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MS21400	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: OBJECTIVE To evaluate the myocardial viability with (201)Tl/(18)F-FDG DISA-SPECT technique in patients with acute myocardial infa rct ion underwent emergent intracoronary autologous bone marrow mononuclear cells ( BM-MNC ) transplantation . METHODS Patients with first acute myocardial infa rct ion underwent emergent percutaneous coronary intervention ( PCI ) were r and omized in a 1:1 ratio to either intracoronary transplantation of autologous BM-MNC ( n = 20 ) or to sodium chloride concluding heparin ( control , n = 20 ) via a micro infusion catheter group immediately after PCI . Change in global left ventricular function ( LVEF measured by echocardiography ) and the myocardial viability detected by (201)Tl/(18)F-FDG DISA-SPECT from baseline and 6-months post transplantation were analyzed . RESULTS Left ventricular ejection fraction ( LVEF ) was improved in both groups and the absolute increase ( DeltaLVEF ) in BM-MNC group was significantly higher than that in control group ( 7.6 % + /- 2.8 % vs. 3.0 % + /- 2.8 % , P < 0.001 ) . In addition , the absolute decrease of myocardial infusion defect detected by (201)Tl SPECT was more significant in BM-MNC group than that in control group ( 6.7 % + /- 3.0 % vs. 2.6 % + /- 2.6 % , P < 0.001 ) and the number of mismatched segments ( indicating viable myocardium ) detected by (18)F-FDG SPECT in border zone was also significantly higher in BM-MNC group than that in control group . CONCLUSION Improved myocardial viability and reduced myocardial infusion defect post emergent intracoronary transplantation of autologous BM-MNC in patients with acute myocardial infa rct ion could be detected by (201)Tl/(18)F-FDG DISA-SPECT technique AIMS Intracoronary administration of autologous bone marrow cells ( BMC s ) leads to a modest improvement in cardiac function , but the effect on myocardial viability is unknown . The aim of this r and omized multicentre study was to evaluate the effect of BMC therapy on myocardial viability in patients with decreased left ventricular ejection fraction ( LVEF ) after acute myocardial infa rct ion ( AMI ) and to identify predictive factors for improvement of myocardial viability . METHODS AND RESULTS One hundred and one patients with AMI and successful reperfusion , LVEF ≤45 % , and decreased myocardial viability ( resting Tl201-SPECT ) were r and omized to either a control group ( n = 49 ) or a BMC group ( n = 52 ) . Primary endpoint was improvement of myocardial viability 3 months after AMI . Baseline mean LVEF measured by radionuclide angiography was 36.3 ± 6.9 % . Bone marrow cell infusion was performed 9.3 ± 1.7 days after AMI . Myocardial viability improved in 16/47 ( 34 % ) patients in the BMC group compared with 7/43 ( 16 % ) in the control group ( P = 0.06 ) . The number of non-viable segments becoming viable was 0.8 ± 1.1 in the control group and 1.2 ± 1.5 in the BMC group ( P = 0.13 ) . Multivariate analysis including major post-AMI prognostic factors showed a significant improvement of myocardial viability in BMC vs. control group ( P = 0.03 ) . Moreover , a significant adverse role for active smoking ( P = 0.04 ) and a positive trend for microvascular obstruction ( P = 0.07 ) were observed . CONCLUSION Intracoronary autologous BMC administration to patients with decreased LVEF after AMI was associated with improvement of myocardial viability in multivariate-but not in univariate- analysis . A large multicentre international trial is warranted to further document the efficacy of cardiac cell therapy and better define a group of patients that will benefit from this therapy . CLINICAL TRIAL REGISTRATION INFORMATION URL : http://www . clinical trials.gov . Unique identifier NCT00200707 Aims To evaluate the safety profile and efficacy of bone marrow mononuclear cells ( BMMNC ) transplantation for ST-segment elevation myocardial infa rct ion ( STEMI ) by assessing patients and their left ventricular function at up to 4 years follow-up . Methods and results Eighty-six patients with STEMI who had successfully undergone percutaneous coronary intervention ( PCI ) were r and omized to receive intracoronary injection of BMMNC ( n = 41 ) or saline ( n = 45 ) . Left ventricular ejection fraction , as evaluated by UCG , was markedly improved at 6 months ( 0.484 ± 0.5 vs. 0.457 ± 0.6 , P = 0.001 ) , 1 year ( 0.482 ± 0.7 vs. 0.446 ± 0.6 , P < 0.001 ) , and 4 years ( 0.505 ± 0.8 vs. 0.464 ± 0.8 , P < 0.001 ) after BMMNC transplant when compared with control group . However , the current cell therapy did not improve the myocardial viability of the infa rct ed area as assessed by single-photon emission computed tomography analysis at 4 years post-transplant ( 0.263 ± 0.007 in BMMNC group vs. 0.281 ± 0.008 in control group , P = 0.10 ) . During the follow-up period , one control group case ( 2.2 % ) of in-stent restenosis was confirmed by coronary angiography and underwent repeat PCI . Also during follow-up , one death ( 2.2 % ) occurred in the control group , and one patient ( 2.4 % ) in the BMMNC group had transient acute heart failure . Conclusion This study indicates that intracoronary delivery of autologous BMMNC is safe and feasible for STEMI patients who have undergone PCI , and can lead to long-term improvement in myocardial function Background — Intracoronary administration of autologous bone marrow – derived mononuclear cells ( BM-MNC ) may improve remodeling of the left ventricle ( LV ) after acute myocardial infa rct ion . The optimal time point of administration of BM-MNC is still uncertain and has rarely been addressed prospect ively in r and omized clinical trials . Methods and Results — In a multicenter study , we r and omized 200 patients with large , successfully reperfused ST-segment elevation myocardial infa rct ion in a 1:1:1 pattern into an open-labeled control and 2 BM-MNC treatment groups . In the BM-MNC groups , cells were administered either early ( ie , 5 to 7 days ) or late ( ie , 3 to 4 weeks ) after acute myocardial infa rct ion . Cardiac magnetic resonance imaging was performed at baseline and after 4 months . The primary end point was the change from baseline to 4 months in global LV ejection fraction between the 2 treatment groups and the control group . The absolute change in LV ejection fraction from baseline to 4 months was −0.4±8.8 % ( mean±SD ; P=0.74 versus baseline ) in the control group , 1.8±8.4 % ( P=0.12 versus baseline ) in the early group , and 0.8±7.6 % ( P=0.45 versus baseline ) in the late group . The treatment effect of BM-MNC as estimated by ANCOVA was 1.25 ( 95 % confidence interval , −1.83 to 4.32 ; P=0.42 ) for the early therapy group and 0.55 ( 95 % confidence interval , −2.61 to 3.71 ; P=0.73 ) for the late therapy group . Conclusions — Among patients with ST-segment elevation myocardial infa rct ion and LV dysfunction after successful reperfusion , intracoronary infusion of BM-MNC at either 5 to 7 days or 3 to 4 weeks after acute myocardial infa rct ion did not improve LV function at 4-month follow-up . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT00355186 AIMS R and omized trial to assess change in left ventricle ejection fraction ( LVEF ) and myocardial perfusion in patients with acute myocardial infa rct ion ( AMI ) of anterior wall treated with bone marrow stem cells ( BMSCs ) , compared with control group-from baseline in the acute phase up to 12 months of follow-up . METHODS AND RESULTS Forty-five patients were r and omized 2:1 to BMSC group ( n= 31 ) or to control group ( n = 14 ) . Bone marrow stem cells were administered into infa rct -related artery ( IRA ) at 4 - 6 day after primary PCI . Groups were followed up with Tc-99m-MIBI SPECT , radionuclide ventriculography ( EF-RNV ) , echocardiography ( ECHO ) , and spiroergometric stress test . Coronary angiography was repeated after 6 months . EF-RNV did not differ significantly in both groups , but trend towards increase in EF at 6 months and its maintenance after 12 months was noticed in the BMSC group . At rest study , perfusion index ( PI ) of region supplied with blood by IRA distal to its previous occlusion ( PI-IRA ) improved significantly in the BMSC group at 6 months : PI-IRA at 4 - 6 days vs. PI-IRA at 6 months ( 3.00 + /- 0.97 vs. 2.65 + /- 0.64 ; P = 0.017 ) . At 12 months , PI-IRA at rest was 2.66 + /- 0.55 ; P = 0.07 . The difference between BMSC and control groups at rest study in PI-IRA was not observed . At dipyridamole study ( PI-dip ) , perfusion in the BMSC group was better compared with controls at 6 months ( 2.26 + /- 0.44 vs. 2.47 + /- 0.40 ; P = 0.033 ) and at 12 months ( 2.34 + /- 0.55 vs. 2.52 + /- 0.42 ; P = 0.014 ) , also for region supplied with blood by IRA ( PI-IRA-dip ; at 6 months 2.63 + /- 0.77 vs. 3.06 + /- 0.46 ; P = 0.021 and at 12 months 2.71 + /- 0.63 vs. 3.15 + /- 0.51 ; P = 0.001 ) . Results of LVEF , LVEDV , LVESV in ECHO and results of spiroergometric stress test did not differ significantly between groups . Major adverse cardiac events occurred more often in the control group ( P = 0.027 ) . CONCLUSION In our study , BMSC intracoronary transplantation in patients with anterior AMI did not result in increase in EF . Slight improvement of myocardial perfusion was noticed in the BMSC group . This finding may indicate better microcirculation enhanced by BMSCs , but small number of patients allow for hypothesis rather than final statement BACKGROUND Previous studies have shown improvement in left ventricular function after intracoronary injection of autologous cells derived from bone marrow ( BMC ) in the acute phase of myocardial infa rct ion . We design ed a r and omized , controlled trial to further investigate the effects of this treatment . METHODS Patients with acute ST-elevation myocardial infa rct ion of the anterior wall treated with percutaneous coronary intervention were r and omly assigned to the group that underwent intracoronary injection of autologous mononuclear BMC or to the control group , in which neither aspiration nor sham injection was performed . Left ventricular function was assessed with the use of electrocardiogram-gated single-photon-emission computed tomography ( SPECT ) and echocardiography at baseline and magnetic resonance imaging ( MRI ) 2 to 3 weeks after the infa rct ion . These procedures were repeated 6 months after the infa rct ion . End points were changes in the left ventricular ejection fraction ( LVEF ) , end-diastolic volume , and infa rct size . RESULTS Of the 50 patients assigned to treatment with mononuclear BMC , 47 underwent intracoronary injection of the cells at a median of 6 days after myocardial infa rct ion . There were 50 patients in the control group . The mean ( + /-SD ) change in LVEF , measured with the use of SPECT , between baseline and 6 months after infa rct ion for all patients was 7.6+/-10.4 percentage points . The effect of BMC treatment on the change in LVEF was an increase of 0.6 percentage point ( 95 % confidence Output:	Overall , stem cell therapy is efficacious in the treatment of patients with STEMI , with low rates of adverse events compared with control group patients
MS21401	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: BACKGROUND AND PURPOSE The goal of the present study was to examine the re source and economic implication s of an early hospital discharge and home-based rehabilitation scheme for patients with acute stroke . METHODS A cost minimization analysis in conjunction with a r and omized controlled trial was carried out at 2 affiliated teaching hospitals in the southern metropolitan region of Adelaide , South Australia , between 1997 and 1998 . Eighty-six hospitalized patients with acute stroke who required rehabilitation were r and omized to receive both early hospital discharge and home-based rehabilitation , or conventional in-hospital rehabilitation and community care . Direct and indirect costs related to stroke rehabilitation were calculated , including hospital bed days , home-based intervention program , community services , and personal expenses during the 6 months after r and omization . RESULTS The mean cost per patient was lower for patients r and omized to the early hospital discharge and home-based rehabilitation ( $ 8040 ) compared with those who received conventional care ( $ 10 054 ) . This cost saving was not statistically significant ( P=0.14 ) . However , sensitivity analyses indicated that the cost of home-based rehabilitation was consistently lower than that of conventional care except when hospital costs were assumed to be 50 % less than those used in the main analysis . Multiple regression analysis demonstrated that the cost of the home-based program was significantly related to a patient 's level of disability after adjustment for age , comorbidity , and the presence or absence of a caregiver . CONCLUSIONS The early hospital discharge and home-based rehabilitation scheme was less costly than conventional hospital care for patients with stroke . Limitation of the provision of such services to patients with mild disability is likely to be most cost effective Objectives : There is inconclusive evidence of the effectiveness of stroke rehabilitation by a community stroke team . The aim was to evaluate a specialist multiprofessional team in a community setting . Design : R and omized controlled trial . Setting : Community . Participants : Stroke patients and their informal carers who were referred to receive rehabilitation from a community stroke team . Outcome measures : Barthel Index , Extended Activities of Daily Living Scale ( EADL ) , General Health Question naire ( GHQ-12 ) by patient and carer , Carer Strain Index ( CSI ) , Euroquol , knowledge of stroke and satisfaction with services six months after recruitment . Results : There were no significant differences between patients who received rehabilitation from community stroke team ( n = 189 ) and those who received routine care ( n = 232 ) in their independence in activities of daily living , mood , quality of life or knowledge of stroke . The patients in the community stroke team group were significantly more satisfied with the emotional support they had received ( p < 0.01 ) . There were no significant differences between the groups in satisfaction with practical help or overall satisfaction . Carers of patients in the community stroke team were under significantly less strain than carers in the routine care group ( p < 0.04 ) . Carers of patients in the community stroke team group were significantly more satisfied with their knowledge of stroke ( p < 0.01 ) and were more satisfied overall ( p < 0.01 ) . Conclusions : The patients treated by the community stroke team were more satisfied with the emotional support they received and had equivalent outcomes in terms of independence in activities of daily living and mood . Their carers were under less strain and were more satisfied with their knowledge of stroke recovery , the emotional support they received and overall satisfaction with services . The results support the provision of rehabilitation by a community-based specialist multiprofessional team BACKGROUND AND PURPOSE Many stroke survivors have minimal to moderate neurological deficits but are physically deconditioned and have a high prevalence of cardiovascular problems ; all of these are potentially modifiable with exercise . The purpose s of this r and omized , controlled pilot study were ( 1 ) to develop a home-based balance , strength , and endurance program ; ( 2 ) to evaluate the ability to recruit and retain stroke subjects ; and ( 3 ) to assess the effects of the interventions used . METHODS Twenty minimally and moderately impaired stroke patients who had completed inpatient rehabilitation and who were 30 to 90 days after stroke onset were r and omized to a control group or to an experimental group that received a therapist-supervised , 8-week , 3-times-per-week , home-based exercise program . The control group received usual care as prescribed by the patients ' physicians . Baseline and postintervention assessment s included the Fugl-Meyer Motor Assessment , the Barthel Index of Activities of Daily Living ( ADL ) , the Lawton Scale of Instrumental ADL , and the Medical Outcomes Study -36 Health Status Measurement . Functional assessment s of balance and gait included a 10-m walk , 6-Minute Walk , and the Berg Balance Scale . Upper extremity function was evaluated by the Jebsen Test of H and Function . RESULTS Of 22 patients who met study criteria , 20 completed the study and 2 refused to participate . The experimental group tended to improve more than the control group in motor function ( Fugl-Meyer Upper Extremity : mean change in score , 8 . 4 versus 2.2 ; Fugl-Meyer Lower Extremity : 4.7 versus -0.9 ; gait velocity : median change , 0.25 versus .09 m/s ; 6-Minute Walk : 195 versus 114 ft ; Berg Balance Score : 7.8 versus 5 ; and Medical Outcomes Study -36 Health Status Measurement of Physical Function : 15 . 5 versus 9 ) . There were no trends in differences in change scores by the Jebsen Test of H and Function , Barthel Index , and Lawton Instrumental ADL Scale . CONCLUSIONS This study demonstrated that a r and omized , controlled clinical trial of a poststroke exercise program is feasible . Measures of neurological impairments and lower extremity function showed the most benefit . Effects of the intervention on upper extremity dexterity and functional health status were equivocal . The lasting effects of the intervention were not assessed Abstract Objective : To establish if a brief programme of domiciliary occupational therapy could improve the recovery of patients with stroke discharged from hospital . Design : Single blind r and omised controlled trial . Setting : Two hospital sites within a UK teaching hospital . Subjects : 138 patients with stroke with a definite plan for discharge home from hospital . Intervention : Six week domiciliary occupational therapy or routine follow up . Main outcome measures : Nottingham extended activities of daily living score and “ global outcome ” ( deterioration according to the Barthel activities of daily living index , or death ) . Results : By eight weeks the mean Nottingham extended activities of daily living score in the intervention group was 4.8 points ( 95 % confidence interval −0.5 to 10.0 , P=0.08 ) greater than that of the control group . Overall , 16 ( 24 % ) intervention patients had a poor global outcome compared with 30 ( 42 % ) control patients ( odds ratio 0.43 , 0.21 to 0.89 , P=0.02 ) . These patterns persisted at six months but were not statistically significant . Patients in the intervention group were more likely to report satisfaction with a range of aspects of services . Conclusion : The functional outcome and satisfaction of patients with stroke can be improved by a brief occupational therapy programme carried out in the patient 's home immediately after discharge . Major benefits may not , however , be sustained OBJECTIVES To compare the effectiveness and costs of a new domiciliary rehabilitation service for elderly stroke patients with geriatric day-hospital care . DESIGN R and omized controlled trial . PARTICIPANTS Stroke patients aged 55 + who required further rehabilitation after hospital discharge or after referral to geriatricians from the community . SETTING Poole area , East Dorset , a mixed urban/rural area on the south coast of Engl and . MAIN OUTCOMES Primary -changes between hospital discharge and 6-month follow-up in physical function as measured by Barthel index . Secondary -changes over this period in Rivermead Mobility Index and mental state ( Philadelphia Geriatric Centre Morale Scale ) and differences in social activity ( Frenchay Activities Index ) and generic health status ( SF-36 ) . Health service and social service cost per patient were compared for the two groups . RESULTS 180 patients were eligible and 140 ( 78 % ) were r and omized . The groups were well balanced for age , sex , social class and initial Barthel index . We achieved follow-up in 88 % of subjects who were alive at 6 months . We detected no significant differences in patient outcomes , although there was a non-significant improvement in measures of physical function and social activity in the domiciliary group . Domiciliary patients had more physiotherapy time per session and more district nurse time , and made greater use of social service day centres and home helps . Total cost per patient did not differ significantly between the two groups , with reduced health service costs in the domiciliary arm offset by higher social service costs . CONCLUSION No significant differences were detected in the effectiveness of the two services . Neither service influenced patients ' mental state , and their social activity remained low . Total costs were similar . A mixed model of day-hospital and domiciliary care may be most cost-effective for community stroke rehabilitation , but this requires further evaluation This study compared the functional ability and perceived health status of stroke patients treated by a domiciliary rehabilitation team or by routine hospital-based services after discharge from hospital . Patients discharged from two acute and three rehabilitation hospitals in Nottingham were r and omly allocated in three strata ( Health Care of the Elderly , General Medical and Stroke Unit ) to receive domiciliary or hospital-based care after discharge . Functional recovery was assessed by the Extended Activities of Daily Living ( ADL ) scale three and six months after discharge and perceived health at six months was measured by the Nottingham Health Profile . A total of 327 eligible patients of 1119 on a register of acute stroke admissions were recruited over 16 months . Overall there were no differences between the groups in their Extended ADL scores at three or six months , or their Nottingham Health Profile scores at six months . In the Stroke Unit stratum , patients treated by the domiciliary team had higher household ( p = 0.02 ) and leisure activity ( p = 0.04 ) scores at six months than those receiving routine care . In the Health Care of the Elderly stratum , death or a move into long-term institutional care at six months occurred less frequently in patients allocated to the routine service , about half of whom attended a geriatric day hospital . Overall there was no difference in the effectiveness of the domiciliary and hospital-based services , although younger stroke unit patients appeared to do better with home therapy while some frail elderly patients might have benefited from day hospital attendance Objective : To describe and compare six community services providing co-ordinated , multidisciplinary rehabilitation to people with stroke . Design : Prospect i ve , descriptive , quantitative study . Setting : Engl and and Northern Irel and . Subjects : Community rehabilitation teams and the patients treated by them . Main outcome measures : Annual numbers treated , Barthel Index , mortality , place of discharge , crude costs . Results : Between mid-1997 and mid-1999 , data were collected on 1076 patients who received community-based rehabilitation of whom 48.7 % were male . Mean age ( SD ) was 71 years ( 13.1 ) ; 115 ( 10.7 % ) were under 55 years of age and 278 ( 25.9 % ) under 65 years of age . Median time between stroke and intervention by the community service was six weeks ( 25th , 75th percentiles 2.6 , 14.4 weeks ) and 80.5 % had been admitted to hospital . The median Barthel score at the start of community rehabilitation was 15 ( 11.0 , 18.0 ) and at the end was 18.0 ( 14.0 , 20.0 ) . Median duration of intervention was 12 weeks ( 6.0 , 22.0 ) . At the end of community rehabilitation 912 patients ( 86.5 % ) were in the community , 52 ( 4.9 % ) had died , 10 ( 0.9 % ) were in hospital and 77 ( 7.3 % ) in long-term care . Comparative data given here are for one year , 1998 , when a total of 519 patients began community rehabilitation . Details of 1855 face-to-face interventions were also recorded from subsets of 10 consecutive patients . Conclusions : Community rehabilitation teams differed in their target population s , in the timing and duration of intervention . A taxonomy of four types of co-ordinated community-based rehabilitation for people with stroke is proposed : ( 1 ) Early-supported discharge rehabilitation aim ed to reduce length of hospital stay and offered an alternative to hospital rehabilitation . ( 2 ) Post-discharge rehabilitation provided additional rehabilitation and aim ed for a seamless transfer of patients from hospital to community . ( 3 ) General practitioner-oriented post-stroke rehabilitation provided an alternative to hospital admission and rehabilitation . ( 4 ) Late community rehabilitation provided patients with the opportunity of an autonomous service , unconnected with hospital or GP referral . Purchasers need to decide for what purpose a team is to be set up . Research ers need to be similarly aware of diversity in community rehabilitation before comparisons are made Objective : To assess the effect of three weeks of rehabilitation in the home setting for younger patients with stroke with the aim of improving activity level . Design : A r and omized controlled study with blinded evaluations at discharge , three weeks , three months and one year after discharge . Setting : Home of the patient or the ordinary day rehabilitation clinic at the university hospital . Subjects : Fifty-eight patients ( median age 53 years ) consecutively discharged from inpatient rehabilitation with a first occurrence of stroke participated in training directly after discharge . Intervention : Rehabilitation was given for 9 hours/week Output:	Individual studies reported cost benefits and increased carer satisfaction in favour of home-based rehabilitation .
MS21402	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: CONTEXT Rapid increases in access to the Internet have made it a viable mode for public health intervention . No controlled studies have evaluated this re source for weight loss . OBJECTIVE To determine whether a structured Internet behavioral weight loss program produces greater initial weight loss and changes in waist circumference than a weight loss education Web site . DESIGN R and omized , controlled trial conducted from April to December 1999 . SETTING AND PARTICIPANTS Ninety-one healthy , overweight adult hospital employees aged 18 to 60 years with a body mass index of 25 to 36 kg/m(2 ) . Analyses were performed for the 65 who had complete follow-up data . INTERVENTIONS Participants were r and omly assigned to a 6-month weight loss program of either Internet education ( education ; n = 32 with complete data ) or Internet behavior therapy ( behavior therapy ; n = 33 with complete data ) . All participants were given 1 face-to-face group weight loss session and access to a Web site with organized links to Internet weight loss re sources . Participants in the behavior therapy group received additional behavioral procedures , including a sequence of 24 weekly behavioral lessons via e-mail , weekly online su bmi ssion of self-monitoring diaries with individualized therapist feedback via e-mail , and an online bulletin board . MAIN OUTCOME MEASURES Body weight and waist circumference , measured at 0 , 3 , and 6 months , compared the 2 intervention groups . RESULTS Repeated- measures analyses showed that the behavior therapy group lost more weight than the education group ( P = .005 ) . The behavior therapy group lost a mean ( SD ) of 4.0 ( 2.8 ) kg by 3 months and 4.1 ( 4.5 ) kg by 6 months . Weight loss in the education group was 1.7 ( 2.7 ) kg at 3 months and 1.6 ( 3.3 ) kg by 6 months . More participants in the behavior therapy than education group achieved the 5 % weight loss goal ( 45 % vs 22 % ; P = .05 ) by 6 months . Changes in waist circumference were also greater in the behavior therapy group than in the education group at both 3 months ( P = .001 ) and 6 months ( P = .005 ) . CONCLUSIONS Participants who were given a structured behavioral treatment program with weekly contact and individualized feedback had better weight loss compared with those given links to educational Web sites . Thus , the Internet and e-mail appear to be viable methods for delivery of structured behavioral weight loss programs PURPOSE The present study evaluated whether an intervention using a short message service ( SMS ) by personal cellular phone and Internet would reduce cardiovascular risk factors in post-menopausal women with abdominal obesity over 12 weeks . METHODS This is a quasi-experimental design with pre and post tests . Participants were recruited from the gynecology outpatient and family medicine departments of a tertiary care hospital located in an urban city of South Korea . Only 67 subjects completed the entire study , 34 in the intervention group and 33 controls . The goal of intervention was to reduce waist circumference ( WC ) , body weight ( BW ) and blood pressure ( BP ) levels . Before the intervention , demographic variables , WC , BW , BP , fasting plasma glucose ( FPG ) and serum lipids were measured as pre-test data . The WC , BW , BP , FPG and serum lipids were measured again 12 weeks later . Patients in the intervention group were requested to record their WC , BW , BP , type and amount of diet and exercise in a weekly web-based diary through the Internet or by cellular phone . The research ers sent weekly recommendations on diet and exercise as an intervention to each patient , by both cellular phone and Internet . The intervention was applied for 12 weeks . RESULTS WC and BW significantly decreased by 3.0 cm and 2.0 kg , respectively , at 12 weeks compared with the baseline in the intervention group . However , the mean changes in the control group significantly increased by 0.9 cm and 0.7 kg . Systolic BP ( SBP ) and diastolic BP ( DBP ) significantly decreased by 6.5 and 4.6 mmHg in the intervention group , respectively . The mean changes in the control group were not significant in either SBP or DBP . A significant mean decrease in total cholesterol ( TC ) was observed for the intervention group by 12.9 mg/dl , while the control group showed a significant mean increase by 1.5mg/dl . Low-density lipoprotein-cholesterol ( LDL-C ) for the intervention group showed a significant mean decrease 11.3mg/dl . The mean change in the control group was , however , not significant . CONCLUSION Web-based individual intervention using both SMS and Internet improved WC , BW , BP , TC , and LDL-C during 12 weeks in post-menopausal women with abdominal obesity BACKGROUND Since many successful dieters regain the weight they lose , programs that teach maintenance skills are needed . We developed a maintenance program based on self-regulation theory and tested the efficacy of delivering the program face to face or over the Internet . METHODS We r and omly assigned 314 participants who had lost a mean of 19.3 kg of body weight in the previous 2 years to one of three groups : a control group , which received quarterly newsletters ( 105 participants ) , a group that received face-to-face intervention ( 105 ) , and a group that received Internet-based intervention ( 104 ) . The content of the programs in the two intervention groups was the same , emphasizing daily self-weighing and self-regulation , as was the frequency of contact with the groups . The primary outcome was weight gain over a period of 18 months . RESULTS The mean ( + /-SD ) weight gain was 2.5+/-6.7 kg in the face-to-face group , 4.7+/-8.6 kg in the Internet group , and 4.9+/-6.5 kg in the control group , with a significant difference between the face-to-face group and the control group ( 2.4 kg ; 95 % confidence interval [ CI ] , 0.002 to 10.8 ; P=0.05 ) . The proportion of participants who regained 2.3 kg or more over the 18-month period was significantly higher in the control group ( 72.4 % ) than in the face-to-face group ( 45.7 % ; absolute difference , 27 % ; 95 % CI , 14 to 39 ; P<0.001 ) or the Internet group ( 54.8 % ; absolute difference , 18 % ; 95 % CI , 5 to 30 ; P=0.008 ) . Daily self-weighing increased in both intervention groups and was associated with a decreased risk of regaining 2.3 kg or more ( P<0.001 ) . CONCLUSIONS As compared with receiving quarterly newsletters , a self-regulation program based on daily weighing improved maintenance of weight loss , particularly when delivered face to face . ( Clinical Trials.gov number , NCT00067145 [ Clinical Trials.gov ] . Background To our knowledge , no studies have evaluated whether weight loss can be promoted in overweight adults through the use of an intervention that is largely based on daily SMS ( Short Message Service : text ) and MMS ( Multimedia Message Service : small picture ) messages transmitted via mobile phones . Objective This paper describes the development and evaluation of a text message – based intervention design ed to help individuals lose or maintain weight over 4 months . Methods The study was a r and omized controlled trial , with participants being exposed to one of the following two conditions , lasting 16 weeks : ( 1 ) receipt of monthly printed material s about weight control ; ( 2 ) an intervention that included personalized SMS and MMS messages sent two to five times daily , printed material s , and brief monthly phone calls from a health counselor . The primary outcome was weight at the end of the intervention . A mixed-model repeated- measures analysis compared the effect of the intervention group to the comparison group on weight status over the 4-month intervention period . Analysis of covariance ( ANCOVA ) models examined weight change between baseline and 4 months after adjusting for baseline weight , sex , and age . Results A total of 75 overweight men and women were r and omized into one of the two groups , and 65 signed the consent form , completed the baseline question naire , and were included in the analysis . At the end of 4 months , the intervention group ( n = 33 ) lost more weight than the comparison group ( −1.97 kg difference , 95 % CI −0.34 to −3.60 kg , P = .02 ) after adjusting for sex and age . Intervention participants ’ adjusted average weight loss was 2.88 kg ( 3.16 % ) . At the end of the study , 22 of 24 ( 92 % ) intervention participants stated that they would recommend the intervention for weight control to friends and family . Conclusions Text messages might prove to be a productive channel of communication to promote behaviors that support weight loss in overweight adults . Trial Registration Clinical trials.gov NCT00415870 ; http:// clinical trials.gov/ct2/show/NCT00415870 ( Archived by WebCite at http://www.webcitation.org/5dnolbkFt Objective To determine the feasibility of recruiting and retaining young adults in a brief behavioral weight loss intervention tailored for this age group , and to assess the preliminary efficacy of an intervention that emphasizes daily self-weighing within the context of a self-regulation model . Methods Forty young adults ( 29.1 ± 3.9 years , range 21–35 , average BMI of 33.36 ± 3.4 ) were r and omized to one of two brief behavioral weight loss interventions : behavioral self-regulation ( BSR ) or adapted st and ard behavioral treatment ( SBT ) . Assessment s were conducted at baseline , post-treatment ( 10 weeks ) , and follow-up ( 20 weeks ) . Intent to treat analyses were conducted using general linear modeling in SPSS version 14.0 . Results Participants in both groups attended an average of 8.7 out of 10 group meetings , and retention rates were 93 % and 88 % for post-treatment and follow-up assessment s , respectively . Both groups achieved significant weight losses at post-treatment ( BSR = -6.4 kg ( 4.0 ) ; SBT = -6.2 kg ( 4.5 ) and follow-up ( BSR = -6.6 kg ( 5.5 ) ; SBT = -5.8 kg ( 5.2 ) , p < .001 ; but the interaction of group × time was not statistically significant , p = .84 . Across groups , there was a positive association between frequency of weighing at follow-up and overall weight change at follow-up ( p = .01 ) . Daily weighing was not associated with any adverse changes in psychological symptoms . Conclusion Young adults can be recruited and retained in a behavioral weight loss program tailored to their needs , and significant weight losses can be achieved and maintained through this brief intervention . Future research on the longer-term efficacy of a self-regulation approach using daily self-weighing for weight loss in this age group is warranted . Clinical Trials Registration # Background : Obesity increases the risk of many health complications such as hypertension , coronary heart disease and type 2 diabetes , needs long-lasting treatment for effective results and involves high public and private care-costs . Therefore , it is imperative that enduring and low-cost clinical programs for obesity and related co-morbidities are developed and evaluated . Information and communication technologies ( ICT ) can help clinicians to deliver treatment in a cost-effective and time-saving manner to a large number of obese individuals with co-morbidities . Objective : To examine ad interim effectiveness of a 12-month multidisciplinary telecare intervention for weight loss provided to obese patients with type 2 diabetes . Design , Setting , and Participants : A single-center r and omized controlled trial ( TECNOB study ) started in December 2008 . At present , 72 obese patients with type 2 diabetes have been recruited and r and omly allocated to the TECNOB program ( n=37 ) or to a control condition ( n=39 ) . However , only 34 participants have completed at least the 3-month follow-up and have been included in this ad interim analysis . 21 out of them have reached also the 6-month follow-up and 13 have achieved the end of the program . Study is still on-going . Intervention : All participants attended 1-month inpatient intensive program that involved individualized medical care , diet therapy , physical training and brief psychological counseling . At discharge , participants allocated to the TECNOB program were instructed to use a weight-loss web-site , a web-based videoconference tool , a dietary software installed into their cellular phones and an electronic armb and measuring daily steps and energy expenditure . Main Outcome Measures : Weight and disordered eating-related behaviors and cognitions ( EDI-2 ) at entry to hospital , at discharge from hospital , at 3,6 and 12 months . Results : Ad interim analysis of data from 34 participants showed no statistically significant difference between groups in weight change at any time-point . However , within-group analysis revealed significant reductions of initial weight at discharge from hospital , at 3 months , at 6 months but not at 12 months . Control group had higher scores in Interpersonal distrust at 12 months . Conclusion : This ad interim findings revealed that the effect of the inpatient treatment was high and probably overwhelmed the effect of the TECNOB intervention . Much statistical power and long-term follow-up may enhance the probability to detect the TECNOB effect over and above the great one exerted by the inpatient program The National Weight Control Registry ( NWCR ) consists of over 480 Output:	There appeared to be a proportional relationship between weight loss and programme use . The programmes most benefited those who took a pro-active approach to everyday problems . Frequent self-recording of weight seemed to be important , as was the personalisation of the intervention ( counselling and individualized feedback ) . Finally , a social support system acted as a motivational tool
MS21403	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: BACKGROUND In third world countries the length of breastfeeding often has a major influence on child mortality , morbidity and nutritional status . When evaluating the impact of length of breastfeeding the reason why a mother terminates breastfeeding is usually not taken into consideration . METHODS Risk factors for termination of breastfeeding were studied in a prospect i ve community study following 1678 children in Guinea Bissau , West Africa from birth to cessation of breastfeeding , migration or death . RESULTS The median weaning age was 22.6 months . Illness of the child , new pregnancy of the mother and illness of the mother were associated with significantly shorter lactation period compared with children weaned because they were ' healthy ' or ' old enough ' . These explanations had an impact independent of other determinants for weaning , including ethnic group , mother 's age , mother 's education , birth order and number of dead siblings . Weaning before 12 months of age was only associated with illness of the mother or child and new pregnancy and not with any socioeconomic or cultural factors . CONCLUSIONS Health workers should pay special attention to the encouragement of breastfeeding in connection with illness of the mother or child ; these considerations may also be important in the planning of breastfeeding promotion campaigns . Since premature termination of breastfeeding is associated with new pregnancy , family planning should be part of any breastfeeding promotion programme In order to identify the reasons for early weaning in Teheran , we interviewed 900 mothers using a systematic r and omized sampling method . A total of 15 % of the mothers were illiterate , 93 % were housewives , and 97 % had given birth in hospitals . Only 3 % of the newborns benefited from rooming-in facilities in hospital , and 68 % were bottle-fed while still in hospital . In 3.1 % of cases the mother had not breast-fed her newborn at all . Of those who had breast-fed their infant , 38 % used only their own milk , whereas 62 % used a combination of breast milk and infant formula . The median duration of breast-feeding was 16 months ( mean , 14 months ) . A total of 74 % of mothers who used supplementary formula and 39 % of those who had completely stopped breast-feeding blamed milk insufficiency , although 67 % of these mothers had reached this conclusion only because their infants cried or were irritable . The following factors had a negative influence on the duration of breast-feeding : use of supplementary formula and of estrogen-containing oral contraceptives ; fathers with high incomes ; and mothers with a high educational level . In contrast , the mother 's religious motive to breast-feed and her insistence on breast-feeding had a positive impact . Unfortunately , 21 % of the mothers started using supplementary formula during the first month postpartum , and two-thirds before the end of the fourth month . Every month that bottle-feeding was started prematurely shortened the duration of breast-feeding by 20 days . ( ABSTRACT TRUNCATED AT 250 WORDS A prospect i ve study of breast-feeding mothers was undertaken to determine the effect of formula sample s and other hospital-related factors on success in breast-feeding . Of the 166 nursing mothers studied for 4 months postpartum , 83 % breast-fed for 1 month , 73 % for 10 weeks , and 58 % for 4 months or longer . Breast-feeding duration was not affected by formula sample s given at discharge from the hospital . Factors correlating significantly with improved breast-feeding rates include maternal age , maternal education , nonsmoking , previous breast-feeding , planned pregnancy , initiation of breast-feeding in the first 16 hours , and minimization of formula supplementation in the nursery . Partial breast-feeding ( supplementing more than one bottle of formula per day , measured at 1 month postpartum ) was associated with shorter breast-feeding duration . This latter effect was minimized by frequent nursing ( seven or more times per day ) , despite formula supplementation A multicenter study of the Lactational Amenorrhea Method ( LAM ) was carried out to test the acceptability and efficacy of the method . Additionally , the data are used to test new constructs for improvement of method criteria . A protocol was design ed at the Institute for Reproductive Health ( IRH ) , Department of Obstetrics and Gynecology , Georgetown University Medical Center , a World Health Organization ( WHO ) Collaborating Center , and was review ed and modified in collaboration with the co-sponsors , the World Health Organization and the South to South Cooperation for Reproductive Health , and the principal investigators from each site . Data were gathered prospect ively on LAM acceptors at 11 sites . Data were entered and cleaned on-site and further cleaned and analyzed at IRH , using country-level and pooled data to produce descriptive statistics and life tables . The 98+% efficacy of LAM is confirmed in a wide variety of setting s. In addition , the results yield insight on the possibility of continued use beyond 6 months . LAM is found to be highly effective as an introductory postpartum method when offered in a variety of cultures , health care setting s , socio-economic strata , and industrial and developing country locales . In addition , LAM acceptance complements breastfeeding behaviors without ongoing breastfeeding support services . The parameters studied yield high efficacy and method continuation . Therefore , the basic tenets of the 1995 Bellagio consensus on LAM is reconfirmed and it is recommended that LAM be reconfirmed and it is recommended that LAM be incorporated into hospital , maternity , family planning , maternal and child health , and other primary health care setting The association between breast-feeding patterns and resumption of menses post-partum was examined in a prospect i ve study in Indonesia . In order to examine these relationships directly in a longitudinal study , it was first necessary to distinguish among women who experienced infant mortality before menses resumed , women who weaned before menses resumed , and women who had return to menses while breast-feeding . Information on suckling patterns and menstrual status was collected by recall for 444 women at monthly visits for 2 years . Three main breast-feeding variables , minutes per episode , number of episodes per day , number of episodes per night , and other breast-feeding variables were derived for each woman , to give the average nursing pattern up to menses or the end of the study , which-ever came first . While high levels of nursing for each of these three main variables were found to be significantly related to delay in return of menses post-partum , the interactions between more minutes per episode , and more frequent day- and night-time feeds , were found to be the most important factors in the delay in onset of post-partum menstruation in those women whose menses resumed while still nursing or who remained amenorrhoeic and nursing at the end of the study This report presents a secondary data analysis based on prospect ively collected records gathered during a field assessment that was carried out in Rw and a in August 1993 . The assessment used service statistics and follow-up interviews to evaluate the efficacy of a modified lactational amenorrhea method ( LAM ) as a nine-month introductory postpartum natural family planning method . The program , carried out by Action Familiale Rw and aise ( AFR ) , reflects high efficacy of the method in a compliant sample that sought this method followed by another form of family planning . These results are promising and provide guidance for the extended use of LAM past six months . Programmatic findings suggest that studies be conducted of the contribution of extended LAM to improved weaning practice s , the high efficacy of continued reliance on substantial lactation and amenorrhea beyond nine months , and male involvement in LAM and breastfeeding BACKGROUND The use of breastfeeding as a method of birth spacing occasionally ends in " unplanned pregnancy . " This is due to unexpected expiration of one or more of the lactation amenorrhea method ( LAM ) prerequisites . The current study tests a new concept that the in-advance provision of single packet of progestogen emergency contraception ( EC ) pills during the postpartum LAM counseling may decrease the incidence of unplanned pregnancy during breastfeeding . STUDY DESIGN This was a registered two-armed r and omized controlled trial ( NCT 01111929 ) . Women intending to breastfeed and to postpone pregnancy for 1 year or more were approached . They received adequate postpartum contraceptive counseling . Women intending to use LAM were r and omly assigned to one of two groups . The LAM-only group received the proper LAM counseling and did not receive counseling about EC . The LAM-EC group received counseling for both LAM and EC with in-advance provision of one packet of EC pills . They were advised to use these pills if one of the prerequisites of LAM expires and sexual relation has occurred before the initiation of another regular contraceptive protection . All the participants were advised that they need to use another regular method upon expiration of any of the LAM prerequisites . RESULTS Eligible women were 1158 parturients r and omized into two equal groups . Forty-four percent of the women provided with EC used them . Significantly more women in the LAM-EC group initiated regular contraception within or shortly after the first 6 months postpartum when compared with those in the LAM-only group ( 30.5 % vs. 7.3 % , respectively ; p=.0004 ) . Pregnancy occurred in 5 % of the LAM-only group as compared with 0.8 % in the LAM-EC group ( p=.005 ) . Minimal side effects were reported after EC use . CONCLUSION In-advance provision of EC pills can increase the rate of initiation of regular contraception once one or more of the prerequisites of LAM expire . Consequently , the use of EC pills as a temporary backup of LAM can decrease the incidence of unplanned pregnancy during breastfeeding . The use of progestogen EC pill during lactation is safe and tolerable BACKGROUND In the hierarchy of research design s , the results of r and omized , controlled trials are considered to be evidence of the highest grade , whereas observational studies are viewed as having less validity because they reportedly overestimate treatment effects . We used published meta-analyses to identify r and omized clinical trials and observational studies that examined the same clinical topics . We then compared the results of the original reports according to the type of research design . METHODS A search of the Medline data base for articles published in five major medical journals from 1991 to 1995 identified meta-analyses of r and omized , controlled trials and meta-analyses of either cohort or case-control studies that assessed the same intervention . For each of five topics , summary estimates and 95 percent confidence intervals were calculated on the basis of data from the individual r and omized , controlled trials and the individual observational studies . RESULTS For the five clinical topics and 99 reports evaluated , the average results of the observational studies were remarkably similar to those of the r and omized , controlled trials . For example , analysis of 13 r and omized , controlled trials of the effectiveness of bacille Calmette-Guérin vaccine in preventing active tuberculosis yielded a relative risk of 0.49 ( 95 percent confidence interval , 0.34 to 0.70 ) among vaccinated patients , as compared with an odds ratio of 0.50 ( 95 percent confidence interval , 0.39 to 0.65 ) from 10 case-control studies . In addition , the range of the point estimates for the effect of vaccination was wider for the r and omized , controlled trials ( 0.20 to 1.56 ) than for the observational studies ( 0.17 to 0.84 ) . CONCLUSIONS The results of well- design ed observational studies ( with either a cohort or a case-control design ) do not systematic ally overestimate the magnitude of the effects of treatment as compared with those in r and omized , controlled trials on the same topic Abstract Objective : To determine the contraceptive efficacy of the lactational amenorrhoea method . Design : Non-comparative prospect i ve trial . Setting : Urban Manila , the Philippines . Subjects : 485 lower income , educated women with extensive experience of breast feeding . Intervention : Women were offered all available contraceptives for use after birth . Those who chose the lactational amenorrhoea method were taught the method , screened for the study , and followed for 12 months to determine the risk of pregnancy when the method was used . Main outcome measures : Life table pregnancy rates during correct and incorrect use of the method , censored monthly in the event of sexual abstinence or the use of another contraceptive method . Results : The lactational amenorrhoea method was 99 % effective when used correctly ( that is , during lactational amenorrhoea and full or nearly full breast feeding for up to six months ) . At 12 months the effectiveness during amenorrhoea dropped to 97 % . Conclusions : The lactational amenorrhoea method provided as much protection from pregnancy as non-breast feeding women experience with non-medicated intrauterine devices and barrier methods . The contraceptive effect of lactation can not be attributed to lactational or postpartum abstinence . Key messages Henceforth , data from clinical trials on contra-ceptives must be subject to the rigours of multiple censoring such as applied here . By excluding periods of abstinence from the calculation of risk of pregnancy , the contraceptive protection of the method can not be attributed to postpartum or lac- tational abstinence During the first year post partum , the rate of pregnancy before the return of menses in lactating women was less than 3 The purpose of this study was to assess the efficacy of the lactational amenorrhea method ( LAM ) for family planning among mothers who are separated from their infants by work . The study population , 170 urban middle class women who planned to return to work before 120 days postpartum , were interviewed monthly for 6 months postpartum and contacted at 12 months . The study population received clinical support for expressing their milk and exclusively breast-milk feeding the infants and for the use of LAM for Output:	We found no clear differences in life table pregnancy rates between women using LAM and being supported in doing so , and fully breastfeeding amenorrheic women not using any method . As the length of lactation amenorrhoea in women using LAM differed greatly between the population s studied , and was population specific , it is uncertain whether LAM extends lactational amenorrhoea
MS21404	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Eosinophilic esophagitis ( EoE ) is a chronic , Th2‐type inflammatory disease . Chemoattractant receptor‐homologous molecule on Th2 cells ( CRTH2 ) is a prostagl and in D2 ( PGD2 ) receptor , expressed by Th2 cells and other inflammatory cells , including eosinophils and basophils , that mediates chemotaxis and activation . OC000459 is a selective CRTH2 antagonist and would be expected to suppress eosinophilic tissue inflammation . The purpose of this study was to evaluate the efficacy and safety of an OC000459 monotherapy in adult patients with active , corticosteroid‐dependent or corticosteroid‐refractory BACKGROUND & AIMS Eosinophilic esophagitis is an increasingly recognized disorder with distinctive endoscopic , histologic , and allergic features . Although several therapies are advocated , no placebo-controlled trials have been conducted . We aim ed to determine the efficacy of swallowed fluticasone propionate ( FP ) in the treatment of eosinophilic esophagitis . METHODS We conducted a r and omized , double-blind , placebo-controlled trial of swallowed FP in pediatric patients with active eosinophilic esophagitis . Thirty-six patients were r and omly assigned to receive either 880 mug of FP ( 21 patients ) or placebo ( 15 patients ) divided twice daily for 3 months . The primary end point was histologic remission , defined by a peak eosinophil count of < /=1 eosinophil in all 400x fields in both the proximal and distal esophagus . RESULTS Fifty percent of FP-treated patients achieved histologic remission compared with 9 % of patients receiving placebo ( P = .047 ) . FP decreased esophageal eosinophil levels , with a more pronounced effect in nonallergic individuals ( 65.9 + /- 25.3 vs 1.4 + /- 1.1 eosinophils/high-power field in the proximal esophagus [ P = .03 ] and 84.6 + /- 19.7 vs 19.6 + /- 12.9 eosinophils/high-power field in the distal esophagus [ P = .04 ] ) . Resolution of vomiting occurred more frequently with FP than placebo ( 67 % vs 27 % ; P = .04 ) . FP-induced resolution of mucosal eosinophilia was associated with resolution of endoscopic findings , epithelial hyperplasia , younger age ( P = .0003 ) , shorter height ( P = .002 ) , and lighter weight ( P = .02 ) . Effective treatment with FP decreased the number of CD8(+ ) T lymphocytes and mast cells in both the proximal and distal esophagus ( P < .05 ) . CONCLUSIONS Swallowed FP is effective in inducing histologic remission in eosinophilic esophagitis , with a more pronounced effect in nonallergic and younger individuals , especially in the proximal esophagus BACKGROUND Eosinophilic esophagitis ( EoE ) is a chronic allergic disease with limited treatment options . OBJECTIVE We evaluated QAX576 , an mAb against IL-13 , in the treatment of patients with EoE. METHODS Patients ( 18 - 50 years ) with proton pump inhibitor-resistant esophageal eosinophilia received intravenous QAX576 ( 6 mg/kg ) or placebo ( 2:1 ) at weeks 0 , 4 , and 8 and were followed for 6 months . The primary end point was the responder rate for a greater than 75 % decrease in peak eosinophil counts at week 12 . Efficacy was to be declared if the lower 90 % confidence limit for the proportion of responders on QAX576 was 35 % or greater . Secondary end points included changes in esophageal eosinophil counts , symptoms assessed by question naire scores , and quantification of a series of biomarkers . RESULTS Twenty-three patients completed the study up to week 12 , and 18 continued to the end of the study . For the proximal and distal esophageal biopsies combined , the responder rate was 12.5 % ( 90 % confidence limit , 1 % to 43 % ) with placebo , compared to 40.0 % ( 90 % confidence limit , 22 % to 61 % ) with QAX576 . Although the primary end point was not met , the mean esophageal eosinophil count decreased by 60 % with QAX576 versus an increase of 23 % with placebo ( P = .004 ) , and the decrease was sustained up to 6 months . There was a trend for improved symptoms , particularly dysphagia . QAX576 improved expression of EoE-relevant esophageal transcripts , including eotaxin-3 , periostin , and markers of mast cells and barrier function , for up to 6 months after treatment . QAX576 was well tolerated . CONCLUSIONS QAX576 significantly improved intraepithelial esophageal eosinophil counts and dysregulated esophageal disease-related transcripts in adults with EoE in a sustained manner Background & Aims : The endoscopic reference score ( EREFS ) is used to determine severity of 5 endoscopic findings : edema , rings , exu date s , furrows , and strictures . Little is known about the relationship between EREFSs and histologic markers of disease activity in children with eosinophilic esophagitis ( EoE ) . We aim ed to determine whether the EREFS can be used to identify children with EoE and how it changes with treatment . Methods : We performed a prospect i ve study of consecutive children ( ages 2–17 years ) undergoing diagnostic or post‐treatment endoscopy scored real‐time with EREFS from December 2012 through 2016 . Findings from 192 diagnostic endoscopies and 229 post‐treatment endoscopies were evaluated , from 371 children . Incident EoE cases were diagnosed based on 2011 consensus guidelines . Patients were treated with either elimination diet or topical steroids . Subjects who underwent endoscopy for symptoms of esophageal dysfunction but had normal esophageal findings from histology analysis were used as controls . EREFS and receiver operating characteristic curves were determined for incident EoE cases ( n = 77 ) vs controls ( n = 115 ) , patients with active EoE ( n = 101 ) vs inactive EoE after treatment ( n = 128 ) , and paired pre‐ and post‐treatment cases of EoE ( n = 85 ) . Component and composite scores were correlated with eosinophilia . Results : Visual detection of more than 1 esophageal abnormality during the diagnostic endoscopy identified children with EoE with 89.6 % sensitivity and 87.9 % specificity . EREFS correlated with peak level of eosinophilia ( P < .001 ) at all esophageal levels . Children who responded to therapy had mean EREFSs of 0.5 compared to 2.4 in non‐responders . In comparing pre‐treatment vs post‐treatment data from 85 patients , we found a significant reduction in the composite EREFS ( from 2.4 to 0.7 ) ( P < .001 ) among patients who responded to treatment ; 92 % of responders had a reduced EREFSs after treatment . EREFSs identified children with EoE with an area under the curve value ( AUC ) of 0.93 . EREFSs identified children with active EoE following treatment with an AUC of 0.81 before treatment and an AUC of 0.79 after treatment . Conclusions : In a prospect i ve study of children undergoing diagnostic or post‐treatment endoscopy , we found the EREFS to accurately identify those with EoE. Children who responded to therapy had lower EREFS scores than non‐responders . EREFSs can be used to measure outcomes of pediatric patients , in conjunction with histology findings , and assess treatments for children with Objectives : For technical reasons , the histologic characterization of eosinophilic esophagitis (EoE)-specific alterations is almost exclusively based on those found in the esophageal epithelium , whereas little is known about subepithelial abnormalities . In this study , we aim ed to systematic ally assess the nature of subepithelial histologic alterations , and analyze their relationship with epithelial histologic findings , endoscopic features , and symptoms . Methods : Adult patients with established EoE diagnosis were prospect ively included during a yearly follow-up visit . Patients underwent assessment of clinical , endoscopic , and histologic disease activity using EoE-specific scores . Results : We included 200 EoE patients ( mean age 43.5±15.7 years , 74 % males ) with a median peak count of 36 intraepithelial eosinophils/hpf ( IQR 14−84 ) . The following histologic features were identified in the subepithelial layer : eosinophilic infiltration ( median peak count of 20 eosinophils/hpf ( IQR 10−51 ) ) , eosinophil degranulation ( 43 % ) , fibrosis ( 82 % ) , and lymphoid follicles ( 56 % ) . Peak intraepithelial eosinophil counts were higher , identical , and lower when compared to the subepithelial layer in 62.5 % , 7 % , and 30.5 % of patients , respectively . Anti-eosinophilic treatment at inclusion did not influence the relation between subepithelial and epithelial peak eosinophil counts . Subepithelial histologic activity correlated with epithelial histologic activity ( rho 0.331 , P<0.001 ) , endoscopic severity ( rho 0.208 , P=0.003 ) , and symptom severity ( rho 0.179 , P=0.011 ) . Forty percent ( 21/52 ) of patients with < 15 intraepithelial eosinophils/hpf had subepithelial peak counts of ≥15/hpf . Conclusions : There is a significant but modest correlation between subepithelial histologic activity and epithelial histologic activity , endoscopic severity , and symptom severity . The long-term clinical impact of assessing subepithelial alterations in EoE needs to be further eluci date BACKGROUND & AIMS Pharmacologic treatment of eosinophilic esophagitis ( EoE ) is limited to off-label use of corticosteroids not optimized for esophageal delivery . We performed a r and omized , controlled phase 2 trial to assess the ability of budesonide oral suspension ( BOS ) , a novel muco-adherent topical steroid formulation , to reduce symptoms and esophageal eosinophilia in adolescents and adults with EoE. METHODS In this multicenter , r and omized , double-blind , placebo-controlled , parallel-group trial , 93 EoE patients between the ages of 11 and 40 years with dysphagia and active esophageal eosinophilia were r and omized to receive either BOS 2 mg or placebo twice daily for 12 weeks . Co- primary outcomes were change in Dysphagia Symptom Question naire ( DSQ ) score from baseline , and proportion of patients with a histologic response ( ≤6 eosinophils/high-power field ) after treatment . Endoscopic severity scores and safety parameters were assessed . RESULTS At baseline , mean DSQ scores were 29.3 and 29.0 , and mean peak eosinophil counts were 156 and 130 per hpf in the BOS and placebo groups , respectively . After treatment , DSQ scores were 15.0 and 21.5 , and mean peak eosinophil counts were 39 and 113 per high-power field , respectively ( P < .05 for all ) . For BOS vs placebo , change in DSQ score was -14.3 vs -7.5 ( P = .0096 ) , histologic response rates were 39 % vs 3 % ( P < .0001 ) , and change in endoscopic severity score was -3.8 vs 0.4 ( P < .0001 ) . Adverse events were similar between groups . CONCLUSIONS Treatment with BOS was well tolerated in adolescent and young adult patients with EoE and result ed in improvement in symptomatic , endoscopic , and histologic parameters using vali date d outcome instruments . Clinical Trials.gov ID NCT01642212 BACKGROUND & AIMS The aim of this study was to assess whether measurements of esophageal distensibility , made by high-resolution impedance planimetry , correlated with important clinical outcomes in patients with eosinophilic esophagitis . METHODS Seventy patients with eosinophilic esophagitis ( 50 men ; age , 18 - 68 y ) underwent endoscopy with esophageal biopsy collection and high-resolution impedance planimetry using the functional lumen-imaging probe . The patients were followed up prospect ively for an average of 9.2 months ( range , 3 - 14 mo ) , and the risk of food impaction , requirement for dilation Output:	The EoE Endoscopic Reference Score is the most commonly applied tool for describing changes in endoscopic appearance .
MS21405	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Objective To evaluate the effectiveness of neuromuscular training in reducing the rate of acute knee injury in adolescent female football players . Design Stratified cluster r and omised controlled trial with clubs as the unit of r and omisation . Setting 230 Swedish football clubs ( 121 in the intervention group , 109 in the control group ) were followed for one season ( 2009 , seven months ) . Participants 4564 players aged 12 - 17 years ( 2479 in the intervention group , 2085 in the control group ) completed the study . Intervention 15 minute neuromuscular warm-up programme ( targeting core stability , balance , and proper knee alignment ) to be carried out twice a week throughout the season . Main outcome measures The primary outcome was rate of anterior cruciate ligament injury ; secondary outcomes were rates of severe knee injury ( > 4 weeks ’ absence ) and any acute knee injury . Results Seven players ( 0.28 % ) in the intervention group , and 14 ( 0.67 % ) in the control group had an anterior cruciate ligament injury . By Cox regression analysis according to intention to treat , a 64 % reduction in the rate of anterior cruciate ligament injury was seen in the intervention group ( rate ratio 0.36 , 95 % confidence interval 0.15 to 0.85 ) . The absolute rate difference was −0.07 ( 95 % confidence interval −0.13 to 0.001 ) per 1000 playing hours in favour of the intervention group . No significant rate reductions were seen for secondary outcomes . Conclusions A neuromuscular warm-up programme significantly reduced the rate of anterior cruciate ligament injury in adolescent female football players . However , the absolute rate difference did not reach statistical significance , possibly owing to the small number of events . Trial registration Clinical trials NCT00894595 Background : Anterior knee pain ( AKP ) is the most common activity-related injury of the knee . The authors investigated the effect of an exercise intervention on the incidence of AKP in UK army recruits undergoing a 14-week physically arduous training program . Hypothesis : Modifying military training to include targeted preventative exercises may reduce the incidence of AKP in a young recruit population . Study Design : R and omized controlled trial ; Level of evidence , 1 . Methods : A single-blind cluster r and omized controlled trial was performed in 39 male and 11 female training groups ( median age : 19.7 years ; interquartile range , 17 - 25 ) undergoing phase 1 of army recruit training . Each group was r and omly assigned to either an intervention ( n = 759 ) or control ( n = 743 ) protocol . The intervention consisted of 4 strengthening and 4 stretching exercises completed during supervised physical training lessons ( 7 per week ) . The control group followed the existing training syllabus warm-up exercises . The primary outcome was a diagnosis of AKP during the 14-week training program . Results : Forty-six participants ( 3.1 % ; 95 % confidence interval [ CI ] , 2.3 - 4.1 ) were diagnosed with AKP . There were 36 ( 4.8 % ; 95%CI , 3.5 - 6.7 ) new cases of AKP in the control group and 10 ( 1.3 % ; 0.7 - 2.4 ) in the intervention group . There was a 75 % reduction in AKP risk in the intervention group ( unadjusted hazard ratio = 0.25 ; 95 % CI , 0.13 - 0.52 ; P < .001 ) . Three participants ( 0.4 % ) from the intervention group were discharged from the military for medical reasons compared to 25 ( 3.4 % ) in the control group . Conclusion : A simple set of lower limb stretching and strengthening exercises result ed in a substantial and safe reduction in the incidence of AKP in a young military population undertaking a physical conditioning program . Such exercises could also be beneficial for preventing this common injury among nonmilitary participants in recreational physical activity Abstract Zouita , S , Zouita , ABM , Kebsi , W , Dupont , G , Ben Abderrahman , A , Ben Salah , FZ , and Zouhal , H. Strength training reduces injury rate in elite young soccer players during one season . J Strength Cond Res 30(5 ) : 1295–1307 , 2016—The purpose of this study was to examine the effect of strength training on physical fitness parameters and injuries occurrence in young elite soccer players . Fifty-two elite young soccer players ( 13–14 years ) were divided on a r and omized order into experimental group ( EG , n = 26 ) and control group ( CG , n = 26 ) . For EG , 2 to 3 sessions of strength training ( 90 minutes ) were introduced weekly in their training program for 12 weeks ( 4 × 3 weeks separated by 1-week recovery ) . Sprint tests ( 10 - 20 - 30 m ) , T-test time , and jumping tests were measured at the start ( T0 ) , at the middle ( T1 ) , and at the end of the experiment period ( T2 ) . The injury rate was recorded by the medical and fitness training staff throughout the soccer season . Compared to CG , EG performed significantly better in sprint running and T-test time at T2 ( p < 0.01 ) . Similarly , the improvement amount for jumping tests was significantly greater ( p ⩽ 0.05 ) in EG than in CG . A total of 17 injuries were recorded over the soccer season . The rate was higher in CG ( 13 injuries ) than in training group ( 4 injuries ) . This study showed that strength training accurately and efficiently scheduled in youth soccer players , induced performance improvement , and reduced the rate of injuries BACKGROUND The risk of musculoskeletal injury with the introduction of moderate-to-vigorous exercise in sedentary adults is not well established . The purpose of this report is to examine the effect of a 12-month exercise intervention on musculoskeletal injury and bodily pain in predominately overweight , sedentary men ( n = 102 ) and women ( n = 100 ) , ages 40 to 75 years . METHODS Participants were r and omized to a moderate-to-vigorous aerobic exercise intervention ( EX ) ( 6 d/wk , 60 min/d , 60 % to 85 % max . heart rate ) or usual lifestyle control ( CON ) . Participants completed a self-report of musculoskeletal injury and body pain at baseline and 12-months . RESULTS The number of individuals reporting an injury ( CON ; 28 % vs. EX ; 28 % , P = .95 ) did not differ by group . The most commonly injured site was lower leg/ankle/foot . The most common causes of injury were sports/physical activity , home maintenance , or " other . " In the control group , bodily pain increased over the 12 months compared with the exercise group ( CON -7.9 , EX -1.4 , P = .05 ) . Baseline demographics and volume of exercise were not associated with injury risk . CONCLUSIONS Previously sedentary men and women r and omized to a 12-month aerobic exercise intervention with a goal of 360 min/wk reported the same number of injuries as those in the control group and less bodily pain Sometimes interventions in r and omized clinical trials are not allocated to individual patients , but rather to patients in groups . This is called cluster allocation , or cluster r and omization , and is particularly common in health services research . Similarly , in some types of observational studies , patients ( or observations ) are found in naturally occurring groups , such as neighborhoods . In either situation , observations within a cluster tend to be more alike than observations selected entirely at r and om . This violates the assumption of independence that is at the heart of common methods of statistical estimation and hypothesis testing . Failure to account for the dependence between individual observations and the cluster to which they belong can have profound implication s on the design and analysis of such studies . Their p-values will be too small , confidence intervals too narrow , and sample size estimates too small , sometimes to a dramatic degree . This problem is similar to that caused by the more familiar " unit of analysis error " seen when observations are repeated on the same subjects , but are treated as independent . The purpose of this paper is to provide an introduction to the problem of clustered data in clinical research . It provides guidance and examples of methods for analyzing clustered data and calculating sample sizes when planning studies . The article concludes with some general comments on statistical software for cluster data and principles for planning , analyzing , and presenting such studies STUDY DESIGN An explorative , 1-year prospect i ve cohort study . Objective To examine whether an association between a sudden change in weekly running distance and running-related injury varies according to injury type . BACKGROUND It is widely accepted that a sudden increase in running distance is strongly related to injury in runners . But the scientific knowledge supporting this assumption is limited . METHODS A volunteer sample of 874 healthy novice runners who started a self-structured running regimen were provided a global-positioning-system watch . After each running session during the study period , participants were categorized into 1 of the following exposure groups , based on the progression of their weekly running distance : less than 10 % or regression , 10 % to 30 % , or more than 30 % . The primary outcome was running-related injury . RESULTS A total of 202 runners sustained a running-related injury . Using Cox regression analysis , no statistically significant differences in injury rates were found across the 3 exposure groups . An increased rate of distance-related injuries ( patellofemoral pain , iliotibial b and syndrome , medial tibial stress syndrome , gluteus medius injury , greater trochanteric bursitis , injury to the tensor fascia latae , and patellar tendinopathy ) existed in those who progressed their weekly running distance by more than 30 % compared with those who progressed less than 10 % ( hazard ratio = 1.59 ; 95 % confidence interval : 0.96 , 2.66 ; P = .07 ) . CONCLUSION Novice runners who progressed their running distance by more than 30 % over a 2-week period seem to be more vulnerable to distance-related injuries than runners who increase their running distance by less than 10 % . Owing to the exploratory nature of the present study , r and omized controlled trials are needed to verify these results , and more experimental studies are needed to vali date the assumptions . Still , novice runners may be well advised to progress their weekly distances by less than 30 % per week over a 2-week period Background : The incidence of acute hamstring injuries is high in several sports , including the different forms of football . Purpose : The authors investigated the preventive effect of eccentric strengthening of the hamstring muscles using the Nordic hamstring exercise compared with no additional hamstring exercise on the rate of acute hamstring injuries in male soccer players . Study Design : R and omized controlled trial ; Level of evidence , 1 . Methods : Fifty Danish male professional and amateur soccer teams ( 942 players ) were allocated to an intervention group ( 461 players ) or a control group ( 481 players ) . Players in the intervention group conducted a 10-week progressive eccentric training program followed by a weekly seasonal program , whereas players in the control group followed their usual training program . The main outcome measures were numbers of overall , new , and recurrent acute hamstring injuries during 1 full soccer season . Results : Fifty-two acute hamstring injuries in the control group compared with 15 injuries in the intervention group were registered . Comparing intervention versus the control group , overall acute hamstring injury rates per 100 player seasons were 3.8 versus 13.1 ( adjusted rate ratio [ RR ] , 0.293 ; 95 % confidence interval [ CI ] , 0.150 - 0.572 ; P < .001 ) . New injury rates per 100 player seasons were 3.1 versus 8.1 ( RR , 0.410 ; 95 % CI , 0.180 - 0.933 ; P = .034 ) , whereas recurrent injury rates per 100 player seasons were 7.1 versus 45.8 ( RR , 0.137 ; 95 % CI , 0.037 - 0.509 ; P = .003 ) . Number needed to treat [ NNT ] to prevent 1 acute hamstring injury ( new or recurrent ) is 13 ( 95 % CI , 9 - 23 ) players . The NNT to prevent 1 new injury is 25 ( 95 % CI , 15 - 72 ) players , and NNT to prevent 1 recurrent injury is 3 ( 95 % CI , 2 - 6 ) players . Conclusion : In male professional and amateur soccer players , additional eccentric hamstring exercise decreased the rate of overall , new , and recurrent acute hamstring injuries Abstract Pedersen , MT , And ersen , LL , Jørgensen , MB , Søgaard , K , and Sjøgaard , G. Effect of specific resistance training on musculoskeletal pain symptoms : Dose-response relationship . J Strength Cond Res 27(1 ) : 229–235 , 2013—The purpose of this study was to investigate the dose-response of strength training for relieving musculoskeletal pain in female office workers . The relation between the dose of training in terms of total training volume ( sets × repetitions × load reported in training diaries ) during a 16-week strength training program and changes in pain ( calculated as pain index , 0–100 % , from self-reported intensities and duration s of pain in the upper body and low back ) was determined by regression analysis . The women were part of a r and omized controlled trial with specific strength training ( SRT ) , all-round physical exercise ( APE ) , and a reference group ( REF ) . Results showed that pain index in SRT and APE decreased significantly from baseline to follow-up Output:	Conclusion The included studies were generally well design ed and executed , had high compliance rates , were safe , and attained consistently favourable results across four different acute and overuse injury outcomes despite considerable differences in population s and interventions . Increasing strength training volume and intensity were associated with sports injury risk reduction . Three characteristically different approaches to prevention mechanisms were identified and incorporated into contemporary strength training recommendations
MS21406	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Introduction This study examined the effectiveness of telemedicine in providing psychotherapy to patients with medically unexplained pain ( MUP ) who may not have access to in-person treatment . The impact of Internet-delivered intensive short-term dynamic psychotherapy ( ID-ISTDP ) was investigated for MUP via video teleconferencing ( Skype ™ ) . Methods A r and omized , controlled trial of ISTDP , an evidence -based intervention for MUP , was conducted to compare delivery modalities on variations in MUP symptoms . Eighty-one participants with MUP were r and omized to either ID-ISTDP ( n = 39 ) or in-person ISTDP ( n = 42 ) . Outcome variables included the Numeric Pain Rating Scale , Depression Anxiety Stress Scale-21 , Emotion Regulation Question naire , Mindful Attention Awareness Scale and the Quality of Life Inventory . In addition , exploratory analyses were used to examine acceptability , satisfaction and compliance in both conditions . Participants were assessed prior to intervention , immediately following the intervention , and 12 months after . Results In the intention-to-treat analysis , in-person ISTDP participants had significantly lower pain intensity than ID-ISTDP participants , both immediately following the intervention ( d = 0.97 ) and at the 12-month follow-up ( d = 0.82 ) . Moreover , there were significant decreases in depression , anxiety and stress as well as a greater increase in emotion regulation functioning , mindfulness and quality of life observed in the in-person ISTDP group at the end of the intervention and 12 months after the treatment when compared to the ID-ISTDP group . Participants rated both treatment conditions as equally credible and satisfying . Conclusion ISTDP seems most effective when delivered in person in treating MUP patients with highly comorbid conditions with benefits maintained over 12 months BACKGROUND AND OBJECTIVE Affect and how it is regulated plays a role in pain perception , maintenance of pain , and its resolution . This r and omized , controlled trial evaluated an innovative affective self-awareness ( ASA ) intervention , which was design ed to reduce pain and improve functioning in individuals with fibromyalgia . PARTICIPANTS AND METHODS Forty-five women with fibromyalgia were r and omized to a manualized ASA intervention ( n = 24 ) or wait-list control ( n = 21 ) . The intervention began with a one-time physician consultation , followed by 3 weekly , 2-h group sessions based upon a mind-body model of pain . Sessions focused on structured written emotional disclosure and emotional awareness exercises . Outcomes in both conditions were measured by a blinded assessor at baseline , post-intervention , and 6-month follow-up . MEASURES The primary outcome was pain severity ( Brief Pain Inventory ) ; secondary outcomes included tender-point threshold and physical function ( SF-36 Physical Component Summary ) . Intent-to-treat analyses compared groups on outcomes using analysis of covariance and on the proportion of patients achieving ≥30 % and ≥50 % pain reduction at 6 months . RESULTS Adjusting for baseline scores , the intervention group had significantly lower pain severity ( p < 0.001 ) , higher self-reported physical function ( p < 0.001 ) , and higher tender-point threshold ( p = 0.02 ) at 6 months compared to the control group . From baseline to 6 months , 45.8 % of the ASA intervention group had ≥30 % reduction in pain severity , compared to none of the controls ( p < 0.001 ) . CONCLUSIONS The affective self-awareness intervention improved pain , tenderness , and self-reported physical function for at least 6 months in women with fibromyalgia compared to wait-list control . This study suggests the value of interventions targeting emotional processes in fibromyalgia , although further studies should evaluate the efficacy of this intervention relative to active controls OBJECTIVES Although high levels of distress are associated with the onset and severity of Irritable bowel syndrome ( IBS ) , it is unclear how this relates to emotional processing , particularly in relation to maintenance of symptoms and treatment outcome . This qualitative study embedded within a r and omized controlled trial aim ed to explore how individuals with refractory IBS experience , express , and manage their emotions after either therapist-delivered cognitive behavioural therapy ( TCBT ) or Web-based CBT ( WBCBT ) compared to treatment as usual ( TAU ) . DESIGN Cross-sectional qualitative study . METHODS Fifty-two semi-structured interviews were conducted at post-treatment with 17 TCBT , 17 WBCBT , and 18 TAU participants . The transcripts were analysed using inductive thematic analysis with grounded theory elements . NVivo 11 was used to compare themes across groups . RESULTS Across all groups , high expectations of self was a recurring reason for how participants experienced and expressed their emotions . Three themes with subthemes captured how high expectations related to specific aspects of emotional processing : perceived causes of emotions , strategies for coping with emotions ( bottling up , avoiding emotions , and active coping strategies ) , and the perceived interplay between emotions and IBS symptoms . CONCLUSIONS Patients recognized that their IBS symptoms both triggered and were triggered by negative emotions . However , there was a tendency to bottle up or avoid negative emotions for reasons of social desirability regardless of whether patients had CBT for IBS or not . Future psychological interventions in IBS may benefit from addressing negative beliefs about expressing emotions , promoting assertive emotional expression , and encouraging the experience of positive emotions . Statement of contribution What is already known on this subject ? High levels of distress are consistently associated with both the onset and maintenance of IBS symptoms . Little is known about how this relates to the concept of emotional processing . Preliminary findings suggest a positive correlation between poor emotional processing and IBS . However , further studies need to confirm its role in relation to aetiology , maintenance of symptoms , and response to treatment . What does this study add ? High expectations of self and social desirability seem to be important aspects shaping the way individuals with IBS experience , express , and manage their emotions . Emotional avoidance and bottling up were reported as key strategies to cope with negative emotions . The study revealed that bottling up is not perceived as an all-or-nothing strategy but can be applied selectively depending on the context . Psychological interventions in IBS may benefit from addressing not only illness-related causes of negative emotions but also personal and social triggers of distress OBJECTIVE Current psychological and behavioral therapies for chronic musculoskeletal pain only modestly reduce pain , disability , and distress . These limited effects may be due to the failure of current therapies : a ) to help patients learn that their pain is influenced primarily by central nervous system psychological processes ; and b ) to enhance awareness and expression of emotions related to psychological trauma or conflict . METHODS We developed and conducted a preliminary , uncontrolled test of a novel psychological attribution and emotional awareness and expression therapy that involves an initial individual consultation followed by 4 group sessions . A series of 72 patients with chronic musculoskeletal pain had the intervention and were assessed at baseline , post-treatment , and 6-month follow-up . RESULTS Participation and satisfaction were high and attrition was low . Intent-to-treat analyses found significant improvements in hypothesized change processes : psychological attributions for pain , emotional awareness , emotional approach coping , and alexithymia . Pain , interference , depression , and distress showed large effect size improvements at post-treatment , which were maintained or even enhanced at 6 months . Approximately two-thirds of the patients improved at least 30 % in pain and other outcomes , and one-third of the patients improved 70 % . Changes in attribution and emotional processes predicted outcomes . Higher baseline depressive symptoms predicted greater improvements , and outcomes were comparable for patients with widespread vs. localized pain . CONCLUSION This novel intervention may lead to greater benefits than available psychological interventions for patients with chronic musculoskeletal pain , but needs controlled testing Background Fibromyalgia ( FM ) is a syndrome primarily characterised by chronic , widespread musculoskeletal pain . In the aetiology of this syndrome a crucial role is played by complex interactions among biological , genetic , psychological , and socio-cultural factors . Recently , research ers have started to explore emotional functioning in FM , with their attention focused on alexithymia , a personality construct that affects the regulation of a person ’s own emotions . On the other h and , the detection and experience of emotional signals from other people have only been sparsely investigated in FM syndrome and no studies have investigated the ability to represent other people ’s mental states ( i.e. Theory of Mind , ToM ) in these patients . Here we present the first study investigating a large set of social-cognitive abilities , and the possible relationships between these abilities and the performance on executive-function tasks , in a homogenous sample of patients with FM . Methodology Forty women with FM and forty-one healthy women matched for education and age were involved in the study . Social cognition was assessed with a set of vali date d experimental tasks . Measures of executive function were used to test the correlations between this dimension and the social-cognitive profile of patients with FM . Relationships between social-cognitive abilities and demographic , clinical and psychological variables were also investigated . Principal Findings Patients with FM have impairments both in the regulation of their own affect and in the recognition of other ’s emotions , as well as in representing other people ’s mental states . No significant correlations were found between social cognition tasks and the subcomponents of the executive function that were analysed . Conclusions The results show the presence of several impairments in social cognition skills in patients with FM , which are largely independent of both executive function deficits and symptoms of psychological distress . The impairments reported highlight the importance of adequately assessing ToM and emotional functioning in clinical practice OBJECTIVE The present study examines the possibility that a chronic pain condition , such as fibromyalgia , was associated with deficits in decision making and associative learning . METHODS Fifteen patients with fibromyalgia ( aged 42 - 59 years ) and 15 healthy controls ( aged 39 - 61 years ) participated in the experiment . Subjects completed anxiety ( STAI ) and depression ( BDI ) question naires , as well as st and ardized neuropsychological tests ( Stroop and WAIS subscales ) . In addition , an emotional decision-making task ( Iowa Gambling Task ) and a conditional associative learning task ( CALT ) were administered to all participants . RESULTS Results indicated that fibromyalgia had a poorer performance than healthy controls in both tasks , showing more perseveration errors in the learning task , and more disadvantageous decisions , as well as a more r and om behavior in the gambling task . Moreover , we observed that poor performance on the associative learning task was mediated by depression , whereas performance on the gambling task was not influenced by depression . No group differences were found on the st and ardized neuropsychological tests . CONCLUSION These findings indicate that pain and depressive symptoms in fibromyalgia might lead to significant deficits in emotionally charged cognitive tasks . Furthermore , it suggests that chronic pain might impose a high cost on executive control , undermining mainly affective processes involved in learning , memory , attention , and decision-making Summary Within‐day associations between behavioral anger expression and momentary chronic pain intensity show significant lagged effects , with elevated behavioral anger expression linked to greater subsequent pain intensity . ABSTRACT Links between elevated trait anger expressiveness ( anger‐out ) and greater chronic pain intensity are well documented , but pain‐related effects of expressive behaviors actually used to regulate anger when it is experienced have been little explored . This study used ecological momentary assessment methods to explore prospect i ve associations between daily behavioral anger expression and daily chronic pain intensity . Forty‐eight chronic low back pain ( LBP ) patients and 36 healthy controls completed electronic diary ratings of momentary pain and behavioral anger expression in response to r and om prompts 4 times daily for 7 days . Across groups , greater trait anger‐out was associated with greater daily behavioral anger expression ( P < 0.001 ) . LBP participants showed higher levels of daily anger expression than controls ( P < 0.001 ) . Generalized estimating equation analyses in the LBP group revealed a lagged main effect of greater behavioral anger expression on increased chronic pain intensity in the subsequent assessment period ( P < 0.05 ) . Examination of a trait × situation model for anger‐out revealed prospect i ve associations between elevated chronic pain intensity and later increases in behavioral anger expression that were restricted largely to individuals low in trait anger‐out ( P < 0.001 ) . Trait × situation interactions for trait anger suppression ( anger‐in ) indicated similar influences of pain intensity on subsequent behavioral anger expression occurring among low anger‐in persons ( P < 0.001 ) . Overlap with trait and state negative affect did not account for study findings . This study for the first time documents lagged within‐day influences of behavioral anger expression on subsequent chronic pain intensity . Trait anger regulation style may moderate associations between behavioral anger expression and chronic pain intensity It is now widely accepted that individuals with autism have a Theory of Mind ( ToM ) or mentalizing deficit . This has traditionally been assessed with false‐belief tasks and , more recently , with silent geometric animations , an on‐line ToM task . In adults with milder forms of autism st and ard false‐belief tests , originally devised for children , often prove insensitive , while the Frith‐Happé animations have had rather better success at capturing the on‐line ToM deficit in this population . However , analysis of participants ' verbal descriptions of these animations , which span scenarios from “ R and om ” to “ Goal ‐Directed ” and “ ToM , ” is time consuming and subjective . In this study , we developed and established the feasibility of an objective method of response through a series of multiple‐choice questions . Sixteen adults with aut Output:	The results indicate that patients show a reduced engagement with cognitive content of emotions . On the other h and , bodily constituents of ER seem to depict an over-reactive pattern . Similarly , the patients tend to encounter difficulties in flexibly disengaging their ( spontaneous ) attention from emotional material .
