgery , younger patients had significantly higher BSAS scores than older patients . There was no significant difference in arm circumference between patients with SLNB and ALND at 12 months . Conclusions Among women undergoing breast-conserving therapy , SLNB has significant sensory morbidity , although approximately half that of ALND . Sensory morbidity improves in the first 3 months after surgery , but patients continue to report sensory morbidity at 1 year . Longitudinal follow-up is required to further assess lymphedema Abstract Background : Sentinel node biopsy is a promising technique that allows the axillary status of breast cancer patients to be predicted with high accuracy . Reducing false negative results remains a major challenge for the improvement of this procedure . Furthermore , new techniques are required to achieve axillary clearing with less morbidity in cases of unsuccessful mapping or multicentric carcinoma . We analyzed whether axilloscopy and endoscopic sentinel node biopsy is a feasible procedure for visualization of the axillary space and resection of the sentinel node using endoscopic techniques . Methods : Following blue dye-guided lymphography and liposuction of the axillary fat , endoscopic axillary sentinel node biopsy was performed in 35 breast cancer patients . We then assessed the exposure of anatomical l and marks , the detection rate of the sentinel node , the false negative rate , and the accuracy of consecutive axillary clearing . Results : In almost every case , an excellent anatomical orientation was achieved . The detection rate for the sentinel node was 83.3 % . In one case , the sentinel node did not reflect the status of the residual axilla . A mean number of 17.1 lymph nodes was harvested at consecutive axillary clearing . Conclusions : Axilloscopy and endoscopic sentinel node biopsy , following liposuction of the axillary fat , is a feasible procedure that allows identification and minimally invasive resection of the sentinel node with high accuracy . The endoscopic approach might help to minimize the pitfalls of sentinel node biopsy by visualizing the axillary space . In future , it may become a technique that enables minimally invasive axillary clearing when complete lymphadenectomy is required BACKGROUND Laparoscopic removal of axillary lymph nodes is possible and affords an excellent view of all structures , allowing preservation of vessels and nerves . The technique uses pediatric trocars and a lifting device to maintain the newly created axillary space . OBJECTIVE To prove that a newly developed technique of balloon axilloscopy can be performed using only one 10-mm and two 5-mm st and ard trocars and constant carbon dioxide flow to preserve the axillary space and that preservation of all nerves and vessels is possible with this approach . DESIGN Prospect i ve study on 4 fresh-frozen human cadavers and 7 live porcine models . SETTING A hospital department of minimal surgery access and a university department of anatomy . RESULTS The balloon dissection consistently revealed and preserved the nerves and vessels , and exposure and dissection of the first rib could similarly be accomplished . An alternative route to the apex of the axilla has been developed -- between the pectoralis minor and pectoralis major muscles -- after their careful separation . The axillary content of surgical interest ( lymph nodes ) is easily separated from the other anatomical elements and is simply dissected under complete visualization and preservation of all vital axillary structures . CONCLUSIONS Balloon axilloscopy was easy to perform , provided the surgeon with constant visualization of vital anatomical structures , and allowed easy separation and dissection of the axillary lymph nodes and the first rib . As a technical aid prior to a conventional axillary dissection , or as part of a pure endoscopic procedure in the axilla , balloon axilloscopy is 100 % reliable in identifying the long thoracic nerve and moving it out of the way , separating the lymph nodes from it and from the intercostobrachial nerve and axillary vein and artery , rendering the whole dissection process safer for both the surgeon and the patient Summary Background . Reports on long-term outcomes after endoscopic axillary lymph node dissection ( ALND ) of breast cancer patients are still lacking in the medical literature . The objective of this prospect i ve study was to assess the oncological and functional outcomes in breast cancer patients after endoscopic ALND . Methods . Fifty-five breast cancer patients were prospect ively enrolled , of whom 52 were available for follow-up with a median of 71.9 months ( range 11–96 ) . The following oncological and functional endpoints were evaluated during follow-up at several time points : occurrence of local , axillary and distant metastases , seroma or infection , shoulder mobility ( range of motion ) , numbness , pain , presence of lymphoedema as well as restriction in activities of daily living . Results . In 52 patients endoscopic ALND of level I and II was successfully performed . Two port-site metastases ( 2/52 , 4 % ) occurred , one of which in a patient with negative axillary lymph nodes . The same patient suffered from the only axillary recurrence ( 1/52 , 2 % ) . Three patients ( 3/52 , 6 % ) developed lymphoedema . No other functional adverse events ( shoulder mobility , pain , numbness , hypertrophic scar ) were noticed at the end of the observation period . Conclusion . The present investigation with long-term follow-up after endoscopic ALND – the first one in the literature – reveals minor morbidity , good functional and cosmetic results . In contrary to conventional surgery , the endoscopic procedure is associated with the occurrence of port-site metastases , not seen in the open approach . Axillary recurrences do not appear more frequently when compared with results after conventional ALND . In the meantime the less invasive sentinel lymph node ( SLN ) biopsy is the established st and ard technique in evaluating the axillary lymph node status Abstract Background : Minimally invasive approaches have changed the practice of surgery in several specialties . The purpose of this study was to develop a reproducible endoscopic technique for the evaluation of the axilla in breast cancer patients . Methods : A total of 23 patients with biopsy-proven breast carcinoma were enrolled . Patients were positioned in the supine position with the ipsilateral arm abducted at 90 ° . A 1-cm skin incision was made at the superior aspect of the axilla . Dissection was carried bluntly to the lateral border of the pectoralis major . A balloon distention device was inserted into the tract and distended under endoscopic vision to create a working space . Insufflation was initiated up to a pressure of 8 mmHg . A 30 ° laparoscope was introduced for visualization of axillary contents . One or two additional 5-mm cannulas were placed as needed under direct visualization . Manipulation of axillary contents was performed , and in 19 patients a sentinel node identification technique was applied . Results : In all patients , using insufflation and minimal instrument dissection , the axillary vein , long thoracic , and thoracodorsal nerves were found in their usual anatomical locations . Utilizing blunt and sharp dissection , the axilla was thoroughly inspected , and individual lymph nodes were easily identified and extracted . In 11 of 19 patients , a sentinel node or blue dye was identified using isosulfan blue . There was a procedure concordance of 84 % , and there were no complications . Conclusions : We describe a novel endoscopic technique for the evaluation of the axilla in breast cancer patients . This technique allows ( a ) creation of a minimally invasive working space within the axilla , ( b ) recognition of key axillary anatomic l and marks , and ( c ) instrument manipulation within the axilla to identify and extract lymph nodes , and apply the sentinel node technique . This is the first report of a minimally invasive approach to axillary exploration to employ sentinel lymph node mapping PURPOSE Experience with sentinel node biopsy ( SNB ) after neoadjuvant chemotherapy is limited . We examined the feasibility and accuracy of this procedure within a r and omized trial in patients treated with neoadjuvant chemotherapy . PATIENTS AND METHODS During the conduct of National Surgical Adjuvant Breast and Bowel Project trial B-27 , several participating surgeons attempted SNB before the required axillary dissection in 428 patients . All underwent lymphatic mapping and an attempt to identify and remove a sentinel node . Lymphatic mapping was performed with radioactive colloid ( 14.7 % ) , with lymphazurin blue dye alone ( 29.9 % ) , or with both ( 54.7 % ) . RESULTS Success rate for the identification and removal of a sentinel node was 84.8 % . Success rate increased significantly with the use of radioisotope ( 87.6 % to 88.9 % ) versus with the use of lymphazurin alone ( 78.1 % , P = .03 ) . There were no significant differences in success rate according to clinical tumor size , clinical nodal status , age , or calendar year of r and om assignment . Of 343 patients who had SNB and axillary dissection , the sentinel nodes were positive in 125 patients and were the only positive nodes in 70 patients ( 56.0 % ) . Of the 218 patients with negative sentinel nodes , nonsentinel nodes were positive in 15 ( false-negative rate , 10.7 % ; 15 of 140 patients ) . There were no significant differences in false-negative rate according to clinical patient and tumor characteristics , method of lymphatic mapping , or breast tumor response to chemotherapy . CONCLUSION These results are comparable to those obtained from multicenter studies evaluating SNB before systemic therapy and suggest that the sentinel node concept is applicable following neoadjuvant chemotherapy Suzanne recently described a new technique of axillary lymphadenectomy in breast cancer to reduce post surgical morbidity . It combines liposuction and endoscopic dissection . To determine whether this technique induces lymph node alterations , we examined retrospectively 111 lymphadenectomies done by this new method and compared them to 41 lymphadenectomies performed by conventional surgery . The percentage of altered lymph nodes , with or without metastasis , was approximately the same with both techniques ( about 19 % ) . Lymph nodes removed by conventional surgical lymphadenectomy had a detached capsule more frequently . Cellular crush was more frequent after liposuction and endoscopic dissection . Liposuction altered more frequently large lymph nodes , which represented , however , the minority of the lymph nodes removed by this technique . No specific alteration was detected in relation to either of the two technics BACKGROUND Although numerous studies have shown that the status of the sentinel node is an accurate predictor of the status of the axillary nodes in breast cancer , the efficacy and safety of sentinel-node biopsy require validation . METHODS From March 1998 to December 1999 , we r and omly assigned 516 patients with primary breast cancer in whom the tumor was less than or equal to 2 cm in diameter either to sentinel-node biopsy and total axillary dissection ( the axillary-dissection group ) or to sentinel-node biopsy followed by axillary dissection only if the sentinel node contained metastases ( the sentinel-node group ) . RESULTS The number of sentinel nodes found was the same in the two groups . A sentinel node was positive in 83 of the 257 patients in the axillary-dissection group ( 32.3 percent ) , and in 92 of the 259 patients in the sentinel-node group ( 35.5 percent ) . In the axillary-dissection group , the overall accuracy of the sentinel-node status was 96.9 percent , the sensitivity 91.2 percent , and the specificity 100 percent . There was less pain and better arm mobility in the patients who underwent sentinel-node biopsy only than in those who also underwent axillary dissection . There were 15 events associated with breast cancer in the axillary-dissection group and 10 such events in the sentinel-node group . Among the 167 patients who did not undergo axillary dissection , there were no cases of overt axillary metastasis during follow-up . CONCLUSIONS Sentinel-node biopsy is a safe and accurate method of screening the axillary nodes for metastasis in women with a small breast cancer A great deal of clinical experience has firmly established the concept of the sentinel lymph node ( SN ) in breast cancer . SN biopsy allows treatment without axillary lymphadenectomy and has made it possible to perform a surgical intervention via just a small skin incision . In partial resection of the breast ( quadrantectomy ) , we use a double retractor to form a workspace under the skin via a small axillary incision . Resection does not require a large incision even in cases in which the cancer lesion is located in the upper inner or lower inner quadrant of the breast , as the endoscope allows the surgeon to see the workspace formed by the double retractors Seroma formation is the most common complication after mastectomy . Among the several known etiological factors the surgical procedure used may be of importance for seroma formation . This prospect i ve study was carried out to evaluate the ultrasonic energy dissection technique and its effect on seroma formation and other complications : 59 patients with operable breast cancer underwent modified radical mastectomy , performed in 30 of them with an Ultracision Harmonic scalpel and in 29 with scissors and electrocautery . In all cases a st and ard level II axillary dissection was performed with scissors . We found no differences in the outcome of surgery . Peroperative bleeding ( median 300 ml , range 100 - 790 vs 300 ml , range 40 - 1400 ) , drain volume ( 585 ml , range 130 - 1455 ) vs 645 ml , range 95 - 1570 ) , seroma formation 50 ( 0 - 580 ) ml vs 105 ( 0 - 3775 ) ml and wound complications were about the same in both groups . In conclusion , neither clinical advantages or disadvantages of the ultrasound dissection technique were found |
10,780 | 24,986,544 | Decisive factors in patients ' preferences for surgery type commonly relate to body image and survival/recurrence .
Most participants judged small to moderate benefits sufficient to consider adjuvant systemic therapy worthwhile , but individual preferences varied widely . | PURPOSE Treatment decisions in early breast cancer can revolve around type of surgery and whether or not to have adjuvant systemic therapy .
This systematic review aims to give an overview of patient self-reported factors affecting preferences for breast conserving surgery ( BCS ) versus mastectomy ( MAST ) , the minimal benefit patients require from adjuvant chemotherapy ( aCT ) and /or adjuvant hormonal therapy ( aHT ) to consider it worthwhile , and factors influencing this minimally-required benefit . | Adjuvant endocrine therapy improves recurrence and survival rates , but has side effects and is inconvenient . The aim of this study was to determine the preferences of premenopausal women who had adjuvant endocrine therapy in a r and omised trial . In all , 85 ( or eighty-five ) women completed semistructured interviews 6–30 months after finishing adjuvant endocrine therapy . Hypothetical scenarios based on known potential survival times ( 5 or 15 years ) and rates ( 60 % or 80 % at 5 years ) without adjuvant endocrine therapy were used to determine the smallest gains women judged necessary to make their adjuvant endocrine therapy worthwhile . Although a third of the women considered gains of 1 % in survival rates or 6 months in survival times sufficient to make their adjuvant endocrine therapy worthwhile , more than half the women required gains of at least 5 % in survival rates or 3 years in survival time as necessary to make adjuvant endocrine therapy worthwhile . Larger benefits were required by women who had longer treatment , worse side effects , and by those who were treated with goserelin alone . The route of administration ( tablet vs injection ) did not affect preferences and some women judged small benefits sufficient to make their adjuvant endocrine therapy worthwhile , but many women required larger benefits than their counterparts in similar studies of preferences for adjuvant chemotherapy OBJECTIVE This study examined the long-term effects on women 's health related quality of life ( HRQOL ) of involvement in decision-making about their treatment for breast cancer and about follow-up care after treatment . METHODS Using a cross-sectional survey design , a sample of breast cancer survivors from Western Washington who were 2 , 5 , and 10 years postdiagnosis were recruited via a cancer registry and interviewed about their HRQOL and their involvement in decision-making about their cancer treatment and follow-up care . MAIN OUTCOME MEASURES HRQOL was assessed using the SF-36 . RESULTS Multiple regression analyses examining demographic and disease characteristics revealed age , and education , but not stage of cancer at diagnosis , to be significant predictors of perceived involvement in decision-making about cancer treatment and follow-up . Controlling for demographic and disease characteristics , perceived involvement in decision-making about treatment overall , surgery , chemotherapeutic treatment , and follow-up care were each associated with improved HRQOL , including the general health and vitality subscales of the SF-36 ( p < .05 ) . Involvement in decision-making about surgery was also associated with better mental health among survivors of breast cancer . Congruence of involvement in decision-making with a patient 's preferred level of involvement was also associated with improved survivor HRQOL on several subscales . CONCLUSIONS Perceived involvement in decision-making about breast cancer treatment , and about follow-up care is associated with better HRQOL for survivors 2 , 5 , and 10 years postdiagnosis . Prospect i ve studies may be warranted to determine the possible mechanisms by which perceived involvement in decision-making about aspects of treatment other than surgery type might influence survivor HRQOL HYPOTHESIS Physician-related factors as well as patient characteristics may explain why women aged 65 years or older with early-stage breast cancer undergo lumpectomy less often than younger women , despite National Institutes of Health recommendations favoring lumpectomy over mastectomy . DESIGN A descriptive and analytical retrospective computer-assisted telephone survey . SETTING A population -based r and om sample of breast cancer survivors in Colorado , identified from the Colorado Central Cancer Registry . PATIENTS Women aged 65 to 84 years when diagnosed as having stage I or II breast cancer , treated 1 to 6 years previously with mastectomy or lumpectomy , and without recurrence or second primary cancers . Among women contacted , 58 % participated . Results of 198 interviews are reported . METHODS Survey questions included patient decision-making participation and physician recommendations , sources and amount of treatment information provided by physicians , physician characteristics , and patient surgery preferences and demographic characteristics . A multivariate logistic regression model identified factors independently associated with lumpectomy . RESULTS Lumpectomy was strongly associated with higher patient education , female physician sex , patient age 75 years or older , and amount of physician-provided information . The number of physician-provided information sources was associated with surgery explanations , and female physicians provided more sources of information . A physician decision or recommendation for surgery type was reported by 61 % of women , of whom 93 % underwent the recommended procedure . A subset of patients ( 13 % ) reported deferring the surgery decision to someone else . CONCLUSIONS These results suggest that better-educated and better-informed older women are more likely to undergo lumpectomy , and that physicians may influence breast cancer patients ' decisions about surgery type PURPOSE To assess the use of breast-conserving surgery in two states reported to differ with respect to surgical treatment of breast cancer . METHODS A retrospective cohort study based on data collected from medical records and patients was performed among 1,514 patients diagnosed with early-stage breast cancer in Massachusetts and 1,061 patients in Minnesota . Patients were identified at 18 r and omly selected hospitals in Massachusetts and at 30 hospitals in Minnesota . The rate of breast-conserving surgery in both states and the correlates of breast-conserving surgery among women eligible for the procedure were determined . RESULTS The rate of breast-conserving surgery in both states was much higher than previously reported . Among those eligible for the procedure , nearly 75 % underwent breast-conserving surgery in Massachusetts and nearly half did so in Minnesota . Significantly ( P < .003 ) more women who underwent mastectomy in Minnesota ( 27 % ) than in Massachusetts ( 15 % ) reported that their surgeon did not discuss breast-conserving surgery with them . Among women who underwent mastectomy and who reported being informed of both surgical alternatives , more women ( P < .001 ) in Minnesota ( 74 % ) than in Massachusetts ( 62 % ) said they ultimately chose mastectomy because their surgeon recommended it . In Massachusetts , women treated at teaching hospitals were twice as likely as other women to undergo breast-conserving surgery . In Minnesota , women over age 70 and those who lived in rural areas were less likely than other women to undergo breast-conserving surgery . CONCLUSION Although the rate of breast-conserving surgery in each state was higher than expected based on earlier reports , the rates differed considerably between states . Additional studies are needed to determine whether variation in practice between geographic areas is due to differences in patients ' preferences and values or to surgeons ' propensity for one type of surgery based on where they practice BACKGROUND Adjuvant endocrine therapies such as tamoxifen , goserelin , and oophorectomy improve survival for premenopausal women diagnosed with early-stage breast cancer . However , these treatments often result in menopausal symptoms , sexual dysfunction , permanent infertility , or the need to delay pregnancy . We aim ed to quantify the survival gains that premenopausal patients with early-stage breast cancer require to justify the side-effects and inconvenience of adjuvant endocrine treatments . METHODS Participants consisted of 102 women who had been diagnosed with early-stage ( stage I-II ) breast cancer 6 - 60 months previously , who were aged 40 years or younger at diagnosis , and who had been treated for a minimum of 3 months with endocrine therapy ( 67 with tamoxifen alone , seven with goserelin alone , and 28 with tamoxifen and goserelin or oophorectomy ) . 76 patients also received chemotherapy , and 75 received radiotherapy . Participants attended a face-to-face patient-preference interview , in which they were presented with four hypothetical clinical scenarios that were used to quantify the gains in survival rate and life expectancy that women judged necessary to make their endocrine therapy worthwhile . They also completed a question naire on st and ard psychological measures . FINDINGS About half of participants thought that adjuvant endocrine therapy was worthwhile for an absolute gain in survival of 2 % from a baseline of either 65 % or 85 % , and for a gain in life expectancy of 3 months from a baseline of 5 years and of 6 months for a baseline of 15 years . Women who had had more severe endocrine side-effects required larger gains to make endocrine therapy worthwhile ( univariate p=0.02 , multivariate p=0.04 ) . INTERPRETATION Modest gains in survival are sufficient to make adjuvant endocrine treatment worthwhile for premenopausal women with early-stage breast cancer . Knowing and incorporating what women think should enhance shared decision-making One hundred and sixty-three patients with primary breast cancer were prospect ively studied . Using recently developed selection criteria 91 patients were offered a choice of treatment . Forty-one chose to undergo conservation treatment and 47 chose to undergo simple mastectomy . In those women who were offered a choice of treatment there was a significant tendency for younger patients to choose breast conserving treatment BACKGROUND In 1976 , we initiated a r and omized trial to determine whether lumpectomy with or without radiation therapy was as effective as total mastectomy for the treatment of invasive breast cancer . METHODS A total of 1851 women for whom follow-up data were available and nodal status was known underwent r and omly assigned treatment consisting of total mastectomy , lumpectomy alone , or lumpectomy and breast irradiation . Kaplan-Meier and cumulative-incidence estimates of the outcome were obtained . RESULTS The cumulative incidence of recurrent tumor in the ipsilateral breast was 14.3 percent in the women who underwent lumpectomy and breast irradiation , as compared with 39.2 percent in the women who underwent lumpectomy without irradiation ( P<0.001 ) . No significant differences were observed among the three groups of women with respect to disease-free survival , distant-disease-free survival , or overall survival . The hazard ratio for death among the women who underwent lumpectomy alone , as compared with those who underwent total mastectomy , was 1.05 ( 95 percent confidence interval , 0.90 to 1.23 ; P=0.51 ) . The hazard ratio for death among the women who underwent lumpectomy followed by breast irradiation , as compared with those who underwent total mastectomy , was 0.97 ( 95 percent confidence interval , 0.83 to 1.14 ; P=0.74 ) . Among the lumpectomy-treated women whose surgical specimens had tumor-free margins , the hazard ratio for death among the women who underwent postoperative breast irradiation , as compared with those who did not , was 0.91 ( 95 percent confidence interval , 0.77 to 1.06 ; P=0.23 ) . Radiation therapy was associated with a marginally significant decrease in deaths due to breast cancer . This decrease was partially offset by an increase in deaths from other causes . CONCLUSIONS Lumpectomy followed by breast irradiation continues to be appropriate therapy for women with breast cancer , provided that the margins of resected specimens are free of tumor and an acceptable cosmetic result can be obtained PURPOSE The purpose of this study was to measure the degree to which informed women chose mastectomy , and to reveal their reasons for this choice . PATIENTS AND METHODS This was a prospect i ve cohort study of patients radiographically and pathologically eligible for either mastectomy or breast-conserving surgery ( BCS ; n = 125 ) . Participants completed question naires at three time points : baseline , after viewing a decision aid , and after a surgical consultation . Question naires assessed clinical history , preference for participation in decision making , information comprehension , values , decisional conflict , and preferred treatment . RESULTS Of 125 participants , 44 ( 35 % ) chose mastectomy . Most understood that BCS and mastectomy offer an equivalent survival benefit ( 98 % ) and that BCS has a slightly higher local recurrence risk ( 63 % ) ; most accurately identified the magnitude of ipsilateral local recurrence risk ( 91 % ) . Values assigned to three treatment attributes/ outcomes ( " remove breast for peace of mind , " " avoid radiation , " and " keep breast " ) clearly discriminated between patients choosing mastectomy or BCS . High decisional conflict scores improved after both the decision aid and surgical consultation . CONCLUSION Although conventional wisdom may view BCS as the preferred treatment , a notable proportion of well informed women choose mastectomy . Whereas prior studies have linked objective factors to treatment choice , this study reveals subjective preferences that underlie decision making . The systematic use of a decision aid before the surgical consultation may help women make informed , values-based decisions , while clearly reducing decisional conflict This study was performed to describe women 's satisfaction with body image before and 8 weeks after the surgical treatment of breast cancer compared with women without breast cancer . Additional aims were to describe women 's perceived participation in decisions regarding choice of surgical procedure to treat their breast cancer , and postoperative satisfaction with their breast cancer treatment , as well as to explore factors influencing women 's decisions regarding choice of surgical procedure . The design was prospect i ve with a descriptive , comparative design . The convenience sample included 31 women with breast cancer from an urban breast health center , and 30 women without breast cancer from the community . The majority were college educated , white , ranging in age from 29 - 82 years . Women with breast cancer completed instruments before and 8 weeks after surgery . Women without breast cancer completed the instruments two times 8 weeks apart . Three instruments measuring body image satisfaction were used . Participation in treatment decision-making , having a treatment choice , and posttreatment satisfaction , along with a description of important factors in decision making , were measured with open and closed-ended questions . During the study period , women with breast cancer experienced a significant decrease in satisfaction with body image after surgery ( p < .004 ) . Satisfaction with body image remained constant in the women without breast cancer . Most ( 94 % ) of the women with breast cancer reported participating in treatment decisions about the type of surgical procedure used to treat their breast cancer , had a treatment choice ( 77 % ) , and were moderately to very satisfied with the outcome of their surgeries ( 94 % ) . Qualitative data results suggest that women 's treatment decisions were based on their perceptions of " survival , " that is , which type of surgery offered the best chance for long-term survival . These data suggest that satisfaction with body image is disturbed by surgery for breast cancer despite active participation in decisions regarding selection of treatment or postoperative satisfaction with type of surgical treatment received . These outcomes suggest that women need assistance in adjusting to alterations in body image from nurses and the need for research to describe effective interventions . Future studies of body image and breast cancer treatment should be conducted with larger sample s , and at different points after surgery to determine the effects of mastectomy and breast-conserving surgery on the body image of breast cancer survivors over time Background Mastectomy rates have been assumed to be a function of physician recommendations , although they correlate with patient involvement in decision making . The influence of age on the decision-making process and treatment choice is poorly described . Methods All women with ductal carcinoma in situ ( DCIS ) and a r and om sample with invasive breast cancer were identified from two Surveillance Epidemiology and End Results ( SEER ) program registries and surveyed 6 months postoperatively . Women older than 79 years with noninvasive or localized invasive breast cancer diagnosed in 2002 were included . Women with breast-conserving therapy ( BCT ) contraindications were excluded . Women were question ed about involvement in surgical decision-making , inquiring if this decision was patient-based , surgeon-based , or shared . Knowledge and concerns were assessed . Results The response rate was 77.0 % . There were 1,259 patients who met the study eligibility criteria and age data was available for 1,131 . Median patient age was 59.9 years . The frequency of patient-based decisions did not vary with age ( p = 0.20 ) , but older women had less knowledge for decision making . The mastectomy rate overall was 19.7 % , with no differences in mastectomy choice by age ( p = 0.18 ) . In logistic regression for the likelihood of undergoing mastectomy , patient involvement ( p < 0.0001 ) , larger tumor size ( p < 0.0001 ) , lower education ( p = 0.0002 ) , number of surgeons consulted ( p = 0.0005 ) , and nonwhite race origin ( p = 0.011 ) were significant predictors , while age , invasion , and comorbidities were not significant . Conclusion Older women participate equally in breast cancer surgical decision making and are equally likely to select mastectomy , but use less knowledge to make the decision . The impact of education and ethnic origin on mastectomy use indicates the need for improved educational strategies for these groups BACKGROUND We conducted 20 years of follow-up of women enrolled in a r and omized trial to compare the efficacy of radical ( Halsted ) mastectomy with that of breast-conserving surgery . METHODS From 1973 to 1980 , 701 women with breast cancers measuring no more than 2 cm in diameter were r and omly assigned to undergo radical mastectomy ( 349 patients ) or breast-conserving surgery ( quadrantectomy ) followed by radiotherapy to the ipsilateral mammary tissue ( 352 patients ) . After 1976 , patients in both groups who had positive axillary nodes also received adjuvant chemotherapy with cyclophosphamide , methotrexate , and fluorouracil . RESULTS Thirty women in the group that underwent breast-conserving therapy had a recurrence of tumor in the same breast , whereas eight women in the radical-mastectomy group had local recurrences ( P<0.001 ) . The crude cumulative incidence of these events was 8.8 percent and 2.3 percent , respectively , after 20 years . In contrast , there was no significant difference between the two groups in the rates of contralateral-breast carcinomas , distant metastases , or second primary cancers . After a median follow-up of 20 years , the rate of death from all causes was 41.7 percent in the group that underwent breast-conserving surgery and 41.2 percent in the radical-mastectomy group ( P=1.0 ) . The respective rates of death from breast cancer were 26.1 percent and 24.3 percent ( P=0.8 ) . CONCLUSIONS The long-term survival rate among women who undergo breast-conserving surgery is the same as that among women who undergo radical mastectomy . Breast-conserving surgery is therefore the treatment of choice for women with relatively small breast cancers |
10,781 | 29,279,982 | Additional analyses revealed a significant effect size advantage for explicit instruction tasks compared with implicit instructions , yet yielded no difference for the role of expertise on SNARC-like effects .
The similarities in the response properties for the spatial mappings of numerical and non-numerical domains support the concept of a general higher order magnitude system . | The spatial numerical association of response code ( SNARC ) effect is characterized by low numbers mapped to the left side of space and high numbers mapped to the right side of space .
In addition to numbers , SNARC-like effects have been found in non-numerical magnitude domains such as time , size , letters , luminance , and more , whereby the smaller/earlier and larger/later magnitudes are typically mapped to the left and right of space , respectively .
The purpose of this systematic and meta-analytic review was to identify and summarise all empirical papers that have investigated horizontal ( left – right ) SNARC-like mappings using non-numerical stimuli . | Access to mental representations of smaller vs. larger number symbols is associated with leftward vs. rightward spatial locations , as represented on a number line . The well-replicated SNARC effect ( Spatial-Numerical Association of Response Codes ) reveals that simple decisions about small numbers are facilitated when stimuli are presented on the left , and large numbers facilitated when on the right . We present novel evidence that the size of the SNARC effect is relatively stable within individuals over time . This enables us to take an individual differences approach to investigate how the SNARC effect is modulated by spatial and numerical cognition . Are number-space associations linked to spatial operations , such that those who have greater facility in spatial computations show the stronger SNARC effects , or are they linked to number semantics , such that those showing stronger influence of magnitude associations on number symbol decisions show stronger SNARC effects ? Our results indicate a significant correlation between the SNARC effect and a 2D mental rotation task , suggesting that spatial operations are at play in the expression of this effect . We also uncover a significant correlation between the SNARC effect and the distance effect , suggesting that the SNARC is also related to access to number semantics . A multiple regression analysis reveals that the relative contributions of spatial cognition and distance effects represent significant , yet distinct , contributions in explaining variation in the size of the SNARC effect from one individual to the next . Overall , these results shed new light on how the spatial-numerical associations of response codes are influenced by both number semantics and spatial operations |
10,782 | 29,337,860 | Indeterminate bone scan for staging of prostate cancer was insufficiently reported in clinical trials .
In the case of indeterminate scans , most studies provided adequate measures to obtain the final status of the patients | Bone scintigraphy is key in imaging skeletal metastases in newly diagnosed prostate cancer .
Unfortunately , a notable proportion of scans are not readily classified as positive or negative but deemed indeterminate .
The extent of reporting of indeterminate bone scans and how such scans are h and led in clinical trials are not known . | BACKGROUND Multiparametric magnetic resonance imaging ( mpMRI ) is the st and ard for local prostate cancer ( PCa ) staging . Whole-body MRI ( wbMRI ) has shown capabilities for metastatic screening . This study assesses the feasibility and value of an all-in-one AJCC TNM staging of PCa during a unique MRI session combining mpMRI and wbMRI . METHODS Thirty consecutive patients with " high-risk " PCa prospect ively underwent mpMRI of the prostate and wbMRI , in addition to ( 99 m ) Tc bone scan ( BS ) , completed with st and ard X-rays ( ±TXR ) and contrast enhanced CT for distant staging . For the statistical analysis , a " best valuable comparator " ( BVC ) combining a panel review of all available baseline and follow-up imaging , biological , and clinical data was used to adjudicate lymph node and bone metastatic status . RESULTS Prostate mpMRI was analyzed using ESUR guidelines . Sensitivity of BS ± TXR combined with CT and of wbMRI for detecting metastases ( bones or nodes ) was 85 % and 100 % , respectively , and specificity was 88 % and 100 % , respectively . For the overall staging of the patients as being either N0M0 or having disease extension beyond the prostate , wbMRI was superior to the combination of BS and CT ( improvement in all ROC characteristics and of AUC by 13.6 % ( 95 % CI : + 0.7 % to + 26.5 % , P = 0.039 ) ) . The main limitation is the limited number of patients . CONCLUSIONS AJCC M and N staging using wbMRI is feasible during the same imaging session as mpMRI performed for T staging , in less then one hour . wbMRI outperforms BS ± TXR and abdomino-pelvic CT work up for discriminating subsets of patients with or without distant spread of the cancer Purpose This study was design ed to assess the additional value of SPECT/CT of the trunk used in conjunction with conventional nuclear imaging and its effects on patient management in a large patient series . Methods In 353 patients , whole-body scintigraphy ( WBS ) , SPECT , and SPECT/CT were prospect ively performed for staging and restaging . SPECT/CT of the trunk was performed in all patients . In the 308 evaluable patients ( 211 with breast cancer , 97 with prostate cancer ) , clinical follow-up was used as the gold st and ard . Bone metastases were confirmed in 72 patients and excluded in 236 . Multistep analyses per lesion and per patient were performed . Clinical relevance was expressed in terms of downstaging and upstaging rates on a per-patient basis . Results In the total patient group , sensitivities , specificities , and negative and positive predictive values on a per-patient basis were 93 % , 78 % , 95 % and 59 % for WBS , 94 % , 71 % , 97 % and 53 % for SPECT , and 97 % , 94 % , 97 % and 88 % for SPECT/CT , respectively . In all subgroups , specificity and positive predictive value were significantly ( p < 0.01 ) better with SPECT/CT . Downstaging of metastatic disease in the total , breast cancer and prostate cancer groups using SPECT/CT was possible in 32.1 % , 33.8 % and 29.5 % of patients , respectively . Upstaging in previously negative patients by additional SPECT/CT was observed in three breast cancer patients ( 2.1 % ) . Further diagnostic imaging procedures for unclear scintigraphic findings were necessary in only 2.5 % of patients . SPECT/CT improved diagnostic accuracy for defining the extent of multifocal metastatic disease in 34.6 % of these patients . Conclusions SPECT/CT significantly improved the specificity and positive predictive value of bone scintigraphy in cancer patients . In breast cancer patients , we found a slight increase in sensitivity . SPECT/CT had a significant effect on clinical management because of correct downstaging and upstaging , better definition of the extent of metastases , and a reduction in further diagnostic procedures Purpose The aim of our study was to compare the diagnostic performance of 68Ga-PSMA PET and 99mTc bone scintigraphy ( BS ) for the detection of bone metastases in prostate cancer ( PC ) patients . Methods One hundred twenty-six patients who received planar BS and PSMA PET within three months and without change of therapy were extracted from our data base . Bone lesions were categorized into benign , metastatic , or equivocal by two experienced observers . A best valuable comparator ( BVC ) was defined based on BS , PET , additional imaging , and follow-up data . The cohort was further divided into clinical subgroups ( primary staging , biochemical recurrence , and metastatic castration-resistant prostate cancer [ mCRPC ] ) . Additionally , subgroups of patients with less than 30 days delay between the two imaging procedures and with additional single-photon emission computed tomography ( SPECT ) were analyzed . Results A total of 75 of 126 patients were diagnosed with bone metastases . Sensitivities and specificities regarding overall bone involvement were 98.7–100 % and 88.2–100 % for PET , and 86.7–89.3 % and 60.8–96.1 % ( p < 0.001 ) for BS , with ranges representing results for ‘ optimistic ’ or ‘ pessimistic ’ classification of equivocal lesions . Out of 1115 examined bone regions , 410 showed metastases . Region-based analysis revealed a sensitivity and specificity of 98.8–99.0 % and 98.9–100 % for PET , and 82.4–86.6 % and 91.6–97.9 % ( p < 0.001 ) for BS , respectively . PSMA PET also performed better in all subgroups , except patient-based analysis in mCRPC . Conclusion Ga-PSMA PET outperforms planar BS for the detection of affected bone regions as well as determination of overall bone involvement in PC patients . Our results indicate that BS in patients who have received PSMA PET for staging only rarely offers additional information ; however , prospect i ve studies , including a st and ardized integrated x-ray computed tomography ( SPECT/CT ) protocol , should be performed in order to confirm the presented results OBJECTIVES The aim of this study was to correlate the prostate-specific antigen ( PSA ) level and Gleason score with staging bone scan result in patients with a new diagnosis of prostate cancer in order to establish the feasibility of implementing the European Association Urology guidelines , which state that a bone scan may not be indicated when PSA < 20 in well-moderately differentiated tumours . METHODS We identified 633 patients retrospectively and 186 patients prospect ively with a new diagnosis of prostate cancer undergoing a staging bone scan between March 2005 and January 2010 . Patients were excluded if there was no Gleason score available or if the PSA level was checked over 3 months prior to bone scan . Bone scan results were analysed with respect to age , PSA level and Gleason score . In the case of an equivocal result , subsequent imaging was taken into consideration or the initial bone scan was re- review ed . In persistently equivocal cases , all relevant imaging was assessed by a blinded panel of radiologists to allow a final decision to be made . RESULTS Of 672 patients aged 39 - 93 years ( median 71 years ) , who fulfilled the inclusion criteria , 54 ( 8 % ) had evidence of bony metastases . PSA level and Gleason score were both independent predictors of bone scan positivity and their predictive value was additive p<0.01 . None of the 357 patients with a PSA level of < 20 and a Gleason score of < 8 had a positive bone scan . CONCLUSION Staging bone scans in newly diagnosed prostate cancer patients with a PSA level of < 20 and a Gleason score of < 8 can be safely omitted , with these criteria having a negative predictive value of 100 % in our series Background International guidelines uniformly suggest no routine staging of bone metastasis in patients with bone scintigraphy ( BS ) in low-risk prostate cancer ( PCa ) . These recommendations are based on retrospective investigations only . In addition , BS has most often been reported as a definitive investigation with no room for equivocal cases . Objective The objective of this study was to determine the diagnostic value of BS in a large cohort of consecutive patients with newly diagnosed PCa . Design , Setting , and Participants Over a period of 1.5 years in 2008 to 2009 , consecutive patients with newly diagnosed PCa were enrolled in a noninterventional , multicenter , observational study . All patients had a whole-body , planar BS . Clinical history and clinical , pathological , and biochemical data were obtained from electronic patient files and question naires . Outcome Measurements and Statistical Analysis Bone scintigraphy was classified into 4 categories as nonmalignant , equivocal , likely malignant , or multiple metastasis . The primary end point was final imaging , which was a composite end point of BS and additional CT and MRI investigations . Results and Limitations A total of 635 eligible patients were recruited . Their median prostate-specific antigen ( PSA ) was 15 ng/mL , median Gleason was 7 , and 80 % of patients had local disease ( T1 or T2 ) . The proportion of nonmalignant BS was 61 % , equivocal scans 26 % , and likely or definitive metastasis 13 % . A total of 154 patients had additional CT or MRI investigations . The final imaging diagnosis showed a prevalence of bone metastases in 87 ( 13.7 % ) of 635 patients . No bone metastases were observed in ( 1 ) patients with PSA of less than 10 ng/mL , independently of the clinical Tstage and Gleason score ( n = 212 ) and ( 2 ) PSA of less than 20 ng/mL if Tstage is less than T3 and Gleason score is less than 8 ( n = 97 ) . Approximately 50 % of the patients enrolled in this study met these criteria . Conclusion This is the first prospect i ve trial to demonstrate that BS can be avoided in patients with low-risk PCa Background The majority of enhancing renal masses are unable to be effectively characterized as benign or malignant using st and ard cross-sectional imaging modalities including multi-phase computed tomography ( CT ) [ 1 ] and magnetic resonance imaging ( MRI ) [ 2 ] . This is particularly unfortunate in light of the steady increase in the incidence of these lesions , many of which are discovered incidentally on imaging studies performed for nonurologic indications [ 3 , 4 ] . Moreover , it has been estimated that upwards of 5600 unnecessary partial and radical nephrectomies are performed each year in the USA for the false presumption of cancer [ 5 ] . In light of these data , recently , there has been a growing interest in the use of molecular imaging to characterize the aggressiveness of renal masses [ 6 , 7 ] . To date , several reports have been published on the ability of Tc-sestamibi planar and single photon emission computed tomography (SPECT)/CT imaging to differentiate mitochondrial-rich benign and indolent renal masses such as oncocytomas and hybrid oncocytic/ chromophobe tumors ( HOCTs ) from more aggressive renal tumor histologies including the clear cell subtype of renal cell carcinoma ( RCC ) [ 8–10 ] . In this issue of European Journal of Nuclear Medicine and Molecular Imaging Research , Tzortzakakis et al. [ 11 ] add to this body of literature with a prospect i ve study evaluating Tc-sestamibi SPECT/CT in 24 patients with 31 clinical ly localized T1 renal masses planned for biopsy or surgery . The authors reported that 11 of 12 ( 92 % ) oncocytomas and 3 of 3 ( 100 % ) HOCTs demonstrated Tc-sestamibi uptake , while all other lesions were negative for uptake with the exception of mild uptake in a single papillary RCC . These findings are concordant with earlier studies [ 9 , 10 ] and dramatically increase the number of Tc-sestamibi positive oncocytomas and HOCTs reported in the literature . As a brief aside , it should be mentioned that there is also a growing interest in the use of renal mass biopsy for determining the histology of renal tumors , particularly as data from two recent systematic review s have suggested that the rates of complications and nondiagnostic biopsies are tolerable [ 12 , 13 ] . However , limitations of renal mass biopsy remain , including the intrinsically invasive nature of this procedure , the inaccessibility of some tumors to safe approaches for biopsy , and the heterogeneous population of renal masses that can present as oncocytic neoplasms on biopsy [ 14 , 15 ] . As such , the non-invasive characterization of renal masses with molecular imaging techniques continues to be of interest and may serve as an adjunct to , or even a replacement of , biopsy in selected cases Presently , the st and ard staging evaluation of prostate cancer includes digital rectal examination , measurement of serum tumor markers and a radionuclide bone scan . To evaluate the ability of local clinical stage , tumor grade , serum acid phosphatase , serum prostatic acid phosphatase ( PAP ) and serum prostate specific antigen ( PSA ) to predict bone scan findings , a retrospective review of 521 r and omly chosen patients ( mean age 70 years , range 44 to 92 years ) with newly diagnosed , untreated prostate cancer was performed . Local clinical stage , tumor grade , acid phosphatase , PAP and PSA all correlated positively with bone scan findings ( p less than 0.0001 ) . Using receiver operating characteristic curves , however , PSA had the best over-all correlation with bone scan results . The median serum PSA concentration in patients with a positive bone scan was 158.0 ng./ml . , whereas men with a negative bone scan had a median serum PSA level of 11.3 ng./ml . ( p less than 0.0001 ) . Using multivariate logistic regression analysis , local clinical stage , tumor grade , acid phosphatase and PAP were evaluated in combination with PSA to assess whether these parameters increased the ability of PSA alone to predict bone scan findings . None of these clinical parameters , irrespective of the combination used , contributed appreciably to the predictive power of PSA alone . A probability plot with 95 % confidence intervals was constructed that allows the practicing urologist to estimate on an individual basis the probability of a positive bone scan for any given serum PSA value . The most significant finding of this study , however , was the negative predictive value of a low serum PSA concentration for bone scan findings . In 306 men with a serum PSA level of 20 ng./ml . or less only 1 ( PSA 18.2 ng./ml . ) had a positive bone scan ( negative predictive value 99.7 % ) . This finding would suggest that a staging radionuclide bone scan in a previously untreated prostate cancer patient with a low serum PSA concentration may not be necessary Purpose Ventilation and perfusion ( VQ ) imaging is common following suboptimal CT pulmonary angiogram ( CTPA ) for pulmonary embolism ( PE ) evaluation ; however , the results of this diagnostic pathway are unclear . The purpose of our study is to determine the incidence of PE diagnosed on VQ scans performed in patients with suboptimal CTPAs . Methods One hundred twenty-two suboptimal CTPAs with subsequent VQ scans within 1 week were retrospectively identified . VQ reports utilizing modified prospect i ve investigation of pulmonary embolism diagnosis ( PIOPED ) and prospect i ve investigative study of acute pulmonary embolism diagnosis ( PISAPED ) criteria were evaluated for presence of PE ; intermediate probability , high probability , and PE present were considered PE positive . Three hundred consecutive reports of each diagnostic CTPA and diagnostic VQ studies were review ed to estimate baseline PE positive rates at our institution . These were compared to the positive VQ scan rate after suboptimal CTPA by Fisher ’s exact test . Reported reason for suboptimal CTPA was noted . When contrast bolus timing was suboptimal , we measured main pulmonary artery ( mPA ) Hounsfield units ( HU ) . Potential alternative diagnoses in CTPA reports were noted . Results 97.5 % ( 119/122 ) of VQ scans following suboptimal CTPA were negative for PE , and 2.5 % ( 3/122 ) were positive for PE . This was significantly lower than baseline PE positive rate of 10.7 % ( 32/300 , p < 0.01 ) for VQ imaging , and 10.3 % ( 31/300 , p < 0.01 ) for CTPA at our institution . Most ( 79.5 % ) CTPAs were suboptimal due to contrast timing . Average mPA density in these cases was 164 ± 61 HU . Most of these studies ruled out central PE . Potential alternative diagnosis was reported in 34/122 ( 28 % ) of suboptimal CTPAs , for which pneumonia accounted 59 % . Conclusion There is very low incidence of PE diagnosed on VQ imaging performed after suboptimal CTPA . This may be attributed to the ability of most suboptimal CTPAs to rule out central PE INTRODUCTION The objective was to describe regional variations in M-staging in patients with newly diagnosed prostate cancer within a Danish county and to compare clinical practice with guideline recommendations . METHODS Data were as captured from 1 ) a prospect i ve , non-interventional study counting 635 consecutive patients referred for M-staging in the 2008 - 2009 period at three regional hospitals within one county , and 2 ) a question naire on M-staging practice completed by the five sites performing M-staging in the same county in 2015 . RESULTS All three sites referred patients for M-staging in 2008 , irrespective of their risk factors . Two of the three sites maintained this practice in 2015 . Furthermore , in 2015 , three of five sites performed M-staging in intermediate and high-risk patients only . Planar whole-body bone scans were st and ard in all sites in 2008 with single photon emission computed tomography/computed tomography ( SPECT/CT ) being performed if required and if available . In 2015 , two sites used choline positron emission tomography/CT for primary staging of high-risk patients against guideline recommendations . The use of SPECT/CT showed wide variations from " if required " to " m and atory " head-to-thigh imaging . There were notable variations between clinical practice and guidelines in 2008 , and this was even more evident in 2015 . CONCLUSION Considerable variations existed with respect to the M-staging imaging practice s in prostate cancer within a single Danish county . The variation was more pronounced in 2015 than in 2008 . Clinical practice conflicted in part with European and national Danish guidelines . FUNDING none . TRIAL REGISTRATION not relevant The purpose of this study was to determine the utility of prostate specific antigen ( PSA ) level and Gleason score in the prediction of disease stage in men with newly diagnosed prostate cancer . 102 consecutive men , newly diagnosed with prostate cancer and c and i date s for radical therapy , underwent contrast enhanced pelvic CT and skeletal scintigraphy . Staging examinations used the TNM classification and were reported prospect ively with the radiologist blinded to the patient 's Gleason score and level of PSA . Lymph node metastasis was confirmed by CT guided biopsy , lymphadenectomy or response to therapy in some cases of massive disease . There were significant differences between the mean PSA values of 18 men with and 84 men without skeletal metastases ( p = 0.01 ) and between men with locally confined and non-confined disease ( p = 0.02 ) . There was no difference between PSA values of 13 men with and 89 men without lymph node metastasis ( p = 0.9 ) . Only one man with CT evidence of nodal metastasis ( N + ve ) had a PSA value below 20 ng ml-1 . Two men with Gleason scores below 6 were N + ve and both had PSA values over 20 ng ml-1 . One man with skeletal metastasis had a PSA value below 20 ng ml-1 but had bone pain . For this study group if only those men with PSA values over 20 ng ml-1 had been examined , sensitivity for lymphatic and skeletal metastasis would have been 92 % . Using this threshold about one-third would have been spared imaging investigation . In conclusion , pelvic CT and skeletal scintigraphy are unlikely to show metastatic disease in a man newly diagnosed with prostate cancer who has no suggestive clinical features , a PSA level below 20 ng ml-1 and a Gleason score below 6 R and om bone marrow aspiration biopsies of iliac crests and bone scans/skeletal X-rays were evaluated in 163 new cases of carcinoma of the prostate in order to assess the incidence of bone metastases and to compare the sensitivity of these two methods . Bone marrow biopsy revealed cancer cells in 18.4 % of all cases . The detection rate of skeletal metastases of bone scan/skeletal X-ray was 32.5 % . In this series all patients with positive biopsies had also positive scans . The superior sensitivity of bone scans compared with bone marrow biopsies in detecting metastatic spread of prostatic cancer is shown Abstract Objective . The aim of this study was to evaluate the efficiency of [18F]fluorocholine positron emission tomography/computed tomography ( FCH PET/CT ) in detecting lymph-node and bone involvement in comparison with conventional imaging , such as abdominal – pelvic CT and bone scan , in the initial staging of prostate cancer ( PCa ) . Material s and methods . The study retrospectively evaluated 48 patients who had FCH PET/CT for the initial staging of PCa . At the same time , 32 of the 48 patients had a bone scan and 26 of the 48 patients had abdominal – pelvic diagnostic CT . Diagnostic performance of FCH PET/CT , i.e. sensitivity , specificity and accuracy , was evaluated on a per-patient basis for the whole population and then separately on a per-risk classification , and later in comparison with conventional imaging . Histological specimens or follow-up data were used as the st and ard of reference . Results . The overall accuracy of FCH PET/CT for lymph-node involvement was 83.3 % . The sensitivity of FCH was higher in the high-risk subset ( 83.3 % ) than in the intermediate-risk group ( 33.3 % ) , whereas FCH specificity was similar . In comparison with dedicated CT scan , FCH PET/CT showed a higher sensitivity and a similar specificity ( 46.2 % vs 69.2 % and 92.3 % vs 92.3 % , respectively ) . Moreover , the sensitivity and specificity of PET/CT were higher than those of bone scan ( 100 % vs 90 % and 86.4 % vs 77.2 % , respectively ) . In contrast with conventional imaging , PET/CT changed the staging of the PCa in 33.3 % patients . Conclusions . The efficiency of FCH PET/CT in detecting both bone and lymph-node involvement of PCa at initial staging was found to be higher than that of conventional imaging . Prospect i ve clinical trials are needed to confirm these findings An analysis was made of a prospect i ve data base of 614 men with newly diagnosed carcinoma of the prostate who presented between January 1978 and December 1990 ; 3-monthly up date s were available on their clinical , haematological and biochemical parameters and 6-monthly up date s on chest X-rays , bone scans and skeletal X-rays . It was found that 107 men ( mean age 73.5 years ) had early disease at presentation . Their management was based on regular surveillance and the treatment deferred until disease progression or development of symptoms . The audit of outcome measured various clinical events . Four patients ( 3.7 % ) developed local failure , 11 ( 10.3 % ) developed bone metastases , 3 ( 2.8 % ) died of cancer with a median survival of 6.3 years , and 34 ( 31.8 % ) died of intercurrent disease with a median survival of 2.6 years . The observed survival for 12 years of the whole group was similar to the expected survival for an age-matched population in Scotl and . The st and ardised mortality ratio was 81 ( 95 % confidence limits 57 - 112 ) CONTEXT The most recent summary of the European Association of Urology ( EAU ) guidelines on prostate cancer ( PCa ) was published in 2011 . OBJECTIVE To present a summary of the 2013 version of the EAU guidelines on screening , diagnosis , and local treatment with curative intent of clinical ly organ-confined PCa . EVIDENCE ACQUISITION A literature review of the new data emerging from 2011 to 2013 has been performed by the EAU PCa guideline group . The guidelines have been up date d , and levels of evidence and grade s of recommendation have been added to the text based on a systematic review of the literature , which included a search of online data bases and bibliographic review s. EVIDENCE SYNTHESIS A full version of the guidelines is available at the EAU office or online ( www.uroweb.org ) . Current evidence is insufficient to warrant widespread population -based screening by prostate-specific antigen ( PSA ) for PCa . Systematic prostate biopsies under ultrasound guidance and local anesthesia are the preferred diagnostic method . Active surveillance represents a viable option in men with low-risk PCa and a long life expectancy . A biopsy progression indicates the need for active intervention , whereas the role of PSA doubling time is controversial . In men with locally advanced PCa for whom local therapy is not m and atory , watchful waiting ( WW ) is a treatment alternative to and rogen-deprivation therapy ( ADT ) , with equivalent oncologic efficacy . Active treatment is recommended mostly for patients with localized disease and a long life expectancy , with radical prostatectomy ( RP ) shown to be superior to WW in prospect i ve r and omized trials . Nerve-sparing RP is the approach of choice in organ-confined disease , while neoadjuvant ADT provides no improvement in outcome variables . Radiation therapy should be performed with ≥ 74 Gy in low-risk PCa and 78 Gy in intermediate- or high-risk PCa . For locally advanced disease , adjuvant ADT for 3 yr results in superior rates for disease-specific and overall survival and is the treatment of choice . Follow-up after local therapy is largely based on PSA and a disease-specific history , with imaging indicated only when symptoms occur . CONCLUSIONS Knowledge in the field of PCa is rapidly changing . These EAU guidelines on PCa summarize the most recent findings and put them into clinical practice . PATIENT SUMMARY A summary is presented of the 2013 EAU guidelines on screening , diagnosis , and local treatment with curative intent of clinical ly organ-confined prostate cancer ( PCa ) . Screening continues to be done on an individual basis , in consultation with a physician . Diagnosis is by prostate biopsy . Active surveillance is an option in low-risk PCa and watchful waiting is an alternative to and rogen-deprivation therapy in locally advanced PCa not requiring immediate local treatment . Radical prostatectomy is the only surgical option . Radiation therapy can be external or delivered by way of prostate implants . Treatment follow-up is based on the PSA level OBJECTIVE We performed a multicenter Phase IIb clinical trial of NMK36 , a novel amino acid analog for positron emission tomography containing trans-1-amino-3-[(18)F]fluorocyclobutanecarboxylic acid , to evaluate its safety and diagnostic performance for primary prostate cancer . METHODS Sixty-eight subjects with primary prostate cancer scheduled for radical prostatectomy or hormone therapy underwent whole-body positron emission tomography/computed tomography after injection of NMK36 . The diagnostic performances of NMK36-positron emission tomography/computed tomography were evaluated for ( i ) regional lymph node metastasis : comparison with contrast-enhanced computed tomography under setting reference st and ard ( histopathology or 6-month follow-up ) , ( ii ) bone metastasis : concordance rate with conventional imaging ( combination of bone scintigraphy and contrast-enhanced computed tomography ) and ( iii ) primary lesion : comparison with histopathological findings . RESULTS The accuracy of NMK36-positron emission tomography/computed tomography and contrast-enhanced computed tomography for regional lymph node metastasis were 85.5 and 87.3 % , respectively . NMK36-positron emission tomography/computed tomography showed positive findings for regional lymph nodes with short-axis diameters of 5 - 9 mm at 23 regions in 13 patients of hormone therapy cohort , but they were not confirmed with reference st and ard in this study . The concordance rate of NMK36-positron emission tomography/computed tomography with conventional imaging for bone metastases was 83.3 % , and seven patients had positive findings only by NMK36-positron emission tomography/computed tomography . The sensitivity and specificity of NMK36-positron emission tomography/computed tomography for primary lesion in six-segment analysis was 92.5 and 90.1 % , respectively . Seven of non-serious adverse events were observed in six patients . CONCLUSIONS This study showed the comparable diagnostic performance of NMK36-positron emission tomography/computed tomography compared with conventional imaging . Some lesions of lymph node and bone were positive solely by NMK36-positron emission tomography/computed tomography , which needs to be confirmed with reference st and ard in future study to evaluate the usefulness of NMK36-positron emission tomography/computed tomography in staging prostate cancer |
10,783 | 28,698,222 | Summary / conclusion Dietary protein supplementation significantly enhanced changes in muscle strength and size during prolonged RET in healthy adults .
Increasing age reduces and training experience increases the efficacy of protein supplementation during RET .
With protein supplementation , protein intakes at amounts greater than ~1.6 g/kg/day do not further contribute RET-induced gains in FFM | Objective We performed a systematic review , meta- analysis and meta-regression to determine if dietary protein supplementation augments resistance exercise training (RET)-induced gains in muscle mass and strength . | INTRODUCTION Resistance training has been well established as an effective treatment strategy to increase skeletal muscle mass and strength in the elderly . We assessed whether dietary protein supplementation can further augment the adaptive response to prolonged resistance-type exercise training in healthy elderly men and women . METHODS Healthy elderly men ( n = 31 , 70 ± 1 yr ) and women ( n = 29 , 70 ± 1 yr ) were r and omly assigned to a progressive , 24-wk resistance-type exercise training program with or without additional protein supplementation ( 15 g·d-1 ) . Muscle hypertrophy was assessed on a whole-body Dual-energy X-ray absorptiometry ( DXA ) , limb ( computed tomography ) , and muscle fiber ( biopsy ) level . Strength was assessed regularly by 1-repetition maximum ( RM ) strength testing . Functional capacity was assessed with a sit-to-st and and h and grip test . RESULTS One-RM strength increased by 45 % ± 6 % versus 40 % ± 3 % ( women ) and 41 % ± 4 % versus 44 % ± 3 % ( men ) in the placebo versus protein group , respectively ( P < 0.001 ) , with no differences between groups . Leg muscle mass ( women , 4 % ± 1 % vs 3 % ± 1 % ; men , 3 % ± 1 % vs 3 % ± 1 % ) and quadriceps cross-sectional area ( women , 9 % ± 1 % vs 9 % ± 1 % ; men , 9 % ± 1 % vs 10 % ± 1 % ) increased similarly in the placebo versus protein groups ( P < 0.001 ) . Type II muscle fiber size increased over time in both placebo and protein groups ( 25 % ± 13 % vs 30 % ± 9 % and 23 % ± 12 % vs 22 % ± 10 % in the women and men , respectively ) . Sit-to-st and improved by 18 % ± 2 % and 19 % ± 2 % in women and men , respectively ( P < 0.001 ) . CONCLUSION Prolonged resistance-type exercise training increases skeletal muscle mass and strength , augments functional capacity , improves glycemia and lipidemia , and reduces blood pressure in healthy elderly men and women . Additional protein supplementation ( 15 g·d-1 ) does not further increase muscle mass , strength , and /or functional capacity BACKGROUND A dietary protein intake higher than the Recommended Dietary Allowance during an energy deficit helps to preserve lean body mass ( LBM ) , particularly when combined with exercise . OBJECTIVE The purpose of this study was to conduct a proof-of-principle trial to test whether manipulation of dietary protein intake during a marked energy deficit in addition to intense exercise training would affect changes in body composition . DESIGN We used a single-blind , r and omized , parallel-group prospect i ve trial . During a 4-wk period , we provided hypoenergetic ( ~40 % reduction compared with requirements ) diets providing 33 ± 1 kcal/kg LBM to young men who were r and omly assigned ( n = 20/group ) to consume either a lower-protein ( 1.2 g · kg(-1 ) · d(-1 ) ) control diet ( CON ) or a higher-protein ( 2.4 g · kg(-1 ) · d(-1 ) ) diet ( PRO ) . All subjects performed resistance exercise training combined with high-intensity interval training for 6 d/wk . A 4-compartment model assessment of body composition was made pre- and postintervention . RESULTS As a result of the intervention , LBM increased ( P < 0.05 ) in the PRO group ( 1.2 ± 1.0 kg ) and to a greater extent ( P < 0.05 ) compared with the CON group ( 0.1 ± 1.0 kg ) . The PRO group had a greater loss of fat mass than did the CON group ( PRO : -4.8 ± 1.6 kg ; CON : -3.5 ± 1.4 kg ; P < 0.05 ) . All measures of exercise performance improved similarly in the PRO and CON groups as a result of the intervention with no effect of protein supplementation . Changes in serum cortisol during the intervention were associated with changes in body fat ( r = 0.39 , P = 0.01 ) and LBM ( r = -0.34 , P = 0.03 ) . CONCLUSIONS Our results showed that , during a marked energy deficit , consumption of a diet containing 2.4 g protein · kg(-1 ) · d(-1 ) was more effective than consumption of a diet containing 1.2 g protein · kg(-1 ) · d(-1 ) in promoting increases in LBM and losses of fat mass when combined with a high volume of resistance and anaerobic exercise . Changes in serum cortisol were associated with changes in body fat and LBM , but did not explain much variance in either measure . This trial was registered at clinical trials.gov as NCT01776359 Background The effects of protein supplementation on muscle thickness and strength seem largely dependent on its composition . The current study aim ed at comparing the impact of an oral supplementation with vegetable Pea protein ( NUTRALYS ® ) vs. Whey protein and Placebo on biceps brachii muscle thickness and strength after a 12-week resistance training program . Methods One hundred and sixty one males , aged 18 to 35 years were enrolled in the study and underwent 12 weeks of resistance training on upper limb muscles . According to r and omization , they were included in the Pea protein ( n = 53 ) , Whey protein ( n = 54 ) or Placebo ( n = 54 ) group . All had to take 25 g of the proteins or placebo twice a day during the 12-week training period . Tests were performed on biceps muscles at inclusion ( D0 ) , mid ( D42 ) and post training ( D84 ) . Muscle thickness was evaluated using ultrasonography , and strength was measured on an isokinetic dynamometer . Results Results showed a significant time effect for biceps brachii muscle thickness ( P < 0.0001 ) . Thickness increased from 24.9 ± 3.8 mm to 26.9 ± 4.1 mm and 27.3 ± 4.4 mm at D0 , D42 and D84 , respectively , with only a trend toward significant differences between groups ( P = 0.09 ) . Performing a sensitivity study on the weakest participants ( with regards to strength at inclusion ) , thickness increases were significantly different between groups ( + 20.2 ± 12.3 % , + 15.6 ± 13.5 % and + 8.6 ± 7.3 % for Pea , Whey and Placebo , respectively ; P < 0.05 ) . Increases in thickness were significantly greater in the Pea group as compared to Placebo whereas there was no difference between Whey and the two other conditions . Muscle strength also increased with time with no statistical difference between groups . Conclusions In addition to an appropriate training , the supplementation with pea protein promoted a greater increase of muscle thickness as compared to Placebo and especially for people starting or returning to a muscular strengthening . Since no difference was obtained between the two protein groups , vegetable pea proteins could be used as an alternative to Whey-based dietary products . Trial registration The present trial has been registered at Clinical Trials.gov ( NCT02128516 ) PURPOSE To determine the effects of whey protein before and during resistance exercise ( RE ) on body composition and strength in young adults . METHODS Participants were r and omized to ingest whey protein ( PRO ; 0.3 g/kg protein ; n = 9 , 24.58 ± 1.8 yr , 88.3 ± 17.1 kg , 172.5 ± 8.0 cm ) or placebo ( PLA ; 0.2 g/kg cornstarch maltodextrin + 0.1 g/kg sucrose ; n = 8 , 23.6 ± 4.4 yr , 82.6 ± 16.1 kg , 169.4 ± 9.2 cm ) during RE ( 3 sets of 6 - 10 repetitions for 9 whole-body exercises ) , which was performed 4 d/wk for 8 wk . PRO and PLA were mixed with water ( 600 ml ) ; 50 % of the solution containing 0.15 g/kg of PRO or PLA was consumed immediately before the start of exercise , and ~1.9 % of the remaining solution containing ~0.006 g/kg of PRO or PLA was consumed immediately after each training set . Before and after the study , measures were taken for lean-tissue mass ( dual-energy X-ray absorptiometry ) , muscle size of the elbow and knee flexors and extensors and ankle dorsiflexors and plantar flexors ( ultrasound ) , and muscle strength ( 1-repetition-maximum chest press ) . RESULTS There was a significant increase ( p < .05 ) in muscle size of the knee extensors ( PRO 0.6 ± 0.4 cm , PLA 0.1 ± 0.5 cm ) , knee flexors ( PRO 0.4 ± 0.6 cm , PLA 0.5 ± 0.7 cm ) and ankle plantar flexors ( PRO 0.6 ± 0.7 cm , PLA 0.8 ± 1.4 cm ) and chest-press strength ( PRO 16.6 ± 11.1 kg , PLA 9.1 ± 14.6 kg ) over time , with no differences between groups . CONCLUSION The ingestion of whey protein immediately before the start of exercise and again after each training set has no effect on muscle mass and strength in untrained young adults BACKGROUND Acute consumption of fat-free fluid milk after resistance exercise promotes a greater positive protein balance than does soy protein . OBJECTIVE We aim ed to determine the long-term consequences of milk or soy protein or equivalent energy consumption on training-induced lean mass accretion . DESIGN We recruited 56 healthy young men who trained 5 d/wk for 12 wk on a rotating split-body resistance exercise program in a parallel 3-group longitudinal design . Subjects were r and omly assigned to consume drinks immediately and again 1 h after exercise : fat-free milk ( Milk ; n = 18 ) ; fat-free soy protein ( Soy ; n = 19 ) that was isoenergetic , isonitrogenous , and macronutrient ratio matched to Milk ; or maltodextrin that was isoenergetic with Milk and Soy ( control group ; n = 19 ) . RESULTS Muscle fiber size , maximal strength , and body composition by dual-energy X-ray absorptiometry ( DXA ) were measured before and after training . No between-group differences were seen in strength . Type II muscle fiber area increased in all groups with training , but with greater increases in the Milk group than in both the Soy and control groups ( P < 0.05 ) . Type I muscle fiber area increased after training only in the Milk and Soy groups , with the increase in the Milk group being greater than that in the control group ( P < 0.05 ) . DXA-measured fat- and bone-free mass increased in all groups , with a greater increase in the Milk group than in both the Soy and control groups ( P < 0.05 ) . CONCLUSION We conclude that chronic postexercise consumption of milk promotes greater hypertrophy during the early stages of resistance training in novice weightlifters when compared with isoenergetic soy or carbohydrate consumption BACKGROUND The anabolic effect of resistance exercise is enhanced by the provision of dietary protein . OBJECTIVES We aim ed to determine the ingested protein dose response of muscle ( MPS ) and albumin protein synthesis ( APS ) after resistance exercise . In addition , we measured the phosphorylation of c and i date signaling proteins thought to regulate acute changes in MPS . DESIGN Six healthy young men reported to the laboratory on 5 separate occasions to perform an intense bout of leg-based resistance exercise . After exercise , participants consumed , in a r and omized order , drinks containing 0 , 5 , 10 , 20 , or 40 g whole egg protein . Protein synthesis and whole-body leucine oxidation were measured over 4 h after exercise by a primed constant infusion of [1-(13)C]leucine . RESULTS MPS displayed a dose response to dietary protein ingestion and was maximally stimulated at 20 g. The phosphorylation of ribosomal protein S6 kinase ( Thr(389 ) ) , ribosomal protein S6 ( Ser(240/244 ) ) , and the epsilon-subunit of eukaryotic initiation factor 2B ( Ser(539 ) ) were unaffected by protein ingestion . APS increased in a dose-dependent manner and also reached a plateau at 20 g ingested protein . Leucine oxidation was significantly increased after 20 and 40 g protein were ingested . CONCLUSIONS Ingestion of 20 g intact protein is sufficient to maximally stimulate MPS and APS after resistance exercise . Phosphorylation of c and i date signaling proteins was not enhanced with any dose of protein ingested , which suggested that the stimulation of MPS after resistance exercise may be related to amino acid availability . Finally , dietary protein consumed after exercise in excess of the rate at which it can be incorporated into tissue protein stimulates irreversible oxidation Abstract Herda , AA , Herda , TJ , Costa , PB , Ryan , ED , Stout , JR , and Cramer , JT . Muscle performance , size , and safety responses after eight weeks of resistance training and protein supplementation : A r and omized , double-blinded , placebo-controlled clinical trial . J Strength Cond Res 27(11 ) : 3091–3100 , 2013—The purpose of this study was to examine the effects of 2 different types of protein supplementation on thigh muscle cross-sectional area ( CSA ) , blood markers , muscular strength , endurance , and body composition after 8 weeks of low- or moderate-volume resistance training in healthy , recreationally trained , college-aged men . One hundred and six men were r and omized into 5 groups : low-volume resistance training with bioenhanced whey protein ( BWPLV ; n = 22 ) , moderate-volume resistance training with BWP ( BWPMV ; n = 20 ) , moderate-volume resistance training with st and ard whey protein ( SWPMV ; n = 22 ) , moderate-volume resistance training with a placebo ( PLA ; n = 21 ) , or moderate-volume resistance training with no supplementation ( CON ; n = 21 ) . Except for CON , all groups consumed 1 shake before and after each exercise session and one each on the nontraining day . The BWPLV , BWPMV , and SWPMV groups received approximately 20 g of whey protein per shake , whereas the BWP groups received 5 g of additional polyethylene glycosylated ( PEG ) leucine . Resistance training sessions were performed 3 times per week for 8 weeks . There were no interactions ( p > 0.05 ) for muscle strength and endurance variables , body composition , muscle CSA , and safety blood markers , but the main effects for training were observed ( p ⩽ 0.05 ) . However , the Albumin : Globulin ratio for SWPMV was lower ( p = 0.037 ) than BWPLV and BWPMV . Relative protein intake ( PROREL ) indicated a significant interaction ( p < 0.001 ) with no differences across groups at pre ; however , BWPLV , BWPMV , and SWPMV had a greater intake than did PLA or CON at post ( p < 0.001 ) . This study indicated that 8 weeks of resistance training improved muscle performance and size similarly among groups regardless of supplementation Our purpose was to assess muscular adaptations during 6 weeks of resistance training in 36 males r and omly assigned to supplementation with whey protein ( W ; 1.2 g/kg/day ) , whey protein and creatine monohydrate ( WC ; 0.1 g/kg/day ) , or placebo ( P ; 1.2 g/kg/day maltodextrin ) . Measures included lean tissue mass by dual energy x-ray absorptiometry , bench press and squat strength ( 1-repetition maximum ) , and knee extension/flexion peak torque . Lean tissue mass increased to a greater extent with training in WC compared to the other groups , and in the W compared to the P group ( p < .05 ) . Bench press strength increased to a greater extent for WC compared to W and P ( p < .05 ) . Knee extension peak torque increased with training for WC and W ( p < .05 ) , but not for P. All other measures increased to a similar extent across groups . Continued training without supplementation for an additional 6 weeks result ed in maintenance of strength and lean tissue mass in all groups . Males that supplemented with whey protein while resistance training demonstrated greater improvement in knee extension peak torque and lean tissue mass than males engaged in training alone . Males that supplemented with a combination of whey protein and creatine had greater increases in lean tissue mass and bench press than those who supplemented with only whey protein or placebo . However , not all strength measures were improved with supplementation , since subjects who supplemented with creatine and /or whey protein had similar increases in squat strength and knee flexion peak torque compared to subjects who received placebo Beef is a nutrient-rich , high- quality protein containing all the essential amino acids in proportions similar to those found in human skeletal muscle . In order to investigate the efficacy of a beef supplementation strategy on strength and body composition , we recruited 26 young healthy adults to participate in a resistance-training program of eight weeks , based on the use of isotonic machines and free weights at 75 % of one repetition maximum . Subjects were r and omly divided into two groups , food group and control group , of 12 and 14 subjects respectively . Food group were supplemented after resistance training with a 135 g serving of lean beef ( tinned meat ) , providing 20 g of protein and 1.7 g of fat . No supplementation was provided to control group . Fat mass , fat free mass , lean mass , assessed by bioelectrical impedance analyzer , and muscle strength , assessed by one repetition maximum test , were evaluated in all subjects both at the beginning ( week 0 ) and at the end ( week 8) of the study . Pre- and post-training differences were evaluated with paired t-tests while group differences for each outcome parameter was evaluated with independent t-tests . At the end of the study the food group showed a significantly decrease in fat mass ( week 0 : 15.0 ± 6.7 kg ; week 8 : 13.1 ± 7.6 kg ; Δ : −1.9 ± 2.9 kg ; p < 0.05 ) and a significantly increase in fat free mass ( week 0 : 52.8 kg ± 9.4 ; week 8 : 55.1 kg ± 10.9 ; Δ : 2.3 ± 2.5 kg ; p < 0.01 ) . No significant differences in lean mass were found in either food group or control group . No significant differences in one repetition maximum tests were found between food group and control group . Tinned meat can be considered a nutrition strategy in addition to other proteins or amino acid supplements , but as with any other supplementation strategy , a proper nutrition plan must be coupled BACKGROUND Considerable discrepancy exists in the literature on the proposed benefits of protein supplementation on the adaptive response of skeletal muscle to resistance-type exercise training in the elderly . OBJECTIVE The objective was to assess the benefits of timed protein supplementation on the increase in muscle mass and strength during prolonged resistance-type exercise training in healthy elderly men who habitually consume adequate amounts of dietary protein . DESIGN Healthy elderly men ( n = 26 ) aged 72 + /- 2 y were r and omly assigned to a progressive , 12-wk resistance-type exercise training program with ( protein group ) or without ( placebo group ) protein provided before and immediately after each exercise session ( 3 sessions/wk , 20 g protein/session ) . One-repetition maximum ( 1RM ) tests were performed regularly to ensure a progressive workload during the intervention . Muscle hypertrophy was assessed at the whole-body ( dual-energy X-ray absorptiometry ) , limb ( computed tomography ) , and muscle fiber ( biopsy ) level . RESULTS The 1RM strength increased approximately 25 - 35 % in both groups ( P < 0.001 ) . Dual-energy X-ray absorptiometry and computed tomography scans showed similar increases in leg muscle mass ( 6 + /- 1 % in both groups ; P < 0.001 ) and in the quadriceps ( 9 + /- 1 % in both groups ) , from 75.9 + /- 3.7 and 73.8 + /- 3.2 to 82.4 + /- 3.9 and 80.0 + /- 3.0 cm2 in the placebo and protein groups , respectively ( P < 0.001 ) . Muscle fiber hypertrophy was greater in type II ( placebo : 28 + /- 6 % ; protein : 29 + /- 4 % ) than in type I ( placebo : 5 + /- 4 % ; protein : 13 + /- 6 % ) fibers , but the difference between groups was not significant . CONCLUSION Timed protein supplementation immediately before and after exercise does not further augment the increase in skeletal muscle mass and strength after prolonged resistance-type exercise training in healthy elderly men who habitually consume adequate amounts of dietary protein . This trial was registered at clinical trials.gov as NCT00744094 PURPOSE To assess the effects of a one year nutritional supplementation and resistance training program on muscle strength and walking capacity in the elderly . MATERIAL AND METHODS Elderly subjects from two outpatient clinics received a nutritional supplement , that provided 400 Kcal , 15 g/protein and 50 % of vitamin DRVs per day . Half the subjects receiving and not receiving the supplement were r and omly assigned to a resistance exercise training program with two sessions per week . Every six months , body composition using DEXA , limb muscle strength , maximal inspiratory and expiratory pressures and walking capacity were assessed . RESULTS One hundred forty nine subjects were considered eligible and 101 ( 31 supplemented and trained , 28 supplemented , 16 trained and 26 without supplementation nor training ) completed the year of follow up . Overall compliance with the supplement was 48 22 % and trained subjects attended 56 21 % of programmed sessions . No changes in fat free mass were observed in any of the groups , but fat mass increased from 22.5 7.3 to 23.2 7.3 kg in all groups ( p < 0.001 ) . Upper and lower limb strength and walking capacity increased significantly in trained subjects whether supplemented or not . Maximal inspiratory pressure and right h and grip strength increased only in the supplemented and trained group . CONCLUSIONS Resistance training improved muscle strength and walking capacity PURPOSE We aim ed to determine whether women consuming fat-free milk versus isoenergetic carbohydrate after resistance exercise would see augmented gains in lean mass and reductions in fat mass similar to what we observed in young men . METHODS Young women were r and omized to drink either fat-free milk ( MILK : n = 10 ; age ( mean + /- SD ) = 23.2 + /- 2.8 yr ; BMI = 26.2 + /- 4.2 kg x m(-2 ) ) or isoenergetic carbohydrate ( CON : n = 10 ; age = 22.4 + /- 2.4 yr ; BMI = 25.2 + /- 3.8 kg x m(-2 ) ) immediately after and 1 h after exercise ( 2 x 500 mL ) . Subjects exercised 5 d x wk(-1 ) for 12 wk . Body composition changes were measured by dual-energy x-ray absorptiometry , and subjects ' strength and fasting blood were measured before and after training . RESULTS CON gained weight after training ( CON : + 0.86 + /- 0.4 kg , P < 0.05 ; MILK : + 0.50 + /- 0.4 kg , P = 0.29 ) . Lean mass increased with training in both groups ( P < 0.01 ) , with a greater net gain in MILK versus CON ( 1.9 + /- 0.2 vs 1.1 + /- 0.2 kg , respectively , P < 0.01 ) . Fat mass decreased with training in MILK only ( -1.6 + /- 0.4 kg , P < 0.01 ; CON : -0.3 + /- 0.3 kg , P = 0.41 ) . Isotonic strength increased more in MILK than CON ( P < 0.05 ) for some exercises . Serum 25-hydroxyvitamin D increased in both groups but to a greater extent in MILK than CON ( + 6.5 + /- 1.1 vs + 2.8 + /- 1.3 nM , respectively , P < 0.05 ) , and parathyroid hormone decreased only in MILK ( -1.2 + /- 0.2 pM , P < 0.01 ) . CONCLUSIONS Heavy , whole-body resistance exercise with the consumption of milk versus carbohydrate in the early postexercise period result ed in greater muscle mass accretion , strength gains , fat mass loss , and a possible reduction in bone turnover in women after 12 wk . Our results , similar to those in men , highlight that milk is an effective drink to support favorable body composition changes in women with resistance training PURPOSE Studies that have attributed gains in lean body mass to dietary supplementation during resistance exercise ( RE ) training have not reported these changes alongside adaptations at the cellular and subcellular levels . Therefore , the purpose of this study was to examine the effects of two popular supplements -- whey protein ( WP ) and creatine monohydrate ( CrM ) ( both separately and in combination)--on body composition , muscle strength , fiber-specific hypertrophy ( i.e. , type I , IIa , IIx ) , and contractile protein accrual during RE training . METHODS In a double-blind r and omized protocol , resistance-trained males were matched for strength and placed into one of four groups : creatine/carbohydrate ( CrCHO ) , creatine/whey protein ( CrWP ) , WP only , or carbohydrate only ( CHO ) ( 1.5 g x kg(-1 ) body weight per day ) . All assessment s were completed the week before and after an 11-wk structured , supervised RE program . Assessment s included strength ( 1RM , three exercises ) , body composition ( DEXA ) , and vastus lateralis muscle biopsies for determination of muscle fiber type ( I , IIa , IIx ) , cross-sectional area ( CSA ) , contractile protein , and creatine ( Cr ) content . RESULTS Supplementation with CrCHO , WP , and CrWP result ed in significantly greater ( P < 0.05 ) 1RM strength improvements ( three of three assessment s ) and muscle hypertrophy compared with CHO . Up to 76 % of the strength improvements in the squat could be attributed to hypertrophy of muscle involved in this exercise . However , the hypertrophy responses within these groups varied at the three levels assessed ( i.e. , changes in lean mass , fiber-specific hypertrophy , and contractile protein content ) . CONCLUSIONS Although WP and /or CrM seem to promote greater strength gains and muscle morphology during RE training , the hypertrophy responses within the groups varied . These differences in skeletal muscle morphology may have important implication s for various population s and , therefore , warrant further investigation Background Nutrition intake in the context of a resistance training ( RT ) bout may affect body composition and muscle strength . However , the individual and combined effects of whey protein and carbohydrates on long-term resistance training adaptations are poorly understood . Methods A four-week preparatory RT period was conducted in previously untrained males to st and ardize the training background of the subjects . Thereafter , the subjects were r and omized into three groups : 30 g of whey proteins ( n = 22 ) , isocaloric carbohydrates ( maltodextrin , n = 21 ) , or protein + carbohydrates ( n = 25 ) . Within these groups , the subjects were further r and omized into two whole-body 12-week RT regimens aim ing either for muscle hypertrophy and maximal strength or muscle strength , hypertrophy and power . The post-exercise drink was always ingested immediately after the exercise bout , 2–3 times per week depending on the training period . Body composition ( by DXA ) , quadriceps femoris muscle cross-sectional area ( by panoramic ultrasound ) , maximal strength ( by dynamic and isometric leg press ) and serum lipids as basic markers of cardiovascular health , were analysed before and after the intervention . Results Twelve-week RT led to increased fat-free mass , muscle size and strength independent of post-exercise nutrient intake ( P < 0.05 ) . However , the whey protein group reduced more total and abdominal area fat when compared to the carbohydrate group independent of the type of RT ( P < 0.05 ) . Thus , a larger relative increase ( per kg bodyweight ) in fat-free mass was observed in the protein vs. carbohydrate group ( P < 0.05 ) without significant differences to the combined group . No systematic effects of the interventions were found for serum lipids . The RT type did not have an effect on the adaptations in response to different supplementation paradigms . Conclusions Post-exercise supplementation with whey proteins when compared to carbohydrates or combination of proteins and carbohydrates did not have a major effect on muscle size or strength when ingested two to three times a week . However , whey proteins may increase abdominal fat loss and relative fat-free mass adaptations in response to resistance training when compared to fast-acting carbohydrates Summary .This study examined 10 wks of resistance training and the ingestion of supplemental protein and amino acids on muscle performance and markers of muscle anabolism . Nineteen untrained males were r and omly assigned to supplement groups containing either 20 g protein ( 14 g whey and casein protein , 6 g free amino acids ) or 20 g dextrose placebo ingested 1 h before and after exercise for a total of 40 g/d . Participants exercised 4 times/wk using 3 sets of 6–8 repetitions at 85–90 % of the one repetition maximum . Data were analyzed with two-way ANOVA ( p < 0.05 ) . The protein supplement result ed in greater increases in total body mass , fat-free mass , thigh mass , muscle strength , serum IGF-1 , IGF-1 mRNA , MHC I and IIa expression , and myofibrillar protein . Ten-wks of resistance training with 20 g protein and amino acids ingested 1 h before and after exercise is more effective than carbohydrate placebo in up-regulating markers of muscle protein synthesis and anabolism along with subsequent improvements in muscle performance Background The consumption of dietary protein is important for resistance-trained individuals . It has been posited that intakes of 1.4 to 2.0 g/kg/day are needed for physically active individuals . Thus , the purpose of this investigation was to determine the effects of a very high protein diet ( 4.4 g/kg/d ) on body composition in resistance-trained men and women . Methods Thirty healthy resistance-trained individuals participated in this study ( mean ± SD ; age : 24.1 ± 5.6 yr ; height : 171.4 ± 8.8 cm ; weight : 73.3 ± 11.5 kg ) . Subjects were r and omly assigned to one of the following groups : Control ( CON ) or high protein ( HP ) . The CON group was instructed to maintain the same training and dietary habits over the course of the 8 week study . The HP group was instructed to consume 4.4 grams of protein per kg body weight daily . They were also instructed to maintain the same training and dietary habits ( e.g. maintain the same fat and carbohydrate intake ) . Body composition ( Bod Pod ® ) , training volume ( i.e. volume load ) , and food intake were determined at baseline and over the 8 week treatment period . Results The HP group consumed significantly more protein and calories pre vs post ( p < 0.05 ) . Furthermore , the HP group consumed significantly more protein and calories than the CON ( p < 0.05 ) . The HP group consumed on average 307 ± 69 grams of protein compared to 138 ± 42 in the CON . When expressed per unit body weight , the HP group consumed 4.4 ± 0.8 g/kg/d of protein versus 1.8 ± 0.4 g/kg/d in the CON . There were no changes in training volume for either group . Moreover , there were no significant changes over time or between groups for body weight , fat mass , fat free mass , or percent body fat . Conclusions Consuming 5.5 times the recommended daily allowance of protein has no effect on body composition in resistance-trained individuals who otherwise maintain the same training regimen . This is the first interventional study to demonstrate that consuming a hypercaloric high protein diet does not result in an increase in body fat Objectives Creatine and protein supplementation can enhance the training outcomes of young subjects , but it is not clear if there are benefits for older individuals . Therefore , the purpose of this study was to determine the effects of creatine and protein supplementation on strength gains following a traditional resistance training program for middle-aged and older men . Design , Setting , Participants This study assessed changes in strength of men aged 48–72 years following 14 weeks of resistance training supplemented with creatine and /or protein . A double-blind , r and omized , placebo-controlled design placed 42 males into one of four groups : Resistance Trained Placebo ( RTP , n=10 ) ; Resistance Trained Creatine ( RTCr , 5 g Cr , n=10 ) ; Resistance Trained Protein ( RTPr , 35 g whey Pr , n=11 ) ; or Resistance Trained Creatine and Protein ( RTCrPr , 5 g Cr and 35 g Pr , n=11).InterventionAll groups trained 3 days per week for 14 weeks . The resistance training program was based on progressive overload . Training loads corresponded to 80 % 1RM ( one repetition maximum strength ) , 3 sets of 8 repetitions for the following exercises : knee extension/knee flexion ; bicep curl/tricep extension ; military press ; lat pull down ; seated leg press ; and bench press . Measurements 1 RM for each exercise and measures of lean body mass were assessed prior to and following the 14 week program . Results Each group significantly ( p<0.05 ) increased strength and lean body mass , however , there were no significant group effects or group X trial interactions . Conclusion Resistance training in middle-aged and older men significantly increased muscular strength and added muscle mass with no additional benefits from creatine and /or protein supplementation The purpose of this study was to examine the effects of whey protein supplementation on body composition , muscular strength , muscular endurance , and anaerobic capacity during 10 weeks of resistance training . Thirty-six resistance-trained males ( 31.0 ± 8.0 years , 179.1 ± 8.0 cm , 84.0 ± 12.9 kg , 17.8 ± 6.6 % ) followed a 4 days-per-week split body part resistance training program for 10 weeks . Three groups of supplements were r and omly assigned , prior to the beginning of the exercise program , in a double-blind manner to all subjects : 48 g per day ( g·d−1 ) carbohydrate placebo ( P ) , 40 g·d−1 of whey protein + 8 g·d−1 of casein ( WC ) , or 40 g·d−1 of whey protein + 3 g·d−1 branched-chain amino acids + 5 g·d−1 L-glutamine ( WBG ) . At 0 , 5 , and 10 weeks , subjects were tested for fasting blood sample s , body mass , body composition using dual-energy x-ray absorptiometry ( DEXA ) , 1 repetition maximum ( 1RM ) bench and leg press , 80 % 1RM maximal repetitions to fatigue for bench press and leg press , and 30-second Wingate anaerobic capacity tests . No changes ( p > 0.05 ) were noted in all groups for energy in-take , training volume , blood parameters , and anaerobic capacity . WC experienced the greatest increases in DEXA lean mass ( P = 0.0 ± 0.9 ; WC = 1.9 ± 0.6 ; WBG = -0.1 ± 0.3 kg , p < 0.05 ) and DEXA fat-free mass ( P = 0.1 ± 1.0 ; WC = 1.8 ± 0.6 ; WBG = −0.1 ± 0.2 kg , p < 0.05 ) . Significant increases in 1RM bench press and leg press were observed in all groups after 10 weeks . In this study , the combination of whey and casein protein promoted the greatest increases in fat-free mass after 10 weeks of heavy resistance training . Athletes , coaches , and nutritionists can use these findings to increase fat-free mass and to improve body composition during resistance training Background The effects of protein supplementation on muscle thickness , strength and fatigue seem largely dependent on its composition . The current study compared the effects of soluble milk protein , micellar casein , and a placebo on strength and fatigue during and after a resistance training program . Methods Sixty-eight physically active men participated in this r and omized controlled trial and underwent 10 weeks of lower-body resistance training . Participants were r and omly assigned to the Placebo ( PLA ) , Soluble Milk Protein ( SMP , with fast digestion rate ) or Micellar Casein ( MC , with slow digestion rate ) group . During the 10-week training period , participants were instructed to take 30 g of the placebo or protein twice a day , or three times on training days . Tests were performed on quadriceps muscles at inclusion ( PRE ) , after 4 weeks ( MID ) and after 10 weeks ( POST ) of training . They included muscle endurance ( maximum number of repetitions during leg extensions using 70 % of the individual maximal load ) , fatigue ( decrease in muscle power after the endurance test ) , strength , power and muscle thickness . Results Muscle fatigue was significantly lower ( P < 0.05 ) in the SMP group at MID and POST ( -326.8 ± 114.1 W and -296.6 ± 130.1 W , respectively ) as compared with PLA ( -439.2 ± 153.9 W and -479.2 ± 138.1 W , respectively ) and MC ( -415.1 ± 165.1 W and -413.7 ± 139.4 W , respectively ) . Increases in maximal muscle power , strength , endurance and thickness were not statistically different between groups . Conclusions The present study demonstrated that protein composition has a large influence on muscular performance after prolonged resistance training . More specifically , as compared with placebo or micellar casein , soluble milk protein ( fast digestible ) appeared to significantly reduce muscle fatigue induced by intense resistance exercise The response to resistance training and protein supplementation in the latissimus dorsi muscle ( LDM ) has never been investigated . We investigated the effects of resistance training ( RT ) and protein supplementation on muscle mass , strength , and fiber characteristics of the LDM . Eighteen healthy young subjects were r and omly assigned to a progressive eight-week RT program with a normal protein diet ( NP ) or high protein diet ( HP ) ( NP 0.85 vs. HP 1.8 g of protein·kg−1·day−1 ) . One repetition maximum tests , magnetic resonance imaging for cross-sectional muscle area ( CSA ) , body composition , and single muscle fibers mechanical and phenotype characteristics were measured . RT induced a significant gain in strength ( + 17 % , p < 0.0001 ) , whole muscle CSA ( p = 0.024 ) , and single muscle fibers CSA ( p < 0.05 ) of LDM in all subjects . Fiber isometric force increased in proportion to CSA ( + 22 % , p < 0.005 ) and thus no change in specific tension occurred . A significant transition from 2X to 2A myosin expression was induced by training . The protein supplementation showed no significant effects on all measured outcomes except for a smaller reduction of 2X myosin expression . Our results suggest that in LDM protein supplementation does not further enhance RT-induced muscle fiber hypertrophy nor influence mechanic muscle fiber characteristics but partially counteracts the fast-to-slow fiber shift The effect of protein supplementation on athletic performance and hormonal changes was examined in 21 experienced collegiate strength/power athletes participating in a 12-week resistance training program . Subjects were r and omly assigned to either a protein supplement ( PR ; n = 11 ) or a placebo ( PL ; n = 10 ) group . During each testing session subjects were assessed for strength ( one repetition maximum [ 1-RM ] bench press and squat ) , power ( Wingate anaerobic power test ) and body composition . Resting blood sample s were analyzed at weeks 0 ( PRE ) , 6 ( MID ) and 12 ( POST ) for total testosterone , cortisol , growth hormone , and IGF-1 . No difference was seen in energy intake between PR and PL ( 3034 ± 209 kcal and 3130 ± 266 kcal , respectively ) , but a significant difference in daily protein intake was seen between PR ( 2.00 g·kg body mass[BM](-1)·d(-1 ) ) and PL ( 1.24 g·kgBM(-1)·d(-1 ) ) . A greater change ( p < 0.05 ) in the ∆ 1-RM squat was seen in PR ( 23.5 ± 13.6 kg ) compared to PL ( 9.1 ± 11.9 kg ) . No other significant strength or power differences were seen between the groups . Cortisol concentrations were significantly lower at MID for PL and this difference was significantly different than PR . No significant changes were noted in resting growth hormone or IGF-1 concentrations in either group . Although protein supplementation appeared to augment lower body strength development , similar upper body strength , anaerobic power and lean tissue changes do not provide clear evidence supporting the efficacy of a 12-week protein supplementation period in experienced resistance trained athletes . Key pointsCollegiate strength/power athletes may not meet daily recommended energy or protein needs . When athletes are provided a protein supplement they appear to meet the recommended daily protein intake for strength/power athletes . Protein supplementation did augment lower body strength development in experienced strength/power athletes . Results of upper body strength , anaerobic power and lean tissue changes did not support the efficacy of a 12-week protein supplementation period in experienced resistance trained athletes Signaling pathways sense local and systemic signals and regulate muscle hypertrophy . The effects of whey protein ingestion on acute and long-term signaling responses of resistance exercise are not well known . Previously untrained young men were r and omized into protein ( n = 9 ) , placebo ( n = 9 ) , and control ( n = 11 ) groups . Vastus lateralis ( VL ) muscle biopsies were taken before and 1 h and 48 h after a leg press of 5 x 10 repetitions [ resistance exercise ( RE ) ] and after 21 wk ( 2 times per week ) of resistance training ( RT ) . Protein ( 15 g of whey ) or nonenergetic placebo was ingested before and after a single RE bout and each RE workout throughout the RT . The protein group increased its body mass and VL muscle thickness ( measured by ultrasonography ) already at week 10.5 ( P < 0.05 ) . At week 21 , the protein and placebo groups had similarly increased their myofiber size . No changes were observed in the nonexercised controls . However , the phosphorylation of p70(S6 K ) and ribosomal protein S6 ( rpS6 ) were increased at 1 h post-RE measured by Western blotting , the former being the greatest with protein ingestion . Mammalian target of rapamycin ( mTOR ) phosphorylation was increased after the RE bout and RT only in the protein group , whereas the protein ingestion prevented the post-RE decrease in phosphorylated eukaryotic initiation factor 4E binding protein 1 ( p-4E-BP1 ) . Akt phosphorylation decreased after RT , whereas no change was observed in phosphorylated eukaryotic elongation factor 2 . A post-RE decrease in muscle myostatin protein occurred only in the placebo group . The results indicate that resistance exercise rapidly increases mTOR signaling and may decrease myostatin protein expression in muscle and that whey protein increases and prolongs the mTOR signaling response Compared to soy , whey protein is higher in leucine , absorbed quicker and results in a more pronounced increase in muscle protein synthesis . Objective : To determine whether supplementation with whey promotes greater increases in muscle mass compared to soy or carbohydrate , we r and omized non-resistance-trained men and women into groups who consumed daily isocaloric supplements containing carbohydrate ( carb ; n = 22 ) , whey protein ( whey ; n = 19 ) , or soy protein ( soy ; n = 22 ) . Methods : All subjects completed a supervised , whole-body periodized resistance training program consisting of 96 workouts ( ∼9 months ) . Body composition was determined at baseline and after 3 , 6 , and 9 months . Plasma amino acid responses to resistance exercise followed by supplement ingestion were determined at baseline and 9 months . Results : Daily protein intake ( including the supplement ) for carb , whey , and soy was 1.1 , 1.4 , and 1.4 g·kg body mass−1 , respectively . Lean body mass gains were significantly ( p < 0.05 ) greater in whey ( 3.3 ± 1.5 kg ) than carb ( 2.3 ± 1.7 kg ) and soy ( 1.8 ± 1.6 kg ) . Fat mass decreased slightly but there were no differences between groups . Fasting concentrations of leucine were significantly elevated ( 20 % ) and postexercise plasma leucine increased more than 2-fold in whey . Fasting leucine concentrations were positively correlated with lean body mass responses . Conclusions : Despite consuming similar calories and protein during resistance training , daily supplementation with whey was more effective than soy protein or isocaloric carbohydrate control treatment conditions in promoting gains in lean body mass . These results highlight the importance of protein quality as an important determinant of lean body mass responses to resistance training BACKGROUND The current estimated average requirement ( EAR ) and RDA for protein of 0.66 and 0.8 g ⋅ kg-1 ⋅ d-1 , respectively , for adults , including older men , are based on nitrogen balance data analyzed by monolinear regression . Recent studies in young men and older women that used the indicator amino acid oxidation ( IAAO ) technique suggest that those values may be too low . This observation is supported by 2-phase linear crossover analysis of the nitrogen balance data . OBJECTIVE The main objective of this study was to determine the protein requirement for older men by using the IAAO technique . METHODS Six men aged > 65 y were studied ; each individual was tested 7 times with protein intakes ranging from 0.2 to 2.0 g ⋅ kg-1 ⋅ d-1 in r and om order for a total of 42 studies . The diets provided energy at 1.5 times the resting energy expenditure and were isocaloric . Protein was consumed hourly for 8 h as an amino acid mixture with the composition of egg protein with l-[1 - 13C]phenylalanine as the indicator amino acid . The group mean protein requirement was determined by applying a mixed-effects change-point regression analysis to F13CO2 ( label tracer oxidation in breath 13CO2 ) , which identified a breakpoint in F13CO2 in response to grade d intakes of protein . RESULTS The estimated protein requirement and RDA for older men were 0.94 and 1.24 g ⋅ kg-1 ⋅ d-1 , respectively , which are not different from values we published using the same method in young men and older women . CONCLUSIONS The current intake recommendations for older adults for dietary protein of 0.66 g ⋅ kg-1 ⋅ d-1 for the EAR and 0.8 g ⋅ kg-1 ⋅ d-1 for the RDA appear to be underestimated by ∼30 % . Future longer-term studies should be conducted to vali date these results . This trial was registered at clinical trials.gov as NCT01948492 Background / objectives : A few previous studies indicate that protein supplementation increases gains in muscle mass and strength during a resistance exercise program . The purpose of this study was to investigate whether whey protein supplementation results in greater increases in lean body mass , muscle strength and physical function in elderly individuals during 12 weeks of resistance exercise when compared to isocaloric carbohydrate supplementation . Subjects/ Methods : A total of 161 men and women , 65–91 years old , participated in a r and omized , controlled , double-blind intervention study , involving dietary supplementation and a 12-week resistance exercise program , design ed to increase muscle mass and strength of all major muscle groups . Participants exercised three times a week and received either 20 g of whey protein ( n=83 ) or isocaloric carbohydrate ( n=78 ) in liquid form immediately after each workout . Data were obtained at baseline and end point . Results : The primary outcomes , lean body mass , strength and physical function increased significantly during the course of the study . Type of dietary supplementation did not influence gains in lean body mass ( P=0.365 ) , quadriceps strength ( P=0.776 ) or performance during a 6-min walk ( P=0.726 ) or a timed up- and -go test ( P=0.151 ) . Twenty participants discontinued the intervention . Conclusions : Ingestion of 20 g of whey protein immediately after resistance exercise three times per week , does not lead to greater gains in lean body mass , strength and physical function in elderly people with sufficient energy and protein intakes when compared to isocaloric carbohydrate The purpose was to compare changes in lean tissue mass , strength , and myofibrillar protein catabolism result ing from combining whey protein or soy protein with resistance training . Twenty-seven untrained healthy subjects ( 18 female , 9 male ) age 18 to 35 y were r and omly assigned ( double blind ) to supplement with whey protein ( W ; 1.2 g/kg body mass whey protein + 0.3 g/kg body mass sucrose power , N = 9 : 6 female , 3 male ) , soy protein ( S ; 1.2 g/kg body mass soy protein + 0.3 g/kg body mass sucrose powder , N= 9 : 6 female , 3 male ) or placebo ( P ; 1.2 g/kg body mass maltodextrine + 0.3 g/kg body mass sucrose powder , N = 9 : 6 female , 3 male ) for 6 wk . Before and after training , measurements were taken for lean tissue mass ( dual energy X-ray absorptiometry ) , strength ( 1-RM for bench press and hack squat ) , and an indicator of myofibrillar protein catabolism ( urinary 3-methylhistidine ) . Results showed that protein supplementation during resistance training , independent of source , increased lean tissue mass and strength over isocaloric placebo and resistance training ( P < 0.05 ) . We conclude that young adults who supplement with protein during a structured resistance training program experience minimal beneficial effects in lean tissue mass and strength The effect of 10 wk of protein-supplement timing on strength , power , and body composition was examined in 33 resistance-trained men . Participants were r and omly assigned to a protein supplement either provided in the morning and evening ( n = 13 ) or provided immediately before and immediately after workouts ( n = 13 ) . In addition , 7 participants agreed to serve as a control group and did not use any protein or other nutritional supplement . During each testing session participants were assessed for strength ( one-repetition-maximum [ 1RM ] bench press and squat ) , power ( 5 repetitions performed at 80 % of 1RM in both the bench press and the squat ) , and body composition . A significant main effect for all 3 groups in strength improvement was seen in 1RM bench press ( 120.6 + /- 20.5 kg vs. 125.4 + /- 16.7 at Week 0 and Week 10 testing , respectively ) and 1RM squat ( 154.5 + /- 28.4 kg vs. 169.0 + /- 25.5 at Week 0 and Week 10 testing , respectively ) . However , no significant between-groups interactions were seen in 1RM squat or 1RM bench press . Significant main effects were also seen in both upper and lower body peak and mean power , but no significant differences were seen between groups . No changes in body mass or percent body fat were seen in any of the groups . Results indicate that the time of protein-supplement ingestion in resistance-trained athletes during a 10-wk training program does not provide any added benefit to strength , power , or body-composition changes Whey protein ingestion has been shown to effectively stimulate postpr and ial muscle protein accretion in older adults . However , the impact of the amount of whey protein ingested on protein digestion and absorption kinetics , whole body protein balance , and postpr and ial muscle protein accretion remains to be established . We aim ed to fill this gap by including 33 healthy , older men ( 73 ± 2 yr ) who were r and omly assigned to ingest 10 , 20 , or 35 g of intrinsically l-[1-¹³C]phenylalanine-labeled whey protein ( n = 11/treatment ) . Ingestion of labeled whey protein was combined with continuous intravenous l-[ring-²H₅]phenylalanine and l-[ring-²H₂]tyrosine infusion to assess the metabolic fate of whey protein-derived amino acids . Dietary protein digestion and absorption rapidly increased following ingestion of 10 , 20 , and 35 g whey protein , with the lowest and highest ( peak ) values observed following 10 and 35 g , respectively ( P < 0.05 ) . Whole body net protein balance was positive in all groups ( 19 ± 1 , 37 ± 2 , and 58 ± 2 μmol/kg ) , with the lowest and highest values observed following ingestion of 10 and 35 g , respectively ( P < 0.05 ) . Postpr and ial muscle protein accretion , assessed by l-[1-¹³C]phenylalanine incorporation in muscle protein , was higher following ingestion of 35 g when compared with 10 ( P < 0.01 ) or 20 ( P < 0.05 ) g. We conclude that ingestion of 35 g whey protein results in greater amino acid absorption and subsequent stimulation of de novo muscle protein synthesis compared with the ingestion of 10 or 20 g whey protein in healthy , older men Background and Purpose : Isotonic strength training can result in neuromuscular improvements evidence d in other forms of muscular effort , ie , isokinetic or isometric , especially in young subjects ; however , it is unclear if older muscle maintains this same adaptive ability . Additionally , it is not known if the benefits of resistance training can be augmented by creatine and protein supplementation in older men . Therefore , the purpose of this study was to assess changes in isokinetic parameters at varying speeds in men aged 48 to 72 years ( mean = 57 ± 2.1 ) following 16 weeks of isotonic resistance training and creatine and /or protein supplementation . Methods : Forty‐two male subjects were r and omly assigned to 1 of 4 training groups : ( 1 ) resistance training placebo ( n = 10 ) , ( 2 ) resistance trained creatine supplemented ( n = 10 ) , ( 3 ) resistance trained protein supplemented ( n = 11 ) , and ( 4 ) resistance trained creatine and protein supplemented ( n = 11 ) . The program consisted of progressive overload resistance training ( 3 d/wk ) and supplement consumption following the workout . Results : There were significant time effects ( P ≤ .05 ) for peak torque ( PT ) , time to PT , and average power for both the knee extensors and flexors at all velocities . However , no significant group or group by time interactions were noted , indicating that the supplementation protocol s had no added benefits . Conclusions : Men aged 48 to 72 years maintained their ability to improve isokinetic muscle function following isotonic training , however , supplementation did not enhance muscle adaptability We determined the effects of protein supplementation immediately before ( PRO-B ) and after ( PRO-A ) resistance training ( RT ; 12 weeks ) in older men ( 59–76 years ) , and whether this reduces deficits in muscle mass and strength compared to younger men ( 18–40 years ) . Older men were r and omized to PRO-B ( 0.3 g/kg protein before RT + placebo after RT , n=9 ) , PRO-A ( placebo before + protein after RT , n=10 ) , or PLA ( placebo before and after RT , n=10 ) . Lean tissue mass , muscle thickness of the elbow , knee , and ankle flexors and extensors , and leg and bench press strength were measured before and after RT and compared to data bases of younger subjects ( n=22–60 ) . Myofibrillar protein degradation ( 3-methylhistidine ) and bone resorption ( cross-linked N-telopeptides ) were also measured before and after RT . Lean tissue mass , muscle thickness ( except ankle dorsi flexors ) , and strength increased with training ( P<0.05 ) , with little difference between groups . There were no changes in 3-methylhistidine or cross-linked N-telopeptides . Before RT , all measures were lower in the older compared to younger groups ( P<0.05 ) , except for elbow extensor muscle thickness . Following training , muscle thickness of the elbow flexors and ankle dorsi flexors and leg press strength were no longer different than the young , and elbow extensor muscle thickness was greater in the old men ( P<0.05 ) . Supplementation with protein before or after training has no effect on muscle mass and strength in older men . RT was sufficient to overcome deficits in muscle size of the elbow flexors and ankle dorsi flexors and leg press strength in older compared to younger men BACKGROUND Muscle mass maintenance is largely regulated by basal muscle protein synthesis rates and the ability to increase muscle protein synthesis after protein ingestion . To our knowledge , no previous studies have evaluated the impact of habituation to either low protein intake ( LOW PRO ) or high protein intake ( HIGH PRO ) on the postpr and ial muscle protein synthetic response . OBJECTIVE We assessed the impact of LOW PRO compared with HIGH PRO on basal and postpr and ial muscle protein synthesis rates after the ingestion of 25 g whey protein . DESIGN Twenty-four healthy , older men [ age : 62 ± 1 y ; body mass index ( in kg/m2 ) : 25.9 ± 0.4 ( mean ± SEM ) ] participated in a parallel-group r and omized trial in which they adapted to either a LOW PRO diet ( 0.7 g · kg-1 · d-1 ; n = 12 ) or a HIGH PRO diet ( 1.5 g · kg-1 · d-1 ; n = 12 ) for 14 d. On day 15 , participants received primed continuous l-[ring-2H5]-phenylalanine and l-[1 - 13C]-leucine infusions and ingested 25 g intrinsically l-[1 - 13C]-phenylalanine- and l-[1 - 13C]-leucine-labeled whey protein . Muscle biopsies and blood sample s were collected to assess muscle protein synthesis rates as well as dietary protein digestion and absorption kinetics . RESULTS Plasma leucine concentrations and exogenous phenylalanine appearance rates increased after protein ingestion ( P < 0.01 ) with no differences between treatments ( P > 0.05 ) . Plasma exogenous phenylalanine availability over the 5-h postpr and ial period was greater after LOW PRO than after HIGH PRO ( 61 % ± 1 % compared with 56 % ± 2 % , respectively ; P < 0.05 ) . Muscle protein synthesis rates increased from 0.031 % ± 0.004 % compared with 0.039 % ± 0.007%/h in the fasted state to 0.062 % ± 0.005 % compared with 0.057 % ± 0.005%/h in the postpr and ial state after LOW PRO compared with HIGH PRO , respectively ( P < 0.01 ) , with no differences between treatments ( P = 0.25 ) . CONCLUSION Habituation to LOW PRO ( 0.7 g · kg-1 · d-1 ) compared with HIGH PRO ( 1.5 g · kg-1 · d-1 ) augments the postpr and ial availability of dietary protein-derived amino acids in the circulation and does not lower basal muscle protein synthesis rates or increase postpr and ial muscle protein synthesis rates after ingestion of 25 g protein in older men . This trial was registered at clinical trials.gov as NCT01986842 Myostatin ( MSTN ) is a negative regulator of muscle growth even if some studies have shown a counterintuitive positive correlation between MSTN and muscle mass ( MM ) . Our aim was to investigate the influence of 2 months of resistance training ( RT ) and diets with different protein contents on plasma MSTN , interleukin 1 beta ( IL-1β ) , interleukin 6 ( IL-6 ) , tumor necrosis factor alpha ( TNF-α ) , and insulin-like growth factor 1 ( IGF-1 ) . Eighteen healthy volunteers were r and omly divided in two groups : high protein ( HP ) and normal protein ( NP ) groups . Different protein diet contents were 1.8 and 0.85 g of protein·kg bw(-1)·day(-1 ) for HP and NP , respectively . Subjects underwent 8 weeks of st and ardized progressive RT . MSTN , IGF-1 , IL-1β , IL-6 , and TNF-α were analyzed before and after the first and the last training sessions . Lean body mass , MM , upper-limb muscle area , and strength were measured . Plasma MSTN showed a significant increase ( P<.001 ) after the last training in the HP group compared with NP group and with starting value . IGF-1 plasma concentration showed a positive correlation with MSTN in HP after the last training ( r(2)=0.6456 ; P=.0295 ) . No significant differences were found between NP and HP for IL-1β , IL-6 , TNF-α , and strength and MM or area . These findings suggest a " paradoxical " postexercise increase of plasma MSTN after 8 weeks of RT and HP diets . This MSTN elevation correlates positively with IGF-1 plasma level . This double increase of opposite ( catabolic/anabolic ) mediators could explain the substantial overlapping of MM increases in the two groups The effects of timed ingestion of high- quality protein before and after resistance exercise are not well known . In this study , young men were r and omized to protein ( n = 11 ) , placebo ( n = 10 ) and control ( n = 10 ) groups . Muscle cross-sectional area by MRI and muscle forces were analyzed before and after 21 weeks of either heavy resistance training ( RT ) or control period . Muscle biopsies were taken before , and 1 and 48 h after 5 × 10 repetition leg press exercise ( RE ) as well as 21 weeks after RT . Protein ( 15 g of whey both before and after exercise ) or non-energetic placebo were provided to subjects in the context of both single RE bout ( acute responses ) as well as each RE workout twice a week throughout the 21-week-RT . Protein intake increased ( P ≤ 0.05 ) RT-induced muscle cross-sectional area enlargement and cell-cycle kinase cdk2 mRNA expression in the vastus lateralis muscle suggesting higher proliferating cell activation response with protein supplementation . Moreover , protein intake seemed to prevent 1 h post-RE decrease in myostatin and myogenin mRNA expression but did not affect activin receptor IIb , p21 , FLRG , MAFbx or MyoD expression . In conclusion , protein intake close to resistance exercise workout may alter mRNA expression in a manner advantageous for muscle hypertrophy Background : To our knowledge the efficacy of soy-dairy protein blend ( PB ) supplementation with resistance exercise training ( RET ) has not been evaluated in a longitudinal study . Objective : Our aim was to determine the effect of PB supplementation during RET on muscle adaptation . Methods : In this double-blind r and omized clinical trial , healthy young men [ 18–30 y ; BMI ( in kg/m2 ) : 25 ± 0.5 ] participated in supervised whole-body RET at 60–80 % 1-repetition maximum ( 1-RM ) for 3 d/wk for 12 wk with r and om assignment to daily receive 22 g PB ( n = 23 ) , whey protein ( WP ) isolate ( n = 22 ) , or an isocaloric maltodextrin ( carbohydrate ) placebo [ ( MDP ) n = 23 ] . Serum testosterone , muscle strength , thigh muscle thickness ( MT ) , myofiber cross-sectional area ( mCSA ) , and lean body mass ( LBM ) were assessed before and after 6 and 12 wk of RET . Results : All treatments increased LBM ( P < 0.001 ) . ANCOVA did not identify an overall treatment effect at 12 wk ( P = 0.11 ) . There tended to be a greater change in LBM from baseline to 12 wk in the PB group than in the MDP group ( 0.92 kg ; 95 % CI : −0.12 , 1.95 kg ; P = 0.09 ) ; however , changes in the WP and MDP groups did not differ . Pooling data from combined PB and WP treatments showed a trend for greater change in LBM from baseline to 12 wk compared with MDP treatment ( 0.69 kg ; 95 % CI : −0.08 , 1.46 kg ; P = 0.08 ) . Muscle strength , mCSA , and MT increased ( P < 0.05 ) similarly for all treatments and were not different ( P > 0.10 ) between treatments . Testosterone was not altered . Conclusions : PB supplementation during 3 mo of RET tended to slightly enhance gains in whole-body and arm LBM , but not leg muscle mass , compared with RET without protein supplementation . Although protein supplementation minimally enhanced gains in LBM of healthy young men , there was no enhancement of gains in strength . This trial was registered at clinical trials.gov as NCT01749189 BACKGROUND Seventy-three healthy , male subjects r and omly divided into 3 groups participated in a study to determine the effects of 2 high-calorie nutritional supplements on body composition , body segment circumferences , and muscular strength following a resistance-training ( RT ) program . METHODS In addition to their normal diets group 1 ( CHO/PRO ; n=26 ) consumed a 8.4 Mj x day(-1 ) ( 2010 kcal ) high calorie , high protein supplement containing 356 g carbohydrate and 106 g protein . Group 2 ( CHO ; n=25 ) consumed a carbohydrate supplement that was isocaloric with CHO/PRO . Group 3 ( CTRL ; n=22 ) received no supplement and served as a control . All subjects were placed on a 4-day x week(-1 ) RT program for 8 weeks . RESULTS Dietary analysis revealed no significant differences in total energy consumption or nutrients at any time in the non-supplemented diets of the 3 groups . Significant ( p= or < 0.05 ) increases in body mass ( BM ) and fat-free mass ( FFM ) were observed in CHO/PRO and CHO compared to CTRL . Mean ( + /- SD ) increases in BM were 3.1+/-3.1 kg and 3.1+/-2.2 kg , respectively . Fat-free mass significantly ( p= or < 0.05 ) increased 2.9+/-3.4 kg in CHO/PRO and 3.4+/-2.5 kg in CHO . Muscular strength , as measured by a one-repetition maximum in the bench press , leg press , and lat-pull down increased significantly ( p= or < 0.05 ) in all groups . No significant differences in strength measures were observed among groups following training . CONCLUSIONS Results indicate that high-calorie supplements are effective in increasing BM and FFM when combined with RT . However , once individual protein requirements are met , energy content of the diet has the largest effect on body composition OBJECTIVES To evaluate the effects of elastic b and resistance training in combination with nutrient supplementation on muscular strength and the ability to perform mobility-related activities of daily living in older adults living in retirement care facilities . DESIGN R and omized controlled trial , with a 6-month intervention period . SETTING A retirement care facility , Vienna , Austria . PARTICIPANTS One hundred and seventeen older adults ( 14 males ( 12 % ) and 103 females ( 88 % ) ) , aged 65 to 97 years ( mean age : 82.8 ± 6.0 ) , having a mini-mental state examination score ≥ 23 and no chronic diseases posing a medical contraindication to training therapy . INTERVENTION Participants were r and omly assigned , but stratified by sex , to one of three intervention groups : supervised resistance exercise training ( RT ) , RT in combination with nutrient supplementation ( RTS ) , or cognitive training group ( CT ) . All interventions were performed two times a week for 6 months . RT was design ed to train all major muscle groups using elastic b and s. The nutrient supplement ( rich in proteins , vitamin D , B2 , B12 ) was distributed every morning as well as after each RT session . MEASUREMENTS A battery of motor ability tests and functional test were performed prior to as well as following 3 months and finally after 6 months of intervention . These tests included isokinetic torque measurements of the knee extensors and flexors in concentric mode at 60 and 120 ° /s , isometric h and grip strength , senior arm-lifting test , chair st and test , maximum walking speed and a 6-minute walking test ( 6 MWT ) . RESULTS A repeated- measures ANOVA analysis revealed significant improvements in physical function of lower ( p=0.002 ) and upper extremities ( p=0.006 ) for RT and /or RTS in comparison to CT . For isokinetic measurements , 6 MWT , and gait speed time effects ( p<0.05 ) were detected without any group × time interaction effects . Dropouts showed lower performance in chair st and test ( p=0.012 ) , 6 MWT ( p=0.003 ) , and gait speed ( p=0.013 ) at baseline than that of the finishers of the study . CONCLUSION Six months of a low intensity resistance exercise using elastic b and s and own body weight is safe and beneficial in improving functional performance of institutionalised older people . Multinutrient supplementation did not offer additional benefits to the effects of RT in improving muscular performance Objective : Athletes are interested in nutritional manipulations that may enhance lean tissue gains stimulated by resistance training . Some research demonstrates that acute consumption of food containing protein causes superior muscle protein synthesis compared to isoenergetic foods without protein . This benefit has not been verified in longer-term training studies . We compared body composition and muscle function responses to resistance training in males who consumed a carbohydrate or a multi-macronutrient beverage following each training session . Methods : Nineteen , untrained men ( 18–25 years ) consumed either a milk ( MILK ) or a carbohydrate-electrolyte ( CHO ) drink immediately following each workout during a 10 week resistance training program . Muscle strength ( 1RM for seven exercises ) , body composition ( DXA scan ) , fasted , resting concentrations of serum total and free testosterone , cortisol , IGF-1 , and resting energy expenditure ( REE ) were measured prior to and at the end of training . Results : Resistance training caused an increase ( 44 ± 4 % , p < 0.001 ) in muscular strength for all subjects . The training program reduced percent body fat ( 8 % , p < 0.05 , −0.9 ± 0.5 kg ) and increased fat-free soft tissue ( FFST ) mass ( 2 % , 1.2 ± 0.3 kg , p < 0.01 ) . MILK tended to increase body weight and FFST mass ( p=0.10 and p=0.13 , respectively ) compared to CHO . Resting total and free testosterone concentrations decreased from baseline values in all subjects ( 16.7 % , 11 % , respectively , p < 0.05 ) . Significant changes in fasting IGF-1 , cortisol , and REE across training were not observed for either group . Conclusion : Post-resistance exercise consumption of MILK and CHO caused similar adaptations to resistance training . It is possible that a more prolonged training with supplementation period would exp and the trend for greater FFST gains in MILK BACKGROUND It has been demonstrated that protein ingestion before sleep increases muscle protein synthesis rates during overnight recovery from an exercise bout . However , it remains to be established whether dietary protein ingestion before sleep can effectively augment the muscle adaptive response to resistance-type exercise training . OBJECTIVE Here we assessed the impact of dietary protein supplementation before sleep on muscle mass and strength gains during resistance-type exercise training . METHODS Forty-four young men ( 22 ± 1 y ) were r and omly assigned to a progressive , 12-wk resistance exercise training program . One group consumed a protein supplement containing 27.5 g of protein , 15 g of carbohydrate , and 0.1 g of fat every night before sleep . The other group received a noncaloric placebo . Muscle hypertrophy was assessed on a whole-body ( dual-energy X-ray absorptiometry ) , limb ( computed tomography scan ) , and muscle fiber ( muscle biopsy specimen ) level before and after exercise training . Strength was assessed regularly by 1-repetition maximum strength testing . RESULTS Muscle strength increased after resistance exercise training to a significantly greater extent in the protein-supplemented ( PRO ) group than in the placebo-supplemented ( PLA ) group ( + 164 ± 11 kg and + 130 ± 9 kg , respectively ; P < 0.001 ) . In addition , quadriceps muscle cross-sectional area increased in both groups over time ( P < 0.001 ) , with a greater increase in the PRO group than in the PLA group ( + 8.4 ± 1.1 cm(2 ) vs. + 4.8 ± 0.8 cm(2 ) , respectively ; P < 0.05 ) . Both type I and type II muscle fiber size increased after exercise training ( P < 0.001 ) , with a greater increase in type II muscle fiber size in the PRO group ( + 2319 ± 368 μm(2 ) ) than in the PLA group ( + 1017 ± 353 μm(2 ) ; P < 0.05 ) . CONCLUSION Protein ingestion before sleep represents an effective dietary strategy to augment muscle mass and strength gains during resistance exercise training in young men . This trial was registered at clinical trials.gov as NCT02222415 PURPOSE It is unclear whether protein supplementation augments the gains in muscle strength and size observed after resistance training ( RT ) because limitations to previous studies include small cohorts , imprecise measures of muscle size and strength , and no control of prior exercise or habitual protein intake . We aim ed to determine whether whey protein supplementation affected RT-induced changes in elbow flexor muscle strength and size . METHODS We pair-matched 33 previously untrained , healthy young men for their habitual protein intake and strength response to 3-wk RT without nutritional supplementation ( followed by 6 wk of no training ) and then r and omly assigned them to protein ( PRO , n = 17 ) or placebo ( PLA , n = 16 ) groups . Participants subsequently performed elbow flexor RT 3 d · wk(-1 ) for 12 wk and consumed PRO or PLA immediately before and after each training session . We assessed elbow flexor muscle strength ( unilateral 1-repetition maximum and isometric maximum voluntary force ) and size ( total volume and maximum anatomical cross-sectional area determined with magnetic resonance imaging ) before and after the 12-wk RT . RESULTS PRO and PLA demonstrated similar increases in muscle volume ( PRO 17.0 % ± 7.1 % vs PLA 14.9 % ± 4.6 % , P = 0.32 ) , anatomical cross-sectional area ( PRO 16.2 % ± 7.1 % vs PLA 15.6 % ± 4.4 % , P = 0.80 ) , 1-repetition maximum ( PRO 41.8 % ± 21.2 % vs PLA 41.4 % ± 19.9 % , P = 0.97 ) , and maximum voluntary force ( PRO 12.0 % ± 9.9 % vs PLA 14.5 % ± 8.3 % , P = 0.43 ) . CONCLUSIONS In the context of this study , protein supplementation did not augment elbow flexor muscle strength and size changes that occurred after 12 wk of RT BACKGROUND Data on the protein requirements of elderly adults are limited , because it is impractical to conduct repeated nitrogen balance protocol s in these vulnerable humans . OBJECTIVE This study was design ed to determine the dietary protein requirement of elderly women by using the recently developed minimally invasive indicator amino acid oxidation ( IAAO ) technique . DESIGN Six white women aged 80 - 87 y [ mean ± SEM : 82 ± 1 y and body mass index ( in kg/m² ) 26 ± 2 ] completed a 3-d protocol 7 times . Each woman consumed an adaptation diet for 2 d and on day 3 consumed a complete test diet with a crystalline amino acid mixture containing 1 of 7 protein intakes ( 0.1 , 0.3 , 0.6 , 0.9 , 1.2 , 1.5 , or 1.8 g · kg⁻¹ · d⁻¹ ) tested r and omly . A group-based protein requirement was assessed by using a nonlinear mixed model of protein intake and L-[1-¹³C]phenylalanine oxidation . The breakpoint , at which there was no further decline in the rate of appearance of ¹³C in the breath , was used as an index of the mean protein requirement . RESULTS The mean protein requirement ( 95 % CI ) was 0.85 ( 0.60 , 1.09 ) g · kg⁻¹ · d⁻¹. This requirement is 29 % higher than the current Estimated Average Requirement ( EAR ) for adults of 0.66 g · kg⁻¹ · d⁻¹ based on the nitrogen balance technique , although the 95 % CI includes the current EAR . The corresponding adequate protein allowance of 1.15 ( 0.77 , 1.54 ) g · kg⁻¹ · d⁻¹ is 44 % higher , although the 95 % CI includes the Recommended Dietary Allowance ( RDA ) of 0.80 g · kg⁻¹ · d⁻¹. CONCLUSIONS Notwithst and ing uncertainty about the validity of the use of the IAAO technique to assess protein requirements , the results of this study with octogenarian women suggest that the current EAR and RDA for elderly women may be underestimated . The limitations of this short-term , noninvasive method underscore the need for new research that uses alternative experimental design s and measuring physiologic , morphologic , and health-related outcomes BACKGROUND Physical inactivity , inadequate dietary protein , and low- grade systemic inflammation contribute to age-related muscle loss , impaired function , and disability . OBJECTIVE We assessed the effects of progressive resistance training ( PRT ) combined with a protein-enriched diet facilitated through lean red meat on lean tissue mass ( LTM ) , muscle size , strength and function , circulating inflammatory markers , blood pressure , and lipids in elderly women . DESIGN In a 4-mo cluster r and omized controlled trial , 100 women aged 60 - 90 y who were residing in 15 retirement villages were allocated to receive PRT with lean red meat ( ∼160 g cooked ) to be consumed 6 d/wk [ resistance training plus lean red meat ( RT+Meat ) group ; n = 53 ] or control PRT [ 1 serving pasta or rice/d ; control resistance training ( CRT ) group ; n = 47 ) ] . All women undertook PRT 2 times/wk and received 1000 IU vitamin D3/d . RESULTS The mean ( ± SD ) protein intake was greater in the RT+Meat group than in the CRT group throughout the study ( 1.3 ± 0.3 compared with 1.1 ± 0.3 g · kg⁻¹ · d⁻¹ , respectively ; P < 0.05 ) . The RT+Meat group experienced greater gains in total body LTM ( 0.45 kg ; 95 % CI : 0.07 , 0.84 kg ) , leg LTM ( 0.22 kg ; 95 % CI : 0.02 , 0.42 kg ) , and muscle strength ( 18 % ; 95 % CI : 0.03 , 0.34 ) than did the CRT group ( all P < 0.05 ) . The RT+Meat group also experienced a 10 % greater increase in serum insulin-like growth factor I ( P < 0.05 ) and a 16 % greater reduction in the proinflammatory marker interleukin-6 ( IL-6 ) ( P < 0.05 ) after 4 mo . There were no between-group differences for the change in blood lipids or blood pressure . CONCLUSION A protein-enriched diet equivalent to ∼1.3 g · kg⁻¹ · d⁻¹ achieved through lean red meat is safe and effective for enhancing the effects of PRT on LTM and muscle strength and reducing circulating IL-6 concentrations in elderly women . This trial was registered at the Australian Clinical Trials Registry as ACTRN12609000223235 Resistance exercise training ( RET ) is widely used to increase muscle mass in athletes and also aged/cachectic population s. However , the time course and metabolic and molecular control of hypertrophy remain poorly defined . Using newly developed deuterium oxide (D2O)-tracer techniques , we investigated the relationship between long-term muscle protein synthesis ( MPS ) and hypertrophic responses to RET . A total of 10 men ( 23 ± 1 yr ) undertook 6 wk of unilateral ( 1-legged ) RET [ 6 × 8 repetitions , 75 % 1 repetition maximum ( 1-RM ) 3/wk ] , rendering 1 leg untrained ( UT ) and the contralateral , trained ( T ) . After baseline bilateral vastus lateralis ( VL ) muscle biopsies , subjects consumed 150 ml D2O ( 70 atom percentage ; thereafter 50 ml/wk ) with regular body water monitoring in saliva via high-temperature conversion elemental analyzer : isotope ratio mass spectrometer . Further bilateral VL muscle biopsies were taken at 3 and 6 wk to temporally quantify MPS via gas chromatography : pyrolysis : isotope ratio mass spectrometer . Expectedly , only the T leg exhibited marked increases in function [ i.e. , 1-RM/maximal voluntary contraction ( 60 ° ) ] and VL thickness ( peaking at 3 wk ) . Critically , whereas MPS remained unchanged in the UT leg ( e.g. , ∼1.35 ± 0.08%/d ) , the T leg exhibited increased MPS at 0 - 3 wk ( 1.6 ± 0.01%/d ) , but not at 3 - 6 wk ( 1.29 ± 0.11%/d ) ; this was reflected by dampened acute mechanistic target of rapamycin complex 1 signaling responses to RET , beyond 3 wk . Therefore , hypertrophic remodeling is most active during the early stages of RET , reflecting longer-term MPS . Moreover , D2O heralds promise for coupling MPS and muscle mass and providing insight into the control of hypertrophy and efficacy of anabolic interventions Objectives : Creatine and whey protein are supplements believed to have an ergogenic effect . Very little is known regarding the effects of these dietary supplements in older men . The purpose of this study was to determine the effect of creatine and whey protein supplements , consumed independently and in combination , on total and regional body composition in middle-aged men during a resistance-training program . Design , Setting , Participants : Forty-two men were r and omly assigned to four groups to receive supplements according to a double-blind protocol . Groups consumed their supplements three times per week immediately following their resistance training sessions . The groups were : 1 ) placebo ( 480 ml of Gatorade ® ) ; 2 ) creatine ( 480 ml of Gatorade ® plus 5 grams of creatine ) ; 3 ) whey protein ( 480 ml of Gatorade ® plus 35 grams of whey protein powder ) ; and 4 ) whey protein/creatine ( 480 ml of Gatorade ® plus 5 grams of creatine and 35 grams of whey protein powder ) . All groups participated in resistance training 3 times per week for 14 weeks . Measurements : At the beginning and end of the study , total and regional measures of body composition ( DXA ) and total ( TBW ) , intracellular ( ICW ) , and extracellular ( ECW ) body water ( Multifrequency BIA ) were measured and 3-day diet records were completed . Results : There were significant training effects for regional arm fat ( decrease ) , regional arm bone free-fat free mass ( BF-FFM-increase ) , total body BF-FFM ( increase ) , ICW ( increase ) , and ECW ( increase ) but no significant group effects and only one significant group by training interaction ( ECW ) . There were no significant changes for total calorie , carbohydrate , fat or protein intake for any of the groups from pre study to post- study testing . Conclusion : The results from this study suggest that supplementation with creatine , whey protein , or a combination of creatine and whey protein , when combined with resistance training in middle-aged men , have no added benefit to changes that occur to body composition due to resistance training alone Acute muscle protein metabolism is modulated not only by resistance exercise but also by amino acids . However , less is known about the long-term hypertrophic effect of protein supplementation in combination with resistance training . The present study was design ed to compare the effect of 14 weeks of resistance training combined with timed ingestion of isoenergetic protein vs carbohydrate supplementation on muscle fiber hypertrophy and mechanical muscle performance . Supplementation was administered before and immediately after each training bout and , in addition , in the morning on nontraining days . Muscle biopsy specimens were obtained from the vastus lateralis muscle and analyzed for muscle fiber cross-sectional area . Squat jump and countermovement jump were performed on a force platform to determine vertical jump height . Peak torque during slow ( 30 degrees s-1 ) and fast ( 240 degrees s-1 ) concentric and eccentric contractions of the knee extensor muscle was measured in an isokinetic dynamometer . After 14 weeks of resistance training , the protein group showed hypertrophy of type I ( 18 % + /- 5 % ; P < .01 ) and type II ( 26 % + /- 5 % ; P < .01 ) muscle fibers , whereas no change above baseline occurred in the carbohydrate group . Squat jump height increased only in the protein group , whereas countermovement jump height and peak torque during slow isokinetic muscle contraction increased similarly in both groups . In conclusion , a minor advantage of protein supplementation over carbohydrate supplementation during resistance training on mechanical muscle function was found . However , the present results may have relevance for individuals who are particularly interested in gaining muscle size |
10,784 | 28,926,630 | CONCLUSIONS Despite the high heterogeneity and low method ological quality of studies , an indirect comparison shows that the antimony infiltration efficacy rate is similar to that reported for antimony systemic use .