MS21407	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Background Nonventilated hospital-acquired pneumonia ( NVHAP ) is a serious nosocomial infection that is increasingly attributed to antibiotic-resistant bacteria . Methods This is a retrospective case-control study comparing patients with and those without NVHAP from January 1 , 2014 to December 31 , 2014 at Barnes-Jewish Hospital , a 1,300-bed urban academic medical center in St. Louis , Missouri . Results One hundred seventy-four consecutive patients with NVHAP were enrolled . A r and om sample of 696 control patients matched by age , sex , race , and hospital admission date were selected from a total of 5,322 potential matched control subjects . NVHAP was pathogen-negative in 98 cases ( 56.3 % ) . Respiratory viruses were identified in 42 patients ( 24.1 % ) , gram-negative bacteria were seen in 25 patients ( 14.4 % ) , and gram-positive bacteria were identified in 20 patients ( 11.5 % ) . Individuals in whom NVHAP developed were more likely to die ( 15.5 % vs 1.6 % ; P < .01 ) , to require intensive care ( 56.3 % vs 22.8 % ; P < .01 ) or mechanical ventilation ( 19.0 % vs 3.9 % ; P < 0.01 ) , and to have a longer hospital length of stay ( 15.9 days [ range , 9.8 - 26.3 days ] vs 4.4 days [ range , 2.9 - 7.3 days ] ; P < 0.01 ) . This case-control study identified a strong association between hospital mortality and NVHAP , with patients who acquired NVHAP having an 8.4 times greater odds of death ( 95 % CI , 5.6 - 12.5 ) . Conclusions The occurrence of NVHAP was associated with significant increases in mortality , the use of intensive care and mechanical ventilation , and hospital length of stay . We also found that respiratory viruses were an important cause of NVHAP . These findings suggest that efforts aim ed at the successful prevention of NVHAP could improve patient outcomes and reduce health-care costs Background and Purpose — Dysphagia can lead to pneumonia and subsequent death after acute stroke . However , no prospect i ve study has demonstrated reduced pneumonia prevalence after implementation of a dysphagia screen . Methods — We performed a single-center prospect i ve interrupted time series trial of a quality initiative to improve dysphagia screening . Subjects included all patients with ischemic or hemorrhagic stroke admitted to our institution over 42 months with a 31-month ( n=1686 ) preintervention and an 11-month ( n=648 ) postintervention period . The intervention consisted of a dysphagia protocol with a nurse-administered bedside dysphagia screen and a reflexive rapid clinical swallow evaluation by a speech pathologist . Results — The dysphagia initiative increased the percentage of patients with stroke screened from 39.3 % to 74.2 % ( P<0.001 ) . Furthermore , this initiative coincided with a drop in hospital-acquired pneumonia from 6.5 % to 2.8 % among patients with stroke ( P<0.001 ) . Patients admitted postinitiative had 57 % lower odds of pneumonia , after controlling for multiple confounds ( odds ratio=0.43 ; confidence interval , 0.255–0.711 ; P=0.0011 ) . The best predictors of pneumonia were stroke type ( P<0.0001 ) , oral intake status ( P<0.0001 ) , dysphagia screening status ( P=0.0037 ) , and hospitalization before the beginning of the quality improvement initiative ( P=0.0449 ) . Conclusions — A quality improvement initiative using a nurse-administered bedside screen with rapid bedside swallow evaluation by a speech pathologist improves screening compliance and correlates with decreased prevalence of pneumonia among patients with stroke Abstract Objective To assess the efficacy of a single preoperative physiotherapy session to reduce postoperative pulmonary complications ( PPCs ) after upper abdominal surgery . Design Prospect i ve , pragmatic , multicentre , patient and assessor blinded , parallel group , r and omised placebo controlled superiority trial . Setting Multidisciplinary preadmission clinics at three tertiary public hospitals in Australia and New Zeal and . Participants 441 adults aged 18 years or older who were within six weeks of elective major open upper abdominal surgery were r and omly assigned through concealed allocation to receive either an information booklet ( n=219 ; control ) or preoperative physiotherapy ( n=222 ; intervention ) and followed for 12 months . 432 completed the trial . Interventions Preoperatively , participants received an information booklet ( control ) or an additional 30 minute physiotherapy education and breathing exercise training session ( intervention ) . Education focused on PPCs and their prevention through early ambulation and self directed breathing exercises to be initiated immediately on regaining consciousness after surgery . Postoperatively , all participants received st and ardised early ambulation , and no additional respiratory physiotherapy was provided . Main outcome measures The primary outcome was a PPC within 14 postoperative hospital days assessed daily using the Melbourne group score . Secondary outcomes were hospital acquired pneumonia , length of hospital stay , utilisation of intensive care unit services , and hospital costs . Patient reported health related quality of life , physical function , and post-discharge complications were measured at six weeks , and all cause mortality was measured to 12 months . Results The incidence of PPCs within 14 postoperative hospital days , including hospital acquired pneumonia , was halved ( adjusted hazard ratio 0.48 , 95 % confidence interval 0.30 to 0.75 , P=0.001 ) in the intervention group compared with the control group , with an absolute risk reduction of 15 % ( 95 % confidence interval 7 % to 22 % ) and a number needed to treat of 7 ( 95 % confidence interval 5 to 14 ) . No significant differences in other secondary outcomes were detected . Conclusion In a general population of patients listed for elective upper abdominal surgery , a 30 minute preoperative physiotherapy session provided within existing hospital multidisciplinary preadmission clinics halves the incidence of PPCs and specifically hospital acquired pneumonia . Further research is required to investigate benefits to mortality and length of stay . Trial registration Australian New Zeal and Clinical Trials Registry ANZCTR 12613000664741 ABSTRACT Hospital-acquired pneumonia ( HAP ) contributes greatly to patient mortality and healthcare costs . Studies have shown that aggressive oral care in intensive care units ( ICUs ) can significantly reduce pneumonia rates , and hospitals have implemented stringent protocol s in this setting . However , little is known about the effectiveness of aggressive oral care in reducing HAP in non – intensive care wards , prompting us to conduct a nonr and omized controlled clinical trial . A structured toothbrushing program was provided to an experimental cohort of patients . A control group received usual care . Patient demographics , toothbrushing frequency , and pneumonia diagnosis were recorded over a 3.5-month period . Difference in pneumonia rates was computed using unadjusted and multivariate logistic regression analyses . No significant difference in pneumonia rates between control and experimental groups was found ( 1.7 % versus 1.8 % ) . Toothbrushing rates increased significantly in the experimental group ( p = .002 ) but fell short of protocol frequency . It became apparent that aggressive toothbrushing program implementation requires nursing-led interdisciplinary involvement , more intensive training , a streamlined documentation system , and efficient compliance tracking . Lessons from this study should be used for future large-scale research . A secondary analysis of these data did , however , suggests that increasing toothbrushing rates may have the potential to reduce pneumonia in the non-ICU acute care setting OBJECTIVES Aspiration of oral secretions and their bacteria is increasingly being recognized as an important factor in pneumonia . We investigated whether oral care lowers the frequency of pneumonia in institutionalized older people . DESIGN Survey . SETTING Eleven nursing homes in Japan . PARTICIPANTS Four hundred seventeen patients r and omly assigned to an oral care group or a no oral care group . INTERVENTION Nurses or caregivers cleaned the patients ' teeth by toothbrush after each meal . Swabbing with povidone iodine was additionally used in some cases . Dentists or dental hygienists provided professional care once a week . MEASUREMENTS Pneumonia , febrile days , death from pneumonia , activities of daily living , and cognitive functions . RESULTS During follow-up , pneumonia , febrile days , and death from pneumonia decreased significantly in patients with oral care . Oral care was beneficial in edentate and dentate patients . Activities of daily living and cognitive functions showed a tendency to improve with oral care . CONCLUSION We suggest that oral care may be useful in preventing pneumonia in older patients in nursing homes BACKGROUND Currently , no single U.S. surveillance system can provide estimates of the burden of all types of health care-associated infections across acute care patient population s. We conducted a prevalence survey in 10 geographically diverse states to determine the prevalence of health care-associated infections in acute care hospitals and generate up date d estimates of the national burden of such infections . METHODS We defined health care-associated infections with the use of National Healthcare Safety Network criteria . One-day surveys of r and omly selected in patients were performed in participating hospitals . Hospital personnel collected demographic and limited clinical data . Trained data collectors review ed medical records retrospectively to identify health care-associated infections active at the time of the survey . Survey data and 2010 Nationwide Inpatient Sample data , stratified according to patient age and length of hospital stay , were used to estimate the total numbers of health care-associated infections and of in patients with such infections in U.S. acute care hospitals in 2011 . RESULTS Surveys were conducted in 183 hospitals . Of 11,282 patients , 452 had 1 or more health care-associated infections ( 4.0 % ; 95 % confidence interval , 3.7 to 4.4 ) . Of 504 such infections , the most common types were pneumonia ( 21.8 % ) , surgical-site infections ( 21.8 % ) , and gastrointestinal infections ( 17.1 % ) . Clostridium difficile was the most commonly reported pathogen ( causing 12.1 % of health care-associated infections ) . Device-associated infections ( i.e. , central -catheter-associated bloodstream infection , catheter-associated urinary tract infection , and ventilator-associated pneumonia ) , which have traditionally been the focus of programs to prevent health care-associated infections , accounted for 25.6 % of such infections . We estimated that there were 648,000 patients with 721,800 health care-associated infections in U.S. acute care hospitals in 2011 . CONCLUSIONS Results of this multistate prevalence survey of health care-associated infections indicate that public health surveillance and prevention activities should continue to address C. difficile infections . As device- and procedure-associated infections decrease , consideration should be given to exp and ing surveillance and prevention activities to include other health care-associated infections INTRODUCTION The purpose of this point-of-care study was to test the efficacy of a prevention-based oral care protocol in reducing non-ventilator-associated hospital-acquired pneumonia in a neurosurgical population outside the critical care environment . The research ers hypothesized that an enhanced oral care protocol would decrease the incidence of pneumonia . METHODS This quasi-experimental , comparative study took place on an acute neurosurgical unit at a tertiary care trauma hospital in Western Canada . Subjects were non-intubated , care-dependent adults with a primary diagnosis of neurologic injury/insult , and at high risk for pneumonia . The prospect i ve study group comprised 34 subjects ; two subjects were excluded from the study analysis . The retrospective study group comprised 51 subjects . Data were collected for both groups for a six-month period . Retrospective data were collected through chart review . The prospect i ve group were eligible neurosurgical patients who received the enhanced oral care protocol . Data collection tools were developed and diagnostic criteria for hospital-acquired pneumonia were determined . The pneumonia rates between subjects who received st and ard oral care ( retrospective group ) and those who received an enhanced , prevention-based , oral care protocol ( prospect i ve group ) were compared . RESULTS A statistically significant decrease in the pneumonia rate occurred in the prospect i ve group ( p < 0.05 ) . DISCUSSION An enhanced oral care protocol was beneficial in reducing the incidence of non-ventilator-associated hospital-acquired pneumonia . IMPLICATION S Nurses play a vital role in preventing hospital-acquired pneumonia . Foundational nursing practice s , such as regular oral hygiene , are important aspects of care in preventing nosocomial infections and related costs , optimizing health , and promoting quality care BACKGROUND Hospital-acquired pneumonia ( HAP ) is one of the leading nosocomial infections and is associated with high morbidity and mortality . Numerous studies on HAP have been performed in intensive care units ( ICUs ) , whereas very few have focused on patients in general wards . This study examined the incidence of , risk factors for , and outcomes Output:	To date , interventions to reduce NV-HAP appear to be based broadly on the themes of improving oral care , increased mobility or movement and dysphagia management
MS21408	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Study Design . A clinical prospect i ve observational cohort study of 15 patients undergoing cervical intervertebral disc replacement . Objective . To assess the safety , clinical stability , and capacity of a newly design ed cervical intervertebral disc replacement for preserving motion in the cervical spine of patients with degenerative disc disease . Summary of Background Data . Anterior cervical discectomy and interbody fusion results in loss of motion segments and there is evidence of accelerated degenerative changes occurring at adjacent levels . Intervertebral disc replacement may be a valid alternative to fusion . There is a need for cervical disc replacement to be evaluated in prospect i ve studies before it can be adopted as an acceptable surgical technique . Methods . The study enrolled 15 patients with cervical radiculopathy or myelopathy and radiologically confirmed cervical disc herniation or posterior vertebral body osteophytes . Eligibility for the study required that patients have either a previous adjacent-level surgical or congenital spinal fusion or radiologic evidence of adjacent-level degenerative disc disease . After decompressive surgery via an anterior approach , all 15 patients received the artificial joint . Follow-up visits were at set intervals and included clinical examination , radiologic assessment , and evaluation by patient-completed question naires . Results . In all cases , the artificial joint maintained motion at the operative levels while reestablishing intervertebral height . The procedure was considered safe for experienced spine surgeons to perform , and the device was stable , with no dislocation of components or backing out of screws . Two screws broke , but without any consequence . Improvements in assessment scores were noted . Conclusions . Cervical intervertebral motion can be maintained with the new device , which is clinical ly stable . Meticulous attention must be paid to the surgical technique to maximize the chances of a good result . The pilot study was successful , although it has yet to be determined what conditions will benefit most from this technology BACKGROUND CONTEXT Cervical total disc replacement ( TDR ) is intended to address radicular pain and preserve functional motion between two vertebral bodies in patients with symptomatic cervical disc disease ( SCDD ) . PURPOSE The purpose of this trial is to compare the safety and efficacy of cervical TDR , ProDisc-C ( Synthes Spine Company , L.P. , West Chester , PA ) , to anterior cervical discectomy and fusion ( ACDF ) surgery for the treatment of one-level SCDD between C3 and C7 . STUDY DESIGN / SETTING The study was conducted at 13 sites . A noninferiority design with a 1:1 r and omization was used . PATIENT SAMPLE Two hundred nine patients were r and omized and treated ( 106 ACDF ; 103 ProDisc-C ) . OUTCOME MEASURES Visual analog scale ( VAS ) pain and intensity ( neck and arm ) , VAS satisfaction , neck disability index ( NDI ) , neurological exam , device success , adverse event occurrence , and short form-36 ( SF-36 ) st and ardized question naires . METHODS A prospect i ve , r and omized , controlled clinical trial was performed . Patients were enrolled and treated in accordance with the US Food and Drug Administration ( FDA ) -approved protocol . Patients were assessed pre- and postoperatively at six weeks , 3 , 6 , 12 , 18 , and 24 months . RESULTS Demographics were similar between the two patient groups ( ProDisc-C : 42.1+/-8.4 years , 44.7 % males ; Fusion : 43.5 + /- 7.1 years , 46.2 % males ) . The most commonly treated level was C5-C6 ( ProDisc-C : 56.3 % ; Fusion=57.5 % ) . NDI and SF-36 scores were significantly less compared with presurgery scores at all follow-up visits for both the treatment groups ( p<.0001 ) . VAS neck pain intensity and frequency as well as VAS arm pain intensity and frequency were statistically lower at all follow-up timepoints compared with preoperative levels ( p<.0001 ) but were not different between treatments . Neurologic success ( improvement or maintenance ) was achieved at 24 months in 90.9 % of ProDisc-C and 88.0 % of Fusion patients ( p=.638 ) . Results show that at 24 months postoperatively , 84.4 % of ProDisc-C patients achieved a more than or equal to 4 degrees of motion or maintained motion relative to preoperative baseline at the operated level . There was a statistically significant difference in the number of secondary surgeries with 8.5 % of Fusion patients needing a re-operation , revision , or supplemental fixation within the 24 month postoperative period compared with 1.8 % of ProDisc-C patients ( p=.033 ) . At 24 months , there was a statistically significant difference in medication usage with 89.9 % of ProDisc-C patients not on strong narcotics or muscle relaxants , compared with 81.5 % of Fusion patients . CONCLUSIONS The results of this clinical trial demonstrate that ProDisc-C is a safe and effective surgical treatment for patients with disabling cervical radiculopathy because of single-level disease . By all primary and secondary measures evaluated , clinical outcomes after ProDisc-C implantation were either equivalent or superior to those same clinical outcomes after Fusion OBJECT The authors report the results of a prospect i ve r and omized multicenter study in which the results of cervical disc arthroplasty were compared with anterior cervical discectomy and fusion ( ACDF ) in patients treated for symptomatic single-level cervical degenerative disc disease ( DDD ) . METHODS Five hundred forty-one patients with single-level cervical DDD and radiculopathy were enrolled at 32 sites and r and omly assigned to one of two treatment groups : 276 patients in the investigational group underwent anterior cervical discectomy and decompression and arthroplasty with the PRESTIGE ST Cervical Disc System ( Medtronic Sofamor Danek ) ; 265 patients in the control group underwent decompressive ACDF . Eighty percent of the arthroplasty-treated patients ( 223 of 276 ) and 75 % of the control patients ( 198 of 265 ) completed clinical and radiographic follow-up examinations at routine intervals for 2 years after surgery . Analysis of all currently available postoperative 12- and 24-month data indicated a two-point greater improvement in the neck disability index score in the investigational group than the control group . The arthroplasty group also had a statistically significant higher rate of neurological success ( p = 0.005 ) as well as a lower rate of secondary revision surgeries ( p = 0.0277 ) and supplemental fixation ( p = 0.0031 ) . The mean improvement in the 36-Item Short Form Health Survey Physical Component Summary scores was greater in the investigational group at 12 and 24 months , as was relief of neck pain . The patients in the investigational group returned to work 16 days sooner than those in the control group , and the rate of adjacent-segment reoperation was significantly lower in the investigational group as well ( p = 0.0492 , log-rank test ) . The cervical disc implant maintained segmental sagittal angular motion averaging more than 7 degrees . In the investigational group , there were no cases of implant failure or migration . CONCLUSIONS The PRESTIGE ST Cervical Disc System maintained physiological segmental motion at 24 months after implantation and was associated with improved neurological success , improved clinical outcomes , and a reduced rate of secondary surgeries compared with ACDF BACKGROUND Ten-year follow-up data from the US Food and Drug Administration investigational device exemption trial comparing BRYAN ® Cervical Disc ( Medtronic , Dublin , Irel and ) arthroplasty to anterior cervical discectomy and fusion ( ACDF ) demonstrated that disc arthroplasty maintained range of motion and improvements in overall success and neck disability . OBJECTIVE To compare the 10-yr rates of symptomatic adjacent level disease requiring surgery ( SALDRS ) . METHODS Prospect i ve r and omized trial data were analyzed comparing BRYAN ® Cervical Disc arthroplasty to ACDF for single-level cervical disc disease with concordant radiculopathy or myelopathy with clinicoradiographic analysis at 10 yr . Secondarily , 84-mo data were pooled with PRESTIGE ® Cervical Disc arthroplasty ( Medtronic ) study data to provide overall rates of SALDRS . RESULTS Significantly greater overall success was maintained at every postoperative interval with an overall success rate of 81.3 % with BRYAN ® disc and 66.3 % with ACDF ( P = .005 ) without loss of motion preservation ( 8.69 ° vs 0.60 ° ) . Reoperation at adjacent levels up to the 120-mo visit was 9.7 % in the arthroplasty group and 15.8 % in the ACDF group ( P = .146 ) . The combined data from BRYAN ® and Prestige ST demonstrate that BRYAN ® and Prestige disc groups had a lower rate of second surgeries at the adjacent levels , up to the 84-mo visit , compared to the combined ACDF groups ( 6.9 % vs 11.7 % ; P = .023 ) . CONCLUSION Compared with ACDF , fewer patients with the BRYAN ® disc required surgery for symptomatic adjacent level degeneration , but this did not achieve statistical significance . Analysis of combined study data using Bryan and Prestige discs shows significant differences in SADLRS as early as 7 yr Study Design . Prospect i ve , multicenter , r and omized , and controlled Investigational Device Exemption clinical trial . Objective . To compare the clinical safety and effectiveness of the selectively constrained SECURE-C ( Globus Medical , Audubon , PA ) Cervical Artificial Disc to anterior cervical discectomy and fusion ( ACDF ) . Summary of Background Data . Cervical total disc replacement has been developed as an alternative to ACDF by allowing segmental motion . Current cervical total disc replacement design s incorporate constrained and unconstrained metal-on-metal or metal-on-polymer articulating design s with various means of fixation . Methods . A total of 380 patients from 18 investigational sites were prospect ively enrolled in the study . Patients were r and omized , treated surgically , and evaluated postoperatively at 6 weeks , 3 months , 6 months , 12 months , and 24 months . Clinical outcomes include overall success , visual analogue scale pain ( right arm , left arm , and neck ) , neck disability index , neurological status , Short Form 36 ( SF-36 ) Health Status Survey question naires , range of motion , and adverse events . Bayesian statistical methods were used to analyze the outcomes . Results . Overall success results demonstrated statistical superiority of the r and omized SECURE-C group compared with the r and omized ACDF group at 24 months , with a posterior probability of 100 % using the protocol -specified criteria and 98.1 % using Food and Drug Administration-defined criteria . At 24 months postoperatively , SECURE-C demonstrated clinical ly significant improvement in pain and function in terms of neck disability index , visual analogue scale , and 36-Item Short Form Health Survey . At 24 months , the percentage of patients experiencing secondary surgical interventions at the index level was statistically lower for the SECURE-C group ( 2.5 % ) than the ACDF group ( 9.7 % ) . At 24 months , 84.6 % of as-treated SECURE-C patients were range-of-motion successes . Satisfaction was high among SECURE-C patients . Conclusion . The selectively constrained SECURE-C Cervical Artificial Disc is as safe and effective as the st and ard of care , an anterior cervical discectomy and fusion . SECURE-C is statistically superior in terms of overall success , index-level subsequent surgical procedures , and patient satisfaction , making it an attractive surgical option for patients with symptomatic cervical disc disease . Level of Evidence : BACKGROUND In patients with single-level cervical degenerative disc disease , total disc arthroplasty can relieve radicular pain and preserve functional motion between two vertebrae . We compared the efficacy and safety of cervical total disc arthroplasty with that of anterior cervical discectomy and fusion ( ACDF ) for the treatment of single-level cervical degenerative disc disease between C3-C4 and C6-C7 . METHODS Two hundred and nine patients at thirteen sites were r and omly treated with either total disc arthroplasty with ProDisc-C ( n = 103 ) or with ACDF ( n = 106 ) . Patients were assessed preoperatively ; at six weeks and three , six , twelve , eighteen , and twenty-four months postoperatively ; and then annually until seven years postoperatively . Outcome measures included the Neck Disability Index ( NDI ) , the Short Form-36 ( SF-36 ) , postoperative neurologic parameters , secondary surgical procedures , adverse events , neck and arm pain , and satisfaction scores . RESULTS At seven years , the overall follow-up rate was 92 % ( 152 of 165 ) . There were no significant differences in demographic factors , follow-up rate , or patient-reported outcomes between groups . Both procedures were effective in reducing neck and arm pain and improving and maintaining function and health-related quality of life . Neurologic status was improved or maintained in 88 % and 89 % of the patients in the ProDisc-C and ACDF groups , respectively . After seven years of follow-up , thirty secondary surgical procedures had been performed in nineteen ( 18 % ) of 106 patients in the ACDF group compared with seven secondary surgical procedures in seven ( 7 % ) of 103 patients in the ProDisc-C Output:	However , around 5 years , a statistically significant divergence emerged , where the rate of adjacent-level surgery rose steeply for ACDF . Index-level reoperations were less frequent with CDA in both the short- and long-term . These data indicate CDA may have a superior longevity to ACDF with regard to need for subsequent adjacent-level operation
MS21409	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Essentials Perioperative bleeding during prostate surgery is still a common morbidity . Anticoagulant and antiplatelet medications contribute to the risk of hemorrhage and prolonged hospital stay . Multiple pharmacological agents have been proposed , but none of them have been widely accepted . It is crucial to find a safe and effective modality to reduce hemorrhage . SUMMARY Background Hemorrhage during transurethral resection of the prostate ( TUR-P ) has always been a concern . Several studies have shown preoperative administration of fibrinogen concentrate to have promising results in reducing hemorrhage in cardiac surgery . Objectives To investigate the hemostatic effect of fibrinogen concentrate administration on reducing the amount of bleeding during TUR-P in patients with benign prostatic hyperplasia . Methods Sixty men with benign prostatic hyperplasia , who were chosen to undergo TUR-P , entered this prospect i ve r and omized double-blind placebo-controlled study . The participants were r and omly assigned to two groups : treatment ( n = 31 ) and placebo ( n = 29 ) . They received an infusion of 2 g of fibrinogen concentrate ( treatment group ) or normal saline ( placebo group ) before surgery . Data regarding the amount of bleeding , the operation and complications were recorded and analyzed . Results No difference was observed in bleeding between the fibrinogen and placebo groups during ( 521 mL versus 557 mL , respectively ) and after ( 291 mL versus 341 mL , respectively ) surgery . This lack of difference was also seen in operation time ( 43 min versus 42 min ) , irrigating fluid volume used during ( 17 L versus 19 L ) and after ( 29 L versus 28 L ) surgery , and resected adenoma volume ( 19 g versus 19 g ) . The mean blood pressure was also similar in both groups as a confounding factor for the amount of bleeding . Conclusion Preoperative administration of fibrinogen concentrate had no significant influence on intraoperative and postoperative bleeding in TUR-P surgery Background Postoperative bleeding after heart operations is still a common finding , leading to allogeneic blood products transfusion . Fibrinogen and coagulation factors deficiency are possible determinants of bleeding . The experimental hypothesis of this study is that a first-line fibrinogen supplementation avoids the need for fresh frozen plasma ( FFP ) and reduces the need for any kind of transfusions . Methods and Results This was a single-center , prospect i ve , r and omized , placebo-controlled , double-blinded study . One-hundred sixteen patients undergoing heart surgery with an expected cardiopulmonary bypass duration > 90 minutes were admitted to the study . Patients in the treatment arm received fibrinogen concentrate after protamine administration ; patients in the control arm received saline solution . In case of ongoing bleeding , patients in the treatment arm could receive prothrombin complex concentrates ( PCCs ) and those in the control arm saline solution . The primary endpoint was avoidance of any allogeneic blood product . Patients in the treatment arm had a significantly lower rate of any allogeneic blood products transfusion ( odds ratio , 0.40 ; 95 % confidence interval , 0.19 to 0.84 , P=0.015 ) . The total amount of packed red cells and FFP units transfused was significantly lower in the treatment arm . Postoperative bleeding was significantly ( P=0.042 ) less in the treatment arm ( median , 300 mL ; interquartile range , 200 to 400 mL ) than in the control arm ( median , 355 mL ; interquartile range , 250 to 600 mL ) . Conclusions Fibrinogen concentrate limits postoperative bleeding after complex heart surgery , leading to a significant reduction in allogeneic blood products transfusions . No safety issues were raised . Clinical Trial Registration URL : http://www . clinical trials.gov . Unique identifier : NCT01471730 We hypothesized that preemptive fibrinogen administration to obtain an initial plasma level of 2.9 g/L would reduce transfusion requirements in liver transplantation . A r and omized , multicenter , hemoglobin‐stratified , double‐blind , fibrinogen‐versus‐saline – controlled trial was conducted . The primary end point was the percentage of patients requiring red blood cells . We evaluated 51 patients allocated to fibrinogen and 48 allocated to saline ; the primary end point was assessed using data for 92 patients because the electronic record forms were offline for three patients in the fibrinogen group and four in the saline group . We injected a median of 3.54 g fibrinogen preemptively in the fibrinogen group . Nine patients in the saline group ( 20.9 % ) required fibrinogen at graft reperfusion ( compared with one patient [ 2.1 % ] in the fibrinogen group ; p = 0.005 ) . Blood was transfused to 52.9 % ( 95 % confidence interval [ CI ] 42.5–63.3 % ) in the fibrinogen group and 42.74 % ( 95 % CI 28.3–57.2 % ) in the saline group ( p = 0.217 ) . Relative risk for blood transfusion was 0.80 ( 95 % CI 0.57–1.13 ) . Thrombotic events occurred in one patient ( 2.1 % ) and five patients ( 11.4 % ) in the fibrinogen and saline groups , respectively . Seven patients ( 14.6 % ) in the fibrinogen group and nine ( 20.3 % ) in the saline group required reoperation . Preemptive administration of fibrinogen concentrate did not influence transfusion requirements BACKGROUND Low fibrinogen levels immediately after cardiac surgical procedures have been associated with postoperative bleeding and transfusions . However , no sound data on the adequate trigger values for fibrinogen supplementation and target values for fibrinogen concentration exist . METHODS This retrospective study examined prospect ively collected data , including data on 2,800 adult patients undergoing cardiac operations . St and ard coagulation parameters at the arrival in the intensive care unit were retrieved , inclusive of fibrinogen levels . Postoperative bleeding was assessed based on the chest drain output ( mL/12 h ) . Severe bleeding ( SB ) was defined as chest drain output greater than 1,000 mL/12 h. RESULTS Postoperative blood loss was associated with low values of fibrinogen and platelet count , as well as with a prolonged activated partial thromboplastin time and international normalized ratio . At multivariable analysis , fibrinogen levels lower than 220 mg/dL remained independently associated with SB ( odds ratio : 2.25 ; 95 % confidence interval : 1.54 to 3.28 ) . A cutoff value of 115 mg/dL yielded a positive predictive value for SB of 50 % and may be proposed as a trigger value for fibrinogen supplementation , with a target value of 280 mg/dL ( 98 % negative predictive value for SB ) . In actively bleeding patients , these values are increased to 215 and 375 mg/dL , respectively . CONCLUSIONS These data confirm the independent role of fibrinogen levels as determinants of SB after cardiac surgical procedures and suggest adequate cutoff values and fibrinogen concentrate doses to prevent or treat SB . However , the identified trigger and target values should be confirmed in prospect i ve series of patients undergoing fibrinogen supplementation Background Surgery for benign disease is associated with a low-risk of developing venous thromboembolism ( VTE ) . Despite a relatively low incidence of postoperative VTE in patients after elective cholecystectomy and abdominal hernia repair there are data proving hypercoagulability in the early postoperative period . We focused on assessment of the systemic inflammatory response and coagulation status in these surgical patients after hospital discharge . Methods Prospect ively , patients who underwent surgery for benign disease were included . Two hundred sixteen patients were enrolled - 90 patients in laparoscopic cholecystectomy ( LC ) group and 126 patients in hernia surgery ( HS ) group . Risk assessment of VTE according to the Caprini risk assessment model was performed in all patients . Prevalence of VTE in postoperative period was observed . Markers of systemic inflammatory response ( IL-6 , CRP , α-1-acid glycoprotein , transferrin ) and coagulation markers ( PLT , fibrinogen , prothrombin fragment F1 + 2 and D-dimer ) were measured before surgery , on 7–10th postoperative day and on 28–30th postoperative day . Results Clinical ly apparent deep vein thrombosis was diagnosed in only one patient - 0.46 % . Statistically significant elevation of inflammatory markers IL-6 , CRP and α-1-acid glycoprotein ( p < 0.001 ; all ) were proved in both groups of patients on 7–10th postoperative day . Statistically significant elevation of coagulation markers PLT , fibrinogen , prothrombin fragment F1 + 2 and D-dimer ( p < 0.001 ; all ) were proved in LC and HS groups on 7–10th postoperative day . No statistical difference was observed in IL-6 , CRP and α-1-acid glycoprotein levels a month after surgery as compared with preoperative levels within each group . Statistically significant elevation of fibrinogen and prothrombin fragment F1 + 2 levels ( p < 0.001 ; both ) persisted on 28–30th postoperative day in both groups . Persisted elevation of D-dimer levels was proved only in HS group ( p < 0.001 ) , not in LC group ( p = 0.138 ) , a month after surgery . Conclusions Activated systemic inflammatory response and hypercoagulable condition were verified in patients after laparoscopic cholecystectomy and hernia surgery after their hospital discharge . Hypercoagulability persisted even a month after surgery . Nevertheless , we observed very low prevalence of clinical ly apparent VTE in patients with in-hospital postoperative VTE prophylaxis . Trial registration Trials of the Czech Ministry of Health No. RVO-VFN64165 and NT 13251 - 4 BACKGROUND In early postpartum haemorrhage ( PPH ) , a low concentration of fibrinogen is associated with excessive subsequent bleeding and blood transfusion . We hypothesized that pre-emptive treatment with fibrinogen concentrate reduces the need for red blood cell ( RBC ) transfusion in patients with PPH . METHODS In this investigator-initiated , multicentre , double-blinded , parallel r and omized controlled trial , we assigned subjects with severe PPH to a single dose of fibrinogen concentrate or placebo ( saline ) . A dose of 2 g or equivalent was given to all subjects independent of body weight and the fibrinogen concentration at inclusion . The primary outcome was RBC transfusion up to 6 weeks postpartum . Secondary outcomes were total blood loss , total amount of blood transfused , occurrence of rebleeding , haemoglobin < 58 g litre(-1 ) , RBC transfusion within 4 h , 24 h , and 7 days , and as a composite outcome of ' severe PPH ' , defined as a decrease in haemoglobin of > 40 g litre(-1 ) , transfusion of at least 4 units of RBCs , haemostatic intervention ( angiographic embolization , surgical arterial ligation , or hysterectomy ) , or maternal death . RESULTS Of the 249 r and omized subjects , 123 of 124 in the fibrinogen group and 121 of 125 in the placebo group were included in the intention-to-treat analysis . At inclusion the subjects had severe PPH , with a mean blood loss of 1459 ( sd 476 ) ml and a mean fibrinogen concentration of 4.5 ( sd 1.2 ) g litre(-1 ) . The intervention group received a mean dose of 26 mg kg(-1 ) fibrinogen concentrate , thereby significantly increasing fibrinogen concentration compared with placebo by 0.40 g litre(-1 ) ( 95 % confidence interval , 0.15 - 0.65 ; P=0.002 ) . Postpartum blood transfusion occurred in 25 ( 20 % ) of the fibrinogen group and 26 ( 22 % ) of the placebo group ( relative risk , 0.95 ; 95 % confidence interval , 0.58 - 1.54 ; P=0.88 ) . We found no difference in any predefined secondary outcomes , per- protocol analyses , or adjusted analyses . No thromboembolic events were detected . CONCLUSIONS We found no evidence for the use of 2 g fibrinogen concentrate as pre-emptive treatment for severe PPH in patients with normofibrinogenaemia . CLINICAL TRIAL REGISTRATION Clinical Trials.gov : http:// clinical trials.gov/show/NCT01359878 . Published protocol : http://www.trialsjournal.com/content/pdf/1745-6215-13-110.pdf Background : Fibrinogen is suggested to play an important role in managing major bleeding . However , clinical evidence regarding the effect of fibrinogen concentrate ( derived from human plasma ) on transfusion is limited . The authors assessed whether fibrinogen concentrate can reduce blood transfusion when given as intraoperative , targeted , first-line hemostatic therapy in bleeding patients Output:	No significant differences were demonstrated in the adverse events associated with fibrinogen concentrate use , namely incidence of thromboembolism , myocardial infa rct ion and acute kidney injury . CONCLUSIONS In this meta- analysis of 13 r and omized trials , low level of evidence and substantial heterogeneity with small sample size limit strong recommendation on the use of fibrinogen concentrate in adult surgical patients . However , its use is tolerable without any notable adverse events .
MS21410	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Introduction The aim of the study was to assess the prognostic importance of basal cortisol concentrations and cortisol response to corticotropin , and to determine the effects of physiological dose steroid therapy on mortality in patients with sepsis . Methods Basal cortisol level and corticotropin stimulation test were performed within 24 hours in all patients . One group ( 20 patients ) received st and ard therapy for sepsis and physiological-dose steroid therapy for 10 days ; the other group ( 20 patients ) received only st and ard therapy for sepsis . Basal cortisol level was measured on the 14th day in patients who recovered . The outcome of sepsis was compared . Results Only Sequential Organ Failure Assessment ( SOFA ) score was found related to mortality , independent from other factors in multivariate analysis . No significant difference was found between the changes in the percentage of SOFA scores of the steroid therapy group and the st and ard therapy group in survivors , nor between the groups in basal and peak cortisol levels , cortisol response to corticotropin test and mortality . The mortality rates among patients with occult adrenal insufficiencies were 40 % in the steroid therapy group and 55.6 % in the st and ard therapy group . Discussion There was a trend towards a decrease in the mortality rates of the patients with sepsis who received physiological-dose steroid therapy . In the advancing process from sepsis to septic shock , adrenal insufficiency was not frequent as supposed . There was a trend ( that did not reach significance ) towards a decrease in the mortality rates of the patients with sepsis who received physiological-dose steroid therapy Objective : To develop consensus statements for the diagnosis and management of corticosteroid insufficiency in critically ill adult patients . Participants : A multidisciplinary , multispecialty task force of experts in critical care medicine was convened from the membership of the Society of Critical Care Medicine and the European Society of Intensive Care Medicine . In addition , international experts in endocrinology were invited to participate . Design / Methods : The task force members review ed published literature and provided expert opinion from which the consensus was derived . The consensus statements were developed using a modified Delphi methodology . The strength of each recommendation was quantified using the Modified GRADE system , which classifies recommendations as strong ( grade 1 ) or weak ( grade 2 ) and the quality of evidence as high ( grade A ) , moderate ( grade B ) , or low ( grade C ) based on factors that include the study design , the consistency of the results , and the directness of the evidence . Results : The task force coined the term critical illness – related corticosteroid insufficiency to describe the dysfunction of the hypothalamic-pituitary-adrenal axis that occurs during critical illness . Critical illness – related corticosteroid insufficiency is caused by adrenal insufficiency together with tissue corticosteroid resistance and is characterized by an exaggerated and protracted proinflammatory response . Critical illness – related corticosteroid insufficiency should be suspected in hypotensive patients who have responded poorly to fluids and vasopressor agents , particularly in the setting of sepsis . At this time , the diagnosis of tissue corticosteroid resistance remains problematic . Adrenal insufficiency in critically ill patients is best made by a delta total serum cortisol of < 9 & mgr;g/dL after adrenocorticotrophic hormone ( 250 & mgr;g ) administration or a r and om total cortisol of < 10 & mgr;g/dL. The benefit of treatment with glucocorticoids at this time seems to be limited to patients with vasopressor-dependent septic shock and patients with early severe acute respiratory distress syndrome ( Pao2/Fio2 of < 200 and within 14 days of onset ) . The adrenocorticotrophic hormone stimulation test should not be used to identify those patients with septic shock or acute respiratory distress syndrome who should receive glucocorticoids . Hydrocortisone in a dose of 200 mg/day in four divided doses or as a continuous infusion in a dose of 240 mg/day ( 10 mg/hr ) for ≥7 days is recommended for septic shock . Methylprednisolone in a dose of 1 mg·kg−1·day−1 for ≥14 days is recommended in patients with severe early acute respiratory distress syndrome . Glucocorticoids should be weaned and not stopped abruptly . Reinstitution of treatment should be considered with recurrence of signs of sepsis , hypotension , or worsening oxygenation . Dexamethasone is not recommended to treat critical illness – related corticosteroid insufficiency . The role of glucocorticoids in the management of patients with community-acquired pneumonia , liver failure , pancreatitis , those undergoing cardiac surgery , and other groups of critically ill patients requires further investigation . Conclusion : Evidence -linked consensus statements with regard to the diagnosis and management of corticosteroid deficiency in critically ill patients have been developed by a multidisciplinary , multispecialty task force Introduction In a study conducted by Annane , patients with septic shock and unresponsive to adrenocorticotropic hormone stimulation receiving low-dose steroid therapy had prolonged survival but not significantly improved 28-day mortality . The present study examines intravenous steroid use in PROWESS ( Recombinant Human Activated Protein C Worldwide Evaluation in Severe Sepsis ) patients meeting the Annane enrollment criteria ( AEC ) . Methods Adrenocorticotropic hormone stimulation tests were not done in PROWESS . Steroids were allowed but their use was not directed . Patients were identified using AEC ( all of : r and omization to study drug treatment within 8 hours of shock onset ; infection , fever , or hypothermia ; tachycardia ; systolic blood pressure < 90 mmHg on vasopressors ; mechanical ventilation ; and one of urine < 0.5 ml/kg per hour , lactic acidosis , or arterial oxygen tension/inspired fractional oxygen < 280 ) . We examined steroid use and mortality data ; additional analyses were done outside the 8-hour window . Results Steroid-treated patients were older , had higher Acute Physiology and Chronic Health Evaluation scores and more organ dysfunctions , and were more commonly receiving mechanical ventilation . Among patients meeting AEC , regardless of steroid treatment ( n = 97 ) , mortality in the placebo and drotrecogin alfa ( activated ) groups was 38 % ( 19/50 ) and 28 % ( 13/47 ) , respectively ( relative risk [ RR ] = 0.73 , 95 % confidence interval [ CI ] 0.41–1.30 ) . When using AEC but excluding the requirement for r and omization within 8 hours of shock onset ( n = 612 ) , placebo mortality was 38 % ( 118/313 ) and drotrecogin alfa ( activated ) mortality was 29 % ( 88/299 ; RR = 0.78 , 95 % CI 0.62–0.98 ) . Using AEC but excluding the 8-hour window and with steroids initiated at baseline and /or infusion ( n = 228 ) result ed in mortality for placebo and drotrecogin alfa ( activated ) groups of 43 % ( 51/118 ) and 33 % ( 36/110 ) , respectively ( RR = 0.76 , 95 % CI 0.54–1.06 ) . Conclusion Patients with severe sepsis from the PROWESS trial who were likely to respond to low-dose steroids according to the AEC were those patients at a high risk for death . However , when using the AEC , regardless of steroid use , patients exhibited a survival benefit from treatment with drotrecogin alfa ( activated ) STUDY OBJECTIVE To evaluate the relationship between the adequacy of antimicrobial treatment for bloodstream infections and clinical outcomes among patients requiring ICU admission . DESIGN Prospect i ve cohort study . SETTING A medical ICU ( 19 beds ) and a surgical ICU ( 18 beds ) from a university-affiliated urban teaching hospital . PATIENTS Between July 1997 and July 1999 , 492 patients were prospect ively evaluated . INTERVENTION Prospect i ve patient surveillance and data collection . RESULTS One hundred forty-seven patients ( 29.9 % ) received inadequate antimicrobial treatment for their bloodstream infections . The hospital mortality rate of patients with a bloodstream infection receiving inadequate antimicrobial treatment ( 61.9 % ) was statistically greater than the hospital mortality rate of patients with a bloodstream infection who received adequate antimicrobial treatment ( 28.4 % ; relative risk , 2 . 18 ; 95 % confidence interval [ CI ] , 1.77 to 2.69 ; p < 0.001 ) . Multiple logistic regression analysis identified the administration of inadequate antimicrobial treatment as an independent determinant of hospital mortality ( adjusted odds ratio [ AOR ] , 6.86 ; 95 % CI , 5.09 to 9.24 ; p < 0.001 ) . The most commonly identified bloodstream pathogens and their associated rates of inadequate antimicrobial treatment included vancomycin-resistant enterococci ( n = 17 ; 100 % ) , C and ida species ( n = 41 ; 95.1 % ) , oxacillin-resistant Staphylococcus aureus ( n = 46 ; 32.6 % ) , coagulase-negative staphylococci ( n = 96 ; 21.9 % ) , and Pseudomonas aeruginosa ( n = 22 ; 10.0 % ) . A statistically significant relationship was found between the rates of inadequate antimicrobial treatment for individual microorganisms and their associated rates of hospital mortality ( Spearman correlation coefficient = 0.8287 ; p = 0.006 ) . Multiple logistic regression analysis also demonstrated that a bloodstream infection attributed to C and ida species ( AOR , 51.86 ; 95 % CI , 24.57 to 109.49 ; p < 0.001 ) , prior administration of antibiotics during the same hospitalization ( AOR , 2.08 ; 95 % CI , 1.58 to 2.74 ; p = 0.008 ) , decreasing serum albumin concentrations ( 1-g/dL decrements ) ( AOR , 1.37 ; 95 % CI , 1.21 to 1.56 ; p = 0.014 ) , and increasing central catheter duration ( 1-day increments ) ( AOR , 1.03 ; 95 % CI , 1.02 to 1.04 ; p = 0.008 ) were independently associated with the administration of inadequate antimicrobial treatment . CONCLUSIONS The administration of inadequate antimicrobial treatment to critically ill patients with bloodstream infections is associated with a greater hospital mortality compared with adequate antimicrobial treatment of bloodstream infections . These data suggest that clinical efforts should be aim ed at reducing the administration of inadequate antimicrobial treatment to hospitalized patients with bloodstream infections , especially individuals infected with antibiotic-resistant bacteria and C and ida species Arterial hypotension often signifies inadequate systemic perfusion . We hypothesize that in a heterogeneous emergency department ( ED ) population with clinical ly suspected circulatory shock , the severity of hypotension on presentation predicts in-hospital outcome . We performed a secondary analysis of patients with nontraumatic shock enrolled in a noninterventional , r and omized , controlled trial . The setting was an urban , tertiary ED , census > 100,000 visits per year . Patients included nontrauma ED patients , aged > 17 years , with initial ED vital signs consistent with shock ( systolic blood pressure < 100 mmHg or shock index > 1.0 ) , and agreement of two independent observers for at least one sign and symptom of inadequate tissue perfusion . Measurements included interobserver agreement for signs and symptoms of shock , relationship between the depth and duration of ED hypotension and adverse hospital outcome ( in-hospital mortality , need for intensive care unit services , and acute organ failure ) and logistic regression analysis for independent predictors of adverse hospital outcome . Of 202 patients who qualified , 190 patients were included ; the in-hospital mortality rate was 15 % . The sign or symptom of shock with the highest interobserver agreement was “ unresponsive ” ( κ = 0.74 ) . The adverse hospital outcomes increased with each decile decrease in the lowest ED systolic blood pressure ( SBP ) from 17 % if SBP > 89 mmHg versus 50 % if SBP < 80 mmHg . Forty percent of patients with an adverse hospital outcome had sustained hypotension ( all ED SBP < 100 mmHg for ≥60 min ) . Sustained hypotension was the strongest independent predictor of an adverse hospital outcome ( odds ratio 3.1 ; 95 % CI 1.5–7.1 ) . Mortality among patients who present to the ED with undifferentiated shock is high . The depth and duration of systolic blood pressure appears to have a dose – response relationship to adverse hospital outcome PURPOSE To examine the effect of inappropriate initial antimicrobial therapy on the prognosis of patients with sepsis who were enrolled in a clinical trial of an immun Output:	In patients with septic shock , corticosteroid therapy appears to be safe but does not reduce 28-day all-cause mortality rates . It does , however , significantly reduce the incidence of vasopressor-dependent shock , which may be a clinical ly worthwhile goal
MS21411	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: To confirm the inhibitory effect of etidronate on the progression of vascular calcification ( VC ) , 21 patients were r and omly enrolled . All 21 patients had end-stage renal disease and were undergoing hemodialysis ( HD ) three times per week . Patients were observed clinical ly for 12 months before etidronate treatment and then etidronate was given orally just prior to sleep on the days of dialysis for 23 months . The aortic calcification area ( ACA ) increased significantly during the 12 months before etidronate treatment . While the ACA of the drug-treated group did not change 12 and 23 months after the initiation of etidronate treatment , the ACA in the control group was significantly elevated 23 months later . These results strongly indicate that etidronate inhibits the progression of VC . Bone mineral density did not change during etidronate treatment . Our findings suggest that etidronate might effectively protect against progressive VC in HD patients BACKGROUND Vitamin D deficiency may be involved in the development of atherosclerosis and coronary heart disease in humans . METHODS We assessed prospect ively whether plasma 25-hydroxyvitamin D ( 25[OH]D ) concentrations are associated with risk of coronary heart disease . A nested case-control study was conducted in 18,225 men in the Health Professionals Follow-up Study ; the men were aged 40 to 75 years and were free of diagnosed cardiovascular disease at blood collection . The blood sample s were returned between April 1 , 1993 , and November 30 , 1999 ; 99 % were received between April 1 , 1993 , and November 30 , 1995 . During 10 years of follow-up , 454 men developed nonfatal myocardial infa rct ion or fatal coronary heart disease . Using risk set sampling , controls ( n = 900 ) were selected in a 2:1 ratio and matched for age , date of blood collection , and smoking status . RESULTS After adjustment for matched variables , men deficient in 25(OH)D ( < or=15 ng/mL [ to convert to nanomoles per liter , multiply by 2.496 ] ) were at increased risk for MI compared with those considered to be sufficient in 25(OH)D ( > or=30 ng/mL ) ( relative risk [ RR ] , 2.42 ; 95 % confidence interval [ CI ] , 1.53 - 3.84 ; P < .001 for trend ) . After additional adjustment for family history of myocardial infa rct ion , body mass index , alcohol consumption , physical activity , history of diabetes mellitus and hypertension , ethnicity , region , marine omega-3 intake , low- and high-density lipoprotein cholesterol levels , and triglyceride levels , this relationship remained significant ( RR , 2.09 ; 95 % CI , 1.24 - 3.54 ; P = .02 for trend ) . Even men with intermediate 25(OH)D levels were at elevated risk relative to those with sufficient 25(OH)D levels ( 22.6 - 29.9 ng/mL : RR , 1.60 [ 95 % CI , 1.10 - 2.32 ] ; and 15.0 - 22.5 ng/mL : RR , 1.43 [ 95 % CI , 0.96 - 2.13 ] , respectively ) . CONCLUSION Low levels of 25(OH)D are associated with higher risk of myocardial infa rct ion in a grade d manner , even after controlling for factors known to be associated with coronary artery disease Background —Osteoprotegerin is a novel member of the tumor necrosis factor receptor superfamily and a soluble decoy receptor of the receptor activator of nuclear factor-κB lig and . Recent experimental research has implicated osteoprotegerin in atherogenesis , but epidemiological confirmation of this concept is sparse . Methods and Results —As part of the prospect i ve , population -based Bruneck Study , severity , initiation , and progression of atherosclerosis were assessed in carotid arteries . Cases of incident cardiovascular disease and vascular mortality were carefully recorded over a 10-year period ( 1990 to 2000 ) . Osteoprotegerin levels were measured in sample s obtained at baseline and during follow-up . Serum osteoprotegerin showed a strong association with numerous vascular risk factors , including age , diabetes , markers of systemic inflammation , chronic infection , and smoking . In multivariate analyses , osteoprotegerin was significantly related to severity and 10-year progression of carotid atherosclerosis . Furthermore , a high level of osteoprotegerin was an independent risk factor for incident cardiovascular disease ( adjusted relative risk for the top versus bottom tertile group for osteoprotegerin 2.2 [ 1.3 to 3.8 ] ; P = 0.001 ) and vascular mortality ( adjusted relative risk for the top versus bottom tertile group for osteoprotegerin 3.1 [ 1.2 to 8.2 ] ; P = 0.010 ) but not for mortality due to nonvascular causes . Conclusions —Osteoprotegerin is an independent risk factor for the progression of atherosclerosis and onset of cardiovascular disease Animal experiments revealed conflicting results as to the impact of bisphosphonate treatment on atherosclerosis and related vascular calcification . The effect of long-term treatment with clinical doses of bisphosphonates on aortic calcification ( AC ) in an “ at-risk ” population of osteoporotic elderly women has not been assessed systematic ally . In the present analysis including 474 women ( 55–80 years ) participating in two 3-year r and omized , placebo-controlled clinical trials , we assessed the simultaneous impact of ib and ronate given either orally ( 2.5 mg daily or 20 mg intermittently ) or intravenously ( 0.5 mg or 1.0 mg IV every 3 months ) on bone mass and AC . All women received calcium and vitamin D supplements . Bone mineral density ( BMD ) was measured at the lumbar spine and the total hip using dual-energy X-ray absorptiometry ( DXA ) . Calcified deposits of the lumbar aorta ( L1–L4 ) were visualized on lateral radiographs and severity was grade d by a vali date d scoring system . Measurements were performed at baseline and at years 1 , 2 , and 3 . At baseline , there was a significant inverse correlation between the severity of AC and BMD at the hip ( r=−0.151 , P=0.003 ) , but not at the lumbar spine . The two oral doses and the 1.0 mg IV dose evoked statistically significant increases in both hip and spine BMD compared with placebo , whereas the effect of 0.5 mg was significant only at the hip ( P<0.05 ) . No differences in the yearly rate of progression or the 3-year change in AC was observed between the different intervention groups . Furthermore , there were no statistically significant correlations between the 3-year change in BMD and the simultaneous change in AC . These findings thus suggest that 3-year treatment with effective doses of ib and ronate does not pose any cardiovascular risk in terms of altering vascular calcification Kidney transplant recipients develop secondary osteoporosis induced by immunosuppressive medication , with a high risk of fracture , and abdominal aortic calcification ( AC ) is a known predictor of cardiovascular mortality . In this study of 12 stable kidney recipients , we estimated the preventive effect of bisphosphonate treatment on bone loss and progression of AC . We r and omly divided the subjects into a treatment group with alendronate ( group A : 5 subjects ) and a control group ( group C : 7 subjects ) . Group A patients received 35 mg/week of alendronate over 24 months , while group C patients were not administered with any bisphosphonates . Two major endpoints were established : ( 1 ) the time-dependent change in bone mineral density ( BMD ) estimated with DEXA and ( 2 ) progression of abdominal AC , calculated twice as an index ( ACI ) using computed tomography data . Over the 2-year study period , group A patients showed significantly increased BMD of 1.86 ± 0.85 % ( P = 0.015 versus baseline ) , and almost complete inhibition of ACI progression ( 38.2 ± 24.2 % to 39.6 ± 24.3 % ) , but group C patients showed a decrease in BMD decline with bone loss and progression of ACI ( 32.8 ± 25.0 % to 37.8 ± 29.2 % , P = 0.061 ) . In conclusion , alendronate therapy was an effective treatment in kidney transplant recipients for secondary osteoporosis and vascular calcification as ectopic calcification . This clinical trial is registered with number JMA-IIA00155 of JMACCT CTR BACKGROUND : Mortality is increased after a hip fracture , and strategies that improve outcomes are needed . METHODS : In this r and omized , double-blind , placebo-controlled trial , 1065 patients were assigned to receive yearly intravenous zoledronic acid ( at a dose of 5 mg ) , and 1062 patients were assigned to receive placebo . The infusions were first administered within 90 days after surgical repair of a hip fracture . All patients received supplemental vitamin D and calcium . The median follow-up was 1.9 years . The primary end point was a new clinical fracture . RESULTS : The rates of any new clinical fracture were 8.6 % in the zoledronic acid group and 13.9 % in the placebo group , a 35 % risk reduction ( P = 0.001 ) ; the respective rates of a new clinical vertebral fracture were 1.7 % and 3.8 % ( P = 0.02 ) , and the respective rates of new nonvertebral fractures were 7.6 % and 10.7 % ( P = 0.03 ) . In the safety analysis , 101 of 1054 patients in the zoledronic acid group ( 9.6 % ) and 141 of 1057 patients in the placebo group ( 13.3 % ) died , a reduction of 28 % in deaths from any cause in the zoledronic-acid group ( P = 0.01 ) . The most frequent adverse events in patients receiving zoledronic acid were pyrexia , myalgia , and bone and musculoskeletal pain . No cases of osteonecrosis of the jaw were reported , and no adverse effects on the healing of fractures were noted . The rates of renal and cardiovascular adverse events , including atrial fibrillation and stroke , were similar in the two groups . CONCLUSIONS : An annual infusion of zoledronic acid within 90 days after repair of a low-trauma hip fracture was associated with a reduction in the rate of new clinical fractures and improved survival . ( Clinical Trials.gov number , NCT00046254 . ) OBJECTIVE Osteoporosis and atherosclerosis are interconnected entities and share also some pathophysiological mechanisms . Moreover , recent literature data have supported the hypothesis that bisphosphonates ( BPs ) may have some antiatherogenic actions . This study aim ed to evaluate the effects of one year with zoledronate or ib and ronate given intravenously on lipid profile and on carotid artery intima-media thickness ( CA-IMT ) . METHODS Sixty postmenopausal osteoporotic women ( mean age : 66.6±7.8years ) were r and omly assigned to 1-year treatment with zoledronate 5 mg i.v . annually or ib and ronate 3 mg i.v . every 3 months . In all patients at baseline and after 12months we measured CA-IMT , total cholesterol ( TC ) , high-density lipoprotein cholesterol ( HDL-C ) , low-density lipoprotein cholesterol ( LDL-C ) , 25-hydroxyvitamin D ( 25OHD ) , bone alkaline phosphatase ( B-ALP ) , type I collagen β carboxy telopeptide ( βCTX ) , osteocalcin ( OC ) , fibroblast growth factor 23 ( FGF-23 ) and sclerostin . RESULTS The osteoporotic women treated with zoledronate showed a greater reduction in CA-IMT than those treated with ib and ronate . HDL-C and HDL-C/LDL-C ratio showed a significant ( p<0.01 ) increase in the 2 groups , whereas , LDL-C showed a reduction in the two groups which , however , reached statistical significance ( p<0.05 ) only in the zoledronate group . FGF-23 serum levels showed a similar and significant decrease in both the women treated with zoledronate and in those treated with ib and ronate . At the end of the study period sclerostin serum levels showed a higher increase in the patients treated with zoledronate than in those treated with ib and ronate . CONCLUSION In osteoporotic women both zoledronate and ib and ronate given intravenously result ed in an increase in HDL-C/LDL-C ratio and a reduction of CA-IMT which was significant only for zoledronate . Further prospect Output:	Results In several studies , etidronate limited the progression of aortic and coronary calcification in hemodialysis patients , whereas the nitrogen-containing-BPs given orally did not significantly reduce vascular calcifications in patients with chronic kidney disease , kidney trasplant or in those with osteoporosis . Nitrogen-containing-BPs present favorable effects both on vessel wall thickness and on arterial elasticity due to both a reduction in serum lipids and the interaction of BPs with the bone tissue , with the consequent release of bone turnover markers and cytokines into the bloodstream .
MS21412	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Objectives We tested a dental health program in remote Aboriginal communities of Australia 's Northern Territory , hypothesizing that it would reduce dental caries in preschool children . Methods In this 2-year , prospect i ve , cluster-r and omized , concurrent controlled , open trial of the dental health program compared to no such program , 30 communities were allocated at r and om to intervention and control groups . All residents aged 18–47 months were invited to participate . Twice per year for 2 years in the 15 intervention communities , fluoride varnish was applied to children 's teeth , water consumption and daily tooth cleaning with toothpaste were advocated , dental health was promoted in community setting s , and primary health care workers were trained in preventive dental care . Data from dental examinations at baseline and after 2 years were used to compute net dental caries increment per child ( d3mfs ) . A multi-level statistical model compared d3mfs between intervention and control groups with adjustment for the clustered r and omization design ; four other models used additional variables for adjustment . Results At baseline , 666 children were examined ; 543 of them ( 82 % ) were re-examined 2 years later . The adjusted d3mfs increment was significantly lower in the intervention group compared to the control group by an average of 3.0 surfaces per child ( 95 % CI = 1.2 , 4.9 ) , a prevented fraction of 31 % . Adjustment for additional variables yielded caries reductions ranging from 2.3 to 3.5 surfaces per child and prevented fractions of 24–36 % . Conclusions These results corroborate findings from other studies where fluoride varnish was efficacious in preventing dental caries in young children Objective : We aim ed to evaluate the efficacy of oral hygiene instruction , fluoride varnish and casein phosphopeptide-amorphous calcium phosphate ( CPP-ACP ) for remineralizing white spot lesions ( WSL ) , and the effect of these on the dmft index in primary teeth . Subjects and Methods : In this 1-year , r and omized clinical trial , 140 children aged 12 - 36 months with WSL in the anterior maxillary teeth were selected and r and omly divided into 4 groups of 35 children each . Group 1 ( control ) received no preventive intervention . In group 2 , there was oral hygiene and dietary counseling . In group 3 , there was oral hygiene and the application of fluoride varnish at 4 , 8 and 12 months after baseline . In group 4 , there was oral hygiene and tooth mousse was applied by the parents twice a day over a 12-month period . At baseline and 4 , 8 and 12 months after the intervention , the size of WSL in millimeters and the dmft index were recorded . One hundred and twenty-two children completed the study . Data were analyzed using the repeated- measures ANOVA test . Results : In group 1 , the mean percent WSL area and dmft index values had increased significantly at 12 months after baseline ( p < 0.001 ) . The interventions led to significant decreases in the size of the WSL ; the greatest reduction was in group 4 ( 63 % ) followed by group 3 ( 51 % ) and group 2 ( 10 % ) after 12 months . The smallest increase in the dmft index was in group 4 ( 0.17 ) , followed by groups 3 ( 0.3 ) and 2 ( 0.42 ) . However , there were no significant differences between the groups ( p < 0.001 ) . Conclusions : Oral hygiene along with four fluoride varnish applications or constant CPP-ACP during the 12- month period reduced the size of WSL in the anterior primary teeth and caused a small increase in dmft index values OBJECTIVES To determine the efficacy of 5 % sodium fluoride ( NaF ) varnish application in reducing caries increments in the permanent dentition of rural Brazilian school children over the course of 12 months . METHODS A double-blind , r and omized , placebo-controlled trial was conducted with 379 children aged 7 - 14 years who attended three schools in Brazil between January 2006 and December 2007 . During this period , each school was visited four times at 6-month interval for recruitment , dental examinations , and fluoride varnish applications . Recruited children were r and omly assigned to either a treatment ( 5 % NaF varnish , n = 198 ) or a control group ( placebo , n = 181 ) . Trained interviewers collected data on oral health habits and sociodemographic characteristics from the children . Information on the child 's diet was collected through a 7-day food frequency diary . Caries examinations were conducted using the International Caries Detection and Assessment System ( ICDAS ) . The efficacy of fluoride varnish application on caries prevention was reported as a preventive fraction ( PF ) . Crude caries increments of decayed and filled surfaces ( DFS ) were compared between fluoride varnish and placebo groups . A generalized linear model ( GLM ) was constructed to test the differences in DFS increments between the groups after accounting for confounding factors . RESULTS Of the total sample ( N = 379 ) , 210 ( 55.4 % ) children had completed 12 months of follow-up including one or two applications of fluoride varnish or placebo . At the baseline examination , the children in the treatment and control groups presented on average 6.2 and 5.6 DFS , respectively ( P < 0.001 ) . After 12 months of follow-up , the children in the varnish group showed significantly lower DFS increments than did children in the control group ( 10.8 versus 13.3 ; P < 0.007 ) , with PF of 40 % ( 95 % CI : 34.3 - 45.7 % ; P < 0.0001 ) . CONCLUSIONS The results of this study suggest that applications of 5 % NaF varnish can be recommended as a public health measure for reducing caries incidence in this high-caries-risk population 1 The AAPD encourages oral health care providers and caregivers to implement 17 simple preventive practice s that can decrease a childs risks of developing this devastating disease . 18 19 20 21 Methods This policy revision is based on a review of the current pediatric dental , medical , and public health literature related to ECC , including 22 the proceedings of the 2005 Symposium on the Prevention of Oral Disease in Children and Adolescents , Chicago , Illinois1997 Conference on Early Childhood Caries , Bethesda , Md.1 A MEDLINE search was conducted using the terms early childhood caries , nursing caries , and baby bottle caries. 25 The literature includes studies that used sound scientific methodology , were reported in refereed journals , and are accepted by the dental profession as state of the art in caries causes and prevention . The literature on the consequences of ECC is based on both prospect i ve and retrospective clinical studies that followed accepted clinical protocol s. Preventive recommendations were based primarily upon review of published studies and proceedings . In cases where the data did not appear sufficient or were inconclusive , recommendations were based upon expert and consensus opinion . 23 OBJECTIVE To measure the effectiveness of fluoride varnish ( FV ) ( Duraflor ) , 5 % sodium fluoride , Pharmascience Inc. , Montréal , QC , Canada ) and caregiver counseling in preventing early childhood caries ( ECC ) in Aboriginal children in a 2-year community-r and omized controlled trial . METHODS Twenty First Nations communities in the Sioux Lookout Zone ( SLZ ) , Northwest Ontario , Canada were r and omized to two study groups . All caregivers received oral health counseling , while children in one group received FV twice per year and the controls received no varnish . A total of 1275 , 6 months to 5-year-old children from the SLZ communities were enrolled . In addition , a convenience sample of 150 primarily non-Aboriginal children of the same age were recruited from the neighboring community of Thunder Bay and used as comparisons . Longitudinal examinations for the dmft/s indices were conducted by calibrated hygienists in 2003 , 2004 and 2005 . RESULTS Aboriginal children living in the SLZ or in Thunder Bay had significantly higher caries prevalence and severity than non-Aboriginal children in Thunder Bay . FV treatment conferred an 18 % reduction in the 2-year mean ' net ' dmfs increment for Aboriginal children and a 25 % reduction for all children , using cluster analysis to adjust for the intra-cluster correlation among children in the same community . Adjusted odds ratio for caries incidence was 1.96 times higher in the controls than in the FV group ( 95 % CI = 1.08 - 3.56 ; P = 0.027 ) . For those caries-free at baseline , the number ( of children ) needed to treat ( NNT ) equaled 7.4 . CONCLUSIONS Findings support the use of FV at least twice per year , in conjunction with caregiver counseling , to prevent ECC , reduce caries increment and oral health inequalities between young Aboriginal and non-Aboriginal children For children in the primary dentition with high caries prevalence the st and ard semiannual application of fluoride varnish may not be successful in preventing tooth decay . Oftentimes this population is mobile and does not receive consistent preventive care . This trial tested whether an intensive fluoride 5 % sodium varnish regimen ( three applications/2 weeks ) applied annually has an equivalent effect on caries progression in the primary dentition compared to single applications applied semiannually . This study was a r and omized clinical trial with two treatment groups . All participants ( n = 600 ; mean age ± SD = 55.3 ± 4.6 months ) received three varnish applications ( active varnish or placebo ) at semiannual visits over 3 years . Once per year the intensive-treatment group received one set of three active treatments and three placebo treatments 6 months later , each time within 2 weeks . The st and ard group received one active and two placebo treatments every 6 months . Children were assessed clinical ly at baseline and 12 , 24 and 36 months after the initiation of the study . The mean ( SD ) numbers of newly decayed primary tooth surfaces observed over 3 years were 9.8 ( 8.6 ) and 7.4 ( 7.7 ) in the intensive and st and ard groups , respectively . The adjusted rate ratio was 1.13 ( 95 % CI = 0.94–1.37 , p = 0.20 ) . In conclusion , the trial failed to demonstrate clear evidence of a difference in efficacy . However , differences of up to 36 % greater rates of caries in the intensive group could not be ruled out , thus equivalence of the treatments can not be concluded The aim was to study the effect of substitution of invert sugar for sucrose , in combination with fluoride varnish ( Duraphat ) treatment twice a year , on caries development in preschool children . One hundred and eighty-seven 4-years-olds were divided r and omly into four sugar groups : ( 1 ) sucrose ( S ) , ( 2 ) sucrose-Duraphat ( SD ) , ( 3 ) invert sugar ( I ) , and ( 4 ) invert sugar-Duraphat ( ID ) . All families were asked to buy beverages , biscuits , breakfast cereals , marmalade , ice cream , jam , ketchup , sweets and table sugar , totally 32 different food items , sweetened with invert sugar or sucrose . The substitution was , thus , restricted to a number of sugar-rich between-meal products . The study was carried out double-blind for 2 years . The children of those parents who did not want to participate in the sugar groups were divided r and omly into one of the following two groups : ( 5 ) Duraphat ( D ) , and control ( C ) . Because of lack of cooperation , only 114 of the 187 children ( 61 % ) were considered to have completed the study . The mean caries increment , including initial lesions , was 3.86 dmfs in the combined groups S and SD ( n = 63 ) and 3.10 dmfs in the combined groups I and ID ( n = 51 ) during the 2 years ( p = 0.34 ) . The corresponding values for the 2nd year only were 1.84 and 0.67 dmfs , respectively ( p = 0.09 ) . The mean caries increment was 2.86 dmfs in group D ( n = 113 ) and 4.10 dmfs ( p = 0.08 ) in group C ( n = 93 ) . If initial caries lesions were excluded from the index , the difference between groups D and C was significant ( p = 0.008 ) . ( ABSTRACT TRUNCATED AT 250 WORDS Untreated dental caries in Chinese pre-school children is common . This prospect i ve controlled clinical trial investigated the effectiveness of topical fluoride applications in arresting dentin caries . Three hundred seventy-five children , aged 3 - 5 years , with carious upper anterior teeth were divided into five groups . Children in the first and second groups received annual applications of silver diamine fluoride solution ( 44,800 ppm F ) . Sodium fluoride varnish ( 22,600 ppm F ) was applied every three months to the lesions of children in the third and fourth groups . For children in the first and third groups , soft carious tissues were removed prior to fluoride application . The fifth group was the control . Three hundred eight children were followed for 30 months . The respective mean numbers of arrested carious tooth surfaces in the five groups were 2.5 Output:	The results showed that fluoride varnishes have been used at concentrations of 1 % and 5 % in the prevention of ECC . The preventive fraction was influenced by the frequency of application , the duration of study and sample size .
MS21413	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: 4 successive cohorts of low-income families were r and omly assigned either to a home-based intervention program that focused on modeling verbal interaction between mother and child around selected toys and books or to comparison treatments . Large program effects were found on maternal interaction styles in videotaped observations . Small IQ and program-specific effects were found for children in contrast to much larger IQ effects found in earlier research . IQ effects did not appear to have been mediated by changes in maternal behavior . A variation in which toys and books were supplied without home visits was as effective as the full program on IQ but not on maternal behavior . 3 years postprogram , there were no detectable effects in achievement or IQ tests or in first grade teachers ' ratings of school adjustment and performance , but IQ and achievement scores were near national norms . Reasons for discrepancies with earlier results are discussed . The results highlight the need for continued experimental evaluation of early intervention programs with safeguards to insure that sample s are educationally at risk OBJECTIVE --To see whether non-professional volunteer community mothers could deliver a child development programme to disadvantaged first time mothers for children aged up to 1 year . DESIGN --R and omised controlled trial . SETTING --A regional health authority in Dublin . SUBJECTS--262 first time mothers who were delivered during six months in 1989 and who lived in a deprived area of Dublin ; 30 experienced mothers from the same community recruited as community mothers . INTERVENTIONS --All the first time mothers received st and ard support from the public health nurse . In addition , those in the intervention group received the services of a community mother , who was scheduled to visit monthly during the first year of the child 's life . RESULTS --232 ( 89 % ) first time mothers completed the study --127 in the intervention group , 105 controls . At the end of the study children in the intervention group were more likely to have received all of their primary immunisations , to be read to , and to be read to daily , played more cognitive games ; and were exposed to more nursery rhymes . They were less likely to begin cows ' milk before 26 weeks and to receive an inappropriate energy intake and inappropriate amounts of animal protein , non-animal protein , wholefoods , vegetables , fruit , and milk . Mothers in the intervention group also had a better diet than controls . At the end of the study they were less likely to be tired , feel miserable , and want to stay indoors ; had more positive feelings ; and were less likely to display negative feelings . CONCLUSION --Non-professionals can deliver a health promotion programme on child development effectively . Whether they can do so as effectively as professionals requires further study OBJECTIVE To evaluate the efficacy of home intervention with drug-abusing women on parenting behavior and attitudes , and on children 's development . DESIGN A r and omized , clinical trial of 60 drug-abusing women recruited prenatally and r and omized into an intervention ( n = 31 ) or comparison ( n = 29 ) group . There were no group differences in gestational age , 1-minute Apgar scores , duration of hospital stay , or neonatal abstinence score . Intervention infants were slightly heavier ( P = .098 ) and had slightly lower 5-minute Apgar scores ( P = .089 ) . Most mothers were single , African-American , multiparous , and non-high school graduates from low income families . Approximately 40 % of the women were human immunodeficiency virus (HIV)-positive , all admitted to either cocaine and /or heroin use , and 62 % had a history of incarceration . Intervention and comparison group women did not differ on any background variables . INTERVENTIONS All children received primary care in a multidisciplinary clinic . Biweekly home visits were provided by a nurse beginning before delivery and extending through 18 months of life . The intervention was design ed to provide maternal support and to promote parenting , child development , the utilization of informal and formal re sources , and advocacy . MEASUREMENTS Behavioral measures included self-reported ongoing drug abuse , compliance with primary care appointments , and an observation of the child-centered quality of the home ( HOME Scale ) . Parenting attitudes were measured by the Child Abuse Potential Inventory ( CAPI ) and the Parenting Stress Index . The CAPI was administered before initiating the intervention and the Parenting Stress Index was administered when the children were 3 months of age . Both scales were repeated when the children were 18 months of age . Developmental status was measured with the Bayley Scales of Infant Development administered at 6 , 12 , and 18 months . ANALYSES Repeated measures multivariate analyses of variance were used to examine changes in parenting attitudes and children 's development . Analyses of covariance were used to examine compliance with primary care appointments and the quality of the home . Logistic regression was used to examine ongoing drug abuse . Birth weight and maternal education were used as covariates in all analyses . To control for social desirability , the faking-good index of the CAPI was included as a covariate in analyses involving self-report measures . MAIN RESULTS Women in the intervention group were marginally more likely to report being drug-free ( P = .059 ) and were compliant with primary care appointments for their children ( P = .069 ) . Based on the HOME Scale , women in the intervention group were more emotionally responsive ( P = .033 ) and provided marginally more opportunities for stimulation ( P = .065 ) . At 18 months parents reported more normative attitudes regarding parenting and more child-related stress than they had initially , but the differences were not related to intervention status . At 6 months infants in the intervention group obtained marginally higher cognitive scores ( P = .099 ) ; at 12 and 18 months there were no differences . CONCLUSIONS The findings suggest a cautious optimism regarding the efficacy of early home intervention among drug-abusing women in promoting positive behaviors . Subsequent investigations of home intervention should include larger sample sizes and more intensive options 65 families with children at risk for cognitive difficulties were r and omly assigned at the time of the child 's birth to 1 of 3 groups , 2 intervention and 1 control . For the most intensive intervention group , family education was combined with a center-based educational day-care program ; the less intensive intervention group received the home-based family education program only . To assess the cognitive performance of children , The Bayley Scales of Infant Development were administered at 6 , 12 , and 18 months ; the Stanford-Binet Intelligence Test at 24 , 36 , and 48 months ; and the McCarthy Scales of Children 's Abilities at 30 , 42 , and 54 months . On each test after the 6-month assessment , scores of children in the educational day-care plus family support group were greater than those in the other 2 groups . No cognitive intervention effects were obtained for the family education group . Group effects were not obtained for measures of either the quality of the home environment or parent attention Physicians are often faced with conflicting recommendations from therapeutic studies . An evaluation form is proposed to facilitate the evaluation of the quality of therapeutic studies and the result ing treatment or management recommendations in any area of medicine . Twelve major topics for evaluation include sample size determination , r and omization , selection of control group(s ) , " blinding , " and support for treatment recommendations . Emphasis is placed on study design and performance rather than data analysis . Thirty-four primary criteria based on accepted research st and ards are design ated as most important , and examples from the literature are provided to illustrate their use . The form provides a comprehensive set of well-accepted st and ards of research in a format that encourages detailed , consistent , and thoughtful evaluation of therapeutic studies . The evaluation form is recommended as a tool for physicians who wish to develop and exercise skill in evaluating therapeutic studies Evaluation of high-risk cases treated via a tri-agency , interdisciplinary , early-intervention program suggests that a better outcome was achieved in the treatment program than in a control group of similar high-risk families receiving st and ard care . The number of treated cases requiring child protection services decreased during treatment , and confirmed episodes of child abuse were fewer in the treated group than in the control group A r and omized trial tested the psychosocial efficacy of a home visitation model for women at risk of out-of-home placement of their newborns . After an average of ten months of exposure , the experimental group reported significantly increased social support , greater access to services , and decreased psychological distress . Implication s of the findings for interventions with at-risk families are discussed Effects of early and extended postpartum contact and paraprofessional home visits on maternal attachment , reports of child abuse and neglect , and health care utilization were determined by r and om assignment of 321 low-income women to intervention or control groups immediately after delivery . Observations of maternal attachment were made at four months and 12 months . Hospital , health and welfare agency records , and interviews were used to determine reports of child abuse and neglect and health care utilization . After establishing a control for maternal background variables , early and extended contact explained statistically significant but small amounts of variance in several of the attachment measures . There were no statistically significant effects of the home visit interventions on maternal attachment , and neither intervention was related to reports of child abuse and neglect and health care utilization . Although the study supported earlier findings that early and extended contact has a significant effect , additional interventions are needed to support mother-infant attachment To determine if a relationship exists between structured , informative inhome teaching concerning infant behavior and primiparous mothers ' perceptions of their newborn . 30 primip-aras completed Broussard 's Neonatal Perception Inventories I and II . The sample —30 women between the ages of 18 and 30 who had had no chronic disorders and had experienced normal pregnancy , labor , delivery , and postpartal course — was deliberately selected from a 489-bed community teaching hospital ; 15 women were assigned r and omly to a control group and 15 to an experimental group . All participants completed NPII on their first or second postpartum day . Experimental participants received structured , informative teaching concerning infant behavior two to four days after discharge . All subjects were again visited at one month to complete NPI II . Data were analyzed by t test ; significance was set at p=.05 . No significant difference was found between the groups in NPI I perceptions . On NPI II a significantly positive change in perception was found for the experimental group , but not for the control group OBJECTIVE To examine , during the 3rd and 4th years of life , the health , development , rates of child maltreatment , and living conditions of children who had been enrolled in a r and omized trial of nurse home visitation during pregnancy and first 2 years of their lives . DESIGN Prospect i ve follow-up of families who had been r and omly assigned to nurse-visited and comparison conditions . SETTING Study conducted in semirural community in upstate New York . Families dispersed among 14 other states during 2-year period after children 's second birthdays . PARTICIPANTS Four hundred women were recruited through a health department antepartum clinic and offices of private obstetricians and were registered before 30th week of pregnancy . All women had no previous live births and 85 % were either teenaged ( < 18 years at registration ) , unmarried , or from Hollingshead social classes IV or V. Analysis focused on whites , who comprised 89 % of sample . INTERVENTION Nurse home visitation from pregnancy through second year of the child 's life . MAIN RESULTS There were no treatment differences in the rates of child abuse and neglect or children 's intellectual functioning from 25 to 48 months of age . Nurse-visited children , nevertheless , lived in homes with fewer hazards for children ; they had 40 % fewer injuries and ingestions and 45 % fewer behavioral and parental coping problems noted in the physician record ; and they made 35 % fewer visits to the emergency department than did children in the comparison group . Nurse-visited mothers were observed to be more involved with and to punish their children to a greater extent than were mothers in the comparison group . The functional meaning of punishment differed between the nurse-visited and comparison families . CONCLUSIONS The program does have enduring effects on certain aspects of parental caregiving , safety of the home , and children 's use of the health care system , but it may be necessary to extend the length of the program for families at highest risk to produce lasting reductions in child abuse and neglect We investigated the effects of a year-long home intervention with a sample of preterm infants r and omly assigned to 1 of 3 groups : a developmental intervention , a parent-infant intervention , and a no-treatment control group . A full-term no-treatment control was also used . Both intervention approaches focused on the parent-child unit , providing training for parents to improve observational skills , emotional support , and information about community re sources . However , whereas specific tasks to facilitate the child 's development were provided in the developmental intervention group , the quality of the parent-infant interaction was the target for treatment in the other group . All infants were assessed at 4 , 8 , 12 , and 16 months of age corrected for prematurity . The results suggest that although both intervention approaches were effective in modifying some aspects of the home environment and , to a lesser degree , in improving infants ' cognitive development , the parent-infant interaction approach seemed to have the greater impact . These findings confirm previous observations regarding the cognitive development of preterm and full-term infants during the first 18 months of life and demonstrate changes in behavior and behavior styles in both pre- and full-term infants as they become older CONTEXT Interest in home-visitation services as a way of improving maternal and child outcomes has grown out of the favorable results of a trial in semirural New York . The findings have not been replicated in other population s. OBJECTIVE To test the effect of prenatal and infancy home visits by nurses on pregnancy-induced hypertension , preterm delivery , and low birth weight ; on children 's injuries , immunizations , mental development , and behavioral problems ; and on maternal life course . DESIGN R and omized controlled trial . Output:	Home visiting programmes were associated with an improvement in the quality of the home environment .
MS21414	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: PURPOSE We evaluated the difference in the febrile urinary tract infection rate in small children with dilating vesicoureteral reflux r and omly allocated to 3 management alternatives , including antibiotic prophylaxis , endoscopic treatment or surveillance only as the control . MATERIAL S AND METHODS At 23 centers a total of 203 children were included in the study , including 128 girls and 75 boys 1 to younger than 2 years . Vesicoureteral reflux grade III in 126 cases and IV in 77 was detected after a febrile urinary tract infection ( 194 ) after prenatal screening ( 9 ) . Voiding cystourethrography and dimercapto-succinic acid scintigraphy were done before r and omization and after 2 years . The febrile urinary tract infection rate was analyzed by the intent to treat principle . RESULTS We noted a total of 67 febrile recurrences in 42 girls and a total of 8 in 7 boys ( p = 0.0001 ) . There was a difference in the recurrence rate among treatment groups in girls with febrile infection in 8 of 43 ( 19 % ) on prophylaxis , 10 of 43 ( 23 % ) with endoscopic therapy and 24 of 42 ( 57 % ) on surveillance ( p = 0.0002 ) . In girls the recurrence rate was associated with persistent reflux after 2 years ( p = 0.0095 ) . However , reflux severity ( grade III or IV ) at study entry did not predict recurrence . CONCLUSIONS In this r and omized , controlled trial there was a high rate of recurrent febrile urinary tract infection in girls older than 1 year with dilating vesicoureteral reflux at study entry but not in boys . Antibiotic prophylaxis and endoscopic treatment decreased the infection rate IMPORTANCE Existing data regarding the association between delayed initiation of antimicrobial therapy and the development of renal scarring are inconsistent . OBJECTIVE To determine whether delay in the initiation of antimicrobial therapy for febrile urinary tract infections ( UTIs ) is associated with the occurrence and severity of renal scarring . DESIGN , SETTING , AND PARTICIPANTS Retrospective cohort study that combined data from 2 previously conducted longitudinal studies ( the R and omized Intervention for Children With Vesicoureteral Reflux trial and the Careful Urinary Tract Infection Evaluation Study ) . Children younger than 6 years with a first or second UTI were followed up for 2 years . EXPOSURE Duration of the child 's fever prior to initiation of antimicrobial therapy for the index UTI . MAIN OUTCOMES AND MEASURES New renal scarring defined as the presence of photopenia plus contour change on a late dimercaptosuccinic acid renal scan ( obtained at study exit ) that was not present on the baseline scan . RESULTS Of the 482 children included in the analysis , 434 were female ( 90 % ) , 375 were white ( 78 % ) , and 375 had vesicoureteral reflux ( 78 % ) . The median age was 11 months . A total of 35 children ( 7.2 % ) developed new renal scarring . Delay in the initiation of antimicrobial therapy was associated with renal scarring ; the median ( 25th , 75th percentiles ) duration of fever prior to initiation of antibiotic therapy in those with and without renal scarring was 72 ( 30 , 120 ) and 48 ( 24 , 72 ) hours , respectively ( P = .003 ) . Older age ( OR , 1.03 ; 95 % CI , 1.01 - 1.05 ) , Hispanic ethnicity ( OR , 5.24 ; 95 % CI , 2.15 - 12.77 ) , recurrent urinary tract infections ( OR , 0.97 ; 95 % CI , 0.27 - 3.45 ) , and bladder and bowel dysfunction ( OR , 6.44 ; 95 % CI , 2.89 - 14.38 ) were also associated with new renal scarring . Delay in the initiation of antimicrobial therapy remained significantly associated with renal scarring even after adjusting for these variables . CONCLUSIONS AND RELEVANCE Delay in treatment of febrile UTIs and permanent renal scarring are associated . In febrile children , clinicians should not delay testing for UTI BACKGROUND Antibiotics are widely administered to children with the intention of preventing urinary tract infection , but adequately powered , placebo-controlled trials regarding efficacy are lacking . This study from four Australian centers examined whether low-dose , continuous oral antibiotic therapy prevents urinary tract infection in predisposed children . METHODS We r and omly assigned children under the age of 18 years who had had one or more microbiologically proven urinary tract infections to receive either daily trimethoprim-sulfamethoxazole suspension ( as 2 mg of trimethoprim plus 10 mg of sulfamethoxazole per kilogram of body weight ) or placebo for 12 months . The primary outcome was microbiologically confirmed symptomatic urinary tract infection . Intention-to-treat analyses were performed with the use of time-to-event data . RESULTS From December 1998 to March 2007 , a total of 576 children ( of 780 planned ) underwent r and omization . The median age at entry was 14 months ; 64 % of the patients were girls , 42 % had known vesicoureteral reflux ( at least grade III in 53 % of these patients ) , and 71 % were enrolled after the first diagnosis of urinary tract infection . During the study , urinary tract infection developed in 36 of 288 patients ( 13 % ) in the group receiving trimethoprim-sulfamethoxazole ( antibiotic group ) and in 55 of 288 patients ( 19 % ) in the placebo group ( hazard ratio in the antibiotic group , 0.61 ; 95 % confidence interval , 0.40 to 0.93 ; P = 0.02 by the log-rank test ) . In the antibiotic group , the reduction in the absolute risk of urinary tract infection ( 6 percentage points ) appeared to be consistent across all subgroups of patients ( P > or = 0.20 for all interactions ) . CONCLUSIONS Long-term , low-dose trimethoprim-sulfamethoxazole was associated with a decreased number of urinary tract infections in predisposed children . The treatment effect appeared to be consistent but modest across subgroups . ( Australian New Zeal and Clinical Trials Registry number , ACTRN12608000470392 . BACKGROUND AND OBJECTIVES The main objectives of the R and omized Intervention for Children with Vesicoureteral Reflux ( RIVUR ) trial were to evaluate the role of antimicrobial prophylaxis in the prevention of recurrent urinary tract infection ( UTI ) and renal scarring in children with vesicoureteral reflux ( VUR ) . We present a comprehensive evaluation of renal scarring outcomes in RIVUR trial participants . DESIGN , SETTING , PARTICIPANTS , & MEASUREMENTS This multicenter , r and omized , placebo-controlled trial enrolled 607 children aged 2 - 71 months with grade 1 - 4 VUR diagnosed after a first or second febrile or symptomatic UTI . Study participants received trimethoprim-sulfamethoxazole or placebo and were followed for 2 years . Renal scarring was evaluated by baseline and follow-up (99m)technetium dimercaptosuccinic acid ( DMSA ) renal scans that were review ed independently by two blinded reference radiologists . RESULTS At the end of the study , 58 ( 10 % ) of 599 children and 63 ( 5 % ) of 1197 renal units had renal scarring . New renal scarring did not differ between the prophylaxis and placebo groups ( 6 % versus 7 % , respectively ) . Children with renal scarring were significantly older ( median age , 26 versus 11 months ; P=0.01 ) , had a second UTI before enrollment ( odds ratio [ OR ] , 2.85 ; 95 % confidence interval [ 95 % CI ] , 1.38 to 5.92 ) , were more likely to be Hispanic ( OR , 2.22 ; 95 % CI , 1.13 to 4.34 ) , and had higher grade s of VUR ( OR , 2.79 ; 95 % CI , 1.56 to 5.0 ) . The proportion of new scars in renal units with grade 4 VUR was significantly higher than in units with no VUR ( OR , 24.2 ; 95 % CI , 6.4 to 91.2 ) . CONCLUSIONS Significantly more renal scarring was seen in relatively older children and in those with a second episode of febrile or symptomatic UTI before r and omization . Preexisting and new renal scars occurred significantly more in renal units with grade 4 VUR than in those with low- grade or no VUR . Antimicrobial prophylaxis did not decrease the risk of renal scarring INTRODUCTION AND OBJECTIVE While open ureteral reimplantation remains the gold st and ard for surgical treatment of vesicoureteral reflux ( VUR ) , minimally invasive approaches offer potential benefits . This study evaluated the outcomes of children undergoing complex robot-assisted laparoscopic ureteral reimplantation ( RALUR ) for failed previous anti-reflux surgery , complex anatomy , or ureterovesical junction obstruction ( UVJO ) , and compared them with patients undergoing open extravesical repair . STUDY DESIGN Children undergoing complex RALUR or open extravesical ureteral reimplantation ( OUR ) were identified . Reimplantation was classified as complex if ureters : 1 ) had previous anti-reflux surgery , 2 ) required tapering and /or dismembering , or 3 ) had associated duplication or diverticulum . RESULTS Seventeen children underwent complex RALUR during a 24-month period , compared with 41 OUR . The mean follow-up was 16.6 ± 6.5 months . The RALUR children were significantly older ( 9.3 ± 3.7 years ) than the OUR patients ( 3.1 ± 2.7 years ; P < 0.001 ) . All RALUR patients were discharged on postoperative day one , while 24.4 % of children in the open group required longer hospitalization ( mean 1.3 ± 0.7 days ; P = 0.03 ) . Adjusting for age , there was no significant difference in inpatient analgesic usage between the two cohorts . Three OUR patients ( 7.3 % ) developed postoperative febrile urinary tract infection compared with a single child ( 5.9 % ) undergoing RALUR ( P = 1.00 ) . There was no significant difference in complication rate between the two groups ( 12.2 % OUR versus 11.8 % RALUR ; P = 1.00 ) . A postoperative cystogram was performed in the majority of RALUR patients , with no persistent VUR detected , and one child ( 6.7 % ) was diagnosed with contralateral reflux . DISCUSSION Reported VUR resolution rates following robot-assisted ureteral reimplantation are varied . In the present series , children undergoing RALUR following failed previous anti-reflux surgery , with complex anatomy , or UVJO experienced a shorter length of stay but had similar analgesic requirements to those undergoing open repair . Radiographic , clinical success rates and complication risk were comparable . This study had several limitations , aside from lack of r and omization . Analgesic use was limited to an inpatient setting , and pain scores were not assessed . Not all children underwent a postoperative VCUG , so the true radiographic success rate is unknown . A larger patient cohort with longer follow-up is necessary to determine predictors of radiographic and clinical failure . CONCLUSION Older children with a previous history of anti-reflux surgery were more likely to undergo RALUR . These children had success and complication rates comparable to younger patients following complex open extravesical reimplantation , which underscores the exp and ing role of robot-assisted lower urinary tract reconstructive surgery in the pediatric population INTRODUCTION Voiding dysfunction after bilateral extravesical ureteral reimplantation for vesicoureteral reflux has long remained a concern . Robotic approach with improved visualization that enables focused and minimal dissection may help with this concern . OBJECTIVES To compare postoperative outcomes after bilateral robot-assisted laparoscopic ureteral reimplantation to unilateral robot-assisted laparoscopic ureteral reimplantation . STUDY DESIGN This was a retrospective study using data abstract ed from an institutional review board-approved registry prospect ively maintained at our institution since 2012 . Patient demographics , preoperative characteristics , and postoperative outcomes were analyzed . Patients with postoperative febrile urinary tract infection ( UTI ) underwent voiding cystourethrogram ( VCUG ) . Surgical success is defined as absence of febrile UTI or febrile UTI with negative VCUG . RESULTS 92 patients with a median follow-up of 14 ( 25th and 75th IQR 5 , 28 ) months . Median operative time ( 150 vs. 178 Output:	EVIDENCE SYNTHESIS Despite the striking results of previous studies revealing the ineffectiveness of CAP , more recent studies and their two fresh meta-analyses revealed a positive role for CAP in the contemporary management of VUR . One of the most interesting findings is the redundant rising of endoscopic correction and its final settlement to real indicated cases . The evidence in the literature showed a safe and effective use of laparoscopic and robot-assisted laparoscopic reimplantations . CONCLUSIONS The goal of VUR treatment is to prevent the occurrence of febrile urinary tract infections and formation of scars in the renal parenchyma .