The evidence gathered thus far is insufficient to identify the ideal IL therapeutic regime or estimate the rates of adverse events and mucosal late complications | BACKGROUND The mainstays of cutaneous leishmaniasis ( CL ) treatment , in several world regions , are pentavalent antimony ( Sbv ) compounds administered parenterally , despite their recognized toxicity , which requires frequent laboratory monitoring and complicates their use in areas with scarce infrastructure .
As result of these drawbacks , the WHO Expert Committee on leishmaniasis has exp and ed the recommendations for the use of local therapies , including Sbv intralesional infiltration ( IL-Sbv ) , as CL therapy alternatives even in the New World .
However , the efficacy of these approaches has never been compiled .
The aim of this study was to critically and systematic ally assess the efficacy of IL-Sbv for CL treatment . | Cutaneous leishmaniasis ( CL ) treatment is based on pentavalant antimony ( sbv ) drugs which are accompanied by many side effects and are facing ever-increasing resistance . Topical treatment of CL is an attractive alternative avoiding toxicities of parenteral therapy while being administered through a simple painless route . The liposomal formulations of different drugs have recently been increasingly used in the treatment of several types of leishmaniasis . The efficacy of a topical liposomal azithromycin formulation was compared with intralesional meglumine antimoniate ( glucantime ) in the treatment of CL . Sixty-six patients with 97 lesions who met our inclusion criteria were r and omly divided into two groups . One group was administered with the topical liposomal form of azithromycin twice daily . The other group was treated by weekly intralesional injections of glucantime with a volume of 0.5 - 2 cm3 into each lesion till complete blanching of the lesion occurred . Clinical evaluations were performed weekly during the treatment course ( 8 weeks ) by a single dermatologist for both groups . Per- protocol analysis showed no statistically significant difference between the two groups ( p = 0.84 , 95 % confidence interval ( CI ) = 0.764 ( 0.714 - 0.821 ) . Serious drug side effects were not observed in either group . Topical liposomal azithromycin has the same efficacy as intralesional glucantime in the treatment of CL Background Cutaneous leishmaniasis ( CL ) is a disfiguring disease that confronts clinicians with a qu and ary : leave patients untreated or engage in a complex or toxic treatment . Topical treatment of CL offers a practical and safe option . Accordingly , the treatment of CL with WR279,396 , a formulation of paromomycin and gentamicin in a hydrophilic base , was investigated in a phase 2 clinical study in Tunisia and France . Methods A phase 2 , r and omized , double blind , vehicle-controlled study was conducted to assess the safety and efficacy of topical WR279,396 when applied twice a day for 20 days as treatment for parasitologically confirmed CL . The study protocol established the primary efficacy end point as complete clinical response ( CCR ) defined as 50 % or greater reduction in the ulceration size of an index lesion by day 50 ( D50 ) followed by complete re-epithelialization by D100 , and no relapse through D180 . Results Ninety-two subjects were r and omized . Leishmania major was identified in 66 of 68 isolates typed ( 97 % ) . In the intent-to-treat population , 47 of 50 WR279,396 treated participants ( 94 % ) met the definition of CCR , compared with 30 of 42 vehicle-placebo participants ( 71 % ) [ p = 0.0045 ] . Erythema occurred in 30 % and 24 % of participants receiving WR279,396 and placebo , respectively [ p = 0.64 ] . There was no clinical or laboratory evidence of systemic toxicity . Conclusion Application of WR279,396 for 20 days was found to be safe and effective in treating L. major CL , and offers great potential as a new , simple , easily applicable , and inexpensive topical therapy for this neglected disease . Trial Registration Clinical Trials.gov Background Leishmaniasis is an endemic disease in Iran . Although many treatments have been suggested for this disease , there has n't been an effective and safe treatment yet . Regarding the healing effect of honey in the chronic ulcers and its reported therapeutic effect in cutaneous leishmaniasis , we performed a study to better evaluate the efficacy of honey in cutaneous leishmaniasis and its final scar . Methods In a prospect i ve clinical trial , 100 patients with confirmed cutaneous leishmaniasis were selected and r and omized into 2 groups . Group A were treated with topical honey twice daily along with intralesional injection of glucantime once weekly until complete healing of the ulcer or for maximum of 6 weeks . Group B were treated with intralesional injection of glucantime alone until complete healing of the ulcer or for a maximum of 6 weeks , too . The patients were followed for 4 months . The collected data were analyzed statistically using statistical tests including Chi-square , Mann Whitney and Kaplan – Mayer tests . Results In this study , 45 patients that had cutaneous leishmaniasis were treated with intralesional glucantime alone and 45 patients were treated with topical honey and glucantime . Ten patients left out the study . In the glucantime alone treated group , 32 patients ( 71.1 % ) had complete cure whereas in the group treated with both glucantime & topical honey , 23 patients ( 51.1 % ) achieved complete cure . This difference was significant statistically ( p = 0.04 ) . Conclusion Further studies to better clarify the efficacy of honey in cutaneous leishmaniasis is needed . We suggest that in another study , the efficacy of honey with st and ardized level of antibacterial activity is evaluated against cutaneous leishmaniasis Cutaneous leishmaniasis ( CL ) is endemic in the Bikaner region situated in the Thar Desert of Rajasthan , India . This study describes clinicoepidemiological data of pediatric CL in pre-school children ( 0 - 5 years of age ) from this region during 2001 - 2012 . In total , 151 patients with 217 lesions were reported during the study period . The mean age of the study group was 3.29 ± 1.43 years ( 0.25 - 5 years ) , with many ( 41.7 % ) cases being in the age group of 2 - 4 years . Face was the most common site involved , and morphologically , the lesions were either plaque type or papulonodular . Smear for parasitologic examination was positive in 84 ( 70 % ) of 120 cases , and histopathologic examination confirmed CL in 10 ( 55.55 % ) of 18 cases . Parasite species identification conducted for 13 r and omly selected patients by polymerase chain reaction identified Leishmania tropica as the causative species . Intralesional sodium stibogluconate was the most commonly used treatment and found to be well-tolerated . Other therapies that were effective included oral rifampicin , oral dapsone , radiofrequency heat therapy ( RFHT ) , and combinations of the three therapies This is an open study to compare the cure rate of cutaneous leishmaniasis caused by L. major and treated with either paromomycin sulfate or intralesional injection of meglumine antimoniate . Sixty parasitologically proven cases with 1 - 3 lesions were included and divided r and omly into two equal groups ; one group received 1 ml of meglumine antimonate intradermally every other day for 20 days , the other group received the ointment containing 15 % parmomycin sulfate in urea twice daily for 20 days . The patients were clinical ly evaluated at 1 and 6 weeks after treatment was completed . The results of clinical evaluation at 1 week after treatment completed showed a cure rate of 18 out of 27 ( 66 % ) in the meglumine antimonate injected group and 20 out of 29 ( 68 % ) in the paromomycin sulfate treated group . The chi square test was used to compare the cure rate between the two groups and showed no significant difference ( p = 0.85 ) BACKGROUND Intralesional 7 % hypertonic saline ( HS ) has been shown to be effective and safe against Leishmania donovani and Leishmania major cutaneous leishmaniasis ( CL ) , with cure rates of 92 % and 96 % , respectively . This study was design ed to assess the efficacy and safety of 10 % and 15 % HS in CL . METHODS A total of 444 patients ( 643 lesions ) were r and omly allocated to sodium stibogluconate ( SSG ) , 10 % HS and 15 % HS at a ratio of 2 : 2 : 1 , taking into consideration any unwanted side effects that might arise with 15 % HS . The follow-up period was 18 months . Survival analysis using Cox proportional hazard regression was performed to assess the effectiveness of the three treatment modalities . The clinical trial was registered at the Sri Lanka Clinical Trial Registry ( SLCTR/2013/024 ) . RESULTS Treatment with SSG result ed in a cure rate of 96.3 % within one to seven injections ( mean : 3.6 injections ) ; the mean ( median ) duration of treatment was six weeks ( 6 weeks ) per lesion . Treatment with 10 % HS showed a cure rate of 93.0 % within one to 10 injections ( mean : 5.28 injections ) ; the mean ( median ) duration of treatment was 9.3 weeks ( 9 weeks ) per lesion . Treatment with 15 % HS showed a cure rate of 93.6 % within two to 10 injections ( mean : 5.3 injections ) ; the mean ( median ) duration of treatment was 11.3 weeks ( 10.0 weeks ) per lesion . Treatment with 10 % HS and 15 % HS caused cutaneous necrosis in 3.1 % and 30.6 % of lesions , respectively . Despite continuous data collection for 14 months , we were unable to recruit a sample of sufficient size . Seventeen ( 3.8 % ) patients were lost to follow-up , and 24 ( 5.4 % ) were partial or non-responders . CONCLUSIONS This study found 10 % HS to be an effective and safe alternative to SSG . Treatment with HS at concentrations of 15 % or above was not safe as a result of cutaneous necrosis . Safety was not studied for concentrations of 11 - 14 % , and these concentrations should be avoided pending further evidence . Hypertonic saline is very cheap ( < US$ 1 per 100 ml , whereas SSG is priced at US$ 160 per 100 ml ) , is prepared locally and has no systemic side effects and minimal local side effects Background A previously published proof of principle phase IIa trial with 113 patients from Kabul showed that bipolar high-frequency ( HF ) electro-cauterization ( EC ) of cutaneous leishmaniasis ( CL ) ulcers and subsequent moist wound treatment ( MWT ) closed 85 % of all Leishmania ( L. ) tropica lesions within 60 days . Methods A three-armed phase IIb , r and omized and controlled clinical trial was performed in Mazar-e-Sharif . L. tropica- or L. major-infected CL patients received intradermal sodium stibogluconate ( SSG ) ( Group I ) ; HF-EC followed by MWT with 0.045 % DAC N-055 ( Group II ) ; or MWT with 0.045 % DAC N-055 in basic crème alone ( Group III ) . The primary outcome was complete epithelialisation before day 75 after treatment start . Results 87 patients enrolled in the trial were r and omized into group I ( n = 24 ) , II ( n = 32 ) and III ( n = 31 ) . The per- protocol analysis of 69 ( 79 % ) patients revealed complete epithelialisation before day 75 in 15 ( of 23 ; 65 % ) patients of Group I , in 23 ( of 23 ; 100 % ) patients of Group II , and in 20 ( of 23 ; 87 % ) patients of Group III ( p = 0.004 , Fisher ’s Exact Test ) . In the per- protocol analysis , wound closure times were significantly different between all regimens in a pair-wise comparison ( p = 0.000039 , Log-Rank ( Mantel-Cox ) test ) . In the intention-to-treat analysis wound survival times in Group II were significantly different from those in Group I ( p = 0.000040 , Log-Rank ( Mantel-Cox ) test ) . Re-ulcerations occurred in four ( 17 % ) , three ( 13 % ) and seven ( 30 % ) patients of Group I , II or III , respectively ( p = 0.312 , Pearson Chi-Square Test ) . Conclusions Treatment of CL ulcers with bipolar HF-EC followed by MWT with 0.045 % DAC N-055 or with DAC N-055 alone showed shorter wound closure times than with the st and ard SSG therapy . The results merit further exploration in larger trials in the light of our current knowledge of in vitro and in vivo activities of chlorite . Clinical trials.gov ID : NCT00996463 . Registered : 15th October 2009 Background . Cutaneous leishmaniasis is an endemic disease in Iran . Pentavalent antimonial drugs have been the first line of therapy in cutaneous leishmaniasis for many years . However , the cure rate of these agents is still not favorable . This study was carried out to compare the efficacies of intralesional glucantime with topical trichloroacetic acid 50 % ( TCA 50 % ) + glucantime and fractional carbon dioxide laser + glucantime in the treatment of cutaneous leishmaniasis . Methods . A total of 90 patients were r and omly divided into three groups of 30 to be treated with intralesional injection of glucantime , a combination of topical TCA 50 % and glucantime , or a combination of fractional laser and glucantime . The overall clinical improvement and changes in sizes of lesions and scars were assessed and compared among three groups . Results . The mean duration of treatment was 6.1 ± 2.1 weeks in all patients ( range : 2–12 weeks ) and 6.8 ± 1.7 , 5.2 ± 1.0 , and 6.3 ± 3.0 weeks in glucantime , topical TCA plus glucantime , and fractional laser plus glucantime groups , respectively ( P = 0.011 ) . Complete improvement was observed in 10 ( 38.5 % ) , 27 ( 90 % ) , and 20 ( 87 % ) patients of glucantime , glucantime + TCA , and glucantime + laser groups , respectively ( P < 0.001 ) . Conclusion . Compared to glucantime alone , the combination of intralesional glucantime and TCA 50 % or fractional CO2 laser had significantly higher and faster cure rate in patients with cutaneous leishmaniasis BACKGROUND There is a need for a simple and efficacious treatment for cutaneous leishmaniasis with an acceptable side-effect profile . METHODS We conducted a r and omized , vehicle-controlled phase 3 trial of topical treatments containing 15 % paromomycin , with and without 0.5 % gentamicin , for cutaneous leishmaniasis caused by Leishmania major in Tunisia . We r and omly assigned 375 patients with one to five ulcerative lesions from cutaneous leishmaniasis to receive a cream containing 15 % paromomycin-0.5 % gentamicin ( called WR 279,396 ) , 15 % paromomycin alone , or vehicle control ( with the same base as the other two creams but containing neither paromomycin nor gentamicin ) . Each lesion was treated once daily for 20 days . The primary end point was the cure of the index lesion . Cure was defined as at least 50 % reduction in the size of the index lesion by 42 days , complete reepithelialization by 98 days , and absence of relapse by the end of the trial ( 168 days ) . Any withdrawal from the trial was considered a treatment failure . RESULTS The rate of cure of the index lesion was 81 % ( 95 % confidence interval [ CI ] , 73 to 87 ) for paromomycin-gentamicin , 82 % ( 95 % CI , 74 to 87 ) for paromomycin alone , and 58 % ( 95 % CI , 50 to 67 ) for vehicle control ( P<0.001 for each treatment group vs. the vehicle-control group ) . Cure of the index lesion was accompanied by cure of all other lesions except in five patients , one in each of the paromomycin groups and three in the vehicle-control group . Mild-to-moderate application-site reactions were more frequent in the paromomycin groups than in the vehicle-control group . CONCLUSIONS This trial provides evidence of the efficacy of paromomycin-gentamicin and paromomycin alone for ulcerative L. major disease . ( Funded by the Department of the Army ; Clinical Trials.gov number , NCT00606580 . ) Background . Topical treatment of cutaneous leishmaniasis is an attractive alternative avoiding toxicities of parenteral therapy while being administered through a simple painless route . Recently liposomal formulations of amphotericin B have been increasingly used in the treatment of several types of leishmaniasis . Aims . The efficacy of a topical liposomal amphotericin B formulation was compared with intralesional glucantime in the treatment of cutaneous leishmaniasis . Methods . From 110 patients , the r and omly selected 50 received a topical liposomal formulation of amphotericin B into each lesion , 3–7 drops twice daily , according to the lesion 's size and for 8 weeks . The other group of 60 patients received intralesional glucantime injection of 1 - 2 mL once a week for the same period . The clinical responses and side effects of both groups were evaluated weekly during the treatment course . Results . Per- protocol analysis showed no statistically significant difference between the two groups ( P = 0.317 , 95 % confidence interval ( CI ) = 1.610 ( 0.632–4.101 ) ) . Moreover , after intention-to-treat analysis , the same results were seen ( P = 0.650 , 95 % CI = 0.1.91 ( 0.560–2.530 ) ) . Serious post treatment side effects were not observed in either group . Conclusions . Topical liposomal amphotericin B has the same efficacy as intralesional glucantime in the treatment of cutaneous leishmaniasis BACKGROUND Cutaneous leishmaniasis is an ultimately self-curing disease for which systemic therapy with pentavalent antimony ( Sb ) is effective but with side effects . We evaluated 2 local treatments , intralesional ( IL ) Sb and cryotherapy , for single lesions due to Bolivian Leishmania ( v. ) braziliensis in a placebo-controlled study . METHODS Patients were r and omized between IL Sb ( 650 µg/mm(2 ) of lesion area on days 1 , 3 , and 5 ) , cryotherapy ( days 1 and 14 ) , and placebo cream ( daily for 20 days ) in a 3:2:3 allocation . Lesion area was measured prior to therapy , and at 1 , 3 , and 6 months after therapy . The criteria for lesion cure were as follows : not doubling in size at 1 month , at least 50 % diminution in size at 3 months , and complete reepithelialization at 6 months . Local adverse effects were recorded . RESULTS Cure rates were 21 of 30 ( 70 % ; 95 % confidence interval [ CI ] , 52%-83 % ) for IL Sb , 4 of 20 ( 20 % ; 95 % CI , 8%-42 % ) for cryotherapy , and 5 of 30 ( 17 % ; 95 % CI , 7%-34 % ) for placebo cream ( P < .001 for IL Sb vs each other group ) . IL Sb adverse events were limited to injection site pain , with a mean value of 1.0 ( mild ) . CONCLUSIONS The comparative cure rate , small amount of drug administered , and tolerance data for IL Sb suggest that if local therapy for single L. braziliensis lesions is chosen , this treatment is attractive . Given the difficulties of performing placebo-controlled trials in the New World , the combined placebo and cryotherapy cure rate ( 18 % ; 95 % CI , 10%-31 % ) is likely to become the st and ard against which future interventions for L. braziliensis are compared . CLINICAL TRIALS REGISTRATION NCT01300975 Ninety‐six patients with a clinical and parasitological diagnosis of cutaneous leishmaniasis were recruited to a comparative r and omized clinical trial evaluating the efficacy of topical paromomycin vs. weekly intralesional injections of meglumine antimoniate . The patients were r and omly divided into two treatment groups : one group was treated with topical paromomycin ointment and the other with intralesional meglumine antimoniate . Treatment was continued in both groups until complete recovery occurred ( defined as healing in less than 2 months with no residual scar or relapse for up to 1 year post treatment ) . Treatment failure was defined as an increase in the number and size of pre‐existing lesions or untoward side‐effects . The maximum treatment period was 3 months . The patients were followed up for 1 year . The results showed that intralesional meglumine antimoniate led to 41.7 % complete recovery , However , topical paromomycin gave a lower cure rate of 16.6 % ( P < 0.05 ) . Treatment failure was observed in 39.7 % of the group receiving intralesional meglumine and in 72.9 % of those on topical paromomycin ( P < 0.05 ) . This study indicates that intralesional meglumine antimoniate is superior to topical paromomycin in the treatment of cutaneous leishmaniasis Introduction : Cutaneous leishmaniasis is an endemic disease in developing countries caused by different species of leishmania parasite , and if left untreated , it will result in a deformed scar after a relatively long period . Although various systemic and topical treatments have been proposed for leishmaniasis , pentavalent Antimony compounds remain the first-line treatment for it . Considering the cases with treatment failure , potential side effects and reluctance of patients to receive the drug , there are continuing efforts to find better treatment alternatives . Aim : Comparison of the effect of intralesional 2 % zinc sulfate injection with Glucantime in treatment of acute cutaneous leishmaniasis . Material s and Methods : In this clinical trial , 45 patients with clinical diagnosis of cutaneous leishmaniasis and positive direct smear for leishman body were treated by intralesional injection of either 2 % zinc sulfate or Glucantime . After simple r and omization , in one group the patients were treated with 2 bouts of intralesional 2 % zinc sulfate with a 2-week interval , and in the other group they were treated with 6 weekly bouts of intralesional Glucantime . The patients were monitored in two week intervals for 8 weeks . Healing of the lesions was evaluated clinical ly and by direct smear , and the data were analyzed using SPSS ( 11.5 ) software , t-Student , Mann-Whitney and Analysis of covariance ( ANCOVA ) statistical tests . Findings : In the end of study , 34 patients completed the study , 10 of whom received intralesional Glucantime and 24 of whom received intralesional 2 % zinc sulfate . The healing rate after 8 weeks was 80 % in the group receiving intralesional Glucantime and 33.3 % in the one receiving 2 % zinc sulfate ( P=0.009 ) . Conclusion : Based on the results of this study , intralesional injection of 2 % zinc sulfate was less effective in treatment of cutaneous leishmaniasis than intralesional Glucantime Cutaneous leishmaniasis caused by Leishmania major infection affected 172 ( 18.3 % ) of 938 Dutch military troops deployed in northern Afghanistan in 2005 . The high attack rate was a result of initial insufficient availability of means of prevention and insufficient adherence to preventive measures . At presentation , the lymphatic system was involved in 24.8 % . Treatment with intralesional injections of antimony with or without cryotherapy was satisfactory , but 19.5 % of patients received secondary treatment with miltefosine . Six months after treatment , 128 ( 77.1 % ) of 166 treated patients were cured , 16 ( 9.6 % ) were lost to follow-up , and 22 ( 13.3 % ) already experienced cure at six weeks but were not seen at six months . Natural evolution played a role in this observational study , which showed cure of all patients seen at six months . In general , management of cutaneous leishmaniasis was feasible under field conditions Anthroponotic cutaneous leishmaniasis ( CL ) is a common cause of ulcerative lesions and disfiguring scarring among children in Afghanistan . Most lesions occur on the face and are commonly caused by the trypanosome protozoan parasite Leishmania tropica , transmitted by the bite of an infected s and fly ( Phlebotomus sergenti ) . This study compared the effectiveness of a single localized treatment with thermotherapy to 5 days of intralesional administration of Glucantime for the treatment of CL . Three hundred and eighty-two patients with CL were r and omly assigned to the two treatment groups and followed for 6 months . The cure rate for the thermotherapy group was 82.5 % , compared to 74 % in the Glucantime group . The authors concluded that a single localized treatment with thermotherapy was more effective than 5 days of intralesional administration of Glucantime . Additionally , thermotherapy was more cost-effective , with fewer side effects , of shorter duration , and with better patient compliance than intralesional Glucantime A r and omized placebo-controlled trial treating cutaneous lesions due to Leishmania major with intralesionnel glucantime , was conducted in El Guettar between december 1994 and June 1995 , in order to assess efficacy of this therapy under field conditions . It included 109 patients : 52 were administrated glucantime and 57 received local treatment ( eosin 5 % and alcohol 95 % ) . Prognostic factors were similar in both groups . Results did not reveal a significant difference between glucantime and eosin regarding the rapidity of the healing of lesions . However , scars seem to be of better quality among the glucantime group . Bacterial super infection was noticed among 57.6 % of humid lesions sample d among 33 patients . Isolated strains included group A streptococcus ( 22 % ) , staphylococcus aureus ( 16.7 % ) or an association of both agents ( 61.1 % ) . Resistance profile indicated that streptococcus and staphylococcus respond well to macrolids compared to other antibiotic groups Pentavalent antimony ( Sbv ) , formulated as sodium stibogluconate or meglumine antimoniate , is the st and ard treatment for the leishmaniases . In 16 of 17 consecutive , prospect ively observed patients in Washington D.C. , serum levels of amylase and lipase rose to abnormal values after therapy with sodium stibogluconate was started ; 12 of 17 had symptoms of pancreatitis . Sbv therapy was continued to completion in 7 of 17 patients and interrupted in 10 of 17 . Pancreatitis improved in every patient after Sbv therapy was stopped . Sbv treatment was resumed after brief interruptions in 6 of 10 patients . All six of these patients had flares of pancreatitis , but each completed therapy . Subsequently , we measured amylase and lipase levels in stored sera from 32 patients treated in Peru with either sodium stibogluconate or meglumine antimoniate for mucosal leishmaniasis . In all 32 Peruvian patients , serum amylase and lipase rose to abnormal levels during Sbv therapy ; 11 of 32 had symptoms of pancreatitis . St and ard Sbv regimens induce pancreatitis in almost all patients , but continued therapy is often tolerated ; pancreatitis subsides when therapy is stopped , and rechallenge may be tolerated after a brief halt in treatment UNLABELLED Glucantime remains the first-line treatment for cutaneous leishmaniasis . In a prospect i ve study , we evaluated its efficacy and side effects in patients treated in Yazd from 2010 to 2011 . METHODS Patients with lesions compatible with cutaneous leishmaniasis were considered eligible for inclusion in this study if the disease was confirmed parasitologically . The exclusion criteria were as follows : the patient preferred a treatment modality other than Glucantime ; there was no indication for treatment ; the patient had underlying kidney , liver , or cardiac disease ; or was pregnant and lactating . Patients with ≤3 lesions and /or lesions <3 cm in diameter were treated with Glucantime intralesionally if the lesions were not located on the face , neck or joints ; sporotrichoid ; or superinfected with bacteria . All other patients were prescribed intramuscular Glucantime at 10 - 20mg/kg/day for 20 days . RESULTS The failure rate for patients treated with one course of Glucantime was 22.6 % overall . There were no associations between age , sex , weight , the route of administration , the number and size of lesions , the adequacy of the dose of the drug injected intramuscularly , the number of intralesional injections ( < 6 or ≥6 ) and the duration of therapy . The only factor associated with failure was reported previous exposure to antimony ( p value 0.047 ) . Adverse effects occurred in 14.2 % of patients ( 22/155 ) . CONCLUSION Glucantime is an effective drug for the treatment of cutaneous leishmaniasis in central Iran . However , because cutaneous leishmaniasis heals spontaneously and to prevent the acquisition of resistance , the indications for treatment in each region should be defined carefully INTRODUCTION Cutaneous leishmaniasis is a common parasitic disease in Iran , especially in Isfahan . First line treatment for this disease is antimonial compounds ; however , owing to the intermittent failure of this treatment and its significant side-effects alternative therapeutic measures have been advocated . OBJECTIVE Evaluating the efficacy of pentoxifylline plus glucantime in the treatment of cutaneous leishmaniasis . METHODS This double-blind , r and omized , controlled clinical trial with simple sampling was performed on 64 patients with cutaneous leishmaniasis referred to the Skin Diseases & Leishmaniasis Research Center from an endemic foci of L. major in Isfahan . The patients r and omly were divided into two groups . One group was treated with systemic Glucantime ( 20 mg pentavalent antimony/kg/day ) combined with pentoxifylline ( 400 mg three times daily ) and the other group were treated with Glucantime ( 20 mg pentavalent antimony/kg/day ) plus placebo ( three tablets daily ) for 20 days . Follow up lasted 3 months . Response to treatment was grouped as complete improvement ( lesions had been flattened , no in duration , and epidermal creases had appeared ) , partial improvement ( reduction in lesion size , but without the appearance of epidermal creases ) and poor response ( no reduction in lesion size ) . RESULTS Of 64 participants , 32 patients in the trial group and 31 patients in the control group were followed for 3 months . One patient in group B discontinued withdrew . After this time , complete improvement , partial improvement and poor response to treatment were 81.3 % , 12.5 % and 6.2 % in the trial group and 51.6 % , 29 % and 19.4 % in the control group , respectively . We also observed no adverse effect result ing from pentoxifylline . DISCUSSION The result obtained by two therapeutic methods indicates that combined therapy with Glucantime and pentoxifylline is more effective than Glucantime alone ( P < 0.05 ) A combination of both intralesional stibogluconate injection and superficial cryotherapy ( not including the base of the lesion nor the 1 - 2 mm rim of the surrounding normal skin ) was performed in an attempt to improve the therapeutic efficacy of either of the two modalities when used separately in the treatment of cutaneous leishmaniasis . This combined therapy result ed in a 100 % cure rate in 15 patients with 23 lesions of cutaneous leishmaniasis . Two control groups , one treated with superficial cryo and the other treated with intralesional stibogluconate injection alone were included in the study for evaluation . The results obtained by combined superficial freezing and intralesional stibogluconate injection were much more impressive than those obtained by each of the two modalities when used alone BACKGROUND Cutaneous leishmaniasis ( CL ) is a parasitic disease caused by Leishmania species . There is a need for more effective and less time-consuming therapeutic methods for this condition . AIM To evaluate the efficacy of combined cryotherapy and intralesional meglumine antimoniate ( MA ) ( Glucantime , Specia , Paris , France ) for the treatment of CL . METHODS Patients were divided into three groups : Group 1 , 100 patients with 149 lesions were treated with cryotherapy plus intralesional MA ; Group 2 , 200 patients with 230 lesions were treated with cryotherapy ; Group 3 , 100 patients with 160 lesions were treated with intralesional MA . These groups were followed for 6 months after the end of treatment . RESULTS The results showed complete cure in 90.9 % of cases in Group 1 , 57.15 % of cases in Group 2 , and 55.63 % of cases in Group 3 . The difference between Group 1 and the other groups was statistically significant ( P < 0.05 ) . CONCLUSIONS Combined cryotherapy and intralesional MA is more effective than either cryotherapy or intralesional MA alone for the treatment of CL Abstract Introduction : Since cutaneous leishmaniasis ( CL ) is a self healing disease , an ideal therapy should be rapidly effective , easily administered , cheap , available at all times at all centers and should have no side effects . Objectives : To determine the efficacy and safety of intralesional 7 % hypertonic saline in comparison to intralesional sodium stibogluconate against L. donovani CL . Methods : Intralesional hypertonic saline ( HS ) and sodium stibogluconate ( SSG ) were r and omly allocated to 154 patients ( 229 lesions ) ; these were followed-up for 18 months . Results : The M : F ratio was 1.8:1 ( 99:55 ) . The average age of our population was 32 years . SSG was given to 87 patients ( 136 lesions ) ; HS was given to 67 patients ( 93 lesions ) . SSG showed a 100 % cure rate within one to six injections ( average 3.24 ) ; HS showed a 92.2 % cure rate within one to 10 injections ( average 5.27 ) . The average duration of treatment with SSG and HS was 5.11 and 8.78 weeks respectively . There was no difference in efficacy for both therapies with regard to ulcers or papules , and small or large , exposed or unexposed lesions . There was no association between the rapidity of clinical response and the duration and location of lesions . There were no local or systemic side effects except pain during injection . The lesions in the two groups showed post-inflammatory hyperpigmentation after treatment . During 18 months of follow-up there were no recurrences and no visceralization . Conclusions : The most effective therapy for Leishmania donovani cutaneous leishmaniasis was intralesional SSG ( average 3.24 injections ) . HS was effective , but needed an average of 5.27 injections in total per lesion . HS was cheap , with no risk of systemic side effects and was easily available at all centers A novel therapy , intralesional ( IL ) pentamidine , was compared to intralesional therapy with antimony ( ILSb ) , a World Health Organization-recommended therapy , for single Bolivian Leishmania braziliensis lesions . In Study 1 , 90 patients were r and omized equally between three injections of ILSb over 5 days , five injections of ILSb over 11 days , and three injections of IL pentamidine ( 120 μg/mm(2)lesion area [ ILPenta-120 - 3 ] ) over 5 days . Cure rates at 6 months were 57 % for ILSb-3 injections , 73 % for ILSb-5 injections , and 72 % for ILPenta-120 - 3 injections . Adverse effects were local irritation and injection-site pain-ILSb ( 60 patients ): mild ( 25 ) , moderate ( 4 ) ; IL pentamidine ( 30 patients ): mild ( 4 ) , moderate ( 3 ) . In Study 2 , 60 patients were r and omized equally between five injections of ILSb and three injections of a double dose of IL pentamidine ( 240 μg/mm(2)[ILPenta-240 - 3 ] ) . In Study 2 , cure rates were 67 % for ILSb-5 injections and 73 % for ILPenta-240 - 3 . For three IL injections of pentamidine , efficacy was optimized at a dose of 120 μg/mm(2)lesion area . The cure rate of that regimen was similar to that for ILSb-5 injections and nonstatistically larger than that of ILSb-3 injections . IL pentamidine is an attractive alternative to ILSb on the basis of efficacy for Bolivian L. braziliensis , the threat of Sb-resistant parasites , tolerance , and patient convenience of three visits over 5 days Background : There are several therapies for treating lupoid leishmaniasis . We compared the effectiveness of intralesional meglumine antimoniate ( MA ) and topical application of trichloroacetic acid ( TCA ) 50 % solution . Methods : This study was a r and omized clinical trial comprising 60 lupoid leishmaniasis patients . The first group received intralesional MA once a week , and the second group was treated once weekly with TCA 50 % topical solution . The results were recorded once after 8 weeks and then 3 months after the termination of treatment . Results : The total clearance rates after treatment and after the 3-month follow-up were , respectively , 48.1 % and 40 % in the first group and 44.4 % and 36.6 % in the second group . There was no significant difference between the two treatment groups ( p = .25 and p = .26 ) . In both groups , the most common side effect was scarring . Conclusion : Having almost the same efficacies , TCA as a topical approach could be as effective as MA in the lupoid leishmaniasis treatment plan |
10,785 | 24,901,467 | Overall , no difference in mortality ( RR 0.91 ; 95 % CI 0.64 to 1.28 ; low- quality of evidence ) , graft loss including death ( RR 0.92 ; 95 % CI 0.71 to 1.19 ; low- quality of evidence ) , and adverse events ( ( RR 0.97 ; 95 % CI 0.93 to 1.02 ; low- quality evidence ) outcomes was observed between any kind of T-cell specific antibody induction compared with no induction when the T-cell specific antibody induction agents were analysed together or separately .
T-cell specific antibody induction seems to reduce acute rejection when compared with no induction .
No other clear benefits or harms were associated with the use of any kind of T-cell specific antibody induction compared with no induction , or when compared with another type of T-cell specific antibody . | BACKGROUND Liver transplantation is an established treatment option for end-stage liver failure .
To date , no consensus has been reached on the use of immunosuppressive T-cell antibody induction for preventing rejection after liver transplantation .
OBJECTIVES To assess the benefits and harms of immunosuppressive T-cell specific antibody induction compared with placebo , no induction , or another type of T-cell specific antibody induction for prevention of acute rejection in liver transplant recipients .
We planned to include trials with all of the different types of T-cell specific antibodies that are or have been used for induction ( ie . , | This r and omized , prospect i ve , multicenter trial compared the safety and efficacy of steroid-free immunosuppression ( IS ) to the safety and efficacy of 2 st and ard IS regimens in patients undergoing transplantation for hepatitis C virus ( HCV ) infection . The outcome measures were acute cellular rejection ( ACR ) , severe HCV recurrence , and survival . The patients were r and omized ( 1:1:2 ) to tacrolimus ( TAC ) and corticosteroids ( arm 1 ; n = 77 ) , mycophenolate mofetil ( MMF ) , TAC , and corticosteroids ( arm 2 ; n = 72 ) , or MMF , TAC , and daclizumab induction with no corticosteroids ( arm 3 ; n = 146 ) . In all , 295 HCV RNA-positive subjects were enrolled . At 2 years , there were no differences in ACR , HCV recurrence ( biochemical evidence ) , patient survival , or graft survival rates . The side effects of IS did not differ , although there was a trend toward less diabetes in the steroid-free group . Liver biopsy sample s revealed no significant differences in the proportions of patients in arms 1 , 2 , and 3 with advanced HCV recurrence ( ie , an inflammation grade ≥ 3 and /or a fibrosis stage ≥ 2 ) in years 1 ( 48.2 % , 50.4 % , and 43.0 % , respectively ) and 2 ( 69.5 % , 75.9 % , and 68.1 % , respectively ) . Although we have found that steroid-free IS is safe and effective for liver transplant recipients with chronic HCV , steroid sparing has no clear advantage in comparison with traditional IS The immunosuppressive effect of a monoclonal antibody ( moAb ) , BT563 , directed to the alpha-chain of the IL-2R ( CD25 ) , was analyzed in a prospect i ve nonr and omized trial and a prospect i ve r and omized trial . Primary objectives were evaluation of the incidence of acute rejections and infections ; secondary objectives were safety and tolerability of the moAb . A total of 28 patients were enrolled ( phase II ) to receive 10 mg/day of BT563 ( 12 days ) as immunoprophylaxis in combination with cyclosporine , azathioprine , and low-dose steroids . Subsequently 32 patients were r and omly assigned ( phase III ) to receive BT563 ( 10 mg/day ) for 12 days or ATG ( 5 mg/kg/day ) for 7 days in addition to cyclosporine and low-dose steroids . No side effects of the BT563 treatment were noted . The actuarial survival was 82 % at 12 months in the phase II trial and 92 % at 12 months in both arms of the phase III trial . There was one acute rejection in the phase II trial . No acute rejections were noted in the BT arm of the phase III trial and 5 acute rejections were treated in the ATG arm . In the phase II trial 7 infectious episodes were observed , while one infection was seen in the BT arm and 7 in the ATG arm of the triple immunosuppression phase III trial . In all patients circulation of coated CD25 + lymphocytes was observed during BT563 treatment ; there was no evidence of depletion or modulation of CD25 + cells . Mean serum levels of BT563 ranged from 1.6 to 7.6 microgram/ml throughout the therapy . An antimurine response was seen in 82 % ( phase II ) and 100 % ( phase III ) of the patients . Antirabbit antibodies were found in 56 % of the patients treated with ATG . Analysis of the antimurine response specificity revealed in 56 % blocking anti-isotypic antibodies and only in 3 % of the patients an anti-idiotypic response . The data of the study presented suggest that therapy with an anti IL-2R moAb is at least equal to ATG application according to the incidence of acute rejections and infections Basiliximab , a high-affinity chimeric monoclonal antibody , is effective in reducing acute rejection episodes in renal allograft recipients . We assessed the ability of this antibody to similarly improve the outcome in liver transplant recipients . Adult recipients of a primary cadaveric liver transplant were r and omized to treatment , stratified by hepatitis C virus ( HCV ) seropositivity . Patients were administered 40 mg of basiliximab ( n = 188 ) or placebo ( n = 193 ) as two 20-mg bolus injections days 0 and 4 , plus cyclosporine and steroids . Primary efficacy variables were biopsy-confirmed acute rejection and its composite end point , including death or graft loss , and were assessed at 6 and 12 months and by HCV cohort . Because of differential efficacy responses between HCV-positive and HCV-negative cohorts , an additional analysis incorporating HCV recurrence as a component of treatment failure , termed problem-free transplant , was introduced . Safety and tolerability were monitored over the 12 months of the study . All 381 patients were assessable , and no meaningful differences in background characteristics were apparent between treatment groups . Biopsy-confirmed acute rejection rates 6 months after transplantation were 35.1 % in the basiliximab group versus 43.5 % in the placebo group . For death , graft loss , or first biopsy-confirmed acute rejection , rates were 44.1 % versus 52.8 % , respectively . The reduction in rejection episodes was concentrated in the HCV-negative cohort ( 14.5 % relative to placebo ; P = .034 ) , with a much smaller difference ( 2.9 % ) in the HCV-positive cohort . For HCV-positive patients , problem-free transplant was shown at 12 months in 26.6 % of the basiliximab group versus 11.6 % in the placebo group ( P = .020 ) and for all patients at 12 months in 39.7 % of the basiliximab group versus 30.1 % in the placebo group ( P = .035 ) . The incidence of infection and other adverse events was similar across the two treatment groups . There were 56 deaths ( 25 deaths , basiliximab group ; 31 deaths , placebo group ) over the 12-month study . The intravenous bolus injection was well tolerated . Immunoprophylaxis with 40 mg of basiliximab , in combination with cyclosporine and steroids , reduces the incidence of acute rejection episodes with no clinical ly relevant safety or tolerability concerns . The influence of HCV recurrence on efficacy results can be accounted for in future trials by using the concept of problem-free transplant , incorporating recurrence as a component of treatment failure Background . Calcineurin inhibitor-induced renal dysfunction is a major problem in liver transplantation . Interleukin-2 receptor antagonist induction followed by delayed tacrolimus ( Tac ) administration may minimize the renal insult without compromising immunoprotection . Methods . This open , r and omized , multicenter trial evaluated the benefit of daclizumab induction with delayed Tac on renal function at 6 months ; an observational study was continued for 18 months . Liver transplant patients with a 12-hr serum creatinine ( SrC ) level less than 180 & mgr;mol/L received either delayed Tac with daclizumab induction ( n=98 ) or st and ard Tac ( n=101 ) both combined with mycophenolate mofetil and steroids . The primary endpoint was the incidence of SrC level more than 130 & mgr;mmol/L at 6 months . Results . The incidence was 22.4 % with delayed Tac and 29.7 % with st and ard Tac ( P = ns ) , which remained unchanged at 12 months ( 21.6 % and 23.9 % ) but increasing slightly at 24 months ( 29.0 % and 32.9 % ) , respectively . A post hoc analysis of renal function was done based on patients stratification by SrC at 12 hr ( ≤100&mgr;mol/L or > 100 & mgr;mol/L ) showing no difference in SrC values at 6 months regardless of the 12-hr values despite a trend toward better estimated glomerular filtration rate for patients with 12-hr value less than 100 & mgr;mol/L in the delayed Tac group . Biopsy-proven acute rejection was similar at 6 months ( 17.5 % and 18.75 % ) , 12 months ( 23.5 % and 23.8 % ) , and 24 months ( 24.5 % and 25.7 % ) , respectively . Patient and graft survival in both groups were comparable and good . Similar types and incidences of adverse events were reported in both groups at all time . Conclusions . Delay of Tac does not benefit renal function in liver transplant recipients with a good renal function at baseline 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 We report the results of a prospect i ve r and omized controlled trial in liver transplantation assessing the efficacy and safety of antithymocyte globulin ( ATG‐Fresenius ) plus tacrolimus monotherapy at gradually decreasing doses . Patients were r and omized to either : ( a ) st and ard‐dose tacrolimus plus steroids;or ( b ) peritransplant ATG‐Fresenius plus reduced‐dose tacrolimus monotherapy followed by weaning of tacrolimus starting 3 months after transplantation . The primary end‐point was the achievement of very low‐dose tacrolimus ( every‐other‐day or once daily dose with < 5 ng/mL trough levels ) at 12 months after transplantation . Acute rejection occurring during the first 3 months after transplantation was more frequent in the ATG group ( 52.4 % vs. 25 % ) . Moreover , late acute rejection episodes occurred in all recipients in whom weaning was attempted and no recipients reached the primary end‐point . This motivated the premature termination of the trial . Tacrolimus trough levels were lower in the ATG‐Fresenius group but no benefits in terms of improved renal function , lower metabolic complications or increased prevalence of tolerance‐related biomarkers were observed . In conclusion , the use of ATG‐Fresenius and tacrolimus at gradually decreasing doses was associated with a high rate of rejection , did not allow for the administration of very low doses of tacrolimus and failed to provide detectable clinical benefits . Clinical Trials.gov identifier : NCT00436722 BACKGROUND Calcineurin inhibitors are the most commonly used immunosuppressive drugs in liver transplantation , but the optimum initial immunosuppression regimen is not known . The aim of our study was to compare tacrolimus with microemulsified ciclosporin , in a regimen with st and ardised concomitant immunosuppressive therapy . METHODS In all liver transplant centres in the UK and Republic of Irel and , 606 patients undergoing a first orthotopic liver transplantation were r and omly assigned open-label tacrolimus or microemulsified ciclosporin . Primary outcome was the combined frequency ( whichever occurred first ) of death , retransplantation , or treatment failure for immunological reasons , analysed by intention to treat . FINDINGS 96 % of patients received the treatment allocated to them . The primary outcome was reached in 62 ( 21 % ) of 301 patients in the tacrolimus group versus 99 ( 32 % ) of 305 allocated microemulsified ciclosporin ( relative risk 0.63 [ 95 % CI 0.48 - 0.84 ] , p=0.001 ; time-to-event analysis log-rank test p=0.002 ) : deaths ( 50 [ 17 % ] vs 72 [ 24 % ] ) ; retransplantations ( 11 [ 4 % ] vs 31 [ 10 % ] ) treatment failure for immunological reasons ( 6 [ 2 % ] vs 12 [ 4 % ] ) . The relative risk for the composite outcome was in favour of tacrolimus . The main causes of death in both trial groups were sepsis and multiple organ failure ( 31 [ 10 % ] vs 30 [ 10 % ] ) , and the main cause for retransplantation was hepatic artery thrombosis ( 6 [ 2 % ] vs 17 [ 6 % ] ) . Renal dysfunction and the need for antihypertensive therapy were much the same in both groups . Tacrolimus was more diabetogenic . INTERPRETATION Clinical outcome at 1 year was better with tacrolimus-based immunosuppression than with microemulsified ciclosporin during the first year after liver transplantation . Tacrolimus should be the first choice of calcineurin inhibitor for patients receiving their first liver graft This r and omized , comparative study assessed the long-term efficacy and tolerability of thymoglobulin ( TMG ) induction in 93 liver transplant patients with an initial regimen of tacrolimus ( Tac ) , mycophenolate mofetil ( MMF ) , and steroids . Forty-four patients were r and omly allocated to the TMG+ group , and 49 patients were r and omly allocated to the TMG- group . In both groups , Tac was given orally at the initial daily dose of 0.075 mg/kg twice daily , and MMF was given at the initial daily dose of 2 g/day . Steroid withdrawal was planned at 3 months after liver transplantation . The results were evaluated with respect to acute rejection incidence , patient and graft survival , graft function , and medical complications until 5 years or death for all patients . No significant differences were found between groups for the incidence of acute rejection at 5 years ( 11.4 % versus 14.3 % ) , 5-year patient survival ( 77.3 % versus 87.8 % ) , graft function , or postoperative renal function . One patient in the TMG- group underwent retransplantation . There was no difference between groups with respect to the incidence of medical complications , excepted for a higher rate of leukopenia in the TMG+ group , during the 5-year follow-up . In conclusion , the results of this prospect i ve r and omized study suggest that the addition of TMG to a triple immunosuppressive regimen ( Tac , MMF , and steroids ) did not modify the incidence of acute rejection episodes or long-term survival and was responsible for increased leukopenia rates In a r and omized prospect i ve study of liver transplant recipients , we compared prophylaxis with OKT3 , steroids , and azathioprine to cyclosporine , steroids , and azathioprine . Seventy-two percent of patients receiving OKT3 prophylaxis were rejection free in the first 14 days compared to 41 % in the cyclosporine group ( P=0.02 ) . However , after 14 days through a mean of 6.3 months , the overall incidence of rejection did not differ between the two groups ( 74 % for the cyclosporine group and 48 % for the OKT3 group ) . There was no increase in the rate of infectious complications noted in the OKT3-treated group . Thirty-nine percent of the OKT3-treated patients developed anti-OKT3 antibodies . Eight patients in the OKT3 group required reuse of OKT3 for rejection . Six of these continued to have greater than 10 % CD3-positive cells with retreatment . Five were rescued successfully . With a mean survival of greater than 674±209 days in the OKT3-treated group and 626±242 days in the cyclosporine-treated group , no overall differences in graft and patient survival , liver function , renal function , late rejection incidence , or infectious complications were evident between the two groups . We conclude that OKT3 offers no long-term benefit compared to cyclosporine prophylaxis and should be reserved for treatment of rejection in patients in whom cyclosporine may be contraindicated A group of 52 liver transplant patients was prospect ively r and omized to receive prophylactic immunosuppressive therapy consisting of either Orthoclone OKT3 for 14 days , azathioprine , and steroids ( 25 patients ) ; or cyclosporine , azathioprine , and steroids ( 27 patients ) . The groups were similarly matched for age , diagnosis , and Child 's classification . The patients were studied to determine the effect of these two regimens on the incidence of rejection , infection , renal dysfunction , and mortality . Seven rejection episodes , as determined by clinical and histological criteria , occurred in seven of 25 patients ( 28 % ) receiving OKT3 compared with 18 episodes in 27 patients ( 67 % ) receiving cyclosporine during the first 14 days after transplantation ( P less than 0.02 ) . In 20 % of the OKT3 patients , CD3 + levels of greater than 10 % developed during therapy , and 16 % of the patients developed anti-OKT3 antibodies during OKT3 treatment . Five patients were retreated with OKT3 for steroid-resistant acute rejection episodes ; all had resolution of the rejection episode . Infectious complications were similar in each group . Renal function , as measured by serum creatinine , was significantly better with OKT3 than with cyclosporine ( P less than 0.003 ) at 14 days . We conclude that prophylactic OKT3 is effective in reducing the number of early rejection episodes after liver transplantation ; after 14 days the incidence of rejection is similar ; reuse of OKT3 has been successful in liver transplant patients ; infectious complications are similar between OKT3 and cyclosporine ; and OKT3 preserves renal function better than cyclosporine and is thus indicated in patients with compromised preoperative renal function Allograft reinfection with hepatitis C virus ( HCV ) occurs universally in liver transplant recipients . Corticosteroids can contribute to HCV recurrence . This r and omized study evaluated HCV recurrence in HCV-positive liver allograft recipients using steroid-free immunosuppression . All patients received tacrolimus ( TAC ) at an initial dose of 0.10–0.15 mg/kg . The steroid-free arm ( TAC/daclizumab ( TAC/DAC , n = 67 ) ) received daclizumab induction , and the steroid arm ( TAC/steroid ( TAC/STR , n = 68 ) ) received a steroid bolus ( ≤ 500 mg ) followed by 15–20 mg/day with discontinuation after month 3 . Median HCV viral load at month 12 , the primary endpoint , was similar at 5.46 ( 0.95–6.54 ) IU/mL with TAC/DAC and 5.91 ( 0.95–6.89 ) IU/mL with TAC/STR . Small numerical differences in the estimated rate of freedom from HCV recurrence ( 19.1 versus 13.8 % ) and freedom from biopsy proven rejection ( 78.4 versus 66.1 % ) were observed between TAC/DAC and TAC/STR . Patient survival estimates were significantly lower with TAC/DAC than with TAC/STR ( 83.1 versus 95.5 % ; 95 % CI , −0.227 to −0.019 % ) , and graft survival was numerically lower ( 80.1 versus 91.1 % , P = NS ) . Completion rates ( 45 versus 82 % ) indicated poorer tolerability with TAC/DAC than with TAC/STR . Steroid-free immunosuppression had no real impact on HCV viral load . HCV recurrence was higher with TAC/STR . Results are inconclusive due to the unexpected lower completion rates in the TAC/DAC arm A multicenter r and omized trial was performed to compare two immunosuppressive protocol s after first ABO-compatible liver transplantation . Forty six patients were r and omized to a 14-day treatment with Orthoclone ( OKT3 ) in association with steroids and azathioprine , cyclosporine being progressively introduced on day 11 posttransplant . Fifty patients were r and omized to a st and ard protocol of cyclosporine with steroids and azathioprine . Minimum follow-up was 1 year and graft and patient survivals were up date d for the purpose of the study . The cumulative 1-year incidence of acute rejection tended to be greater in the cyclosporine group ( 75 % ) than in the OKT3 group ( 67 % ) , especially when patients who did not receive full-course treatment with OKT3 were excluded ( 59 % ) . Renal function was better preserved during the first two postoperative weeks in the OKT3 group than in the control group but plasma creatinine levels were comparable in both groups thereafter . The incidence of severe infections was lower in the OKT3 group ( 13.6 % ) than in the cyclosporine group ( 32 % ) . The 4-year incidences of patient and graft survival in the OKT3 group ( 69 % and 61 % , respectively ) were not different from those in the cyclosporine group ( 62 % versus 54 % , respectively ) . Thus this prospect i ve trial shows that OKT3 immunoprophylaxis is a safe alternative to cyclosporine immunoprophylaxis in unselected recipients of a first liver graft Background . Blockade of costimulation and adhesion signaling is an attractive approach to interfere with graft rejection Methods . Between January 1997 and May 1999 , forty adults having benign liver diseases were included in a prospect i ve , r and omized study comparing tacrolimus plus low-dose short-term steroids without ( n=20 , TAC group ) or with a 10-day course of antihuman CD2 monoclonal antibody ( n=20 , BTI group ) . Results . At day 7 , histological rejection expressed by mean Banff scores ( 2.3±1.6 vs. 5.4±1.6 in the TAC group ; P < 0.0001 ) and incidence of moderate to severe rejection ( score ≥6 ) ( 0 vs. 10 [ 50 % ] in the TAC group ; P<0.001 ) were significantly lower in the BTI group . Rejection was treated in 10 % ( two patients ) of BTI patients during the first 3 months and in 15 % during the whole follow-up and in 25 % ( five patients ) of TAC patients ( P = NS ) . None of the BTI- patients presented with an adverse event . Three-month , 1-year , and 5-year actual patient survival rates were 100 % , 95 % , and 95 % in the BTI group and 100 % , 100 % , and 85 % in the TAC group . Graft survival rates were 100 % , 90 % , and 90 % in the BTI group and 95 % , 95 % , and 80 % in the TAC group ( P = NS ) . The mAb had no negative impact on infectious or tumor events . Conclusions . Antihuman CD2 monoclonal antibody is a safe immunosuppressive drug which has a favorable impact on early immunological follow-up of liver transplanted patients . The antibody had no impact on late patient and graft survival We report a multicenter , prospect i ve , r and omized , open‐label trial investigating the effect of lower levels and delayed introduction of tacrolimus on renal function in liver transplant recipients . Adult patients with good renal function undergoing primary liver transplant were r and omized to either : group A ( st and ard‐dose tacrolimus [ target trough levels > 10 ng/mL ] and corticosteroids ; n = 183 ) ; group B ( mycophenolate mofetil [ MMF ] 2g/day , reduced‐dose tacrolimus [ target trough levels ≤8 ng/mL ] , and corticosteroids ; n = 170 ) ; group C ( daclizumab induction , MMF , reduced‐dose tacrolimus delayed until the fifth day posttransplant and corticosteroids , n = 172 ) . The primary endpoint was change from baseline in estimated glomerular filtration rate ( eGFR ) at 52 weeks . The eGFR decreased by 23.61 , 21.22 and 13.63 mL/min in groups A , B and C , respectively ( A vs C , p = 0.012 ; A vs B , p = 0.199 ) . Renal dialysis was required less frequently in group C versus group A ( 4.2 % vs. 9.9 % ; p = 0.037 ) . Biopsy‐proven acute rejection rates were 27.6 % , 29.2 % and 19.0 % , respectively . Patient and graft survival was similar . In conclusion , daclizumab induction , MMF , corticosteroids and delayed reduced‐dose tacrolimus was associated with less nephrotoxicity than therapy with st and ard‐dose tacrolimus and corticosteroids without compromising efficacy or tolerability This open , r and omized ( 1 : 1 ) , multicenter , 3-month study compared a dual tacrolimus plus steroids ( Tac / steroids ) regimen with a steroid-free immunosuppressive regimen of tacrolimus following daclizumab induction therapy ( Tac / Dac ) in adult liver transplant recipients . The full analysis set comprised 347 patients in the Tac / steroids group and 351 in the Tac / Dac group . Mean tacrolimus dose during month 3 was 0.11 mg/kg/day in both groups ; mean whole-blood trough levels during month 3 were 10.9 ng/mL ( Tac / steroids ) and 10.6 ng/mL ( Tac / Dac ) . The incidence of biopsy-confirmed acute rejection that required treatment was similar in both groups : 26.5 % in the Tac / steroids group and 25.4 % in the Tac / Dac group ( P = .727 ) . However , the incidence of biopsy-confirmed corticosteroid-resistant acute rejection was higher in the Tac / steroids group than in the Tac / Dac group ( 6.3 vs. 2.8 % ; P = .027 ) . Kaplan-Meier estimates of graft survival ( 92.2 vs. 90.5 % ) and patient survival ( 94.5 vs. 93.7 % ) were similar in both groups . While also the overall adverse event profiles were similar , the incidences of diabetes mellitus ( 15.3 vs. 5.7 % , respectively ; P < .001 ) and cytomegalovirus infection ( 11.5 vs. 5.1 % , respectively ; P = .002 ) were higher in the Tac / steroids group compared with the Tac / Dac group . Mean cholesterol levels increased by 16 % in the Tac / steroids group , but were unchanged in the Tac / Dac group during the study . In conclusion , tacrolimus monotherapy following daclizumab induction is an effective and safe regimen , with an advantage over concomitant steroid-maintenance therapy in terms of a lower incidence of diabetes and viral infection , and a lower incidence of steroid-resistant acute rejection A prospect i ve trial was conducted to assess the efficacy of induction immunosuppression with antilymphocyte monoclonal antibodies in 129 primary liver transplant patients who were r and omly divided into three groups according to immunosuppression during the first 10 days post-OLT : triple drug therapy only ( TDIS : cy-closporine , steroids , azathioprine ) ( group I : n=42 ) ; TDIS with a 10-day course of OKT3 ( group II : n=44 ) ; and LO-Tact-1 ( anti-IL-2 receptor mAb ) ( group III : n=43 ) . Biopsy-proved acute rejection ( AR ) was treated using the same biopsy-guided protocol in the 3 groups . One-year patient survival rates were 67 % , 84 % , and 93 % in groups I , II , and III , respectively ( I vs. II , NS ; I vs. III , P=0.001 ; II vs. III , P=0.044 ) . Incidences of AR were studied in the subgroup of 100 patients who were exposed to the risk of developing rejection , with Abstract : Background : Interventions that minimize hepatic ischemia/reperfusion injury ( IRI ) can exp and the donor organ pool . Thymoglobulin ( TG ) induction therapy has been shown to ameliorate delayed graft function and possibly decrease IRI in cadaver renal transplants recipients . This controlled r and omized trial was design ated to assess the ability of TG to protect against IRI in liver transplant recipients Recurrence of hepatitis C ( HepC ) has been a most difficult dilemma in liver transplantation ( OLT ) because the effects of immunosuppression with steroid , mycophenolate mofetil ( MMF ) calcineurin antagonists , and anti-interleukin-2 antibody as well as the role of preemptive antiviral therapy are uncertain . In this study , we r and omized OLT recipients with HepC into two treatment arms : tacrolimus+daclizumab+MMF ( study arm ) versus tacrolimus+steroids+MMF ( control arm ) . The study arm only received steroids for the treatment of biopsy-proven rejection episodes . Both arms received preemptive anti-viral therapy with Pegasys and ribavirin . The 39 enrolled patients ( among 50 to be enrolled ) have median follow-up of 458 days with 23 patients ( 8 in study arm , 15 in control arm ) having reached 1 year . The incidences of rejection episodes within 0 to 3 months , 3 to 6 months , and 6 to 12 months were ( study vs control ) : 0 % vs 28 % ; 0 % vs 6 % ; and 13 % vs 20 % ; respectively ( P = NS ) . The 1-year protocol biopsies showed advanced fibrosis ( stage 3 or greater ) in 20 % ( 3 of 15 ) of the control arm , but none ( 0 of 7 ) of the study arm ( P = NS ) . We compared anticipated side effects of steroids in the first 3 months ( study vs control ) : hypertension ( 36 % vs 58 % , P = NS ) , PTDM ( 7 % vs 43 % , P = .02 ) , and wound infections ( 14 % vs 37 % , P = NS ) . In conclusion , liver transplant recipients with HepC tolerate a steroid-free protocol . There was a trend toward reduced steroid side effects and a lower incidence of advanced fibrosis in 1-year biopsy sample s among patients receiving the steroid-free protocol Background . Basiliximab ( B ) , an anti-CD25 monoclonal antibody , may represent an alternative to steroids ( S ) in immunosuppression after liver transplantation ( LTx ) . The aim of this prospect i ve r and omized clinical trial was to compare B with S in a cyclosporin A (CsA)-based immunosuppression regimen in primary LTx . Methods . Forty-seven adult recipients of LTx were r and omly assigned to receive B or S. CsA was administered at the initial dose of 10 mg/kg/day and adjusted to the target C2 level of 800 to 1000 ng/mL by day 7 . Clinical ly suspected acute cellular rejection ( ACR ) was histologically confirmed . Endpoints include ACR , survival , and disease-free survival . Results . In group B ( 26 patients ) , there were seven biopsy-confirmed ACR with an ACR rate of 15.4 % ; in group S ( 21 patients ) , 8 ACR with an ACR rate of 28.6 % ( P = n.s . ) . Cumulative survival at 36 months after transplantation was 84.3 % for group B and 61.0 % for group S. In hepatitis C virus patients ( n=20 : 12 in group B , 8 in group S ) , the ACR rate was 25 % in group B and 50 % in group S. The incidence of infection and other adverse events was similar in the two treatment groups . Conclusions . B may represent a valid alternative to S in the induction of immunosuppression in LTx . Further studies of basiliximab in a large cohort are needed Background . Due to the known high recurrence rate of hepatitis C virus ( HCV ) among orthotopic liver transplant ( OLT ) recipients who receive tacrolimus+corticosteroid maintenance , use of steroid-free induction was considered . Methods . OLT recipients with HCV were r and omized to receive tacrolimus+daclizumab ( steroid-free ) vs. tacrolimus+corticosteroids during 1999–2001 and then tacrolimus+mycophenolate mofetil (MMF)+daclizumab ( steroid-free ) vs. tacrolimus+MMF+corticosteroids during 2002–2005 . Patients in the steroid-free arm of both periods received no steroids except for treating biopsy-proven rejection . Primary objective was to compare mean fibrosis stage at the 1-year protocol biopsy , between the steroid-free and corticosteroid arms , stratifying by period . Results . No noticeable differences in mean fibrosis stage between the two treatment arms , either averaging across periods ( P=0.99 ) or during either period ( P>0.35 ) were found . Occurrence of acute rejection during the first year was the only factor associated with a significantly increased fibrosis stage at 1 year ( P=0.0003 ) ; stage ≥2 was seen in 63 % ( 17 of 27 ) vs. 19 % ( 8 of 43 ) of those with vs. without rejection . In addition , MMF use was associated with significantly fewer patients experiencing acute rejection during the first 6 and 12 months posttransplant ( P=0.006 and 0.046 ) . Regarding steroid-related side effects , posttransplant diabetes mellitus occurred in 10 % vs. 45 % , and wound infection in 6 % vs. 31 % of steroid-free vs. corticosteroid patients ( P=0.003 and 0.01 ) . Conclusions . OLT recipients with HCV tolerated the steroid-free protocol with fewer side effects ; however , its use had no apparent impact on hepatic fibrosis progression . Occurrence of acute rejection was strongly associated with increased hepatic fibrosis at 1 year , and MMF use appears to have significantly reduced the rejection rate BACKGROUND In OLT induction therapy with interleukin-2-receptor antibodies is often applied as part of the st and ard immunosuppression protocol . It was the aim of this study to determine if Basilixirnab mduction therapy serves to reduce the incidence of acute rejection episodes and improves graft function and survival in the long term after OLT . MATERIAL / METHODS We prospect ively analysed 99 patients transplanted at our institution ( 1997 - 2000 ) . Patients were r and omised to two study groups : 51 patients received Basiliximab induction combined with Calcineurin inhibitors and steroids , 48 patients received CNIs and steroids only . Incidence and severity of rejection , graft and patient survival and intensity of long-term immunosuppression were analysed . Frequency of CNI and steroid induced adverse effects were recorded . RESULTS In our patient collective we could not detect a significant impact of Basiliximab induction therapy on the fre queny of acute or chronic rejection . CNI levels were almost identical in both groups ; graft and patient survival rates were not influenced by the application of induction therapy . CONCLUSIONS In our patient collective induction therapy does not have a general positive influence on the post transplant course . A slight improvement in long term renal function could be detected for Basiliximab treated patients This study compares the clinical course of recurrent hepatitis C virus ( HCV ) infection between 64 patients , who were r and omized to receive either rabbit antithymocyte globulin ( RATG ) or steroids as induction therapy with tacrolimus for maintenance . The HCV recurrence was assessed by HCV RNA levels , peak ALT at 3–6 months , the grade of inflammation at biopsy at 3–6 months posttransplant , progression of fibrosis , and survival . All patients had also received antiviral therapy with interferon alpha 2b and ribavirin , if there were no contraindications . There was no statistically significant difference between the two groups in terms of inflammation at 3 months , peak ALT , or HCV RNA . The survival between the two groups of patients was similar . It appears that steroid-free liver transplantation with RATG induction does not have any negative influence on HCV recurrence in hepatitis C patients after liver transplantation Posttransplant chronic renal failure , secondary to calcineurin inhibitor agents , is emerging as a major problem in liver transplantation . We report a r and omized clinical trial comparing daclizumab , delayed low-dose tacrolimus ( target trough level 4 - 8 ng/mL , starting day 4 - 6 ) , Investigational Arm ( n = 72 ) , to st and ard tacrolimus induction/maintenance dosing , St and ard Arm ( n = 76 ) , with mycophenolate mofetil and tapering corticosteroids in both study arms . The end-points were renal function indicated by the Modification of Diet in Renal Disease ( MDRD ) . There was no significant difference in patient survival ( 86.6 % Investigational Arm vs. 92.9 % St and ard Arm ; P = 0.21 ) or acute rejection ( 23.2 % vs. 27.7 % , respectively ; P = 0.68 ) . Statistically significant differences in median glomerular filtration rate ( GFR ) were found in favor of the Investigational Arm . With the CG equation , the GFR at the end of the first week was 110.7 vs. 89.6 mL/min ( P = 0.019 ) without significant differences thereafter . With the MDRD , statistically significant differences extended to the first posttransplant month ( 86.8 vs. 70.1 mL/min/1.73 m(2 ) ; P < 0.001 ) with and was seen at month 6 ( 75.4 vs. 69.5 mL/min/1.73 m(2 ) ; P = 0.038 ) . In conclusion , delayed low-dose tacrolimus , in combination with daclizumab and mycophenolate mofetil , preserves early renal function post-liver transplantation without the cost of increased acute rejection BACKGROUND Thymoglobulin induction therapy has been shown to ameliorate delayed graft function and possibly decrease ischemia reperfusion injury in cadaver renal transplant recipients . This controlled r and omized trial was design ed to assess whether thymoglobulin also protects liver transplant recipients from ischemia reperfusion injury . PATIENTS AND METHODS Twenty-two cadaver liver transplant recipients were r and omized to receive either thymoglobulin ( 1.5 mg/kg per dose ) during the anhepatic period and two doses every other day or no thymoglobulin . No differences in recipient or donor demographics were present . Maintenance immunosupression consisted of tacrolimus ( or cyclosporine ) and steroids for both groups . Donor biopsies were obtained during organ procurement , cold storage , and 1 hour after revascularization . Postoperative liver function tests were monitored . Early graft function , length of stay , patient and graft survival rates , incidence of primary nonfunction , and rate of rejection were assessed . RESULTS Patient and graft survival at 3 months was 100 % . There was no incidence of primary graft nonfunction and no need for retransplantation . The incidence of acute rejection was similar between the two groups . Although donor livers r and omized to thymoglobulin had less optimal preimplantation biopsies , these recipients had significant decreases in ALT at day 1 compared to the control group ( P = .02 ) , near significant decreases of total bilirubin at day 5 , and shorter length of hospitalization . CONCLUSION Thymoglobulin allowed for more compromised liver grafts to be transplanted with less clinical evidence of ischemia reperfusion injury and improved function Treatment with monoclonal IL-2 receptor antibodies has been successfully used for immunosuppressive induction therapy following organ transplantation in the recent past . The present study was conducted to compare for the first time a cyclosporine-based quadruple immunosuppressive regimen including a monoclonal IL-2 receptor antibody or ATG as induction therapy after orthotopic liver transplantation . In two groups of 33 patients each , postoperative survival , graft biopsies , liver function enzymes , and the clinical courses after OLT were evaluated . Our results indicate that monoclonal IL-2 receptor antibody therapy as part of a quadruple immunosuppressive regimen is better tolerated and is at least as effective as ATG in prevention of allograft rejection following OLT . Furthermore , our data indicate that a slightly better liver function in general and a lower incidence of rejection reactions necessitating treatment could be observed in the group of patients treated with the monoclonal IL-2 receptor antibody . This study provides evidence that monoclonal IL-2 receptor antibody therapy may be a useful tool for the immunosuppressive induction therapy following clinical orthotopic liver transplantation The immunological effects of therapeutic monoclonal antibodies ( mAbs ) depend upon their interaction with the target structure as well as the isotype of the mAb which is responsible for the binding to Fc receptors of accessory cells . The aim of the presented analysis was the evaluation of the in vivo immunosuppressive effect of BT 563 , a mAb directed to the alpha-chain of the interleukin-2 receptor ( IL-2R ) . Thirty-eight patients following liver transplantation were treated prophylactically for 12 days with 10 mg/day BT 563 ( clinical phase II and III study ) . As baseline immunosuppression cyclosporin ( CyA ) and low dose steroids were administered . BT 563 levels , lymphocyte sub population s , levels of soluble CD25 and Fc receptor polymorphism were evaluated and compared to the clinical outcome . Preoperatively in all patients a small subset of CD45R0 + cells expressed CD25 with detectable density . These cells were coated by BT 563 . There was no evidence for depletion of IL-2R+ cells or modulation of the IL-2R . During therapy stable levels of the soluble IL-2R were measured in patient sera . Throughout the therapy high levels of unbound BT 563 were found in sera , suggesting that IL-2R newly expressed on cells activated by the allograft could also be inhibited by BT 563 . No acute rejections were observed in these patients and no side effects of BT 563 were noted . There were only minor bacterial infections , while mycotic or viral infections did not appear . Administration of BT 563 together with CyA and low dose steroids to liver allografted patients represents a safe and effective protocol . Its action is likely to be mediated by turning off the pathway of signal transduction of the IL-2R in T-cells by the antibody while IL-2 gene transcription is simultaneously modified by CyA and steroids . The addition of all three immunosuppressive mechanisms is suggested to lead to a state of anergy during mAb application that is reversible at the end of antibody therapy but does not lead to rebound rejections . Analysis of the phenotype of CD25 + cells showed that they preferentially belonged to the CD45R0 + cell type . Thus we assume that BT 563 specifically turns off preactivated cells enabling rather selective and effective immunoprophylaxis in liver allografted patients Steroids have been 1 of the primary modes of immunosuppression since the inception of transplantation and have been credited with both the prevention and treatment of rejection . Steroids also have been held responsible for increased infections , posttransplantation diabetes , and recurrent hepatitis after orthotopic liver transplantation ( OLT ) . The purpose of this ongoing prospect i ve r and omized trial is to eliminate steroid use in OLT through induction with rabbit antithymocyte globulin ( RATG ) . This is the first report of a prospect i ve r and omized trial in OLT achieving complete absence of steroids . Seventy-one adult patients were prospect ively r and omized to administration of RATG or steroids . Thirty-six patients were r and omized to the administration of RATG induction at a dose of 1.5 mg/kg intravenously ( IV ) beginning during the anhepatic phase . No steroids were administered . Patients were administered a second 1.5-mg/kg dose of RATG post-OLT day 1 . Thirty-five patients were r and omized to the administration of methylprednisolone , which had been our st and ard immunosuppressive protocol . These patients were administered methylprednisolone , 1,000 mg IV , initiated during the anhepatic phase and followed by steroid taper . Maintenance immunosuppression consisted of tacrolimus and mycophenolate , with or without prednisone . Three patients died in each group , for an overall survival rate of 91 % in each group . One patient in each group required re-OLT , for a graft survival rate of 89 % in each group . Seven patients administered RATG had biopsy-proven rejection ( 20.5 % ) , all of whom were successfully treated by increasing tacrolimus doses . Eleven patients administered steroid had biopsy-proven rejection ( 32 % ) , 7 ( 64 % ) of whom required additional steroids for treatment , whereas 4 patients ( 36 % ) were successfully treated by increasing tacrolimus doses . The incidence of rejection was not statistically significant ; however , there was a significant difference in the incidence of steroid-requiring rejection ( P = .01 ) . The incidence of recurrent hepatitis C was 50 % in RATG patients and 71 % in steroid patients ( P = not significant ) . The incidence and severity of infectious complications were slightly lower in RATG patients , accounted for by a greater incidence of cytomegalovirus ( CMV ) infection in the steroid patients . RATG induction enables complete avoidance of steroid use in OLT with a trend toward a lower rejection rate , decreased incidence of post-OLT diabetes and recurrent hepatitis C , and decreased CMV infection . This prospect i ve r and omized trial gives encouraging support that steroids can be safely eliminated in OLT The introduction of quadruple induction therapy after liver transplantation with the murine anti-interleukin-2 receptor ( IL-2R ) antibody ( BT563 ) has decreased the incidence of serious side effects , such as tachycardia , hypertension , rash , fever and nausea since it does not lyse its target cell . To investigate the immunosuppressive efficacy of BT563 , a placebo-controlled trial was performed and BT563 was added to the st and ard triple induction after liver transplantation . Forty consecutive recipients of primary orthotopic liver transplants ( OLT ) ( median age 47 yr [ range 18 - 65 ] ) were r and omized . All patients received triple immunosuppression with cyclosporine A ( CyA ) , prednisolone ( PRED ) and azathioprine ( AZA ) . In addition , 19 patients received BT563 ( Biotest , Dreieich , Germany ) at a dose of 10 mg/d from day 0 until day 12 . The remaining 21 patients received a placebo infusion at the same days after transplantation . Minimal follow-up for all patients was 3 yr . Patient survival at 3 yr was 74 % in the BT563 group and 90 % in placebo group . Similar results were observed for graft survival . Two acute rejection episodes were detected in the BT563 group and 9 acute rejections ( 5 steroid-resistant ) were observed in the placebo group ( p < 0.034 ) . The incidences of sepsis , pneumonia , cholangitis , urinary tract infections as well as cytomegalo-virus ( CMV ) infections were similar in both groups . Side effects of the BT563 therapy and /or post-transplant lymphoproliferative disease ( PTLD ) were not detected . Quadruple induction therapy with BT563 significantly reduces the incidence of rejection episodes after liver transplantation , while infectious complications and /or PTLD is not increased . Therefore , the anti-IL2 receptor antibody BT563 constitutes a safe and efficient addition to the immunosuppressive induction regimen following OLT This work is a 1-yr interim analysis of a prospect i ve , r and omized , multicenter trial evaluating the effect of corticosteroid-free immunosuppression on hepatitis C virus-positive ( HCV(+ ) ) liver transplant recipients following liver transplantation ( LT ) . Patients received tacrolimus and corticosteroids ( Arm 1 ; n = 80 ) ; tacrolimus , corticosteroids , and mycophenolate mofetil ( MMF ) ( Arm 2 ; n = 79 ) ; or daclizumab induction , tacrolimus , and MMF ( Arm 3 ; n = 153 ) . At 1 yr , 64.1 % , 63.4 % , and 69.4 % of patients achieved the composite primary endpoint of freedom from rejection , freedom from HCV recurrence , and freedom from treatment failure , respectively . Excellent patient and graft survival did not differ significantly among treatment arms . Freedom from HCV recurrence at 1 yr was 61.8 + /- 6.2 % , 60.1 + /- 6.1 % , and 67.0 + /- 4.3 % in Arms 1 , 2 , and 3 , respectively ( P = not significant ) . Freedom from rejection was significantly higher in Arm 3 compared to Arm 1 ( 93.0 + /- 2.2 % vs. 81.9 + /- 4.4 % ; P = 0.011 ) . Multivariate analysis identified acute rejection ( hazard ratio = 2.692 ; P = 0.001 ) and donor age ( hazard ratio = 1.015 ; P = 0.001 ) as significant risk factors for HCV recurrence . HCV recurrence was not influenced by recipient demographics , HCV genotype , or immunosuppression . In conclusion , these results suggest that a corticosteroid-free regimen of tacrolimus and MMF following daclizumab induction is safe and effective in HCV(+ ) liver transplant recipients Avoidance of corticosteroids could be beneficial after pediatric liver transplantation ( LTx ) . To test this hypothesis , we performed a r and omized prospect i ve study to compare immunosuppression with tacrolimus ( TAC ) and steroids versus TAC and basiliximab ( BAS ) after pediatric LTx . Seventy‐two patients were recruited , 36 receiving TAC and steroids and 36 TAC and BAS . The primary endpoint was the occurrence of the first rejection episode . Secondary endpoints were the cumulative incidence and severity of rejection , patient and graft survival , and incidence of adverse events . Overall 1‐year patient and graft survival rates were 91.4 % and 85.5 % in the steroid group , and 88.6 % and 80 % in the BAS group ( p = NS ) . Patients free from rejection were 87.7 % in the BAS group and 67.7 % in the steroid group ( p = 0.036 ) . The use of BAS was associated with a 63.6 % reduction in incidence of acute rejection episodes . Overall incidence of infection was 72.3 % in the steroid group and 50 % in the BAS group ( p = 0.035 ) . We conclude that the combination of TAC with BAS is an alternative to TAC and steroid immunosuppression in pediatric LTx , which allows for a significant reduction in the incidence of acute rejection and infectious complications Background . In 2001 , we published early results of a prospect i ve r and omized trial of 71 patients who received either steroids or rabbit antithymocyte globulin ( RATG ) for orthotopic liver transplantation ( OLT ) . We now report follow-up on these patients and additional patients undergoing steroid-free OLT . Methods . A total of 119 adult OLT recipients were prospect ively r and omized to receive either methylprednisolone 1,000 mg followed by a 3-month steroid taper or a steroid-free regimen of RATG 1.5 mg/kg during the anhepatic phase followed by a 1.5 mg/kg dose on posttransplant day 1 . Maintenance immunosuppression consisted of tacrolimus and mycophenolate mofetil in both groups . Mycophenolate mofetil was weaned over 3 months in the first 71 patients and over 2 weeks in the last 48 patients , achieving tacrolimus monotherapy by 2 weeks posttransplant . Subsequently , a group of 24 sequential OLT recipients received the steroid-free ( RATG ) protocol . Endpoints of the study were survival , rejection , infectious complications , posttransplant diabetes , and recurrent hepatitis C virus . Results . One-year patient survival was 85 % in each group of the prospect i ve r and omized trial with a mean follow-up of 18.5 months . One-year graft survival was 82 % in the RATG group and 80 % in the steroid group ( P = not significant ) . Patient and graft survival of the 24 nonr and omized RATG patients was 96 % with a mean follow-up of 3 months . The incidence of rejection was not significantly different ; however , 50 % of the patients in the steroid group required pulse steroids to reverse the rejection compared with only one patient ( 1.6 % ) in the RATG group ( P = .03 ) . The incidence of cytomegalovirus infection ( P < .05 ) and posttransplant diabetes was higher in the steroid group ( P = .03 ) . There was a trend toward decreased severity of hepatitis C virus in the RATG group . Conclusions . Steroid-free liver transplantation using RATG and early tacrolimus monotherapy effectively reduces immunosuppression-related complications with excellent survival Seventy-nine hepatic allograft recipients were r and omized to receive either conventional immunosuppression , including cyclosporine , azathioprine , and steroids ( 41 patients ) , or investigational therapy in which OKT3 replaced cyclosporine during the first postoperative week ( 38 patients ) . Early rejection occurred in 29 patients ( 71 % ) in the conventional group and 15 patients ( 39 % ) in the OKT3 group . Posttransplantation renal dysfunction occurred in 12 patients ( 29 % ) in the conventional group and 6 patients ( 16 % ) in the OKT3 group . Mean initial hospital stay was 34.1 + /- 18.8 days in the conventional group compared with 29.1 + /- 16.8 days in the OKT3 group . Cumulative patient survival ( mean follow-up , 17.8 + /- 7.1 months ) was 73.2 % ( 30/41 ) for the conventional group and 84.2 % ( 32/38 ) for the OKT3 group . Prophylactic OKT3 is indicated especially for liver allograft recipients with other complicating conditions that make management of early rejection unusually difficult BACKGROUND Quadruple immunosuppressive induction therapy has been shown to markedly reduce the incidence of acute rejection episodes without increasing the incidence of infectious complications after liver transplantation . However , the use of polyclonal antibody preparations ( e.g. antithymocyte globulin [ ATG ] ) is associated with side effects such as fever and tachycardia . To evaluate the efficacy and the safety of a monoclonal antibody directed against the interleukin-2 receptor ( BT563 ) in comparison with ATG as part of a quadruple induction regimen , a prospect i ve , r and omized study was conducted . METHODS Eighty consecutive adult recipients of primary orthotopic liver transplants were r and omized to receive either BT563 ( 10 mg/day ; days 0 - 12 ; n=39 ) or ATG ( 5 mg/kg/day ; days 0 - 6 ; n=41 ) in addition to the st and ard immunosuppressive protocol consisting of cyclosporine , and prednisolone , and azathioprine . RESULTS Patients treated with BT563 had a significantly lower incidence of steroid-sensitive rejection episodes ( 3 vs. 11 ; P<0.025 ) and also significantly fewer drug-related side effects ( 4 vs. 18 , P<0.038 ) when compared with patients treated with ATG . The incidence of infectious complications was not different between the two groups . Patient survival did not differ significantly between the two groups ( 84.6 % at 1 , 2 , and 3 years in the BT563 group and 90.2 % at 1 year and 87.8 % at 2 and 3 years for the ATG group ) . Analysis of graft function showed an advantage for the BT563 group in terms of postoperative bilirubin levels . However , no differences were observed in long-term follow-up between the two groups . CONCLUSIONS Our results indicate that treatment with anti-interleukin-2 receptor antibody as part of quadruple induction therapy after orthotopic liver transplantation is safe and effective and shows fewer steroid-sensitive rejection episodes as well as fewer side effects when compared with quadruple induction therapy including ATG BACKGROUND Corticosteroids have long been a cornerstone of orthotopic liver transplant ( OLTx ) immunosuppression . Newer , more potent , agents have successfully allowed for more rapid tapering and discontinuation of corticosteroids in OLTx recipients . We hypothesize that corticosteroids can be safely avoided after the first postoperative day ( POD ) using these newer agents . METHODS Thirty adult OLTx recipients were prospect ively enrolled in a r and omized open-label , institutional review board-approved protocol . Fifteen patients ( group A ) received our st and ard regimen of tacrolimus , mycophenolate mofetil , and corticosteroids , and 15 patients ( group B ) received daclizumab , 2 mg/kg on POD 0 and 14 , with tacrolimus , mycophenolate mofetil , and corticosteroids on POD 0 and 1 and then discontinuation . In both groups , mycophenolate mofetil was tapered off between 3 and 4 months after OLTx . Bone mineral densitometry was performed at 1 , 3 , and 6 months after OLTx . Quantitative hepatitis C virus ( HCV ) polymerase chain reaction was obtained at days 0 , 7 , 14 , 21 , and 28 . Retransplant recipients , patients with autoimmune hepatitis , or status 1 or 2A patients were excluded . RESULTS Patient and graft survival rates were 93 % ( group A ) and 100 % ( group B ) with mean follow-up of 18 months . Patients in group B had more rejection diagnosed ( 25 % ) compared with group A ( 6.7 % ) . Yet , the incidence of biopsy-proven acute rejection requiring steroid therapy was 6.7 % in both groups . Hispanic race was common in groups A and B ( 87 % and 74 % ) . A total of six biopsies were performed in group B , with three patients having mild rejection responding to an increase in tacrolimus without the need for corticosteroids . One patient in group B was switched to cyclosporine for severe neurotoxicity and remains on monotherapy with normal graft function . No patient in either group developed a requirement for additional antihypertensive medication . Likewise , there were no patients with new-onset diabetes . The bone mineral densitometry was higher in group B at every time point but did not reach statistical significance . Serum cholesterol level was significantly ( P=0.03 ) lower in group B at 6 months after OLTx . Serum triglycerides were also lower , but the difference was not significant . Quantitative polymerase chain reaction for HCV-positive patients ( group A , n=7 ; group B , n=8 ) frequently increased after OLTx . There was no correlative decrease associated with daclizumab . At present , two patients in group A have documented HCV recurrence . CONCLUSION Corticosteroids can be safely avoided after POD 1 with the current regimen . With early follow-up , there is no difference in hypertension or diabetes or bone density . Lipid panels tended to be lower in patients who were not on corticosteroids . Longer term follow-up will be needed to demonstrate the potential advantage of corticosteroid avoidance in regard to hypertension , diabetes , and possibly HCV recurrence A prospect i ve trial was conducted in 129 recipients of primary liver transplantation , to compare induction immunosuppression using triple drug therapy ( cyclosporine , steroids , and azathioprine ; group 1 , n = 42 ) , versus triple drug therapy with a 10-day course of OKT3 ( group 2 , n = 44 ) or of the anti-interleukin-2 receptor monoclonal antibody LO-Tact-1 ( group 3 , n = 43 ) . Two-year actual patient survival rates were 64 % , 79 % , and 93 % in groups 1 , 2 , and 3 , respectively ( 1 vs. 2 , NS ; I vs. III , P = 0.003 ; 2 vs. 3 , NS ) . Up to 2 years after transplantation , 18 % , 44 % , and 53 % of the grafts in groups 1 , 2 , and 3 , respectively , had not experienced steroid-resistant acute rejection ( 1 vs. 2 , P = 0.002 ; 1 vs. 3 , P = 0.007 ; 2 vs. 3 , NS ) . The overall incidence of chronic rejection was 4 % . OKT3 therapy , but not LO-Tact-1 , significantly increased the incidence of cytomegalovirus infections ( P = 0.019 ) . In conclusion , immunoprophylaxis with LO-Tact-1 seemed to provide a liver graft acceptance rate at least as satisfactory as that with OKT3 , without an increase in the incidence of infections We report the long-term follow-up ( > 1 year ) of 46 patients ( 12 pediatric ) r and omized to receive OKT3 for the first 14 days after OLT with low-dose steroids compared with 39 patients ( 8 pediatric ) who received cyclosporine , steroids , and azathioprine . The mean period of follow-up for survivors was 648±261 days for the OKT3 group and 682±216 days for the cyclosporine group . Of the OKT3 patients , 46 % were rejection-free in the first month compared with 31 % of CsA-treated patients ( P = NS ) . Rejection occurred after 1 month in 21 % of the OKT3 group patients compared with 19 % of the CsA group patients . One patient in each group developed vanishing bile duct syndrome . Eight patients in the OKT3 group and 13 in the CsA group experienced steroid-resistant rejection and required OKT3 rescue . In the 8 patients in whom OKT3 was reused , 4 had a positive ELISA after prophylaxis , and in 6 , CD3-positive cells were greater than 10 % during OKT3 reuse . Five patients resolved the episode . Of patients receiving OKT3 prophylaxis , 39 % developed anti-OKT3 antibodies . In the OKT3 group 83 % of patients and in the CsA group 75 % currently have normal liver function . There was no difference in serum creatinine for either adult or pediatric recipients at 12 months in the two groups . Eight episodes ( 2 CMV ) of severe infection occurred after 1 month in the OKT3 group compared to 11 ( 4 CMV ) in the CsA group . Graft survival , 63 % for the OKT3 group and 73 % for the CsA group , and patient survival , 67 % for the OKT3 group and 84 % for the CsA group , were not significantly different in the two groups . We recommend reserving the use of OKT3 for resistant rejection or when cyclosporine is contraindicated , as we can show no long-term benefit from its routine prophylactic use 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 |
10,786 | 27,744,650 | Therefore , there is currently insufficient evidence to clarify whether soil abatement or a combination of interventions reduces blood lead levels .
Based on current knowledge , household educational interventions are ineffective in reducing blood lead levels in children as a population health measure .
Dust control interventions may lead to little or no difference in blood lead levels ( the quality of evidence was moderate to low , meaning that future research is likely to change these results ) .
There is currently insufficient evidence to draw conclusions about the effectiveness of soil abatement or combination interventions . | BACKGROUND Lead poisoning is associated with physical , cognitive and neurobehavioural impairment in children , and trials have tested many household interventions to prevent lead exposure .
This is an up date of the original review , first published in 2008 .
OBJECTIVES To assess the effects of household interventions for preventing or reducing lead exposure in children , as measured by improvements in cognitive and neurobehavioural development , reductions in blood lead levels and reductions in household dust lead levels . | Background . Dust control is recommended as one of the primary strategies to prevent or control children 's exposure to residential lead hazards , but the effect of dust control on children 's blood lead levels is poorly understood . Objective . To determine the effectiveness of dust control in preventing children 's exposure to lead , as measured by blood lead levels , during their peak age of susceptibility . Design . A r and omized , controlled trial . Setting . Rochester , NY . Participants . A total of 275 urban children were r and omized at 6 months of age , of whom 246 ( 90 % ) were available for the 24-month-old follow-up visit . Interventions . Children and their families were r and omly assigned to an intervention group ( n = 140 ) , which received cleaning equipment and up to eight visits by a dust control advisor , or a control group ( n = 135 ) . Outcome Measures . Geometric mean blood lead levels and prevalence of elevated blood lead levels ( ie , > 10 μg/dL , 15 μg/dL , and 20 μg/dL ) . Results . At baseline , children 's geometric mean blood lead levels were 2.9 μg/dL ( 95 % confidence interval [ CI ] = 2.7 , 3.1 ) ; there were no significant differences in characteristics or lead exposure by group assignment , with the exception of water lead levels . For children in the intervention group , the mean number of visits by a dust control advisor during the 18-month study period was 6.2 ; 51 ( 36 % ) had 4 to 7 visits , and 69 ( 49 % ) had 8 visits . At 24 months of age , the geometric mean blood lead was 7.3 μg/dL ( 95 % CI = 6.6 , 8.2 ) for the intervention group and 7.8 μg/dL ( 95 % CI = 6.9 , 8.7 ) for the control group . The percentage of children with a 24-month blood lead ≥10 μg/dL , ≥15 μg/dL , and ≥20 μg/dL was 31 % versus 36 % , 12 % versus 14 % , and 5 % versus 7 % in the intervention and control groups , respectively . Conclusions . We conclude that dust control , as performed by families and in the absence of lead hazard controls to reduce ongoing contamination from lead-based paint , is not effective in the primary prevention of childhood lead exposure . blood lead , lead-contaminated house dust , r and omized trial , children , environmental exposure , lead poisoning , primary prevention , prevention BACKGROUND Contaminated household dust is believed to be a major source of exposure for most children with elevated blood lead levels . To determine if a vigorous dust clean-up effort would reduce this exposure we conducted a r and omized controlled field trial . METHODS We r and omized 113 urban children between the ages of 6 and 36 months : 56 children to a lead dust intervention composed of maternal education and biweekly assistance with household cleaning and 57 children to a control group . Household cleaning was done by two trained lay workers who focused their efforts on wet mopping of floors , damp-sponging of walls and horizontal surfaces , and vacuuming with a high-efficiency particle accumulating vacuum . Household dust lead levels , child blood lead levels , and maternal knowledge of lead poisoning and sources of exposure were measured before and after the intervention . RESULTS Ninety-nine children were successfully followed for 12 + /- 3 months : 46 children in the lead group and 53 children in the control group . Age and blood lead were similar in the two groups at baseline and averaged 20 months and 12.0 micrograms/dL , respectively . Blood lead fell 17 % in the intervention group and did not change among controls . Household dust and dust lead measures also fell significantly in the intervention group . Children in homes cleaned 20 or more times throughout the year had an average blood lead reduction of 34 % . CONCLUSIONS Regular home cleaning , accompanied by maternal education , is a safe and partially effective intervention that should be recommended for the large majority of lead-exposed children for whom , unfortunately , removal to lead-safe housing is not an option In this article we report on the effectiveness of a community-based , culture-specific , controlled trial of intensive peer education aim ed at preventing lead burden in children 0 - 36 months of age within a neighborhood with high risk for lead exposure . Mothers ( n = 594 ) were r and omly assigned to control or intervention groups . Offspring blood lead levels were assessed every 4 months . All participants received brochures on basic lead prevention strategies . Intervention participants were offered 20 bi-weekly educational sessions by same-ethnicity peer educators over the course of 1 year , and quarterly booster sessions for 2 years afterward . The intervention group 's educational curriculum included information on lead sources ( e.g. , paint , dust , water , soil , and risks from home repairs and remodeling ) , health consequences of lead burden , and strategies to reduce lead exposure , including household cleaning , hygiene , safe use of water , and nutritional recommendations . Results indicated that of the 378 children contributing sufficient blood data for analysis , 23 % had blood lead levels > 10 micro g/dL before 3 years of age . Intervention participants were more likely to maintain blood lead levels < 10 micro g/dL than were controls ( 81 % vs. 73 % ; p = 0.08 ) . Multivariate analyses demonstrated that the intervention reduced the risk of blood lead levels > 10 micro g/dL by approximately 34 % . We conclude that although intensive education result ed in a lower proportion of children with elevated lead levels , education alone can not be relied upon to prevent lead burden OBJECTIVES The aim of this study was to quantify the relative contributions to surface lead contamination of boat-caulkers ' houses of three contamination modes , namely " take-home " lead from the caulker , " natural " spatial dispersal from boatyard to household and " redistribution " of accumulated lead-laden dust within the house . METHODS Boat-caulkers ' houses situated in areas surrounding boat repair yards were recruited . Caulkers ' houses that were located close together were divided into location-matched pairs , within which one was r and omly assigned to be given a cleaning and design ated a CL house , and the other was to be left uncleaned and design ated a NCL house . Geographically isolated caulker 's houses were r and omly assigned to one of the two categories . The nearest non-boatyard worker 's house ( NB ) was additionally recruited for each set . The surface lead loading rate ( SLLR ) , defined as the mass of lead deposited in dust per unit area of surface per unit time , was measured over a period of 3 mo in all houses , and the data were modeled using linear mixed effects regression . RESULTS Adjusted values of SLLR differed only slightly between CL and NCL houses ( 0.96 to 1.02 times ) but were between 1.65 and 2.03 times higher in CL and NCL houses than in NB houses depending on proximity to the boatyard and between 2.12 and 2.61 times higher in houses within one km of a boatyard than in more distant houses depending on category of house . CONCLUSIONS Newly deposited dust lead likely result ed from the take-home and spatial dispersion modes . The contribution of redistribution is very small OBJECTIVES This study assessed the relationship between lead-contaminated house dust and urban children 's blood lead levels . METHODS A r and om- sample survey was used to identify and enroll 205 children , 12 to 31 months of age , who had resided in the same house since at least 6 months of age . Children 's blood and household dust , water , soil , and paint were analyzed for lead , and interviews were conducted to ascertain risk factors for elevated blood lead ( > or = 10 micrograms/dL ) . RESULTS Children 's mean blood lead level was 7.7 micrograms/dL. In addition to dust lead loading ( micrograms of lead per square foot ) , independent predictors of children 's blood lead were Black race , soil lead levels , ingestion of soil or dirt , lead content and condition of painted surfaces , and water lead levels . For dust lead st and ards of 5 micrograms/sq ft , 20 micrograms/sq ft , and 40 micrograms/sq ft on noncarpeted floors , the estimated percentages of children having blood lead levels at or above 10 micrograms/dL were 4 % , 15 % , and 20 % , respectively , after adjusting for other significant covariates . CONCLUSIONS Lead-contaminated house dust is a significant contributor to lead intake among urban children who have low-level elevations in blood lead . A substantial proportion of children may have blood lead levels of at least 10 micrograms/dL at dust lead levels considerably lower than current st and ards Background . Dust control is recommended to prevent children 's exposure to residential lead hazards , but the long-term effect of dust control on children 's exposure to environmental lead is unknown . Objective . To determine the effect of dust control on children 's exposure to lead , as measured by blood lead concentration at 48 months of age . Design . A r and omized , controlled trial . Setting . Rochester , New York . Participants . A total of 275 urban children were r and omized at 6 months of age ; 189 ( 69 % ) were available for the 48-month follow-up blood test . Intervention . Children and their families were r and omly assigned to an intervention group that received cleaning equipment and up to 8 visits by a trained lead hazard control advisor or to a control group . The intervention was terminated when the children were 24 months of age . Outcome Measures . Geometric mean blood lead concentration and prevalence of elevated blood lead concentration ( ie , ≥10 μg/dL , ≥15 μg/dL , and ≥20 μg/dL ) , by group assignment . Results . For children with 48-month blood tests , baseline geometric mean blood lead concentrations were 2.8 μg/dL ( 95 % confidence interval [ CI ] : 2.6,3.0 ) ; there were no significant differences in baseline characteristics or lead exposure by group assignment . At 48 months of age , the geometric mean blood lead was 5.9 μg/dL ( 95 % CI : 5.3,6.7 ) for the intervention group and 6.1 μg/dL ( 95 % CI : 5.5,6.9 ) for the control group . The percentage of children with a 48-month blood lead ≥10 μg/dL , ≥15 μg/dL , and ≥20 μg/dL was 19 % versus 19 % , 2 % versus 9 % , and 1 % versus 2 % in the intervention and control groups , respectively . Conclusions . We conclude that dust control , as performed by families and in the absence of lead hazard controls to reduce ongoing contamination from lead-based paint , was not effective in preventing children 's exposure to residential lead hazards OBJECTIVE Some children in the United States continue to be exposed to levels of lead that increase their risk for lowered intellectual functioning and behavior problems . It is unclear whether chelation therapy can prevent or reverse the neurodevelopmental sequelae of lead toxicity . The objective of this study was to determine whether chelation therapy with succimer ( dimercaptosuccinic acid ) in children with referral blood lead levels between 20 and 44 microg/dL ( 0.96 - 2.12 micromol/L ) at 12 to 33 months of age has neurodevelopmental benefits at age 7 years . METHODS The Treatment of Lead-Exposed Children ( TLC ) study is a r and omized , double-blind , placebo-controlled trial that was conducted between September 1994 and June 2003 in Philadelphia , PA ; Newark , NJ ; Cincinnati , OH ; and Baltimore , MD . Of 1854 referred children who were between the ages of 12 to 33 months and screened for eligibility , 780 were r and omized to the active drug and placebo groups stratified by clinical center , body surface area , blood lead level , and language spoken at home . At 7 years of age , 647 subjects remained in the study . Participants were r and omly assigned to receive oral succimer or placebo . Up to 3 26-day courses of succimer or placebo therapy were administered depending on response to treatment in those who were given active drug . Eighty-nine percent had finished treatment by 6 months , with all children finishing by 13 months after r and omization . All participants received residential lead hazard control measures before treatment . TLC subjects also received a daily multivitamin supplement before and after treatment(s ) with succimer or placebo . Scores on st and ardized neuropsychological measures that tap cognition , behavior , learning and memory , attention , and neuromotor skills were measured . RESULTS Chelation therapy with succimer lowered average blood lead levels for approximately 6 months but result ed in no benefit in cognitive , behavioral , and neuromotor endpoints . CONCLUSION These new follow-up data confirm our previous finding that the TLC regimen of chelation therapy is not associated with neurodevelopmental benefits in children with blood lead levels between 20 and 44 microg/dL ( 0.96 - 2.17 micromol/L ) . These results emphasize the importance of taking environmental measures to prevent exposure to lead . Chelation therapy with succimer can not be recommended for children with blood lead levels between 20 and 44 microg/dL ( 0.96 - 2.12 micromol/L ) OBJECTIVE Dust control is recommended as one of the cornerstones of controlling childhood lead exposure ; however , the effectiveness of dust control has not been demonstrated for children who have low to mild elevations in blood lead ( ie , less than 25 micrograms/dL ) . The objective of this study was to determine whether dust control , as performed by families , had an effect on children 's blood lead levels and dust lead levels in children 's homes . DESIGN R and omized , controlled trial . SETTING Community-based trial in Rochester , NY . PARTICIPANTS One hundred four children , 12 to 31 months of age at baseline . INTERVENTION Families and children were r and omized to one of two groups . Families of children in the intervention group received cleaning supplies , information about cleaning areas that are often contaminated with lead , and a cleaning demonstration . Families in the control group received only a brochure about lead poisoning prevention . OUTCOME MEASURES Baseline measurements of lead in blood , house dust , soil , water , and paint were taken from both groups . Seven months after enrollment , a second blood lead assay was obtained , and lead levels in household dust were measured . The main outcome measures were change in blood lead levels and dust lead levels by treatment group . RESULTS The median blood lead level of children enrolled in the study was 6.7 micrograms/dL ( range , 1.7 to 30.6 micrograms/dL ) . There was no significant difference in the change of children 's blood lead levels or dust lead levels by treatment group . The median change in blood lead levels among children in the intervention group was -0.05 micrograms/dL compared with -0.60 micrograms/dL among those in the control group . There also was no significant difference in the change of dust lead by group assignment , although there was a trend toward a significant difference in the percentage of change in dust lead levels on noncarpeted floors , which was greater among houses in the intervention group . CONCLUSIONS These data suggest that an intervention that consists only of providing cleaning supplies and a brief description of dust control is not effective at reducing blood lead levels among urban children with low to mild elevations in blood lead levels at a 7-month follow-up OBJECTIVES This prospect i ve study describes the impact of residential lead-based-paint hazard remediations on children with mildly elevated blood lead levels . METHODS Changes in blood lead levels were observed following paint hazard remediation alone and in combination with soil abatement . RESULTS After adjustment for the confounding variables paint hazard remediation alone was associated with a blood lead increase of 6.5 micrograms/dL ( P = 0.5 ) , and paint hazard remediation combined with soil abatement was associated with an increase of 0.9 microgram/dL ( P = 36 ) . CONCLUSIONS Lead-based-paint hazard remediation as performed in this study , is not an effective secondary prevention strategy among children with mildly elevated blood lead levels In this study , the authors evaluated whether a combination of tailored education , lead dust removal by trained cleaning specialists , and family follow-up visits would be more effective than conventional health educational programs in reducing elevated blood lead levels in children living in or near lead mining hazardous waste sites . The authors r and omized children between 6 and 72 mo of age with blood lead levels between 10 and 20 μg/dl into 3 groups : st and ard care , tailored newsletters , or tailored newsletters and specialized cleaning . The authors obtained question naires , blood lead levels , and environmental lead sample s during initiation and compared them with the same items obtained at 3 , 6 , and 9 mo follow-up . They used a linear mixed effect model to evaluate the intervention effect . Blood lead levels decreased overall 1.54 μg/dl ( 12.1 % ) during the study . The authors found that tailored newsletters and specialized cleaning produced the greatest decline in blood lead levels , but no statistical differences were found among the method ologies . The small decline observed in blood lead levels reduced levels to below 10 mUg/dl for 40 % of the children Lead-contaminated house dust is one factor in childhood lead poisoning ; however , most lead-reduction programs do not emphasize the control of house dust . We studied whether lead-reduction plus dust-control measures would lower blood lead levels in children with Class II or III poisoning ( blood lead levels , 30 to 49 micrograms per deciliter ) more effectively than lead reduction alone . An experimental group of 14 children and a control group of 35 children whose homes had already been treated were studied . In experimental homes , sites with elevated lead levels ( greater than 100 micrograms per 930 cm2 ) were wet-mopped twice monthly and families were encouraged to clean and to wash the child 's h and s frequently . After one year blood lead levels fell an average of 6.9 micrograms per deciliter in the experimental group , as compared with 0.7 micrograms per deciliter in controls ( P less than 0.001 ) . Children in the experimental group with the highest blood lead levels had the most marked reduction . Four children in the control group ( and none in the experimental group ) required chelation therapy for blood levels greater than 50 micrograms per deciliter . These results show that a focused dust-control program can reduce blood lead levels more than st and ard lead removal in the home OBJECTIVE . The objective of this study was to measure the effectiveness of intensive case management to reduce blood lead levels ( BLLs ) in children . Lead poisoning remains a common , preventable pediatric condition despite advances in reducing children 's BLLs in the United States . Substantial evidence implicates lead paint – contaminated house dust as the most common high-dose source of lead in children 's environments . Housekeeping and parental supervision also may contribute to risk for lead exposure . METHODS . We conducted a community-based , r and omized trial of comprehensive education and home visiting for families of children with BLLs 15 to 19 μg/dL. BLLs after 1 year of follow-up were compared for intervention group children , whose families received individualized education that was design ed to address specific risks factors in a child 's environment , and comparison group children , whose families received customary care , usually 1 or 2 educational visits . Environmental sample s were collected at baseline and after 1 year of follow-up for intervention group children and compared with those of comparison group children , collected only at the end of study . RESULTS . During the follow-up period , parents of intervention group children ( n = 92 ) successfully decreased dust lead levels and significantly improved parent-child interaction and family housekeeping practice s compared with comparison group children ( n = 83 ) . Overall geometric mean BLLs declined by 47 % , and the difference in BLL by group was not significant ( 9 vs 8.3 μg/dL for intervention versus comparison group children , respectively . ) After 1 year , nearly half of enrolled children had BLLs ≥10 μg/dL. CONCLUSIONS . Until a reservoir of lead-safe housing is created , programs that educate families to reduce environmental exposure are needed . Although providing families with quantitative information regarding lead contamination may have a role in short-term efforts to prevent lead exposure , these null findings suggest that it has little benefit once BLLs are elevated BACKGROUND Thous and s of children , especially poor children living in deteriorated urban housing , are exposed to enough lead to produce cognitive impairment . It is not known whether treatment to reduce blood lead levels prevents or reduces such impairment . METHODS We enrolled 780 children with blood lead levels of 20 to 44 microg per deciliter ( 1.0 to 2.1 micromol per liter ) in a r and omized , placebo-controlled , double-blind trial of up to three 26-day courses of treatment with succimer , a lead chelator that is administered orally . The children lived in deteriorating inner-city housing and were 12 to 33 months of age at enrollment ; 77 percent were black , and 5 percent were Hispanic . Follow-up included tests of cognitive , motor , behavioral , and neuropsychological function over a period of 36 months . RESULTS During the first six months of the trial , the mean blood lead level in the children given succimer was 4.5 microg per deciliter ( 0.2 micromol per liter ) lower than the mean level in the children given placebo ( 95 percent confidence interval , 3.7 to 5.3 microg per deciliter [ 0.2 to 0.3 micromol per liter ] ) . At 36 months of follow-up , the mean IQ score of children given succimer was 1 point lower than that of children given placebo , and the behavior of children given succimer was slightly worse as rated by a parent . However , the children given succimer scored slightly better on the Developmental Neuropsychological Assessment , a battery of tests design ed to measure neuropsychological deficits thought to interfere with learning . All these differences were small , and none were statistically significant . CONCLUSIONS Treatment with succimer lowered blood lead levels but did not improve scores on tests of cognition , behavior , or neuropsychological function in children with blood lead levels below 45 microg per deciliter . Since succimer is as effective as any lead chelator currently available , chelation therapy is not indicated for children with these blood lead levels OBJECTIVE To test the hypothesis that a reduction of 1000 ppm or more of lead in soil accessible to children would result in a decrease of at least 0.14 mumol/L ( 3 micrograms/dL ) in blood lead levels . SETTING Urban neighborhoods with a high incidence of childhood lead poisoning and high soil lead levels . DESIGN R and omized controlled trial of the effects of lead-contaminated soil abatement on blood lead levels of children followed up for approximately 1 year after the intervention . PATIENTS A total of 152 children less than 4 years of age with venous blood lead levels of 0.34 to 1.16 mumol/L ( 7 to 24 micrograms/dL ) . Children were largely poor and had a mean age at baseline of 32 months , a mean blood lead level of 0.60 mumol/L ( 12.5 micrograms/dL ) , and a median surface soil lead level of 2075 ppm . INTERVENTIONS Children were r and omized to one of three groups : the study group , whose homes received soil and interior dust abatement and loose paint removal ; comparison group A , whose homes received interior dust abatement and loose paint removal ; and comparison group B , whose homes received only interior loose paint removal . MAIN OUTCOME MEASURES Change in children 's blood lead levels from preabatement levels to levels approximately 6 and 11 months after abatement . RESULTS The mean decline in blood lead level between preabatement and 11 months after abatement was 0.12 mumol/L ( 2.44 micrograms/dL ) in the study group ( P = .001 ) , 0.04 mumol/L ( 0.91 microgram/dL ) in group A ( P = .04 ) , and 0.02 mumol/L ( 0.52 microgram/mL ) in group B ( P = .31 ) . The mean blood lead level of the study group declined 0.07 mumol/L ( 1.53 micrograms/dL ) more than that of group A ( 95 % confidence interval [ CI ] , -0.14 to -0.01 mumol/L [ -2.87 to -0.19 micrograms/dL ] ) and 0.09 mumol/L ( 1.92 micrograms/dL ) more than group B ( 95 % CI , -0.16 to -0.03 mumol/L [ -3.28 to -0.56 micrograms/dL ] ) . When adjusted for preabatement lead level , the 11-month mean blood lead level was 0.06 mumol/L ( 1.28 micrograms/dL ) lower in the study group as compared with group A ( P = .02 ) and 0.07 mumol/L ( 1.49 micrograms/dL ) lower than in group B ( P = .01 ) . The magnitude of the decline independently associated with soil abatement ranged from 0.04 to 0.08 mumol/L ( 0.8 to 1.6 micrograms/dL ) when the impact of potential confounders , such as water , dust , and paint lead levels , children 's mouthing behaviors , and other characteristics , was controlled for . CONCLUSIONS These results demonstrate that lead-contaminated soil contributes to the lead burden of urban children and that abatement of lead-contaminated soil around homes results in a modest decline in blood lead levels . The magnitude of reduction in blood lead level observed , however , suggests that lead-contaminated soil abatement is not likely to be a useful clinical intervention for the majority of urban children in the United States with low-level lead exposure OBJECTIVES Parents need meaningful and actionable information if they are to reduce household environmental health risks to their children . To address this issue , we tested the effectiveness of a multi-risk social/cognitive intervention on rural low-income parents ' ( 1 ) environmental health self-efficacy and ( 2 ) stage of environmental health pre caution ary adoption . METHODS Biomarker ( lead , cotinine ) and household sample s ( carbon monoxide , radon , mold/mildew , and drinking water contaminants ) were collected from 235 families ( 399 adults , 441 children ) in Montana and Washington states . Families were r and omly assigned to intervention or control groups ; intervention families received 4 visits from public health nurses who provided tailored information and guidance to parents ; controls received usual and customary public health services . RESULTS At 3 months , the intervention group had significantly higher scores on ( 1 ) all 6 risk-specific self-efficacy subscales ( P < .01 ) , ( 2 ) general environmental health self-efficacy ( P < .001 ) , ( 3 ) 5 of 6 risk-specific pre caution adoption subscales ( P < .05 ) , and ( 4 ) general environmental health pre caution adoption ( P < .001 ) . CONCLUSIONS The intervention yielded significant improvements in both outcomes . This evidence supported the need for a policy discussion addressing the added value that broadbased public health nurse interventions might bring to children 's environmental health The changes in dust loading , lead loading and lead concentration , determined from vacuum sample s and wipe sample s collected during the Childhood Lead Exposure Assessment and Reduction Study ( CLEARS ) were analyzed to determine the efficacy of the cleaning protocol in homes of children found to have moderate lead poisoning , e.g. levels between 10 - 20 micrograms/dL. The sample s were collected at least twice , and in 65 homes three times , during the course of a year long intervention in homes where half were r and omized into a group which received a st and ardized Lead Intervention program for lead reduction , and the other homes only received an Accident Intervention program . The homes with lead burdened children were located in Hudson County , New Jersey ( primarily in Jersey City ) , and were referred to the CLEARS by a number of private and public sources . Each home had wipe sampling conducted with the LWW Sample r ( patented ) , and vacuum sampling was completed using a device described by Wang et al. in Applied Occupational and Environmental Hygiene . The results were compared in two ways : ( 1 ) between the two intervention groups , and ( 2 ) over the time course of the intervention period . When compared to the values seen in the first visit vacuum sampling results showed statistically significant decreases in lead loading and dust loading by the third sampling visit for the Lead Intervention homes . Substantial reductions in lead loading and dust loading were also seen when the Lead Intervention values were compared to values obtained in the Accident Intervention homes over the course of the year long intervention . The wipe sampling results for the 65 homes with three visits found no significant reductions in dust loading and lead loading among any of the room surfaces sample d in the Accident Intervention homes . There were 75 % and 50 % reductions observed on the window sills and on the bedroom floors of the homes which participated in the Lead Intervention . The levels in the living room and the kitchen showed very little change in loadings . This appeared to be due to the fact these rooms were near a background or baseline value of 0.3 g/cm2 and 0.12 mg/cm2 for dust loading and lead , respectively . This was substantiated by the window sills and bedroom wipe sampling results since each surface approached these values by the third visit . Significant reductions in lead concentrations found in the wipe sample s from the intervention homes appeared to be related to the absence of historically active sources of lead in these homes , rather than elimination of current sources . The results of the micro-environmental sampling program in CLEARS indicated that a year long cleaning protocol can significantly decrease lead levels in rugs and on other exposed surfaces . This will reduce the potential for exposure to lead among the occupants , especially children , that come in contact with such surfaces In 1994 a comprehensive program was established to reduce children 's blood lead levels in Broken Hill , NSW , Australia . Home remediation ( abatement of lead hazards in a child 's home ) was included as part of a case management strategy for children with blood lead levels > or=15 microg/dL. Children with blood lead levels > or=30 microg/dL were offered immediate home remediation . Children with blood lead levels of 15 - 29 microg/dL were allocated to ' immediate ' or ' delayed ' home remediation ; a subset of these participated in a r and omized controlled trial ( RCT ) to evaluate the effectiveness of home remediation for reducing blood lead levels . One hundred and seventeen children received home remediation . One hundred and thirteen returned for follow-up blood tests , 88 of whom participated in the RCT . On average children 's blood lead levels decreased by 1.7 microg/dL ( 10 % ) in the 6 months after remediation and by 2.2 microg/dL ( 13 % ) in the 6 - 12 months after remediation . However , remediation did not significantly change the rate of decline in blood lead levels ( P=0.609 ) . There was no evidence of association between change in children 's blood lead levels and changes in lead loading in their homes . The results are consistent with the published literature , which suggests that home remediation does not reduce children 's exposure to lead sufficiently to cause a moderate or greater decrease in their blood lead level . In communities where lead is widely dispersed , the study suggests that it is important to assess potential sources and pathways by which children are exposed to lead when developing an intervention plan , and the need for multiple interventions to effectively reduce blood lead levels . The findings reinforce the ongoing need for rigorous epidemiological evaluation of lead management programs to improve the evidence base , and for effective primary prevention to avoid children being exposed to lead in the first place This study was undertaken to determine whether home remediation effectively reduced indoor lead levels in Broken Hill , a long-established silver-lead-zinc mining town in outback Australia . A before-after study of the effect of home remediation on indoor lead levels was embedded into a r and omized controlled trial of the effectiveness of remediation for reducing elevated blood lead levels in young children . Moist towelettes were used to measure lead loading ( microg/m2 ) on internal windowsills and internal and entry floors of 98 homes ; sample s were collected before , immediately after , and 2 , 4 , 6 , 8 , and 10 months after remediation . Data were log(10 ) transformed for the analysis . Remediation reduced average indoor lead levels by approximately 50 % , and lead levels remained low for the duration of the follow-up period ( 10 months ) . The greatest gains were made in homes with the highest initial lead levels ; homes with low preremediation lead levels showed little or no benefit . Before remediation , homes located in areas with high soil lead levels or with " poor " dust proofing had higher lead levels than those in areas with lower soil lead levels or with " medium " or " good " dust proofing ; these relative differences remained after remediation . There was no evidence that lead loading was reduced by an increased opportunity to become aware of lead issues . We conclude that remediation is an effective strategy for reducing the lead exposure of children living in homes with high indoor lead levels This prospect i ve environmental intervention study was conducted to determine the impact of low-technology lead hazard reduction activities among children with mildly elevated blood lead levels . Children whose homes had severe lead hazards were automatically assigned to the intervention group . Children whose homes had lesser hazards were r and omly assigned to the intervention group or comparison group . The one-time intervention focused mainly on cleaning and repainting window areas and educating caregivers to maintain effective housekeeping techniques . Changes in blood lead and dust lead loading levels were observed following the interventions . Analysis of covariance was used to adjust comparisons of postintervention levels for preintervention levels and other variables . The lead hazard reduction activities were associated with a modest decline in blood lead levels among children with severe hazards . The magnitude of the decline depended on the confounder that was controlled ; the majority ranged from-1.1 . to-1.6 microgram/dL. A moderate reduction in window well dust lead loading levels was also observed . While low-technology lead hazard reduction measures appeared to be an effective secondary prevention strategy among children with severe household lead hazards , larger studies are needed to confirm these results OBJECTIVES The effect of abating soil lead was assessed among Baltimore children . The hypothesis was that a reduction of 1000 parts per million would reduce children 's blood lead levels by 0.14 to 0.29 mumol/L ( 3 - 6 micrograms/dL ) . METHODS In 2 neighborhoods ( study and control ) , 187 children completed the protocol . In the study area , contaminated soil was replaced with clean soil . RESULTS Soil lead abatement in this study did not lower children 's blood lead . CONCLUSIONS Although it did not show an effect in this study , soil lead abatement may be useful in certain areas The Boston Lead-In-Soil Demonstration Project was a r and omized environmental intervention study of the impact of urban soil lead abatement on children 's blood lead levels . Lead-contaminated soil abatement was associated with a modest reduction in children 's blood lead levels in both phases of the project ; however , the reduction in Phase II was somewhat greater than that in Phase I. The combined results from both phases suggest that a soil lead reduction of 2060 ppm is associated with a 2.25 to 2.70 micrograms/dl decline in blood lead levels . Low levels of soil recontamination 1 to 2 years following abatement indicate that the intervention is persistent , at least over the short-term . Furthermore , the intervention appears to benefit most children since no measurable differences in efficacy were observed for starting blood and soil lead level , race , neighborhood , gender , and many other characteristics . However , soil abatement did appear to be more beneficial to children in the higher socioeconomic classes , with low baseline ferritin levels , and who spent time away from home on a regular basis and lived in nonowner occupied housing , and with adults who had lead-related hobbies and almost always washed their h and s before meals . Children who lived in apartments with consistently elevated floor dust lead loading levels derived almost no benefit from the soil abatement . It was not possible to separate the effects of the variables that had a beneficial impact on efficacy because they were closely correlated and the number of subjects was small . We recommend that further research be conducted to identify subgroups of children to whom soil lead abatement might be targeted Objective . Screening children to identify those with blood lead levels ⩾10 μg/d fails to protect children from lead-associated cognitive deficits and behavioral problems . To broaden our efforts at primary prevention , screening criteria are needed to identify lead-contaminated housing before children are unduly exposed . The purpose of this study was to identify and vali date housing characteristics associated with children having elevated blood lead levels ( ⩾10 μg/dl ) . Methods . Two existing studies were used to examine housing characteristics linked with undue lead exposure : a cross-sectional study of 205 children aged 12 to 31 months , and a r and om sample from a longitudinal study of 276 children followed from 6 to 24 months of age . Logistic regression analysis was conducted to examine the association of children 's blood lead levels > 10 μg/dl . Results . The mean age of the 481 children was 17.8 months ; 99 ( 20.6 % ) had a blood lead concentration of 10 μg/dl or higher . The following characteristics were associated with blood lead concentration > 10 μg/dl : floor lead loading > 15 μg/ft2 ( odds ratio [OR]=2.2 ; 95 % confidence interval [ CI ] 1.3 , 3.8 ) ; rental housing ( OR=3.2 ; 95 % CI 1.3 , 7.6 ) ; poor housing condition ( OR=2.1 ; CI 1.2 , 3.6 ) ; African American race ( OR=3.3 ; CI 1.9 , 6.1 ) ; paint chip ingestion ( OR=5.8 ; CI 1.3 , 26.5 ) ; and soil ingestion ( OR=2.2 ; CI 1.1 , 4.2 ) . Housing characteristics including rental status , lead-contaminated floor dust , and housing condition had a range of sensitivity from 47 % to 92 % ; specificity from 28 % to 76 % ; a positive predictive value from 25 % to 34 % ; and a negative predictive value of 85 % to 93 % . Conclusions . Housing characteristics and floor dust lead levels can be used to screen housing to identify lead hazards prior to occupancy , before purchasing a home , or after renovation to prevent children 's exposure to lead hazards Blood lead data for a childhood lead exposure study have been reanalyzed to examine the impact of carpets on the effectiveness of a cleaning intervention in 39 New Jersey urban houses . All eligible houses in the study were classified as carpeted and uncarpeted depending on the number of rooms that were carpeted . The cleaning protocol was associated with a significant reduction in the blood lead concentrations for the uncarpeted homes ( P = 0.004 ) , whereas no significant change was found for the carpeted homes ( P = 0.566 ) . We also completed correlation analyses between the number of cleaning visits and the percentage reduction in blood lead for the carpeted/uncarpeted houses . There was a significant correlation ( r = 0.67 ) between the number of cleanings and blood lead reduction for the uncarpeted homes , but no correlation ( r = 0.04 ) for the carpeted homes . In a multiple regression model that took confounding variables into account , the carpet status ( carpeted or uncarpeted ) remained a factor of the effect of cleaning on blood lead ( P = 0.05 ) . We conclude that the presence of contaminated carpets inhibits the effectiveness of home cleaning despite a high-efficiency particulate air filtered vacuum protocol that removes a substantial amount of lead dust Objective . Lead exposure in children can lead to neuropsychological impairment . This study tested whether primary prevention interventions in the newborn period prevent elevated blood lead levels ( BLLs ) . Methods . The Philadelphia Lead Safe Homes ( LSH ) Study offered parental education , home evaluation , and lead remediation to the families of urban newborns . Households were r and omized to a st and ard lead education group or maintenance education group . We conducted home visits at baseline , six months , and 12 months . To compare BLLs , we identified a matched comparison group . Results . We enrolled and r and omized 314 newborns in the intervention component ; 110 completed the study . There were few significant differences between the r and omized groups . In the combined intervention groups , positive results on visual inspection declined from baseline to 12 months ( 97.0 % to 90.6 % , p=0.007 ) . At baseline , 36.9 % of homes were above the U.S. Environmental Protection Agency 's lead dust st and ard , compared with 26.9 % at 12 months ( p=0.032 ) , mainly due to a drop in windowsill dust levels . Both groups showed a significant increase in parental scores on a lead education test . Children in the intervention and matched control groups had similar geometric mean initial BLLs ( 2.6 vs. 2.7 , p=0.477 ) , but a significantly higher percentage of children in the intervention group had an initial blood lead screening compared with those in the matched group ( 88.9 % vs. 84.4 % , p=0.032 ) . Conclusions . A study of primary prevention of lead exposure showed a higher blood lead screening rate for the combined intervention groups and mean BLLs at one year of age not statistically different from the comparison group . Most homes had lead hazards . Lead education significantly increased knowledge |
10,787 | 27,353,220 | Major benefits were observed for reducing alcohol-associated injuries , recovery of ventricular heart function in alcoholic cardiomyopathy , blood pressure lowering , normalization of biochemical parameter , body weight reduction , histological improvement in pre-cirrhotic alcohol-related liver disease and slowed progression of an already existing alcohol-attributable liver fibrosis .
Furthermore , reduced withdrawal symptoms , prevalence of psychiatric episodes and duration of in-patient hospital days , improvement of anxiety and depression symptoms , self-confidence , physical and mental quality of life , fewer alcohol-related adverse consequences as well as lower psychosocial stress levels and better social functioning can result from reduced alcohol intake .
The review ed literature demonstrated remarkable socioeconomic cost benefits in areas such as the medical health-care system or workforce productivity .
Individuals with heightened vulnerability further benefit significantly from alcohol reduction ( e.g. hypertension , hepatitis C , psychiatric co-morbidities , pregnancy , but also among adolescents and young adults ) . | Based on the knowledge that alcohol misuse causes a multitude of diseases and increased mortality , this systematic review examines whether a reduction of the individual alcohol consumption can contribute to a minimization of health risks within a harm reduction approach . | We have examined the independent and combined effects on blood pressure and blood lipids of alcohol restriction and weight loss in overweight male drinkers with a view to assessing overall effects on cardiovascular risk of two widely promoted nonpharmacological approaches for hypertension . Eighty-six men with a mean age of 44.3 years , a mean regular alcohol intake of 440 ml/wk ( five or six st and ard drinks per day ) , a mean blood pressure of 137.4 mm Hg systolic and 84.8 mm Hg diastolic , and a mean body mass of 92.5 kg entered a controlled two-way factorial study . The subjects were r and omly assigned to four groups for an 18-week intervention in which members of two groups drank only low-alcohol beer , thereby reducing their alcohol intake by 374 ml/wk , while those of the other two groups continued their normal alcohol intake . Within the low and normal alcohol intake groups subjects either continued their usual diet or reduced their caloric intake by 4,200 - 6,300 kJ/day ( 1,000 - 1,500 kcal/day ) ( with protein , fat , and carbohydrate provided as 15 % , 30 % , and 55 % of total calories , respectively ) . Calorie reduction and alcohol restriction caused weight losses of 7.5 ( p less than 0.001 ) and 2.1 ( p less than 0.01 ) kg , respectively . Calorie reduction and alcohol restriction were associated with decreases in systolic blood pressure of 5.4 ( p less than 0.001 ) and 4.8 ( p less than 0.01 ) mm Hg , respectively , and in diastolic blood pressure of 4.2 ( p less than 0.001 ) and 3.3 ( p less than 0.01 ) mm Hg , respectively . ( ABSTRACT TRUNCATED AT 250 WORDS The aim of this study was to determine whether moderate restriction of dietary salt intake leads to an additional fall in blood pressure in treated hypertensive men who are asked to simultaneously reduce their usual alcohol intake . Sixty-three subjects entered an initial 2-week familiarization period during which they continued their usual alcohol intake and commenced a " low sodium " diet ( less than 60 mmol/day ) supplemented with 100 mmol sodium chloride per day as enteric-coated tablets . Subjects were then r and omly assigned to either drink a low alcohol beer alone for a 4-week period ( reducing their self-reported alcohol consumption from 537 to 57 ml/week ) or to continue their usual alcohol intake ( 543 versus 557 ml/week ) . Within the low and normal alcohol intake groups , subjects were assigned to either a low or normal sodium intake . The low sodium groups continued the sodium-restricted diet but were switched to placebo sodium chloride tablets for the 4 weeks . This result ed in a fall in the 24-hour urinary sodium excretion from 144 to 69 mmol/day . The normal sodium groups continued the low sodium diet but kept taking 100 mmol/day of the sodium chloride tablets , and their urinary sodium excretion remained unchanged ( 125 versus 142 mmol/day ) . Regular antihypertensive therapy was continued throughout . Fifty-nine subjects completed the trial . In those who reduced their alcohol intake there was a fall in both systolic blood pressure ( -5.4 mm Hg supine , p less than 0.01 ) and diastolic blood pressure ( -3.2 mm Hg supine , p less than 0.01 ) . ( ABSTRACT TRUNCATED AT 250 WORDS A direct pressor effect of alcohol is proposed as the basis for the association between regular alcohol consumption and an increase in blood pressure found in population studies . To examine this further , a r and omized controlled crossover trial of the effects of varying alcohol intake on blood pressure in 46 healthy male drinkers was conducted . From an average of 336 ml of ethanol per week , alcohol consumption was reduced by 80 % for 6 weeks by drinking a low alcohol content beer alone . This reduction was associated with a significant reduction in systolic and diastolic blood pressure ( p less than 0.001 and p less than 0.05 respectively ) . The mean difference in supine systolic blood pressure during the last 2 weeks of normal or low alcohol intake was 3.8 mm Hg , which correlated significantly with change in alcohol consumption ( r = 0.53 , p less than 0.001 ) . Reduction of alcohol intake also caused a significant decrease in weight ( p less than 0.001 ) . After adjustment for weight change , an independent effect of alcohol on systolic but not diastolic blood pressure was still evident , with a 3.1 mm Hg fall predicted for a decrease in consumption from 350 ml of ethanol equivalent per week to 70 ml per week ( p less than 0.01 ) . Systolic blood pressure rose again when normal drinking habits were resumed . These results provide clear evidence for a direct and reversible pressor effect of regular moderate alcohol consumption in normotensive men and suggest that alcohol may play a major role in the genesis of early stages of blood pressure elevation UNLABELLED Introduction Recent pharmacotherapy findings from new alcohol reduction programmes could change the paradigm of alcohol-dependence treatment . MATERIAL AND METHOD This study review s the neurobiological background and pharmacotherapy of alcohol-dependence disorder , focusing on opioid receptor antagonists , abstinence-oriented treatment and moderation-oriented treatment . RESULTS 1 . Alcohol-dependence treatment programs show only low to moderate efficacy . 2 . Patients usually show low motivation to sustain abstinence but high motivation to reduce alcohol use . 3 . A treatment program based on continued reduction of drinking and associated with intermittent treatment with naltrexone can be useful for low-severity alcohol-dependent patients . DISCUSSION Although high severity alcohol-dependent patients should stop drinking alcohol , low severity patients may have the option of reducing their alcohol consumption if they take an opioid antagonist medication every day that they decide to drink alcohol . In the short term , the continuing drinking-reduction programmes may reduce the number of drinks per drinking day and in the long term , they may progressively decrease the obsession for drinking , alcohol seeking behavior , and related medical , behavioral and social disorders . To change the paradigm in the treatment of alcohol-dependence disorder there is a need for further r and omized controlled trials in order to assess their efficacy and tolerability Objective : The aim of the present study was to conduct a cross-validation trial of the efficacy of a computerized school-based intervention for alcohol misuse in adolescents . Method : A cluster r and omized control trial was carried out . Intervention and control groups were assessed at baseline , immediately after and 6 months after the intervention . A total of 764 Year 8 students from 10 independent secondary schools in Sydney , Australia participated in the study . Half of the schools were r and omly allocated to the computerized prevention programme ( n=397 ) , and half to their usual classes ( n=367 ) . The six-lesson computerized intervention was evidence and curriculum based while having a focus on harm-minimization . Knowledge , expectancies , alcohol consumption ( frequency , quantity and binging ) , patterns of use , and harms associated with one 's own use of alcohol were assessed . Results : There were significant improvements in knowledge regarding alcohol use at immediate and 6 month follow up . Average weekly alcohol consumption was reduced immediately after the intervention . No differences between groups were found on alcohol expectancies , frequency of drinking to excess and harms related to alcohol use over time . Conclusions : The present results support the Climate Management and Treatment Education ( CLIMATE ) Schools : alcohol module as an effective intervention in increasing alcohol knowledge and reducing alcohol use in the short term AIMS To compare 5 year outcomes ( general hospital and mental health morbidity and mortality ) among general hospital psychiatric in- patients r and omized to receive either an alcohol reduction motivational interview ( MI ) or information pack ( IP ) , and compare these to matched controls . DESIGN We recruited 120 patients aged 18 - 64 years who scored > /=8 on the Alcohol Use Disorders Identification Test ( AUDIT ) . We selected matched controls from in- patients not recruited but who reached the same AUDIT threshold . At 5 years , follow-up data were collected via a state-wide hospital record system . FINDINGS There were no significant differences between the MI and IP groups in terms of ' survival ' to their first alcohol-related , other general hospital or mental health admission over 5 years . Matched controls had significantly more mental health in-patient episodes ( F[1,226 ] 4.4 , P < 0.05 ) and greater length of hospital stay ( F[1,226 ] 4.8 , P < 0.05 ) than the combined MI-IP group . Furthermore , the MI-IP group had longer ' survival ' times to both first general hospital ( mean 583 versus 392 days ) and mental health in-patient ( mean 788 versus 580 days ) events . Collapsed across groups , dependent and harmful consumers had shorter ' survival ' times than hazardous consumers ( AUDIT classifications ) . CONCLUSIONS Alcohol interventions have medium-term health benefits for those with mental health and alcohol use problems . Importantly , there were no differences in outcome between the intervention groups . The low cost of providing an IP makes it attractive as an alcohol intervention . The AUDIT provided an effective means of identifying those who are at risk of subsequent alcohol-related admissions and may benefit from intervention 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 AIMS The School Health and Alcohol Harm Reduction Project ( SHAHRP study ) aim ed to reduce alcohol-related harm in secondary school students . DESIGN The study used a quasi-experimental research design in which r and omly selected and allocated intervention and comparison groups were assessed at eight , 20 and 32 months after baseline . SETTING Metropolitan , government secondary schools in Perth , Western Australia . PARTICIPANTS The sample involved over 2300 students . The retention rate was 75.9 % over 32 months . INTERVENTION The evidence -based intervention , a curriculum programme with an explicit harm minimization goal , was conducted in two phases over a 2-year period . MEASURES Knowledge , attitude , total alcohol consumption , risky consumption , context of use , harm associated with own use and harm associated with other people 's use of alcohol . FINDINGS There were significant knowledge , attitude and behavioural effects early in the study , some of which were maintained for the duration of the study . The intervention group had significantly greater knowledge during the programme phases , and significantly safer alcohol-related attitudes to final follow-up , but both scores were converging by 32 months . Intervention students were significantly more likely to be non-drinkers or supervised drinkers than were comparison students . During the first and second programme phases , intervention students consumed 31.4 % and 31.7 % less alcohol . Differences were converging 17 months after programme delivery . Intervention students were 25.7 % , 33.8 % and 4.2 % less likely to drink to risky levels from first follow-up onwards . The intervention reduced the harm that young people reported associated with their own use of alcohol , with intervention students experiencing 32.7 % , 16.7 % and 22.9 % less harm from first follow-up onwards . There was no impact on the harm that students reported from other people 's use of alcohol . CONCLUSIONS The results of this study support the use of harm reduction goals and classroom approaches in school drug education Fifty-four untreated , mildly hypertensive men whose daily alcohol consumption was > or = 28 ml ethanol and who drank at least 4 times per week took part in a r and omized , controlled crossover trial . The purpose of the trial was to test the effects of alcohol reduction on blood pressure . After a 2-week familiarization period , the participants were assigned to either a reduced alcohol drinking group or a usual drinking group for 3 weeks ( experimental period 1 ) . The situation was then reversed for the next 3 weeks ( experimental period 2 ) . The participants were requested to limit their daily alcohol consumption to zero or reduce it as much as possible for the reduced alcohol consumption period . The self-reported alcohol consumption was 56.1 + /- 3.6 ( SEM ) ml/day during the usual alcohol drinking period and 26.1 + /- 3.0 ml/day during the period of reduced alcohol consumption . Systolic and diastolic blood pressures in the intervention group were found by analysis of variance to be significantly lower ( 2.6 - 4.8 and 2.2 - 3.0 mm Hg , respectively ) than those in the control group during experimental period 2 for systolic blood pressure and experimental period 1 for diastolic blood pressure . Significant ( 3.6 mm Hg ) and nonsignificant ( 1.9 mm Hg ) decreases in systolic and diastolic blood pressure , respectively , were observed . The method of Hills and Armitage was used , reducing ethanol in daily alcohol consumption by 28 ml . The lowering effect of reduced alcohol consumption on blood pressure was independent of changes in salt consumption , which were estimated by 24-hour urine collection and body weight . ( ABSTRACT TRUNCATED AT 250 WORDS 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 BACKGROUND Polyenylphosphatidylcholine ( PPC ) has been shown to prevent alcoholic cirrhosis in animals . Our aims were to determine the effectiveness of PPC in preventing or reversing liver fibrosis in heavy drinkers and to assess the extent of liver injury associated with the reduced drinking achieved in these patients . METHODS This r and omized , prospect i ve , double-blind , placebo-controlled clinical trial was conducted in 20 Veterans Affairs Medical Centers with 789 patients ( 97 % male ; mean age , 48.8 years ) averaging 16 drinks per day ( 1 drink = 14 g of alcohol ) for 19 years . A baseline liver biopsy confirmed the presence of perivenular or septal fibrosis or incomplete cirrhosis . They were r and omly assigned either PPC or placebo . Liver biopsy was repeated at 24 months , and the main outcome measure was the stage of fibrosis compared with baseline . Progression was defined as advancing to a more severe stage . RESULTS The 2-year biopsy was completed in 412 patients . PPC did not differ significantly from placebo in its effect on the main outcome . Alcohol intake was unexpectedly reduced in both groups to approximately 2.5 drinks per day . With this intake , 21.4 % advanced at least one stage ( 22.8 % of PPC patients and 20.0 % of placebo patients ) . The hepatitis C virus-positive subgroup exhibited accelerated progression . Improvement in transaminases and bilirubin favoring PPC was seen at some time points in other subgroups ( hepatitis C virus-positive drinkers or heavy drinkers ) . CONCLUSIONS PPC treatment for 2 years did not affect progression of liver fibrosis . A trend in favor of PPC was seen for transaminases and bilirubin ( in subgroups ) . One of five patients progressed even at moderate levels of drinking , and thus health benefits commonly associated with moderate drinking do not necessarily extend to individuals in the early stages of alcoholic liver disease OBJECTIVE The objective of this study was to investigate the association of 4-year changes in alcohol consumption with a subsequent risk of type 2 diabetes . RESEARCH DESIGN AND METHODS We prospect ively examined 38,031 men from the Health Professionals Follow-Up Study who were free of diagnosed diabetes or cancer in 1990 . Alcohol consumption was reported on food frequency question naires and up date d every 4 years . RESULTS A total of 1,905 cases of type 2 diabetes occurred during 428,497 person-years of follow-up . A 7.5 g/day ( approximately half a glass ) increase in alcohol consumption over 4 years was associated with lower diabetes risk among initial nondrinkers ( multivariable hazard ratio [ HR ] 0.78 ; 95 % CI : 0.60–1.00 ) and drinkers initially consuming < 15 g/day ( HR 0.89 ; 95 % CI : 0.83–0.96 ) , but not among men initially drinking ≥15 g/day ( HR 0.99 ; 95 % CI : 0.95–1.02 ; Pinteraction < 0.01 ) . A similar pattern was observed for levels of total adiponectin and hemoglobin A1c , with a better metabolic profile among abstainers and light drinkers who modestly increased their alcohol intake , compared with men who either drank less or among men who were already moderate drinkers and increased their intake . Likewise , compared with stable light drinkers ( 0–4.9 g/day ) , light drinkers who increased their intake to moderate levels ( 5.0–29.9 g/day ) had a significantly lower risk of type 2 diabetes ( HR 0.75 ; 95 % CI : 0.62–0.90 ) . CONCLUSIONS Increases in alcohol consumption over time were associated with lower risk of type 2 diabetes among initially rare and light drinkers . This lower risk was evident within a 4-year period following increased alcohol intake 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 Recognizing the need to offer alternative methods of brief interventions , this study developed correspondence treatments for low-dependent problem drinkers and evaluated their impact . One hundred and twenty-one problem drinkers were recruited by media advertisements and were r and omly allocated to a full cognitive-behavioural treatment programme ( CBT ) or to a minimal intervention condition ( MI ) that gave information regarding alcohol misuse and instructions to record drinking++ . As predicted , CBT was more effective than MI in reducing alcohol consumption over the 4-month controlled trial period . CBT produced a 50 % fall in consumption , bringing the average intake of subjects within recommended maximum levels . Treatment gains at 6 months were well maintained to 12 months . High levels of consumer satisfaction , a high representation of women and a substantial participation from isolated rural areas attested to the feasibility of the correspondence programme as an alternative treatment . However , some drinking occasions still involved high intake for a significant subgroup of subjects , and this issue will be addressed in future programmes . The results supported the use of correspondence delivery as a means of promoting early engagement and equity of access between city and country areas Alcoholics from two hospital-based treatment centers participated in an experimental test of the effects of extended aftercare on inpatient recovery rates . At discharge from inpatient treatment , subjects were r and omly assigned either to an experimental group scheduled to be called by a center counselor every 2 weeks for 1 year or to a control group that experienced only the usual treatment . Follow-up interviews conducted approximately 12 months after hospital discharge found that the experimental group had no higher recovery rates than the control group . There was weak evidence that the calls reduced the burden that alcoholics place on community control and service agencies . There was no evidence that either the phone calls were more effective for some patients than for others or that some kinds of phone calls were more effective than others . Although most subjects said they liked the calls , wanted them to continue and perceived them as " good treatment , " only one subject gave the calls credit for helping him maintain sobriety 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 OBJECTIVE To determine whether blood pressure is reduced for at least 6 months with an intervention to lower alcohol intake in moderate to heavy drinkers with above optimal to slightly elevated diastolic blood pressure , and whether reduction of alcohol intake can be maintained for 2 years . DESIGN A r and omized controlled trial . METHODS Six hundred forty-one outpatient veterans with an average intake of 3 or more alcoholic drinks per day in the 6 months before entry into the study and with diastolic blood pressure 80 to 99 mm Hg were r and omly assigned to a cognitive-behavioral alcohol reduction intervention program or a control observation group for 15 to 24 months . The goal of the intervention was the lower of 2 or fewer drinks daily or a 50 % reduction in intake . A subgroup with hypertension was defined as having a diastolic blood pressure of 90 to 99 mm Hg , or 80 to 99 mm Hg if recently taking medication for hypertension . RESULTS Reduction in average weekly self-reported alcohol intake was significantly greater ( P<.001 ) at every assessment from 3 to 24 months in the intervention group vs the control group : levels declined from 432 g/wk at baseline by 202 g/wk in the intervention group and from 445 g/wk by 78 g/wk in the control group in the first 6 months , with similar reductions after 24 months . The intervention group had a 1.2/0.7-mm Hg greater reduction in blood pressure than the control group ( for each , P = .17 and P = .18 ) for the 6-month primary end point ; for the hypertensive stratum the difference was 0.9/0.7 mm Hg ( for each , P = .58 and P = .44 ) . CONCLUSIONS The 1.3 drinks per day average difference between changes in self-reported alcohol intake observed in this trial produced only small nonsignificant effects on blood pressure . The results from the Prevention and Treatment of Hypertension Study ( PATHS ) do not provide strong support for reducing alcohol consumption in nondependent moderate drinkers as a sole method for the prevention or treatment of hypertension 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 BACKGROUND Few studies have examined whether changes in alcohol consumption influence future cardiovascular risk . OBJECTIVE To examine whether 7-year changes in alcohol consumption are associated with the subsequent risk of cardiovascular disease ( CVD ) . METHODS We prospect ively followed up 18,455 men aged 40 to 84 years from the Physicians ' Health Study with no history of CVD or cancer . Alcohol consumption was reported on the baseline and the 7-year question naires ; follow-up for this analysis began after the 7-year question naire ( median follow-up , 5.8 years ) . There were 1091 CVD cases , including myocardial infa rct ion , angina pectoris , revascularization , stroke , and CVD-related death . RESULTS Among men initially consuming 1 drink per week or less ( n=7360 ) , those with moderate increases ( > 1 to < 6 drinks per week ) in alcohol consumption had a borderline significant ( P=.05 ) 29 % reduced risk of CVD compared with men with no changes ( -1 to 1 drink per week ) . Among men initially consuming greater than 1 to 6 drinks per week ( n=6612 ) , those with moderate increases had a nonsignificant ( P=.32 ) 15 % decrease in CVD risk compared with men with no changes . Finally , among men initially consuming 1 drink per day or more ( n=4483 ) , those who increased intake had a 63 % increased risk of CVD compared with men with no changes . CONCLUSIONS These prospect i ve data suggest that , among men with initially low alcohol consumption ( < /=1 drink per week ) , a subsequent moderate increase in alcohol consumption may lower their CVD risk . The possible reduction in CVD risk from increasing alcohol intake did not extend to men initially consuming greater than 1 drink per week . Given the potential risks and benefits associated with alcohol consumption , physician counseling of patients must be individualized in the context of the primary prevention of CVD 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 In 1980 , 89,538 U.S. women 34 to 59 years of age , with no history of cancer , completed an independently vali date d dietary question naire that included the use of beer , wine , and liquor . During the ensuring four years , 601 cases of breast cancer were diagnosed among cohort members . Among the women consuming 5 to 14 g of alcohol daily ( about three to nine drinks per week ) , the age-adjusted relative risk of breast cancer was 1.3 ( 95 percent confidence limits , 1.1 and 1.7 ) . Consumption of 15 g of alcohol or more per day was associated with a relative risk of 1.6 ( 95 percent confidence limits , 1.3 and 2.0 ; Mantel extension chi for linear trend = + 4.2 ; P less than 0.0001 ) . Adjustment for known breast cancer risk factors and a variety of nutritional variables did not material ly alter this relation . Significant associations were observed for beer and liquor when considered separately . Among women without risk factors for breast cancer who were under 55 years of age , the relative risk associated with consumption of 15 g of alcohol or more per day was 2.5 ( 95 percent confidence limits , 1.5 and 4.2 ) . These prospect i ve data derived from measurements of alcohol intake recorded before the diagnosis of breast cancer confirm the findings of several previous case-control studies . Viewed collectively , they suggest that alcohol intake may contribute to the risk of breast cancer BACKGROUND University students drink more heavily than their nonstudent peers and are often unaware that their drinking is risky and exceeds normative levels . We tested the efficacy of a proactive Web-based alcohol screening and brief intervention program . METHODS A r and omized controlled trial was conducted at an Australian university in 2007 . Invitations were sent to 13 000 undergraduates ( age range , 17 - 24 years ) to complete a Web-based Alcohol Use Disorders Identification Test . Of 7237 students who responded , 2435 scored in the hazardous/harmful range ( > or = 8) and were r and omized , and 2050 ( 84 % ) completed at least 1 follow-up assessment . Intervention was 10 minutes of Web-based motivational assessment and personalized feedback . Controls received only screening . Follow-up assessment s were conducted at 1 and 6 months with observers and participants blinded to allocation . Outcome measures were drinking frequency , typical occasion quantity , overall volume , number of personal problems , an academic problems score , prevalence of binge drinking , and prevalence of heavy drinking . RESULTS Mean ( SD ) baseline Alcohol Use Disorders Identification Test scores for control and intervention groups were 14.3 ( 5.1 ) and 14.2 ( 5.1 ) , respectively . After 1 month , participants receiving intervention drank less often ( rate ratio [ RR ] , 0.89 ; 95 % confidence interval [ CI ] , 0.83 - 0.94 ) , smaller quantities per occasion ( RR , 0.93 ; 95 % CI , 0.88 - 0.98 ) , and less alcohol overall ( RR , 0.83 ; 95 % CI , 0.78 - 0.90 ) than did controls . Differences in alcohol-related harms were nonsignificant . At 6 months , intervention effects persisted for drinking frequency ( RR , 0.91 ; 95 % CI , 0.85 - 0.97 ) and overall volume ( RR , 0.89 ; 95 % CI , 0.82 - 0.96 ) but not for other variables . CONCLUSION Proactive Web-based screening and intervention reduces drinking in undergraduates , and such a program could be implemented widely PURPOSE Restriction of alcohol intake is widely recommended in the treatment of hypertension . However , we have observed that alcohol may have biphasic effects on blood pressure in Japanese men with hypertension . METHODS Hypertensive men ( n = 34 ) who habitually drank alcohol were r and omly assigned to keep their drinking habits constant for 4 weeks , or to abstain ( or reduce alcohol intake to a maximum of 15 mL/day ) for 4 weeks in a crossover design . Amount of alcohol intake was recorded by each patient throughout the study . Office and 24-hour ambulatory blood pressure were measured at the end of both periods . RESULTS After alcohol restriction , mean ( + /-SD ) ethanol intake decreased from 66+/-26 mL/day to 11+/-10 mL/day . Office systolic blood pressure decreased slightly from 142+/-12 mm Hg to 139+/-11 mm Hg , and diastolic blood pressure decreased significantly from 95+/-7 mm Hg to 93+/-7 mm Hg in the low-alcohol period . Daytime systolic blood pressure fell by 3+/-9 mm Hg ( P < 0.05 ) , but nighttime systolic blood pressure rose by 4+/-9 mm Hg ( P < 0.05 ) with restriction of alcohol intake . Thus , average 24-hour blood pressure did not change , although 24-hour heart rate and day-night difference in blood pressure decreased significantly in the low-alcohol period . CONCLUSION In Asian men with hypertension , restriction of alcohol intake reduces daytime blood pressure but not night-time or 24-hour blood pressure Objective To evaluate the effects of patterns of drinking ( weekend versus daily drinking ) on the pressor responses to alcohol in 55 male drinkers using clinic and 24 h ambulatory blood pressure monitoring . Design A r and omized , controlled cross-over trial . Methods Recruitment required a regular alcohol intake of 210–500 ml absolute alcohol/week , with > 60 % consumed as beer . Fourteen subjects were categorized as predominantly weekend drinkers , whereas the remaining 41 subjects regularly drank on a daily basis . After 4 weeks of familiarization , all subjects were r and omly allocated to drinking low-alcohol beer ( 0.9 % vol : vol ) only or to maintain their usual drinking habits with provision of full-strength beer ( 5 % vol : vol ) for 4 weeks . They then switched back to their usual drinking habits or low-alcohol beer , respectively , for a further 4 weeks while maintaining their usual drinking pattern . Results Baseline ambulatory systolic blood pressure in weekend but not in daily drinkers was 2.4 mmHg higher on Monday than it was on Thursday ( P = 0.02 ) . This Monday-Thursday difference was lost during intervention . When subjects switched from the high-alcohol to the low-alcohol period the falls in ambulatory systolic blood pressure in weekend ( 3.1 mmHg , P < 0.001 ) and daily drinkers ( 2.2 mmHg , P < 0.001 ) were similar . Most of the fall was evident during week 1 of the low-alcohol period for weekend drinkers but not until week 4 for daily drinkers . Conclusion The pressor response to alcohol consumption is similar in magnitude in weekend and daily drinkers , present throughout a 24 h period and has a rapid onset/offset in weekend drinkers but is more sustained in daily drinkers Please cite this paper as : Robinson M , Oddy W , McLean N , Jacoby P , Pennell CE , de Klerk N , Zubrick S , Stanley F , Newnham J. Low – moderate prenatal alcohol exposure and risk to child behavioural development : a prospect i ve cohort study . BJOG 2010;117:1139–1152 The patterns of drinking and variations in blood pressure and gamma-glutamyl transferase ( GGT ) by day of examination have been examined in a large prospect i ve study of cardiovascular disease in 7,735 middle-aged men drawn from general practice s in 24 British towns . Overall , mean systolic and diastolic BP levels , as well as the prevalence of measured hypertension , were significantly higher on Mondays and lower on Fridays than on other weekdays . Among occasional , moderate weekend ( 3 - 6 ) and heavy weekend ( greater than 6 drinks/day ) drinkers , although mean BPs were higher in the heavier drinkers , there was little variation in BP from Monday to Thursday in these groups . In all three groups there was a significant fall in mean BP and in the prevalence of hypertension on Friday , more apparent for systolic than for diastolic pressure and more marked in older men . Among daily drinkers , BP tended to be high on Mondays but was not particularly low on Fridays . Heavy weekend drinkers had higher daily BPs than moderate daily drinkers except on a Friday , even though the estimated total weekly intake was similar . The variations in BP by day of examination were not mirrored by changes in GGT concentrations . The different effect of daily and weekend patterns of drinking on BP may explain some of the discrepancies observed between different alcohol-blood pressure studies . Findings from this study have important implication s for the detection of hypertension in population s as well as for clinical practice 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 AIMS Hazardous alcohol use is a leading cause of death among adolescents and young adults world-wide , yet few effective prevention interventions exist . This study was the first to examine a computerized harm minimization intervention to reduce alcohol misuse and related harms in adolescents . DESIGN Cluster r and omized controlled trial of a six-session curriculum-integrated harm minimization prevention program . The intervention was delivered by computer in the form of a teenage drama , which provided education through alcohol-related scenarios to which young people could relate . SETTING Schools in Australia . PARTICIPANTS A total of 1466 year 8 students ( 13 years ) from 16 high schools in Australia were allocated r and omly to a computerized prevention program ( n = 611 , eight schools ) or usual classes ( n = 855 , eight schools ) . MEASUREMENTS Change in knowledge , alcohol use , alcohol-related harms and alcohol expectancies . FINDINGS A computerized prevention program was more effective than usual classes in increasing alcohol-related knowledge of facts that would inform safer drinking choices and decreasing the positive social expectations which students believed alcohol may afford . For females it was effective in decreasing average alcohol consumption , alcohol-related harms and the frequency of drinking to excess ( more than four st and ard drinks ; 10 g ethanol ) . For males the behavioural effects were not significant . CONCLUSIONS A harm minimization approach is effective in educating young people about alcohol-related risks and is effective in reducing risky drinking and harms among girls . Reduction of problems among boys remains a challenge 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 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 151 problem drinkers ( 105 men and 46 women ) were recruited from the general medical and psychiatric services of a district general hospital and were allocated r and omly to a community-based day centre ( ACCEPT ) or st and ard hospital inpatient and outpatient services . 115 patients ( 79 % ) were followed up at 12 months . The group as a whole showed improvement in all outcome indices at the 3-month follow-up , and this was maintained at 6 and 12 months . Patients assigned to ACCEPT services cl aim ed to have reduced their alcohol intake ( 55 % ) more than their hospital counterparts ( 37 % ) , and this was confirmed by their informants . Patients referred from the psychiatric services reduced their alcohol intake more than those from general medical services . It is concluded that treatment at a community day centre is at least as cost effective as hospital treatment of alcohol abuse OBJECTIVES --To improve blood pressure control among hypertensive ( > 140/90 mmHg ) excessive alcohol drinkers . DESIGN --Fourteen worksite physicians were r and omised onto an intervention group and a control group . The intervention was based on training the worksite physicians and follow up of those hypertensive subjects defined as excessive drinkers . Follow up was based on self monitoring of alcohol consumption by the subject , in view of the results of their gamma glutamyl transferase ( GGT ) activity determination . SETTING --Fourteen workplaces in France - mainly in the industrial sector . SUBJECTS -- Altogether 15 301 subjects were screened by the 14 physicians : 129 of these were included in the study . MAIN OUTCOME MEASURES --This was the difference between the initial systolic blood pressure ( SBP ) and the SBP one year later ( delta BP ) . Secondary criteria were the difference between the initial and final diastolic blood pressure ( delta DBP ) and delta BP at two years ; antihypertensive treatment ; state alcohol consumption ( delta AC ) ; delta GGT ; and body mass index ( delta BMI ) . RESULTS --The decrease in SBP levels was significantly larger in the intervention group than in the control group : at one year , delta SBP values were -11.9 ( 15.6 ) mmHg and -4.6 ( 13.8 ) respectively ( p < 0.05 ) . This benefit was still observed after two years of follow up ( -13.8 ( 17.4 ) mmHg v -7.5 ( 14.2 ) mmHg ( p < 0.05 ) ) . No difference was observed in DBP . The percentage of treated subjects did not differ between groups . At one year , delta AC was larger in the intervention group ( -2.8 ( 5.2 ) U/d ) than in the control group ( -1.6 ( 3.4 ) ( p < 0.1 ) ) . delta GGT and delta BMI did not differ between the two groups . A weak positive correlation was observed between delta AC and delta SBP ( r = 0.16 ) . CONCLUSION --An intervention aim ed at the hypertensive excessive drinkers in a working population was found to be effective in reducing SBP on a long term basis ( two years ) . The mechanisms of reduction in alcohol consumption and improved drug compliance can not be ascertained in this pragmatic study . From a public health point of view , reducing the excess cardiovascular risk among a " hard to reach " population seems feasible with a strategy specifically design ed for this high risk group A r and omised double-blind trial of (+)-cyanidanol-3(Catechin ) , 2 g/day versus placebo , was carried out in 40 patients with pre-cirrhotic alcohol-related liver disease over a three month period . Twenty received the active drug and 20 placebo ; one non-compliant patient in the treatment group was withdrawn . Forty-one per cent ( 16/39 ) abstained from alcohol and showed significant improvements ( P < 0.005 ) in mean values for serum aspartate transaminase , serum gamma glutamyl transpeptidase , and mean corpuscular volume . Ten of the 16 showed overall histological improvement on liver biopsy . Fifty-nine pr cent ( 23/39 ) continued to drink , though significantly reducing their mean daily alcohol intake ( P < 0.001 ) . No significant changes occurred in this group in mean serum enzyme values , though the mean value for mean corpuscular volume improved significantly ( P < 0.01 ) and 16 of the 23 showed overall histological improvement . Changes occurred irrespective of treatment with Catechin which suggests that , over a three month period , this drug did not influence the course of alcohol-related liver disease 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 To date , the published controlled trials on exposure to alcohol cues have had an abstinence treatment goal . A modification of cue exposure ( CE ) for moderation drinking , which incorporated priming doses of alcohol , could train participants to stop drinking after 2 to 3 drinks . This study examined the effects of modified CE within sessions , combined with directed homework practice . Nondependent problem drinkers who requested a moderation drinking goal were r and omly allocated to modified CE or st and ard cognitive-behavior therapy ( CBT ) for alcohol abuse . Both interventions were delivered in 6 90-min group sessions . Eighty-one percent of eligible participants completed treatment and follow-up assessment . Over 6 months , CE produced significantly greater reductions than CBT in participants ' reports of drinking frequency and consumption on each occasion . No pretreatment variables significantly predicted outcome . The modified CE procedure appears viable for nondependent drinkers who want to adopt a moderate drinking goal 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 Objectives To determine whether vigorous exercise and alcohol restriction have additive and independent effects in reducing blood pressure in sedentary male alcohol drinkers . Also to assess whether 4 weeks of vigorous exercise could offset the fall in high-density lipoprotein cholesterol ( HDL-cholesteroI ) usually observed after alcohol restriction . Design Seventy-five sedentary men were r and omly assigned to drink low-alcohol beer or continue their normal drinking habits . Within these two groups subjects were further assigned either to a vigorous exercise programme of three 30-min sessions a week of cycling at 60 - 70 % of maximum workload or to a control light-exercise programme . Results Seventy-two subjects completed the trial . Alcohol consumption fell by 85 % in the low-alcohol group . Fitness increased by 10 % following vigorous exercise , with a significant improvement in maximum oxygen uptake . After adjustment for weight loss , a significant effect of alcohol restriction in reducing both systolic and diastolic blood pressure was demonstrated . There was no effect of vigorous exercise on blood pressure . Serum total cholesterol , low-density lipoprotein cholesterol and apolipoprotein B were not influenced by alcohol restriction or vigorous exercise . However , alcohol restriction significantly reduced triglyceride , HDL-cholesteroI , its subfractions HDL2-cholesterol and HDL3-cholesterol , and its major apolipoproteins apo A-l and apo A-ll . These reductions were unaffected by moderate exercise . Conclusions This study provides further evidence that alcohol restriction results in reductions in blood pressure in men who are regular alcohol drinkers . However , a simultaneous increase in fitness did not lead to lower blood pressures than those achieved with alcohol restriction alone , and was unable to offset alcohol-related falls in HDL-cholesteroI , its subfractions and its major apolipoproteins It is known that moderation of alcohol intake reduces blood pressure , although the exact mechanism has not yet been established . To clarify the hypotensive mechanism of alcohol reduction , we evaluated the change in cellular magnesium and sodium metabolism during alcohol reduction in mild hypertensive patients . We measured intraerythrocyte sodium and magnesium , intraplatelet free magnesium concentrations , and erythrocyte ouabain-sensitive 22Na efflux rate constant ( Kos ) in 17 mild essential hypertensive patients regularly consuming more than 40 g/day of alcohol , before and after 4 weeks of alcohol reduction , and 12 age-matched nondrinking hypertensives . Intraerythrocyte magnesium ( P < .01 ) and intraplatelet free magnesium ( P < .05 ) concentrations were significantly lower in drinkers than in nondrinkers . In drinkers , advice to reduce alcohol intake for 4 weeks result ed in a reduction in self-reported alcohol consumption from 461.7 to 71.6 g/week , a significant fall in both supine systolic blood pressure ( 136.3 + /- 10.8 to 130.8 + /- 11.3 mm Hg , P < .001 ) and supine diastolic blood pressure ( 85.1 + /- 8.6 to 82.6 + /- 8.7 mm Hg , P < .05 ) . The fall in mean blood pressure correlated positively with the reduction in weekly alcohol consumption . Intraerythrocyte magnesium and Kos were increased ( P < .05 , P < .01 , respectively ) , while intraerythrocyte sodium was decreased ( P < .01 ) . The increase in intraerythrocyte magnesium correlated negatively with the fall in mean blood pressure and positively with the increase in Kos , which correlated negatively with the decrease in intraerythrocyte sodium . ( ABSTRACT TRUNCATED AT 250 WORDS AIMS To evaluate the effectiveness of a brief intervention in hospitalized Taiwanese men to reduce unhealthy alcohol consumption . DESIGN R and omized controlled trial . SETTING Medical/surgical wards of a medical centre in Taipei , Taiwan . PARTICIPANTS Of 3669 consecutive adult male in- patients , 616 were identified as unhealthy alcohol users ( > 14 drinks/week ) and assigned r and omly to either usual care ( n = 308 ) or a brief intervention ( n = 308 ) . MEASUREMENTS Primary outcomes were changes in alcohol consumption at 4 , 9 and 12 months , including self-reported weekly alcohol consumption , drinking days and heavy drinking episodes assessed by 7-day time-line follow-back . Secondary outcomes were ( i ) self-reported alcohol problems , ( ii ) health-care utilization ( hospital days and emergency department visits ) , ( iii ) self-reported seeking of speciality treatment for alcohol problems and ( iv ) 3-month Quick Drinking Screen . FINDINGS Based on intention-to-treat analyses , the intervention group consumed significantly less alcohol than the control group among both unhealthy drinkers and the subgroup of alcohol-dependent participants over 12 months , on both 7-day and 3-month assessment s. Adjunctive analyses of only those who completed all assessment s found that total drinks consumed did not remain significant . Significantly more participants with alcohol use disorders in the intervention than in the control group ( 8.3 % , 19 of 230 versus 2.1 % , four of 189 ) consulted specialists by 12 months ( P = 0.01 ) . However , alcohol-related problems and health-care utilization did not differ significantly in the two groups during follow-up . CONCLUSIONS Data from Taiwan confirm that brief in-hospital intervention can result in a reduction in alcohol intake by men who drink heavily or are diagnosed with an alcohol use disorder AIMS The aim of this study was to evaluate long-term outcomes in alcohol-dependent patients following outpatient treatment and gender differences in drinking outcome and mortality . METHODS A 20-year longitudinal prospect i ve study was done with interim analyses at 1 , 5 and 10 years . Of the original sample of 850 patients , 767 ( 90 % ) were located 20 years later and 393 of these were interviewed . 273 ( 32 % ) patients died during the intervening period and 101 ( 12 % ) no longer wished to participate in the study . Drinking status was assigned based on the 12 months prior to the follow-up interview . RESULTS At the 20-year follow-up , 277 ( 32.6 % ) of the 393 patients for whom drinking status could be assigned were abstinent ( defined never drinking or drinking on less than occasion per month and never more than four drinks/drinking occasion . ) , 29 ( 3.4 % ) were controlled drinkers and 87 ( 10.2 % ) were heavy drinkers . Controlled drinking was the least stable category , with 23 % continuing from year 5 to year 10 in that category , and 10 % continuing in that category from year 10 to year 20 . Mortality was higher ( 39.1 % ) in those who had been categorized at year 5 as heavy drinkers compared to those who had been categorized as controlled drinkers or abstinent . Abstinent patients reported fewer alcohol-related problems and better psychosocial functioning than heavy drinkers . Women achieved higher abstinence rates ( 47.2 % versus 29.0 % , P = 0.005 ) and had lower mortality ( 22.4 % versus 34.5 % , P = 0.03 ) than men . CONCLUSIONS Over the long-term , abstinence is the most frequent and stable drinking outcome achieved and is associated with fewer problems and better psychosocial functioning . Controlled drinking is rarely achieved and sustained . Women appear to do better than men in the long term |
10,788 | 27,855,334 | There is insufficient investigation of protective factors to adequately guide prevention initiatives . | This systematic review aim ed to identify early risk and protective factors ( in childhood , adolescence or young adulthood ) longitudinally associated with the subsequent development of gambling problems . | Abstract From an eligible population of 9,943 casino employees , 6,067 volunteered to participate in this study . Of this sample , 1,176 provided data at 3 observation points approximately 12 months apart . Using the South Oaks Gambling Screen ( SOGS ; H. R. Lesieur & S. B. Blume , 1987 ) and the CAGE ( J. A. Ewing , 1984 ) question naire , the authors prospect ively examined the prevalence and patterns of alcohol and gambling problems among those employees . Among the casino employees with gambling and drinking problems , a segment displayed the capacity to diminish those problems even when the difficulties had reached disordered levels . The authors also examined the comorbidity of gambling and drinking as well as the relationships among changes in SOGS scores and CAGE scores and changes in demographic and biological variables . The women were more likely to decrease their problem-drinking scores , but not their gambling scores , when compared with the men . In addition , 2 key variables ( i.e. , disabling depression and dissatisfaction with one 's personal life ) emerged as predictors of transitions to healthier levels of disordered gambling . The authors cautiously suggest , in light of the results taken together , that more fluctuation is associated with gambling and drinking problems than previously thought and that the conventional wisdom about disordered gambling as “ always progressive ” needs reconsideration Youth gambling was investigated in a prospect i ve sample of 532 Minnesota adolescents and young adults . Of particular interest was the possible impact among the study sample of a recent state lottery and of reaching the legal age for gambling on changes in the rate and type of gambling . Overall rates of gambling involvement and pathological gambling did not change across the 1.5 year interval . However , a preference for certain types of gambling activities ( e.g. , lottery , casino machines ) significantly increased , whereas more informal and unregulated games ( e.g. , betting on games of personal skill ) significantly decreased . Also , access to gambling activities by underage youths was high , suggesting the need for tighter controls of legalized games and greater awareness of this problem by the gaming industry and public health officials A r and om telephone survey was conducted with a representative sample of 2,274 U.S. residents aged 14–21 . The prevalence of problem gambling , as measured by the SOGS-RA , was 2.1 % . Sixty-eight percent ( 68 % ) of the respondents had gambled in the past year , and 11 % had gambled more often than twice per week . Males had much higher gambling involvement than females , and gambling involvement increased among older respondents . Blacks were less likely than average to have gambled in the past year , but if they gambled , they were more likely to do so frequently . Low SES respondents were less likely to have gambled in the past year , but if they gambled , they were more likely to be problem gamblers . Life transitions that are associated with assuming adult roles ( employment , living independently of parents , non-student status ) are also associated with greater gambling involvement . The rates of problem and pathological gambling were lower than those in an adult survey conducted earlier , when measured with the same question naire UNLABELLED Previous survey research with both clinical population s and r and om sample s of the general population has established that individuals may experience harmful impacts arising from both their gambling and their consumption of alcohol . Experimental study of the interaction of alcohol consumption on gambling is notable for its absence from the literature . AIM To experimentally study the interaction of alcohol consumption and gambling behaviour . DESIGN Participants were r and omly allocated into two groups -- placebo administered and alcohol administered , thus making an independent sample s experimental design . SETTING Laboratory . PARTICIPANTS Forty young , male , regular EGM players , who also regularly consumed alcohol . MEASUREMENTS The NEO Personality Inventory ; The Scale of Gambling Choices ( Revised ) ( SGC ) ; persistence at gambling while losing , as measured by the number of gambling trials played and amount wagered . FINDINGS Subjects either received a prior intake of three alcoholic drinks each containing approximately 10 g of pure alcohol ( beer or wine ) or an equal volume of an equivalent non-alcoholic beverage . The alcohol group persisted for twice as many gaming trials as the placebo group with significantly more players who had consumed alcohol losing all their original cash stake ( 50 % compared with 15 % of the placebo group ) . CONCLUSIONS The consumption of alcohol appeared to eliminate the strong associations found in placebo group between individual difference measures and persistence . The analogue game was accepted by participants as a valid form of gambling . The result showed that relatively small quantities of alcohol have a significant effect on the psychological processes that underpin self-control over gambling . This finding challenges the conceptual research paradigm of study ing co-morbidity or dual-addicted clinical population s as the most appropriate method of underst and ing how two addictive behaviours interact Using data from the large , 30-year prospect i ve Dunedin cohort study , we examined whether preexisting individual differences in childhood temperament predicted adulthood disordered gambling ( a diagnosis covering the full continuum of gambling-related problems ) . A 90-min observational assessment at age 3 was used to categorize children into five temperament groups , including one primarily characterized by behavioral and emotional undercontrol . The children with undercontrolled temperament at 3 years of age were more than twice as likely to evidence disordered gambling at ages 21 and 32 than were children who were well-adjusted at age 3 . These associations could not be explained by differences in childhood IQ or family socioeconomic status . Cleanly demonstrating the temporal relation between behavioral undercontrol and adult disordered gambling is an important step toward building more developmentally sensitive theories of disordered gambling and may put research ers in a better position to begin considering potential routes to disordered-gambling prevention through enhancing self-control and emotional regulation PURPOSE Communities That Care ( CTC ) is a prevention system design ed to reduce levels of adolescent delinquency and substance use through the selection and use of effective preventive interventions tailored to a community 's specific profile of risk and protection . This article describes early findings from the first group-r and omized trial of CTC . METHODS A panel of 4407 fifth- grade students was surveyed annually through seventh grade . Analyses were conducted to assess the effects of CTC on reducing levels of targeted risk factors and reducing initiation of delinquent behavior and substance use in seventh grade , 1.67 years after implementing preventive interventions selected through the CTC process . RESULTS Mean levels of targeted risks for students in seventh grade were significantly lower in CTC communities compared with controls . Significantly fewer students in CTC communities than in control communities initiated delinquent behavior between grade s 5 and 7 . No significant intervention effect on substance use initiation by spring of seventh grade was observed . CONCLUSIONS CTC 's theory of change hypothesizes that it takes from 2 to 5 years to observe community-level effects on risk factors and 5 or more years to observe effects on adolescent delinquency or substance use . The early findings indicating hypothesized effects of CTC on targeted risk factors and initiation of delinquent behavior are promising AIMS Problem gambling can create major financial , emotional and sometimes criminal problems for an individual . This study prospect ively investigated the association between impulsive behavior at age 7 and the development of life-time problem gambling by adulthood . We also examined the specificity of any observed association between impulsive behaviors and problem gambling by conducting parallel analyses examining the link between respondents ' shy/depressed behavior in childhood and later problem gambling . DESIGN , SETTING AND PARTICIPANTS Cohort study of 958 offspring of mothers enrolled in the Collaborative Perinatal Project who participated in an adult follow-up study at a mean age of 39.2 years . MEASUREMENTS Multivariable logistic regression models were fitted to determine associations between psychologist-rated impulsive and shy/depressed behaviors at age 7 and life-time self-reported gambling as measured by the South Oaks Gambling Screen administered during the adult follow-up study . FINDINGS Children who exhibited impulsive behaviors at age 7 , compared to their non-impulsive counterparts , were 3.09 ( 95 % confidence interval : 1.40 - 6.82 ) times as likely to report problem gambling years later . In contrast , we did not find a significant association between childhood shy/depressed behavior and problem gambling by adulthood in adjusted analyses . CONCLUSIONS Impulsive behaviors at age 7 are a specific and significant risk factor for later problem gambling AIMS This study investigated whether impulsivity measured in 12 - 14-year-olds could predict problem gambling in late adolescence , above and beyond other personality factors such as aggressiveness and anxiety . DESIGN A prospect ive-longitudinal design was used , thus overcoming limitations of past studies which used concurrent or retrospective design s. PARTICIPANTS AND MEASUREMENTS The sample included 154 boys living in economically deprived neighborhoods . Impulsivity measures comprised self-reports , teacher ratings and laboratory tasks , and were administered during early adolescence . Gambling behavior was assessed at age 17 using a self-report measure . Early gambling behavior and socio-demographic information were also collected for control purpose s. FINDINGS Results revealed that a self-report measure of impulsiveness and a card-sorting task significantly predicted problem gambling , even after controlling for socio-demographic variables , early gambling behavior and other personality variables such as aggressiveness and anxiety . Moreover , the predictive link held across all levels of aggressiveness and anxiety . Both impulsivity measures seemed to tap an inability to foresee negative consequences and an inability to stop responding despite unfavorable contingencies . CONCLUSION These findings suggest that disinhibited individuals with response modulation deficits are at risk for problem gambling , thus supporting the DSM-IV classification of pathological gambling as an impulse control deficit OBJECTIVE To test whether the Communities That Care ( CTC ) prevention system reduces adolescent alcohol , tobacco , and other drug use and delinquent behavior communitywide . DESIGN The Community Youth Development Study is the first r and omized trial of CTC . SETTING In 2003 , 24 small towns in 7 states , matched within state , were r and omly assigned to control or CTC conditions . PARTICIPANTS A panel of 4407 fifth- grade students was surveyed annually through eighth grade . Intervention A coalition of community stakeholders received training and technical assistance to install the CTC prevention system . They used epidemiological data to identify elevated risk factors and depressed protective factors in the community , and chose and implemented tested programs to address their community 's specific profile from a menu of effective programs for families , schools , and youths aged 10 to 14 years . MAIN OUTCOME MEASURES Incidence and prevalence of alcohol , tobacco , and other drug use and delinquent behavior by spring of grade 8 . RESULTS The incidences of alcohol , cigarette and smokeless tobacco initiation , and delinquent behavior were significantly lower in CTC than in control communities for students in grade s 5 through 8 . In grade 8 , the prevalences of alcohol and smokeless tobacco use in the last 30 days , binge drinking in the last 2 weeks , and the number of different delinquent behaviors committed in the last year were significantly lower for students in CTC communities . CONCLUSION Using the CTC system to reduce health-risking behaviors in adolescents can significantly reduce these behaviors communitywide AIM Building on the recent emerging literature on the impulsivity trajectory-gambling association , this study investigated the association between developmental trajectories of teacher-rated impulsivity in early adolescence ( ages 11 - 15 years ) and subsequent gambling and gambling problems ( i.e. at-risk and problem gambling ) by age 19 . DESIGN Prospect i ve cohort design . SETTING Urban communities in Baltimore , Maryl and . PARTICIPANTS The sample consists of 310 predominately minority ( 87 % ) and low socio-economic status ( SES ) ( 70 % ) males followed from first grade to late adolescence . MEASUREMENTS Impulsivity was measured using teacher ratings of classroom behavior . Self-reported gambling behavior was assessed using the South Oaks Gambling Screen-Revised for Adolescents ( SOGS-RA ) . FINDINGS Results from a conventional growth model suggest that the intercept of the impulsivity development ( as measured by the repeated assessment s of impulsivity across the entire developmental period ) was associated significantly with gambling . Results from a general growth mixture model evidence d two distinct trajectories : a high impulsivity trajectory ( 41 % of the sample ) and a low impulsivity trajectory ( 59 % of the sample ) . Despite its non-significant association with any gambling , heterogeneity in impulsivity development was associated significantly with gambling problems . Specifically , being in the high impulsivity trajectory doubled the odds of meeting criteria for at-risk or problem gambling [ odds ratio ( OR ) = 2.09 , 95 % confidence interval ( CI ) : 1.02 , 4.27 ) ] and tripled the odds of meeting criteria for problem gambling ( OR = 2.84 , 95 % CI : 1.02 , 7.91 ) . CONCLUSIONS Development in impulsivity is associated strongly with problem/at-risk gambling in adolescence among urban male youth . Findings highlight the importance of distinguishing gambling problems from any gambling when evaluating programs aim ed at reducing youth gambling problems through reducing impulsivity This paper reports the results of a preliminary investigation into whether the drinking of alcohol contributes to impaired control of gambling behaviour . The sampling method consisted of a two-phase survey design , collecting data both prospect ively ‘ within session ’ and retrospectively via a take-home question naire . One hundred sixteen people were interviewed while in a gaming venue playing on an electronic gaming machine ( egm ) of whom 34 men and 11 women also returned take-home surveys . Comparisons of the sample to previous studies suggested that the sample was representative of the population of egm players . Results indicated a consistent theme of alcohol use contributing significantly to impaired control of gambling behaviour , with level of involvement ( Corless & Dickerson , 1989 ) contributing the most significant variance in the independent variables . Limitations of the study are discussed , but the case is argued that this type of ‘ process ’ research is essential in better underst and ing how these two types of popular leisure activities may interact , possibly leading to the previously recorded chronic , excessive alcohol intake and problematic gambling ( e.g. McCormick , Russo , Ramirez & Taber , 1984 ) Little is known about the course and outcomes of adolescent gambling . This prospect i ve study describes findings from a 3-wave ( Time 1 [ T1 ] , Time 2 [ T2 ] , and Time 3 [ T3 ] ) assessment of gambling behaviors among youth ( N = 305 ) . Stable rates of any gambling and regular gambling ( weekly or daily ) were observed across T1 , T2 , and T3 . The rate of at-risk gambling significantly increased at T3 ( young adulthood ) , whereas the rate of problem gambling remained stable over time . Several adolescent risk factors were associated with either T3 at-risk or problem gambling , many of which are risk factors for adolescent substance abuse . Findings suggest that important to the origins of young adult gambling problems are risk factors associated with the problem behavior syndrome of adolescence There is a paucity of research examining prospect i ve predictors of problem gambling . The current study utilised a large longitudinal data set ( N = 2328 ) to examine a large range of adolescent risk and protective factors for problem gambling in young adulthood . These risk and protective factors covered the domains of the community , family , school , peer group and individual . Numerous predictors associated with the family , school and peer-individual were statistically significant in analyses adjusted for gender and age . However , in the fully adjusted multivariate analyses , only two predictors were statistically significant . Within this model , gender ( female ) was associated with a reduced risk of young adult problem gambling , while family rewards for prosocial involvement moderated the risk relationship between adolescent alcohol use and young adult problem gambling . These findings highlight the importance of adolescent alcohol use and family environment as potentially modifiable predictors of young adult problem gambling Concurrent drinking and gambling is prevalent among young adults and may increase negative consequences associated with each behavior . The effects of alcohol , initial gambling outcomes , gambling-related cognitions , and impulsivity on gambling behavior were evaluated . Initial gambling outcomes , gambling-related cognitions , and impulsivity were also assessed as potential moderators of the relation between alcohol and gambling behavior . Participants ( N = 130 ) were r and omly assigned to receive active placebo or alcohol ( 0.84 g/kg and 0.76 g/kg for men and women , respectively ) and were invited to wager on a simulated slot machine programmed to produce 1 of 3 initial outcomes ( win , breakeven , or loss ) before beginning a progressive loss schedule . Alcohol consumption was associated with larger average bets and more rapid loss of all available funds , though no evidence was found for predicted main effects and interactions for gambling persistence . The effect of impulsivity was moderated by beverage condition , such that higher levels of impulsivity were associated with larger average bets for participants in the placebo but not the alcohol group . Results have direct implication s for individual-focused and public-health interventions |