MS21415	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: A study was conducted to determine whether a direct relationship exists between β-lactam and /or aminoglycoside activity measured in vitro and bacteriological outcome in acute pulmonary exacerbations of cystic fibrosis . Twenty-seven patients , aged between 6 months and 24 years ( mean age 10 1/2 years ) , were included in the study and received 41 i.v . courses of a β-lactam agent combined with an aminoglycoside . A total of 63Pseudomonas aeruginosa strains were found in sputum taken on admission at densities exceeding 106 cfu/g of sputum . For each episode , the serum inhibitory quotient ( SIQ ) and the serum bactericidal quotient ( SBQ ) of the β-lactam agent and of the aminoglycoside administered were determined for thePseudomonas aeruginosa isolate(s ) . The SIQs and SBQs were calculated by dividing the average peak serum levels achievable in the patients by the minimal inhibitory concentrations and minimal bactericidal concentrations , respectively . The SIQs and SBQs were compared to bacteriological outcome . Bacteriological success was defined as a decrease of 2 log10 counts or more in thePseudomonas aeruginosa density in sputum between days 0 and 7 of therapy . The SIQ and SBQ of β-lactam agents were good predictors of bacteriological outcome : SIQs of < 1:16 were 100 % predictive of failure ( χ2 28 ; p<0.001 ) and of ≥ 1:64 were 92.9 % predictive of success ( χ2 35.68 ; p<0.001 ) ; SBQs of < 1:8 were 100 % predictive of failure ( χ2 42.78 ; p<0.001 ) and of ≥ 1:32 were 95.8 % predictive of success ( χ2 31.5 ; p<0.001 ) . Aminoglycoside SIQs and SBQs were not predictive of outcome BACKGROUND Previous aztreonam for inhalation solution ( AZLI ) studies included patients with cystic fibrosis , Pseudomonas aeruginosa ( PA ) airway infection , and forced expiratory volume in 1s ( FEV(1 ) ) 25 % to 75 % predicted . This double-blind , multicenter , r and omized , placebo-controlled trial enrolled patients ( ≥6 years ) with FEV(1)>75 % predicted . METHODS AZLI 75 mg ( n=76 ) or placebo ( n=81 ) was administered 3-times daily for 28days with a 14-day follow-up . RESULTS Day 28 treatment effects were 1.8points for CFQ-R-Respiratory Symptoms Scale ( 95%CI : -2.8 , 6.4 ; p=0.443 ; primary endpoint ) ; -1.2 for log(10 ) sputum PA colony-forming units ( p=0.016 ; favoring AZLI ) , and 2.7 % for relative FEV(1)% predicted ( p=0.021 ; favoring AZLI ) . Treatment effects favoring AZLI were larger for patients with baseline FEV(1 ) < 90 % predicted compared to ≥90 % predicted . AZLI was well-tolerated . CONCLUSIONS Effects on respiratory symptoms were modest ; however , FEV(1 ) improvements and bacterial density reductions support a possible role for AZLI in these relatively healthy patients CONTEXT Treatment strategies for cystic fibrosis ( CF ) lung disease include antibiotics , mucolytics , and anti-inflammatory therapies . Increasing evidence suggests that macrolide antibiotics might be beneficial in patients with CF . OBJECTIVE To determine if an association between azithromycin use and pulmonary function exists in patients with CF . DESIGN AND SETTING A multicenter , r and omized , double-blind , placebo-controlled trial conducted from December 15 , 2000 , to May 2 , 2002 , at 23 CF care centers in the United States . PARTICIPANTS Of the 251 screened participants with a diagnosis of CF , 185 ( 74 % ) were r and omized . Eligibility criteria included age 6 years or older , infection with Pseudomonas aeruginosa for 1 or more years , and a forced expiratory volume in 1 second ( FEV1 ) of 30 % or more . Participants were stratified by FEV1 ( > or = 60 % predicted vs < 60 % predicted ) , weight of less than 40 kg vs 40 kg or more , and CF center . INTERVENTION The active group ( n = 87 ) received 250 mg ( weight < 40 kg ) or 500 mg ( weight > or = 40 kg ) of oral azithromycin 3 days a week for 168 days ; placebo group ( n = 98 ) received identically packaged tablets . MAIN OUTCOME MEASURES Change in FEV1 from day 0 to completion of therapy at day 168 and determination of safety . Secondary outcomes included pulmonary exacerbations and weight gain . RESULTS The azithromycin group had a mean 0.097-L ( SD , 0.26 ) increase in FEV1 at day 168 compared with 0.003 L ( SD , 0.23 ) in the placebo group ( mean difference , 0.094 L ; 95 % confidence interval [ CI ] , 0.023 - 0.165 ; P = .009 ) . Nausea occurred in 17 % more participants in the azithromycin group ( P = .01 ) , diarrhea in 15 % more ( P = .009 ) , and wheezing in 13 % more ( P = .007 ) . Participants in the azithromycin group had less risk of experiencing an exacerbation than participants in the placebo group ( hazard ratio , 0.65 ; 95 % CI , 0.44 - 0.95 ; P = .03 ) and weighed at the end of the study an average 0.7 kg more than participants receiving placebo ( 95 % CI , 0.1 - 1.4 kg ; P = .02 ) . CONCLUSION Azithromycin treatment was associated with improvement in clinical ly relevant end points and should be considered for patients with CF who are 6 years or older and chronically infected with P aeruginosa Chronic airway infection with Pseudomonas aeruginosa ( PA ) causes morbidity and mortality in patients with cystic fibrosis ( CF ) . Additional anti-PA therapies are needed to improve health status and health-related quality of life . AIR-CF3 was an international 18-month , open-label study to evaluate the safety and efficacy of repeated courses of aztreonam for inhalation solution ( AZLI , now marketed as Cayston ® ) in patients aged ≥ 6 years with CF and PA infection who previously participated in one of two Phase 3 studies : AIR-CF1 or AIR-CF2 . Patients received up to nine courses ( 28 days on/28 days off ) of 75 mg AZLI two ( BID ) or three times daily ( TID ) based on r and omization in the previous trials . 274 patients , mean age 28.5 years ( range : 8 - 74 years ) , participated . Mean treatment adherence was high ( 92.0 % BID group , 88.0 % TID group ) . Hospitalization rates were low and adverse events were consistent with CF . With each course of AZLI , FEV(1 ) and scores on the Cystic Fibrosis Question naire-Revised Respiratory Symptom scale improved and bacterial density in sputum was reduced . Benefits waned in the 28 days off therapy , but weight gain was sustained over the 18 months . There were no sustained decreases in PA susceptibility . A dose response was observed ; AZLI TID-treated patients demonstrated greater improvements in lung function and respiratory symptoms over 18 months . Repeated intermittent 28-day courses of AZLI treatment were well tolerated . Clinical benefits in pulmonary function , health-related quality of life , and weight were observed with each course of therapy . AZLI is a safe and effective new therapy in patients with CF and PA airway infection BACKGROUND Pulmonary exacerbations are associated with significant lung function decline from baseline in cystic fibrosis ( CF ) and it is not well understood why some patients do not respond to antibiotic therapy . The objective of this study was to identify factors associated with lung function response to antibiotic treatment of pulmonary exacerbations . METHODS As a secondary analysis of a r and omized , controlled trial of intravenous antibiotic treatment for pulmonary exacerbations in CF patients , we investigated whether baseline factors and changes in sputum bacterial density , serum or sputum inflammatory markers were associated with recovery of lung function and risk of subsequent exacerbation . RESULTS In 36 of the 70 exacerbations ( 51 % ) , patients ' lung function returned to > 100 % of their baseline at day 14 of antibiotic treatment ; 34 exacerbations were classified as non-responders . Baseline characteristics were not significantly different between responders and non-responders . Less of a drop in FEV1 from baseline to exacerbation ( OR 1.09 , 95 % CI 1.0 , 1.18 , p=0.04 ) as well as a greater decrease in sputum neutrophil elastase ( OR 2.94 , 95 % CI 1.07 , 8.06 , p=0.04 ) were associated with response to antibiotic treatment at day 14 . In addition , higher CRP ( HR 1.35 ( 95 % CI : 1.01 , 1.78 ) , p=0.04 ) and sputum neutrophil elastase ( HR 1.71 ( 95 % CI : 1.02 , 2.88 ) , p=0.04 ) at day 14 of antibiotic therapy were associated with an increased risk of subsequent exacerbation . CONCLUSIONS Inadequate reduction of inflammation during an exacerbation is associated with failure to recover lung function and increased risk of subsequent re-exacerbation in CF patients OBJECTIVE To assess the potential role of multiple bronchoalveolar lavages ( BALs ) in the treatment of children with lipoid pneumonia ( LP ) . MATERIAL S AND METHODS This prospect i ve study included 10 children ( 7 female , 3 male ) with LP secondary to mineral oil aspiration . The age ranged from 3 months to 7 years and 1 - 60 days history of mineral oil intake , with a 6 months clinic follow-up . High-resolution computer tomography ( CT ) was performed 1 - 7 days prior to treatment and 2 - 20 days after the last therapeutic BAL , and review ed by two experienced chest radiologists . Oxygen saturation was measured with digital oximetry . Therapeutic BAL was performed weekly until BAL fluid was nearly transparent and the cell count returned to normal range values . RESULTS In all children , the initial CT scans showed multifocal bilateral consolidation involving mainly the dorsal and central regions . The areas of consolidation had foci of decreased attenuation in eight patients . Following a total of 4 - 10 therapeutic BALs , the CT scans returned to normal in 3 patients , improved considerably in 5 , and showed only slight improvement in 2 . Oxygen saturation increased from 88.8 + /- 3.4 % at presentation to 96.2 + /- 0.8 % after treatment ( P < 0.0001 ) . Multiple lavages reduced ( P < 0.003 ) numbers of lipid-laden macrophages and restored BAL cellularity to normal range values . CONCLUSION Multiple therapeutic BAL of children with LP results in significant improvement of CT findings , oxygen saturation , restoration of BAL fluid cellularity and clinical recover without any evidence of respiratory distress at the end of treatment and 6 months after the last BAL We evaluated patients with cystic fibrosis ( CF ) and moderate obstructive lung disease in pulmonary exacerbation in a double-blind placebo-controlled trial to determine the contribution of antibiotic-mediated reduction in sputum bacterial density to clinical improvement . For the first 4 days of study , all patients received bronchodilating aerosols and chest physiotherapy but no antibiotics . During this time , the patients showed significant improvement in mean FVC , FEV1 , and maximal midexpiratory flow rate ( FEF25 - 75 ) . In 12 of 13 trials , the patients showed no significant increases in the density of Pseudomonas aeruginosa during these first 4 days . In these 12 trials , the patients were stratified by their initial FVC and r and omized to receive either parenteral tobramycin and ticarcillin ( n = 7 ) or placebo ( n = 5 ) , in addition to continued aerosol and chest physiotherapy . In the remaining trial , the patient had a significant rise in the density of P. aeruginosa and was assigned to the antibiotic group . During the next 14 days of therapy , the antibiotic group showed significantly ( p less than 0.01 ) greater reductions in log10 colony-forming units ( cfu ) of P. aeruginosa per gram of sputum and greater increases in FVC , FEV1 , and FEF25 - 75 than did the placebo group . The degree of decrease in Output:	This study prospect ively assessed whether the use of multiple combination bactericidal antibiotic testing improved clinical outcomes in participants with acute pulmonary exacerbations of cystic fibrosis who were infected with multiresistant bacteria . The quality of the evidence was moderate for the only outcome providing data solely for individuals with infection due to Pseudomonas aeruginosa . The current evidence , limited to one study , shows that there is insufficient evidence to determine effect of choosing antibiotics based on combination antimicrobial susceptibility testing compared to choosing antibiotics based on conventional antimicrobial susceptibility testing in the treatment of acute pulmonary exacerbations in people with cystic fibrosis with chronic Pseudomonas aeruginosa infection .
MS21416	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: After more than three decades of clinical trials testing various st and ard-dose chemotherapy regimens , the disease course of patients with multiple myeloma has not changed appreciably . Conventional chemotherapy can provide effective palliation but is not curative ( 1 ) . Case series have described encouraging results in patients with myeloma undergoing allogeneic or autologous bone marrow or peripheral blood stem-cell transplantation ( 2 ) . Other studies of transplantation , including r and omized trials , have been reported in the past 6 years ( 3 , 4 ) . To facilitate decisions about treatment options , practice guidelines have been developed for use by health care providers and consumers . In Ontario , Canada , cancer treatments and policies are led by a state-funded organization , Cancer Care Ontario . To help derive treatment options , Cancer Care Ontario has developed the Program in Evidence -Based Care , which includes the Practice Guidelines Initiative . Disease Site Groups ( DSGs ) , which comprise physicians , epidemiologists , and consumers , develop guidelines through a systematic process that involves assessment of evidence , consensus , and a validation process involving practitioners from across the province . Guideline topics are chosen through a prioritization process that includes the burden of illness , availability of evidence , perceived variation in practice , the potential to affect treatment decisions , and re source utilization . The Hematology DSG noted that the use of transplantation for patients with myeloma varied among practice s across the province . Variability in practice and emerging evidence of higher quality made this a priority topic for guideline development . To approach this topic , the DSG addressed the following questions : What is optimal st and ard-dose chemotherapy for patients with myeloma ? In terms of survival , is peripheral blood stem-cell or marrow transplantation better than conventional chemotherapy ? What is the relative efficacy of autologous versus allogeneic transplantation ? What specifics of the transplantation process can be recommended ? When should transplantation be performed ? Who should ( or should not ) receive a transplant ? Methods Overview of Guideline Development This guideline was developed by the Cancer Care Ontario Practice Guidelines Initiative ( CCOPGI ) using the methods of the Practice Guidelines Development Cycle ( 5 ) . Members of the CCOPGI 's Hematology DSG selected , review ed , and interpreted the evidence . This DSG comprises 25 members , including hematologists , medical and radiation oncologists , an epidemiologist , and 2 lay representatives . Several of the physician members have background training in epidemiology ; 8 hematologists regularly perform stem-cell transplantation in clinical practice . The DSG 's draft recommendations were circulated through a mailed survey to hematologists and medical or radiation oncologists in Ontario for feedback and involvement in a consensus process . Responses were used to guide the reformatting of the draft into the final guideline recommendations . The Practice Guidelines Co-ordinating Committee ( PGCC ) , which ensures consistency of guideline development across the DSGs of various tumor sites , approved the guideline . The CCOPGI has a st and ardized process to up date each guideline report ; the current guideline was up date d and review ed by the PGCC in October 2000 . Literature Search Strategy We search ed the MEDLINE , CANCERLIT , and Cochrane Library data bases for literature published from 1992 to December 1997 and subsequently up date d the search in October 1998 , June 1999 , and April 2000 . For the search es , we combined multiple myeloma ( as a Medical Subject Heading [ MeSH ] and text word ) with bone marrow transplantation ( MeSH and text word ) and drug therapy ( MeSH ) . Then , we combined these terms with the search terms for the following study design s : practice guidelines ; systematic review s or meta-analyses ; review s ; r and omized , controlled trials ; controlled clinical trials ; and comparative studies . In addition , we search ed the PubMed and Physician Data Query ( PDQ ) ( www.cancer.gov/ search / clinical _ trials/ ) data bases and review ed relevant conference proceedings ( American Society of Hematology , 1997 to 1999 , and American Society of Clinical Oncology , 1999 to 2000 ) , article bibliographies , and personal files . To address the issue of optimal chemotherapy , we performed an additional search of the same data bases using the term multiple myeloma ( MeSH ) combined with r and omized , controlled trials ( MeSH ) and the text word r and om in the title . Inclusion Criteria We selected study reports meeting one of the three following criteria : r and omized trial or meta- analysis of therapy for patients with myeloma that reported survival or quality -of-life outcomes ; nonr and omized comparative trial that addressed transplantation strategy , including a contemporaneous control group , and that reported survival or quality -of-life outcomes ; or economic evaluation that addressed transplantation strategy . Because of insufficient data on the specifics of the transplantation process and the patients who would be most likely to benefit from transplantation , we performed a second search , which identified data from noncomparative case-series studies . Data Extraction and Interpretative Summary Three members of the DSG , including an epidemiologist , determined eligibility of the articles and abstract s obtained from the literature search . The lead DSG member for this guideline extracted and summarized relevant data according to the guideline question addressed . The DSG members then review ed the summarized data and key articles . The DSG met formally three to four times annually ; at these meetings , the members method ologically assessed the articles , interpreted the data , and debated specific points in an attempt to reach a consensus . Synthesizing the Evidence Because all of the nine r and omized trials on transplantation addressed different questions , we did not statistically pool the data . DSG Consensus Process Through an iterative process that included debate at formal meetings and circulation of draft recommendations , we considered the implication s of the appraised data for each guideline question . With this process , attempts were made to reach consensus ; when this was impossible , minority opinions were recorded . Approval by each member of the DSG was required before circulation of the draft version for practitioner feedback and su bmi ssion of the final guideline to the PGCC . Practitioner Feedback To obtain practitioner feedback , we mailed a survey to 211 practitioners in Ontario ( 94 hematologists , 93 medical oncologists , and 24 radiation oncologists ) . The survey consisted of st and ardized items asking the practitioner to rate the quality of each draft guideline and to judge whether the draft recommendations should serve as a practice guideline . Written comments were invited . Follow-up reminders were sent at 2 weeks ( by postcard ) and 4 weeks ( entire package ) . After exclusion of 18 retired practitioners , 137 of 193 practitioners ( 71 % ) responded ; 90 of 137 respondents ( 66 % ) indicated that the guideline was relevant to their practice . Approval of the draft guideline was strong among these 90 practitioners : 91 % agreed or strongly agreed that the summary of the evidence was acceptable , 87 % agreed with the draft recommendations , and 81 % approved of the recommendations as a practice guideline . Thirty-nine respondents provided written comments ; these comments were , like the other responses , incorporated in the final guideline . Results Sixty-six reports met the criteria for inclusion and are categorized in Table 1 . In each section below , we describe the studies , summarize results , and describe the guideline development . Table 1 . Evidence Included in This Practice Guideline Report What Is Optimal St and ard-Dose Chemotherapy for Patients with Multiple Myeloma ? To properly compare transplantation with conventional chemotherapy , we must define optimal conventional chemotherapy . We identified 30 r and omized trials comparing therapies in previously untreated patients . Four meta-analyses ( 6 - 9 ) evaluated these data . The Myeloma Trialists ' Collaborative Group ( 7 ) compared combination chemotherapy with melphalan plus prednisone in a meta- analysis of 27 trials . Twenty of these trials supplied individual-patient data . No difference in survival was detected . The proportional reduction in the annual odds of death was 1.5 % in favor of combination chemotherapy ( 95 % CI , 8 % to 5 % ; P > 0.2 ) , with an odds ratio ( OR ) of 0.99 ( CI , 0.93 to 1.05 ) . An earlier literature -based meta- analysis ( 6 ) of 18 trials also failed to detect a survival difference between groups ( OR , 1.04 [ CI , 0.90 to 1.19 ] ; P > 0.2 ) . Two meta-analyses evaluated interferon for multiple myeloma . An overview of 24 r and omized trials published in abstract form ( 8) demonstrated that interferon improved recurrence-free survival by 6 months and improved 3-year overall survival by 4 % . Another meta- analysis ( 9 ) measured survival by a unique measure called the mean lifetime survival . This meta- analysis found no difference in survival rate between the group receiving interferon and the group not receiving interferon ( 3.9 vs. 3.4 years , respectively ; P = 0.095 ) . Guideline Recommendation Multiagent chemotherapy or melphalan plus prednisone is appropriate therapy for a control group in a comparison of transplantation versus st and ard-dose therapy . The addition of interferon is unlikely to influence outcomes in the control group . In Terms of Survival , Is Autologous Peripheral Blood Stem-Cell or Bone Marrow Transplantation Better than Conventional Chemotherapy ? We review ed two r and omized and three nonr and omized comparisons ( Table 2 ) . Attal and colleagues ( 3 ) r and omly assigned 200 previously untreated patients younger than 65 years of age with stage II or III ( 40 ) myeloma to conventional chemotherapy or to a strategy that included autologous bone marrow transplantation . Patients were r and omly This report of a phase 2 trial of thalidomide ( THAL ) ( 200 mg/d ; 200 mg increment every 2 weeks to 800 mg ) for 169 patients with advanced myeloma ( MM ) ( abnormal cytogenetics ( CG ) , 67 % ; prior autotransplant , 76 % ) extends earlier results in 84 patients . A 25 % myeloma protein reduction was obtained in 37 % of patients ( 50 % reduction in 30 % of patients ; near-complete or complete remission in 14 % ) and was more frequent with low plasma cell labeling index ( PCLI ) ( below 0.5 % ) and normal CG . Two-year event-free and overall survival rates were 20 % + /- 6 % and 48 % + /- 6 % , respectively , and these were superior with normal CG , PCLI of less than 0.5 % , and beta(2)-microglobulin of 3 mg/L. Response rates were higher and survival was longer especially in high-risk patients given more than 42 g THAL in 3 months ( median cumulative dose ) ( l and mark analysis ) ; this supports a THAL dose-response effect in advanced MM BACKGROUND This study compared bortezomib with high-dose dexamethasone in patients with relapsed multiple myeloma who had received one to three previous therapies . METHODS We r and omly assigned 669 patients with relapsed myeloma to receive either an intravenous bolus of bortezomib ( 1.3 mg per square meter of body-surface area ) on days 1 , 4 , 8 , and 11 for eight three-week cycles , followed by treatment on days 1 , 8 , 15 , and 22 for three five-week cycles , or high-dose dexamethasone ( 40 mg orally ) on days 1 through 4 , 9 through 12 , and 17 through 20 for four five-week cycles , followed by treatment on days 1 through 4 for five four-week cycles . Patients who were assigned to receive dexamethasone were permitted to cross over to receive bortezomib in a companion study after disease progression . RESULTS Patients treated with bortezomib had higher response rates , a longer time to progression ( the primary end point ) , and a longer survival than patients treated with dexamethasone . The combined complete and partial response rates were 38 percent for bortezomib and 18 percent for dexamethasone ( P<0.001 ) , and the complete response rates were 6 percent and less than 1 percent , respectively ( P<0.001 ) . Median times to progression in the bortezomib and dexamethasone groups were 6.22 months ( 189 days ) and 3.49 months ( 106 days ) , respectively ( hazard ratio , 0.55 ; P<0.001 ) . The one-year survival rate was 80 percent among patients taking bortezomib and 66 percent among patients taking dexamethasone ( P=0.003 ) , and the hazard ratio for overall survival with bortezomib was 0.57 ( P=0.001 ) . Grade 3 or 4 adverse events were reported in 75 percent of patients treated with bortezomib and in 60 percent of those treated with dexamethasone . CONCLUSIONS Bortezomib is superior to high-dose dexamethasone for the treatment of patients with multiple myeloma who have had a relapse after one to three previous therapies PURPOSE To determine the antitumor activity of the novel proteasome inhibitor bortezomib in patients with indolent and mantle-cell lymphoma ( MCL ) . PATIENTS AND METHODS Patients with indolent and MCL were eligible . Bortezomib was given at a dose of 1.5 mg/m2 on days 1 , 4 , 8 , and 11 . Patients were required Output:	Bortezomib is recommended as the preferred treatment option in patients with myeloma relapsing within 1 year of the conclusion of initial treatment ; it may also be a reasonable option in patients relapsing at least 1 year after autologous stem-cell transplantation . Bortezomib is also a reasonable option for patients relapsing at least 1 year after autologous stem-cell transplantation .
MS21417	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: In ventral fusion after anterior cervical discectomy there is still a remarkable number of cage subsidence and segmental kyphosis seen . The aim of the present study is to assess whether the cage design influences the extent of correction loss during follow-up . Sixty patients with single-level cervical disc herniation were r and omly treated with two different cervical inter-body cages ( group1 : Solis ™ cage , Stryker Company and group2 : Shell ™ cage , AMT Company ) . Clinical and radiological follow-up was done before and after surgery , 3 and 6 months post-surgery . Clinical follow-up was done with the help of Odom ’s criteria . Both groups were similar in the baseline parameters ( age , sex , treated level ) . Statistically , the subsidence was significantly higher at 3 and 6-month follow-ups in group1 than in group2 , however , clinical results showed no significant differences . In 67 % , subsidence was seen in the anterior lower aspect of the treated segment . Segmental kyphosis was seen in seven patients of group1 and two patients of group2 . A significant correlation is found between Odom ’s criteria and subsidence . Although there was no significant difference in a short-term clinical result between the two treatment groups , we recommend the use of cages which preserve the determined segmental height and lordosis OBJECT The authors compare clinical outcome and fusion rates after iliac crest autograft (ICAG)- and rectangular titanium cage (RTC)-augmented fusion in patients undergoing anterior cervical discectomy ( ACD ) . METHODS One hundred consecutive patients with 127 levels of cervical disc disease refractory to conservative treatment were r and omized into one of the two treatment groups ( ICAG/RTC fusion ) . The visual analog scale was used by the patient to rate overall pain and head , neck , arm , and donor site pain separately . Myelopathy was documented according to Japanese Orthopaedic Association and Nurick grading systems . Outcome was analyzed using Odom criteria , the 36-Item Short Form ( SF-36 ) , and Patient Satisfaction Index scales . Fusion rates were assessed on st and ard and flexion-extension radiographs . Follow-up data of at least 12 months ' duration were available for 95 patients . More residual overall pain after 12 months was documented in patients who underwent ICAG fusion ( 3.3 + /- 2.5 [ ICAG ] and 2.2 + /- 2.4 [ RTC ] ; p < 0.05 ) . Although arm and head pain were minimal in both groups , neck pain proved to be the predominant symptom ( 2.7 + /- 2.5 [ ICAG ] and 1.9 + /- 2.1 [ RTC ] ) , which resolved in only 67 and 48 % of RTC- and ICAG-treated patients , respectively ( p < 0.05 ) . Myelopathy improved comparably in both groups . Regardless of increased pain in ICAG-treated patients , PSI and SF-36 scores were not significantly different between groups ( only four [ 8 % ] of 47 ICAG-treated patients and five [ 10 % ] of 48 RTC-treated patients were unsatisfied ) . Good to excellent functional recovery according to Odom criteria was observed in 75 and 79 % of ICAG- and RTC-treated patients , respectively . Fusion rates were 81 and 74 % , respectively ( p = 0.51 ) . CONCLUSIONS Fusion rates and clinical outcome at 12 months after ACD were comparable between patients who underwent ICAG and RTC fusion . The use of rectangular cages , however , avoids donor site morbidity and reduces overall pain and , thus , seems to be an advantageous treatment alternative OBJECT The aim of this in vitro study was to determine the influence of simulated postoperative neck movements on the stabilizing effect and subsidence of four different anterior cervical interbody fusion devices . Emphasis was placed on the relation between subsidence and spinal stability . METHODS The flexibility of 24 human cervical spine specimens was tested before and directly after being stabilized with a WING , BAK/C , AcroMed I/F cage , or with bone cement in st and ard flexibility tests under 50 N axial preload . Thereafter , 700 pure moment loading cycles ( + /- 2 Nm ) were applied in r and omized directions to simulate physiological neck movements . Additional flexibility tests in combination with measurements of the subsidence depth were conducted after 50 , 100 , 200 , 300 , 500 , and 700 loading cycles . In all four groups , simulated postoperative neck movements caused an increase of the range of motion ( ROM ) ranging from 0.4 to 3.1 degrees and of the neutral zone from 0.1 to 4.2 degrees . This increase in flexibility was most distinct in extension followed by flexion , lateral bending , and axial rotation . After cyclic loading , ROM tended to be lower in the group fitted with AcroMed cages ( 3.3 degrees in right lateral bending , 3.5 degrees in left axial rotation , 7.8 degrees in flexion , 8.3 degrees in extension ) and in the group in which bone cement was applied ( 5.4 degrees , 2.5 degrees , 7.4 degrees , and 8.8 degrees , respectively ) than in those fixed with the WING ( 6.3 degrees , 5.4 degrees , 9.7 degrees , and 6.9 degrees , respectively ) and BAK cages ( 6.2 degrees , 4.5 degrees , 10.2 degrees , and 11.6 degrees , respectively ) . CONCLUSIONS Simulated repeated neck movements not only caused an increase of the flexibility but also subsidence of the implants into the adjacent vertebrae . The relation between flexibility increase and subsidence seemed to depend on the implant design : subsiding BAK/C cages partially supported stability whereas subsiding WING cages and AcroMed cages did not The complications of autogenous bone grafting cause spinal surgeons to seek alternative methods for cervical spinal fusion . This prospect i ve study was conducted to evaluate the safety and efficacy of rectangular titanium cages as compared to the widely performed iliac crest autograft fusion . Thirty-six patients with cervical disc disease in whom an anterior cervical approach was indicated for discectomy were included in a prospect i ve controlled study protocol with 1-year follow-up . The first 18 consecutive patients received iliac crest autograft , while the next 18 received rectangular titanium cages . According to Odom 's criteria , 15 of 18 ( 83 % ) patients in both groups experienced good to excellent functional recovery . According to the patient satisfaction index , 17 of 18 ( 94 % ) in both groups were satisfied . There were no significant differences in neck or arm pain . Fusion was present after 1 year in 16 of 18 ( 89 % ) patients in the iliac crest autograft group and 15 of 18 ( 83 % ) in the rectangular titanium cage group . In the autograft group , one case of pseudarthrosis was present , and marked hip pain was observed in four patients . There were no implant-related complications in the cage group . The authors conclude that titanium cages in anterior cervical discectomy constitute a safe and efficient alternative to iliac crest bone autograft We carried out a prospect i ve study to determine whether the addition of a recombinant human bone morphogenetic protein ( rhBMP-2 ) to a machined allograft spacer would improve the rate of intervertebral body fusion in the spine . We studied 77 patients who were to undergo an interbody fusion with allograft and instrumentation . The first 36 patients received allograft with adjuvant rhBMP-2 ( allograft/rhBMP-2 group ) , and the next 41 , allograft and demineralised bone matrix ( allograft/demineralised bone matrix group ) . Each patient was assessed clinical ly and radiologically both pre-operatively and at each follow-up visit using st and ard methods . Follow-up continued for two years . Every patient in the allograft/rhBMP-2 group had fused by six months . However , early graft lucency and significant ( > 10 % ) subsidence were seen radiologically in 27 of 55 levels in this group . The mean graft height subsidence was 27 % ( 13 % to 42 % ) for anterior lumbar interbody fusion , 24 % ( 13 % to 40 % ) for transforaminal lumbar interbody fusion , and 53 % ( 40 % to 58 % ) for anterior cervical discectomy and fusion . Those who had undergone fusion using allograft and demineralised bone matrix lost only a mean of 4.6 % ( 0 % to 15 % ) of their graft height . Although a high rate of fusion ( 100 % ) was achieved with rhBMP-2 , significant subsidence occurred in more than half of the levels ( 23 of 37 ) in the lumbar spine and 33 % ( 6 of 18 ) in the cervical spine . A 98 % fusion rate ( 62 of 63 levels ) was achieved without rhBMP-2 and without the associated graft subsidence . Consequently , we no longer use rhBMP-2 with allograft in our practice if the allograft has to provide significant structural support Study Design All patients of spinal interbody fusion using polyetheretherketone ( PEEK ) cages and recombinant human bone morphogenetic protein (rhBMP)-2 performed over a 16-month period were review ed . Objective To determine the suitability of PEEK cages when used in conjunction with rhBMP-2 in interbody spinal fusion . Summary of Background Data Bone morphogenetic proteins are increasingly being used in spinal fusion to promote osteogenesis . PEEK is a semicrystalline aromatic polymer that is used as a structural spacer to maintain the disc and foraminal height . Their use has led to increased and predictable rates of fusion . However , not many reports of the adverse effects of their use are available . Methods Fifty-nine consecutive patients of interbody spinal fusion in the cervical or lumbar spine using a PEEK cage and rhBMP-2 were followed for an average of 26 months after surgery . A clinical examination and a record of Oswestry Disability Index , Visual Analog Scale for pain , and a pain diagram were performed preoperatively and at every follow-up visit . All patients had plain radiographs carried out to assess fusion . Ten patients of lumbar spine fusion were additionally evaluated with a computed tomography scan . Results All cases demonstrated an appreciable amount of new bone formation by 6 to 9 months in the cervical spine and by 9 to 12 months in the lumbar spine . End plate resorption was visible radiologically in all cervical spine fusions and majority of lumbar fusions . Cage migration was observed to occur maximally in patients with transforaminal lumbar interbody fusion and posterior lumbar interbody fusion . Disc space subsidence was seen in both cervical and lumbar arthrodesis with the latter showing a lesser incidence , but with a greater degree of collapse . Conclusions PEEK cages and rhBMP-2 when used in spinal fusion give consistently good fusion rates . However , the early role of BMP in the resorptive phase may cause loosening , cage migration , and subsidence A variety of bone graft substitutes , interbody cages , and anterior plates have been used in cervical interbody fusion , but no controlled study was conducted on the clinical performance of β-tricalcium phosphate ( β-TCP ) and the effect of supplemented anterior plate fixation . The objective of this prospect i ve , r and omized clinical study was to evaluate the effectiveness of implanting interbody fusion cage containing β-TCP for the treatment of cervical radiculopathy and /or myelopathy , and the fusion rates and outcomes in patients with or without r and omly assigned plate fixation . Sixty-two patients with cervical radiculopathy and /or myelopathy due to soft disc herniation or spondylosis were treated with one- or two-level discectomy and fusion with interbody cages containing β-TCP . They were r and omly assigned to receive supplemented anterior plate ( n = 33 ) or not ( n = 29 ) . The patients were followed up for 2 years postoperatively . The radiological and clinical outcomes were assessed during a 2-year follow-up . The results showed that the fusion rate ( 75.0 % ) 3 months after surgery in patients treated without anterior cervical plating was significantly lower than that ( 97.9 % ) with plate fixation ( P < 0.05 ) , but successful bone fusion was achieved in all patients of both groups at 6-month follow-up assessment . Patients treated without anterior plate fixation had 11 of 52 ( 19.2 % ) cage subsidence at last follow-up . No difference ( P > 0.05 ) was found regarding improvement in spinal curvature as well as neck and arm pain , and recovery rate of JOA score at all time intervals between the two groups . Based on the findings of this study , interbody fusion cage containing β-TCP following one- or two-level discectomy proved to be an effective treatment for cervical spondylotic radiculopathy and /or myelopathy . Supplemented anterior plate fixation can promote interbody fusion and prevent cage subsidence but do not improve the 2-year outcome when compared with those treated without anterior plate fixation In a multicenter , prospect i ve , r and omized , nonblinded , 2-year study , 279 patients with degenerative lumbar disc disease were r and omly divided into two groups that underwent interbody fusion using two tapered threaded fusion cages . The investigational group ( 143 patients ) received rhBMP-2 on an absorbable collagen sponge , and a control group ( 136 patients ) received autogenous iliac crest bone graft . Plain radiographs and computed tomographic scans were used to evaluate fusion at 6 , 12 , and 24 months after surgery Output:	Subsidence irrespective of the measurement technique or definition does not appear to have an impact on successful fusion and /or clinical outcomes .
MS21418	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: A prospect i ve clinical trial comparing flushing and ice storage using a new hypertonic citrate solution , with machine preservation by continuous perfusion showed early graft function was similar with each method , and preservation times were comparable . Good early function occurred in half the grafts with preservation times up to 24 hours . Graft survival at three and 12 months was similar with each method of preservation . Graft survival at 12 months was worsened by poor early graft function , whereas patient survival at 12 months was unaffected by early function or by the method of preservation Outcome in eighty-eight recipients of cadaveric donor renal allografts preserved before implantation by machine perfusion with a solution of human albumin was compared to that for eighty-three recipients of similar kidneys implanted after simple cold storage . Average total ischaemic intervals for machine-perfused and cold-stored kidneys were 18 and 4 1/4 hours , respectively . Machine-perfused kidneys were implanted regardless of perfusion characteristics . Initial function and 1-month and 1-year graft survivals for the machine-perfused group ( 58 % , 85 % , 68 % , respectively ) were either similar or improved compared to those of cold-stored kidneys ( 58 % , 81 % , 52 % , respectively ) . Improved 1-year survival for machine-perfused grafts was dependent upon reduced rejection . Careful donor selection and management ensured good machine perfusion of kidneys on 90 % of occasions . In the other 10 % , despite poor perfusion characteristics , outcome for kidneys was similar to those with good perfusion characteristics . Antilymphocyte globulin treatment reduced rejection whether allografts were machine perfused or not . In the absence of antilymphocyte globulin treatment , machine-perfused kidneys did much better than cold-stored kidneys . Machine perfusion had important advantages and improved the results in kidney-graft recipients One third of deceased donor kidneys for transplantation in the UK are donated following cardiac death ( DCD ) . Such kidneys have a high rate of delayed graft function ( DGF ) following transplantation . We conducted a multicenter , r and omized controlled trial to determine whether kidney preservation using cold , pulsatile machine perfusion ( MP ) was superior to simple cold storage ( CS ) for DCD kidneys . One kidney from each DCD donor was r and omly allocated to CS , the other to MP . A sequential trial design was used with the primary endpoint being DGF , defined as the necessity for dialysis within the first 7 days following transplant . The trial was stopped when data were available for 45 pairs of kidneys . There was no difference in the incidence of DGF between kidneys assigned to MP or CS ( 58 % vs. 56 % , respectively ) , in the context of an asystolic period of 15 min and median cold ischemic times of 13.9 h for MP and 14.3 h for CS kidneys . Renal function at 3 and 12 months was similar between groups , as was graft and patient survival . For kidneys from controlled DCD donors ( with mean cold ischemic times around 14 h ) , MP offers no advantage over CS , which is cheaper and more straightforward Objective : Hypothermic machine perfusion may improve outcome after transplantation of kidneys donated after cardiac death ( DCD ) , but no sufficiently powered prospect i ve studies have been reported . Because organ shortage has led to an increased use of DCD kidneys , we aim ed to compare hypothermic machine perfusion with the current st and ard of static cold storage preservation . Methods : Eighty-two kidney pairs from consecutive , controlled DCD donors 16 years or older were included in this r and omized controlled trial in Eurotransplant . One kidney was r and omly assigned to machine perfusion and the contralateral kidney to static cold storage according to computer-generated lists created by the permuted block method . Kidneys were allocated according to st and ard rules , with concealment of the preservation method . Primary endpoint was delayed graft function ( DGF ) , defined as dialysis requirement in the first week after transplantation . All 164 recipients were followed until 1 year after transplantation . Results : Machine perfusion reduced the incidence of DGF from 69.5 % to 53.7 % ( adjusted odds ratio : 0.43 ; 95 % confidence interval 0.20–0.89 ; P = 0.025 ) . DGF was 4 days shorter in recipients of machine-perfused kidneys ( P = 0.082 ) . Machine-perfused kidneys had a higher creatinine clearance up to 1 month after transplantation ( P = 0.027 ) . One-year graft and patient survival was similar in both groups ( 93.9 % vs 95.1 % ) . Conclusions : Hypothermic machine perfusion was associated with a reduced risk of DGF and better early graft function up to 1 month after transplantation . Routine preservation of DCD kidneys by hypothermic machine perfusion is therefore advisable Output:	Pulsatile machine perfusion of donation after cardiac death kidneys appears to decrease the delayed graft function rate . We noted no benefit in 1-year graft survival .
MS21419	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: AIMS To assess the effect of regular diabetic health education on cardiovascular risk factors in Chinese Type 2 diabetic patients . METHODS This was a 1-year prospect i ve r and omized study . One hundred and eighty Type 2 diabetic subjects were recruited from three regional diabetic centres in Hong Kong . Ninety received additional structured reinforcement of diabetic health education by a trained nurse after the doctors ' consultations every 3 months ( intervention group ) . The others received the same medical care except no nursing reinforcement ( control group ) . Outcome measures included fasting plasma glucose , HbA(1c ) , body mass index , waist circumference , blood pressure and lipid profiles , which were assessed before the study and after 1 year . RESULTS Two of the controls defaulted follow-up . The intervention group and controls had similar age and sex distribution . At the end of study , the intervention group had reducted their waist circumference , diastolic blood pressure , HbA(1c ) , total cholesterol and low-density lipoprotein cholesterol levels . The controls had reduced their total cholesterol and low-density lipoprotein cholesterol levels . Other cardiovascular risk factors were not significantly changed in the controls . Addition of drugs and /or dosage increment of anti-diabetic drugs , lipid-lowering agents and anti-hypertensive agents were similar between the two groups . CONCLUSIONS Regular structured reinforcement with diabetic health education is useful . It helps to control more successfully some of the cardiovascular risk factors in Chinese Type 2 diabetic patients OBJECTIVE To evaluate an intervention to improve food label knowledge and skills in diabetes management among older adults with diabetes mellitus . DESIGN A r and omized pretest-posttest control group design was used . SUBJECTS/ SETTING Participants ( 48 experimental , 50 control ) were aged 65 years and older with type 2 diabetes for 1 year or longer ; 93 participants ( 95 % ) completed the study , conducted in an outpatient setting . INTERVENTION The intervention included 10 weekly group sessions led by a dietitian . Information processing , learning theory , and Social Cognitive Theory principles were used in program development and evaluation . MAIN OUTCOME MEASURES Participants ' knowledge , outcome expectations ( expected results of behavior ) , self-efficacy , and decision-making skills were assessed . Instrument validity and reliability were established before program evaluation . STATISTICAL ANALYSES PERFORMED Factor analysis identified underlying factor structures . Analysis of covariance with pretest score as covariate was used to compare groups at posttest . Paired t tests compared results within groups . RESULTS Two factors were identified for outcome expectations ( positive and negative ) and for self-efficacy ( promoters of and barriers to diabetes management ) . The experimental group had greater improvement in total knowledge scores ( mean + /- st and ard error of the mean : 7.8+/-0.7 ) than the control group ( 0.2+/-0.7 ) ( P < .0001 ) , positive outcome expectations ( 0.59+/-0.15 vs 0.06+/-0.15 , P = .01 ) , promoters of diabetes management ( 0.83+/-0.12 vs -0.09+/-0.18 , P < or = .001 ) and decision-making skills ( 5.1+/-0.5 vs 0.3+/-0.5 , P < .0001 ) and greater reduction in barriers to diabetes management ( 1.1+/-0.16 vs 0.34+/-0.16 , P < .01 ) . No significant difference in negative outcome expectations occurred between groups at posttest . APPLICATIONS/ CONCLUSIONS Older adults with diabetes can benefit from nutrition education design ed to improve knowledge and skills necessary for diabetes management Introduction Diabetes self-management education interventions in community gathering places have been moderately effective , but very few studies of intervention effectiveness have been conducted among African Americans with type 2 diabetes . This paper describes a church-based diabetes self-management education intervention for African Americans , a r and omized controlled trial to evaluate the intervention , and baseline characteristics of study participants . Methods A New DAWN : Diabetes Awareness & Wellness Network was conducted among 24 churches of varying size in North Carolina . Each church recruited congregants with type 2 diabetes and design ated a diabetes advisor , or peer counselor , to be part of the intervention team . Participants were enrolled at each church and r and omized as a unit to either the special intervention or the minimal intervention . The special intervention included one individual counseling visit , twelve group sessions , three postcard messages from the participant 's diabetes care provider , and twelve monthly telephone calls from a diabetes advisor . Baseline data included measures of weight , hemoglobin A1c , blood pressure , physical activity , dietary and diabetes self-care practice s , and psychosocial factors . The study to evaluate the intervention ( from enrollment visit to last follow-up ) began in February 2001 and ended in August 2003 . Results Twenty-four churches ( with 201 total participants ) were r and omized . Sixty-four percent of the participants were women . On average , the participants were aged 59 years and sedentary . They had an average of 12 years of education , had been diagnosed with diabetes for 9 years , had a body mass index of 35 , had a hemoglobin A1c level of 7.8 % , and had a reported dietary intake of 39 % of calories from fat . Conclusion A New DAWN is a culturally sensitive , church-based diabetes self-management education program for African Americans with type 2 diabetes that is being evaluated for effectiveness in a r and omized controlled trial . The outcomes of A New DAWN will contribute to the literature on community-based interventions for minority population s and help to inform the selection of approaches to improve diabetes care in this population We investigated the effect of a structured group diabetes education program ( 1 ) on insulin-treated patients who had received individual counseling ( at the time of diagnosis and insulin initiation ) . A total of 1,369 type 1 and insulin-treated type 2 diabetic patients with mean disease duration of 11.7 and 13.7 years , respectively , were allocated to receive or not receive structured group education , which was delivered in 10 45-min sessions over 3–5 days . Baseline GHb levels of type 1 diabetic patients were 9.3 % for Aims To examine whether motivating patients to gain expertise and closely follow their risk parameters will attenuate the course of microvascular and cardiovascular sequelae of diabetes This study compared an activation intervention to passive education in a r and omized attention-control trial of 232 patients with type 2 diabetes . The activation intervention was based on Exp and ing Patient Involvement in Care ( EPIC ) trials , and was compared to time-matched passive education viewing of ADA video-tapes . Patient demographics and clinical characteristics of their diabetes were assessed with question naires , active involvement was assessed via ratings of taped interactions between patients and providers , and serum sample s were analyzed for HbA1c . Patients in the activation condition were rated as more actively involved in discussion s of diabetes self-management , and rated active involvement was predictive of improvement in glycemic control . No effect of the activation intervention was found on HbA1c . Thus , the activation intervention increased the active involvement of patients with type 2 diabetes in visits with practitioners , and active involvement led to improved glycemic control . However , the activation intervention did not improve glycemic control directly Background Epidemiologic data have shown that the prevalence of Type 2 diabetes varies with ethnic origin . Type 2 diabetes is up to four times more common in British South Asians than in the indigenous white population . The aim of this study was to develop a culturally appropriate educational intervention programme for South Asians with Type 2 diabetes . We then investigated whether this intervention could produce an improvement , and finally whether any improvement was greater than background changes in knowledge in comparison groups . Methods A multi-site prospect i ve , r and omised controlled study was conducted in all day care centres and three general practice registers with high proportion patients from different ethnic minority groups in Glasgow , Scotl and . The intervention consisted of 18 educational sessions in 6 separate programmes . A modified question naire was used to measure the knowledge , attitudes , and practice of diabetes before and after intervention . Results Baseline assessment showed that Indian and Pakistani subjects had less knowledge about diabetes , regarded the disease less seriously , and had a lesser underst and ing of the relationship between control and complications than the white population . No differences in initial responses were found between those who completed the second assessment and those who did not . The intervention group showed significant improvements in scores for Knowledge ( + 12.5 % ) ; Attitudes toward seriousness ( + 13.5 % ) , complications ( + 8.1 % ) , Practice ( + 20.0 % ) . However there were also changes in the ethnic control group scores ; respectively + 5.0 % , + 16.3 % ( significant P < 0.001 ) , + 1.5 % , + 1.7 % . The single white control group also showed some improvements ; respectively + 12.2 % , + 12.4 % ( P = 0.04 ) , + 6.0 % , + 25.0 % ( P = 0.007 ) , but the differences in improvement between these two control groups were not significant . Overall , the improvement seen was similar in both intervention and ethnic control groups and there was no significant difference in the amount of change ( P = 0.36 CI -0.9 to + 2.6 ) . Conclusion This study has shown that conducting a culturally-competent educational intervention in patients with Type 2 diabetes from ethnic minority groups is feasible and can improve their knowledge and attitudes and practice . However there was no net benefit compared with the control group BACKGROUND In Turkish immigrant diabetics , problems with communication and cultural differences may hinder delivery of diabetes care . METHODS In a prospect i ve controlled study , the effect of an ethnic-specific diabetes education programme on glycaemic control and cardiovascular risk factors in Turkish type 2 diabetes patients was assessed , by comparing Turkish diabetics who were offered the education programme with Turkish diabetics offered routine care only ( control group ) . From 16 general practice s ( 31 GPs ) in Rotterdam , 104 Turkish type 2 diabetes patients were recruited , 85 of whom could be assessed at one-year follow-up . Glycaemic control , lipid concentrations , blood pressure and body mass index were measured . RESULTS Compared with the control group , mean HbA(1C ) in the intervention group decreased by 0.3 % ( 95 % CI -0.8 to 0.2 ) . A significant decrease in HbA(1C ) was observed in women with HbA(1C ) > 7 % at baseline ( -0.9 % ; 95 % CI -1.73 to -0.09 ) but not in the other subgroups studied . serum lipid concentrations , blood pressure and body mass index remained unchanged in the intervention group . CONCLUSION Ethnic-specific diabetes education by Turkish female educators has no obvious beneficial effect on glycaemic control or cardiovascular risk profile . More focus on specific patient selection and gender e quality between educators/ patients may prove worthwhile BACKGROUND Lifestyle modifications may affect the development of diabetes and prevent complications . However , there is no direct evidence to show that lifestyle intervention is beneficial for patients with established type 2 diabetes . OBJECTIVE The ultimate goal is to determine whether long-term lifestyle intervention can improve glycemic control and prevent complications in patients with type 2 diabetes . This initial report on a multi-year study describes protocol s and the analysis of baseline data and three-year interim results . DESIGN The study was a r and omized , controlled , multi-centre , prospect i ve intervention trial . The trial included patients from 59 Japanese institutes specializing in diabetes care . PATIENTS The study enrolled 2 205 patients with previously diagnosed type 2 diabetes . INTERVENTION The lifestyle modification program included intensive lifestyle management at each outpatient clinic visit and frequent telephone counseling . The intervention group received educational material s concerning the importance of lifestyle and behavioural changes , a diary to record progress of laboratory and other data , and a pedometer . MEASUREMENTS Parameters and indices related to glycemic control , diabetic complications , dyslipidemia , hypertension , obesity , and atherosclerosis were measured several times a year . RESULTS Small but significant differences in HbA1c levels between the intervention ( INT ) and conventional ( CON ) therapy groups appeared as early as two years after the start of intervention and were maintained in the third year ( CON group , 7.78 + /- 1.27 % vs. INT group , 7.62 + /- 1.20 % , the initial HbA1c level was 7.80 + /- 1.42 % for the CON group and 7.68 + /- 1.28 % for the INT group ) . Data on differences in occurrence of micro- or macrovascular complications are not yet available . CONCLUSIONS The effect of lifestyle modification on improving the glycemic control of patients with established type 2 diabetes mellitus was small but significant three years after initiation of the intervention AIMS Scarcity of re sources , expertise and evidence -based models have so far limited delivery of patient-centred diabetes education . We have developed and vali date d a group care approach that is applicable to everyday clinical practice and cost-effective in improving metabolic control , knowledge of diabetes , health behaviours , and quality of life in Type 2 diabetes . A clinical trial ( ROMEO ) was Output:	Positive effects may be attributable to longer-term interventions with a shorter duration between the end of the intervention and the follow-up evaluation point . There may also be an effect of having a multi-professional team delivering the educational programme . Studies of focused educational interventions did not yield consistent results . Some effects were shown on measures of diabetic control in studies that focused on diet or exercise alone . Although the effects shown were generally small , those that were present did appear to be relatively long-lasting . Based on the evidence , it would seem that education delivered by a team of educators , with some degree of reinforcement of that education made at additional points of contact , may provide the best opportunity for improvements in patient outcomes . From the evidence reported it is unclear what re sources would need to be directed at the educators themselves to ensure that they can deliver programmes successfully .
MS21420	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Introduction Stoma closure is one of the most frequently performed surgeries . The common complications are surgical site infection ( SSI ) and poor scar cosmesis . Purse-string sutures are expected to have less incidence of SSI due to the free drainage of secretions from the wound and possibly the early detection of a wound infection . Compared to the conventional linear closure , the purse-string closure technique is expected to have less wound infection , improved scar cosmesis , and good patient satisfaction because of a smaller size scar . Hence , a well-structured study is required to substantiate the advantage of this technique . Methodology This r and omized control trial was carried out for two years in a tertiary care centre in Southern India . Patients with various stoma reversals , including colostomy , as well as ileostomy reversal , were included in the study . Patients were divided into Group I - conventional linear skin suturing ( n = 40 ) and Group II - purse-string closure ( n = 40 ) . After the closure of rectus muscle , the skin is closed using the purse-string method ( subcuticular ) in the experimental group . Results Both the groups were comparable with respect to age , gender , body mass index ( BMI ) , the presence of co-morbidities , and indication for surgery . Stomal procedures were done ( 26.3 % ) for malignant cases . The difference in mean hospital days for both groups were statistically insignificant ( 11.95 vs. 9.9 ; p = 0.927 ) . The incidence of SSI between the groups were statistically significant ( 17 vs. 3 ; p = 0.003 ) . The mean Patient and Observer Scar Assessment Scoring ( POSAS ) scores between the groups ( 65.30 vs. 83.40 ; p = 0.012 ) were statistically significant . This proved significant improvement in scar cosmesis in purse-string skin closure . At one month postoperative , the purse-string group had better patient satisfaction ( 3.08 vs. 4.48 ; p = 0.001 ) , which was evidence d by a mean Likert 3 scale score . The mean visual analogue scale ( VAS ) score did not show any significant difference in pain between the groups . Conclusion Purse-string skin closure for stoma reversal had significantly less incidence of SSI . The duration of antibiotic therapy was also less in purse-string skin closure patients as compared to linear skin closure patients . Purse-string skin closures significantly improved the scar outcome and patient satisfaction 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 The creation of a stoma is commonplace in colorectal surgery . Circumferential subcuticular wound approximation ( CSWA ) is a method of wound closure following stoma reversal that has been reported to result in decreased wound infection rates and more desirable aesthetic outcomes . The aim of the present study was to determine the effectiveness of the CSWA method , in terms of wound infection and cosmesis by comparing the technique to the conventional method of wound closure . Methods All adult patients who presented for stoma reversal at the outpatient clinic of the Division of Colorectal Surgery at the Philippine General Hospital were r and omized into two groups , CSWA and conventional . Patients were followed up for up to 30 days postoperatively , photographic documentation of wound appearance was obtained , and wound infections and complications were documented . Patients were asked to complete a satisfaction survey at the end of the follow-up period . Results A total of 121 patients were included in the study . One ( 1.6 % ) patient in the CSWA group developed wound infection , while six ( 10 % ) patients in the conventional group had a wound infection ( p = 0.061 ) . The CSWA group had a higher total satisfaction score than the conventional group ( 25 and 24 , respectively , p = 0.012 ) . Conclusions With regard to wound infection rates , the CSWA method was better than the conventional method , although this was found to be borderline significant . With regard to patient satisfaction , the CSWA method proved to be superior to the conventional method , and this was found to be statistically significant . In addition , the technique is applicable to all forms of stoma regardless of the bowel segment involved , trephine size , and indication for diversion Purpose Infection is one of the most frequent complications that can occur after ileostomy closure . The incidence of wound infection depends on the skin closure technique , but there is no agreement on the perfect closure method for an ileostomy wound . The aim of this study was to evaluate the incidence of infection , the patient 's approval , and the patient 's pain between purse-string closure ( PSC ) and the usual linear closure ( LC ) of a stoma wound . Methods This r and omized clinical trial enrolled 66 patients who underwent a stoma closure from February 2015 to May 2015 in Sari Emam Khomeini Hospital . Patients were divided into 2 groups according to the stoma closing method : the PSC group ( n = 34 ) and the LC group ( n = 32 ) . The incidences of infection for the 2 groups were compared , and the patients ' satisfaction and pain with the stoma were determined by using a question naire . Results Infection occurred in 1 of 34 PSC patients ( 2.9 % ) and in 7 of 32 LC patients ( 21.8 % ) , and this difference was statistically significant ( P = 0.021 ) . Patients in the PSC group were more satisfied with the result ing wound scar and its cosmetic appearance at one month and three months after surgery ( P = 0.043 ) . Conclusion After stoma closure , PSC was associated with a significantly lower incidence of wound infection and greater patient satisfaction compared to LC . However , the healing period for patients who underwent PSC was longer than it was for those who underwent LC Background This study aim ed to compare quality of life ( QOL ) , functional outcome , body image , and cosmesis after h and -assisted laparoscopic ( LRP ) versus open restorative proctocolectomy ( ORP ) . The potential long-term advantages of LRP over ORP remain to be determined . The most likely advantage of LRP is the superior cosmetic result . It is , however , unclear whether the size and location of incisions affect body image and QOL . Methods In a previously conducted r and omized trial comparing LRP with ORP , 60 patients were prospect ively evaluated . The primary end points were body image and cosmesis . The secondary end points were morbidity , QOL , and functional outcome . A body image question naire was used to evaluate body image and cosmesis . The Short Form-36 Health Survey and the Gastrointestinal Quality of Life Inventory were used to assess QOL . Body image and QOL also were assessed preoperatively . Results A total of 53 patients completed the QOL and functional outcome question naires . There were no differences in functional outcome , morbidity , or QOL between LRP and ORP . At a median of 2.7 years after surgery , 46 patients returned the question naires regarding body image , cosmesis , and morbidity . The body image and cosmesis scores of female patients were significantly higher in the LRP group than in the ORP group ( body image , 17.4 vs 14.9 ; cosmesis , 19.1 vs 13.0 , respectively ) . The female patients in the ORP group had significantly lower body image scores than the male patients ( 14.9 vs 18.3 ) . Conclusions This study is the first to show that ORP has a negative impact on body image and cosmesis as compared with LRP . Functional outcome , QOL , and morbidity are similar for the two approaches . The advantages of a long-lasting improved body image and cosmesis for this relatively young patient population may compensate for the longer operating times and higher costs , particularly for women Background Ileostomy reversal is associated with surgical site infection ( SSI ) rates as high as 37 % . Recent literature suggests that employing a purse-string approximation ( PSA ) of the reversal wound reduces this rate of SSI . Thus we wished to perform a r and omised controlled trial to compare SSI rates in purse-string versus linear closure ( PLC ) wounds following ileostomy reversal . Methods A r and omised , controlled trial was conducted at University Hospital Limerick . Sixty-one patients undergoing ileostomy reversal were included . Thirty-four patients were r and omised to PSA and 27 patients to linear closure . The primary endpoint was incidence of SSI and secondary endpoints measured were quality of life and satisfaction with cosmesis . Statistical analysis was performed on a per protocol basis using SPSS version 22.0 . Results Three patients in the PSA group developed an SSI compared to 8 in the PLC group at 30 days ( 8 vs 30 % , p = 0.03 ) . The mean time to SSI diagnosis was faster in the PSA group ( 3 vs 12.3 days , p = 0.08 ) . Patients who developed SSI experienced a longer mean length of stay ( 6.8 vs 11.4 days , p = 0.012 ) . On multivariate analysis , PLC was the only predictive factor of SSI formation ( p < 0.001 ) . There was no difference in patient satisfaction between the two study groups ( p = 0.14 ) . Conclusions PSA of wounds following ileostomy reversal significantly reduces SSI formation compared to linear approximation without any effect on patient satisfaction BACKGROUND : Surgical site infection after stoma reversal is common . The optimal skin closure technique after stoma reversal has been widely debated in the literature . OBJECTIVE : We hypothesized that pursestring near-complete closure of the stoma site would lead to fewer surgical site infections compared with conventional primary closure . DESIGN : This study was a parallel prospect i ve multicenter r and omized controlled trial . SETTING S : This study was conducted at 2 university medical centers . PATIENTS : Patients ( N = 122 ) presenting for elective colostomy or ileostomy reversal were selected . INTERVENTIONS : Pursestring versus conventional primary closure of stoma sites were compared . MAIN OUTCOME MEASURES : Stoma site surgical site infection within 30 days of surgery , overall surgical site infection , delayed healing ( open wound for > 30 days ) , time to wound epithelialization , and patient satisfaction were the primary outcomes measured . RESULTS : The pursestring group had a significantly lower stoma site infection rate ( 2 % vs 15 % , p = 0.01 ) . There was no difference in delayed healing or patient satisfaction between groups . Time to epithelialization was measured in only 51 patients but was significantly longer in the pursestring group ( 34.6 ± 20 days vs 24.1 ± 17 days , p = 0.02 ) . LIMITATIONS : This study was limited by the variability in procedures and surgeons , the limited follow-up after 30 days , and the inability to perform blinding . CONCLUSION : Pursestring closure after stoma reversal has a lower risk of stoma site surgical site infection than conventional primary closure , although wounds may take longer to heal with the use of this approach . Registration number : NCT01713452 ( www . clinical trials.gov ) Surgical site infection ( SSI ) is a common complication following ileostomy closure with a frequency of up to 40 % . This prospect i ve r and omized controlled trial was initiated to compare two surgical techniques – direct suture ( DS ) and purse‐string suture ( PSS ) – used to close the wound following ileostomy closure . The primary end‐point was the SSI rate . Secondary end‐points were cosmetic outcome [ using two vali date d scales : the Patient and Observer Scar Assessment Scale ( POSAS ) and the Body Image Question naire ( BIQ ) ] and the influence of other factors on the SSI rate Ileostomy closure is an operation with an underappreciated morbidity , including surgical‐site infection , small bowel obstruction and anastomotic leakage . Surgical‐site infections , in particular , are a frequent occurrence following closure of contaminated wounds . This r and omized controlled trial compared a purse‐string closure technique with conventional linear closure BACKGROUND : The use of temporary stomas has been demonstrated to reduce septic complications , especially in high-risk anastomosis ; therefore , it is necessary to reduce the number of complications secondary to ostomy takedowns , namely wound infection , anastomotic leaks , and intestinal obstruction . OBJECTIVE : To compare the rates of superficial wound infection and patient satisfaction after pursestring closure of ostomy wound vs conventional linear closure . DESIGN : Patients undergoing colostomy or ileostomy closure between January 2010 and February 2011 were r and omly assigned to linear closure ( n = 30 ) or pursestring closure ( n = 31 ) of their ostomy wound . Wound infection within 30 days of surgery was defined as the presence of purulent discharge , pain , erythema , warmth , or positive culture for bacteria . Patient satisfaction , healing time , difficulty managing the wound , and limitation of activities were analyzed with the Likert question naire . RESULTS : The infection rate for the control group was 36.6 % ( n = 11 ) vs 0 % in the pursestring closure group ( p < 0.0001 ) . Healing time was 5.9 weeks in the linear closure group and 3.8 weeks in the pursestring group ( p = 0.0002 ) . Seventy percent of the patients with pursestring closure were very satisfied in comparison with 20 % in the other group ( p = 0.0001 ) . LIMITATIONS : This study was limited by the heterogeneity in the type of stoma in both groups . CONCLUSION : The pursestring method result ed in the absence of infection after ostomy wound closure ( shorter healing time and improved patient satisfaction ) Output:	Discussion QoL was similar in both patients groups after the first postoperative week . PSA significantly reduced SSI rate . No difference was observed in incisional hernia rate , operative time , or length of hospital stay
MS21421	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Goals of workProstate cancer patients receiving and rogen deprivation therapy ( ADT ) are vulnerable to a number of potentially debilitating side effects , which can significantly impact quality of life . The role of alternate therapies , such as physical activity ( PA ) , in attenuating these side effects is largely understudied for such a large population . Thus , the purpose of this study was to investigate the effects of PA intervention for men receiving ADT on PA behavior , quality of life , and fitness measures . Patients and methods One hundred participants were r and omized into an intervention ( n = 53 ) or a wait-list control group ( n = 47 ) , with 11 dropping out of the intervention group and 23 dropping out of the wait-list control group prior to post-testing . The intervention consisted of both an individually tailored home-based aerobic and light resistant training program and weekly group sessions . PA , quality of life , fitness , and physiological outcomes were assessed pre and post the 16-week intervention . Results Significant increases in PA , supported by changes in girth measures and blood pressure , support the beneficial impact of the intervention . Positive trends were also evident for depression and fatigue . However , due to the high dropout rate , these results must be interpreted with caution . Conclusions PA effectively attenuates many of the side effects of ADT and should be recommended to prostate survivors as an alternate therapy . Determining the maintenance of this behavior change will be important for underst and ing how the long-term benefits of increased activity levels may alleviate the late effects of ADT Multiple exercise interventions have shown beneficial effects on fatigue and quality of life ( QoL ) in cancer patients , but various psychosocial interventions as well . It is unclear to what extent the observed effects of exercise interventions are based on physical adaptations or rather on psychosocial factors associated with supervised , group-based programs . It needs to be determined which aspects of exercise programs are truly effective . Therefore , we aim ed to investigate whether resistance exercise during chemotherapy provides benefits on fatigue and QoL beyond potential psychosocial effects of group-based interventions . One-hundred-one breast cancer patients starting chemotherapy were r and omly assigned to resistance exercise ( EX ) or a relaxation control ( RC ) group . Both interventions were supervised , group-based , 2/week over 12 weeks . The primary endpoint fatigue was assessed with a 20-item multidimensional question naire , QoL with the EORTC QLQ-C30/BR23 . Analyses of covariance for individual changes from baseline to Week 13 were calculated . In RC , total and physical fatigue worsened during chemotherapy , whereas EX showed no such impairments ( between-group p = 0.098 and 0.052 overall , and p = 0.038 and 0.034 among patients without severe baseline depression ) . Differences regarding affective or cognitive fatigue were not significant . Benefits of EX were also seen to affect role and social function . Effect sizes were between 0.43 and 0.48 . Explorative analyses indicated significant effect modification by thyroxin use ( p-interaction = 0.044 ) . In conclusion , resistance exercise appeared to mitigate physical fatigue and maintain QoL during chemotherapy beyond psychosocial effects inherent to supervised group-based setting s. Thus , resistance exercise could be an integral part of supportive care for breast cancer patients undergoing chemotherapy Purpose This study aims to evaluate the feasibility and efficacy of an 8-week supervised exercise program in de-conditioned cancer survivors within 2–6 months of chemotherapy completion . Methods Participants were r and omly assigned to an 8-week , twice-weekly , supervised aerobic exercise training regime ( n = 23 ) or a usual care group ( n = 20 ) . Feasibility was assessed by recruitment rate , program adherence and participant feedback . The primary outcome was aerobic fitness assessed by the Modified Bruce fitness test at baseline ( 0 weeks ) , post-intervention ( 8 weeks ) and at 3-month follow-up . Secondary outcomes included physical activity , waist circumference , fatigue and quality of life . Results The recruitment rate was 81 % and adherence to the supervised exercise was 78.3 % . Meaningful differences in aerobic fitness between the exercise and usual care groups at both the 8-week [ mean 3.0 mL kg−1 min−1 ( 95 % CI −1.1–7.0 ) ] and 3-month follow-up [ 2.1 mL kg−1 min−1 ( −2.3–6.6 ) ] were found , although these differences did not achieve statistical significance ( p values > 0.14 ) . Self-reported physical activity increased in the exercise group ( EG ) compared to the usual care group at both 8-week ( p = 0.01 ) and 3-month follow-up ( p = 0.03 ) and significant differences in favour of the EG were found for physical well-being at both the 8-week ( p = 0.03 ) and 3-month follow-up ( p = 0.04 ) . Improvements in fatigue ( p = 0.01 ) , total quality of life plus fatigue ( p = 0.04 ) , and a composite physical functioning score ( p = 0.01 ) at the 3-month follow-up were also found . Conclusion The PEACH trial suggests that 8 weeks of supervised aerobic exercise training was feasible and may improve aerobic fitness , fatigue and quality of life in de-conditioned cancer survivors during the early survivorship phase . Implication s for Cancer SurvivorsExercise interventions commenced in the early survivorship phase appear safe , feasible and may lead to improvements in QOL and fatigue Background Today , the 5-year relative survival rate for cancer is 65 % and there are 10.5 million survivors . The largest group of survivors are those of breast cancer . Reductions in mortality are occurring at a greater rate for women under age 50 at diagnosis than among older women . Aims Our goal was to design a socio-educational intervention for 5-year survivors aged 50 or younger at diagnosis and test the hypotheses that women in the intervention group would show greater improvement than controls with respect to ( 1 ) knowledge of breast cancer , its treatment , and long-term health concerns ; ( 2 ) lifestyle habits ( i.e. , exercise and diet ) ; and ( 3 ) communication with family and physicians . Methods Using a r and omized controlled trial with a pre-post design , 404 women who were 5 years from diagnosis and cancer-free ( response rate 54 % ) were r and omly assigned to an intervention or delayed intervention ( control ) group and were assessed at pre-test ( baseline ) and 6 months later ( 96 % retention ) . The intervention consisted of three 6-h workshops over a 3 month period . Four series of workshops were held at different geographical areas in the greater San Francisco Bay Area . The workshops included activities and information to promote physical , social , emotional , and spiritual well-being . The intervention design was based on findings from focus groups and a survey of 185 cancer-free 5-year survivors that assessed changes since the early months after diagnosis in physical , social , emotional , and spiritual concerns ( response rate 73 % ) . Results Consistent with our first hypothesis , at post-test , women in the intervention group , on average , had greater knowledge regarding breast cancer , its treatment , and their own future health than did those in the control group ( p = 0.015 ) . Hypothesis 2 was partially supported as women in the intervention group were more likely than the control group to report an increased amount of physical activity ( p = 0.036 ) , but not significant dietary changes . Social support was related to increased self report of physical activity . With the exception of the last series of workshops , the intervention group did not report improved communications with family , friends , and physicians ( hypothesis 3 ) . Conclusions A short-term intervention can affect knowledge levels and physical activity but not diet or communication in the family . Implication s for Cancer SurvivorsThe intervention was related to greater knowledge related to breast cancer , and increased report of physical activity . The program was not related to changes in reported diet or family communication PURPOSE Interventions to increase physical activity among breast cancer survivors are needed to improve health and quality of life and possibly to reduce the risk of disease recurrence and early mortality . Therefore , we report the feasibility and preliminary outcomes of a pilot r and omized trial design ed to increase physical activity in sedentary breast cancer survivors receiving hormone therapy . METHODS Forty-one sedentary women on estrogen receptor modulators or aromatase inhibitors for stage I , II , or IIIA breast cancer were r and omly assigned to receive a 12-wk multidisciplinary physical activity behavior change intervention or usual care . RESULTS Recruitment was 34 % , intervention adherence was 99 % , and complete follow-up data were obtained on 93 % . Most participants ( 93 % ) were white with mean age of 53 + /- 9 yr . Differences favoring the intervention group were noted for accelerometer physical activity counts ( mean difference = 72,103 ; 95 % confidence interval ( CI ) = 25,383 - 119,000 ; effect size ( d ) = 1.02 ; P = 0.004 ) , aerobic fitness ( mean difference = 2.9 ; 95 % CI = -0.1 to 5.8 ; d = 0.64 ; P = 0.058 ) , back/leg muscle strength ( mean difference = 12.3 ; 95 % CI = 0.4 - 15.9 ; d = 0.81 ; P = 0.017 ) , waist-to-hip ratio ( mean difference = -0.05 ; 95 % CI = -0.01 to -0.08 ; d = -0.77 ; P = 0.018 ) , and social well-being ( mean difference = 2.0 ; 95 % CI = 0.3 - 3.8 ; d = 0.76 ; P = 0.03 ) . However , the intervention group also reported a greater increase in joint stiffness ( mean difference = 1.1 ; 95 % CI = 0.1 - 2.2 ; d = 0.70 ; P = 0.04 ) . CONCLUSIONS A behavior change intervention for breast cancer survivors based on the social cognitive theory is feasible and results in potentially meaningful improvements in physical activity and selected health outcomes . Confirmation in a larger study is warranted Physical activity has been deemed safe and effective in reducing many negative side effects of treatment for cancer survivors and promoting better overall health . However , most of this research has focused on highly controlled r and omized trials and little of this research has been translated into care or policy for survivors . The purpose of the present article is to present a research agenda for the field to accelerate the dissemination and implementation of empirically supported physical activity interventions into care . We provide rationale for the role of basic , behavioral , clinical implementation , and population scientists in moving this science forward and call for a more coordinated effort across different phases of research . In addition , we provide key strategies and examples for ongoing and future studies using the RE- AIM ( reach , efficacy/effectiveness , adoption , implementation , and maintenance ) framework and pose recommendations for collaborations between research ers and stakeholders to enhance the integration of this research into policy and practice . Overall , we recommend that physical activity and cancer survivorship research use additional study design s , include relevant stakeholders , and be more collaborative , integrated , context ual , and representative in terms of both setting and participants . Cancer Epidemiol Biomarkers Prev ; 23(5 ) ; 687–99 . © 2014 AACR Background . Physical activity has been demonstrated to increase survival in breast cancer patients , but few breast cancer patients meet the general recommendations for physical activity . The aim of this pilot study was to investigate if a supervised integrated counseling and group-based exercise program could increase leisure-time activity in women with breast cancer . Methods . This pilot project , design ed as a single-arm study with pre-post testing , consisted of 24 classes of combined aerobic and strength exercise training as well as classes on dietary and health behavior . A total of 48 women with breast cancer who were undergoing or had recently completed anticancer treatment completed the study . Leisure-time physical activity , grip strength , functional capacity , quality of life ( QoL ) , and depression were assessed at baseline , after intervention , and at the 12-week follow-up after intervention . Results . The breast cancer patients increased their leisure-time physical activity ( P = .004 ) , global strength ( P = .004 ) , functional capacity ( P = .001 ) , and QoL ( P = .009 ) , and their depression score ( P = .004 ) significantly decreased . These improvements were independent of whether the patients were in ongoing therapy or had completed their treatment . Conclusion . This integrated intervention may produce lifestyle changes in breast cancer patients and survivors using the teachable moment to increase their leisure-time physical activity and , thereby , their Introduction Breast cancer survival rates are lower for African American women than for white women . Obesity , high-fat diets , and lack of regular physical activity increase risk for breast cancer recurrence , comorbid conditions , and premature death . Eighty-two percent of African American women are overweight or obese , partly because of unhealthy eating and exercise patterns . Although successful weight loss and lifestyle interventions for breast cancer survivors are documented , none has considered the needs of African American breast cancer survivors . This study assessed the feasibility and impact of Moving Forward , a culturally tailored weight loss program for African American breast cancer survivors . Methods The study used a pre-post design with a convenience sample of 23 African American breast cancer survivors . The 6-month intervention was theory-based and incorporated qualitative data from focus groups with the targeted community , urban African American breast cancer survivors . Data on weight , body mass index ( BMI ) , diet , physical activity , social support , and quality of Output:	Conclusions The additional benefit of group dynamics – based interventions for increasing PA in cancer survivors remains unclear .