10,789 | 15,121,496 | Exercise training is safe and effective in patients with heart failure . | PURPOSE To determine the efficacy of exercise training and its effects on outcomes in patients with heart failure . | Objective —To assess the effects of exercise training on ventilatory function in chronic heart failure . Design —Observer blinded r and om allocation crossover training and detraining trial . Setting — Assessment in hospital based clinical laboratory ; training home based . Patients —22 patients with chronic heart failure ( New York Heart Association ( NYHA ) class II or III ) recruited from a tertiary referral centre . All finished the study . Intervention — Bicycle ergometer exercise for 20 minutes a day , five days a week for eight weeks at 70%–80 % of maximum heart rate . Main outcome measures —Exercise capacity on grade d incremental exercise test , minute ventilation , oxygen consumption and carbon dioxide output . Results —Peak work load increased from 96 W to 112 W and peak oxygen consumption from 14·1 ml`/kg/min to 15·4 ml/kg/min ( p < 0·01 ) . At submaximal workloads carbon dioxide excretion ( Vco2 ) and minute ventilation ( Vi ) decreased significantly ( p < 0·05 ) though oxygen consumption was unchanged . The relation between Vi and carbon dioxide excretion changed : the slope of the Vi to Vco2 plot decreased from 38·6 to 35·3 , indicating an improvement in overall ventilary efficiency . The instantaneous carbon dioxide ventilatory equivalent ( Vi/Vco2 ) decreased at submaximal workloads , and reached a lower mimimum value after training , indicating that optimum ventilatory performance improved . The exercise capacity of patients was related to the optimum ventilatory performance . It is suggested that this may in part be mediated through changes in skeletal muscles . Conclusion —Exercise training reduces the ventilatory abnormalities in chronic heart failure ; thus some of these changes may be due to physical deconditioning Heart failure is a debilitating disorder which limits exercise capacity and produces a poor quality of life . The present study was design ed to determine the effects of an exercise training program on patients with CHF NYHA functional class II-III , attributed to left ventricular systolic dysfunction and dilated left ventricle . Twenty-two ambulatory male patients with stable CHF were r and omised to a training ( n = 15 ) and a control group ( n = 7 ) . A symptom limited ramp cardiopulmonary exercise test with gas exchange analysis was performed at baseline after 4 and 8 weeks . The training group underwent an exercise training program at 50 % of peak oxygen uptake for eight weeks . The control group was not exercised . After 8 weeks , compared with baseline , there were statistically significant increase in peak oxygen uptake , peak workload , anaerobic threshold , oxygen pulse , RPP , ventilation and the duration of the test only in trained patients . The reduction in scores tested by the Minnesota Living with Heart Failure question naire ( p < 0.001 ) and Borg dyspnea rating score ( p < 0.001 ) reflect the reduction of symptoms and the improvement in health-related quality of life . Carefully selected patients with moderate to severe CHF can achieve significant improvements of exercise capacity and quality of life with exercise training and can safely participate in a conditioning program AIMS Recent guidelines recommend regular exercise in the management of patients with chronic heart failure ( CHF ) . This study was design ed to compare the safety and efficacy of conventional bicycle exercise and functional electrical stimulation ( FES ) of the legs as forms of home-based exercise training for patients with stable CHF . METHODS AND RESULTS Forty-six patients ( 38 male ) with stable NYHA Class II/III heart failure underwent a 6-week training programme using either a bicycle ergometer or electrical stimulation of the quadriceps and gastrocnemius muscles . In the bike group , significant increases were seen in 6-min walk ( 44.6 m , 95 % confidence interval ( CI ) 29.3 - 60.9 m ) , treadmill exercise time ( 110 s , 95 % CI 72.2 - 148.0 s ) , maximum leg strength ( 5.32 kg , 95 % CI 3.18 - 7.45 kg ) , and quadriceps fatigue index ( 0.08 , 95 % CI 0.04 - 0.12 ) following training . In the stimulator group , similar significant increases were seen following training for 6-min walk ( 40.6 m , 95 % CI 28.2 - 53.0 m ) , treadmill exercise time ( 67 s , 95 % CI 11.8 - 121.8s ) , maximum leg strength ( 5.35 kg , 95 % CI 1.53 - 9.17 kg ) , and quadriceps fatigue index ( 0.10 , 95 % CI 0.04 - 0.17 ) . Peak VO(2)did not change in either group following training , indicating a low-intensity regime . Quality of life scores improved following training when the bicycle and stimulator groups were considered together , but not when considered separately ( -0.43 , 95 % CI -8.13 to -0.56 ) . CONCLUSIONS FES produces beneficial changes in muscle performance and exercise capacity in patients with CHF . Within this study , the benefits were similar to those observed following bicycle training . FES could be offered to patients with heart failure as an alternative to bicycle training as part of a home-based rehabilitation programme Systemic arterial compliance ( SAC ) makes an important contribution to cardiac afterload , and thus is a significant determinant of left ventricular work . Previous studies have suggested that arterial compliance may be reduced in patients with congestive heart failure ( CHF ) , and that SAC is increased after a 4-week exercise training programme in healthy , sedentary individuals . The present study aim ed to investigate the effects of an 8-week exercise training programme on arterial mechanical properties , left ventricular performance and quality of life in CHF patients . A total of 21 patients with NYHA class II or III CHF ( mean+/-S.D. age 55+/-13 years ) were r and omly allocated to either an 8-week exercise training group or a " usual lifestyle " control group . SAC , as determined non-invasively using applanation tonometry and Doppler aortic velocimetry , increased from 0.57+/-0.11 to 0.77+/-0.14 arbitrary compliance units ( mean+/-S.E.M. ; P=0.01 ) in the exercise group , while no change occurred in the control group . Left ventricular structure and function was assessed by echocardiography , and these parameters were unchanged over the 8-week study period . Exercise training significantly increased exercise capacity , measured by a 6-min walking test ( 474+/-27 to 547+/-34 m ; P=0.008 ) . Quality of life , as assessed using the Minnesota Living with Heart Failure Evaluation , demonstrated a decrease in heart failure symptoms from 46+/-7 to 24+/-5 units ( P=0.01 ) following the exercise training programme . These data show that exercise training improves SAC in patients with CHF . The accompanying improvement in exercise capacity may be due , in part , to an improvement in arterial function In the six years from 1975 through 1980 , a total of 12 men died during jogging in the state of Rhode Isl and . The cause of death in 11 was coronary heart disease ( CHD ) . One man died of an acute gastrointestinal hemorrhage . The prevalence of jogging in the Rhode Isl and population was determined using a r and om-digit telephone survey . Among men aged 30 through 64 years , 7.4 % + /- 2.6 % ( mean + /- SEE ) reported jogging at least twice a week . The incidence of death during jogging for men of this age group was one death per year for every 7,620 joggers , or approximately one death per 396,000 man-hours of jogging . This rate is seven times the estimated death rate from CHD during more sedentary activities in Rhode Isl and and suggests that exercise contributes to sudden death in susceptible persons . The occurrence of only one death per 7,620 joggers per year demonstrates that the risk of exercise is small and suggests that the routine exercise testing of healthy subjects before exercise training in not justified AIMS Hydrotherapy , i.e. exercise in warm water , as a rehabilitation program has been considered potentially dangerous in patients with chronic heart failure ( CHF ) due to the increased venous return caused by the hydrostatic pressure . However , hydrotherapy has advantages compared to conventional training . We studied the applicability of an exercise programme in a temperature-controlled swimming pool , with specific reference to exercise capacity , muscle function , quality of life and safety . METHODS AND RESULTS Twenty-five patients with CHF ( NYHA II-III , age 72.1+/-6.1 ) were r and omised into either 8 weeks of hydrotherapy ( n=15 ) , or into a control group ( n=10 ) . The training program was well tolerated with no adverse events . Patients in the hydrotherapy group improved their maximal exercise capacity ( + 6.5 vs.-5.9 W , P=0.001 ) , isometric endurance in knee extension ( + 4 vs.-9 s , P=0.01 ) together with an improvement in the performance of heel-lift ( + 4 vs. -3 n.o . , P=<0.01 ) , shoulder abduction ( + 12 vs. -8 s , P=0.01 ) and shoulder flexion ( + 6 vs. + 4 , P=0.01 ) in comparison to patients in the control group . CONCLUSION Physical training in warm water was well tolerated and seems to improve exercise capacity as well as muscle function in small muscle groups in patients with CHF . This new approach broadens the variety of training regimes for older patients with CHF Background This study was design ed to determine the controlled effects of a short-term exercise rehabilitation program on patients with moderate-to-severe left ventricular dysfunction after a recent myocardial infa rct ion . Methods and Results Thirty-nine male patients 51 + 8 years old with a large anterior myocardial infa rct ion less than 10 weeks old were recruited for the study . The patients were r and omly assigned to either one of two training or control groups on the basis of their resting ejection fraction : training , less than 30 % ; control , less than 30 % ; training , 31–50%1 ; or control , 31–50 % . Patients were evaluated for filling pressures , radionuclide ventriculography , heart volume , echocardiography , and work capacity . Patients who underwent training participated in an intensive 4-week in-hospital exercise program , whereas the control patients were restricted to a minimal activity program . Results indicated that there were no significant improvements in resting , submaximal , and maximal hemodynamic measurements as a result of the program . Mean work capacity and peak oxygen consumption improved significantly in the less-than-30 % training group but was accompanied by a significant increase in mean pulmonary wedge pressure . Resting ejection fraction improved markedly in both less-than-30Q% training and control patients , but ejection fraction measures were not associated with work capacity . Training did not cause further deterioration in ventricular function . Conclusions It was concluded that in the present study , exercise training had little or no effect on hemodynamic measurements and that the training effects achieved in patients with left ventricular dysfunction are most likely due to corrected impaired vasodilation , not necessarily to cardiac function . The importance ofusing a control group in this type of study and the wide intefindividual variations in training responses are emphasized Benefit from exercise training programmes for patients with chronic heart failure has been demonstrated in relatively young ( mean age 60 years ) and predominantly male subjects . This study was undertaken to assess the effect of an exercise programme for older subjects more representative of the general heart failure population OBJECTIVES The aim of this study was to assess the effects of regular physical exercise on local inflammatory parameters in the skeletal muscle of patients with chronic heart failure ( CHF ) . BACKGROUND Inflammatory activation with increased serum cytokine levels and expression of inducible nitric oxide synthase ( iNOS ) in the myocardium and peripheral skeletal muscles has been described in CHF . METHODS Twenty male patients with stable CHF ( left ventricular ejection fraction 25 + /- 2 % ; age 54 + /- 2 years ) were r and omized to a training group ( n = 10 ) or a control group ( n = 10 ) . At baseline and after six months , serum sample s and vastus lateralis muscle biopsies were obtained . Serum tumor necrosis factor (TNF)-alpha , interleukin (IL)-6 , and IL-1-beta levels were measured by enzyme-linked immunosorbent assay , local cytokine , and iNOS expression by real-time polymerase chain reaction . RESULTS Exercise training improved peak oxygen uptake by 29 % in the training group ( from 20.3 + /- 1.0 to 26.1 + /- 1.5 ml/kg . min ; p < 0.001 vs. control group ) . While serum levels of TNF-alpha , IL-6 , and IL-1-beta remained unaffected by training , local skeletal muscle TNF-alpha decreased from 1.9 + /- 0.4 to 1.2 + /- 0.3 relative U ( p < 0.05 for change vs. control group ) , IL-6 from 71.3 + /- 16.5 to 41.3 + /- 8.8 relative U ( p < 0.05 vs. begin ) , and IL-1-beta from 2.7 + /- 1.1 to 1.4 + /- 0.6 relative U ( p = 0.02 vs. control group ) . Exercise training also reduced local iNOS expression by 52 % ( from 6.3 + /- 1.2 to 3.0 + /- 1.0 relative U ; p = 0.007 vs. control group ) . CONCLUSIONS Exercise training significantly reduced the local expression of TNF-alpha , IL-1-beta , IL-6 , and iNOS in the skeletal muscle of CHF patients . These local anti-inflammatory effects of exercise may attenuate the catabolic wasting process associated with the progression of CHF OBJECTIVE : To examine the long-term benefits and safety of aerobic training in patients with chronic heart failure . DESIGN : Non-r and omised control trial with 52 weeks follow up . SETTING : Outpatient cardiac rehabilitation referral centre . PATIENTS : Patients with compensated chronic heart failure ( mean ( SD ) age 62 ( 6 ) years , New York Heart Association stage III , initial resting ejection fraction 22 (7)% ) . Experimental group of 17 men , 4 women ; control group 8 men , 1 woman . INTERVENTIONS : Experimental group : progressive , supervised aerobic walking programme for 52 weeks . Control group : st and ard medical treatment . MAIN OUTCOME MEASURES : Six-minute walk distance , progressive cycle ergometer test to subjective exhaustion , disease-specific quality of life question naire , and st and ard gamble test , all measured at entry , 4 , 8 , 12 , 16 , 26 , and 52 weeks . RESULTS : Control data showed no changes except a small trend to improved emotional function ( P = 0.02 at 12 weeks only ) . Fifteen of the 21 patients completed all 52 weeks of aerobic training ; two withdrew for non-cardiac reasons ( 16 , 52 weeks ) . Three were withdrawn because of worsening cardiac failure unrelated to their exercise participation ( 4 , 4 , 8 weeks ) , and one had a non-fatal cardiac arrest while shopping ( 16 weeks ) . Gains of cardiorespiratory function plateaued at 16 - 26 weeks , with 10 - 15 % improvement in six-minute walk , peak power output , and peak oxygen intake linked to gains in oxygen pulse and ventilatory threshold and reductions in resting heart rate . Marked improvements in quality of life followed a parallel course . CONCLUSIONS : Aerobic training is safe and beneficial in compensated chronic heart failure . Gains in aerobic function and quality of life persisted over a programme lasting 52 weeks PURPOSE The aim of this study was to compare the effects of endurance training alone ( ET ) with combined endurance and strength training ( CT ) on hemodynamic and strength parameters in patients with congestive heart failure ( CHF ) . METHODS Twenty male patients with CHF were r and omized into one of two training regimens consisting of endurance training or a combination of endurance and resistance training . Group ET had 40-min interval cycle ergometer endurance training three times per week . Group CT combined endurance and strength training with the same interval endurance training for 20 min , followed by 20 min of strength training . Left ventricular function was assessed at baseline and after 40 training sessions by echocardiography and radionuclide ventriculography . Work capacity was measured with cardiopulmonary exercise test ( CPX ) and lactate determination . Strength was measured with an isokinetic dynamometer . RESULTS After 40 sessions , the ET group improved functional class , work capacity , peak torque , and muscular endurance . However , peak O2 remained unchanged . Left ventricular ejection fraction ( LVEF ) and fractional shortening ( FS ) decreased , whereas left ventricular end-diastolic diameter ( LVED ) increased . The CT group improved NYHA score , working capacity , peak O2 , and peak lactate ; peak torque and muscular endurance , LVEF , and FS increased , whereas LVED decreased . Compared with ET , CT was significantly ( P < 0.05 ) better in improving LV function . CONCLUSION Combined endurance/strength training was superior to endurance training alone concerning improvement of LV function , peak VO2 , and strength parameters . It appears that for stable CHF patients , a greater benefit can be derived from this training modality BACKGROUND The purpose of this study was to determine the effects of systemic exercise training on endothelium-mediated arteriolar vasodilation of the lower limb and its relation to exercise capacity in chronic heart failure ( CHF ) . Endothelial dysfunction is a key feature of CHF , contributing to increased peripheral vasoconstriction and impaired exercise capacity . Local h and grip exercise has previously been shown to enhance endothelium-dependent vasodilation in conduit and resistance vessels in CHF . METHODS AND RESULTS Twenty patients were prospect ively r and omized to a training group ( n=10 , left ventricular ejection fraction [ LVEF ] 24+/-4 % ) or a control group ( n=10 , LVEF 23+/-3 % ) . At baseline and after 6 months , peak flow velocity was measured in the left femoral artery using a Doppler wire ; vessel diameter was determined by quantitative angiography . Peripheral blood flow was calculated from average peak velocity ( APV ) and arterial cross-sectional area . After exercise training , nitroglycerin-induced endothelium-independent vasodilation remained unaltered ( 271 % versus 281 % , P = NS ) . Peripheral blood flow improved significantly in response to 90 microg/min acetylcholine by 203 % ( from 152+/-79 to 461+/-104 mL/min , P<0.05 versus control group ) and the inhibiting effect of L-NMMA increased by 174 % ( from -46+/-25 to -126+/-19 mL/min , P<0.05 versus control group ) . Peak oxygen uptake increased by 26 % ( P<0.01 versus control group ) . The increase in peak oxygen uptake was correlated with the endothelium-dependent change in peripheral blood flow ( r=0.64 , P<0 . 005 ) . CONCLUSIONS Regular physical exercise improves both basal endothelial nitric oxide ( NO ) formation and agonist-mediated endothelium-dependent vasodilation of the skeletal muscle vasculature in patients with CHF . The correction of endothelium dysfunction is associated with a significant increase in exercise capacity To evaluate prospect ively the impact of carvedilol on a short‐term physical training program in stable patients with moderate chronic heart failure ( CHF ) , and to analyze parameters predictive of improvement after training BACKGROUND Exercise training in heart failure patients improves exercise capacity , physical function , and quality -of-life . Prior studies indicate a rapid loss of these effects following termination of the training . We wanted to assess any sustained post-training effects on patients global assessment of change in quality -of-life ( PGACQoL ) and physical function . METHODS Fifty-four stable heart failure patients were r and omised to exercise or control . The 4-month exercise programme consisted of bicycle training at 80 % of maximal intensity three times/week , and 49 patients completed the active study period . At 10 months ( 6 months post training ) 37 patients were assessed regarding PGACQoL , habitual physical activity , and dyspnea-fatigue-index . RESULTS Both post-training patients ( n=17 ) and controls ( n=20 ) deteriorated PGACQoL during the 6-month extended follow-up , although insignificantly . However , post-training patients improved PGACQoL slightly but significantly from baseline to 10 months ( P=0.006 ) , differing significantly ( P=0.023 ) from controls who were unchanged . Regarding dyspnea-fatigue-index , post-training patients were largely unchanged and controls deteriorated insignificantly , during the extended follow-up as well as from baseline to 10 months . Both groups decreased physical activity insignificantly during the extended follow-up , and from baseline to 10 months post-training patients tended to decrease whereas controls significantly ( P=0.007 ) decreased physical activity . CONCLUSION There was no important sustained benefit 6 months after termination of an exercise training programme in heart failure patients . A small , probably clinical ly insignificant sustained improvement in PGACQoL was seen in post-training patients . Controls significantly decreased the habitual physical activity over 10 months and post-training patients showed a similar trend . Exercise training obviously has to be continuing to result in sustained benefit OBJECTIVES We sought to investigate the effects of physical training on circulating proinflammatory cytokines and the soluble apoptosis mediators Fas ( sFas ) and Fas lig and ( sFasL ) in patients with chronic heart failure ( CHF ) . BACKGROUND Recent investigations have shown an overexpression of circulating proinflammatory cytokines and soluble apoptosis mediators in patients with CHF , which may be related to their exercise intolerance and clinical deterioration . METHODS Plasma levels of tumor necrosis factor-alpha ( TNF-alpha ) , soluble TNF receptors I and II ( sTNF-RI and sTNF-RII , respectively ) , interleukin-6 ( IL-6 ) , soluble IL-6 receptor ( sIL-6R ) , sFas and sFasL were measured in 24 patients with stable CHF ( New York Heart Association functional class II/III ; left ventricular ejection fraction 23.2 + /- 1.3 % ) and in 20 normal control subjects before and after a 12-week program of physical training in a r and omized , crossover design . Functional status of patients with CHF was evaluated by using a cardiorespiratory exercise test to measure peak oxygen consumption ( VO2max ) . RESULTS Physical training produced a significant reduction in plasma levels of TNF-alpha ( 7.5 + /- 1.0 pg/ml vs. 4.6 + /- 0.7 pg/ml , p < 0.001 ) , sTNF-RI ( 3.3 + /- 0.2 ng/ml vs. 2.7 + /- 0.2 ng/ml , p < 0.005 ) , sTNF-RII ( 2.6 + /- 0.2 ng/ml vs. 2.3 + /- 0.2 ng/ml , p = 0.06 ) , IL-6 ( 8.3 + /- 1.2 pg/ml vs. 5.9 + /- 0.8 pg/ml , p < 0.005 ) , sIL-6R ( 34.0 + /- 3.0 ng/ml vs. 29.2 + /- 3.0 ng/ml , p < 0.01 ) , sFas ( 5.5 + /- 0.7 ng/ml vs. 4.5 + /- 0.8 ng/ml , p = 0.05 ) and sFasL ( 34.9 + /- 5.0 pg/ml vs. 25.2 + /- 4.0 pg/ml , p < 0.05 ) , as well as a significant increase in VO2max ( 16.3 + /- 0.7 ml/kg per min vs. 18.7 + /- 0.8 ml/kg per min , p < 0.001 ) . Good correlations were found between a training-induced increase in VO2max and a training-induced reduction in levels of the proinflammatory cytokine TNF-alpha ( r = -0.54 , p < 0.01 ) and the apoptosis inducer sFasL ( r = -0.57 , p < 0.005 ) in patients with CHF . In contrast , no significant difference in circulating cytokines and apoptotic markers was found with physical training in normal subjects . CONCLUSIONS Physical training reduces plasma levels of proinflammatory cytokines and the sFas/sFasL system in patients with CHF . These immunomodulatory effects may be related to the training-induced improvement in functional status of patients with CHF BACKGROUND Exercise training is now an accepted component of the therapeutic regimen in patients with heart failure and underlying ischemia , but few data are available on the effects of training in patients with nonischemic dilated cardiomyopathy . METHODS Twenty-four patients ( mean age 55 + /- 9 years , mean ejection fraction 26.6 % + /- 10 % ) were r and omized to an exercise ( n = 12 ) or a control ( n = 12 ) group . Patients in the exercise group underwent 5 45-minute sessions of supervised training per week . Before and after the 2-month study period , exercise testing with respiratory gas exchange and lactate analysis was performed , left ventricular volumes and ejection fraction were measured with magnetic resonance imaging , and left ventricular rotation and relaxation velocities were measured with a novel magnetic resonance imaging tagging technique . RESULTS Training result ed in increases in peak oxygen uptake ( VO2 ) ( 21.7 + /- 4 mL/kg/min to 25.3 + /- 5 mL/kg/min , P < .05 ) and VO2 at the lactate threshold ( 12.8 + /- 4 mL/kg/min to 19.0 + /- 5 mL/kg/min , P < .01 ) . No differences were observed within or between groups in left ventricular end-diastolic volume , end-systolic volume , or ejection fraction . Velocity of left ventricular rotation during systole was unchanged in both groups , and relaxation velocity was higher after training in the exercise group ( 21.2 + /- 5 degrees/s versus 29.7 + /- 12 degrees/s , P < .05 ) . CONCLUSION Training result ed in increases in peak VO2 and VO2 at the lactate threshold . Left ventricular volumes and systolic function ( ie , ejection fraction and rotation velocity ) were unchanged with training , suggesting that training in patients with dilated cardiomyopathy does not lead to further myocardial damage . However , the increase in relaxation velocity after exercise training indicates an improvement in diastolic function . The latter finding suggests an additional potential benefit of exercise training in patients with dilated cardiomyopathy This study examined the effect of a novel circuit weight training ( CWT ) program on cardiorespiratory fitness , muscular strength , and body composition in 13 patients with chronic heart failure ( CHF ) , using a prospect i ve r and omized crossover protocol . Peak exercise oxygen uptake ( VO(2 peak ) ) increased after the 8-wk CWT program ( 19 . 5 + /- 1.2 vs. 22.0 + /- 1.5 ml . kg(-1 ) . min(-1 ) , P < 0.01 ) , as did exercise test duration ( 15.2 + /- 0.9 vs. 18.0 + /- 1.1 min , P < 0 . 001 ) . Submaximal exercise heart rate was lower after training at 60 and 80 W ( 121 + /- 3 vs. 134 + /- 5 beats/min , P < 0.01 ) as was rate pressure product , whereas ventilatory threshold increased , from 52 + /- 3 to 58 + /- 3 % of VO(2 peak ) ( P < 0.05 ) . CWT also increased maximal isotonic voluntary contractile strength for seven different muscle groups , from 392 to 462 kg ( P = 0.001 ) . CWT , an exercise prescription specifically targeting peripheral abnormalities in CHF , improves functional capacity and muscular strength in these patients OBJECTIVES The aim of this study was to analyze whether L-arginine ( L-arg . ) has comparable or additive effects to physical exercise regarding endothelium-dependent vasodilation in patients with chronic heart failure ( CHF ) . BACKGROUND Endothelial dysfunction in patients with CHF can be corrected by both dietary supplementation with L-arg . and regular physical exercise . METHODS Forty patients with severe CHF ( left ventricular ejection fraction 19 + /- 9 % ) were r and omized to an L-arg . group ( 8 g/day ) , a training group ( T ) with daily h and grip training , L-arg . and T ( L-arg . + T ) or an inactive control group ( C ) . The mean internal radial artery diameter was determined at the beginning and after four weeks in response to brachial arterial administration of acetylcholine ( ACh ) ( 7.5 , 15 , 30 microg/min ) and nitroglycerin ( 0.2 mg/min ) with a transcutaneous high-resolution 10 MHz A-mode echo tracking system coupled with a Doppler device . The power of the study to detect clinical ly significant differences in endothelium-dependent vasodilation was 96.6 % . RESULTS At the beginning , the mean endothelium-dependent vasodilation in response to ACh , 30 microg/min was 2.54 + /- 0.09 % ( p = NS between groups ) . After four weeks , internal radial artery diameter increased by 8.8 + /- 0.9 % after ACh 30 microg/min in L-arg . ( p < 0.001 vs. C ) , by 8.6 + /- 0.9 % in T ( p < 0.001 vs. C ) and by 12.0 + /- 0.3 % in L-arg . + /- T ( p < 0.005 vs. C , L-arg . and T ) . Endothelium-independent vasodilation as assessed by infusion of nitroglycerin was similar in all groups at the beginning and at the end of the study . CONCLUSIONS Dietary supplementation of L-arg . as well as regular physical exercise improved agonist-mediated , endothelium-dependent vasodilation to a similar extent . Both interventions together seem to produce additive effects with respect to endothelium-dependent vasodilation BACKGROUND Exercise is currently recommended for patients after myocardial infa rct ion ; however , the effects of regular exercise on the remodeling process remain to be defined . The aim of this multicenter , r and omized study was to investigate whether a long-term physical training program influences left ventricular size and function in postinfa rct ion patients with systolic dysfunction . METHODS AND RESULTS Consecutive patients with < 40 % ejection fraction after a first Q-wave myocardial infa rct ion were r and omly assigned to a 6-month exercise training program ( n=39 ) or control group ( n=38 ) . After 6 months , a significant increase in work capacity was observed only in the training group ( from 4.462+/-1.095 to 5.752+/-1.749 kilopond-meters [ Kp-m ] , P<.01 ) , not in the control group ( from 4.375+/-1.143 to 4.388+/-1.199 Kp-m ) , whereas left ventricular volumes had increased in the control group ( end-diastolic volume , from 94+/-26 to 99+/-27 mL/m2 , P<.01 ; end-systolic volume , from 62+/-20 to 67+/-23 mL/m2 , P<.01 ) but not in the training group ( end-diastolic volume , from 93+/-28 to 92+/-28 mL/m2 , P = NS ; end-systolic volume , from 61+/-22 to 57+/-23 mL/m2 , P = NS ) . Conversely , ejection fraction had improved in the training group ( from 34+/-5 % to 38+/-8 % , P<.01 ) but not in the control group ( from 34+/-5 % to 33+/-7 % , P = NS ) . CONCLUSIONS In postinfa rct ion patients with systolic dysfunction , long-term exercise training may attenuate the unfavorable remodeling response and even improve ventricular function over time BACKGROUND Long-term beta-adrenergic blockade does not appear to be associated with drug-induced training in patients with congestive heart failure ( CHF ) ; whether exercise training can increase peak aerobic capacity in patients with CHF who are treated with beta-adrenergic blockers is currently unknown . METHODS AND RESULTS We studied 23 patients with CHF who were treated with carvedilol or propranolol in addition to ACE inhibitors , furosemide , and digoxin . Of the patients treated with carvedilol , 8 underwent exercise training and 8 remained sedentary . All 7 patients treated with propranolol underwent exercise training . Peak oxygen consumption ( mL.kg-1.min-1 ) was serially measured in trained and sedentary patients . Peak reactive hyperemia ( mL.min-1.100 mL-1 ) was determined in the calf and forearm immediately before and after 12 weeks of training . The peak oxygen consumption of trained patients treated with either carvedilol or propranolol increased from 12.9 + /- 1.4 to 16.0 + /- 1.6 ( P < .001 ) and 12.4 + /- 1.0 to 15.7 + /- 0.9 ( P < .001 ) mL.kg-1.min-1 , respectively , whereas it did not change in the sedentary patients . Peak reactive hyperemia increased significantly in the calves but not the forearms of trained patients . CONCLUSIONS Long-term , nonselective beta-adrenergic blockade with carvedilol or propranolol does not prevent patients with CHF from deriving systemic and regional benefits from physical training A new program of rehabilitation is less dem and ing on cardiac output than st and ard programs . Twenty-five patients with chronic heart failure ( ejection fraction [ EF ] : 0.26 + /- 0.10 ) were r and omized into 2 groups : a control group with 13 patients and a rehabilitation group of 12 patients . In the control group , 2 did not complete the study ( cancer , cardiac transplantation ) . For the 11 others , the different parameters studied were comparable at day 0 with group R and did not significantly change over 3 months outside of a spontaneous improvement in endurance performance by 22 % . In the rehabilitation group ( 40 sessions over 90 days ; specialized equipment ) there were no incidents . Tolerance was excellent ( heart rate during sessions less than 115 bpm ) and all functional parameters improved . Training did not modify the isotopic ejection fraction . The quality of life score increased respectively by 52 % ( p less than 0.0001 in comparison with the control group ) and by 63 % ( p less than 0.0001 ) ; 80 % of the patients requested that training be prolonged . The functional improvement obtained by purely peripheral effect had no adverse effect on the heart BACKGROUND There is evidence that exercise training can induce myocardial and coronary adaptations in both animals and humans . However , the significance of these potentially important changes remains to be determined in patients with ischemic heart disease and left ventricular ( LV ) systolic dysfunction . METHODS AND RESULTS To investigate whether exercise training can improve thallium uptake and the contractile response to low-dose dobutamine of dysfunctional myocardium , 46 patients ( 42 men , 4 women ; mean age , 57+/-9 years ) with chronic coronary artery disease and impaired LV systolic function ( ejection fraction < 40 % ) were r and omly assigned to two groups . The exercise group ( n = 26 ) underwent exercise training at 60 % of peak oxygen uptake for 8 weeks . The control group ( n = 20 ) was not exercised . At baseline and after 8 weeks all patients underwent an exercise test with gas exchange analysis and stress echocardiography using low-dose dobutamine ( 5 to 10 microg/kg per minute ) followed by thallium myocardial scintigraphy . Coronary angiography was performed in 23 patients at baseline and after 8 weeks . After 8 weeks , peak oxygen uptake increased significantly only in trained patients ( 24 % ) . Significant improvements in the contractile response to dobutamine and thallium activity were observed in trained patients ( 28 % and 31 % , respectively ; trained versus control : P<.001 for both ) . In a subgroup of trained patients , both improvements were correlated with an increase in the coronary collateral score ( P<.005 and P<.001 , respectively ) . CONCLUSIONS Moderate exercise training improves both thallium activity and the contractile response of dysfunctional myocardium to low doses of dobutamine in patients with ischemic cardiomyopathy . The implication of this study is that even a short-term exercise training may improve quality of life by improvement of LV systolic function during mild-to-moderate physical activity in patients with ischemic cardiomyopathy Background : Reduced heart pump function and skeletal muscle abnormalities are considered important determinants for the low physical exercise capacity in chronic heart failure . Because of reduced ventricular function , traditional physical rehabilitation may cause underperfusion and low local work intensity , thereby producing suboptimal conditions for skeletal muscle training Background —The effects of exercise training ( ET ) on left ventricular ( LV ) remodeling in chronic heart failure are not definitively established , and the safety of ET in these patients is still debated . Methods and Results —This multicenter study investigated the long-term effect of moderate ET on LV remodeling , work capacity , and quality of life ( QoL ) in 90 patients with stable chronic heart failure caused by LV systolic dysfunction , r and omized to a 6-month ET program ( T , n=45 ) or a control group ( C , n=45 ) . All patients underwent resting echocardiography , a cardiopulmonary exercise test , 6-minute walking test , and QoL assessment at entry and after 6 months . At entry , end-diastolic ( EDV ) and end-systolic ( ESV ) volume , ejection fraction , work capacity , peak & OV0312;o2 , and walking distance were similar in the 2 groups . After 6 months , LV volumes diminished in T ( EDV , from 142±26 to 135±26 mL/m2 , P < 0.006 ; ESV , from 107±24 to 97±24 mL/m2 , P < 0.05 ) but increased in C ( EDV , from 147±41 to 156±42 mL/m2 , P < 0.01 ; ESV , from 110±34 to 118±34 mL/m2 , P < 0.01 ) . Ejection fraction improved in T ( P < 0.001 ) but was unchanged in C ( P = NS ) . Significant improvement in work capacity ( P < 0.001 ) , peak & OV0312;o2 ( P < 0.006 ) , walking distance ( P < 0.001 ) , and QoL ( P < 0.01 ) was observed in T but not in C ( P = NS ) . T showed a trend toward fewer ( P = 0.05 ) hospital readmissions for worsening dyspnea in the absence of other adverse cardiac events . Conclusions —In stable chronic heart failure , long-term moderate ET has no detrimental effect on LV volumes and function ; rather , it attenuates abnormal remodeling . Furthermore , ET is safe and effective in improving exercise tolerance and AIMS Previous studies have shown an abnormal expression of cellular adhesion molecules and cytokines in chronic heart failure , which may be related to endothelial dysfunction characterizing this syndrome . Our study investigates the effects of physical training on serum activity of some peripheral inflammatory markers associated with endothelial dysfunction , such as granulocyte-macrophage colony-stimulating factor ( GM-CSF ) , macrophage chemoattractant protein-1 ( MCP-1 ) , soluble intercellular adhesion molecule-1 ( sICAM-1 ) and soluble vascular cell adhesion molecule-1 ( sVCAM-1 ) in patients with chronic heart failure . METHODS AND RESULTS Serum levels of GM-CSF , MCP-1 , sICAM-1 and sVCAM-1 were determined in 12 patients with stable chronic heart failure ( ischaemic heart failure : 6/12 , dilated cardiomyopathy : 6/12 , New York Heart Association : II-III , ejection fraction : 24+/-2 % ) before and after a 12-week programme of physical training in a r and omized crossover design . In addition , the functional status of chronic heart failure patients was evaluated by using a cardiorespiratory exercise stress test to measure peak oxygen consumption . Physical training produced a significant reduction in serum GM-CSF ( 28+/-2 vs 21+/-2 pg . ml(-1 ) , P<0.001 ) , MCP-1 ( 192+/-5 vs 174+/-6 pg . ml(-1 ) , P<0.001 ) , sICAM-1 ( 367+/-31 vs 314+/-29 ng . ml(-1 ) , P<0.01 ) and sVCAM-1 ( 1247+/-103 vs 1095+/-100 ng . ml(-1 ) , P<0.01 ) as well as a significant increase in peak oxygen consumption ( 14.6+/-0.5 vs 16.5+/-0.5 ml . kg(-1)min(-1 ) , P<0.005 ) . A significant correlation was found between the training-induced improvement in peak oxygen consumption and percentage reduction in soluble adhesion molecules sICAM-1 ( r=-0.72 , P<0.01 ) and sVCAM-1 ( r=-0.67 , P<0.02 ) . CONCLUSION Physical training affects beneficially peripheral inflammatory markers reflecting monocyte/macrophage-endothelial cell interaction . Training-induced improvement in exercise tolerance is correlated with the attenuation of the inflammatory process , indicating that inflammation may contribute significantly to the impaired exercise capacity seen in chronic heart failure AIMS To assess whether a domiciliary programme of specific inspiratory muscle training in stable chronic heart failure results in improvements in exercise tolerance or quality of life . METHODS AND RESULTS We conducted a r and omized controlled trial of 8 weeks of inspiratory muscle training in 18 patients with stable chronic heart failure , using the Threshold trainer . Patients were r and omized either to a training group inspiring for 30 min daily at 30 % of maximum inspiratory mouth pressure , or to a control group of ' sham ' training at 15 % of maximum inspiratory mouth pressure . Sixteen of the 18 patients completed the study . Maximum inspiratory mouth pressure improved significantly in the training group compared with controls , by a mean ( SD ) of 25.4 ( 11.2 ) cmH2O ( P=0.04 ) . There were , however , no significant improvements in treadmill exercise time , corridor walk test time or quality of life scores in the trained group compared with controls . CONCLUSION Despite achieving a significant increase in inspiratory muscle strength , this trial of simple domiciliary inspiratory muscle training using threshold loading at 30 % of maximum inspiratory mouth pressure did not result in significant improvements in exercise tolerance or quality of life in patients with chronic heart failure OBJECTIVES We sought to analyze the systemic effects of lower-limb exercise training ( ET ) on radial artery endothelial function in patients with chronic heart failure ( CHF ) . BACKGROUND Local ET has the potential to improve local endothelial dysfunction in patients with CHF . However , it remains unclear whether the systemic effects can be achieved by local ET . METHODS Twenty-two male patients with CHF were prospect ively r and omized to either ET on a bicycle ergometer ( ET group , n = 11 ; left ventricular ejection fraction [ LVEF ] 26 + /- 3 % ) or an inactive control group ( group C , n = 11 ; LVEF 24 + /- 2 % ) . At the beginning of the study and after four weeks , endothelium-dependent and -independent vasodilation of the radial artery was determined by intra-arterial infusion of acetylcholine ( ACh-7.5 , 15 and 30 microg/min ) and nitroglycerin ( 0.2 mg/min ) . The mean internal diameter ( ID ) of the radial artery was assessed using a high resolution ultrasound system ( NIUS-02 , Asulab Research Laboratories , Neuchâtel , Switzerl and ) with a 10-MHz probe . RESULTS After four weeks of ET , patients showed a significant increase in the baseline-corrected mean ID in response to ACh ( 30 microg/min ) , from 33 + /- 10 to 127 + /- 25 microm ( p < 0.001 vs. control group at four weeks ) . In the control group , the response to ACh ( 30 microg/min ) remained unchanged . Endothelium-independent vasodilation was similar in both groups at the beginning of the study and at four weeks . In the training group , increases in agonist-mediated , endothelium-dependent vasodilation correlated to changes in functional work capacity ( r = 0.63 , p < 0.05 ) . CONCLUSIONS In patients with stable CHF , bicycle ergometer ET leads to a correction of endothelial dysfunction of the upper extremity , indicating a systemic effect of local ET on endothelial function BACKGROUND The improvement of exercise capacity in patients with chronic heart failure ( CHF ) by physical training has been connected with reversal of the abnormalities in muscle fiber distribution and with the reduced activity of the enzymes of oxidative metabolism in skeletal muscle . However , the change in fiber type distribution induced by training is controversial and in previous studies the activities of the rate-limiting enzymes of the metabolic pathways have not been measured . AIMS To examine the effect of dynamic training on percentage distribution of muscle fibers , on activities of the rate-limiting enzymes of the metabolic pathways and on electrophysiology in skeletal muscle . METHODS A total of 27 patients with stable CHF ( NYHA class II-III ) were r and omized to a training ( N=12 ) or a control ( N=15 ) group . The training group exercised on a bicycle ergometer for 30 min three times a week for 3 months using a load corresponding to 50 - 60 % of their peak oxygen consumption . This was followed by a 3-month training period at home according to personal instructions . The control group did not change its physical activities . We studied muscle histology and measured the activities of the rate-limiting enzymes of anaerobic glycolysis ( phosphofructokinase , PFK ) , glycogenolysis ( phosphorylase ) , citric acid cycle ( alpha-ketoglurate dehydrogenase , KGDH ) and fatty acid oxidation ( carnitinepalmitoyl transferase I and II , CPT I and II ) from biopsies of the vastus lateralis muscle at baseline and after 3 and 6 months . Muscle strength and strength endurance with surface EMG and macro EMG of the right knee extensors were also determined . RESULTS Exercise capacity , particularly submaximal , improved in the training group . The activity of PFK rose significantly but that of the other enzymes did not when compared with the change in the controls . Training had no effect on the percentage distribution of slow-twitch and fast-twitch muscle fibers or on capillary density around these fibers in skeletal muscle . Maximum voluntary force , strength endurance and the function of motor units remained unaffected . CONCLUSIONS Dynamic training results in improved exercise endurance in CHF . In skeletal muscle , the capacity of anaerobic glycolysis is increased but that of the citric acid cycle and fatty acid oxidation is not . Furthermore , the improvement in exercise endurance seems to be independent of changes in the percentage distribution of muscle fibers , capillarity or electrophysiological factors Background Many secondary abnormalities in chronic heart failure ( CHF ) may reflect physical deconditioning . There has been no prospect i ve , controlled study of the effects of physical training on hemodynamics and autonomic function in CHIF . Methods and Results In a controlled crossover trial of 8 weeks of exercise training , 17 men with stable moderate to severe CHF ( age , 61.8±1.5 years ; left ventricular ejection fraction , 19.6±2.3 % ) , increased exercise tolerance ( 13.9±1.0 to 16.5±1.0 minutes , p<0.001 ) , and peak oxygen uptake ( 13.2±0.9 to 15.6±1.0 mI/kg/min , p<0.01 ) significantly compared with controls . Training increased cardiac output at submaximal ( 5.9 - 6.7 1/min , p<0.05 ) and peak exercise ( 6.3 - 7.1 /min , p<0.05 ) , with a significant reduction in systemic vascular resistance . Training reduced minute ventilation and the slope relating minute ventilation to carbon dioxide production ( −10.5 % , p<0.05 ) . Sympathovagal balance was altered by physical training when assessed by three methods : 1 ) RR variability ( + 19.2 % , p<0.05 ) ; 2 ) autoregressive power spectral analysis of the resting ECG divided into low-frequency ( −21.2 % , p<0.01 ) and high-frequency ( + 51.3 % , p<0.05 ) components ; and 3 ) whole-body radiolabeled norepinephrine spillover ( −16 % , p<0.05 ) . These measurements all showed a significant shift away from sympathetic toward enhanced vagal activity after training . Conclusions Carefully selected patients with moderate to severe CHF can achieve significant , worthwhile improvements with exercise training . Physical deconditioning may be partly responsible for some of the associated abnormalities and exercise limitation of CHF , including abnormalities in autonomic balance Impaired insulin sensitivity has been linked with chronic heart failure ( CHF ) . Exercise has a beneficial effect on insulin sensitivity in healthy subjects . It is used also as an adjunctive therapy in patients with CHF . We studied the effect of r and omized treatment with celiprolol , a vasodilating β1‐adrenoceptor antagonist , 200 mg once daily ( n=20 ) or placebo ( n=11 ) on serum lipid levels and insulin sensitivity in patients with CHF . In addition , all subjects participated in a 6‐month exercise training protocol . Thirteen subjects in the celiprolol and eight subjects in the control group were on additional β1‐adrenoceptor antagonist as part of their tailored CHF therapy . Insulin sensitivity was determined using the hyperinsulinemic euglycemic clamp test ( diabetic subjects excluded , n=11 for the celiprolol group and n=8 for the placebo group ) We looked at the benefits and complications of a home-based exercise programme in patients with ischaemic and idiopathic dilated cardiomyopathy . Twenty-four patients with left ventricular end-diastolic dimension > 6.5 cm and fractional shortening < 25 % entered a cross-over trial of 8 weeks training versus 8 weeks rest . Echocardiography , electrocardiogram and cardiopulmonary exercise testing were performed at baseline , after training and after detraining . Training result ed in a higher peak oxygen consumption ( 26.5 versus 21.3 ml/kg/min , P=0.004 ) , a higher peak heart rate ( 161 versus 152 bpm , P=0.02 ) and improved well-being . Patients with idiopathic dilated cardiomyopathy showed a significant increase in exercise time ( 879 versus 828 s , P=0.03 ) and peak oxygen consumption ( 31.3 versus 24.3 ml/kg/min , P=0.02 ) and a decrease in left ventricular end-diastolic dimension ( 6.4 versus 6.9 cm , P=0.01 ) and end-systolic dimension ( 5.3 versus 5.8 cm , P=0.04 ) in contrast to those with coronary artery disease , who developed a reduction in septal excursion and shortening rate following training . Complications of training were more common in those patients with ischaemic cardiomyopathy , greater left ventricular dimensions , poorer exercise tolerance and greater ventilation drive at baseline , and included fluid retention and exercise-induced ventricular tachycardia . We found that this group of patients with a dilated , poorly functioning left ventricle can safely derive benefit from a home-based exercise programme , particularly those of idiopathic origin , but they should be closely monitored for the development of complications BACKGROUND Data of training effects in chronic heart failure patients are based on findings in men . The purpose of this study was to compare the effects of skeletal muscle endurance training between men and women with chronic heart failure . METHODS AND RESULTS Twelve consecutive men ( mean [ + /- SD ] age 58 + /- 9 years , left ventricular ejection fraction 29 + /- 9 % ) and 12 women ( 60 + /- 10 years , left ventricular ejection fraction 28 + /- 7 % ) with moderate , chronic heart failure stratified according to age and inclusion criteria were investigated at baseline and after 8 weeks of knee extensor endurance training . The activity of skeletal muscle citrate synthase and resting heart rate were similar in men and women at baseline and with training improved ( P < .0001 ) similarly in both genders . Peak work rate ( P < .0001 ) , peak oxygen uptake ( P < .001 ) and muscle strength ( P < .05 ) at baseline were higher in men than in women . Training improved peak work rate ( P < .0001 ) and muscle strength ( P < .0001 ) similarly in both genders , while improvement in peak oxygen uptake was better in women ( P < .001 ) . The distance ambulated during 6 minutes was similar in both genders at baseline and increased after training more in men ( P < .004 ) . The overall and physical Sickness Impact Profile indicated similarly reduced health-related quality of life in men and women , while worse psychosocial quality of life was observed in men ( P < .05 ) . Both genders improved after exercise training in the overall , physical , and psychosocial Sickness Impact Profile ( P < .01 ) . CONCLUSIONS Exercise-based rehabilitation improves skeletal muscle capacity , exercise tolerance , and the health-related quality of life in women as well as in men with moderate , chronic heart failure The effect of exercise training on quality of life and exercise capacity was studied in 67 patients with mild to moderate chronic heart failure ( CHF ; age : 65.6+/-8.3 years ; left ventricular ejection fraction : 26.5+/-9.6 % ) . Patients were r and omly allocated to either a training group or to a control group . After intervention a significantly larger decrease in Feelings of Being Disabled ( a subscale of the Heart Patients Psychological Question naire ) and a significantly larger increase in the Self- Assessment of General Well-Being ( SAGWB ) were observed in the training group . Exercise time and anaerobic threshold were increased in the training group only . The increase in exercise time was related to both Feelings of Being Disabled and SAGWB . We conclude that supervised exercise training improves both quality of life and exercise capacity and can be safely performed by chronic heart failure patients 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 OBJECTIVES The aim of this study was to evaluate the effects of high intensity exercise training on left ventricular function and hemodynamic responses to exercise in patients with reduced ventricular function . BACKGROUND Results of studies on central hemodynamic adaptations to exercise training in patients with chronic heart failure have been contradictory , and some research has suggested that training causes further myocardial damage in these patients after a myocardial infa rct ion . METHODS Twenty-five men with left ventricular dysfunction after a myocardial infa rct ion or coronary artery bypass graft surgery were r and omized to an exercise training group ( mean age + /- SD 56 + /- 5 years , mean ejection fraction [ EF ] 32 + /- 7 % , n = 12 ) or a control group ( mean age 55 + /- 7 years , mean EF 33 + /- 6 % , n = 13 ) . Patients in the exercise group performed 2 h of walking daily and four weekly sessions of high intensity monitored stationary cycling ( 40 min at 70 % to 80 % peak capacity ) at a residential rehabilitation center for a period of 2 months . Ventilatory gas exchange and upright hemodynamic measurements ( rest and peak exercise cardiac output ; pulmonary artery , wedge and mean arterial pressures ; and systemic vascular resistance ) were performed before and after the study period . RESULTS Maximal oxygen uptake ( VO2max ) increased by 23 % after 1 month of training , and by an additional 6 % after month 2 . The increase in VO2max in the trained group paralleled an increase in maximal cardiac output ( 12.0 + /- 1.8 liters/min before training vs. 13.7 + /- 2.5 liters/min after training , p < 0.05 ) , but maximal cardiac output did not change in the control group . Neither stroke volume nor hemodynamic pressures at rest or during exercise differed within or between groups . Rest left ventricular mass , volumes and EF determined by magnetic resonance imaging were unchanged in both groups . CONCLUSIONS High intensity exercise training in patients with reduced left ventricular function results in substantial increases in VO2max by way of an increase in maximal cardiac output combined with a widening of maximal arteriovenous oxygen difference , but not changes in contractility . Training did not worsen hemodynamic status or cause further myocardial damage BACKGROUND Beneficial training outcomes have been reported in sedentary patients with chronic heart failure ( CHF ) after exercise training . However , data on training effects in previously trained patients , as well as comparisons of different exercise modes , are lacking . The aim of this study is to compare exercise training on a cycle ergometer ( major muscle mass ) and aerobic knee-extensor training ( minor muscle mass ) in previously trained patients with CHF . METHODS AND RESULTS Twenty-four men and women ( age , 63 + /- 10 years [ mean + /- SD ] ) with stable , moderate CHF ( left ventricular ejection fraction , 30 % + /- 11 % ) who had completed their first exercise training period more than 1 year ago were allocated to either the exercise or control group . After stratification for sex , age , ejection fraction , and cardiac output response , the training group was further r and omized to either cycle ergometer or knee-extensor training for 8 weeks . The control and training patients did not differ at baseline , and the measured variables did not change in the control group during the 8 weeks . Citrate synthase activity in skeletal muscle increased after cycle training ( 23 % ; P < .02 ) and knee-extensor training ( 45 % ; P < .008 ) , and blood lactate concentration at submaximal intensities decreased ( P < .04 ) in both groups . However , only after knee-extensor training did the peak oxygen uptake increase ( 19 % ; P < .01 ) and sympathetic nervous system activity , measured as plasma norepinephrine concentration at rest ( P < .05 ) and during exercise ( P < .008 ) , decrease . Minnesota Living with Heart Failure question naire scores also showed improvement in the health-related quality of life ( P < .05 ) only after knee-extensor training . CONCLUSION Physical training is beneficial in previously trained patients with CHF . Aerobic training involving a minor muscle mass shows greater efficiency than training involving a major muscle mass CONTEXT Exercise training in patients with chronic heart failure improves work capacity by enhancing endothelial function and skeletal muscle aerobic metabolism , but effects on central hemodynamic function are not well established . OBJECTIVE To evaluate the effects of exercise training on left ventricular ( LV ) function and hemodynamic response to exercise in patients with stable chronic heart failure . DESIGN Prospect i ve r and omized trial conducted in 1994 - 1999 . SETTING University department of cardiology/outpatient clinic in Germany . PATIENTS Consecutive sample of 73 men aged 70 years or younger with chronic heart failure ( with LV ejection fraction of approximately 0.27 ) . INTERVENTION Patients were r and omly assigned to 2 weeks of in-hospital ergometer exercise for 10 minutes 4 to 6 times per day , followed by 6 months of home-based ergometer exercise training for 20 minutes per day at 70 % of peak oxygen uptake ( n=36 ) or to no intervention ( control group ; n=37 ) . MAIN OUTCOME MEASURES Ergospirometry with measurement of central hemodynamics by thermodilution at rest and during exercise ; echocardiographic determination of LV diameters and volumes , at baseline and 6-month follow-up , for the exercise training vs control groups . RESULTS After 6 months , patients in the exercise training group had statistically significant improvements compared with controls in New York Heart Association functional class , maximal ventilation , exercise time , and exercise capacity as well as decreased resting heart rate and increased stroke volume at rest . In the exercise training group , an increase from baseline to 6-month follow-up was observed in mean ( SD ) resting LV ejection fraction ( 0.30 [ 0.08 ] vs 0.35 [ 0.09 ] ; P=.003 ) . Mean ( SD ) total peripheral resistance ( TPR ) during peak exercise was reduced by 157 ( 306 ) dyne/s/cm(-5 ) in the exercise training group vs an increase of 43 ( 148 ) dyne/s/cm(-5 ) in the control group ( P=.003 ) , with a concomitant increase in mean ( SD ) stroke volume of 14 ( 22 ) mL vs 1 ( 19 ) mL in the control group ( P=.03 ) . There was a small but significant reduction in mean ( SD ) LV end diastolic diameter of 4 ( 6 ) mm vs an increase of 1 ( 4 ) mm in the control group ( P<.001 ) . Changes from baseline in resting TPR for both groups were correlated with changes in stroke volume ( r=-0.76 ; P<.001 ) and in LV end diastolic diameter ( r=0.45 ; P<.001 ) . CONCLUSIONS In patients with stable chronic heart failure , exercise training is associated with reduction of peripheral resistance and results in small but significant improvements in stroke volume and reduction in cardiomegaly . JAMA . 2000 BACKGROUND Among the factors that contribute to limiting exercise tolerance in chronic heart failure are reduced peripheral blood flow and impaired vasodilatory capacity . Exercise training improves vasodilatory capacity in normal subjects , but controlled studies of exercise training evaluating upper and lower limb blood flow rates have not been performed in patients with reduced ventricular function . Improved vasodilatory capacity could help explain how training increases exercise capacity in these patients . METHODS Twenty patients ( mean age 55 + /- 6 years ) with reduced left ventricular function ( mean ejection fraction 32 % + /- 6 % ) after a myocardial infa rct ion were r and omized to a 2-month high-intensity residential rehabilitation program or to a control group and were monitored over the subsequent year . Both groups were treated according to current practice with angiotensin-converting enzyme inhibition therapy . Training began 1 month after myocardial infa rct ion . Baseline and postischemic flow rates were measured by plethysmography in both the upper and lower limbs 1 month , 3 months , and 1 year after the infa rct ion . Peak oxygen uptake ( VO2 ) and cardiac output were measured before and after training , and peak VO2 was determined again after 1 year . RESULTS After 2 months of training peak VO2 increased 25 % , VO2 at the lactate threshold increased 40 % , and maximal cardiac output increased from 12.1 + /- 1.6 L/min to 13.9 + /- 2.4 L/min in the exercise group ( all p < 0.05 ) , whereas no differences were observed in the control group . At the 1-year follow-up no further increases in peak VO2 were noted in either group , but the higher value persisted in the trained group . However , changes in limb flow rates were poorly related to changes in both peak VO2 and maximal cardiac output . Improvements in baseline and postischemic flow rates occurred mainly in the lower limbs and were observed in the two groups to a similar degree . CONCLUSION Exercise training is highly effective in improving exercise capacity in patients with reduced ventricular function after myocardial infa rct ion . These improvements parallel an increase in maximal cardiac output , but they are unrelated to vasodilatory capacity . In patients with reduced ventricular function after myocardial infa rct ion , lower limb vasodilatory capacity improves gradually over the subsequent year , and these improvements occur irrespective of exercise training We prospect ively assessed whether baseline central hemodynamics and exercise capacity can predict improvement of VO2 at ventilatory threshold ( VT ) after exercise training in patients with severe chronic congestive heart failure . Eighteen patients ( mean + /- SEM ; age 52 + /- 2 years ) , half of them listed for transplant , underwent 3 weeks of exercise training ( interval cycle and treadmill walking ; 5 x/week ) and 3 weeks of activity restriction in a r and om-order crossover trial . Baseline data were not significantly different for groups with exercise training first and activity restriction first : cardiac index at rest ( 2.1 + /- 0.1 L/m2/min ) , maximum cardiac index ( 3.1 + /- 0.2 L/m2/min ) ( Fick ) , and echocardiographic ejection fraction ( 21 + /- 1 % ) . The same was true for cardiopulmonary exercise data ( cycle ergometry ; up 12.5 W/min ) : VO2 at VT ( 9.3 + /- 0.4 ml/kg/min ) , maximum VO2 ( 12.2 + /- 0.7 ml/kg/min ) , VT in percentage of predicted maximum VO2 ( 31 + /- 2 % ) , heart rate at VT ( 95 + /- 4 beats/min ) , and decrease of dead space-to-tidal volume ratio from rest to VT ( 33 + /- 1 -- > 29 + /- 1 ) . Improvement of VO2 at VT after training ( 2.2 + /- 0.4 ml/kg/min ; p < 0.001 ) was not related to baseline central hemodynamics ( r = < 0.10 for each ) , but was greater in patients with a lower baseline VO2 at VT ( r = -0.65 ; p < 0.01 ) , peak VO2 ( r = -0.66 ; p < 0.01 ) , VT in percentage of predicted maximum VO2 ( r = -0.74 ; p < 0.001 ) , heart rate at VT ( r = -0.63 ; p < 0.01 ) , and smaller decrease of dead space-to-tidal volume ratio from rest to VT ( r = 0.65 ; p < 0.01 ) . Ejection fraction after exercise training ( 24 + /- 2 % ) and activity restriction ( 23 + /- 2 % ) did not differ significantly compared with baseline , and patient status ( heart failure and cardiac rhythm ) remained stable . Three parameters accounted for 84 % of the variance of improvement in VO2 at VT : VO2 at VT in percent predicted maximum VO2 , decrease of dead space-to-tidal volume ratio , and heart rate at VT . The findings suggest that there was a greater increase in VO2 at VT after exercise training in patients with greater peripheral deconditioning at baseline . The improvement was unrelated to central hemodynamics . Clinical ly stable patients with severe chronic congestive heart failure , potential heart transplant c and i date s , and those awaiting transplantation may benefit from involvement in a short-term exercise training program BACKGROUND The purpose of this study was to examine the effects of exercise training on functional capacity in patients with heart failure . METHODS One hundred eighty-one patients in New York Heart Association class I to III , with ejection fraction < 40 % and 6-minute walk distance < 500 meters , were recruited into a r and omized , controlled , single-blind trial comparing 3 months of supervised training , then 9 months of home-based training with usual care . RESULTS There was a significant increase in 6-minute walk distance at 3 and 12 months but no between-group differences . Incremental peak oxygen uptake increased in the exercise group compared with the control group at 3 months ( 0.104 + /- 0.026 L/min vs 0.025 + /- 0.023 L/min ; P = .026 ) and 12 months ( 0.154 + /- 0.074 L/min vs 0.024 + /- 0.027 L/min ; P = .081 ) . Compared with the control group , significant increases were observed in the exercise group for arm and leg strength . No significant changes were observed in cardiac function or quality of life . Adherence to exercise was good during supervised training but reduced during home-based training . CONCLUSIONS Exercise training improves peak oxygen uptake and strength during supervised training . Over the final 9 months of the study , there was little further improvement , suggesting that some supervision is required for these patients . There were no adverse effects on cardiac function or clinical events BACKGROUND Beneficial training outcomes have been reported in patients with chronic heart failure ( CHF ) following leg exercise training . However , data from more comprehensive training programs are limited . The aim of this study was to test the hypothesis that exercise training applying the concept of comprehensive local muscle training can improve aerobic and functional working capacity as well as quality of life in patients with CHF . METHODS Twenty-four men and women [ age 63+/-9 years ( mean+/-S.D. ) ] with stable , moderate chronic heart failure ( left ventricular ejection fraction 30+/-10 % ) , were investigated in a r and omized controlled study with a training group of 16 patients and a control group of 8 patients . The training was performed as an aerobic resistance training by activating all the main muscle groups , one at a time . The patients exercised for 1 h , three times per week for 8 weeks . RESULTS Patient groups did not differ at baseline . Peak oxygen uptake ( 8 % , P<0.03 ) , the distance walked in a 6-min walking test ( 11 % , P<0.002 ) , the health-related quality of life ( P<0.001 ) and plasma norepinephrine levels at rest ( 32 % , P<0.003 ) and at submaximal intensities ( P<0.03 ) improved after training . No changes were found in the control group , except for decreased peak oxygen uptake ( P<0.02 ) and quality of life scores ( P<0.03 ) . CONCLUSIONS Since comprehensive physical training activating a minor muscle mass at a time markedly improves exercise capacity and quality of life and reduces catecholamine levels , it can be recommended for the rehabilitation of patients with CHF under supervision of a physical therapist The present study investigates whether lower-limb dominant exercise training in patients with chronic heart failure ( CHF ) improves endothelial function primarily in the trained lower extremities or equally in the upper and lower extremities . Twenty-eight patients with CHF were r and omized to the exercise or control group . The exercise group underwent cycle ergometer training for 3 months while controls continued an inactive sedentary lifestyle . Exercise capacity ( 6-min walk test ) and flow-mediated vasodilation in the brachial and posterior tibial arteries were evaluated . After 3 months , walking performance increased only in the exercise group ( 488+/-16 to 501+/-14 m [ control ] ; 497+/-23 to 567+/-39 m [ exercise , p<0.05 ] ) . The flow-mediated vasodilation in the brachial arteries did not change in either group ( 4.2+/-0.5 to 4.5+/-0.4 % [ control ] ; 4.3+/-0.5 to 4.6+/-0.4 % [ exercise ] ) , but that in the posterior tibial arteries increased only in the exercise group ( 4.1+/-0.5 to 4.1+/-0.3 % [ control ] ; 3.6+/-0.3 to 6.4+/-0.6 % [ exercise , p<0.01 ] ) . Cycle ergometer training improved flow-mediated vasodilation in the trained lower limbs , but not in the untrained upper limbs . Exercise training appears to correct endothelial dysfunction predominantly by a local effect in the trained extremities BACKGROUND AND PURPOSE Whilst cardiac rehabilitation is regularly offered to patients recovering from a myocardial infa rct ion , people with chronic heart failure are often excluded from exercise training programmes . This study was design ed to investigate the effects of eight weeks ' exercise training in patients with moderate chronic heart failure . METHOD Eight male patients entered a 16-week r and omized , controlled , crossover study of two months ' exercise training versus a control period . They performed supervised training three times a week and measures of indices of aerobic function and exercise tolerance were performed monthly throughout the study period . RESULTS After training , the time walked on a treadmill during an exercise tolerance test increased from 14.8 min ( 95 % CI ; range 10.4 - 18.1 min ) to 15.9 min ( range 12.1 - 15.9 min ) . Significant changes at peak exercise levels ( p < 0.05 ) were seen in oxygen uptake increasing from 3.4 metabolic equivalents ( METs ) ( 95 % CI ; range 2.6 - 4.2 METs ) to 4.0 METs ( range 3.2 - 4.9 METs ) , and in cardiac index , improving from 5.0 l/min-1/m-2 ( 95 % CI ; range 2.9 - 8.1 l/min-1/m-2 ) to 5.5 l/min-1/m-2 ( range 3.0 - 9.4 l/min-1/m-2 ) . Resting heart rate decreased significantly ( p < 0.05 ) , from 84 beats/min-1 ( 95 % CI ; range 73 - 105 beats/min-1 ) to 76 beats/min-1 ( range 64 - 90 beats/min-1 ) . Blood flow measurements by venous occlusion plethysmography showed a 21.5 % decrease ( range 58.5 - 238.9 % ) in resting blood flow to the lower leg and a 31.6 % increase ( range -7.2 % to 52.5 % ) after submaximal exercise , but these changes were not significant ( p > 0.05 ) . All benefits were lost within two months of ceasing regular exercise . CONCLUSION This study demonstrated that patients with moderate chronic heart failure derived beneficial physiological responses from eight weeks ' exercise training , but these were soon lost after cessation of regular exercise Eleven patients with chronic heart failure secondary to ischaemic heart disease ( mean [ SEM ] age 63.0 [ 2.3 ] years ; left ventricular ejection fraction 19 [8]% undertook 8 weeks of home-based bicycle exercise training and 8 weeks of activity restriction ( rest ) in a physician-blind , r and om-order , crossover trial . Training increased exercise duration from 14.2 ( 1.1 ) min to 16.8 ( 1.3 ) min and peak oxygen consumption from 14.3 ( 1.1 ) ml.min-1.kg-1 to 16.7 ( 1.3 ) ml.min-1.kg-1 . Heart rates at submaximum workloads and rate-pressure products were significantly reduced by training , and there was also a significant improvement in patient-rated symptom scores . No adverse events occurred during the training phase . Thus home-based physical training programmes are feasible even in severe chronic heart failure and have a beneficial effect on exercise tolerance , peak oxygen consumption , and symptoms . The commonly held belief that rest is the mainstay of treatment of chronic heart failure should no longer be accepted The aim of this study was to evaluate the impact of a three-month exercise program on the perception of quality of life in patients with severe chronic heart failure . In a r and omized controlled setting , 27 patients with a left ventricular ejection fraction of 18.1 + /- 8.0 % were entered into the study . The training group performed aerobic exercises for three hours/week while the control group continued their usual activities of daily living . Quality of life was measured using the German version of the MOS SF-36 . Two patients required a change in their drug regimen and were therefore withdrawn from the study . Twenty-five patients completed the study . In the exercise group the perception of quality of life improved significantly in the domains of vitality ( p = 0.0001 ) , physical role fulfillment ( p = 0.001 ) , physical ( p = 0.02 ) and social ( p = 0.0002 ) functioning . Exercise was effective in increasing peak oxygen uptake and exercise time ( p < 0.01 ) . Only weak correlations were registered between parameters of physical performance and quality of life domains . The results of the study indicate that aerobic exercise can improve the perception of quality of life in patients with severe chronic heart failure PURPOSE Increased respiratory muscle endurance and peak oxygen consumption ( VO(2peak ) ) induced by respiratory muscle training support the relationship between respiratory muscle function and exercise capacity in patients with heart failure . This raises the question whether exercise-training results in increased respiratory muscle function contributing to an increased exercise tolerance , a decreased perception of breathlessness , and an improved quality of life . METHODS Prospect i ve cohort analysis was completed on 24 patients with New York Heart Association ( NYHA ) Class III heart failure [ 18 men , 6 women ; aged = 64 ( SD 7.9 ) years ; percent ejection fraction ( % EF ) = 24.0 ( SD 7.8 ) ] . Maximal sustainable ventilatory capacity ( MSVC ) , submaximal and peak exercise responses , perception of breathlessness , and quality of life were measured before ( baseline ) and after ( end of study ) 12 weeks of exercise training . RESULTS As a result of exercise training , VO(2peak ) ( P=.01 ) and MSVC ( P<.001 ) increased , with MSVC contributing to a larger proportion of the variability for VO(2peak ) at study completion ( r=0.57 vs 0.42 ) . Although stroke volume did not increase beyond exercise at 25 W and did not change with exercise training , ventilation decreased during exercise ( P<.05 ) , perception of breathing difficulty ( P<.05 ) was reduced , and quality of life was enhanced ( P=.008 ) . CONCLUSIONS Despite no increase in cardiac output and stroke volume , respiratory muscle endurance improved with exercise training , contributing to increased exercise capacity , decreased breathlessness , and decreased perception of breathlessness . Practical implication s can include less frequent rest periods and fatigue , greater confidence , maintenance of independence , and enhanced quality of life The aim of the study was to evaluate , in a controlled setting , the effects of a 5-month dynamic peripheral training programme in patients with clinical signs of congestive heart failure with special reference to their anaerobic threshold , muscle function , heart rate variability and quality of life . Twenty-four r and omized patients with clinical signs of heart failure in NYHA II-III entered the study . Training result ed in a significant ( p = 0.01 ) change in the anaerobic threshold , the patients ' ability to lift weights ( p = 0.01 ) and performance of heel-lift ( p = 0.01 ) . The heart rate recorded during the training exercises decreased significantly ( p = 0.04 ) . There were no significant differences in peak oxygen uptake , isokinetic and isometric strength , HRV and quality of life except for three items in the control group . The results of this study indicate that peripheral training is beneficial for patients with clinical signs of congestive heart failure To determine the incidence of major cardiovascular complications in outpatient cardiac rehabilitation programs , we obtained data from 167 r and omly selected cardiac rehabilitation programs via mailed question naires and follow-up telephone calls . These 167 programs reported that 51 303 patients exercised 2 351 916 hours from January 1980 through December 1984 . Twenty-one cardiac arrests ( 18 in which the patient was successfully resuscitated and three fatal ) and eight nonfatal myocardial infa rct ions were reported . The incidence rates per million patient hours of exercise were 8.9 for cardiac arrests ( one per 111 996 patient-hours ) , 3.4 for myocardial infa rct ions ( one per 293 990 patient-hours ) , and 1.3 for fatalities ( one per 783 972 patient-hours ) . There was no statistically significant difference in frequency of these events among programs of varying size or extent of electrocardiographic monitoring . These data indicate that current cardiac rehabilitation practice allows for prescribed supervised exercise by patients with cardiovascular disease to be performed at a low risk of major cardiovascular complications Patients with heart failure ( HF ) often have profound activity limitations and diminished quality of life ( QOL ) due to symptoms of dyspnea and fatigue . Although recent studies demonstrate positive physiologic and psychological benefits of low to moderate intensity , supervised , aerobic exercise training performed 3 to 5 days/ week for 20 to 40 minutes ' duration , in a monitored setting , the efficacy of a home-based exercise program combining endurance and resistance exercise on symptoms and QOL , are unknown . This r and omized controlled study examined the efficacy , safety , and adherence rates of a 3-month home-based combined walking and resistance exercise program on symptoms and QOL in 40 women and men aged 30 to 76 years with New York Heart Association class II to III HF . Baseline and 3-month evaluations consisted of a chronic HF question naire to assess symptoms and QOL and exercise capacity by symptom-limited treadmill exercise test with respiratory gas analysis . The exercise intervention improved fatigue ( p = 0.02 ) , emotional function ( p = 0.01 ) , and mastery ( p = 0.04 ) . Overall exercise adherence was excellent ( 90 % ) and there were no reported adverse events . A moderate intensity home-based combined walking and resistance program for patients with class II to III HF is safe and effective in reducing symptoms and improving QOL The role of exercise training in the treatment of heart failure remains a paradox , because exercise intolerance is a characteristic finding in patients with this condition . Improved exercise performance after exercise training has been seen in patients with heart failure , but such training is not yet widely incorporated into clinical practice . In addition , the mechanisms by which this improvement occurs are uncertain . Factors that may explain the improvement include an increase in cardiac output [ 1 , 2 ] , an improvement in skeletal muscle metabolism [ 3 - 5 ] , and an increase in peak blood flow to the exercising limb that is caused by a decrease in vascular resistance [ 1 , 2 , 5 ] . Five r and omized trials [ 5 - 9 ] have assessed exercise performance after exercise training in patients with symptomatic heart failure . Two trials that assessed cardiorespiratory fitness as measured by oxygen consumption ( Vo 2 ) showed a 22 % improvement in peak Vo 2 after 4 weeks of exercise training [ 6 ] and a 31 % improvement after 6 months of exercise training [ 5 ] . Two other trials [ 7 , 8 ] showed an increase in exercise duration after 12 weeks of exercise training , and a fifth trial [ 9 ] recently found no significant increase in peak Vo 2 after exercise training . We sought to assess the benefit of exercise training in patients with heart failure caused by left ventricular systolic dysfunction and to further describe the physiologic changes associated with exercise training . Functional capacity and cardiorespiratory fitness were measured before and after exercise training in patients with compensated heart failure who were receiving st and ard medical therapy . Patients were r and omly assigned either to a group that participated in a program of three supervised exercise sessions per week for 24 weeks ( exercise group ) or to a control group that did not exercise . Methods Patients Forty men with compensated heart failure and left ventricular dysfunction were r and omly assigned to the exercise group ( n = 21 ) or the control group ( n = 19 ) . R and omization was done according to a computer-generated r and omization list . Patients were recruited from the outpatient heart failure clinic of a tertiary care hospital or from the office of a cardiologist practicing in the community . Patients meeting the eligibility criteria for the study first received a brief explanation of the study from their cardiologist . Patients willing to participate in the r and omized trial were then referred . The hospital 's institutional review board approved our study , and all patients provided written informed consent . Inclusion criteria were New York Heart Association class II or III , a resting ejection fraction of 35 % or less as measured by echocardiography or gated equilibrium radionuclide angiography , and no change in medical therapy for 30 days before r and omization . Exclusion criteria were atrial fibrillation , acute myocardial infa rct ion within the previous 3 months , angina pectoris at rest or induced by exercise , current enrollment in another clinical trial , and current participation in a regular exercise program ( at least twice weekly ) . Patients were classified as having ischemic cardiomyopathy if they had had a myocardial infa rct ion or had angiographic evidence of coronary artery disease that could explain the extent of ventricular dysfunction . If they did not meet these criteria , they were classified as having idiopathic dilated cardiomyopathy . Study Design Exercise tests were completed before and after a 30-day pre study period . The pre study period was used to document the stability of exercise tolerance , clinical conditions , and prescribed medications . Immediately after completing the second exercise test , patients were r and omly assigned to the exercise group or the control group . Each patient 's assignment was sealed in an envelope until completion of the second exercise test . Exercise testing was repeated at weeks 12 and 24 for patients in both groups . Each patient 's physician was asked not to change a patient 's drug regimen during the study , if possible . Patients in the control group were instructed to maintain their normal daily activity habits and not to begin an exercise regimen . Controls were contacted by telephone every 2 to 3 weeks to assess compliance , cardiac-related symptoms , and continued avoidance of a regular activity program . Exercise Testing Symptom-limited , maximal exercise tests were completed using an upright stationary cycle ergometer ( Monark , Stockholm , Sweden ) , starting at a power output of 25 W and increasing by 25 W every 3 minutes . Tests were discontinued when dyspnea or calf , thigh , or generalized fatigue developed . Patients were monitored by electrocardiography ( Q-3000 , Quinton Instruments , Seattle , Washington ) at rest , during exercise , and during 8 minutes of recovery . Blood pressure , heart rate , rating of perceived exertion ( categorized on the Borg scale ; range , 6 to 20 ) , and a 12-lead electrocardiogram were obtained after 30 minutes of supine rest , within the last 25 seconds of each stage of exercise , and during peak exercise . Air expired during exercise testing was analyzed using a Horizon II Metabolic System ( Sensormedics , Yorba Linda , California ) . Direct measurement and calculations were used to determine peak Vo 2 , carbon dioxide production ( Vco 2 ) , ventilation , oxygen ( O2 ) pulse , and respiratory exchange ratio . Expired air was sample d at a rate of 10 per second and reported as a 15-second average . Exercise tests in the exercise group and the control group represented peak effort , as evidence d by ratings of perceived exertion that were generally 16 or more and respiratory exchange ratios that were greater than 1.1 . Ventilatory derived anaerobic threshold ( V-AT ) was determined using the V-slope method , originally defined by Beaver and colleagues [ 10 ] and later simplified by others [ 11 - 13 ] . This measure , in which Vco 2 is plotted as a function of Vo 2 , can be used to detect the beginning of excess carbon dioxide production caused by the buffering of H+ that arise from lactic acid . Two independent , experienced review ers blinded to the patients ' group assignment and testing periods determined V-AT . For four patients in the exercise group and five patients in the control group , a review er could not determine V-AT in at least one of each patient 's three exercise tests . We also computed the slope of the relation between ventilation and Vco 2 as a marker of the severity of heart failure [ 14 ] . Exercise Training Each exercise training session lasted 43 minutes . During each session , patients completed a 5-minute , slow warm-up phase , a 33-minute aerobic phase ( three different types of exercise equipment were used for 11 minutes each ) , and a 5-minute cool-down phase . Exercise equipment included motor-driven treadmills , stationary cycles , rowing machines , and arm ergometers . Patients attended the exercise training program three times per week . Using the heart rate reserve method [ 15 ] , we set exercise intensity at 60 % for the first 2 weeks and then increased it , as tolerated , to as high as 80 % . A rating of perceived exertion of 12 to 14 was also used to guide exercise intensity . Heart rate and rhythm were monitored during exercise using a single-lead electrocardiography telemetry system . Statistical Analysis Of the 40 patients entered into the study , only those who also completed the exercise tests at weeks 12 and 24 were considered in the data analysis . The 5 patients who dropped out for nonmedical reasons were asked to return for follow-up testing , but they refused . We compared patient characteristics at baseline using an unpaired t-test or the Fisher exact test . We used univariate repeated- measures analysis of variance with the Greenhouse-Geisser [ 16 ] sphericity correction to determine whether a significant ( P < 0.05 ) difference in the change across time occurred between the two groups . For variables for which a significant ( or a tendency toward a significant ) time-group interaction was detected , we used analysis of variance to assess a within-group time effect and used a Student two- sample t-test to assess a group effect . For the latter two analyses , we used the Bonferroni multiple testing adjustment to reduce the level accordingly . Values are expressed as means SE . The SAS software package ( SAS Institute , Cary , North Carolina ) was used for all analyses . Results Compliance , Medical Therapy , and Safety Among patients who completed the study , no differences in demographic characteristics were seen between the two study groups after r and omization ( Table 1 ) . Of the 40 patients r and omly assigned at baseline , 29 completed the study and 11 dropped out ( Table 1 ) . Regardless of the reason for drop out , patients with ischemic cardiomyopathy tended to drop out more frequently ( 7 of 16 patients [ 44 % ] ) than did patients with dilated cardiomyopathy ( 4 of 24 patients [ 17 % ] ) ( P = 0.08 ) . In addition , ejection fraction tended to be lower in patients who dropped out than in those who did not ( 18 % 5 % compared with 23 % 8 % ; P = 0.09 ) , and patients who dropped out tended to be older ( 61 10 years compared with 54 11 years ; P = 0.07 ) . No differences were seen in New York Heart Association class ( II compared with III ) between patients who completed the study and those who dropped out . Table 1 . Baseline Patient Characteristics * Fifteen patients in the exercise group completed the study . Two patients dropped out because of noncardiac medical conditions ( progressive , limiting arthritis in one patient and newly diagnosed cancer in the other ) that developed within 1 month of the start of the exercise program . One patient developed atrial fibrillation between week 12 and week 24 ; 3 other patients stopped exercising for personal reasons before week 12 and refused follow-up testing . Fourteen of the 19 patients in the control group completed the study . Two dropped out for personal reasons and refused follow-up testing , 1 developed atrial fibrillation between week 12 and week 24 , 1 was PURPOSE Systolic left ventricular dysfunction is a weak predictor of exercise tolerance in patients with chronic congestive heart failure . This study aim ed to determine physiologic and other predictors of effort tolerance and adaptability to training in a wide variety of patients with coronary artery disease . METHODS One hundred seventy-one patients ( group 0 ) with documented coronary artery disease and various degrees of left ventricular dysfunction were enrolled into a medically supervised exercise training program for 6 months . One hundred six patients had an ejection fraction greater than 50 % ( group 1 ) , 38 patients between 35 % and 50 % ( group 2 ) , and 27 patients less than 35 % ( group 3 ) . RESULTS Resting parameters of systolic and diastolic left ventricular function did not predict the effort tolerance of patients with coronary artery disease at any level of left ventricular impairment . Noncardiac factors including age , gender , Broca index , and forced vital capacity explained 50 % of the variation in peak oxygen uptake in group 0 . Peak oxygen uptake , ventilatory threshold , and treadmill time to exhaustion increased significantly after training in all groups . The magnitude of the improvement in these variables was the same for all groups . CONCLUSIONS Noncardiac factors were better predictors of the effort tolerance of patients with coronary artery disease than parameters of left ventricular function at entry to an exercise program or after 6 months of training . A similar degree of adaptation to training was seen in all patients regardless of their degree of left ventricular systolic or diastolic dysfunction Skeletal muscle adaptations to high intensity knee extensor strength and /or endurance training in patients with chronic heart failure were investigated . Eleven patients with chronic heart failure were r and omized into two groups and exercised the m. quadriceps femoris 3 days/week for 8 weeks . After training , the maximal exercise intensity tolerated on the ergometer cycle was raised from 99 ( 32 ) to 114 ( 40 ) watts ( W , P < 0.05 ) for all 11 patients . Peak dynamic knee extensor work rate showed the greatest increase after endurance training ( 40 % , P < 0.01 ) . Maximal dynamic and isometric strength were elevated by 40 - 45 % ( P < 0.05 ) after strength training . The cross-sectional area of m. quadriceps femoris was increased in the strength-trained legs ( 9 % , P < 0.05 ) , and the capillary per fibre ratio of m. vastus lateralis was raised by 47 and 58 % in the endurance-trained legs ( P < 0.05 ) . The oxidative enzyme activity in m. vastus lateralis was significantly raised above 50 % after endurance training , whereas glycolytic enzyme activity was unaltered . The peripheral skeletal musculature in patients with chronic heart failure adapts fairly quickly to high intensity knee extensor training . This results in a marked rise in local , and a small rise in total work capacity , indicating maintained plasticity of skeletal muscle in chronic heart failure patients OBJECTIVE To describe the effects of exercise training on chronotropic incompetence in patients with stable heart failure , as measured by their inability to achieve a peak exercise heart rate greater than 85 % of maximum . BACKGROUND Exercise intolerance and chronotropic incompetence are characteristic of patients with heart failure . Exercise training improves exercise capacity in these patients ; however , to what extent reversal of chronotropic incompetence contributes to such a response remains uncertain . METHODS Fifty-one patients undergoing st and ard medical therapy were r and omly assigned to a 24-week exercise training program or a no exercise control group . Twenty-one of 26 patients assigned to the exercise group and 22 of 25 control patients completed the study . Peak oxygen consumption , resting and exercise plasma norepinephrine level , and quality of life ( Living With Heart Failure Question naire ) were assessed . RESULTS A significant ( P < .05 ) increase in peak heart rate was observed in the exercise group ( 9 + /- 3 beats/min ) when compared with the control group ( 1 + /- 3 beats/min ) . Among exercise-trained patients with chronotropic incompetence at baseline ( n = 14 ) , the increase in peak heart rate at week 24 was 12 + /- 3 beats/min . Peak oxygen consumption was significantly ( P < .05 ) increased in the exercise group ( 204 + /- 57 mL/min ) versus the control group ( 72 + /- 33 mL/min ) . Health-related quality of life was not significantly changed with exercise training . Twenty-four weeks of exercise training induced a greater ( P < .05 ) reduction in plasma norepinephrine at rest and during exercise in patients with a nonischemic cardiomyopathy versus those with ischemic cardiomyopathy . CONCLUSIONS Exercise training results in an increase in peak heart rate and partial reversal of chronotropic incompetence among patients with stable heart failure . These responses contribute , in part , to the exercise training-induced increase in exercise capacity that occurs in these patients BACKGROUND Beneficial effects of physical training on exercise tolerance , autonomic and skeletal muscle function and limb blood flow have been demonstrated in chronic heart failure . Because this rehabilitation is expensive , may involve risk , and has unknown effects on prognosis , the possibility of predicting benefit on the basis of individual patient data is intriguing . The most suitable exercise training programme has not yet been established . METHODS AND RESULTS We review ed the progress of 134 stable heart failure patients studied in r and omized controlled trials of physical training . A significant training effect ( + 13 % peak oxygen consumption , + 17 % exercise duration ) was associated with improved autonomic indices ( resting catecholamines and hormones , heart rate variability ) , without significant side-effects . No ventilatory , haemodynamic , autonomic or clinical factor at baseline was a predictor of outcome . Similar beneficial effects were observed in both male and female patients . The improvement in oxygen consumption after 16 weeks training was higher than after 6 weeks ( + 2.6 + /- 3.0 vs + 0.3 + /- 3.1 ml.kg.min-1 , P < 0.05 ) . The combination of cycle ergometer with calisthenic exercises was more beneficial than cycle ergometer alone ( + 2.7 + /- 4.2 vs 1.2 + /- 2.0 ml.kg.min-1 , P < 0.01 ) . The presence of nonsustained ventricular tachycardia did not preclude a training effect . Patients older than 70 years were able to train , although less effectively than the younger ones . No difference in exercise gain was observed whether the patients trained in the hospital or at home . CONCLUSION The positive effects of physical rehabilitation in chronic stable heart failure patients are confirmed . No baseline patient factor was significantly correlated with outcome . A tailored , moderate , home-based , combined cycle ergometer , plus calisthenic exercise training seems safe and beneficial in a large cohort of heart failure patients , with similar benefits in a variety of conditions and different hospital setting BACKGROUND Cardiac rehabilitation with exercise training alters sympathovagal control of heart rate variability ( HRV ) toward parasympathetic dominance in patients after acute myocardial infa rct ion ( MI ) . However , its effects on HRV in patients after MI with new-onset left ventricular dysfunction are yet unknown . We aim ed to investigate the effects of 8 weeks of supervised , high-intensity exercise training on time- and frequency-domain measures of HRV in this selected patient population . METHODS AND RESULTS Twenty-five men with an acute MI and a low ejection fraction were r and omly assigned to enter or not to enter a training program in a regional rehabilitation center . HRV was evaluated before and after 1 and 2 months of training and at 12 months . Maximal exercise testing with respiratory gas exchange was performed at baseline and after training . Resting heart rate decreased ( P < . 01 ) and the percentage of R-R intervals differing > 50 ms from the preceding one ( pNN50 ) increased ( P < .05 ) after training . The st and ard deviation of R-R intervals ( SDRR ) tended to increase , but frequency-domain indexes remained unchanged . There was a significant decrease in SDRR ( P < .05 ) and high-frequency power ( P < .01 ) at 12 months in untrained patients . Exercise time increased by 38 % and maximal oxygen uptake increased by 29 % in the training group ( P < . 01 ) . CONCLUSIONS Despite beneficial effects on clinical variables , exercise training did not markedly alter HRV indexes . A significant decrease in SDRR and high-frequency power in the control group suggests an ongoing process of sympathovagal imbalance in favor of sympathetic dominance in untrained patients after MI with new-onset left ventricular dysfunction To characterize the differences in adaptations to endurance exercise training and prognosis between patients with depressed and normal left ventricular ( LV ) function , 20 patients with coronary artery disease were studied and followed for 7 years . Patients with normal LV function had enhancement of LV systolic function , but the group with LV dysfunction did not exhibit cardiac adaptations and had more cardiac events than those with normal LV function OBJECTIVES The goal of this study was to test the hypothesis that exercise training reduces resting sympathetic neural activation in patients with chronic advanced heart failure . BACKGROUND Exercise training in heart failure has been shown to be beneficial , but its mechanisms of benefit remain unknown . METHODS Sixteen New York Heart Association class II to III heart failure patients , age 35 to 60 years , ejection fraction < or = 40 % were divided into two groups : 1 ) exercise-trained ( n = 7 ) , and 2 ) sedentary control ( n = 9 ) . A normal control exercise-trained group was also studied ( n = 8) . The four-month supervised exercise training program consisted of three 60 min exercise sessions per week , at heart rate levels that corresponded up to 10 % below the respiratory compensation point . Muscle sympathetic nerve activity ( MSNA ) was recorded directly from peroneal nerve using the technique of microneurography . Forearm blood flow was measured by venous plethysmography . RESULTS Baseline MSNA was greater in heart failure patients compared with normal controls ; MSNA was uniformly decreased after exercise training in heart failure patients ( 60 + /- 3 vs. 38 + /- 3 bursts/100 heart beats ) , and the mean difference in the change was significantly ( p < 0.05 ) greater than the mean difference in the change in sedentary heart failure or trained normal controls . In fact , resting MSNA in trained heart failure patients was no longer significantly greater than in trained normal controls . In heart failure patients , peak VO(2 ) and forearm blood flow , but not left ventricular ejection fraction , increased after training . CONCLUSIONS These findings demonstrate that exercise training in heart failure patients results in dramatic reductions in directly recorded resting sympathetic nerve activity . In fact , MSNA was no longer greater than in trained , healthy controls PURPOSE This study determined the amplitude and rate of adaptation to 10 wk of continuous ( CEx ) and intermittent exercise ( IEx ) in a group of older men when the training intensity and total amount of work completed by each exercise group were the same . METHODS Ten healthy men were assigned to either a CEx ( 63 + /- 1 yr ) or IEx ( 65 + /- 1 yr ) group while a further five subjects ( 65 + /- 1 yr ) acted as nonexercising controls ( CON ) . The three groups ( CEx , IEx , and CON ) were matched for age , peak oxygen uptake ( VO2peak ) , and cardiac output ( Qpeak ) before commencing training . The CEx group trained for 30 min at an intensity corresponding to 70 - 75 % VO2peak , and the IEx group trained for a total exercise time of 30 min using intermittent exercise ( 60-s exercise , 60-s rest ) at the same absolute intensity as the CEx group ( CEx 112 + /- 5W ; IEx 112 + /- 5W ) . The exercise groups trained three times per week and completed a similar amount of work during each training session ( CEx , 199 + /- 9 kJ ; IEx 195 + /- 9 kJ , P = 0.67 ) . RESULTS The CEx and IEx groups had similar and significant amplitude increases in peak VO2 , ventilation ( VEpeak ) , power , Q , and SV after training . Peak VO2 , Qpeak , SVpeak , and peak arteriovenous O2 difference for the CON group were unchanged . The change in VO2peak , peak ventilation , and peak power for CEx and IEx groups were best described by a linear model . Moreover , the CEx and IEx groups had the same rate of change in VO2peak ( CEx : 0.02 + /- 0.00 L x min(-1 ) x wk(-1 ) , IEx : 0.02 + /- 0.00 L x min(-1 ) x wk(-1 ) , P = 0.32 ) , VEpeak ( CEx : 2.0 + /- 0.2 L x min(-1 ) x wk(-1 ) , IEx : 1.2 + /- 0.5 L x min(-1 ) x wk(-1 ) , P = 0.10 ) , and peak power ( CEx : 2.6 + /- 0.4 W x wk(-1 ) , IEx : 2.6 + /- 0.4 W x wk(-1 ) , P = 0.92 ) . CONCLUSION These results suggest that the amplitude and rate of change of select adaptations in men aged 60 - 70 yr are independent of the mode of training ( i.e. , continuous or intermittent exercise ) when the absolute training intensity and the total amount of work completed were similar A total of 12 patients ( mean age + /- SEM 63 + /- 2.6 years ) with moderate to severe heart failure ( ejection fraction = 23 + /- 3.2 % ) were included in a placebo-controlled crossover trial . Patients were r and omly allocated to 4 periods of 6 weeks each : placebo , placebo and physical training , lisinopril 10 mg daily , and lisinopril and physical training . The exercise time increased from 13.6 + /- 0.9 min with placebo to 15 + /- 1 min with training alone , and to 16.1 + /- 0.7 min with lisinopril and training . With lisinopril alone there was a non-significant increase in exercise time , to 14.5 + /- 0.6 min . Improvements in exercise time were accompanied by a similar increase in peak oxygen consumption . Overall , the most significant improvements in symptoms and indices of cardiorespiratory fitness were achieved with a combination of lisinopril and training . Thus physical training is not only a useful adjunct to the existing medical therapy for heart failure , but it may also provide symptomatic benefits in its own right |
10,790 | 23,658,120 | Significant correlations were observed between responses to analgesics and several QST parameters including ( 1 ) heat pain threshold in experimental human pain , ( 2 ) electrical and heat pain thresholds , pressure pain tolerance and suprathreshold heat pain in surgical patients , and ( 3 ) electrical and heat pain threshold and conditioned pain modulation in patients with chronic pain .
Although promising , the current evidence is not sufficiently robust to recommend the use of any specific QST parameter in predicting analgesic response . | The role of quantitative sensory testing ( QST ) in prediction of analgesic effect in humans is scarcely investigated .