MS21422	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: EDITORIAL COMMENT : This vignette draws attention to a detail of surgical technique familiar to all surgeons who perform the Pfannenstiel incision . Freeing the insertion of the pyramidalis muscles from the rectus sheath is often untidy and can cause considerable haemorrhage . Our literature search confirms the opinion of the review ers of this paper that nonfreeing of the lower leaf of the rectus sheath at Caesarean section is a new idea and so this brief ‘ r and omized controlled trial ’ was accepted for publication . One review er wondered if the trauma to the pyramidalis muscles often encountered at Caesarean section is due to variation in the level ( i.e. distance above pubic symphysis ) of the transverse skin incision , or variation in the anatomy of the pyramidalis muscles . Readers will accept the shorter time interval to reach the abdominal cavity with the technique described but may wonder if the time from entry of the abdomen to exit of the fetus from the uterus was affected , especially in cases of repeat Caesarean section where scar tissue might affect the ease of manipulation . One review er of this manuscript stated that the concept of not separating the rectus sheath from the underlying muscles is not entirely new since S. Joel Cohen advocated the technique in 1972 ( Joel Cohen , S. A technique of abdominal and vaginal hysterectomy based on time and motion studies . Heinemann , London 1972 , p10 ) OBJECTIVE A new technical variant of caesarean section was described a few years ago , which is characterised by blunt surgical preparation and simplified seam technique . A prospect i ve investigation compared the differences in the surgery and postoperative process as well as the rate of complications between this Misgav Ladach method and the conventional technique of Sectio . The individual postoperative well-being of the women was recorded by visual analog scales . - PATIENTS AND METHODS Women , whom realize the including criteria s ( first caesarean section , > /= 32 . week of pregnancy , one baby ) , were examined in this study over one year : 105 patients operated with the Misgav Ladach method and 67 conventionally operated patients . The patients were r and omized in a function of the first letter of the surname ( A-K : Misgav-Ladach method ; L-Z : classical technique ) . - RESULTS The surgical time from the cut to the seam was significantly shorter ( 29.8 vs. 49.3 min ; p < 0,001 ) in the Misgav Ladach group . There were no differences between the two methods in the rate of postoperative complications . The febrile morbidity was equivalent in both groups ( 7.6 % vs. 9 % ) , likewise the frequency of postoperative hematomas ( 3.8 % vs. 3 % ) . The postoperative period with consumption of analgetics was significantly longer in the group of conventionally operated patients ( 1.9 d vs. 2.4 d ; p < 0.01 ) . The postoperative presentness was estimated significantly better ( p < 0,.01 ) by the patients of the Misgav ladach group - probably caused by the significantly earlier mobilization ( p < 0.05 ) . - CONCLUSION The surgical technique described by Misgav and Ladach allows a safe execution of the caesarean section and represents an alternative to the conventional method . The duration of operation ( cut-seam-time ) was significantly shorter . The technique of less traumatising of tissue caused a significantly earlier mobilisation and a significantly shorter requirement of analgetics . The women estimated her postoperative physical condition as better The Joel-Cohen incision followed by nonclosure of pelvic and parietal peritoneum has been advocated as an alternative method to the Pfannenstiel incision with peritonealization at cesarean section . A r and omized trial was design ed to compare intra- and postoperative morbidity between the two techniques . Women to undergo a cesarean section were r and omly allocated to have either the Joel-Cohen incision with the parietal and pelvic peritoneum left open ( group 1 ) or to have the Pfannenstiel incision with both peritoneal layers sutured ( group 2 ) . The myometrium was closed with 1 - 0 polyglactin 910 suture using a continuous single-layer nonlocking technique . Patients in group 2 had the peritoneum approximated with 2 - 0 polyglactin 910 suture . The fascia was sutured with continuous 1 - 0 polyglactin 910 suture in all cases . Opening time was defined as the interval from skin incision to the opening of the uterine cavity . Febrile morbidity was defined as a temperature > or = 38 degrees C on two occasions 4 hours ( hr ) apart excluding the first postoperative day . Endometritis was defined as postpartum temperature > or = 38 degrees C on two occasions 4 hr apart , with uterine tenderness and /or foul-smelling lochia . One hundred forty-nine and 150 patients were allocated to group 1 and to group 2 , respectively . A shorter median ( range ) opening time [ 4 min ( 2 - 21 ) vs. 6 min ( 2 - 19 ) , respectively , p < 0.01 ] and a shorter median ( range ) operative time [ 30 min ( 10 - 65 ) vs. 40 min ( 20 - 110 ) , respectively , p < 0.01 ] were observed in group 1 . No difference was found in terms of intraoperative complications , proportion of patients who required transfusion , endometritis , sepsis , febrile morbidity , and urinary tract infections . A higher rate of wound infections was found in group 2 than in group 1 [ 14 of 150 ( 9.3 % ) vs. 2 of 149 ( 1.3 % ) , respectively , p < 0.01 ] . The Joel-Cohen incision without peritonealization result ed in a shorter opening and total operative time than the Pfannenstiel laparotomy with peritonealization . This was accomplished with a reduction of wound infections Design CORONIS is a pragmatic multicentre fractional factorial r and omised controlled trial and is being conducted in sites in Argentina , Chile , Ghana , India , Kenya , Pakistan and Sudan [ 1 ] . Women are eligible if they are undergoing their first or second caesarean section through a transverse abdominal incision . Five comparisons will be carried out using a 2 balanced incomplete block factorial design . Each woman is allocated THREE of the five pairs of interventions using a bespoke secure webbased r and omisation system ( with 24/7 automated backup telephone system ) hosted by the NPEU Clinical Trials Unit . The 5 pairs of interventions are : i. Blunt versus sharp abdominal entry ii . Exteriorisation of the uterus for repair versus intraabdominal repair iii . Single versus double layer closure of the uterus iv . Closure versus non-closure of the peritoneum ( pelvic and parietal ) v. Chromic catgut versus Polyglactin-910 for uterine repair Primary outcome : death or maternal infectious morbidity ( one or more of the following : antibiotic use for maternal febrile morbidity during postnatal hospital stay , antibiotic use for endometritis , wound infection or peritonitis ) or further operative procedures or blood transfusion . Sample size required : 15,000 women in total ; minimum 9,000 women per comparison pair In recent years Stark and colleagues ( 1 , 2 ) proposed the application to the cesarean section of a number of new surgical techniques adopted from various sources : the differences with respect to the traditional procedures were the Joel-Cohen methods for opening the abdomen , suturing the uterus in one layer , and non-closure of the visceral and parietal peritoneal layers . They demonstrated that this cesarean section procedure is safe , fast and has a low risk of postoperative complications in the mothers ( 2 ) and therefore this technique has been adopted in many centers . Nevertheless , the possible consequences of these changes on the short-term outcome of the newborn have never been evaluated . Cesarean section and maternal anesthesia are risk factors for the respiratory distress syndrome , transient tachypnea and respiratory depression in the newborn infants ( 3 ) and , therefore , we wanted to evaluate if a cesarean section technique presumably faster than the traditional procedure could improve the short-term outcome of the newborns Background Caesarean section is one of the most commonly performed operations on women throughout the world . Rates have increased in recent years – about 20–25 % in many developed countries . Rates in other parts of the world vary widely . A variety of surgical techniques for all elements of the caesarean section operation are in use . Many have not yet been rigorously evaluated in r and omised controlled trials , and it is not known whether any are associated with better outcomes for women and babies . Because huge numbers of women undergo caesarean section , even small differences in post-operative morbidity rates between techniques could translate into improved health for substantial numbers of women , and significant cost savings . Design CORONIS is a multicentre , fractional , factorial r and omised controlled trial and will be conducted in centres in Argentina , Ghana , India , Kenya , Pakistan and Sudan . Women are eligible if they are undergoing their first or second caesarean section through a transverse abdominal incision . Five comparisons will be carried out in one trial , using a 2 × 2 × 2 × 2 × 2 fractional factorial design . This design has rarely been used , but is appropriate for the evaluation of several procedures which will be used together in clinical practice . The interventions are : • Blunt versus sharp abdominal entry • Exteriorisation of the uterus for repair versus intra-abdominal repair • Single versus double layer closure of the uterus • Closure versus non-closure of the peritoneum ( pelvic and parietal ) • Chromic catgut versus Polyglactin-910 for uterine repair The primary outcome is death or maternal infectious morbidity ( one or more of the following : antibiotic use for maternal febrile morbidity during postnatal hospital stay , antibiotic use for endometritis , wound infection or peritonitis ) or further operative procedures ; or blood transfusion . The sample size required is 15,000 women in total ; at least 7,586 women in each comparison . Discussion Improvements in health from optimising caesarean section techniques are likely to be more significant in developing countries , because the rates of postoperative morbidity in these countries tend to be higher . More women could therefore benefit from improvements in techniques . Trial registration The CORONIS Trial is registered in the Current Controlled Trials registry . ISCRTN31089967 The ease of execution and the post-operative quality of 2 types of incision commonly performed in pelvic surgery were compared in a prospect i ve r and omised study : Pfannenstiel 's incision was used in 59 patients and Mouchel 's low transverse abdominal incision ( LTA ) in 60 patients . Results were evaluated 8 days and 3 months after the operation . There was no difference in immediate post-operative results between these two groups of patients . At the 3 month examination , hypoaesthesia of the skin was less frequent in patients who had been operated upon through the LTA incision . The authors conclude that the transmuscular incision is innocuous OBJECTIVE To compare the Pfannenstiel incision with transverse muscle‐cutting Maylard incision in women who had cesarean delivery . METHODS Patients were assigned r and omly to a Pfannenstiel or Maylard incision . Postoperative ttreatment was similar for each group . Surgical characteristics , complications , postoperative pain ( visual analog scale , analgesic use ) , and related quality of life ( 1‐ and 3‐month self‐administered question naires ) were analyzed . Abdominal wall muscle recovery was compared objective ly by dynamometer . RESULTS Fifty‐four women had a Pfannenstiel incision and 43 had the Maylard incision . There were no differences in intraoperative characteristics , postoperative morbidity , or pain . Women 's responses to the Nottingham Health Profile question naire at 1 and 3 months postoperatively and clinical and isokinetic testing for abdominal wall strength were similar between the two groups . CONCLUSION Transecting the rectus muscle was no more deleterious than the Pfannenstiel incision . There was no difference in objective ly measured abdominal wall strength OBJECTIVE The aim of the study was to evaluate the outcome of two different methods of cesarean section ( CS ) . DESIGN The study was design ed as a prospect i ve , r and omized , controlled trial . SETTING All CS were performed at the University Hospital in Uppsala , Sweden . POPULATION Fifty women admitted to hospital for a first elective CS were consecutively included in the study . They were r and omly allocated to two groups . METHODS One group was operated on by the Misgav Ladach method for CS and the other group by the Pfannenstiel method . All operations were performed by the same surgeon . MAIN OUTCOME MEASURES Duration of operation , amount of bleeding , analgesics required , scar appearance and length of hospitalization . RESULTS Operating time was significantly different between the two methods , with an average of 12.5 minutes with the Misgav Ladach method and 26 minutes with the Pfannenstiel method ( p<0.001 ) . The amount of blood loss differed significantly , with 448 ml and 608 ml respectively ( p=0.017 ) . Significantly less analgesic injections and tablets ( p=0.004 ) were needed after the Misgav Ladach method . CONCLUSION The Misgav Ladach method of CS has advantages over the Pfannenstiel method by being significantly quicker to perform , with a reduced amount of bleeding and diminished postoperative pain . The women were satisfied with the appearance of their scars . In this study no negative effects of the new operation technique were discovered Cesarean delivery may be complicated by dystocia if the incision size is in Output:	The Joel-Cohen incision has advantages compared with the Pfannenstiel incision . These are : less fever , pain and analgesic requirements ; less blood loss ; shorter duration of surgery and hospital stay . These advantages for the mother could be extrapolated to savings for the health system . However , these trials do not provide information on severe or long-term morbidity and mortality
MS21423	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Objective To investigate whether sleep deprived people are perceived as less healthy , less attractive , and more tired than after a normal night ’s sleep . Design Experimental study . Setting Sleep laboratory in Stockholm , Sweden . Participants 23 healthy , sleep deprived adults ( age 18 - 31 ) who were photographed and 65 untrained observers ( age 18 - 61 ) who rated the photographs . Intervention Participants were photographed after a normal night ’s sleep ( eight hours ) and after sleep deprivation ( 31 hours of wakefulness after a night of reduced sleep ) . The photographs were presented in a r and omised order and rated by untrained observers . Main outcome measure Difference in observer ratings of perceived health , attractiveness , and tiredness between sleep deprived and well rested participants using a visual analogue scale ( 100 mm ) . Results Sleep deprived people were rated as less healthy ( visual analogue scale scores , mean 63 ( SE 2 ) v 68 ( SE 2 ) , P<0.001 ) , more tired ( 53 ( SE 3 ) v 44 ( SE 3 ) , P<0.001 ) , and less attractive ( 38 ( SE 2 ) v 40 ( SE 2 ) , P<0.001 ) than after a normal night ’s sleep . The decrease in rated health was associated with ratings of increased tiredness and decreased attractiveness . Conclusion Our findings show that sleep deprived people appear less healthy , less attractive , and more tired compared with when they are well rested . This suggests that humans are sensitive to sleep related facial cues , with potential implication s for social and clinical judgments and behaviour . Studies are warranted for underst and ing how these effects may affect clinical decision making and can add knowledge with direct implication s in a medical context Converging evidence from animal and human studies suggest that rapid eye movement ( REM ) sleep modulates emotional processing . The aim of the present study was to explore the effects of selective REM sleep deprivation ( REM-D ) on emotional responses to threatening visual stimuli and their brain correlates using functional magnetic resonance imaging ( fMRI ) . Twenty healthy subjects were r and omly assigned to two groups : selective REM-D , by awakening them at each REM sleep onset , or non-rapid eye movement sleep interruptions ( NREM-I ) as control for potential non-specific effects of awakenings and lack of sleep . In a within-subject design , a visual emotional reactivity task was performed in the scanner before and 24 h after sleep manipulation . Behaviorally , emotional reactivity was enhanced relative to baseline ( BL ) in the REM deprived group only . In terms of fMRI signal , there was , as expected , an overall decrease in activity in the NREM-I group when subjects performed the task the second time , particularly in regions involved in emotional processing , such as occipital and temporal areas , as well as in the ventrolateral prefrontal cortex , involved in top-down emotion regulation . In contrast , activity in these areas remained the same level or even increased in the REM-D group , compared to their BL level . Taken together , these results suggest that lack of REM sleep in humans is associated with enhanced emotional reactivity , both at behavioral and neural levels , and thus highlight the specific role of REM sleep in regulating the neural substrates for emotional responsiveness The aim of this pilot study was to quantify the impact of sleep deprivation on psychophysiological reactivity to emotional stimuli . Following an adaptation night of sleep in the lab , healthy young adults were r and omly assigned to either one night of total sleep deprivation or to a normal sleep control condition . The next afternoon , responses to positive , negative , and neutral picture stimuli were examined with pupillography , an indicator of cognitive and affective information processing . Only the sleep-deprived group displayed significantly larger pupil diameter while viewing negative pictures compared to positive or neutral pictures . The sleep-deprived group also showed anticipatory pupillary reactivity during blocks of negative pictures . These data suggest that sleep deprivation is associated with increased reactions to negative emotional information . Such responses may have important implication s for psychiatric disorders , which may be triggered or characterized by sleep disturbances This study examines the individual reproducibility of alterations of subjective , objective , and EEG measures of alertness during 27 h of continuous wakefulness and analyzes their interrelationships . Eight subjects were studied twice under similar constant-routine conditions . Scales and performance tasks were administered at hourly intervals to define temporal changes in subjective and objective alertness . The wake EEG was recorded every 2 h , 2 min with eyes open and 2 min with eyes closed . Plasma glucose and melatonin levels were measured to estimate brain glucose utilization and individual circadian phase , respectively . Decrements of subjective alertness and performance deficits were found to be highly reproducible for a given individual . Remarkably , there was no relationship between the impairments of subjective and objective alertness . With increased duration of wakefulness , EEG activity with eyes closed increased in the delta range and decreased in the alpha range , but the magnitudes of these changes were also unrelated . These findings indicate that sleep deprivation has highly reproducible , but independent , effects on brain mechanisms controlling subjective and objective alertness OBJECTIVES To inform the debate over whether human sleep can be chronically reduced without consequences , we conducted a dose-response chronic sleep restriction experiment in which waking neurobehavioral and sleep physiological functions were monitored and compared to those for total sleep deprivation . DESIGN The chronic sleep restriction experiment involved r and omization to one of three sleep doses ( 4 h , 6 h , or 8 h time in bed per night ) , which were maintained for 14 consecutive days . The total sleep deprivation experiment involved 3 nights without sleep ( 0 h time in bed ) . Each study also involved 3 baseline ( pre-deprivation ) days and 3 recovery days . SETTING Both experiments were conducted under st and ardized laboratory conditions with continuous behavioral , physiological and medical monitoring . PARTICIPANTS A total of n = 48 healthy adults ( ages 21 - 38 ) participated in the experiments . INTERVENTIONS Noctumal sleep periods were restricted to 8 h , 6 h or 4 h per day for 14 days , or to 0 h for 3 days . All other sleep was prohibited . RESULTS Chronic restriction of sleep periods to 4 h or 6 h per night over 14 consecutive days result ed in significant cumulative , dose-dependent deficits in cognitive performance on all tasks . Subjective sleepiness ratings showed an acute response to sleep restriction but only small further increases on subsequent days , and did not significantly differentiate the 6 h and 4 h conditions . Polysomnographic variables and delta power in the non-REM sleep EEG-a putative marker of sleep homeostasis -- displayed an acute response to sleep restriction with negligible further changes across the 14 restricted nights . Comparison of chronic sleep restriction to total sleep deprivation showed that the latter result ed in disproportionately large waking neurobehavioral and sleep delta power responses relative to how much sleep was lost . A statistical model revealed that , regardless of the mode of sleep deprivation , lapses in behavioral alertness were near-linearly related to the cumulative duration of wakefulness in excess of 15.84 h ( s.e . 0.73 h ) . CONCLUSIONS Since chronic restriction of sleep to 6 h or less per night produced cognitive performance deficits equivalent to up to 2 nights of total sleep deprivation , it appears that even relatively moderate sleep restriction can seriously impair waking neurobehavioral functions in healthy adults . Sleepiness ratings suggest that subjects were largely unaware of these increasing cognitive deficits , which may explain why the impact of chronic sleep restriction on waking cognitive functions is often assumed to be benign . Physiological sleep responses to chronic restriction did not mirror waking neurobehavioral responses , but cumulative wakefulness in excess of a 15.84 h predicted performance lapses across all four experimental conditions . This suggests that sleep debt is perhaps best understood as result ing in additional wakefulness that has a neurobiological " cost " which accumulates over time STUDY OBJECTIVES Investigate the impact of sleep deprivation on the ability to recognize the intensity of human facial emotions . DESIGN R and omized total sleep-deprivation or sleep-rested conditions , involving between-group and within-group repeated measures analysis . SETTING Experimental laboratory study . PARTICIPANTS Thirty-seven healthy participants , ( 21 females ) aged 18 - 25 y , were r and omly assigned to the sleep control ( SC : n = 17 ) or total sleep deprivation group ( TSD : n = 20 ) . INTERVENTIONS Participants performed an emotional face recognition task , in which they evaluated 3 different affective face categories : Sad , Happy , and Angry , each ranging in a gradient from neutral to increasingly emotional . In the TSD group , the task was performed once under conditions of sleep deprivation , and twice under sleep-rested conditions following different duration s of sleep recovery . In the SC group , the task was performed twice under sleep-rested conditions , controlling for repeatability . MEASUREMENTS AND RESULTS In the TSD group , when sleep-deprived , there was a marked and significant blunting in the recognition of Angry and Happy affective expressions in the moderate ( but not extreme ) emotional intensity range ; differences that were most reliable and significant in female participants . No change in the recognition of Sad expressions was observed . These recognition deficits were , however , ameliorated following one night of recovery sleep . No changes in task performance were observed in the SC group . CONCLUSIONS Sleep deprivation selectively impairs the accurate judgment of human facial emotions , especially threat relevant ( Anger ) and reward relevant ( Happy ) categories , an effect observed most significantly in females . Such findings suggest that sleep loss impairs discrete affective neural systems , disrupting the identification of salient affective social cues Objectives Sleep debt reportedly increases emotional instability , such as anxiety and confusion , in addition to sleepiness and psychomotor impairment . However , the neural basis of emotional instability due to sleep debt has yet to be eluci date d. This study investigated changes in emotional responses that are elicited by the simulation of short-term sleep loss and the brain regions responsible for these changes . Subjects and Methods Fourteen healthy adult men aged 24.1±3.3 years ( range , 20–32 years ) participated in a within-subject crossover study consisting of 5-day sessions of both sleep debt ( 4 h for time in bed ) and sleep control ( 8 h for time in bed ) . On the last day of each session , participants underwent polysomnography and completed the State-Trait Anxiety Inventory and Profile of Mood States question naires . In addition , functional magnetic resonance imaging was conducted while performing an emotional face viewing task . Results Restricted sleep over the 5-day period increased the activity of the left amygdala in response to the facial expression of fear , whereas a happy facial expression did not change the activity . Restricted sleep also result ed in a significant decrease in the functional connectivity between the amygdala and the ventral anterior cingulate cortex ( vACC ) in proportion to the degree of sleep debt ( as indicated by the percentage of slow wave sleep and δ wave power ) . This decrease was significantly correlated with activation of the left amygdala and deterioration of subjective mood state . Conclusion The results of this study suggest that continuous and accumulating sleep debt that can be experienced in everyday life can downregulate the functional suppression of the amygdala by the vACC and consequently enhance the response of the amygdala to negative emotional stimuli . Such functional alteration in emotional control may , in part , be attributed to the neural basis of emotional instability during sleep debt STUDY OBJECTIVES This study investigated the extent to which sleep disturbance in the period immediately prior to a traumatic event predicted development of subsequent psychiatric disorder . DESIGN Prospect i ve design cohort study . SETTING Four major trauma hospitals across Australia . PATIENTS A total of 1033 traumatically injured patients were initially assessed during hospital admission and followed up at 3 months ( 898 ) after injury . MEASURES Lifetime psychiatric disorder was assessed in hospital with the Mini-International Neuropsychiatric Interview . Sleep disturbance in the 2 weeks prior to injury was also assessed using the Sleep Impairment Index . The prevalence of psychiatric disorder was assessed 3 months after traumatic injury . RESULTS There were 255 ( 28 % ) patients with a psychiatric disorder at 3 months . Patients who displayed sleep disturbance prior to the injury were more likely to develop a psychiatric disorder at 3 months ( odds ratio : 2.44 , 95 % CI : 1.62 - 3.69 ) . In terms of patients who had never experienced a prior disorder ( n = 324 ) , 96 patients ( 30 % ) had a psychiatric disorder at 3 months , and these patients were more likely to develop disorder if they displayed prior sleep disturbance ( odds ratio : 3.16 , 95 % CI : 1.59 - 4.75 ) . CONCLUSIONS These findings provide evidence that sleep disturbance prior to a traumatic event is a risk factor for development of posttraumatic psychiatric disorder The purpose of this study was to evaluate the influence of sleep deprivation on emotional expression and subjective emotional experience in a highly controlled , laboratory setting . Twenty-three healthy adult participants watched positive ( amusing ) and negative ( sad ) film clips before and after they were r and omly assigned to a night of sleep deprivation or a normal sleep control condition . The intensity of their facial expressiveness while viewing the films was coded by human judges and compared to their subjective emotional responses . Relative to the control group , sleep-deprived participants demonstrated less expressiveness , especially in response to positive stimuli . Subjective responses were not significantly different between the sleep-deprived and control groups . These preliminary results suggest that sleep deprivation is associated with attenuated emotional expressiveness in healthy adults Cognitive abilities such as vigilance , attention , memory , and executive functioning can be de grade d significantly following extended periods of wakefulness Output:	From the review ed literature , sleep deprivation is associated with diminished emotional expressivity and impaired emotion recognition , and this has particular relevance for social interactions . Sleep deprivation also increases emotional reactivity ; results which are most apparent with neuro-imaging studies investigating amygdala activity and its prefrontal regulation . Evidence of emotional dysregulation in insomnia and poor sleep has also been reported .
MS21424	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: BACKGROUND We previously reported urinary podocytes to be a marker of glomerular injury . The aim of the present study was to determine whether cerivastatin , a newly developed , potent synthetic statin , affects proteinuria and urinary podocyte excretion in patients with chronic glomerulonephritis ( CGN ) . METHODS We r and omly assigned 40 normotensive hypercholesterolemic patients with CGN to receive either cerivastatin 0.15 mg/day ( n=20 ) or placebo ( n=20 ) . Subjects comprised 24 men and 16 women , with a mean age of 40.8+/-14.4 years ; 27 had IgA nephropathy and 13 had non-IgA proliferative glomerulonephritis . Treatment was continued for 6 months . Plasma total cholesterol , HDL-cholesterol , LDL-cholesterol and triglycerides , urinary protein excretion and the number of podocytes were measured before treatment and at 3 and 6 months after treatment . RESULTS After 6 months , a significant reduction in total cholesterol ( P<0.001 ) , LDL-cholesterol ( P<0.001 ) and triglycerides ( P<0.05 ) , and a significant increase in HDL-cholesterol ( P<0.001 ) were observed in the group treated with cerivastatin . Urinary protein excretion decreased from 1.8+/-0.6 to 0.8+/-0.4 g/day , ( P<0.01 ) in this group , and urinary podocyte excretion decreased from 1.6+/-0.6 to 0.9+/-0.4 cells/ml ( P<0.01 ) . However , placebo showed little effect on these lipid levels , urinary protein excretion and urinary podocyte excretion . The differences between the cerivastatin group and the placebo group were significant ( cholesterol , P<0.001 ; LDL-cholesterol , P<0.001 ; triglycerides , P<0.05 ; HDL-cholesterol , P<0.001 ; urinary protein , P<0.01 ; and urinary podocytes , P<0.01 ) . CONCLUSION Statins such as cerivastatin may be beneficial for restoration of injured podocytes in patients with CGN and hypercholesterolaemia BACKGROUND Serum creatinine-based estimates of glomerular filtration rate ( eGFR ) are frequently used to identify patients with chronic kidney disease and assess cardiovascular risk both in clinical trials and in clinical practice . Although change in eGFR may be useful to assess change in renal function in patients with chronic kidney disease , the utility of serum creatinine-based eGFR is uncertain , particularly among individuals with normal or only mildly impaired renal function . OBJECTIVE The goal of this study was to examine the relationship between baseline serum creatinine and eGFR , as well as changes in these parameters , in apparently healthy adults in a post hoc analysis of data obtained in participants in the JUPITER study ( Justification for the Use of Statins in Prevention : An Intervention Trial Evaluating Rosuvastatin ) . METHODS JUPITER was a r and omized study of rosuvastatin 20 mg versus placebo in apparently healthy adults with high-sensitivity C-reactive protein levels ≥ 2.0 mg/L , LDL-C < 130 mg/dL , and serum creatinine ≤ 2.0 mg/dL. Changes from baseline in serum creatinine and eGFR , based on the Modification of Diet in Renal Disease ( MDRD ) and Chronic Kidney Disease Epidemiology Collaboration ( CKD-EPI ) equations , were assessed in the entire population and in subsets classified according to baseline eGFR status . RESULTS Baseline characteristics of the 16,279 JUPITER study participants ( mean age , 66 years ; 62 % men ; 72 % white ; and 58 % with a history of hypertension ) who had both a baseline and ≥ 1 postbaseline serum creatinine measurement were similar to the entire population of 17,802 patients who entered the trial . The mean age of the study population was 66 years , 62 % were men , 72 % were white , and 58 % had a history of hypertension . Mean ( SD ) serum creatinine increased from baseline by 0.08 ( 0.16 ) mg/dL and 0.09 ( 0.14 ) mg/dL in the rosuvastatin and placebo groups , respectively ( P = 0.001 ) at year 1 and by 0.09 ( 0.18 ) and 0.10 ( 0.16 ) mg/dL ( P = 0.0045 ) at the final visit . Reductions in MDRD and CKD-EPI eGFR were ∼ 0.5 mL/min/1.73 m(2 ) greater with placebo than with rosuvastatin ( P < 0.004 ) at year 1 and the final visit . The magnitude of eGFR change was closely related to baseline eGFR , with greater reductions among subjects with eGFR ≥ 60 mL/min/1.73 m(2 ) in both the rosuvastatin and placebo groups . Among those with an eGFR ≥ 90 mL/min/1.73 m(2 ) , mean changes at year 1 and final visit ranged from -16 to -23 mL/min/1.73 m(2 ) with MDRD and CKD-EPI , respectively ; in contrast , mean changes were < 1 mL/min/1.73 m(2 ) in subjects with eGFR < 60 mL/min/1.73 m(2 ) . CONCLUSIONS In JUPITER , reductions in MDRD or CKD-EPI eGFR levels were greater in study participants with higher baseline eGFR levels but less in the rosuvastatin than in the placebo group . Future studies are required to assess the reliability of serum creatinine-based estimates of GFR to assess change in renal function , particularly among individuals with normal serum creatinine levels Objective . Autosomal dominant polycystic kidney disease ( ADPKD ) is progressive , result ing in end-stage kidney failure in most patients . Experimental and clinical studies have suggested that statins may slow the progression of chronic kidney disease in general and ADPKD specifically . Material and methods . This r and omized open-label clinical trial was conducted to assess the effect of pravastatin 20 mg on kidney function and urinary protein excretion in patients with ADPKD . Sixty patients were initially recruited but 49 of these received either pravastatin 20 mg or no treatment for 2 years . Trial visits were conducted every 3 months , assessing kidney function by estimated glomerular filtration rate and 24 h urine creatinine clearance and urinary protein excretion . Results . There were no significant ( p > 0.05 ) changes in markers of kidney function or urinary protein excretion between groups over the 2 years despite a significant fall in total serum cholesterol in pravastatin-treated patients ( p = 0.029 ) . Conclusion . This trial found that taking 20 mg pravastatin for 2 years had no significant effect on kidney function or urinary protein excretion in patients with ADPKD . The lack of statistical power limits the external validity of these findings . A larger , longer duration study using a higher dose of a more potent statin is required BACKGROUND Chronic kidney disease ( CKD ) is associated with an increased risk of incident cardiovascular disease ( CVD ) ; however , the role of statins for the primary prevention of acute cardiovascular events in patients with CKD and the effect of statins on kidney function loss in persons without prevalent CVD have not been studied . STUDY DESIGN Post hoc analysis of the Air Force/Texas Coronary Atherosclerosis Prevention Study . SETTING & PARTICIPANTS Multicenter , r and omized , double-blind , placebo-controlled trial of 5,608 men and 997 women without CVD r and omly assigned to treatment with lovastatin or placebo . INTERVENTION Placebo or lovastatin , 20 mg/d . OUTCOMES & MEASUREMENTS First major acute cardiovascular event in participants with mild CKD and kidney function loss in persons with or without CKD . Estimated glomerular filtration rate was calculated using the 4-variable Modification of Diet in Renal Disease Study equation . RESULTS At baseline , mean estimated glomerular filtration rate in participants with CKD ( n = 304 ) was 53.0 + /- 6.0 mL/min/1.73 m(2 ) . After an average follow-up of 5.3 + /- 0.8 years , the incidence of a fatal and nonfatal CVD event was lower in participants with CKD receiving lovastatin than in those receiving placebo ( adjusted relative risk [ RR ] , 0.31 ; 95 % CI , 0.13 - 0.72 ; P = 0.01 ) . Tests for interaction suggested that the benefit of lovastatin was independent of the presence of CKD . Lovastatin did not reduce the annualized mean decrease in estimated glomerular filtration rate ( -1.3 + /- 0.07 vs -1.4 + /- 0.07 mL/min/1.73 m(2)/y , respectively ; P = 0.1 ) or the frequency of a > or = 25 % decrease in kidney function ( adjusted RR , 1.10 ; 95 % CI , 0.96 - 1.28 ; P = 0.2 ) or incident CKD ( adjusted RR , 1.04 ; 95 % CI , 0.86 - 1.27 ; P = 0.6 ) . LIMITATIONS Unable to determine the cause and duration of kidney disease , and information regarding proteinuria was not available . CONCLUSIONS Lovastatin is effective for the primary prevention of CVD in patients with CKD , but is not effective in decreasing kidney function loss in persons with no CVD In this study 43 patients with idiopathic nephrotic syndrome were r and omly distributed into 2 age- and sex-matched groups . The first group was given fluvastatin while the second was used as control . The cases in the 2 groups were evaluated clinical ly , biochemically ( creatinine clearance , albumin , 24-hour proteinuria , and lipogram ) , neurologically , and histopathologically ( examination of renal biopsies obtained basally and after 1 year of treatment with fluvastatin ) . In the fluvastatin-treated group but not in the control group , we observed a significant reduction in cholesterol , low-density lipoprotein , and triglyceride . Clinical and laboratory assessment showed satisfactory tolerance of the drug by the patients . Proteinuria , serum albumin and creatinine clearance values were significantly better in the statin-treated patients . There was no difference in glomerular sclerosis between the 2 groups while interstitial fibrosis and renal fat deposits were less in the statin-treated group . The reduction in renal fat deposits in the statin-treated group was highly significant , while that of interstitial fibrosis was not . We conclude that : ( 1 ) statin can be safely and effectively used in the treatment of dyslipidemia in patients with persistent idiopathic nephrotic syndrome ; ( 2 ) control of dyslipidemia in nephrotic patients is associated with better control of proteinuria and creatinine clearance ; ( 3 ) statin treatment may cause regression of renal fat deposits in patients with nephrotic syndrome , and ( 4 ) longer term studies are still required to study further possible beneficial effects on renal histology and disease progression BACKGROUND The effect of atorvastatin on kidney function was assessed in patients with stages 2 - 4 chronic kidney disease . METHODS We conducted a r and omised , double-blind , placebo-controlled trial in chronic kidney disease clinics in Northern Tasmania and enrolled 132 patients with serum creatinine levels > 120 μmol/l , not taking lipid-lowering therapy and at all levels of proteinuria and serum cholesterol . Patients were r and omly assigned to receive either 10 mg of atorvastatin/day ( 64 ) or placebo ( 68 ) and were followed with trial visits 3-monthly for a mean of 2.5 yrs . The primary outcome was the rate of both MDRD eGFR and Cockcroft-Gault creatinine clearance ( C-G CrCl ) decline . Analysis was based on intention to treat and included all patients that had at least one follow-up visit . RESULTS The rate of MDRD eGFR decline was 29 % lower ; 1.04 ± 3.84 vs. 1.47 ± 3.74 ml/min/1.73 m(2)/yr ( P=0.53 ) , and the C-G CrCl was 20 % lower ; 1.88 ± 5.07 vs. 2.36 ± 4.61 ml/min/1.73 m(2)/yr ( P=0.58 ) in atorvastatin-treated , compared with placebo-treated patients . Although blood pressure decreased in both atorvastatin and placebo-treated groups there were no differences between groups . In addition , there was no difference in concomitant medication intake including angiotensin converting enzyme inhibitors and angiotensin receptor blockers between groups . CONCLUSIONS There was a trend toward a slower eGFR decline in the atorv Output:	CONCLUSIONS Statin therapy does not reduce the risk for kidney failure events in adults not receiving dialysis for whom kidney disease outcomes were reported , but may modestly reduce proteinuria and rate of eGFR decline
MS21425	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: BACKGROUND CONTEXT Patients with approved workers ' compensation injuries receive guaranteed compensation for the duration of their injury , whereas patients with personal injury cl aims are only compensated , if at all , at the time of a successful settlement or trial verdict at a time point distant from their injury . PURPOSE This study compares the financial impact and loss of work patterns due to a workers ' compensation ( WC ) cl aim or personal injury in patients with a symptomatic cervical disc herniation result ing from a motor vehicle collision . STUDY DESIGN A prospect i ve study of patients who were seen by a single spine specialist between 1/2/96 and 9/1/01 . PATIENT SAMPLE A consecutive evaluation of 531 patients who were treated for a cervical pain syndrome caused by a motor vehicle collision . OUTCOME MEASURES Mechanism of injury and insurance type , ie , workers ' compensation or personal injury , was recorded for each patient as well as treatment response and return to work patterns . The data were analyzed using the two-way Z test . METHODS All patients were managed in a similar manner with noninvasive treatment initially , followed by injections , and finally surgical intervention in those who failed conservative measures . Return to work rates and work disability were determined at either final follow-up or at the last doctor 's visit before loss to follow-up . RESULTS 270 of 531 patients were diagnosed with a symptomatic one or two level disc herniation by a cervical magnetic resonance imaging scan . Fifty-four patients were insured through the workers ' compensation board , and 216 reported their crash as a personal injury cl aim . In the WC group the work disability at 3 months follow-up revealed a cumulative 2,262 total lost days of work ( average 37.1 days per person ) . At the point of maximal medical improvement ( MMI ) or 2-year follow-up , total days lost from work were 7,107 ( average 131.6 days per person . ) In the personal injury non-WC group , the 3-month follow-up of lost days of work was 1,093 days ( average 5.1 days per person . ) At 2 years follow-up , the total lost days of work were 6,206 ( average 28.7 days per person . ) CONCLUSIONS Participants compensated through the workers ' compensation system demonstrated a significant loss of days of work as compared with injured patients who received compensation by other means . This may be a reflection of the guaranteed method of compensation afforded to WC patients as opposed to patients who receive no form of financial support ( i.e. , personal injury ) during the recuperative process . Further analysis as to injury severity and a stratification of non-workers ' compensation reimbursement methods are needed to further improve the validity of this study Study Design . A prospect i ve cohort study . Objective . To assess 10-year outcomes of patients with sciatica result ing from a lumbar disc herniation treated surgically or nonsurgically . Summary of Background Data . There is little information comparing long-term outcomes of surgical and conservative therapy of lumbar disc herniation in contemporary clinical practice . Prior studies suggest that these outcomes are similar . Methods . Patients recruited from the practice s of orthopedic surgeons , neurosurgeons , and occupational medicine physicians throughout Maine had baseline interviews with follow-up question naires mailed at regular intervals over 10 years . Clinical data were obtained at baseline from a physician question naire . Primary analyses were based on initial treatment received , either surgical or nonsurgical . Secondary analyses examined actual treatments received by 10 years . Outcomes included patient-reported symptoms of leg and back pain , functional status , satisfaction , and work and disability compensation status . Results . Of 507 eligible consenting patients initially enrolled , 10-year outcomes were available for 400 of 477 ( 84 % ) surviving patients ; 217 of 255 ( 85 % ) treated surgically , and 183 of 222 ( 82 % ) treated nonsurgically . Patients undergoing surgery had worse baseline symptoms and functional status than those initially treated nonsurgically . By 10 years , 25 % of surgical patients had undergone at least one additional lumbar spine operation , and 25 % of nonsurgical patients had at least one lumbar spine operation . At 10-year follow-up , 69 % of patients initially treated surgically reported improvement in their predominant symptom ( back or leg pain ) versus 61 % of those initially treated nonsurgically ( P = 0.2 ) . A larger proportion of surgical patients reported that their low back and leg pain were much better or completely gone ( 56 % vs. 40 % , P = 0.006 ) and were more satisfied with their current status ( 71 % vs. 56 % , P = 0.002 ) . Treatment group differences persisted after adjustment for other determinants of outcome in multivariate models . Change in the modified Rol and back-specific functional status scale favored surgical treatment , and the relative benefit persisted over the follow-up period . Despite these differences , work and disability status at 10 years were comparable among those treated surgically or nonsurgically . Conclusions . Surgically treated patients with a herniated lumbar disc had more complete relief of leg pain and improved function and satisfaction compared with nonsurgically treated patients over 10 years . Nevertheless , improvement in the patient ’s predominant symptom and work and disability outcomes were similar regardless of treatment received . For patients in whom elective discectomy is a treatment option , an individualized treatment plan requires patients and their physicians to integrate clinical findings with patient preferences based on their symptoms and goals Study Design Epidemiological review of a prospect ively collected military data base . Objective This investigation sought to determine the incidence of cervical radiculopathy and risk factors for its development within the population of the United States military from 2000 to 2009 . Summary of Background Data Currently , the epidemiology of cervical radiculopathy remains poorly understood and risk factors for its development have not been reliably defined . Methods The military 's Defense Medical Epidemiological Data base was used to identify all servicemembers diagnosed with cervical radiculopathy ( International Classification of Diseases code 723.4 ) between 2000 and 2009 . Demographic data was obtained for all identified individuals including age group , sex , race , military rank , and branch of service . Like data was recorded for all servicemembers within the Armed Forces during the time period under study . The incidence of cervical radiculopathy was calculated and unadjusted incidence rate ratios were determined . Risk factors were analyzed by performing multivariate Poisson regression analysis , controlling for all other factors within the model . Results Between 2000 and 2009 , about 24,742 individuals were diagnosed with cervical radiculopathy among a population -at-risk of 13,813,333 , for an incidence of 1.79 per 1000 person-years . Statistically significant differences ( P<0.001 ) in adjusted incidence rate ratios were identified for each successive age group with mutually exclusive 95 % confidence intervals . Those age 40 years and above were found to have the greatest risk of cervical radiculopathy . Female sex ( P<0.001 ) , White race ( P<0.001 ) , senior positions within the rank structure ( P<0.001 ) , and service in the Army ( P<0.001 ) or Air Force ( P=0.01 ) were also identified as significant risk factors for cervical radiculopathy . Conclusions This study is the first to attempt to define the incidence of cervical radiculopathy and characterize risk factors for its development within an American population . Findings presented here indicate that age is most likely the greatest risk factor for cervical radiculopathy , with female sex , White race , senior military positions , and Army or Air Force service also influencing risk to varying degrees & NA ; The objective of this study is to determine whether depression is an independent risk factor for onset of an episode of troublesome neck and low back pain . There is growing evidence that pain problems increase the risk of depression . However , the evidence about the role of depression as a risk factor for onset of pain problems is contradictory . This lack of consistency in research findings may be due in part to method ological weaknesses in existing studies , for example , use of an inappropriate study design and inadequate consideration of confounding . A population ‐based r and om sample of adults was surveyed and followed at 6 and 12 months . Individuals at risk of troublesome ( intense and /or disabling ) neck or low back pain are the subjects of this report ( n=790 ) . We used Cox proportional hazards models to measure the time‐varying effect of depressive symptoms on the onset of troublesome neck and low back pain . Our multivariable analysis considered the possible confounding effects of demographic and socio‐economic factors , health status , co‐morbid medical conditions and injuries to the neck or low back . We found an independent and robust relationship between depressive symptoms and onset of an episode of pain . In comparison with the lowest quartile of scores ( the least depressed ) , those in the highest quartile of depression scores had a four‐fold increased risk of troublesome neck and low back pain ( adjusted HRR 3.97 ; 95 % CI 1.81–8.72 ) . Depression is a strong and independent predictor for the onset of an episode of intense and /or disabling neck and low back pain The therapeutic modalities available for the conservative management of chronic cervical and lumbar pain include underwater traction , the usefulness of which is not universally acknowledged . No reports have been published on clinical trials evaluating underwater traction . This study was intended to ascertain any beneficial impact of weightbath therapy on the clinical parameters and quality of life of patients with cervical/lumbar discopathy . The study population comprised 72 subjects . Two groups of 18 patients each received underwater traction therapy of the cervical or lumbar spine with add-on McKenzie exercises and iontophoresis . The remaining two groups , treated with exercises and iontophoresis , served as controls . VAS and SF36 scores , range of motion were monitored to appraise therapeutic efficacy in cervical discopathy , whereas these parameters were supplemented by the Oswestry index in lumbar discopathy . A MRI scan was done at baseline and after 3 months of follow-up . Underwater cervical or lumbar traction therapy for discopathy achieved significant improvement of all study parameters , which was still evident 3 months later . Among the controls , significant improvement of just a single parameter was seen in patients with lumbar , and of two parameters in those with cervical discopathy . Underwater traction therapy effectively mitigates pain , enhances joint flexibility , and improves the quality of life of patients with cervical or lumbar discopathy . The equipment required to administer weightbath therapy is simple to install and treatment technique is straightforward & NA ; Although neck pain is a common source of disability , little is known about its incidence and course . We conducted a population ‐based cohort study of 1100 r and omly selected Saskatchewan adults to determine the annual incidence of neck pain and describe its course . Subjects were initially surveyed by mail in September 1995 and followed‐up 6 and 12 months later . The age and gender st and ardized annual incidence of neck pain is 14.6 % ( 95 % confidence interval : 11.3 , 17.9 ) . Each year , 0.6 % ( 95 % confidence interval : 0.0–1.1 ) of the population develops disabling neck pain . The annual rate of resolution of neck pain is 36.6 % ( 95 % confidence interval : 32.7 , 40.5 ) and another 32.7 % ( 95 % confidence interval : 25.5 , 39.9 ) report improvement . Among subjects with prevalent neck pain at baseline , 37.3 % ( 95 % confidence interval : 33.4 , 41.2 ) report persistent problems and 9.9 % ( 95 % confidence interval : 7.4 , 12.5 ) experience an aggravation during follow‐up . Finally , 22.8 % ( 95 % confidence interval : 16.4 , 29.3 ) of those with prevalent neck pain at baseline report a recurrent episode . Women are more likely than men to develop neck pain ( incidence rate ratio=1.67 , 95 % confidence interval 1.08–2.60 ) ; more likely to suffer from persistent neck problems ( incidence rate ratio=1.19 , 95 % confidence interval 1.03–1.38 ) and less likely to experience resolution ( incidence rate ratio=0.75 , 95 % confidence interval 0.63–0.88 ) . Neck pain is a disabling condition with a course marked by periods of remission and exacerbation . Contrary to prior belief , most individuals with neck pain do not experience complete resolution of their symptoms and disability Study Design The Maine Lumbar Spine Study is a prospect i ve cohort study of patients recruited from the practice s of orthopedic surgeons , neurosurgeons , and occupational medicine physicians throughout Maine . Objective To assess 1‐year outcomes of patients with sciatica believed to be due to a herniated lumbar disc treated surgically or nonsurgically . Summary of Background Data Lumbar spine surgery rates vary by geographic region and may reflect uncertainty about optimal clinical use . Methods Eligible consenting patients participated in a baseline interview performed by study personnel and then were mailed follow‐up question naires at 3 , 6 , and 12 months . Clinical data were obtained from a physician question naire . Outcomes included patient‐reported symptoms of leg and back pain , functional status , disability , quality of life , and satisfaction with care . Results Five hundred seven patients with sciatica , 275 treated surgically and 232 treated nonsurgically initially , were enrolled . Surgically treated patients , on average , had more severe symptoms and had more severe physical and imaging findings than nons Output:	Most patients with symptomatic cervical disc herniations with radiculopathy initially present with intense pain and moderate levels of disability . However , substantial improvements tend to occur within the first 4 to 6 months post-onset . Patients with a workers ' compensation cl aim appeared to have a poorer prognosis . Most patients with symptomatic cervical spine disc herniation with radiculopathy recover .
MS21426	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: PURPOSE We determined the differences in outcome between ureteral stenting and nonstenting following uncomplicated ureteroscopy for distal ureteral stones . MATERIAL S AND METHODS A total of 220 patients treated with successful ureteroscopy for distal ureteral stones were r and omized to 2 equal groups according to postoperative placement of a ureteral stent ( Cook Irel and , National Technological Park , Irel and ) , including group 1 - -without a stent and group 2 - -with a stent . Outcome measures were flank pain and dysuria at 48 hours and 1 week , early postoperative complications , analgesia need , rehospitalization , return to normal physical activity , stone-free rate , stone recurrence and late postoperative complications . Patients were followed a mean + /- SD of 25 + /- 9 months ( range 12 to 49 ) . RESULTS Early postoperative complications , including low grade fever , hematuria and urinary tract infection , were observed in 22 patients ( 20 % ) in group 1 and 19 ( 19 % ) in group 2 , a difference of no significant value . Mean initial hospitalization and time to return to normal physical activity were not different between the 2 groups . At 48 hours and 1 week there was no significant difference in flank pain between the 2 groups , while dysuria was significantly less in the nonstented group . The amount of analgesics required in the recovery room was not different but after discharge from the hospital stented patients used a larger amount of analgesia while the stent was still in the ureter . The stone-free rate at 4 weeks was 100 % in each group . Late postoperative sequelae , including stone recurrence and ureteral narrowing , were reported in 6 patients ( 5.5 % ) in group 1 and 4 ( 3.6 % ) in group 2 , a difference of no significant value . CONCLUSIONS Uncomplicated ureteroscopy for treatment of distal ureteral stones is safe without stent placement . Patients without stents have significantly fewer irritative bladder symptoms and are not at risk of increased complications PURPOSE We assessed the cost-effectiveness of routine ureteral stenting after ureteroscopic stone removal . MATERIAL S AND METHODS Of 295 consecutive patients who underwent rigid ureteroscopic stone removal 133 in group 1 and 162 in group 2 were r and omized to receive and not receive a stent , respectively , after the procedure . Operative time , stone size , stone location , success rate , postoperative pain and complications were analyzed in each group . RESULTS There were no statistically significant differences in the 2 groups regarding stone size , stone location , success rate , postoperative pain or complications . However , in group 1 operative time was significantly longer than in group 2 ( chi-square test p = 0.019 ) . The hospital charge per patient when placing and not placing a stent after ureteroscopy for stone removal was $ 9,900.95 and $ 3,661.78 , respectively . The female patients with a stent without a suture required an extra charge for stent removal in the operating room , while no men had a stent with a suture . CONCLUSIONS Routine catheter placement after ureteroscopic stone removal increased operative time and did not seem to improve patient outcome . The cost was 30 % that without a stent OBJECTIVES We conducted a study to assess the need for routine ureteral stenting after ureteroscopic stone removal using Lithoclast pneumatic intracorporeal lithotripsy . MATERIAL S AND METHODS A total of 104 patients , prospect ively divided in two groups to receive ( group A , 52 patients ) or not ( group B , 52 patients ) a stent after stone removal , underwent ureteroscopy for the treatment of ureteral lithiasis . The procedure was performed with the patient under either general or epidural anesthesia . A semirigid ureteroscope ( Wolf 8.9 Fr ) was used in all cases and intracorporeal lithotripsy with ballistic energy was performed . In group A a double pigtail ureteral 4.8 or 6 Fr polyurethane stent was placed following ureteroscopy . All patients were closely evaluated on follow-up examinations . The outcomes measured were postoperative patient pain , lower urinary tract symptoms , the need for hospital care as a result of the postoperative pain and late postoperative complications . RESULTS The two patient groups were comparable with respect to the baseline variables of patient gender and age , stone location and mean stone size . Mean operative time plus or minus st and ard deviation ( S.D. ) in group A was 42 + /- 15 minutes ( range 20 - 65 ) compared to 37 + /- 20 ( range 15 - 60 ) in group B. Operative time was not significantly longer when a stent was placed ( p = 0.17 ) . At day 3 the mean visual analog pain score in group B was much higher than in group A ( p = 0.01 ) . Dysuria , hematuria and frequency/urgency were more prevalent in the stented group , although without statistically significant difference . Readmission to the hospital for unremitting pain was necessary in 12 of 104 patients ( 11.5 % ) all being in unstented group ( p < 0.05 ) . The incidence of anatomical ureteral narrowing on IVP at 6 months follow-up was not statistically different between the two groups . CONCLUSIONS In our experience , using Swiss Lithoclast ballistic energy to fragment stones , routine stent placement is advisable also after uncomplicated ureteroscopic lithotripsy without ureteral dilation . Further prospect i ve r and omized studies are needed to assess the role of stenting after ureteroscopic lithotripsy , considering different energies sources , scopes , diameter and site of the stones in the ureter PURPOSE Foregoing ureteral stents following ureteroscopy for urinary calculi is an evolving practice . R and omized trials support stent omission in select cases though generalizability is unclear and criteria for stentless ureteroscopy are unknown . Therefore , we sought to identify significant clinical characteristics affecting postoperative morbidity in unstented patients to provide a context for future r and omized trials . MATERIAL S AND METHODS Of 837 ureteroscopic procedures for urolithiasis performed at our institution from January 1997 through January 2002 a ureteral stent was not placed in 226 ( 32 % ) . Among these patients 47 had no stone at the time of the procedure leaving 219 ( 26 % ) who were treated for urinary calculus disease . Multivariate logistic regression was used to determine the association of 24 variables with postoperative morbidity . RESULTS Of the 219 patients treated with ureteroscopy 39 ( 18 % ) had a postoperative complication , which was obstructive in 26 ( 12 % ) , infectious in 10 ( 5 % ) , and related to patient co-morbidity in 3 ( 1 % ) . Factors associated with postoperative morbidity included renal pelvic location ( p = 0.02 ) , lithotripsy ( p = 0.03 ) , bilateral procedure ( p = 0.07 ) , history of urolithiasis ( p < 0.0001 ) , diabetes mellitus ( p = 0.06 ) , recent/recurrent infection ( p < 0.0001 ) , operative time 45 minutes or greater ( p = 0.07 ) , operative time 45 minutes or greater plus lithotripsy ( p = 0.0004 ) , operative time 45 minutes or greater plus ureteral dilation ( p = 0.07 ) and bilateral stentless procedure ( p = 0.005 ) . CONCLUSIONS Multiple patient and operative factors may predispose a patient to postoperative morbidity after a stentless procedure . Future trials should prospect ively vali date the role of these factors in either promoting ( e.g. , history of urolithiasis ) or preventing ( e.g. , preoperative stent ) a postoperative complication in the setting of stentless ureteroscopy PURPOSE A prospect i ve r and omized controlled trial was conducted to evaluate whether postoperative ureteral stenting is necessary after ureteroscopic laser lithotripsy . MATERIAL S AND METHODS A total of 58 patients with unilateral ureteral stones were r and omized into either stented or unstented groups . Ureteroscopic laser lithotripsy was performed using a semirigid ureteroscope ( 6.5/7Fr ) and holmium laser without ureteral orifice dilation . There were no selection criteria regarding stone size , location , preoperative ureteral obstruction and hydronephrosis . Endoscopic evidence of stone impaction or mucosal edema/damage did not exclude a patient from the study . Ureteral perforation on completion retro grade pyelogram was the only intraoperative criterion for study exclusion . Postoperative pain scores and symptoms were recorded . Excretory urography was performed to document stone-free status and stricture formation . Radionuclide scan was performed selectively to exclude functional obstruction when ureteral narrowing was found on excretory urogram . RESULTS Mean stone size + /- SD was 9.7 + /- 4.0 mm . ( range 4 to 27 ) . Proximal ureteral stones accounted for 43 % of all stones . Stented and unstented groups were comparable with respect to demographic data , stone parameters , preoperative obstruction and hydronephrosis . There was no significant difference in operating time , laser energy used , stone impaction and mucosal edema/damage between the 2 groups . Postoperative pain and symptoms were more severe and frequent ( p < 0.05 ) in the stented group . However , there was no difference in the incidence of postoperative sepsis and unplanned medical visits . The stone-free and stricture formation rates showed no statistical difference between the 2 groups . CONCLUSIONS Ureteral stenting is not necessary after uncomplicated ureteroscopic laser lithotripsy for ureteral stones . Ureteral stent increases the incidence of pain and urinary symptoms but does not prevent postoperative urinary sepsis and unplanned medical visits . Severity of preoperative obstruction and intraoperative ureteral trauma were not shown to be determining factors for stenting BACKGROUND / PURPOSE Whether the length of stent affects stent-related symptoms after urological procedures remains controversial . We aim ed to evaluate the predictive factors for stent-related urinary tract symptoms after uncomplicated ureteroscopic lithotripsy ( URSL ) . METHODS We prospect ively recruited a total of 59 patients who underwent URSL and 6-Fr double-J ureteral stent placement . The demographic and perioperative data and stent characteristics , including the length ( 22 , 24 or 26 cm ) , position of proximal end ( upper calyx or pelvis ) , position of distal end ( crossing midline or not ) , and configurations of both ends ( complete or incomplete curl ) were recorded . All patients completed a self-administered question naire to evaluate the stent-related urinary symptoms , bladder pain , flank pain and hematuria 1 week after the procedure . All variables were analyzed by a proportional odds logistic regression model . RESULTS Twenty-two male ( 37.3 % ) and 37 ( 62.7 % ) female patients were enrolled in this study . Their mean age was 53.7 ± 12.9 years . The mean body height was 161.9 ± 7.9 cm ( range , 145.9 - 178 cm ) . In multivariate analysis , the 26-cm stent was independently associated with the severity of frequency , urgency , and nocturia symptoms . Crossing the midline of the distal end was significantly associated with urge incontinence . The 24-cm and 26-cm stents were both very strongly associated with the severity of hematuria . Crossing the midline of the distal end was significantly associated with bladder pain . CONCLUSION The length of stent and crossing the midline of the distal end were significantly associated with stent-related symptoms after URSL . Selection of the proper length of double-J stent is the most important factor in minimizing stent-related symptoms Output:	This fact does not exclude transurethral surgery using all new modifications of classic TURP . Transurethral surgery has a significantly lower complication rate compared to open prostatectomy , although not with the laparoscopic modification . A longitudinal incision can be dangerous when a huge adenoma ( for example 150 ml ) is removed because then damage of the sphincter during finger enucleation could occur . Endolaparoscopic vision allows us to perform the incision precisely and enucleate a medium sized adenoma safely . Longer catheterization than usual can be acceptable for any new/ developing procedure . The approach and surgical space creation using EndoVision ® control is a bona fide advantage of laparoscopy . On the other h and , finger enucleation allows substantial shortening of the operative time .
MS21427	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: PURPOSE Mutations affecting the KRAS gene are established predictive markers of outcome with anti-epithelial growth factor receptor ( EGFR ) antibodies in advanced colorectal cancer ( CRC ) . The relevance of these markers for anti-vascular endothelial growth factor ( VEGF ) therapy is controversial . This analysis was performed to assess the predictive and prognostic impact of KRAS and BRAF gene mutation status in patients receiving capecitabine with bevacizumab ( CG ) or capecitabine without bevacizumab in the phase III AGITG MAX ( Australasian Gastrointestinal Trials Group MAX ) study . PATIENTS AND METHODS Mutation status was determined for 315 ( 66.9 % ) of the original 471 patients . Mutation status was correlated with efficacy outcomes ( response rate , progression-free survival [ PFS ] , and overall survival [ OS ] ) , and a predictive analyses was undertaken . RESULTS Mutations in KRAS and BRAF genes were observed in 28.8 % and 10.6 % of patients , respectively . KRAS gene mutation status ( wild type [ WT ] v mutated [ MT ] ) had no prognostic impact for PFS ( hazard ratio [ HR ] , 0.89 ; CI , 0.69 to 1.14 ) or OS ( HR , 0.97 ; CI , 0.73 to 1.28 ) . BRAF mutation status ( WT v MT ) was not prognostic for PFS ( HR , 0.80 ; CI , 0.54 to 1.18 ) but was prognostic for OS ( HR , 0.49 ; CI , 0.33 to 0.73 ; P = .001 ) . By using the comparison of capecitabine versus capecitabine and bevacizumab ( CB ) and CB plus mitomycin ( CBM ) , KRAS gene mutation status was not predictive of the effectiveness of bevacizumab for PFS or OS ( test for interaction P = .95 and 0.43 , respectively ) . Similarly , BRAF gene mutation status was not predictive of the effectiveness of bevacizumab for PFS or OS ( test for interaction P = .46 and 0.32 , respectively ) . CONCLUSION KRAS gene mutation status was neither prognostic for OS nor predictive of bevacizumab outcome in patients with advanced CRC . BRAF gene mutation status was prognostic for OS but was not predictive of outcome with bevacizumab PURPOSE Mutations within the KRAS proto-oncogene have predictive value but are of uncertain prognostic value in the treatment of advanced colorectal cancer . We took advantage of PETACC-3 , an adjuvant trial with 3,278 patients with stage II to III colon cancer , to evaluate the prognostic value of KRAS and BRAF tumor mutation status in this setting . PATIENTS AND METHODS Formalin-fixed paraffin-embedded tissue blocks ( n = 1,564 ) were prospect ively collected and DNA was extracted from tissue sections from 1,404 cases . Planned analysis of KRAS exon 2 and BRAF exon 15 mutations was performed by allele-specific real-time polymerase chain reaction . Survival analyses were based on univariate and multivariate proportional hazard regression models . RESULTS KRAS and BRAF tumor mutation rates were 37.0 % and 7.9 % , respectively , and were not significantly different according to tumor stage . In a multivariate analysis containing stage , tumor site , nodal status , sex , age , grade , and microsatellite instability ( MSI ) status , KRAS mutation was associated with grade ( P = .0016 ) , while BRAF mutation was significantly associated with female sex ( P = .017 ) , and highly significantly associated with right-sided tumors , older age , high grade , and MSI-high tumors ( all P < 10(-4 ) ) . In univariate and multivariate analysis , KRAS mutations did not have a major prognostic value regarding relapse-free survival ( RFS ) or overall survival ( OS ) . BRAF mutation was not prognostic for RFS , but was for OS , particularly in patients with MSI-low ( MSI-L ) and stable ( MSI-S ) tumors ( hazard ratio , 2.2 ; 95 % CI , 1.4 to 3.4 ; P = .0003 ) . CONCLUSION In stage II-III colon cancer , the KRAS mutation status does not have major prognostic value . BRAF is prognostic for OS in MS-L/S tumors Purpose : Alterations in the RAS-RAF-MAP2 K (MEK)-MAPK signaling pathway are major drivers in colorectal carcinogenesis . In colorectal cancer , BRAF mutation is associated with microsatellite instability ( MSI ) , and typically predicts inferior prognosis . We examined the effect of BRAF mutation on survival and treatment efficacy in patients with stage III colon cancer . Methods : We assessed status of BRAF c.1799T > A ( p . V600E ) mutation and MSI in 506 stage III colon cancer patients enrolled in a r and omized adjuvant chemotherapy trial [ 5-fluorouracil and leucovorin ( FU/LV ) vs. irinotecan ( CPT11 ) , FU and LV ( IFL ) ; CALGB 89803 ] . Cox proportional hazards model was used to assess the prognostic role of BRAF mutation , adjusting for clinical features , adjuvant chemotherapy arm , and MSI status . Results : Compared with 431 BRAF wild-type patients , 75 BRAF-mutated patients experienced significantly worse overall survival [ OS ; log-rank P = 0.015 ; multivariate HR = 1.66 ; 95 % CI : 1.05–2.63 ] . By assessing combined status of BRAF and MSI , it seemed that BRAF-mutated MSS ( microsatellite stable ) tumor was an unfavorable subtype , whereas BRAF wild-type MSI-high tumor was a favorable subtype , and BRAF-mutated MSI-high tumor and BRAF wild-type MSS tumor were intermediate subtypes . Among patients with BRAF-mutated tumors , a nonsignificant trend toward improved OS was observed for IFL versus FU/LV arm ( multivariate HR = 0.52 ; 95 % CI : 0.25–1.10 ) . Among patients with BRAF wild-type cancer , IFL conferred no suggestion of benefit beyond FU/LV alone ( multivariate HR = 1.02 ; 95 % CI : 0.72–1.46 ) . Conclusions : BRAF mutation is associated with inferior survival in stage III colon cancer . Additional studies are necessary to assess whether there is any predictive role of BRAF mutation for irinotecan-based therapy . Clin Cancer Res ; 18(3 ) ; 890–900 . © 2011 AACR Purpose Mutations in KRAS and BRAF genes were associated with treatment failure from EGF receptor inhibitors in colorectal cancer ( CRC ) patients . However , whether these mutations were associated with survival in patients not treated with EGF receptor inhibitors remained controversial . Moreover , few data were available in Chinese . Therefore , we aim ed to evaluate the impact of KRAS and BRAF mutations on the survival of Chinese CRC patients . Methods CRC patients who underwent surgery between October 2003 and April 2006 were included in this study . They were observed until June 30 , 2010 or when death was ascertained by the National Death Registration System . Prospect ively collected fresh frozen tumor tissues were used for detection of mutations at codons 12 , 13 , and 61 of the KRAS gene and exons 11 and 15 of BRAF gene by PCR amplification followed by direct sequencing . Results Among the 314 patients , KRAS and BRAF mutations were detected in 65 ( 20.7 % ) and 12 ( 3.8 % ) patients , respectively . KRAS mutations appeared to occur more frequently in females than males ( p = 0.039 ) and in non-smokers ( p = 0.039 ) . KRAS and BRAF mutations were significantly associated with the proximal location of cancer ( p = 0.017 and 0.001 , respectively ) . In the univariate analysis , KRAS and BRAF mutations were not associated with survival . However , BRAF mutations were associated with a significantly worse overall survival ( hazard ratio = 3.91 , 95 % confidence interval 1.31 to 11.66 , p = 0.014 ) in the multivariate Cox proportional hazard model after adjustment for all direct clincopathological variables . Conclusion BRAF mutations , but not KRAS mutations , were associated with a worse outcome in Chinese CRC patients Networks of investigators have begun sharing best practice s , tools and methods for analysis of associations between genetic variation and common diseases . A Network of Investigator Networks has been set up to drive the process , sponsored by the Human Genome Epidemiology Network . A workshop is planned to develop consensus guidelines for reporting results of genetic association studies . Published literature data bases will be integrated , and unpublished data , including ' negative ' studies , will be captured by online journals and through investigator networks . Systematic review s will be exp and ed to include more meta-analyses of individual-level data and prospect i ve meta-analyses . Field synopses will offer regularly up date d overviews A quantitative systematic review , or meta- analysis , uses statistical methods to combine the results of multiple studies . Meta-analyses have been done for systematic review s of therapeutic trials , diagnostic test evaluations , and epidemiologic studies . Although the statistical methods involved may at first appear to be mathematically complex , their purpose is simple : They are trying to answer four basic questions . Are the results of the different studies similar ? To the extent that they are similar , what is the best overall estimate ? How precise and robust is this estimate ? Finally , can dissimilarities be explained ? This article provides some guidance in underst and ing the key technical aspects of the quantitative approach to these questions . We have avoided using equations and statistical notations ; interested readers will find implementations of the described methods in the listed references . We focus here on the quantitative synthesis of reports of r and omized , controlled , therapeutic trials because far more meta-analyses on therapeutic studies than on other types of studies have been published . For practical reasons , we present a stepwise description of the tasks that are performed when statistical methods are used to combine data . These tasks are 1 ) deciding whether to combine data and defining what to combine , 2 ) evaluating the statistical heterogeneity of the data , 3 ) estimating a common effect , 4 ) exploring and explaining heterogeneity , 5 ) assessing the potential for bias , and 6 ) presenting the results . Deciding Whether To Combine Data and Defining What To Combine By the time one performs a quantitative synthesis , certain decisions should already have been made about the formulation of the question and the selection of included studies . These topics were discussed in two previous articles in this series [ 1 , 2 ] . Statistical tests can not compensate for lack of common sense , clinical acumen , and biological plausibility in the design of the protocol of a meta- analysis . Thus , a reader of a systematic review should always address these issues before evaluating the statistical methods that have been used and the results that have been generated . Combining poor- quality data , overly biased data , or data that do not make sense can easily produce unreliable results . The data to be combined in a meta- analysis are usually either binary or continuous . Binary data involve a yes/no categorization ( for example , death or survival ) . Continuous data take a range of values ( for example , change in diastolic blood pressure after antihypertensive treatment , measured in mm Hg ) . When one is comparing groups of patients , binary data can be summarized by using several measures of treatment effect that were discussed earlier in this series [ 3 ] . These measures include the risk ratio ; the odds ratio ; the risk difference ; and , when study duration is important , the incidence rate . Another useful clinical measure , the number needed to treat ( NNT ) , is derived from the inverse of the risk difference [ 3 ] . Treatment effect measures , such as the risk ratio and the odds ratio , provide an estimate of the relative efficacy of an intervention , whereas the risk difference describes the intervention 's absolute benefit . The various measures of treatment effect offer complementary information , and all should be examined [ 4 ] . Continuous data can be summarized by the raw mean difference between the treatment and control groups when the treatment effect is measured on the same scale ( for example , diastolic blood pressure in mm Hg ) , by the st and ardized mean difference when different scales are used to measure the same treatment effect ( for example , different pain scales being combined ) , or by the correlation coefficients between two continuous variables [ 5 ] . The st and ardized mean difference , also called the effect size , is obtained by dividing the difference between the mean in the treatment group and the mean in the control group by the SD in the control group . Evaluating the Statistical Heterogeneity of the Data This step is intended to answer the question , Are the results of the different studies similar ( homogeneous ) ? It is important to answer this question before combining any data . To do this , one must calculate the magnitude of the statistical diversity ( heterogeneity ) of the treatment effect that exists among the different sets of data . Statistical diversity can be thought of as attributable to one or both of two causes . First , study results can differ because of r and om sampling error . Even if the true effect is the same in each study , the results of different studies would be expected to vary r and omly around the true common fixed effect . This diversity is called the within- study variance . Second , each study may have been Output:	BRAF mutation appears to be associated with distinct , unfavourable clinicopathological characteristics in colorectal cancer
MS21428	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: ABSTRACT Lifestyle interventions can prevent diabetes through weight loss , but they are rarely translated for use in underserved communities . The aim of this study was to describe how a community – academic partnership formed and developed a program to address local health disparities by developing a low-cost , culturally and economically appropriate , peer-led community-based diabetes prevention program . Using a participatory approach , the partnership chose to focus on diabetes prevention , and co-developed all intervention , recruitment , research , and evaluation strategies . The partnership 's philosophy to maintain high clinical and scientific st and ards paired with their ability to represent and engage the community facilitated the development of a r and omized controlled trial that achieved statistically significant and sustained weight loss , and the recruitment of a largely Spanish-speaking , low income , uninsured population . The success of this intervention lies in the partnership 's commitment to the community , co-ownership of research , and a careful balance between academic rigor and community engagement and relevance BACKGROUND Since the Diabetes Prevention Project ( DPP ) demonstrated that lifestyle weight-loss interventions can reduce the incidence of diabetes by 58 % , several studies have translated the DPP methods to public health-friendly context s. Although these studies have demonstrated short-term effects , no study to date has examined the impact of a translated DPP intervention on blood glucose and adiposity beyond 12 months of follow-up . PURPOSE To examine the impact of a 24-month , community-based diabetes prevention program on fasting blood glucose , insulin , insulin resistance as well as body weight , waist circumference , and BMI in the second year of follow-up . DESIGN An RCT comparing a 24-month lifestyle weight-loss program ( LWL ) to an enhanced usual care condition ( UCC ) in participants with prediabetes ( fasting blood glucose=95 - 125 mg/dL ) . Data were collected in 2007 - 2011 ; analyses were conducted in 2011 - 2012 . SETTING / PARTICIPANTS 301 participants with prediabetes were r and omized ; 261 completed the study . The intervention was held in community-based sites . INTERVENTION The LWL program was led by community health workers and sought to induce 7 % weight loss at 6 months that would be maintained over time through decreased caloric intake and increased physical activity . The UCC received two visits with a registered dietitian and a monthly newsletter . MAIN OUTCOME MEASURES The main measures were fasting blood glucose , insulin , insulin resistance , body weight , waist circumference , and BMI . RESULTS Intent-to-treat analyses of between-group differences in the average of 18- and 24-month measures of outcomes ( controlling for baseline values ) revealed that the LWL participants experienced greater decreases in fasting glucose ( -4.35 mg/dL ) ; insulin ( -3.01 μU/ml ) ; insulin resistance ( -0.97 ) ; body weight ( -4.19 kg ) ; waist circumference ( -3.23 cm ) ; and BMI ( -1.40 ) , all p-values < 0.01 . CONCLUSIONS A diabetes prevention program administered through an existing community-based system and delivered by community health workers is effective at inducing significant long-term reductions in metabolic indicators and adiposity Purpose The objective was to take prevention from the clinic to the community by including a high-risk group and working with the community to tailor , enhance , deliver , and evaluate a community-based version of the Diabetes Prevention Program ’s ( DPP ) clinic-based lifestyle intervention . Methods This was a nonr and omized prospect i ve study using a single-group design . Study eligibility included a screening glucose value in the normal to prediabetes range with no current diagnosis of diabetes , overweight , not pregnant nor planning to become pregnant during study period , aged 18 to 65 , Latino , living in the study target communities , and no reported medical restrictions related to the program goals . A total of 69 individuals participated . The Healthy Living Program ( HLP ) was based on the DPP ’s 1-year intensive lifestyle program , was tailored and enhanced for a Latino community , and was delivered by community health workers . Anthropometric and paper and pencil measures were administered to examine program outcome at 6 months and 12 months . Results In general , results indicate statistically significant improvements in anthropometrics and many behavioral outcomes , particularly at 6 months . Participants demonstrated forward movement through the stages of change during the program . Conclusions Results support the effectiveness of the intervention and show that delivery of the translated version of the DPP ’s lifestyle intervention in the community by community residents holds promise as one strategy to reach people at increased risk of developing diabetes . Use of this translation model , including collaboration with community health workers , offers diabetes educators an opportunity to extend their reach into underserved communities Introduction Hispanics are at increased risk of developing type 2 diabetes . Lifestyle interventions are effective in preventing diabetes and restoring glucose regulation . Methods We recruited Hispanic men and women ( N = 320 ) who were residents of the Lower Yakima Valley , Washington , aged 18 years or older with hemoglobin A1c ( HbA1c ) levels higher than 6 % to a parallel 2-arm r and omized-controlled trial conducted from 2008 through 2012 . The trial compared participants in the intervention arm , who received an immediate educational curriculum ( n = 166 ) , to participants in the control arm , who received a delayed educational curriculum ( n = 154 ) . The home-based curriculum consisted of 5 sessions led by community health workers and was design ed to inform participants about diabetes , diabetes treatment , and healthy dietary and physical activity behaviors . Participants were r and omly assigned to the intervention and control arms , and analysts were blinded as to participant arm . We evaluated intervention effects on HbA1c levels ; frequency ( times per week ) of fruit and vegetable consumption ; and frequency ( times per week ) of mild , moderate , and strenuous leisure-time physical activity . At baseline , 3 months , and 6 months after r and omization , participants completed a question naire and provided a blood sample . Analysts were blinded to intervention arm . Results The immediate intervention group ( −0.64 % [ st and ard error ( SE ) 0.10 ] ) showed a significant improvement in HbA1c scores ( –37.5 % , P = .04 ) compared with the delayed intervention group ( –0.44 % , P = .14 ) . No significant changes were seen for dietary end points or changes in physical activity . We did observe a trend of greater increases in frequency of moderate and vigorous physical activity and a smaller increase in mild physical activity in the immediate intervention group than in the delayed intervention group . Conclusion This home-based intervention delivered by CHWs was associated with a clinical ly and statistically significant reduction in HbA1c levels in Hispanic adults with HbA1c levels higher than 6 % Asian Americans experience diabetes at a higher rate than non-Hispanic whites . Diabetes prevention programs using lifestyle interventions have been shown to produce beneficial results , yet there have been no culturally-tailored programs for diabetes prevention in the Korean community . We explore the impact and feasibility of a pilot Community Health Worker ( CHW ) intervention to improve health behaviors and promote diabetes prevention among Korean Americans using a r and omized controlled trial . Between 2011 and 2012 , a total of 48 Korean Americans at risk for diabetes living in New York City ( NYC ) participated in the intervention . Participants were allocated to treatment or control groups . A community-based participatory research approach guided development of the intervention , which consisted of 6 workshops held by CHWs on diabetes prevention , nutrition , physical activity , diabetes complications , stress and family support , and access to health care . Changes over 6 months were examined for clinical measurements ( weight , BMI , waist circumference , blood pressure , glucose , and cholesterol ) ; health behaviors ( physical activity , nutrition , food behaviors , diabetes knowledge , self-efficacy , and mental health ) ; and health access ( insurance and self-reported health ) . In this small pilot study , changes were seen in weight , waist circumference , diastolic blood pressure , physical activity nutrition , diabetes knowledge , and mental health . Qualitative findings provide additional context ual information that inform ways in which CHWs may influence health outcomes . These findings demonstrate that a diabetes prevention program can be successful among a Korean American population in NYC , and important insight is provided for ways that programs can be tailored to meet the needs of vulnerable population Purpose . To evaluate the effectiveness of FUEL Your Life , a translation of the Diabetes Prevention Program for worksites . Design . A r and omized control group design was conducted in five worksites of a large transportation company . Measures were collected pretest , posttest ( 6 months ) , and follow-up ( 12 months ) . Setting . Railroad maintenance facilities of Union Pacific Railroad . Subjects . Participants consisted of 362 workers ( 227 treatment , 135 control ) . Intervention . FUEL Your Life was translated from the Diabetes Prevention Program to better fit within the context of the worksite . The primary difference was the use of peer health coaches to provide social support and reinforcement and an occupational nurse to provide lesson content ( six sessions of 10 minutes ) to participants instead of the lifestyle coaches employed by the Diabetes Prevention Program , result ing in a less structured meeting schedule . Measures . The primary outcomes were weight and body mass index ( BMI ) , with secondary outcomes including eating behaviors , physical activity , and social support . Analysis . Latent growth modeling was used to measure changes in the outcomes over time . Results . Participants in the intervention group maintained weight/ BMI ( –.1 pounds/–.1 BMI ) , whereas the control participants gained weight/ BMI ( + 2.6 pounds/+.3 BMI ) , result ing in a statistically significant difference between groups . Fifty-five percent of intervention participants lost some weight , whereas only 35 % of the control group lost weight . Conclusions . FUEL Your Life , a low intensity intervention , was not effective for promoting weight loss , but was effective for helping workers maintain weight over a 12-month period OBJECTIVE The progression from impaired glucose tolerance (IGT)/impaired fasting glucose ( IFG ) to type 2 diabetes can be prevented or delayed through intensive lifestyle changes . How to translate this to implementation across whole communities remains unclear . We now describe the results to a pilot of a personal trainer ( Maori Community Health Worker , MCHW ) approach among Maori in New Zeal and . DESIGN , SETTING AND SUBJECTS A r and omised cluster-controlled trial of intensive lifestyle change was commenced among 5,240 non-pregnant Maori family members without diabetes from 106 rural and 106 urban geographical clusters . Baseline assessment s included lifestyle question naires , anthropometric measurements and venesection . A pilot study ( Vanguard Study ) cohort of 160 participants were weighed before and during MCHW intervention , and compared with fifty-two participants weighed immediately before intervention and with 1,143 participants from the same geographical area . Interactions between participants and the MCHW were reported using personal digital assistants with a programmed detailed structured approach to each interview . RESULTS During the Vanguard Study , participants and MCHW found the messages , toolkit and delivery approach acceptable . Those with IGT/IFG diagnosed ( n 27 ) experienced significant weight loss after screening and during the Vanguard Study ( 5.2 ( sd 6.6 ) kg , paired t test P < 0.01 ) . Significant weight loss occurred during the Vanguard Study among all participants ( -1.3 ( sd 3.6 ) kg , P < 0.001 ) . CONCLUSIONS Comparable initial weight loss was shown among those with IGT/IFG and those from existing trials . Community-wide prevention programmes are feasible among Maori and are likely to result in significant reductions in the incidence of diabetes Purpose The purpose of this study was to describe the feasibility of using a community-based participatory research ( CBPR ) approach to implement the Power to Prevent ( P2P ) diabetes prevention education curriculum in rural African American ( AA ) setting s. Methods Trained community health workers facilitated the 12-session P2P curriculum across 3 community setting s. Quantitative ( based on the pre- and post-curriculum question naires and changes in blood glucose , blood pressure [ BP ] , and weight at baseline and 6 months ) and qualitative data ( based on semi-structured interviews with facilitators ) were collected . Indicators of feasibility included : dem and , acceptability , implementation fidelity , and limited efficacy testing . Results Across 3 counties , 104 AA participants were recruited ; 43 % completed ≥ 75 % of the sessions . There was great dem and for the program . Fifteen community health ambassadors ( CHAs ) were trained , and 4 served as curriculum facilitators . Content and structure of the intervention was acceptable to facilitators but there were challenges to implementing the program as design ed . Improvements were seen in diabetes knowledge and the impact of healthy eating and physical activity on diabetes prevention , but there were no significant changes in blood glucose , BP , or weight . Conclusion While it is feasible to use a CBPR approach to recruit participants and implement the P2P curriculum in AA community setting s , there are significant challenges that must be overcome Background India currently has more than 60 million people with Type 2 Diabetes Mellitus ( T2DM ) and this is predicted to increase by nearly two-thirds by 2030 . While management of those with T2DM is important , preventing or delaying the onset of the disease , especially in those individuals at ‘ high risk ’ of developing T2DM , is urgently needed , particularly in re source -constrained setting s. This Output:	Overall the training was culturally sensitive and /or appropriate , covering topics such as the importance of good nutrition and the benefits of increased physical activity , communication and leadership . CHWs delivered a variety of interventions and also screened or recruited participants . The shared culture and language between CHWs and participants likely contributed to better programme implementation and successful outcomes . The complexity of DPPs and the diverse CHW roles preclude attributing specific outcomes to CHW involvement .
MS21429	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Codeine is generally accepted as the st and ard antitussive against which new antitussive medications are compared . This presents a problem because the support for codeine 's antitussive activity comes from studies on cough in animals , and chronic and induced cough models in man , whereas antitussives are almost exclusively used for the treatment of cough associated with acute upper respiratory tract infection ( URTI ) . The aims of this study were twofold . Firstly , to study the antitussive efficacy of codeine in cough associated with URTI and , secondly , to vali date a sound meter as tool for quantifying cough . The efficacy of codeine was assessed in a double-blind , stratified , placebo-controlled , parallel-group , clinical trial using three different measures of cough : cough sound-pressure levels ( CSPLs ) measured on a sound meter ; subjective scores of cough severity ; and cough frequency recorded by means of a microphone connected to an ink-pen recorder . A group of 82 subjects ( 51 females and 31 males ; mean age 23.5 years , range 18 - 46 years ) with cough owing to acute URTI were included in the study . The study took place on two separate study days . On study day 1 cough measurements were made before and 90 min after treatment with a single dose of either 50 mg codeine or matched placebo in capsule form . The same three measures of cough were repeated 2 - 5 days later ( study day 2 ) . On study day 1 a highly significant ( P < 0.0001 ) decrease in all three measures of cough was found after treatment with both placebo and codeine yet there was no significant difference between the treatment groups . A highly significant ( P < 0.0001 ) decrease in the three measures of cough was also found between days 1 and 2 . The results demonstrate that codeine is no more effective than placebo in reducing cough associated with acute URTI , as measured by CSPLs , cough frequency or subjective symptom scores . This result might be explained on the basis of two central pathways for cough ; a reflex pathway via the brain-stem which is sensitive to codeine and a voluntary pathway via the cortex which is unaffected by codeine . The results also demonstrate that the sound-level meter appears to be a potentially useful investigative tool for the assessment of cough and antitussive efficacy BACKGROUND The role of certified respiratory educators ( CREs ) is to educate , assess , and help to manage patients with asthma and COPD in Canada . This study was undertaken to see whether CREs could assist pulmonologists ( MDs ) in managing patients with chronic cough . METHODS An 8-week prospect i ve , parallel design , r and omized , controlled trial to determine whether CREs using a protocol -driven algorithmic approach could assist in the management of patients referred to a university tertiary care medical center for the assessment and treatment of chronic cough . Patients were r and omly assigned to a CRE-led or MD study arm for the management of chronic cough . Patients were screened to exclude those patients whose cough was due to life-threatening conditions . The primary outcome was measured with the cough-specific quality -of-life question naire ( CQLQ ) . RESULTS A total of 198 patients were r and omized , and 8-week results were available on 151 patients ( mean [ + /- SD ] age , 49.8 + /- 13.4 years ; female gender , 70 % ; median cough duration , 16 months ) . At 8 weeks , total CQLQ scores improved in the CRE-led patients ( score [ + /- SD ] range , 58.1 + /- 14.9 to 50.0 + /- 15.8 ; p = 0.0003 ) . CQLQ scores improved in four of six domains but not in the physical or emotional domains . Improvements in CRE-led patients were similar to those in MD-managed patients ( initial CQLQ score , p = 0.261 [ CRE vs MD ] ; CQLQ score at 8 weeks , p = 0.42 [ CRE vs MD ] ) . In a composite analysis of both CRE and MD patient data , CQLQ scores improved in patients whose cough resolved ( 56.3 + /- 13.6 to 41.5 + /- 13.6 ; p < 0.0001 ) , in those whose cough improved but did not disappear ( 60.9 + /- 14.2 to 50.5 + /- 13.9 ; p < 0.0001 ) , but did not improve in those whose cough did not improve ( 58.1 + /- 13.3 to 58.6 + /- 12.7 ; difference not significant ) . CONCLUSIONS CREs can help to safely , economically , and effectively manage properly screened patients with chronic cough . The use of CREs may shorten wait times for specialist consultation for these patients OBJECTIVES : To compare the effects of a single nocturnal dose of 3 honey products ( eucalyptus honey , citrus honey , or labiatae honey ) to placebo ( silan date extract ) on nocturnal cough and difficulty sleeping associated with childhood upper respiratory tract infections ( URIs ) . METHODS : A survey was administered to parents on 2 consecutive days , first on the day of presentation , when no medication had been given the previous evening , and the following day , when the study preparation was given before bedtime , based on a double-blind r and omization plan . Participants included 300 children aged 1 to 5 years with URIs , nocturnal cough , and illness duration of ≤7 days from 6 general pediatric community clinics . Eligible children received a single dose of 10 g of eucalyptus honey , citrus honey , labiatae honey , or placebo administered 30 minutes before bedtime . Main outcome measures were cough frequency , cough severity , bothersome nature of cough , and child and parent sleep quality . RESULTS : In all 3 honey products and the placebo group , there was a significant improvement from the night before treatment to the night of treatment . However , the improvement was greater in the honey groups for all the main outcome measures . CONCLUSIONS : Parents rated the honey products higher than the silan date extract for symptomatic relief of their children ’s nocturnal cough and sleep difficulty due to URI . Honey may be a preferable treatment for cough and sleep difficulty associated with childhood URI A double-blind cross-over trial was carried out to evaluate the antitussive activity of viminol p-hydroxybenzoate ; the comparison was done with three preparations : a placebo and the drug at two doses , 70 and 140 mg respectively . The responses were scored hourly up to 4 hours after the administration of single doses in the morning to subjects with persistent cough . The highest dose of viminol showed a definite antitussive activity , whereas the lowest did not differ from the placebo . The antitussive effect appears clinical ly useful for the treatment of cough , but further studies are indicated to define optimal dosage schedules BACKGROUND Cough is a frequent complaint of patients with a variety of respiratory disorders , including seasonal allergic rhinitis ( SAR ) , and it is often evaluated subjectively to determine disease status and response to treatment . However , it is not known whether subjective reports of cough from patients with SAR are accurate . OBJECTIVE To compare a novel objective measurement with subjective reports of cough frequency in a subset of 28 patients ( aged > or = 12 years ) with active SAR who were enrolled in a large , multicenter trial examining the efficacy of an active treatment for SAR . METHODS In this supplemental pilot study , subjective data were collected on a diary card and objective data were collected using home-based telemetry . Three 24-hour recording sessions were conducted with each patient : 2 consecutive baseline sessions ( day 1 and day 2 ) and 1 session after r and omization to placebo or active cough treatment ( day 3 ) . RESULTS Strong correlations existed between cough frequency data for days 1 and 2 ( Spearman correlation coefficient = 0.91 ; P < .001 ) and between subjective and objective data for days 1 , 2 , and 3 ( daytime greater than nighttime ) ( Spearman correlation coefficient = 0.51 ; P < .001 ) . CONCLUSION These results have implication s for the design and interpretation of results from clinical trials that evaluate cough frequency as a treatment outcome OBJECTIVES The goals of this study were to : ( 1 ) determine if management according to a st and ardized clinical management pathway/algorithm ( compared with usual treatment ) improves clinical outcomes by 6 weeks ; and ( 2 ) assess the reliability and validity of a st and ardized clinical management pathway for chronic cough in children . METHODS : A total of 272 children ( mean ± SD age : 4.5 ± 3.7 years ) were enrolled in a pragmatic , multicenter , r and omized controlled trial in 5 Australian centers . Children were r and omly allocated to 1 of 2 arms : ( 1 ) early review and use of cough algorithm ( “ early-arm ” ) ; or ( 2 ) usual care until review and use of cough algorithm ( “ delayed-arm ” ) . The primary outcomes were proportion of children whose cough resolved and cough-specific quality of life scores at week 6 . Secondary measures included cough duration postr and omization and the algorithm ’s reliability , validity , and feasibility . RESULTS : Cough resolution ( at week 6 ) was significantly more likely in the early-arm group compared with the delayed-arm group ( absolute risk reduction : 24.7 % [ 95 % confidence interval : 13–35 ] ) . The difference between cough-specific quality of life scores at week 6 compared with baseline was significantly better in the early-arm group ( mean difference between groups : 0.6 [ 95 % confidence interval : 0.29–1.0 ] ) . Duration of cough postr and omization was significantly shorter in the early-arm group than in the delayed-arm group ( P = .001 ) . The cough algorithm was reliable ( κ = 1 in key steps ) . Feasibility was demonstrated by the algorithm ’s validity ( 93%–100 % ) and efficacy ( 99.6 % ) . Eighty-five percent of children had etiologies easily diagnosed in primary care . CONCLUSIONS : Management of children with chronic cough , in accordance with a st and ardized algorithm , improves clinical outcomes irrespective of when it is implemented . Further testing of this st and ardized clinical algorithm in different setting s is recommended RATIONALE Cough is the most common complaint for which medical attention is sought , and chronic cough can be both physically and mentally debilitating . There is currently no evidence supporting the use of antitussives in chronic treatment-resistant cough . OBJECTIVES We tested the hypothesis that morphine sulfate in the dose of 5 mg twice daily would bring about a reduction in cough frequency and severity in patients failing to respond to specific measures . METHODS Patients recruited from the Hull Cough Clinic were enrolled into a r and omized double-blind placebo-controlled study using 4 weeks of slow-release morphine sulfate and a corresponding period of matched placebo . An open-labeled extension of the core study allowed dose escalation to 10 mg twice daily . Cough was assessed using the Leicester Cough Question naire , daily symptom diary , and citric acid cough challenge . RESULTS Twenty-seven patients completed the core study . A significant improvement of 3.2 points over baseline was noted on the Leicester Cough Question naire ( p < 0.01 ) . A rapid and highly significant reduction by 40 % in daily cough scores was noted among patients on slow-release morphine sulfate ( p < 0.01 ) . Objective testing of the cough reflex using citric acid cough challenge tests did not show any significant changes . Eighteen patients continued into the extension study . Two-thirds of these patients opted to increase the morphine to 10 mg twice daily . At the end of 3 months , there was a similar improvement in cough between the 5- and 10-mg groups . CONCLUSION Morphine sulfate is an effective antitussive in intractable chronic cough at the doses of 5 to 10 mg twice daily Background Chronic cough patients are rendered therapies for gastro-esophageal reflux ( GERD ) , upper airway cough syndrome ( UACS ) and cough-variant asthma ( CVA ) with varying benefit . Idiopathic or unexplained cough has emerged as an important clinical entity in both primary care and subspecialty clinics . Recent evidence points to a link between chronic cough and untreated obstructive sleep apnea ( OSA ) . Methods A prospect i ve observational study was done to evaluate the effect of OSA therapy in patients with chronic cough . Patients enrolled into the study underwent question naires to evaluate for GERD , UACS and CVA along with screening question naires for OSA and daytime sleepiness . The Leicester cough question naire ( LCQ ) was done at baseline and during serial visits to evaluate cough intensity and was used as the primary outcome measure of the effect of CPAP therapy on chronic cough . Results Out of 37 patients enrolled into the study , only 28 patients had follow up LCQ scores available and therefore underwent analysis . 22/28 patients were suspected to have OSA based on abnormal STOP-BANG screening question naire scores and overnight oximetry abnormalities . Of these 19/28 patients had overnight attended polysomnography with definitive diagnosis of OSA yielding a 68 % prevalence of OSA in our chronic cough population . Chronic cough patients treated for OSA tended to be older with a significantly higher BMI than chronic cough patients without OSA . Significant improvement of LCQ scores occurred with CPAP therapy for OSA in chronic cough Output:	Finally , in research setting s , tussigenic challenges play a role in underst and ing mechanisms of cough
MS21430	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Previous work suggests that exercise-induced arterial hypoxaemia ( EIAH ) , causing only moderate arterial oxygen desaturation ( SaO2 : 92 + /- 1 % ) , does not exaggerate diaphragmatic fatigue exhibited by highly trained endurance athletes . Since changes in arterial O2 tension have a significant effect on the rate of development of locomotor muscle fatigue during strenuous exercise , the present study investigated whether hypoxia superimposed on EIAH exacerbates the exercise-induced diaphragmatic fatigue in these athletes . Eight trained cyclists ( VO2max : 67.0 + /- 2.6 ml kg(-1 ) min(-1 ) ; mean + /- S.E.M. ) completed in balanced order four 5 min exercise tests leading to different levels of end-exercise SaO2 ( 64 + /- 2 , 83 + /- 1 , 91 + /- 1 and 96 + /- 1 % ) via variations in inspired O2 fraction ( FiO2 : 0.13 , 0.17 , 0.21 and 0.26 , respectively ) . Measurements were made at corresponding intensities ( 65 + /- 3 , 80 + /- 3 , 85 + /- 3 and 90 + /- 3 % of normoxic maximal work rate , respectively ) in order to produce the same tidal volume , breathing frequency and respiratory muscle load at each FiO2 . The mean pressure time product of the diaphragm did not differ across the four exercise tests and ranged between 312 + /- 28 and 382 + /- 22 cmH2O s min(-1 ) . Ten minutes into recovery , twitch transdiaphragmatic pressure ( P(di , tw ) ) determined by bilateral phrenic nerve stimulation , was significantly ( P = 0.0001 ) reduced after all tests . After both hypoxic tests ( FiO2 : 0.13 , 0.17 ) the degree of fall in P(di , tw ) ( by 26.9 + /- 2.7 and 27.4 + /- 2.6 % , respectively ) was significantly greater ( P < 0.05 ) than after the normoxic test ( by 20.1 + /- 3.4 % ) . The greater amount of diaphragmatic fatigue in hypoxia at lower leg work rates ( presumably requiring smaller leg blood flow compared with normoxia at higher leg work rates ) , suggests that when ventilatory muscle load is similar between normoxia and hypoxia , hypoxia exaggerates diaphragmatic fatigue in spite of potentially greater respiratory muscle blood flow availability While sustaining a load that leads to task failure , it is unclear whether diaphragmatic fatigue develops progressively or occurs only at task failure . We hypothesized that incremental loading produces a progressive decrease in diaphragmatic contractility ever before task failure . Ten subjects generated 60 % of maximal transdiaphragmatic pressure ( Pdimax ) for 2 min , 4 min , and until task failure . Before loading , 20 min after each period of loading , and approximately 20 h after the last period of loading , Pdimax , nonpotentiated and potentiated Pdi twitch pressure ( Pditw ) , and the pattern of respiratory muscle recruitment during a CO2 challenge were recorded . Sensation of inspiratory effort at the 4th min of the task-failure protocol was greater than at the same time in the preceding 4-min protocol . Surprisingly , potentiated Pditw and Pdimax were reduced after 2 min of loading and decreased further after 4 min of loading and after task failure ; nonpotentiated Pditw was reduced after 4 min of loading and after task failure . The gastric pressure contribution to tidal breathing during a CO2 challenge decreased progressively in relation to duration of the preceding loading period , whereas expiratory muscle recruitment progressively increased . A rest period of approximately 20 h after task failure was not sufficient to normalize these alterations in respiratory muscle recruitment or fatigue-induced changes in diaphragmatic contractility . In conclusion , while sustaining a mechanical load , the diaphragm progressively fatigued , ever before task failure , and when challenged the rib cage-to-diaphragmatic contribution to tidal breathing and recruitment of the expiratory muscles increased pari passu with duration of the preceding loading Background Greater diaphragm fatigue has been reported after hypoxic versus normoxic exercise , but whether this is due to increased ventilation and therefore work of breathing or reduced blood oxygenation per se remains unclear . Hence , we assessed the effect of different blood oxygenation level on isolated hyperpnoea-induced inspiratory and expiratory muscle fatigue . Methods Twelve healthy males performed three 15-min isocapnic hyperpnoea tests ( 85 % of maximum voluntary ventilation with controlled breathing pattern ) in normoxic , hypoxic ( SpO2 = 80 % ) and hyperoxic ( FiO2 = 0.60 ) conditions , in a r and om order . Before , immediately after and 30 min after hyperpnoea , transdiaphragmatic pressure ( Pdi , tw ) was measured during cervical magnetic stimulation to assess diaphragm contractility , and gastric pressure ( Pga , tw ) was measured during thoracic magnetic stimulation to assess abdominal muscle contractility . Two-way analysis of variance ( time x condition ) was used to compare hyperpnoea-induced respiratory muscle fatigue between conditions . Results Hypoxia enhanced hyperpnoea-induced Pdi , tw and Pga , tw reductions both immediately after hyperpnoea ( Pdi , tw : normoxia -22 ± 7 % vs hypoxia -34 ± 8 % vs hyperoxia -21 ± 8 % ; Pga , tw : normoxia -17 ± 7 % vs hypoxia -26 ± 10 % vs hyperoxia -16 ± 11 % ; all P < 0.05 ) and after 30 min of recovery ( Pdi , tw : normoxia -10 ± 7 % vs hypoxia -16 ± 8 % vs hyperoxia -8 ± 7 % ; Pga , tw : normoxia -13 ± 6 % vs hypoxia -21 ± 9 % vs hyperoxia -12 ± 12 % ; all P < 0.05 ) . No significant difference in Pdi , tw or Pga , tw reductions was observed between normoxic and hyperoxic conditions . Also , heart rate and blood lactate concentration during hyperpnoea were higher in hypoxia compared to normoxia and hyperoxia . Conclusions These results demonstrate that hypoxia exacerbates both diaphragm and abdominal muscle fatigability . These results emphasize the potential role of respiratory muscle fatigue in exercise performance limitation under conditions coupling increased work of breathing and reduced O2 transport as during exercise in altitude or in hypoxemic patients Inspiratory muscle fatigue may occur in as little as 6 min during high-intensity spontaneously breathing exercise . The aims of this study were to determine whether inspiratory muscle fatigue occurs during swimming exercise and whether inspiratory muscle strength differs between the supine and st and ing body positions . Seven competitive swimmers were recruited to perform a single 200 m front-crawl swim , corresponding to 90 - 95 % of race pace . Inspiratory muscle strength was measured at residual volume using a h and -held mouth pressure meter that measured maximal inspiratory pressure in the upright and supine positions . At baseline , maximal inspiratory pressure in the supine position was significantly lower than maximal inspiratory pressure in the upright position ( 112±20.4 and 133±16.7 cmH2O , respectively ; P⩽0.01 ) . Post-exercise maximal inspiratory pressure in the supine position ( 80±15.7 cmH2O ) was significantly lower than baseline maximal inspiratory pressure in the supine position ( P⩽0.01 ) . The results indicate that a single 200 m front-crawl swim corresponding to 90 - 95 % of race pace was sufficient to induce inspiratory muscle fatigue in less than 2.7 min . Furthermore , although diaphragm muscle length is optimized when supine , our results indicate that the force output of the diaphragm and inspiratory accessory muscles is greater when upright than when supine The use of noninvasive techniques to measure respiratory muscle performance after different types of endurance exercise has not been entirely successful , as the results have not consistently indicated diminished performance for similar types of exercise . The aim of the present study was 1 ) to compare different , noninvasive methods to assess respiratory muscle performance before and after an exhaustive cycling endurance test ( which has previously been shown to induce diaphragmatic fatigue ) and 2 ) to determine which of the tests best reflect published results of measurements of diaphragmatic fatigue . Twelve healthy subjects participated in the study and performed three different test series in a r and om order on three different days . These tests were performed before , and 5 , 40 and 75 min after an exhausting task ( a cycling endurance run at 85 % of maximal oxygen uptake ( V'O2,max ) ) . The tests of the three test series were 1 ) breathing against a constant inspiratory resistance to task failure , 2 ) determination of 12-min sustained ventilatory capacity , and 3 ) spirometric and maximal inspiratory and expiratory mouth pressure measurements . The only measurement that was affected by exhaustive cycling was the time to task failure breathing against inspiratory resistance . It was significantly reduced from ( mean+/-sD ) 364+/-88 s before exercise to 219+/-122 s at 5 min after cessation of exercise . It is concluded that the constant-load resistive breathing test to task failure is the only noninvasive respiratory muscle performance test evaluated in this study which shows a decrease in respiratory muscle performance after exhaustive endurance exercise Exercise-induced inspiratory muscle fatigue ( IMF ) has been reported in males but there are few reports of IMF in females . It is not known if a gender difference exists for inspiratory muscle strength following heavy exercise , as is reported in locomotor muscles . Therefore , the relationship between fatigue and subsequent recovery of maximal inspiratory pressure ( MIP ) following exercise to maximal oxygen consumption $ $ ( \dot V_{{\text{O}}_{{\text{2max}}}})$$ was examined in a group of moderately trained males and females . Eighteen males ( 23±3 years ; mean ± SD ) and 16 females ( 23±2 years ) completed ten MIP and ten maximal h and grip ( HG ) strength maneuvers to establish baseline . Post-exercise MIP and HG were assessed successively immediately following a progressive intensity $ $ \dot V_{{\text{O}}_{{\text{2max } } } } $ $ test on a cycle ergometer and at 1 , 2 , 3 , 4 , 5 , 10 , and 15 min . $ $ \dot V_{{\text{O}}_{{\text{2max } } } } , $ $ relative to fat-free mass was not statistically different between males ( 62±7 ml kg−1 min−1 ) and females ( 60±8 ml kg−1 min−1 ) . Males had higher absolute MIP values than females at all time intervals ( P<0.05 ) . Immediately following exercise , MIP was significantly reduced in both genders ( M=83±16 % ; F=78±15 % of baseline ) but HG values were not different than resting values . MIP values remained depressed for both males and females throughout the 15 min ( P<0.05 ) . Differences for MIP between males and females were not statistically significant at any measurement time ( P>0.05 ) . The findings in this study conclude that IMF , observed immediately following maximal exercise , demonstrated the same pattern of recovery for both genders The purpose of this study was to determine whether the human diaphragm , like limb muscle , has a threshold of force output at which a metaboreflex is activated causing systemic vasoconstriction . We used Doppler ultrasound techniques to quantify leg blood flow ( Q(L ) ) and utilized the changes in mouth twitch pressure ( DeltaP(M)T ) in response to bilateral phrenic nerve stimulation to quantify the onset of diaphragm fatigue . Six healthy male subjects performed four r and omly assigned trials of identical duration ( 8 + /- 2 min ) and breathing pattern [ 20 breaths/min and time spent on inspiration during the duty cycle ( time spent on inspiration/total time of one breathing cycle ) was 0.4 ] during which they inspired primarily with the diaphragm . For trials 1 - 3 , inspiratory resistance and effort was gradually increased [ 30 , 40 , and 50 % maximal inspiratory pressure ( MIP ) ] , diaphragm fatigue did not occur , and Q(L ) , limb vascular resistance ( LVR ) , and mean arterial pressure remained unchanged from control ( P > 0.05 ) . The fourth trial utilized the same breathing pattern with 60 % MIP and caused diaphragm fatigue , as shown by a 30 + /- 12 % reduction in P(M)T with bilateral phrenic nerve stimulation . During the fatigue trial , Q(L ) and LVR were unchanged from baseline at minute 1 , but LVR rose 36 % and Q(L ) fell 25 % at minute 2 and by 52 % and 30 % , respectively , during the final minutes of the trial . Both LVR and Q(L ) returned to control within 30 s of recovery . In summary , voluntary increases in inspiratory muscle effort , in the absence of fatigue , had no effect on LVR and Q(L ) , whereas fatiguing the diaphragm elicited time-dependent increases in LVR and decreases in Q(L ) . We attribute the limb vasoconstriction to a metaboreflex originating in the diaphragm , which reaches its threshold for activation during fatiguing contractions BACKGROUND --Diaphragm strength can be assessed by the measurement of Output:	Inspiratory resistive loadings at intensities of 60 - 80 % of maximum , and cycling at 85 % of maximum were found to produce IMF most consistently .
MS21431	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: BACKGROUND To analyze the effectiveness of a second-line treatment of Helicobacter pylori infection in patients with duodenal ulcer based on previous antibiotic regimen . PATIENTS AND METHODS Open , prospect i ve , uncontrolled study , but guided by protocol including 30 consecutive patients with endoscopic diagnosis of active duodenal ulcer and failure of a first-line H. pylori eradication treatment diagnosed by urea breath test or a new endoscopy with histology and positive urease test . Treatment consisted in 10 days with omeprazole ( 20 mg/12 h ) , bismuth subcitrate ( 120 mg/6 h ) , tetracycline ( 500 mg/6 h ) and metronidazole ( 500 mg/8 h ) ( OBTM ) if previous regimen was with clarithromycin ; or 10 days with omeprazole ( 20 mg/12 h ) , clarithromycin ( 500 mg/12 h ) and amoxycillin ( 1g/12 h ) ( OCA ) if previous regimen did not include clarithromycin ; using metronidazole ( 500 mg/8 h ) instead of amoxycillin ( OCM ) in case of allergy . Eradication was defined as a negative 13C-urea breath test 2 months after the end of therapy . RESULTS One patient had to stop treatment due to the side effects and in 2 patients urea breath test was not performed ( 3 patients due to the OBTM group ) . Per protocol eradication was achieved in 25 out of 27 patients ( 92.6 % ) and by intention-to-treat eradication was attained in 25 out of 30 cases ( 83.3 % ) . When both groups analyzed separately , the OCA combination was successful in 5 from 6 patients ( 83.3 % ; 95 % CI 35.9 - 99.6 ) ; while the OBTM combination was successful in 20 from 21 valuable patients ( 95 . 2 % ; 95 % CI 76.2 - 99.9 ) . In this second case we make an intention to treat analysis and eradication was achieved in 20 from 24 ( 83.3 % ; 95 % CI 62.6 - 95.3 ) . CONCLUSION The eradicative treatment for H. pylori based in different antibiotics used in subsequent attempts get high eradication rates in patients with duodenal ulcer To the Editor H. pylori is a very common infection worldwide and has a substantial role in the development of gastritis , peptic ulcer , and gastric malignancies . Eradication rates of firstline regimens have been reduced in less than 80 % during the last decade because of the increasing prevalence of antibiotic resistance . A 10-day sequential treatment containing a proton pump inhibitor ( PPI ) and amoxicillin for 5 days followed by a PPI , clarithromycin and tinidazole for an additional 5 days , has been proven to be very effective , achieving per- protocol ( PP ) cure rates around 90 % [ 1 ] . Levofloxacin-based regimens have recently been shown to be encouraging second-line options . In a meta- analysis , levofloxacin triple therapy had higher eradication rates and was better tolerated compared to the quadruple therapy [ 2 ] . The aim of this pilot study was to evaluate the efficacy and tolerability of a 10-day sequential second-line levofloxacin-based regimen and to compare it to the usually prescribed 10-day concomitant one in patients after one H. pylori eradication failure . Fifty-six patients ( F : 30 , M : 26 ; mean age : 52 , range : 18–75 years ) were r and omized to receive either a 10-day treatment with omeprazole 20 mg b.i.d . , amoxicillin 1 g b.i.d . and levofloxacin 500 mg b.i.d . ( group A ) or a sequential 10-day treatment as follows : ( a ) from day 1 to 5 : omeprazole 20 mg b.i.d . and amoxicillin 1 g b.i.d . ( b ) from day 6 to 10 : omeprazole 20 mg b.i.d . and levofloxacin 500 mg b.i.d . ( group B ) . H. pylori eradication was confirmed with a negative breath test performed at least 4 weeks after treatment end . Success rates were 72.4 % ( 21/29 ) ( 95 % CI : 52.8–87.2 % ) and 77.8 % ( 21/27 ) ( 95 % CI : 57.7–91.4 % ) in groups A and B , respectively , in the intention-to-treat analysis and 80.8 % ( 21/26 ) ( 95 % CI : 60.7–93.5 % ) and 84 % ( 21/25 ) ( 95 % CI : 63.9–95.5 % ) , respectively , in the per- protocol analysis ( p [ 0.05 , NS ) . Three patients failed to complete the treatment because of severe allergic reaction and another seven complained of minor side-effects . However , no significant differences were observed between the two groups concerning adverse effects . The idea of a sequential regimen was launched in Mediterranean countries in an attempt to provide a more effective first-line and relatively simple therapy against H. pylori . In a meta- analysis , Essa et al. proved that a 10-day concomitant regimen with three antibiotics ( amoxicillin , clarithromycin , and tinidazole ) was superior over triple therapy and concluded that it was less complex than the sequential one [ 3 ] . To the best of our knowledge , our study is the first one to evaluate a second-line sequential , levofloxacin-based treatment , including patients where there was a failure to eradicate H. pylori after classical triple therapy . Aydin et al. treated both naive and previous treatment failures with a modified 14-day sequential regimen using rabeprazole and amoxicillin for 7 days , and rabeprazole , levofloxacin , and metronidazole for another 7 days and found acceptable eradication rates only in naive patients [ 4 ] . Graham et al. used a 12-day sequential therapy with high dose of esomeprazole and amoxicillin followed by gatifloxacin and showed that this was effective . However , in contrast to our study , amoxicillin was given during the whole period and patients were both naive and previous failures [ 5 ] . Minor adverse effects of levofloxacin can occur in up to 22 % of the patients [ 6 ] . Although we did not observe any differences between the two groups , other authors found significantly less C. Krystallis ( & ) D. Kamberoglou D. Pistiolas C. Anifanti A. Koutsoumbas V. Doulgeroglou V. Tzias Department of Gastrointestinal Endoscopy , 1st IKA Hospital , End of Z aim i Str , 15127 Melissia , Athens , Greece e-mail : Abstract Objective . To test the efficacy of lansoprazole , bismuth , levofloxacin , and amoxicillin therapy compared to bismuth metronidazole tetracycline ( BMT ) quadruple therapy for second-line treatment of Helicobacter pylori infection . Methods . A total of 284 patients who failed prior H. pylori eradication were r and omized to receive 14-day regimens containing lansoprazole 30 mg twice a day ( b.i.d . ) , bismuth subcitrate 240 mg b.i.d . , and either amoxcillin , 1 g b.i.d . and levofloxacin 500 mg once daily ( qd ) ( levofloxacin/bismuth therapy ) or metronidazole 400 mg four times daily ( q.i.d . ) and tetracycline , 500 mg q.i.d . ( BMT quadruple therapy ) . Endoscopy and culture were performed before treatment . Antimicrobial susceptibility was by agar dilution . H. pylori status was determined 6 weeks after the end of therapy using a 13C-urea breath test . Results . The metronidazole , levofloxacin , tetracycline , and amoxicillin resistance rates were 85.3 % , 40.2 % , 1.1 % , and 0.5 % , respectively . The intention-to-treat and per- protocol ( PP ) eradication rates were 83 % ( 95 % confidence interval [ CI ] : 75.9–88.3 % ) and 88.1 % ( 95 % CI : 81.2–92.4 % ) ( p = 0.22 ) for levofloxacin-bismuth ( levo-bismuth ) versus BMT quadruple , respectively , and PP rates were 85.4 % ( 95 % CI : 78.5–90.3 % ) and 90.6 % ( 95 % CI : 84.6–94.5 % ) ( p = 0.18 ) . Moderate and severe side effects were significantly higher with BMT quadruple than levo-bismuth ( 22.4 % vs. 5 % , p < 0.001 ) and higher in women ( 28.4 % ) than men ( 10.4 % ) in BMT quadruple therapy group ( p = 0.015 ) . Conclusion . Increasing fluoroquinolone resistance has undermined levo-bismuth quadruple therapy making BMT quadruple therapy a better choice empiric second-line therapy for H. pylori infection . However , compliance was significantly higher with levo-bismuth quadruple therapy , especially among women The bismuth-based quadruple regimen has been applied in Helicobacter pylori rescue therapy worldwide . The non-bismuth-based quadruple therapy or “ concomitant therapy ” is an alternative option in first-line eradication but has not been used in second-line therapy . Discovering a valid regimen for rescue therapy in bismuth-unavailable countries is important . We conducted a r and omized controlled trial to compare the efficacies of the st and ard quadruple therapy and a modified concomitant regimen . One hundred and twenty-four patients were r and omly assigned into two groups : RBTM ( rabeprozole 20 mg bid . , bismuth subcitrate 120 mg qid , tetracycline 500 mg qid , and metronidazole 250 mg qid ) and RATM ( rabeprozole 20 mg bid . , amoxicillin 1 g bid . , tetracycline 500 mg qid , and metronidazole 250 mg qid ) for 10 days . The eradication rate of the RBTM and RATM regimen was 92.1 % and 90.2 % , respectively , in intention-to-treat analysis . Patients in both groups had good compliance ( ~96 % ) . The overall incidence of adverse events was higher in the RATM group ( 42.6 % versus 22.2 % , P = 0.02 ) , but only seven patients ( 11.5 % ) experienced grade s 2 - 3 events . In conclusion , both regimens had good efficacy , compliance , and acceptable side effects . The 10-day RATM treatment could be an alternative rescue therapy in bismuth-unavailable countries Background / Aims Several rescue therapies have been recommended to eradicate Helicobacter pylori infection in patients with a failure of first-line eradication therapy , but they still fail in more than 20 % of cases . The aim of this study was to evaluate the efficacy and safety of levofloxacin , metronidazole , and lansoprazole ( LML ) triple therapy relative to quadruple therapy as a second-line treatment . Methods In total , 113 patients who failed first-line triple therapy for H. pylori infection were r and omly assigned to two groups : LML for 7 days and tetracycline , bismuth subcitrate , metronidazole and lansoprazole ( quadruple ) for 7 days . Results According to intention-to-treat analysis , the infection was eradicated in 38 of 56 patients ( 67.9 % ) in the LML group and 48 of 57 ( 84.2 % ) in the quadruple group ( p=0.042 ) . Per- protocol analysis showed successful eradication in 38 of 52 patients ( 73.1 % ) from the LML group and 48 of 52 ( 92.3 % ) from the quadruple group ( p=0.010 ) . There were no significant differences in the adverse effects in either treatment group . Conclusions LML therapy is less effective than quadruple therapy as a second-line treatment for H. pylori infection . Therefore , quadruple therapy should be considered as the primary second-line strategy for patients experiencing a failure of first-line H. pylori therapy in Korea Background Increasing resistance to clarithromycin and nitroimidazole is the main cause of failure in the Helicobacter pylori eradication . The ideal retreatment regimen remains unclear , especially in developing countries , where the infection presents high prevalence and resistance to antibiotics . The study aim ed at determining the efficacy , compliance and adverse effects of a regimen that included fur Output:	The meta-regression did not find any particular characteristics of the studies to be associated with excellent cure rates . CONCLUSION Second-line Helicobacter pylori treatments achieving>90 % cure rates are extremely heterogeneous . Quadruple therapy and 14-day treatments seem better than triple therapies and 7-day ones . No single characteristic of the treatments was related to excellent cure rates .
MS21432	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: BACKGROUND Finasteride , an inhibitor of type 2 5alpha-reductase , decreases serum and scalp dihydrotestosterone ( DHT ) by inhibiting conversion of testosterone to DHT and has been shown to be effective in men with and rogenetic alopecia ( AGA ) . The effects of finasteride in women with AGA have not been evaluated . OBJECTIVE The purpose of this study was to evaluate the efficacy of finasteride in postmenopausal women with AGA . METHODS In this 1-year , double-blind , placebo-controlled , r and omized , multicenter trial , 137 postmenopausal women ( 41 - 60 years of age ) with AGA received finasteride 1 mg/day or placebo . Efficacy was evaluated by scalp hair counts , patient and investigator assessment s , assessment of global photographs by a blinded expert panel , and histologic analysis of scalp biopsy specimens . RESULTS After 1 year of therapy , there was no significant difference in the change in hair count between the finasteride and placebo groups . Both treatment groups had significant decreases in hair count in the frontal/parietal ( anterior/mid ) scalp during the 1-year study period . Similarly , patient , investigator , and photographic assessment s as well as scalp biopsy analysis did not demonstrate any improvement in slowing hair thinning , increasing hair growth , or improving the appearance of the hair in finasteride-treated subjects compared with the placebo group . Finasteride was generally well tolerated . CONCLUSION In postmenopausal women with AGA , finasteride 1 mg/day taken for 12 months did not not increase hair growth or slow the progression of hair thinning The aim of this study was to assess the usefulness of ketoconazole as a therapeutic alternative to polycystic ovary syndrome . The study group comprised 37 women with signs of hyper and rogenism ( hirsutism , acne ) and oligomenorrhea . A low dose ( 400 mg/day ) of ketoconazole was tested in a 9-month prospect i ve clinical study . Clinical response ( Ferriman & Gallway score , acne ) and modifications in hormone pattern ( luteinizing hormone , follicle-stimulating hormone , estradiol , testosterone , prolactin , 17-hydroxy-progesterone , and rostenedione , steroid hormone-binding globulin , dehydroepi and rosterone sulfate , cortisol , adrenocorticotropin ( ACTH ) and free testesterone index ) were measured , and ACTH stimulation tests were performed . Tolerance and side-effect also were assessed . After 9 months of ketoconazole treatment , the patients ' Ferriman & Gallway scores ( 18.26 + /- 4.6 vs 12.4 + /- 4.1 ; p < 0.001 ) and acne had improved markedly . Hormone patterns also became more favorable , with decreases in and rogenic steroids ( testosterone , and rostenedione , free testosterone index and dehydroepi and rosterone sulfate ; p < 0.01 ) and increases in estradiol ( p < 0.01 ) . Basal cortisol levels and cortisol after ACTH stimulation were not changed significantly , remaining within the reference range . Increases in ACTH were observed only in the 3rd month ( p < 0.01 ) . Initial levels of and rogenic steroids were correlated inversely with their percentage decrease in successive samplings . Decreases in adrenal and rogenic steroids were associated with an increase in steroid hormone-binding globulin . The side-effects of treatment , although not severe , caused some discomfort and led to a high drop-out rate ( 30 % ) . ( ABSTRACT TRUNCATED AT 250 WORDS BACKGROUND Topical minoxidil and oral finasteride have been used to treat men with and rogenetic alopecia ( AGA ) . There are concerns about side effects of oral finasteride especially erectile dysfunction . OBJECTIVE To compare the efficacy and safety of the 24 weeks application of 3 % minoxidil lotion ( MNX ) versus combined 3 % minoxidil and 0.1 % finasteride lotion ( MFX ) in men with AGA . MATERIAL AND METHOD Forty men with AGA were r and omized treated with MNX or MFX . Efficacy was evaluated by hair counts and global photographic assessment . Safety assessment was performed by history and physical examination . RESULTS At week 24 , hair counts were increased from baseline in both groups . However paired t-test revealed statistical difference only in MFX group ( p = 0.044 ) . Unpaired t-test revealed no statistical difference between two groups with respect to change of hair counts at 24 weeks from baseline ( p = 0.503 ) . MFX showed significantly higher efficacy than MNX by global photographic assessment ( p = 0.003 ) . There was no significant difference in side effects between both groups . CONCLUSION Although change of hair counts was not statistically different between two groups , global photographic assessment showed significantly greater improvement in the MFX group than the MNX group . There was no sexual side effect . MFX may be a safe and effective treatment option OBJECTIVE To determine the effectiveness of various anti and rogens for the treatment of premenopausal women with hyper and rogenic alopecia . DESIGN R and omized , unmasked trial of three treatments in 36 hyper and rogenic women with alopecia and observation , without treatment , in 12 other similar patients . SETTING Endocrinologic outpatient practice in Italy . PARTICIPANT(S ) A total of 48 hyper and rogenic women with alopecia and 30 age- and weight-matched controls for the assessment of and rogen levels . INTERVENTION(S ) R and omization to cyproterone acetate ( 50 mg ) with ethinyl estradiol ( EE ) in a reverse sequential regimen ; flutamide ( 250 mg ) or finasteride ( 5 mg ) daily ; all for 1 year . Twelve similar patients were observed without treatment for 1 year . MAIN OUTCOME MEASURE(S ) Ludwig scores for hair thinning as well as patient and investigator assessment s of treatment effectiveness . RESULT ( S ) Flutamide result ed in a reduction of 21 % in Ludwig scores ( 2.3 + /- 0.2 to 1.8 + /- 0.1 ) . The other treatment effects were not statistically significant . Patient and investigator assessment s showed a similar trend . CONCLUSION ( S ) Flutamide at a dose of 250 mg daily induced a modest improvement in alopecia after 1 year , whereas cyproterone acetate and finasteride were not effective . Treatment for more than 1 year may be required for better results Background : The pathogenesis of and rogenic alopecia is not fully understood . A microbial-driven inflammatory reaction abutting on the hair follicles might participate in the hair status anomaly . Objective : The aim of our study was to determine if ketoconazole ( KCZ ) which is active against the scalp microflora and shows some intrinsic anti-inflammatory activity might improve alopecia . Method : The effect of 2 % KCZ shampoo was compared to that of an unmedicated shampoo used in combination with or without 2 % minoxidil therapy . Results : Hair density and size and proportion of anagen follicles were improved almost similarly by both KCZ and minoxidil regimens . The sebum casual level appeared to be decreased by KCZ . Conclusion : Comparative data suggest that there may be a significant action of KCZ upon the course of and rogenic alopecia and that Malassezia spp . may play a role in the inflammatory reaction . The clinical significance of the results awaits further controlled study in a larger group of subjects BACKGROUND Finasteride , a type II-selective 5alpha-reductase inhibitor , as a causative agent of decreasing dihydroxy testosterone ( DHT ) level , is effective in the treatment of male and rogenic alopecia . AIM We compared the local and oral finasteride in the treatment of and rogenic alopecia . METHOD This is a double blind , r and omized clinical trial study of 45 male patients , who were referred with alopecia to the private clinics and departments in Boo-Ali Sina Hospital , in Sari . Patients with male and rogenic alopecia were selected according to the history and physical examinations . The patients were r and omly divided into two : topical finasteride ( A ) and oral finasteride ( B ) groups . Topical finasteride group ( A ) received a topical gel of 1 % finasteride and placebo tablets , while the oral finasteride group ( B ) received finasteride tablets ( 1 mg ) and gel base ( without drug ) as placebo for 6 months . The patients were followed by clinical observation and recording of side effects prior to the treatment and at the end of first week , and then by a monthly follow-up . The size of bald area , total hair count , and terminal hair were studied . Data were analyzed by descriptive and Chi-square statistical test . RESULTS The mean duration of hair loss was 18.8+/-23.10 months . Each month the terminal hair , size of bald area and hair count between the two groups were compared . There were no significant differences between the two groups as a viewpoint of hair thickness , hair counts and the size of bald area . Serial measurements indicated a significant increase in hair counts and terminal hair counts between the two groups . CONCLUSIONS The results of this study showed that the therapeutic effects of both finasteride gel and finasteride tablet were relatively similar to each other OBJECTIVE The effects on scalp and serum dihydrotestosterone ( DHT ) of different doses of a novel topical solution of 0.25 % finasteride ( P-3074 ) , a type 2 5α-reductase , were investigated in men with and rogenetic alopecia . METHODS Two r and omized , parallel-group studies were conducted . Study I : 18 men received 1 mL ( 2.275 mg ) P-3074 , applied to the scalp once a day ( o.d . ) or twice a day ( b.i.d ) , or 1 mg oral tablet o.d . for 1 week . Study II : 32 men received P-3074 at the dose of 100 ( 0.2275 mg ) , 200 ( 0.455 mg ) , 300 ( 0.6285 mg ) , or 400 ( 0.91 mg ) μL or the vehicle o.d . for 1 week . Scalp and serum DHT and serum testosterone were evaluated at baseline and treatment end . RESULTS Change from baseline in scalp DHT was -70 % for P-3074 o.d . and approx . -50 % for P-3074 b.i.d . and the tablet . Serum DHT decreased by 60 - 70 % . The doses of 100 and 200 μL P-3074 result ed in a -47/-52 % scalp DHT reduction , similar to the 300 and 400 μL doses ( i.e. , -37/-54 % ) . A -5.6 % inhibition was observed for the vehicle . Serum DHT was reduced by only -24/-26 % with 100 and 200 μL P-3074 and by -44/-48 % with 300 and 400 μL P-3074 . No relevant changes occurred for serum testosterone . CONCLUSIONS The novel finasteride 0.25 % solution applied o.d . at the doses of 100 and 200 μL results in an appropriate inhibition of scalp DHT potentially minimizing the untoward sexual side-effects linked to a systemic DHT reduction BACKGROUND The synergism of combined use between oral finasteride and topical minoxidil has been established in treating and rogenetic alopecia among men . However , the concern regarding adverse effects of finasteride use has been rising . OBJECTIVE To compare the efficacy and safety of topical solution of 0.25 % finasteride admixed with 3 % minoxidil vs. 3 % minoxidil solution in men with and rogenetic alopecia . METHODS Forty men aged 18 - 60 years with and rogenetic alopecia were r and omized to 24 weeks of treatment with a finasteride/minoxidil or minoxidil solution twice daily . Primary efficacy endpoint was the change from baseline in hair density and hair diameter at week 24 . Secondary endpoints included global photographic assessment by treatment-blinded investigators and subjects . Changes in plasma dihydrotestosterone levels and adverse events were recorded . RESULTS At week 24 , the combined solution of finasteride and minoxidil was significantly superior to minoxidil alone in improvements of hair density , hair diameter and global photographic assessment ( all P < 0.05 ) . About 90 % of patients treated with the combined solution experienced moderate to marked improvement . The combined solution also had minimal effect on plasma dihydrotestosterone levels , approximately 5 % reduction . There were also no systemic adverse events reported by patients in both groups . CONCLUSION Treatment with topical solution of 0.25 % finasteride admixed with 3 % minoxidil was significantly superior to 3 % minoxidil solution for promoting hair growth in male and rogenetic alopecia , and well tolerated Background The relationship between female pattern hair loss ( FPHL ) and and rogenic hormones is not well established , but some evidence indicates oral finasteride may be efficacious in FPHL . Use of a topical formulation has been Output:	The results demonstrated that topical formulations of finasteride , ketoconazole , and C17P are promising treatments for male pattern hair loss , especially topical finasteride in combination with topical minoxidil . Limited studies have shown C17P to have potential in treating acne vulgaris in both males and females . Minimal adverse effects have been reported in clinical trials for all topical therapies , although topical finasteride is still contraindicated in pregnancy .
MS21433	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Purpose The study was focused on the influence of the kinesitherapy on fatigue and the quality of life in the terminal hospice cancer patients . Patients and methods Forty-nine patients were included into the study and divided into experimental group A ( with kinesitherapy ) with 30 subjects and control group B ( without kinesitherapy ) with 19 subjects . Patients from group A did the exercises three times a week , for 20–30 min , for the period of 3–4 weeks . The exercises were individually supervised by a physiotherapist , following a carefully worked out pattern . In both groups , the changes in the intensity of fatigue and the quality of life were observed by means of using Rotterdam symptom checklist , brief fatigue inventory , and visual analogue fatigue scale . Results In group A , the intensity of fatigue decreased significantly after 3 weeks of kinesitherapy . In group B , fatigue deteriorated significantly in comparison with the initial measurement . The intensity of physical symptoms in group A decreased significantly after 2 weeks of kinesitherapy , whereas in group B , increased after 2 weeks of observation . The quality of life in group A remained stable throughout the study . A tendency towards the deterioration of the quality of life with the time passing in group B was noticeable . Conclusion Our analysis showed that , on average , after 3 weeks of kinesitherapy , a significant decrease of the intensity of fatigue was observed , while in the control group , it increased after 2 weeks of observation . The obtained results provide evidence that a planned set of exercises decreases cancer-related fatigue effectively Until now , little research has been conducted examining the reactive dimension , or the degree to which a symptom limits an individual 's life , in a multiplicity of symptoms . This research examines how problem-solving therapy organizes an intervention to decrease symptom limitations . The purpose was threefold : to determine if a cognitive behavioral intervention decreases the impact of symptom limitations among individuals newly diagnosed with cancer , who are receiving chemotherapy ; to determine , after adjusting for covariates , how symptom limitations change over time ; and to describe which symptoms are most limiting . This r and omized control trial was conducted in two comprehensive and four community cancer centers . Two hundred thirty-seven individuals , aged 31 - 87 , newly diagnosed with solid tumor cancers , participated . The experimental group ( 118 individuals ) received a 10-contact , 18-week cognitive behavioral intervention focused on cancer- and chemotherapy-related symptoms . The control group ( 119 individuals ) received conventional care . Interviews occurred at baseline , 10 , 20 , and 32 weeks . Data analysis used a two-level hierarchical linear model . Participants receiving the cognitive behavioral intervention had lower scores of symptom limitation than did participants in the control group . At the onset of the study , younger patients reported more symptom limitations than their older counterparts ; however , this was reversed by the end of the study . The cognitive behavioral intervention was key to decreasing symptom limitations . Findings also suggest that nursing interventions may be particularly helpful to younger individuals in managing cancer-related symptom limitations OBJECTIVE Head and neck cancer ( HNC ) patients have a high incidence of cancer-related posttraumatic stress disorder ( PTSD ) and other anxiety and depressive disorders . We report the results from the first pilot r and omized controlled trial in which the efficacy of an early cognitive-behavioral therapy ( CBT ) program was compared with a non-directive supportive counseling ( SC ) intervention in reducing PTSD , general anxiety and depressive symptoms , and improving perceived quality of life in newly diagnosed , distressed HNC patients undergoing radiotherapy . PATIENTS AND METHODS Thirty-five HNC patients ( mean age=54.8 years ; 80 % males ) with elevated levels of PTSD , depression or anxiety were r and omized to seven individual sessions of a multi-modal CBT or non-directive SC , concurrent with patients ' radiotherapy . The SC intervention provided non-directive counseling support . PTSD , anxiety and depressive symptoms ( primary outcomes ) , and cancer-related appraisal s and quality of life ( secondary outcomes ) were assessed pre-intervention ( baseline ) , 1 month , 6 months and 12 months post-intervention by diagnostic clinical interviews and vali date d self-report question naires . RESULTS The CBT and SC interventions were found to be equal in their effects in reducing PTSD and anxiety symptoms both in the short and longer term . However , up to 67 % of patients in the CBT program no longer met clinical or sub- clinical PTSD , anxiety and /or depression by 12 months post-treatment compared with 25 % of patients who received SC . CONCLUSION Findings indicate that the early provision of psychotherapy has utility in reducing PTSD , anxiety and depressive symptoms , and preventing chronic psychopathology in distressed HNC patients Background Many patients with cancer experience depression and anxiety , and an associated decrease in quality of life ( QOL ) during radiation therapy ( RT ) . The main objective of the study was to determine the benefits of psychosocial interventions for cancer patients who received RT . Methods Patients with cancer ( n = 178 ) who agreed to participate in the study were r and omized to the intervention arm ( n = 89 ) or the control arm ( n = 89 ) . Patients in the intervention group received psychosocial care during RT , whereas the control group received RT only . The benefits of the intervention were evaluated using the Zung Self-rating Depression Scale ( SDS ) to measure depression , the Self-rating Anxiety Scale ( SAS ) to assess anxiety , and the European Organization for Research and Treatment of Cancer Quality of Life Question naire-Core 30 ( EORTC QLQ-C30 ) to survey health-related QOL . The association between intervention and survival was also assessed . Results Patients r and omly assigned to the intervention arm showed significant improvements on symptoms of depression ( p < 0.05 ) and anxiety ( p < 0.05 ) , health-related QOL ( p < 0.05 ) ( i.e. better global health status , and physical and emotional functioning , and less insomnia ) when compared with controls . In the subset analysis , female patients , those that received high dose irradiation , and those that underwent adjuvant chemotherapy could benefit more from psychosocial intervention . There was no difference between the two groups in disease-free survival ( DFS ) ( 2-year DFS 79.8 % in the intervention arm and 76.4 % in the control arm ; p = 0.527 ) and overall survival ( OS ) ( 2-year OS 83.1 % in the intervention arm and 84.3 % in the control arm ; p = 0.925 ) Conclusions Psychosocial intervention is a cost-effective approach that can improve a patient ’s mood and QOL both during and after RT . However , the intervention was not found to reduce the risk of cancer recurrence and death . Trial registration OBJECTIVE Breast cancer patients receiving adjuvant chemotherapy often experience functional effects of treatment that limit participation in life activities . The purpose of this study was to examine the feasibility of conducting a r and omized controlled trial ( RCT ) of a novel intervention for these restrictions , determine acceptability of the intervention , and preliminarily assess its effects . METHODS A pilot RCT of a telephone-delivered Problem-solving and Occupational Therapy intervention ( PST-OT ) to improve participation restrictions in rural breast cancer patients undergoing chemotherapy . Thirty-one participants with Stages 1 - 3 breast cancer were r and omized to 6 weekly sessions of PST-OT ( n = 15 ) and usual care ( n = 16 ) . The primary study outcome was the feasibility of conducting the trial . Secondary outcomes were functional , quality of life and emotional status as assessed at baseline , 6 and 12 weeks . RESULTS Of 46 patients referred 31 were enrolled ( 67 % recruitment rate ) , of which 6 participants withdrew ( 81 % retention rate ) . Twenty-four participants completed all study -related assessment s ( 77 % ) . Ninety-two percent of PST-OT participants were highly satisfied with the intervention , and 92 % reported PST-OT to be helpful/very helpful for overcoming participation restrictions . Ninety-seven percent of planned PST-OT treatment sessions were completed . Completion rates for PST-OT homework tasks were high . Measures of functioning , quality of life , and emotional state favored the PST-OT condition . CONCLUSION This pilot study suggests that an RCT of the PST-OT intervention is feasible to conduct with rural breast cancer patients undergoing adjuvant chemotherapy and that PST-OT may have positive effects on function , quality of life , and emotional state PURPOSE / OBJECTIVES To evaluate the effects of a rehabilitation program on quality of life , fatigue , fear of movement ( kinesiophobia ) , distress , anxiety , depression , and physical condition . DESIGN Pretest/post-test . SETTING An outpatient rehabilitation setting in the Oncology Centre at the University Hospital Brussels in Belgium . SAMPLE 36 patients who had completed cancer treatment with a curative potential . METHODS Participants completed a question naire and underwent a physical test at baseline and at the end of the program . The measurement instruments used included the European Organisation for Research and Treatment of Cancer Quality -of-Life Question naire-Core 30 , Functional Assessment of Cancer Therapy-Fatigue , Hospital Anxiety and Depression Scale , R AND -36 , Tampa Scale for Kinesiophobia , Distress Barometer , and Tecumseh Step Test . MAIN RESEARCH VARIABLES Quality of life , fatigue , kinesiophobia , distress , anxiety , depression , and physical condition . FINDINGS Significant improvement was observed in quality of life ( p < 0.001 ) , physical condition ( p = 0.007 ) , fatigue ( p = 0.01 ) , and depression ( p = 0.012 ) . In contrast , kinesiophobia ( p = 0.229 ) , distress ( p = 0.344 ) , and anxiety ( p = 0.101 ) did not change significantly . CONCLUSIONS A general and significant improvement in all aspects affecting quality of life and rehabilitation was observed , but less so for aspects that might be influenced by prognostic concerns . The relative contribution of the program versus spontaneous recovery and long-term impact need to be determined further in a prospect i ve r and omized study . IMPLICATION S FOR NURSING Multidisciplinary rehabilitation should become part of the total care plan for patients with cancer CONTEXT There is a little information about effective psychotherapies to enhance the spiritual well-being of terminally ill cancer patients . OBJECTIVES The primary aim of the study was to examine the efficacy of a one-week Short-Term Life Review for the enhancement of spiritual well-being , using a r and omized controlled trial . The secondary aim was to assess the effect of this therapy on anxiety and depression , suffering , and elements of a good death . METHODS The subjects were 68 terminally ill cancer patients r and omly allocated to a Short-Term Life- Review interview group or a control group . The patients completed question naires pre- and post-treatment , including the meaning of life domain from the Functional Assessment of Chronic Illness Therapy-Spiritual ( FACIT-Sp ) scale , the Hospital Anxiety and Depression Scale ( HADS ) , a numeric scale for psychological suffering , and items from the Good Death Inventory ( Hope , Burden , Life Completion , and Preparation ) . RESULTS The FACIT-Sp , Hope , Life Completion , and Preparation scores in the intervention group showed significantly greater improvement compared with those of the control group ( FACIT-Sp , P<0.001 ; Hope , P<0.001 ; Life Completion , P<0.001 ; and Preparation , P<0.001 ) . HADS , Burden , and Suffering scores in the intervention group also had suggested greater alleviation of suffering compared with the control group ( HADS , P<0.001 ; Burden , P<0.007 ; Suffering , P<0.001 ) . CONCLUSION We conclude that the Short-Term Life Review is effective in improving the spiritual well-being of terminally ill cancer patients , and alleviating psychosocial distress and promoting a good death Background : Individuals with cancer receiving chemotherapy suffer deterioration in physical functioning due to symptoms arising from the cancer disease process and its treatment . Objectives : To determine if age , chronic health conditions ( comorbidity ) , stage of cancer , depressive symptomatology , symptom limitations , sex , and site of cancer moderate the effects of cognitive behavioral intervention on physical function and to determine if symptom limitations mediate the effect of the intervention on physical functioning . Methods : Two hundred thirty-seven individuals with solid tumor cancer ( 118 experimental and 119 control group ) participated in this 10-contact , 18-week r and omized control trial . Cognitive behavioral theory guided the nurse-delivered problem-solving experimental intervention . The control group received conventional care . Interviews occurred at baseline and 10 , 20 , and 32 weeks . Results : Women with breast cancer had significantly better physical functioning than women with lung cancer . Chronic health conditions , symptom limitation , and depressive symptomatology at baseline were found to moderate the effect of intervention on physical function . Symptom limitation , however , was not found to mediate the effect of intervention on physical functioning . Discussion : The intervention was shown to affect physical function trajectories differently for individuals with different personal and health characteristics . Because poor physical functioning is strongly associated with mortality and poor quality of life , this information may be used by health professionals to target interventions to those who might be most responsive OBJECTIVE Major depression is the most common psychiatric disorder among breast cancer patients and is associated with substantial impairment . Although some research has explored the utility of psychotherapy with breast cancer patients , only 2 small trials have investigated the potential benefits of behavior Output:	Strong evidence indicates that multidisciplinary rehabilitation benefits cancer survivors and that psychosocial strategies can reduce anxiety and depression . Moderate evidence indicates that interventions can support survivors in returning to the level of sexuality desired and help with return to work .
MS21434	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: A new guar-containing wheatflake product was developed to assess its effect on carbohydrate tolerance in normal-weight , healthy subjects . The extruded wheatflake breakfast cereals containing 0 ( control ) or approximately 90 g guar gum/kg DM were fed to ten fasting , normal-weight , healthy subjects using a repeated measures design . The meals were similar in energy ( approximately 1.8 MJ ) , available carbohydrate ( 78 g ) , protein ( 15 g ) and fat ( 5.4 g ) content . The guar gum content of the test meals was 6.3 g. Venous blood sample s were taken fasting and at 15 , 30 , 45 , 60 , 90 , 120 , 150 and 240 min after commencing each breakfast and analysed for plasma glucose , insulin and C-peptide . The guar wheatflake meal produced a significant main effect for glucose and insulin at 0 - 60 min and 0 - 240 min time intervals respectively , but not for the C-peptide levels compared with the control meal . Significant reductions in postpr and ial glucose and insulin responses were seen following the guar wheatflake meal compared with the control meal at 15 and 60 min ( glucose ) and 15 , 60 , 90 and 120 min ( insulin ) . The 60 and 120 min areas under the curve for glucose and insulin were significantly reduced by the guar gum meal , as was the 240 min area under the curve for insulin . Thus , it can be concluded that the use of a severe method of heat extrusion to produce guar wheatflakes does not diminish the physiological activity of the guar gum Reliable tables of glycemic index ( GI ) compiled from the scientific literature are instrumental in improving the quality of research examining the relation between GI , glycemic load , and health . The GI has proven to be a more useful nutritional concept than is the chemical classification of carbohydrate ( as simple or complex , as sugars or starches , or as available or unavailable ) , permitting new insights into the relation between the physiologic effects of carbohydrate-rich foods and health . Several prospect i ve observational studies have shown that the chronic consumption of a diet with a high glycemic load ( GI x dietary carbohydrate content ) is independently associated with an increased risk of developing type 2 diabetes , cardiovascular disease , and certain cancers . This revised table contains almost 3 times the number of foods listed in the original table ( first published in this Journal in 1995 ) and contains nearly 1300 data entries derived from published and unpublished verified sources , representing > 750 different types of foods tested with the use of st and ard methods . The revised table also lists the glycemic load associated with the consumption of specified serving sizes of different foods The determine the effect of different foods on the blood glucose , 62 commonly eaten foods and sugars were fed individually to groups of 5 to 10 healthy fasting volunteers . Blood glucose levels were measured over 2 h , and expressed as a percentage of the area under the glucose response curve when the same amount of carbohydrate was taken as glucose . The largest rises were seen with vegetables ( 70 + /- 5 % ) , followed by breakfast cereals ( 65 + /- 5 % ) , cereals and biscuits ( 60 + /- 3 % ) , fruit ( 50 + /- 5 % ) , dairy products ( 35 + /- 1 % ) , and dried legumes ( 31 + /- 3 % ) . A significant negative relationship was seen between fat ( p less than 0.01 ) and protein ( p less than 0.001 ) and postpr and ial glucose rise but not with fiber or sugar content The effectiveness of guar gum in reducing post-pr and ial blood glucose and plasma insulin levels in human subjects seems to depend mainly on its ability to increase the viscosity of digesta in the small intestine . However , the precise relationship between the rheological properties of guar gum ( either in vitro or in vivo ) and the changes in blood metabolites and hormones is unknown . The aim of the present study , therefore , was to investigate the effects of wheat breads containing guar gum sample s varying in molecular weight ( Mw ) and particle size ( characteristics that strongly influence the rheological properties of guar gum ) on post-pr and ial blood glucose and plasma insulin levels in healthy subjects . The sensory qualities of breads containing guar-gum flours of different Mw were also evaluated using a hedonic scoring technique . No significant differences in the post-pr and ial blood glucose responses were found between the control and guar breads . However , all the guar breads elicited significant ( P less than 0.05 ) decreases in the post-pr and ial rise in plasma insulin , an effect that did not appear to be influenced by large variations in Mw or particle size of guar gum . Moreover , the sensory qualities of guar bread were markedly improved by using low Mw grade s of guar gum Objective : Arabinoxylan ( AX ) consumption is associated with metabolic improvement during diabetes and with modulation of ghrelin , an orexigenic gut hormone . The effect of AX consumption on ghrelin secretion in disturbed metabolic states is unknown . Therefore , we investigated the postpr and ial responses to AX consumption of serum glucose , insulin and triglycerides and plasma total and acylated ghrelin in subjects with impaired glucose tolerance ( IGT ) . Design : R and omized , single-blind , controlled , crossover intervention trial . Subjects : Seven female and four male adults with IGT , aged 55.5 years , and body mass index ( BMI ) 30.1 kg/m2.Intervention : Subjects received either placebo or 15 g AX supplement for 6 weeks with a 6-week washout period in-between . Main outcome measurements : Postpr and ial responses of serum glucose , insulin and triglycerides , and plasma total and acylated ghrelin after a liquid meal challenge test ( LMCT ) measured at the beginning and at the end of the dietary intervention at −20 , −5 , 0 , 15 , 30 , 45 , 60 , 90 , 120 , 150 , 180 , 210 and 240 min . Results : After LMCT , AX consumption result ed in lower postpr and ial responses in serum glucose , insulin and triglycerides ( P<0.05 ) . Compared to placebo , total plasma ghrelin was also reduced by 42±8 pg/ml ( P<0.001 ) after AX consumption with no difference in plasma acylated ghrelin . Conclusion : AX consumption improved postpr and ial metabolic responses after an LMCT in subjects with IGT and reduced total ghrelin response . However , acylated ghrelin responses were unchanged , suggesting that the acylated ghrelin-mediated orexigenic regulation is not improved as only total plasma ghrelin decreased . Sponsorship : Federal Ministry of Education and Research Germany ( PTJ-BIO/0313042C ) Diets with a high-fiber content have been shown to produce some beneficial effects on metabolic factors in subjects with NIDDM . However , some controversies still exist . In this report , the long-term effect of guar gum ( Guarina ) on both glycemic and blood lipid profiles was assessed in a r and omized , double-blind and cross-over study on 16 ( seven male and nine female ) subjects with NIDDM . Each subject received placebo ( P ) and Guarina ( G ) treatment for two eight-week periods separated by a four-week period to facilitate wash-out . Fasting plasma glucose levels showed significant improvement during G treatment but not during P treatment ( 151.7 + /- 7.9 vs 168.6 + /- 12.2 mg/dl , p less than 0.01 by paired Student 's t test ) . Hemoglobin Alc levels decreased significantly during G treatment but not during P treatment ( 6.9 + /- 0.2 vs 7.2 + /- 0.8 % , p less than 0.001 ) . Fasting insulin concentrations also showed significant lowering during G treatment but not during P treatment ( 18.3 + /- 2.1 vs 23.1 + /- 2.9 U/ml , p less than 0.005 ) . Other variables , including serum total cholesterol , triglyceride , HDLc , LDLc , sodium , potassium , chloride , magnesium and calcium levels showed no significant changes during G or P treatment . Ten out of the 16 patients ( 62.5 % ) suffered from side effects ; these included abdominal cramps ( one case ) , diarrhea ( seven cases ) and skin itching ( one case ) . In conclusion , guar gum effectively lowers fasting plasma glucose and HbAlc levels in subjects with NIDDM . Hyperinsulinemia could also be ameliorated . The effectiveness and side effects of guar gum treatment should be cautiously evaluated in each NIDDM subject Output:	Percentage attenuation was significant , dose-dependent , and independent of the amount of available carbohydrate coingested . A nonviscous palatable soluble polysaccharide can attenuate the glycemic response to carbohydrate foods . Evidence of an effect was stronger for RMD in drinks than in foods
MS21435	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: PURPOSE To compare the early psychological changes of cleft lip and palate ( CLP ) and noncleft patients after maxillofacial corrective surgery , including maxillary distraction osteogenesis and conventional orthognathic surgery . MATERIAL S AND METHODS Nine CLP patients were compared with a group of 9 non-CLP patients having similar dentofacial deformities in a prospect i ve longitudinal cohort study . Five of the CLP patients underwent maxillary distraction osteogenesis and 4 underwent conventional orthognathic surgery . A control group of 9 noncleft patients received conventional orthognathic surgery . All patients completed a set of question naires to enable their psychological profile to be assessed . The data were collected immediately before surgery ( T1 ) , and at 3 weeks ( T2 ) and 12 weeks ( T3 ) after surgery . RESULTS The CLP patients treated with distraction osteogenesis were happier , but had a higher level of social anxiety and distress than the CLP patients receiving conventional orthognathic surgery . On the other h and , the CLP patients overall were happier , with lower social anxiety and distress , than the noncleft control group . The CLP patients showed a higher level of parental self-esteem than the noncleft patients . CONCLUSION This preliminary study shows that CLP patients were generally happier , and had a higher level of parental support , than normal patients suffering from dentofacial deformities . Maxillary distraction osteogenesis seemed to induce a higher level of anxiety and distress in CLP patients than conventional orthognathic surgery in both cleft and noncleft patients OBJECTIVE The objective of this study was to compare the long-term stability of distraction osteogenesis ( DO ) and conventional orthognathic surgery ( CO ) in patients with cleft lip and palate ( CLP ) . STUDY DESIGN CLP patients requiring maxillary advancement of 4 to 10 mm were r and omized and assigned to either CO or DO . In the CO group , the maxilla was fully mobilized to the preplanned position and fixed using titanium miniplates . In the DO group , the maxilla was mobilized to a limited extent and distractors were fixed on each side of the maxilla . Serial lateral cephalographs were taken for the assessment of stability at different postoperative periods up to 5 years . RESULTS In the CO group , the maxilla relapsed backward and upward , whereas in the DO group , it advanced more forward and downward over 5 years . CONCLUSIONS Distraction of the cleft maxilla can achieve better long-term skeletal stability in maintaining its advanced position than CO Surgery and other invasive therapies are complex interventions , the assessment of which is challenged by factors that depend on operator , team , and setting , such as learning curves , quality variations , and perception of equipoise . We propose recommendations for the assessment of surgery based on a five-stage description of the surgical development process . We also encourage the widespread use of prospect i ve data bases and registries . Reports of new techniques should be registered as a professional duty , anonymously if necessary when outcomes are adverse . Case series studies should be replaced by prospect i ve development studies for early technical modifications and by prospect i ve research data bases for later pre-trial evaluation . Protocol s for these studies should be registered publicly . Statistical process control techniques can be useful in both early and late assessment . R and omised trials should be used whenever possible to investigate efficacy , but adequate pre-trial data are essential to allow power calculations , clarify the definition and indications of the intervention , and develop quality measures . Difficulties in doing r and omised clinical trials should be addressed by measures to evaluate learning curves and alleviate equipoise problems . Alternative prospect i ve design s , such as interrupted time series studies , should be used when r and omised trials are not feasible . Established procedures should be monitored with prospect i ve data bases to analyse outcome variations and to identify late and rare events . Achievement of improved design , conduct , and reporting of surgical research will need concerted action by editors , funders of health care and research , regulatory bodies , and professional societies OBJECTIVE The objective of this study was to compare the psychological changes of patients with cleft lip and palate ( CLP ) undergoing maxillary Le Fort I advancement by distraction osteogenesis ( DO ) and conventional orthognathic surgery ( CO ) . STUDY DESIGN Prospect i ve r and omized controlled study . Participants completed a set of question naires to measure their psychological states preoperatively and postoperatively . RESULT When compared with CO , CLP patients treated with DO had lower social self-esteem and higher social avoidance and distress levels during the first 3 postoperative months . Their self-esteem , social avoidance , and distress levels improved after the distractors were removed . Both CO and DO patients had similar levels of self-esteem , social avoidance , and distress levels 2 years postoperatively . The CLP patients treated with DO were more satisfied with their lives after 2 years . CONCLUSIONS DO may induce short-term distress to patients up to 3 months but CLP patients who received DO were more satisfied with their lives in the long term This clinical r and omized controlled trial was performed to compare the effects of distraction osteogenesis ( DO ) and conventional orthognathic surgery ( CO ) on velopharyngeal function and speech outcomes in cleft lip and palate ( CLP ) patients . Twenty-one CLP patients who required maxillary advancement ranging from 4 to 10 mm were recruited and r and omly assigned to either CO or DO . Evaluation of resonance and nasal emission , nasoendoscopic velopharyngeal assessment and nasometry were performed preoperatively and at a minimum of two postoperative times : 3 - 8 months ( mean 4 months ) and 12 - 29 months ( mean 17 months ) . Results showed no significant differences in speech and velopharyngeal function changes between the two groups . No correlation was found between the amount of advancement and the outcome measures . It was concluded that DO has no advantage over CO for the purpose of preventing velopharyngeal incompetence and speech disturbance in moderate cleft maxillary advancement Background : This is the first r and omized controlled study aim ing to compare the postoperative clinical morbidities in cleft lip and palate patients treated with distraction osteogenesis versus conventional orthognathic surgery . Methods : Twenty-nine cleft lip and palate patients with moderate maxillary hypoplasia requiring a maxillary Le Fort I advancement of 4 to 10 mm were r and omized into two groups for either internal maxillary distractors or immediate fragment transposition using miniplates and screw fixation . Clinical morbidities were recorded using st and ardized question naires . Skeletal and dental relapses were assessed using lateral cephalometric l and marks . Results : In the distraction group , two of 15 patients developed infection around the distractors and one patient had an occlusal relapse . Among the 14 patients who received conventional orthognathic surgery , the complications included intraoperative hemorrhage ( n = 1 ) , plate exposure leading to sinusitis ( n = 1 ) , and occlusal relapse ( n = 1 ) . In the skeletal relapses of the osteotomy group , a statistically significant vertical relapse of the A point was noted during the second to twelfth weeks when compared with the distraction group . A statistically significant horizontal relapse of the A and P points during the eighth to twelfth weeks was noted when the osteotomy group was compared with the distraction group . Conclusions : There were no major differences in the clinical morbidities between the osteotomy and distraction groups . Distraction provided better skeletal stability , whereas there was a significant amount of skeletal relapse in the first 12 weeks after conventional cleft maxillary osteotomy The teratogenic potential of oral and topical corticosteroid treatment during pregnancy was evaluated in the population -based large data set of the Hungarian Case-Control Surveillance of Congenital Abnormalities , 1980 - 1994 . Corticosteroid tablet pregnancy exposure was 1.55 % among 20,830 malformed cases and 1.41 % among 35,727 healthy control births ( P = 0.2 ) . Corticosteroid ointment pregnancy exposure was 0.35 % among malformed and 0.33 % among control births ( P = 0.7 ) . The absolute risk of oral and ointment corticosteroid treatment was low in pregnancy and particularly in the second and third months of gestation , i.e. , in the critical period for major congenital abnormalities . The adjusted odds ratio and the analysis of case-control pairs did not show any association between the rate of different congenital abnormalities and the corticosteroid treatment in the second and third months of gestation . Thus , treatments with corticosteroids in pregnancy do not appear to noticeably increase the risk of congenital abnormalities in humans PURPOSE Conventional maxillary distraction osteogenesis and anterior maxillary segmental distraction were applied in the treatment of severe maxillary hypoplasia secondary to cleft clip and palate . The aim of the present study was to compare the difference between these 2 osteotomy modalities used for rigid external distraction . PATIENTS AND METHODS Ten patients with severe maxillary hypoplasia secondary to CLP were enrolled in our study . They were r and omly divided into 2 groups . Conventional maxillary distraction osteogenesis was performed in 5 patients and anterior maxillary segmental distraction in 5 patients . The preoperative and postoperative lateral cephalograms were compared , and cephalometric analysis was performed . The independent sample t test was used to evaluate the differences between the 2 groups . RESULTS All patients healed uneventfully , and the maxillae moved forward satisfactorily . The sella-nasion-point A angles , nasion-point A-Frankfort horizontal plane angles , overjets , and 0-meridian to subnasale distances had increased significantly after distraction osteogenesis . Significant differences were found in the changes in palatal length between the 2 groups ( P < .05 ) . A mean increase of 7.50 mm in palatal length was found in the anterior maxillary segmental distraction group . No significant difference in the changes in palatopharyngeal depth or soft palatal length was found . CONCLUSIONS With the ability of increasing the palatal and arch length , avoiding changes in palatopharyngeal depth , and preserving palatopharyngeal closure function , anterior maxillary segmental distraction has great value in the treatment of maxillary hypoplasia secondary to CLP . It is a promising and valuable technique in this potentially complicated procedure Objective : To compare speech outcome and velopharyngeal ( VP ) status of subjects with repaired cleft palate who underwent either conventional Le Fort I osteotomy or maxillary distraction osteogenesis to correct maxillary hypoplasia . Design : Prospect i ve r and omized study with blind assessment of speech outcome and VP status . Subjects : Twenty-two subjects were r and omized into conventional Le Fort I osteotomy and Le Fort I distraction groups . All were native Chinese ( Cantonese ) speakers . Method : Perceptual judgment of resonance and nasal emission , study of VP structures by nasoendoscopy , and instrumental measurement by nasometry . Assessment s were performed preoperatively and at 3 months postoperatively . Main Outcome Measures : Assessment of VP closure , perceptual rating of hypernasality and nasal emission , nasalance , and amount of maxillary advancement . Results : There was no statistical difference in any of the outcome measures between the 10 subjects with conventional Le Fort I osteotomy and the 12 subjects with maxillary distraction : hypernasality ( chi-square = 3.850 , p = 0.221 ) , nasal emission ( chi-square = 0.687 , p = 0.774 ) , VP gap size ( chi-square = 1.527 , p = 0.635 , and nasalance ( t = −0.145 , p = 0.886 ) . There was no correlation between amount of maxillary advancement and any of the outcome measures ( p = .05 for all ) . Changes in VP gap size and resonance are described . Conclusion : Results need to be interpreted with caution because of the small sample size and early follow-up . However , this study utilized an assessment protocol involving a variety of outcome measures and careful consideration of reliability factors , which can be a model for further and follow-up studies PURPOSE The purpose of this study was to investigate the changes in and stability of the maxilla and soft tissue profile achieved after the application of distraction osteogenesis ( DO ) by use of rigid external distraction ( RED ) with a retention plate system in unilateral cleft lip and palate ( UCLP ) adult patients . We compared 2 treatment methods in the management of maxillary hypoplasia : Le Fort I osteotomy and DO . MATERIAL S AND METHODS Six UCLP adult patients who underwent treatment with the RED retention plate system were examined ( DO group ) . Changes in the positions of soft and hard tissue l and marks were calculated from lateral cephalograms taken before distraction , at the removal of the halo , and 1 year after surgery and were compared with those in 7 other UCLP patients who underwent Le Fort I osteotomy ( LF1 group ) . RESULTS The mean maxillary advancement was significantly larger in the DO group than in the LF1 group after distraction . During the follow-up period , the relapse rate of the maxilla was significantly smaller in the DO group . An undesirable labial inclination of the upper incisors was found in the LF1 group , which may have been due to relapse . The DO group tended to have a higher soft tissue-to-hard tissue anterior movement ratio from the time of distraction to follow-up . CONCLUSIONS The RED retention plate system improved the midfacial profile by advancement of soft and hard tissue and minimized the risk of injury to the upper lip . Using the RED system with retention plates prevented the undesirable labial inclination of upper incisors that was found in the LF Output:	Both interventions produced notable hard and soft tissue improvements . Horizontal relapse of the maxilla was significantly less in the distraction osteogenesis group five years after surgery .
MS21436	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Background : Lateral ligament ankle sprains are the single most common sports injury . Objective : To determine the functional outcome of the ankle joint after a moderate or severe inversion injury , comparing st and ard treatment with an elastic support b and age against an Aircast ankle brace . Design : Prospect i ve , r and omised controlled trial . Setting : Two accident and emergency departments . Method : Fifty patients presenting consecutively were r and omised into two equal groups : one group was treated with an elastic support b and age and the other with an Aircast ankle brace . All patients were given a st and ardised advice sheet referring to rest , ice , compression , and elevation . Patients were review ed after 48–72 hours , 10 days , and one month . Primary outcome measure : Ankle joint function assessed at 10 days and one month using the modified Karlsson scoring method ( maximum score 90 ) . Secondary outcome measure : The difference in ankle girth ( swelling ) and pain score at 10 days . Results : Seventeen patients in the elastic support b and age group ( six defaulted , two excluded ) and 18 patients in the Aircast ankle brace group ( six defaulted , one excluded ) completed the study . There were no significant differences between the two groups at presentation in terms of age ( mean 35.3 and 32.6 years respectively ) , sex , dominant leg , left or right ankle injured , previous injury , time to presentation ( median three and four hours respectively ) , difference in ankle girth ( mean 14.5 and 14.3 mm respectively ) , and pain scores ( mean 6.2 and 5.8 respectively ) . The Karlsson score was significantly higher in the Aircast ankle cast group than in the elastic b and age group at 10 days ( mean 50 v 35 , p = 0.028 , 95 % confidence interval ( CI ) 1.7 to 27.7 ) and one month ( mean 68 v 55 , p = 0.029 , 95 % CI 1.4 to 24.8 ) ( Student ’s t test ) . There was no difference between the groups in the secondary outcome measures ( swelling , p = 0.09 ; pain , p = 0.07 ) . When hierarchical multiple regression analysis was used to correct for possible baseline confounding factors , the Aircast ankle brace group was significantly associated with higher Karlsson scores at 10 days ( p = 0.009 ) and one month ( p = 0.024 ) . Conclusion : The use of an Aircast ankle brace for the treatment of lateral ligament ankle sprains produces a significant improvement in ankle joint function at both 10 days and one month compared with st and ard management with an elastic support b and age 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 purpose of this study was to examine a young athletic population to up date the data regarding epidemiology and disability associated with ankle injuries . At the United States Military Academy , all cadets presenting with ankle injuries during a 2-month period were included in this prospect i ve observational study . The initial evaluation included an extensive question naire , physical examination , and radiographs . Ankle sprain treatment included a supervised rehabilitation program . Subjects were reevaluated at 6 weeks and 6 months with subjective assessment , physical examination , and functional testing . The mean age for all subjects was 20 years ( range , 17–24 years ) . There were 104 ankle injuries accounting for 23 % of all injuries seen . There were 96 sprains , 7 fractures , and 1 contusion . Of the 96 sprains , 4 were predominately medial injuries , 76 were lateral , and 16 were syndesmosis sprains . Ninety-five percent had returned to sports activities by 6 weeks ; however , 55 % of these subjects reported loss of function or presence of intermittent pain , and 23 % had a decrement of > 20 % in the lateral hop test when compared with the uninjured side . At 6 months , all subjects had returned to full activity ; however , 40 % reported residual symptoms and 2.5 % had a decrement of > 20 % on the lateral hop test . Neither previous injury nor ligament laxity was predictive of chronic symptomatology . Furthermore , chronic dysfunction could not be predicted by the grade of sprain ( grade I vs. II ) . The factor most predictive of residual symptoms was a syndesmosis sprain , regardless of grade . Syndesmosis sprains were most prevalent in collision sports . This study demonstrates that even though our knowledge and underst and ing of ankle sprains and rehabilitation of these injuries have progressed in the last 20 years , chronic ankle dysfunction continues to be a prevalent problem . The early return to sports occurs after almost every ankle sprain ; however , dysfunction persists in 40 % of patients for as long as 6 months after injury . Syndesmosis sprains are more common than previously thought , and this confirms that syndesmosis sprains are associated with prolonged disability In this r and omised controlled trial , we evaluated the role of elastic compression using ankle injury stockings ( AIS ) in the management of fractures of the ankle . A total of 90 patients with a mean age of 47 years ( 16 to 79 ) were treated within 72 hours of presentation with a fracture of the ankle , 31 of whom were treated operatively and 59 conservatively , were r and omised to be treated either with compression by AIS plus an Aircast boot or Tubigrip plus an Aircast boot . Male to female ratio was 36:54 . The primary outcome measure was the functional Olerud-Mol and er ankle score ( OMAS ) . The secondary outcome measures were ; the American Orthopaedic Foot and Ankle Society score ( AOFAS ) ; the Short Form (SF)-12v2 Quality of Life score ; and the frequency of deep vein thrombosis ( DVT ) . Compression using AIS reduced swelling of the ankle at all time points and improved the mean OMAS score at six months to 98 ( 95 % confidence interval ( CI ) 96 to 99 ) compared with a mean of 67 ( 95 % CI 62 to 73 ) for the Tubigrip group ( p < 0.001 ) . The mean AOFAS and SF-12v2 scores at six months were also significantly improved by compression . Of 86 patients with duplex imaging at four weeks , five ( 12 % ) of 43 in the AIS group and ten ( 23 % ) of 43 in the Tubigrip group developed a DVT ( p = 0.26 ) . Compression improved functional outcome and quality of life following fracture of the ankle . DVTs were frequent , but a larger study would be needed to confirm that compression with AISs reduces the incidence of DVT Objective Acute lateral ankle sprain accounts for 85 % of all sprains , being generally accepted as the most common sports-related ligamentous injury . There is a lack of consensus about the optimal management of these injuries despite their frequency . The time-honoured mantra of rest , ice , elevation and compression is still commonly used , even though the current evidence for compression is conflicting . Methods A prospect i ve r and omized controlled clinical trial was carried out in the emergency department of a regional hospital in Irel and to compare outcomes , in terms of ankle function , pain improvement and return-to-work times , in adults presenting within 24 h of first-time acute lateral ankle sprain , among three external supports . Results We found no statistically significant differences among all three treatments in terms of ankle joint function , using the Karlsson ankle function scale , at 10 or 30-days follow-up . There was a tendency for Elastoplast b and aging to provide better average ankle function at both time points , when compared with double tubigrip and no support . Participants returned to work an average 2 days earlier , if treated with Elastoplast . Conclusion This study found no statistically significant difference in ankle function between double tubigrip b and age , Elastoplast b and age and no support at 10 or 30-days follow-up 1 . The pressure exerted by two types of b and age used to treat sprained ankles were compared in a study . 2 . Wool and crepe b and ages exert more pressure than elasticated tubular b and age , but this advantage is likely to be short lived . 3 . Neither b and age exerts significant pressure over the sprained ligament OBJECTIVE To compare functional outcome in patients with acute grade 1 or 2 ( mild to moderate ) lateral ankle sprains r and omised to treatment with or without a double tubigrip b and age ( DTG ) . METHODS 400 patients presenting to the accident and emergency ( A&E ) departments of a teaching hospital and a district general hospital and diagnosed with grade 1 or 2 lateral ankle sprains were r and omised to treatment with or without a DTG b and age . A st and ardised telephone question naire was performed one week after presentation . The main outcome measures were : number of days until walking unaided , number of days off work , whether the injury kept the patient awake at night , whether analgesia was taken . RESULTS 197 of 400 patients completed follow up . There were no significant differences in terms of age , sex and occupation between the treatment groups . There were no significant differences between those who did and those who did not complete follow up . There was no significant difference between the treatment groups for number of days until walking unaided ( 95 % CI -0.21 to 0.88 days ) , number of days off work ( 95 % CI -0.70 to 1.02 days ) or whether the injury kept the patient awake at night ( 95 % CI -10 to 17 % ) . There was a significant difference between the groups in the use of analgesia ( 95 % CI 10 to 36 % ) ; the difference seemed to be that patients treated with DTG required significantly more analgesia . CONCLUSIONS Treatment of grade 1 and 2 ankle sprins with DTG does not seem to lead to a shorter time to functional recovery and may increase the requirement for analgesia BACKGROUND Ankle sprains are common and generally believed to be benign and self-limiting . However , a significant proportion of patients with ankle sprains have persistent symptoms for months or even years . AIMS The study aim ed to evaluate whether elastic stockings improve recovery following ankle sprain . METHODOLOGY All patients within 72 h of ankle sprain were identified in Accident & Emergency or the Fracture Clinic . Consenting patients , stratified for sex , were r and omised to either : ( i ) Tubigrip or ( ii ) class II below knee elastic stockings ( ESs , Medi UK Ltd. ) which were fitted immediately and worn until the patient was pain-free and fully mobile . The deep veins of the injured legs were imaged by duplex Doppler for deep vein thrombosis ( DVT ) at 4 weeks . Outcome was compared using the American Orthopaedic Foot and Ankle Score ( AOFAS ) and SF12v2 for quality of life . RESULTS In the 36 r and omised patients , the mean ( 95 % confidence interval ( CI ) ) circumference of the injured ankle treated by ES was 23.5 (23 - 24)cm initially and 22 ( 22 - 23 ) and 22 (21 - 22.5)cm at 4 and 8 weeks ( p<0.001 ) compared with 24 ( 23 - 25 ) cm initially and 24 ( 23 - 25 ) and 24 ( 23 - 24.5 ) cm using Tubigrip ( p<0.001 ) . By 8 weeks , the mean AOFAS and SF12v2 scores were significantly improved by ES at 99 ( 8.1 ) and 119 ( 118 - 121 ) compared with 88 ( 11 ) and 102 ( 99 - 107 ) with Tubigrip ( p<0.001 ) . Of the 34 duplex images at 4 weeks , none had a DVT . CONCLUSION Elastic compression improves recovery following ankle sprain BACKGROUND Severe ankle sprains are a common presentation in emergency departments in the UK . We aim ed to assess the effectiveness of three different mechanical supports ( Aircast brace , Bledsoe boot , or 10-day below-knee cast ) compared with that of a double-layer tubular compression b and age in promoting recovery after severe ankle sprains . METHODS We did a pragmatic , multicentre r and omised trial with blinded assessment of outcome . 584 participants with severe ankle sprain were recruited between April , 2003 , and July , 2005 , from eight emergency departments across the UK . Participants were provided with a mechanical support within the first 3 days of attendance by a trained health-care professional , and given advice on reducing swelling and pain . Functional outcomes were measured over 9 months . The primary outcome was quality of ankle function at 3 months , measured using the Foot and Ankle Score ; analysis was by intention to treat . This study is registered as an International St and ard R and omised Controlled Trial , number IS RCT N37807450 . RESULTS Patients who received the below-knee cast had a more rapid recovery than those given the tubular compression b and age . We noted clinical ly important benefits at 3 months in quality of ankle function with the cast compared with tubular compression b and age ( mean difference 9 % ; 95 % CI 2.4 - 15.0 ) , as well as in pain , symptoms , Output:	Conclusion Compression may be an effective tool in the management of ankle injuries and has been shown to reduce swelling and improve quality of life in single studies .