This up date d review assesses the effectiveness in predicting analgesic effects in healthy volunteers , surgical patients and patients with chronic pain . | & NA ; The large inter‐individual variability in the magnitude of analgesia in response to opioids and the high prevalence of adverse events associated with their use underline the clinical importance of being able to predict who will or will not respond to opioid treatment . The present study used both static and dynamic quantitative sensory testing ( QST ) on 40 healthy volunteers in order to test whether this methodology can predict the analgesic effects of oral oxycodone , as compared to a placebo , on latency to onset , pain intensity , and tolerance to the cold pressor test ( CPT ) . Static QST consisted of measuring heat and cold pain thresholds . Dynamic QST included measurements of the magnitude of the diffuse noxious inhibitory control (DNIC)‐like effect and of temporal summation ( TS ) . Results showed that oxycodone , but not the placebo , significantly elevated the latency and tolerance to cold pain and significantly reduced pain intensity . The static QST results showed that heat pain thresholds predicted the magnitude of reduction in pain intensity in response to oxycodone treatment ( F(1,22 ) = 5.63 , p = 0.027 , R2 = 0.17 ) . The dynamic QST results showed that TS predicted the effect of oxycodone on the tolerance to CPT ( F(1,38 ) = 9.11 , p = 0.005 , R2 = 0.17 ) . These results suggest that both static and dynamic QST have the potential to be useful in the prediction of the response to opioid treatment Prognosis studies are investigations of future events or the evaluation of associations between risk factors and health outcomes in population s of patients ( 1 ) . The results of such studies improve our underst and ing of the clinical course of a disease and assist clinicians in making informed decisions about how best to manage patients . Prognostic research also informs the design of intervention studies by helping define subgroups of patients who may benefit from a new treatment and by providing necessary information about the natural history of a disorder ( 2 ) . There has recently been a rapid increase in the use of systematic review methods to synthesize the evidence on research questions related to prognosis . It is essential that investigators conducting systematic review s thoroughly appraise the method ologic quality of included studies to be confident that a study 's design , conduct , analysis , and interpretation have adequately reduced the opportunity for bias ( 3 , 4 ) . Caution is warranted , however , because inclusion of method ologically weak studies can threaten the internal validity of a systematic review ( 4 ) . This follows abundant empirical evidence that inadequate attention to biases can cause invalid results and inferences ( 5 - 9 ) . However , there is limited consensus on how to appraise the quality of prognosis studies ( 1 ) . A useful framework to assess bias in such studies follows the basic principles of epidemiologic research ( 10 , 11 ) . We focus on 6 areas of potential bias : study participation , study attrition , prognostic factor measurement , confounding measurement and account , outcome measurement , and analysis . The main objectives of our review of review s are to describe methods used to assess the quality of prognosis studies and to describe how well current practice s assess potential biases . Our secondary objective is to develop recommendations to guide future quality appraisal , both within single studies of prognostic factors and within systematic review s of the evidence . We hope this work facilitates future discussion and research on biases in prognosis studies and systematic review s. Methods Literature Search and Study Selection We identified systematic review s of prognosis studies by search ing MEDLINE ( 1966 to October 2005 ) using the search strategy recommended by McKibbon and colleagues ( 12 ) . This strategy combines broad search terms for systematic review s ( systematic review .mp ; meta- analysis .mp ) and a sensitive search strategy for prognosis studies ( cohort , incidence , mortality , follow-up studies , prognos * , predict * , or course ) . We also search ed the reference lists of included review s and method ologic papers to identify other relevant publications . We restricted our search to English- language publications . One review er conducted the search and selected the studies . Systematic review s , defined as review s of published studies with a comprehensive search and systematic selection , were included if they assessed the method ologic quality of the included studies by using 1 or more explicit criteria . We excluded studies if they were meta-analyses of independent patient data only , if their primary goal was to investigate the effectiveness of an intervention or specific diagnostic or screening tests , or if they included studies that were not done on humans . Data Extraction and Synthesis Individual items included in the quality assessment of the systematic review s were recorded as they were reported in the publication ( that is , the information that would be available to readers and future review ers ) . We review ed journal Web sites and contacted the authors of the systematic review s for additional information when authors made such an offer in their original papers . When review s assessed different study design s by using different sets of quality items , we extracted only those items used to assess cohort studies . We constructed a comprehensive list of distinct items that the review s used to assess the quality of their included studies . The full text of each review was screened . All items used by the review authors to assess the quality of studies were extracted into a computerized spreadsheet by 1 review er . Two experienced review ers , a clinical epidemiologist and an epidemiologist , independently synthesized the quality items extracted from the prognosis review s to determine how well the systematic review s assessed potential biases . We did this in 3 steps : 1 ) identified distinct concepts or domains addressed by the quality items ; 2 ) grouped each extracted quality item into the appropriate domain or domains ; and 3 ) identified the domains necessary to assess potential biases in prognosis studies . We then used this information to assess how well the review s ' quality assessment included items from the domains necessary to assess potential biases . After completing each of the first 3 steps , the review ers met to attempt to reach a consensus . The consensus process involved each review er presenting his or her observations and results , followed by discussion and debate . A third review er was available in cases of persistent disagreement or uncertainty . In the first step , all domains addressed by the quality items were identified . The first review er iteratively and progressively defined the domains as items were extracted from the included review s. The second review er defined domains from a r and om list of all extracted quality items . Limited guidance was provided to the review ers so that their assessment s and definitions of domains would be independent . The review ers agreed on a final set of domains that adequately and completely defined all of the extracted items . In the second step , review ers independently grouped each extracted item into the appropriate domains . Review ers considered each extracted item by asking , What is each particular quality item addressing ? or What are the review 's authors getting at with the particular quality assessment item ? . Items were grouped into the domain or domains that best represented the concepts being addressed . For example , the extracted items at least 80 % of the group originally identified was located for follow-up and follow-up was sufficiently complete or does n't jeopardize validity were each independently classified by both review ers as assessing the domain completeness of follow-up adequate , whereas the extracted item quantification and description of all subjects lost to follow-up was classified as assessing the domain completeness of follow-up described . In the third step , we identified the domains necessary to assess potential biases . Each review er considered the ability of the identified domains to adequately address , at least in part , 1 of the following 6 potential biases : 1 ) study participation , 2 ) study attrition , 3 ) prognostic factor measurement , 4 ) confounding measurement and account , 5 ) outcome measurement , and 6 ) analysis . Domains were considered to adequately address part of the framework if information garnered from that domain would inform the assessment of potential bias . For example , both review ers judged that the identified domain study population represents source population or population of interest assessed potential bias in a prognosis study , whereas the domain research question definition did not , although the latter is an important consideration in assessing the inclusion of studies in a systematic review . Finally , on the basis of our previous ratings , we looked at whether each review included items from the domains necessary to assess the 6 potential biases . We calculated the frequency of systematic review s by assessing each potential bias and the number of review s that adequately assessed bias overall . From this systematic synthesis , we developed recommendations for improving quality appraisal in future systematic review s of prognosis studies . We used Microsoft Access and Excel 2002 ( Microsoft Corp. , Redmond , Washington ) for data management and SAS for Windows , version 9.1 ( SAS Institute , Inc. , Cary , North Carolina ) for descriptive statistics . Role of the Funding Sources The funding sources , the Canadian Institutes of Health Research , the Canadian Chiropractic Research Foundation , the Ontario Chiropractic Association , and the Ontario Ministry of Health and Long Term Care , did not have a role in the collection , analysis , or interpretation of the data or in the decision to su bmi t the manuscript for publication . Results We identified 1384 potentially relevant articles . Figure 1 shows a flow chart of studies that were included and excluded . Figure 2 shows the number of review s identified by year of publication . We excluded 131 systematic review s of prognosis studies that did not seem to include any quality assessment of the included studies ; this represented 44 % of prognosis review s. We included 163 review s of prognosis studies in our analysis ( 13 - 175 ) . The most common topics were cancer ( 15 % ) , musculoskeletal disorders and rheumatology ( 13 % ) , cardiovascular ( 10 % ) , neurology ( 10 % ) , and obstetrics ( 10 % ) . Other review s included a wide range of health and health care topics . Sixty-three percent of the review s investigated the association between a specific prognostic factor and a particular outcome ; the remainder investigated multiple prognostic factors or models . The number of primary studies included in each systematic review ranged from 3 to 167 ( median , 18 [ interquartile range , 12 to 31 ] ) . A complete description of the included review s is available from the authors on request . Figure 1 . Flow diagram of inclusion and exclusion criteria of systematic review s. Figure 2 . Number of systematic review s of prognosis studies identified over time . Quality Items One hundred fifty-three review s provided adequate detail to allow extraction of quality items . Eight hundred eighty-two distinct quality items were extracted from the review s. Most review s developed their own set of quality items , with only a few applying criteria from previous review s. Most quality items Objective To examine the prevalence of outcome reporting bias — the selection for publication of a subset of the original recorded outcome variables on the basis of the results — and its impact on Cochrane review s. Design A nine point classification system for missing outcome data in r and omised trials was developed and applied to the trials assessed in a large , unselected cohort of Cochrane systematic review s. Research ers who conducted the trials were contacted and the reason sought for the non-reporting of data . A sensitivity analysis was undertaken to assess the impact of outcome reporting bias on review s that included a single meta- analysis of the review primary outcome . Results More than half ( 157/283 ( 55 % ) ) the review s did not include full data for the review primary outcome of interest from all eligible trials . The median amount of review outcome data missing for any reason was 10 % , whereas 50 % or more of the potential data were missing in 70 ( 25 % ) review s. It was clear from the publications for 155 ( 6 % ) of the 2486 assessable trials that the research ers had measured and analysed the review primary outcome but did not report or only partially reported the results . For reports that did not mention the review primary outcome , our classification regarding the presence of outcome reporting bias was shown to have a sensitivity of 88 % ( 95 % CI 65 % to 100 % ) and specificity of 80 % ( 95 % CI 69 % to 90 % ) on the basis of responses from 62 trialists . A third of Cochrane review s ( 96/283 ( 34 % ) ) contained at least one trial with high suspicion of outcome reporting bias for the review primary outcome . In a sensitivity analysis undertaken for 81 review s with a single meta- analysis of the primary outcome of interest , the treatment effect estimate was reduced by 20 % or more in 19 ( 23 % ) . Of the 42 meta-analyses with a statistically significant result only , eight ( 19 % ) became non-significant after adjustment for outcome reporting bias and 11 ( 26 % ) would have overestimated the treatment effect by 20 % or more . Conclusions Outcome reporting bias is an under-recognised problem that affects the conclusions in a substantial proportion of Cochrane review s. Individuals conducting systematic review s need to address explicitly the issue of missing outcome data for their review to be considered a reliable source of evidence . Extra care is required during data extraction , review ers should identify when a trial reports that an outcome was measured but no results were reported or events observed , and contact with trialists should be encouraged Postoperative pain remains a significant problem and the individual variance in postoperative pain is not fully understood . In recent years , there has been focus on identifying risk factors predicting patients with high postoperative pain intensity or consumption of analgesics , which may facilitate an improvement in rehabilitation . This study evaluates the relationship between preoperative experimental pain assessment and postoperative pain and opioid consumption . Forty-four patients with uni- or bilateral kidney stone disease scheduled for percutaneous nephrolithotomy were included . The preoperative pain thresholds were measured using electrical ( single and 5 repeated ) and pressure pain stimulation over the flank bilaterally ( stone-side = operation side and control-side = non-operation side ) . Postoperative pain scores were recorded on a numerical rating scale and analgesic consumption was registered . The responses to repeated electrical stimuli ( temporal summation ) were preoperatively increased on the stone-side compared to the control-side ( P = 0.016 ) . Preoperative electrical pain thresholds from the control-side correlated inversely with postoperative opioid consumption ( single stimuli : ρ = −0.43 , P < 0.01 ; repeated stimuli : ρ = −0.45 , P < 0.005 ) . This correlation was more pronounced for the 22 patients with unilateral renal calculi ( single stimuli : ρ = −0.54 , P < 0.02 ; repeated stimuli : ρ = −0.58 , P < 0.01 ) . There were no other correlations between the preoperative sensory tests and postoperative pain or opioid consumption . This study showed a correlation between the preoperative electrical pain thresholds on the control-side and postoperative opioid consumption after percutaneous nephrolithotomy . Preoperative measurement of the electrical pain thresholds may , therefore , be useful as a screening tool to identify patients at high risk of postoperative pain Background : Treatment of post‐operative pain is still a significant problem . Recently , interest has focused on pre‐operative identification of patients who may experience severe post‐operative pain in order to offer a more aggressive analgesic treatment . The nociceptive stimulation methods have included heat injury and pressure algometry . A simple method , Pain Matcher ® ( PM ) , using electrical stimulation , is vali date d for pain assessment , but has not been evaluated as a tool for prediction of post‐operative pain . Our aim was to assess the predictive value of pre‐caesarean section pain threshold on intensity of post‐caesarean section pain using the PM Pain is a ubiquitous phenomenon , but the experience of pain varies considerably from person to person . Advances in underst and ing of the growing number of pathophysiologic mechanisms that underlie the generation of pain and the influence of the brain on the experience of pain led to the investigation of numerous compounds for treating pain . Improved knowledge of the subjective nature of pain , the variations in the measurement of pain , the mind-body placebo effect and the impact of differences in the conduct of a clinical trial on the outcome have changed approaches to design and implement studies . Careful consideration of how these concepts affect the choice of study population , the r and omization and blinding process , the measurement and collection of data , and the analysis and interpretation of results should improve the quality of clinical trials for potential pain therapies . Objective : To investigate the effects of IV lidocaine on spontaneous and evoked pain ( allodynia and hyperalgesia ) due to peripheral nerve injury ( postherpetic neuralgia or nerve trauma ) using quantitative sensory testing . Method : The authors r and omized 22 patients to receive lidocaine 5 mg/kg IV during 30 minutes or placebo in a double-blind crossover design and 16 patients subsequently received mexiletine on an open basis titrated from 400 to 1,000 mg per day ( mean 737 mg/day ) . Results : Lidocaine induced a significant decrease in ongoing pain for up to 6 hours with a peak effect 60 to 120 minutes postinjection . The drug also decreased mechanical dynamic allodynia and static ( punctate ) mechanical allodynia/hyperalgesia , but not thermal allodynia and hyperalgesia . The effects of lidocaine and mexiletine on spontaneous pain intensity were significantly higher in patients with concomitant mechanical allodynia in comparison with those without allodynia . Conclusions : These data indicate modality-specific antihyperalgesic effects of IV lidocaine in patients with peripheral nerve injury . Patients with mechanical allodynia may be good c and i date s for treatment with local anesthetic-like drugs and possibly with other sodium-channel blockers BACKGROUND & AIMS Pain is a disabling symptom for patients with chronic pancreatitis ( CP ) and difficult to treat . Evidence from basic science and human studies indicates that pain processing by the central nervous system is abnormal and resembles that observed in patients with neuropathic pain disorders . We investigated whether agents used to treat patients with neuropathic pain are effective in CP . METHODS We conducted a r and omized , double-blind , placebo-controlled trial to evaluate the effects of the gabapentoid pregabalin as an adjuvant analgesic . We measured pain relief , health status , quality of life , and tolerability in 64 patients with pain from CP ; they were r and omly assigned to groups given increasing doses of pregabalin or placebo ( control ) for 3 consecutive weeks . The primary end point was pain relief , based on a visual analogue scale documented by a pain diary . Secondary end points included Patients ' Global Impression of Change ( PGIC ) score , changes in physical and functional scales , pain character , quality of life , and tolerability . RESULTS Pregabalin , compared with placebo , caused more effective pain relief after 3 weeks of treatment ( 36 % vs 24 % ; mean difference , 12 % ; 95 % confidence interval , 22%-2 % ; P = .02 ) . The percentage of patients with much or very much improved health status ( PGIC score ) at the end of the study was higher in the pregabalin than the control group ( 44 % vs 21 % ; P = .048 ) . Changes in physical and functional scales , pain character , quality of life , and number of serious adverse events were comparable between groups . CONCLUSIONS In a placebo-controlled trial , pregabalin is an effective adjuvant therapy for pain in patients with CP Background Altered central nervous system sensory processing ( neuroplasticity ) is a basic mechanism underlying postoperative pain that can be made visible using quantitative sensory testing . Using quantitative sensory testing , the authors investigated how perioperative analgesia affects postoperative neuroplasticity and how this relates to clinical pain measures . Methods Patients undergoing back surgery received placebo , fentanyl , or ketorolac ( n = 15 per group ) before isoflurane-nitrous oxide anesthesia . Preoperatively to 5 days postoperatively , we measured thresholds to electrical skin stimulation at the incision site , arm , and leg ; pain scores ; and morphine patient-controlled analgesia consumption . Results Decreased pain thresholds versus preoperatively were seen 5 days postoperatively , with decreases greater for ketorolac ( −63%;P = 0.00005 vs. preoperatively ) than placebo ( −45%;P = 0.008 vs. preoperatively ) but nonsignificant for fentanyl ( −36%;P = 0.9 vs. preoperatively ) . Mainly nonnociceptive thresholds were increased up to 24 h postoperatively . Postoperative clinical pain measures were similar across drug groups . Postoperative pain tolerance threshold changes did not correlate with preoperative clinical pain measures but were inversely related to preoperative thresholds for placebo and ketorolac but not fentanyl . Conclusions Without analgesia , neuroplasticity after surgery was inhibitory the first 24 h and followed at 5 days by excitation . Fentanyl efficiently preempted this hyperalgesia , but hyperalgesia was greater with ketorolac than with placebo . Clinical pain measures neither reflected the different effects of ketorolac and fentanyl on postoperative neuroplasticity nor permitted prediction of postoperative neuroplasticity . The information obtained by perioperative quantitative sensory testing is separate from and additional to that from clinical pain measures and may enable more mechanism-based approaches to surgical analgesia management in the future Quantitative Sensory Testing ( QST ) is a psycho-physiological test used to identify dysfunction of individual nerve fiber types . In the present study , we investigated whether selective nerve fiber dysfunction , as assessed by QST , correlates with the effectiveness of epidural steroid injections ( ESI ) in patients with lumbar radiculopathy . Twenty patients with unilateral painful sciatica caused by disc herniation participated in this open study . Before ESI , quantitative thermal and mechanical sensory testing was conducted at the most painful dermatome and the contralateral dermatome . The primary outcome measure used was the self-recording of pain intensity twice daily with a 0–10 numerical pain scale ( NPS ) . Secondary efficacy measures included the Short Form of the McGill Pain Question naire , the straight leg raising test , and the lumbar range of motion . A significant difference in all types of sensory thresholds between the affected and the contralateral dermatomes was detected at baseline . All outcome measures improved subsequent to the ESI . A significant positive correlation was found between the increase in cold sensation thresholds of the affected dermatome ( A&dgr;-fiber dysfunction ) and the improvement in NPS . The increase in touch and vibration thresholds ( A&bgr;-fiber dysfunction ) was found to be inversely correlated with the improvement in NPS . No correlation was found between heat sensation thresholds ( C fibers ) and any of the outcome measures . These results suggest that QST has the potential to be an important tool in the selection of the appropriate treatment ( e.g. , ESI versus surgery ) for patients with sciatica and may assist in identifying the mechanisms of pain generation in these patients Summary Conditioned pain modulation ( CPM ) predicts efficacy of duloxetine in painful diabetic neuropathy ; patients with less efficient CPM are more likely to benefit from the drug . ABSTRACT This study aims to individualize the selection of drugs for neuropathic pain by examining the potential coupling of a given drug ’s mechanism of action with the patient ’s pain modulation pattern . The latter is assessed by the conditioned pain modulation ( CPM ) and temporal summation ( TS ) protocol s. We hypothesized that patients with a malfunctioning pain modulation pattern , such as less efficient CPM , would benefit more from drugs augmenting descending inhibitory pain control than would patients with a normal modulation pattern of efficient CPM . Thirty patients with painful diabetic neuropathy received 1 week of placebo , 1 week of 30 mg/d duloxetine , and 4 weeks of 60 mg/d duloxetine . Pain modulation was assessed psychophysically , both before and at the end of treatment . Patient assessment of drug efficacy , assessed weekly , was the study ’s primary outcome . Baseline CPM was found to be correlated with duloxetine efficacy ( r = 0.628 , P < .001 , efficient CPM is marked negative ) , such that less efficient CPM predicted efficacious use of duloxetine . Regression analysis ( R2 = 0.673 ; P = .012 ) showed that drug efficacy was predicted only by CPM ( P = .001 ) and not by pretreatment pain levels , neuropathy severity , depression level , or patient assessment of improvement by placebo . Furthermore , beyond its predictive value , the treatment‐induced improvement in CPM was correlated with drug efficacy ( r = −0.411 , P = .033 ) . However , this improvement occurred only in patients with less efficient CPM ( 16.8 ± 16.0 to −1.1 ± 15.5 , P < .050 ) . No predictive role was found for TS . In conclusion , the coupling of CPM and duloxetine efficacy highlights the importance of pain pathophysiology in the clinical decision‐making process . This evaluative approach promotes personalized pain therapy & NA ; Quantitative sensory testing ( QST ) is an instrument to assess positive and negative sensory signs , helping to identify mechanisms underlying pathologic pain conditions . In this study , we evaluated the test – retest reliability ( TR‐R ) and the interobserver reliability ( IO‐R ) of QST in patients with sensory disturbances of different etiologies . In 4 centres , 60 patients ( 37 male and 23 female , 56.4 ± 1.9 years ) with lesions or diseases of the somatosensory system were included . QST comprised 13 parameters including detection and pain thresholds for thermal and mechanical stimuli . QST was performed in the clinical ly most affected test area and a less or unaffected control area in a morning and an afternoon session on 2 consecutive days by examiner pairs ( 4 QSTs/patient ) . For both , TR‐R and IO‐R , there were high correlations ( r = 0.80–0.93 ) at the affected test area , except for wind‐up ratio ( TR‐R : r = 0.67 ; IO‐R : r = 0.56 ) and paradoxical heat sensations ( TR‐R : r = 0.35 ; IO‐R : r = 0.44 ) . Mean IO‐R ( r = 0.83 , 31 % unexplained variance ) was slightly lower than TR‐R ( r = 0.86 , 26 % unexplained variance , P < .05 ) ; the difference in variance amounted to 5 % . There were no differences between study centres . In a subgroup with an unaffected control area ( n = 43 ) , reliabilities were significantly better in the test area ( TR‐R : r = 0.86 ; IO‐R : r = 0.83 ) than in the control area ( TR‐R : r = 0.79 ; IO‐R : r = 0.71 , each P < .01 ) , suggesting that disease‐related systematic variance enhances reliability of QST . We conclude that st and ardized QST performed by trained examiners is a valuable diagnostic instrument with good test – retest and interobserver reliability within 2 days . With st and ardized training , observer bias is much lower than r and om variance . Quantitative sensory testing performed by trained examiners is a valuable diagnostic instrument with good interobserver and test – retest reliability for use in patients with sensory disturbances of different etiologies to help identify mechanisms of neuropathic and non‐neuropathic pain OBJECTIVE Although numerous studies have reported ethnic differences in the prevalence and severity of clinical pain , little is known about how these differences affect the perception of experimental pain . The present experiment examined the effects of ethnicity ( African American vs. white ) on thermal pain responses in a healthy undergraduate population . METHODS Thirty white subjects ( 16 women and 14 men ) and 18 African Americans ( 10 women and 8 men ) participated in the study . Thermal testing included evaluation of the following : warmth thresholds , thermal pain thresholds , thermal pain tolerances , and magnitude estimates of both the intensity and unpleasantness of thermal pain ( at 46 degrees , 47 degrees , 48 degrees , and 49 degrees C ) . RESULTS Although no group differences emerged for warmth thresholds , thermal pain thresholds , or pain intensity ratings , African Americans demonstrated lower thermal pain tolerances than whites . In addition , African Americans had smaller slopes and larger intercepts than whites for ratings of pain unpleasantness . Additional analyses suggested that these findings were a consequence of group differences in thermal pain unpleasantness ratings at the lowest temperatures assessed ( 46 degrees and 47 degrees C ) ; at these temperatures , African Americans rated the stimuli as more unpleasant than whites . Finally , group differences in thermal pain tolerance and thermal pain unpleasantness ratings seemed to partially account for greater self-reported daily pain symptoms among African Americans . CONCLUSIONS Collectively , these findings seem to suggest ethnic differences in the perception of the affective-motivational dimension of thermal pain Background Tricyclic antidepressants ( TCA ) provide less than satisfactory pain relief for postherpetic neuralgia ( PHN ) , and the role of opioids is controversial . Objective To compare the analgesic and cognitive effects of opioids with those of TCA and placebo in the treatment of PHN . Methods Seventy-six patients with PHN were r and omized in a double-blind , placebo-controlled , crossover trial . Each subject was scheduled to undergo three treatment periods ( opioid , TCA , and placebo ) , approximately 8 weeks ’ duration each . Doses were titrated to maximal relief or intolerable side effects . The primary outcome measures were pain intensity ( 0 to 10 scale ) , pain relief ( 0 to 100 % ) , and cognitive function . Analyses included patients who provided any pain ratings after having received at least a single dose of a study medication . Results Fifty patients completed two periods , and 44 patients completed all three . Mean daily maintenance doses were morphine 91 mg or methadone 15 mg and nortriptyline 89 mg or desipramine 63 mg . Opioids and TCA reduced pain ( 1.9 and 1.4 ) more than placebo ( 0.2;p < 0.001 ) , with no appreciable effect on any cognitive measure . The trend favoring opioids over TCA fell short of significance ( p = 0.06 ) , and reduction in pain with opioids did not correlate with that following TCA . Treatment with opioids and TCA result ed in greater pain relief ( 38 and 32 % ) compared with placebo ( 11%;p < 0.001 ) . More patients completing all three treatments preferred opioids ( 54 % ) than TCA ( 30%;p = 0.02 ) . Conclusions Opioids effectively treat PHN without impairing cognition . Opioids and TCA act via independent mechanisms and with varied individual effect Abstract Background and purpose Conditioned pain modulation ( CPM ) is a phenomenon in which pain is inhibited by heterotopic noxious stimulation . It is not known how the experimental condition affects the magnitude of the CPM response and the inter- and intra-individual variations . It is important to get the information of the test – retest reliability and inter – individual variations of CPM to apply CPM as a diagnostic tool or for screening analgesic compounds . This study evaluated ( 1 ) the magnitude of CPM , ( 2 ) the inter-individual coefficient of variation ( inter-CV ) and ( 3 ) the intra-individual coefficient of variation ( intra-CV ) to ( A ) different stimulus modalities to evoke CPM and ( B ) different assessment sites . Methods Twelve healthy men ( age 19–38 years ) participated in this study . Cold pressor pain ( CPP ) ( immersing the h and into cold water ) , tourniquet pain ( cuff around the upper arm ) and mechanical pressure pain ( craniofacial region ) were used in r and omized order as conditioning stimuli ( CS ) . The test stimulus ( TS ) was pressure pain applied to the right masseter muscle , left forearm and leg ( bilateral tibialis anterior : TA ) . The responses were pressure pain thresholds ( PPT ) , pressure pain tolerance ( PPTol ) thresholds and the pain intensity which was assessed on a visual analogue scale ( VAS , 0–10 cm ) following 1.4 and 1.6 × PPT applied to TA . The TS was applied before , during and 10 min after the CS . The intra-individual CV was estimated between different days . Results CPP induced the most powerful CPM on PPT ( 66.3 ± 10.0 % increase ) , VAS ratings ( 41.5 ± 5.3 % reduction ) and PPTol ( 32.6±4.6 % increase ) , especially at TA , and result ed in the smallest inter-CV ( 41.4–60.1 % ) . Independently of the CS , the inter-CV in general showed that the recordings from the orofacial region and the forearm had smaller values than from the leg . The smallest intra-CV value was obtained in pain ratings with CPP ( 27.0 % ) . Conclusions This study suggests that ( 1 ) the CPP evokes the largest CPM , ( 2 ) the leg as the assessment site results in the largest CPM responses and ( 3 ) the CPP causes the smallest inter- and intra-CV . Implication The present investigation implicates that the CPP is the most efficient conditioning stimulus to induce CPM when assessed by pressure pain thresholds |
10,791 | 27,883,925 | For drugs that reached Phase III , lack of a biomarker-driven strategy and failure to attain proof of concept in phase II are potential risk factors for later discontinuation , especially for targeted agents | BACKGROUND We aim ed to describe the reasons for failure of experimental anticancer drugs in late-stage clinical development . | PURPOSE The r and omized controlled trial ( RCT ) is the gold st and ard for establishing new therapies in clinical oncology . Here we document changes with time in design , sponsorship , and outcomes of oncology RCTs . METHODS Reports of RCTs evaluating systemic therapy for breast , colorectal ( CRC ) , and non-small-cell lung cancer ( NSCLC ) published 1975 to 2004 in six major journals were review ed . Two authors abstract ed data regarding trial design , results , and conclusions . Conclusions of authors were grade d using a 7-point Likert scale . For each study the effect size for the primary end point was converted to a summary measure . RESULTS A total of 321 eligible RCTs were included ( 48 % breast , 24 % CRC , 28 % NSCLC ) . Over time , the number and size of RCTs increased considerably . For-profit/mixed sponsorship increased substantially during the study period ( 4 % to 57 % ; P < .001 ) . There was increasing use of time-to-event measures ( 39 % to 78 % ) and decreasing use of response rate ( 54 % to 14 % ) as primary end point ( P < .001 ) . Effect size remained stable over the study period . Authors have become more likely to strongly endorse the experimental arm ( P = .017 ) . A significant P value for the primary end point and industry sponsorship were each independently associated with endorsement of the experimental agent ( odds ratio [ OR ] = 19.6 , 95 % CI , 8.9 to 43.1 , and OR = 3.5 , 95 % CI , 1.6 to 7.5 , respectively ) . CONCLUSION RCTs in oncology have become larger and are more likely to be sponsored by industry . Authors of modern RCTs are more likely to strongly endorse novel therapies . For-profit sponsorship and statistically significant results are independently associated with endorsement of the experimental arm PURPOSE Historical data from pilot , Phase II , and Phase III studies for patients with advanced-stage non-small cell lung cancer ( NSCLC ) were used to evaluate a statistical model developed to provide assistance in selecting regimens from pilot studies for subsequent use in larger Phase III r and omized studies . EXPERIMENTAL DESIGN Information from 33 Phase III trials for patients with advanced-stage NSCLC performed from 1973 and 1994 in the United States and Canada was collected . The data from antecedent pilot or Phase II and subsequent Phase III trials were analyzed using a predictive statistical model . This model uses the number of patients in the pilot/Phase II study , the median survival of patients in the pilot , and the number of deaths observed , to estimate the statistical likelihood that the pilot regimen will be shown superior to st and ard therapy in a subsequent Phase III trial . RESULTS Ten pilot/Phase II studies were identified that preceded eleven subsequent Phase III studies . The three pilot regimens associated with Phase III trials , revealing statistically significant longer survival , had an expected power of 0.69 , 0.85 , and 0.94 respectively . The regimens from the seven other pilot studies for which the median power expected was 0.38 ( range , 0.07 - 0.80 ) showed no difference when compared with st and ard treatment in a Phase III trial . CONCLUSION The use of the expected power model provides an important enhancement to the screening of new therapies . Regimens with an expected power of > 0.55 may be good c and i date s for testing in Phase III trials BACKGROUND Non-small-cell lung cancer ( NSCLC ) harboring the anaplastic lymphoma kinase gene ( ALK ) rearrangement is sensitive to the ALK inhibitor crizotinib , but resistance invariably develops . Ceritinib ( LDK378 ) is a new ALK inhibitor that has shown greater antitumor potency than crizotinib in pre clinical studies . METHODS In this phase 1 study , we administered oral ceritinib in doses of 50 to 750 mg once daily to patients with advanced cancers harboring genetic alterations in ALK . In an expansion phase of the study , patients received the maximum tolerated dose . Patients were assessed to determine the safety , pharmacokinetic properties , and antitumor activity of ceritinib . Tumor biopsies were performed before ceritinib treatment to identify resistance mutations in ALK in a group of patients with NSCLC who had had disease progression during treatment with crizotinib . RESULTS A total of 59 patients were enrolled in the dose-escalation phase . The maximum tolerated dose of ceritinib was 750 mg once daily ; dose-limiting toxic events included diarrhea , vomiting , dehydration , elevated aminotransferase levels , and hypophosphatemia . This phase was followed by an expansion phase , in which an additional 71 patients were treated , for a total of 130 patients overall . Among 114 patients with NSCLC who received at least 400 mg of ceritinib per day , the overall response rate was 58 % ( 95 % confidence interval [ CI ] , 48 to 67 ) . Among 80 patients who had received crizotinib previously , the response rate was 56 % ( 95 % CI , 45 to 67 ) . Responses were observed in patients with various resistance mutations in ALK and in patients without detectable mutations . Among patients with NSCLC who received at least 400 mg of ceritinib per day , the median progression-free survival was 7.0 months ( 95 % CI , 5.6 to 9.5 ) . CONCLUSIONS Ceritinib was highly active in patients with advanced , ALK-rearranged NSCLC , including those who had had disease progression during crizotinib treatment , regardless of the presence of resistance mutations in ALK . ( Funded by Novartis Pharmaceuticals and others ; Clinical Trials.gov number , NCT01283516 . ) Purpose : We hypothesized that chemotherapy synergizes with VEGF/VEGFR ( VEGF/R ) inhibitors in patients with advanced solid malignancies . Experimental Design : Patients treated on phase I protocol s between December 2004 and July 2013 ( n = 1,498 ) were included in this analysis . The primary outcome was clinical benefit , defined as stable disease ≥6 months , complete response , or partial response . Two odds ratios ( OR ) for achieving clinical benefit were calculated : one for patients treated with VEGF/R inhibitors ( OR with VEGF/R ) and another for patients treated without ( OR without VEGF/R ) . To compare these two ORs , an interaction term was included in the multivariate model : ( chemotherapy/factor of interest) × (VEGF/R ) . We took significant interaction terms ( Pinteraction < 0.05 ) to suggest effect modification ( either synergy or antagonism ) with VEGF/R inhibitors . Results : All patients treated with VEGF/R inhibitors exhibited higher OR for clinical benefit than those who were not [ OR = 1.9 ; 95 % confidence interval ( CI ) , 1.5–2.4 ; P < 0.0001 ] . Use of chemotherapy agents concomitant with VEGF/R inhibitors was associated with significantly higher OR for clinical benefit compared with chemotherapy use without VEGF/R inhibitors [ OR with VEGF/R = 1.6 ( 95 % CI , 1.1–2.5 ) vs. OR without VEGF/R = 0.4 ( 95 % CI , 0.3–0.6 ) , Pinteraction = 0.02 ] . Specifically , the antimetabolite class was associated with the greatest increase in OR for clinical benefit [ OR with VEGF/R = 2.7 ( 95 % CI , 1.5–4.7 ) vs. OR without VEGF/R = 0.2 ( 95 % CI 0.1–0.3 ) , Pinteraction = 0.004 ] . Conclusions : VEGF/R inhibitor was found to synergize with chemotherapeutics . This effect was most pronounced with the antimetabolite class . Clin Cancer Res ; 20(23 ) ; 5956–63 . © 2014 AACR BACKGROUND Talactoferrin alfa is an oral dendritic cell (DC)-mediated immunotherapy ( DCMI ) . We tested whether talactoferrin was superior to placebo in advanced non-small-cell lung cancer ( NSCLC ) . PATIENTS AND METHODS An FORTIS-M trial was an international , multicenter , r and omized , double-blind comparison of talactoferrin ( 1.5 g p.o . BID ) versus placebo BID , in patients with stage IIIB/IV NSCLC whose disease had failed two or more prior regimens . Treatment was administered for a maximum of five 14-week cycles . The primary efficacy end point was overall survival ( OS ) ; secondary end points included 6- and 12-month survival , progression-free survival ( PFS ) , and disease control rate ( DCR ) . RESULTS Seven hundred and forty-two patients were r and omly assigned ( 2:1 ) to talactoferrin ( 497 ) or placebo ( 245 ) . The median OS in the intent-to-treat ( ITT ) population was 7.66 months in the placebo arm and 7.49 months in the talactoferrin arm [ hazard ratio ( HR ) , 1.04 ; 95 % CI , 0.873 - 1.24 ; P = 0.6602 ] . The 6-month survival rates were 59.9 % ( 95 % CI , 53.4 % to 65.8 % ) and 55.7 % ( 95 % CI , 51.1 % to 59.9 % ) , respectively . The 12-month survival rates were 32.2 % ( 95 % CI , 26.3 % to 38.2 % ) and 30.9 % ( 95 % CI , 26.8 % to 35 % ) , respectively . The median PFS rates were 1.64 months and 1.68 months , respectively ( HR , 0.99 ; 95 % CI , 0.835 - 1.16 ; P = 0.8073 ) . The DCRs were 38.4 and 37.6 % , respectively [ stratified odds ratio ( OR ) , 0.96 ; 95 % CI , 0.698 - 1.33 ; P = 0.8336 ] . The safety profiles were comparable between arms . CONCLUSIONS There was no improvement in efficacy with talactoferrin alfa in patients with advanced NSCLC whose disease had failed two or more previous regimens PURPOSE We conducted a phase III trial comparing intravenous ( IV ) diaziquone ( AZQ ) and carmustine ( BCNU ) as single agents in patients with cerebral anaplastic gliomas who had received surgery and radiotherapy . Its purpose was to compare the efficacy of AZQ with that of BCNU , the st and ard agent for brain tumor chemotherapy . PATIENTS AND METHODS R and omization between the two regimens occurred 8 weeks after completion of radiotherapy . A total of 251 patients were r and omized to receive either AZQ or BCNU , and there were no significant differences between the two treatment arms in any of the known prognostic variables , including age , histologic grade , and Karnofsky performance status ( KPS ) . RESULTS There was no significant difference in either time to tumor progression or survival between the two treatment arms . Age and histology were strong predictors of outcome , whereas KPS had relatively less effect . Three groups of patients with distinctly different outcomes could be identified : ( 1 ) older age ( 45 + ) and glioblastoma/gliosarcoma ( GBM/GS ) patients had a median survival of 37 weeks after r and omization ; ( 2 ) patients with either older age or GBM/GS had a median survival of 61 weeks ; and ( 3 ) younger age ( < 45 ) and non-GBM/GS ( usually anaplastic astrocytoma ) patients had a median survival of 147 weeks . Toxicity was primarily hematologic , although acute gastrointestinal toxicity and chronic pulmonary toxicity were more common with BCNU . Patients r and omized to AZQ who had significant hematologic toxicity that required dose reduction after the first treatment cycle had significantly longer time to tumor progression and survival than those who did not require dose reduction ( P = .011 and .016 , respectively ) . CONCLUSION There was no significant difference in efficacy between AZQ and BCNU in patients with anaplastic gliomas as tested in this study , although AZQ was somewhat better tolerated BACKGROUND Everolimus ( RAD001 ) is an orally administered inhibitor of the mammalian target of rapamycin ( mTOR ) , a therapeutic target for metastatic renal cell carcinoma . We did a phase III , r and omised , double-blind , placebo-controlled trial of everolimus in patients with metastatic renal cell carcinoma whose disease had progressed on vascular endothelial growth factor-targeted therapy . METHODS Patients with metastatic renal cell carcinoma which had progressed on sunitinib , sorafenib , or both , were r and omly assigned in a two to one ratio to receive everolimus 10 mg once daily ( n=272 ) or placebo ( n=138 ) , in conjunction with best supportive care . R and omisation was done central ly via an interactive voice response system using a vali date d computer system , and was stratified by Memorial Sloan-Kettering Cancer Center prognostic score and previous anticancer therapy , with a permuted block size of six . The primary endpoint was progression-free survival , assessed via a blinded , independent central review . The study was design ed to be terminated after 290 events of progression . Analysis was by intention to treat . This study is registered with Clinical Trials.gov , number NCT00410124 . FINDINGS All r and omised patients were included in efficacy analyses . The results of the second interim analysis indicated a significant difference in efficacy between arms and the trial was thus halted early after 191 progression events had been observed ( 101 [ 37 % ] events in the everolimus group , 90 [ 65 % ] in the placebo group ; hazard ratio 0.30 , 95 % CI 0.22 - 0.40 , p<0.0001 ; median progression-free survival 4.0 [ 95 % CI 3.7 - 5.5 ] vs 1.9 [ 1.8 - 1.9 ] months ) . Stomatitis ( 107 [ 40 % ] patients in the everolimus group vs 11 [ 8 % ] in the placebo group ) , rash ( 66 [ 25 % ] vs six [ 4 % ] ) , and fatigue ( 53 [ 20 % ] vs 22 [ 16 % ] ) were the most commonly reported adverse events , but were mostly mild or moderate in severity . Pneumonitis ( any grade ) was detected in 22 ( 8 % ) patients in the everolimus group , of whom eight had pneumonitis of grade 3 severity . INTERPRETATION Treatment with everolimus prolongs progression-free survival relative to placebo in patients with metastatic renal cell carcinoma that had progressed on other targeted therapies BACKGROUND Liarozole is an imidazole derivative that has been identified as an inhibitor of the cytochrome P450-dependent all-trans retinoid acid ( RA ) breakdown . RA is one of the principal endogenous compounds that controls growth and differentiation of epithelial tissues in mammals . METHODS Fifty-five patients with hormone-resistant prostate cancer in progression , following at least first-line and rogen ablation therapy , were evaluated . Thirty-one patients were treated with liarozole 300 mg b.i.d . , while 24 patients started with 150 mg b.i.d . , which was increased to 300 mg b.i.d . after 4 or 8 weeks . Two patients were not evaluable because they withdrew after initial consent . The WHO performance status was 0 ( n = 18 ) , 1 ( n = 22 ) , 2 ( n = 17 ) , and 3 ( n = 6 ) . Most patients ( 80 % ) used analgesics . RESULTS For 11 out of the 53 patients , treatment lasted less than 1 month ( they were therefore not evaluable for response ) due to : poor compliance ( n = 1 ) ; early death ( n = 3 ) ; side-effects ( n = 2 ) ; and decline of physical condition and continuous progression ( n = 4 ) . One patient refused to report for follow-up . In all responders , except one , the dose was increased to 300 mg b.i.d . In 23 of the 42 patients evaluable for response , the pain score improved . In 5 patients the pain score had reduced from 2 or 3 to 0 . In 11 out of the 42 patients there was a 1-point improvement of WHO performance status . The prostatic-specific antigen ( PSA ) response rate was 41 % ; 15 out of 42 evaluable patients presented a decrease of > or = 50 % , whereas PSA normalized in 2 further patients . Most of the side effects mimicked retinoid acid toxicity : cutaneous manifestations ( such as dry skin , dry lips , sticky skin , brittle nails , erythema , or itch ) . All patients experienced one or more of these side effects . Other side effects include nausea , fatigue , and slight alopecia . CONCLUSIONS Liarozole can be an enrichment of the therapeutic armamentarium for treatment of hormone-resistant prostate cancer patients after first-line and rogen ablation therapy without serious toxicity BACKGROUND AND AIM The primary aim of this study was to determine whether r and omised phase 2 ( RP2 ) trials predict phase 3 trial outcome better than single arm phase 2 ( SAP2 ) studies . Although theoretical superiority of RP2 trials has been postulated , no empiric studies have been conducted . METHODS Published phase 3 trials testing systemic cancer therapy were identified through a Medline search . Those of superiority design , which cited phase 2 trials supporting the experimental arm , were included . Trial design and outcome details were extracted . Statistical analysis was performed using the Generalized Estimating Equation method correlating phase 2 features with phase 3 outcome , accounting for any phase 3 duplication . RESULTS Of 189 eligible phase 3 trials , 18.5 % were in haematological malignancies and 81.5 % in solid tumors . The primary outcome was positive in 79 ( 41.8 % ) . These were supported by 336 phase 2 trials ( range 1 - 9 per phase 3 trial ) including 66 RP2 trials . Positive phase 2 outcome , r and omised or not , correlated with positive phase 3 outcome ( p=0.03 ) . RP2 studies were not superior to SAP2 studies at predicting phase 3 study success . Phase 2 trial features not predictive of phase 3 outcome included primary endpoint , sponsorship , sample size , similarity in patient population and therapy . CONCLUSIONS RP2 studies were not superior to SAP2 trials at predicting phase 3 study success . Further research into phase 2 trial design is required given the added re sources required to conduct RP2 studies and the lack of empiric evidence supporting superiority over single arm studies BACKGROUND The anti-programmed-death-receptor-1 ( PD-1 ) antibody pembrolizumab has shown potent antitumour activity at different doses and schedules in patients with melanoma . We compared the efficacy and safety of pembrolizumab at doses of 2 mg/kg and 10 mg/kg every 3 weeks in patients with ipilimumab-refractory advanced melanoma . METHODS In an open-label , international , multicentre expansion cohort of a phase 1 trial , patients ( aged ≥18 years ) with advanced melanoma whose disease had progressed after at least two ipilimumab doses were r and omly assigned with a computer-generated allocation schedule ( 1:1 final ratio ) to intravenous pembrolizumab at 2 mg/kg every 3 weeks or 10 mg/kg every 3 weeks until disease progression , intolerable toxicity , or consent withdrawal . Primary endpoint was overall response rate ( ORR ) assessed with the Response Evaluation Criteria In Solid Tumors ( RECIST , version 1.1 ) by independent central review . Analysis was done on the full- analysis set ( all treated patients with measurable disease at baseline ) . This study is registered with Clinical Trials.gov , number NCT01295827 . FINDINGS 173 patients received pembrolizumab 2 mg/kg ( n=89 ) or 10 mg/kg ( n=84 ) . Median follow-up duration was 8 months . ORR was 26 % at both doses--21 of 81 patients in the 2 mg/kg group and 20 of 76 in the 10 mg/kg group ( difference 0 % , 95 % CI -14 to 13 ; p=0·96 ) . Treatment was well tolerated , with similar safety profiles in the 2 mg/kg and 10 mg/kg groups and no drug-related deaths . The most common drug-related adverse events of any grade in the 2 mg/kg and 10 mg/kg groups were fatigue ( 29 [ 33 % ] vs 31 [ 37 % ] ) , pruritus ( 23 [ 26 % ] vs 16 [ 19 % ] ) , and rash ( 16 [ 18 % ] vs 15 [ 18 % ] ) . Grade 3 fatigue , reported in five ( 3 % ) patients in the 2 mg/kg pembrolizumab group , was the only drug-related grade 3 to 4 adverse event reported in more than one patient . INTERPRETATION The results suggest that pembrolizumab at a dose of 2 mg/kg or 10 mg/kg every 3 weeks might be an effective treatment in patients for whom there are few effective treatment options . FUNDING Merck Sharp and Dohme BACKGROUND Ipilimumab is a human monoclonal antibody that blocks cytotoxic T-lymphocyte antigen 4 and has shown promising activity in advanced melanoma . We aim ed to ascertain the antitumour efficacy of ipilimumab in patients with advanced melanoma . METHODS We undertook a r and omised , double-blind , phase 2 trial in 66 centres from 12 countries . 217 patients with previously treated stage III ( unresectable ) or stage IV melanoma were r and omly assigned a fixed dose of ipilimumab of either 10 mg/kg ( n=73 ) , 3 mg/kg ( n=72 ) , or 0.3 mg/kg ( n=72 ) every 3 weeks for four cycles ( induction ) followed by maintenance therapy every 3 months . R and omisation was done with a permuted block procedure , stratified on the basis of type of previous treatment . The primary endpoint was best overall response rate ( the proportion of patients with a complete or partial response , according to modified WHO criteria ) . Efficacy analyses were done by intention to treat , whereas safety analyses included patients who received at least one dose of ipilimumab . This study is registered with Clinical Trials.gov , number NCT00289640 . FINDINGS The best overall response rate was 11.1 % ( 95 % CI 4.9 - 20.7 ) for 10 mg/kg , 4.2 % ( 0.9 - 11.7 ) for 3 mg/kg , and 0 % ( 0.0 - 4.9 ) for 0.3 mg/kg ( p=0.0015 ; trend test ) . Immune-related adverse events of any grade arose in 50 of 71 , 46 of 71 , and 19 of 72 patients at doses of 10 mg/kg , 3 mg/kg , and 0.3 mg/kg , respectively ; the most common grade 3 - 4 adverse events were gastrointestinal immune-related events ( 11 in the 10 mg/kg group , two in the 3 mg/kg group , none in the 0.3 mg/kg group ) and diarrhoea ( ten in the 10 mg/kg group , one in the 3 mg/kg group , none in the 0.3 mg/kg group ) . INTERPRETATION Ipilimumab elicited a dose-dependent effect on efficacy and safety measures in pretreated patients with advanced melanoma , lending support to further studies at a dose of 10 mg/kg . FUNDING Bristol-Myers Squibb CONTEXT Large clinical trials are the criterion st and ard for making treatment decisions , and nonpublication of the results of such trials can lead to bias in the literature and contribute to inappropriate medical decisions . OBJECTIVES To determine the rate of full publication of large r and omized trials presented at annual meetings of the American Society of Clinical Oncology ( ASCO ) , quantify bias against publishing nonsignificant results , and identify factors associated with time to publication . DESIGN Survey of 510 abstract s from large ( sample size , > or = 200 ) , phase 3 , r and omized controlled trials presented at ASCO meetings between 1989 and 1998 . Trial results were classified as significant ( P < or = .05 for the primary outcome measure ) or nonsignificant ( P>.05 or not reported ) , and the type of presentation and sponsorship were identified . Subsequent full publication was identified using a search of MEDLINE and EMBASE , completed November 1 , 2001 ; the search was up date d in November 2002 , using the Cochrane Register of Controlled Trials . Authors were contacted if the search es did not find evidence of publication . MAIN OUTCOME MEASURES Publication rate at 5 years ; time from presentation to full publication . RESULTS Of 510 r and omized trials , 26 % were not published in full within 5 years after presentation at the meeting . Eighty-one percent of the studies with significant results had been published by this time compared with 68 % of the studies with nonsignificant results ( P<.001 ) . Studies with oral or plenary presentation were published sooner than those not presented ( P = .002 ) , and studies with pharmaceutical sponsorship were published sooner than studies with cooperative group sponsorship or studies for which sponsorship was not specified ( P = .02 ) . These factors remained significant in a multivariable model . The most frequent reason cited by authors for not publishing was lack of time , funds , or other re sources . CONCLUSIONS A substantial number of large phase 3 trials presented at an international oncology meeting remain unpublished 5 years after presentation . Bias against publishing nonsignificant results is a problem even for large r and omized trials . Nonpublication breaks the contract that investigators make with trial participants , funding agencies , and ethics boards OBJECTIVES To compare the efficacy of oral liarozole , the first retinoic acid metabolism-blocking agent ( RAMBA ) to be developed as differentiation therapy for human solid tumors , with that of cyproterone acetate ( CPA ) , an anti and rogen for the treatment of metastatic prostate cancer . Liarozole promotes differentiation of cancer cells by increasing the intratumoral levels of retinoic acid . METHODS A total of 321 patients with metastatic prostate cancer in relapse after first-line endocrine therapy entered a Phase III international multicenter study ( recruitment from February 1992 to August 1994 ) comparing liarozole ( 300 mg two times daily ) with CPA ( 100 mg two times daily ) . RESULTS Accounting for differences in baseline prognostic factors , the adjusted hazard ratio for survival was 0.74 in favor of liarozole ( P = 0.039 ) , indicating a 26 % lower risk of death than in patients treated with CPA . Median crude ( unadjusted ) survival time was the same in the liarozole group as in the CPA group ( 10.3 months ) . More patients showed a PSA response ( at least 50 % reduction in PSA from baseline ) when treated with liarozole ( 20 % ) than with CPA ( 4 % ) ( P < 0.001 ) . Prostate-specific antigen ( PSA ) responders had a median survival benefit of 10 months over nonresponders , irrespective of treatment ( hazard ratio 0.43 ; P = 0.0018 ) . PSA response was apparent within 3 months in approximately 90 % of patients who responded . Pain improved more in the liarozole group than in the CPA group ( P = 0.03 ) . PSA responders had lower median pain scores than nonresponders ( 1.7 versus 2.5 ) and better quality of life ( median Functional Living Index-Cancer score 108 versus 98 ) at end point , ie , treatment discontinuation , as well as throughout the treatment period . Among the most frequently occurring adverse events in the liarozole group were dry skin ( 51 % of patients ) , pruritus ( 25 % ) , rash ( 16 % ) , nail disorders ( 16 % ) , and hair loss ( 15 % ) . These adverse events were generally mild to moderate in severity and did not affect the overall quality of life score . There were no detectable effects of either treatment on vital signs such as blood pressure , heart rate , electrocardiogram , and body weight . CONCLUSIONS Liarozole is superior to CPA in terms of PSA response , PSA progression , and survival , and is capable of maintaining patients ' quality of life . The observed adverse events were mild to moderate in nature . These results show that liarozole is a possible treatment option after first-line endocrine therapy has failed BACKGROUND Many more phase II studies have favorable outcomes than the subsequent phase III trials . We used historical data from phase II and phase III studies for patients with extensive-stage small-cell lung cancer ( SCLC ) to generate a statistical model to provide assistance in selecting chemotherapy regimens from phase II studies for subsequent use in phase III r and omized studies . METHODS Information from 21 phase III trials for patients with extensive-stage SCLC initiated during the period from 1972 through 1990 was review ed to identify those that were preceded by phase II studies of the same regimen . We used data from all the trial pairs to develop a statistical model in which the number of patients , the median survival of patients , and the number of deaths observed in the phase II trial are used to estimate the statistical power of the subsequent phase III trial . All statistical tests were two-sided . RESULTS Nine phase II studies were identified that preceded phase III trials of the same regimen . The regimens from two phase II studies with the greatest expected power in the phase III trial ( 0 . 62 and 0.58 ) both demonstrated significantly prolonged survival when compared with st and ard treatment in subsequent phase III trials ( P<. 001 and P = .002 , respectively ) . The regimens from six of the other phase II studies , for which the median power expected in the phase III trial was 0.28 ( range , 0.19 - 0.52 ) , showed no difference when compared with st and ard treatment in a phase III trial . CONCLUSIONS Phase II studies for particular regimens that have an expected power of greater than 0.55 provide a reasonable basis for proceeding with a phase III trial BACKGROUND This placebo-controlled phase III study investigated the effect on survival of gefitinib as second-line or third-line treatment for patients with locally advanced or metastatic non-small-cell lung cancer . METHODS 1692 patients who were refractory to or intolerant of their latest chemotherapy regimen were r and omly assigned in a ratio of two to one either gefitinib ( 250 mg/day ) or placebo , plus best supportive care . The primary endpoint was survival in the overall population of patients and those with adenocarcinoma . The primary analysis of the population for survival was by intention to treat . This study has been su bmi tted for registration with Clinical Trials.gov , number 1839IL/709 . FINDINGS 1129 patients were assigned gefitinib and 563 placebo . At median follow-up of 7.2 months , median survival did not differ significantly between the groups in the overall population ( 5.6 months for gefitinib and 5.1 months for placebo ; hazard ratio 0.89 [ 95 % CI 0.77 - 1.02 ] , p=0.087 ) or among the 812 patients with adenocarcinoma ( 6.3 months vs 5.4 months ; 0.84 [ 0.68 - 1.03 ] , p=0.089 ) . Preplanned subgroup analyses showed significantly longer survival in the gefitinib group than the placebo group for never-smokers ( n=375 ; 0.67 [ 0.49 - 0.92 ] , p=0.012 ; median survival 8.9 vs 6.1 months ) and patients of Asian origin ( n=342 ; 0.66 [ 0.48 - 0.91 ] , p=0.01 ; median survival 9.5 vs 5.5 months ) . Gefitinib was well tolerated , as in previous studies . INTERPRETATION Treatment with gefitinib was not associated with significant improvement in survival in either co primary population . There was pronounced heterogeneity in survival outcomes between groups of patients , with some evidence of benefit among never-smokers and patients of Asian origin PURPOSE Figitumumab ( CP-751,871 ) , a fully human immunoglobulin G2 monoclonal antibody , inhibits the insulin-like growth factor 1 receptor ( IGF-1R ) . Our multicenter , r and omized , phase III study compared figitumumab plus chemotherapy with chemotherapy alone as first-line treatment in patients with advanced non-small-cell lung cancer ( NSCLC ) . PATIENTS AND METHODS Patients with stage IIIB/IV or recurrent NSCLC disease with nonadenocarcinoma histology received open-label figitumumab ( 20 mg/kg ) plus paclitaxel ( 200 mg/m(2 ) ) and carboplatin ( area under the concentration-time curve , 6 mg · min/mL ) or paclitaxel and carboplatin alone once every 3 weeks for up to six cycles . The primary end point was overall survival ( OS ) . RESULTS Of 681 r and omly assigned patients , 671 received treatment . The study was closed early by an independent Data Safety Monitoring Committee because of futility and an increased incidence of serious adverse events ( SAEs ) and treatment-related deaths with figitumumab . Median OS was 8.6 months for figitumumab plus chemotherapy and 9.8 months for chemotherapy alone ( hazard ratio [ HR ] , 1.18 ; 95 % CI , 0.99 to 1.40 ; P = .06 ) ; median progression-free survival was 4.7 months ( 95 % CI , 4.2 to 5.4 ) and 4.6 months ( 95 % CI , 4.2 to 5.4 ) , respectively ( HR , 1.10 ; P = .27 ) ; the objective response rates were 33 % and 35 % , respectively . The respective rates of all-causality SAEs were 66 % and 51 % ; P < .01 ) . Treatment-related grade 5 adverse events were also more common with figitumumab ( 5 % v 1 % ; P < .01 ) . CONCLUSION Adding figitumumab to st and ard chemotherapy failed to increase OS in patients with advanced nonadenocarcinoma NSCLC . Further clinical development of figitumumab is not being pursued |
10,792 | 28,485,121 | WHAT IS NEW AND CONCLUSION Riboflavin is well tolerated , inexpensive and has demonstrated efficacy in the reduction of adult patient 's migraine headache frequency . | WHAT IS KNOWN AND OBJECTIVE Migraine headache is a relatively common , debilitating condition that costs our healthcare system over 78 billion dollars per year .
Riboflavin has been advocated as a safe , effective prophylactic therapy for the prevention of migraines .
The purpose of this study was to provide a systematic review of the current role of riboflavin in the prophylaxis of migraine headache . | The pharmacokinetics and utilization ( flavocoenzyme synthesis ) of orally and intravenously administered riboflavin in healthy humans were assessed . After the determination of circadian rhythms of riboflavin concentrations in blood plasma and urine of four males and five females ( control period ) , each of these subjects received three different oral riboflavin doses ( 20 , 40 , and 60 mg ) and one intravenous bolus injection of riboflavin ( 11.6 mg ) . Vitamins were administered in a r and omized , cross-over design with 2 wk between each administration . Blood plasma and urine specimens were collected repeatedly over a period of 48 h after each administration . Concentrations of flavocoenzymes and riboflavin were analyzed in blood plasma ; riboflavin was assayed in urine . During the control period , a small circadian variation was observed : plasma concentrations and urinary excretion of riboflavin were low during the afternoon ( P < 0.05 ) . Pharmacokinetics were calculated using a two-compartment open model . The maximal amount of riboflavin that can be absorbed from a single dose was 27 mg per adult . Half-life of absorption was 1.1 h. First-order rate constants describing distribution and elimination of riboflavin were significantly higher after intravenous than after oral administration ( P < 0.01 ) . Release of flavocoenzymes into plasma was low compared with the increase of riboflavin concentrations . 7 alpha-Hydroxyriboflavin was identified in plasma . Clearance data indicated that urinary excretion of riboflavin contributes to one-half of the overall removal of riboflavin from plasma . No sex differences were observed for any of the pharmacokinetic variables ( P > 0.05 ) Background Non-medical , non-pharmacological and pharmacological treatments are recommended for the prevention of migraine . The purpose of this r and omized double-blind placebo controlled , multicenter trial was to evaluate the efficacy of a proprietary nutritional supplement containing a fixed combination of magnesium , riboflavin and Q10 as prophylactic treatment for migraine . Methods 130 adult migraineurs ( age 18 – 65 years ) with ≥ three migraine attacks per month were r and omized into two treatment groups : dietary supplementation or placebo in a double-blind fashion . The treatment period was 3 months following a 4 week baseline period without prophylactic treatment . Patients were assessed before r and omization and at the end of the 3-month-treatment-phase for days with migraine , migraine pain , burden of disease ( HIT-6 ) and subjective evaluation of efficacy . Results Migraine days per month declined from 6.2 days during the baseline period to 4.4 days at the end of the treatment with the supplement and from 6.2.days to 5.2 days in the placebo group ( p = 0.23 compared to placebo ) . The intensity of migraine pain was significantly reduced in the supplement group compared to placebo ( p = 0.03 ) . The sum score of the HIT-6 question naire was reduced by 4.8 points from 61.9 to 57.1 compared to 2 points in the placebo-group ( p = 0.01 ) . The evaluation of efficacy by the patient was better in the supplementation group compared to placebo ( p = 0.01 ) . Conclusions Treatment with a proprietary supplement containing magnesium , riboflavin and Q10 ( Migravent ® in Germany , Dolovent ® in USA ) had an impact on migraine frequency which showed a trend towards statistical significance . Migraine symptoms and burden of disease , however , were statistically significantly reduced compared to placebo in patients with migraine attacks Objective To determine the prevalence and distribution of migraine in the United States as well as current patterns of health care use . Methods A r and om-digit-dial , computer-assisted telephone interview ( CATI ) survey was conducted in Philadelphia County , PA , in 1998 . The CATI identifies individuals with migraine ( categories 1.1 and 1.2 ) as defined by the diagnostic criteria of the International Headache Society with high sensitivity ( 85 % ) and specificity ( 96 % ) . Interviews were completed in 4,376 subjects to identify 568 with migraine . Those with 6 or more attacks per year ( n = 410 ) were invited to participate in a follow-up interview about health care utilization and family impact of migraine ; 246 ( 60.0 % ) participated . Results The 1-year prevalence of migraine was 17.2 % in females and 6.0 % in males . Prevalence was highest between the ages of 30 and 49 . Whereas 48 % of migraine sufferers had seen a doctor for headache within the last year ( current consulters ) , 31 % had never done so in their lifetimes and 21 % had not seen a doctor for headache for at least 1 year ( lapsed consulters ) . Of current or lapsed consulters , 73 % reported a physician-made diagnosis of migraine ; treatments varied . Of all migraine sufferers , 49 % were treated with over-the-counter medications only , 23 % with prescription medication only , 23 % with both , and 5 % with no medications at all . Conclusion Relative to prior cross-sectional surveys , epidemiologic profiles for migraine have remained stable in the United States over the last decade . Self-reported rates of current medical consultation have more than doubled . Moderate increases were seen in the percentage of migraine sufferers who use prescription medications and in the likelihood of receiving a physician diagnosis of migraine If the brain of migraineurs is characterized between attacks by a reduction of mitochondrial phosphorylation potential , riboflavin , which has the potential of increasing mitochondrial energy efficiency , might have prophylactic effects in migraine . In this preliminary open pilot study , 49 patients suffering from migraine ( 45 without aura , 4 with aura ) were treated with 400 mg of riboflavin as a single oral dose for at least 3 months . Twenty-three patients received in addition 75 mg of aspirin . Mean global improvement after therapy was 68.2 % and there was no difference between the two groups of patients . With the exception of one patient in the riboflavin plus aspirin group who withdrew because of gastric intolerance , no drug-related side effects were reported . High-dose riboflavin could thus be an effective , low-cost prophylactic treatment of migraine devoid of short-term side effects . A placebo-controlled trial of its efficacy seems worthwhile Background : Riboflavin seems to have a promising effect on migraine in adults . The present study examines whether riboflavin has a prophylactic effect on migraine in children . Objective : To investigate whether riboflavin in a dosage of 50 mg/day has a prophylactic effect on migraine attacks in young children . Subjects and methods : This r and omised , placebo-controlled , double-blind , cross-over trial included 42 children ( aged 6–13 years ) with migraine of whom 14 children were also suffering from tension-type headache . Following a 4-week baseline period , all children received placebo for 16 weeks then riboflavin for 16 weeks ( or vice versa ) with a washout period of 4 weeks in between . The primary outcome measure was reduction in mean frequency of migraine attacks and tension-type headache in the last 4 weeks at the end of the riboflavin and placebo phase , compared with the preceding baseline or wash-out period . Secondary outcome measures were mean severity and mean duration of migraine and tension-type headaches in the last 4 weeks at the end of the riboflavin and placebo phase , compared with the preceding baseline or wash-out period . Results : No significant difference in the reduction of mean frequency of migraine attacks in the last month of treatment was found between placebo and riboflavin ( P = 0.44 ) . However , a significant difference in reduction of mean frequency of headaches with a tension-type phenotype was found in favour of the riboflavin treatment ( P = 0.04 ) . Conclusions : In this group of children with migraine , there is no evidence that 50 mg riboflavin has a prophylactic effect on migraine attacks . We found some evidence that 50 mg riboflavin may have a prophylactic effect on interval headaches that may correspond to mild migraine attacks or tension-type headache attacks in children with migraine Objectives : In migraine , an interictal reduction of mitochondrial energy metabolism and a preventive effect of high-dose riboflavin were reported . To explore the relation between the two , we tested if the therapeutic response to riboflavin is associated with specific mitochondrial DNA ( mtDNA ) haplogroups . We focused our attention on haplogroup H , which is known to differ from others in terms of energy metabolism . Methods : Sixty-four migraineurs completed a 4-month open trial with riboflavin ( 400 mg QD ) and were genotyped blindly for mtDNA haplogroups . Results : Forty patients responded to riboflavin treatment and 24 were nonresponders . The mtDNA haplogroup H was found in 29 subjects ( 20 migraine without aura , 9 migraine with aura ) . Riboflavin responders were more numerous in the non-H group ( 67.5 % ) . Conversely , nonresponders were mostly H ( 66.7 % ) . The difference between the two groups was significant ( χ2 = 7.07 ; p = 0.01 ) . The presence of aura had no influence on riboflavin 's effectiveness ( χ2 = 0.113 ; p = 0.74 ) and was not associated with a particular haplogroup ( χ2 = 0.55 ; p = 0.46 ) . Conclusions : In this pharmacogenetic study , riboflavin appears to be more effective in patients with migraine with non-H mitochondrial DNA haplotypes . The underlying mechanisms are unknown , but could be related to the association of haplogroup H with increased activity in complex I , which is a major target for riboflavin . Our results may have ethnic implication s , since haplogroup H is chiefly found in the European population The familial occurrence and mode of inheritance were analysed in families with migraine without aura ( MO ) and migraine with aura ( MA ) . The prob and s were found among 4000 persons from the general population . All persons with MA were included as prob and s , and an equivalent number of prob and s with MO was selected as a r and om sample among those with MO . Spouses and first-degree relatives were blindly interviewed . All interviews were performed by one neurological research fellow . The distinct familial patterns indicate that MO and MA have a different aetiology . Compared with the general population , the first-degree relatives of prob and s with MO had a 1.9-fold increased risk of MO while spouses had a 1.5-fold increased risk of MO , indicating that both genetic and environmental factors are important in MO . The first-degree relatives of prob and s with MA had a four-fold increased risk of MA while spouses had no increased risk of MA , indicating that MA is determined largely by genetic factors . The complex segregation analysis indicate that both MO and MA have multifactorial inheritance without generational difference A deficit of mitochondrial energy metabolism may play a role in migraine pathogenesis . We found in a previous open study that high-dose riboflavin was effective in migraine prophylaxis . We now compared riboflavin ( 400 mg ) and placebo in 55 patients with migraine in a r and omized trial of 3 months duration . Using an intention-to-treat analysis , riboflavin was superior to placebo in reducing attack frequency ( p = 0.005 ) and headache days ( p = 0.012 ) . Regarding the latter , the proportion of patients who improved by at least 50 % , i.e. “ responders , ” was 15 % for placebo and 59 % for riboflavin ( p = 0.002 ) and the number-needed-to-treat for effectiveness was 2.3 . Three minor adverse events occurred , two in the riboflavin group ( diarrhea and polyuria ) and one in the placebo group ( abdominal cramps ) . None was serious . Because of its high efficacy , excellent tolerability , and low cost , riboflavin is an interesting option for migraine prophylaxis and a c and i date for a comparative trial with an established prophylactic drug OBJECTIVE To determine the efficacy for migraine prophylaxis of a compound containing a combination of riboflavin , magnesium , and feverfew . BACKGROUND Previous studies of magnesium and feverfew for migraine prophylaxis have found conflicting results , and there has been only a single placebo-controlled trial of riboflavin . DESIGN / METHODS R and omized double-blind placebo-controlled trial of a compound providing a daily dose of riboflavin 400 mg , magnesium 300 mg , and feverfew 100 mg . The placebo contained 25 mg riboflavin . The study included a 1-month run-in phase and 3-month trial . The protocol allowed for 120 patients to be r and omized , with a preplanned interim analysis of the data after 48 patients had completed the trial . RESULTS Forty-nine patients completed the 3-month trial . For the primary outcome measure , a 50 % or greater reduction in migraines , there was no difference between active and " placebo " groups , achieved by 10 ( 42 % ) and 11 ( 44 % ) , respectively ( P=.87 ) . Similarly , there was no significant difference in secondary outcome measures , for active versus placebo groups , respectively : 50 % or greater reduction in migraine days ( 33 % and 40 % , P=.63 ) ; or change in mean number of migraines , migraine days , migraine index , or triptan doses . Compared to baseline , however , both groups showed a significant reduction in number of migraines , migraine days , and migraine index . This effect exceeds that reported for placebo agents in previous migraine trials . CONCLUSION Riboflavin 25 mg showed an effect comparable to a combination of riboflavin 400 mg , magnesium 300 mg , and feverfew 100 mg . The placebo response exceeds that reported for any other placebo in trials of migraine prophylaxis , and suggests that riboflavin 25 mg may be an active comparator . There is at present conflicting scientific evidence with regard to the efficacy of these compounds for migraine prophylaxis Migraine headache is a very common condition affecting about 10 % of the population that results in substantial morbidity and economic loss . The two most common variants are migraine with ( MA ) and without ( MO ) aura . Often considered to be a migraine‐like variant , cyclic vomiting syndrome ( CVS ) is a predominately childhood condition characterized by severe , discrete episodes of nausea , vomiting , and lethargy . Disease‐associated mitochondrial DNA ( mtDNA ) sequence variants are suggested in common migraine and CVS based upon a strong bias towards the maternal inheritance of disease , and several other factors . Temporal temperature gradient gel electrophoresis ( TTGE ) followed by cyclosequencing and RFLP was used to screen almost 90 % of the mtDNA , including the control region ( CR ) , for heteroplasmy in 62 children with CVS and neuromuscular disease ( CVS+ ) and in 95 control subjects . One or two rare mtDNA‐CR heteroplasmic sequence variants were found in six CVS+ and in zero control subjects ( P = 0.003 ) . These variants comprised 6 point and 2 length variants in hypervariable regions 1 and 2 ( HV1 and HV2 , both part of the mtDNA‐CR ) , one half of which were clustered in the nt 16040–16188 segment of HV1 that includes the termination associated sequence ( TAS ) , a functional location important in the regulation of mtDNA replication . Based upon our findings , sequencing and statistical analysis looking for homoplasmic nucleotide changes was performed in HV1 among 30 CVS+ , 30 r and omly‐ascertained CVS ( rCVS ) , 18 MA , 32 MO , and 35 control haplogroup H cases . Within the nt 16040–16188 segment , homoplasmic sequence variants were three‐fold more common relative to control subjects in both CVS groups ( P = 0.01 combined data ) and in MO ( P = 0.02 ) , but not in MA ( P = 0.5 vs. control subjects and 0.02 vs. MO ) . No group differences were noted in the remainder of HV1 . We conclude that sequence variation in this small “ peri‐TAS ” segment is associated with CVS and MO , but not MA . These variants likely constitute risk factors for disease development . Our findings are consistent with previous data demonstrating progression of CVS into MO in many cases , and the co‐segregation in a maternal inheritance pattern of CVS and MO within families . A mitochondrial component in the pathogenesis of migraine and CVS has therapeutic implication s , especially concerning the avoidance of fasting . © 2004 Wiley‐Liss , OBJECTIVES The primary objective of this guideline is to assist the practitioner in choosing an appropriate prophylactic medication for an individual with migraine , based on current evidence in the medical literature and expert consensus . This guideline is focused on patients with episodic migraine ( headache on ≤ 14 days a month ) . METHODS Through a comprehensive search strategy , r and omized , double blind , controlled trials of drug treatments for migraine prophylaxis and relevant Cochrane review s were identified . Studies were grade d according to criteria developed by the US Preventive Services Task Force . Recommendations were grade d according to the principles of the Grading of Recommendations Assessment , Development and Evaluation ( GRADE ) Working Group . In addition , a general literature review and expert consensus were used for aspects of prophylactic therapy for which r and omized controlled trials are not available . RESULTS Prophylactic drug choice should be based on evidence for efficacy , side-effect profile , migraine clinical features , and co-existing disorders . Based on our review , 11 prophylactic drugs received a strong recommendation for use ( topiramate , propranolol , nadolol , metoprolol , amitriptyline , gabapentin , c and esartan , butterbur , riboflavin , coenzyme Q10 , and magnesium citrate ) and 6 received a weak recommendation ( divalproex sodium , flunarizine , pizotifen , venlafaxine , verapamil , and lisinopril ) . Quality of evidence for different medications varied from high to low . Prophylactic treatment strategies were developed to assist the practitioner in selecting a prophylactic drug for specific clinical situations . These strategies included : first time strategies for patients who have not had prophylaxis before ( a beta-blocker and a tricyclic strategy ) , low side effect strategies ( including both drug and herbal/vitamin/mineral strategies ) , a strategy for patients with high body mass index , strategies for patients with co-existent hypertension or with co-existent depression and /or anxiety , and additional monotherapy drug strategies for patients who have failed previous prophylactic trials . Further strategies included a refractory migraine strategy and strategies for prophylaxis during pregnancy and lactation . CONCLUSIONS There is good evidence from r and omized controlled trials for use of a number of different prophylactic medications in patients with migraine . Medication choice for an individual patient requires careful consideration of patient clinical features The aim of this study was to investigate the efficacy of riboflavin for the prevention of migraine . An open label study was performed in a specialized outpatient clinic . Patients received 400 mg riboflavin capsules per day . Headache frequency , duration , intensity and the use of abortive drugs were recorded at baseline and 3 and 6 months after treatment . Headache frequency was significantly reduced from 4 days/month at baseline to 2 days/month after 3 and 6 months ( P < 0.05 ) . The use of abortive drugs decreased from 7 units/month to 4.5 units/month after 3 and 6 months of treatment ( P < 0.05 ) . In contrast , headache hours and headache intensity did not change significantly . We could demonstrate a significant reduction of headache frequency following riboflavin treatment . In addition , the number of abortive anti‐migraine tablets was reduced . In line with previous studies our findings show that riboflavin is a safe and well‐tolerated alternative in migraine prophylaxis |
10,793 | 25,768,935 | The adverse events in the BoNT-A trials mostly involved those who received the intervention drug and involved seizures .
Gastrointestinal problems were the most frequent adverse event in those who received alendronate .
The trial investigating pamidronate found no evidence of a difference in pain compared to the control group .
Based on current data this systematic review is unable to determine the effects of pharmacological interventions for pain for CYP with LLCs . | BACKGROUND Pain is one of the most common symptoms in children and young people ( CYP ) with life-limiting conditions ( LLCs ) which include a wide range of diagnoses including cancer .
The current literature indicates that pain is not well managed , however the evidence base to guide clinicians is limited .
There is a clear need for evidence from a systematic review to inform prescribing .
OBJECTIVES To evaluate the evidence on the effectiveness of different pharmacological interventions used for pain in CYP with LLCs . | BACKGROUND Pediatric osteoporosis is uncommon but can result in painful and debilitating insufficiency fractures . Treatment options for osteoporosis in children are few . Bisphosphonate therapy for children has not been approved by the Food and Drug Administration ( FDA ) in the United States , but its use in that population has been increasing . R and omized controlled studies have not been done because of the small subject pool and the difficulty in r and omizing a child with an insufficiency fracture to a placebo arm of a study . This retrospective case-control study of a population of children with primarily neuromuscular disease was done to review changes in bone mineral density as reflected by dual x-ray absorptiometry ( DXA ) scanning . METHODS Medical records and DXA scans were screened to identify children with low bone density who had been treated with alendronate as well as similar control subjects with low bone density for their age who had not received alendronate . Medication acquisition was confirmed by refill records , and cumulative exposure was calculated . Interval DXA scans were review ed to correlate bone mineral density change in grams per square centimeter as well as the percent change and percent change over time for both alendronate-treated and control subjects . RESULTS Twenty-eight alendronate-treated subjects and thirty control subjects met the inclusion criteria . No significant improvement in bone mineral density was seen in the alendronate-treated subjects as compared with the control subjects . Some patients in both groups exhibited marked improvement , with improvement of > 31 % seen only in the alendronate-treated subjects . CONCLUSIONS Alendronate does not reliably improve bone density in children and young adults with primarily neuromuscular disease and without osteogenesis imperfecta . Individual patients treated with bisphosphonates must be carefully followed to ensure medication compliance and appropriate response OBJECTIVE To evaluate feasibility and utility of the soleus H-reflex and tibialis anterior flexor reflex ( FR ) in identifying spinal cord neuronal response to intrathecal baclofen ( ITB ) in children with severe spastic cerebral palsy . METHODS During a r and omized , double-blind , placebo-controlled dose-escalation test treatment , maximum H amplitude/maximum M amplitude ( H/M ratio ) and FR parameters were bilaterally recorded at baseline and 2 - 3 h after intrathecal bolus administration of placebo and increasing doses of baclofen until both an improvement in the individual treatment goal ( s ) and a one-point reduction on the Ashworth scale were observed . RESULTS Electrophysiological data of 14 children were studied . The H-reflex was feasible in 13 children , the FR threshold area in 9 and the FR , elicited with supramaximal stimulation , in only one child . After ITB , the H/M ratio significantly decreased ( left : 0.67+/-0.47 to 0.15+/-0.18 , P=0.005 ; right : 0.55+/-0.32 to 0.14+/-0.19 , P=0.002 ) without placebo effect . FR threshold area after ITB , only decreased significantly in children not taking oral baclofen ( left : 146+/-53 to 41+/-54 mV ms , P=0.000 ; right : 156+/-80 to 66+/-48 mV ms , P=0.002 ) . CONCLUSIONS This is the first r and omized , double-blind , placebo-controlled dose-escalation study in spastic children demonstrating the soleus H-reflex to be a feasible and objective measure to quantify the decreasing motoneuron excitability in response to ITB bolus administration . Only in children not taking oral baclofen , FR threshold area can also be used as an objective outcome measure , yet feasibility is limited . SIGNIFICANCE We suggest introducing the H-reflex as the electrophysiological gold st and ard for the evaluation of the effect of ITB in spastic children BACKGROUND Severe osteogenesis imperfecta ( OI ) is a disorder characterized by osteopenia , frequent fractures , progressive deformity , loss of mobility , and chronic bone pain . There has been no effective therapy for the disorder until recently . The main objective of this study was to determine the efficacy and safety of pamidronate in improving bone mineralization and reducing fracture incidence in osteogenesis imperfecta . METHODS Intravenous pamidronate was administered to 64 children ( from 21 months to 10 years old ) with severe OI , in a 1 mg/kg single daily dose for 3 sequential days at 4-month intervals , over 24 - 48 months duration . Clinical status , biochemical characteristics including bone turnover markers , bone mineral density of the lumbar spine and femoral neck , and radiological changes were assessed regularly during treatment . RESULTS The number of fractures decreased from a median of 8 ( range 4 - 11 ) to 0 fractures/year ( range 0 - 4 ) ( p < 0.05 ) . After 16 months of treatment , there was significant improvement in bone mineral density ( BMD-DEXA ) z-score of the lumbar spine from a median of -5.90 ( range -7.01 to -4.76 ) to -2.70 ( range -4.46 to -1.98 ) ( p < 0.001 ) . Serum alkaline phosphatase ( ALP ) ( bone formation marker ) decreased from a median of 731.0 U/l ( range 438 - 998 U/l ) to 183 U/l ( range 95 - 286 U/l ) ( p < 0.001 ) , implying a significant reduction in bone turnover and resorption and increase in bone mineralization . There was no improvement in growth velocity or height SDS . Mobility and ambulation improved in all but five children ( all five had taken the drug for less than 2.5 years ) . There was a significant relief of chronic pain and fatigue but no adverse effects in all children using the drug . CONCLUSION Cyclic pamidronate administration is effective in improving bone mineralization and reducing fracture incidence in childhood osteogenesis imperfecta Over the past 20 years , orally administered biphosphonates have been used extensively in the management of a number of common skeletal disorders of different etiology . Recently , in clinical practice , in a number of cases in whom oral therapy is insufficient or contraindicated , intravenous administration of pamidronate presents an alternative therapeutic option . In order to investigate the clinical and radiological effects of cyclic intravenous pamidronate administration in children with osteogenesis imperfecta , a prospect i ve open study of pamidronate treatment was undertaken in a cohort of eight bed-bounded ( 3.6 - 13.8 years ) patients with severe osteoporosis and vertebral deformities . Pamidronate was administered at a dose of 0.5 mg/kg/ day for three days . Tri-monthly cyclic intravenous infusions were performed over-one year . Bone density , verebral corpus heights , estimated volumetric bone density and biochemical measurements were analyzed . Side effects of the therapy were determined via question naire . Significant reductions in the number of bone fractures and pain were observed in all patients . Ambulation scores were significantly altered and seven of eight patients became independent . Serum alkaline phosphatase levels decreased significantly . Lumbar X-ray and densitometry showed a striking improvement by the end of the treatment period . Even spaced dense lines corresponding to infusion periods were observed on roentgenograms of the radio-ulnar region . Pubertal progression and growth velocity were not affected inversely during therapy . Although we did not observe any severe side effect , one patient 's blood urea nitrogen level was altered slightly . In conclusion , one year cyclical pamidronate treatment seems to be effective and safe in improving bone mineralization and in reducing fracture incidence in severe osteoporosis BACKGROUND The current study investigated the efficacy , safety , tolerability , and compliance of a transdermal buprenorphine delivery system for the management of chronic cancer pain in the pediatric population . PROCEDURE Sixteen pediatric patients with moderate to severe cancer-related pain not satisfactorily controlled with previous non-opioid therapies were enrolled . Transdermal buprenorphine was administered following a 72 hour schedule and rescue medication ( tramadol ) was allowed for breakthrough pain . Pain intensity was assessed using the Wong-Baker faces pain rating scale ( WBS ) and other parameters related to the global quality of life were evaluated . Children 's evaluations of efficacy , compliance , and tolerability were recorded using numerical scales . Adverse events were monitored during the study and the medications needed to control opioid-related nausea and constipation were recorded . RESULTS Eleven patients ( 68.75 % ) responded to transdermal buprenorphine after 2 weeks of treatment . Pain intensity measured with WBS decreased from 6.25 at baseline to 1.38 at Day + 60 ( P < 0.001 ) . All outcome measures of global quality of life ( quality of sleep , alimentation , play and activity , speech , and crying ) significantly improved over the 60-day study period . Children 's evaluations of compliance and tolerability of the drug were always positive over the entire period of treatment . No severe adverse events were recorded . Opioid-related nausea was well controlled with medication on request , and the need for laxative therapy was greater at the end of the second month of treatment . CONCLUSIONS Transdermal buprenorphine was found to represent an efficient , safe and well tolerated approach to the management of children 's chronic cancer pain OBJECTIVE . Sedating critically ill patients often involves prolonged opioid infusions causing opioid tolerance . Naloxone has been hypothesized to limit opioid tolerance by decreasing adenylate cyclase/cyclic adenosine monophosphate activation . The study purpose was to investigate the effect of low-dose naloxone on the maximum cumulative daily fentanyl dose in critically ill children . METHODS . We conducted a double-blinded , r and omized , placebo-control trial from December 2002 through July 2004 in a university PICU . We enrolled 82 children age 1 day to 18 years requiring mechanical ventilation and fentanyl infusions anticipated to last for > 4 days were eligible for enrollment . Those receiving additional oral analgesia or sedation , having a history of drug dependence or withdrawal , or having significant neurologic , renal , or hepatic disease were excluded . In addition to fentanyl infusions , patients received low-dose naloxone or placebo infusions . Medications were adjusted using the Modified Motor Activity Assessment Scale . Withdrawal was monitored using the Modified Narcotic Withdrawal Scale . Intervention was a low-dose naloxone infusion ( 0.25 μg/kg per hour ) and the main outcome variable was the maximum cumulative daily fentanyl dose ( micrograms per kilogram per day ) . RESULTS . There was no difference in the maximum cumulative daily fentanyl dose between patients treated with naloxone ( N = 37 ) or those receiving placebo ( N = 35 ) . Adjustment for the starting fentanyl dose also failed to reveal group differences . Total fentanyl dose received throughout the study in the naloxone group ( 360 μg/kg ) versus placebo ( 223 μg/kg ) was not statistically different . Placebo patients trended toward fewer rescue midazolam boluses ( 10.7 vs 17.8 ) , lower total midazolam dose ( 11.6 mg/kg vs 23.9 mg/kg ) , and fewer rescue fentanyl boluses ( 18.5 vs 23.9 ) . CONCLUSIONS . We conclude that administration of low-dose naloxone ( 0.25 μg/kg per hour ) does not decrease fentanyl requirements in critically ill , mechanically ventilated children CONTEXT Information on the use of oral bisphosphonate agents to treat pediatric osteogenesis imperfecta ( OI ) is limited . OBJECTIVE The objective of the investigation was to study the efficacy and safety of daily oral alendronate ( ALN ) in children with OI . DESIGN AND PARTICIPANTS We conducted a multicenter , double-blind , r and omized , placebo-controlled study . One hundred thirty-nine children ( aged 4 - 19 yr ) with type I , III , or IV OI were r and omized to either placebo ( n = 30 ) or ALN ( n = 109 ) for 2 yr . ALN doses were 5 mg/d in children less than 40 kg and 10 mg/d for those 40 kg and greater . MAIN OUTCOME MEASURES Spine areal bone mineral density ( BMD ) z-score , urinary N-telopeptide of collagen type I , extremity fracture incidence , vertebral area , iliac cortical width , bone pain , physical activity , and safety parameters were measured . RESULTS ALN increased spine areal BMD by 51 % vs. a 12 % increase with placebo ( P < 0.001 ) ; the mean spine areal BMD z-score increased significantly from -4.6 to -3.3 ( P < 0.001 ) with ALN , whereas the change in the placebo group ( from -4.6 to -4.5 ) was insignificant . Urinary N-telopeptide of collagen type I decreased by 62 % in the ALN-treated group , compared with 32 % with placebo ( P < 0.001 ) . Long-bone fracture incidence , average midline vertebral height , iliac cortical width , bone pain , and physical activity were similar between groups . The incidences of clinical and laboratory adverse experiences were also similar between the treatment and placebo groups . CONCLUSIONS Oral ALN for 2 yr in pediatric patients with OI significantly decreased bone turnover and increased spine areal BMD but was not associated with improved fracture outcomes Background Dystonic cerebral palsy is primarily caused by damage to the basal ganglia and central cortex . The daily care of these patients can be difficult due to dystonic movements . Intrathecal baclofen treatment is a potential treatment option for dystonia and has become common practice . Despite this widespread adoption , high quality evidence on the effects of intrathecal baclofen treatment on daily activities is lacking and prospect i ve data are needed to judge the usefulness and indications for dystonic cerebral palsy . The primary aim of this study is to provide level one clinical evidence for the effects of intrathecal baclofen treatment on the level of activities and participation in dystonic cerebral palsy patients . Furthermore , we hope to identify clinical characteristics that will predict a beneficial effect of intrathecal baclofen in an individual patient . Methods / Design A double blind placebo-controlled multi-center r and omized clinical trial will be performed in 30 children with dystonic cerebral palsy . Patients aged between 4 and 25 years old with a confirmed diagnosis of dystonic cerebral palsy , Gross Motor Functioning Classification System level IV or V , with lesions in the cerebral white matter , basal ganglia or central cortex and who are eligible for intrathecal baclofen treatment will be included . Group A will receive three months of continuous intrathecal baclofen treatment and group B will receive three months of placebo treatment , both via an implanted pump . After this three month period , all patients will receive intrathecal baclofen treatment , with a follow-up after nine months . The primary outcome measurement will be the effect on activities of and participation in daily life measured by Goal Attainment Scaling . Secondary outcome measurements on the level of body functions include dystonia , spasticity , pain , comfort and sleep-related breathing disorders . Side effects will be monitored and we will study whether patient characteristics influence outcome . Discussion The results of this study will provide data for evidence -based use of intrathecal baclofen in dystonic cerebral palsy . Trial registration Nederl and s Trial Register , Severe osteogenesis imperfecta ( OI ) is a hereditary disorder characterized by increased bone fragility and progressive bone deformity . Cyclical pamidronate infusions improve clinical outcome in children older than 3 yr of age with severe OI . Because earlier treatment may have potential to prevent deformities and improve functional prognosis in young children , we studied nine severely affected OI patients under 2 yr of age ( 2.3 - 20.7 months at entry ) for a period of 12 months . Pamidronate was administered i.v . in cycles of 3 consecutive days . Patients received four to eight cycles during the treatment period , with cumulative doses averaging 12.4 mg/kg . Clinical changes were evaluated regularly during treatment , and radiological changes were assessed after 6 - 12 months of treatment . The control group consisted of six age-matched , severely affected OI patients , who had not received pamidronate treatment . During treatment bone mineral density ( BMD ) increased between 86 - 227 % . The deviation from normal , as indicated by the z-score , diminished from -6.5 + /- 2.1 to -3.0 + /- 2.1 ( P < 0.001 ) . In the control group the BMD z-score worsened significantly . Vertebral coronal area increased in all treated patients ( 11.4 + /- 3.4 to 14.9 + /- 1.8 cm2 ; P < 0.001 ) , but decreased in the untreated group ( P < 0.05 ) . In the treated patients , fracture rate was lower than in control patients ( 2.6 + /- 2.5 vs. 6.3 + /- 1.6 fractures/year ; P < 0.01 ) . No adverse side-effects were noted , apart from the well known acute phase reaction during the first infusion cycle . Pamidronate treatment in severely affected OI patients under 3 yr of age is safe , increases BMD , and decreases fracture rate Aim : To find an effective symptomatic treatment for osteogenesis imperfecta ( OI ) . Methods : In a prospect i ve observational study disodium pamidronate ( APD ) was given as monthly intravenous infusions to 28 children and adolescents ( aged 0.6–18 years ) with severe OI or a milder form of the disease , but with spinal compression fractures . Results : During treatment for 2–9 years , dual energy x ray absorptiometry measurements of the total body and of the lumbar spine showed a gradual increase in bone density . All bone metabolism variables in serum ( alkaline phosphatase , osteocalcin , procollagen 1 C-terminal peptide , collagen 1 teleopeptide ) and urine ( deoxypyridinoline ) indicated that there was a decrease in bone turnover . All patients experienced beneficial effects and the younger patients reported a major improvement in wellbeing , pain , and mobility without significant side effects . Vertebral remodelling was also seen . Conclusions : APD seems to be an efficient symptomatic treatment for children and adolescents with OI UNLABELLED A 2-year prospect i ve , partially r and omized open-label trial comparing oral alendronate with intravenous pamidronate therapy in children with OI showed equivalence in increasing total body BMD , spine BMD , and linear growth , and decreasing bone turnover and fracture incidence . Children with mild OI had greater responses than severe OI in BMD and growth . INTRODUCTION Bisphosphonate therapies increase BMD and may reduce fractures in children with osteogenesis imperfecta ( OI ) . A study directly comparing oral with intravenous bisphosphonate has not been published . This clinical trial compares oral alendronate with intravenous pamidronate in children with OI using an open-label , prospect i ve , 2-year , r and omized design . MATERIAL S AND METHODS Children over the age of 3 years were stratified by bone age , pubertal stage , and type of OI and then r and omized to receive oral alendronate 1 mg/kg/day in tablet form or intravenous pamidronate , 3 mg/kg/4 months . One child was assigned to pamidronate . One child r and omized to intravenous pamidronate changed to oral alendronate . Eighteen children completed 12 months of therapy : nine on oral alendronate and nine on intravenous pamidronate . Primary outcome efficacy was increase in BMD . Secondary outcomes included changes in bone turnover biomarkers , fracture incidence , and growth . RESULTS Total body and lumbar spine BMD increased , turnover markers decreased , and linear growth increased equivalently with oral and intravenous therapy . Fracture incidence showed a trend to decrease in both groups , with a significant decrease in fracture rates when the oral and intravenous groups were pooled . There were greater responses in BMD and growth in children with milder OI ( type I ) than those with more severe disease ( types III and IV ) , but there were no significant effects of age or pubertal stage . CONCLUSIONS Oral and intravenous bisphosphonate therapies are equally effective in children with OI and are particularly effective in milder forms . The oral route is highly acceptable in children and has practical advantages over the intravenous route OBJECTIVE : To describe demographic and clinical characteristics and outcomes of patients who received hospital-based pediatric palliative care ( PPC ) consultations . DESIGN , SETTING , AND PATIENTS : Prospect i ve observational cohort study of all patients served by 6 hospital-based PPC teams in the United States and Canada from January to March 2008 . RESULTS : There were 515 new ( 35.7 % ) or established ( 64.3 % ) patients who received care from the 6 programs during the 3-month enrollment interval . Of these , 54.0 % were male , and 69.5 % were identified as white and 8.1 % as Hispanic . Patient age ranged from less than one month ( 4.7 % ) to 19 years or older ( 15.5 % ) . Of the patients , 60.4 % lived with both parents , and 72.6 % had siblings . The predominant primary clinical conditions were genetic/congenital ( 40.8 % ) , neuromuscular ( 39.2 % ) , cancer ( 19.8 % ) , respiratory ( 12.8 % ) , and gastrointestinal ( 10.7 % ) . Most patients had chronic use of some form of medical technology , with gastrostomy tubes ( 48.5 % ) being the most common . At the time of consultation , 47.2 % of the patients had cognitive impairment ; 30.9 % of the cohort experienced pain . Patients were receiving many medications ( mean : 9.1 ) . During the 12-month follow-up , 30.3 % of the cohort died ; the median time from consult to death was 107 days . Patients who died within 30 days of cohort entry were more likely to be infants and have cancer or cardiovascular conditions . CONCLUSIONS : PPC teams currently serve a diverse cohort of children and young adults with life-threatening conditions . In contrast to the reported experience of adult-oriented palliative care teams , most PPC patients are alive for more than a year after initiating PPC Painful episodes of vaso-occlusion are the leading cause of hospitalizations and emergency department visits in sickle cell disease , and are associated with increased mortality . Low nitric oxide bioavailability contributes to vasculopathy in sickle cell disease . Since arginine is the obligate substrate for nitric oxide production , and an acute deficiency is associated with pain , we hypothesized that arginine may be a beneficial treatment for pain related to sickle cell disease . Thirty-eight children with sickle cell disease hospitalized for 56 episodes of pain were r and omized into this double-blinded placebo-controlled trial . Patients received L-arginine ( 100 mg/kg tid ) or placebo for 5 days or until discharge . A significant reduction in total parenteral opioid use by 54 % ( 1.9±2.0 mg/kg versus 4.1±4.1 mg/kg , P=0.02 ) and lower pain scores at discharge ( 1.9±2.4 versus 3.9±2.9 , P=0.01 ) were observed in the treatment arm compared to the placebo one . There was no significant difference in hospital length of stay ( 4.1±01.8 versus 4.8±2.5 days , P=0.34 ) , although a trend favored the arginine arm , and total opioid use was strongly correlated with the duration of the admission ( r=0.86 , P<0.0001 ) . No drug-related adverse events were observed . Arginine therapy represents a novel intervention for painful vaso-occlusive episodes . A reduction of narcotic use by > 50 % is remarkable . Arginine is a safe and inexpensive intervention with narcotic-sparing effects that may be a beneficial adjunct to st and ard therapy for sickle cell-related pain in children . A large multi-center trial is warranted in order to confirm these observations BACKGROUND Severe osteogenesis imperfecta is a disorder characterized by osteopenia , frequent fractures , progressive deformity , loss of mobility , and chronic bone pain . There is no effective therapy for the disorder . We assessed the effects of treatment with a bisphosphonate on bone resorption . METHODS In an uncontrolled observational study involving 30 children who were 3 to 16 years old and had severe osteogenesis imperfecta , we administered pamidronate intravenously ( mean [ + /-SD ] dose , 6.8+/-1.1 mg per kilogram of body weight per year ) at 4-to-6-month intervals for 1.3 to 5.0 years . Clinical status , biochemical characteristics reflecting bone turnover , the bone mineral density of the lumbar spine , and radiologic changes were assessed regularly during treatment . RESULTS Administration of pamidronate result ed in sustained reductions in serum alkaline phosphatase concentrations and in the urinary excretion of calcium and type I collagen N-telopeptide . There was a mean annualized increase of 41.9+/-29.0 percent in bone mineral density , and the deviation of bone mineral density from normal , as indicated by the z score , improved from -5.3+/-1.2 to -3.4+/-1.5 . The cortical width of the metacarpals increased by 27+/-20.2 percent per year . The increases in the size of the vertebral bodies suggested that new bone had formed . The mean incidence of radiologically confirmed fractures decreased by 1.7 per year ( P<0.001 ) . Treatment with pamidronate did not alter the rate of fracture healing , the growth rate , or the appearance of the growth plates . Mobility and ambulation improved in 16 children and remained unchanged in the other 14 . All the children reported substantial relief of chronic pain and fatigue . CONCLUSIONS In children with severe osteogenesis imperfecta , cyclic administration of intravenous pamidronate improved clinical outcomes , reduced bone resorption , and increased bone density BACKGROUND Prospect i ve studies that address both efficacy and safety of continuous infusion of intrathecal baclofen ( CITB ) in children with spastic cerebral palsy ( CP ) , and that use outcome measures beyond muscle tone are lacking . AIMS To study the efficacy at 12 months and safety up to 24 months after start of CITB in children with intractable spastic CP . METHODS Nine girls and eight boys , aged 13.7 years ( SD 2.9 ) , received a SynchroMed pump for CITB . We prospect ively recorded effects and adverse events at regular follow-up visits up to 24 months . Outcome measures included the 0 - 10 visual analogue scale ( VAS ) for individual problems , Gross Motor Function Measure ( GMFM ) and health related quality of life as measured with the Child Health Question naire-PF50 . RESULTS CITB for 12 months significantly improved the VAS for individual problems with 4.7 ( SD 2.0 ; p=0.000 ) , VAS for ease of care with 5.2 ( SD 2.1 ; p=0.000 ) , VAS for pain with 5.4 ( SD 2.7 ; p=0.002 ) ; GMFM sitting dimension with 3.3 ( range -4.0 to 22.0 ; p=0.022 ) , GMFM goal dimension with 4.0 ( range 0.0 - 26.0 ; p=0.007 ) ; and Child Health Question naire-PF50 domains of bodily pain/discomfort with 25.6 ( SD 35.9 ; p=0.016 ) and mental health with 9.8 ( SD 11.3 ; p=0.007 ) . During a mean follow-up of 18.4 months ( range 12 - 24 ) , we recorded 80 adverse events . Eight adverse events were serious , but not life-threatening . CONCLUSIONS CITB was effective at 12 months and safe up to 24 months for carefully selected children with intractable spastic CP . CITB relieved pain , facilitated ease of care and improved mental health . The majority of children could extend their activities and participation Cyclical intravenous treatment with pamidronate is of clinical benefit in children with moderate to severe osteogenesis imperfecta ( OI ) types I , III and IV , but there is no information on the effects of this treatment on the newly described OI type VI . Here , we report on the results of 3 years of pamidronate treatment in 10 children and adolescents with OI type VI ( age range 0.8 to 14.5 years , three girls ) . Treatment effects were compared to those of 10 patients with OI types I , III , and IV , who were matched for age and disease severity ( based on height and lumbar spine areal bone mineral density ) . During pamidronate therapy , lumbar spine areal bone mineral density z scores increased and lumbar spine vertebral bodies improved in shape . Iliac bone histomorphometry showed a tendency to higher cortical thickness ( + 53 % , P=0.06 ) but the mineralization defect , a characteristic feature of OI type VI , did not change during pamidronate treatment . Annualized fracture incidence decreased from 3.1 per year before treatment to 1.4 fractures per year during treatment ( P<0.05 ) . Regarding mobility , the Pediatric Evaluation of Disability Inventory gross motor score increased by 42 % during pamidronate treatment ( P<0.005 ) . Significant improvements were also found for age-related z scores of maximal isometric grip force . In comparison to the OI control group , the fracture incidence was higher and the gross motor scores were lower in OI type VI , both before and after pamidronate treatment ( P<0.05 for each parameter ) . No differences were found between the groups for changes in densitometric measures and cortical thickness during pamidronate treatment . Our results suggest that 3 years of intravenous pamidronate therapy led to improvements in bone mineral mass , gross motor function , muscle force and fracture incidence in patients with OI type VI . However , the gains in mobility scores and reductions in fracture incidence during pamidronate treatment are less than in other OI types Abstract Pamidronate ( PAM ) infusion is the st and ard treatment in children with osteogenesis imperfecta ( OI ) . Zoledronic acid ( ZOL ) is a bisphosphonate with higher potency and faster intravenous infusion , but its efficacy and safety has not been established for OI patients . We report an open-label , prospect i ve , and r and omized clinical analysis to study the safety and efficacy of ZOL compared with PAM in 23 children with OI . They were selected to receive PAM ( PAM group ) , 1 mg/kg/day , over 2 days or ZOL ( ZOL group ) , 0.025–0.05 mg/kg/day , over 2 days every 3–4 months according to their ages , during a 1-year follow-up . They were observed for clinical and biochemical parameters , side effects , bone mineral density ( BMD ) , and fracture rate . After treatment , the PAM and ZOL groups average lumbar spine ( LS ) BMD increased by 51.8 % ( p=0.053 ) and 67.6 % ( p=0.003 ) , respectively . Parallel improvement was seen in LS Z-score in the PAM and ZOL groups , with scores of –5.3 to –3.8 ( p=0.032 ) and –4.8 to –2.3 ( p=0.007 ) , respectively . LS Z-score for the ZOL group at the end of treatment was higher compared with the PAM group but only a borderline significance ( p=0.053 ) . The total alkaline phosphatase ( AP ) in the ZOL group significantly decreased from baseline at third and fourth infusion ( p=0.032 ) . Mild side effects were similar in both groups , but no severe clinical symptoms were reported . In conclusion , the present study shows that the use of ZOL in the dosage and period studied was safe and efficient to promote a clinical and densitometric improvement , similarly to PAM . Further studies are needed to establish optimal dosing and long-term safety OBJECTIVES To examine the efficacy and safety of intramuscular botulinum toxin A ( BoNT-A ) to reduce spasticity and improve comfort and ease of care in nonambulant children with cerebral palsy ( CP ) . STUDY DESIGN Nonambulant children with CP ( n = 41 ; Gross Motor Function Classification System level IV = 3 , level V = 38 ; mean age 7.1 years , range 2.3 - 16 years , 66 % male ) were r and omly allocated to receive either intramuscular BoNT-A injections ( n = 23 ) or sham procedure ( n = 18 ) combined with therapy . The analysis used generalized estimating equations with primary outcome the Canadian Occupational Performance Measure ( COPM ) at 4 weeks postintervention and retention of effects at 16 weeks . Adverse events ( AE ) were collected at 2 , 4 , and 16 weeks by a physician masked to group allocation . RESULTS There were significant between group differences favoring the BoNT-A-treated group on COPM performance at 4 weeks ( estimated mean difference 2.2 , 95 % CI 0.8 , 3.5 ; P = .002 ) and for COPM satisfaction ( estimated mean difference 2.2 , 95 % CI 0.5 , 3.9 ; P = .01 ) . These effects were retained at 16 weeks for COPM satisfaction ( estimated mean difference 1.8 , 95 % CI 0.1 , 3.5 ; P = .04 ) . There were more mild AE at 4 weeks for the BoNT-A group ( P = .002 ) , however , there were no significant between-group differences in the reporting of moderate and serious AE . CONCLUSIONS In a double-blind r and omized sham-controlled trial , intramuscular BoNT-A and therapy were effective for improving ease of care and comfort for nonambulant children with CP . There was no increase in moderate and severe AE in the children who had BoNT-A injections compared with the sham group OBJECTIVES . The purpose of this work was to assess the effect of botulinum toxin A and occupational therapy compared with occupational therapy alone on body structure , activities participation , and self-perception in a sample of children ( aged 3–16 years ) with hemiplegic cerebral palsy recruited from a statewide register . PATIENTS AND METHODS . Participants of this single-blind , r and omized , controlled trial identified from a population -based cerebral palsy register received either an individually prescribed and localized injection of botulinum toxin A with 4 sessions of occupational therapy over 4 weeks ( intervention ) or occupational therapy alone ( control ) . Outcomes were assessed from 2 domains of the World Health Organization International Classification of Functioning , Disability , and Health : body structure ( Modified Ashworth Scale and Tardieu Scale ) and activities participation ( Assessment of Motor and Process Skills , Goal Attainment Scale , Pediatric Evaluation of Disability Inventory , and Pediatric Quality of Life Inventory ) . Self-perception was also measured . RESULTS . All of the participants ( intervention : n = 21 ; control : n = 22 ) provided data at baseline and 3 and 6 months . Mean age was 8.6 years ; 23 were boys and 20 were girls . At 3 months , children allocated to receive the intervention performed significantly better in terms of body structure and activities participation . They reported improvements in self-perception for the global self-worth domain . At 6 months , the differences between the intervention and control groups persisted for the measures of body structure but not for activities participation or self-perception . CONCLUSION . Botulinum toxin A injection combined with a low-intensity occupational therapy program achieves significant improvements in body structure , activity participation , and self-perception OBJECTIVE Several studies have reported beneficial effects of bisphosphonates in children with osteogenesis imperfecta ( OI ) ; however , these studies have differed in the protocol s they used , and none has been independently replicated . We intended to confirm the efficacy of a specific intravenous bisphosphonate protocol in children with moderate to severe OI . METHODS We used the protocol described by Glorieux et al and performed a prospect i ve clinical trial in 6 children who were aged 22 months to 14 years . Each patient received intravenous pamidronate therapy for a minimum of 2 years in cycles of 1 mg/kg daily over 3 consecutive days at a mean cycle interval of 3.8 months . Outcome measures included lumbar spine areal bone mineral density ( BMD ) and z score , fracture rate , and occupational therapy functional assessment with serial Pediatric Evaluation of Disability Inventory . RESULTS While on therapy , the average annual increase in areal BMD was 48 % and the average annual increase in BMD z score was 1.0 . This increase in z score is statistically significant . There was no clear correlation between changes in BMD and fracture rate . All patients experienced functional improvement in mobility . CONCLUSIONS Our results support the findings of Glorieux et al that cyclic administration of intravenous pamidronate in children with OI has beneficial effects with respect to BMD z scores and physical disability . Long-term follow-up will be required to determine whether bisphosphonate therapy will decrease fracture rates and increase mobility in children with moderate to severe OI OBJECTIVE To compare the efficacy and adverse effects of fentanyl or morphine analgesia during the first 2 days of life in newborn infants who underwent mechanical ventilation . STUDY DESIGN In a r and omized double-blind trial , 163 infants were allocated to receive a continuous infusion of fentanyl ( 10.5 microg/kg over a 1-hour period followed by 1.5 microg/kg/hr ) or morphine ( 140 microg/kg over a 1-hour period followed by 20 microg/kg/hr ) for at least 24 hours . The severity of pain was assessed with physiological parameters , a behavioral pain scale , and stress hormone concentrations before and 2 and 24 hours after the start of treatment . RESULTS The analgesic effect was similar in both groups , as judged by the pain scale . Plasma adrenaline and noradrenaline concentrations decreased significantly from 0 to 24 hours in both groups . Median adrenaline decrease was 0.5 nmol/L ( interquartile range [ IQR ] 1.1;0.0 ) in the fentanyl and 0.7 nmol/L ( IQR 1.3;0.1 ) in the morphine group , noradrenaline 2.1 nmol/L ( IQR 9.0;0.2 ) , and 3.0 nmol/L ( IQR 7 . 5;0.3 ) , respectively . beta-endorphin decreased significantly only in the fentanyl group ( 14 pmol/L ( IQR 28 ; 7 ) , P < .05 ) . Decreased gastrointestinal motility was less frequent in the fentanyl group ( 23 % vs 47 % , P < .01 ) . CONCLUSIONS With at least as effective analgesia as with morphine , fentanyl had fewer side effects . Fentanyl may be superior to morphine for short-term postnatal analgesia in newborn infants UNLABELLED Bisphosphonates have been widely administered to children with OI based on observational trials . A r and omized controlled trial of q3 m intravenous pamidronate in children with types III and IV OI yielded positive vertebral changes in DXA and geometry after 1 year of treatment , but no further significant improvement during extended treatment . The treated group did not experience significantly decreased pain or long bone fractures or have increased motor function or muscle strength . INTRODUCTION Bisphosphonates , antiresorptive drugs for osteoporosis , are widely administered to children with osteogenesis imperfecta ( OI ) . Uncontrolled pamidronate trials in OI reported increased BMD , vertebral coronal area , and mobility , and decreased pain . We conducted a r and omized controlled trial of pamidronate in children with types III and IV OI . MATERIAL S AND METHODS This r and omized trial included 18 children ( 4 - 13 years of age ) with types III and IV OI . The first study year was controlled ; 9 children received pamidronate ( 10 mg/m2/day IV for 3 days every 3 months ) . Four children in each group also received recombinant growth hormone ( rGH ) injections ( 0.06 mg/kg/day for 6 days/week ) . Seven children in the treatment group received pamidronate for an additional 6 - 21 months . All patients had L1-L4 DXA , spine QCT , spine radiographs , and musculoskeletal and functional testing . RESULTS In the controlled phase , treated patients experienced a significant increase in L1-L4 DXA z score ( p < 0.001 ) and increased L1-L4 mid-vertebral height ( p = 0.014 ) and total vertebral area ( p = 0.003 ) compared with controls . During extended treatment , DXA z scores and vertebral heights and areas did not increase significantly beyond the 12-month values . Fracture rate decreased significantly in the upper extremities ( p = 0.04 ) but not the lower extremities ( p = 0.09 ) during the first year of treatment . Gross motor function , muscle strength , and pain did not change significantly during the controlled or extended treatment phases . CONCLUSIONS A controlled trial confirmed the spine benefits of short-term pamidronate treatment in children with types III and IV OI . Pamidronate increased L1-L4 vertebral DXA and decreased vertebral compressions and upper extremity fractures . Vertebral measures did not improve during the extended treatment phase . The treatment group did not experience decreased lower extremity long bone fractures , significant improvement in growth , ambulation , muscle strength , or pain . There was substantial variability in individual response to treatment BACKGROUND Non-r and omised studies have suggested beneficial effects of bisphosphonates in osteogenesis imperfecta . We assessed the effects of oral olpadronate in children with this disorder in a r and omised double-blind placebo-controlled trial . METHODS 34 children recruited from the Dutch national centre for osteogenesis imperfecta were r and omly assigned olpadronate ( 10 mg/m2 daily ; n=16 ) or placebo ( n=18 ) for 2 years . All children also received calcium and vitamin D supplements . Primary endpoints were incident fractures of long bones and changes in bone mineral content ( BMC ) , bone mineral density ( BMD ) , and functional outcome . Anthropometry , vertebral height , and urinary markers of bone resorption were also studied . Analyses were by intention to treat . FINDINGS Fracture follow-up was complete for all the children , including two who withdrew from the study ( one from each group ) . Olpadronate treatment was associated with a 31 % reduction in relative risk of fracture of long bones ( hazard ratio 0.69 [ 95 % CI 0.52 - 0.91 ] , p=0.01 ) . The olpadronate group showed significantly greater increases than the placebo group in spinal BMC ( difference between groups 2.24 g/year [ 0.20 - 4.29 ] , p=0.03 ) and spinal BMD ( difference between groups 0.054 g/cm2 per year [ 0.012 - 0.096 ] , p=0.01 ) . There were no detectable effects on functional outcome , anthropometrics , or vertebral height and no differences between the groups in changes in urinary markers of bone resorption . INTERPRETATION Oral treatment with olpadronate at a daily dose of 10 mg/m2 results in a reduction of fracture risk of long bones in children with osteogenesis imperfecta . However , the issue of whether bisphosphonates will alter the natural course of osteogenesis imperfecta remains unresolved , and further studies are needed BACKGROUND Intractable spasticity can be treated effectively with continuous infusion of intrathecal baclofen . Because evidence for its use in the treatment of children with spastic cerebral palsy is lacking , we conducted a r and omised controlled trial . AIMS To test whether continuous infusion of intrathecal baclofen is effective in comparison with st and ard treatment only . METHODS Seventeen children , aged 13.2 ( SD 2.8 ) years , with intractable spastic cerebral palsy were r and omised to receive a Synchromed pump for continuous infusion of intrathecal baclofen after either 1 month ( CITB group ) or 6 months ( Control group ) . Primary outcomes were the 6-month-change scores on the 0 - 10 visual analogue scale for individually formulated problems and the caregiver assistance scale of the Pediatric Evaluation of Disability Inventory self-care domain . One of the secondary outcome measures was health related quality of life as measured with the Child Health Question naire-PF50 . RESULTS Nine children were r and omly assigned to the CITB group and eight to the Control group . The visual analogue scale for individual problems improved with 4.0 ( SD 1.7 ) in the CITB group and changed with -0.2 ( SD 1.3 ) in the Control group ( p=0.001 ) . Pediatric Evaluation of Disability Inventory scores did not change significantly . The Child Health Question naire-PF50 6-month-change score significantly differed in favour of the CITB group for the domains of bodily pain/discomfort ( p=0.014 ) , mental health ( p=0.045 ) , psychosocial status ( p=0.027 ) and parents ' personal time limitation ( p=0.043 ) . CONCLUSION The results of this r and omised controlled trial establish continuous infusion of intrathecal baclofen to be effective in carefully selected children with problems caused by intractable spastic cerebral palsy BACKGROUND Children with osteogenesis imperfecta are often treated with intravenous bisphosphonates . We aim ed to assess the safety and efficacy of risedronate , an orally administered third-generation bisphosphonate , in children with the disease . METHODS In this multicentre , r and omised , parallel , double-blind , placebo-controlled trial , children aged 4 - 15 years with osteogenesis imperfecta and increased fracture risk were r and omly assigned by telephone r and omisation system in a 2:1 ratio to receive either daily risedronate ( 2·5 or 5 mg ) or placebo for 1 year . Study treatment was masked from patients , investigators , and study centre personnel . Thereafter , all children received risedronate for 2 additional years in an open-label extension . The primary efficacy endpoint was percentage change in lumbar spine areal bone mineral density ( BMD ) at 1 year . The primary efficacy analysis was done by ANCOVA , with treatment , age group , and pooled centre as fixed effects , and baseline as covariate . Analyses were based on the intention-to-treat population , which included all patients who were r and omly assigned and took at least one dose of assigned study treatment . The trial is registered with Clinical Trials.gov , number NCT00106028 . FINDINGS Of 147 patients , 97 were r and omly assigned to the risedronate group and 50 to the placebo group . Three patients from the risedronate group and one from the placebo group did not receive study treatment , leaving 94 and 49 in the intention-to-treat population , respectively . The mean increase in lumbar spine areal BMD after 1 year was 16·3 % in the risedronate group and 7·6 % in the placebo group ( difference 8·7 % , 95 % CI 5·7 - 11·7 ; p<0·0001 ) . After 1 year , clinical fractures had occurred in 29 ( 31 % ) of 94 patients in the risedronate group and 24 ( 49 % ) of 49 patients in the placebo group ( p=0·0446 ) . During years 2 and 3 ( open-label phase ) , clinical fractures were reported in 46 ( 53 % ) of 87 patients in the group that had received risedronate since the start of the study , and 32 ( 65 % ) of 49 patients in the group that had been given placebo during the first year . Adverse event profiles were otherwise similar between the two groups , including frequencies of reported upper-gastrointestinal and selected musculoskeletal adverse events . INTERPRETATION Oral risedronate increased areal BMD and reduced the risk of first and recurrent clinical fractures in children with osteogenesis imperfecta , and the drug was generally well tolerated . Risedronate should be regarded as a treatment option for children with osteogenesis imperfecta . FUNDING Alliance for Better Bone Health ( Warner Chilcott and Sanofi ) Bone mineral density and fracture rates in children with osteogenesis imperfecta improve with intravenous bisphosphonates . The efficacy of oral bisphosphonates has not been established . This report is an analysis of an open-label , prospect i ve , r and omized clinical trial of oral compared to intravenous bisphosphonate medications in children with osteogenesis imperfecta . Children were stratified according to bone age , pubertal stage , and type of osteogenesis imperfecta and then r and omized to receive intravenous pamidronate , 3 mg/kg over 3 days every 4 months , or oral alendronate 1 mg/kg , from a minimum of 10 mg to a maximum of 20 mg daily . The primary efficacy outcome was change in bone mineral density . Secondary outcomes included change in biomarkers of bone turnover , fracture incidence , and growth rate . Ten children were r and omized ( 6 oral and 4 intravenous ) . Two other children were assigned to intravenous treatment due to chronic abdominal pain . In each group , three patients had type III/IV osteogenesis imperfecta , while three had type I. All 12 children completed 8 months of therapy ; nine completed 12 months . Bone mineral density increased in both oral and intravenous groups equally and beyond that expected with normal growth . All children had a decrease in biochemical markers of bone turnover . Linear growth showed a moderate increase above that for age . There was a non-significant decrease in fracture incidence in both groups CONTEXT Alendronate ( ALN ) is a bisphosphonate compound that can be administered orally and has potential use in pediatric osteoporotic conditions . OBJECTIVE The objective was to evaluate the pharmacokinetics and single-dose tolerability of ALN in children with osteogenesis imperfecta . DESIGN ALN was administered iv and orally in a two-period , r and omized crossover study , with doses separated by a 2-wk washout and follow-up carried out within 2 wk after the last ALN dose . SETTING The study was conducted at the pediatric metabolic bone research unit at the Shriners Hospital for Children , Montréal , Canada . PATIENTS Twenty-four children ( aged 4 - 16 yr ; eight girls ) with osteogenesis imperfecta type I participated . INTERVENTIONS All patients received iv ALN at a dose of 125 mug . In addition , patients weighing less than 40 kg received an oral dose of ALN 35 mg , whereas those weighing 40 kg or more received ALN 70 mg orally . MAIN OUTCOME MEASURES Total urinary excretion and oral bioavailability of ALN , blood and urine safety parameters , and adverse events were the main outcome measures . RESULTS The total urinary excretion of ALN after the iv dose was similar for both weight groups . The mean oral bioavailability ( 95 % confidence interval ) was 0.43 % ( 0.28 , 0.64 % ) for patients weighing less than 40 kg and 0.56 % ( 0.36 , 0.87 % ) for patients weighing 40 kg or more . Eighteen patients reported a total of 44 clinical adverse experiences , none of which were serious . The most common adverse experiences were mild to moderate headache ( n = 7 ) , nausea ( n = 7 ) , fever ( n = 5 ) , and abdominal pain ( n = 6 ) . Eighty percent of the adverse experiences ( 35 of 44 ) occurred within 48 h of medication administration , 91 % ( 40 of 44 ) lasted less than 24 h , and 84 % ( 37 of 44 ) were reported after oral dosing . Laboratory safety monitoring revealed a marginal decrease in absolute lymphocyte count and serum alkaline phosphatase after the study compared with baseline for both weight categories . CONCLUSIONS The mean oral bioavailability of 35- and 70-mg ALN tablets was less than 0.6 % , comparable to adult studies . Adverse experiences from single-dose ALN were minor , and the drug was generally well-tolerated The aim of this study was to characterize the pharmacokinetics and pharmacodynamics of morphine and morphine 6‐glucuronide ( M6 G ) in children with cancer Osteogenesis imperfecta ( OI ) is a debilitating clinical condition characterized by fragile bone and skeletal deformity . Over the past decade frequent reports have suggested that the cyclical administration of intravenous pamidronate has a positive impact on bone density and skeletal fractures ; however , the impact of such therapy on the quality of life ( QOL ) has rarely been reported . Alendronate , an oral bisphosphonate , is widely used to treat osteoporosis . The purpose of this study was to evaluate the impact of daily alendronate on QOL and bone parameters in children with OI . A prospect i ve double-blind crossover study was design ed in which placebo was alternated with daily alendronate . Twenty children with types I , III , and IV OI were recruited . Seventeen patients completed the study . Markers of QOL were measured in children with type III and IV OI ( n = 15 ) using total mobility ( PEDI ) , self-care ( WeeFIM ) , well-being , pain , and use of analgesic scores . After 1 year of alendronate therapy , vertebral bone mineral density ( BMD ) improved from a change in st and ard deviation score ( z-score ) of 0.89 ± 0.19 to −0.12 ± 0.14 after 1 year of placebo ( P < 0.001 ) . All QOL markers , except for mobility score , improved in response to alendronate therapy . Change in height z-score also improved in response to 1 year of alendronate therapy ( 0.41 ± 0.21 vs. −0.09 ± 0.11 , P < 0.05 ) . Alendronate therapy did not alter serum levels of calcium , osteocalcin , parathyroid hormone ( PTH ) , 1 , 5 (OH)2 vitamin D , cholesterol , or urinary hydroxyproline or any other biochemical marker evaluated . Alendronate decreased by 56 % urinary cross-linked N-telopeptide of type 1 collagen divided by urinary creatinine ( uNTX/uCr ) . Daily alendronate therapy was well tolerated . Only two patients had mild gastrointestinal discomfort , responding to minor adjustments in alendronate intake . Daily alendronate therapy is safe and effective in improving QOL in children with OI BACKGROUND In the present study , we investigated the situation of children who had succumbed to their malignancy in Germany as perceived by their parents . Specifically , we were interested in bereaved parents ' perspective on five essential areas : 1 ) symptoms and quality of life , 2 ) characteristics of the child 's death , 3 ) anticipation of their child 's death and care delivery , 4 ) end-of-life decisions and 5 ) impact of the child 's death on the parents and perceived social support by the health care team . MATERIAL S AND METHODS We contacted all existing departments for paediatric oncology in the German federal state of Nordrhein Westfalen and asked them to contact all parents for participation in our study who had lost their child to cancer in 1999 and 2000 . Upon agreement , we interviewed the parents utilising a vali date d semi-structured interview on distressing symptoms and quality of life of their children during the end-of-life care period . RESULTS Six of the 19 departments agreed to participate . Parents of 48 children ( 31 boys , 17 girls ) were interviewed . The main distressing symptoms were fatigue , pain , loss of appetite , and dyspnoea according to the parents . While parents perceived pain and constipation to have been treated successfully , loss of appetite and anxiety were not treated effectively . 75 % of the children died due to a progression of their malignancy . Of these , 50 % obtained cancer-directed therapy at the end of life , which was negatively rated by the parents in hindsight . 48 % of the children died at home even though 88 % of the parents chose ' at home ' as the most appropriate locale of death in hindsight . Parents anticipated their child 's death on average 9 weeks prior to the child 's death . 41 % of the parents provided palliative home care for their child and the majority ( 88 % ) rated the quality of care as good or very good . 64 % discussed end-of-life decisions with the health care team , 36 % did not have a discussion . Parents were clearly affected by their child 's death . However , 15 % of the parents were not contacted by the health care team following the child 's death . CONCLUSIONS The present study demonstrated that psychological symptoms ( e.g. anxiety ) are frequent symptoms in the end-of-life care period and cause severe suffering in the children . Questions in terms of benefits and costs of cancer-directed therapy in the end-of-life care period need to be addressed in future prospect i ve studies . Parents ' perspective on their child 's death and related end-of-life decisions highlighted the importance of communication between parents and the health care team . Future studies need to investigate potential barriers in the communication between parents and the team to optimise end-of-life decisions and hence , reduce parents ' long-term distress . In line with the previous , the present data demonstrated that there is still a lack of routine contact from the health care team following the child 's death despite existing guidelines . Research is therefore needed into the implementation of guidelines for routine contact into clinical practice following a child 's death OBJECTIVE To conduct a placebo-controlled prospect i ve study of the effectiveness of intrathecal bolus injections and continuous administration of baclofen on functional parameters in patients with severe spasticity of cerebral origin . To compare this functional evaluation with spasticity scores in different muscle groups . METHODS In 11 patients with spasticity of cerebral origin ( mainly cerebral palsy ) , double-blind scoring of spasticity ( Ashworth scale score and visual analog score ) , spasms , pain , and functional abilities was performed during tests with bolus injections including a placebo control . Eight patients were considered good responders and received a subcutaneous device for intrathecal drug delivery . Six of these patients were followed up for 2 years , during which they underwent the same scoring procedures as after their bolus injections . These patients were subjected to a blinded dose reduction test . RESULTS There was a noticeable placebo effect on spasticity scores during tests with bolus injections . Eight patients demonstrated a significant beneficial effect of intrathecal bolus injections compared with this placebo effect . Functional improvements were noted in most patients . During continuous infusion , Ashworth scale scores were less favorable but still significantly lower than at baseline . Subjective evaluation ( visual analog scores ) remained positive , functional improvements were maintained , and patient comfort was invariably and significantly improved . CONCLUSION Intrathecal administration of baclofen is a safe and effective treatment for spasticity of cerebral origin . Functional improvement was demonstrated . The presence of a placebo effect on the spasticity scores suggests the need for double-blind screening in each patient AIM Treatment options for dystonic cerebral palsy ( CP ) are limited . Our aims were to determine whether intrathecal baclofen ( ITB ) improves daily care , decreases dystonia and decreases pain in patients with dystonic CP . METHODS Patients received r and omized blinded treatment with ITB or placebo . Scores on problems of daily care were recorded and dystonia , pain and comfort were assessed . RESULTS Four patients ( three males , average age 12 years 6 months ) were included ( all Gross Motor Function Classification System level V ) . During the trial period problem scores and dystonia scores decreased in all four patients . CONCLUSION In this pilot study we report positive functional effects of ITB trial treatment in four patients with dystonic CP . A r and omized trial with a larger cohort is needed to verify these results Intravenous pamidronate is the most widely used treatment for moderate to severe osteogenesis imperfecta ( OI ) . Currently , there is no medical treatment for patients with mild OI . We conducted a single-center r and omized double-blind placebo-controlled trial to examine the efficacy and safety of oral risedronate in the treatment of pediatric patients with mild OI . A total of 26 children and adolescents ( age , 6.1 - 17.7 yr ; 11 girls ) with OI type I were r and omized to either placebo ( N = 13 ) or risedronate ( N = 13 ) for 2 yr . Risedronate doses were 15 mg once per week in patients weighing < 40 kg and 30 mg once per week in patients weighing > 40 kg . After 2 yr of treatment , risedronate decreased serum levels of the bone resorption marker collagen type I N-telopeptide by 35 % compared with a 6 % reduction with placebo ( p = 0.003 ) . Risedronate increased lumbar spine areal BMD Z-scores by 0.65 , whereas patients receiving placebo experienced a decrease of 0.15 ( p = 0.002 ) . In contrast , no significant treatment differences in bone mass and density were found at the radial metaphysis and diaphysis , the hip , and the total body . Histomorphometric analysis of transiliac bone biopsies at the end of the study period did not show a significant treatment difference in cortical width , trabecular bone volume , or parameters of bone turnover . Similarly , there was no detectable treatment effect on vertebral morphometry , second metacarpal cortical width , grip force , bone pain , or number of new fractures . Regarding safety , risedronate was generally well tolerated , and the incidence of clinical or laboratory adverse experiences was similar among treatment groups . These results suggest that the skeletal effects of oral risedronate are weaker than those that are commonly observed with intravenous pamidronate treatment but still lead to an increase in lumbar spine areal BMD . Future studies should investigate whether oral risedronate is effective in reducing fracture rates in children and adolescents with mild OI type We report results of 2–5 y treatment with intravenous disodium pamidronate ( APD ) in three girls with severe osteogenesis imperfecta ( OI ) . Treatment was given as monthly infusions . Additional oral 1,25‐dihydroxy‐cholecalciferol was given to compensate for a transient decrease in serum calcium levels . During treatment , DEXA measurements showed a gradual increase in bone density in all patients . All parameters analysed in serum ( ALP , osteocalcin , PICP , ICTP ) and in urine ( deoxypyridinoline and pyridinoline ) showed a decreased bone turnover . The two younger patients reported a major improvement in well‐being , pain and activities of daily life . The effect on the older patient was less pronounced . No negative side effects in clinical or laboratory variables were observed . This study indicates that APD is of value in the symptomatic treatment of children with severe OI Intrathecal baclofen ( ITB ) therapy can be very effective in the treatment of intractable spasticity , but its effectiveness and safety have not yet been thoroughly studied in children with cerebral palsy ( CP ) . The aims of this double-blind , r and omized , placebo-controlled , dose-finding study were to select children eligible for continuous ITB infusion , to assess the effective ITB bolus dose , and to evaluate the effects , side effects , and complications . Outcome measures included the original Ashworth scale and the Visual Analogue Scale for individually formulated problems . We studied nine females and eight males , aged between 7 and 16 years ( mean age 13y 2mo [ SD 2y 9mo ] ) . Twelve children had spastic CP and five had spastic-dyskinetic CP . One child was classified on the Gross Motor Function Classification System at Level III , two at Level I V , and 14 at Level V. The test treatment worked successfully for all 17 children with an effective ITB bolus dose of 12.5 microg in one , 20 microg in another , 25 microg in 10 , and 50 microg in five children . ITB significantly reduced muscle tone , diminished pain , and facilitated ease of care . The placebo did not have these effects . Nine side effects of ITB were registered , including slight lethargy in seven children . Fourteen children had symptoms of lowered cerebrospinal fluid pressure . We conclude that ITB bolus administration is effective and safe for carefully selected children with intractable spastic CP Making a diagnosis is the bread and butter of clinical practice , but in light of the number of tests now available to clinician , diagnosing illness has become a complicated process . Guidelines for making an evidence -based diagnosis abound , but those making recommendations about diagnostic tests or test strategies must realize that clinicians require support to make diagnostic decisions that they can easily implement in daily practice . The Grading of Recommendations Assessment , Development and Evaluation ( GRADE ) Working Group has developed a rigorous , transparent , and increasingly adopted approach for grading the quality of research evidence and strength of recommendations to guide clinical practice . This editorial summarizes GRADE 's process for developing recommendations for tests ( 1 ) . Clinicians are trained to use tests for screening and diagnosis ; identifying physiologic derangements ; establishing a prognosis ; and monitoring illness and treatment response by assessing signs and symptoms , imaging , biochemistry , pathology , and psychological testing techniques ( 2 ) . Sensitivity , specificity , positive predictive value , likelihood ratios , and diagnostic odds ratios are among the challenging terms that diagnostic studies typically deliver to clinicians , and all have to do with diagnostic accuracy . Not only do clinicians have difficulties remembering the definitions and calculations for these terms , application of the concepts to individual patients is often complicated . Many clinicians order a test despite uncertainty about how to interpret the result , and they also contribute to testing errors by incorrectly ordering tests ( 3 , 4 ) . GRADE 's framework for developing recommendations for diagnostic management studies is based on what is needed for practical clinical applicationthat is , how to weigh the benefits and harms of ordering and using a diagnostic test in caring for patients ( 1 ) . The approach begins with specifying the PICO : the relevant population ( P ) , diagnostic intervention or test ( I ) ( including its purpose , such as triage , replacement , or an add-on test ) , comparison test ( C ) , and patient-important outcomes ( O ) related to the use of a test for a focused clinical question . If a test fails to improve patient-important outcomes , there is no reason to use it , whatever its accuracy . For example , the results of genetic testing for Huntington chorea , an untreatable condition , may provide either welcome reassurance that a patient will not have the condition or the ability to plan for his future knowing that he will sadly fall victim ( 1 ) . Here , the ability to plan is analogous to an effective treatment , and the benefits of planning need to be balanced against the downsides of receiving an early diagnosis ( 5 - 7 ) . The best evidence of test performance comes from large r and omized trials of diagnostic strategies that directly measure patient-important outcomes ( 1 ) . However , these trials are few and far between : An informal review of the Cochrane data base of r and omized trials revealed < 100 such studies . Therefore , most recommendations about diagnostic testing are based on an implicit 2-step process of how the accuracy of a test indirectly changes patient-important outcomes . In the first step , a diagnostic-test accuracy study ( Figure ) , patients may receive both a new test and a reference test ( i.e. , the best available method for detecting the target condition ) . Investigators can then calculate the accuracy of the test compared with the reference test ( first step ) . In the second step , judgments about the patient importance of test accuracy are based on the consequences of being correctly or incorrectly classified as having or not having the disease . These include the benefits and harms of receiving treatment or follow-up tests for those correctly classified as having the disease , reassurance or receipt of other follow-up tests for those correctly classified as not having the disease , receipt of unnecessary treatment or additional tests for those incorrectly classified as having the disease , delayed or no treatment for those incorrectly classified as not having the disease , and any adverse effects of the diagnostic test ( e.g. , from invasive tests ) . Those making recommendations about diagnostic tests must then compare patient-important outcomes ( and costs ) in all patients receiving the new test with all patients receiving the old , or comparator , test . For the first step ( i.e. , assessing test accuracy ) , there are well-described method ological criteria for assessing risk for bias in an estimate of test accuracy , ideally based on a systematic review of relevant studies . For instance , studies of diagnostic test accuracy with a low risk for bias enroll consecutive patients for whom there is legitimate diagnostic uncertaintythat is , the type of patients to whom clinicians would apply the test in the course of regular clinical practice . If studies fail this criterion ( e.g. , only enroll patients with severe disease and healthy controls ) , the apparent accuracy of a test is likely to be misleadingly high ( 8 , 9 ) . The second step shown in the Figure is , in most situations , based on judgments of test accuracy as a surrogate for patient-important outcomes . The key issue about these judgments is that they should be made transparent to those using the recommendations . For example , in the diagnosis of suspected acute urolithiasis , well- design ed studies demonstrate fewer false-negative results with noncontrast helical computed tomography ( CT ) than with intravenous pyelography ( IVP ) ( 10 ) . However , those ureteric stones that CT detects but IVP misses are smaller and therefore are more likely to spontaneously pass . Before r and omized trials evaluating outcomes in patients treated for smaller stones , evidence from observational studies was of lower quality . Thus , it remained uncertain how patients were affected by missed cases and follow-up of incidental findings unrelated to renal calculi with CT . Recommendations about using one test ( IVP ) over the other ( helical CT ) were based on judgments of how the cases that were detected or missed would fare with or without treatment ( 11 ) . These judgments were likely to be based on indirect evidence and would be less certain than judgments based on direct evidence from a r and omized trial comparing the 2 tests . The GRADE approach requires making these judgments about the relation between accuracy and patient-important outcomes transparent . The example of IVP versus helical CT for patients with suspected acute shows exemplifies how the quality of evidence for an accurate test would be down grade d because of the lack of direct evidence on patient-important outcomes . Uncertainty about patient-important consequences and associated uncertainty about benefits and harms would probably have result ed in weak GRADE recommendations about the use of IVP compared with helical CT . Those making recommendations using the GRADE approach should also explicitly consider judgments and evidence about the values and preferences that patients attach to important consequences , as described more fully elsewhere ( 1 ) . Acknowledgments : This work was partially funded by a The human factor , mobility and Marie Curie Actions Scientist Reintegration European Commission Grant ( IGR 42192 ) GRADE to Dr. Schnemann The current study was conducted to assess the safety and tolerability of a transdermal fentanyl delivery system for the relief of chronic pain in a pediatric population , and also to vali date titration recommendations and conversion to transdermal fentanyl from oral opioid therapy BACKGROUND Cyclic intravenous pamidronate treatment is widely used for symptomatic therapy of osteogenesis imperfecta ( OI ) . However , data after discontinuation are very limited . AIM The results of cyclical pamidronate treatment in 14 patients with moderate/severe OI and follow up of six of them after discontinuation are presented to assess the effects of pamidronate and its discontinuation . PATIENTS AND METHODS Pamidronate was administered at a dosage of 0.5 mg/kg for 3 successive days every 2 months in 14 patients with OI aged 5.10 + /- 3.68 years . Treatment was stopped in six patients after a duration of 16.33 + /- 4.63 months , due to stable bone mineral density ( BMD ) values and /or no fracture in the last 6 months , or due to family dem and . The main outcome measures were areal BMD ( aBMD ) of the lumbar spine , biochemical markers of bone metabolism , fracture rate , and clinical evaluation . RESULTS Areal BMD and aBMD z-scores showed significant improvement during the treatment period . Both serum and bone-specific alkaline phosphatase values were significantly decreased . Fracture rate reduced significantly from 3.5 + /- 1.01 to 0.83 + /- 0.77 fractures/year . Bone pain , which was severe in five patients , disappeared just after the first cycle , and the activity and mobility of patients increased . aBMD and aBMD z-scores were decreased 1.5 years after discontinuation , although not statistically significant . Annual fracture rate increased significantly . Bone pain recurred in four patients . Pamidronate treatment was reinstituted in five of these patients at the end of 1.5 years . CONCLUSION Cyclical pamidronate treatment is very effective in children with moderate/severe OI . This treatment should be started early enough before the occurrence of irreversible deformities and must be given for a longer time during the growth period |
10,794 | 28,444,987 | Platelet count-to-spleen length ratio could be used to stratify the risk of oesophageal varices .
This test can be used as a triage test before endoscopy , thus ruling out adults without varices .
In the case of a ratio > 909 (n/mm3)/mm , the presence of oesophageal varices of any size can be excluded and only 7 % of adults with varices of any size would be missed , allowing investigators to spare the number of oesophago-gastro-duodenoscopy examinations .
This test is not accurate enough for identification of oesophageal varices at high risk of bleeding that require primary prophylaxis . | BACKGROUND Current guidelines recommend screening of people with oesophageal varices via oesophago-gastro-duodenoscopy at the time of diagnosis of hepatic cirrhosis .
This requires that people repeatedly undergo unpleasant invasive procedures with their attendant risks , although half of these people have no identifiable oesophageal varices 10 years after the initial diagnosis of cirrhosis .
Platelet count , spleen length , and platelet count-to-spleen length ratio are non-invasive tests proposed as triage tests for the diagnosis of oesophageal varices .
OBJECTIVES Primary objectives To determine the diagnostic accuracy of platelet count , spleen length , and platelet count-to-spleen length ratio for the diagnosis of oesophageal varices of any size in paediatric or adult patients with chronic liver disease or portal vein thrombosis , irrespective of aetiology .
To investigate the accuracy of these non-invasive tests as triage or replacement of oesophago-gastro-duodenoscopy .
Secondary objectives To compare the diagnostic accuracy of these same tests for the diagnosis of high-risk oesophageal varices in paediatric or adult patients with chronic liver disease or portal vein thrombosis , irrespective of aetiology .
We aim ed to perform pair-wise comparisons between the three index tests , while considering predefined cut-off values . | Because several studies have suggested that beta blockers are effective in the prophylaxis of first variceal bleeding in cirrhosis , screening for oesophageal varices might be appropriate . We prospect ively studied 84 cirrhotic patients without obvious evidence of large oesophageal varices and previous bleeding during a mean follow up of 16 months . At entry to the study 41 patients had no oesophageal varices and in 43 these were grade 1 . The subsequent percentages of patients without large oesophageal varices were 74 % at one year and 52 % at two years . Univariate analysis showed that a longer duration of cirrhosis ( p less than 0.05 ) and grade 1 oesophageal varices at entry ( p less than 0.001 ) were predictive factors for the occurrence of large oesophageal varices , whereas , multivariate analysis showed that the initial size of the oesophageal varices ( p less than 0.001 ) , a high initial Child-Pugh score , and a smaller improvement in Child-Pugh score during the study were independent risk factors . Among patients with grade s 0 and 1 oesophageal varices at the start of the study the proportions with large oesophageal varices at two years were 31 % and 70 % respectively . We have calculated that , accepting a maximum risk of first bleeding of 10 % without prophylactic treatment , a patient without oesophageal varices should be screened endoscopically every other year , while a patient with grade 1 disease should benefit from one annual upper gastrointestinal endoscopy BACKGROUND The current guidelines recommend the screening of all cirrhotic patients by endoscopy , but repeated endoscopic examinations are unpleasant for patients and have a high cost impact and burden on endoscopic units . The aim of this study is to evaluate the optimal liver lobe size/albumin ratio and to compare this ratio with spleen size , platelet count and platelet count/spleen diameter ratio as potential noninvasive predictors of oesophageal varices in hepatitis C virus (HCV)-related liver cirrhosis in Egyptian patients . METHODS This prospect i ve study included one hundred patients with HCV-related liver cirrhosis . All studied subjects underwent a detailed clinical examination , biochemical workup , upper gastrointestinal endoscopy and abdominal ultrasound . The platelet count/spleen diameter ratio and the right liver lobe/albumin concentration ratio for all patients were calculated . RESULTS The 4 predictors demonstrated a high statistically significant correlation with the presence and grade of oesophageal varices ( P values<0.001 ) . The platelet count/spleen diameter ratio had the highest accuracy , followed by the right liver lobe/albumin concentration ratio , spleen size and then platelet count . CONCLUSION The use of the studied noninvasive predictors , especially the platelet count/spleen diameter ratio and the right liver lobe/albumin concentration ratio , can help physicians by restricting the use of endoscopic screening only to patients presenting a high probability of oesophageal varices . This is especially useful in clinical setting s where re sources are limited and endoscopic facilities are not present in all areas . Such is the case in Egypt , where there is a large number of patients who require oesophageal screening for oesophageal varices Background Esophageal variceal hemorrhage is a devastating complication of portal hypertension that occurs in approximately one-third of cirrhotic patients . Objectives We assessed the value of the platelet count/ bipolar spleen diameter ratio as a noninvasive parameter for the prediction of esophageal varices ( EVs ) in Egyptian cirrhotic patients . Patients and Methods Laboratory and ultrasonographic and imaging variables were prospect ively evaluated in 175 patients with liver cirrhosis . All patients underwent upper gastrointestinal endoscopy . Patients with active gastrointestinal bleeding at the time of admission were excluded . Results The platelet count/ bipolar spleen diameter ratio in patients with EVs was significantly lower than in patients without EVs . In an analysis of the receiver operating characteristic curves ( ROCs ) , we calculated an optimal cutoff value of 939.7 for this ratio , which gave 100 % sensitivity and negative predictive values , 86.3 % specificity , a 95.6 % positive predictive value , and an area under the ROC curve of 0.94 ± 0.02 , reflecting its overall diagnostic accuracy . These findings were extended to a subset analysis of compensated cirrhotic patients . Conclusions The platelet count/ bipolar spleen diameter ratio has excellent accuracy in the noninvasive assessment of EVs in patients with compensated or decompensated liver cirrhosis . It is easy to calculate and can lower the financial and sanitary burdens of endoscopy units , especially in developing countries BACKGROUND Current medical management dictates that all cirrhotic patients without a history of variceal hemorrhage undergo endoscopic screening to detect large varices . However , referral for endoscopic screening of only patients at highest risk for varices may be most cost-effective . The aim of this case-control study was to identify clinical , laboratory , and radiologic findings that predict the presence of varices in patients with cirrhosis . METHODS Three hundred patients without a history of variceal hemorrhage underwent upper endoscopy as part of an evaluation before liver transplantation . Cases defined as the presence of any varices and cases defined as the presence of large varices were used for examining the risks associated with finding varices on upper endoscopy . Logistic regression was performed to evaluate associations between the presence of varices and patient characteristics . RESULTS Platelet count and Child-Pugh class were independent risk factors for the presence of any varices and the presence of large varices . For the presence of any varices , a platelet count of 90 x 10(3)/microL or less ( odds ratio [ OR ] , 2.4 ; 95 % confidence interval [ CI ] , 1.4 - 4.0 ) and advanced Child-Pugh class ( OR , 3.0 ; 95 % CI , 1.6 - 5.6 ) were independent risk factors . For large varices , a platelet count of 80 x 10(3)/microL or less ( OR , 2.3 ; 95 % CI , 1.4 - 3.9 ) and advanced Child-Pugh class ( OR , 2.8 ; 95 % CI , 1.3 - 5.8 ) were independent risk factors associated with varices . CONCLUSIONS Low platelet count and advanced Child-Pugh class were associated with the presence of any varices and with large varices . These factors allow identification of a subgroup of cirrhotic patients who would benefit most from referral for endoscopic screening for varices This guidance provides a data -supported approach to risk stratification , diagnosis , and management of patients with cirrhosis and portal hypertension ( PH ) . A guidance document is different from a guideline . Guidelines are developed by a multidisciplinary panel of experts who rate the quality ( level ) of the evidence and the strength of each recommendation using the Grading of Recommendations Assessment , Development , and Evaluation system . A guidance document is developed by a panel of experts in the topic , and guidance statements , not recommendations , are put forward to help clinicians underst and and implement the most recent evidence . This guidance focuses on PH , varices , and variceal hemorrhage ( VH ) , and statements are based on the following : ( 1 ) review of the recent literature using PubMed , giving more weight to large , well- design ed , prospect i ve trials and well-performed meta-analyses ; ( 2 ) several consensus conferences among experts ; and ( 3 ) the authors ’ years of experience caring for patients with cirrhosis and varices . Management of ascites and encephalopathy is addressed in other documents BACKGROUND All patients with liver cirrhosis are recommended for evaluation of oesophagogastric varices ( EGV ) regularly . This prospect i ve study was design ed to develop a predictive model for EGV in cirrhotic patients . METHODS Ninety-two patients were recruited . From all patients studied , the size of palpable spleen , liver chemistry value , platelet count , prothrombin time , diameter of main portal vein and splenic length as assessed by ultrasonography were determined . Upper endoscopy was performed . Oesophageal varices ( EV ) and gastric varices ( GV ) were grade d ( EV , grade 1 - 4 ; GV , grade 1 - 3 ) . In the predictive model , the EGV was classified into two grade s ( low , grade 1 - 2 EV or grade 1 GV ; high , grade 3 - 4 EV or grade 2 - 3 GV ) . RESULTS There were 53 patients with EGV and 39 patients without EGV as determined by endoscopy . Patients with EGV had a significantly higher degree of ascites and hepatic encephalopathy , lower platelet count and longer splenic length than those without EGV . Low platelet count and presence of ascites were the significant independent predictors for high- grade EGV ( concordance rate 0.83 ) . The optimal critical value for the platelet count was 150 x 10(9)/L. Of patients without thrombocytopenia and ascites , 37 % had low- grade EGV but none had high- grade EGV , whereas 38 and 35 % of patients with thrombocytopenia or ascites had low and high- grade EGV , respectively . Therefore , this predictive model for high- grade varices had a positive and negative predictive value of 35 and 100 % , respectively . CONCLUSION Endoscopic screening for EGV was not necessary until thrombocytopenia or ascites occurred Background and aims : Risk factors for mortality and re-bleeding following acute variceal haemorrhage ( AVH ) are incompletely understood . The aim of this study was to determine risk factors for 6-week mortality , and re-bleeding within 5 days in patients with cirrhosis and AVH . Methods : Kaplan – Meier and Cox proportional hazards regression analyses were used to determine risk factors among 256 patients with AVH entered into a r and omised , prospect i ve trial . Results : Thirty-five patients ( 14 % ) died within 6 weeks of AVH ; 14 deaths ( 40 % ) occurred within 5 days . Only the Model for End-stage Liver Disease ( MELD ) score and units of packed red blood cells ( PRBCs ) transfused in the first 24 h were associated with 6-week mortality univariately ( HR 1.11 , p<0.001 ; HR 1.22 , p<0.001 ) and bivariately ( HR MELD = 1.10 , p<0.001 ; HR per unit of PRBCs transfused = 1.15 , p = 0.005 ) . Re-bleeding within 5 days occurred in 37 patients ( 15 % ) ; MELD score ( p = 0.01 ) and a clot on a varix ( p = 0.05 ) predicted re-bleeding . Patients with a MELD score ⩾18 ; both MELD score ⩾18 and ⩾4 units of PRBCs transfused ; both MELD score ⩾18 and active bleeding at index endoscopy ; and variceal re-bleeding had increased risk of death 6 weeks post-AVH ( HR = 7.4 , p<0.001 ; 11.3 , p<0.001 ; 9.9 , p<0.001 ; 10.2 , p<0.001 respectively ) . Conclusions : Patients with AVH and MELD score ⩾18 , requiring ⩾4 units of PRBCs within the first 24 h or with active bleeding at endoscopy are at increased risk of dying within 6 weeks . MELD score ⩾18 is also a strong predictor of variceal re-bleeding within the first 5 days BACKGROUND AND AIMS : Noninvasive assessment of esophageal varices ( EV ) may improve the management of patients with cirrhosis and decrease both the medical and financial burden related to screening . In this multicenter , international study , our aim was to prospect ively vali date the use of the platelet count/spleen diameter ratio for the noninvasive diagnosis of EV . METHODS : A total of 218 cirrhotic patients underwent screening endoscopy for EV . Platelet count/spleen diameter ratio ( (N/mm3)/mm ) was assessed in all patients and its diagnostic accuracy was calculated . On the basis of previous results , a platelet count/spleen diameter ratio cutoff of 909 was applied to this population . The diagnostic accuracy of the platelet count/spleen diameter ratio was further evaluated for both severity and etiology of disease subgroups . RESULTS : Prevalence of EV was 54.1 % . The platelet count/spleen diameter ratio had 86.0 % ( 95 % CI , 80.7–90.4 % ) diagnostic accuracy for EV , which was significantly greater as compared with either accuracy of platelet count alone ( 83.6 % , 95 % CI 78.0–88.3 % , P = 0.038 ) or spleen diameter alone ( 80.2 % , 95 % CI 74.3–85.3 % , P = 0.018 ) . The 909 cutoff had 91.5 % sensitivity ( 95 % CI 85.0–95.9 % ) , 67.0 % specificity ( 95 % CI 56.9–76.1 % ) , 76.6 % positive predictive value , 87.0 % negative predictive value , 2.77 positive likelihood ratio , and 0.13 negative likelihood ratio for the diagnosis of EV . Accuracy of the platelet count/spleen diameter ratio was maintained for both severity and etiology of disease subgroups . CONCLUSIONS : The platelet count/spleen diameter ratio may be proposed as a safe and reproducible means to improve the management of cirrhotic patients who should undergo screening endoscopy for EV In order to evaluate the reliability of the endoscopic assessment of variceal features , 6 skilled endoscopists separately examined 28 patients with liver cirrhosis and varices . Definitions of variceal features were set up on the basis of the classification of the Japanese Research Society for Portal Hypertension . A new item , i.e. oesophageal lumen occupancy , and a semiquantitative rating system of endoscopic findings were introduced . Beyond chance agreement ( Kappa index ) was poor on the assessment of the extension of blue colour ( 0.33 ) and prevalence of cherry red spots or red weal marking ( 0.17 ) whereas was fair to good ( 0.40 - 0.66 ; P less than 10(-5 ) ) on the following : location , size , lumen occupancy , presence of blue colour , presence and extension of red colour sign , haematocystic spot . We conclude that the endoscopic assessment of oesophageal varices based on these features is reliable ; their prognostic value as predictors of bleeding risk should be prospect ively assessed BACKGROUND Nonselective beta-adrenergic blockers decrease portal pressure and prevent variceal hemorrhage . Their effectiveness in preventing varices is unknown . METHODS We r and omly assigned 213 patients with cirrhosis and portal hypertension ( minimal hepatic venous pressure gradient [ HVPG ] of 6 mm Hg ) to receive timolol , a nonselective beta-blocker ( 108 patients ) , or placebo ( 105 patients ) . The primary end point was the development of gastroesophageal varices or variceal hemorrhage . Endoscopy and HVPG measurements were repeated yearly . RESULTS During a median follow-up of 54.9 months , the rate of the primary end point did not differ significantly between the timolol group and the placebo group ( 39 percent and 40 percent , respectively ; P=0.89 ) , nor were there significant differences in the rates of ascites , encephalopathy , liver transplantation , or death . Serious adverse events were more common among patients in the timolol group than among those in the placebo group ( 18 percent vs. 6 percent , P=0.006 ) . Varices developed less frequently among patients with a baseline HVPG of less than 10 mm Hg and among those in whom the HVPG decreased by more than 10 percent at one year and more frequently among those in whom the HVPG increased by more than 10 percent at one year . CONCLUSIONS Nonselective beta-blockers are ineffective in preventing varices in unselected patients with cirrhosis and portal hypertension and are associated with an increased number of adverse events . ( Clinical Trials.gov number , NCT00006398 . The predictors for developing varices in patients with primary sclerosing cholangitis ( PSC ) have not been well studied prospect ively . We sought to define the predictors for the presence of varices at baseline and for newly developing varices in patients with PSC . We used prospect ively collected data from a multicenter r and omized trial of high dose ursodeoxycholic acid for PSC . All 150 patients enrolled were review ed for predictors of varices and we excluded 26 patients who had esophageal varices at baseline so that predictors of newly developing varices could be determined . Clinical examination , blood tests , and upper endoscopy were done before r and omization , at 2 years and after 5 years . Liver biopsy was performed at entry and at 5 years . The median age ( interquartile range ) of patients was 45.9 years ( 35.8 , 54.9 ) . In a multivariable logistic regression , a higher Mayo risk score ( ≥0.87 ) or a higher aspartate/alanine aminotransferase ( AST/ALT ) ratio ( ≥1.12 ) were significantly associated with the presence of varices at initial endoscopy ( odds ratio = 1.9 and 3.9 ) . By the end of the study , 25 patients had new varices ( 20.2 % ) . In a Cox model , after adjustment for baseline variables lower platelet count and higher total bilirubin at 2 years were significantly associated with the presence of new varices . The platelet count of 205 ( × 109/L ) and the total bilirubin level of 1.7 mg/dL were the best cutoff values for the detection of new varices . Conclusion : A higher Mayo risk score and higher AST/ALT ratio were significantly associated with the presence of varices at initial endoscopy . Lower platelet count and higher total bilirubin at 2 years were significantly associated with an increased risk of developing new varices in patients with PSC . ( HEPATOLOGY 2010 . BACKGROUND & AIMS We evaluated whether spleen stiffness ( SS ) , measured by acoustic radiation force impulse imaging , can identify patients who have esophageal varices ( EVs ) ; those without EVs would not require endoscopic examination . METHODS In a prospect i ve study , we measured SS and liver stiffness ( LS ) in 340 patients with cirrhosis undergoing endoscopic screening for EVs and 16 healthy volunteers ( controls ) at the Kurashiki Central Hospital in Okayama , Japan . The diagnostic accuracy of SS for the presence of EVs was compared with that of other noninvasive parameters ( LS , spleen diameter , and platelet count ) . Optimal cutoff values of SS were chosen to confidently rule out the presence of varices . RESULTS Patients with cirrhosis had significantly higher SS and LS values than controls ( P < .0001 and P < .0001 , respectively ) . Levels of SS were higher among patients with EVs ( n = 132 ) than controls , and values were highest among patients with high-risk EVs ( n = 87 ) . SS had the greatest diagnostic accuracy for the identification of patients with EVs or high-risk EVs compared with other noninvasive parameters , independent of the etiology of cirrhosis . An SS cutoff value of 3.18 m/s identified patients with EVs with a 98.4 % negative predictive value , 98.5 % sensitivity , 75.0 % accuracy , and 0.025 negative likelihood ratio . An SS cutoff value of 3.30 m/s identified patients with high-risk EVs with a 99.4 % negative predictive value , 98.9 % sensitivity , 72.1 % accuracy , and 0.018 negative likelihood ratio . SS values less than 3.3 m/s ruled out the presence of high-risk varices in patients with compensated or decompensated cirrhosis . SS could not be measured in 16 patients ( 4.5 % ) . CONCLUSIONS Measurements of SS can be used to identify patients with cirrhosis with EVs or high-risk EVs . A cutoff SS was identified that could rule out the presence of varices and could be used as an initial noninvasive screening test ; UMIN Clinical Trials Registry number , UMIN000004363 Several treatments have been proven to be effective for variceal bleeding in patients with cirrhosis . The aim of this multicenter , prospect i ve , cohort study was to assess how these treatments are used in clinical practice and what are the posttherapeutic prognosis and prognostic indicators of upper digestive bleeding in patients with cirrhosis . A training set of 291 and a test set of 174 bleeding cirrhotic patients were included . Treatment was according to the preferences of each center and the follow-up period was 6 weeks . Predictive rules for 5-day failure ( uncontrolled bleeding , rebleeding , or death ) and 6-week mortality were developed by the logistic model in the training set and vali date d in the test set . Initial treatment controlled bleeding in 90 % of patients , including vasoactive drugs in 27 % , endoscopic therapy in 10 % , combined ( endoscopic and vasoactive ) in 45 % , balloon tamponade alone in 1 % , and none in 17 % . The 5-day failure rate was 13 % , 6-week rebleeding was 17 % , and mortality was 20 % . Corresponding findings for variceal versus nonvariceal bleeding were 15 % versus 7 % ( P = .034 ) , 19 % versus 10 % ( P = .019 ) , and 20 % versus 15 % ( P = .22 ) . Active bleeding on endoscopy , hematocrit levels , aminotransferase levels , Child-Pugh class , and portal vein thrombosis were significant predictors of 5-day failure ; alcohol-induced etiology , bilirubin , albumin , encephalopathy , and hepatocarcinoma were predictors of 6-week mortality . Prognostic re assessment including blood transfusions improved the predictive accuracy . All the developed prognostic models were superior to the Child-Pugh score . In conclusion , prognosis of digestive bleeding in cirrhosis has much improved over the past 2 decades . Initial treatment stops bleeding in 90 % of patients . Accurate predictive rules are provided for early recognition of high-risk patients 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 To assess prospect ively the accuracy of transient elastography ( TE , FibroScan ) for the detection of cirrhosis and oesophageal varices ( OV ) in chronic hepatitis C ( CHC ) , as compared with currently available non-invasive methods ( AST/ALT ratio ( AAR ) , APRI , prothrombin index ( PI ) , platelet count ( PC ) , FibroTest ( FT ) and Lok index ) . METHODS All tests were performed the day of liver biopsy ( LB ) , taken as reference , in 298 consecutive CHC patients ( cirrhosis : 70 ; Child-Pugh A : 70 ; OV : 25 ) . RESULTS TE had the best diagnostic accuracy for detection of cirrhosis ( AUROCs : TE 0.96 vs. FT 0.82 , Lok and APRI 0.80 , PC 0.79 , PI 0.73 , AAR 0.61 , respectively ; p < 0.0001 ) . Overall , the percentage of saved LB was : TE ( cut-off : 12.5 kPa ) 90 % , PC 82 % , FT 79 % , PI 77 % , AAR 76 % , APRI 70 % , and Lok 45 % , respectively . At a cut-off of 21.5 kPa , TE predicted the presence of OV with 76 % sensitivity and 78 % specificity and correctly classified 73 % of patients vs. AAR 81 % , Lok 77 % , FT , PI 70 % , PC 69 % , and APRI 66 % , respectively . CONCLUSIONS TE is currently the most accurate non-invasive method for early detection of cirrhosis in CHC ( cut-off : 12.5 kPa ) , as compared with other available methods , but can not replace endoscopy for OV screening BACKGROUND Data on complications of gastrointestinal endoscopic procedures are limited . We evaluated prospect ively the incidence and cost of hospital visits result ing from outpatient endoscopy . METHODS We developed an electronic medical record-based system to record automatically admissions to the emergency department ( ED ) within 14 days after endoscopy . Physicians evaluated all reported cases for relatedness of the ED visit to the prior endoscopy based on predetermined criteria . RESULTS We evaluated 6383 esophagogastroduodenoscopies ( EGDs ) and 11 632 colonoscopies ( 7392 for screening and surveillance ) . Among these , 419 ED visits and 266 hospitalizations occurred within 14 days after the procedure . One hundred thirty-four ( 32 % ) of the ED visits and 76 ( 29 % ) of the hospitalizations were procedure related , whereas 31 complications were recorded by st and ard physician reporting ( P < .001 ) . Procedure-related hospital visits occurred in 1.07 % , 0.84 % , and 0.95 % of all EGDs , all colonoscopies , and screening colonoscopies , respectively . The mean costs were $ 1403 per ED visit and $ 10 123 per hospitalization based on Medicare st and ardized rates . Across the overall screening/surveillance colonoscopy program , these episodes added $ 48 per examination . CONCLUSIONS Using a novel automated system , we observed a 1 % incidence of related hospital visits within 14 days of outpatient endoscopy , 2- to 3-fold higher than recent estimates . Most events were not captured by st and ard reporting , and strategies for automating adverse event reporting should be developed . The cost of unexpected hospital visits postendoscopy may be significant and should be taken into account in screening or surveillance programs BACKGROUND / AIMS The incidence and natural history of small esophageal varices ( EV ) in cirrhotics may influence the frequency of endoscopies and the decision to start a pharmacological treatment in these patients . METHODS We prospect ively evaluated 206 cirrhotics , 113 without varices and 93 with small EV , during a mean follow-up of 37+/-22 months . Patients with previous gastrointestinal bleeding or receiving any treatment for portal hypertension were excluded . Endoscopy was performed every 12 months . RESULTS The rate of incidence of EV was 5 % ( 95%CI : 0.8 - 8.2 % ) at 1 year and 28 % ( 21.0 - 35.0 % ) at 3 years . The rate of EV progression was 12 % ( 5.6 - 18.4 % ) at 1 year and 31 % ( 21.2 - 40.8 % ) at 3 years . Post-alcoholic origin of cirrhosis , Child-Pugh 's class ( B or C ) and the finding of red wale marks at first examination were predictors for the variceal progression . The two-years risk of bleeding from EV was higher in patients with small varices upon enrollment than in those without varices : 12 % ( 95 % CI : 5.2 - 18.8 % ) vs. 2 % ( 0.1 - 4.1 % ) ; ( P<0.01 ) . Predictor for bleeding was the presence of red wale marks at first endoscopy . CONCLUSIONS In patients with no or small EV , endoscopy surveillance should be planned taking into account cause and degree of liver dysfunction BACKGROUND The factors predictive of the presence or the absence of esophageal varices in hepatitis C virus ( HCV ) and advanced fibrosis have not been defined . OBJECTIVES To define the prevalence of esophageal varices and the factors that are positively and negatively with such varices in hepatitis C and advanced fibrosis . DESIGN A prospect i ve study of esophageal varices and associated risk factors in subjects with hepatitis C and advanced fibrosis . SETTING Prer and omization data from the HALT-C ( hepatitis C long-term antiviral treatment against cirrhosis ) clinical trial . PATIENTS AND INTERVENTION Subjects with bridging fibrosis or cirrhosis , who were virologic nonresponders to treatment with pegylated interferon alpha 2a and ribavirin , underwent endoscopy . RESULTS Sixteen percent of subjects with bridging fibrosis ( 95/598 ) and 39 % of subjects with cirrhosis ( 164/418 ) had varices ( P < .0001 ) ; 2 % of subjects with bridging fibrosis ( 13/598 ) and 11 % of those with cirrhosis ( 48/418 ) had medium or large varices . Subjects with bridging fibrosis and varices had a significantly lower platelet count and higher bilirubin and international normalized ratio ( INR ) compared with those without varices , suggesting that the biopsy may have underestimated the severity of fibrosis . A platelet count > 150,000/mm(3 ) was associated with a negative predictive value of 99 % for esophageal varices . By logistic regression modeling , African American race and female sex were protective , whereas a lower platelet count and higher bilirubin and INR predicted varices ( c statistic , 0.758 ) . CONCLUSIONS The risk of having varices increases with decreasing platelet counts , increasing bilirubin , and INR . The probability of having medium or large varices at platelet counts > 150,000/mm(3 ) is negligible in this population Many r and omized controlled trials ( RCTs ) have advanced the knowledge of the complications of portal hypertension , specifically in the management of varices and variceal hemorrhage . The endpoints in most of these trials have used definitions attained at international consensus workshops that have been published in medical journals since the first Baveno conference in 1992.1 Three more international consensus conferences have helped further define clinical endpoints and practice recommendations .2 - 5 This article summarizes the results of an Endpoints Single Topic Conference on “ Portal Hypertension and Variceal Bleeding — Unresolved Issues ” that took place in Atlanta , GA , in June 4 - 6 , 2007 and that was sponsored jointly by the American Association for the Study of Liver Diseases ( AASLD ) and the European Association for the Study of the Liver and constitutes the 6th international consensus conference in the area of varices and variceal hemorrhage . As outcomes have improved and knowledge has been gained , it is necessary to prioritize areas that require further research , to define surrogate markers of outcome and to stratify patients in different risk groups . These were the objectives of this single-topic conference . For areas in the management of varices and variceal hemorrhage in which it was decided that no further trials were necessary or plausible , practice recommendations were put forward . In some instances , these differed from recommendations put forward at the most recent consensus conference in Baveno 20045 and were incorporated into the recently published AASLD/ American College of Gastroenterology (ACG)-sponsored recommendations .6,7 Recommendations were obtained by majority agreement defined as agreement by greater than 70%of 23 expert participants ( listed at the end of the article ) Background & Aims Few noninvasive methods can accurately identify esophageal varices ( EVs ) in patients with compensated cirrhosis . We developed and vali date d a novel , acoustic radiation force impulse ( ARFI ) elastography-based prediction model for high-risk EVs ( HEVs ) in patients with compensated cirrhosis . Methods A total of 143 patients with compensated cirrhosis between February , 2010 and February , 2013 ( training set ) and 148 between June , 2010 and May , 2013 ( validation set ) who underwent ARFI elastography and endoscopy were prospect ively recruited . Independent predictors of HEVs were used to construct a prediction model . Results Based on multivariate analysis , we developed two new statistical models , a varices risk score and ARFI-spleen diameter-to-platelet ratio score ( ASPS ) , the latter of which was calculated as ARFI velocity × spleen diameter/platelet count . The area under receiver operating characteristic curve ( AUROC ) of the varices risk score and ASPS to predict HEVs were 0.935 ( 95 % confidence interval [ CI ] 0.882–0.970 ) and 0.946 ( 95 % CI 0.895–0.977 ) , respectively . When ASPS , a simpler model with a higher AUROC , was applied in the validation set , acceptable diagnostic accuracy for HEVs was observed ( AUROC = 0.814 [ 95 % CI 0.743–0.885 ] ) . To detect HEVs , a negative predictive value of 98.3 % was achieved at ASPS < 2.83 , whereas a positive predictive value of 100 % was achieved at ASPS > 5.28 . Conclusions ASPS , a novel noninvasive ARFI-based prediction model , can accurately identify HEVs in patients with compensated cirrhosis . ASPS < 2.83 may safely rule out the presence of HEVs , whereas patients with ASPS > 5.28 should be considered for endoscopic examinations or appropriate prophylactic treatment Abstract Screening endoscopy is recommended for early detection of esophageal varices ( EVs ) in cirrhotic patients with portal hypertension . However , this approach is limited by its invasiveness and cost . The aim of the study was to determine if platelet count can predict the presence of EVs , especially large ( grade III , IV ) EVs in need of prophylactic therapy , in a cohort of Egyptian patients with liver cirrhosis . In all , 110 patients with cirrhosis were prospect ively analyzed . The presence of medium or large EVs was correlated with patients ’ platelet count and FIB-4 . Esophageal varices were present in 87 ( 79.09 % ) patients . Among those with thrombocytopenia ( platelet level below 150,000 ) , 25.97 % ( 20 patients ) and 27.27 % ( 21 patients ) had EV grade II and EV grade III or IV , respectively . Whereas in patients in whom the platelet count was above 150,000 , only 21.21 % ( 7 patients ) and 9.09 % ( 3 patients ) of patients had grade II EV and EV grade III or IV , respectively . A platelet count cut-off value of 149,000 was found to have specificity of 82 % and sensitivity 39 % for detection of presence of varices . A FIB-4 cut-off value of 3.175 was found to have an 83.3 % sensitivity and 39.5 % specificity in detecting large ( grade III , IV ) EVs . Platelet count is a noninvasive parameter with high accuracy for prediction of EVs . Cirrhotic patients with normal platelet counts ( above 150,000 ) , especially in financially deprived developing countries , can avoid screening endoscopy as they are at a low risk for variceal bleeding , and presence of large EVs in these patients is much less common than in those with thrombocytopenia . A 3.175 cut-off value of FIB-4 could be useful as a noninvasive predictor of large varices requiring prophylactic b and ing in cirrhotic patients Background and Objectives : Identification of children who are at high risk for having varices using noninvasive tests would enable the selection of children for future studies of primary prophylaxis of variceal hemorrhage , but this has been inadequately studied . The objective of the study was to derive a noninvasive clinical prediction rule that is able to identify children with esophageal varices . Methods : Fifty-one consecutive children with liver disease or portal hypertension who underwent endoscopy were included in the present retrospective study . At endoscopy , variceal size was grade d on a 4-point Likert scale . Results of physical examination , blood tests , and abdominal ultrasound scan ( USS ) were recorded . Spleen length on USS was expressed as a st and ard deviation score ( z score ) . A descriptive univariate analysis was performed on variables that were potentially associated with esophageal varices and multivariate logistic regression was then modeled to derive a clinical prediction rule . Results : Esophageal varices were found in 17 of the 51 children ( 33 % ) . Variables found to differ significantly between children with and without varices included platelet/spleen-length z score ratio ( P < 0.001 ) , platelet count ( P < 0.001 ) , international normalized ratio ( P = 0.001 ) , aspartate aminotransferase/alanine aminotransferase ratio ( P = 0.002 ) , and albumin ( P = 0.003 ) . Using multivariate logistic regression , a model with platelet count , spleen length z score , and albumin as the independent variables had the best fit . Area under the receiver operating characteristic curve for this clinical prediction rule was 0.93 ( 95 % confidence interval 0.85–0.99 ) , sensitivity 94 % , specificity 81 % , positive predictive value 0.83 , negative predictive value 0.94 , positive likelihood ratio 5 , and negative likelihood ratio 0.06 . Conclusions : This clinical prediction rule is a simple noninvasive measure that may identify children at high risk for esophageal varices . A prospect i ve validation study is in progress Objective To determine whether Model for End-stage Liver Disease ( MELD ) Child – Turcotte – Pugh ( CTP ) classification , AST to platelet ratio index ( APRI ) , and laboratory tests could predict the presence of esophageal varices ( EV ) or varices which need prophylactic therapy ( medium or large size EV ) . Methods Three hundred patients with cirrhosis ( 193 men ; mean age 53.1 years ; majority with chronic C hepatitis ) were prospect ively analyzed . The presence of EV ( any size and medium or large EV ) was correlated with patients ' characteristics ( MELD , CTP classification , APRI , platelets count , and liver tests ) . Results One hundred and seventy-one patients ( 57 % ) had EV , of whom 35 % ( 105 ) had varices which need prophylactic therapy ( VPT ) . The distribution of EV according to CTP classification was as follows : A , 49 % ; B , 75.3 % and C , 80 % . Independent predictors of EV were : MELD higher than 8 ( P=0.02 ) ; APRI higher than 1.64 ( P=0.01 ) ; platelet count lower than 93 000/mm3 ( P<0.01 ) ; aspartate aminotransferase higher than 1.34 × UNL ( P=0.01 ) , and total bilirubin higher than 1 mg/dl ( P=0.04 ) . MELD higher than 8 had the highest discriminative value for presence of EV ( sensitivity=80.1 % ; specificity=51.2 % ; area under receiver operating characteristics=0.68 ) . Factors independently associated with VPT were : thrombocytopenia ( < 92 000/mm3 ; P<0.01 ) and aspartate aminotransferase higher than 1.47 × UNL ( P=0.03 ) . Platelet count lower than 92 000/mm3 had sensitivity of 65.7 % , specificity of 57.9 % , and an area under receiver operating characteristics of 0.62 for the presence of VPT . Conclusion High values on MELD are associated with EV and thrombocytopenia , with varices which need prophylactic therapy . As a result of their low sensitivity and specificity , it is suggested to maintain the recommendation of upper gastrointestinal endoscopy for all patients with cirhosis AIM To study the value of platelet count to spleen diameter ratio as a noninvasive parameter for diagnosing esophageal varices ( EVs ) in liver cirrhosis . METHODS The laboratory and ultrasonographic variables were prospect ively evaluated in 150 patients with liver cirrhosis . Only stable patients were included in the study . Patients with active gastrointestinal bleeding at the time of admission were excluded . All patients underwent screening upper gastrointestinal endoscopy . RESULTS The platelet count , spleen diameter and platelet count to spleen diameter ratio in patients with EVs were significantly different from patients without EVs . The platelet count to spleen diameter ratio had the highest accuracy among the three parameters . By applying receiver operating characteristic curves , a platelet count to spleen diameter ratio cut-off value of 1014 was obtained , which gave positive and negative predictive values of 95.4 % and 95.1 % , respectively . The accuracy of this cut-off value as evaluated by applying receiver operating characteristic curves was 0.942 ( 95 % CI 0.890 to 0.995 ) . CONCLUSION Among the noninvasive parameters studied , platelet count to spleen diameter ratio had the highest accuracy for diagnosing EVs . However , the evidence for the noninvasive diagnosis is not yet sufficient to replace endoscopy as a diagnostic screening tool for EVs in all cirrhotic patients . The platelet count to spleen diameter ratio may be a useful tool for diagnosing EVs in liver cirrhosis noninvasively when endoscopy facilities are not available OBJECTIVE To evaluate prospect ively the complications that occurred during consecutive endoscopies of the upper gastrointestinal tract . PATIENTS AND METHODS We evaluated all endoscopies of the upper gastrointestinal tract ( except endoscopic retro grade cholangiopancreatography and endosonography ) performed at the Ambulatory Surgical Center at the Mayo Clinic in Jacksonville , Fla , between January 1999 and June 2002 . A staff gastroenterologist with or without a trainee performed these procedures . Therapeutic procedures included esophageal b and ligation , injection sclerotherapy , botulinum toxin injection , extended upper endoscopy , pneumatic balloon dilation , endoscopic mucosal resection , and endoscopic ablation using thermal laser , argon beam coagulator , or photodynamic therapy . All complications were tabulated prospect ively as per m and atory state licensure reporting . RESULTS Complications after diagnostic endoscopy of the upper gastrointestinal tract were related to anesthesia in 2 of the 12,841 patients . Perforations in 5 patients were associated with esophageal dilation ( 2 ) , resection of duodenal lesions ( 2 ) , or passage of a side-viewing instrument into the duodenum ( 1 ) . No deaths occurred . CONCLUSIONS Diagnostic endoscopy of the upper gastrointestinal tract is safe , with a complication rate of less than 1 per 5000 cases . Therapeutic endoscopy increases the risk of complications . Compared with complication rates published previously , our results from a single center indicate a favorable reduction in complications related to endoscopy of the upper gastrointestinal tract BACKGROUND It is currently recommended that all patients with liver cirrhosis undergo upper gastrointestinal endoscopy ( UGIE ) to identify those who have large esophageal varices ( LEVx ) that carry a high risk of bleeding and may benefit from prophylactic measures . This approach leads to unnecessary UGIE in those without LEVx . We tried to identify clinical , laboratory and imaging parameters that may predict the presence of LEVx and help select patients for UGIE . METHODS This prospect i ve study included newly diagnosed patients with cirrhosis and no history of gastrointestinal bleeding scheduled to undergo UGIE . Patients underwent detailed clinical examination , blood tests ( hematology , liver function tests ) and ultrasonography . Size of esophageal varices was assessed at UGIE ; Paquet 's grade s 0-II were classified as small varices , and III-IV as LEVx . Association of LEVx with qualitative and quantitative parameters was studied using chi(2 ) and Mann-Whitney U-tests , respectively . Parameters found to be significant were tested in a forward-conditional multivariate logistic regression analysis to identify independent predictors . Receiver operating characteristic curve analysis was used to assess the efficacy of prediction models . RESULTS Of the 101 patients ( median age 45 ; range 15 - 74 years ; 87 male ; Child-Pugh class : A 18 , B 31 , C 52 ) , 46 had LEVx . On univariate analysis , five variables were significantly associated with the presence of LEVx . These included pallor ( P = 0.026 ) , palpable spleen ( P = 0.009 ) , platelet count ( P < 0.002 ) , total leukocyte count ( P < 0.0004 ) and liver span on ultrasound ( P = 0.031 ) . On multivariate analysis , two of these parameters , namely low platelet count and presence of palpable spleen , were found to be independent predictors of the presence of LEVx . A receiver-operating characteristics curve using the predictor function arrived at from this analysis had an area under the curve of 0.760 . CONCLUSION Presence of palpable spleen and low platelet count are independent predictors of presence of LEVx in patients with cirrhosis . Use of these parameters may help identify patients with a low probability of LEVx who may not need UGIE . This may help reduce costs and discomfort for these patients and the burden on endoscopy units Endoscopic detection of esophageal varices ( EV ) especially the high risk esophageal varices ( HREV ) is recommended in cirrhotic patients . There are several studies about non-invasive markers to predict the presence of EV . The aim of this study was to evaluate platelet count to spleen diameter ( P/D ) ratio and platelet count to spleen area ( P/A ) ratio as predictors for EV and HREV in patients with liver cirrhosis . This prospect i ve study included 100 cirrhotic patients without previous variceal hemorrhage or endoscopic intervesion . Biochemical , imaging and endoscopic findings were collected in all patients . Several parameters including P/D and P/A ratio were measured and their association with the presence of EV and HREV was tested . The results showed that only P/D and P/A ratios were found to be independent predictors for the presence of EV and HREV in multivariant analysis . For prediction of the EV formation in cirrhotic patients , P/D ratio at value < or = 979.9 and P/A ratio of < or = 20.6 had area under the curve ( AUC ) 0.922 and 0.975 respectively with sensitivity 100 % , specificity 30 % for P/D ratio and sensitivity 100 % , specificity 75 % for P/A ratio . For prediction of the HREV formation , P/D ratio at value < or = 587.9 and P/A ratio of 513.7 had AUC 0.867 and 0.991 respectively with sensitivity 100 % , specificity 50 % for P/D ratio and sensitivity 100 % , specificity 88 % for P/A ratio The aim of this study was to prospect ively evaluate the usefulness of the Italian Liver Cirrhosis Project ( ILCP ) classification of esophageal varices , together with the gastric features of portal hypertension , in predicting the first upper gastrointestinal bleeding in cirrhosis . The efficiency of these endoscopic parameters in predicting bleeding was also compared with the efficiency of the North Italian Endoscopic Club ( NIEC ) index . Three hundred forty-four cirrhotic patients with esophageal varices but without any previous bleeding were enrolled in the study . The following endoscopic parameters of esophageal varices were recorded : location , size , occupancy , blue tone , and red color signs . Gastric varices were grade d as absent or present , while congestive gastropathy was considered as absent , mild to moderate , or severe . All patients were followed until the first upper gastrointestinal bleeding and /or death , or for at least 24 months . No patient received any treatment to prevent bleeding . Sixty-five patients bled from the upper gastrointestinal tract during the study . Univariate analysis showed that all endoscopic parameters were predictors of bleeding . According to multivariate analysis ( Cox 's model ) , size , gastric varices and congestive gastropathy were the only independent predictors of bleeding , and the following prognostic index ( PI ) was developed : PI = ( size x 0.0395 ) + ( congestive gastropathy x 0.878 ) + ( gastric varices x 0.705 ) . This index , which was vali date d using a split- sample technique , and which appears to be superior to the NIEC index in predicting bleeding , may be useful in decision making for primary prophylaxis BACKGROUND AND AIM Transient elastography ( TE ) has been useful in esophageal varices ( EV ) diagnosis for chronic hepatitis C patients . In the present study , we evaluate the usefulness of TE and simple blood markers in the EV diagnosis of patients with hepatitis B virus (HBV)-related cirrhosis , prospect ively . METHODS Consecutive patients with compensated cirrhosis and positive HBV surface antigen were enrolled , prospect ively . At enrollment , the aspartate aminotransferase ( AST ) to alanine aminotransferase ratio ( AAR ) and the AST to platelet ratio index ( APRI ) were recorded , and TE was performed . Two experienced endoscopists assessed EV independently . High-risk EV was defined as small size with a red color sign , and medium or large in size . The diagnostic performances , optimal cut-offs , and the validities of TE , APRI , platelet count ( PLT ) , and AAR in EV diagnosis were assessed . RESULTS A total of 126 patients ( male/female : 93/33 ; mean age : 54.5 years ) with reliable TE results were analyzed . There was good agreement between two endoscopists in assessing the presence of EV and high-risk EV ( kappa value : 0.82 and 0.96 ) . Forty-eight ( 38.1 % ) patients had EV ( small : 35 ; high risk : 13 ) . There was correlation between TE result and EV size ( r = 0.515 , P < 0.001 ) . TE , APRI , and PLT were similar ; however , superior to AAR in the diagnostic accuracies for EV and high-risk EV . In high-risk EV prediction , the negative predictive value ( NPV ) was 97 % , 98 % , and 98 % , with cut-offs of 21 kPa , 1.24 , and 110 ( × 10(9 ) /L ) for TE , APRI , and PLT , respectively . CONCLUSIONS For compensated patients with HBV-related cirrhosis , TE , APRI , and PLT are useful in excluding high-risk EV with high NPV Objective : Recently it has been recommended that all cirrhotic patients without previous variceal hemorrhage undergo endoscopic screening to detect varices and that those with large varices should be treated with β-blockers ( American College of Gastroenterology guidelines ) . However , endoscopic screening only of patients at highest risk for varices may be the most cost effective . Methods : Ninety-eight patients without a history of variceal hemorrhage underwent esophagogastroduodenoscopy as part of a liver transplant evaluation . Univariate/multivariate analysis was used to evaluate associations between the presence of varices and patient characteristics including etiology of liver disease , Child – Pugh class , physical findings ( spider angiomata , splenomegaly , and ascites ) , encephalopathy , laboratory parameters ( prothrombin time , albumin , bilirubin , BUN , creatinine , and platelets ) , and abdominal ultrasound findings ( portal vein diameter/flow , splenomegaly , and ascites ) . Results : The causes of cirrhosis among the 67 men and 31 women ( mean age , 48 yr ) included 28 % Hepatitis C/alcoholism , 25 % Hepatitis C , 13 % alcoholism , 9 % primary sclerosing cholangitis/ primary biliary cirrhosis , 9 % cryptogenic , 6 % Hepatitis B , 1 % Hepatitis B and C , and 9 % other . Patients were Child – Pugh class A 34 % , B 51 % , and C 15 % . Endoscopic findings included esophageal varices in 68 % of patients ( 30 % were large ) , gastric varices in 15 % , and portal hypertensive gastropathy in 58 % . Platelet count < 88,000 was the only parameter identified by univariate/multivariate analysis ( p < 0.05 ) as associated with the presence of large esophageal varices ( odds ratio 5.5 ; 95 % confidence interval 1.8–20.6 ) or gastric varices ( odds ratio 5 ; 95 % confidence interval 1.4–23 ) . Conclusions : Platelet count < 88,000 is associated with the presence of esophagogastric varices . A large prospect i ve study is needed to verify and vali date these findings and may allow identification of a group of patients who would most benefit from endoscopic screening for varices UNLABELLED Current guidelines recommend esophagogastroduodenoscopy ( EGD ) in patients with cirrhosis to screen for gastroesophageal varices ( GEV ) . Thrombocytopenia has been proposed as a noninvasive test to predict the presence of GEV . There is no agreement regarding a specific platelet count ( PLT ) that can reliably predict GEV . The present longitudinal study aims to ( 1 ) further investigate the relationship between varices and PLT at the time of endoscopy , ( 2 ) investigate whether changes in PLT from the baseline over time can predict the development of GEV , and ( 3 ) investigate whether changes in PLT correlate with the hepatic venous pressure gradient ( HVPG ) . A secondary analysis was conducted for 213 subjects with compensated cirrhosis with portal hypertension but without GEV enrolled in a r and omized , placebo-controlled , double-blind trial of a nonselective beta-blocker used to prevent GEV . PLTs were obtained every 3 months , and HVPG measurements and EGD were done annually . The PLTs were compared between subjects who did and did not develop GEV . In a median follow-up of 54.9 months , 84 patients developed GEV . PLT was greater than 150,000 in 15 % of patients at the development of GEV . A receiver operating curve did not show any PLT with high sensitivity or specificity for the presence of GEV . Subjects with clinical ly insignificant portal hypertension ( HVPG < 10 mm Hg ) whose PLT remained greater than 100,000 had a 2-fold reduction in the occurrence of GEV ( P = 0.0374 ) . A significant correlation was found between HVPG and PLT at the baseline , year 1 , and year 5 ( P < 0.0001 ) . CONCLUSION Cross-sectional or longitudinal evaluations of PLTs are inadequate noninvasive markers for GEV . Patients with mild portal hypertension whose PLT remains greater than 100,000 have significantly less risk of GEV . Although HVPG correlates somewhat with PLT , changes in PLT can not be used as a surrogate for HVPG changes PURPOSE To evaluate the accuracy of spleen stiffness ( SS ) and liver stiffness ( LS ) measured by using acoustic radiation force impulse imaging in the diagnosis of portal hypertension in patients with liver cirrhosis , with the hepatic venous pressure gradient ( HVPG ) as a reference st and ard . MATERIAL S AND METHODS Institutional review board approval and informed consent were obtained for this prospect i ve single-center study . From February 2012 to August 2013 , 60 patients with liver cirrhosis ( mean age , 70.8 years ; age range , 34 - 88 years ; 34 men , 26 women ) with HVPG , LS , and SS measurements and gastrointestinal endoscopy and laboratory data were included if they met the following criteria : no recent episodes of gastrointestinal bleeding , no history of splenectomy , no history of partial splenic embolization , no history of β-blocker therapy , and absence of portal thrombosis . The efficacy of the parameters for the evaluation of portal hypertension was analyzed by using the Spearman rank-order correlation coefficient and receiver operating characteristic ( ROC ) curve analysis . RESULTS The correlation coefficient between SS and HVPG ( r = 0.876 ) was significantly better than that between LS and HVPG ( r = 0.609 , P < .0001 ) . The areas under the ROC curve of SS for the identification of clinical ly important portal hypertension ( HVPG ≥ 10 mm Hg ) , severe portal hypertension ( HVPG ≥ 12 mm Hg ) , esophageal varices ( EVs ) , and high-risk EVs were significantly higher ( 0.943 , 0.963 , 0.937 , and 0.955 , respectively ) than those of LS , spleen diameter , platelet count , and platelet count to spleen diameter ratio ( P < .05 for all ) . SS could be used to accurately rule out the presence of clinical ly important portal hypertension , severe portal hypertension , EVs , and high-risk EVs ( negative likelihood ratios , 0.051 , 0.056 , 0.054 , and 0.074 , respectively ) . CONCLUSION SS is reliable and has better diagnostic performance than LS for identifying portal hypertension in liver cirrhosis Background / Aim : Esophageal varices ( EVs ) are a serious consequence of portal hypertension in patients with liver diseases . Several studies have evaluated possible noninvasive markers of EVs to reduce the number of unnecessary endoscopies in patients with cirrhosis but without varices . This prospect i ve study was conducted to evaluate noninvasive predictors of large varices ( LV ) . Patients and Methods : The study analyzed 106 patients with liver diseases from January 2007 to March 2008 . Relevant clinical parameters assessed included Child-Pugh class , ascites and splenomegaly . Laboratory parameters like hemoglobin level , platelet count , prothrombin time , serum bilirubin , albumin and ultrasonographic characteristics like splenic size , splenic vein size , portal vein diameter were assessed . Univariate and multivariate analysis was done on the data for predictors of large EVs . Results : Incidence of large varices was seen in 41 % . On multivariate analysis , independent predictors for the presence of LV were palpable spleen , low platelet count , spleen size > 13.8 mm , portal vein > 13 mm , splenic vein > 11.5 mm . The receiver operating characteristic ( ROC ) curve showed 0.883 area under curve . Platelet spleen diameter ratio 909 had a sensitivity and specificity of 88.5 % , 83 % respectively . Conclusion : Thrombocytopenia , large spleen size , portal vein size and platelet spleen diameter ratio strongly predicts large number of EVs Background / Aim : Current guidelines recommend screening cirrhotic patients with an endoscopy to detect esophageal varices and to institute prophylactic measures in patients with large esophageal varices . In this study , we aim ed at identifying non-endoscopic parameters that could predict the presence and grade s of esophageal varices . Patients and Methods : In a prospect i ve study , 229 newly diagnosed patients with liver cirrhosis , without a history of variceal bleeding , were included . Demographic , clinical , biochemical and ultrasonographic parameters were recorded . Esophageal varices were classified as small and large , at endoscopy . Univariate analysis and multivariate logistic regression analysis were done to identify independent predictors for the presence and grade s of varices . Results : Of the 229 patients ( 141 males ; median age 42 years ; range 17 - 73 years ) with liver cirrhosis , 97 ( 42.3 % ) had small and 81 ( 35.4 % ) had large varices . On multivariate analysis , low platelet count ( Odd ’s Ratio [ OR ] , 4.3 ; 95 % confidence interval [ CI ] , 1.2 - 14.9 ) , Child Pugh class B/C ( OR , 3.3 ; 95 % CI , 1.8 - 6.3 ) , spleen diameter ( OR , 4.3 ; 95 % CI , 1.6 - 11.9 ) and portal vein diameter ( OR , 2.4 ; 95 % CI , 1.1 - 5.3 ) were independent predictors for the presence of varices . Likewise , for the presence of large esophageal varices , low platelet count ( OR , 2.7 ; 95 % CI , 1.4 - 5.2 ) , Child Pugh class B/C ( OR , 3.8 ; 95 % CI , 2.3 - 6.5 ) and spleen diameter ( OR , 3.1 ; 95 % CI , 1.6 - 6.0 ) were the independent risk factors . Conclusion : The presence and higher grade s of varices can be predicted by a low platelet count , Child-Pugh class B/C and spleen diameter . These may be considered as non-endoscopic predictors for the diagnosis and management of large grade varices BACKGROUND AND AIM To determine and compare the adverse events and long-term effectiveness for patients with small hepatocellular carcinoma ( HCC ) ( ≤ 3 cm ) treated by percutaneous radiofrequency ablation ( RFA ) or hepatectomy . METHODS Small HCC from 120 patients were r and omized into either percutaneous RFA therapy or hepatectomy group , and the effectiveness and complications of two treatment modalities were analyzed . The complications of post-RFA or hepatectomy , the complete treatment rate , treatment-related mortality , and disease-free and overall survival rate were followed up and conducted . RESULTS In patients with small HCC , complete remission rates were achieved in 95 % and 96.7 % in the percutaneus RFA and hepatectomy groups , respectively ( P > 0.05 ) . Hepatic function at day-7 status post-treatment , including albumin and bilirubin levels , were significantly worse in the hepatectomy group ( P < 0.01 ) . Compared with the RFA group , the incidence of postoperative complications ( 27.5 % vs 5.0 % ) and hospital stay ( 11.8 ± 3.1 vs 4.3 ± 1.5 ) were significantly higher in the hepatectomy group ( P < 0.01 ) . After a mean follow-up of 40 months , 22 patients ( 36.6 % ) in the RFA group and 21 patients ( 35.0 % ) in the hepatectomy group developed a recurrence ( P > 0.05 ) . There was no significant difference of the disease-free and overall survival rates at 1 , 2 , and 3 years between the RFA group and the surgical hepatectomy group ( P = 0.443 and P = 0.207 , respectively ) . CONCLUSIONS In patients with small HCC , percutaneous RFA showed similar local control and long-term survival compared with hepatectomy . Importantly , percutaneous RFA are accompanied with a lower complication rate and shorter hospital stay day BACKGROUND AND OBJECTIVE Prophylaxis therapy is indicated in cirrhotic patients with large esophageal varices or small varices with red wale signs ( high risk esophageal varices ; HREV ) . Endoscopic surveillance to detect HREV is currently recommended . The objective of this study is to identify non-invasive predictors of HREV in cirrhotic patients . DESIGN AND METHODS Adult cirrhotic patients without previous variceal bleeding were prospect ively included . All patients underwent a complete biochemical workup , upper digestive endoscopy , and ultrasonographic measurement of spleen bipolar diameter . Platelet count/spleen diameter ratio ( PC/SD ) was calculated for all patients . The association of these variables with the presence of HREV in upper endoscopy was tested using univariate and multivariate analysis . Receiver operating characteristic ( ROC ) curves were constructed for variables associated with HREV . RESULTS Sixty-seven patients were included . The prevalence rate of HREV was 50 % . Age , gender ( female ) , platelet count , spleen diameter , PC/SD ratio , total bilirrubin , prothrombin activity ( INR ) , Child-Pugh score , clinical and ultrasonographic ascites were significantly associated with presence of HREV in univariate analysis . Age and PC/SD ratio were the parameters independently associated with HREV in a multivariate analysis , with OR 8.81 ( CI 95 % : 1.7 - 44.9 ) and OR 11.21 ( CI 95 % : 2.8 - 44.6 ) respectively . A PC/SD ratio cut-off value under 830.8 predicted HREV with 76.9 % sensitivity , 74.2 % specificity and 77.8 % negative predictive value ( ROC curve area : 0.78 ) . CONCLUSIONS The PC/SD ratio was significantly associated with HREV , but with suboptimal sensitivity and specificity . Therefore , the results of this study do not support the routine clinical use of PC/SD ratio for screening of HREV BACKGROUND / AIMS The primary prevention of bleeding from esophageal varices is a major therapeutic issue requiring early screening of esophageal varices . Our aim was to study the diagnostic accuracy of non-endoscopic means for the diagnosis of esophageal varices . METHODS Sixty-three clinical , biochemical , endoscopic and Doppler ultrasound variables were prospect ively recorded in 207 consecutive patients with chronic liver disease . Diagnostic accuracy was evaluated by discriminant analysis , first globally using all variables with diagnostic accuracy > or = 65 % in univariate analysis , then by stepwise regression . RESULTS A ) whole group ( n=207 ) , 1 ) diagnosis of esophageal varices : diagnostic accuracy was globally 81 % , and 81 % with 1 variable : irregular liver surface at ultrasound , 2 ) Diagnosis of large esophageal varices ( grade s 2 + 3 ) : diagnostic accuracy was globally 80 % , and 79 % with 2 variables : prothrombin index , gamma-globulins . B ) patients with cirrhosis ( n=116 ) , 1 ) diagnosis of esophageal varices : diagnostic accuracy was globally 71 % , and 72 % with 2 variables : platelet count , prothrombin index , 2 ) diagnosis of large esophageal varices ( grade s 2 + 3 ) : diagnostic accuracy was globally 71 % , and 72 % with 3 variables : platelet count , prothrombin index , spider naevi . The ROC curve showed that the best threshold for the diagnostic accuracy of platelet count was 160 G/l providing a sensitivity of 80 % and a specificity of 58 % . Platelet count > or = 260 G/l has a negative predictive value > or = 91 % . CONCLUSIONS Using a few non-endoscopic criteria , esophageal varices can be correctly diagnosed in 81 % of patients with chronic liver disease and in 71 % of patients with cirrhosis . These results show that the non-invasive screening of patients who are c and i date s for the primary prevention of variceal bleeding is possible , but should be improved before being used in a clinical setting c f s a a e l This is one of a series of statements discussing the use of GI endoscopy in common clinical situations . The St and ards of Practice Committee of the American Society for Gastrointestinal Endoscopy ( ASGE ) prepared this text . In preparing this document , a search of the medical literature was performed by using PubMed . Additional references were obtained from the bibliographies of the identified articles and from recommendations of expert consultants . When few or no data exist from well- design ed prospect i ve trials , emphasis is given to results of large series and reports from recognized experts . This document is based on a critical review of the available data and expert consensus at the time that the document was drafted . Further controlled clinical studies may be needed to clarify aspects of this document . This document may be revised as necessary to account for changes in technology , new data , or other aspects of clinical practice . This document is intended to be an educational device to provide information that may assist endoscopists in providing care to patients . This document is not a rule and should not be construed as establishing a legal st and ard of care or as encouraging , advocating , requiring , or discouraging any particular treatment . Clinical decisions in any particular case involve a complex analysis of the patient ’s condition and available courses of action . Therefore , clinical considerations may lead an endoscopist to take a course of action that varies from this document BACKGROUND & AIMS Preliminary data suggest that non-invasive methods could be useful to assess presence of oesophageal varices ( OV ) in cirrhotic patients . We aim ed to further investigate simple serum non-invasive markers for diagnosing and grading OV . METHODS A retrospective set of 510 cirrhotics and a prospect i ve set of 110 cirrhotics were enrolled consecutively in five centers . Platelets , AST-to-ALT ratio , AST-to-platelet-ratio index , Forns ' index , Lok index , Fib-4 , and Fibroindex were measured within 2 months from upper endoscopy , taken as a gold st and ard . Performance was expressed as sensitivity , specificity , positive , and negative predictive values ( PPV , NPV ) , accuracy , and area under the curve ( AUC ) . RESULTS A combination of Lok index ( cutoff=1.5 ) and Forns ' index ( cutoff=8.8 ) had 0.80 AUC ( 0.76 - 0.84 , 95 % CI ) , and high NPV ( > 90 % ) to exclude clinical ly relevant OV , defined as large OV or small OV with red signs or in Child-Pugh C cirrhosis . By applying this combination , upper endoscopy would have been avoided in 1/3 of our cirrhotics . Large OV could be excluded with 96 % NPV by Lok index ( cutoff=1.5 ) . A combination of Lok index ( cutoff=0.9 ) and Forns ' index ( cutoff=8.5 ) predicted presence of any grade OV with good performance : 0.82 AUC ( 0.76 - 0.88 , 95 % CI ) , 88 % PPV . CONCLUSIONS Serum non-invasive markers may be useful as a first line tool to identify cirrhotic patients in which the risk of clinical ly relevant OV is trivial , and to reduce the number of upper endoscopies . However , we are still far from the possibility of replacing upper endoscopy by simple serum non-invasive markers in the vast majority of patients |
10,795 | 30,715,359 | The pre-operative weighted mean difference ( WMD ) showed that serum AMH levels did not differ significantly between the groups .
WIDER IMPLICATION S Our results challenge the concept that endometrioma per se adversely affects ovarian reserve , whereas endometrioma cystectomy , especially as bilateral operation , has a deleterious and sustained effect on ovarian reserve .
AMH seems to be a more appropriate biomarker of ovarian reserve than AFC in cases with endometrioma . | BACKGROUND Ovarian endometrioma is a frequent manifestation of endometriosis in women of reproductive age .
Several issues related to its space occupying effects , local reactions and surgical removal continue to be actively debated today .
The impact of ovarian endometrioma per se on ovarian reserve is still controversial and the effect of ovarian surgery is still actively discussed .
Furthermore , the optimal biomarker of ovarian reserve estimation in women with ovarian endometrioma is still under examination .
Additionally , there is no consistent agreement on the effect of endometrioma bilaterality on ovarian reserve .