MS21437	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: OBJECTIVES Motivating adolescents to adopt proper nutrition and physical activity behaviors is important in this nation 's fight to prevent obesity and chronic diseases . This study was conducted to determine which health education delivery method would elicit a greater behavior change . METHOD The intervention was conducted in three schools ( control , computer-based , and traditional education ) . RESULTS Students who received the computer-based intervention showed increased knowledge ( p<0.001 ) , physical activity ( p=0.001 ) , self-efficacy ( p<0.001 ) , and social support ( p<0.001 ) , and decreased meals skipped ( p<0.001 ) . CONCLUSION The computer-based group showed more positive behavior changes . However , future programs may be enhanced by including group discussion and individual feedback PURPOSE To compare the effectiveness of two school-based internet obesity prevention programs for diverse adolescents on body mass index ( BMI ) , health behaviors , and self-efficacy , and to explore moderators of program efficacy . It was hypothesized that the addition of coping skills training to a health education and behavioral support program would further enhance health outcomes . METHODS A r and omized clinical trial with cluster r and omization by class and repeated measures with follow-up at 3 and 6 months was conducted ( n = 384 ) . BMI was assessed by use of st and ard procedures . Sedentary behavior , physical activity , nutrition behavior , self-efficacy , and satisfaction were assessed with self-report measures . Data analysis consisted of mixed model analyses with autoregressive covariance structure for repeated data by use of intent-to-treat procedures . RESULTS The mean age of students was 15.31 years ( ±0.69 ) , with a mean BMI of 24.69 ( ±5.58 ) . The majority were girls ( 62 % ) and of diverse race/ethnicity ( 65 % non-white ) . There were no significant differences between groups on any outcomes and no change in BMI over time . There were significant improvements in health behaviors ( sedentary behavior , moderate and vigorous physical activity , healthy eating , fruit and vegetable intake , sugar beverages , and junk food intake ) and self-efficacy . Gender and lesson completion moderated select health outcomes . There was excellent participation and high satisfaction with the programs . CONCLUSIONS School-based internet obesity prevention programs are appealing to adolescents and improve health behaviors . The differential effect of coping skills training may require longer follow-up Background Computer tailoring may be a promising technique for prevention of overweight in adolescents . However , very few well-developed , evidence -based computer-tailored interventions are available for this target group . We developed and evaluated a computer-tailored intervention for adolescents targeting energy balance-related behaviours : i.e. consumption of snacks , sugar-sweetened beverages , fruit , vegetables , and fibre , physical activity , and sedentary behaviours . This paper describes the planned development of a school-based computer-tailored intervention aim ed at improving energy balance-related behaviours in order to prevent excessive weight gain in adolescents , and the protocol for evaluating this intervention . Methods / design Intervention development : Informed by the Pre caution Adoption Process Model and the Theory of Planned Behaviour , the computer-tailored intervention provided feedback on personal behaviour and suggestions on how to modify it . The intervention ( VETisnietVET translated as ' FATaintPHAT ' ) has been developed for use in the first year of secondary school during eight lessons . Evaluation design : The intervention will be evaluated in a cluster-r and omised trial including 20 schools with a 4-months and a 2-years follow-up . Outcome measures are BMI , waist circumference , energy balance-related behaviours , and potential determinants of these behaviours . Process measures are appreciation of and satisfaction with the program , exposure to the program 's content , and implementation facilitators and barriers measured among students and teachers . Discussion This project result ed in a theory and evidence -based intervention that can be implemented in a school setting . A large-scale r and omised controlled trial with a short and long-term follow-up will provide sound statements about the effectiveness of this computer-tailored intervention in adolescents . Trial Registration IS RCT Background : Because physical inactivity poses serious health risks , interventions are urgently needed to reverse the increasingly sedentary lifestyles of adolescent girls . Objective : The aim of this study was to determine the feasibility of " Girls on the Move , " an individually tailored computerized physical activity ( PA ) program plus nurse counseling intervention , in increasing PA . Methods : A pretest-posttest control group design was used with 77 racially diverse sedentary girls in Grade s 6 , 7 , and 8 from two middle schools . Each of the instructional grade s was r and omly assigned to either an intervention or control condition . After completing computerized question naires , each girl in the control group received a h and out listing the PA recommendations . To encourage PA , each girl in the intervention group received computerized , individually tailored feedback messages based on her responses to the question naires , individual counseling from the school 's pediatric nurse practitioner ( PNP ) , and telephone calls and mailings from a trained research assistant . At 12 weeks , girls in both groups responded to the question naires . Results : No differences in self-reported PA emerged between the intervention and control groups at Weeks 1 ( baseline ) and 12 ( postintervention ) . Repeated measures ANOVA showed a significant interaction between group and time for social support for PA , F(1 , 69 ) = 5.73 , p = .019 , indicating that the intervention group had significantly greater social support across time than did the control group . From baseline to postintervention , social support increased for the intervention group but decreased for the control group . Discussion : Reasons for the lack of significant differences between the groups on the PA measures were cited . Important information that could inform subsequent studies that test interventions to increase youth PA was acquired from conducting this study . Future efforts to increase PA participation might include this approach for enhancing social support for PA BACKGROUND This study reports on effectiveness trial outcomes of Health in Motion , a computer tailored multiple behavior intervention for adolescents . METHODS Using school as level of assignment , students ( n=1800 ) from eight high schools in four states ( RI , TN , MA , and NY ) were stratified and r and omly assigned to no treatment or a multi-media intervention for physical activity , fruit and vegetable consumption , and limited TV viewing between 2006 and 2007 . RESULTS Intervention effects on continuous outcomes , on movement to action and maintenance stages , and on stability within action and maintenance stages were evaluated using r and om effects modeling . Effects were most pronounced for fruit and vegetable consumption and for total risks across all time points and for each behavior immediately post intervention . Co-variation of behavior change occurred within the treatment group , where individuals progressing to action or maintenance for one behavior were 1.4 - 4.2 times more likely to make similar progress on another behavior . CONCLUSION Health in Motion is an innovative , multiple behavior obesity prevention intervention relevant for all adolescents that relies solely on interactive technology to deliver tailored feedback . The outcomes of the effectiveness trial demonstrate both an ability to initiate behavior change across multiple energy balance behaviors simultaneously and feasibility for ease of dissemination PURPOSE To test the effects of a classroom and World Wide Web ( WWW ) educational intervention on self-efficacy ( SE ) for healthy eating ( HE ) and to examine the relationship of the theoretical concepts in a hypothesized model of eating behavior in adolescents . DESIGN A quasiexperimental pretest , posttest design was used in a r and om sample of students in two junior high schools . METHODS The intervention consisted of a combination of 5 hours of Web-based instruction and 10 hours of classroom curriculum , compared to nutrition education embedded in the st and ard school curriculum during a 1-month period . Participants completed six question naires . Data were analyzed using descriptive statistics , t tests , and Pearson 's r correlation coefficient . FINDINGS AND CONCLUSIONS The intervention group had significantly higher scores for SE for fruits and vegetables , SE for lower fat , usual food choices , and dietary knowledge of fat compared to the control group . No difference was found between groups in food consumption . Self-efficacy was significantly associated with dietary knowledge of lower fat , usual food choices , and was inversely associated with lower-fat consumption in the hypothesized model of eating behavior . The intervention was tailored to the social and developmental preferences of adolescents and effectively increased SE for HE . The mediating role of SE in the hypothesized model of adolescent eating behavior warrants further investigation 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 PURPOSE To compare the effectiveness of a Web-based physical activity ( PA ) intervention with identical content delivered in a printed workbook among a sample of adolescent girls . METHODS Participants consisted of 319 girls with home Internet access enrolled in four middle schools within one school district . A r and omized trial design was used to compare changes in PA self-efficacy and intentions after two weeks of exposure to either a Web- or print-based intervention delivered to their home . Self-reported physical activity was assessed as a secondary outcome . Analysis of covariance was conducted to determine changes between the intervention groups while controlling for baseline levels of PA constructs . RESULTS Both Web and print groups had significant changes in physical activity self-efficacy ( Web : t[155 ] = 2.58 , p = .01 ; print : t[156 ] = 3.11 , p = .002 ) and intentions ( Web : t[157 ] = 2.27 , p = .02 ; print : t[159 ] = 6.32 , p < or = .001 ) . The print group demonstrated significantly greater increases in intentions compared with the Web group ( F [ 1,315 ] = 13.53 , p < or = .001 ) . Self-reported physical activity increased significantly in the print group only ( t[159 ] = 3.21 , p = .002 ) . CONCLUSIONS It can not be assumed that new media technologies are superior to traditional media such as print for health communication to adolescents . These results suggest that a printed workbook was more effective than an identical website for increasing physical activity intentions and behavior among a sample of middle school girls Objective : This r and omized controlled trial tested the efficacy of an internetbased lifestyle behavior modification program for weight management in African-American girls . Design : African-American girls were r and omly assigned to an interactive behavioral internet program or an internet health education program , the control condition . The behavioral intervention included internet counseling and was highly interactive . The control intervention was a passive ( non-interactive ) educational program . Parents were also participants in the study . Participants in both treatment groups met in face-to-face sessions on four occasions over the first 12 weeks of a 6-month intervention . Subjects : The study enrolled 57 African-American adolescent girls ( ages 11 to 15 years ) who were overweight or obese and had at least one biological parent who was obese [ body mass index ( BMI ) > 30 kg/m2 ] . Of the 57 participants , 50 ( 88 % ) completed the 6-month trial . Measurements : Outcome data , including BMI , body weight , body composition , dietary intake , and weight loss behaviors were collected at baseline and 6-months later . A computer server tracked utilization of the websites . Participation in the program was measured by number of “ hits ” on the website . Results : Compared to the control condition , adolescents in the behavioral treatment lost more body fat ( group difference = 1.6 % body fat ) and parents lost significantly more body weight ( group difference = 2.1 kg ) . Utilization of the behavioral website by adolescents and parents Output:	Though few authors reported on implementation processes or body mass index ( BMI ) outcomes , the majority of studies were effective in improving health behaviors in the short term .
MS21438	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: To determine the major stimuli for the release of brain natriuretic peptide ( BNP ) and atrial natriuretic peptide ( ANP ) , we measured their plasma concentrations in 14 normal subjects and 19 patients with essential hypertension during exercise with a bicycle ergometer . The plasma levels of both hormones at baseline were significantly higher in the hypertensive group than in the controls ( p < 0.05 ) . The exercise raised both the plasma BNP and ANP , with concomitant increases in systolic blood pressure ( SBP ) , heart rate ( HR ) and plasma norepinephrine ( NE ) or epinephrine ( Epi ) in each group . In the controls the change in ANP correlated with those in SBP , HR and NE ( p < 0.05 ) , and similarly the change in BNP with those in SBP , HR , NE and Epi ( p < 0.05 ) . In multivariate regression analysis only NE was found to be a significant stimulus for ANP secretion , whereas SBP or Epi was related to BNP release . In the hypertensives the change in ANP correlated with those in HR and NE , but on multivariate regression analysis the change in ANP correlated only with that in HR . The change in BNP in the hypertensives correlated only with that in HR . These findings indicate that in normal subjects the exercise-induced release of BNP and ANP is more sensitive to a similar but slightly different sympathetic stimulus , whereas in hypertensives the major stimulus for the release of both hormones is heart rate , indicating that the mediators for BNP or ANP release are altered by some factors involved in hypertension OBJECTIVE Heart failure is common in individuals with type 2 diabetes , and early detection of individuals at risk may offer opportunities for prevention . We aim ed to explore 1 ) prospect i ve associations of B-type natriuretic peptide ( BNP ) levels in a non – heart failure range with changes in markers of left ventricular ( LV ) function and 2 ) possible effect modification by type 2 diabetes in a population -based cohort . RESEARCH DESIGN AND METHODS Echocardiographic measurements were performed at baseline ( 2000–2001 ) and follow-up ( 2007–2009 ) , together with st and ardized physical examinations and BNP measurements on 300 individuals ( mean age 66 years , 32 % with type 2 diabetes ) of the longitudinal Hoorn Study . Multivariate linear regression analyses were performed to investigate associations of baseline BNP ( < 100 pg/mL ) in individuals without prevalent heart failure at baseline with changes in LV mass index , LV ejection fraction , left atrial volume index , and ratio of early diastolic LV inflow velocity ( E ) to early diastolic lengthening velocity ( e′ ) ( E/e′ ) . RESULTS In all individuals , higher BNP was associated with 8-year increases in left atrial volume index . Higher BNP was also associated with increasing LV mass index and E/e′. These associations were significantly stronger in individuals with type 2 diabetes compared with the nonsignificant associations in individuals without type 2 diabetes . CONCLUSIONS This 8-year follow-up study shows that higher BNP levels in a non – heart failure range were associated with an increased LV mass and deteriorated LV diastolic function , particularly in individuals with type 2 diabetes . This implies that the presence or absence of type 2 diabetes should be taken into account if BNP levels are used to assess future heart failure risk OBJECTIVE —Atrial natriuretic peptide ( ANP ) regulates arterial blood pressure . In addition , ANP has recently been shown to promote human adipose tissue lipolysis through cGMP-mediated hormone-sensitive lipase activation . We hypothesized that ANP increases postpr and ial free fatty acid ( FFA ) availability and energy expenditure while decreasing arterial blood pressure . RESEARCH DESIGN AND METHODS —We infused human ANP ( 25 ng · kg−1 · min−1 ) in 12 men ( age 32 ± 0.8 years , BMI 23.3 ± 0.4 kg/m2 ) before , during , and 2 h after ingestion of a st and ardized high-fat test meal in a r and omized , double-blind , cross-over fashion . Cardiovascular changes were monitored by continuous electrocardiogram and beat-by-beat blood pressure recordings . Metabolism was monitored through venous blood sampling , intramuscular and subcutaneous abdominal adipose tissue microdialysis , and indirect calorimetry . RESULTS —ANP infusion decreased mean arterial blood pressure by 4 mmHg during the postpr and ial phase ( P < 0.01 vs. placebo ) . At the same time , ANP induced lipolysis systemically ( P < 0.05 vs. placebo ) and locally in subcutaneous abdominal adipose tissue ( P < 0.0001 vs. placebo ) , leading to a 50 % increase in venous glycerol ( P < 0.01 ) and FFA ( P < 0.05 ) concentrations compared with placebo . The increase in FFA availability with ANP was paralleled by a 15 % increase in lipid oxidation rates ( P < 0.05 vs. placebo ) , driving a substantial increase in postpr and ial energy expenditure ( P < 0.05 vs. placebo ) . CONCLUSIONS —Our data identify the ANP system as a novel pathway regulating postpr and ial lipid oxidation , energy expenditure , and concomitantly arterial blood pressure . The findings could have therapeutic implication BACKGROUND The natriuretic peptides are counterregulatory hormones involved in volume homeostasis and cardiovascular remodeling . The prognostic significance of plasma natriuretic peptide levels in apparently asymptomatic persons has not been established . METHODS We prospect ively studied 3346 persons without heart failure . Using proportional-hazards regression , we examined the relations of plasma B-type natriuretic peptide and N-terminal pro-atrial natriuretic peptide to the risk of death from any cause , a first major cardiovascular event , heart failure , atrial fibrillation , stroke or transient ischemic attack , and coronary heart disease . RESULTS During a mean follow-up of 5.2 years , 119 participants died and 79 had a first cardiovascular event . After adjustment for cardiovascular risk factors , each increment of 1 SD in log B-type natriuretic peptide levels was associated with a 27 percent increase in the risk of death ( P=0.009 ) , a 28 percent increase in the risk of a first cardiovascular event ( P=0.03 ) , a 77 percent increase in the risk of heart failure ( P<0.001 ) , a 66 percent increase in the risk of atrial fibrillation ( P<0.001 ) , and a 53 percent increase in the risk of stroke or transient ischemic attack ( P=0.002 ) . Peptide levels were not significantly associated with the risk of coronary heart disease events . B-type natriuretic peptide values above the 80th percentile ( 20.0 pg per milliliter for men and 23.3 pg per milliliter for women ) were associated with multivariable-adjusted hazard ratios of 1.62 for death ( P=0.02 ) , 1.76 for a first major cardiovascular event ( P=0.03 ) , 1.91 for atrial fibrillation ( P=0.02 ) , 1.99 for stroke or transient ischemic attack ( P=0.02 ) , and 3.07 for heart failure ( P=0.002 ) . Similar results were obtained for N-terminal pro-atrial natriuretic peptide . CONCLUSIONS In this community-based sample , plasma natriuretic peptide levels predicted the risk of death and cardiovascular events after adjustment for traditional risk factors . Excess risk was apparent at natriuretic peptide levels well below current thresholds used to diagnose heart failure BACKGROUND Now that marathon racing is growing in popularity , many thous and s of enthusiastic athletes are participating in various ultramarathons all over the world each year . However , it remains controversial whether such a sport contributes to the promotion of health . The occurrence of transient cardiac dysfunction and irreversible myocardial injury has been reported in association with such exercise in healthy individuals . Brain natriuretic peptide ( BNP ) is a cardiac hormone , as is atrial natriuretic peptide ( ANP ) , and its measurement has been widely used for clinical evaluation of cardiac dysfunction . However , little is known about the response of plasma BNP to prolonged strenuous exercise . We hypothesized that confirmation of minimal cardiac dysfunction or myocardial injury may be made by measurements of plasma BNP . METHODS Levels of plasma ANP , BNP , catecholamines , blood lactate , and serum cardiac troponin T ( cTnT ) were determined before and after a 100-km ultramarathon in 10 healthy men to examine the effects of the exercise on levels of ANP and BNP and correlations between the natriuretic peptides and cTnT as a marker for myocardial damage . RESULTS Whereas all variables significantly increased after the race , increased levels of ANP and BNP were most strongly correlated with increases in cTnT levels . The cTnT level after the race was greater than the upper reference limit in 9 of 10 men . CONCLUSIONS Such exercise significantly increased ANP and BNP levels in healthy men , and the increases could be partially attributed to myocardial damage during the race BACKGROUND C-type natriuretic peptide ( CNP ) is structurally related to cardiac natriuretic peptides and is currently considered as an endothelium-derived hyperpolarizing factor . Endothelial dysfunction , commonly observed in chronic heart failure ( HF ) patients is positively affected by physical training . METHODS To evaluate the effect of aerobic physical training on the expression of CNP , 90 HF patients on optimal pharmacological treatment ( age 62+/-2 years , mean+/-SEM ) , r and omly assigned in a 3 : 1 ratio to either control group ( C , 19 patients ) or home-based aerobic exercise-training program group ( T , 71 patients ) , completed the protocol . Plasma assay of CNP , brain natriuretic peptide or B-type natriuretic peptide ( BNP ) , and norepinephrine ; echocardiogram ; and cardiopulmonary-stress test were performed in all patients at enrollment and after 9 months . RESULTS At baseline , in both groups , CNP plasma level was significantly related to BNP ( R=0.50 ) , ejection fraction ( R=0.43 ) , and peak oxygen uptake ( VO2 , R=0.43 , all P<0.001 ) . After 9 months , trained patients showed an improvement in peak VO2 ( P<0.001 ) and ejection fraction ( P<0.05 ) , whereas norepinephrine ( P<0.05 ) , BNP ( P<0.001 ) , and CNP ( P<0.001 ) decreased . No changes occurred in group C. In group T , the decrease in CNP was significantly related to the increase in peak VO2 ( R=0.31 , P<0.01 ) , and the relation between CNP and BNP was preserved at the end of the program ( R=0.41 , P<0.001 ) . CONCLUSION Clinical and functional improvement after physical training in HF patients is associated with a decrease in adrenergic activation and in both CNP and BNP concentration . Changes in CNP plasma concentration after physical training might reflect an improvement in endothelial function BACKGROUND Walking is associated with reduced diabetes incidence , but few studies have examined whether it reduces mortality among those who already have diabetes . OBJECTIVE To estimate the association between walking and the risk for all-cause and cardiovascular disease ( CVD ) mortality among persons with diabetes . DESIGN Prospect i ve cohort study of a representative sample of the US population . SETTING Interviewer-administered survey in the general community . PARTICIPANTS We sample d 2896 adults 18 years and older with diabetes as part of the 1990 and 1991 National Health Interview Survey . MAIN OUTCOME MEASURE All-cause and CVD mortality for 8 years . RESULTS Compared with inactive individuals , those who walked at least 2 h/wk had a 39 % lower all-cause mortality rate ( hazard rate ratio [ HRR ] , 0.61 ; 95 % confidence interval [ CI ] , 0.48 - 0.78 ; 2.8 % vs 4.4 % per year ) and a 34 % lower CVD mortality rate ( HRR , 0.66 ; 95 % CI , 0.45 - 0.96 ; 1.4 % vs 2.1 % per year ) . We controlled for sex , age , race , body mass index ( calculated as weight in kilograms divided by the square of height in meters ) , smoking , and comorbid conditions . The mortality rates were lowest for persons who walked 3 to 4 h/wk ( all-cause mortality HRR , 0.46 ; 95 % CI , 0.29 - 0.71 ; CVD mortality HRR , 0.47 ; 95 % CI , 0.24 - 0.91 ) and for those who reported that their walking involved moderate increases in heart and breathing rates ( Output:	In athletes and young , healthy subjects , the NP concentration at rest is not elevated , but strenuous endurance exercise significantly increases NPs . The exercise-induced increase in NPs may be caused by transient myocardial wall stress , cardiomyocyte metabolic changes , or neuroendocrinological response , which may have cytoprotective and growth-regulating effects on the heart . On the other h and , in elderly , overweight/obese subjects , and patients with hypertension , NP concentrations also increase during exercise ; however , NP secretion may be more susceptible to cardiac stress compared to young , healthy individuals . Recent studies have shown that NPs are associated with thermogenesis in fat tissue and oxidative capacity in skeletal muscles .
MS21439	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: The sperm – hyaluronan binding assay ( HBA ) is a diagnostic kit for assessing sperm maturity , function and fertility . The aim of this prospect i ve cohort pilot study was to evaluate the relationship between HBA and WHO sperm parameters ( motility , concentration and detailed morphology ) and possible influence of sperm processing on hyaluronic acid binding . A cohort of 68 patients undergoing a first combo in vitro fertilisation/intracytoplasmic sperm injection treatment after failure of three or more intrauterine insemination cycles were included in the study . Outcome measures studied were fertilisation rate , embryo quality , ongoing pregnancy rate and cumulative pregnancy rate . HBA outcome improved after sperm preparation and culture , but was not correlated to detailed sperm morphology , concentration or motility . HBA did not provide additional information for identifying patients with poor or absent fertilisation , although the latter had more immature sperm cells and cells with cytoplasmic retention present in their semen . HBA outcome in the neat sample was significantly correlated with embryo quality , with miscarriage rates and ongoing pregnancy rates in the fresh cycles , but not with the cumulative ongoing pregnancy rate . No threshold value for HBA and outcome in combo IVF/ICSI treatment could be established . The clinical value for HBA in addition to routine semen analysis for this patient population seems limited The purpose of this study was to investigate whether sperm selection by hyaluronic acid ( HA ) binding could improve fertilization rate and embryo quality in intracytoplasmic sperm injection ( ICSI ) cycles . Two hundred nineteen oocytes obtained from eighteen women were injected with either HA-bound ( n = 107 ) or conventionally selected spermatozoa ( n = 112 ) in a r and omized way . All of the participants were infertile couples who had normal sperm parameters but low fertilization rate in previous in vitro fertilization ( IVF ) cycle ( n = 5 ) or experienced multiple IVF failures ( n = 13 ) . Lower fertilization ( 75.7 % vs 83.0 % ) and cleavage rate on day 2 ( 72.9 % vs 83.0 % ) was observed in oocytes injected with HA-bound spermatozoa than the conventional group , but the difference was not significant . Significantly lower cleavage rate was observed on day 3 in HA group ( 56.0 % vs 69.6 % , P = 0.038 ) . Blastocyst formation rate and the number of transferred embryos were similar in both groups . In multiple IVF failure patients , significantly reduced fertilization rate ( 71.8 % vs 85.3 % , P = 0.046 ) and cleavage rate on day 2 ( 70.4 % vs 85.3 % , P = 0.029 ) and day 3 ( 53.5 % vs 77.3 % , P = 0.002 ) were noticed in HA group . Five women achieved pregnancy continuing more than 12 weeks after transfer ( 27.8 % ) . Success of ICSI was not related with the number of embryos fertilized by HA-bound spermatozoa . Application of ICSI by sperm selection using HA binding is not helpful in couples with repeated poor fertilization or implantation despite normal sperm parameters STUDY QUESTION Does the selection of sperm for ICSI based on their ability to bind to hyaluronan improve the clinical pregnancy rates ( CPR ) ( primary end-point ) , implantation ( IR ) and pregnancy loss rates ( PLR ) ? SUMMARY ANSWER In couples where ≤65 % of sperm bound hyaluronan , the selection of hyaluronan-bound ( HB ) sperm for ICSI led to a statistically significant reduction in PLR . WHAT IS KNOWN AND WHAT THIS PAPER ADDS HB sperm demonstrate enhanced developmental parameters which have been associated with successful fertilization and embryogenesis . Sperm selected for ICSI using a liquid source of hyaluronan achieved an improvement in IR . A pilot study by the primary author demonstrated that the use of HB sperm in ICSI was associated with improved CPR . The current study represents the single largest prospect i ve , multicenter , double-blinded and r and omized controlled trial to evaluate the use of hyaluronan in the selection of sperm for ICSI . DESIGN Using the hyaluronan binding assay , an HB score was determined for the fresh or initial ( I-HB ) and processed or final semen specimen ( F-HB ) . Patients were classified as > 65 % or ≤65 % I-HB and stratified accordingly . Patients with I-HB scores ≤65 % were r and omized into control and HB selection ( HYAL ) groups whereas patients with I-HB > 65 % were r and omized to non-participatory ( NP ) , control or HYAL groups , in a ratio of 2:1:1 . The NP group was included in the > 65 % study arm to balance the higher prevalence of patients with I-HB scores > 65 % . In the control group , oocytes received sperm selected via the conventional assessment of motility and morphology . In the HYAL group , HB sperm meeting the same visual criteria were selected for injection . Patient participants and clinical care providers were blinded to group assignment . PARTICIPANTS AND SETTING Eight hundred two couples treated with ICSI in 10 private and hospital-based IVF programs were enrolled in this study . Of the 484 patients stratified to the I-HB > 65 % arm , 115 participants were r and omized to the control group , 122 participants were r and omized to the HYAL group and 247 participants were r and omized to the NP group . Of the 318 patients stratified to the I-HB ≤ 65 % arm , 164 participants were r and omized to the control group and 154 participants were r and omized to the HYAL group . MAIN RESULTS AND THE ROLE OF CHANCE HYAL patients with an F-HB score ≤65 % demonstrated an IR of 37.4 % compared with 30.7 % for control [ n = 63 , 58 , P > 0.05 , ( 95 % CI of the difference −7.7 to 21.3 ) ] . In addition , the CPR associated with patients r and omized to the HYAL group was 50.8 % when compared with 37.9 % for those r and omized to the control group ( n = 63 , 58 , P > 0.05 ) . The 12.9 % difference was associated with a risk ratio ( RR ) of 1.340 ( RR 95 % CI 0.89–2.0 ) . HYAL patients with I-HB and F-HB scores ≤65 % revealed a statistically significant reduction in their PLR ( I-HB : 3.3 versus 15.1 % , n = 73 , 60 , P = 0.021 , RR of 0.22 ( RR 95 % CI 0.05–0.96 ) ( F-HB : 0.0 % , 18.5 % , n = 27 , 32 , P = 0.016 , RR not applicable due to 0.0 % value ) over control patients . The study was originally planned to have 200 participants per arm providing 86.1 % power to detect an increase in CPR from 35 to 50 % at α = 0.05 but was stopped early for financial reasons . As a pilot study had demonstrated that sperm preparation protocol s may increase the HB score , the design of the current study incorporated a priori collection and analysis of the data by both the I-HB and the F-HB scores . Analysis by both the I-HB and F-HB score acknowledged the potential impact of sperm preparation protocol s. BIAS , CONFOUNDING AND OTHER REASONS FOR CAUTION Selection bias was controlled by r and omization . Geographic and seasonal bias was controlled by recruiting from 10 geographically unique sites and by sampling over a 2-year period . The potential for population effect was controlled by adjusting for higher prevalence rates of > 65 % I-HB that naturally occur by adding the NP arm and to concurrently recruit > 65 % and ≤65 % I-HB subjects . Monitoring and site audits occurred regularly to ensure st and ardization of data collection , adherence to the study protocol and subject recruitment . Subgroup analysis based on the F-HB score was envisaged in the study design . GENERALIZABILITY TO OTHER POPULATION S The study included clinics using different sperm preparation methods , located in different regions of the USA and proceeded in every month of the year . Therefore , the results are widely applicable . STUDY FUNDING /COMPETING INTEREST(S ) This study was funded by Biocoat , Inc. , Horsham , PA , USA . The statistical analysis plan and subsequent analyses were performed by Sherrine Eid , a biostatistician . The manuscript was prepared by Kathryn C. Worrilow , Ph.D. and the study team members . Biocoat , Inc. was permitted to review the manuscript and suggest changes , but the final decision on content was exclusively retained by the authors . K.C.W is a scientific advisor to Biocoat , Inc. S.E. is a consultant to Biocoat , Inc. D.W. has nothing to disclose . M.P. , S.S. , J.W. , K.I. , C.K. and T.E. have nothing to disclose . G.D.B. is a consultant to Cooper Surgical and Unisense . J.L. is on the scientific advisory board of Origio . TRIAL REGISTRATION NUMBER NCT00741494 Purpose Hyaluronic Acid ( HA ) has a role as “ physiologic selector ” for spermatozoa prior to intracytoplasmic sperm injection ( ICSI ) . The objective of this study is to analyze the results achievable by the introduction of a routine HA-ICSI programme . Methods We retrospectively observed 293 couples treated with HA-ICSI versus 86 couples treated with conventional PVP-ICSI ( historical control group ) . ICSI was performed on a limited number of oocytes per patient ( 1–3 ) according to Italian IVF law at the time of the study . Main outcome measures observed were : fertilization , embryo quality , implantation and pregnancy . Results This study showed that Injection of HA-bound spermatozoa ( HA-ICSI ) significantly improves embryo quality and implantation . Conclusions If wider multi-center r and omized studies will confirm these beneficial effects on ICSI outcome , HA could be considered as a routine choice for “ physiologic ” sperm selection prior to ICSI BACKGROUND There is a growing awareness of potential problems in exposing sperm to polyvinylpyrrolidone ( PVP ) to slow their motility , a procedure commonly used prior to ICSI . The study presented here evaluates an alternative product for slowing sperm motility , which contains hyaluronate , a substance found naturally in the reproductive tract . METHODS Computerized sperm motility analysis was used to compare the motilities of sperm exposed to either a PVP-containing product ( ICSI-100 ) , or a hyaluronate-containing product ( SpermCatch ) , or control sperm resuspended in a sperm maintenance medium . A subjective assessment was made of the ease with which sperm could be isolated and be drawn into , and expelled from , an injection pipette after having their tails nicked . Sperm exposed to either ICSI-100 or SpermCatch were used for ICSI . Fertilization rate , zygote development , grading , and outcome of transfer were recorded for the two treatment groups . RESULTS The hyaluronate-containing product slowed sperm motility sufficiently for the sperm to be captured in an injection pipette , was easy to draw into and expel from the pipette , prevented sperm sticking to plastic or glassware , and did not affect post-injection zygote development . Clinical pregnancy rates were similar for the two groups . CONCLUSIONS This product represents an alternative to PVP for slowing sperm motility prior to ICSI OBJECTIVE : To test the feasibility of creating a valid and reliable checklist with the following features : appropriate for assessing both r and omised and non-r and omised studies ; provision of both an overall score for study quality and a profile of scores not only for the quality of reporting , internal validity ( bias and confounding ) and power , but also for external validity . DESIGN : A pilot version was first developed , based on epidemiological principles , review s , and existing checklists for r and omised studies . Face and content validity were assessed by three experienced review ers and reliability was determined using two raters assessing 10 r and omised and 10 non-r and omised studies . Using different raters , the checklist was revised and tested for internal consistency ( Kuder-Richardson 20 ) , test-retest and inter-rater reliability ( Spearman correlation coefficient and sign rank test ; kappa statistics ) , criterion validity , and respondent burden . MAIN RESULTS : The performance of the checklist improved considerably after revision of a pilot version . The Quality Index had high internal consistency ( KR-20 : 0.89 ) as did the subscales apart from external validity ( KR-20 : 0.54 ) . Test-retest ( r 0.88 ) and inter-rater ( r 0.75 ) reliability of the Quality Index were good . Reliability of the subscales varied from good ( bias ) to poor ( external validity ) . The Quality Index correlated highly with an existing , established instrument for assessing r and omised studies ( r 0.90 ) . There was little difference between its performance with non-r and omised and with r and omised studies . Raters took about 20 minutes to assess each paper ( range 10 to 45 minutes ) . CONCLUSIONS : This study has shown that it is feasible to develop a checklist that can be used to assess the method ological Output:	Evidence does not support routine use of hyaluronic acid binding assays in all ICSI cycles .
MS21440	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: AIMS To compare the effects of lifestyle modification programs that prescribe low-glycemic load ( GL ) vs. low-fat diets in a r and omized trial . METHODS Seventy-nine obese adults with type 2 diabetes received low-fat or low-GL dietary instruction , delivered in 40-week lifestyle modification programs with identical goals for calorie intake and physical activity . Changes in weight , HbA(1c ) , and other metabolic parameters were compared at weeks 20 and 40 . RESULTS Weight loss did not differ between groups at week 20 ( low-fat : -5.7±3.7 % ; low-GL : -6.7±4.4 % , p=.26 ) or week 40 ( low-fat : -4.5±7.5 % ; low-GL : -6.4±8.2 % , p=.28 ) . Adjusting for changes in antidiabetic medications , subjects on the low-GL diet had larger reductions in HbA(1c ) than those on the low-fat diet at week 20 ( low-fat : -0.3±0.6 % ; low-GL : -0.7±0.6 % , p=.01 ) , and week 40 ( low-fat : -0.1±1.2 % ; low-GL : -0.8±1.3 % ; p=.01 ) . Groups did not differ significantly on any other metabolic outcomes ( p≥.06 ) . CONCLUSIONS Results suggest that targeting GL , rather than dietary fat , in a low-calorie diet can significantly enhance the effect of weight loss on HbA(1c ) in patients with type 2 diabetes Background Increasing evidence supports carbohydrate restricted diets ( CRD ) for weight loss and improvement in traditional markers for cardiovascular disease ( CVD ) ; less is known regarding emerging CVD risk factors . We previously reported that a weight loss intervention based on a CRD ( % carbohydrate : fat : protein = 13:60:27 ) led to a mean weight loss of 7.5 kg and a 20 % reduction of abdominal fat in 29 overweight men . This group showed reduction in plasma LDL-cholesterol and triglycerides and elevations in HDL-cholesterol as well as reductions in large and medium VLDL particles and increases in LDL particle size . In this study we report on the effect of this intervention with and without fiber supplementation on plasma homocysteine , lipoprotein ( a ) [ Lp(a ) ] , C-reactive protein ( CRP ) , interleukin-6 ( IL-6 ) , and tumor necrosis factor alpha ( TNF-α ) . Methods Twenty nine overweight men [ body mass index ( BMI ) 25–35 kg/m2 ] aged 20–69 years consumed an ad libitum CRD ( % carbohydrate : fat : protein = 13:60:27 ) including a st and ard multivitamin every other day for 12 wk . Subjects were matched by age and BMI and r and omly assigned to consume 3 g/d of either a soluble fiber supplement ( n = 14 ) or placebo ( n = 15 ) . Results There were no group or interaction ( fiber × time ) main effects , but significant time effects were observed for several variables . Energy intake was spontaneously reduced ( -30.5 % ) . This was accompanied by an increase in protein intake ( 96.2 ± 29.8 g/d to 107.3 ± 29.7 g/d ) and methionine intake ( 2.25 ± 0.7 g/d , to 2.71 ± 0.78 g/d ; P < 0.001 ) . Trans fatty acid intake was significantly reduced ( -38.6 % ) while dietary folate was unchanged , as was plasma homocysteine . Bodyweight ( -7.5 ± 2.5 kg ) was reduced as was plasma Lp(a ) ( -11.3 % ) . Changes in plasma Lp(a ) correlated with reductions in LDL-cholesterol ( r = .436 , P < 0.05 ) and fat loss ( r = .385 , P < 0,05 ) . At wk 12 , both CRP ( -8.1 % ) and TNF-α ( -9.3 % ) were reduced ( P < 0.05 ) independently of weight loss . IL-6 concentrations were unchanged . Conclusion A diet based on restricting carbohydrates leads to spontaneous caloric reduction and subsequent improvement in emerging markers of CVD in overweight/obese men who are otherwise healthy Background Control of body weight by balancing energy intake and energy expenditure is of major importance for the prevention of type 2 diabetes , but the role of specific dietary factors in the etiology of type 2 diabetes is less well established . We evaluated intakes of whole grain , bran , and germ in relation to risk of type 2 diabetes in prospect i ve cohort studies . Methods and Findings We followed 161,737 US women of the Nurses ' Health Studies ( NHSs ) I and II , without history of diabetes , cardiovascular disease , or cancer at baseline . The age at baseline was 37–65 y for NHSI and 26–46 y for NHSII . Dietary intakes and potential confounders were assessed with regularly administered question naires . We documented 6,486 cases of type 2 diabetes during 12–18 y of follow-up . Other prospect i ve cohort studies on whole grain intake and risk of type 2 diabetes were identified in search es of MEDLINE and EMBASE up to January 2007 , and data were independently extracted by two review ers . The median whole grain intake in the lowest and highest quintile of intake was , respectively , 3.7 and 31.2 g/d for NHSI and 6.2 and 39.9 g/d for NHSII . After adjustment for potential confounders , the relative risks ( RRs ) for the highest as compared with the lowest quintile of whole grain intake was 0.63 ( 95 % confidence interval [ CI ] 0.57–0.69 ) for NHSI and 0.68 ( 95 % CI 0.57–0.81 ) for NHSII ( both : p-value , test for trend < 0.001 ) . After further adjustment for body mass index ( BMI ) , these RRs were 0.75 ( 95 % CI 0.68–0.83 ; p-value , test for trend < 0.001 ) and 0.86 ( 95 % CI 0.72–1.02 ; p-value , test for trend 0.03 ) respectively . Associations for bran intake were similar to those for total whole grain intake , whereas no significant association was observed for germ intake after adjustment for bran . Based on pooled data for six cohort studies including 286,125 participants and 10,944 cases of type 2 diabetes , a two-serving-per-day increment in whole grain consumption was associated with a 21 % ( 95 % CI 13%–28 % ) decrease in risk of type 2 diabetes after adjustment for potential confounders and BMI . Conclusions Whole grain intake is inversely associated with risk of type 2 diabetes , and this association is stronger for bran than for germ . Findings from prospect i ve cohort studies consistently support increasing whole grain consumption for the prevention of type 2 diabetes BACKGROUND Recent prospect i ve data suggest that intake of rapidly digested and absorbed carbohydrates with a high dietary glycemic load is associated with an increased risk of ischemic heart disease . OBJECTIVE We examined whether a high dietary glycemic load was associated with elevated hs-CRP concentrations and whether this association was modified by body mass index ( BMI ; in kg/m(2 ) ) . DESIGN In 244 apparently healthy women , we measured plasma hs-CRP concentrations and determined average dietary glycemic loads with a vali date d semiquantitative food-frequency question naire . Using multiple regression models , we evaluated the association between dietary glycemic load and plasma hs-CRP after adjusting for age ; treatment status ; smoking status ; BMI ; physical activity level ; parental history of myocardial infa rct ion ; history of hypertension , diabetes , and high cholesterol ; postmenopausal hormone use ; alcohol intake ; and other dietary variables . RESULTS We found a strong and statistically significant positive association between dietary glycemic load and plasma hs-CRP . The median hs-CRP concentration for the lowest quintile of dietary glycemic load was 1.9 mg/L and for the highest quintile was 3.7 mg/L ; corresponding multivariate-adjusted geometric means were 1.4 and 3.8 mg/L , respectively ( P for trend < 0.01 ) . This association was significantly modified by BMI . Among women with a BMI greater-than-or-equal 25 , the multivariate-adjusted geometric mean hs-CRP concentration in the lowest quintile was 1.6 mg/L and in the highest quintile was 5.0 mg/L ; however , among women with a BMI < 25 , the corresponding means were 1.1 and 3.1 mg/L , respectively ( P = 0.01 for interaction ) . CONCLUSIONS Dietary glycemic load is significantly and positively associated with plasma hs-CRP in healthy middle-aged women , independent of conventional risk factors for ischemic heart disease . Exacerbation of the proinflammatory process may be a mechanism whereby a high intake of rapidly digested and absorbed carbohydrates increases the risk of ischemic heart disease , especially in overweight women prone to insulin resistance High intakes of whole grain foods are inversely related to the incidence of coronary heart diseases and type 2 diabetes , but the mechanisms remain unclear . Our study aim ed to evaluate the effects of a diet rich in whole grains compared with a diet containing the same amount of refined grains on insulin sensitivity and markers of lipid peroxidation and inflammation . In a r and omized crossover study , 22 women and 8 men ( BMI 28 + /- 2 ) were given either whole-grain or refined-grain products ( 3 bread slices , 2 crisp bread slices , 1 portion muesli , and 1 portion pasta ) to include in their habitual daily diet for two 6-wk periods . Peripheral insulin sensitivity was determined by euglycemic hyperinsulinemic clamp tests . 8-Iso-prostagl and in F(2alpha ) ( 8-iso PGF(2alpha ) ) , an F(2)-isoprostane , was measured in the urine as a marker of lipid peroxidation , and highly sensitive C-reactive protein and IL-6 were analyzed in plasma as markers of inflammation . Peripheral insulin sensitivity [ mg glucose . kg body wt(-1 ) . min(-1 ) per unit plasma insulin ( mU/L ) x 100 ] did not improve when subjects consumed whole-grain products ( 6.8 + /- 3.0 at baseline and 6.5 + /- 2.7 after 6 wk ) or refined products ( 6.4 + /- 2.9 and 6.9 + /- 3.2 , respectively ) and there were no differences between the 2 periods . Whole-grain consumption also did not affect 8-iso-PGF(2alpha ) in urine , IL-6 and C-reactive protein in plasma , blood pressure , or serum lipid concentrations . In conclusion , substitution of whole grains ( mainly based on milled wheat ) for refined-grain products in the habitual daily diet of healthy moderately overweight adults for 6-wk did not affect insulin sensitivity or markers of lipid peroxidation and inflammation BACKGROUND The optimal source and amount of dietary carbohydrate for managing type 2 diabetes ( T2DM ) are unknown . OBJECTIVE We aim ed to compare the effects of altering the glycemic index or the amount of carbohydrate on glycated hemoglobin ( HbA1c ) , plasma glucose , lipids , and C-reactive protein ( CRP ) in T2DM patients . DESIGN Subjects with T2DM managed by diet alone ( n=162 ) were r and omly assigned to receive high-carbohydrate , high-glycemic-index ( high-GI ) , high-carbohydrate , low-glycemic-index ( low-GI ) , or low-carbohydrate , high-monounsaturated-fat ( low-CHO ) diets for 1 y. RESULTS The high-GI , low-GI , and low-CHO diets contained , respectively , 47 % , 52 % , and 39 % of energy as carbohydrate and 31 % , 27 % , and 40 % of energy as fat ; they had GIs of 63 , 55 , and 59 , respectively . Body weight and HbA1c did not differ significantly between diets . Fasting glucose was higher ( P=0.041 ) , but 2-h postload glucose was lower ( P=0.010 ) after 12 mo of the low-GI diet . With the low-GI diet , overall mean triacylglycerol was 12 % higher and HDL cholesterol 4 % lower than with the low-CHO diet ( P<0.05 ) , but the difference in the ratio of total to HDL cholesterol disappeared by 6 mo Output:	Evidence from intervention studies for antiinflammatory benefits is less consistent for higher-fiber or whole-grain diets than for low-GI/GL diets . Benefits of higher fiber and whole-grain intakes suggested by observational studies may reflect confounding
MS21441	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Background : Vitamin D , from diet and sunlight exposure , may be associated with reduced breast-cancer risk . This study investigated if c and i date gene variants in vitamin D pathways are associated with breast cancer risk , or modify the associations between breast cancer and vitamin D exposure . Methods : Breast cancer cases aged 25 to 74 years were identified from the Ontario Cancer Registry ( histopathologically confirmed and diagnosed 2002–2003 ) and population -based controls were identified through r and om digit dialing of Ontario households . Saliva ( DNA ) was available for 1,777 cases and 1,839 controls . Multivariate logistic regression was used to evaluate associations between 19 single nucleotide polymorphisms ( SNP ) in vitamin D related genes , including vitamin D binding protein ( GC ) , vitamin D receptor ( VDR ) , and cytochrome P450 type 24A1 ( CYP24A1 ) . Statistical interactions were assessed using the likelihood ratio test . Results : Some SNPs were found to be significantly associated with breast cancer risk . For example , breast cancer risk was associated with the GC rs7041 TT genotype ( age-adjusted odds ratio ( OR ) = 1.23 ; 95 % CI : 1.01 , 1.51 ) and inversely with the VDR Fok1 ( rs2228570 ) ff genotype ( OR = 0.71 ; 95 % CI : 0.57 , 0.88 ) . Few significant gene-environment interactions were observed between dietary vitamin D and genetic variants . Conclusion : Our study suggests certain vitamin D related genetic variants may influence breast-cancer risk and we found limited evidence that genetic variants modify the associations between vitamin D exposure and breast cancer risk . Impact : Variation in vitamin D-related genotypes may help to explain inconsistent results from previous epidemiologic studies and may lead to targeted prevention strategies . Cancer Epidemiol Biomarkers Prev ; 20(8 ) ; 1708–17 . © 2011 AACR Background Higher sunlight exposure is correlated with lower incidence of breast cancer in ecological studies , but findings from prospect i ve studies regarding the association of circulating levels of vitamin D with the risk of breast cancer have been null . The objective of this study was to examine the relation between plasma levels of vitamin D and the risk of postmenopausal breast cancer . Methods We conducted a nested case – control study within the Multiethnic Cohort Study of five race/ethnic groups ( white , African-American , Native Hawaiian , Japanese , and Latino ) from Hawaii and Los Angeles between 2001 and 2006 . Pre-diagnostic plasma levels of 25-hydroxyvitamin D2 [ 25(OH)D2 ] , 25-hydroxyvitamin D3 [ 25(OH)D3 ] and 25(OH)D ( sum of 25(OH)D2 and 25(OH)D3 ) were examined among 707 postmenopausal breast cancer cases and matched controls . Results Using conditional logistic regression models , 20 ng/mL increases of plasma 25(OH)D3 ( odds ratio ( OR ) 0.28 ; 95 % confidence interval ( CI ) 0.14 - 0.56 ) and 25(OH)D ( OR 0.43 ; 95 % CI 0.23 - 0.80 ) were inversely associated with breast cancer risk among white women , but not among women in other race/ethnic groups . Using two-segmented , piecewise-linear logistic regression models , the change-points of the ORs , either for 25(OH)D3 or for 25(OH)D , were detected as 20 ng/mL among whites . Conclusions Circulating 25(OH)D3 and 25(OH)D were associated with a reduced risk of postmenopausal breast cancer among whites , but not in other ethnic groups , who reside in low latitude regions Background : Calcium , vitamin D , and dairy products are highly correlated factors , each with potential roles in breast carcinogenesis . Few prospect i ve studies have examined these relationships in postmenopausal women . Methods : Participants in the Cancer Prevention Study II Nutrition Cohort completed a detailed question naire on diet , vitamin and mineral supplement use , medical history , and lifestyle in 1992 to 1993 . After exclusion of women with a history of cancer and incomplete dietary data , 68,567 postmenopausal women remained for analysis . During follow-up through August 31 , 2001 , we identified 2,855 incident cases of breast cancer . Multivariate-adjusted rate ratios ( RR ) were calculated using Cox proportional hazards models . Results : Women with the highest intake of dietary calcium ( > 1,250 mg/d ) were at a lower risk of breast cancer than those reporting ≤500 mg/d [ RR , 0.80 ; 95 % confidence interval ( 95 % CI ) , 0.67 - 0.95 ; Ptrend = 0.02 ] ; however , neither use of supplemental calcium nor vitamin D intake was associated with risk . Consumption starting at two or more servings of dairy products per day was likewise inversely associated with risk ( RR , 0.81 ; 95 % CI , 0.69 - 0.95 ; Ptrend = 0.002 , compared with < 0.5 servings/d ) . The associations were slightly stronger in women with estrogen receptor – positive tumors comparing highest to lowest intake : dietary calcium ( RR , 0.67 ; 95 % CI , 0.51 - 0.88 ; Ptrend = 0.004 ) ; dairy products ( RR , 0.73 ; 95 % CI , 0.57 - 0.93 ; Ptrend = 0.0003 ) , and dietary vitamin D ( RR , 0.74 ; 95 % CI , 0.59 - 0.93 ; Ptrend = 0.006 ) . Conclusions : Our results support the hypothesis that dietary calcium and /or some other components in dairy products may modestly reduce risk of postmenopausal breast cancer . The stronger inverse associations among estrogen receptor – positive tumors deserve further study . ( Cancer Epidemiol Biomarkers Prev 2005;14(12):2898–904 Purpose Prior prospect i ve studies , including our own , have evaluated total plasma 25-hydroxyvitamin D [ 25(OH)D ] and breast cancer risk with inconsistent results . However , recent studies suggest that some vitamin D functions may be more relevant to the unbound ( free ) fraction of 25(OH)D. Vitamin D binding protein ( DBP ) influences the free 25(OH)D levels and thus possibly the biological activities of vitamin D. Methods We conducted a case – control study nested within the Nurses ’ Health Study II to evaluate the association of plasma free 25(OH)D and DBP with breast cancer risk in predominantly premenopausal women . Plasma sample s were assayed for 25(OH)D and DBP in 584 case – control pairs . Free 25(OH)D levels were calculated based on plasma levels of total 25(OH)D , DBP , and a constant value representing average albumin levels . Conditional logistic regression was used to estimate relative risks ( RRs ) and 95 % confidence intervals ( CIs ) . Results We found no association between plasma calculated free 25(OH)D and risk of breast cancer overall ( highest vs. lowest quartile RR 1.21 , 95 % CI 0.83–1.77 , trend test p value = 0.50 ) . No association was observed for plasma DBP as well ( highest vs. lowest quartile RR 0.95 , 95 % CI 0.67–1.36 , trend test p value = 0.96 ) . Results were similar by tumor hormone receptor status . Neither the total nor the calculated free 25(OH)D and breast cancer association substantially varied by plasma DBP levels . Conclusions Our study does not support an important role of either calculated circulating free 25(OH)D or circulating DBP levels in breast cancer risk among predominantly premenopausal women Several lines of evidence suggest that vitamin D may reduce incidence of breast cancer , but few epidemiologic studies have addressed the relation of plasma vitamin D metabolites to the risk of this disease . We prospect ively examined the relationship between plasma levels of 25-hydroxyvitamin D [ 25(OH)D ] and 1,25-dihydroxyvitamin D [ 1,25(OH)2D ] and risk of breast cancer in a case-control study nested within the Nurses ' Health Study cohort . Blood sample s were collected from study participants in 1989 - 1990 . Breast cancer cases developing between blood collection and June 1 , 1996 , were matched to cancer-free controls on the basis of age , menopausal status , and other factors . Stored plasma sample s from 701 cases and 724 controls were available for metabolite analysis . Cases had a lower mean 25(OH)D level than controls ( P = 0.01 ) , but mean 1,25(OH)2D levels were similar ( P = 0.49 ) . High levels of both metabolites were associated with a nonsignificant lower risk of breast cancer . Women in the highest quintile of 25(OH)D had a relative risk of 0.73 ( 95 % confidence interval = 0.49 - 1.07 ; Ptrend = 0.06 ) compared with those in the lowest quintile . For 1,25(OH)2D , the comparable relative risk was 0.76 ( 95 % confidence interval = 0.52 - 1.11 ; Ptrend = 0.39 ) . For both metabolites , the association was stronger in women ages 60 years and older , but results were not statistically significant . Our findings suggest that high levels of 25(OH)D , and perhaps 1,25(OH)2D , may be modestly associated with reduced risk of breast cancer Introduction Experimental evidence indicates vitamin D may play an important role in breast cancer etiology but epidemiologic evidence to date is inconsistent . Vitamin D comes from dietary intake and sun exposure and plasma levels of 25-hydroxyvitamin D ( 25(OH)D ) are considered the best measure of vitamin D status . Methods We conducted a prospect i ve nested case-control study within the Nurses ' Health Study II ( NHSII ) . Plasma sample s collected in 1996 to 1999 were assayed for 25(OH)D in 613 cases , diagnosed after blood collection and before 1 June 2007 , and in 1,218 matched controls . Multivariate relative risks ( RR ) and 95 % confidence intervals ( CI ) were calculated by conditional logistic regression , adjusting for several breast cancer risk factors . Results No significant association was observed between plasma 25(OH)D levels and breast cancer risk ( top vs. bottom quartile multivariate RR = 1.20 , 95 % CI ( 0.88 to 1.63 ) , P-value , test for trend = 0.32 ) . Results were similar when season-specific quartile cut points were used . Results did not change when restricted to women who were premenopausal at blood collection or premenopausal at diagnosis . Results were similar between estrogen receptor (ER)+/progesterone receptor (PR)+ and ER-/PR- tumors ( P-value , test for heterogeneity = 0.51 ) . The association did not vary by age at blood collection or season of blood collection , but did vary when stratified by body mass index ( P-value , test for heterogeneity = 0.01 ) . Conclusions Circulating 25(OH)D levels were not significantly associated with breast cancer risk in this predominantly premenopausal population Background Early life exposures , including diet , have been implicated in the etiology of breast cancer . Methods A nested case-control study was conducted among participants in the Nurses ' Health Study who completed a 24-item question naire about diet during high school . There were 843 eligible cases diagnosed between onset of study ( 1976 ) and before the return of the high school diet question naire ( 1986 ) , who were matched 10:1 with controls on the basis of age . Results Women who had , during adolescence , a higher consumption of eggs , vegetable fat and fiber had a lower risk of breast cancer , whereas risk of breast cancer was increased among women who consumed more butter . Conclusions A possible association of elements of adolescent diet with risk of breast cancer is reported , but the findings require confirmation in prospect i ve study Background Vitamin D deficiency , which has been linked to an increased risk of colorectal cancer , is particularly common among African Americans . Previous studies of vitamin D status and breast cancer risk , mostly conducted in white women , have had conflicting results . We examined the relationship between predicted vitamin D status and incidence of breast cancer in a cohort of 59,000 African American women . Methods Participants in the Black Women ’s Health Study have been followed by biennial mail question naires since 1995 , with self-reported diagnoses of cancer confirmed by hospital and cancer registry records . Repeated five-fold cross-validation with linear regression was used to derive the best 25-hydroxyvitamin D ( 25(OH)D ) prediction model based on measured 25(OH)D in plasma specimens obtained from 2856 participants in 2013–2015 and question naire-based variables from the same time frame . In the full cohort , including 1454 cases of incident invasive breast cancer , Cox proportional ha Output:	Conclusion : This systematic review suggests a protective relationship between circulating vitamin D ( measured as 25(OH ) D ) and breast cancer development in premenopausal women
MS21442	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: BACKGROUND Heart failure treatment guidelines emphasize daily weight monitoring for patients with heart failure , but data to support this practice are lacking . Using a technology-based heart failure monitoring system , we determined whether daily reporting of weight and symptoms in patients with advanced heart failure would reduce rehospitalization and mortality rates despite aggressive guideline -driven heart failure care . METHODS This was a r and omized , controlled trial . Patients hospitalized with New York Heart Association class III or IV heart failure , with a left ventricular ejection fraction < or = 35 % were r and omized to receive heart failure program care or heart failure program care plus the AlereNet system ( Alere Medical , Reno , Nev ) and followed-up for 6 months . The primary end point was 6-month hospital readmission rate . Secondary end points included mortality , heart failure hospitalization readmission rate , emergency room visitation rate , and quality of life . RESULTS Two hundred eighty patients from 16 heart failure centers across the United States were r and omized : 138 received the AlereNet system and 142 received st and ard care . Mean age was 59 + /- 15 years and 68 % were male . The population had very advanced heart failure , New York Heart Association class III ( 75 % ) or IV ( 25 % ) , as evidence d by serum norepinepherine levels , 6-minute walk distance and outcomes . No differences in hospitalization rates were observed . There was a 56.2 % reduction in mortality ( P < .003 ) for patients r and omized to the AlereNet group . CONCLUSIONS This is the largest multicenter , r and omized trial of a technology-based daily weight and symptom-monitoring system for patients with advanced heart failure . Despite no difference in the primary end point of rehospitalization rates , mortality was significantly reduced for patients r and omized to the AlereNet system without an increase in utilization , despite specialized and aggressive heart failure care in both groups CONTEXT Comprehensive discharge planning by advanced practice nurses has demonstrated short-term reductions in readmissions of elderly patients , but the benefits of more intensive follow-up of hospitalized elders at risk for poor outcomes after discharge has not been studied . OBJECTIVE To examine the effectiveness of an advanced practice nurse-centered discharge planning and home follow-up intervention for elders at risk for hospital readmissions . DESIGN R and omized clinical trial with follow-up at 2 , 6 , 12 , and 24 weeks after index hospital discharge . SETTING Two urban , academically affiliated hospitals in Philadelphia , Pa. PARTICIPANTS Eligible patients were 65 years or older , hospitalized between August 1992 and March 1996 , and had 1 of several medical and surgical reasons for admission . INTERVENTION Intervention group patients received a comprehensive discharge planning and home follow-up protocol design ed specifically for elders at risk for poor outcomes after discharge and implemented by advanced practice nurses . MAIN OUTCOME MEASURES Readmissions , time to first readmission , acute care visits after discharge , costs , functional status , depression , and patient satisfaction . RESULTS A total of 363 patients ( 186 in the control group and 177 in the intervention group ) were enrolled in the study ; 70 % of intervention and 74 % of control subjects completed the trial . Mean age of sample was 75 years ; 50 % were men and 45 % were black . By week 24 after the index hospital discharge , control group patients were more likely than intervention group patients to be readmitted at least once ( 37.1 % vs 20.3 % ; P<.001 ) . Fewer intervention group patients had multiple readmissions ( 6.2 % vs 14.5 % ; P = .01 ) and the intervention group had fewer hospital days per patient ( 1.53 vs 4.09 days ; P<.001 ) . Time to first readmission was increased in the intervention group ( P<.001 ) . At 24 weeks after discharge , total Medicare reimbursements for health services were about $ 1.2 million in the control group vs about $ 0.6 million in the intervention group ( P<.001 ) . There were no significant group differences in post-discharge acute care visits , functional status , depression , or patient satisfaction . CONCLUSIONS An advanced practice nurse-centered discharge planning and home care intervention for at-risk hospitalized elders reduced readmissions , lengthened the time between discharge and readmission , and decreased the costs of providing health care . Thus , the intervention demonstrated great potential in promoting positive outcomes for hospitalized elders at high risk for rehospitalization while reducing costs BACKGROUND Case management is believed to promote continuity of care and decrease hospitalization rates , although few controlled trials have tested this approach . OBJECTIVE To assess the effectiveness of a st and ardized telephonic case-management intervention in decreasing re source use in patients with chronic heart failure . METHODS A r and omized controlled clinical trial was used to assess the effect of telephonic case management on re source use . Patients were identified at hospitalization and assigned to receive 6 months of intervention ( n = 130 ) or usual care ( n = 228 ) based on the group to which their physician was r and omized . Hospitalization rates , readmission rates , hospital days , days to first rehospitalization , multiple readmissions , emergency department visits , inpatient costs , outpatient re source use , and patient satisfaction were measured at 3 and 6 months . RESULTS The heart failure hospitalization rate was 45.7 % lower in the intervention group at 3 months ( P = .03 ) and 47.8 % lower at 6 months ( P = .01 ) . Heart failure hospital days ( P = .03 ) and multiple readmissions ( P = .03 ) were significantly lower in the intervention group at 6 months . Inpatient heart failure costs were 45.5 % lower at 6 months ( P = .04 ) . A cost saving was realized even after intervention costs were deducted . There was no evidence of cost shifting to the outpatient setting . Patient satisfaction with care was higher in the intervention group . CONCLUSIONS The reduction in hospitalizations , costs , and other re source use achieved using st and ardized telephonic case management in the early months after a heart failure admission is greater than that usually achieved with pharmaceutical therapy and comparable with other disease management approaches A multifaceted intervention was hypothesized to increase postdischarge ambulatory contacts and to reduce nonelective readmissions . Patients ( N=1,001 ) discharged from the general medicine service were stratified by risk for nonelective readmission and r and omized to the control or intervention group . Intervention patients received phone calls from nurses , mailings of appointment reminders and lists of early warning signs , and prompt rescheduling of visit failures . Patients were followed for 6 months , and the results were computed in units per patient per month . The intervention group had 10.4 % more total office contacts ( 0.53 vs 0.48 , P=0.005 ) than the control group . Although the intervention group had 7.6 % fewer nonelective readmission days ( 0.85 vs 0.92 ) , this was not statistically significant ( P=0.5 ) . Patients in the intervention group at high risk ( N=181 ) had 28.1 % more office visits ( 0.73 vs 0.57 , P<0.01 ) and 31.9 % fewer nonelective readmission days ( 1.13 vs 1.66 ) , but this was also not statistically significant ( P=0.06 ) . Thus , the intervention significantly increased postdischarge contacts , primarily in high-risk patients , but failed to reduce the incidence of nonelective readmission days significantly 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 OBJECTIVE to prove the effectiveness of geriatric evaluation and management for elderly , hospitalized patients , combined with post-discharge home intervention by an interdisciplinary team . DESIGN r and omized controlled trial with outcome and costs assessed for 12 months after the date of admission . SETTING university-affiliated geriatric hospital and the homes of elderly patients . SUBJECTS 545 patients with acute illnesses admitted from home to the geriatric hospital . INTERVENTIONS patients were r and omly assigned to receive either comprehensive geriatric assessment and post-discharge home intervention ( intervention ) , comprehensive geriatric assessment alone ( assessment ) or usual care . MAIN OUTCOME MEASURES survival , functional status , rehospitalization , nursing home placement and direct costs over 12 months . RESULTS the intervention group showed a significant reduction in length of hospital stay ( 33.49 days vs 40.7 days in the assessment group and 42.7 days in the control group ; P < 0.05 ) and rate of immediate nursing home placement ( 4.4 % vs 7.3 % and 8.1 % ; P < 0.05 ) . There was no difference in survival , acute care hospital readmissions or new admissions to nursing homes but the intervention group had significantly shorter hospital readmissions ( 22.2 days vs 34.2 days and 35.7 days ; P < 0.05 ) and nursing home placements ( 114.7 days vs 161.6 days and 170.0 days ; P < 0.05 ) . Direct costs were lower in the intervention group [ about DM 7000 ( US $ 4000 ) per person per year ] . Functional capacities were significantly better in the intervention group . CONCLUSIONS comprehensive geriatric assessment in combination with post-discharge home intervention does not improve survival , but does improve functional status and can reduce the length of the initial hospital stay and of subsequent readmissions . It can reduce the rate of immediate nursing home admissions and delay permanent nursing home placement . It may also substantially reduce direct costs of hospitalized patients Background .The high cost of caring for patients with congestive heart failure ( CHF ) results primarily from frequent hospital readmissions for exacerbations . Home nurse visits after discharge can reduce readmissions , but the intervention costs are high . Objectives .To compare the effectiveness of three hospital discharge care models for reducing CHF-related readmission charges : 1 ) home telecare delivered via a 2-way video-conference device with an integrated electronic stethoscope ; 2 ) nurse telephone calls ; and 3 ) usual outpatient care . Research Design . One-year r and omized trial . Subjects . English-speaking patients 40 years of age and older with a primary hospital admission diagnosis of CHF . Measures .Our primary outcome was CHF-related readmission charges during a 6-month period after r and omization . Secondary outcomes included all-cause readmissions , emergency department ( ED ) visits , and associated charges . Results .Thirty-seven subjects were r and omized : 13 to home telecare , 12 each telephone care and 12 to usual care . Mean CHF-related readmission charges were 86 % lower in the telecare group ( $ 5850 , SD $ 21,094 ) and 84 % lower in the telephone group ( $ 7320 , SD $ 24,440 ) than in the usual care group ( $ 44,479 , SD $ 121,214 ) . However , the between-group difference was not statistically significant . Both intervention groups had significantly fewer CHF-related ED visits ( P = 0.0342 ) and charges ( P = 0.0487 ) than the usual care group . Trends favoring both interventions were noted for all other utilization outcomes . Conclusions .Substantial reductions in hospital readmissions , emergency visits , and cost of care for patients with CHF might be achieved by widespread deployment of distance technologies to provide posthospitalization monitoring . Home telecare may not offer incremental benefit beyond telephone follow-up and is more expensive Background Telemonitoring of patients with chronic heart failure ( CHF ) is an emerging concept to detect early warning signs of impending acute decompensation in order to prevent hospitalization . Objective The goal of the MOBIle TELemonitoring in Heart Failure Patients Study ( MOBITEL ) was to evaluate the impact of home-based telemonitoring using Internet and mobile phone technology on the outcome of heart failure patients after an episode of acute decompensation . Methods Pat Output:	Conclusions Interventions with components that influenced learning and self-organization were associated with a significant improvement in hospital readmissions-related outcomes . Learning alone might be necessary but not be sufficient for improving transitions . However , building self-organization into the intervention might help people effectively respond to problems and adapt in uncertain situations to reduce the likelihood of readmission
MS21443	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: A double-blind controlled trial of ECT versus simulated ECT is described . The results show that real ECT is significantly superior to simulated ECT in the treatment of depressive illness Objectives Anesthesia is required for both magnetic seizure therapy ( MST ) and electroconvulsive therapy ( ECT ) , although it has anticonvulsant properties . In this case , bispectral index ( BIS ) monitoring , a specific electroencephalogram-derived monitoring , can be used to find the optimal seizure induction time during anesthesia to elicit adequate seizures . A measurement of seizure adequacy in electroencephalogram is the postictal suppression . The purpose of this study was to investigate the influence of seizure induction time on the degree of postictal suppression by comparing BIS versus no-BIS monitoring in MST and ECT . Methods Twenty patients with treatment-resistant depression were r and omly assigned to either MST or ECT . Each patient underwent 3 treatments with the determination of seizure induction time by defined prestimulation BIS ( BIS condition ) and 3 treatments with determination of seizure induction time by controlled clinical trial protocol ( no-BIS condition ) . Statistical analysis was calculated by repeated- measures analysis of variance . Results The degree of postictal suppression was more pronounced in both MST and ECT , with BIS monitoring . In this connection , no differences between MST and ECT were found . Seizure induction time was significantly later in the BIS condition ( 181.3 ± 6 seconds ) compared with the no-BIS condition ( 114.3 ± 12 seconds ) ( P < 0.001 ) . Conclusions Adequacy of seizures , in the form of the degree of postictal suppression , was superior by determining the seizure induction time with BIS in both MST and ECT . Further research is needed to investigate the correlation between the degree of postictal suppression and treatment response Major depressive disorder ( MDD ) is a prevalent and disabling condition , and many patients do not respond to available treatments . Deep transcranial magnetic stimulation ( dTMS ) is a new technology allowing non-surgical stimulation of relatively deep brain areas . This is the first double-blind r and omized controlled multicenter study evaluating the efficacy and safety of dTMS in MDD . We recruited 212 MDD out patients , aged 22 - 68 years , who had either failed one to four antidepressant trials or not tolerated at least two antidepressant treatments during the current episode . They were r and omly assigned to monotherapy with active or sham dTMS . Twenty sessions of dTMS ( 18 Hz over the prefrontal cortex ) were applied during 4 weeks acutely , and then biweekly for 12 weeks . Primary and secondary efficacy endpoints were the change in the Hamilton Depression Rating Scale ( HDRS-21 ) score and response/remission rates at week 5 , respectively . dTMS induced a 6.39 point improvement in HDRS-21 scores , while a 3.28 point improvement was observed in the sham group ( p=0.008 ) , result ing in a 0.76 effect size . Response and remission rates were higher in the dTMS than in the sham group ( response : 38.4 vs. 21.4 % , p=0.013 ; remission : 32.6 vs. 14.6 % , p=0.005 ) . These differences between active and sham treatment were stable during the 12-week maintenance phase . dTMS was associated with few and minor side effects apart from one seizure in a patient where a protocol violation occurred . These results suggest that dTMS constitutes a novel intervention in MDD , which is efficacious and safe in patients not responding to antidepressant medications , and whose effect remains stable over 3 months of maintenance treatment Background The treatment of depression remains a challenge since at least 40 % of patients do not respond to initial antidepressant therapy and 20 % present chronic symptoms ( more than 2 years despite st and ard treatment administered correctly ) . Repetitive transcranial magnetic stimulation ( rTMS ) is an effective adjuvant therapy but still not ideal . Intermittent Theta Burst Stimulation ( iTBS ) , which has only been used recently in clinical practice , could have a faster and more intense effect compared to conventional protocol s , including 10-Hz high-frequency rTMS ( HF-rTMS ) . However , no controlled study has so far highlighted the superiority of iTBS in resistant unipolar depression . Methods / design This paper focuses on the design of a r and omised , controlled , double-blind , single-centre study with two parallel arms , carried out in France , in an attempt to assess the efficacy of an iTBS protocol versus a st and ard HF- rTMS protocol . Sixty patients aged between 18 and 75 years of age will be enrolled . They must be diagnosed with major depressive disorder persisting despite treatment with two antidepressants at an effective dose over a period of 6 weeks during the current episode . The study will consist of two phases : a treatment phase comprising 20 sessions of rTMS to the left dorsolateral prefrontal cortex , localised via a neuronavigation system and a 6-month longitudinal follow-up . The primary endpoint will be the number of responders per group , defined by a decrease of at least 50 % in the initial score on the Montgomery and Asberg Rating Scale ( MADRS ) at the end of rTMS sessions . The secondary endpoints will be : response rate 1 month after rTMS sessions ; number of remissions defined by a MADRS score of < 8 at the endpoint and 1 month after ; the number of responses and remissions maintained over the next 6 months ; quality of life ; and the presence of predictive markers of the therapeutic response : clinical ( dimensional scales ) , neuropsychological ( evaluation of cognitive functions ) , motor ( objective motor testing ) and neurophysiological ( cortical excitability measurements ) . Discussion The purpose of our study is to check the assumption of iTBS superiority in the management of unipolar depression and we will discuss its effect over time . In case of a significant increase in the number of therapeutic responses with a prolonged effect , the iTBS protocol could be considered a first-line protocol in resistant unipolar depression . Trial registration Clinical Trials.gov , Identifier NCT02376491 . Registered on 17 February 2015 at http:// clinical trials.gov BACKGROUND Bipolar depression ( BD ) is a highly prevalent condition associated with marked cognitive deficits that persist even in the euthymic phase of the illness . Pharmacological treatments for BD might further aggravate cognitive impairment , highlighting the need of developing interventions that present cognitive safety . In this study , we evaluated the cognitive effects of H1-coil ( deep ) transcranial magnetic stimulation ( TMS ) in patients with treatment-resistant bipolar depression . METHODS Fourty-three patients were r and omized to receive 20 sessions of active ( 55 trains , 18 Hz , 120 % resting motor threshold intensity ) or sham rTMS within a double-blind , sham-controlled trial . A battery of 20 neuropsychological assessment s , grouped in 6 domains ( attention and processing speed , working memory and executive function , inhibitory control , language , immediate verbal memory , and long-term verbal memory ) was performed at baseline and after 4 and 8 weeks of trial onset . Depressive symptoms were assessed with the 17-item Hamilton Rating Scale for Depression . RESULTS Cognitive improvement was shown for all cognitive domains . It occurred regardless of intervention group and depression improvement . For the language domain , greater improvement was observed in the sham group over time . No correlations between depression ( at baseline or during treatment ) and cognitive improvement were found . LIMITATIONS Absence of healthy control group . CONCLUSION The results of this exploratory study provide evidence on the cognitive safety of H1-coil TMS for BD patients . Putative pro-cognitive effects of rTMS in BD were not observed and thus should be further investigated OBJECTIVES There is little evidence for differences in response and speed of response to electroconvulsive therapy ( ECT ) between patients with bipolar and patients with unipolar depressive disorder . In the only prospect i ve study to date , Daly et al. ( Bipolar Disord 2001 ; 3 : 95 - 104 ) found patients with bipolar depression to show more rapid clinical improvement and require fewer treatments than unipolar patients . In this study , response and speed of response of patients with unipolar and bipolar depression treated with ultra-brief pulse ECT were compared . METHODS All patients ( n = 64 ) participated in a r and omized trial comparing ultra-brief pulse bifrontal ECT at 1.5 times seizure threshold and unilateral ECT at 6 times seizure threshold . Thirteen patients ( 20.3 % ) had DSM-IV-defined bipolar depression . The Hamilton Rating Scale for Depression and Clinical Global Impression scale were administered at baseline and repeated weekly during and after the course of treatment by a blinded rater . At the same time point , the Beck Depression Inventory and the Patient Global Impression scale were administered . Speed of response was analyzed using survival analyses . RESULTS Patients with bipolar and unipolar depression did not differ in rates of response or remission following the ECT course , nor in response to unilateral or bifrontal ECT . Patients with bipolar depression , however , showed a more rapid response than patients with unipolar depression . CONCLUSIONS Patients with bipolar depression tend to show more rapid clinical improvement with ECT than patients with unipolar depression OBJECTIVE Substantial progress has been made in identifying how the treatment parameters used in ECT impact on cognitive side effects . However , there is limited information regarding individual differences in vulnerability to these side effects . The authors examined patients ' pretreatment global cognitive status and postictal orientation recovery time as potential predictors of the magnitude of retro grade amnesia for autobiographical memories after ECT . METHOD Seventy-one in patients with major depressive disorder were r and omly assigned to four ECT conditions that varied in electrode placement ( right unilateral versus bilateral ) and stimulus dosage ( low versus high intensity ) . Orientation recovery time was assessed at virtually every session during the course of ECT . Global cognitive status was assessed with the modified Mini-Mental State examination before treatment , during the week after termination of treatment , and 2 months after treatment ended . Retro grade amnesia was assessed at these same time points with the Autobiographical Memory Interview . RESULTS Pre-ECT global cognitive status and the duration of postictal disorientation were strong predictors of the magnitude of retro grade amnesia in the week after the course of ECT and at 2-month follow-up . In general , these relationships were maintained regardless of technical parameters in the administration of the ECT . CONCLUSIONS Patients who manifest global cognitive impairment before treatment and patients who experience prolonged disorientation in the acute postictal period may be the most vulnerable to persistent retro grade amnesia for autobiographical information Electroconvulsive therapy was investigated in a double blind trial . Altogether 186 clinical ly selected patients were referred to the trial , but 48 of these did not participate . According to the present state examination , 95 of the remaining 138 patients fell into one of the classes of major depression . Patients were r and omly allocated to a course of real or simulated electroconvulsive therapy . Treatment was given twice a week with a maximum of eight treatments . On the Hamilton depressive rating scale the improvement in the group given real treatment was significantly greater than that in the group given simulated treatment both at two weeks ( p = 0.014 ) and at four weeks ( p = 0.0001 ) . At follow up at 12 and 28 weeks there was no difference between the treatment groups . At the end of the four week trial consultants , who were blind to the allocation of treatment , rated the patients who had received real treatment as having made a significantly greater improvement than the patients who had received simulated treatment ( p less than 0.00005 ) . Further analysis showed that electroconvulsive therapy was effective in depression associated with delusions and in depression associated with retardation Since electroconvulsive therapy ( ECT ) can result in generalized seizures that lack efficacy , physiological markers of treatment adequacy are needed . Specific electroencephalographic ( EEG ) features differentiate seizures produced with barely suprathreshold right unilateral ( RUL ) ECT , an ineffective treatment , from effective forms of ECT . This study determined whether EEG features are sensitive to treatment condition using a broad dosing range for RUL ECT , as well as predictive of clinical and cognitive outcomes . Quantitative EEG measures and observer ratings were compared in predictive power . From a larger study , 54 in- patients with major depression were r and omized to low ( 1.5 × seizure threshold ( ST ) ) , moderate ( 2.5 × ST ) , or high-dose ( 6 × ST ) RUL ECT , or high-dose ( 2.5 × ST ) bilateral ( BL ) ECT . High dosage RUL and BL ECT were comparable in efficacy , and superior to low and moderate dosage RUL ECT . In the slow frequency b and s ( δ ) , BL ECT result ed in greater ictal power , ictal coherence , and postictal suppression than each RUL ECT condition , but the EEG measures failed to discriminate the RUL ECT groups . EEG measures were modestly associated with clinical outcome , with greater ictal power , δ coherence , and postictal suppression positive predictors . None of the EEG measures were associated with cognitive outcomes . Inability to distinguish forms of RUL ECT differing markedly in dosage and efficacy suggests that EEG measures have limited potential as markers of treatment adequacy . Rather than assaying treatment adequacy , the EEG features associated with efficacy may reflect individual differences in the strength of inhibitory processes that terminate Output:	The most studied treatment comparisons were high frequency left rTMS and tDCS versus sham therapy , whereas recent treatments remain understudied . All treatment strategies were at least as acceptable as sham therapy .
MS21444	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: The optimal retreatment strategy for patients chronically infected with hepatitis C virus who experience virologic failure after treatment with direct‐acting antiviral – based therapies remains unclear . In this multicenter , open‐label , phase 2 study , we evaluated the efficacy and safety of a fixed‐dose combination of sofosbuvir‐velpatasvir ( 400 mg/100 mg ) plus weight‐adjusted ribavirin administered for 24 weeks in patients who did not achieve sustained virologic response after prior treatment with direct‐acting antiviral regimens that included the nucleotide analogue nonstructural protein 5B inhibitor sofosbuvir plus the nonstructural protein 5A inhibitor velpatasvir with or without the nonstructural protein 3/4A protease inhibitor voxilaprevir . The primary efficacy endpoint was the proportion of patients achieving sustained virologic response at 12 weeks after the cessation of treatment . In total , 63 of 69 ( 91 % ; 95 % confidence interval , 82%‐97 % ) patients achieved sustained virologic response at 12 weeks , including 36 of 37 ( 97 % ; 95 % confidence interval , 86%‐100 % ) patients with hepatitis C virus genotype 1 infection , 13 of 14 ( 93 % ; 95 % confidence interval , 66%‐100 % ) patients with genotype 2 infection , and 14 of 18 ( 78 % ; 95 % confidence interval , 52%‐94 % ) patients with genotype 3 infection . Most adverse events were of mild or moderate severity . The most frequently reported adverse events were fatigue , nausea , headache , insomnia , and rash . One patient ( 1 % ) with genotype 1a infection discontinued all study drugs due to an adverse event ( irritability ) . Conclusion : Retreatment of patients who previously failed direct‐acting antiviral – based therapies with sofosbuvir‐velpatasvir plus ribavirin for 24 weeks was well tolerated and effective , particularly those with hepatitis C virus genotype 1 or 2 infection . ( Hepatology 2017;66:1083‐1089 ) BACKGROUND Interferon-based treatment is not suitable for many patients with hepatitis C virus ( HCV ) infection because of contraindications such as psychiatric illness , and a high burden of adverse events . We assessed the efficacy and safety of an interferon-free regimen -- a fixed-dose combination of the nucleotide polymerase inhibitor sofosbuvir ( 400 mg ) and the HCV NS5A inhibitor ledipasvir ( 90 mg ) , with and without ribavirin -- in patients with genotype-1 hepatitis C infection who were treatment-naive or previously treated with a protease-inhibitor regimen . METHODS For this open-label study , we enrolled 100 adult patients ( > 18 years ) with HCV infection at a centre in the USA between Nov 2 , 2012 , and Dec 21 , 2012 . In cohort A , we used a computer-generated sequence to r and omly assign ( 1:1:1 ; stratified by HCV genotype [ 1a vs 1b ] ) 60 non-cirrhotic , treatment-naive patients to receive sofosbuvir plus ledipasvir for 8 weeks ( group 1 ) , sofosbuvir plus ledipasvir and ribavirin for 8 weeks ( group 2 ) , or sofosbuvir plus ledipasvir for 12 weeks ( group 3 ) . In cohort B , we r and omly allocated ( 1:1 ; stratified by genotype and presence or absence of cirrhosis ) 40 patients who previously had virological failure after receiving a protease inhibitor regimen to receive sofosbuvir plus ledipasvir for 12 weeks ( group 4 ) or sofosbuvir plus ledipasvir and ribavirin for 12 weeks ( group 5 ) . 22 ( 55 % ) of 40 patients in cohort B had compensated cirrhosis . The primary endpoint was sustained virological response 12 weeks after treatment ( SVR12 ) , analysed by intention to treat . This study is registered with Clinical Trials.gov , number NCT01329978 . FINDINGS In cohort A , SVR12 was achieved by 19 ( 95 % ) of 20 patients ( 95 % CI 75 - 100 ) in group 1 , by 21 ( 100 % ) of 21 patients ( 84 - 100 ) in group 2 , and by 18 ( 95 % ) of 19 patients ( 74 - 100 ) in group 3 . In cohort B , SVR12 was achieved by 18 ( 95 % ) of 19 patients ( 74 - 100 ) in group 4 and by all 21 ( 100 % ) of 21 patients ( 84 - 100 ) in group 5 . Two patients had viral relapse ; one patient was lost to follow-up after achieving sustained virological response 8 weeks after treatment . The most common adverse events were nausea , anaemia , upper respiratory tract infection , and headache . One patient in group five had a serious adverse event of anaemia , thought to be related to ribavirin treatment . INTERPRETATION These findings suggest that the fixed-dose combination of sofosbuvir-ledipasvir alone or with ribavirin has the potential to cure most patients with genotype-1 HCV , irrespective of treatment history or the presence of compensated cirrhosis . Further clinical trials are needed to establish the best treatment duration and to further assess the contribution of ribavirin . FUNDING Gilead Sciences BACKGROUND The once-daily , ribavirin-free , pangenotypic , direct-acting antiviral regimen , glecaprevir coformulated with pibrentasvir , has shown high rates of sustained virological response in phase 2 and 3 studies . We aim ed to assess the efficacy and safety of 12 weeks of coformulated glecaprevir and pibrentasvir in patients with hepatitis C virus ( HCV ) infection and compensated cirrhosis . METHODS We did this single-arm , open-label , multicentre phase 3 study at 40 sites in Belgium , Canada , Germany , South Africa , Spain , and the USA . We enrolled patients aged 18 years or older with HCV genotype 1 , 2 , 4 , 5 , or 6 infection and compensated cirrhosis . Patients were either HCV treatment-naive or had not responded to treatment with interferon or pegylated interferon with or without ribavirin , or sofosbuvir plus ribavirin with or without pegylated interferon . Oral glecaprevir ( 300 mg ) coformulated with pibrentasvir ( 120 mg ) was administered once daily for 12 weeks . The primary efficacy endpoint was sustained virological response at post-treatment week 12 ( HCV RNA < 15 IU/mL ) . We assessed efficacy and safety in all patients who received at least one dose of study drug ( intention-to-treat population ) . This study is registered with Clinical Trials.gov , number NCT02642432 . FINDINGS Between Dec 7 , 2015 , and May 4 , 2016 , we enrolled 146 patients with compensated cirrhosis , of whom 48 ( 33 % ) had genotype 1a HCV infection , 39 ( 27 % ) had genotype 1b infection , 34 ( 23 % ) had genotype 2 infection , 16 ( 11 % ) had genotype 4 infection , two ( 1 % ) had genotype 5 infection , and seven ( 5 % ) had genotype 6 infection . 12 weeks after treatment , 145 patients ( 99 % , 95 % CI 98 - 100 ) achieved sustained virological response , with one ( 1 % ) relapse at post-treatment week 8 . We recorded 101 ( 69 % ) adverse events , of which 65 ( 64 % ) were mild . The most common adverse events were fatigue ( n=28 [ 19 % ] ) and headache ( n=20 [ 14 % ] ) . 11 ( 8 % ) patients had serious adverse events , none of which were deemed related to study drugs . No patients had elevations in alanine aminotransferase and no patients prematurely discontinued treatment because of adverse events . INTERPRETATION Our results show that 99 % of patients treated with once-daily glecaprevir plus pibrentasvir achieved a sustained virological response at 12 weeks . Furthermore , this drug regimen had a favourable safety profile in previously treated or untreated patients with chronic HCV genotype 1 , 2 , 4 , 5 , or 6 infection and compensated cirrhosis . These findings could help simplify treatment algorithms and reduce treatment burden . FUNDING AbbVie Glecaprevir ( nonstructural protein 3/4A protease inhibitor ) and pibrentasvir ( nonstructural protein 5A inhibitor ) ( G/P ) , a coformulated once‐daily , all oral , ribavirin (RBV)‐free , direct‐acting antiviral regimen , was evaluated for safety and efficacy in hepatitis C virus genotype 2 (GT2)–infected Japanese patients , including those with compensated cirrhosis . CERTAIN‐2 is a phase 3 , open‐label , multicenter study assessing the safety and efficacy of G/P ( 300/120 mg ) once daily in treatment‐naive and interferon ± RBV treatment – experienced Japanese patients without cirrhosis but with GT2 infection . Patients were r and omized 2:1 to receive 8 weeks of G/P ( arm A ) or 12 weeks of sofosbuvir ( 400 mg once daily ) + RBV ( 600‐1000 mg weight‐based , twice daily ) ( arm B ) . The primary endpoint was noninferiority of G/P compared to sofosbuvir + RBV by assessing sustained virologic response at posttreatment week 12 ( SVR12 ) among patients in the intent‐to‐treat population . SVR12 was also assessed in treatment‐naive and interferon ± RBV treatment‐experienced patients with GT2 infection and compensated cirrhosis who received G/P for 12 weeks in the CERTAIN‐1 study . A total of 136 patients were enrolled in CERTAIN‐2 . SVR12 was achieved by 88/90 ( 97.8 % ) patients in arm A and 43/46 ( 93.5 % ) patients in arm B. No patient in arm A experienced virologic failure , while 2 did in arm B. The primary endpoint was achieved . In CERTAIN‐1 , 100 % ( 18/18 ) of GT2‐infected patients with compensated cirrhosis achieved SVR12 . Treatment‐emergent serious adverse events were experienced by 2 patients without cirrhosis in each arm and no patient with cirrhosis . Conclusion : The results demonstrate high efficacy and favorable tolerability of G/P in GT2‐infected Japanese patients . ( Hepatology 2018;67:505‐513 ) The phase 2 , open-label ACCORDION ( Clinical Trials.gov : NCT02349048 ) study investigated the efficacy , safety and pharmacokinetics of a 6- or 8-week regimen of simeprevir , daclatasvir and sofosbuvir in treatment-naïve patients with chronic hepatitis C virus ( HCV ) genotype ( GT ) 1 infection and either early-stage fibrosis or compensated cirrhosis . Patients were assigned to treatment groups according to their fibrosis stage . Early-stage fibrosis : simeprevir 150 mg , daclatasvir 60 mg , sofosbuvir 400 mg once daily for 6 weeks ; compensated cirrhosis : same regimen for 8 weeks . The primary endpoint was sustained virologic response 12 weeks after the end of treatment ( SVR12 ) . Safety , tolerability and pharmacokinetics of simeprevir , daclatasvir and sofosbuvir were investigated . Sixty-eight patients were treated ( 6-week group : n = 59 ; 8-week group : n = 9 ) . SVR12 was achieved by 86.4 % ( 51/59 ) of patients with early-stage fibrosis and by 100 % ( 9/9 ) of patients with cirrhosis . The main reason for not achieving SVR12 in the 6-week group was viral relapse ( 11.9 % ; 7/59 ) . One patient had on-treatment failure due to an early withdrawal ( lost to follow-up due to incarceration ) . One patient with SVR12 in the 6-week group had a late viral relapse at post-treatment week 24 . No clinical ly significant drug-drug interactions were observed . Adverse events were reported in 63.2 % of patients ( 43/68 ) and were mainly grade 1/2 . None of these led to treatment discontinuation . The 3 direct-acting antiviral regimens of simeprevir , daclatasvir and sofosbuvir were safe and well tolerated in treatment-naïve , HCV GT1-infected patients Output:	Personalised strategies ( 100 % vs 87.6 % ; p<0.001 ) and therapy shortened according to ≥3 host/viral factors ( 92.9 % vs 81.4 % or 87.2 % for 1 or 2 host/viral factors , respectively ; p=0.008 ) offer higher SVR rates when shortening therapy . Conclusions : Treatment optimisation for individuals with multiple predictors of treatment failure can offer high SVR rates .