OBJECTIVE AND RATIONALE The objective of this systematic review and meta- analysis was to study the impact of unilateral versus bilateral ovarian endometrioma on ovarian reserve biomarkers before and after endometrioma cystectomy . | OBJECTIVE Retrospective studies suggest that laparoscopic excision of endometriomas is associated with a reduced responsiveness to ovarian hyperstimulation . In this study , we prospect ively evaluated ovarian response to hyperstimulation in women selected for in vitro fertilization and intracytoplasmic sperm injection cycles who previously underwent laparoscopic enucleation of a monolateral endometrioma . STUDY DESIGN Operated and contralateral intact ovaries of the same patient were compared in terms of number of follicles , number of oocytes retrieved , fertilization rate , and rate of high- quality embryos . RESULTS Thirty-eight subjects were included . A reduced number of dominant follicles , oocytes , embryos , and high- quality embryos was observed in the operated gonad . The mean percentage of reduction was 60 % ( 95 % confidence interval 38 - 81 % ) , 53 % ( 95 % confidence interval 30 - 75 % ) , 55 % ( 95 % confidence interval 28 - 81 % ) , and 52 % ( 95 % confidence interval 17 - 87 % ) , respectively . Fertilization rate and rate of good- quality embryos were similar . CONCLUSION Laparoscopic excision of endometriomas is associated with a quantitative but not a qualitative damage to ovarian reserve Laparoscopic ovarian cystectomy is recommended for surgical procedure of endometrioma . The negative impact on ovarian reserve following removal had been documented . Little evidence had been reported for nonovarian originated effects . Objective . To evaluate the impact of laparoscopic ovarian cystectomy for endometrioma on ovarian reserve , measured by serum antimullerian hormone ( AMH ) , compared to nonovarian pelvic surgery . Material s and Methods . A prospect i ve study was conducted . Women who underwent laparoscopic ovarian cystectomy ( LOC ) and laparoscopic nonovarian pelvic surgery ( NOS ) were recruited and followed up through 6 months . Clinical baseline data and AMH were evaluated . Results . 39 and 38 participants were enrolled in LOC and NOS groups , respectively . Baseline characteristics ( age , weight , BMI , and height ) and preoperative AMH level between 2 groups were not statistically different . After surgery , AMH of both groups decreased since the first week , at 1 month and at 3 months . However , as compared to the LOC group at 6 months after operation , the mean AMH of the NOS group had regained its value with a highly significant difference . Conclusion . This study demonstrated the negative impact of nonovarian or indirect effects of laparoscopic surgery to ovarian reserve . The possible mechanisms are necessary for more investigations AIM We aim ed to evaluate the impact of topical hemostatic sealants and bipolar coagulation during laparoscopic ovarian endometriotic cyst resection on ovarian reserve by comparing the rates of decrease in anti-Müllerian hormone ( AMH ) . METHODS A r and omized prospect i ve data collection was made on women aged 19 - 45 years who planned to have laparoscopic ovarian cystectomy at one of two institutions ( n = 80 ) , Kangbuk Samsung Hospital , Seoul , Korea or National Health Insurance Service Ilsan Hospital , Goyang , Korea , from January 2014 to April 2016 . Patients were r and omly divided into two groups treated with either a topical hemostatic sealant or bipolar coagulation for hemostasis . The hemostatic group was r and omized to the FloSeal or TachoSil subgroups . Preoperative and 3-month postoperative AMH levels were checked and the rates of decrease of AMH were compared . All patients enrolled were treated with dienogest ( Visanne ) for 6 - 12 months . None were lost to follow-up at postoperative 3 months , but about one-third of the patients had been lost to follow-up by 6 - 12 months . RESULTS AMH was significantly decreased in both groups 3 months postoperatively ; however , the rate of decrease in the bipolar coagulation group was greater than that in the hemostatic sealant group , 41.9 % ( interquartile range [ IQR ] , 22.29 - 65.24 ) versus 18.1 % ( IQR , 10.94 - 29.90 ) , P = 0.007 . Between the two hemostatic subgroups , there was no significant difference in AMH decrease rate , 14.95 % ( IQR , 11.34 - 21.21 ) versus 18.1 % ( IQR 9.76 - 40.70 ) , P = 0.204 . CONCLUSION Hemostatic sealants may be an alternative to bipolar coagulation for preservation of ovarian reserve after laparoscopic ovarian cystectomy for endometriosis STUDY QUESTION Is there an association between the endometriosis phenotype and presentation with infertility ? SUMMARY ANSWER In a population of operated patients with histologically proven endometriosis , ovarian endometrioma ( OMA ) per se is not associated with an increased risk of presentation with infertility , while previous surgery for endometriosis was identified as a risk factor for infertility . WHAT IS KNOWN ALREADY The increased prevalence of endometriosis among subfertile women indicates that endometriosis impairs reproduction for reasons that are not completely understood . STUDY DESIGN , SIZE , DURATION This was an observational , cross-sectional study using data prospect ively collected in all non-pregnant patients aged between 18 and 42 years , who were surgically explored for benign gynaecological conditions at our institution between January 2004 and March 2013 . For each patient , a st and ardized question naire was completed during a face-to-face interview conducted by the surgeon during the month preceding surgery . PARTICIPANTS / MATERIAL S , SETTING , METHODS Surgery was performed in 2208 patients , of which 2066 signed their informed consent . Of the 1059 women with a visual diagnosis of endometriosis , 870 had histologically proven endometriosis and complete treatment for their endometriotic lesions , including 307 who presented with infertility . Univariate analysis and multiple logistic regression analysis were performed to determine factors associated with infertility . MAIN RESULTS AND THE ROLE OF CHANCE The following variables were identified as risk factors for endometriosis-related infertility : age > 32 years ( odds ratio [ OR ] = 1.9 ; 95 % confidence interval [ CI ] : 1.4 - 2.4 ) , previous surgery for endometriosis ( OR = 1.9 ; 95 % CI : 1.3 - 2.2 ) , as well as peritoneal superficial endometriosis ( OR = 3.1 ; 95 % CI : 1.9 - 4.9 ) ; Conversely , previous pregnancy was associated with a lower rate of infertility ( OR = 0.7 ; 95 % CI : 0.6 - 0.9 and OR = 0.6 ; 95 % CI : 0.4 - 0.9 , respectively ) . OMA is not selected as a significant risk factor for infertility . LIMITATIONS , REASON FOR CAUTION The selection of our study population was based on a surgical diagnosis . We can not exclude that infertile women with OMA associated with a diminished ovarian reserve , as assessed during their infertility work-up , were referred less frequently to surgery and might therefore be underrepresented . In addition we can not exclude that our group of infertile women present associated other causes of infertility . WIDER IMPLICATION S OF THE FINDINGS Identification of risk and preventive factors of endometriosis-related infertility can help improve clinical and surgical management of endometriosis in the setting of infertility . STUDY FUNDING /COMPETING INTERESTS None . TRIAL REGISTRATION NUMBER None Objective . To evaluate whether a change takes place in antimullerian hormone ( AMH ) levels reflecting the ovarian reserve after laparoscopic endometrioma stripping surgery and to demonstrate if there is any correlation between AMH levels and the sizes of endometriomas . Method . Fourty-seven women participated as the study group in this prospect i ve controlled trial , 33 of whom ( 70.2 % ) had unilateral and 14 ( 29.7 % ) of whom had bilateral endometriomas . Pre- and post-operative serum AMH levels were measured and compared with 17 normo-ovulatory control cases and also correlated with endometrioma sizes . Result ( s ) . Mean pre-operative AMH levels of the study group and the normo-ovulatory control cases did not reveal a statistically significant difference ( 1.62 ± 1.09 ng/ml and 2.06 ± 0.51 ng/ml , P > 0.05 ) . Mean level of post-operative serum AMH of the study group decreased from 1.62 ± 1.09 to 1.39 ± 1.16 . However , this reduction was not statistically significant . ( P > 0.05 ) . Pre- and post-operative AMH levels do not reveal a correlation with the size of endometrioma in both group of patients with either unilateral or bilateral endometrioma . Conclusion ( s ) . The presence of the endometrioma does not impair the AMH levels . Laparoscopic endometrioma stripping surgery do not appear to cause a damage in the AMH secreting healthy ovarian tissue , in the short-term follow-up . Laparoscopic stripping surgery of endometriomas in experienced h and s is currently a valid approach OBJECTIVE To investigate whether the serum antimüllerian hormone ( AMH ) levels recover within 1 year after cystectomy for endometriomas , and to analyze the pattern of sequential changes in the serum AMH levels . DESIGN Prospect i ve study . SETTING University hospital . PATIENT(S ) Thirty-nine patients undergoing cystectomy for unilateral endometrioma ( n = 22 ) and bilateral endometriomas ( n = 17 ) . INTERVENTION(S ) Serum sample s collected 2 weeks before , and 1 month and 1 year after surgery were assayed for AMH levels . MAIN OUTCOME MEASURE(S ) Assessment of the ovarian reserve damage based on alterations in the serum AMH levels and the association with parameters of endometriosis and surgery for endometriomas . RESULT ( S ) The median AMH levels were 3.56 , 1.90 , and 2.10 ng/mL before , 1 month after , and 1 year after surgery , respectively . Twenty patients showed higher AMH levels 1 year after surgery than 1 month after surgery ( increase group ) ; 19 patients showed lower AMH levels ( decrease group ) . We found a statistically significant difference in the number of follicles removed by surgery between the two groups . CONCLUSION ( S ) The decrease in the serum AMH levels caused by cystectomy can recover . Our results suggest that removal of ovarian cortex might be involved in the decrease of the ovarian reserve just after surgery , and that a continuous decrease of the ovarian reserve after cystectomy might be attributed to other mechanisms Background Endometriosis is a well-known cause of infertility , and the anti-Mullerian hormone ( AMH ) is an accepted biomarker of ovarian reserve and response to artificial reproductive technology procedures . The present study was a prospect i ve analysis of age-dependent AMH serum concentration in women with bilateral and unilateral ovarian endometriomas before therapy onset compared with healthy controls . Methods This prospect i ve cross-sectional study included 384 women aged 18–48 years . AMH serum concentration was assessed between days 3 and 6 of the menstrual cycle in 78 patients with bilateral and 157 patients with unilateral ovarian endometriomas and compared with 149 healthy controls . Ovarian endometriosis was confirmed histopathologically , and data were presented as medians with interquartile range ( IQR ) . Results Stage III endometriosis was diagnosed in 53.2 % , stage IV in 18.3 % , stage V in 23.4 % and stage VI in 5.4 % of the patients . Patients with bilateral ovarian endometriomas showed the lowest median AMH levels compared with patients suffering from unilateral ovarian endometriosis ( 0.55 ; IQR : 0.59 vs. 2.00 ; IQR : 2.80 ; p < 0.001 ) and the control group ( 0.55 ; IQR : 0.59 vs. 2.84 ; IQR : 3.2 ; p < 0.001 ) . Median AMH concentration values were not significantly different between patients with unilateral ovarian endometriosis and the healthy controls ( 2.00 ; IQR : 2.80 vs. 2.84 ; IQR : 3.2 ; p = 0.182 ) . A strongly negative correlation between AMH levels and age was confirmed in healthy individuals ( R = −0.834 ; p < 0.001 ) and women with unilateral ovarian endometriomas ( R = −0.774 ; p < 0.001 ) . Patients with bilateral ovarian endometriosis showed a significantly negative but only moderate correlation between AMH levels and age ( R = −0.633 ; p < 0.001 ) , which was significantly lower than in the healthy controls ( R = −0.633 vs. R = −0.834 ; p = 0.006 ) but not in the patients with unilateral ovarian endometriosis ( R = −0.663 vs. R-0.774 ; p = 0.093 ) . Based on a multivariate regression analysis , only bilateral localization of ovarian endometrial cysts ( p = 0.003 ) and patient age ( p < 0.001 ) , but not left/right localization of unilateral cyst or cyst volume , were negatively associated with AMH serum concentration . Conclusion According to our data , unilateral ovarian endometriosis had a moderately negative and nonsignificant effect on AMH-based ovarian reserve evaluated prior to surgery , irrespective of age . In contrast , the ovarian reserve was significantly reduced in women with bilateral ovarian endometriomas Background To evaluate the impact of the presence of endometrioma and laparoscopic cystectomy on ovarian reserve as assessed by serum anti-Müllerian hormone ( AMH ) level . In addition , factors related to the decline in ovarian reserve were analyzed . Methods From June 2013 to January 2014 , we prospect ively included 40 women with endometriomas as the study group ( group A ) , 36 women with tubal factor infertilities as control group 1 ( group B ) and 22 women with the other benign ovarian cysts as control group 2 ( group C ) . The women with ovarian cysts underwent laparoscopic cystectomy . Serum AMH levels were determined preoperatively and at 1 month after surgery . Results The endometrioma group had lower AMH levels ( 1.53 ± 1.37 ng/ml ) compared with the other benign ovarian cyst group ( 2.20 ± 1.23 ng/ml ) and the tubal factor infertility group ( 2.82 ± 1.74 ng/ml ) . The rate of serum AMH decline 1 month after surgery in the endometrioma group ( 0.62 ± 0.35 ) was larger than the decline in the other benign ovarian cyst group ( 0.32 ± 0.30 ) . The preoperative AMH level showed a significant correlation with patient age ( group A , r = −0.32 ; group B , r = −0.54 ; group C , r = −0.71 ) ; there was a statistically significant correlation between the rate of serum AMH decline and endometrioma diameter as well as with the preoperative serum AMH level . In addition , the rate of serum AMH decline was larger for bilateral endometriomas than for unilateral endometriomas , but there was no similar correlation in the other benign ovarian cyst group . The rate of AMH decline after surgery in the subgroup of > 7 cm was significantly higher than in the subgroup of ≤7 cm . Conclusions Ovarian endometriomas per se may damage ovarian reserve , and cystectomy of endometriomas may cause greater damage to ovarian reserve compared with other benign ovarian cysts . The operation-related damage to the ovarian reserve was positively related to whether the endometriomas were bilateral , as well as cyst size ( especially for cysts > 7 cm ) , but was negatively related to the preoperative serum AMH level . Age was a negative factor that affected the ovarian reserve OBJECTIVE To assess the impact of prior unilateral or bilateral endometrioma cystectomy on controlled ovarian hyperstimulation ( COH ) and intracytoplasmic sperm injection ( ICSI ) outcome . DESIGN Retrospective case-control study . SETTING Department of Obstetrics and Gynecology , School of Medicine , Hacettepe University , Ankara , Turkey . PATIENT(S ) Fifty-seven consecutive infertile patients were enrolled who had previously undergone unilateral ( n = 34 ) or bilateral ( n = 23 ) laparoscopic cystectomy for endometriomas more than 3 cm in diameter and underwent ICSI . The control group consisted of 99 patients with tubal factor infertility . INTERVENTION(S ) Controlled ovarian hyperstimulation and ICSI . MAIN OUTCOME MEASURE(S ) Cycle cancellation rate , number of oocytes , fertilization rate , embryo quality , clinical pregnancy rate ( PR ) , and implantation rate . RESULT ( S ) The mean number of oocytes , metaphase II oocytes , and two-pronucleated oocytes were significantly lower in the bilateral cystectomy group compared to the unilateral cystectomy and control groups . However , all other parameters , including fertilization rate , the mean number of embryos transferred , the mean number of grade 1 embryos transferred , the clinical PR per embryo transfer , and implantation rate , were comparable among the three groups . Within the unilateral cystectomy group , the mean number of oocyte retrieved from the operated site was significantly less than in the contralateral nonoperated site . CONCLUSION ( S ) Laparoscopic endometrioma cystectomy does reduce the ovarian reserve . However , diminished ovarian reserve does not translate into impaired pregnancy outcome OBJECTIVE To investigate the effect of laparoscopic endometrioma stripping on serum antimüllerian hormone ( AMH ) and the correlation between the clinicopathologic factors . DESIGN Prospect i ve study . SETTING University hospital . PATIENT(S ) Sixty-five women with endometriomas . INTERVENTION(S ) All patients underwent laparoscopic cystectomy . Serum AMH , FSH , LH , E(2 ) , and antral follicle count ( AFC ) were measured preoperatively , at 6 weeks , and at 6 months postoperatively . Specimens were analyzed histopathologically . MAIN OUTCOME MEASURE(S ) The primary end point was to assess the ovarian reserve damage based on alterations of AMH and the secondary end point was to detect the changes in FSH , LH , E(2 ) , and AFC . RESULT ( S ) Serum AMH decreased significantly at the sixth month ( 61 % ) postoperatively . The FSH level increased significantly at the sixth week , but returned to normal at the sixth month . The AFC increased significantly at the sixth week and at the sixth month . The AMH level decrease was more evident in patients with the cyst < 5 cm ( 65.7 % vs. 41.3 % ) . The AMH decrease was more in bilateral compared with unilateral endometriomas ( 67 % versus 57 % , respectively ) . No correlation was detected between the histopathologic analyses and tAMH level . Initially the AMH level was the only independent factor affecting the AMH decrease ( odds ratio , 3.68 ; 95 % confidence interval 1.66 - 8.14 ) . CONCLUSION ( S ) Laparoscopic cystectomy of ovarian endometriomas causes a significant and progressive decline in serum AMH levels STUDY QUESTION Do endometriotic ovarian cysts influence the rate of spontaneous ovulation ? SUMMARY ANSWER Endometriotic cysts , no matter what their volume , do not influence the rate of spontaneous ovulation in the affected ovary . WHAT IS KNOWN ALREADY Endometriotic ovarian cysts may negatively affect spontaneous ovulation in the affected ovary . STUDY DESIGN , SIZE , DURATION This was a prospect i ve observational study performed between September 2009 and June 2013 . PARTICIPANTS / MATERIAL S , SETTING , METHODS This study included women of reproductive age with regular menstrual cycles and unilateral ovarian endometriomas ( diameter ≥20 mm ) desiring to conceive . Exclusion criteria were : hormonal therapies in the 3 months prior to study entry and previous adnexal surgery . Patients underwent serial transvaginal ultrasound to assess the side of ovulation ( for up to six cycles ) . MAIN RESULTS AND THE ROLE OF CHANCE Ovulation was monitored in 1199 cycles in 244 women ( age , mean ± SD , 34.3 ± 4.9 years ) . 55.3 % of the patients had left endometriomas and 44.7 % had right endometriomas ( P = 0.024 ) . The mean ( ±SD ) diameter of the endometriomas was 5.3 cm ( ±1.7 cm ) . Ultrasonographically documented ovulation occurred in 596 cycles in the healthy ovary ( 49.7 % ; 95 % CI , 46.8 - 52.6 % ) and in 603 cycles in the affected ovary ( 50.3 % ; 95 % CI , 47.1 - 53.2 % ; P = 0.919 ) . This observation was confirmed in patients with diameter of the cyst ≥4 cm ( n = 166 ) and in those with diameter of the cyst ≥6 cm ( n = 45 ) . One hundred and five patients spontaneously conceived ( 43.0 % ; 95 % CI , 36.7 - 49.5 % ) . LIMITATIONS , REASON FOR CAUTION The high pregnancy rate reported in this study was observed in a selected population of women with endometriomas and can not be extrapolated to all patients with endometriosis . WIDER IMPLICATION S OF THE FINDINGS Since ovarian endometriomas do not impair spontaneous ovulation , the impact on fertility of surgical excision of ovarian endometriomas should be further investigated BACKGROUND Questions remain as to whether surgical excision of ovarian endometriomas might cause damage to ovarian function . To test the hypothesis that ovarian surgery for endometrioma compromises ovarian function and accelerates ovarian failure . METHODS In a tertiary university Clinic , longitudinal prospect i ve cohort study . Patients who underwent laparoscopy for endometriosis between March 1993 and November 2007 were assessed for inclusion in the study . A prospect i ve follow-up at 3 , 6 and 12 months then yearly was conducted . Evolution of menstrual pattern , symptoms and reproductive outcomes were investigated . RESULTS From over the 14-year period , 302 patients were included in the study . The mean age ( ±SD ) of patients was 32.6 ± 5.6 years ; the median duration of follow-up was 8.5 years ( range 2 - 17 years ) . Menopause was documented in 43 women ( 14.3 % ) at a mean age of 45.3 ± 4.3 years ( range 32 - 52 years ) . Women previously su bmi tted to bilateral cystectomy were younger at menopause than those with monolateral endometrioma ( 42.1 ± 5.1 years versus 47.1 ± 3.5 years , P = 0.003 ) . Premature ovarian failure ( POF ) was observed in 7 of 43 ( 16.3 % ) menopausal patients ; the majority ( 4 , 57.1 % ) after bilateral cystectomy . The relationship between the preoperative ovarian endometriomas total diameter and menopausal age was significant in case of surgery for bilateral endometriomas ( R(2 ) = 0.754 , P = 0.002 ) . CONCLUSIONS Patients who had been operated on for bilateral endometriomas have an increased risk of POF . Ovarian parenchyma loss at the time of surgery seems related to cyst diameter . In the case of unilateral ovarian endometrioma , the contralateral intact ovary might adequately compensate OBJECTIVE To evaluate the ovarian reserve changes after laparoscopic cystectomy , we prospect ively evaluated pre- and postoperative serum anti-Müllerian hormone ( AMH ) level , and ovarian volumes . DESIGN Prospect i ve longitudinal study . SETTING University Hospital . PATIENT(S ) Twenty women with benign ovarian masses participated ; endometrioma [ 13 ] , mature teratoma [ 6 ] , and mucinous cystadenoma [ 1 ] . Seven patients had bilateral ovarian masses . INTERVENTION(S ) All patients had undergone laparoscopic ovarian cystectomy . Serum AMH levels were serially measured : preoperative , 1 week , 1 month , and 3 months after operation . Volumes of total ovary and ovarian mass were measured by 3D ultrasonography before operation . MAIN OUTCOME MEASURE(S ) Postoperative serum AMH level and ovarian volume . RESULT ( S ) Median AMH level was 2.23 ng/mL ( 95 % confidence interval [ CI ] 1.35 - 3.41 ng/mL ) before operation , but reduced to 0.67 ng/mL ( 95 % CI 0.44 - 1.70 ng/mL ) at the first week postoperatively and then increased to 1.14 ng/mL ( 95 % CI 0.79 - 2.36 ng/mL ) in the first month and 1.50 ng/mL ( 95 % CI 0.58 - 3.26 ng/mL ) in the third month . The serum AMH level after 3 months postoperatively was recovered to about 65 % of the preoperative level . The serum AMH level at postoperative 1 week was more decreased in endometrioma compared with nonendometrioma ( 33.9 % vs. 69.2 % of preoperative level ) , and in bilateral group compared with unilateral group ( 16.9 % vs. 62.9 % ) . CONCLUSION ( S ) This study suggests that ovarian reserve could be reduced after laparoscopic cystectomy ; however , it could be restored thereafter up to 3 months postoperative in reproductive women STUDY QUESTION Do the presence of endometriomas and their laparoscopic excision lead to a decrease in ovarian reserve as assessed by serum anti-Müllerian hormone ( AMH ) levels ? SUMMARY ANSWER Both the presence and excision of endometriomas cause a significant decrease in serum AMH levels , which is sustained 6 months after surgery . WHAT IS KNOWN ALREADY No previous comparison of serum AMH levels between women with and without endometrioma has been reported . However , studies have suggested a decline in serum AMH levels 1 - 3 months after endometrioma excision but long-term data are needed . STUDY DESIGN , SIZE , DURATION A prospect i ve cohort study including 30 women with endometrioma > 2 cm were age matched with 30 healthy women without ovarian cysts . PARTICIPANTS / MATERIAL S , SETTING , METHODS Women with endometrioma underwent laparoscopic excision with the stripping technique . Serum AMH level and antral follicle count ( AFC ) were determined preoperatively , 1 and 6 months after surgery . Correlation analyses were undertaken in order to identify determinants of surgery-related change in ovarian reserve . MAIN RESULTS AND THE ROLE OF CHANCE Compared with controls at baseline , women with endometrioma had lower AMH levels ( 4.2 ± 2.3 versus 2.8 ± 2.2 ng/ml , respectively , P = 0.02 ) and AFC ( 14.7 ± 4.1 versus 9.7 ± 4.8 , respectively , P < 0.01 ) . Serum AMH levels were further decreased 6 months after surgery ( 2.8 ± 2.2 versus 1.8 ± 1.3 ng/ml , P = 0.02 ) , while AFC remained unchanged ( 9.7 ± 4.8 versus 10.4 ± 4.2 , P = 0.63 ) . The rate of decline in AMH was not correlated with age , laterality of endometrioma , cyst diameter or the number of primordial follicles on the surgical specimens . The preoperative serum AMH level was positively correlated with the rate of decline in serum AMH after surgery ( r = 0.47 , P = 0.02 ) . LIMITATIONS , REASONS FOR CAUTION The absence of a non-treated group of women with endometriomas as a further control prevents comment on the presence of a progressive decline in ovarian reserve related to endometrioma per se . The sample size may be too small for detection of factors correlated with the extent of ovarian damage . WIDER IMPLICATION S OF THE FINDINGS While the findings are mostly in agreement with previous studies , the present study is the first to show that the presence of endometrioma per se is associated with a decrease in ovarian reserve . The extent of surgery-related decline in ovarian reserve is not predictable using preoperative or perioperative factors . It may be prudent to measure AMH levels preoperatively and delay/avoid surgical excision as far as is possible if subsequent fertility is a concern . Additional studies are required to further investigate whether the endometrioma-related decline in ovarian reserve per se is progressive in nature and whether it exceeds the surgery-related decline . STUDY FUNDING /COMPETING INTEREST(S ) This study was funded by the Research Fund of the Uludag University School of Medicine . The authors have no conflict of interest associated with this study OBJECTIVE To evaluate the effects of laparoscopic cystectomy on ovarian reserve in patients with endometriomas . DESIGN Prospect i ve study . SETTING Private and university hospitals . PATIENT(S ) A total of 193 patients with endometriomas undergoing laparoscopic cyctectomy . INTERVENTION(S ) Serum levels of antimüllerian hormone ( AMH ) , FSH , and E₂ , as well as antral follicle count ( AFC ) were measured preoperatively and 1 week , 3 and 9 months postoperatively for AMH , and 3 months for other values . MAIN OUTCOME MEASURE(S ) Ovarian reserve based on the comparison of AMH alterations . The secondary end points are changes in FSH , E₂ , and AFC . RESULT ( S ) Serum AMH level decreased significantly from the baseline ( 3.86 ± 3.58 ng/mL ) to 1 week ( 1.66 ± 1.92 ng/mL ) , 3 months ( 2.06 ± 2.5 ng/mL ) , and 9 months ( 1.77 ± 1.76 ng/mL ) postoperatively . Those patients with bilateral endometriomas had significantly lower levels of AMH , 1 week , 3 and 9 months after operation . Also , patients older than 38 years had lower postoperative AMH levels . The FSH levels increased significantly from baseline to 3 months postoperatively . The AFC level increased significantly from baseline to 3 months after operation . CONCLUSION ( S ) The AMH level decreased and the FSH level increased after laparoscopic cystectomy for endometriomas , especially in older patients and those with bilateral cysts STUDY OBJECTIVE To evaluate the short-term changes in ovarian reserve markers after laparoscopic cystectomy performed for endometriotic and nonendometriotic cysts . DESIGN Prospect i ve case-control study ( Canadian Task Force classification II-2 ) . SETTING The Reproductive Endocrinology Clinic of a training and research hospital . PATIENTS Thirty-four women with endometrioma ≥ 4 mm ( group 1 ) and 33 women with nonendometriotic cysts of matched size ( group 2 ) who underwent surgery during the same period . INTERVENTIONS The follicular phase follicle-stimulating hormone ( FSH ) , estradiol ( E2 ) , and antimüllerian hormone ( AMH ) levels and the antral follicle count ( AFC ) of both groups were analyzed preoperatively and 2 months after laparoscopic cystectomy . The pre- and postoperative values were compared within the same group and between the 2 groups . MEASUREMENT AND MAIN RESULTS Preoperative FSH and E2 levels were similar in both groups . However , preoperative AMH levels and AFC were significantly lower in group 1 ( endometrioma ) compared with group 2 ( nonendometrioma ; p = .004 and p = .025 , respectively ) . In both groups there was a significant decrease in the AMH levels after surgery ( 3.1 ± 1.9 ng/mL to 2.5 ± 1.6 ng/mL , p < .001 , and 5.7 ± 3.7 ng/mL to 4.8 ± 3.3 ng/mL , p = .04 ) . AMH levels exhibited a significant decrease in the unilateral and bilateral endometrioma groups after cystectomy ( p < .001 and p = .025 , respectively ) . However , preoperative and postoperative changes in AMH and AFC were similar in groups 1 and 2 for both unilateral and bilateral cysts ( p = .586 and p = .267 ) . CONCLUSION Preoperative AMH and AFC levels are lower in both unilateral and bilateral endometriomas compared with nonendometriotic cysts . The AMH levels decreased after cystectomy in both endometriotic and nonendometriotic cysts . However , in the short-term period the amount of change in ovarian reserve tests in both unilateral and bilateral cysts was similar for both endometrioma and nonendometriotic cysts OBJECTIVE To evaluate the effects of laparoscopic cystectomy on serum anti-Müllerian hormone ( AMH ) level as a marker of ovarian reserve in patients with endometrioma . METHODS A prospect i ve observational study enrolled patients aged younger than 40 years who were referred to a tertiary center in Tehran , Iran , between January 1 , 2013 and December 31 , 2014 to undergo laparoscopic cystectomy for ovarian endometriomas at least 30 mm in diameter , or regardless of size for patients with infertility , dysmenorrhea , dyspareunia , or dyschezia . Baseline and 6-month post-operative AMH levels were compared . RESULTS Data from 70 patients were included in the analyses . Among patients with unilateral endometriomas , lower pre-operative AMH levels were observed in patients with endometriomas at least 50 mm in diameter ( P=0.027 ) , whereas cyst size was not associated with differences in pre-operative AMH level in patients with bilateral endometriomas ( P=0.227 ) . Across the entire study population , post-operative AMH levels were lower than the baseline ( P=0.008 ) . Greater post-operative decreases in AMH were associated with bilateral cysts compared with unilateral cysts ( P=0.046 ) , cysts being at least 50 mm in diameter among patients with unilateral cysts ( P=0.028 ) , and both cysts being at least 50 mm in diameter among patients with bilateral cysts ( P=0.025 ) . CONCLUSION Laparoscopic cystectomy was associated with post-operative decreases in serum AMH , particularly with bilateral involvement and endometriomas at least 50 mm in diameter STUDY OBJECTIVE To evaluate how endometriotic cystectomy and vaporization affect ovarian reserve after conservative surgery . DESIGN Prospect i ve study ( Canadian Task Force classification II-1 ) . SETTING Hokusetsu General Hospital . PATIENTS Ninety-nine women who underwent conservative surgery to treat endometriotic cysts from June 2011 to July 2013 . INTERVENTIONS Vaporization with bipolar current was performed in nulligravid women , and cystectomy in those who had a child . In women with endometriotic cysts , bilateral cystectomy was performed in 28 , bilateral vaporization in 15 , unilateral cystectomy in 40 , and unilateral vaporization in 16 . In all patients , preoperative and postoperative serum anti-müllerian hormone ( AMH ) and follicle-stimulating hormone ( FSH ) concentrations at the early proliferative phase were assayed , and the change in concentrations was evaluated for each operation . MEASUREMENT AND MAIN RESULTS In the bilateral cystectomy group , the mean ( SD ) postoperative FSH concentration ( 19.3 [ 21.8 ] IU/mL ) was statistically higher than the preoperative concentration ( 9.0 [ 6.2 ] IU/mL ) ( p < .01 ) . AMH significantly declined after all operations to treat endometriotic cysts , and the rate of decline in the AMH concentration was > 50 % compared with preoperative concentrations . CONCLUSION Whether endometriotic cysts are unilateral or bilateral , both cystectomy and vaporization using bipolar current can lower ovarian reserve . Therefore , it is necessary to develop more effective surgical procedures to prevent ovarian damage BACKGROUND The aim of this study was to estimate whether or not the size of an endometrioma is related to the thickness of the ovarian parenchyma inadvertently excised along with the cyst wall . METHODS We performed a retrospective study including 35 women who had undergone endometrioma cystectomy , using an ovarian tissue sparing procedure . In total 38 specimens were studied by three pathologists as three women presented bilateral localizations , and all cyst diameters measured at least 30 mm . For each endometrioma , serial sections were performed , and on each section four different sites were r and omly chosen to measure the thickness of gl and ular epithelium and stroma , of subjacent fibrosis , depending on the cyst , and of the ovarian parenchyma removed with the cyst . The diameter of the ovary was measured preoperatively either by MRI or ultrasound , and the area of the internal wall was then calculated . The relationships between the mean thickness of ovarian parenchyma removed and the variables were estimated and a multiple regression model identified independent predictors for ovarian parenchyma thickness . RESULTS Adjacent ovarian tissue was found in 37 cases ( 97 % ) . The mean thickness of ovarian tissue removed was 1173 + /- 711 microm and that of the cyst wall was 851 + /- 499 microm . The thickness of the ovarian parenchyma removed presented a direct proportional relationship with cyst diameter ( P = 0.015 ) , and consequently with cyst wall area ( P = 0.032 ) . This relationship with cyst diameter was independent after adjustment on other variables ( P = 0.032 ) . CONCLUSION Endometrioma cystectomy even though performed with an accurate surgical technique leads to significant ovarian tissue removal , the thickness of which increases proportionally with cyst diameter BACKGROUND Many women who experience endometriosis and endometriomas also encounter problems with fertility . OBJECTIVE The purpose of this study was to determine the impact of surgical excision of endometriosis and endometriomas compared with control subjects on ovarian reserve . STUDY DESIGN This was a prospect i ve cohort study of 116 women aged 18 - 43 years with pelvic pain and /or infertility who underwent surgical treatment of suspected endometriosis ( n=58 ) or endometriomas ( n=58 ) . Based on surgical findings , the suspected endometriosis group was further separated into those with evidence of peritoneal disease ( n=29 ) and those with no evidence of endometriosis ( n=29 ) . Ovarian reserve was measured by anti-Müllerian hormone and compared before surgery and at 1 month and 6 months after surgery . RESULTS Baseline anti-Müllerian hormone values were significantly lower in the endometrioma vs negative laparoscopy group ( 1.8 ng/mL [ 95 % confidence interval , 1.2 - 2.4 ng/mL ] vs 3.2 ng/mL [ 95 % confidence interval , 2.0 - 4.4 ng/mL ] ; P<.02 ) , but the peritoneal endometriosis group was not significantly different than either of these groups . Only patients with endometriomas had a significant decline in ovarian reserve at 1 month ( -48 % ; 95 % confidence interval , -54 to -18 % ; P<.01 ; mean anti-Müllerian hormone baseline value , 1.77 - 1.12 ng/mL at 1 month ) . Six months after surgery , anti-Müllerian hormone values continued to be depressed from baseline but were no longer significantly different . The rate of anti-Müllerian hormone decline was correlated positively with baseline preoperative anti-Müllerian hormone values and the size of endometrioma that was removed . Those with bilateral endometriomas ( n=19 ) had a significantly greater rate of decline ( 53.0 % [ 95 % confidence interval , 35.4 - 70.5 % ] vs 17.5 % [ 95 % confidence interval , 3.2 - 31.8 % ] ; P=.002 ) . CONCLUSION At baseline , patients with endometriomas had significantly lower anti-Müllerian hormone values compared with women without endometriosis . Surgical excision of endometriomas appears to have temporary detrimental effects on ovarian reserve OBJECTIVE To evaluate whether the amount of ovarian tissue inadvertently removed along with the endometrioma cyst wall at laparoscopy differs in relation to the operating surgeon 's level of expertise . DESIGN Multicenter , prospect i ve trial . SETTING Four tertiary care university hospitals . PATIENT(S ) Fifty patients , aged 25 to 40 years , with monolateral ovarian endometriomas who underwent laparoscopic excision . INTERVENTION(S ) Operation with the stripping technique by surgeons with specific expertise in endometriosis surgery in four centers ( groups A , B , C , and D ) and by residents with average training in laparoscopic surgery ( group E ) . MAIN OUTCOME MEASURE(S ) Histologic examination for the evaluation of the mean thickness of the cyst wall from each specimen , and the mean thickness and morphologic characteristics of any ovarian tissue removed . RESULT ( S ) No statistically significant differences were present in the rate of presence of ovarian tissue in the endometrioma wall specimens from the different groups ( 44 % , 45 % , 55 % , 56 % , and 60 % in groups A , B , C , D , and E , respectively ) . For groups A+B+C+D versus group E , a statistically significant difference was found in the mean thickness of the tissue specimens ( 1.51 mm vs. 1.91 mm , respectively ) and in the mean thickness of ovarian tissue inadvertently excised ( 0.49 mm vs. 0.97 mm , respectively ) . CONCLUSION ( S ) Level of expertise in endometriosis surgery is inversely correlated with inadvertent removal of healthy ovarian tissue along with the endometrioma capsule OBJECTIVE To investigate the impact on ovarian reserve of second laparoscopic surgery for recurrent unilateral endometriomas . DESIGN Case-control study . SETTING University teaching hospital . PATIENT(S ) This study included patients who underwent stripping of endometriomas ( diameter ≥4 cm ) and were followed-up at our institution . Case subjects had second surgery for recurrent unilateral endometriomas ( n = 18 ) ; control subjects had no recurrence and no second surgery ( n = 18 ) . INTERVENTION(S ) This case-control study was based on a retrospective analysis of a prospect ively collected data base including patients who underwent surgery for endometriomas at our institution . MAIN OUTCOME MEASURE(S ) The primary outcome of the study was to assess the changes in antimüllerian hormone ( AMH ) levels in each study group and between the two study groups . The secondary outcomes of the study were to assess the changes in basal FSH , antral follicle count ( AFC ) , and ovarian volume in each study group and between the two study groups . RESULT ( S ) In both study groups , primary surgery decreased AMH , increased basal FSH , and decreased the AFC of the operated ovary . Before second surgery , case subjects had AMH , basal FSH , and AFC similar to control subjects . After second surgery , case subjects had lower AMH , higher basal FSH , and lower AFC of the affected ovary than before surgery ; the volume of the operated ovary was lower than that of the contralateral ovary . CONCLUSION ( S ) The laparoscopic stripping of recurrent ovarian endometriomas is associated with a high risk of ovarian reserve damage and ovarian failure . CLINICAL TRIAL REGISTRATION NUMBER NCT02047838 To assess the impact of laparoscopic surgery on ovarian reserve , we evaluated pre- and postoperative levels of serum anti-Müllerian hormone ( AMH ) in comparison with basal levels of FSH . The median AMH level was 2.98 ng/mL and 3.92 ng/mL before operation and was significantly reduced to a median level of 2.24 ng/mL and 3.29 ng/mL at 1 month after operation in the endometrioma group ( n = 29 ) and the nonendometrioma group ( n = 21 ) , respectively , whereas postoperative basal FSH levels did not significantly change in comparison with preoperative levels STUDY OBJECTIVE To compare the postoperative decrease in ovarian reserve between hemostasis by bipolar coagulation and suture during laparoendoscopic single-site cystectomy ( LESS-C ) for ovarian endometriomas . DESIGN Prospect i ve comparative study ( Canadian Task Force Classification II-1 ) . SETTING University hospital . PATIENTS One hundred twenty-five patients with ovarian endometriomas . INTERVENTIONS Patients with endometrioma were managed by hemostasis with either bipolar coagulation ( n = 62 ) or suturing ( n = 63 ) during LESS-C. We evaluated the impact of surgery on ovarian reserve using serum anti-Müllerian hormone ( AMH ) levels , which were measured before surgery and 3 months after surgery in all patients . MEASUREMENT AND MAIN RESULTS Baseline characteristics such as age , bilaterality of endometriomas , and preoperative AMH levels were similar between the 2 study groups . There were also no differences between the 2 groups in surgical outcomes , such as operative time , operative blood loss , or operative complications . In both study groups , postoperative AMH levels were lower than preoperative AMH levels ( p < .001 ) . The decline rate of AMH levels was significantly greater in the bipolar coagulation group than in the suture group ( 42.2 % [ interquartile range , 16.5%-53.0 % ] and 24.6 % [ interquartile range , 11.6%-37.0 % ] , respectively , p = .001 ) . CONCLUSION Hemostasis by bipolar coagulation after stripping of the endometrioma during LESS-C reduces ovarian reserve more than suturing does , as determined by serial AMH levels . Therefore , suturing may be a better hemostatic choice after stripping ovarian endometriomas OBJECTIVE To develop an optimal model and age-specific centiles for the decline in antimüllerian hormone ( AMH ) as measured by the new Beckman Coulter AMH Generation II ( Gen II ) assay and compare this to the previous nomogram derived for the Diagnostics Systems Laboratory ( DSL ) assay . DESIGN Multicenter retrospective population study , with validation of linear , biphasic linear , differential , power , and quadratic equations . SETTING Two clinical pathology laboratories . PATIENT(S ) A new cohort of 10,984 women aged 25 to 45 years old attending infertility clinics , r and omly divided into a training cohort of 5,492 women and a validation cohort of 5,492 women , and an existing cohort of 9,601 women , who had contributed to the development and validation of a nomogram for AMH measured by the DSL assay . INTERVENTION(S ) Serum measurement of AMH as determined by the Beckman Coulter AMH Generation II assay in 10,984 women . MAIN OUTCOME MEASURE(S ) Optimal model for the decline in AMH as measured by the AMH Gen II assay with age , with age-specific 5th , 10th , 25th , 50th , 75th , 90th , and 95th percentiles . RESULT ( S ) A quadratic model defined as ( 2.431 + 0.089 * Age + -0.003 * Age(2 ) ) fitted the decline in AMH with age . The anticipated 40 % increase in age-specific population values relative to the previously vali date d DSL assay nomogram was not observed . CONCLUSION ( S ) Age-specific reference ranges for the AMH gen II assay suggest a systematic shift in assay calibration since initial evaluation and commercial release of the AMH Gen II assay STUDY QUESTION Are anti-Müllerian hormone ( AMH ) levels lower in women with endometriosis , notably those with endometriomas ( OMAs ) and deep infiltrating lesions , compared with controls without endometriosis ? SUMMARY ANSWER Endometriosis and OMAs per se do not result in lower AMH levels . AMH levels are decreased in women with previous OMA surgery independently of the presence of current OMAs . WHAT IS KNOWN ALREADY The impact of endometriosis and OMAs per se on the ovarian reserve is controversial . Most previous studies have been conducted in infertile women . The strength of our study lies in the following points : ( i ) the selection of women undergoing surgery and not only according to the presence of infertility , ( ii ) the classification of women with endometriosis and controls based on strict surgical and histological criteria . STUDY DESIGN , SIZE , DURATION Cross-sectional study using data prospect ively collected in all non-pregnant < 42-year-old patients , who were surgically explored for a benign gynaecological condition at a university tertiary referral centre between 2004 and 2008 . For each patient , a structured question naire was completed during a face-to-face interview conducted by the surgeon during the month preceding surgery . AMH levels were measured in serum sample s drawn in the month preceding surgery , without regard to menstrual phase or hormonal therapy . PARTICIPANTS / MATERIAL S , SETTING , METHODS Operations were done on 1262 women between 2004 and 2008 , of which 1133 signed the informed consent . Of the 566 women with a visual diagnosis of endometriosis , 411 had histologically proven endometriosis . Frozen serum sample s for the AMH measurement were available in 313 of them . Out of the 554 women without visual endometriosis and without past endometriosis surgery , 413 had a frozen serum sample for the AMH measurement . Univariate analysis examined AMH levels according to baseline patient characteristics , the presence and type of endometriosis ( superficial lesion , OMA , deep infiltrating lesion ) and previous OMA surgery . Analysis of variance-covariance then examined the effects of co-variables on AMH levels . Finally , logistic regressions were conducted to examine the odds ratio ( OR ) of having AMH levels < 1 ng/ml according to the same co-variables . MAIN RESULTS AND THE ROLE OF CHANCE The difference in AMH levels between women with endometriosis and controls did not reach significance ( 3.6 ± 3.1 versus 4.1 ± 3.4 ng/ml , P = 0.06 ) . Analysis of variance-covariance demonstrated that AMH levels significantly decreased with age ( P < 0.001 ) and in women with prior OMA surgery irrespective of whether OMAs were present or not at the time of study ( P < 0.05 ) . Logistic regression revealed that two major factors were related to AMH levels < 1 ng/ml : ( i ) age ( compared with < 29 years ; 30 - 34 years OR = 3.1 , 95 % CI : 1.5 - 6.4 , P = 0.01 ; 35 - 39 years OR = 7.0 , 95 % CI : 3.5 - 14.1 , P = 0.001 ; ≥40 years OR = 20.8 , 95 % CI : 9.1 - 47.4 , P = 0.001 ) and ( ii ) prior OMA surgery ( OR = 3.0 , 95 % CI : 1.4 - 6.41 , P = 0.01 ) . LIMITATIONS , REASONS FOR CAUTION The selection of our study population was based on a surgical diagnosis . Women with an asymptomatic form of endometriosis are therefore not included in our study . We can not exclude that infertile women with OMAs associated with a diminished ovarian reserve , as assessed during their infertility work-up , were less likely to be referred for surgery and might therefore be underrepresented . WIDER IMPLICATION S OF THE FINDINGS Our findings suggest that OMAs per se do not diminish the ovarian reserve reflected by AMH levels but that alterations seen in women with endometriosis are a deleterious consequence of OMA surgery . These findings should be taken into account in the decision to operate OMAs in women with a desire for future pregnancy . STUDY FUNDING /COMPETING INTERESTS STUDY FUNDING none . Potential competing interests : none STUDY OBJECTIVE To evaluate the effects of laparoscopic cystectomy of endometrioma and nonendometrioma ovarian cyst on ovarian reserve . DESIGN Prospect i ve follow-up study of patients after laparoscopic ovarian cystectomy ( Canadian Task Force II-2 ) . SETTING Academic hospital . PATIENTS Seventy patients underwent laparoscopic ovarian cystectomy , with bilateral endometrioma ( n = 21 ) , unilateral endometrioma ( n = 29 ) , and unilateral other benign ovarian cyst ( n = 20 ) from February 2011 and May 2012 . The control group ( n = 20 ) comprised patients treated with laparoscopic myomectomy or laparoscopic hydrotubation and fimbrioplasty at the same time period . INTERVENTIONS All laparoscopic operations were applied by suture homeostasis . Ovarian reserve was assessed by serum levels of anti-Müllerian hormone ( AMH ) and follicle-stimulating hormone ( FSH ) and by antral follicle count ( AFC ) , ovarian volume , ovarian stromal pulsatility index , and resistance index on the third day of menstruation preoperatively and in postoperative months 1.6 and 12 . MEASUREMENTS AND MAIN RESULTS FSH levels increased significantly but the AMH and AFC levels declined significantly in the bilateral endometrioma group at 1 month postoperatively compared with preoperative levels ( p < .05 ) but did not differ significantly at 6 and 12 months postoperatively . The ovarian stromal pulsatility and resistance indices in the ipsilateral ovaries decreased significantly in all patients with unilateral ovarian cysts at 6 and 12 months postoperatively compared with preoperative levels ( p < .05 ) , although the mean ipsilateral ovarian volume was significant smaller than the unaffected side . CONCLUSION There was no detectable difference on ovarian reserve marker levels between 4 groups and from baseline values at 6 and 12 months after laparoscopic ovarian cystectomy of endometrioma , although these levels significantly declined in the first month postoperatively STUDY OBJECTIVE Because laparoscopic ovarian cystectomy of endometriomas is known to adversely impact patient ovarian reserve , the search for other techniques of surgical management is ongoing . The present study was undertaken to evaluate laparoscopic cyst deroofing as a feasible alternative . STUDY DESIGN Prospect i ve , r and omized clinical trial ( Canadian Task Force classification I ) . SETTING University maternity hospital . PATIENTS Women diagnosed with unilateral or bilateral ovarian endometriomas . INTERVENTIONS Patients were managed with either laparoscopic ovarian cystectomy or cyst deroofing . MEASUREMENTS AND MAIN RESULTS A total of 122 women with endometriomas were r and omized to either laparoscopic cystectomy ( group 1 ) or laparoscopic cyst deroofing ( group 2 ) . The primary endpoint was the effect on ovarian reserve based on changes in anti-Müllerian hormone ( AMH ) values . At 1 month postsurgery , anti-Müllerian hormone values were significantly decreased ( p < .001 ) from preoperative values , from 4.25 ± 0.87ng/mL to 1.66 ± 1.02ng/mL in group 1 and from 4.2 ± 1.69ng/mL to 2.15 ± 1.48ng/mL in group 2 . In addition , antral follicle count and ovarian volume decreased significantly ( p < .001 ) in both groups by 1 month postsurgery . The decreases in these 3 parameters were more significant ( p < .001 ) in group 1 than in group 2 . CONCLUSION Laparoscopic cyst deroofing of endometriomas appears to be a promising alternative to laparoscopic cystectomy , with less postoperative decrease in ovarian reserve ; however , the higher rate of endometrioma recurrence warrants future clinical research to determine the optimal surgical management of endometriomas Abstract STUDY QUESTION Does CO2 laser vaporization offer better results in treating endometrioma in terms of ovarian reserve preservation compared to traditional cystectomy ? SUMMARY ANSWER Assessing both antral follicle count ( AFC ) and serum anti-Müllerian hormone ( AMH ) levels as measures of ovarian reserve , the results suggest that CO2 technology may be an alternative treatment for endometrioma , causing minimal damage to adjacent healthy ovarian tissue . WHAT IS KNOWN ALREADY Excisional surgery has been question ed as an ideal surgical approach for endometriomas because it is associated with potential reduction of ovarian reserve . Recently , vaporization with CO2 laser in-line-of-sight , according to the ‘ three-step procedure ’ , has been proposed as the best method to preserve ovarian function . However , no r and omized controlled trials have been conducted to compare cystectomy and ‘ one-step ’ CO2 fiber laser vaporization ( without GnRH agonist therapy ) with respect to the ovarian reserve . STUDY DESIGN , SIZE , DURATION A multicentre r and omized clinical trial including 60 patients was performed between July 2017 and February 2018 . Computerized r and omization was conducted to allocate them in a proportion of 1:1 either to Group 1 ( laparoscopic stripping : cystectomy ) or Group 2 ( CO2 laser vaporization ) . Patients in Group 1 underwent a st and ardized laparoscopic stripping technique ; patients in Group 2 underwent drainage of the cyst content , biopsy and vaporization of the internal wall with a CO2 fiber laser . Patients underwent pelvic ultrasound examination to determine the AFC and blood sampling to determine AMH levels before surgery and at 1- and 3-month follow-up . PARTICIPANTS / MATERIAL S , SETTING , METHODS Patients undergoing surgery for symptomatic endometriomas ( infertility and /or pelvic pain ) larger than 3 cm were r and omized in two groups according to the surgical technique . Patients aged ≥40 years , or with deep infiltrating endometriosis/adenomyosis , or previously su bmi tted to surgical procedures on the ovaries or to hysterectomy were excluded from the study . The primary endpoint was the comparison of intra-group AFC changes before and after surgery ( ΔAFC ) between the two groups ( ΔAFC Group 1 versus ΔAFC Group 2 ) . The secondary endpoint was the modification of serum AMH before and after surgery ( ΔAMH ) between the two groups ( ΔAMH Group 1 versus ΔAMH Group 2 ) . MAIN RESULTS AND THE ROLE OF CHANCE The AFC of the operated ovary was significantly increased in Group 2 ( laser vaporization ) compared with Group 1 ( cystectomy ) after surgery ( Group 1 : from 4.1 ± 2.2 [ mean ± SD ] at baseline to 6.3 ± 3.5 at 3-month follow-up ; 95 % CI : 0.9–4 ; Group 2 : from 3.6 ± 1.9 at baseline to 8.6 ± 4.2 at 3-month follow-up ; 95 % CI : 2.8–7.1 ; P = 0.016 ) ; serum AMH levels were significantly reduced at 3 months in Group 1 ( from 2.6 ± 1.4 ng/mL at baseline to 1.8 ± 0.8 ng/mL at 3-month follow-up ; 95 % CI : −1.3 to −0.2 ; P = 0.012 ) compared with no reduction in Group 2 ( from 2.3 ± 1.1 ng/mL at baseline to 1.9 ± 0.9 ng/mL at 3-month follow-up ; 95 % CI : −1 to −0.2 ; P = 0.09 ) . LIMITATIONS , REASON FOR CAUTION The key limitations of the trial were the low accuracy of AFC in estimating the ovarian reserve in ovaries with endometriomas , the limited study size and the relatively short follow-up , which do not allow us to draw definitive conclusions . WIDER IMPLICATION S OF THE FINDINGS The present study suggests that CO2 technology may treat endometrioma with minimal damage to the adjacent healthy ovarian tissue ; however , this study should be considered as a preliminary clinical trial , intended to stimulate future larger trials to address this clinical ly relevant issue . STUDY FUNDING /COMPETING INTEREST(S ) None . TRIAL REGISTRATION NUMBER Clinical Trials.gov NCT03227640 . TRIAL REGISTRATION DATE 9 July 2017 . DATE OF FIRST PATIENT ’S ENROLLMENT 24 July 2017 OBJECTIVE To investigate the impact of laparoscopic endometrioma cystectomy on the ovarian reserve and to identify the most important factors that predict the ovarian reserve in patients with endometriomas . DESIGN Prospect i ve study . SETTING S Endoscopy unit of a general hospital . PATIENT(S ) Fifty-four patients with unilateral ( n = 37 ) and bilateral endometriomas ( n = 17 ) . INTERVENTIONS ( S ) The serum antimüllerian hormone ( AMH ) concentration was assessed before surgery and at 6 and 12 months after surgery . MAIN OUTCOME MEASURE(S ) The primary outcome was the damage to the ovarian reserve , as assessed by the serum AMH concentration . Secondary end points were the persistence or recovery of ovarian damage after 1 year . RESULT ( S ) AMH concentrations decreased after the laparoscopic excision of cystic ovarian endometriomas . Before surgery and at 6 and 12 months after surgery , the concentrations were , respectively 3.07 , 1.29 , and 1.46 ng/mL. In the unilateral group , the median AMH levels were 3.31 , 1.43 , and 1.72 ng/mL , and in the bilateral group the levels were 2.55 , 0.98 , and 0.89 ng/mL. The serum AMH concentrations thus decreased by 53.27 ± 38.2 % and 49.43 ± 38.3 % at 6 and 12 months after cystectomy , respectively . CONCLUSION ( S ) In patients with endometriomas , the decrease in ovarian reserve occurs immediately after the excision of the endometrioma . Significant predictors of AMH values at 6 and 12 months after surgery include the baseline AMH level , patient age , and bilateral endometriomas OBJECTIVE The objective of the study was to evaluate whether anti-Müllerian hormone ( AMH ) is associated with fecundability among women with proven fecundity and a history of pregnancy loss . DESIGN This was a prospect i ve cohort study within a multicenter , block-r and omized , double-blind , placebo-controlled clinical trial ( clinical trials.gov , number NCT00467363 ) . SETTING The study was conducted at four US medical centers ( 2006 - 2012 ) . PARTICIPANTS Participating women were aged 18 - 40 years , with a history of one to two pregnancy losses who were actively attempting pregnancy . MAIN OUTCOME MEASURES Time to human chorionic gonadotropin detected and clinical pregnancy were assessed using Cox proportional hazard regression models to estimate fecundability odds ratios ( fecundability odds ratios with 95 % confidence interval [ CI ] ) adjusted for age , race , body mass index , income , low-dose aspirin treatment , parity , number of previous losses , and time since most recent loss . Analyses examined by preconception AMH levels : low ( < 1.00 ng/mL , n = 124 ) ; normal ( referent 1.00 - 3.5 ng/mL , n = 595 ) ; and high ( > 3.5 ng/mL , n = 483 ) . RESULTS Of the 1202 women with baseline AMH levels , 82 women with low AMH ( 66.1 % ) achieved an human chorionic gonadotropin detected pregnancy , compared with 383 with normal AMH ( 65.2 % ) and 315 with high AMH level ( 65.2 % ) . Low or high AMH levels relative to normal AMH ( referent ) were not associated with fecundability ( low AMH : fecundability odds ratios 1.13 , 95 % CI 0.85 - 1.49 ; high AMH : FOR 1.04 , 95 % CI 0.87 - 1.24 ) . CONCLUSIONS Lower and higher AMH values were not associated with fecundability in unassisted conceptions in a cohort of fecund women with a history of one or two prior losses . Our data do not support routine AMH testing for preconception counseling in young , fecund women |
10,796 | 28,853,146 | We found very low- quality evidence with conflicting results , when comparing the effectiveness of computer-based stress management interventions with in-person stress management interventions in employees . | BACKGROUND Chronic exposure to stress has been linked to several negative physiological and psychological health outcomes .
Among employees , stress and its associated effects can also result in productivity losses and higher healthcare costs .
In-person ( face-to-face ) and computer-based ( web- and mobile-based ) stress management interventions have been shown to be effective in reducing stress in employees compared to no intervention .
However , it is unclear if one form of intervention delivery is more effective than the other .
It is conceivable that computer-based interventions are more accessible , convenient , and cost-effective .
OBJECTIVES To compare the effects of computer-based interventions versus in-person interventions for preventing and reducing stress in workers . | This study examined effects of web-based psychoeducation on self-efficacy , problem solving behavior , stress responses and job satisfaction . The program was based on social cognitive theory and was primarily aim ed at increasing knowledge of stress , self-efficacy , and the use of problem solving behavior . A total of 225 employees were invited to participate in the study . Participants were assigned to an intervention ( n=112 ) or waiting list control group ( n=113 ) . Those in the intervention group were asked to access the website and to complete learning within 1 month . To investigate the intervention effect , the change score in the outcome variable was calculated by subtracting the score at pre-intervention from that at post-intervention ( 1 week after completion of the learning period ) . Then , the difference in the scores between groups was examined using analyses of covariance ( ANCOVA ) with the pre-intervention score as the covariate . We detected a marginally significant difference between groups in changes in job satisfaction from pre- to post-intervention ( p=0.081 ) . Participants in the intervention group showed an increase in job satisfaction score , while those in the waiting list control group showed a decrease in it . No significant differences were detected between groups in the other indicators ( p>.10 ) . We detected significant or marginally significant intervention effects on self-efficacy , problem solving behavior , stress responses , and job satisfaction among males and younger individuals , and those who had initially higher job strain and higher interest in managing stress . Further research is required with longer time periods ( controlled follow-up ) and a broader sample to fully determine the intervention effect In web-based health promotion programs , large variations in participant engagement are common . The aim was to investigate determinants of high use of a worksite self-help web-based program for stress management . Two versions of the program were offered to r and omly selected departments in IT and media companies . A static version of the program including health screening tool , diary and information about stress was offered to the control group . Additional material s , i.e. interactive , cognitive-based and classical stress management exercises and a chat room , were offered to the intervention group . Baseline data regarding participants ' demographics , health ( self-ratings and biological measures ) , lifestyle , work-related factors and group membership were analyzed to study determinants of employees ' participation in the program during a period of 12 months . Multiple logistic regression analysis was used and found intervention group membership , being a woman , having at most a secondary education , regular physical exercise habits and having positive expectations of the program were significant predictors of high use . The findings demonstrate that the interactivity of a web-based program is an important factor for determining participation in a web-based worksite stress management program . Implication s for those developing and implementing future web-based health promotion activities are discussed Background Stress is commonly experienced by many people and it is a contributing factor to many mental and physical health conditions , However , few efforts have been made to develop and test the effects of interventions for stress . Objective The aim of this study was to examine the effects of a Web-based stress-reduction intervention on stress , investigate mindfulness and procrastination as potential mediators of any treatment effects , and test whether the intervention is equally effective for females as males , all ages , and all levels of education . Methods We employed a r and omized controlled trial in this study . Participants were recruited online via Facebook and r and omly assigned to either the stress intervention or a control condition . The Web-based stress intervention was fully automated and consisted of 13 sessions over 1 month . The controls were informed that they would get access to the intervention after the final data collection . Data were collected at baseline and at 1 , 2 , and 6 months after intervention onset by means of online question naires . Outcomes were stress , mindfulness , and procrastination , which were all measured at every measurement occasion . Results A total of 259 participants were included and were allocated to either the stress intervention ( n=126 ) or the control condition ( n=133 ) . Participants in the intervention and control group were comparable at baseline ; however , results revealed that participants in the stress intervention followed a statistically different ( ie , cubic ) developmental trajectory in stress levels over time compared to the controls . A growth curve analysis showed that participants in the stress intervention ( unst and ardized beta coefficient [B]=–3.45 , P=.008 ) recovered more quickly compared to the control group ( B=–0.81 , P=.34 ) from baseline to 1 month . Although participants in the stress intervention did show increases in stress levels during the study period ( B=2.23 , P=.008 ) , long-term stress levels did decrease again toward study end at 6 months ( B=–0.28 , P=.009 ) . Stress levels in the control group , however , remained largely unchanged after 1 month ( B=0.29 , P=.61 ) and toward 6 months ( B=–0.03 , P=.67 ) . Mediation analyses showed nonlinear ( ie , cubic ) specific indirect effects of mindfulness and a linear specific indirect effect of procrastination on stress . In simple terms , the intervention increased mindfulness and decreased procrastination , which was related to lower stress levels . Finally , the effect of the stress intervention was independent of participants ’ gender , age , or education . Conclusions The results from this r and omized controlled trial suggest that a Web-based intervention can reduce levels of stress in a normal population and that both mindfulness and procrastination may be important components included in future eHealth interventions for stress . Trial Registration International St and ard R and omized Controlled Trial Number ( IS RCT N ) : 25619675 ; http://controlled-trials.com/IS RCT N25619675 ( Archived by Webcite at http://www.webcitation.org/6FxB1gOKY Background Most work sites engage in some form of health promotion programming design ed to improve worker health and reduce health care costs . Although these programs have typically been delivered through combinations of seminars and print material s , workplace health promotion programs are increasingly being delivered through the Internet . Objective The purpose of this research was to evaluate the effectiveness of a Web-based multimedia health promotion program for the workplace , design ed to improve dietary practice s , reduce stress , and increase physical activity . Methods Using a r and omized controlled trial design with pretest-posttest comparisons within each group , 419 employees of a human re sources company were r and omly assigned to the Web-based condition or to a condition that provided print material s on the same topics . All subjects were assessed at pretest and posttest through an online question naire containing multiple measures of health behavior and attitudes . The test period was 3 months . Question naire data were analyzed mainly by analysis of covariance and t tests . Results Retention rates were good for both groups—85 % for the Web-based group and 87 % for the print group . Subjects using the Web-based program performed significantly better than the print group on Attitudes Toward a Healthful Diet ( F1,415 = 7.104 , P = .008 ) and Dietary Stage of Change ( F1,408 = 6.487 , P = .01 ) , but there were no significant group differences on the five other dietary measures . Both groups also showed improvement from pretest to posttest on most dietary measures , as indicated by significant t tests . Within the Web-based group , dosage analyses showed significant effects of the number of times the subject accessed the program on measures of Dietary Self-Efficacy ( F2,203 = 5.270 , P = .003 ) , Attitudes Toward a Healthful Diet ( F2,204 = 2.585 , P = .045 ) , and Dietary Stage of Change ( F2,200 = 4.627 , P = .005 ) . No significant differences were found between the two groups on measures of stress or physical activity , although t tests of pretest-posttest changes indicated that both groups improved on several of these measures . The Web-based group gave significantly higher ratings to the program material s than the print group on all health topics and in their overall evaluation ( F1,410 = 9.808 , P = .002 ) . Conclusions The Web-based program was more effective than print material s in producing improvements in the areas of diet and nutrition but was not more effective in reducing stress or increasing physical activity . The higher ratings given to the Web-based program suggest that workers preferred it to the print material s. Both groups showed numerous pretest-posttest improvements in all health topics , although such improvements might be attributable in part to a Hawthorne effect . Results suggest that a multimedia Web-based program can be a promising means of delivering health promotion material to the workforce , particularly in the area of diet and nutrition Background Depression and anxiety are major causes of absence from work and underperformance in the workplace . Cognitive behavioural therapy ( CBT ) can be effective in treating such problems and online versions offer many practical advantages . The aim of the study was to investigate the effectiveness of a computerized CBT intervention ( MoodGYM ) in a workplace context . Method The study was a phase III two-arm , parallel r and omized controlled trial whose main outcome was total score on the Work and Social Adjustment Scale ( WSAS ) . Depression , anxiety , psychological functioning , costs and acceptability of the online process were also measured . Most data were collected online for 637 participants at baseline , 359 at 6 weeks marking the end of the intervention and 251 participants at 12 weeks post-baseline . Results In both experimental and control groups depression scores improved over 6 weeks but attrition was high . There was no evidence for a difference in the average treatment effect of MoodGYM on the WSAS , nor for a difference in any of the secondary outcomes . Conclusions This study found no evidence that MoodGYM was superior to informational websites in terms of psychological outcomes or service use , although improvement to subthreshold levels of depression was seen in nearly half the patients in both groups Background Recent studies have shown the potential of Web-based interventions for changing dietary and physical activity ( PA ) behavior . However , the pathways of these changes are not clear . In addition , nonusage poses a threat to these interventions . Little is known of characteristics of participants that predict usage . Objective In this study we investigated the users and effect of the Healthy Weight Assistant ( HWA ) , a Web-based intervention aim ed at healthy dietary and PA behavior . We investigated the value of a proposed framework ( including social and economic factors , condition-related factors , patient-related factors , reasons for use , and satisfaction ) to predict which participants are users and which participants are nonusers . Additionally , we investigated the effectiveness of the HWA on the primary outcomes , self-reported dietary and physical activity behavior . Methods Our design was a two-armed r and omized controlled trial that compared the HWA with a waiting list control condition . A total of 150 participants were allocated to the waiting list group , and 147 participants were allocated to the intervention group . Online question naires were filled out before the intervention period started and after the intervention period of 12 weeks . After the intervention period , respondents in the waiting list group could use the intervention . Objective usage data was obtained from the application itself . Results In the intervention group , 64 % ( 81/147 ) of respondents used the HWA at least once and were categorized as “ users . ” Of these , 49 % ( 40/81 ) used the application only once . Increased age and not having a chronic condition increased the odds of having used the HWA ( age : beta = 0.04 , P = .02 ; chronic condition : beta = 2.24 , P = .003 ) . Within the intervention group , users scored better on dietary behavior and on knowledge about healthy behavior than nonusers ( self-reported diet : χ2 2 = 8.4 , P = .02 ; knowledge : F1,125 = 4.194 , P = .04 ) . Furthermore , users underestimated their behavior more often than nonusers , and nonusers overestimated their behavior more often than users ( insight into dietary behavior : χ2 2 = 8.2 , P = .02 ) . Intention-to-treat analyses showed no meaningful significant effects of the intervention . Exploratory analyses of differences between pretest and posttest scores of users , nonusers , and the control group showed that on dietary behavior only the nonusers significantly improved ( effect size r = −.23 , P = .03 ) , while on physical activity behavior only the users significantly improved ( effect size r = −.17 , P = .03 ) . Conclusions Respondents did not use the application as intended . From the proposed framework , a social and economic factor ( age ) and a condition-related factor ( chronic condition ) predicted usage . Moreover , users were healthier and more knowledgeable about healthy behavior than nonusers . We found no apparent effects of the intervention , although exploratory analyses showed that choosing to use or not to use the intervention led to different outcomes . Combined with the differences between groups at baseline , this seems to imply that these groups are truly different and should be treated as separate entities . Trial registration Trial ID number : IS RCT N42687923 ; http://www.controlled-trials.com/IS RCT N42687923/ ( Archived by WebCite at http://www.webcitation.org/5xnGmvQ9Y BACKGROUND Fatigue is a common complaint that may lead to long-term sick leave and work disability . AIMS To assess the efficacy of cognitive-behavioural therapy by general practitioners for unexplained , persistent fatigue among employees . METHOD A r and omised controlled trial , using a pre-r and omisation design in primary care , investigated 151 employees on sick leave with fatigue . Participants in the experimental group were offered five to seven 30 min sessions of cognitive-behavioural therapy by a general practitioner ; those in the control group were offered no treatment . Main outcome measures ( fatigue severity , self-reported absenteeism , registered absenteeism and clinical recovery ) were assessed at 4 months , 8 months and 12 months . RESULTS At baseline , 44 % of the patients already met research criteria for chronic fatigue syndrome . There was no significant difference between the experimental group and the control group on primary or secondary outcomes at any point . CONCLUSIONS Cognitive-behavioural therapy by general practitioners for unexplained , persistent fatigue did not prove to be an effective intervention . Since these doctors were unable to deliver this therapy effectively under ideal circumstances , it is unlikely that doctors in routine practice would be more successful in doing so Background Internet- and mobile based stress-management interventions ( iSMI ) may be an effective means to address the negative consequences of occupational stress . However , available results from r and omised controlled trials are conflicting . Moreover , it is yet not clear whether guided or unguided self-help iSMI provide better value for money . Internet-based mental health interventions without guidance are often much less effective than interventions including at least some guidance from a professional . However , direct comparisons in r and omised controlled trials are scarce and , to the best of our knowledge , the comparative (cost)-effectiveness of guided vs. unguided iSMI has not yet been studied . Hence , this study investigates the acceptability and ( cost- ) effectiveness of minimal guided and unguided iSMI in employees with heightened levels of perceived stress . Methods A three-armed r and omised controlled trial ( RCT ) will be conducted to compare a minimal guided and unguided iSMI with a waiting list control condition ( WLC ) . Both active conditions are based on the same iSMI , i.e. GET.ON Stress , and differ only with regard to the guidance format . Employees with heightened levels of perceived stress ( PSS ≥ 22 ) will be r and omised to one of three conditions . Primary outcome will be comparative changes in perceived stress ( PSS ) . Secondary outcomes include changes in self-reported depression , work-engagement , presenteeism and absenteeism . Moreover , a cost-effectiveness analysis will be conducted from a societal perspective , including both direct medical costs and costs related to productivity losses . In addition , a cost-benefit analysis will be conducted from the employer ’s perspective . Incremental net-benefit regression analyses will address the question if there are any baseline factors ( i.e. subgroups of employees ) associated with particularly favorable cost-effectiveness when the experimental intervention is offered . Assessment s take place at baseline , 7 weeks post-treatment and 6 months after r and omisation . Discussion Online-based ( guided ) self-help interventions could be an acceptable , effective and economically sustainable approach to offer evidence -based intervention alternatives to reduce the negative consequences associated with work-related stress . This study evaluates the ( cost- ) effectiveness of two versions of an iSMI , minimal guided and unguided iSMI . Thus , the present study will further enhance the evidence -base for iSMI and provide valuable information about the optimal balance between outcome and economic costs . Trial registration German Clinical Trial Registration ( DRKS ) : DRKS00005687 Highly stressed employees are subject to greater health risks , increased cost , and productivity losses than those with normal stress levels . To address this issue in an evidence -based manner , worksite stress management programs must be able to engage individuals as well as capture data on stress , health indices , work productivity , and health care costs . In this r and omized controlled pilot , our primary objective was to evaluate the viability and proof of concept for two mind-body workplace stress reduction programs ( one therapeutic yoga-based and the other mindfulness-based ) , in order to set the stage for larger cost-effectiveness trials . A second objective was to evaluate 2 delivery venues of the mindfulness-based intervention ( online vs. in-person ) . Intention-to-treat principles and 2 ( pre and post ) × 3 ( group ) repeated- measures analysis of covariance procedures examined group differences over time on perceived stress and secondary measures to clarify which variables to include in future studies : sleep quality , mood , pain levels , work productivity , mindfulness , blood pressure , breathing rate , and heart rate variability ( a measure of autonomic balance ) . Two hundred and thirty-nine employee volunteers were r and omized into a therapeutic yoga worksite stress reduction program , 1 of 2 mindfulness-based programs , or a control group that participated only in assessment . Compared with the control group , the mind-body interventions showed significantly greater improvements on perceived stress , sleep quality , and the heart rhythm coherence ratio of heart rate variability . The two delivery venues for the mindfulness program produced basically equivalent results . Both the mindfulness-based and therapeutic yoga programs may provide viable and effective interventions to target high stress levels , sleep quality , and autonomic balance in employees Background A number of psychoeducational programs based on cognitive behavioral therapy ( CBT ) to alleviate psychological distress have been developed for implementation in clinical setting s. However , while these programs are considered critical components of stress management education in a workplace setting , they are required to be brief and simple to implement , which can hinder development . Objective The intent of the study was to examine the effects of a brief training program based on CBT in alleviating psychological distress among employees and facilitating self-evaluation of stress management skills , including improving the ability to recognize dysfunctional thinking patterns , transform dysfunctional thoughts to functional ones , cope with stress , and solve problems . Methods Of the 187 employees at an information technology company in Tokyo , Japan , 168 consented to participate in our non-blinded r and omized controlled study . The training group received CBT group education by a qualified CBT expert and 1 month of follow-up Web-based CBT homework . The effects of this educational program on the psychological distress and stress management skills of employees were examined immediately after completion of training and then again after 6 months . Results Although the training group did exhibit lower mean scores on the Kessler-6 ( K6 ) scale for psychological distress after 6 months , the difference from the control group was not significant . However , the ability of training group participants to recognize dysfunctional thinking was significantly improved both immediately after training completion and after 6 months . While the ability of participants to cope with stress was not significantly improved immediately after training , improvement was noted after 6 months in the training group . No notable improvements were observed in the ability of participants to transform thoughts from dysfunctional to functional or in problem-solving skills . A sub- analysis of participants who initially exhibited clinical ly significant psychological distress ( K6 score ≥5 ) showed that the mean K6 score was significantly improved immediately after training completion for the training group compared to the control group ( −2.50 vs −0.07 ; mean difference 2.43 , 95 % CI 0.55 - 4.31 ; d=0.61 ) , with this effect remaining even after 6 months ( −3.49 vs −0.50 ; mean difference 2.99 , 95 % CI 0.70 - 5.29 ; d=0.60 ) . Conclusions Our results suggest that a brief stress management program that combines group CBT education with Web-based CBT homework moderately alleviates the distress of employees with clinical ly significant psychological distress . In addition , the program might help improve employees ’ ability to evaluate their own stress management skills Background A considerable percentage of flight crew reports to be fatigued regularly . This is partly caused by irregular and long working hours and the crossing of time zones . It has been shown that persistent fatigue can lead to health problems , impaired performance during work , and a decreased work-private life balance . It is hypothesized that an intervention consisting of tailored advice regarding exposure to daylight , optimising sleep , physical activity , and nutrition will lead to a reduction of fatigue in airline pilots compared to a control group , which receives a minimal intervention with st and ard available information . Methods / design The study population will consist of pilots of a large airline company . All pilots who posses a smartphone or tablet , and who are not on sick leave for more than four weeks at the moment of recruitment , will be eligible for participation . In a two-armed r and omised controlled trial , participants will be allocated to an intervention group that will receive the tailored advice to optimise exposure to daylight , sleep , physical activity and nutrition , and a control group that will receive st and ard available information . The intervention will be applied using a smartphone application and a website , and will be tailored on flight- and participant-specific characteristics . The primary outcome of the study is perceived fatigue . Secondary outcomes are need for recovery , duration and quality of sleep , dietary and physical activity behaviours , work-private life balance , general health , and sickness absence . A process evaluation will be conducted as well . Outcomes will be measured at baseline and at three and six months after baseline . Discussion This paper describes the development of an intervention for airline pilots , consisting of tailored advice ( on exposure to daylight and sleep- , physical activity , and nutrition ) applied into a smartphone application . Further , the paper describes the design of the r and omised controlled trial evaluating the effect of the intervention on fatigue , health and sickness absence . If proven effective , the intervention can be applied as a new and practical tool in fatigue management . Results are expected at the end of 2013.Trial registration Netherl and s Trial Register : Background Work-related stress is highly prevalent among employees and is associated with adverse mental health consequences . Web-based interventions offer the opportunity to deliver effective solutions on a large scale ; however , the evidence is limited and the results conflicting . Objective This r and omized controlled trial evaluated the efficacy of guided Web- and mobile-based stress management training for employees . Methods A total of 264 employees with elevated symptoms of stress ( Perceived Stress Scale-10 , PSS-10≥22 ) were recruited from the general working population and r and omly assigned to an Internet-based stress management intervention ( iSMI ) or waitlist control group . The intervention ( GET.ON Stress ) was based on Lazarus ’s transactional model of stress , consisted of seven sessions , and applied both well-established problem solving and more recently developed emotion regulation strategies . Participants also had the opportunity to request automatic text messages on their mobile phone along with the iSMI . Participants received written feedback on every completed session from an e-coach . The primary outcome was perceived stress ( PSS-10 ) . Web-based self-report assessment s for both groups were scheduled at baseline , 7 weeks , and 6 months . At 12 months , an extended follow-up was carried out for the iSMI group only . Results An intention-to-treat analysis of covariance revealed significantly large effect differences between iSMI and waitlist control groups for perceived stress at posttest ( F 1,261=58.08 , P<.001 ; Cohen ’s d=0.83 ) and at the 6-month follow-up ( F 1,261=80.17 , P<.001 ; Cohen ’s d=1.02 ) . The effects in the iSMI group were maintained at 12-month follow-up . Conclusions This Web- and mobile-based intervention has proven effective in reducing stress in employees in the long term . Internet-based stress management interventions should be further pursued as a valuable alternative to face-to-face interventions . Trial Registration German Clinical Trials Register ( DRKS ) : 00004749 ; http://drks-neu.uniklinik-freiburg.de/ drks_web/setLocale_EN.do ( Archived by WebCite at http://www.webcitation.org/6e8rl98nl PURPOSE Our goal was to evaluate the efficacy of a multimedia support program delivered over the Internet to employed family caregivers of persons with dementia . DESIGN AND METHODS The evaluation of this program involved 299 employed family caregivers participating in a pretest-posttest r and omized clinical trial with a 30-day follow-up and a waitlist control condition . Vali date d instruments include the Center for Epidemiologic Studies -Depression scale , the State-Trait Anxiety Inventory , the Caregiver Strain scale from Benjamin Rose , and Positive Aspects of Caregiving used in the nationwide REACH study . RESULTS Those who viewed Caregiver 's Friend : Dealing with Dementia 30 days postexposure demonstrated significant improvements in depression , anxiety , level and frequency of stress , caregiver strain , self-efficacy , and intention to seek help , as well as perceptions of positive aspects of caregiving . IMPLICATION S Interactive multimedia interventions delivered over the Internet appear to be uniquely suited to provide low-cost , effective , convenient , individually tailored programs that present educational information , cognitive and behavioral skills , and affective learning opportunities . This makes Web-based multimedia a promising avenue for work-life balance programs , employee-assistance providers , and organizations interested in improving family caregiver health and well-being Background There has been continuing change in the nature of care homes in the UK with 80 % of residents now living with some form of dementia or memory problem . Caring in this environment can be complex , challenging and stressful for staff ; this can affect the quality of care provided to residents , lead to staff strain and burnout , and increase sickness , absence and turnover rates . It is therefore important to find interventions to increase the wellbeing of staff that will not only benefit staff themselves but also residents and care providers . Mindfulness training is known to be effective in treating a variety of physical and mental health conditions . Methods and design The study uses mixed methods centred on a stepped-wedge cluster r and omised trial . Thirty care homes in Wales are implementing a brief web-based mindfulness training course , starting in r and om sequence . Four to ten consenting staff from each facility undertake the course and complete vali date d question naires at baseline and after eight and 20 weeks . We shall also interview a stratified sample of ten trained staff and analyse the transcripts thematically . The primary outcome is stress ; secondary outcomes include job satisfaction , attitudes towards residents and sickness absence rates . Discussion With increasing numbers of people living with dementia in care homes and causing stress in their carers , it is important to evaluate support strategies for staff . Mindfulness-based therapies may be of potential benefit and need detailed examination . Trial registration IS RCT N registry . IS RCT N80487202 . Registered 24 July 2013 Objective : Mental health problems often affect functioning to such an extent that they result in sick leave . The worldwide reported prevalence of mental health problems in the working population is 10%–18 % . In developed countries , mental health problems are one of the main grounds for receiving disability benefits . In up to 90 % of cases the cause is stress-related , and health-care utilisation is mainly restricted to primary care . The aim of this study was to assess the effectiveness of our Minimal Intervention for Stress-related mental disorders with Sick leave ( MISS ) in primary care , which is intended to reduce sick leave and prevent chronicity of symptoms . Design : Cluster-r and omised controlled educational trial . Setting : Primary health-care practice s in the Amsterdam area , The Netherl and s. Participants : A total of 433 patients ( MISS n = 227 , usual care [ UC ] n = 206 ) with sick leave and self-reported elevated level of distress . Interventions : Forty-six primary care physicians were r and omised to either receive training in the MISS or to provide UC . Eligible patients were screened by mail . Outcome Measures : The primary outcome measure was duration of sick leave until lasting full return to work . The secondary outcomes were levels of self-reported distress , depression , anxiety , and somatisation . Results : No superior effect of the MISS was found on duration of sick leave ( hazard ratio 1.06 , 95 % confidence interval 0.87–1.29 ) nor on severity of self-reported symptoms . Conclusions : We found no evidence that the MISS is more effective than UC in our study sample of distressed patients . Continuing research should focus on the potential beneficial effects of the MISS ; we need to investigate which elements of the intervention might be useful and which elements should be adjusted to make the MISS effective Background Insomnia and work-related stress often co-occur . Both are associated with personal distress and diminished general functioning , as well as substantial socio-economic costs due to , for example , reduced productivity at the work place and absenteeism . Insomnia complaints by people experiencing work-related stress are correlated with a deficient cognitive detachment from work . Diffuse boundaries between work and private life can additionally complicate the use of recreational activities that facilitate cognitive detachment . Cognitive behavioral therapy for insomnia is effective but rarely implemented . Internet-based cognitive behavioral therapy for insomnia could potentially reduce this deficit given its demonstrated effectiveness . Less is known , however , about the efficacy of internet-based cognitive behavioral therapy for insomnia in population s affected by high work stress . Thus , the aim of the present study is to evaluate the efficacy and cost-effectiveness of a newly developed , guided online training which is based on Cognitive Behavioral Therapy for insomnia and tailored to teachers affected by occupational stress . Methods / Design In a two-arm r and omized controlled trial ( N = 128 ) , the effects of a guided online sleep training will be compared to a waitlist-control condition . German teachers with significant clinical insomnia complaints ( Insomnia Severity Index ≥15 ) and work-related rumination ( Irritation Scale , subscale Cognitive Irritation ≥15 ) will be included in the study . The primary outcome measure will be insomnia severity . Additionally , an economic evaluation from a societal perspective will be conducted . Data from the intention-to-treat sample will be analyzed two and six months after r and omization . Discussion To the best of our knowledge , this is the first study to evaluate an online sleep training tailored to a specific population with work stress , that is , teachers . If this type of intervention is effective , it could reduce the paucity of cognitive behavioral therapy for insomnia and augment the support for teachers in coping with their insomnia problems . Trial registration German Clinical Trial Register Background Mental health issues pose a serious concern in the workplace for the huge productivity loss and financial burden associated with it . Unlike the traditional ‘ fixing-what-is-wrong ’ approach , positive psychology offers a less-stigmatized way to promote mental health . Psychological capital , a concept originated from positive psychology , has been proven effective in improving mental well-being and work performance . However , little evidence exists for its implementation among Asian working population or its cost-benefit for organizations adopting such promotion strategy . The current study is design ed to assess the protective effects of a web-based psychology capital intervention among Hong Kong working population on individuals ’ mental health and work performance , as well as organizations ’ return-on-investment . Methods / Design A two-arm r and omized controlled trial design will be adopted . Eligible working adults will be r and omly allocated to either the intervention group or the waiting-list control group , with 177 participants in each arm . The intervention , which consists of four web-based training sessions , each targeting one of the psychological capital components ( hope , efficacy , optimism and resilience ) , will be implemented over a 4-week period . On-line surveys will assess the participants in each group at baseline , intervention completion , 1 and 3 months after the completion . The primary outcome is individuals ’ psychological capital level ; secondary outcomes include individuals ’ well-being , depressive symptoms , work engagement and productivity . Return-on-investment will be calculated from the employers ’ perspective based on productivity gain , savings in medical expenditure , as well as operation and time costs . Analysis will follow the intention-to-treat principle . Discussion This is the first experimental study that explores the applicability of psychological capital development among Asian population . Through investigating changes in individuals ’ work productivity from absenteeism and presenteeism , this will be one of the few studies that quantify productivity gains from any type of mental health promotion . By demonstrating effectiveness in improving mental well-being and a positive return-on-investment rate , the study may help convince more uptake of similar positive psychology interventions at workplace in Asia and elsewhere . Trail Registration Number ( assigned by Centre for Clinical Trials , Clinical Trials Registry , The Chinese University of Hong Kong ) : CUHK_CCT00396 . Registration Date : Objectives To investigate the feasibility of recruitment , adherence and likely effectiveness of an e-learning intervention for managers to improve employees ’ well-being and reduce sickness absence . Methods The GEM Study ( guided e-learning for managers ) was a mixed methods pilot cluster r and omised trial . Employees were recruited from four mental health services prior to r and omising three services to the intervention and one to no-intervention control . Intervention managers received a facilitated e-learning programme on work-related stress . Main outcomes were Warwick Edinburgh Mental Wellbeing Scale ( WEMWBS ) , 12-item GHQ and sickness absence < 21 days from human re sources . 35 in-depth interviews were undertaken with key informants , managers and employees , and additional observational data collected . Results 424 of 649 ( 65 % ) employees approached consented , of whom 350 provided WEMWBS at baseline and 284 at follow-up ; 41 managers out of 49 were recruited from the three intervention clusters and 21 adhered to the intervention . WEMWBS scores fell from 50.4–49.0 in the control ( n=59 ) and 51.0–49.9 in the intervention ( n=225 ) , giving an intervention effect of 0.5 ( 95 % CI −3.2 to 4.2 ) . 120/225 intervention employees had a manager who was adherent to the intervention . HR data on sickness absence ( n=393 ) showed no evidence of effect . There were no effects on GHQ score or work characteristics . Online quiz knowledge scores increased across the study in adherent managers . Qualitative data provided a rich picture of the context within which the intervention took place and managers ’ and employees ’ experiences of it . Conclusions A small benefit from the intervention on well-being was explained by the mixed methods approach , implicating a low intervention uptake by managers and suggesting that education alone may be insufficient . A full trial of the guided e-learning intervention and economic evaluation is feasible . Future research should include more active encouragement of manager motivation , reflection and behaviour change . Trial Registration number IS RCT N58661009 This study evaluated the effectiveness of a computer-based stress management training ( SMT ) program in improving employees ’ psychological well-being and work performance . A total of 12 work units ( N=263 ) were r and omly assigned to either an intervention group ( 8 work units , n=142 ) or to a wait-list control group ( 4 work units , n=121 ) . All participants were requested to answer online question naires assessing psychological well-being as a primary outcome , and coping style , social support , and knowledge about stress management as secondary outcomes at baseline ( T0 ) , immediately after the intervention ( T1 ) , and 2 months after the intervention ( T2 ) . The group × time interaction was tested using a mixed-model repeated measures ANOVA . Results showed a group × time interaction for “ knowledge about stress management ” in the entire sample . Among participants who had more than 3 d of training , a significant group × time interaction was observed for “ problem-solving ” and “ avoidance and suppression ” as well as “ knowledge about stress management . ” Our computer-based stress management program was effective for improving knowledge about stress management . It was also effective for improving coping skills in instances where participants had enough time ( at least 3 d ) to complete all sessions Objective : The objective of this study was to determine whether a mindfulness program , created for the workplace , was both practical and efficacious in decreasing employee stress while enhancing resiliency and well-being . Methods : Participants ( 89 ) recruited from The Dow Chemical Company were selected and r and omly assigned to an online mindfulness intervention ( n = 44 ) or wait-list control ( n = 45 ) . Participants completed the Perceived Stress Scale , the Five Facets of Mindfulness Question naire , the Connor-Davidson Resiliency Scale , and the Shirom Vigor Scale at pre- and postintervention and 6-month follow-up . Results : The results indicated that the mindfulness intervention group had significant decreases in perceived stress as well as increased mindfulness , resiliency , and vigor . Conclusions : This online mindfulness intervention seems to be both practical and effective in decreasing employee stress , while improving resiliency , vigor , and work engagement , thereby enhancing overall employee well-being Objective : To evaluate the effectiveness of a web-based multimedia health promotion program for the workplace , design ed to help reduce stress and to prevent depression , anxiety , and substance abuse . Methods : Using a r and omized controlled trial design , 309 working adults were r and omly assigned to the web-based condition or to a wait-list control condition . All participants were assessed on multiple self-reported outcomes at pretest and posttest . Results : Relative to controls , the web-based group reduced their stress , increased their knowledge of depression and anxiety , developed more positive attitudes toward treatment , and adopted a more healthy approach to alcohol consumption . Conclusions : We found that a brief and easily adaptable web-based stress management program can simultaneously reduce worker stress and address stigmatized behavioral health problems by embedding this prevention material into a more positive stress management framework Background . As distress in society increases , including work environments , individual capacities to compete with stress have to be strengthened . Objective . We examined the impact of a web-based happiness training on psychological and physiological parameters , by self-report and objective means , in an occupational health setting . Methods . R and omized controlled trial with 147 employees . Participants were divided into intervention ( happiness training ) and control groups ( waiting list ) . The intervention consisted of a seven-week online training . Question naires were administered before , after , and four weeks after training . The following scales were included : VAS ( happiness and satisfaction ) , WHO-5 Well-being Index , Stress Warning Signals , Freiburg Mindfulness Inventory , Recovery Experience Question naire , and Flourishing Scale . Subgroup sample s for saliva cortisol and alpha-amylase determinations were taken , indicating stress , and Attention Network Testing for effects on attention regulation . Results . Happiness ( P = 0.000 ; d = 0.93 ) , satisfaction ( P = 0.000 ; d = 1.17 ) , and quality of life ( P = 0.000 ; d = 1.06 ) improved ; perceived stress was reduced ( P = 0.003 ; d = 0.64 ) ; mindfulness ( P = 0.006 ; d = 0.62 ) , flourishing ( P = 0.002 ; d = 0.63 ) , and recovery experience ( P = 0.030 ; d = 0.42 ) also increased significantly . No significant differences in the Attention Network Tests and saliva results occurred ( intergroup ) , except for one saliva value . Conclusions . The web-based training can be a useful tool for stabilizing health/psychological well-being and work/life balance OBJECTIVES In case of long-term sick leave , gradually increasing workload appears to be an effective component of work-directed interventions to reduce sick leave due to common mental disorders ( CMD ) . CMD are defined as stress-related , adjustment , anxiety , or depressive disorders . We developed an exposure-based return-to-work ( RTW-E ) intervention and evaluated the effect on time-to-full return to work ( RTW ) among workers who were on sick leave due to CMD in comparison to those treated with care-as-usual ( CAU ) . CAU is guideline -directed and consists of problem-solving strategies and grade d activities . METHODS Using a two-armed cluster-r and omized trial , we r and omized 56 occupational physicians ( OP ) . Of these , 35 OP treated 160 workers at the start of their sick leave ; 75 workers received RTW-E and 85 workers received CAU . These workers were followed over a 12-month follow-up period . The time-to-full RTW lasting ≥28 days without recurrence was the primary outcome measure . To evaluate differences between groups , we used intention-to-treat and multilevel Cox 's regression analysis . RESULTS The median time-to-full RTW differed significantly between groups [ hazard ratio ( HR ) 0.55 ; 95 % confidence interval ( 95 % CI ) 0.33 - 0.89 ] . The workers receiving RTW-E ( 209 days ; 95 % CI 62 - 256 ) had a prolonged time-to-full RTW compared to workers receiving CAU ( 153 days ; 95 % CI 128 - 178 ) . CONCLUSIONS Workers on sick leave due to CMD treated with RTW-E showed a prolonged time-to-full RTW compared to those treated with CAU . We recommend that OP do not apply RTW-E but continue counseling workers on sick leave due to CMD according to CAU Background Depressive disorders are highly prevalent in the working population and are associated with excessive costs . The evidence for effective worker-directed interventions for employees with depressive symptoms is limited . Treating employees with depressive symptoms via the Internet before they report sick from work could be beneficial and cost saving . Objective In this study , we tested the effectiveness over the period of 1 year of a Web-based guided self-help intervention , called Happy@Work , for employees with depressive symptoms who were not on sick leave . Methods A two-arm r and omized controlled trial comparing a worker-directed , Web-based , guided self-help intervention to care as usual ( CAU ) was carried out . We recruited employees from 6 companies via the company ’s Intranet and by putting up posters . The inclusion criteria were elevated depressive symptoms as measured by a score ≥16 on the Center for Epidemiologic Studies Depression scale ( CES-D ) and not being on sick leave . The intervention contained 6 lessons and consisted of problem-solving treatment and cognitive therapy . Participants were asked to su bmi t weekly assignments via the website after completion of a lesson and they received feedback from a coach via the website . Self-report question naires on depressive symptoms ( CES-D ; primary outcome ) , burnout ( Maslach Burnout Inventory , MBI ) , work performance ( Health and Work Performance Question naire , HPQ ) , duration of absenteeism , and anxiety ( Hospital Anxiety and Depression Scale , HADS ; secondary outcomes ) , were completed at baseline , posttreatment , and at 6- , and 12-month follow-up . Several subgroup and per- protocol analyses were performed . Results A total of 231 employees were r and omized to either the intervention group ( n=116 ) or to CAU ( n=115 ) . Completion of assessment s varied between 54%-74 % . Improvement in depressive symptoms between baseline and posttreatment was shown in all participants and these effects sustained over time . However , there were no differences between the 2 groups ( adjusted regression coefficient=0.46 , 95 % CI –2.11 to 3.03 , P=.72 ; Cohen ’s d=0.05 ) . Differences between groups were also not significant for the secondary outcomes . No subgroups were identified to show differences between the groups , nor did we find a between-group effect in the per- protocol analyses . Conclusions This study showed that a worker-directed , Web-based , guided self-help intervention was not more effective than CAU in reducing depressive symptoms among employees with depressive symptoms who were not on sick leave over the period of 1 year . An intervention for this specific target group might not be necessary because the recovery in the CAU group was comparable to the intervention group and sustained over a 12-month period . Trial Registration Nederl and s Trial Register ( NTR ) : NTR2993 ; http://www.trialregister.nl/trialreg/admin/ rct view.asp?TC=2993 ( Archived by WebCite at http://www.webcitation.org/6PL9pFC0n ) The aim of this study was to examine the efficacy of a 3 week mindfulness inspired protocol , delivered by an And roid application for smartphones , in reducing stress in the adult population . By using a controlled pragmatic trial , a self-help intervention group of meditators was compared with a typical control group listening to relaxing music and a waiting list group . The final sample included 56 Italian workers as participants , block r and omized to the three conditions . The self-reported level of perceived stress was assessed at the beginning and at the end of the protocol . Participants were also instructed to track their heart rate before and after each session . The results did not show any significant differences between groups , but both self-help intervention groups demonstrated an improvement in coping with stress . Nevertheless , meditators and music listeners reported a significant decrease in average heartbeats per minute after each session . Furthermore , both groups perceived a moderate but significant change in stress reduction perceptions , even if with some peculiarities . Limitations and opportunities related to the meditation protocol supported by the mobile application to reduce stress are discussed The goal of this study was to test the effectiveness of a workplace intervention targeting work-life stress and safety-related psychosocial risk factors on health and safety outcomes . Data were collected over time using a r and omized control trial design with 264 construction workers employed in an urban municipal department . The intervention involved family- and safety-supportive supervisor behavior training ( computer-based ) , followed by two weeks of behavior tracking and a four-hour , facilitated team effectiveness session including supervisors and employees . A significant positive intervention effect was found for an objective measure of blood pressure at the 12-month follow-up . However , no significant intervention results were found for self-reported general health , safety participation , or safety compliance . These findings suggest that an intervention focused on supervisor support training and a team effectiveness process for planning and problem solving should be further refined and utilized in order to improve employee health with additional research on the beneficial effects on worker safety Background Cognitive training ( CT ) is effective at improving cognitive outcomes in children with and without clinical impairment as well as older individuals . Yet whether CT is of any preventative health benefit to working age adults is controversial . Our objective was therefore to investigate the real-world efficacy of CT in the workplace , involving employees from across the working-age spectrum and addressing many of the design issues that have limited trials to date . Methods and Findings 135 white collar employees of a large Australian public sector organization were r and omised to either 16 weeks ( 20 minutes three times per week ) of online CT or an active control ( AC ) program of equal length and structure . Cognitive , wellbeing and productivity outcome measures were analysed across three timepoints : baseline , immediately after training and 6 months post-training . CT effects on cognitive outcomes were limited , even after planned subgroup analyses of cognitive capacity and age . Unexpectedly , we found that our AC condition , which comprised viewing short documentaries about the natural world , had more impact . Compared to the CT group , 6 months after the end of training , those in the AC group experienced a significant increase in their self-reported Quality of Life ( Effect Size g = .34 vs −.15 ; TIME × GROUP p = .003 ) , decrease in stress levels ( g = .22 vs −.19 ; TIME x GROUP p = .03 ) , and overall improvement in Psychological Wellbeing ( g = .32 vs −.06 ; TIME × GROUP p = .02 ) . Conclusions CT does not appear to positively impact cognition or wellbeing amongst white collar office workers ; however , short time-out respite activities may have value in the promotion of psychological wellbeing . Given looming challenges to workplace productivity , further work-based interventional research targeting employee mental health is recommended . Trial Registration This trial was registered with the Australian New Zeal and Clinical Trials Registry : ACTRN12610000604000 ( http://www.anzctr.org.au/Trial Search .aspx ) Background Work-related stress is associated with a variety of mental and emotional problems and can lead to substantial economic costs due to lost productivity , absenteeism or the inability to work . There is a considerable amount of evidence on the effectiveness of traditional face-to-face stress-management interventions for employees ; however , they are often costly , time-consuming , and characterized by a high access threshold . Web-based interventions may overcome some of these problems yet the evidence in this field is scarce . This paper describes the protocol for a study that will examine the efficacy and cost-effectiveness of a web-based guided stress-management training which is based on problem solving and emotion regulation and aim ed at reducing stress in adult employees . Methods The study will target stressed employees aged 18 and older . A r and omized controlled trial ( RCT ) design will be applied . Based on a power calculation of d=.35 ( 1-β of 80 % , α = .05 ) , 264 participants will be recruited and r and omly assigned to either the intervention group or a six-month waitlist control group . Inclusion criteria include an elevated stress level ( Cohen ’s Perceived Stress Scale-10 ≥ 22 ) and current employment . Exclusion criteria include risk of suicide or previously diagnosed psychosis or dissociative symptoms . The primary outcome will be perceived stress , and secondary outcomes include depression and anxiety . Data will be collected at baseline and seven weeks and six months after r and omization . An extended follow up at 12 months is planned for the intervention group . Moreover , a cost-effectiveness analysis will be conducted from a societal perspective and will include both direct and indirect health care costs . Data will be analyzed on an intention-to-treat basis and per protocol . Discussion The substantial negative consequences of work-related stress emphasize the necessity for effective stress-management trainings . If the proposed internet intervention proves to be ( cost- ) effective , a preventative , economical stress-management tool will be conceivable . The strengths and limitations of the present study are discussed . Trial registration German Register of Clinical Studies ( DRKS ) : Background The German welfare system follows the principle “ rehabilitation rather than pension , ” but more than the half of all disability pensioners did not utilize medical rehabilitation before their early retirement . A major barrier is the application procedure . Lack of information about the opportunity to utilize rehabilitation services restricts the chance to improve work ability and to prevent health-related early retirement by rehabilitation programs . The establishment of new access paths to medical rehabilitation services was , therefore , identified as a major challenge for rehabilitation research in a recent expertise . Thus , a web-based information guide was developed to support the application for a medical rehabilitation program . Methods / Design For this study , the development of a web-based information guide was based on the health action process approach . Four modules were established . Three modules support forming an intention by strengthening risk perception ( module 1 ) , positive outcome expectancies ( module 2 ) and self-efficacy ( module 3 ) . A fourth module aims at the realization of actual behavior by offering instructions on how to plan and to push the application process . The study on the effectiveness of the web-based information guide will be performed as a r and omized controlled trial . Persons aged 40 to 59 years with prior sick leave benefits during the preceding year will be included . A sample of 16,000 persons will be r and omly drawn from the registers of 3 pension insurance agencies . These persons will receive a question naire to determine baseline characteristics . Respondents of this first survey will be r and omly allocated either to the intervention or the control group . Both study groups will then receive letters with general information about rehabilitation . The intervention group will additionally receive a link to the web-based information guide . After 1 year , a second survey will be conducted . Additionally , administrative data will be used to determine if participants apply for rehabilitation and finally start a rehabilitation program . The primary outcomes are the proportion of applied and utilized medical rehabilitation services . Secondary outcomes are cognitions on rehabilitation , self-rated work ability , health-related quality of life and perceived disability , as well as days with sick leave benefits and days of regular employment . Discussion The r and omized controlled trial will provide highest ranked evidence to clarify whether theory-driven web-based information supports access to rehabilitation services for people with prior sickness benefits .Trial registration German Clinical Trials Register ( Identifier : DRKS00005658 , 16 January 2014 ) Background Depressive disorders are highly prevalent in the working population and are associated with excessive costs for both society and companies . Effective treatment for employees with depressive symptoms in occupational health care is limited . The purpose of this study is to investigate the effectiveness and cost-effectiveness of an indicated preventive web-based guided self-help course for employees with depressive symptoms . Methods The study is a two-arm r and omized controlled trial comparing a web-based guided self-help course with care-as-usual . The self-help course consists of 6 weekly lessons . Weekly support will be provided by a coach via the website . Subjects in the care-as-usual group do not receive any treatment in addition to regular care . 200 white collar workers from several national and international companies in the Netherl and s will be recruited via different methods such as banners on the company ’s intranet , pamphlets and posters . Subjects will be included when they : have elevated depressive symptoms ( score ≥16 on the Center for Epidemiologic Studies Depression scale ) , are 18 years of age or older , have access to the Internet and can be contacted via e-mail . Exclusion criteria are : partial or full work absenteeism , a legal labor dispute with the employer and receiving treatment from the company ’s occupational health care at study entrance . The primary outcome is depressive symptoms . Secondary outcomes include work absenteeism , work performance , burnout , anxiety , quality of life , health care use and production losses . Outcome data will be collected at 8 weeks , 6 months , and 12 months after baseline . Analyses will be based on the intention-to-treat principle . The cost-effectiveness analyses will be performed from a societal and a company ’s perspective . A process evaluation will be conducted alongside the study . Discussion This study evaluates the effectiveness and cost-effectiveness of a web-based guided self-help course for employees with depressive symptoms . This study could stimulate the use of e-mental health interventions in the worksite setting .Trial registration Nederl and s Trial Register ( NTR ) : OBJECTIVE To evaluate the short-term benefits of simple relaxation techniques in white-collar employees . MATERIAL S AND METHODS The study was a two-arm parallel group r and omized controlled trial . 152 employees were r and omly assigned to receive the 8-week programme ( N=80 ) ( relaxation breathing and progressive muscle relaxation , twice a day ) or not ( wait-list group N=72 ) . Self-reported vali date d measures were used to evaluate perceived stress , health locus of control , job and lifestyle related variables . Saliva cortisol were also sample d and measured . Adjusted mean changes on outcomes were estimated by linear mixed model analysis . 127 employees were finally analyzed ( 68 in the intervention and 59 in the control group ) . RESULTS Specific stress-related symptoms , psychological job dem and s and cortisol levels were found to be significantly decreased after 8-weeks in the intervention group . The result was probably affected by the general socio-economic condition during the study period . Cortisol levels were also significantly related with age , family situation , gender and sampling time . CONCLUSIONS Simple relaxation training ( diaphragmatic breathing and progressive muscle relaxation ) could benefit employees and it is strongly proposed that these and other similar techniques should be tested in various labour setting Background The aim of the present study was to assess possible effects on mental and physical well-being and stress-related biological markers of a web-based health promotion tool . Methods A r and omized , prospect ively controlled study was conducted with before and after measurements , involving 303 employees ( 187 men and 116 women , age 23–64 ) from four information technology and two media companies . Half of the participants were offered web-based health promotion and stress management training ( intervention ) lasting for six months . All other participants constituted the reference group . Different biological markers were measured to detect possible physiological changes . Results After six months the intervention group had improved statistically significantly compared to the reference group on ratings of ability to manage stress , sleep quality , mental energy , concentration ability and social support . The anabolic hormone dehydroepi and osterone sulphate ( DHEA-S ) decreased significantly in the reference group as compared to unchanged levels in the intervention group . Neuropeptide Y ( NPY ) increased significantly in the intervention group compared to the reference group . Chromogranin A ( CgA ) decreased significantly in the intervention group as compared to the reference group . Tumour necrosis factor α ( TNFα ) decreased significantly in the reference group compared to the intervention group . Logistic regression analysis revealed that group ( intervention vs. reference ) remained a significant factor in five out of nine predictive models . Conclusion The results indicate that an automatic web-based system might have short-term beneficial physiological and psychological effects and thus might be an opportunity in counteracting some clinical ly relevant and common stress and health issues of today Objective This r and omised controlled trial ( RCT ) aim ed to evaluate the efficacy of a self-guided internet-based stress management intervention ( iSMI ) for employees compared to a 6-month wait-list control group ( WLC ) with full access for both groups to treatment as usual . Method A sample of 264 employees with elevated symptoms of perceived stress ( Perceived Stress Scale , PSS-10 ≥22 ) was r and omly assigned to either the iSMI or to the WLC . The iSMI consisted of seven sessions and one booster session including problem-solving and emotion regulation techniques . Self-report data were assessed at baseline , at 7 weeks and at 6 months following r and omisation . The primary outcome was perceived stress ( PSS-10 ) . The secondary outcomes included other relevant mental-related and work-related health outcomes . Data were analysed based on intention-to-treat principles . Results The iSMI participants showed a significantly higher reduction in perceived stress from baseline to post-treatment at 7 weeks ( d=0.96 , 95 % CI 0.70 to 1.21 ) and to the 6-month follow-up ( d=0.65 , 95 % CI 0.40 to 0.89 ) compared to the WLC . Significant differences with small to moderate effect sizes were also found for depression , anxiety , emotional exhaustion , sleeping problems , worrying , mental health-related quality of life , psychological detachment , emotion regulation skills and presenteeism , in favour of the experimental group . At the 6 -month follow-up , all outcomes remained significantly better for the experimental group with the exception of work engagement , physical health-related quality of life and absenteeism , which were not found to significantly differ between the iSMI and WLC groups . Conclusions The iSMI investigated in this study was found to be effective in reducing typical mental-related and work-related health symptoms of stressed employees . Internet-based self-guided interventions could be an acceptable , effective and potentially cost-effective approach to reduce the negative consequences associated with work-related stress Background Common mental disorders are strongly associated with long-term sickness absence , which has negative consequences for the individual employee ’s quality of life and leads to substantial costs for society . It is important to focus on return to work ( RTW ) during treatment of sick-listed employees with common mental disorders . Factors such as self-efficacy and the intention to resume work despite having symptoms are important in the RTW process . We developed “ E-health module embedded in Collaborative Occupational health care ” ( ECO ) as a blended Web-based intervention with 2 parts : an eHealth module ( Return@Work ) for the employee aim ed at changing cognitions of the employee regarding RTW and a decision aid via email supporting the occupational physician with advice regarding treatment and referral options based on monitoring the employee ’s progress during treatment . Objective This study evaluated the effect of a blended eHealth intervention ( ECO ) versus care as usual on time to RTW of sick-listed employees with common mental disorders . Methods The study was a 2-armed cluster r and omized controlled trial . Employees sick-listed between 4 and 26 weeks with common mental disorder symptoms were recruited by their occupational health service or employer . The employees were followed up to 12 months . The primary outcome measures were time to first RTW ( partial or full ) and time to full RTW . Secondary outcomes were response and remission of the common mental disorder symptoms ( self-assessed ) . Results A total of 220 employees were included : 131 participants were r and omized to the ECO intervention and 89 to care as usual ( CAU ) . The duration until first RTW differed significantly between the groups . The median duration was 77.0 ( IQR 29.0 - 152.3 ) days in the CAU group and 50.0 ( IQR 20.8 - 99.0 ) days in the ECO group ( hazard ratio [ HR ] 1.390 , 95 % CI 1.034 - 1.870 , P=.03 ) . No significant difference was found for duration until full RTW . Treatment response of common mental disorder symptoms did not differ significantly between the groups , but at 9 months after baseline significantly more participants in the ECO group achieved remission than in the CAU group ( OR 2.228 , 95 % CI 1.115 - 4.453 , P=.02 ) . Conclusions The results of this study showed that in a group of sick-listed employees with common mental disorders , applying the blended eHealth ECO intervention led to faster first RTW and more remission of common mental disorder symptoms than CAU . Trial Registration Netherl and s Trial Register NTR2108 ; http://www.trialregister.nl/trialreg/admin/ rct view.asp?TC=2108 . ( Archived by WebCite at http://www.webcitation.org/6YBSnNx3P ) Objective : To evaluate the influence of a web-based stress management program on neck – shoulder – back pain and perceived pain-relatedness to stress in a prospect i ve and controlled study . Methods : Study points were baseline , after 6 months intervention and at 12 months follow-up on 226 news media employees in two study groups and one control group . Results : Between groups no significant differences were found at any study point . Within groups , the study group with less intensive program improved in pain-relatedness to stress at follow-up . Between baseline and after intervention , the group with more intensive program showed decreased low back pain , and the control group showed less pain-relatedness to stress . Within group differences varied according to pain localization and were inconsistent . Conclusion : Present web-based stress management program did not influence neck-shoulder-back pain or perceived pain-relatedness to stress in stress-intensive occupations Using workplaces as a unit for r and omization , a r and omized controlled trial was conducted to determine the effects of web-based supervisor training on the subject of worksite mental health on job stressors , supervisor support and psychological distress among subordinate workers . A total of eight workplaces of a sales and service company were r and omly assigned to either training workplaces or non-training workplaces . Supervisors ( n=23 ) at the training workplaces participated in web-based self-learning training on worksite mental health ; supervisors ( n=23 ) at the non-training workplaces did not . A total of 81 subordinate workers under the trained supervisors ( the intervention group ) and 108 subordinate workers under the non-trained supervisors ( the control group ) completed the Brief Job Stress Question naire ( BJSQ ) at baseline and at a three-month follow-up . No significant intervention effect was observed for any scale of the BJSQ measuring job stressors , supervisor or coworker support , or psychological distress among subordinate workers ( p<0.05 ) . The item score of work autonomy changed very little in the intervention group , while it decreased in the control group during the follow-up period , yielding a significant intervention effect ( p=0.02 ) . The item score for a friendly atmosphere in the workplace increased in the intervention group , while the score remained stable in the control group , yielding a significant intervention effect ( p=0.02 ) . While the present study failed to show any clear effect of the web-based training of supervisors on reduction of job stressors , it may be useful for maintaining worker autonomy and improving the friendliness of the worksite atmosphere Objective : The objective of this study is to determine the effectiveness of an 8-week web-based , mindfulness stress management program ( WSM ) in a corporate call center and added benefit of group support . Methods : One hundred sixty-one participants were r and omized to WSM , WSM with group support , WSM with group and expert clinical support , or wait-list control . Perceived stress , burnout , emotional and psychological well-being , mindfulness , and productivity were measured at baseline , weeks 8 and 16 , and 1 year . Results : Online usage was low with participants favoring CD use and group practice . All active groups demonstrated significant reductions in perceived stress and increases in emotional and psychological well-being compared with control . Group support improved participation , engagement , and outcomes . Conclusion : A self-directed mindfulness program with group practice and support can provide an affordable , effective , and scalable workplace stress management solution . Engagement may also benefit from combining web-based and traditional CD delivery OBJECTIVE This study was design ed to compare the initial efficacy of Motivational Interviewing ( MI ) , Online Transtheoretical Model (TTM)-tailored communications and a brief Health Risk Intervention ( HRI ) on four health risk factors ( inactivity , BMI , stress and smoking ) in a worksite sample . METHOD A r and omized clinical trial assigned employees to one of three recruitment strategies and one of the three treatments . The treatment protocol included an HRI session for everyone and in addition either a recommended three TTM online sessions or three MI in person or telephone sessions over 6 months . At the initial post-treatment assessment at 6 months , groups were compared on the percentage who had progressed from at risk to taking effective action on each of the four risks . RESULTS Compared to the HRI only group , the MI and TTM groups had significantly more participants in the Action stage for exercise and effective stress management and significantly fewer risk behaviors at 6 months . MI and TTM group outcomes were not different . CONCLUSION This was the first study to demonstrate that MI and online TTM could produce significant multiple behavior changes . Future research will examine the long-term impacts of each treatment , their cost effectiveness , effects on productivity and quality of life and process variables mediating outcomes OBJECTIVE To determine whether internet-delivered cognitive behaviour therapy ( iCBT ) for depression and anxiety reduces self-reported absenteeism in employed individuals . DESIGN , PARTICIPANTS AND SETTING We reanalysed data from five r and omised controlled trials of iCBT : two for depression ( conducted from September 2008 to February 2009 and from June 2009 to January 2010 ) , two for generalised anxiety disorder ( conducted from March 2009 to June 2009 and from July 2009 to January 2010 ) and one for social phobia ( conducted from May 2008 to July 2008 ) . Participants across Australia were recruited via a website . The inclusion criteria were : ( i ) meets criteria for the disorder of interest ; ( ii ) aged 18 years or over ; ( iii ) no previous history of a psychotic disorder or drug or alcohol misuse ; ( iv ) not actively suicidal . The iCBT courses each consisted of six online lessons ( to be completed within 11 weeks ) , homework assignments , automatic emails and re source documents . MAIN OUTCOME MEASURE The number of days absent ( self-reported absenteeism ) in the previous week . RESULTS We included 284 participants in our analysis . When data for the three disorders were combined , participants who received iCBT had significant reductions in self-reported absenteeism compared with those in the control groups ( who were on a waitlist ) ( P = 0.03 ) . When data for the three disorders were analysed separately , reductions in self-reported absenteeism for participants who received iCBT were not significantly different to those for participants in the control groups . CONCLUSION Using data from five RCTs , we showed that iCBT was associated with reductions in self-reported absenteeism . Future research should focus on replicating these findings in other context s , such as other disorders and other iCBT courses BACKGROUND A r and omized controlled trial was conducted to determine the effects of web-based supervisor training on worksite mental health on supervisor support and psychological distress among subordinate workers . METHODS Section chiefs in a computer engineering company were r and omly assigned to either a training group ( n = 9 ) or a non-training group ( n = 7 ) . The section chiefs in the training group participated in web-based self-learning training on worksite mental health . A total of 92 subordinate workers under the trained section chiefs ( the intervention group ) and 84 subordinate workers under the untrained section chiefs ( the control group ) completed a question naire at baseline and a 3-month follow-up . RESULTS The score of supervisor support greatly decreased in the control group during the follow-up period , and the score changed very little in the intervention group , with a significant intervention effect ( P = 0.032 ) . This pattern was more pronounced for one particular item dealing with the extent to which a supervisor listens to personal problems of subordinate workers ( the intervention effect , P = 0.012 ) . No intervention effect was observed for the score measuring co-worker support , psychological distress , or other job stressors among subordinate workers ( P > 0.05 ) . CONCLUSIONS It is suggested that the web-based training of supervisors on worksite mental health is useful in improving , or at least maintaining , supervisor support among subordinate workers Background : Stress , mental health and depression at the workplace have emerged as common and significant problems . The effectiveness of a stress-management program at the workplace was investigated . Methods : The effectiveness of a stress-management program was examined in workers at a highly stressful workplace using a r and omized controlled trial . The 58 workers in the office were r and omly assigned into a stress-management group ( n = 28 ) and a control group ( n = 30 ) . The stress-management program included lectures on the perception of stress , measures to cope with it , stress-management recording sheets , and e-mail counseling . This program was based on the cognitive behavioral approach . The stress-management program was carried out for 3 months , and perceived work-related stress and psychological symptoms were evaluated using : General Health Question naire (GHQ)-30 , Center for Epidemiologic Study for Depression ( CES-D ) , the Question naire of Work-Related Stress and the Effort-Reward Imbalance Question naire . Twenty-one out of the 28 in the stress-management group and all in the control group were successfully followed up . Results : In the stress-management group , a significant improvement in the depressive symptoms was observed , compared with the control group in CES-D ( p = 0.003 by two-tailed paired t-test , and p = 0.042 by repeated measure analysis of variance ) . In the multiple regression analysis , the effect of stress management on depressive symptoms at follow-up was significant ( p = 0.041 ) , controlling for potential confounding factors . However , the alleviation of perceived occupational stress was limited . Conclusions : A stress-management program based on the cognitive behavioral approach at the workplace may have potential for the prevention of depression OBJECTIVE The primary purpose of this r and omized controlled trial ( RCT ) was to evaluate the efficacy of internet-based problem-solving training ( iPST ) for employees in the educational sector ( teachers ) with depressive symptoms . The results of training were compared to those of a waitlist control group ( WLC ) . METHODS One-hundred and fifty teachers with elevated depressive symptoms ( Center for Epidemiologic Studies Depression Scale , CES-D ≥16 ) were assigned to either the iPST or WLC group . The iPST consisted of five lessons , including problem-solving and rumination techniques . Symptoms were assessed before the intervention began and in follow-up assessment s after seven weeks , three months , and six months . The primary outcome was depressive symptom severity ( CES-D ) . Secondary outcomes included general and work-specific self-efficacy , perceived stress , pathological worries , burnout symptoms , general physical and mental health , and absenteeism . RESULTS iPST participants displayed a significantly greater reduction in depressive symptoms after the intervention ( d=0.59 , 95 % CI 0.26 - 0.92 ) , after three months ( d=0.37 , 95 % CI 0.05 - 0.70 ) and after six months ( d=0.38 , 95 % CI 0.05 - 0.70 ) compared to the control group . The iPST participants also displayed significantly higher improvements in secondary outcomes . However , workplace absenteeism was not significantly affected . CONCLUSION iPST is effective in reducing symptoms of depression among teachers . Disseminated on a large scale , iPST could contribute to reducing the burden of stress-related mental health problems among teachers . Future studies should evaluate iPST approaches for use in other working population BACKGROUND Nursing is a notoriously high-stress occupation - emotionally taxing and physically draining , with a high incidence of burnout . In addition to the damaging effects of stress on nurses ' health and well being , stress is also a major contributor to attrition and widespread shortages in the nursing profession . Although there exist promising in-person interventions for addressing the problem of stress among nurses , the experience of our group across multiple projects in hospitals has indicated that the schedules and workloads of nurses can pose problems for implementing in-person interventions , and that web-based interventions might be ideally suited to addressing the high levels of stress among nurses . PURPOSE The purpose of this study was to evaluate the effectiveness of the web-based BREATHE : Stress Management for Nurses program . METHODS The r and omized controlled trial was conducted with 104 nurses in five hospitals in Virginia and one hospital in New York . The primary outcome measure was perceived nursing-related stress . Secondary measures included symptoms of distress , coping , work limitations , job satisfaction , use of substances to relieve stress , alcohol consumption , and underst and ing depression and anxiety . RESULTS Program group participants experienced significantly greater reductions than the control group on the full Nursing Stress Scale , and six of the seven subscales . No other significant results were found . Moderator analysis found that nurses with greater experience benefitted more . CONCLUSION Using a web-based program holds tremendous promise for providing nurses with the tools they need to address nursing related stress The aim of this study was to assess the effects of a 7‐week st and ardized cognitive behavioural treatment of work‐related stress conducted via e‐mail . A total of 342 people applied for treatment in reaction to a newspaper article . Initial screening reduced the sample to a heterogeneous ( sub ) clinical group of 239 participants . Participants were assigned r and omly to a waiting list condition ( n = 62 ) , or to immediate treatment ( n = 177 ) . A follow‐up was conducted 3 years after inception of the treatment . The outcome measures used were the Depression Anxiety Stress Scales ( DASS‐42 ) and the Emotional Exhaustion scale of the Maslach Burnout Inventory – General Survey ( MBI‐GS ) . Fifty participants ( 21 % ) dropped out . Both groups showed statistically significant improvements . Intention‐to‐treat analysis of covariance ( ANCOVAs ) revealed that participants in the treatment condition improved significantly more than those in the waiting control condition ( 0.001<p⩽0.025 ) . In the treatment group , the effects were large to moderate ( 0.9 (stress)⩾d⩾0.5 ( anxiety ) ) . The between‐group effects ranged from d = 0.6 ( stress ) to d = 0.1 ( anxiety ) . At follow‐up , the effects were more pronounced , but this result requires replication in view of high attrition at follow‐up . The results warrant further research on Internet‐driven st and ardized cognitive behavioural therapy for work‐related stress . Such research should include the direct comparison of this treatment with face‐to‐face treatment , and should address the optimal level of therapist contact in Internet‐driven treatment Objectives : To examine whether a Web-based cardiovascular health promotion program was associated with changes in self-reported behaviors , attitudes , and biometric indicators in a population of working adults . Methods : Employees ( n = 210 ) were recruited and r and omized into either an Internet-based or control condition . Participants completed pre- and postintervention self-report assessment s on diet , exercise , smoking , and mental health . Pre- and postintervention biometric screenings were also obtained on blood pressure , heart rate , weight , and hip/waist circumference . Results : The intervention was associated with significant improvements in dietary attitudes ( P = 0.003 ; F = 8.83 ) , dietary intentions ( P = 0.031 ; F = 4.72 ) , dietary self-efficacy ( P = 0.015 ; F = 5.97 ) , exercise self-efficacy ( P = 0.002 ; F = 9.51 ) , exercise habits ( P = 0.016 ; F = 5.94 ) , and coping with stress ( P = 0.003 ; F = 8.85 ) and depression ( P = 0.036 ; F = 4.46 ) . Conclusions : The program showed promise for promoting cardiovascular risk reduction behaviors . These results are consistent with similar Web-based interventions Background Nonadherence to treatment is a prevalent issue in Internet interventions . Guidance from health care professionals has been found to increase treatment adherence rates in Internet interventions for a range of physical and mental disorders . Evaluating different guidance formats of varying intensity is important , particularly with respect to improvement of effectiveness and cost-effectiveness . Identifying predictors of nonadherence allows for the opportunity to better adapt Internet interventions to the needs of participants especially at risk for discontinuing treatment . Objective The goal of this study was to investigate the influence of different guidance formats ( content-focused guidance , adherence-focused guidance , and administrative guidance ) on adherence and to identify predictors of nonadherence in an Internet-based mobile-supported stress management intervention ( ie , GET.ON Stress ) for employees . Methods The data from the groups who received the intervention were pooled from three r and omized controlled trials ( RCTs ) that evaluated the efficacy of the same Internet-based mobile-supported stress management intervention ( N=395 ) . The RCTs only differed in terms of the guidance format ( content-focused guidance vs waitlist control , adherence-focused guidance vs waitlist control , administrative guidance vs waitlist control ) . Adherence was defined by the number of completed treatment modules ( 0 - 7 ) . An ANOVA was performed to compare the adherence rates from the different guidance formats . Multiple hierarchical linear regression analysis was conducted to evaluate predictors of nonadherence , which included gender , age , education , symptom-related factors , and hope for improvement . Results In all , 70.5 % ( 93/132 ) of the content-focused guidance sample , 68.9 % ( 91/132 ) of the adherence-focused guidance sample , and 42.0 % ( 55/131 ) of the participants in the administrative guidance sample completed all treatment modules . Guidance had a significant effect on treatment adherence ( F2,392=11.64 , P<.001 ; ω2=.05 ) . Participants in the content-focused guidance ( mean 5.70 , SD 2.32 ) and adherence-focused guidance sample s ( mean 5.58 , SD 2.33 ) completed significantly more modules than participants in the administrative guidance sample ( mean 4.36 , SD 2.78 ; t223=4.53 , P<.001 ; r=.29 ) . Content-focused guidance was not significantly associated with higher adherence compared to adherence-focused guidance ( t262=0.42 , P=.67 ; r=.03 ) . The effect size of r=.03 ( 95 % CI –0.09 to 0.15 ) did not pass the equivalence margin of r=.20 and the upper bound of the 95 % CI lay below the predefined margin , indicating equivalence between adherence-focused guidance and content-focused guidance . Beyond the influence of guidance , none of the predictors significantly predicted nonadherence . Conclusions Guidance has been shown to be an influential factor in promoting adherence to an Internet-based mobile-supported stress management intervention . Adherence-focused guidance , which included email reminders and feedback on dem and , was equivalent to content-focused guidance with regular feedback while requiring only approximately a quarter of the coaching re sources . This could be a promising discovery in terms of cost-effectiveness . However , even after considering guidance , sociodemographic , and symptom-related characteristics , most interindividual differences in nonadherence remain unexplained . Clinical Trial DRKS00004749 ; http://drks-neu.uniklinik-freiburg.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL _ ID = DRKS00004749 ( Archived by WebCite at http://www.webcitation.org/6QiDk9Zn8 ) ; DRKS00005112 ; http://drks-neu.uniklinik-freiburg . de/drks_web/navigate.do?navigationId = trial . HTML&TRIAL_ID = DRKS00005112 ( Archived by WebCite at http://www.webcitation.org/6QiDysvev ) ; DRKS00005384 ; http://drks-neu.uniklinik-freiburg.de/ drks_web/navigate.do?navigationId = trial . HTML&TRIAL_ID = DRKS00005384 ( Archived by WebCite at http://www.webcitation.org/6QiE0xcpE Our objective was to evaluate the effect of 12 weeks of stress management training ( SMT ) , physical exercise ( PE ) and an integrated health programme ( IHP ) in a worksite setting on subjective health complaints . To do this , we r and omly split 860 employees into the following groups : control ( n = 344 ) , PE ( n = 189 ) , IHP ( comprising physical exercise and health information ) ( n = 165 ) and SMT ( n = 162 ) . There were no significant effects on subjective health complaints , sick leave or job stress . However , strong and specific positive effects were experienced for the particular goal areas defined for each intervention . The PE group showed improved general health , physical fitness and muscle pain , while the SMT group showed improved stress management . The IHP group showed the strongest effects , affecting most goals set for treatment This study investigated the effects of an internet-based self-help stress management program with a r and omized controlled design . Of 85 participants , 26 % dropped out , leaving a final sample of 63 participants with 23 in the treatment group and 40 in the waiting list control group . Treatment included applied relaxation , problem solving , time management and cognitive restructuring . All information and treatment interventions were provided via the internet . Results were evaluated with the Perceived Stress Scale and the Hospital Anxiety and Depression Scale . Improvements were seen in both groups , with greater improvements in the self-help treatment group . It is concluded that the internet can be used to provide stress management techniques and result in stress relief . However , spontaneous improvement , differential dropout rate and compliance need to be monitored in future studies The cluster r and omized trial with a concurrent economic evaluation is considered the gold st and ard evaluative design for the conduct of implementation research evaluating different strategies to promote the transfer of research findings into clinical practice . This has implication s for the planning of such studies , as information is needed on the effects of clustering on both effectiveness and efficiency outcomes . This paper describes the design considerations specific to implementation research studies , focusing particularly on the estimation of sample size requirements and on the need for reliable information on intracluster correlation coefficients for both effectiveness and efficiency outcomes BACKGROUND Emotional distress has major implication s for employees and employers . Cognitive behavioural therapy ( CBT ) is a recommended treatment , but dem and outstrips supply . CBT is well suited to computerization . Most employee assistance programmes have not been systematic ally evaluated and computerized CBT has not previously been studied in the workplace . AIMS To evaluate the effect of an 8 week computerized cognitive behavioural therapy programme , ' Beating The Blues ' , on emotional distress in employees with recent stress-related absenteeism , and to explore the reasons for non-participation . METHODS An open , r and omized trial in a London NHS occupational health department . Forty-eight public sector employees , with 10 or more cumulative days stress-related absenteeism in the last 6 months , r and omized equally to ' Beating The Blues ' plus conventional care , or conventional care alone . Main outcome measures were Hospital Anxiety and Depression Scale and Attributional Style Question naire scores at end of treatment and 1 , 3 and 6 months later ; and reasons for non-participation . RESULTS At end of treatment and 1 month later , adjusted mean depression scores and adjusted mean negative attributional style scores were significantly lower in the intervention group . One month post-treatment , adjusted mean anxiety scores were also significantly lower in the intervention group . The differences were not statistically significant at 3 and 6 months post-treatment . Non-participation was common and related to access problems , preference for other treatments , time commitment , scepticism about the intervention and the employer connection . CONCLUSIONS ' Beating The Blues ' may accelerate psychological recovery in employees with recent stress-related absenteeism . Greater flexibility and accessibility might improve uptake BACKGROUND Stress is a common and costly behavioral health issue . Technology-based behavioral health programs ( e.g. , computer or web-based programs ) are effective for treating anxiety or depression . These programs increase availability of evidence -based interventions to individuals who are not able or willing to receive such in-person treatments . Stress management training has empirical support , but little data exists on its efficacy with stressed but healthy individuals , and there are no prior studies employing a self-guided , multimedia intervention . We conducted a r and omized controlled trial of a self-guided , multimedia stress management and resilience training program ( SMART-OP ) with a stressed but healthy sample . METHODS Participants ( N = 66 ) were r and omized to SMART-OP or an attention control ( AC ) group that received marketed videos and published material on stress management . Participants were evaluated on self-report measures and Trier Social Stress Test ( TSST ) performance . Analyses were based on study completers ( N = 59 ) . RESULTS SMART-OP group reported significantly less stress , more perceived control over stress , and rated SMART-OP as significantly more useful than AC . During the TSST , the data suggests the SMART-OP group showed greater within-task α-amylase recovery at post- assessment . CONCLUSIONS SMART-OP is highly usable and is a more effective and useful stress management training program than an educational comparison Purpose Highly stressed employees are subject to greater health risks , costs , and productivity losses than those with normal stress levels . To address this issue , work-site stress management programs must be able to engage individuals as well as capture data on stress , health indices , work productivity , and healthcare costs . In this r and omized controlled pilot , our primary objective was to evaluate the viability and proof of concept for two innovative mind-body workplace stress reduction programs , setting the stage for larger cost-effectiveness trials . A second objective was to evaluate two delivery venues of the mindfulness intervention ( online versus in-person ) . This study examines the moderating role of escapist reasons for drinking alcohol in the job stress/self-reported alcohol use and problems relationship . It was hypothesized that higher levels of job stress would be associated with higher levels of self-reported drinking ( H1 ) and drinking problems ( H2 ) only for those who endorsed escapist reasons for drinking . For those who did not hold such beliefs , higher levels of job stress were predicted to be associated with lower self-reported alcohol intake ( H3 ) and problems ( H4 ) . Survey data from white- and blue-collar workers employed across all paycodes and positions were collected r and omly at a large manufacturing organization ( 62 % response rate ) . Participants responded to questions concerning work stress , reasons for drinking , alcohol intake , and alcohol problems . Using only nonabstainers with complete data ( N = 1,645 ) , results from regression analyses generally supported all hypotheses OBJECTIVES The primary purpose of this r and omized controlled trial ( RCT ) was to evaluate the efficacy of a guided internet-based recovery training for employees who suffer from both work-related strain and sleep problems ( GET.ON Recovery ) . The recovery training consisted of six lessons , employing well-established methods from cognitive behavioral therapy for insomnia ( CBT-I ) such as sleep restriction , stimulus control , and hygiene interventions as well as techniques targeted at reducing rumination and promoting recreational activities . METHODS In a two-arm RCT ( N=128 ) , the effects of GET.ON Recovery were compared to a waitlist-control condition ( WLC ) on the basis of intention-to-treat analyses . German teachers with clinical insomnia complaints ( Insomnia Severity Index ≥15 ) and work-related rumination ( Irritation Scale , cognitive irritation subscale ≥15 ) were included . The primary outcome measure was insomnia severity . RESULTS Analyses of covariance ( ANCOVA ) revealed that , compared to the WLC , insomnia severity of the intervention group decreased significantly stronger ( F=74.11 , P<0.001 ) with a d=1.45 [ 95 % confidence interval ( 95 % CI ) 1.06 - 1.84 ] The number needed to treat ( NNT ) was < 2 for reliable change and NNT < 4 for reduction in expert-rated diagnosis of primary insomnia . CONCLUSION The training significantly reduces sleep problems and fosters mental detachment from work and recreational behavior among adult stressed employees at post-test and 6-months follow up . Given the low threshold access this training could reach out to a large group of stressed employees when results are replicated in other studies Abstract Objective : This study evaluated the efficacy of a comprehensive stress management program in reducing perceived stress among women who reported moderate-to-high stress levels . Methods : A total of 562 highly motivated females , aged 25–45 , with moderate to high stress levels , were enrolled in a 14-week study . Participants were r and omized into one of three groups : Group 1 included Internet-based coaching focusing on behavior modification , daily use of proprietary olfactive-based personal care products , and periodic feedback reports ; Group 2 consisted of only online coaching ; and Group 3 had no active stress management program . Participants in the three groups filled out vali date d psychometric assessment s at baseline and throughout the study period . Several outcomes including Perceived Stress Scale ( PSS ) , Profile of Mood States ( POMS ) , St Mary ’s Hospital Sleep Question naire ( SMS ) , the Trier Inventory of Chronic Stress ( TICS ) , Spielberger State-Trait Anxiety Inventory ( STAI ) , Short-Form-36 ( SF-36 ) and the Work Productivity and Activity Impairment ( WPAI ) , were measured periodically to assess changes in subject-perceived stress , stress-related comorbidities , and sleep quality and to evaluate overall program efficacy . Ethical approval of protocol s was conducted by the Allendale Investigational Review Board ( AIRB ) . Voluntary informed consent was obtained from each subject . Results : At the end of the 14-week study period , subjects in Group 1 had statistically significant improvement in the PSS score vs. Group 3 ( p < 0.01 ) . There were statistically significant improvements in other efficacy outcomes such as POMS total mood disturbance , TICS work overload and social responsibility subscales , STAI and in the number of night awakenings , assessed by the SMS question naire ( p < 0.05 ) . Self-reported program efficacy was also significantly higher for Group 1 ( p < 0.001 ) . Conclusion : Despite study limitations , including reduction of stress in Group 3 , this study demonstrates that this comprehensive stress management program is effective in reducing stress among women with moderate to high stress levels |
10,797 | 28,091,359 | A non-linear inverse association with colorectal cancer risk was found for lignans intake , but no association for circulating enterolactone concentrations was observed .