MS21445	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: The leading cause of postoperative morbidity in patients undergoing major head and neck surgical procedures is postoperative infection . This prospect i ve r and omized multi-institutional clinical trial was design ed to compare the effectiveness of clindamycin phosphate and high-dose cefazolin sodium therapy in preventing postoperative wound sepsis in patients undergoing contaminated head and neck surgical procedures in which flap reconstruction was required . Either clindamycin phosphate ( 900 mg ) or cefazolin sodium ( 2 g ) therapy was instituted intravenously prior to surgery and continued every 8 hours , for a total of 24 hours . The patients received postoperative follow-up , and the wounds were grade d according to the worst condition observed . One hundred cases were evaluated . Fifty-one patients received clindamycin and 49 patients received high doses of cefazolin ; wound infection developed in 10 patients ( 19.6 % ) and 11 patients ( 21.6 % ) , respectively . This difference was not statistically significant . The average duration of surgery was approximately 8 hours for both the infected and the noninfected groups of patients . High-dose cefazolin and clindamycin have similar efficacy when administered prophylactically under these circumstances . Reconstruction with free vascularized tissue may aid in reducing postoperative wound infection Ampicillin plus Cloxacillin ( 2 gm of each daily ) or a placebo were given at r and om and on a double blind basis to 52 and 50 patients undergoing oral , laryngeal or pharyngeal surgery for neoplastic lesions . The frequency of postoperative wound and respiratory infections was significantly higher ( p < 0.05 ) among the placebo-treated patients . Most infections in both groups were caused by gram-negative rods . No untoward effects were related to the use of ampicillin plus cloxacillin and this form of therapy did not increase the rate of pharyngeal or wound asymptomatic colonization by bacteria A r and omized , placebo-controlled , double-blinded trial of cefam and ole in the prophylaxis of infection after major head and neck surgery was performed . Patients were given the drug on call to the operating room , and again four and eight hours after the initial dose . Twenty of 25 patients were evaluable . Wound infection developed in five of nine placebo recipients ( 55 % ) , and three of 11 ( 33 % ) receiving cefam and ole . Mean duration of hospitalization was 91.1 days in the placebo group , 34.3 in the cefam and ole group ( p less than 0.05 ) . The study was stopped because of excessive morbidity in the placebo group . Cefam and ole decreases the duration of hospitalization following major head and neck cancer surgery Objective The aim of this study was to identify risk factors for surgical-site infections ( SSIs ) in patients with head and neck cancer su bmi tted to major clean-contaminated surgery . Study Design This is a prospect i ve study conducted in a tertiary cancer center hospital . Subjects and Methods This study includes 258 patients su bmi tted to a major clean-contaminated head and neck oncologic surgery . Results The overall SSI rate was 38.8 % . The univariate analysis showed the following significant risk factors : race , tobacco consumption , clinical stage , comorbidities , time duration of the surgical procedure , and flap reconstruction . The final model by logistic regression identified the following independent predictors for SSI : tobacco consumption ( odds ratio [ OR ] = 2.96 ) , presence of metastatic lymph nodes ( OR = 2.05 ) , flap reconstruction ( OR = 2.20 ) , and antimicrobial prophylaxis exceeding 48 hours ( OR=1.89 ) . Conclusion The high-risk patients for SSI in head and neck oncologic surgery were those with cancer at advanced stages , those who were smokers , those presenting comorbidities , those who needed major reconstruction of the surgical wound , or those who were su bmi tted to inadequate antibiotic prophylaxis The use of antibiotic prophylaxis in head and neck surgery is controversial . Most surgeons agree that when surgery requires entry into the aerodigestive tract through the skin the wound is by definition contaminated and antibiotic prophylaxis is indicated as it is in other contaminated wounds . There is no general agreement as to which antibiotic or combination of antibiotics to use or what the schedule of dosage administration should be . In order to obtain a meaningful data to help in decision making , a double blind , r and omized study was performed to investigate whether cefazolin alone or a combination of gentamicin and clindamycin was more effective in prophylaxis . All patients entered into the study underwent major oncologic head and neck surgery requiring entry into the upper aerodigestive tract through the skin . Patients were stratified at entry according to the stage of disease , surgical procedure , and the existence of a prior tracheotomy or prior radiation therapy . Subsequently , patients were r and omly assigned to 1 of 4 treatment groups . Group I : Cefazolin 1 day , placebo day 2 to 5 . Group II : Cefazolin days 1 to 5 , Group III : Gentamicin and clindamycin 1 day , placebo days 2 to 5 . Group IV : Gentamicin and clindamycin days 1 to 5 . Drugs were given intravenously beginning 3 hours preoperatively and continued postoperatively every 8 hours , according to the assigned schedule . All wounds were observed daily following surgery and were grade d on a predetermined scale by 3 unbiased observers . Significantly wound infections occurred in 15 % of all patients . Group I , 33 % ; Group II , 20 % ; Group III , 7 % ; Group IV , 4 % . In Group III and Group IV there was a statistically significant ( P less than .05 ) reduction in the rate of postoperative wound infection . Multifactorial analysis demonstrated that patients whose surgery included repair with a regional pectoral flap had a statistically significant increased chance of developing postoperative wound infection ( P less than .05 ) . Patients undergoing laryngectomy , with or without neck dissection , were at less risk of postoperative infection tham patients undergoing oropharyngeal resection ( P less than .05 ) . The preoperative existence of tracheotomy or prior radiation therapy had no demonstrable effect on the incidence of wound infection postoperatively in this study Context : Head and neck surgeries are complex . Wound complications are associated with considerable morbidity and can result in delay in the adjuvant treatment . Identification of factors will help in formulating preventive guidelines . Aims : The aim of this study is to identify perioperative factors responsible for wound complications . Setting s and Design : Prospect i ve study of 186 head and neck patients . Subjects and Methods : Pre-operative , intraoperative and post-operative factors were recorded . Each patient was evaluated for minor and major wound complications twice daily during the hospital stay . Statistical Analysis : Chi-square test was used for univariate and log regression test was used for multivariate analysis . Results : The overall wound complication rate was 29 % with 7 % major and 22 % minor complications . On univariate analysis , laryngeal and hypopharyngeal location , advanced T stage , poor oral hygiene , clean-contaminated surgery , low Karnofsky performance status ( KPS ) , flap reconstruction , blood loss more than 1000 ml , perioperative blood transfusion , duration of surgery greater than 4.3 h and post-operative hemoglobin lesser than 11 g% , post-operative tracheostomy and resection of m and ible were statistical significant factors . On multivariate analysis , post-operative tracheostomy , low KPS , post-operative serum albumin less than 3.7 g/dl and duration of surgery greater than 4.3 h were significant factors . Conclusion : Apart from unavoidable factors , it is essential to take care of certain factors viz nutrition , haemoglobin , oral hygiene , asepsis and repeating antibiotics in prolonged surgery The aim of our study was to evaluate the optimal duration of antibiotic prophylaxis in major oncologic surgery of the head and neck using a novel broad spectrum drug combination : clindamycin and cefonicid . A prospect i ve r and omized study was carried out on 126 evaluable patients undergoing clean-contaminated ( skin to mucosa ) surgery for cancer of larynx , pharynx or oral cavity . Cases at high surgical risk ( because of need of pedicled or microvascular free flaps reconstruction ) , were excluded from the study . Within 20 days after surgery , only one case of wound infection was recorded among the 62 patients treated with the one-day schedule , versus three cases registered among the 64 subjects receiving three-day chemoprophylaxis . Episodes of systemic infections and eventual wound complications occurring in the first 20 days after surgery have also been recorded . The role of potential risk factors for postoperative complications has been evaluated . According to our findings , a three-day antibiotic regimen is not more effective than a short-term ( one-day ) schedule in preventing wound or systemic infection in clean-contaminated head and neck cancer surgery without flap reconstruction BACKGROUND Patients requiring major oncologic head and neck surgery are at high risk for postoperative wound infection when the surgical site is contaminated by secretions from the upper aerodigestive tract . Studies to identify agents active in the prevention of postoperative wound infection may serve to reduce patient morbidity . METHODS Patients scheduled for a major contaminated head and neck surgical procedure were r and omly assigned to receive either ampicillin/sulbactam or clindamycin . Medication was administered 1 to 2 hours prior to surgery and every 6 hours , for a total of five doses . Postoperatively , patients were followed daily for the development of wound infection or other septic complication . RESULTS A total of 242 patients were enrolled in the study ; 119 received ampicillin/sulbactam , and 123 received clindamycin . A total of 169 patients were considered evaluable . Of the evaluable patients , 14 % in each group developed a postoperative wound infection . There were no statistically significant differences between the number of days to onset of wound infection , nor was there a statistically significant difference in the rate of non-wound infections in the two groups . There were no statistically significant differences between the intent to treat group and the evaluable group of patients . CONCLUSION It is concluded that ampicillin/sulbactam is as safe and effective as clindamycin in preventing postoperative wound infection following major head and neck surgery Optimal antimicrobial prophylaxis during head and neck surgery is as yet unclear . The semisynthetic third-generation cephalosporin antibiotics would appear to have potential usefulness because of their broad antibacterial spectrum , favorable pharmacokinetic properties , and record of safety . Eighty patients were prospect ively r and omized into this placebo-controlled , double-blind study to receive either placebo , cefoperazone sodium , or cefotaxime sodium preoperatively and for 24 hours postoperatively . Infection rates were 78 % for the placebo group and 10 % for the group receiving the cephalosporin antibiotics . Infections were polymicrobial . Anaerobic bacteria constituted 42 % of the pathogens isolated . Wound and serum antibiotic concentrations exceeded the minimal inhibitory concentration of the bacterial flora . This study establishes the necessity of antimicrobial prophylaxis for contaminated oncologic procedures of the head and neck . Our experience indicates that cefoperazone and cefotaxime are particularly useful Patients who undergo major contaminated surgery of the head and neck benefit from perioperative antibiotic prophylaxis . This study was developed to determine if 5 days of antibiotic administration would be more effective than 1 day . A multi-institutional prospect i ve r and omized double-blind study was design ed . Patients who were identified as requiring pedicled flap reconstruction were potential c and i date s for the study . Later , patients were r and omly assigned to receive cefoperazone sodium for either 24 hours or 120 hours . In each case , the drug was administered intravenously , beginning 1 to 2 hours preoperatively and continued for the prescribed period . One hundred nine patients were evaluable . Fifty-three patients were assigned to 1 day of perioperative prophylaxis . Wound Infection developed in ten patients ( 18.9 % ) . Fifty-six patients were assigned to 5 days of perioperative antibiotic prophylaxis . Wound infection developed in 14 ( 25 % ) of these patients ( P > .05 ) . These data suggest that no beneficial effect from administration of antibiotics for longer than 24 hours postoperatively can be achieved in patients who undergo myocutaneous flap reconstruction This study aims to give a better underst and ing of the prevalence , patterns , and determinants of postoperative complications , to evaluate the Clavien-Dindo classification of surgical complications , and to set out a protocol to improve postoperative recovery . Over a period of 27 months we studied 192 patients who had had major head and neck operations with free flaps . Data on complications were gathered prospect ively along with patients ' details , comorbidities , factors indicative of the magnitude of the surgical insult , and variations in perioperative care . Complications were classified according to the Clavien-Dindo system . Outcomes analysed comprised any complication , major complications ( Clavien-Dindo III and above ) , wound complications , and pulmonary complications . A total of Output:	Less than or equal to 24 hours of antibiotic prophylaxis in head and neck clean-contaminated free-flap is likely sufficient but a strong conclusion remains elusive . Clindamycin prophylaxis increases the risk of recipient surgical site infection .
MS21446	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: OBJECTIVE To assess differences through grade 8 in diet , physical activity , and related health indicators of students who participated in the Child and Adolescent Trial for Cardiovascular Health ( CATCH ) school and family intervention from grade s 3 through 5 . DESIGN Follow-up of the 4-center , r and omized , controlled field trial with 56 intervention and 40 control elementary schools . PARTICIPANTS We studied 3714 ( 73 % ) of the initial CATCH cohort of 5106 students from ethnically diverse background s in California , Louisiana , Minnesota , and Texas at grade s 6 , 7 , and 8 . RESULTS Self-reported daily energy intake from fat at baseline was virtually identical in the control ( 32.7 % ) and intervention ( 32.6 % ) groups . At grade 5 , the intake for controls remained at 32.2 % , while the intake for the intervention group declined to 30.3 % ( P<.001 ) . At grade 8 , the between-group differential was maintained ( 31.6 % vs 30.6 % , P = .01 ) . Intervention students maintained significantly higher self-reported daily vigorous activity than control students ( P = .001 ) , although the difference declined from 13.6 minutes in grade 5 to 11.2 , 10.8 , and 8.8 minutes in grade s 6 , 7 , and 8 , respectively . Significant differences in favor of the intervention students also persisted at grade 8 for dietary knowledge and dietary intentions , but not for social support for physical activity . No impact on smoking behavior or stages of contemplating smoking was detected at grade 8 . No significant differences were noted among physiologic indicators of body mass index , blood pressure , or serum lipid and cholesterol levels . CONCLUSION The original CATCH results demonstrated that school-level interventions could modify school lunch and school physical education programs as well as influence student behaviors . This 3-year follow-up without further intervention suggests that the behavioral changes initiated during the elementary school years persisted to early adolescence for self-reported dietary and physical activity behaviors 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 Identification of the behavioural , normative and control beliefs influencing children 's behaviour is an important prerequisite in design ing effective interventions . The current study aims to evaluate the effectiveness of an intervention program , based on the Theory of Planned Behaviour ( TPB ) , on obesity indices and blood pressure ( BP ) in Ioannina , Greece . METHODS Participants were 646 fifth grade pupils ( 360 girls and 286 boys ) . The intervention group ( IG ) consisted of 321 children in 13 r and omly selected schools while the rest ( n = 325 children ) served as the control group ( CG ) . Based on the outcome of the TPB question naire , the intervention focused on overcoming the barriers in accessing physical activity areas , increasing the availability of fruits and vegetables and increasing parental support . General linear mixed model and mediating variable analysis were used to evaluate the differences between the two groups and to test whether changes in certain dietary , physical activity and anthropometrical indices mediated the effect of the intervention on BP . RESULTS IG had higher consumption of fruits and lower consumption of fats/oils and sweets/beverages compared with the CG . Intervention 's effect on BMI could be explained by the changes in fruit and fats/oils intake whereas the reduction of systolic and diastolic BP could be explained by the reduction of BMI . CONCLUSIONS The findings indicate favourable changes in BP and obesity indices after the implementation of a 1-year school-based intervention program based on the TPB . These results highlight the importance of developing a social and physical environment that promotes balanced eating behaviours and extra-curricular access to physical activity venues Objective To 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 OBJECTIVE To assess the impact of a 2-year recreational physical activity program in 1044 fourth- and fifth- grade primary schoolchildren from the Province of Cuenca , Spain . STUDY DESIGN Cluster-r and omized controlled trial with 10 intervention and 10 control schools . The program consisted of 3 90-minute sessions of physical activity per week , during 28 weeks every year . Changes in endpoints between baseline ( September 2004 ) and the end of follow-up ( June 2006 ) were compared between the control and intervention group by using mixed regression models , with adjustment for the baseline endpoint value , age , and the school . RESULTS Compared with control subjects , intervention girls reduced the frequency of overweight ( odds ratio , 0.55 ; 95 % CI , 0.39 - 0.78 ; P<.001 ) . However , intervention was associated with an increase in the percentage of body fat in boys ( 0.97 % ; 95 % CI , 0.14 - 1.81 ; P=.02 ) . Girls in the intervention group had lower total cholesterol level ( -6.86 mg/dL ; 95 % CI , -9.70 - -4.01 ; P<.001 ) and apolipoprotein B level ( -3.61 mg/dL ; 95 % CI , -6.27 - -0.95 ; P=.008 ) than control subjects . Results were similar in boys . CONCLUSION In 2 years , the physical activity program lowered the frequency of overweight in girls and reduced total cholesterol and apolipoprotein B in both girls and boys 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 A five-year intervention study of the effectiveness of the " Know Your Body " program in reducing coronary heart disease risk factors among black students in the District of Columbia , who were in grade s 4 - 6 at baseline , was begun in 1983 . Nine schools were stratified on socioeconomic status and r and omly assigned to control and intervention groups . The " Know Your Body " curriculum focuses on nutrition , fitness , and the prevention of cigarette smoking . At baseline , 1,234 students were eligible for the screening in which the following target risk factors were measured : systolic and diastolic blood pressures , ponderosity index , triceps skinfold thickness , postexercise pulse recovery rate , serum total and high density lipoprotein ( HDL ) cholesterol , and serum thiocyanate . After two years of intervention , results indicated that the program may have had a favorable impact on the following risk factors : systolic and diastolic pressures , HDL cholesterol , ratio of total to HDL cholesterol , fitness ( postexercise pulse recovery rate ) , and smoking . Significant net changes in the favorable direction also were found for health knowledge and attitude toward smoking . Blood pressure reduction was associated with decreased ponderosity and improved fitness , and increased HDL cholesterol was associated with decreased ponderosity . These results are consistent with other evaluations of the " Know Your Body " program , suggesting that the program may be effective in reducing chronic disease risk in diverse school population A five-year intervention study of the feasibility and effectiveness of a program aim ed at the primary prevention of chronic disease was initiated in 198 Output:	Obesity prevention programs have a moderate effect on reducing BP , and those targeting both diet and physical activity seem to be more effective
MS21447	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: AIM To assess the prevalence of adjustment for confounding within statistical analysis and matching at the design stage in leading orthodontic journals and to explore potential associations between accounting for confounding and publication characteristics . MATERIAL S AND METHODS Twenty-four issues of four leading orthodontic journals with the highest impact factor were search ed from July 2014 backwards . Confounding adjustment through statistical analysis and study characteristics including journal , study design , region of origin , number of authors , number of centres , involvement of a statistician , significance of results , and type of analysis were recorded . Reporting of matching at the design stage was also recorded . RESULTS Of 426 studies identified , only 71 ( 17 per cent ) accounted for confounding in the statistical analysis . There was evidence that journal , country of authors hip , and involvement of a statistician ( odds ratio = 3.91 , 95 per cent confidence interval : 2.16 - 7.10 ; P < 0.001 ) were significant predictors of accounting for confounding at the analysis level . Reporting of matching at the design stage was identified in 111 of 426 ( 26 per cent ) studies in which 9 studies adjusted for confounding at the analysis level . CONCLUSIONS Appropriate adjustment for confounding in orthodontic literature either at the design or at the analysis stage was identified in less than half of studies overall ( 41 per cent ) , suggesting lack of expertise and awareness in design , conduct , analysis , and reporting of non-r and omized studies in this field . This is a critical limitation that can potentially result in biased estimates and associations between examined exposures and outcomes OBJECTIVES To assess the hypothesis that there is excessive reporting of statistically significant studies published in prosthodontic and implantology journals , which could indicate selective publication . METHODS The last 30 issues of 9 journals in prosthodontics and implant dentistry were h and - search ed for articles with statistical analyses . The percentages of significant and non-significant results were tabulated by parameter of interest . Univariable/multivariable logistic regression analyses were applied to identify possible predictors of reporting statistically significance findings . The results of this study were compared with similar studies in dentistry with r and om-effects meta-analyses . RESULTS From the 2323 included studies 71 % of them reported statistically significant results , with the significant results ranging from 47 % to 86 % . Multivariable modeling identified that geographical area and involvement of statistician were predictors of statistically significant results . Compared to interventional studies , the odds that in vitro and observational studies would report statistically significant results was increased by 1.20 times ( OR : 2.20 , 95 % CI : 1.66 - 2.92 ) and 0.35 times ( OR : 1.35 , 95 % CI : 1.05 - 1.73 ) , respectively . The probability of statistically significant results from r and omized controlled trials was significantly lower compared to various study design s ( difference : 30 % , 95 % CI : 11 - 49 % ) . Likewise the probability of statistically significant results in prosthodontics and implant dentistry was lower compared to other dental specialties , but this result did not reach statistical significant ( P>0.05 ) . CONCLUSIONS The majority of studies identified in the fields of prosthodontics and implant dentistry presented statistically significant results . The same trend existed in publications of other specialties in dentistry Background The extraction rate in orthodontics varies throughout the years . While the extraction decision is easily made or excluded in clear-cut cases , it still remains controversial what makes an orthodontist decide to extract in borderline cases . The aim of this retrospective study was to identify the percentage of extraction cases in a large group of Class I malocclusions and to clarify which variables contributed most to the extraction decision . Methods The sample consisted of 542 r and omly selected records of Class I patients treated in a university graduate program and in five private orthodontic offices . Of these patients , 331 were female and 211 male . The mean age was 14.55 ( st and ard deviation ( SD ) 5.36 ) for the non- extraction group and 14.52 ( SD 4.86 ) for the extraction group . The extensive series of 32 linear and angular measurements derived from the cephalometric analysis and the dental casts , along with the variables of age and gender , fueled a stepwise discriminant analysis . Results The percentage of the patients treated with four first premolar extraction s was 26.8 % . The results showed that the variables of lower crowding , lower lip to E-plane , upper crowding , and overjet accounted most for the decision to extract at a very significant level ( Sig . 0.000 ) . The discriminant analysis assigned a classification power of 83.9 % to the predictive model ( p < 0.0001 ) . Fisher 's linear discriminant functions provided a mathematical model , according to which any case can be classified into the adequate treatment group . Conclusions In a large contemporary sample of 542 Class I patients , the extraction rate was 26.8 % . The most important measurements when the orthodontist decides extraction s in Class I cases are lower crowding , lower lip to E-plane , upper crowding , and overjet . In clinical orthodontic practice , the findings facilitate treatment by providing evidence -based treatment predictors for Class I malocclusions OBJECTIVE : To test the feasibility of creating a valid and reliable checklist with the following features : appropriate for assessing both r and omised and non-r and omised studies ; provision of both an overall score for study quality and a profile of scores not only for the quality of reporting , internal validity ( bias and confounding ) and power , but also for external validity . DESIGN : A pilot version was first developed , based on epidemiological principles , review s , and existing checklists for r and omised studies . Face and content validity were assessed by three experienced review ers and reliability was determined using two raters assessing 10 r and omised and 10 non-r and omised studies . Using different raters , the checklist was revised and tested for internal consistency ( Kuder-Richardson 20 ) , test-retest and inter-rater reliability ( Spearman correlation coefficient and sign rank test ; kappa statistics ) , criterion validity , and respondent burden . MAIN RESULTS : The performance of the checklist improved considerably after revision of a pilot version . The Quality Index had high internal consistency ( KR-20 : 0.89 ) as did the subscales apart from external validity ( KR-20 : 0.54 ) . Test-retest ( r 0.88 ) and inter-rater ( r 0.75 ) reliability of the Quality Index were good . Reliability of the subscales varied from good ( bias ) to poor ( external validity ) . The Quality Index correlated highly with an existing , established instrument for assessing r and omised studies ( r 0.90 ) . There was little difference between its performance with non-r and omised and with r and omised studies . Raters took about 20 minutes to assess each paper ( range 10 to 45 minutes ) . CONCLUSIONS : This study has shown that it is feasible to develop a checklist that can be used to assess the method ological quality not only of r and omised controlled trials but also non-r and omised studies . It has also shown that it is possible to produce a checklist that provides a profile of the paper , alerting review ers to its particular method ological strengths and weaknesses . Further work is required to improve the checklist and the training of raters in the assessment of external validity INTRODUCTION The purpose of this investigation was to determine the long-term differences in soft tissue profile changes between extraction and non extraction patients who had been treated to the same incisor position and lip line . METHODS Twenty extraction and 20 matched non extraction patients , with posttreatment and long-term follow-up ( average 15 years ) records , were selected from a single private orthodontic practice . Posttreatment and long-term follow-up profile photos of the patients ' nose , lip , and chin areas were evaluated by 105 orthodontists and 225 laypeople , who indicated their preferences and the amount of change they perceived among the 40 profiles . The patients had similar dental protrusion , soft tissue profile measurements , and ages at the posttreatment observation . RESULTS No significant cephalometric differences between the extraction and non extraction groups were found at long-term follow-up ; both groups showed similar long-term changes . Significant ( P < .05 ) differences were found between males and females at long-term follow-up ; male lips became relatively more retrusive , and their profiles became flatter . Significant ( P < .05 ) changes in the profiles were also perceived over time , but there was no relationship between the amount of change perceived and profile changes measured cephalometrically . There were also no significant ( P < .05 ) differences in preferences between orthodontists and laypeople , between extraction and non extraction patients , or between males and females . CONCLUSIONS If extraction and non extraction patients are treated to the same incisor position and lip line , the treatment modality does not affect long-term soft tissue profile changes . Furthermore , the amounts of change perceived by either orthodontists or laypeople were not related to the amount of change measured cephalometrically Non-r and omized studies may provide valuable evidence on the effects of interventions . They are the main source of evidence on the intended effects of some types of interventions and often provide the only evidence about the effects of interventions on long-term outcomes , rare events or adverse effects . Therefore , systematic review s on the effects of interventions may include various types of non-r and omized studies . In this second paper in a series , we address how review authors might articulate the particular non-r and omized study design s they will include and how they might evaluate , in general terms , the extent to which a particular non-r and omized study is at risk of important biases . We offer guidance for describing and classifying different non-r and omized design s based on specific features of the studies in place of using non-informative study design labels . We also suggest criteria to consider when deciding whether to include non-r and omized studies . We conclude that a taxonomy of study design s based on study design features is needed . Review authors need new tools specifically to assess the risk of bias for some non-r and omized design s that involve a different inferential logic compared with parallel group trials . Copyright © 2012 John Wiley & Sons , This investigation was design ed to compare the esthetic effects of extraction and non extraction treatments . Panels of 58 laypersons and 42 dentists evaluated r and omly presented pre- and posttreatment profiles of 70 extraction and 50 non extraction Class I and II Caucasian patients . The sample s were similar at the outset ; however , at the end of treatment , the extraction patients ' faces were , on average , 1.8 mm " flatter " than the faces of non extraction subjects . The flatter faces were preferred by both panels , dentists more so than laypersons . In general , non extraction treatment was seen as having little effect on the profile , whereas the perceived effect of extraction treatment was a statistically significant function of initial soft tissue protrusion-the greater the initial protrusion , the greater the benefit . The point at which a reduction in protrusion produces a perceived improvement was explored by way of regression analysis . Both panels saw extraction as being potentially beneficial when the lips were more protrusive than 2 to 3 mm behind Ricketts ' E-plane . It is concluded that extraction treatment can produce improved facial esthetics for many patients who present with some combination of crowding and protrusion Obesity is a widespread chronic inflammatory disorder characterized by an increased overall disease burden and significant association with periodontitis . The aim of this prospect i ve clinical cohort study was to investigate the effect of obesity on orthodontic tooth movement . Fifty-five adolescent patients ( 27 males , 28 females ) with a mean ( SD ) age of 15.1 ( 1.7 ) years and mean ( SD ) body mass index ( BMI ) of 30.2 ( 3.5 ) kg/m2 in obese and 19.4 ( 2.2 ) kg/m2 in normal-weight groups were followed from start of treatment to completion of tooth alignment with fixed orthodontic appliances . Primary outcome was time taken to complete tooth alignment , while secondary outcomes included rate of tooth movement and change in clinical parameters ( plaque/gingival indices , unstimulated whole-mouth salivary flow rate , gingival crevicular fluid biomarkers ) . Data collection took place at baseline ( start of treatment : appliance placement ) , 1 h and 1 wk following appliance placement , and completion of alignment . Results were analyzed by descriptive statistics followed by generalized estimating equation regression modeling . There were no significant differences between groups in time taken to achieve tooth alignment ( mean [ SD ] 158.7 [ 75.3 ] d ; P = 0.486 ) . However , at 1 wk , initial tooth displacement was significantly increased in the obese group ( P < 0.001 ) , and after adjusting for confounders , obese patients had a significantly higher rate of tooth movement compared with normal-weight patients ( + 0.017 mm/d ; 95 % confidence interval , 0.008–0.025 ; P < 0.001 ) over the period of alignment . Explorative analyses indicated that levels of the adipokines leptin and resistin , the inflammatory marker myeloperoxidase ( MPO ) , and the cytokine receptor for nuclear factor kappa-B lig and ( RANKL ) were significantly different between obese- and normal-weight patients and associated with observed rates of tooth movement . This represents the first prospect i ve data demonstrating a different response in obese patients compared with normal-weight patients during early orthodontic treatment . These differences in the response of periodontal tissues to orthodontic force in the presence of obesity have potential short- and long-term clinical implication Output:	Although tooth extraction s seem to affect patient profile , existing studies are heterogenous and no consistent predictions of profile response can be made
MS21448	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Circulating 25-hydroxyvitamin D ( 25(OH)D ) has been associated with cardiovascular disease ( CVD ) risk in observational studies . Also , SNPs to explain variation in 25(OH)D have been identified by genome-wide association studies . Detection of direct associations between SNPs that significantly affect 25(OH)D and CVD risk would indicate a causal role of vitamin D , as reverse causation could be excluded and confounding could be better controlled . Thus , a combined analysis of c and i date SNPs in relation to circulating 25(OH)D and CVD risk was carried out . A case-cohort study within the EPIC-Germany study was conducted comprising a r and omly drawn subcohort of 2,132 subjects ( 57.9 % women , mean age : 50.6 years ) and incident cases of myocardial infa rct ion ( n=559 ) and stroke ( n=471 ) that occurred during a mean follow-up duration of 7.6 years . 25(OH)D concentrations were measured by LC-MS/MS in baseline plasma sample s. Additionally , eight c and i date SNPs were assayed . Associations between 25(OH)D , SNPs and the risks of myocardial infa rct ion and stroke were assessed by multivariable regression analyses . Mean 25(OH)D level was 47.2 nmol/L in the subcohort . Four SNPs were associated with 25(OH)D ( p<0.05 ) . In subjects with 25(OH)D levels < 25 nmol/L , the risks of CVD as composite endpoint ( Hazard Ratio : 1.53 , 95 % confidence interval : 1.12–2.09 ) , myocardial infa rct ion , and stroke were significantly increased compared to subjects with levels ≥50 nmol/L , while no significant linear associations were observed . A SNP score was not related to the risks of total CVD ( Hazard Ratio : 1.0 , 95 % confidence interval : 0.71–1.42 ) , myocardial infa rct ion , or stroke . The same was true concerning single SNPs . Given the lack of association between SNPs and the risks of stroke and myocardial infa rct ion , the present findings do not point to a major causal role of vitamin D in the development of these diseases . However , a detection of modest associations between genetic markers and CVD risk in larger consortia can not be ruled out Background and Purpose — Vitamin D deficiency has been reported to contribute to the risk of cardiovascular disease , especially stroke . We examined the relationship between dietary vitamin D intake and 34-year incident stroke . Methods — The Honolulu Heart Program is a prospect i ve population -based cohort study of 8006 Japanese-American men in Hawaii who were 45 to 68 years old at the baseline examination in 1965 to 1968 . Dietary vitamin D intake was calculated using the Nutritionist IV Version 3 software from a 24-hour dietary recall . Subjects with prevalent stroke were excluded , leaving 7385 men followed through 1999 for incident stroke . Subjects were divided into quartiles of dietary vitamin D for analyses . Results — During 34 years of follow-up , 960 subjects developed stroke . Age-adjusted rates of incident stroke were significantly higher in the lowest dietary vitamin D quartile compared with the highest ( all stroke : 6.38 versus 5.14 per 1000 person-years follow-up , P=0.030 ; thromboembolic stroke : 4.36 versus 3.30 , P=0.033 ) . Using Cox regression , adjusting for age , total kilocalories , body mass index , hypertension , diabetes mellitus , pack-years smoking , physical activity index , serum cholesterol , and alcohol intake , those in the lowest quartile had a significantly increased risk of incident stroke ( all stroke hazard ratio , 1.22 ; 95 % CI , 1.01–1.47 ; P=0.038 ; thromboembolic stroke hazard ratio , 1.27 ; 95 % CI , 1.01–1.59 ; P=0.044 ) with the highest as the reference . We found no significant associations between dietary vitamin D and hemorrhagic stroke . Conclusions — Low dietary vitamin D intake was an independent risk factor for 34-year incidence of all stroke and thromboembolic stroke in Japanese-American men . Additional research is needed on vitamin D supplementation to prevent stroke Background Black individuals are at greater risk of stroke and vitamin D deficiency than white individuals . Epidemiologic studies have shown that low 25-hydroxyvitamin D concentrations are associated with increased risk of stroke , but these studies had limited representation of black individuals . Methods We examined the association of 25-hydroxyvitamin D with incident stroke in the Reasons for Geographic and Racial Differences in Stroke ( REGARDS ) study , a cohort of black and white adults ≥45 years of age . Using a case – cohort study design , plasma 25-hydroxyvitamin D was measured in 610 participants who developed incident stroke ( cases ) and in 937 stroke-free individuals from a stratified cohort r and om sample of REGARDS participants ( comparison cohort ) . Results In multivariable models adjusted for socio-demographic factors , co-morbidities and laboratory values including parathyroid hormone , lower 25-hydroxyvitamin D concentrations were associated with higher risk of stroke ( 25-hydroxyvitamin D > 30 ng/mL reference ; 25-hydroxyvitamin D concentrations 20–30 ng/mL , hazard ratio 1.33 , 95 % confidence interval ( 95 % CI ) 0.89,1.96 ; 25-hydroxyvitamin D < 20 ng/mL , hazard ratio 1.85 , 95 % CI 1.17 , 2.93 ) . There were no statistically significant differences in the association of lower 25-hydroxyvitamin D with higher risk of stroke in black vs. white participants in fully adjusted models ( hazard ratio comparing lowest vs. highest 25-hydroxyvitamin D category 2.62 , 95 % CI 1.18 , 5.83 in blacks vs. 1.64 , 95 % CI 0.83 , 3.24 in whites , Pinteraction = 0.82 ) . The associations were qualitatively unchanged when restricted to ischemic or hemorrhagic stroke subtypes or when using race-specific cut-offs for 25-hydroxyvitamin D categories . Conclusions Vitamin D deficiency is a risk factor for incident stroke and the strength of this association does not appear to differ by race Vitamin D recently has been proposed to play an important role in a broad range of organ functions , including cardiovascular ( CV ) health ; however , the CV evidence -base is limited . We prospect ively analyzed a large electronic medical records data base to determine the prevalence of vitamin D deficiency and the relation of vitamin D levels to prevalent and incident CV risk factors and diseases , including mortality . The data base contained 41,504 patient records with at least one measured vitamin D level . The prevalence of vitamin D deficiency ( ≤30 ng/ml ) was 63.6 % , with only minor differences by gender or age . Vitamin D deficiency was associated with highly significant ( p < 0.0001 ) increases in the prevalence of diabetes , hypertension , hyperlipidemia , and peripheral vascular disease . Also , those without risk factors but with severe deficiency had an increased likelihood of developing diabetes , hypertension , and hyperlipidemia . The vitamin D levels were also highly associated with coronary artery disease , myocardial infa rct ion , heart failure , and stroke ( all p < 0.0001 ) , as well as with incident death , heart failure , coronary artery disease/myocardial infa rct ion ( all p < 0.0001 ) , stroke ( p = 0.003 ) , and their composite ( p < 0.0001 ) . In conclusion , we have confirmed a high prevalence of vitamin D deficiency in the general healthcare population and an association between vitamin D levels and prevalent and incident CV risk factors and outcomes . These observations lend strong support to the hypothesis that vitamin D might play a primary role in CV risk factors and disease . Given the ease of vitamin D measurement and replacement , prospect i ve studies of vitamin D supplementation to prevent and treat CV disease are urgently needed BACKGROUND Vitamin D insufficiency was shown to be associated with adverse musculoskeletal and nonskeletal outcomes in numerous observational studies . However , some studies did not control for confounding factors such as age or seasonal variation of 25-hydroxyvitamin D [ 25(OH)D ] . OBJECTIVE We sought to determine the effect of vitamin D status on health outcomes . DESIGN Healthy community-dwelling women ( n = 1471 ) with a mean age of 74 y were followed in a 5-y trial of calcium supplementation . 25(OH)D was measured at baseline in all women . Skeletal and nonskeletal outcomes were evaluated according to seasonally adjusted vitamin D status at baseline . RESULTS Fifty percent of women had a seasonally adjusted 25(OH)D concentration < 50 nmol/L. These women were significantly older , heavier , and less physically active and had more comorbidities than women with a seasonally adjusted 25(OH)D concentration > or = 50 nmol/L. Women with a seasonally adjusted 25(OH)D concentration < 50 nmol/L had an increased incidence of stroke and cardiovascular events that did not persist after adjustment for between-group differences in age or comorbidities . Women with a seasonally adjusted 25(OH)D concentration < 50 nmol/L were not at increased risk of adverse consequences for any musculoskeletal outcome , including fracture , falls , bone density , or grip strength or any nonskeletal outcomes , including death , myocardial infa rct ion , cancer , heart failure , diabetes , or adverse changes in blood pressure , weight , body composition , cholesterol , or glucose . CONCLUSIONS Vitamin D insufficiency is more common in older , frailer women . Community-dwelling older women with a seasonally adjusted 25(OH)D concentration < 50 nmol/L were not at risk of adverse outcomes over 5 y after control for comorbidities . R and omized placebo-controlled trials are needed to determine whether vitamin D supplementation in individuals with vitamin D insufficiency influences health outcomes . This trial was registered at www.anzctr.org.au as ACTRN 012605000242628 Output:	In conclusion , our meta- analysis supported the hypothesis that lower vitamin D status was associated with an increased risk of ischemic stroke .
MS21449	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: OBJECTIVE To determine immunogenicity and optimum timing for administering the 23-valent pneumococcal vaccine after spinal cord injury ( SCI ) . DESIGN Double-blind , r and omized , placebo control study . SETTING SCI unit in a tertiary care medical center and community . PARTICIPANTS Eighty-seven persons with recent SCI . INTERVENTION Participants were r and omized to receive either placebo or pneumococcal vaccine at 16 to 18 days versus 4 to 6 months postinjury . MAIN OUTCOME MEASURES Antibody concentrations were measured prior to intervention and 1 , 2 , and 12 months afterward to evaluate the immune response to five serotypes of Streptococcus pneumoniae . Effects of demographic and injury-related variables on immune response were also evaluated . RESULTS Timing of vaccination did not influence mean antibody concentrations for any serotype ( p > .05 ) . Ninety-five percent of vaccinated persons had twofold or greater increases in antibody concentration for at least one serotype when measured 1 month after vaccination versus 35 % of placebo groups ( p < .01 ) . After 12 months , 93 % of vaccinated persons in both groups maintained antibody concentrations twofold or greater than baseline values . CONCLUSIONS Most participants developed an immune response to at least one serotype that was maintained for at least 12 months . Immune response varied according to serotype . Given the favorable immune response and no effect of timing , persons with SCI should receive pneumococcal vaccine during initial hospitalization OBJECTIVES To determine whether the addition of deep or superficial heating to stretching produces better clinical outcomes than stretching alone in the management of frozen shoulder . DESIGN A single-blinded , r and omized controlled study . SUBJECTS Thirty subjects suffering from the stiffness phase of frozen shoulder . METHODS Subjects were r and omly allocated to receive : ( i ) deep heating plus stretching ; ( ii ) superficial heating plus stretching ; or ( iii ) stretching alone . Both heating groups received the respective treatments 3 times per week for 4 weeks . All groups received a st and ard set of shoulder stretching exercises . The American Shoulder and Elbow Surgeons assessment form was recorded at the baseline , sessions 6 and 12 , and at the 4-week follow-up session . RESULTS A significant improvement was seen in all groups in all outcome measures except for that of shoulder flexion range . The improvement in the shoulder score index and in the range of motion was significantly better in the deep heating group than in the superficial heating group . CONCLUSION The addition of deep heating to stretching exercises produced a greater improvement in pain relief , and result ed in better performance in the activities of daily living and in range of motion than did superficial heating Investigators should properly calculate sample sizes before the start of their r and omised trials and adequately describe the details in their published report . In these a-priori calculations , determining the effect size to detect -- eg , event rates in treatment and control groups -- reflects inherently subjective clinical judgments . Furthermore , these judgments greatly affect sample size calculations . We question the br and ing of trials as unethical on the basis of an imprecise sample size calculation process . So-called underpowered trials might be acceptable if investigators use method ological rigor to eliminate bias , properly report to avoid misinterpretation , and always publish results to avert publication bias . Some shift of emphasis from a fixation on sample size to a focus on method ological quality would yield more trials with less bias . Unbiased trials with imprecise results trump no results at all . Clinicians and patients deserve guidance now OBJECTIVE To compare the efficacy of aquatic exercise and a l and -based exercise programme vs control in patients with knee osteoarthritis . METHODS Primary outcome was change in pain , and in addition Knee Injury and Osteoarthritis Outcome Score question naire ( KOOS ) . St and ing balance and strength was also measured after and at 3-month follow-up . Seventy-nine patients ( 62 women ) , with a mean age of 68 years ( age range 40 - 89 years ) were r and omized to aquatic exercise ( n = 27 ) , l and -based exercise ( n = 25 ) or control ( n = 27 ) . RESULTS No effect was observed immediately after exercise cessation ( 8 weeks ) . At 3-month follow-up a reduction in pain was observed only in the l and -based exercise group compared with control ( -8.1 mm , ( 95 % confidence interval -15.4 to -0.4 ; p = 0.039 ) , but no differences between groups were observed for KOOS ; and no improvement following aquatic exercise . Eleven patients reported adverse events ( i.e. discomfort ) in l and -based exercise , while only 3 reported adverse events in the aquatic exercise . CONCLUSION Only l and -based exercise showed some improvement in pain and muscle strength compared with the control group , while no clinical benefits were detectable after aquatic exercise compared with the control group . However , aquatic exercise has significantly less adverse effects compared with a l and -based programme OBJECTIVE To compare individual , group and combined intervention formats for improving goal attainment and psychosocial function following acquired brain injury . DESIGN R and omized controlled trial , waiting list controls . PARTICIPANTS Thirty-five participants with a mean time of 5.29 years ( st and ard deviation = 3.9 ) since acquired brain injury were r and omly allocated into 6 groups involving an intervention or waiting list control condition for 1 of 3 intervention formats . METHODS Interventions were 3 h/week for 8 weeks . Formats included : group-based support ( n = 12 ) , individual occupation-based support ( n = 11 ) , and a combined group and individual support intervention ( n = 12 ) . Participant outcomes were examined at pre- , post- , and 3-month follow-up assessment on the Canadian Occupational Performance Measure , Patient Competency Rating Scale , and Brain Injury Community Rehabilitation Outcome 39 Scales . RESULTS Overall , the findings indicated that the individual intervention component appeared to contribute particularly to gains in performance in goal -specific areas . The combined intervention was associated with maintained gains in performance and satisfaction . However , gains in behavioural competency and psychological well-being were more likely to occur after the group and individual interventions . CONCLUSION These findings generally support the efficacy of brief intervention formats following acquired brain injury , although further research is needed to examine clients ' suitability for particular interventions OBJECTIVE To determine whether progressive resistance training improves muscle strength , muscle endurance , and physical function in adults with Down syndrome . DESIGN Single-blind r and omized controlled trial . SETTING General community . PARTICIPANTS Adults ( N=20 ) with Down syndrome ( 13 men , 7 women ; mean age , 26.8+/-7.8 y ) were r and omly assigned through a concealed allocation block r and omized method to either an intervention group ( n=9 ) or a control group ( n=11 ) . INTERVENTION The intervention was a supervised , group progressive resistance training program , consisting of 6 exercises using weight machines performed twice a week for 10 weeks . Participants completed 2 to 3 sets of between 10 to 12 repetitions of each exercise until they reached fatigue . The control group continued with their usual activities . MAIN OUTCOME MEASURES The outcomes measured by blinded assessors were muscle strength ( 1-repetition maximum [ 1-RM ] ) , muscle endurance ( number of repetitions at 50 % of 1-RM ) for chest press and leg press , timed stairs test , and the grocery shelving task . RESULTS The intervention group showed significant improvement in upper-limb muscle endurance compared with the control group ( mean difference in the number of repetitions of the chest press at 50 % of 1-RM was 16.7 , 95 % confidence interval , [ CI ] 7.1 - 26.2 ) ; and a trend toward an improvement in upper-limb muscle strength ( mean difference in chest press 1-RM , 8.6 kg ; 95 % CI , -1.3 to 18.5 kg ) and in upper-limb function ( mean difference in grocery shelving task , -20.3s ; 95 % CI , -45.7 to 5.2s ) . There were no significant differences between the groups for lower-limb muscle performance or physical function measures . No major adverse events for the intervention were noted . CONCLUSIONS Progressive resistance training is a safe and feasible fitness option that can improve upper-limb muscle endurance in adults with Down syndrome ( ACTR identifier ACTRN 012606000515594 . ) Objective : To determine whether protein supplementation could enhance neurological recovery in subacute patients with ischaemic stroke . Design : Alimentation-independent patients with ischaemic stroke were r and omly allocated to either 21 days of protein supplementation ( protein-supplemented group ; n=20 ) or to a spontaneous diet only ( control group ; n=21 ) in order to investigate the recovery of neurological changes ( measured using the National Institute of Health ( NIH ) Stroke Scale ) . Setting : Tertiary care rehabilitation in Italy . Participants : Forty-two patients ( 27 male and 15 female ; 66.4 ± 11 years ) 16 ±2 days after the acute event . Intervention : Supplementation with a hyperproteic nutritional formula ( 10 % protein ) . Main outcome measures : NIH Stroke Scale and protein intake . Results : At admission to rehabilitation , both groups of patients were homogeneous for demographic , clinical and functional characteristics . After 21 days from the start of the protocol , the NIH Stroke Scale was found to be enhanced in the group with supplemental proteins ( -4.4 ± 1.5 score versus -3 ± 1.4 of control group ; P<0.01 ) . When expressed as difference ( ▵ ) between baseline and 21 days , the NIH Stroke Scale correlated negatively with change in protein intake ( g/day ) ( r=-0.50 , P= 0.001 ) and positively with change in carbohydrate/protein ratio ( r=+0.40 , P=0.01 ) Conclusions : Protein supplementation may enhance neurological recovery in subacute patients with ischaemic stroke Objective : To investigate the effect of an additional vestibular stimulated exercise programme on balance for patients with benign paroxysmal positional vertigo . Design : R and omized controlled trial . Setting : Medical centre . Subjects : Twenty-six subjects with benign paroxysmal positional vertigo involving the unilateral posterior semicircular canal . Interventions : Subjects were r and omized into experimental or control groups . Thirteen subjects in the experimental group received the canalith repositioning manoeuvre and vestibular stimulated exercise training three times a week for four weeks . Thirteen subjects in the control group received only the canalith repositioning manoeuvre . Main measures : Static balance tests , t and em walk test , Dynamic Gait Index and subjective rating of the intensity of vertigo were measured at baseline , two-week and four-week assessment s. Results : Compared with the control group , subjects in the experimental group demonstrated a statistically significant improvement in single leg stance with eyes closed at the two-week assessment ( P<0.05 ) . Furthermore , stance on foam surface with eyes closed , single-leg stance with eyes closed , and Dynamic Gait Index at the four-week assessment were also significantly improved ( P<0.05 ) . Conclusion : The present study demonstrated that additional exercise training , which emphasizes vestibular stimulation , can improve balance ability and functional gait performance among patients with benign paroxysmal positional vertigo who had already undergone the canalith repositioning manoeuvre 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 OBJECTIVE To test the efficacy of low-level laser therapy on lateral ankle sprains as an addition to a st and ardized treatment regimen , a trial was conducted in which high-dose laser ( Output:	The study outcome ( positive vs negative ) was not associated with the likelihood of sample size reporting .
MS21450	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Abstract Objective : To compare tension-free vaginal tape with colposuspension as primary treatment for stress incontinence . Design : Multicentred r and omised comparative trial . Setting : Gynaecology or urology departments in 14 centres in the United Kingdom and Eire , including university teaching hospitals and district general hospitals . Participants : 344 women with urodynamic stress incontinence ; 175 r and omised to tension-free vaginal tape and 169 to colposuspension Main outcome measures : Assessment before treatment and at six months postoperatively with the SF-36 , the Bristol female lower urinary tract symptoms question naire , the EQ-5D health question naire , a one week urinary diary , one hour perineal pad test , cystometry , and , in some centres , urethral profilometry . Results : 23 women in the colposuspension group and 5 in the vaginal tape group withdrew before surgery . No significant difference was found between the groups for cure rates : 115 ( 66 % ) women in the vaginal tape group and 97 ( 57 % ) in the colposuspension group were objective ly cured ( 95 % confidence interval for difference in cure −4.7 % to 21.3 % ) . Bladder injury was more common during the vaginal tape procedure ; postoperative complications , in particular delayed resumption of micturition , were more common after colposuspension . Operation time , duration of hospital stay , and return to normal activity were all longer after colposuspension than after the vaginal tape procedure . Conclusion : Surgery with tension-free vaginal tape is associated with more operative complications than colposuspension , but colposuspension is associated with more postoperative complications and longer recovery . Vaginal tape shows promise for the treatment of urodynamic stress incontinence because of minimal access and rapid recovery times ; cure rates at six months were comparable with colposuspension . What is already known on this topic Few r and omised trials exist on surgery for stress incontinence Systematic review s suggest that colposuspension is associated with cure rates of up to 90 % Case series of tension-free vaginal tape suggest cure rates of about 85 % , with rapid return to normal activity What this study adds At six months the tension-free vaginal tape procedure is as effective as colposuspension for the primary treatment of stress incontinence Operative complications were more common with vaginal tape , but duration of hospital stay and return to normal activity were shorter than with colposuspension Postoperative complications were more common after OBJECTIVE The purpose of this study was to prospect ively and r and omly compare tension-free vaginal tape ( TVT ) with transobturator suburethral tape ( T.O.T. ) for the surgical treatment of stress urinary incontinence ( SUI ) in women . STUDY DESIGN Sixty-one women with SUI were r and omly assigned to either TVT ( n=31 ) or T.O.T. ( n=30 ) . The preoperative evaluation included a quality -of-life question naire and a comprehensive urodynamic examination . The 1-year outcome included a detrusor pressure-uroflow study to compare bladder outlet obstruction . RESULTS Patient characteristics , preoperative quality of life , and urodynamic evaluation were similar in the 2 groups . Mean operative time was significantly shorter in the T.O.T. group ( 15 min+/-4 vs 27 min+/-8 , P<.001 ) . No bladder injury occurred in the T.O.T. group versus 9.7 % ( n=3 ) in the TVT group ( P>.05 ) . The rate of postoperative urinary retention was 25.8 % ( n=8 ) in the TVT group versus 13.3 % ( n=4 ) in the T.O.T. group ( P>.05 ) . The rates of cure ( 83.9 % vs 90 % ) , improvement ( 9.7 % vs 3.3 % ) , and failure ( 6.5 % vs 6.7 % ) were similar for the TVT and T.O.T. groups , respectively . The 1-year outcome data were collected in 29 women of the TVT group and 27 women of the T.O.T. group . No vaginal erosion occurred in either of the groups . In terms of bladder outlet obstruction , no differences were found after TVT and T.O.T. CONCLUSION T.O.T. appears to be equally efficient as TVT for surgical treatment of stress urinary incontinence in women , with no reduction of bladder outlet obstruction at 1-year follow-up Objective To compare 1-year cure rates after laparoscopic Burch colposuspension using one double-bite or two single-bite sutures on each side of the urethra . Methods Consecutive women with primary stress urinary incontinence at one university hospital were included . Pre-operative clinical and urodynamic evaluation included cystoscopy , cystouretrometry at rest and stress , and a st and ardized pad test . Immediately before surgery , the patients were r and omized to have one or two polytetrafluoroethylene ( GoreTex CV 2 ; W. L. Gore Inc. , Flagstaff , AZ ) sutures placed on each side of the urethra . During surgery , access to the space of Retzius was achieved by transperitoneal videolaparoscopic technique . Women were scheduled for postoperative interview and pad test 1 year after surgery . Results We included 161 women in the study ; 78 were r and omized to one suture ( group A ) and 83 to two sutures ( group B ) . Median time for surgery was significantly shorter for group A than for group B ( 60 compared with 77 minutes ; P < .001 ) . We examined 158 women 1 year after surgery , at which time 148 performed a pad test . Objective cure rate was significantly higher in group B than in group A ( 83 % compared with 58 % ; P = .001 ) . Conclusion Two single-bite sutures result ed in a significantly higher objective short-term cure rate than one double-bite suture on each side of the urethra A total of 51 consecutive female patients with genuine stress incontinence who underwent a Burch or Stamey operation were clinical ly and urodynamically evaluated preoperatively at least 8 months postoperatively . Our study group consisted of 27 women who underwent the Burch colposuspension and 24 who had the Stamey endoscopic bladder neck suspension . The urodynamic parameters which were studied pre- and postoperatively were the maximum flow rate ( Qmax ) , the residual urine ( Vres ) , the first sensation ( FS ) , the bladder capacity ( BC ) , the maximum vesical pressure ( Pves max ) , the detrusor pressure at maximum flow ( Pdet/Qmax ) , the functional urethral length ( Lfun ) and the maximum closure pressure ( Pclos max ) . The successful results of the operations were 89 % for Burch and 83 % for the Stamey procedure . As for differing objective urodynamic findings , the Qmax , Pclos max , Vres and Lfun for both groups were the only parameters which showed statistically significant difference after surgery . The statistical comparison of the postoperative urodynamic parameters of the two operative techniques showed that Lfun , Pves max and Pclos max had difference in favor of Burch colposuspension . There were not statistical differences in the other studied parameters . In conclusion , according to the differentiation in the values of Pclos max , Lfun and Pves max , the Burch technique seems to result in a higher increase of patient 's urethral resistance One hundred seven consecutive patients with clinical and urodynamic findings of genuine stress incontinence not previously treated were prospect ively allocated in a r and omized manner to one of three surgical procedures : anterior colporrhaphy , revised Pereyra procedure , or Burch retropubic urethropexy . R and omization included the surgical procedure and choice of surgeon ( one of the three authors ) . Clinical and urodynamic evaluations were repeated at 3 months and 1 year after surgery . Differences in cure rates among the three procedures at the 3-month postoperative evaluation were insignificant ( 82 % , 84 % , and 92 % for the anterior colporrhaphy , Pereyra , and Burch respectively ) but became statistically significant at the 1 year postoperative evaluation ( cure rates of 65 % , 72 % , and 91 % for the anterior colporrhaphy , Pereyra , and Burch respectively , p less than 0.05 ) . In our h and s the Burch procedure stabilized the urethrovesical junction and prevented its descent during straining ( evaluated by a postoperative Q-tip test ) more effectively than either the Pereyra or anterior colporrhaphy . No procedure result ed in severe postoperative voiding difficulties . The present prospect i ve r and omized study demonstrates that in our h and s the abdominal retropubic operation for genuine stress incontinence in patients not previously operated on results in a higher cure rate when compared with anterior colporrhaphy or Pereyra procedure Abstract : In a prospect i ve long-term follow-up study we evaluated the results of TVT surgery in 34 women with recurrent stress urinary incontinence in whom previous traditional surgical procedures had failed . The women were followed for a mean of 4 years ( range 3–5 ) after TVT surgery . The mean age was 58.9 ± 10 years and the mean parity 2 ( 0–4 ) . Pre- and postoperative evaluation was performed according to a protocol which included gynecologic examination , urodynamic investigations , quality of life evaluation and 24-hour pad test . According to the protocol 28 patients ( 82 % ) were cured , 3 ( 9 % ) were significantly improved , and the operation failed in 3 cases ( 9 % ) . There were no significant intra- or postoperative complications . All patients were operated on under local anesthesia with a short hospitalization and had no long-term postoperative voiding problems OBJECTIVE Our purpose was to compare the effects of the Burch colposuspension with those of the modified Marshall-Marchetti-Krantz urethropexy . STUDY DESIGN Eighty women underwent the two types of operation . A full urodynamic investigation was repeated 6 months after surgery . RESULTS Clinical follow-up continued for 2 to 7 years . Differences in subjective and objective cure rates were not statistically significant ( respectively , 92 % and 80 % for the Burch colposuspension and 85 and 65 % for the modified Marshall-Marchetti-Krantz urethropexy ) . The latter induced a longer hospital stay ( 7.4 vs 6.3 days , p = 0.001 ) , a later resumption of spontaneous voiding ( 13.8 vs 8.5 days , p = 0.002 ) , and was associated with considerable complications ( one case of blood replacement for retropubic hematoma , one case of severe voiding difficulty , one case of further treatment for stress incontinence , and three cases of symptomatic de novo detrusor instability ) . CONCLUSION For its high cure rate , short time to resumption of spontaneous voiding , short hospital stay , and low associated morbidity , the Burch colposuspension should remain the procedure of choice for stress incontinence PURPOSE There is a lack of consensus regarding indications and long-term efficacy of the many surgical techniques for treating stress incontinence . Historically pubovaginal sling has been reserved for cases of intrinsic sphincter deficiency or prior surgical failure . Transvaginal needle and retropubic suspensions have been used mainly for sphincteric incontinence unassociated with intrinsic sphincter deficiency . We report the long-term results of pubovaginal sling for all types of stress incontinence . MATERIAL S AND METHODS A total of 251 consecutive women with all types of stress incontinence who underwent pubovaginal fascial sling by a single surgeon were retrospectively and prospect ively review ed . Patients were evaluated preoperatively with history , physical examination , st and ardized symptom question naire , voiding diary , pad test , uroflow , post-void residual urine , video urodynamics and cystoscopy . Postoperatively women with at least 1-year followup were assessed by an independent third party ( J. R. ) who had no prior knowledge of them , and who recorded the parameters of the question naire , examination with a full bladder , voiding diary , pad test , uroflow and post-void residual urine . RESULTS Overall stress incontinence was cured or improved in 92 % of the patients with at least 1-year followup ( median 3.1 years , range 1 to 15 ) . The majority of patients with postoperative incontinence had de novo ( 3 % ) or persistent ( 23 % ) urge incontinence . Permanent urinary retention developed in 4 patients ( 2 % ) . CONCLUSIONS Fascial pubovaginal sling is an effective treatment for all types of stress incontinence with acceptable long-term efficacy PURPOSE We compare the efficacy and morbidity of 373 consecutive women who underwent a vaginal wall sling for stress urinary incontinence due either to anatomical incontinence or intrinsic sphincter deficiency . To our knowledge this series is the largest prospect i ve data base on surgical management of stress urinary incontinence in the urological literature . MATERIAL S AND METHODS Preoperative evaluation included history , voiding diary , physical examination , cystoscopy , pad count and video urodynamic study . Outcome measures included postoperative presence of incontinence secondary to either stress and /or detrusor instability , number of pads used , complications , operating time , length of Output:	Use of a range of surgeries that have the highest proven efficacy is most likely to result in long-term patient satisfaction
MS21451	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Objective The efficacy of topical phenytoin in the treatment of diabetic foot ulcers was evaluated in a controlled inpatient study . Research Design and Methods Fifty patients were treated with topical phenytoin , and 50 patients matched for age , sex , and ulcer areas , depth , chronicity , and infection were dressed with dry sterile occlusive dressing . Results Both groups improved , but the ulcers treated with topical phenytoin healed more rapidly . Mean time to complete healing was 21 days with phenytoin and 45 days with control . The differences seen were statistically significant ( P < 0.05 ) via the chi 2 test . Conclusions Phenytoin appears to be useful as a topical agent in promoting the healing of diabetic foot ulcers Honey dressing has been used to promote wound healing for years but scanty scientific studies did not provide enough evidence s to justify it benefits in the treatment of diabetic foot ulcers . We conducted a prospect i ve study to compare the effect of honey dressing for Wagner 's grade -II diabetic foot ulcers with controlled dressing group ( povidone iodine followed by normal saline ) . Surgical debridement and appropriate antibiotics were prescribed in all patients . There were 30 patients age between 31 to 65-years-old ( mean of 52.1 years ) . The mean healing time in the st and ard dressing group was 15.4 days ( range 9 - 36 days ) compared to 14.4 days ( range 7 - 26 days ) in the honey group ( p < 0.005 ) . In conclusion , ulcer healing was not significantly different in both study groups . Honey dressing is a safe alternative dressing for Wagner grade -II diabetic foot ulcers Basic fibroblast growth factor ( bFGF ) has been shown to promote wound healing . The present trial evaluated the clinical efficacy of bFGF for diabetic ulcer , a type of refractory skin ulcer , and the dose-response relationship . This was design ed as a r and omized , double-blind , dose-ranging , placebo-controlled trial . A total of 150 patients with non-ischaemic diabetic ulcers measuring 900 mm2 or less were r and omized into a placebo group ( n = 51 ) , a 0.001 % bFGF group ( n = 49 ) and a 0.01 % bFGF group ( n = 50 ) , and 148 of these patients received treatment for 8 weeks or less . The efficacy evaluation was carried out on 139 patients who met the protocol in this trial . The primary outcome was the percentage of patients showing 75 % or greater reductions in the area of ulcer . The area of ulcer decreased by 75 % or more in 57.5 % ( 27/47 ) , 72.3 % ( 34/47 ) , and 82.2 % ( 37/45 ) in the placebo , 0.001 % bFGF and 0.01 % bFGF groups , respectively , and differences were significant between the 0.01 % bFGF and placebo groups ( p = 0.025 ) . The cure rate was 46.8 % ( 22/47 ) , 57.4 % ( 27/47 ) , and 66.7 % ( 30/45 ) in the placebo , 0.001 % bFGF and 0.01 % bFGF groups , respectively . The findings obtained in this trial showed wound healing accelerating effects of bFGF on diabetic ulcers : In recent years , skin grafting has evolved from the initial autograft and allograft preparations to biosynthetic and tissue-engineered living skin replacements . This review details the pioneering work of numerous investigators that led to the following precursors of tissue-engineered skin replacement : cultured autologous keratinocyte grafts , cultured allogeneic keratinocyte grafts , autologous/allogeneic composites , acellular collagen matrices , and cellular matrices . It also discusses the rationale for the development of the newer products and describes the technical advances leading to the development of Apligraf , a tissue-engineered human skin product Abstract Aims /hypothesis . To re-evaluate the use of Granulocyte-Colony Stimulating Factor ( G-CSF ) in the treatment of infected diabetic foot ulcers . Methods . Thirty-seven diabetic subjects were r and omised to Granulocyte-Colony Stimulating Factor ( G-CSF ) ( n=20 ) or placebo ( n=17 ) . The primary endpoint was resolution of cellulitis , which was evaluated clinical ly and with an infection summary score . Patients were hospitalised for 10 days and received subcutaneously either 5 µg/kg G-CSF or placebo daily . Ulcers were treated with a st and ard wound protocol and the patients were instructed to stay in bed . All subjects received antibiotics ( clindamycin and ciprofloxacin ) intravenously until the inflammation had subsided . Results . Patients who received G-CSF did not have an earlier resolution of clinical ly defined cellulitis ( p=0.57 ) . The infection summary score declined , but comparably , in both groups ( G-CSF : 29.5±18.4 to 6.7±6.3 p<0.001 , placebo : 24.2±16.9 to 8.9±7.2 p<0.001 ) . The ulcer volume , which was not greater among placebo patients , was reduced by 59 % in G-CSF and by 35 % in placebo patients . Conclusion /interpretation . We conclude that antibiotic and non weight-bearing therapy ( bed rest ) accelerated the resolution of cellulitis in infected foot ulcers . Additional treatment with G-CSF had no further beneficial effect This study tests the hypothesis that addition of a protease-modulating matrix enhances the efficacy of autologous growth factors in diabetic ulcers . Fifty-one patients with chronic diabetic foot ulcers were managed as out patients at the Democritus University Hospital of Alex and roupolis and followed up for 8 weeks . All target ulcers were > or = 2.5 cm in any one dimension and had been previously treated only with moist gauze . Patients were r and omly allocated in three groups of 17 patients each : Group A was treated only with the oxidized regenerated cellulose/collagen bio material ( Promogran , Johnson & Johnson , New Brunswick , NJ ) , Group B was treated only with autologous growth factors delivered by Gravitational Platelet Separation System ( GPS , Biomet ) , and Group C was managed by a combination of both . All ulcers were digitally photographed at initiation of the study and then at change of dressings once weekly . Computerized planimetry ( Texas Health Science Center ImageTool , Version 3.0 ) was used to assess ulcer dimensions that were analyzed for homogeneity and significance using the Statistical Package for Social Sciences , Version 13.0 . Post hoc analysis revealed that there was significantly greater reduction of all three dimensions of the ulcers in Group C compared to Groups A and B ( all P<.001 ) . Although reduction of ulcer dimensions was greater in Group A than in Group B , these differences did not reach statistical significance . It is concluded that protease-modulating dressings act synergistically with autologous growth factors and enhance their efficacy in diabetic foot ulcers CONTEXT Foot ulcer is the principal cause of hospitalization for patients with diabetes . Polydeoxyribonucleotide ( PDRN ) , an adenosine A2A receptor agonist , improves wound healing in diabetic mice . OBJECTIVE The aim of this study was to evaluate the effect of PDRN on chronic ulcer healing in patients with diabetes . DESIGN AND SETTING This r and omized , double-blind , placebo-controlled trial , involved two medical centers in Italy . INTERVENTION Patients with diabetes showing hard-to-heal ulcers ( Wagner grade 1 or 2 ) were r and omly assigned to receive placebo ( n = 106 ) or PDRN ( n = 110 ) . The treatments ( PDRN and placebo ) were performed for 8 weeks by intramuscular and perilesional route [ corrected ] . MAIN OUTCOME MEASURES The primary outcome was complete ulcer healing . Secondary outcomes were the days needed to complete wound closure and the reepithelialization of wound surface ( as percentage of the original area ) . RESULTS After 8 weeks , 91 placebo and 101 PDRN subjects completed the study . Complete healing was achieved in 18.9 % [ 95 % confidence interval ( CI ) 11.4 - 26.3 ] of placebo and in 37.3 % ( 95 % CI 28.2 - 46.3 ) of PDRN-treated patients ( P = .0027 ) . After 8 weeks , PDRN increased the closure of foot ulcers in diabetic subjects ( hazard ratio 2.20 ; 95 % CI 1.29 - 3.75 ; P = .004 ) . The median time to complete wound healing was 49 days for placebo ( range 28 - 56 d ) and 30 days for PDRN-treated subjects ( range 14 - 56 d ; P = .0027 ) . The median epithelialized area of the ulcers ( expressed as percentage ) was 49.3 % in the placebo and 82.2 % in the PDRN group ( P < .001 ) . CONCLUSIONS PDRN facilitates the healing of Wagner 1 or 2 diabetic foot ulcers OBJECTIVES To determine the comparative effectiveness and cost-effectiveness of three dressing products , N-A , Inadine and Aquacel , for patients with diabetic foot ulcers , as well as the feasibility and consequences of less frequent dressing changes by health-care professionals . DESIGN A multicentre , prospect i ve , observer-blinded , parallel group , r and omised controlled trial , with three arms . SETTING Established expert multidisciplinary clinics for the management of diabetic foot ulcers across the UK . PARTICIPANTS Patients over age 18 with type 1 or type 2 diabetes with a chronic ( present for at least 6 weeks ) full-thickness foot ulcer ( on or below the malleoli ) not penetrating to tendon , periosteum or bone , and with a cross-sectional area between 25 and 2500 mm(2 ) . INTERVENTIONS Participants were r and omised 1:1:1 to treatment with one of N-A ( a non-adherent , knitted , viscose filament gauze ) , Inadine ( an iodine-impregnated dressing ) , both traditional dressings , or Aquacel , a newer product . MAIN OUTCOME MEASURES The primary outcome measure was the number of ulcers healed in each group at week 24 . Secondary measures included time to healing , new ulcerations , major and minor amputations , and episodes of secondary infection . RESULTS A total of 317 patients were r and omised . After 88 withdrawals , 229 remained evaluable . A greater proportion of smaller ( 25 - 100 mm(2 ) ulcers healed within the specified time ( 48.3 % versus 37.3 % ; p = 0.048 ) . There was , however , no difference between the three dressings in terms of percentage healed by 24 weeks , or in the mean time to healing , whether analysed on the basis of intention to treat ( Inadine 44.4 % , N-A 38.7 % , Aquacel 44.7 % ; not significant ) or per protocol ( Inadine 55.2 % , N-A 59.4 % , Aquacel 63.0 % ; not significant ) . There was no difference in the quality of healing , as reflected in the incidence of recurrence within 12 weeks . Likewise , there was no difference in the incidence of adverse events , although a greater proportion of those r and omised to the non-adherent dressings were withdrawn from the study ( 34.9 % versus 29.1 % Aquacel and 19.4 % Inadine ; p = 0.038 ) . The only statistically significant difference found in the health economic analysis was the cost associated with the provision of dressings ( mean cost per patient : N-A 14.85 pounds , Inadine 17.48 pounds , Aquacel 43.60 pounds ) . The higher cost of Aquacel was not offset by the fewer dressings required . There was no difference in measures of either generic or condition-specific measures of quality of life . However , there was a significant difference in the change in pain associated with dressing changes between the first and second visits , with least pain reported by those receiving non-adherent dressings ( p = 0.012 ) . There was no difference in the costs of professional time , and this may relate to the number of dressing changes undertaken by non-professionals . Fifty-one per cent of all participants had at least one dressing change undertaken by themselves or a non-professional carer , although this ranged from 22 % to 82 % between the different centres . CONCLUSIONS As there was no difference in effectiveness , there is no reason why the least costly of the three dressings could not be used more widely across the UK National Health Service , thus generating potentially substantial savings . The option of involving patients and non-professional carers in changing dressings needs to be assessed more formally and could be associated with further significant reductions in health-care costs . TRIAL REGISTRATION Current Controlled Trials IS RCT N78366977 BACKGROUND Diabetic foot ulcers are associated with significant morbidity . Conventional treatment modalities are often of limited success in promoting complete wound closure . The aim of the present study was to examine the efficacy of noninvasive ozone-oxygen therapy in the treatment of Output:	The present report is an up date of the earlier IWGDF systematic review s , and the conclusion is similar : that with the possible exception of negative pressure wound therapy in post-operative wounds , there is little published evidence to justify the use of newer therapies .
MS21452	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: BACKGROUND Relapse is one of the most costly aspects of schizophrenia . AIMS To compare costs , clinical outcomes and quality of life for patients who experienced relapse in schizophrenia with a control group who did not relapse . METHOD Patients were r and omly selected from current psychiatric case-loads drawn from urban and suburban areas of Leicester . Differences in costs and outcomes by relapse status in the previous 6 months were examined using parametric and non-parametric tests , and multivariate analysis was used to examine factors associated with relapse and costs . RESULTS Costs for the patients who relapsed were over four times higher than those for the non-relapse group . There were few statistically significant differences in clinical and quality of life measures by relapse status . Multivariate analyses suggested some significant correlates of relapse and costs . CONCLUSIONS The higher costs associated with relapse will be of interest to policy-makers who face difficult choices concerning new but more expensive treatments for patients with schizophrenia While weight-management interventions are effective in attenuating antipsychotic-induced weight , there is no available evidence on their long-term effectiveness . This study sought to investigate the 2-year effects of an early behavioural intervention ( EBI ) design ed to prevent antipsychotic-induced weight gain in first-episode psychosis ( FEP ) patients . Sixty-one FEP patients were r and omized to receive either EBI or treatment-as-usual . Intention-to-treat and observed-cases analysis showed that patients in the EBI group gained significantly less weight than those allocated to routine care at intervention completion ( 3-month follow-up ) with treatment effects maintained over 3months . Differences between groups were no longer significant by 12months . Weight-management interventions may need to be offered for longer periods to maintain preventative effects . Alternatively , booster sessions may need to be regularly delivered after intervention completion BACKGROUND Recently , the " Remission in Schizophrenia Working Group " proposed remission criteria consisting of a reduction to mild levels on key symptoms for at least 6 months . AIMS This study applied these remission criteria to a large first-episode psychosis sample in order to ( 1 ) determine the rates of remission ; ( 2 ) explore predictors of remission ; and ( 3 ) test the external validity of these criteria . METHODS We analyzed data from 462 subjects with a first-episode of psychosis who participated in a long-term , multinational , r and omized , double-blinded trial of risperidone and haloperidol over 2 to 4 years . RESULTS At some time point in the study 323 ( 70 % ) of the 462 subjects had a reduction to mild levels on the key symptoms as measured by the PANSS although only 109 ( 23.6 % ) maintained this level for at least 6 months thereby meeting remission criteria . The two strongest predictors of remission were shorter duration of untreated psychosis ( p=0.01 ) and treatment response at 6 weeks ( p=0.001 ) . Compared to non-remitted patients , those in remission experienced greater improvement on all PANSS subscales ( p<.0001 ) , CGI-S ( p<.0001 ) , better quality of life ( p=0.006 ) , fewer relapses ( p<.0001 ) , displayed a more favorable attitude towards their medication ( p=.002 ) , had lower EPS levels according to the ESRS ( p=<.0001 ) and received lower doses of antipsychotic medication ( p=0.003 ) . The remission and non-remission groups did not differ significantly regarding composite cognitive scores , suicidality and body mass index . CONCLUSIONS The results suggest that the remission criteria , although based solely on core symptom improvement , can effectively identify patients who have a more favorable overall outcome To add to the open question whether cognitive impairments predict clinical outcome in schizophrenia , a sample of 125 first episode patients was assessed at the onset and over one year of controlled long-term treatment within a study of the German Research Network on Schizophrenia . No relapse according to predefined criteria occurred within the first year , but a total of 29 patients fulfilled post-hoc criteria of “ clinical deterioration ” . Impairments in cognitive functioning assessed by the Trail-Making Test B at the onset of long-term treatment differentiated between patients with vs. without later clinical deterioration and proved to be a significant predictor of the clinical course in a regression analysis outperforming initial clinical status as predictor . However , low sensitivity ( 72 % ) and specificity ( 51 % ) limit possibilities of a transfer to individual predictions . As a linear combination of neuropsychological and psychopathological variables obtained highest predictive validity , such a combination may improve the prediction of the course of schizophrenic disorders and may ultimately lead to a more efficient and comprehensive treatment planning BACKGROUND Well- design ed prospect i ve studies of substance misuse in first-episode psychosis can improve our underst and ing of the risks associated with comorbid substance misuse and psychosis . AIMS To examine the potential effects of substance misuse on in-patient admission and remission and relapse of positive symptoms in first-episode psychosis . METHOD The study was a prospect i ve 15-month follow-up investigation of 103 patients with first-episode psychosis recruited from three mental health services . RESULTS Substance misuse was independently associated with increased risk of in-patient admission , relapse of positive symptoms and shorter time to relapse of positive symptoms after controlling for potential confounding factors . Substance misuse was not associated with remission or time to remission of positive symptoms . Heavy substance misuse was associated with increased risk of in-patient admission , relapse and shorter time to relapse . CONCLUSIONS Substance misuse is an independent risk factor for a problematic recovery from first-episode psychosis 96 first episode schizophrenic patients were included for a prospect i ve follow-up study on factors affecting course and outcome of schizophrenia . Feighner 's diagnostic criteria were used for inclusion and a yearly assessment was made using the Present State Examination and the Personal and Psychiatric History Schedule . At the end of 3 years , 64 patients had been followed up . Of these , 38 patients had one or more relapses . A comparison of the relapsing group with the non-relapsers revealed certain variables to be significantly associated with relapses . Some of these were regularity of follow-up , presence of affective symptoms and self-neglect and lack of social contacts . The importance of recognising these factors in order to prevent relapses in schizophrenia is discussed " Expressed emotion " ( EE ) is considered a marker of dysfunctional family interaction in patients with schizophrenia . An alternative hypothesis , however , is that at least some of the different elements of EE really represent attempts on the part of carers to cope with and care for a relative with a psychiatric disorder . EE ( criticism and emotional overinvolvement ) was measured in relatives ( n = 31 ) of patients with psychotic illness using the Five-Minute Speech Sample ( FMSS ) . Level of EE was examined in relation to ( 1 ) patient-reported family involvement in care over the previous 2 years as indicated by medication monitoring , involvement in treatment decisions , and providing a substitute for institutional care ; and ( 2 ) symptom severity and number of psychotic episodes . Presence of EE in the relative was strongly associated with the degree of family involvement in care ( odds ratio [ OR ] over three levels : 3.2 ; 95 % confidence interval [ CI ] , 1.1 to 9.0 ) . In addition , presence of high EE was associated with number of psychotic episodes in the previous 5 years in the prob and ( OR over 0 , 1 , or 2 episodes : 6.2 ; 95 % CI , 1.2 to 31.9 ) . The association with family involvement was confined to emotional overinvolvement ( OR = 9.1 ; 95 % CI , 2.0 to 42.2 ) , whereas the association with previous psychotic episodes was confined to criticism ( OR = 20.6 ; 95 % CI , 2.8 to 149.3 ) . Emotional overinvolvement may be a state marker for attempts on the part of relatives to be partners in the care for patients with psychotic illness . High level of criticism may be a trait marker in relatives associated with poor prognosis , but could also develop in reaction to a frequently relapsing illness Background Transcultural studies have found lack of insight to be an almost invariable feature of acute and chronic schizophrenia , but its influence on prognosis is unclear . Aims To investigate the relationship between insight , psychopathology and outcome of first-episode schizophrenia in Vellore , India . Method Patients with a DSM – IV diagnosis of schizophrenia ( n = 131 ) were assessed prospect ively at baseline and at 6-month and 12-month follow-up . Demographic and clinical measures included insight , psychopathology , duration of untreated psychosis ( DUP ) and social functioning . Linear and logistic regression was used to measure predictors of outcome . Results Follow-up data were available for 115 patients at 1 year . All achieved remission , half of them with and half without residual symptoms . Changes in psychopathology and insight during the first 6 months and DUP strongly predicted outcome ( relapse or functional impairment ) , controlling for baseline measures . Conclusions Outcome of schizophrenia in this setting is driven by early symptomatic improvement and is relatively favourable , in line with other studies from low- and middle-income countries . Early improvement in insight might be a useful clinical guide to future outcome . Reduction of DUP should be a target for intervention A tentative model for conceptualizing the interplay of vulnerability factors , stressors , and protective factors in the course of schizophrenia is discussed . A study of the initial years after a first schizophrenic episode is testing the predictive role of key factors . During an initial 1‐year period of depot antipsychotic medication , independent life events and expressed emotion were found to predict the likelihood of psychotic relapse . Initial analyses indicate that independent life events play less of a role in relapse prediction during a medication‐free period . These results suggest that maintenance antipsychotic medication raises the threshold for return of psychotic symptoms , such that relapses are less likely unless major environmental stressors occur . A low expressed emotion environment may be a protective factor Cross-sectional investigations , using the five-factor model of personality have evinced relationships among neuroticism , agreeableness , and psychotic symptoms . The current study examined these relationships via a prospect i ve follow-up study with remitted first-episode psychosis patients . Baseline five-factor model personality profiles , diagnoses , symptom ratings , and premorbid adjustment ratings were followed by nine monthly ratings on Brief Psychiatric Rating Scale psychosis items in 60 first-episode patients . Valid baseline personality profiles were completed by 40 patients . Patients who had a return of symptoms scored higher on baseline neuroticism and agreeableness than those who remained in remission . Premorbid adjustment also predicted return of symptoms . After premorbid adjustment was controlled for , the agreeableness differences remained significant , but the neuroticism scores were no longer significantly different . It is concluded that lower agreeableness acts as a mediating variable in relapse . Further studies should clarify whether agreeableness is associated with specific biases in processing interpersonal information , and interpersonal behaviors Output:	Clinical variables and general demographic variables have little impact on relapse rates . Conversely , non-adherence with medication , persistent substance use disorder , carers ' criticism and poorer premorbid adjustment significantly increase the risk for relapse in FEP .