Thus , study heterogeneity precludes a rigorous conclusion regarding an effect of high exposure to isoflavones on risk of colorectal cancer . | Epidemiological studies suggest that soya consumption as a source of phyto-oestrogens and isoflavones may be associated with a reduced risk of colorectal cancer .
However , findings have not yet been synthesis ed for all groups of phyto-oestrogens .
A meta- analysis was conducted to quantify the association between phyto-oestrogens and colorectal cancer risk . | This case – cohort study examined the association between plasma enterolactone concentration and incidence of colon and rectal cancer in the Diet , Cancer and Health cohort , which enrolled 57,053 participants aged 50–64 . Information about diet and lifestyle was obtained by question naire , and data on prescriptions of antibiotics were obtained from the Danish Prescription Registry . Cases diagnosed during 5.9 years of follow-up and a r and omly selected sample of the cohort had a plasma sample analyzed for enterolactone by time-resolved fluoro-immuno assay . Associations were analyzed by Cox proportional hazards model . A total of 244 colon cancer cases , 137 rectal cancer cases , and 370 sub-cohort members were included in the statistical analyses . For each doubling in enterolactone concentration , we found lower risk of colon cancer among women [ IRR ( 95 % CI ) = 0.76 ( 0.60–0.96 ) ] and a tendency toward lower risk of rectal cancer [ IRR ( 95 % CI ) = 0.83 ( 0.60–1.14 ) ] . Among men , a doubling in enterolactone tended to be associated with higher risk of colon cancer [ IRR ( 95 % CI ) = 1.09 ( 0.89–1.34 ) ] and was associated with statistically significantly higher risk of rectal cancer [ IRR ( 95 % CI ) = 1.74 ( 1.25–2.44 ) ] . Exclusion of antibiotics users strengthened the results slightly . In conclusion , with higher enterolactone levels , we found lower risk of colon cancer among women and higher risk of rectal cancer among men Enterolignans are phytoestrogenic compounds derived from the conversion of dietary lignans by the intestinal microflora that may be protective against cardiovascular diseases and cancer . To evaluate the use of enterolignans as biomarkers of dietary lignan intake , we studied the relation between plasma and dietary lignans . We determined the dietary intake of 4 lignans ( secoisolariciresinol ( SECO ) , matairesinol ( MAT ) , pinoresinol , and lariciresinol ) using the European Prospect i ve Investigation into Cancer and Nutrition FFQ , and plasma enterodiol ( END ) and enterolactone ( ENL ) concentrations were determined by liquid chromatography-t and em mass spectrometry . The population consisted of 637 men and women , aged 19 - 75 y , participating in a case-control study on colorectal adenomas . Participants did not use antibiotics in the preceding calendar year . We found a modest association between lignan intake and plasma END ( Spearman r = 0.09 , P = 0.03 ) and ENL ( Spearman r = 0.18 , P < 0.001 ) . The correlation of total lignan intake with plasma enterolignans was slightly stronger than that of only SECO plus MAT . The plasma concentrations of both END and ENL were associated with intake of dietary fiber and vegetable protein but not with intake of other macronutrients . The relation between lignan intake and plasma END was modulated by age and previous use of antibiotics , whereas for ENL , it was modulated by weight , current smoking , and frequency of defecation . However , even when we included these nondietary factors in the regression models , the explained variance in plasma END and ENL remained low ( 2 and 13 % , respectively ) BACKGROUND Test results on the bioavailability of isoflavones in the aglycone or glucoside form in Eastern and Western human subjects are contradictory . OBJECTIVE The objective was to investigate the bioavailability of the soy isoflavones daidzein and genistein in American women with typical American dietary habits after ingestion of the aglycone or glucoside form of isoflavones . DESIGN Fifteen American women aged 46 + /- 6 y participated in a r and omized , double-blind study . Blood sample s were collected 0 , 1 , 2 , 4 , 8 , 12 , 24 , and 48 h after consumption of aglycone or glucoside tablets with breakfast . The plasma curves for daidzein , genistein , and equol were constructed and the postpr and ial maximum concentration ( C(max ) ) , time to the maximum concentration ( t(max ) ) , and area under the curve ( AUC ) were determined . RESULTS Isoflavone concentrations peaked early ( 1 - 2 h ) in plasma and peaked again at 4 - 8 h. Mean C(max ) , t(max ) , and AUC values for genistein were not significantly different after ingestion of aglycone or glucoside . However , C(max ) and AUC values , but not t(max ) , were significantly higher for daidzein after aglycone ingestion , which was partly due to its higher content in the aglycone tablets . Equol appeared after 4 h and remained elevated after 48 h. Despite a higher content of daidzein in the aglycone tablets , the AUC for equol was significantly higher after ingestion of the glucoside tablets , probably because of the metabolic action of intestinal bacteria during the long intestinal transit time of glucoside . CONCLUSION The apparent bioavailability of genistein and daidzein is not different when consumed as either aglycone or glucoside by American women Enterolignans are biphenolic compounds that possess several biologic activities whereby they may influence carcinogenesis . The authors investigated the association between plasma enterolactone and enterodiol and colorectal cancer risk in a Dutch prospect i ve study . Among more than 35,000 participants aged 20 - 59 years , 160 colorectal cancer cases were diagnosed after 7.5 years of follow-up ( 1987 - 2003 ) . Cohort members who were frequency-matched to the cases on age , sex , and study center were selected as controls ( n = 387 ) . Plasma enterodiol and enterolactone were not associated with risk of colorectal cancer after adjustment for known colorectal cancer risk factors ( highest quartile vs. lowest : for enterodiol , odds ratio = 1.11 , 95 % confidence interval : 0.56 , 2.20 ( p-trend = 0.75 ) ; for enterolactone , odds ratio = 1.70 , 95 % confidence interval : 0.88 , 3.27 ( p-trend = 0.15 ) ) . However , sex ( p-interaction = 0.06 ) and body mass index ( p-interaction < 0.01 ) modified the relation between plasma enterolactone and colorectal cancer risk ; increased risks were observed among women and subjects with a high body mass index . The association between plasma enterodiol and colorectal cancer risk was modified by smoking status ; risk was increased among current smokers ( p-interaction < 0.01 ) . These findings do not support the hypothesis that high plasma enterodiol or enterolactone concentrations are associated with reduced risk of colorectal cancer Several experimental studies have reported that the anticarcinogenic properties of dietary soy play an important role in preventing colorectal cancer . However , few epidemiologic studies have examined this association in general population s and their findings have been inconsistent . We investigated the association between dietary soy and isoflavone intake and incidence of colorectal cancer in a prospect i ve cohort study of 83,063 Japanese men and women , ages 45 to 74 years . Dietary soy and isoflavone intake was measured through a vali date d food frequency question naire in 1995 and 1998 . Throughout 2004 , a total of 886 cases of colorectal cancer were newly identified ( 291 proximal colon , 286 distal colon , and 277 rectum ) . The hazard ratios and 95 % confidence intervals ( 95 % CIs ) were estimated by fitting a Cox proportional hazards model . The intake of isoflavones , miso soup , and soy food was not associated with colorectal cancer in either men or women . By colorectal cancer subsite , the risk of proximal colon cancer in men decreased with increasing consumption of isoflavones , miso soup , and soy food . Compared with men in the lowest quartiles of isoflavones , miso soup , and soy food intake , the hazard ratios in the highest quartiles were 0.55 ( 95 % CI , 0.33 - 0.92 ) , 0.72 ( 95 % CI , 0.43 - 1.21 ) , and 0.51 ( 95 % CI , 0.30 - 0.87 ) , respectively . The results showed no association for distal colon and rectal cancer in men or for subsites of colorectal cancer in women . These findings suggest that the intake of isoflavones , miso soup , and soy food has no substantial effect on the risk of colorectal cancer in Japanese men and women . ( Cancer Epidemiol Biomarkers Prev 2008;17(8):2128–35 Abstract : The relationship of the intake of soy products and the incidence of colon cancer was prospect ively evaluated in a population -based cohort study in Japan . The total intake of soy products and isoflavones in a daily diet was estimated from a vali date d question naire administered at the baseline . The participation rate of the question naire was 92.0 % . The participants were followed from 1992 to 2000 , and colon cancer diagnoses were identified at the main hospitals in the study area . In the analysis , 13,894 men and 16,327 women were included . The medians for energy-adjusted soy product intake were 85.52 g/day for men and 79.60 g/day for women . During follow-up , 111 men and 102 women were diagnosed with colon cancer . A Cox-proportional hazard model was applied to assess the risk of colon cancer incidence . Among women , the risk was reduced with an increased soy product consumption ; the hazard ratio in the highest tertile was 0.56 ( 95 % CI 0.34–0.92 ) compared as the lowest tertile ( trend : P = 0.04 ) , after adjusting for multiple potential confounders . Among men , no significant association was observed . Our results exhibited the weak benefit of soy foods only among women . Further research to confirm our results may be beneficial Dietary phytoestrogens are suggested to reduce the risk of prostate and colorectal cancer , but the results of epidemiologic studies have not yielded consistent support for this proposed effect , possibly due to inadequate data bases of phytoestrogen levels in foods . Biomarkers of phytoestrogen intakes may provide a clearer insight into the relationship between phytoestrogen exposure and the risk of prostate or colorectal cancer risks . From the European Prospect i ve into Cancer-Norfolk cohort ( ages 45 - 75 ) , serum and urine sample s were analyzed for seven phytoestrogens [ daidzein , enterodiol , enterolactone , genistein , glycitein , O-desmethylangolensin ( O-DMA ) , and equol ] among 193 cases of prostate cancer and 828 controls , and 221 cases of colorectal cancer with 889 controls . Summary variables of total lignans ( enterodiol and enterolactone ) and total isoflavones ( daidzein , genistein , O-DMA , equol , and glycitein ) were created and analyzed in conjunction with individual phytoestrogens . Logistic regression analyses revealed that there was no significant association between prostate cancer risk and total serum isoflavones [ odds ratio ( OR ) , 1.01 ; 95 % confidence interval ( CI ) , 0.93 - 1.10 ] or total serum lignans ( OR , 0.94 ; 95 % CI , 0.86 - 1.04 ) or between colorectal cancer risk and total serum isoflavones ( OR , 1.01 ; 95 % CI , 0.94 - 1.08 ) or total serum lignans ( OR , 1.03 ; 95 % CI , 0.94 - 1.12 ) . Similarly , null associations were observed for individual serum phytoestrogens and for all urinary phytoestrogen biomarkers . In conclusion , we have found no evidence to support an inverse association between phytoestrogen exposure and prostate or colorectal cancer risk . ( Cancer Epidemiol Biomarkers Prev 2008;17(10):2891–4 In vitro and in vivo laboratory data point to chemoprotective effects of flavonoids on colorectal cancer . However , there has been limited epidemiologic research on the dietary intake of flavonoids and risk of colorectal cancer . Recent expansions of dietary data bases to include flavonoid data now make such studies feasible . Association between the six main classes of flavonoids and the risk of colorectal cancer was examined using data from a national prospect i ve case-control study in Scotl and , including 1,456 incident cases and 1,456 population -based controls matched on age , sex , and residence area . Dietary , including flavonoid data , were obtained from a vali date d , self-administered food frequency question naire . Risk of colorectal cancer was estimated using conditional logistic regression models in the whole sample and stratified by sex , smoking status , and cancer site and adjusted for established and putative risk factors . After energy adjustment , reductions in colorectal cancer risk associated with the highest quartiles of intake ( versus the lowest quartile ) were 27 % for flavonols [ odds ratio ( OR ) , 0.73 ; Ptrend = 0.012 ] , 32 % for quercetin ( OR , 0.68 ; Ptrend = 0.001 ) , 32 % for catechin ( OR , 0.68 ; Ptrend < 0.0005 ) ; 26 % for epicatechin ( OR , 0.74 ; Ptrend = 0.019 ) , and 22 % for procyanidins ( OR , 0.78 ; Ptrend = 0.031 ) . The significant dose-dependent reductions in colorectal cancer risk that were associated with increased consumption of flavonols , quercetin , catechin , and epicatechin remained robust after controlling for overall fruit and vegetable consumption or for other flavonoid intake . The risk reductions were greater among nonsmokers , but no interaction beyond a multiplicative effect was present . Sex-specific or cancer-type differences were not observed . No risk reductions were associated with intake of flavones ( Ptrend = 0.64 ) , flavonones ( Ptrend = 0.22 ) , and phytoestrogens ( Ptrend = 0.26 ) . This was the first of several a priori hypotheses to be tested in this large study and showed strong and linear inverse associations of flavonoids with colorectal cancer risk . ( Cancer Epidemiol Biomarkers Prev 2007;16(4):684–93 Two recent case-control studies suggested that some flavonoid subgroups may play a role in preventing colorectal cancer . Previous prospect i ve cohort studies generally reported no association ; however , only a small subset of flavonoids was evaluated and partial flavonoid data bases were used . We used the newly constructed U.S. Department of Agriculture flavonoid data base to examine the association between consumption of total flavonoids , 6 flavonoid subgroups , and 29 individual flavonoids with adenomatous polyp recurrence in the Polyp Prevention Trial . The Polyp Prevention Trial was a r and omized dietary intervention trial , which examined the effectiveness of a low-fat , high-fiber , high-fruit , and high-vegetable diet on adenoma recurrence . Intakes of flavonoids were estimated from a food frequency question naire . Multivariate logistic regression models ( adjusted for age , body mass index , sex , regular non – steroidal anti-inflammatory use , and dietary fiber intake ) were used to estimate odds ratios and 95 % confidence intervals for both any and advanced adenoma recurrence within quartiles of energy-adjusted flavonoid intake ( baseline , during the trial , and change during the trial ) . Total flavonoid intake was not associated with any or advanced adenoma recurrence . However , high intake of flavonols , which are at greater concentrations in beans , onions , apples , and tea , was associated with decreased risk of advanced adenoma recurrence ( 4th versus 1st quartile during the trial ; odds ratio , 0.24 ; 95 % confidence interval , 0.11 , 0.53 ; Ptrend = 0.0006 ) . Similar inverse associations were observed to a smaller extent for isoflavonoids , the flavonol kaempferol , and the isoflavonoids genistein and formononetin . Our data suggest that a flavonol-rich diet may decrease the risk of advanced adenoma recurrence . ( Cancer Epidemiol Biomarkers Prev 2008;17(6):1344–53 Lignans and proanthocyanidins are plant polyphenols that have shown protective properties against colorectal neoplasms in some human studies . Using logistic regression , we estimated odds ratios ( ORs ) and 95 % confidence intervals ( CIs ) to prospect ively evaluate the association between lignan and proanthocyanidin intake , estimated from data bases linked to a food frequency question naire , and adenoma recurrence in 1,859 participants of the Polyp Prevention Trial . Overall , individual or total lignans or proanthocyanidins were not associated with colorectal adenoma recurrence . However , in sex‐specific analyses , total lignan intake was positively associated with any adenoma recurrence in women ( highest vs. lowest lignan intake quartile OR = 2.07 , 95 % CI : 1.22–3.52 , p trend = 0.004 ) but not in men ( p interaction = 0.04 ) . To conclude , dietary lignan and proanthocyanidin consumption were not generally related to colorectal adenoma recurrence ; however , high lignan intake may increase the risk of adenoma recurrence in women AIM To assess the safety and effect of the supplementation of a patented blend of dietary phytoestrogens and insoluble fibers on estrogen receptor (ER)-β and biological parameters in sporadic colonic adenomas . METHODS A r and omized , double-blind placebo-controlled trial was performed . Patients scheduled to undergo surveillance colonoscopy for previous sporadic colonic adenomas were identified , and 60 eligible patients were r and omized to placebo or active dietary intervention ( ADI ) twice a day , for 60 d before surveillance colonoscopy . ADI was a mixture of 175 mg milk thistle extract , 20 mg secoisolariciresinol and 750 mg oat fiber extract . ER-β and ER-α expression , apoptosis and proliferation ( Ki-67 LI ) were assessed in colon sample s. RESULTS No adverse event related to ADI was recorded . ADI administration showed a significant increases in ER-β protein ( 0.822 ± 0.08 vs 0.768 ± 0.10 , P = 0.04 ) and a general trend to an increase in ER-β LI ( 39.222 ± 2.69 vs 37.708 ± 5.31 , P = 0.06 ) , ER-β/ER-α LI ratio ( 6.564 ± 10.04 vs 2.437 ± 1.53 , P = 0.06 ) , terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling ( 35.592 ± 14.97 vs 31.541 ± 11.54 , P = 0.07 ) and Ki-67 ( 53.923 ± 20.91 vs 44.833 ± 10.38 , P = 0.07 ) approximating statistical significance . A significant increase of ER-β protein ( 0.805 ± 0.13 vs 0.773 ± 0.13 , P = 0.04 ) , mRNA ( 2.278 ± 1.19 vs 1.105 ± 1.07 , P < 0.02 ) and LI ( 47.533 ± 15.47 vs 34.875 ± 16.67 , P < 0.05 ) and a decrease of ER-α protein ( 0.423 ± 0.06 vs 0.532 ± 0.11 , P < 0.02 ) as well as a trend to increase of ER-β/ER-α protein in ADI vs placebo group were observed in patients without polyps ( 1.734 ± 0.20 vs 1.571 ± 0.42 , P = 0.07 ) . CONCLUSION The role of ER-β on the control of apoptosis , and its amenability to dietary intervention , are supported in our study BACKGROUND / OBJECTIVES : Phytoestrogens are estradiol-like natural compounds found in plants that have been associated with protective effects against chronic diseases , including some cancers , cardiovascular diseases and osteoporosis . The purpose of this study was to estimate the dietary intake of phytoestrogens , identify their food sources and their association with lifestyle factors in the European Prospect i ve Investigation into Cancer and Nutrition ( EPIC ) cohort . SUBJECTS/ METHODS : Single 24-hour dietary recalls were collected from 36 037 individuals from 10 European countries , aged 35–74 years using a st and ardized computerized interview programe ( EPIC-Soft ) . An ad hoc food composition data base on phytoestrogens ( isoflavones , lignans , coumestans , enterolignans and equol ) was compiled using data from available data bases , in order to obtain and describe phytoestrogen intakes and their food sources across 27 redefined EPIC centres . RESULTS : Mean total phytoestrogen intake was the highest in the UK health-conscious group ( 24.9 mg/day in men and 21.1 mg/day in women ) whereas lowest in Greece ( 1.3 mg/day ) in men and Spain-Granada ( 1.0 mg/day ) in women . Northern European countries had higher intakes than southern countries . The main phytoestrogen contributors were isoflavones in both UK centres and lignans in the other EPIC cohorts . Age , body mass index , educational level , smoking status and physical activity were related to increased intakes of lignans , enterolignans and equol , but not to total phytoestrogen , isoflavone or coumestan intakes . In the UK cohorts , the major food sources of phytoestrogens were soy products . In the other EPIC cohorts the dietary sources were more distributed , among fruits , vegetables , soy products , cereal products , non-alcoholic and alcoholic beverages . CONCLUSIONS : There was a high variability in the dietary intake of total and phytoestrogen subclasses and their food sources across European regions BACKGROUND Soy and some of its constituents , such as isoflavones , have been shown to have cancer-inhibitory activities in experimental studies . Data from epidemiologic studies linking usual soy food intake with colorectal cancer are limited and inconsistent . OBJECTIVE The objective was to investigate whether soy food intake is associated with colorectal cancer risk . DESIGN We prospect ively examined 68,412 women aged 40 - 70 y and free of cancer and diabetes at enrollment . Usual soy food intake was assessed at baseline ( 1997 - 2000 ) and reassessed during the first follow-up ( 2000 - 2002 ) through in-person interviews with a vali date d food-frequency question naire . We excluded the first year of observation to minimize lifestyle changes related to pre clinical disease . RESULTS During a mean follow-up of 6.4 y , 321 incident colorectal cancer cases were identified . After adjustment for potential confounding factors , total soy food intake was inversely associated with colorectal cancer risk . Each 5-g/d increment in intake of soy foods as assessed by dry weight [ equivalent to approximately 1 oz ( 28.35 g ) tofu/d ] was associated with an 8 % reduction in risk ( 95 % CI : 3 % , 14 % ) . Women in the highest tertile of intake had a multivariate relative risk of 0.67 ( 95 % CI : 0.49 , 0.90 ) compared with those in the lowest tertile ( P for trend = 0.008 ) . This inverse association was primarily confined to postmenopausal women . Similar results were also found for intakes of soy protein and isoflavones . CONCLUSION This prospect i ve study suggests that consumption of soy foods may reduce the risk of colorectal cancer in postmenopausal women BACKGROUND The characterization of phytoestrogen intake and cancer risk has been hindered by the absence of accurate dietary phytoestrogen values . OBJECTIVE We examined the risk of breast , colorectal , and prostate cancers relative to phytoestrogen intake on the basis of a comprehensive data base . DESIGN Demographic and anthropometric characteristics , a medical history , and 7-d records of diet were collected prospect ively from participants ( aged 40 - 79 y ) in the European Prospect i ve Investigation into Cancer and Nutrition-Norfolk ( EPIC-Norfolk ) . Five hundred nine food items were analyzed by liquid chromatography-mass spectrometry/mass spectrometry , and (13)C(3)-labeled internal st and ards were analyzed for isoflavones ( genistein , daidzein , glycitein , biochanin A , and formononetin ) , lignans ( secoisolariciresinol and matairesinol ) , and enterolignans from gut microbial metabolism in animal food sources ( equol and enterolactone ) . From the direct analysis , values for 10,708 foods were calculated . Odds ratios ( ORs ) for breast ( 244 cases , 941 controls ) , colorectal ( 221 cases , 886 controls ) , and prostate ( 204 cases , 812 controls ) cancers were calculated relative to phytoestrogen intake . RESULTS Phytoestrogen intake was not associated with breast cancer among women or colorectal cancer among men . Among women , colorectal cancer risk was inversely associated with enterolactone ( OR : 0.33 ; 95 % CI : 0.14 , 0.74 ) and total enterolignans ( OR : 0.32 ; 95 % CI : 0.13 , 0.79 ) , with a positive trend detected for secoisolariciresinol ( OR : 1.60 ; 95 % CI : 0.96 , 2.69 ) . A positive trend between enterolignan intake and prostate cancer risk ( OR : 1.27 ; 95 % CI : 0.97 , 1.66 ) was attenuated after adjustment for dairy intake ( OR : 1.19 ; 95 % CI : 0.77 , 1.82 ) . CONCLUSION Dietary phytoestrogens may contribute to the risk of colorectal cancer among women and prostate cancer among men Evidence suggests dietary phytoestrogens may reduce the risk of certain hormonal cancers ( e.g. breast and prostate ) . There is a paucity of data regarding phytoestrogens and colorectal cancer risk . Phytoestrogens are plant compounds with estrogen-like activities . Main classes include isoflavones ( found in legumes such as soy ) and lignans ( found in grains , seeds , nuts , fruits , and vegetables ) . Although isoflavones have dominated phytoestrogen cancer research , lignans may be more relevant to North American diets . Food question naires and analytic data bases have recently been modified to incorporate some lignan information . We conducted a case-control study to evaluate the association between phytoestrogen intake and colorectal cancer risk . Colorectal cancer cases were diagnosed in 1997 - 2000 , aged 20 - 74 y , identified through the population -based Ontario Cancer Registry , and recruited by the Ontario Familial Colorectal Cancer Registry . Controls were a sex and age-group matched r and om sample of the population of Ontario . Epidemiologic and food frequency question naires were completed by 1095 cases and 1890 control subjects . Multivariate logistic regression analysis was used to obtain adjusted odds ratio ( OR ) estimates . Dietary lignan intake was associated with a significant reduction in colorectal cancer risk [ OR ( T3 vs. T1 ) = 0.73 ; 95 % CI : 0.56 , 0.94 ] , as was isoflavone intake [ OR ( T3 vs. T1 ) = 0.71 ; 95 % CI : 0.58 , 0.86 ] . We evaluated interactions between polymorphic genes that encode enzymes possibly involved in metabolism of phytoestrogens ( CYPs , catechol O-methyl transferase , GSTs , and UGTs ) and found no significant effect modification with respect to phytoestrogen intake . This finding that phytoestrogen intake may reduce colorectal cancer risk is important , because dietary intake is potentially modifiable ABSTRACT Dietary phytoestrogen intake has been inversely associated with the risk of prostate and breast cancer and might also affect the risk of colorectal cancer . We evaluated the associations between dietary lignan intake , dietary isoflavonoid intake , dietary coumestrol intake , and dietary enterolignans and equol intake , and risk of colorectal cancer . Data from the Women 's Lifestyle and Health ( WLH ) Cohort study was used . The WLH study is a prospect i ve population -based cohort study including 48,268 Swedish women aged 30–49 years at the time of enrolment in 1991–92 . Follow-up for colorectal cancer incidence , death , and emigration until the end of 2010 was performed through record linkage to the Swedish Cancer Registry and Total Population Register . During follow-up 206 incident colorectal cancer cases were identified . Cox proportional hazards models were fitted to estimate adjusted risk ratios with 95 % confidence intervals . We found no statistically significant association between the intake of dietary lignans , dietary isoflavonoids , coumestrol , or enterolignans and equol , and risk of colorectal cancer . We found no association between dietary phytoestrogen intake and the risk of colorectal cancer . However , since the number of cancer cases was small , our results need to be confirmed . Future studies should investigate colon and rectal cancer separately Flavonoids , which are found in certain plant foods , are thought to lower cancer risk through their antioxidant , antiestrogenic and antiproliferative properties . We examined the association of intake of total flavonoids and 7 flavonoid subclasses with risk of lung , colorectal , breast , pancreatic and upper aerodigestive cancer among women in a large prospect i ve cohort study . Study participants were 34,708 postmenopausal women in the Iowa Women 's Health Study who completed a food frequency question naire and were followed for cancer occurrence from 1986 through 2004 . Flavonoid intake was estimated from 3 data bases developed by the USDA Nutrient Data Laboratory ( NDL ) . Hazard ratios ( HR ) for cancer risk were calculated across total flavonoid and flavonoid subclass intake categories . Interactions between smoking history and flavonoid intake were also examined . After multivariable adjustment , lung cancer incidence was inversely associated with intakes of flavanones ( HR = 0.68 ; 95 % CI : 0.53 - 0.86 , all results highest vs. lowest quintile ) and proanthocyanidins ( HR = 0.75 ; 95 % CI : 0.57 - 0.97 ) . Among current and past smokers , those with intakes in the highest quintile for flavanones ( HR = 0.66 ; 95 % CI : 0.50 - 0.86 ) , and proanthocyanidins ( HR = 0.66 ; 95 % CI ; 0.49 - 0.89 ) had significantly lower lung cancer incidence than those in the lowest quintile . Similar associations were not seen in never smokers . Isoflavone intake was inversely associated with overall cancer incidence ( HR = 0.93 , 95 % CI : 0.86 - 1.00 ) . This study provides further support for a beneficial effect of flavonoid intake on lung cancer risk , especially among current and past smokers |
10,798 | 21,636,817 | Based on observational data , the combination of IV tPA and mechanical thrombectomy for large-vessel ischemic stroke appears to be cost-effective compared to IV tPA alone . | BACKGROUND AND PURPOSE Mechanical thrombectomy has the potential to improve recanalization rates and outcomes for patients with ischemic stroke , but potential gains could be offset by procedural complications and costs .
We evaluated the cost and utility of combined intravenous ( IV ) tissue-type plasminogen activator ( tPA ) and mechanical thrombectomy compared to IV tPA alone for acute large-vessel ischemic stroke . | Background and Purpose — The only Food and Drug Administration ( FDA ) -approved treatment for acute ischemic stroke is tissue plasminogen activator ( tPA ) given intravenously within 3 hours of symptom onset . An alternative strategy for opening intracranial vessels during stroke is mechanical embolectomy , especially for patients ineligible for intravenous tPA . Methods — We investigated the safety and efficacy of a novel embolectomy device ( Merci Retriever ) to open occluded intracranial large vessels within 8 hours of the onset of stroke symptoms in a prospect i ve , nonr and omized , multicenter trial . All patients were ineligible for intravenous tPA . Primary outcomes were recanalization and safety , and secondary outcomes were neurological outcome at 90 days in recanalized versus nonrecanalized patients . Results — Recanalization was achieved in 46 % ( 69/151 ) of patients on intention to treat analysis , and in 48 % ( 68/141 ) of patients in whom the device was deployed . This rate is significantly higher than that expected using an historical control of 18 % ( P<0.0001 ) . Clinical ly significant procedural complications occurred in 10 of 141 ( 7.1 % ) patients . Symptomatic intracranial hemorrhages was observed in 11 of 141 ( 7.8 % ) patients . Good neurological outcomes ( modified Rankin score ≤2 ) were more frequent at 90 days in patients with successful recanalization compared with patients with unsuccessful recanalization ( 46 % versus 10 % ; relative risk [ RR ] , 4.4 ; 95 % CI , 2.1 to 9.3 ; P<0.0001 ) , and mortality was less ( 32 % versus 54 % ; RR , 0.59 ; 95 % CI , 0.39 to 0.89 ; P=0.01 ) . Conclusions — A novel endovascular embolectomy device can significantly restore vascular patency during acute ischemic stroke within 8 hours of stroke symptom onset and provides an alternative intervention for patients who are otherwise ineligible for thrombolytics Background and Purpose — Endovascular mechanical thrombectomy may be used during acute ischemic stroke due to large vessel intracranial occlusion . First-generation MERCI devices achieved recanalization rates of 48 % and , when coupled with intraarterial thrombolytic drugs , recanalization rates of 60 % have been reported . Enhancements in embolectomy device design may improve recanalization rates . Methods — Multi MERCI was an international , multicenter , prospect i ve , single-arm trial of thrombectomy in patients with large vessel stroke treated within 8 hours of symptom onset . Patients with persistent large vessel occlusion after IV tissue plasminogen activator treatment were included . Once the newer generation ( L5 Retriever ) device became available , investigators were instructed to use the L5 Retriever to open vessels and could subsequently use older generation devices and /or intraarterial tissue plasminogen activator . Primary outcome was recanalization of the target vessel . Results — One hundred sixty-four patients received thrombectomy and 131 were initially treated with the L5 Retriever . Mean age±SD was 68±16 years , and baseline median ( interquartile range ) National Institutes of Health Stroke Scale score was 19 ( 15 to 23 ) . Treatment with the L5 Retriever result ed in successful recanalization in 75 of 131 ( 57.3 % ) treatable vessels and in 91 of 131 ( 69.5 % ) after adjunctive therapy ( intraarterial tissue plasminogen activator , mechanical ) . Overall , favorable clinical outcomes ( modified Rankin Scale 0 to 2 ) occurred in 36 % and mortality was 34 % ; both outcomes were significantly related to vascular recanalization . Symptomatic intracerebral hemorrhage occurred in 16 patients ( 9.8 % ) ; 4 ( 2.4 % ) of these were parenchymal hematoma type II . Clinical ly significant procedural complications occurred in 9 ( 5.5 % ) patients . Conclusions — Higher rates of recanalization were associated with a newer generation thrombectomy device compared with first-generation devices , but these differences did not achieve statistical significance . Mortality trended lower and the proportion of good clinical outcomes trended higher , consistent with better recanalization Background and Purpose — Experimental evidence indicates that ultrasound can accelerate thrombolysis . We report our findings on early recanalization during transcranial color-coded Doppler ( TCCD ) continuous monitoring in acute stroke patients with middle cerebral artery ( MCA ) main stem occlusion . Methods — We performed continuous TCCD monitorings in 6 consecutive patients with acute MCA main stem occlusion using a 2-MHz transducer . Patients were not treated with recombinant tissue plasminogen activator . Results — Partial recanalization , defined as blunted waveforms , occurred during monitoring in 5 patients ( 83 % ) . The mean time to beginning of recanalization was 17.2±9.6 minutes . Complete recanalization at 24 hours occurred in only 1 patient . The mean National Institutes of Health Stroke Scale score in the patients who recanalized during monitoring was 21.2±4.1 at baseline , 19.2±5 at 2 hours , and 15.6±3.4 at 24 hours ( P = 0.1 ) . Conclusions — In this short series of patients with acute MCA main stem occlusion , not treated with recombinant tissue plasminogen activator , we found a high rate of early partial recanalization during continuous exposure to 2-MHz ultrasound OBJECT Mechanical thrombectomy is increasingly being used for the treatment of large-vessel ischemic stroke in patients who arrive outside of the 3-hour tissue plasminogen activator time window . In this study , the authors evaluated the cost and effectiveness of mechanical thrombectomy compared with st and ard medical therapy in patients who are ineligible to receive tissue plasminogen activator . METHODS Clinical outcomes of an open-label study of mechanical thrombectomy were compared with a hypothetical control group with a lower recanalization rate ( 18 vs 60 % ) and a lower rate of symptomatic intracranial hemorrhage ( 0.6 vs 7.8 % ) than the active treatment group . A Markov cost-effectiveness model was built to compare the health benefits and costs associated with mechanical thrombectomy compared with st and ard medical therapy . All probabilities , quality -of-life factors , and costs were estimated from the published literature . Univariate sensitivity analyses were performed to assess how variations in model parameters affect health and economic outcomes . RESULTS Treatment of acute ischemic stroke with mechanical thrombectomy increased survival time by 0.54 quality -adjusted life years ( QALYs ) , compared with st and ard medical therapy ( 2.37 vs 1.83 QALYs ) , at an increased cost of $ 6600 . This yielded an incremental cost-effectiveness ratio ( ICER ) of $ 12,120 per QALY gained , a value generally considered cost-effective . Sensitivity analysis showed that mechanical thrombectomy remained cost-effective ( ICER < $ 50,000 per QALY gained ) for all model inputs varied over a reasonable range , except for age at stroke treatment . For patients older than 82 years of age , the treatment was only borderline cost-effective ( ICER of $ 50,000 - 100,000 per QALY gained ) . CONCLUSIONS The treatment of large-vessel ischemic stroke with mechanical thrombectomy appears to be costeffective . These results require validation when data from a r and omized , controlled trial of mechanical thrombectomy become available CONTEXT Intravenous tissue-type plasminogen activator can be beneficial to some patients when given within 3 hours of stroke onset , but many patients present later after stroke onset and alternative treatments are needed . OBJECTIVE To determine the clinical efficacy and safety of intra-arterial ( IA ) recombinant prourokinase ( r-proUK ) in patients with acute stroke of less than 6 hours ' duration caused by middle cerebral artery ( MCA ) occlusion . DESIGN PROACT II ( Prolyse in Acute Cerebral Thromboembolism II ) , a r and omized , controlled , multicenter , open-label clinical trial with blinded follow-up conducted between February 1996 and August 1998 . SETTING Fifty-four centers in the United States and Canada . PATIENTS A total of 180 patients with acute ischemic stroke of less than 6 hours ' duration caused by angiographically proven occlusion of the MCA and without hemorrhage or major early infa rct ion signs on computed tomographic scan . INTERVENTION Patients were r and omized to receive 9 mg of IA r-proUK plus heparin ( n = 121 ) or heparin only ( n = 59 ) . MAIN OUTCOME MEASURES The primary outcome , analyzed by intention-to-treat , was based on the proportion of patients with slight or no neurological disability at 90 days as defined by a modified Rankin score of 2 or less . Secondary outcomes included MCA recanalization , the frequency of intracranial hemorrhage with neurological deterioration , and mortality . RESULTS For the primary analysis , 40 % of r-proUK patients and 25 % of control patients had a modified Rankin score of 2 or less ( P = .04 ) . Mortality was 25 % for the r-proUK group and 27 % for the control group . The recanalization rate was 66 % for the r-proUK group and 18 % for the control group ( P<.001 ) . Intracranial hemorrhage with neurological deterioration within 24 hours occurred in 10 % of r-proUK patients and 2 % of control patients ( P = .06 ) . CONCLUSION Despite an increased frequency of early symptomatic intracranial hemorrhage , treatment with IA r-proUK within 6 hours of the onset of acute ischemic stroke caused by MCA occlusion significantly improved clinical outcome at 90 days BACKGROUND Intravenous thrombolysis with alteplase is the only approved treatment for acute ischemic stroke , but its efficacy and safety when administered more than 3 hours after the onset of symptoms have not been established . We tested the efficacy and safety of alteplase administered between 3 and 4.5 hours after the onset of a stroke . METHODS After exclusion of patients with a brain hemorrhage or major infa rct ion , as detected on a computed tomographic scan , we r and omly assigned patients with acute ischemic stroke in a 1:1 double-blind fashion to receive treatment with intravenous alteplase ( 0.9 mg per kilogram of body weight ) or placebo . The primary end point was disability at 90 days , dichotomized as a favorable outcome ( a score of 0 or 1 on the modified Rankin scale , which has a range of 0 to 6 , with 0 indicating no symptoms at all and 6 indicating death ) or an unfavorable outcome ( a score of 2 to 6 on the modified Rankin scale ) . The secondary end point was a global outcome analysis of four neurologic and disability scores combined . Safety end points included death , symptomatic intracranial hemorrhage , and other serious adverse events . RESULTS We enrolled a total of 821 patients in the study and r and omly assigned 418 to the alteplase group and 403 to the placebo group . The median time for the administration of alteplase was 3 hours 59 minutes . More patients had a favorable outcome with alteplase than with placebo ( 52.4 % vs. 45.2 % ; odds ratio , 1.34 ; 95 % confidence interval [ CI ] , 1.02 to 1.76 ; P=0.04 ) . In the global analysis , the outcome was also improved with alteplase as compared with placebo ( odds ratio , 1.28 ; 95 % CI , 1.00 to 1.65 ; P<0.05 ) . The incidence of intracranial hemorrhage was higher with alteplase than with placebo ( for any intracranial hemorrhage , 27.0 % vs. 17.6 % ; P=0.001 ; for symptomatic intracranial hemorrhage , 2.4 % vs. 0.2 % ; P=0.008 ) . Mortality did not differ significantly between the alteplase and placebo groups ( 7.7 % and 8.4 % , respectively ; P=0.68 ) . There was no significant difference in the rate of other serious adverse events . CONCLUSIONS As compared with placebo , intravenous alteplase administered between 3 and 4.5 hours after the onset of symptoms significantly improved clinical outcomes in patients with acute ischemic stroke ; alteplase was more frequently associated with symptomatic intracranial hemorrhage . ( Clinical Trials.gov number , NCT00153036 . BACKGROUND The MERCI ( Mechanical Embolus Removal in Cerebral Ischemia ) trial reported efficacy of the Merci Retriever for opening intracranial vessels in patients ineligible for intravenous ( IV ) tissue plasminogen activator ( tPA ) . Patients who receive IV tPA but do not recanalize may also benefit from thrombectomy , but the revascularization efficacy and safety of this strategy has not been reported . METHODS Multi MERCI is an ongoing international , multicenter , prospect i ve , single-arm trial of patients with large vessel stroke treated within 8 hours of symptom onset . Patients were enrolled who had received IV tPA but did not recanalize or who were ineligible for IV tPA . Primary outcome was vascular recanalization ( Thrombolysis in Myocardial Infa rct ion [ TIMI ] score II/III ) and safety . RESULTS One hundred eleven patients received the thrombectomy procedure . Mean age + /- SD was 66.2 + /- 17.0 years , and baseline National Institutes of Health Stroke Scale ( NIHSS ) score was 19 + /- 6.3 . Thirty patients ( 27 % ) received IV tPA before intervention . Treatment with the Retriever alone result ed in successful recanalization in 60 of 111 ( 54 % ) treatable vessels and in 77 of 111 ( 69 % ) after adjunctive therapy ( IA tPA , mechanical ) . Symptomatic intracranial hemorrhage ( ICH ) occurred in 10 of 111 ( 9.0 % ) . Clinical ly significant procedural complications occurred in 5 of 111 ( 4.5 % ) patients . The symptomatic ICH rate was 2 of 30 ( 6.7 % ) in patients pretreated with IV tPA and 8 of 81 ( 9.9 % ) in those without ( P > .99 ) . CONCLUSIONS Mechanical thrombectomy after IV tPA seems as safe as mechanical thrombectomy alone . Mechanical thrombectomy with both first- and second-generation Merci devices is efficacious in opening intracranial vessels during acute ischemic stroke in patients who are either ineligible for IV fibrinolytic therapy or have failed IV fibrinolytic therapy BACKGROUND The efficacy of intravenous ( IV ) alteplase is restricted by the speed of recanalisation and the site of the occlusion . The aim of this study was to ascertain the effect of a combined IV-endovascular approach ( intra-arterial alteplase and , if required , additional thrombectomy ) in patients with stroke due to arterial occlusion . METHODS We compared recanalisation rates , neurological improvement at 24 h , and functional outcome at 3 months between two periods ( February , 2002 , to March , 2007 , vs April , 2007 , to October , 2008 ) in patients in a prospect i ve registry who were treated with different regimens of alteplase within 3 h of symptom onset . Patients with confirmed occlusion who were treated before April , 2007 , were treated with IV alteplase ; after April , 2007 , patients were treated with a systematic IV-endovascular approach . Analysis was by intention to treat . FINDINGS 46 ( 87 % ) of 53 patients treated with the IV-endovascular approach achieved recanalisation versus 56 ( 52 % ) of 107 patients in the IV group ( adjusted relative risk [ RR ] 1.49 , 95 % CI 1.21 - 1.84 ; p=0.0002 ) . Early neurological improvement ( NIHSS score of 0 or 1 or an improvement of 4 points or more at 24 h ) occurred in 32 ( 60 % ) patients in the IV-endovascular group and 42 ( 39 % ) patients in the IV group ( adjusted RR 1.36 , 0.97 - 1.91 ; p=0.07 ) . Favourable outcome ( mRS of 0 - 2 at 90 days ) occurred in 30 ( 57 % ) patients in the IV-endovascular group and 47 ( 44 % ) patients in the IV group ( adjusted RR 1.16 , 0.85 - 1.58 ; p=0.35 ) . The mortality rate at 90 days was 17 % in both groups , and symptomatic intracranial haemorrhage was reported in five ( 9 % ) patients in the IV-endovascular group and in 12 ( 11 % ) patients in the IV group . Better clinical outcome was associated with recanalisation in both groups and with time to recanalisation in the IV-endovascular group . INTERPRETATION An IV-endovascular approach is associated with higher recanalisation rates than is IV alteplase in patients with stroke and confirmed arterial occlusion . In patients treated with an IV-endovascular approach , a shorter time from symptom onset to recanalisation is associated with better clinical outcomes BACKGROUND AND PURPOSE : It is unclear whether the costs and risks of mechanical therapies make them cost-effective . We examined whether interventions such as mechanical clot removal or disruption with angioplasty are cost-effective for acute ischemic stroke compared with best medical therapy . MATERIAL S AND METHODS : We performed a cost-utility analysis of patients with acute stroke due to large intracranial artery occlusion presenting beyond the 3-hour window for IV tPA . Model inputs for the mechanical arm were derived from Multi MERCI trial data and a recent meta- analysis . For best medical therapy , we used rates of spontaneous recanalization , ICH , and functional outcomes based on a systematic literature review . Discounted QALYs were determined by using the Markov modeling for 65-year-old patients with acute ischemic stroke . RESULTS : On the basis of a systematic literature review , we modeled an 84 % rate of recanalization with mechanical intervention and a 6.3 % rate of symptomatic ICH . For best medical therapy , we modeled a spontaneous recanalization rate of 24 % with a 2 % rate of symptomatic ICH . Mechanical therapies were associated with a $ 7718 net cost and a gain of a 0.82 QALYs for each use , thus yielding a net of $ 9386/QALY gained . In sensitivity analyses , results were dependent on the rates of recanalization , symptomatic ICH rates , and costs of treatment . CONCLUSIONS : On the basis of available data , mechanical therapies in qualified patients with acute stroke beyond the window for IV tPA appear to be cost-effective . However , the inputs are not derived from r and omized trials , and results are sensitive to several assumptions Tissue plasminogen activator ( tPA ) has been shown to improve 3-month outcome in stroke patients treated within 3 hours of symptom onset . The costs associated with this new treatment will be a factor in determining the extent of its utilization . Data from the NINDS rt-PA Stroke Trial and the medical literature were used to estimate the health and economic outcomes associated with using tPA in acute stroke patients . A Markov model was developed to estimate the costs per 1,000 patients eligible for treatment with tPA compared with the costs per 1,000 untreated patients . One-way and multiway sensitivity analyses ( using Monte Carlo simulation ) were performed to estimate the overall uncertainty of the model results . In the NINDS rt-PA Stroke Trial , the average length of stay was significantly shorter in tPA-treated patients than in placebo-treated patients ( 10.9 versus 12.4 days ; p = 0.02 ) and more tPA patients were discharged to home than to inpatient rehabilitation or a nursing home ( 48 % versus 36%;p = 0.002 ) . The Markov model estimated an increase in hospitalization costs of $ 1.7 million and a decrease in rehabilitation costs of $ 1.4 million and nursing home cost of $ 4.8 million per 1,000 eligible treated patients for a health care system that includes acute through long-term care facilities . Multiway sensitivity analysis revealed a greater than 90 % probability of cost savings . The estimated impact on long-term health outcomes was 564 ( 3 to 850 ) quality -adjusted life-years saved over 30 years of the model per 1,000 patients . Treating acute ischemic stroke patients with tPA within 3 hours of symptom onset improves functional outcome at 3 months and is likely to result in a net cost savings to the health care system OBJECTIVE To examine the cost-effectiveness of prescribing warfarin sodium in patients who have nonvalvular atrial fibrillation ( NVAF ) with or without additional stroke risk factors ( a prior stroke or transient ischemic attack , diabetes , hypertension , or heart disease ) . DESIGN Decision and cost-effectiveness analyses . The probabilities for stroke , hemorrhage , and death were obtained from published r and omized controlled trials . The quality -of-life estimates were obtained by interviewing 74 patients with atrial fibrillation . Costs were estimated from literature review , phone survey , and Medicare reimbursement . PATIENTS In the base case , the patients were 65 years of age and good c and i date s for warfarin therapy . INTERVENTIONS Treatment with warfarin , aspirin , or no therapy in the decision analytic model . MAIN OUTCOME MEASURES Quality -adjusted survival and marginal cost-effectiveness of warfarin as compared with aspirin or no therapy . RESULTS For patients with NVAF and additional risk factors for stroke , warfarin therapy led to a greater quality -adjusted survival and to cost savings . For patients with NVAF and one additional risk factor , warfarin therapy cost $ 8000 per quality -adjusted life-year saved . For 65-year-old patients with NVAF alone , warfarin cost about $ 370,000 per quality -adjusted life-year saved , as compared with aspirin therapy . However , for 75-year-old patients with NVAF alone , prescribing warfarin cost $ 110,000 per quality -adjusted life-year saved . For patients who were not prescribed warfarin , aspirin was preferred to no therapy on the basis of both quality -adjusted survival and cost in all patients , regardless of the number of risk factors present . CONCLUSIONS Treatment with warfarin is cost-effective in patients with NVAF and one or more additional risk factors for stroke . In 65-year-old patients with NVAF but no other risk factors for stroke , prescribing warfarin instead of aspirin would affect quality -adjusted survival minimally but increase costs significantly Rationale The Interventional Management of Stroke ( IMS ) I and II pilot trials demonstrated that the combined intravenous ( i.v . ) and intraarterial ( i.a . ) approach to recanalization may be more effective than st and ard i.v . rt-PA ( Activase ® ) alone for moderate-to-large National Institutes of Health Stroke Scale ( NIHSS ≥ 10 ) strokes , and with a similar safety profile . Aims The primary objective of this NIH-funded , Phase III , r and omized , multicenter , open-label clinical trial is to determine whether a combined i.v./i.a . approach to recanalization is superior to st and ard i.v . rt-PA alone when initiated within 3 h of acute ischemic stroke onset . The IMS III trial will develop and maintain a network of interventional centers to test the safety , feasibility , and potential efficacy of new FDA -approved catheter devices as part of a combined i.v./i.a . approach to recanalization as the IMS III study progresses . A secondary objective of the IMS III trial is to determine the cost-effectiveness of the combined i.v./i.a . approach as compared with st and ard i.v . rt-PA . Trial enrollment began in July of 2006 . Design A projected 900 subjects with moderate-to-large ( NIHSS ≥ 10 ) ischemic strokes between ages 18 and 80 will be enrolled over the next 5 years at 40-plus centers in the United States and Canada . Patients must have i.v . treatment initiated within 3 h of stroke onset in both arms . Subjects will be r and omized in a 2 : 1 ratio with more subjects enrolled in the combined i.v./i.a . group . The i.v . rt-PA alone group will receive the st and ard full dose [ 0·9 mg/kg , 90 mg maximum ( 10 % as bolus ) ] of rt-PA intravenously over an hour . The combined i.v./i.a . group will receive a lower dose of i.v . rt-PA ( ~0·6 mg/kg , 60 mg maximum ) over 40 min , followed by immediate angiography . If a treatable thrombus is not demonstrated , no i.a . therapy will be administered . If an appropriate thrombus is identified , treatment will continue with either the Concentric Merci ® thrombus-removal device , infusion of rt-PA and delivery of low-intensity ultrasound at the site of the occlusion via the EKOS ® Micro-Infusion Catheter , or infusion of rt-PA via a st and ard microcatheter . If i.a . rt-Pa therapy is the chosen strategy , a maximum of 22 mg of i.a . rt-PA may be given . The choice of i.a . strategy will be made by the treating neurointerventionalist . The i.a . treatment must begin within 5 h and be completed within 7 h of stroke onset . Study outcomes The primary outcome measure is a favorable clinical outcome , defined as a modified Rankin Scale Score of 0–2 at 3 months . The primary safety measure is mortality at 3 months and symptomatic ICH within the 24 h of r and omization The American Heart Association/American Stroke Association ( AHA/ASA ) Writing Committee for the Prevention of Stroke in Patients With Stroke and Transient Ischemic Attack ( TIA ) has review ed the results of recent trials that were published after our previous recommendations were issued.1 Our intention in the present statement is to provide a brief review of the new data , to up date specific recommendations , and to provide the reasons for any modifications . The 2 areas in which major new clinical trials have been published are ( 1 ) the use of specific antiplatelet agents for stroke prevention in patients with a history of noncardioembolic ischemic stroke or TIA and ( 2 ) the use of statins in the prevention of recurrent stroke . Recently published trials have added to the evidence of the benefit of the use of specific antiplatelet agents for stroke prevention in patients with a history of noncardioembolic ischemic stroke or TIA . The secondary prevention guidelines 1 have been up date d to reflect this new evidence . # # # Addition of Clopidogrel to Aspirin for Prevention of Vascular Events The Clopidogrel and Aspirin Versus Aspirin Alone for the Prevention of Atherothrombotic Events ( CHARISMA ) trial2 was a double-blinded study that r and omized 15 603 subjects with cardiovascular disease or multiple risk factors for cardiovascular disease to either clopidogrel 75 mg plus low-dose aspirin ( 75 to 162 mg ) or placebo plus aspirin ( 75 to 162 mg ) . Roughly 35 % of subjects ( n=4320 ) qualified on the basis of the presence of cerebrovascular disease within 5 years of enrollment ; approximately a third experienced TIA . The median follow-up was 28 months . No significant differences were seen in the rates of nonfatal ischemic stroke between the 2 groups ( 1.7 % versus 2.1 % , P = 0.07 ) . The placebo plus aspirin group showed a higher rate of nonfatal stroke than did the clopidogrel group ( 1.9 % versus 2.4 % , P = 0.03 ) . The 2 groups experienced no differences in the rate of intracerebral hemorrhage Rationale Stroke is a common and costly condition where an effective early treatment may be expected to affect patients ' future quality of life , the cost of acute medical treatment , and the cost of rehabilitation and any supportive care needed for their remaining lifetime . To assist in informing discussion s on early adoption of potential treatments , economic analyses should accompany investigations that seek to improve outcomes for stroke patients . Aims The primary aim is to assess whether i.v./i.a . rt-PA therapy is cost-effective at 3 months compared with i.v . rt-PA , and provides cost-savings or is cost-neutral by 12 months . Design Cost-effectiveness of the two treatment arms will be measured at months 3 , 6 , 9 , and 12 . Cost-effectiveness will be calculated |
10,799 | 29,143,638 | Improvements to the water supply and water disinfection at source did not show significant effects on diarrhea risk , nor did the one eligible study examining the effect of latrine construction .
Conclusions Various WASH interventions show diarrhea risk reductions between 27 % and 53 % in children 0–5 years old , depending on intervention type , providing ample evidence to support the scale-up of WASH in low and middle-income countries ( LMICs ) . | Background In the Sustainable Development Goals ( SDGs ) era , there is growing recognition of the responsibilities of non-health sectors in improving the health of children .
Interventions to improve access to clean water , sanitation facilities , and hygiene behaviours ( WASH ) represent key opportunities to improve child health and well-being by preventing the spread of infectious diseases and improving nutritional status . | Abstract Objective To compare the effect on prevalence of diarrhoea and mortality of household based treatment of drinking water with flocculant-disinfectant , sodium hypochlorite , and st and ard practice s in areas with turbid water source in Africa . Design Cluster r and omised controlled trial over 20 weeks . Setting Family compounds , each containing several houses , in rural western Kenya . Participants 6650 people in 605 family compounds . Intervention Water treatment : flocculant-disinfectant , sodium hypochlorite , and usual practice ( control ) . Main outcome measures Prevalence of diarrhoea and all cause mortality . Escherichia coli concentration , free residual chlorine concentration , and turbidity in household drinking water as surrogates for effectiveness of water treatment . Results In children < 2 years old , compared with those in the control compounds , the absolute difference in prevalence of diarrhoea was –25 % in the flocculant-disinfectant arm ( 95 % confidence interval –40 to –5 ) and –17 % in the sodium hypochlorite arm ( –34 to 4 ) . In all age groups compared with control , the absolute difference in prevalence was –19 % in the flocculant-disinfectant arm ( –34 to –2 ) and –26 % in the sodium hypochlorite arm ( –39 to –9 ) . There were significantly fewer deaths in the intervention compounds than in the control compounds ( relative risk of death 0.58 , P = 0.036 ) . Fourteen per cent of water sample s from control compounds had E coli concentrations < 1 CFU/100 ml compared with 82 % in flocculant-disinfectant and 78 % in sodium hypochlorite compounds . The mean turbidity of drinking water was 8 nephelometric turbidity units ( NTU ) in flocculant-disinfectant households , compared with 55 NTU in the two other compounds ( P < 0.001 ) . Conclusions In areas of turbid water , flocculant-disinfectant was associated with a significant reduction in diarrhoea among children < 2 years . This health benefit , combined with a significant reduction in turbidity , suggests that the flocculant-disinfectant is well suited to areas with highly contaminated and turbid water We conducted a study to determine if use of a new flocculant-disinfectant home water treatment reduced diarrhea . We r and omly assigned 492 rural Guatemalan households to five different water treatment groups : flocculant-disinfectant , flocculant-disinfectant plus a customized vessel , bleach , bleach plus a vessel , and control . During one year of observation , residents of control households had 4.31 episodes of diarrhea per 100 person-weeks , whereas the incidence of diarrhea was 24 % lower among residents of households receiving flocculant-disinfectant , 29 % lower among those receiving flocculant-disinfectant plus vessel , 25 % lower among those receiving bleach , and 12 % lower among households receiving bleach plus vessel . In unannounced evaluations of home drinking water , free chlorine was detected in sample s from 27 % of flocculant-disinfectant households , 35 % of flocculant-disinfectant plus vessel households , 35 % of bleach households , and 43 % of bleach plus vessel households . In a setting where diarrhea was a leading cause of death , intermittent use of home water treatment with flocculant-disinfectant decreased the incidence of diarrhea Sophie Boisson and colleagues conducted a double-blind , r and omized placebo-controlled trial in Orissa , a state in southeast India , to evaluate the effect of household water treatment in preventing diarrheal illnesses in children aged under five years of age . Please see later in the article for the Editors ' A novel water quality intervention that consists of point-of-use water disinfection , safe storage and community education was field tested in Bolivia . A total of 127 households in two periurban communities were r and omized into intervention and control groups , surveyed and the intervention was distributed . Monthly water quality testing and weekly diarrhoea surveillance were conducted . Over a 5-month period , intervention households had 44 % fewer diarrhoea episodes than control households ( P = 0.002 ) . Infants < 1 year old ( P = 0.05 ) and children 5 - 14 years old ( P = 0.01 ) in intervention households had significantly less diarrhoea than control children . Campylobacter was less commonly isolated from intervention than control patients ( P = 0.02 ) . Stored water in intervention households was less contaminated with Escherichia coli than stored water in control households ( P < 0.0001 ) . Intervention households exhibited less E. coli contamination of stored water and less diarrhoea than control households . This promising new strategy may have broad applicability for waterborne disease prevention Ceramic water filters have been identified as one of the most promising and accessible technologies for treating water at the household level . In a six-month trial , water filters were distributed r and omly to half of the 50 participating households in a rural community in Bolivia ; the remaining households continued to use customary water h and ling practice s and served as controls . In four rounds of sampling following distribution of the filters , 100 % of the 96 water sample s from the filter households were free of thermotolerant coliforms compared with 15.5 % of the control household sample s. Diarrheal disease risk for individuals in intervention households was 70 % lower than for controls ( 95 % confidence interval [ CI ] = 53 - 80 % ; P < 0.001 ) . For children less than five years old , the reduction in risk was 83 % ( 95 % CI = 51 - 94 % ; P < 0.001 ) . These results show that affordable ceramic water filters enable low-income households to treat and maintain the microbiologic quality of their drinking water Background Household water treatment can improve the microbiological quality of drinking water and may prevent diarrheal diseases . However , current methods of treating water at home have certain shortcomings , and there is evidence of bias in the reported health impact of the intervention in open trial design s. Methods and Findings We undertook a r and omised , double-blinded , placebo-controlled trial among 240 households ( 1,144 persons ) in rural Democratic Republic of Congo to assess the field performance , use and effectiveness of a novel filtration device in preventing diarrhea . Households were followed up monthly for 12 months . Filters and placebos were monitored for longevity and for microbiological performance by comparing thermotolerant coliform ( TTC ) levels in influent and effluent water sample s. Mean longitudinal prevalence of diarrhea was estimated among participants of all ages . Compliance was assessed through self-reported use and presence of water in the top vessel of the device at the time of visit . Over the 12-month follow-up period , data were collected for 11,236 person-weeks of observation ( 81.8 % total possible ) . After adjusting for clustering within the household , the longitudinal prevalence ratio of diarrhoea was 0.85 ( 95 % confidence interval : 0.61–1.20 ) . The filters achieved a 2.98 log reduction in TTC levels while , for reasons that are unclear , the placebos achieved a 1.05 log reduction ( p<0.0001 ) . After 8 months , 68 % of intervention households met the study 's definition of current users , though most ( 73 % of adults and 95 % of children ) also reported drinking untreated water the previous day . The filter maintained a constant flow rate over time , though 12.4 % of filters were damaged during the course of the study . Conclusions While the filter was effective in improving water quality , our results provide little evidence that it was protective against diarrhea . The moderate reduction observed nevertheless supports the need for larger studies that measure impact against a neutral placebo . Trial Registration Current Controlled Trials IS RCT We report the results of a r and omized controlled intervention study ( September 2007 to March 2009 ) investigating the effect of solar disinfection ( SODIS ) of drinking water on the incidence of dysentery , nondysentery diarrhea , and anthropometric measurements of height and weight among children of age 6 months to 5 years living in peri-urban and rural communities in Nakuru , Kenya . We compared 555 children in 404 households using SODIS with 534 children in 361 households with no intervention . Dysentery was recorded using a pictorial diary . Incidence rate ratios ( IRR ) for both number of days and episodes of dysentery and nondysentery diarrhea were significantly ( P < 0.001 ) reduced by use of solar disinfection : dysentery days IRR = 0.56 ( 95 % CI 0.40 to 0.79 ) ; dysentery episodes IRR = 0.55 ( 95 % CI 0.42 to 0.73 ) ; nondysentery days IRR = 0.70 ( 95 % CI 0.59 to 0.84 ) ; nondysentery episodes IRR = 0.73 ( 95 % CI 0.63 to 0.84 ) . Anthropometry measurements of weight and height showed median height-for-age was significantly increased in those on SODIS , corresponding to an average of 0.8 cm over a 1-year period over the group as a whole ( 95 % CI 0.7 to 1.6 cm , P = 0.031 ) . Median weight-for-age was higher in those on SODIS , corresponding to a 0.23 kg difference in weight over the same period ; however , the confidence interval spanned zero and the effect fell short of statistical significance ( 95 % CI -0.02 to 0.47 kg , P = 0.068 ) . SODIS and control households did not differ in the microbial quality of their untreated household water over the follow-up period ( P = 0.119 ) , but E. coli concentrations in SODIS bottles were significantly lower than those in storage containers over all follow-up visits ( P < 0.001 ) . This is the first trial to show evidence of the effect of SODIS on childhood anthropometry , compared with children in the control group and should alleviate concerns expressed by some commentators that the lower rates of dysentery associated with SODIS are the product of biased reporting rather than reflective of genuinely decreased incidence A r and omized , controlled intervention trial of two household-scale drinking water filters was conducted in a rural village in Cambodia . After collecting four weeks of baseline data on household water quality , diarrheal disease , and other data related to water use and h and ling practice s , households were r and omly assigned to one of three groups of 60 households : those receiving a ceramic water purifier ( CWP ) , those receiving a second filter employing an iron-rich ceramic ( CWP-Fe ) , and a control group receiving no intervention . Households were followed for 18 weeks post-baseline with biweekly follow-up . Households using either filter reported significantly less diarrheal disease during the study compared with a control group of households without filters as indicated by longitudinal prevalence ratios CWP : 0.51 ( 95 % confidence interval [ CI ] : 0.41 - 0.63 ) ; CWP-Fe : 0.58 ( 95 % CI : 0.47 - 0.71 ) , an effect that was observed in all age groups and both sexes after controlling for clustering within households and within individuals over time Daniel Maeusezahl and colleagues conducted a cluster-r and omized controlled trial in rural Bolivia of solar drinking water disinfection , and find only moderate compliance with the intervention and no evidence of reduction in diarrhea among children Lack of access to safe water and sanitation contributes to diarrhoea moribidity and mortality in developing countries . We evaluated the impact of household water treatment , latrines , shallow wells , and rainwater harvesting on diarrhoea incidence in rural Kenyan children . We compared diarrhoea rates in 960 children aged < 5 years in 556 households in 12 r and omly selected intervention villages and six r and omly selected comparison villages during weekly home visits over an 8-week period . On multivariate analysis , chlorinating stored water [ relative risk ( RR ) 0.44 , 95 % confidence interval ( CI ) 0.28 - 0.69 ] , latrine presence ( RR 0.71 , 95 % CI 0.54 - 0.92 ) , rainwater use ( RR 0.70 , 95 % CI 0.52 - 0.95 ) , and living in an intervention village ( RR 0.31 , 95 % CI 0.23 - 0.41 ) , were independently associated with lower diarrhoea risk . Diarrhoea risk was higher among shallow well users ( RR 1.78 , 95 % CI 1.12 - 2.83 ) . Chlorinating stored water , latrines , and rainwater use all decreased diarrhoea risk ; combined interventions may have increased health impact OBJECTIVES To evaluate the effectiveness of point of use water treatment with flocculent-disinfectant on reducing diarrhoea and the additional benefit of promoting h and washing with soap . METHODS The study was conducted in squatter settlements of Karachi , Pakistan , where diarrhoea is a leading cause of childhood death . Interventions were r and omly assigned to 47 neighbourhoods . Households in 10 neighbourhoods received diluted bleach and a water vessel ; nine neighbourhoods received soap and were encouraged to wash h and s ; nine neighbourhoods received flocculent-disinfectant water treatment and a water vessel ; 10 neighbourhoods received disinfectant-disinfectant water treatment and soap and were encouraged to wash h and s ; and nine neighbourhoods were followed as controls . Field workers visited households at least once a week from April to December 2003 to promote use of the interventions and to collect data on diarrhoea . RESULTS Study participants in control neighbourhoods had diarrhoea on 5.2 % of days . Compared to controls , participants living in intervention neighbourhoods had a lower prevalence of diarrhoea : 55 % ( 95 % CI 17 % , 80 % ) lower in bleach and water vessel neighbourhoods , 51 % ( 95 % CI 12 % , 76 % ) lower in h and washing promotion with soap neighbourhoods , 64 % lower ( 95 % CI 29 % , 90 % ) in disinfectant-disinfectant neighbourhoods , and 55 % ( 95 % CI 18 % , 80 % ) lower in disinfectant-disinfectant plus h and washing with soap neighbourhoods . CONCLUSIONS With an intense community-based intervention and supplies provided free of cost , each of the home-based interventions significantly reduced diarrhoea . There was no benefit by combining h and washing promotion with water treatment Safe domestic potable water supplies are urgently needed to reduce childhood diarrheal disease . In periurban neighborhoods in Cochabamba , Bolivia , we conducted a cluster r and omized controlled trial to evaluate the efficacy of a household-level hollow fiber filter and /or behavior change communication ( BCC ) on water , sanitation , and hygiene ( WASH ) to reduce the diarrheal disease in children less than 5 years of age . In total , 952 households were followed for a period of 12 weeks post-distribution of the study interventions . Households using Sawyer PointONE filters had significantly less diarrheal disease compared with the control arm during the intervention period , which was shown by diarrheal prevalence ratios of 0.21 ( 95 % confidence interval [ 95 % CI ] = 0.15–0.30 ) for the filter arm and 0.27 ( 95 % CI = 0.22–0.34 ) for the filter and WASH BCC arm . A non-significant reduction in diarrhea prevalence was reported in the WASH BCC study arm households ( 0.71 , 95 % CI = 0.59–0.86 ) A number of household water treatment and safe storage technologies , such as chlorine disinfection , solar disinfection , and ceramic filtration , have been documented for their ability to reduce diarrheal disease and improve microbial water quality . The bios and filter ( BSF ) is a promising household water treatment technology in use by > 500,000 people globally . The purpose of this research was to document the ability of BSFs to improve water quality and to reduce diarrheal disease in user compared with non-user households in a r and omized controlled trial in Bonao , Dominican Republic , during 2005 - 2006 . During the 6-month intervention period , 75 BSF households had significantly improved drinking water quality on average compared with 79 control households ( P < 0.001 ) . Based on r and om intercepts logistic regression , BSF households had 0.53 times the odds of diarrheal disease as control households , indicating a significant protective effect of the BSF against waterborne diarrheal disease OBJECTIVE To examine the effect of a new point-of-use treatment for drinking-water , a commercially developed flocculant-disinfectant , on the prevalence of diarrhoea in children . METHODS We conducted a r and omized controlled trial among 514 rural Guatemalan households , divided into 42 neighbourhood clusters , for 13 weeks , from 4 November 2002 through 31 January 2003 . Clusters assigned to water treatment with the flocculant-disinfectant were compared with those using their usual water-h and ling practice s. The longitudinal prevalence of diarrhoea was calculated as the proportion of total days with diarrhoea divided by the total number of days of observation . The prevalence of diarrhoea was compared using the Wilcoxon rank-sum test . FINDINGS The 1702 people in households receiving the disinfectant had a prevalence of diarrhoea that was 40 % lower than that among the 1699 people using st and ard water-h and ling practice s ( 0.9 % versus 1.5 % ; P = 0.001 ) . In households using the flocculant-disinfectant , children < 1 year of age had a 39 % lower prevalence of diarrhoea than those in households using their st and ard practice s ( 3.7 % versus 6.0 % ; P = 0.005 ) . CONCLUSION In setting s where families rarely treat drinking-water , we introduced a novel flocculant-disinfectant that reduced the longitudinal prevalence of diarrhoea , especially among children aged < 1 year , among whom diarrhoea has been strongly associated with mortality . Successful introduction and use of this product could contribute to preventing diarrhoeal disease globally The Jolivert Safe Water for Families program has sold sodium hypochlorite solution ( chlorine ) and conducted household visits in rural Haiti since 2002 . To assess the impact of the program on diarrheal disease , in 2010 we conducted a survey and water quality testing in 201 program participants and 425 control households selected at r and om . Fifty-six percent of participants ( versus 10 % of controls ) had free chlorine residuals between 0.2 and 2.0 mg/L , indicating correct water treatment . Using intention-to-treat analysis , we found that significantly fewer children < 5 in participant households had an episode of diarrhea in the previous 48 hours ( 32 % versus 52 % ; P < 0.001 ) with 59 % reduced odds ( odds ratio = 0.41 , 95 % confidence interval = 0.21–0.79 ) . Treatment-on-treated estimates of the odds of diarrhea indicated larger program effects for participants who met more stringent verifications of participation . Diarrheal disease reduction in this long-term program was comparable with that seen in short-term r and omized , controlled interventions , suggesting that household chlorination can be an effective long-term water treatment strategy During the period September 1991 to February 1992 st and ard chlorination packages of calcium hypochloride were provided for the first time to 171 families residing in the catchment area of the Sabt-Bany Bishr Primary Health Care Centre in the rural areas of the Asir region , south-western Saudi Arabia . The villagers added the packages to their home storage water tanks each time they added water from the 220 nearby wells . Analysis of the water sample s taken from these wells showed that all of them were bacteriologically unfit for human use . By the end of the study period there were no bacteriologically unfit water sample s taken from the tanks of the participating families . Children under 5 years of age whose families were not using chlorinated water had twice the risk of diarrhoea compared to children from the participating families ( odds ratio = 1.98 , P = 0.047 ) . The use of chlorinated water was associated with a 48 % reduction in diarrhoea . These results indicate that the chlorination of water can be successfully carried out locally in rural areas to improve the health of the population About half of the rural population of Cambodia lacks access to improved water ; an even higher percentage lacks access to latrines . More than 35,000 concrete BioS and Water filters ( BSF ) have been installed in the country . However , the concrete BSF takes time to produce and weighs hundreds of pounds . A plastic BSF has been developed but may not perform to the same benchmarks established by its predecessor . To evaluate plastic BSF performance and health impact , we performed a cluster r and omized controlled trial in 13 communities including 189 households and 1147 participants in the Angk Snoul district of K and al Province from May to December 2008 . The results suggest that villages with plastic BSFs had significantly lower concentrations of E. coli in drinking water and lower diarrheal disease ( incidence rate ratio 0.41 , 95 % confidence interval : 0.24 - 0.69 ) compared to control villages . As one of the first studies on the plastic BSF in Cambodia , these are important findings , especially in a setting where the concrete BSF has seen high rates of continued use years after installation . The study suggests the plastic BSF may play an important role in scaling up the distribution/implementation of the BSF , potentially improving water quality and health in the region Background Household water treatment has been advocated as a means of decreasing the burden of diarrheal diseases among young children in areas where piped and treated water is not available . However , its effect size , the target population that benefit from the intervention , and its acceptability especially in rural population is yet to be determined . The objective of the study was to assess the effectiveness of household water chlorination in reducing incidence of diarrhea among children under-five years of age . Method A cluster r and omized community trial was conducted in 36 rural neighborhoods of Eastern Ethiopia . Households with at least one child under-five years of age were included in the study . The study compared diarrhea incidence among children who received sodium hypochlorite ( liquid bleach ) for household water treatment and children who did not receive the water treatment . Generalized Estimation Equation model was used to compute adjusted incidence rate ratio and the corresponding 95 % confidence interval . Result In this study , the incidence of diarrhea was 4.5 episodes/100 person week observations in the intervention arm compared to 10.4 episodes/100 person week observations in the control arm . A statistically significant reduction in incidence of diarrhea was observed in the intervention group compared to the control ( Adjusted IRR = 0.42 , 95 % CI 0.36–0.48 ) . Conclusion Exp and ing access to household water chlorination can help to substantially reduce child morbidity and achieve millennium development goal until reliable access to safe water is achieved . Trial Registration Clinical Trials.gov We conducted a r and omized , placebo-controlled , triple-blinded trial to determine the health impact of daily use of sodium dichloroisocyanurate ( NaDCC ) tablets for household drinking water treatment in periurban Ghana . We r and omized 240 households ( 3,240 individuals ) to receive either NaDCC or placebo tablets . All households received a 20-liter safe water storage vvessel . Over 12 weeks , 446 diarrhea episodes ( 2.2 % ) occurred in intervention and 404 ( 2.0 % ) in control households ( P = 0.38 ) . Residual free chlorine levels indicated appropriate tablet use . Escherichia coli was found in stored water at baseline in 96 % of intervention and 88 % of control households and at final evaluation in 8 % of intervention and 54 % of control households ( P = 0.002 ) . NaDCC use did not prevent diarrhea but improved water quality . Diarrhea rates were low and water quality improved in both groups . Safe water storage vessels may have been protective . A follow-up health impact study of NaDCC tablets is warranted Household water treatment is increasingly recognized as an effective means of reducing the burden of diarrheal disease among low-income population s without access to safe water . Oxfam GB undertook a pilot project to explore the use of household-based ceramic water filters in three remote communities in Colombia . In a r and omized , controlled trial over a period of six months , the filters were associated with a 75.3 % reduction in arithmetic mean thermotolerant coliforms ( TTCs ) ( P < 0.0001 ) . A total of 47.7 % and 24.2 % of the sample s from the intervention group had no detectible TTCs/100 mL or conformed to World Health Organization limits for low risk ( 1 - 10 TTCs/100 mL ) , respectively , compared with 0.9 % and 7.3 % for control group sample s. Overall , prevalence of diarrhea was 60 % less among households using filters than among control households ( odds ratio = 0.40 , 95 % confidence interval = 0.25 , 0.63 , P < 0.0001 ) . However , the microbiologic performance and protective effect of the filters was not uniform throughout the study communities , suggesting the need to consider the circumstances of the particular setting before implementing this intervention A r and omized controlled trial of four interventions was conducted using tubewells ( n=2,486 ) , liquid sodium hypochlorite ( ' Clorin ' ) distributed with an improved water vessel ( n=2,305 ) , hygiene promotion ( n=1,877 ) , and a combination of the three ( n=2,040 ) to create an evidence -base for water policy in Afghanistan . A fifth group served as a control ( n=2,377 ) . Interventions were r and omized across 32 villages in Wardak province . Outcomes were measured through two household surveys separated by one year and twice-weekly household surveillance conducted over 16 months . The households receiving all three interventions showed reduction in diarrhoea compared with the control group , through both longitudinal surveillance data ( IRR [ 95 % CI]=0.61 [ 0.47 - 0.81 ] ) and cross-sectional survey data ( AOR [ 95 % CI]=0.53 [ 0.30 - 0.93 ] ) . This reduction was significant when all household members were included , but did not reach significance when only children under five were considered . These results suggest multi-barrier methods are necessary where there are many opportunities for water contamination . Surveillance data suggested a greater impact of interventions on reducing diarrhoeal diseases than data from the surveys . Higher economic status as measured through household assets was associated with lower rates of diarrhoea and greater intervention uptake , excepting Clorin . Use of soap was also associated with lower prevalence of diarrhoea CONTEXT Washing h and s with soap prevents diarrhea , but children at the highest risk of death from diarrhea are younger than 1 year , too young to wash their own h and s. Previous studies lacked sufficient power to assess the impact of household h and washing on diarrhea in infants . OBJECTIVE To evaluate the effect of promoting household h and washing with soap among children at the highest risk of death from diarrhea . DESIGN , SETTING , AND PARTICIPANTS A cluster r and omized controlled trial of 36 low-income neighborhoods in urban squatter settlements in Karachi , Pakistan . Field workers visited participating households at least weekly from April 15 , 2002 , to April 5 , 2003 . Eligible households located in the study area had at least 2 children younger than 15 years , at least 1 of whom was younger than 5 years . INTERVENTIONS Weekly visits in 25 neighborhoods to promote h and washing with soap after defecation and before preparing food , eating , and feeding a child . Within intervention neighborhoods , 300 households ( 1523 children ) received a regular supply of antibacterial soap and 300 households ( 1640 children ) received plain soap . Eleven neighborhoods ( 306 households and 1528 children ) comprised the control group . MAIN OUTCOME MEASURE Incidence density of diarrhea among children , defined as the number of diarrheal episodes per 100 person-weeks of observation . RESULTS Children younger than 15 years living in households that received h and washing promotion and plain soap had a 53 % lower incidence of diarrhea ( 95 % confidence interval [ CI ] , -65 % to -41 % ) compared with children living in control neighborhoods . Infants living in households that received h and washing promotion and plain soap had 39 % fewer days with diarrhea ( 95 % CI , -61 % to -16 % ) vs infants living in control neighborhoods . Severely malnourished children ( weight for age z score , < -3.0 ) younger than 5 years living in households that received h and washing promotion and plain soap had 42 % fewer days with diarrhea ( 95 % CI , -69 % to -16 % ) vs severely malnourished children in the control group . Similar reductions in diarrhea were observed among children living in households receiving antibacterial soap . CONCLUSION In a setting in which diarrhea is a leading cause of child death , improvement in h and washing in the household reduced the incidence of diarrhea among children at high risk of death from diarrhea Simple , effective and affordable methods are needed to treat and safely store non-piped , gathered household water . This study evaluated point-of-use chlorination and storage in special plastic containers of gathered household water for improving microbial quality and reducing diarrhoeal illness of consumers living under conditions of poor sanitation and hygiene . Community families were recruited and r and omly divided into intervention ( household water chlorination and storage in a special container ) and control ( no intervention ) households . Microbes in stored household water were extensively inactivated by 1 - 5-mg/L doses of hypochlorite . Escherichia coli levels in stored household waters were < 1/100 mL in most intervention households but readily detectable at high levels in control households . Stored water of intervention households was also lower in Clostridium perfringens and heterotrophic plate count bacteria than in control households . The intervention reduced household diarrhoeal illness . In Bolivia , monthly episodes of household diarrhoeal illness were 1.25 and 2.2 in intervention and control families , respectively ( P = < 0.002 ) indicating that 43 % of community diarrhoea was preventable by using the intervention . In Bangladesh , mean episodes of child diarrhoea/1,000 d were 19.6 and 24.8 in intervention and control groups respectively ( P = < 0.03 ) indicating that about 24 % of observed diarrhoea was preventable by using the intervention . Chlorine disinfection and storage in an appropriate container significantly improved the microbiological quality of non-piped household drinking water and reduced community diarrhoeal disease . Widespread use of this simple treatment and storage system for non-piped domestic water has the potential to dramatically reduce the global burden of waterborne diarrhoeal disease We conducted a r and omized controlled trial to assess the Lifestraw Personal pipe-style water treatment device among a rural population in Ethiopia . A total of 313 households ( including 1516 persons ) were r and omly assigned either to an intervention group in which each householder received a Lifestraw Personal or a control . Households were visited fortnightly over a five-month intervention period and asked to report any episode of diarrhea during the previous week . A r and om sample of 160 devices was tested each month to assess the presence of thermotolerant coliforms ( TTC ) and residual iodine in treated water and to measure flow rate under simulated use . Members of the intervention group had 25 % fewer weeks with diarrhea than those of the control group ( longitudinal prevalence ratio = 0.75 ; 95 % CI 0.60 ; 0.95 ) . All 718 filtered water sample s were free of TTC , were free of detectable iodine disinfectant , and showed a constant flow rate over time . After the five-month intervention period , 34 % of participants reported use of device in the preceding week and 13 % reported consistent use . While the device was associated with a 25 % reduction in longitudinal prevalence of diarrhea , low levels of use suggest that much of this effect is likely to be attributable to reporting bias that is common in open trials with non objective outcomes To determine the effectiveness of ceramic filters in reducing diarrhea , we conducted a r and omized controlled trial in Zimbabwe and South Africa , in which 61 of 115 households received ceramic filters . Incidence of non-bloody and bloody diarrhea was recorded daily over 6 months using pictorial diaries for children 24 - 36 months of age . Poisson regression was used to compare incidence rates in intervention and control households . Adjusted for source quality , intervention household drinking water showed reduced Escherichia coli counts ( relative risk , 0.67 ; 95 % CI , 0.50 - 0.89 ) . Zero E. coli were obtained for drinking water in 56.9 % of intervention households . The incidence rate ratio for bloody diarrhea was 0.20 ( 95 % CI , 0.09 - 0.43 ; P < 0.001 ) and for non-bloody diarrhea was 0.17 ( 95 % CI , 0.08 - 0.38 ; P < 0.001 ) , indicating much lower diarrhea incidence among filter users . The results suggest that ceramic filters are effective in reducing diarrheal disease incidence Diarrheal diseases pose a major threat to the health of people living in developing countries , particularly where there is poverty and a poor environment . The effect of h and washing in reducing the incidence of diarrhea in day-care centers has been reported recently . The present study is a prospect i ve community based study conducted to evaluate the effect of h and washing on the incidence of diarrheal disease in Calcutta slums . H and washing was implemented in 1 slum and the other nearby slum , without h and washing program , served as control . The incidence of watery diarrhea during the 13 month period , between the study and control groups was not significantly different . However , the incidence of dysentery in individuals above 5 years of age in the control group was significantly higher as compared to those in the study group ( p 0.05 ) . The results of this study indicate that h and washing with soap may reduce the incidence of dysenteric cases in the community by interruption of transmission of the pathogens from 1 person to the other This study examines the effect of maternal personal and domestic hygiene on the incidence of diarrhoea in children aged 6 - 23 months from rural areas around Teknaf , Bangladesh . The intervention area received augmented water supply through h and pumps and health education while the control area received no project inputs . From July 1980 to June 1983 , diarrhoea incidence was recorded weekly while mothers ' personal and domestic hygiene was observed yearly . Annual incidence of diarrhoea in 314 children from the intervention area and 309 children from the control area was analysed in relation to maternal personal and domestic hygiene , controlling for education and occupation of household head and household size . Results show that , in both areas , use of h and pump water for drinking and washing , removal of child 's faeces from the yard , and maternal h and washing before h and ling food and after defaecation of self and child , observed together , decreased yearly diarrhoea incidence in children by more than 40 % compared to children living in households where none or only one of these practice s was observed OBJECTIVE Measure effectiveness of intermittent slow s and filtration for reducing child diarrhoea among households using unimproved water sources in rural Kenya . METHODS A r and omized controlled trail was conducted among population s meeting a high-risk profile for child diarrhoea from drinking river water in the River Njoro watershed . Intervention households ( 30 ) were provided the concrete BioS and Filter and instructed on filter use and maintenance . Control households ( 29 ) continued normal practice s. Longitudinal monthly monitoring of diarrhoea ( seven-day daily prevalence recall ) and of influent , effluent , and drinking water quality for fecal coliform was conducted for 6 months . RESULTS Intervention households had better drinking water quality than control households ( fecal coliform geometric mean , 30.0 CFU vs. 89.0 CFU/100 ml , P < 0.001 ) and reported significantly fewer diarrhoea days ( 86 days over 626 child-weeks ) compared to controls ( 203 days over 558 child-weeks ) among children up to 15 ( age-adjusted RR 0.46 ; 95 % CI = 0.22 , 0.96 ) . Greater child diarrhoea reduction due to the intervention ( age-adjusted RR 0.23 , 95 % CI = 0.10 , 0.51 ) was observed among the sub-group using unimproved water sources all of the time . CONCLUSION Intermittent slow s and filtration , a non-commercial technology , produces similar observed effects on child diarrhoea as commercial POU products , adding to the range of effective options for poor population s ( chlorination , ceramic filtration , solar disinfection , flocculation/disinfection ) The incidence of diarrhea , respiratory disease , and skin infections was prospect ively determined after the introduction of a system which distributed unlimited quantities of high quality fresh water to each of the 150 housing units on Tupile , an isl and devoid of fresh water located off Panama 's Caribbean coast and inhabited by 1,500 Cuna Indians . Tupile residents used 7.1 liters of water/person/day compared to the 2.3 usage rate of inhabitants on Achutupo , the control isl and . Despite ready availability of water in each household , Tupile residents continued to store water in contaminated vessels prior to use . Forty percent of stored water sample s tested on Tupile and 45 % on Achutupo were contaminated with E. coli organisms . There were 4.7 episodes/child year ( E/Y ) of acute diarrhea on Tupile compared with the 3.5 rate on Achutupo . The rotavirus infection rate on Tupile was 0.8 E/Y compared with 0.2 E/Y on Achutupo . Infection rates for Norwalk virus , respiratory syncytial virus and Coxsackie B 1 - 6 viruses were similar on both isl and s. Respiratory disease rates were high on both isl and s ( 2.2 E/Y on Tupile , 2.7 E/Y on Achutupo ) . Achutupo had much higher rates of impetigo and scabies ( 0.6 E/Y and 2.5 E/Y , respectively ) than Tupile ( 0.2 E/Y and 1.4 E/Y ) . Provision of the water distribution system had a beneficial effect on the incidence of water-washed diseases ( impetigo and scabies ) , but at best had no effect on diarrheal disease Morbidity due to dracunculiasis ( guinea worm disease ) and diarrhoea in persons of all ages , and nutritional status of young children , were used as health impact indicators in the evaluation of the Imo State Drinking Water Supply and Sanitation Project in south-eastern Nigeria . Data were collected using repeated cross-sectional surveys and longitudinal follow-up . The study area was found to have a low level of endemicity of dracunculiasis . While no impact could be demonstrated on overall period or point prevalence rates in the cross-sectional surveys , a prospect i ve longitudinal survey showed a significant reduction in the percentage of person-fortnights positive for dracunculiasis in areas served by the project , while the control areas showed no such change . In the cross-sectional surveys it was found that , in the project villages , those persons drinking only borehole water had significantly lower period prevalence rates one year later than others . Moreover , those living further from the nearest borehole had higher rates of dracunculiasis . An impact of the project on diarrhoea morbidity was found only in limited sub-groups of the population . A greater association with water availability rather than quality was suggested for rates in young children . The prevalence of wasting ( less than 80 % weight-for-height ) among children aged less than 3 years decreased significantly over time in all 3 intervention villages ; there was no such decline in the control villages Background : Solar radiations improve the microbiological quality of water and offer a method for disinfection of drinking water that requires few re sources and no expertise and may reduce the prevalence of diarrhea among under-five children . Aims and Objectives : To find out the reduction in the prevalence of diarrhea in the under-five children after consumption of potable water treated with solar disinfection method . Material s and Methods : This was a population -based interventional prospect i ve study in the urban slum area of Mazegoan , Jorethang , south Sikkim , during the period 1st May 2007 to 30th November 2007 on 136 children in the under-five age group in 102 households selected by r and om sampling . Main outcome measure was the assessment of the reduction of the prevalence of diarrhea among under-five children after consumption of potable water treated with solar disinfection method practice d by the caregivers in the intervention group keeping water in polyethylene terephthalate ( PET ) bottles as directed by the investigators . The data were collected by the interview method using a pre-tested question naire prepared on the basis of socio-demographics and prevalence of diarrhea . The data were subjected to percentages and chi-square tests , which were used to find the significance . Results : After four weeks of intervention among the study group , the diarrhea prevalence was 7.69 % among solar disinfection ( SODIS ) users , while 31.82 % prevalence was observed among non-users in that period ; the reduction in prevalence of diarrhea was 75.83 % . After eight weeks of intervention , the prevalence of diarrhea was 7.58 % among SODIS users and 31.43 % among non-users ; the reduction in diarrhea was 75.88 % in the study group . The findings were found to be statistically significant . Conclusions : In our study , we observed that the prevalence of diarrhea decreased significantly after solar disinfection of water was practice d by the caregivers keeping potable water in PET bottles in the intervention group BACKGROUND A third of the 2·5 billion people worldwide without access to improved sanitation live in India , as do two-thirds of the 1·1 billion practising open defecation and a quarter of the 1·5 million who die annually from diarrhoeal diseases . We aim ed to assess the effectiveness of a rural sanitation intervention , within the context of the Government of India 's Total Sanitation Campaign , to prevent diarrhoea , soil-transmitted helminth infection , and child malnutrition . METHODS We did a cluster-r and omised controlled trial between May 20 , 2010 , and Dec 22 , 2013 , in 100 rural villages in Odisha , India . Households within villages were eligible if they had a child younger than 4 years or a pregnant woman . Villages were r and omly assigned ( 1:1 ) , with a computer-generated sequence , to undergo latrine promotion and construction or to receive no intervention ( control ) . R and omisation was stratified by administrative block to ensure an equal number of intervention and control villages in each block . Masking of participants was not possible because of the nature of the intervention . However , households were not told explicitly that the purpose of enrolment was to study the effect of a trial intervention , and the surveillance team was different from the intervention team . The primary endpoint was 7-day prevalence of reported diarrhoea in children younger than 5 years . We did intention-to-treat and per- protocol analyses . This trial is registered with Clinical Trials.gov , number NCT01214785 . FINDINGS We r and omly assigned 50 villages to the intervention group and 50 villages to the control group . There were 4586 households ( 24,969 individuals ) in intervention villages and 4894 households ( 25,982 individuals ) in control villages . The intervention increased mean village-level latrine coverage from 9 % of households to 63 % , compared with an increase from 8 % to 12 % in control villages . Health surveillance data were obtained from 1437 households with children younger than 5 years in the intervention group ( 1919 children younger than 5 years ) , and from 1465 households ( 1916 children younger than 5 years ) in the control group . 7-day prevalence of reported diarrhoea in children younger than 5 years was 8·8 % in the intervention group and 9·1 % in the control group ( period prevalence ratio 0·97 , 95 % CI 0·83 - 1·12 ) . 162 participants died in the intervention group ( 11 children younger than 5 years ) and 151 died in the control group ( 13 children younger than 5 years ) . INTERPRETATION Increased latrine coverage is generally believed to be effective for reducing exposure to faecal pathogens and preventing disease ; however , our results show that this outcome can not be assumed . As efforts to improve sanitation are being undertaken worldwide , approaches should not only meet international coverage targets , but should also be implemented in a way that achieves uptake , reduces exposure , and delivers genuine health gains . FUNDING Bill & Melinda Gates Foundation , International Initiative for Impact Evaluation ( 3ie ) , and Department for International Development-backed SHARE Research Consortium at the London School of Hygiene & Tropical Medicine Deteriorating water treatment facilities and distribution systems pose a significant public health threat , particularly in republics of the former Soviet Union . Interventions to decrease the disease burden associated with these water systems range from upgrading distribution networks to installing reverse osmosis technology . To provide insight into this decision process , we conducted a r and omized intervention study to provide epidemiologic data for water policy decisions in Nukus , Uzbekistan , where drinking water quality is suboptimal . We interviewed residents of 240 households , 120 with and 120 without access to municipal piped water . Residents of 62 households without piped water were trained to chlorinate their drinking water at home in a narrow-necked water container with a spout . All study subjects ( 1583 individuals ) were monitored biweekly for self-reported diarrheal illness over a period of 9.5 weeks . The home chlorination intervention group had the lowest diarrheal rate ( 28.8/1,000 subjects/month ) despite lack of access to piped water in their homes . Compared with the two groups that did not receive the intervention this rate was one-sixth that of the group with no piped water ( 179.2/1,000 subjects/month ) and one-third that of the households with piped water ( 75.5/1,000 subjects/month ) . More than 30 % of the households with piped water lacked detectable levels of chlorine residues in their drinking water , despite two-stage chlorination of the source water , and were at increased risk of diarrhea . Forty-two percent of these municipal users reported that water pressure had been intermittent within the previous two days . The dramatic reduction in diarrheal rates in the home-chlorination intervention group indicates that a large proportion of diarrheal diseases in Nukus are water-borne . The home-chlorination group had less diarrhea than the group with piped water , implicating the distribution system as a source of disease transmission . Taken together , these epidemiologic data would support the hypothesis that diarrhea in the piped water group could be attributed to cross-contamination between the municipal water supply and sewer , due to leaky pipes and lack of water pressure . Relatively inexpensive steps , including chlorination , maintaining water pressure , and properly maintaining the distribution system , rather than reverse osmosis technology , should reduce diarrheal rates A r and omized controlled trial of the plastic BioS and filter ( BSF ) was performed in rural communities in Tamale ( Ghana ) to assess reductions in diarrheal disease and improvements in household drinking water quality . Few studies of household water filters have been performed in this region , where high drinking water turbidity can be a challenge for other household water treatment technologies . During the study , the longitudinal prevalence ratio for diarrhea comparing households that received the plastic BSF to households that did not receive it was 0.40 ( 95 % confidence interval : 0.05 , 0.80 ) , suggesting an overall diarrheal disease reduction of 60 % . The plastic BSF achieved a geometric mean reduction of 97 % and 67 % for E. coli and turbidity , respectively . These results suggest the plastic BSF significantly improved drinking water quality and reduced diarrheal disease during the short trial in rural Tamale , Ghana . The results are similar to other trials of household drinking water treatment technologies Recent solar disinfection ( SODIS ) studies in Bolivia and South Africa have reported compliance rates below 35 % result ing in no overall statistically significant benefit associated with disease rates . In this study , we report the results of a 1 year r and omized controlled trial investigating the effect of SODIS of drinking water on the incidence of dysentery and nondysentery diarrhea among children of age 6 months to 5 years living in rural communities in Cambodia . We compared 426 children in 375 households using SODIS with 502 children in 407 households with no intervention . Study compliance was greater than 90 % with only 5 % of children having less than 10 months of follow-up and 2.3 % having less than 6 months . Adjusted for water source type , children in the SODIS group had a reduced incidence of dysentery , with an incidence rate ratio ( IRR ) of 0.50 ( 95 % CI 0.27 - 0.93 , p = 0.029 ) . SODIS also had a protective effect against nondysentery diarrhea , with an IRR of 0.37 ( 95 % CI 0.29 - 0.48 , p < 0.001 ) . This study suggests strongly that SODIS is an effective and culturally acceptable point-of-use water treatment method in the culture of rural Cambodia and may be of benefit among similar communities in neighboring South East Asian countries |
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