MS21453	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: CONTEXT Heart failure incidence increases with advancing age , and approximately half of patients with heart failure have preserved left ventricular ejection fraction . Although diastolic dysfunction plays a role in heart failure with preserved ejection fraction , little is known about age-dependent longitudinal changes in diastolic function in community population s. OBJECTIVE To measure changes in diastolic function over time and to determine the relationship between diastolic dysfunction and the risk of subsequent heart failure . DESIGN , SETTING , AND PARTICIPANTS Population -based cohort of participants enrolled in the Olmsted County Heart Function Study . R and omly selected participants 45 years or older ( N = 2042 ) underwent clinical evaluation , medical record abstract ion , and echocardiography ( examination 1 [ 1997 - 2000 ] ) . Diastolic left ventricular function was grade d as normal , mild , moderate , or severe by vali date d Doppler techniques . After 4 years , participants were invited to return for examination 2 ( 2001 - 2004 ) . The cohort of participants returning for examination 2 ( n = 1402 of 1960 surviving [ 72 % ] ) then underwent follow-up for ascertainment of new-onset heart failure ( 2004 - 2010 ) . MAIN OUTCOME MEASURES Change in diastolic function grade and incident heart failure . RESULTS During the 4 ( SD , 0.3 ) years between examinations 1 and 2 , diastolic dysfunction prevalence increased from 23.8 % ( 95 % confidence interval [ CI ] , 21.2%-26.4 % ) to 39.2 % ( 95 % CI , 36.3%-42.2 % ) ( P < .001 ) . Diastolic function grade worsened in 23.4 % ( 95 % CI , 20.9%-26.0 % ) of participants , was unchanged in 67.8 % ( 95 % CI , 64.8%-70.6 % ) , and improved in 8.8 % ( 95 % CI , 7.1%-10.5 % ) . Worsened diastolic dysfunction was associated with age 65 years or older ( odds ratio , 2.85 [ 95 % CI , 1.77 - 4.72 ] ) . During 6.3 ( SD , 2.3 ) years of additional follow-up , heart failure occurred in 2.6 % ( 95 % CI , 1.4%-3.8 % ) , 7.8 % ( 95 % CI , 5.8%-13.0 % ) , and 12.2 % ( 95 % CI , 8.5%-18.4 % ) of persons whose diastolic function normalized or remained normal , remained or progressed to mild dysfunction , or remained or progressed to moderate or severe dysfunction , respectively ( P < .001 ) . Diastolic dysfunction was associated with incident heart failure after adjustment for age , hypertension , diabetes , and coronary artery disease ( hazard ratio , 1.81 [ 95 % CI , 1.01 - 3.48 ] ) . CONCLUSIONS In a population -based cohort undergoing 4 years of follow-up , prevalence of diastolic dysfunction increased . Diastolic dysfunction was associated with development of heart failure during 6 years of subsequent follow-up Background —Although type 2 diabetes mellitus is a risk factor for developing congestive heart failure , the mechanism leading to heart failure is unclear . We examined the prevalence of left ventricular ( LV ) systolic and diastolic dysfunction in patients with type 2 diabetes mellitus in relation to vascular function and myocardial perfusion . Methods and Results —A prospect i ve observational study of 305 patients with type 2 diabetes mellitus ( diabetes duration , 4.5±5.3 years ) referred consecutively to a diabetes clinic were screened for LV systolic and diastolic function by echocardiography . Vascular function was estimated using noninvasive estimation of pulse pressure , carotid arterial compliance , total arterial compliance , and valvulo-arterial impedance . The prevalences of LV diastolic dysfunction and left atrial ( LA ) volume index > 32 mL/m2 were 40 % and 32 % , respectively . The prevalence of myocardial ischemia on myocardial perfusion scintigraphy was more frequent in patients with grade 2 diastolic dysfunction and LA volume index > 32 mL/m2 compared with those having normal or grade 1 diastolic dysfunction ( P=0.002 ) or LA volume index ≤32 mL/m2 ( P<0.001 ) , respectively . Predictors of grade 2 diastolic dysfunction and LA dilation were summed stress score on myocardial perfusion scintigraphy , total arterial compliance , and valvulo-arterial impedance , whereas pulse pressure and carotid arterial compliance were not , after adjusting for age , sex , and diabetes duration . On multivariable modeling , summed stress score ( P<0.001 ) and valvulo-arterial impedance ( P=0.027 ) remained predictors of grade 2 diastolic dysfunction , and only summed stress score ( P<0.001 ) was a predictor of LA dilation . Conclusions —Abnormal LV filling is closely associated with abnormal myocardial perfusion on myocardial perfusion scintigraphy , whereas the association of LV filling with vascular function is less prominent . Clinical Trial Registration —The trial has been registered at www . clinical trial.gov with Identifier : NCT00298844 OBJECTIVES The study sought to assess the primary preventive effect of neurohumoral therapy in high-risk diabetic patients selected by N-terminal pro-B-type natriuretic peptide ( NT-proBNP ) . BACKGROUND Few clinical trials have successfully demonstrated the prevention of cardiac events in patients with diabetes . One reason for this might be an inaccurate selection of patients . NT-proBNP has not been assessed in this context . METHODS A total of 300 patients with type 2 diabetes , elevated NT-proBNP ( > 125 pg/ml ) but free of cardiac disease were r and omized . The " control " group was cared for at 4 diabetes care units ; the " intensified " group was additionally treated at a cardiac outpatient clinic for the up-titration of renin-angiotensin system ( RAS ) antagonists and beta-blockers . The primary endpoint was hospitalization/death due to cardiac disease after 2 years . RESULTS At baseline , the mean age of the patients was 67.5 ± 9 years , duration of diabetes was 15 ± 12 years , 37 % were male , HbA1c was 7 ± 1.1 % , blood pressure was 151 ± 22 mm Hg , heart rate was 72 ± 11 beats/min , median NT-proBNP was 265.5 pg/ml ( interquartile range : 180.8 to 401.8 pg/ml ) . After 12 months there was a significant difference between the number of patients treated with a RAS antagonist/beta-blocker and the dosage reached between groups ( p < 0.0001 ) . Blood pressure was significantly reduced in both ( p < 0.05 ) ; heart rate was only reduced in the intensified group ( p = 0.004 ) . A significant reduction of the primary endpoint ( hazard ratio : 0.351 ; 95 % confidence interval : 0.127 to 0.975 , p = 0.044 ) was visible in the intensified group . The same was true for other endpoints : all-cause hospitalization , unplanned cardiovascular hospitalizations/death ( p < 0.05 for all ) . CONCLUSIONS Accelerated up-titration of RAS antagonists and beta-blockers to maximum tolerated dosages is an effective and safe intervention for the primary prevention of cardiac events for diabetic patients pre-selected using NT-proBNP . ( Nt-proBNP Guided Primary Prevention of CV Events in Diabetic Patients [ PONTIAC ] ; NCT00562952 ) AIMS To determine whether the risk of adverse cardiovascular ( CV ) outcomes associated with diabetes differs in patients with low and preserved ejection fraction ( EF ) heart failure ( HF ) . METHODS AND RESULTS We analysed outcomes in the C and esartan in Heart failure- Assessment of Reduction in Mortality and morbidity ( CHARM ) programme which r and omized 7599 patients with symptomatic HF and a broad range of EF . The prevalence of diabetes was 28.3 % in patients with preserved EF ( > 40 % ) and 28.5 % in those with low EF ( < or=40 % ) . Diabetes was associated with a greater relative risk of CV death or HF hospitalization in patients with preserved EF [ hazard ratio ( HR ) 2.0 ( 1.70 - 2.36 ) ] than in patients with low EF [ HR 1.60 ( 1.44 - 1.77 ) ; interaction test P = 0.0009 ] . For all-cause mortality , the risk conferred by diabetes was similar in both low and preserved EF groups . The effect of c and esartan in reducing CV morbidity and mortality outcomes was not modified by having diabetes at baseline ( P = 0.09 test for interaction ) . CONCLUSION Diabetes was an independent predictor of CV morbidity and mortality in patients with HF , regardless of EF . The relative risk of CV death or HF hospitalization conferred by diabetes was significantly greater in patients with preserved when compared with those with low EF HF Background : The incidence of heart failure in diabetic subjects is high even in the absence of hypertension and coronary artery disease . Aims : The purpose of this study was to study the incidence of diastolic dysfunction in diabetic subjects and its relation to age , duration of diabetes mellitus ( DM ) , Glycosylated hemoglobin ( HbA1c ) levels , obesity indices and diabetic microangiopathies . Setting s and Design : This was a case control prospect i ve study conducted at the teaching hospital during a one year period . Material s and Methods : A total of 127 subjects ( case ) with type 2 diabetes of more than five years duration were studied . Total 100 healthy subjects were included as the control group . Echocardiography was performed to assess left ventricular diastolic function . Results : Out of the total 127 subjects , 69 ( 54.33 % ) from the case group had diastolic dysfunction , and 11 % amongst 100 in the control group population showed the diastolic dysfunction ( P < 0.001 ) . Patients with a longer duration of DM ( of 11 to 15 years ) had a higher prevalence of diastolic dysfunction ( P < 0.02 ) . Subjects with high waist circumference and high waist to hip ratio had statistically significant diastolic dysfunction with ‘ P ’ = 0.001 and ‘ P ’ = < 0.02 respectively . Subjects with HbA1c > 7.5 % had a higher prevalence of diastolic dysfunction than subjects with HbA1c < 7.5 % ( P < 0.02 ) . Diastolic dysfunction was present in majority of the subjects with autonomic neuropathy and retinopathy . Conclusions : Present study reveals high incidence of diastolic dysfunction in asymptomatic diabetic ; subjects and , this finding was correlated with the duration of diabetes , HbA1c levels , obesity indices and diabetic microangiopathies . We conclude that early diagnosis and institution of treatment will reduce morbidity and improve the outcomes , and prevent future heart failure OBJECTIVE In the course of performing systematic review s on the prevalence of low back and neck pain , we required a tool to assess the risk of study bias . Our objectives were to ( 1 ) modify an existing checklist and ( 2 ) test the final tool for interrater agreement . STUDY DESIGN AND SETTING The final tool consists of 10 items addressing four domains of bias plus a summary risk of bias assessment . Two research ers tested the interrater agreement of the tool by independently assessing 54 r and omly selected studies . Interrater agreement overall and for each individual item was assessed using the proportion of agreement and Kappa statistic . RESULTS Raters found the tool easy to use , and there was high interrater agreement : overall agreement was 91 % and the Kappa statistic was 0.82 ( 95 % confidence interval : 0.76 , 0.86 ) . Agreement was almost perfect for the individual items on the tool and moderate for the summary assessment . CONCLUSION We have addressed a research gap by modifying and testing a tool to assess risk of study bias . Further research may be useful for assessing the applicability of the tool across different conditions BACKGROUND Diabetic cardiomyopathy defined as either systolic or diastolic dysfunction in otherwise healthy diabetic persons is not clearly understood . The prevalence and outcomes of this disease in a community-based population have not been defined . METHODS AND RESULTS Cross-sectional survey of 2042 r and omly selected residents of Olmsted County , Minnesota , aged 45 years or older between June 1997 and September 2000 . All patients underwent Doppler echocardiographic assessment of systolic and diastolic function . Output:	Conclusion : The prevalence of left ventricular diastolic dysfunction among type 2 diabetes patients is similarly high in men and women , while heart failure with preserved ejection fraction seems to be more common in women than men , at least in community people with type 2 diabetes
MS21454	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Background Growth of the foreign-born population in the U.S. has led to increasing numbers of limited-English-proficient ( LEP ) patients . Innovative medical interpreting strategies , including remote simultaneous medical interpreting ( RSMI ) , have arisen to address the language barrier . This study evaluates the impact of interpreting method on patient satisfaction . Methods 1,276 English- , Spanish- , M and arin- , and Cantonese-speaking patients attending the primary care clinic and emergency department of a large New York City municipal hospital were screened for enrollment in a r and omized controlled trial . Language -discordant patients were r and omized to RSMI or usual and customary ( U&C ) interpreting . Patients with language -concordant providers received usual care . Demographic and patient satisfaction question naires were administered to all participants . Results 541 patients were language -concordant with their providers and not r and omized ; 371 were r and omized to RSMI , 167 of whom were exposed to RSMI ; and 364 were r and omized to U&C , 198 of whom were exposed to U&C. Patients r and omized to RSMI were more likely than those with U&C to think doctors treated them with respect ( RSMI 71 % , U&C 64 % , p < 0.05 ) , but they did not differ in other measures of physician communication/care . In a linear regression analysis , exposure to RSMI was significantly associated with an increase in overall satisfaction with physician communication/care ( β 0.10 , 95 % CI 0.02–0.18 , scale 0–1.0 ) . Patients r and omized to RSMI were more likely to think the interpreting method protected their privacy ( RSMI 51 % , U&C 38 % , p < 0.05 ) . Patients r and omized to either arm of interpretation reported less comprehension and satisfaction than patients in language -concordant encounters . Conclusions While not a substitute for language -concordant providers , RSMI can improve patient satisfaction and privacy among LEP patients . Implementing RSMI should be considered an important component of a multipronged approach to addressing language barriers in health care Appropriate interpretation is imperative for families with limited English proficiency ( LEP ) . We compared throughput times for ED visits involving families with LEP based on type of interpretation provided : in-person interpretation , remote telephonic interpretation or bilingual providers . This study is a secondary analysis of a prospect i ve study of caretaker satisfaction with different interpreter modalities . We queried the medical record for event time stamps , clinical factors and disposition . The in-person cohort ( 116 min ) had a significantly shorter total throughput time than telephonic ( 141 min ) and bilingual provider ( 153 min ) cohorts ( P < 0.0001 ) , due to a difference in time seen by provider to disposition . Time seen by provider to disposition remained statistically significantly shorter for the in-person cohort when compared to telephonic interpretation when controlling for potential confounders such as admission rate ( P = 0.006 ) . In-person interpretation significantly decreased ED throughput times and may be an important consideration in the choice of interpreter modality Background Ethnic minorities report poorer evaluations of primary health care compared to White British patients . Emerging evidence suggests that when a doctor and patient share ethnicity and /or language this is associated with more positive reports of patient experience . Whether this is true for adults in English general practice s remains to be explored . Methods We analysed data from the 2010/2011 English General Practice Patient Survey , which were linked to data from the NHS Choices website to identify language s which were available at the practice . Our analysis was restricted to single-h and ed practice s and included 190,582 patients across 1,068 practice s. Including only single-h and ed practice s enabled us to attribute , more accurately , reported patient experience to the language s that were listed as being available . We also carried out sensitivity analyses in multi-doctor practice s . We created a composite score on a 0 - 100 scale from seven survey items assessing doctor-patient communication . Mixed-effect linear regression models were used to examine how differences in reported experience of doctor communication between patients of different self-reported ethnicities varied according to whether a South Asian language concordant with their ethnicity was available in their practice . Models were adjusted for patient characteristics and a r and om effect for practice . Results Availability of a concordant language had the largest effect on communication ratings for Bangladeshis and the least for Indian respondents ( p < 0.01 ) . Bangladeshi , Pakistani and Indian respondents on average reported poorer communication than White British respondents [ -2.9 ( 95%CI -4.2 , -1.6 ) , -1.9 ( 95%CI -2.6 , -1.2 ) and -1.9 ( 95%CI -2.5 , -1.4 ) , respectively ] . However , in practice s where a concordant language was offered , the experience reported by Pakistani patients was not substantially worse than that reported by White British patients ( -0.2 , 95%CI -1.5,+1.0 ) , and in the case of Bangladeshi patients was potentially much better ( + 4.5 , 95%CI -1.0,+10.1 ) . This contrasts with a worse experience reported among Bangladeshi ( -3.3 , 95%CI -4.6 , -2.0 ) and Pakistani ( -2.7 , 95%CI -3.6 , -1.9 ) respondents when a concordant language was not offered . Conclusions Substantial differences in reported patient experience exist between ethnic groups . Our results suggest that patient experience among Bangladeshis and Pakistanis is improved where the practice offers a language that is concordant with the patient ’s ethnicity Background Supporting 21st century health care and the practice of evidence -based medicine ( EBM ) requires ubiquitous access to clinical information and to knowledge-based re sources to answer clinical questions . Many questions go unanswered , however , due to lack of skills in formulating questions , crafting effective search strategies , and accessing data bases to identify best levels of evidence . Methods This r and omized trial was design ed as a pilot study to measure the relevancy of search results using three different interfaces for the PubMed search system . Two of the search interfaces utilized a specific framework called PICO , which was design ed to focus clinical questions and to prompt for publication type or type of question asked . The third interface was the st and ard PubMed interface readily available on the Web . Study subjects were recruited from interns and residents on an inpatient general medicine rotation at an academic medical center in the US . Thirty-one subjects were r and omized to one of the three interfaces , given 3 clinical questions , and asked to search PubMed for a set of relevant articles that would provide an answer for each question . The success of the search results was determined by a precision score , which compared the number of relevant or gold st and ard articles retrieved in a result set to the total number of articles retrieved in that set . Results Participants using the PICO templates ( Protocol A or Protocol B ) had higher precision scores for each question than the participants who used Protocol C , the st and ard PubMed Web interface . ( Question 1 : A = 35 % , B = 28 % , C = 20 % ; Question 2 : A = 5 % , B = 6 % , C = 4 % ; Question 3 : A = 1 % , B = 0 % , C = 0 % ) 95 % confidence intervals were calculated for the precision for each question using a lower boundary of zero . However , the 95 % confidence limits were overlapping , suggesting no statistical difference between the groups . Conclusion Due to the small number of search es for each arm , this pilot study could not demonstrate a statistically significant difference between the search protocol s. However there was a trend towards higher precision that needs to be investigated in a larger study to determine if PICO can improve the relevancy of search results Background Cultural and language discordance between patients and providers constitutes a significant challenge to provision of quality healthcare . This study aims to evaluate minority patients ’ discharge from hospital to community care , specifically examining the relationship between patient – provider language concordance and the quality of transitional care . Methods This was a multi- method prospect i ve study of care transitions of 92 patients : native Hebrew , Russian or Arabic speakers , with a pre-discharge question naire and structured observations examining discharge preparation from a large Israeli teaching hospital . Two weeks post-discharge patients were surveyed by phone , on the transition from hospital to community care ( the Care Transition Measure ( CTM-15 , 0–100 scale ) ) and on the primary -care post-discharge visit . Results Overall , ratings on the CTM indicated fair quality of the transition process ( scores of 51.8 to 58.8 ) . Patient – provider language concordance was present in 49 % of minority patients ’ discharge briefings . Language concordance was associated with higher CTM scores among minority groups ( 64.1 in language -concordant versus 49.8 in non- language -concordant discharges , P < 0.001 ) . Other aspects significantly associated with CTM scores : extent of discharge explanations ( P < 0.05 ) , quality of discharge briefing ( P < 0.001 ) , and post-discharge explanations by the primary care physician ( P < 0.01 ) . Conclusion Language -concordant care , coupled with extensive discharge briefings and post-discharge explanations for ongoing care , are important contributors to the quality of care transitions of ethnic minority patients BACKGROUND Many health care providers do not provide adequate language access services for their patients who are limited English-speaking because they view the costs of these services as prohibitive . However , little is known about the costs they might bear because of unaddressed language barriers or the costs of providing language access services . OBJECTIVE To investigate how language barriers and the provision of enhanced interpreter services impact the costs of a hospital stay . DESIGN Prospect i ve intervention study . SETTING Public hospital inpatient medicine service . PARTICIPANTS Three hundred twenty-three adult in patients : 124 Spanish-speakers whose physicians had access to the enhanced interpreter intervention , 99 Spanish-speakers whose physicians only had access to usual interpreter services , and 100 English-speakers matched to Spanish-speaking participants on age , gender , and admission firm . MEASUREMENTS Patient satisfaction , hospital length of stay , number of inpatient consultations and radiology tests conducted in the hospital , adherence with follow-up appointments , use of emergency department ( ED ) services and hospitalizations in the 3 months after discharge , and the costs associated with provision of the intervention and any result ing change in health care utilization . RESULTS The enhanced interpreter service intervention did not significantly impact any of the measured outcomes or their associated costs . The cost of the enhanced interpreter service was $ 234 per Spanish-speaking intervention patient and represented 1.5 % of the average hospital cost . Having a Spanish-speaking attending physician significantly increased Spanish-speaking patient satisfaction with physician , overall hospital experience , and reduced ED visits , thereby reducing costs by $ 92 per Spanish-speaking patient over the study period . CONCLUSION The enhanced interpreter service intervention did not significantly increase or decrease hospital costs . Physician – patient language concordance reduced return ED visit and costs . Health care providers need to examine all the cost implication s of different language access services before they deem them too costly The purpose of this study is to examine the association of ethnicity and language concordance with physician-patient agreement about physicians ' recommendations for patient health behavior in the following areas : diet , exercise , medication , smoking , stress , and weight . Twenty-seven resident physicians at the University of New Mexico 's internal medicine and family practice clinics and 427 of their patients participated . R and om effects models were used to estimate the influence of ethnicity and language concordance on whether patients and physicians agreed about specific recommended changes in patient behavior . Ethnicity concordance was not significantly associated with physician-patient agreement . Language concordance positively influenced the likelihood of agreement about exercise but negatively influenced agreement about medications . The lowest percentage of agreement occurred in the area of medication regimens ( 60 % ) . The results from this study indicate that language is an important barrier to physician-patient agreement , while ethnicity concordance has no effect . However , the influence of whether the physician and patient speak the same language on agreement is unclear and warrants further research Output:	Discussion The findings of this review indicate that , in the majority of situations , language -concordant care improves outcomes . Although most studies included were of good quality , none provided a st and ardized assessment of provider language skills .
MS21455	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: CONTEXT Surgical site infections prolong hospital stays , are among the leading nosocomial causes of morbidity , and a source of excess medical costs . Clinical studies comparing the risk of nosocomial infection after different h and antisepsis protocol s are scarce . OBJECTIVE To compare the effectiveness of h and -cleansing protocol s in preventing surgical site infections during routine surgical practice . DESIGN R and omized equivalence trial . SETTING Six surgical services from teaching and nonteaching hospitals in France . PATIENTS A total of 4387 consecutive patients who underwent clean and clean-contaminated surgery between January 1 , 2000 , and May 1 , 2001 . INTERVENTIONS Surgical services used 2 h and -cleansing methods alternately every other month : a h and -rubbing protocol with 75 % aqueous alcoholic solution containing propanol-1 , propanol-2 , and mecetronium etilsulfate ; and a h and -scrubbing protocol with antiseptic preparation containing 4 % povidone iodine or 4 % chlorhexidine gluconate . MAIN OUTCOME MEASURES Thirty-day surgical site infection rates were the primary end point ; operating department teams ' tolerance of and compliance with h and antisepsis were secondary end points . RESULTS The 2 protocol s were comparable in regard to surgical site infection risk factors . Surgical site infection rates were 55 of 2252 ( 2.44 % ) in the h and -rubbing protocol and 53 of 2135 ( 2.48 % ) in the h and -scrubbing protocol , for a difference of 0.04 % ( 95 % confidence interval , -0.88 % to 0.96 % ) . Based on subsets of personnel , compliance with the recommended duration of h and antisepsis was better in the h and -rubbing protocol of the study compared with the h and -scrubbing protocol ( 44 % vs 28 % , respectively ; P = .008 ) , as was tolerance , with less skin dryness and less skin irritation after aqueous solution use . CONCLUSIONS H and -rubbing with aqueous alcoholic solution , preceded by a 1-minute nonantiseptic h and wash before each surgeon 's first procedure of the day and before any other procedure if the h and s were soiled , was as effective as traditional h and -scrubbing with antiseptic soap in preventing surgical site infections . The h and -rubbing protocol was better tolerated by the surgical teams and improved compliance with hygiene guidelines . H and -rubbing with liquid aqueous alcoholic solution can thus be safely used as an alternative to traditional surgical h and -scrubbing BACKGROUND The effectiveness of an alcoholic solution compared with the st and ard hygienic h and washing procedure during regular work in clinical wards and intensive care units of a large public university hospital in Barcelona was assessed . METHODS A prospect i ve , r and omized clinical trial with crossover design , paired data , and blind evaluation was done . Eligible health care workers ( HCWs ) included permanent and temporary HCWs of wards and intensive care units . From each category , a r and om sample of persons was selected . HCWs were r and omly assigned to regular h and washing ( liquid soap and water ) or h and washing with the alcoholic solution by using a crossover design . The number of colony-forming units on agar plates from h and s printing in 3 different sample s was counted . RESULTS A total of 47 HCWs were included . The average reduction in the number of colony-forming units from sample s before h and washing to sample s after h and washing was 49.6 % for soap and water and 88.2 % for the alcoholic solution . When both methods were compared , the average number of colony-forming units recovered after the procedure showed a statistically significant difference in favor of the alcoholic solution ( P < .001 ) . The alcoholic solution was well tolerated by HCWs . Overall acceptance rate was classified as " good " by 72 % of HCWs after 2 weeks use . Of all HCWs included , 9.3 % stated that the use of the alcoholic solution worsened minor pre-existing skin conditions . CONCLUSIONS Although the regular use of hygienic soap and water h and washing procedures is the gold st and ard , the use of alcoholic solutions is effective and safe and deserves more attention , especially in situations in which the h and washing compliance rate is hampered by architectural problems ( lack of sinks ) or nursing work overload Chlorhexidine surgical scrub was left on the surgeon 's h and s in 50 orthopedic and vascular surgical procedures to determine whether the number of bacteria on the h and s could be decreased postoperatively . After a st and ard 5-minute scrub , one h and was r and omly rinsed prior to gloving ; the other was lightly patted with a sterile towel , leaving some foam on the h and . The surgeon then gloved and performed the procedure in the usual manner . After the operation , both h and s were immersed in a tryptic soy broth for 30 seconds . The broth was then cultured for bacterial species and number . Cases in which glove puncture occurred were not cultured . The results were analyzed using the Wilcoxon signed-rank test . There were fewer bacterial colonies isolated from the h and coated with chlorhexidine scrub versus the other ; this difference was statistically significant ( p less than 0.005 ) . There also seemed to be a trend towards higher bacterial counts after longer operations ; however , the difference was not significant . Neither surgeon noted any evidence of dermatitis during the study . These results suggest that leaving chlorhexidine scrub on the h and s during surgery can lead to lower bacterial counts on the surgeon 's h and s and less chance of wound contamination should glove puncture occur Abstract The efficacy of a povidone-iodine and a chlorhexidine gluconate detergent was evaluated for ‘ hygienic ' and ‘ surgical ' h and disinfection . Rubbing 60 per cent iso -propanol on to the h and s for 1 min was used as a st and ard for ‘ hygienic ' disinfection , with Escherichia coli as the test organism . The mean log reduction obtained was 3.16 with povidone-iodine and 2.92 with chlorhexidine . These were considerably less than obtained with iso -propanol which produced a reduction of 4.23 and 4.30 orders of magnitude . In the ‘ surgical ' h and disinfection tests , a 5 min wash with povidone-iodine and a 3 min wash with chlorhexidine detergent were compared with rubbing 60 per cent n -propanol or iso -propanol on to the h and s for 5 min ; n -propanol was taken as the st and ard preparation . Immediately after disinfection the log reduction in the resident flora was 0.92 with povidone-iodine and 0.78 with chlorhexidine , whereas n -propanol gave a log reduction of 3.43 . After wearing a surgical glove for 3 h a log reduction of 0.24 was obtained with povidoneiodine , 0.75 with chlorhexidine and 2.94 with n -propanol . Treatment with iso -propanol gave a log reduction of 1.04 . Thus , alcohols are shown by these tests to be far more effective than povidone-iodine or chlorhexidine detergent preparations in ‘ hygienic ' as well as ‘ surgical ' h and disinfection The aim of this cluster‐r and omized , crossover trial was to compare the efficacy of plain soap and water with an alcohol‐based h and rub for surgical h and preparation and prevention of surgical‐site infection ( SSI ) in a Kenyan rural hospital OBJECTIVE We describe a r and omized blinded study to evaluate the antimicrobial persistence following saline exposure of 2 commercially available skin antiseptic agents . One agent contained iodine povacrylex in alcohol and the second contained chlorhexidine gluconate in alcohol . METHOD Both agents were applied to the forearms of 36 healthy subjects according to manufacturers ' instructions and allowed to dry . The sites were then exposed to either a saline rinse or to a saline-saturated gauze , similar to the challenges that preps would face during most surgical procedures . Two analyses were performed : ( 1 ) An indicator organism was seeded onto the treated sites . After 30 minutes , sample s were collected from the treated sites and surviving bacterial colonies were enumerated and log reductions calculated . ( 2 ) The saline-saturated gauze was analyzed chemically for presence of chlorhexidine or iodine . RESULTS The baseline densities ( stated as logarithms of colony forming units " log CFU " ) of the sites to which the agents were applied had statistically equivalent microbial densities . Both agents reduced the density of organisms in a statistically significant manner . Chemical analysis of the gauze sample s indicated that 35 of 36 sample s had detectable chlorhexidine while no sample s had detectable iodine ( P < .0001 ) . CONCLUSION The results indicate that chlorhexidine is removed by saline-soaked gauze while the iodine povacrylex water-insoluble film remains intact under the same conditions . The implication is that similar results may occur in surgery when saline is used An evaluation of the effect of total body exhaust clothing on air and wound contamination was made in an operating theatre with a zonal ventilation system . Sixty-four patients who underwent total hip replacement using the Charnley-Müller prosthesis were studied . The members of the surgical team wore total body exhaust suits ( TBE-suit ) , or conventional theatre clothing ( C-clothing ) at alternate operations . Nearly half of the patients in each group were given prophylactic antibiotics . Both the mean and median values of airborne bacteria in the operating theatre were significantly lower during operations with TBE-suits than with conventional theatre clothing . The lowest number , 4.0 cfu/m3 , was found at the site of the operation wound . Cultures from adhesive drapes showed growth in 46 per cent of the C-group and in 43 per cent of the TBE-group sample s. Wound washouts showed growth in 43 per cent of the C-group and in 10 per cent of the TBE-group sample s. Staphylococcus epidermidis was the most frequently isolated bacteria both from adhesive drapes and from wound washouts . The rate of superficial infections was slightly higher when C-clothing was used . Deep infections were found in one patient in the TBE-group and in two patients in the C-group . None of the infected patients had received prophylactic antibiotics A technique for assessing the immediate and prolonged efficacy of surgical scrubs and alcoholic h and rubs is described . A mean baseline count is obtained from all volunteers and logarithmic reductions in resident skin flora immediately after one or more applications , and after wearing gloves for 3 h , are measured . Loose-fitting surgical gloves are used for sampling resident flora . Preparations were applied using a st and ard technique for 2 min , apart from one test with 70 % isopropanol ( IPA ) in which the application time was 30 s. Two studies are described , one of which compared four chlorhexidine scrubs , and the second 70 % IPA , 7.5 % povidone-iodine scrub , 2 % triclosan cleanser and unmedicated bar soap . In spite of their constituent similarity , the four chlorhexidine scrubs varied considerably in efficacy and user acceptability . A 2 min application of 70 % IPA was the most effective treatment , and gave log10 reductions of 1.65 for immediate and 1.58 for prolonged effect . This was marginally more effective than a 30 s application , but the difference was not significant . ' Hibiscrub ' was the most effective aqueous formulation and gave reductions of 1.01 for immediate effect and 1.16 for prolonged effect . The test described could be used by reference centres and manufacturers to assess the efficacy of new and existing surgical h and disinfection formulations The efficacy of 14 h and washing or disinfectant preparations was compared in laboratory tests on staff volunteers . The test organism , Escherichia coli , was applied to the fingertips and log reductions ( LR ) were measured following treatment with the test agent and control preparations ( 70 % isopropanol and non-medicated bar soap ) . Alcoholic preparations , particularly n-propanol and isopropanol were the most effective showing LRs of 3.1 - 3.8 . Chlorhexidine ( LR 2.9 ) and povidone-iodine detergent preparations were significantly more effective than non-medicated soap ( LR 2.1 ) , but triclosan products were not . In addition the residual effect of several of these formulations was assessed after 10 applications by comparing the survival of E. coli on the fingertips over a 32-min period . This number of h and washes compares favourably with those recorded during an 8 h nursing shift . Chlorhexidine-detergent consistently showed the best residual activity . Alcoholic formulations showed little or no residual effect . The survival studies show that on the whole gram-positive organisms ( Staphylococcus aureus and C and ida albicans ) survive better on the skin than Gram-negative bacilli ( GNB ) . However , it would seem that GNB which are considered to be residents ( Acinetobacter calcoaceticus and Enterobacter spp . ) survive much better than many other GNB ( Pseudomonas aeruginosa , E. coli and Proteus vulgaris ) . The Output:	Evidence from 4 studies suggests that chlorhexidine gluconate based aqueous scrubs are more effective than povidone iodine based aqueous scrubs in terms of the numbers of CFUs on the h and s. There is limited evidence regarding the effects on CFUs numbers of different scrub duration s. There is no evidence regarding the effect of equipment such as brushes and sponges
MS21456	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: OBJECTIVE To evaluate the prevalence in normal pregnancies of anti-32 glycoprotein I ( anti-beta2GPI ) antibodies , and their association with obstetrical complications . STUDY DESIGN Prospect i ve study of anti-beta2GPI and anticardiolipin ( CL ) antibodies in 510 healthy pregnant women at 15 - 18 weeks . According to the results , women were categorized into three groups : group I , negative for both antibodies ; group II , positive for anti-beta2GPI antibodies ; group III , positive for aCL only . The rates of fetal loss , abruptio placentae , preeclampsia-eclampsia , and fetal growth retardation were compared in the three groups . RESULTS Anti-beta2GPI antibodies were found in 20 women ( 3.9 % ) and aCL in 8 patients ( 1.6 % ) . Obstetrical complications were more frequent , even if not significantly different , in group II , 15 % , than in group I , 4.1 % ( difference 10.9 % ; 95 % confidence interval ( CI ) : 1.6 - 20.2 % ; p=0.0575 ) , while no complications were seen in group III . Preeclampsia-eclampsia were significantly more frequent in group II ( 10 % ) than in group I ( 0.8 % ; difference 9.2 % ; 95 % CI : 4.4 - 14 % ; p=0.021 ) . The prevalence of fetal growth retardation was not significantly different in the two groups ( 5 % vs. 2 % , respectively ) . COMMENT Our findings indicate that anti-beta2GPI antibodies are associated with some obstetrical complications , mainly preeclampsia-eclampsia , even if more conventional antiphospholipid antibodies are not present . This observation suggests that these antibodies should be investigated in such cases , in order to improve the outcome of subsequent pregnancies , as well as in women with a history of early and /or recurrent severe preeclampsia in order to start a prophylactic treatment ( i.e. low-dose aspirin or heparin ) Objective To investigate the association of anticardiolipin antibody with the genesis of spontaneous abortion , fetal growth restriction ( FGR ) , and preeclampsia . Methods Eight hundred sixty pregnant women constituted the study population . Anticardiolipin antibody was screened by enzyme-linked immunosorbent assay during the first trimester of pregnancy . The outcome of pregnancy in these women was analyzed prospect ively , and the rate of occurrence of spontaneous abortion , preeclampsia , and FGR was compared in the anticardiolipin antibody-positive and -negative groups . Results Anticardiolipin antibody was positive in 60 of the 860 women ( 7.0 % ) and negative in 800 ( 93.0 % ) . The rate of spontaneous abortions in the anticardiolipin antibody-positive group , 25.0 % , was significantly higher than that in the anticardiolipin antibody-negative group , at 9.8 % ( P < .001 ; relative risk [ RR ] 2.56 , 95 % confidence interval ( CI ) 1.37–4.81 ) . The rates of preeclampsia ( 11.7 % ) and FGR ( 11.7 % ) in the anticardiolipin antibody-positive group were also significantly higher than those in the -negative group ( 1.9 and 1.9 % , respectively ; for preeclampsia , P < .001 ; RR 6.22 , 95 % CI 2.43–16.0 and for FGR , P < .001 ; RR 6.22 , 95 % CI 2.43–16.0 ) . Conclusion Anticardiolipin antibody is associated with adverse outcomes of pregnancy such as spontaneous abortion , preeclampsia , and FGR OBJECTIVE To estimate whether antiphospholipid antibodies , specifically anticardiolipin and anti – β2-glycoprotein-Iantibodies , are associated with preeclampsia . METHODS Plasma was prospect ively obtained from four groups of pregnant women : those with 1 ) mild preeclampsia ( n = 109 ) ; 2 ) severe preeclampsia ( n = 134 ) ; 3 ) hemolysis , elevated liver enzymes , low platelets ( HELLP ) syndrome ( n = 57 ) ; and 4 ) normotensive controls ( n = 100 ) . Anticardiolipin and anti – β2-glycoprotein-I levels were determined by enzyme-linked immunoassay . RESULTS Subjects with mild preeclampsia , severe preeclampsia , and HELLP syndrome did not have significantly elevated levels of immunoglobulin G ( IgG ) and IgM anticardiolipin and anti – β2-glycoprotein-I antibodies compared with normotensive controls ( P > .05 , Kruskal – Wallis ) . Similarly , subjects with mild preeclampsia , severe preeclampsia , and HELLP syndrome did not have a significantly higher proportion of women testing positive for each autoantibody compared with normotensive controls ( χ2 ) . The proportion of patients testing positive for anticardiolipin and anti – β2-glycoprotein-I antibodies were similar in patients with preeclampsia developing before and after 34 weeks ' gestation ( χ2 ) . CONCLUSION Circulating levels of both anticardiolipin and anti – β2-glycoprotein-I antibodies were not increased in patients with mild preeclampsia , severe preeclampsia , or HELLP syndrome compared with normotensive controls . Our data do not support routine testing for anticardiolipin and anti – β2-glycoprotein-I antibodies in women with preeclampsia OBJECTIVE To evaluate in preterm infants the role of intrauterine growth retardation and infant body proportionality on subsequent childhood growth . METHODS Preterm infants ( 818 ) prospect ively enrolled in the Infant Health and Development Program were studied from birth to 36 months of corrected age . Weights and lengths were recorded at eight intervals . Growth parameters were compared in preterm infants with differing body symmetry at birth , defined by length-for-age and weight-for-age . Infants with both low length-for-age and low weight-for-age at birth were categorized as symmetrically growth retarded , and infants with normal length-for-age and low weight-for-age were categorized as asymmetrically growth retarded . RESULTS Infants born with low length-for-age demonstrated increased growth velocity until 8 months of corrected age ( p < 0.001 ) . However , infants born with low weight-for-age demonstrated decreased weight-gain velocity compared with preterm infants with appropriate weight for gestational age ( AGA ) until 40 weeks of corrected age ( p < 0.001 ) . Heights and weights of infants with either symmetric or asymmetric intrauterine growth retardation remained significantly retarded compared with AGA preterm patients and the National Child Health Survey ( NCHS ) reference population ( p < 0.001 ) . Infants born short but with normal weight did not significantly differ from AGA preterm infants in either weight or length at 36 months of corrected age . Preterm infants with both symmetric and asymmetric growth retardation demonstrated limited catch-up growth in weight until age 4 months and then paralleled the AGA preterm patients and the NCHS reference population . Very low birth weight ( < or = 1250 gm ) , gestational age , and a broad-based day-care intervention did not influence growth outcome after control for the presence of intrauterine growth retardation . CONCLUSIONS Preterm infants with both symmetric and asymmetric intrauterine growth retardation demonstrate limited catch-up growth . Intrauterine growth deficits persist into early childhood Objective To assess the association between the occurrence first of preeclampsia and antiphospholipid antibodies . Methods We conducted a prospect i ve case-control study of 180 pregnant women with their first incidents of preeclampsia and no histories of thrombosis or systemic autoimmune diseases . Preeclampsia ( n = 180 ) was defined as blood pressure ( BP ) at least 140/90 mmHg after 20 weeks ' gestation and proteinuria at least 0.3 g per 24 hours . Two control subjects were matched to each case ( n = 360 ) . They were pregnant women without hypertension or proteinuria and without histories of thrombosis or systemic autoimmune disease . Lupus anticoagulant ( activated partial thromboplastin time , diluted thromboplastin time , platelet neutralization procedure ) and anticardiolipin antibodies ( immunoenzymatic assays ) were assessed in both groups , and the coagulation state ( levels of thrombin-antithrombin III complexes , fragments 1 + 2 of prothrombin ) was also evaluated . The analysis design was a sequential plan with 5 % type I error and 95 % power . Results There was no association between antiphospholipid antibodies and preeclampsia . The odds ratio for the association was 0.95 ( 95 % confidence interval 0.45 , 2.61 ) . Antiphospholipid antibodies were detected in eight of 180 preeclamptic women and in 19 of 360 controls . In contrast , there was a clear , confirmed activation of coagulation during preeclampsia . Conclusion Despite evidence of a prothrombotic state during preeclampsia , it is unlikely that antiphospholipid antibodies ( lupus anticoagulant and anticardiolipin antibodies ) represent risk factors for preeclampsia among women with no previous preeclampsia and no histories of thrombosis or systemic autoimmune In an attempt to reduce the incidence of pregnancy associated venous thromboembolism ( PA-VTE ) , some research ers have advocated screening of all women for the factor V(Leiden ) mutation during early pregnancy . We have conducted a large retrospective study ( over 72,000 deliveries ) to determine if this would be useful . Sixty-two objective ly confirmed venous thrombotic events ( 51 DVT , 11 PE ) were recorded at two maternity units in the UK . The incidence of DVT was 0.71 per 1000 deliveries ( 95 % CI 0.5 - 0.9 ) with 0.50 occurring in the antenatal period ( 95 % CI 0.34 - 0.66 ) and 0.21 in the puerperium ( 95 % CI 0.11 - 0.31 ) . The incidence of PE was 0.15 per 1000 deliveries ( 95 % CI 0.06 - 0.24 ) , 0.07 antenatal ( 95 % CI 0.01 - 0.13 ) and 0.08 in the puerperium ( 95 % CI 0.02 - 0.14 ) . Of these 62 , 50 attended for follow-up and thrombophilia screening . 28 % of all episodes of PA-VTE had no clinical risk factor for thrombosis or an identifiable thrombophilic abnormality . Deficiency of antithrombin was identified in 12 % of individuals ( 95 % CI 3 - 21 ) and the factor V(Leiden ) mutation in 8 % ( 95 % CI 0.5 - 15.5 ) . Based on estimates of the prevalence of the factor V(Leiden ) mutation in the population , we estimate that the thrombotic risk for a woman during pregnancy or the puerperium with the defect is approximately 1 in 400 - 500 . This figure would not lend support to the idea of r and om screening for the mutation in early pregnancy Antibodies to cardiolipin and the lupus anticoagulant are overlapping subsets of antiphospholipid antibodies ( aPL ) and were originally described in patients with systemic lupus erythematosus [ 1 - 5 ] and subsequently in those with other rheumatic diseases [ 2 , 6 - 8 ] . These antibodies can also occur in nonrheumatologic disorders [ 9 - 12 ] and in healthy persons [ 13 , 14 ] . The presence of these antibodies in patients with systemic lupus erythematosus has been associated with the clinical features of thrombosis , fetal loss , and thrombocytopenia [ 15 - 18 ] . However , in nonautoimmune and healthy persons , the association of aPL with these clinical features has not been proved [ 14 , 19 , 20 ] . In addition , the value of different measures of aPL in predicting clinical symptoms has not been clearly defined . Furthermore , there is a paucity of prospect i ve studies describing the natural history of aPL and identifying the subset of aPL-positive patients who need therapeutic intervention . Recent studies examined the value of aPL in predicting adverse fetal and maternal outcome in healthy pregnant women [ 20 - 24 ] . The correlation of aPL with low birth weight , intrauterine fetal death , and adverse complications of pregnancy was identified by some authors [ 21 , 24 - 26 ] but not by others [ 22 ] . These studies concentrated on the predictive value of aPL as measured by anticardiolipin antibody ( IgG , IgM ) or lupus anticoagulant ( Output:	APLAs appear to be associated with late fetal losses . However , the association between APLAs and other placenta mediated complications is inconsistent . LA is most strongly and consistently associated with placenta mediated complications . There are currently insufficient data to support a significant link between anti-B2 GP1 antibodies and pregnancy morbidity
MS21457	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: BACKGROUND The appropriate dietary intervention for overweight persons with type 2 diabetes mellitus ( DM2 ) is unclear . Trials comparing the effectiveness of diets are frequently limited by short follow-up times and high dropout rates . AIM The effects of a low carbohydrate Mediterranean ( LCM ) , a traditional Mediterranean ( TM ) , and the 2003 American Diabetic Association ( ADA ) diet were compared , on health parameters during a 12-month period . METHODS In this 12-month trial , 259 overweight diabetic patients ( mean age 55 years , mean body mass index 31.4 kg/m(2 ) ) were r and omly assigned to one of the three diets . The primary end-points were reduction of fasting plasma glucose , HbA1c and triglyceride ( TG ) levels . RESULTS 194 patients out of 259 ( 74.9 % ) completed follow-up . After 12 months , the mean weight loss for all patients was 8.3 kg : 7.7 kg for ADA , 7.4 kg for TM and 10.1 kg for LCM diets . The reduction in HbA1c was significantly greater in the LCM diet than in the ADA diet ( -2.0 and -1.6 % , respectively , p < 0.022 ) . HDL cholesterol increased ( 0.1 mmol/l + /- 0.02 ) only on the LCM ( p < 0.002 ) . The reduction in serum TG was greater in the LCM ( -1.3 mmol/l ) and TM ( -1.5 mmol/l ) than in the ADA ( -0.7 mmol/l ) , p = 0.001 . CONCLUSIONS An intensive 12-month dietary intervention in a community-based setting was effective in improving most modifiable cardiovascular risk factors in all the dietary groups . Only the LCM improved HDL levels and was superior to both the ADA and TM in improving glycaemic control Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more OBJECTIVES We studied the effect of the Mediterranean diet on plasma levels of C-reactive protein ( CRP ) , white blood cell counts , interleukin (IL)-6 , tumor necrosis factor (TNF)-alpha , amyloid A , fibrinogen , and homocysteine . BACKGROUND To the best of our knowledge , the mechanism(s ) by which the Mediterranean diet reduces cardiovascular risk are not well understood . METHODS During the 2001 to 2002 period , we r and omly enrolled 1,514 men ( 18 to 87 years old ) and 1,528 women ( 18 to 89 years old ) from the Attica area of Greece ( of these , 5 % of men and 3 % of women were excluded because of a history of cardiovascular disease ) . Among several factors , adherence to the Mediterranean diet was assessed by a diet score that incorporated the inherent characteristics of this diet . Higher values of the score meant closer adherence to the Mediterranean diet . RESULTS Participants who were in the highest tertile of the diet score had , on average , 20 % lower CRP levels ( p = 0.015 ) , 17 % lower IL-6 levels ( p = 0.025 ) , 15 % lower homocysteine levels ( p = 0.031 ) , 14 % lower white blood cell counts ( p = 0.001 ) , and 6 % lower fibrinogen levels ( p = 0.025 ) , as compared with those in the lowest tertile . The findings remained significant even after various adjustments were made . Borderline associations were found regarding TNF-alpha ( p = 0.076 ) , amyloid A levels ( p = 0.19 ) , and diet score . CONCLUSIONS Adherence to the traditional Mediterranean diet was associated with a reduction in the concentrations of inflammation and coagulation markers . This may partly explain the beneficial actions of this diet on the cardiovascular system Context Mediterranean-style diets improve control of coronary risk factors and hyperglycemia , but few direct comparisons of the diet with other st and ard diets have been done . Contribution In this r and omized clinical trial , patients with newly diagnosed type 2 diabetes who were assigned to a low-carbohydrate , Mediterranean-style diet had better glycemic control and were less likely to need oral antihyperglycemic therapy than patients assigned to a low-fat diet . Caution The trial was unblinded , and dietary intake was self-reported . Implication A low-carbohydrate , Mediterranean-style diet seems to be preferable to a low-fat diet for glycemic control in patients with newly diagnosed type 2 diabetes . The Editors The p and emic of type 2 diabetes is an enormous public health problem , with 380 million cases worldwide projected by 2025 ( 1 , 2 ) . Lifestyle intervention studies ( 3 ) have demonstrated large reductions in risk for type 2 diabetes that remain after lifestyle counseling is stopped ( 4 , 5 ) . Despite this beneficial effect , the American Diabetes Association ( ADA ) recommends that patients with newly diagnosed type 2 diabetes be treated with pharmacotherapy as well as lifestyle changes ( 6 ) . The rationale for combination therapy is presumably that each form of treatment alone is imperfect . Lifestyle changes are often inadequate because patients do not lose weight or regain weight or their diabetes worsens independent of weight ( 6 ) . Pharmacotherapy also often fails with time ( 7 ) , and some drugs have associated cardiovascular and other risks ( 8 , 9 ) . For those reasons , lifestyle changes proven to be more effective than what is typically recommended would be welcome . For example , Mediterranean-style ( MED ) diets with a high proportion of monounsaturated fat provide cardiovascular benefits and increase insulin sensitivity ( 1012 ) , and the ADA recommends low-carbohydrate or low-fat , calorie-restricted diets for weight loss in overweight and obese patients with type 2 diabetes ( 13 ) . However , few direct , long-term comparisons of the 2 diets in patients with diabetes have been done ( 11 ) . We conducted a r and omized trial to compare the effectiveness , durability , and safety of a low-carbohydrate MED diet and a low-fat diet on glycemic control in patients with newly diagnosed type 2 diabetes . Methods We conducted the trial between January 2004 ( first patient enrolled ) and September 2008 ( end of follow-up of the last patient ) at the research center of the Diabetes Clinic of the Azienda Ospedaliera Universitaria , Second University of Naples , Naples , Italy , in accordance with the Declaration of Helsinki and with the institutional review board 's approval . Screening Phase We recruited men and women with newly diagnosed type 2 diabetes by ADA criteria who had never been treated with antihyperglycemic drugs from the clinical practice s of trial investigators and screened them for eligibility . Inclusion criteria were age 30 to 75 years , body mass index ( BMI ) greater than 25 kg/m2 , and hemoglobin A1c ( HbA1c ) level less than 11 % . Participants also had to be sedentary ( < 1 hour of physical activity per week ) with no evidence of participation in weight-reduction programs and with a stable weight ( 2 kg ) in the past 6 months . Exclusion criteria included pregnancy or breastfeeding , use of any investigational drug in the previous 3 months , use of agents affecting glycemic control ( such as systemic glucocorticoids and weight loss drugs ) , and any condition that might compromise adherence to diet regimens . To minimize the likelihood of including participants with late-onset type 1 diabetes , we screened c and i date s by testing for antibodies to glutamate decarboxylase and measuring fasting plasma C-peptides . We excluded patients with positive antibodies or C-peptide levels less than 0.25 pmol/L ( < 0.76 ng/L ) . We also excluded patients with abnormal laboratory test results , including liver enzyme levels ( alanine aminotransferase , aspartate aminotransferase , and alkaline phosphatase ) greater than 3 times the upper limit of normal and serum creatinine levels greater than 123.8 mol/L ( > 1.4 mg/dL ) . We required that participants successfully self-monitor their diet and physical activity over a 2-week run-in period . We provided dietary education during that time that emphasized the importance of eating a healthy diet and being physically active for both weight loss and improvement of glycemic control . Participants were also taught to prepare their own meals at home . We encouraged all individuals who smoked to quit and provided self-help material s , referral to local programs , or both , as appropriate . R and omization and Blinding After obtaining informed consent , we r and omly assigned patients to 1 of the 2 study diets by using a computer-generated r and om-number sequence ( simple r and omization ) . Allocation was concealed in sealed study folders that were held in a central , secured location until after informed consent was obtained . The nurses who scheduled the study visits did not have access to the r and omization list , and laboratory staff did not know the participants ' group assignments . Staff members involved in the intervention were aware of group assignments , but those who assessed achievement of the primary outcome were blinded to the intervention . Participants received no financial compensation or gifts . Dietary Interventions We r and omly assigned patients to a low-carbohydrate MED diet or to a low-fat diet . The MED diet was rich in vegetables and whole grains and low in red meat , which was replaced with poultry and fish . We restricted energy intake to 1500 kcal/d for women and 1800 kcal/d for men , with the goal of no more than 50 % of calories from complex carbohydrates , based on evidence that , in the context of a MED diet , a carbohydrate content less than 50 % of daily energy is more beneficial than higher content for weight loss and cardiovascular risk reduction ( 14 ) . The diet had no less than 30 % calories from fat . The main source of added fat was 30 to 50 g of olive oil . The low-fat diet was based on American Heart Association guidelines ( 15 ) ; it was rich in whole grains and restricted additional fats , sweets , and high-fat snacks . We restricted energy intake to 1500 kcal/d for women and 1800 kcal/d for men , with the goal of no more than 30 % of calories from fat and no more than 10 % of calories from saturated fat . Nutritionists and dietitians gave dietary advice to participants in both groups in monthly sessions in the first year and bimonthly sessions thereafter . Participants kept diet diaries after being instructed how to record their intake using food models as examples of portion size and using actual weights or amounts in terms of common measures ( such as cups , teaspoons , and dessert spoons ) . We assessed adherence to the diets by session attendance and review of the diaries . Nondietary Interventions Patients in both groups also received guidance on increasing their level of physical activity , mainly walking for a minimum of 30 minutes per day , but also swimming or aerobic ball games . The physical activity program relied heavily on home-based exercise with gradual progression toward a goal of 175 minutes of moderate-intensity physical activity per week . Although walking was encouraged , participants were allowed to choose other types of moderate-intensity physical activity , and programs were tailored on the basis of the results of a baseline physical fitness test and safety concerns . We asked all patients to record occupational , household , and leisure time physical activity . Outcomes We followed patients for 4 years to assess trial outcomes . The primary outcome measure was time to introduction of antihyperglycemic drug therapy . Trial investigators were responsible for initiating drug therapy by the following protocol . As suggested by the ADA for clinical evaluation and management of diabetic patients ( 16 ) , we measured HbA1c at baseline and every 3 months thereafter . Participants who had a HbA1c level greater than 7 % were given an additional 3 months to reinforce dietary guidance and physical activity ; if the HbA1c level remained greater than 7 % , a drug regimen was introduced . Participants with an HbA1c level greater than 7 % at baseline were counted as having experienced the primary outcome if they still had that level at first follow-up . Trial investigators were also responsible for initiating or titrating antihypertensive or lipid-lowering therapy . Secondary outcome measures were changes in weight ( including BMI and waist circumference ) , glycemic control ( HbA1c , glucose , serum insulin , and adiponectin levels and homeostasis model assessment of insulin sensitivity ) , coronary risk factors ( lipid levels and blood pressure ) , and medications and meeting ADA coronary risk factor goals ( HbA1c level < 7 % , blood pressure < 130/80 mm Hg , and low-density lipoprotein cholesterol level < 2.59 mmol/L [ < 100 mg/dL ] ) ( 16 ) . Participants were weighed without shoes and in lightweight clothing to the nearest 0.1 kg at baseline and every month . Height at bas Output:	Moreover , the Mediterranean diet was generally similar to comparator diets at improving other cardiovascular risk factor levels , including blood pressure and lipid levels . Our findings suggest that the Mediterranean diet results in similar weight loss and cardiovascular risk factor level reduction as comparator diets in overweight or obese individuals trying to lose weight
MS21458	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Background Distress and burnout among medical and psychology professionals are commonly reported and have implication s for the quality of patient care delivered . Already in the course of university studies , medicine and psychology students report mental distress and low life satisfaction . There is a need for interventions that promote better coping skills in students in order to prevent distress and future burnout . This study examines the effect of a seven-week Mindfulness-Based Stress Reduction ( MBSR ) programme on mental distress , study stress , burnout , subjective well-being , and mindfulness of medical and psychology students . Methods A total of 288 students ( mean age = 23 years , 76 % female ) from the University of Oslo and the University of Tromsø were r and omly allocated to an intervention or control group . The control group continued with their st and ard university courses and received no intervention . Participants were evaluated using self-reported measures both before and after the intervention . These were : the ‘ General Health Question naire , Maslach Burnout Inventory Student version , Perceived Medical School Stress , Subjective Well-being , and Five Facet Mindfulness Question naire ’ and additional indices of compliance . Results Following the intervention , a moderate effect on mental distress ( Hedges’g 0.65 , CI = .41 , .88 ) , and a small effect on both subjective well-being ( Hedges’g 0.40 , CI = .27 , .63 ) and the mindfulness facet ‘ non-reacting ’ ( Hedges’g 0.33 , CI = .10 , .56 ) were found in the intervention group compared with the control group . A higher level of programme attendance and reported mindfulness exercises predicted these changes . Significant effects were only found for female students who additionally reported reduced study stress and an increase in the mindfulness facet ‘ non-judging ’ . Gender specific effects of participation in the MBSR programme have not previously been reported , and gender differences in the present study are discussed . Conclusion Female medical and psychology students experienced significant positive improvements in mental distress , study stress , subjective well-being and mindfulness after participating in the MBSR programme . Trial registration There is often wide variability in the reported effects of complex behavioral interventions . Effectiveness can vary across studies , sites , and providers . A factor that has been insufficiently considered is the fidelity of the behavioral treatment that was provided . Low quality practice could be likened to partial doses of a vaccine or antibiotic : the right idea but insufficient strength . Using motivational interviewing ( MI ) as an example , the authors describe three quality conditions that should be present for a study to be regarded as a trial of a complex behavioral intervention : ( 1 ) The treatment should clearly contain the components that are theoretically or empirically related to its efficacy ; ( 2 ) providers should be trained to an adequate and specified criterion of proficiency before treating trial patients ; and ( 3 ) the fidelity of treatment should be documented by reliable coding of practice throughout the study and reported in a manner that permits comparison with skill levels in other trials . The authors also discuss bona fide intervention failures despite strong clinical trial methodology , offering recommendations for future outcome research Background : Although mindfulness meditation interventions have recently shown benefits for reducing stress in various population s , little is known about their relative efficacy compared with relaxation interventions . Purpose : This r and omized controlled trial examines the effects of a 1-month mindfulness meditation versus somatic relaxation training as compared to a control group in 83 students ( M age=25 ; 16 men and 67 women ) reporting distress . Method : Psychological distress , positive states of mind , distractive and ruminative thoughts and behaviors , and spiritual experience were measured , while controlling for social desirability . Results : Hierarchical linear modeling reveals that both meditation and relaxation groups experienced significant decreases in distress as well as increases in positive mood states over time , compared with the control group ( p<.05 in all cases ) . There were no significant differences between meditation and relaxation on distress and positive mood states over time . Effect sizes for distress were large for both meditation and relaxation ( Cohen ’s d=1.36 and .91 , respectively ) , whereas the meditation group showed a larger effect size for positive states of mind than relaxation ( Cohen ’s d=.71 and .25 , respectively ) . The meditation group also demonstrated significant pre-post decreases in both distractive and ruminative thoughts/behaviors compared with the control group ( p<.04 in all cases ; Cohen ’s d=.57 for rumination and .25 for distraction for the meditation group ) , with mediation models suggesting that mindfulness meditation ’s effects on reducing distress were partially mediated by reducing rumination . No significant effects were found for spiritual experience . Conclusions : The data suggest that compared with a no-treatment control , brief training in mindfulness meditation or somatic relaxation reduces distress and improves positive mood states . However , mindfulness meditation may be specific in its ability to reduce distractive and ruminative thoughts and behaviors , and this ability may provide a unique mechanism by which mindfulness meditation reduces distress The inability to cope successfully with the enormous stress of medical education may lead to a cascade of consequences at both a personal and professional level . The present study examined the short-term effects of an 8-week meditation-based stress reduction intervention on premedical and medical students using a well-controlled statistical design . Findings indicate that participation in the intervention can effectively ( 1 ) reduce self-reported state and trait anxiety , ( 2 ) reduce reports of overall psychological distress including depression , ( 3 ) increase scores on overall empathy levels , and ( 4 ) increase scores on a measure of spiritual experiences assessed at termination of intervention . These results ( 5 ) replicated in the wait-list control group , ( 6 ) held across different experiments , and ( 7 ) were observed during the exam period . Future research should address potential long-term effects of mindfulness training for medical and premedical students Background Determining the effectiveness of social and psychological interventions is important for improving individual and population health . Such interventions are complex and , where possible , are best evaluated by r and omised controlled trials ( RCTs ) . The use of research findings in policy and practice decision making is hindered by poor reporting of RCTs . Poor reporting limits the ability to replicate interventions , synthesis e evidence in systematic review s , and utilise findings for evidence -based policy and practice . The lack of guidance for reporting the specific method ological features of complex intervention RCTs contributes to poor reporting . We aim to develop an extension of the Consoli date d St and ards of Reporting Trials Statement for Social and Psychological Interventions ( CONSORT-SPI ) . Methods / design This research project will be conducted in five phases . The first phase was the project launch , which consisted of the establishment of a Project Executive and International Advisory Group , and recruitment of journal editors and the CONSORT Group . The second phase involves a Delphi process that will generate a list of possible items to include in the CONSORT Extension . Next , there will be a formal consensus meeting to select the reporting items to add to , or modify for , the CONSORT-SPI Extension . Fourth , guideline documents will be written , including an explanation and elaboration ( E&E ) document that will provide detailed advice for each item and examples of good reporting . The final phase will comprise guideline dissemination , with simultaneous publication and endorsement of the guideline in multiple journals , endorsement by funding agencies , presentations at conferences and other meetings , and a dedicated website that will facilitate feedback about the guideline . Conclusion As demonstrated by previous CONSORT guidelines , the development of an evidence -based reporting guideline for social and psychological intervention RCTs should improve the accuracy , comprehensiveness , and transparency of study reports . This , in turn , promises to improve the critical appraisal of research and its use in policy and practice decision making . We invite readers to participate in the project by visiting our website ( http://tinyurl.com/CONSORT- study ) CONTEXT Primary care physicians report high levels of distress , which is linked to burnout , attrition , and poorer quality of care . Programs to reduce burnout before it results in impairment are rare ; data on these programs are scarce . OBJECTIVE To determine whether an intensive educational program in mindfulness , communication , and self-awareness is associated with improvement in primary care physicians ' well-being , psychological distress , burnout , and capacity for relating to patients . DESIGN , SETTING , AND PARTICIPANTS Before- and -after study of 70 primary care physicians in Rochester , New York , in a continuing medical education ( CME ) course in 2007 - 2008 . The course included mindfulness meditation , self-awareness exercises , narratives about meaningful clinical experiences , appreciative interviews , didactic material , and discussion . An 8-week intensive phase ( 2.5 h/wk , 7-hour retreat ) was followed by a 10-month maintenance phase ( 2.5 h/mo ) . MAIN OUTCOME MEASURES Mindfulness ( 2 subscales ) , burnout ( 3 subscales ) , empathy ( 3 subscales ) , psychosocial orientation , personality ( 5 factors ) , and mood ( 6 subscales ) measured at baseline and at 2 , 12 , and 15 months . RESULTS Over the course of the program and follow-up , participants demonstrated improvements in mindfulness ( raw score , 45.2 to 54.1 ; raw score change [ Delta ] , 8.9 ; 95 % confidence interval [ CI ] , 7.0 to 10.8 ) ; burnout ( emotional exhaustion , 26.8 to 20.0 ; Delta = -6.8 ; 95 % CI , -4.8 to -8.8 ; depersonalization , 8.4 to 5.9 ; Delta = -2.5 ; 95 % CI , -1.4 to -3.6 ; and personal accomplishment , 40.2 to 42.6 ; Delta = 2.4 ; 95 % CI , 1.2 to 3.6 ) ; empathy ( 116.6 to 121.2 ; Delta = 4.6 ; 95 % CI , 2.2 to 7.0 ) ; physician belief scale ( 76.7 to 72.6 ; Delta = -4.1 ; 95 % CI , -1.8 to -6.4 ) ; total mood disturbance ( 33.2 to 16.1 ; Delta = -17.1 ; 95 % CI , -11 to -23.2 ) , and personality ( conscientiousness , 6.5 to 6.8 ; Delta = 0.3 ; 95 % CI , 0.1 to 5 and emotional stability , 6.1 to 6.6 ; Delta = 0.5 ; 95 % CI , 0.3 to 0.7 ) . Improvements in mindfulness were correlated with improvements in total mood disturbance ( r = -0.39 , P < .001 ) , perspective taking subscale of physician empathy ( r = 0.31 , P < .001 ) , burnout ( emotional exhaustion and personal accomplishment subscales , r = -0.32 and 0.33 , respectively ; P < .001 ) , and personality factors ( conscientiousness and emotional stability , r = 0.29 and 0.25 , respectively ; P < .001 ) . CONCLUSIONS Participation in a mindful communication program was associated with short-term and sustained improvements in well-being and attitudes associated with patient-centered care . Because before- and -after design s limit inferences about intervention effects , these findings warrant r and omized trials involving a variety of practicing physicians This article is the second in a series reporting on research exploring the effects of Mindfulness-based Stress Reduction on nurses and describes the quantitative data . The third article describes qualitative data . Treatment group participants reduced scores on 2 of 3 subscales of the Maslach Burnout Inventory significantly more than wait-list controls ; within-group comparisons for both groups pretreatment and posttreatment revealed similar findings . Changes were maintained as long as 3-month posttreatment . Implication s of these findings are discussed OBJECTIVES The objectives of the study were ( 1 ) to evaluate self-reported stress levels and daily spiritual experiences in academic health care employees before , immediately after , and 1 year after enrolling in a mindfulness-based stress reduction ( MBSR ) course ; and ( 2 ) to evaluate the correlation between a potential measure of pulse rate variability and self-reported stress levels . SUBJECTS Fifty-nine ( 59 ) participants in the MBSR course offered to employees at the University of Texas Medical Branch in Galveston ( UTMB ) comprised the intervention group , and 94 health care providers in the neonatal nurseries comprised the control group . INTERVENTION MBSR is an 8-week course that introduces mindfulness meditation practice s. No intervention was offered to the control group . All participants were employees ( or relatives of employees ) at UTMB . DESIGN All MBSR participants completed Cohen 's Perceived Stress Scale , the SCL-90 , the SF-36 Measure of Health and Well-Being , the Daily Spiritual Experiences Scale , and a 5-minute measure of pulse rate coherence . This testing was done before and after the MBSR course and 1 year later . Ninety-four ( 94 ) neonatal health care providers completed the same series of question naires and pulse rate variability ( PRV ) measures , with 49 of the 94 completing the question naires 2 months and 1 year later . RESULTS MBSR participants improved on all measures except the physical component score of the SF-36 upon completion of the MBSR course , and these results were maintained at the 1-year follow-up . The control group did not significantly change on any of the measures . PRV as measured by the Heart Math system did not correlate with any of the self-report question naires . CONCLUSIONS MBSR effectively reduces self-report measures of stress and increases daily spiritual experiences in employees in an academic health care setting , and these effects are stable for at least 1 year . Output:	Evidence regarding the effects of MBSR in professionals suggests this intervention is associated with improvements in burnout , stress , anxiety and depression . Improvements in empathy are also suggested but no clear evidence is currently available on emotional competencies . High quality evidence is available on the effect of MBSR on professionals ' mental health .
MS21459	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: OBJECTIVE To determine the safety of laparoscopy-assisted distal gastrectomy ( LADG ) compared with open distal gastrectomy ( ODG ) in patients with clinical stage I gastric cancer in Korea . BACKGROUND There is still a lack of large-scale , multicenter r and omized trials regarding the safety of LADG . METHODS A large-scale , phase 3 , multicenter , prospect i ve r and omized controlled trial was conducted . The primary end point was 5-year overall survival . Morbidity within 30 postoperative days and surgical mortality were compared to evaluate the safety of LADG as a secondary end point RESULTS : A total of 1416 patients were r and omly assigned to the LADG group ( n = 705 ) or the ODG group ( n = 711 ) between February 1 , 2006 , and August 31 , 2010 , and 1384 patients were analyzed for modified intention-to-treat analysis ( ITT ) and 1256 were eligible for per protocol ( PP ) analysis ( 644 and 612 , respectively ) . In the PP analysis , 6 patients ( 0.9 % ) needed open conversion in the LADG group . The overall complication rate was significantly lower in the LADG group ( LADG vs ODG ; 13.0 % vs 19.9 % , P = 0.001 ) . In detail , the wound complication rate of the LADG group was significantly lower than that of the ODG group ( 3.1 % vs 7.7 % , P < 0.001 ) . The major intra-abdominal complication ( 7.6 % vs 10.3 % , P = 0.095 ) and mortality rates ( 0.6 % vs 0.3 % , P = 0.687 ) were similar between the 2 groups . Modified ITT analysis showed similar results with PP analysis . CONCLUSIONS LADG for patients with clinical stage I gastric cancer is safe and has a benefit of lower occurrence of wound complication compared with conventional ODG BACKGROUND Laparoscopic surgery as an alternative to open surgery in patients with rectal cancer has not yet been shown to be oncologically safe . The aim in the COlorectal cancer Laparoscopic or Open Resection ( COLOR II ) trial was to compare laparoscopic and open surgery in patients with rectal cancer . METHODS A non-inferiority phase 3 trial was undertaken at 30 centres and hospitals in eight countries . Patients ( aged ≥18 years ) with rectal cancer within 15 cm from the anal verge without evidence of distant metastases were r and omly assigned to either laparoscopic or open surgery in a 2:1 ratio , stratified by centre , location of tumour , and preoperative radiotherapy . The study was not masked . Secondary ( short-term ) outcomes -including operative findings , complications , mortality , and results at pathological examination-are reported here . Analysis was by modified intention to treat , excluding those patients with post-r and omisation exclusion criteria and for whom data were not available . This study is registered with Clinical Trials.gov , number NCT00297791 . FINDINGS The study was undertaken between Jan 20 , 2004 , and May 4 , 2010 . 1103 patients were r and omly assigned to the laparoscopic ( n=739 ) and open surgery groups ( n=364 ) , and 1044 were eligible for analyses ( 699 and 345 , respectively ) . Patients in the laparoscopic surgery group lost less blood than did those in the open surgery group ( median 200 mL [ IQR 100 - 400 ] vs 400 mL [ 200 - 700 ] , p<0·0001 ) ; however , laparoscopic procedures took longer ( 240 min [ 184 - 300 ] vs 188 min [ 150 - 240 ] ; p<0·0001 ) . In the laparoscopic surgery group , bowel function returned sooner ( 2·0 days [ 1·0 - 3·0 ] vs 3·0 days [ 2·0 - 4·0 ] ; p<0·0001 ) and hospital stay was shorter ( 8·0 days [ 6·0 - 13·0 ] vs 9·0 days [ 7·0 - 14·0 ] ; p=0·036 ) . Macroscopically , completeness of the resection was not different between groups ( 589 [ 88 % ] of 666 vs 303 [ 92 % ] of 331 ; p=0·250 ) . Positive circumferential resection margin ( < 2 mm ) was noted in 56 ( 10 % ) of 588 patients in the laparoscopic surgery group and 30 ( 10 % ) of 300 in the open surgery group ( p=0·850 ) . Median tumour distance to distal resection margin did not differ significantly between the groups ( 3·0 cm [ IQR 2·0 - 4·8 ] vs 3·0 cm [ 1·8 - 5·0 ] , respectively ; p=0·676 ) . In the laparoscopic and open surgery groups , morbidity ( 278 [ 40 % ] of 697 vs 128 [ 37 % ] of 345 , respectively ; p=0·424 ) and mortality ( eight [ 1 % ] of 699 vs six [ 2 % ] of 345 , respectively ; p=0·409 ) within 28 days after surgery were similar . INTERPRETATION In selected patients with rectal cancer treated by skilled surgeons , laparoscopic surgery result ed in similar safety , resection margins , and completeness of resection to that of open surgery , and recovery was improved after laparoscopic surgery . Results for the primary endpoint-locoregional recurrence-are expected by the end of 2013 . FUNDING Ethicon Endo-Surgery Europe , Swedish Cancer Foundation , West Gothia Region , Sahlgrenska University Hospital Background The purpose of this study is to compare and evaluate the security and efficacy of 3D vs 2D laparoscopy in rectal cancer treatment . Methods Forty-six patients who suffered from rectal cancer and went on laparoscopic radical resection of rectal carcinoma in Peking University Shougang Hospital from Feb. 2015 to Mar. 2016 were included in the study . They were r and omly divided into two groups . The 23 patients operated with the 3D system were compared with 23 patients operated with the 2D system by perioperative data . Results There were no significant differences in age , sex , pathological type , tumor differentiation , TNM staging , and surgical procedures ( P > 0.05 ) . The average operating time of 3D laparoscopic surgery group ( 172.2 ± 27.5 min ) was shorter than that of 2D group ( 192.6 ± 22.3 ) ( P < 0.05 ) ; the rate of transfer to laparotomy is lower in 2D group ( 72.7 % ) than in 3D group ( 86.4 % ) , but they have no significant difference ; and the intraoperative blood loss ( 247.0 ± 173.6 ml vs 282.6 ± 195.6 ml ) , postoperative passage of flatus ( 2.8 ± 0.8 days vs 3.1 ± 1.0 days ) , and indwelling catheter time ( 5.6 ± 1.9 days vs 6.3 ± 2.0 days ) in 3D group and 2D group ( P > 0.05 ) were not significantly different . There were no differences in other complications between the two groups . No significantly different recrudescence and death rates were found between the two groups ( P > 0.05 ) . Conclusion The 3D laparoscopy shortens the operation time of rectum cancer . 3D laparoscopic surgery is more efficient in treatment of rectal cancer than 2D laparoscopy and is worth of being generalized Non-r and omised studies of the effects of interventions are critical to many areas of healthcare evaluation , but their results may be biased . It is therefore important to underst and and appraise their strengths and weaknesses . We developed ROBINS-I ( “ Risk Of Bias In Non-r and omised Studies - of Interventions ” ) , a new tool for evaluating risk of bias in estimates of the comparative effectiveness ( harm or benefit ) of interventions from studies that did not use r and omisation to allocate units ( individuals or clusters of individuals ) to comparison groups . The tool will be particularly useful to those undertaking systematic review s that include non-r and omised studies BACKGROUND Several three-dimensional video-endoscopic systems have been introduced to enhance depth perception during minimum-access surgery . However , there is no conclusive evidence of benefit , and these systems are more expensive than conventional two-dimensional systems . We undertook a prospect i ve r and omised comparison of two-dimensional and three-dimensional imaging in elective laparoscopic cholecystectomy for symptomatic gallstone disease . METHODS The operations were done by four specialist registrars as part of their higher surgical training . 60 operations were r and omised for execution by either two-dimensional or three-dimensional imaging display ( 30 by each method ) . The degree of difficulty of the operation was grade d by a consultant surgeon on a st and ard grading system . The primary endpoints were execution time and the errors made during the procedure . The secondary endpoints were subjective assessment of the image quality and adverse effects on the surgeon . FINDINGS There was no difference between the two-dimensional and three-dimensional display groups in median execution time ( 3160 [ IQR 2735 - 4335 vs 3100 [ 2379 - 3710 ] s ; p = 0.2 ) or error rate ( six vs six ) . Surgeons reported adverse symptoms immediately after the operations with both systems . The scores for visual strain , headache , and facial discomfort were higher with the three-dimensional system . INTERPRETATION With the current technology , three-dimensional systems based on sequential imaging show no advantage over two-dimensional systems in the conduct of laparoscopic cholecystectomy Objective To determine the relative safety and efficacy of 3D laparoscopic gastrectomy and 2D laparoscopic surgery in patients with gastric cancer . Background There is still a lack of r and omized controlled trials regarding the safety and efficacy of 3D versus 2D laparoscopic surgery for gastric cancer . Methods A large‐scale , phase 3 , prospect i ve , r and omized controlled trial was conducted . ( Clinical Trials.gov number NCT02327481 ) . Results A total of 438 patients were r and omized ( 3D group : 219 cases ; 2D group : 219 cases ) between January 1 , 2015 , and April 1 , 2016 ; 19 patients were excluded . Finally , data from 419 patients were analyzed ( 3D group : 211 cases ; 2D group : 208 cases ) . There were no differences between the 2 groups regarding the operation time ( 3D versus 2D , 176 ± 35 min vs. 174 ± 33 min , P = .562 ) . The intraoperative blood loss in the 3D group was somewhat less than in the 2D group ( 61 ± 83 mL vs. 82 ± 119 mL , P = .045 ) . Further analysis suggested that the use of 3D laparoscopic surgery was a protective factor against excessive blood loss ( ≥200 mL ) . Conclusion 3D laparoscopic gastrectomy did not shorten the operation time compared with 2D laparoscopic gastrectomy , but provided the benefit of less intraoperative blood loss and a lesser occurrence of excessive bleeding than the conventional 2D laparoscopic gastrectomy ; the clinical value of the difference is limited Purpose 3D imaging is an upcoming technology in laparoscopic surgery , and recent studies have shown that the modern 3D technique is superior in an experimental setting . Methods All 14 members of the Asklepios Klinik Langen Department of Visceral and Thoracic Surgery , as well as two gynaecologists , were asked to undertake 2D vs. 3D laparoscopic black box skill training . The black box training was adapted to the “ fundamentals of laparoscopic surgery ” programme provided by the Society of American Gastrointestinal and Endoscopic Surgeons ( SAGES ) . First , the participants categorised themselves as beginner , advanced or expert in laparoscopic surgery . Then , they were r and omised in terms of whether the black box training commenced with 2D or 3D vision . The exercises included peg transfer with the dominant h and and the non-dominant h and ( with and without transfer between the graspers ) , needle capping and cutting a sutured knot . The time taken to complete these exercises was measured . After the training , each participant was asked to describe his/her personal impression of the imaging systems employed . Results Overall , for the participants in all groups , the time required for all exercises showed a significant advantage for 3D imaging ( 3D vs. 2D ; Wilcoxon matched pair test ; mean 68.0 ± 94.9 s ( 3D ) vs. 90.1 ± 69.4 s ( 2D ) ; p = 0.002 ) . Regarding the subgroups , the experts significantly improved their time in completing the exercises in 3D vs. 2 Output:	Main advantages of 3D laparoscopic gastrectomy for gastric cancer were that it could shorten the operation time and reduce the amount of intraoperative blood loss . However , 3D laparoscopic surgery had no obvious advantage over 2D laparoscopic surgery for colorectal cancer patients
MS21460	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: BACKGROUND Treatment-resistant depression ( TRD ) is an extremely prevalent clinical condition . Although Interpersonal Psychotherapy ( IPT ) is an established treatment for uncomplicated depression , its effectiveness has never before been studied in patients with TRD in real-world setting s. We investigate IPT as an adjunct strategy to treatment as usual ( TAU ) for TRD patients in a pragmatic , r and omized , controlled trial . METHODS A total of 40 adult patients with TRD ( satisfying the criteria for major depressive disorder despite adequate antidepressant treatment ) were recruited from a tertiary care facility for this pragmatic trial and blinded to the evaluator . Patients were r and omized to one of two treatment conditions : ( 1 ) TAU - pharmacotherapy freely chosen by the clinician ( n=23 ) and ( 2 ) TAU+IPT ( n=17 ) . Assessment s were performed at weeks 8 , 12 , 19 and 24 . Changes in the estimated means of the Hamilton Depression Rating Scale score were the primary outcome measure . Secondary outcomes included patient-rated scales and quality of life scales . We used a linear mixed model to compare changes over time between the two groups . RESULTS Both treatments lead to improvements in depressive symptoms from baseline to week 24 with no significant between group differences in either primary : TAU ( mean difference : 4.57 ; CI95 % : 0.59 - 8.55 ; d=0.73 ) vs. IPT+TAU ( mean difference : 5.86 , CI95 % : 1.50 - 10.22 ; d=0.93 ) or secondary outcomes . LIMITATIONS Our relatively small sample limits our ability to detect differences between treatments . CONCLUSIONS Both treatments lead to equal improvements in depressive symptoms . We found no evidence to support adding IPT to pharmacotherapy in patients with TRD . TRIAL REGISTRATION Clinical Trials.gov-NCT01896349 Background The scale-up of antiretroviral treatment ( ART ) programmes has seen HIV/AIDS transition to a chronic condition characterised by high rates of comorbidity with tuberculosis , non-communicable diseases ( NCDs ) and mental health disorders . Depression is one such disorder that is associated with higher rates of non-adherence , progression to AIDS and greater mortality . Detection and treatment of comorbid depression is critical to achieve viral load suppression in more than 90 % of those on ART and is in line with the recent 90 - 90 - 90 Joint United Nations Programme on HIV/AIDS ( UNAIDS ) targets . The CobALT trial aims to provide evidence on the effectiveness and cost-effectiveness of scalable interventions to reduce the treatment gap posed by the growing burden of depression among adults on lifelong ART . Methods The study design is a pragmatic , parallel group , stratified , cluster r and omised trial in 40 clinics across two rural districts of the North West Province of South Africa . The unit of r and omisation is the clinic , with outcomes measured among 2000 patients on ART who screen positive for depression using the Patient Health Question naire ( PHQ-9 ) . Control group clinics are implementing the South African Department of Health ’s Integrated Clinical Services Management model , which aims to reduce fragmentation of care in the context of rising multimorbidity , and which includes training in the Primary Care 101 ( PC101 ) guide covering communicable diseases , NCDs , women ’s health and mental disorders . In intervention clinics , we supplemented this with training specifically in the mental health components of PC101 and clinical communications skills training to support nurse-led chronic care . We strengthened the referral pathways through the introduction of a clinic-based behavioural health counsellor equipped to provide manualised depression counselling ( eight sessions , individual or group ) , as well as adherence counselling sessions ( one session , individual ) . The co- primary patient outcomes are a reduction in PHQ-9 scores of at least 50 % from baseline and viral load suppression rates measured at 6 and 12 months , respectively . Discussion The trial will provide real-world effectiveness of case detection and collaborative care for depression including facility-based counselling on the mental and physical outcomes for people on lifelong ART in re source -constrained setting s . Trial registration Clinical Trials.gov ( NCT02407691 ) registered on 19 March 2015 ; Pan African Clinical Trials Registry ( 201504001078347 ) registered on 19/03/2015 ; South African National Clinical Trials Register ( SANCTR ) ( DOH-27 - 0515 - 5048 ) NHREC number 4048 issued on 21/04/2015 OBJECTIVE This r and omized , placebo-controlled study evaluated the efficacy and safety of a fixed dose ( 3mg/day ) and flexible dose ( 3 - 15 mg/day ) schedule of aripiprazole as augmentation therapy in Japanese patients with inadequate response to antidepressant therapy ( ADT ) . METHOD During an 8-week prospect i ve treatment phase , patients experiencing a major depressive episode received clinicians ' choice of ADT . Subjects with inadequate response to ADT were r and omized to receive adjunctive treatment with placebo ( n=195 ) , fixed dose aripiprazole ( n=197 ) or flexible dose aripiprazole ( n=194 ) for 6 weeks . The primary efficacy endpoint was mean change in the Montgomery-Åsberg Depression Rating Scale ( MADRS ) total score from the end of prospect i ve treatment ( baseline ) to the end of r and omized treatment . RESULTS More than 90 % of patients in all treatment groups completed the 6-week double-blind treatment phase . Mean MADRS total score was improved to a significantly greater extent with fixed dose aripiprazole and flexible dose aripiprazole ( -10.5 and -9.6 , respectively ) than with placebo ( -7.4 ) . Aripiprazole was well tolerated . The incidence of akathisia observed in the flexible dose group may relate to a higher prevalence of the CYP2D6(*)10 allele in Asian population s. LIMITATIONS Six weeks of adjunctive treatment is insufficient to draw conclusions about the long-term benefits of aripiprazole . Exclusion of patients with established medical comorbidities does not reflect real-world practice . CONCLUSIONS Aripiprazole augmentation at a fixed or flexible dose was superior to ADT alone and was reasonably well tolerated in Japanese patients with inadequate response to ADT Background Most evidence on the effect of collaborative care for depression is derived in the selective environment of r and omised controlled trials . In collaborative care , practice nurses may act as case managers . The Primary Care Services Improvement Project ( PCSIP ) aim ed to assess the cost-effectiveness of alternative models of practice nurse involvement in a real world Australian setting . Previous analyses have demonstrated the value of high level practice nurse involvement in the management of diabetes and obesity . This paper reports on their value in the management of depression . Methods General practice s were assigned to a low or high model of care based on observed levels of practice nurse involvement in clinical -based activities for the management of depression ( i.e. percentage of depression patients seen , percentage of consultation time spent on clinical -based activities ) . Linked , routinely collected data was used to determine patient level depression outcomes ( proportion of depression-free days ) and health service usage costs . St and ardised depression assessment tools were not routinely used , therefore a classification framework to determine the patient ’s depressive state was developed using proxy measures ( e.g. symptoms , medications , referrals , hospitalisations and suicide attempts ) . Regression analyses of costs and depression outcomes were conducted , using propensity weighting to control for potential confounders . Results Capacity to determine depressive state using the classification framework was dependent upon the level of detail provided in medical records . While antidepressant medication prescriptions were a strong indicator of depressive state , they could not be relied upon as the sole measure . Propensity score weighted analyses of total depression-related costs and depression outcomes , found that the high level model of care cost more ( 95 % CI : -$314.76 to $ 584 ) and result ed in 5 % less depression-free days ( 95 % CI : -0.15 to 0.05 ) , compared to the low level model . However , this result was highly uncertain , as shown by the confidence intervals . Conclusions Classification of patients ’ depressive state was feasible , but time consuming , using the classification framework proposed . Further validation of the framework is required . Unlike the analyses of diabetes and obesity management , no significant differences in the proportion of depression-free days or health service costs were found between the alternative levels of practice nurse involvement Abstract Background Health guidelines are developed to improve patient care by ensuring the most recent and ‘ best available evidence ’ is used to guide treatment recommendations . The National Institute for Health and Care Excellence 's ( NICE 's ) guideline development methodology acknowledges that evidence needed to answer one question ( treatment efficacy ) may be different from evidence needed to answer another ( cost‐effectiveness , treatment acceptability to patients ) . This review uses counselling in the treatment of depression as a case study , and interrogates the constructs of ‘ best ’ evidence and ‘ best ’ guideline method ologies . Method The review comprises six sections : ( i ) implication s of diverse definitions of counselling in research ; ( ii ) research findings from meta‐analyses and r and omised controlled trials ( RCTs ) ; ( iii ) limitations to trials‐based evidence ; ( iv ) findings from large routine outcome data sets ; ( v ) the inclusion of qualitative research that emphasises service‐user voices ; and ( vi ) conclusions and recommendations . Results Research from meta‐analyses and RCTs contained in the draft 2018 NICE Guideline is limited but positive in relation to the effectiveness of counselling in the treatment for depression . The weight of evidence suggests little , if any , advantage to cognitive behaviour therapy ( CBT ) over counselling once risk of bias and research er allegiance are taken into account . A growing body of evidence from large NHS data sets also evidence s that , for depression , counselling is as effective as CBT and cost‐effective when delivered in NHS setting s. Conclusion Specifications in NICE 's up date d guideline procedures allow for data other than RCTs and meta‐analyses to be included . Accordingly , there is a need to include large st and ardised collected data sets from routine practice as well as the voice of patients via high‐ quality qualitative research A report of a r and omized , controlled trial ( RCT ) should convey to the reader , in a transparent manner , why the study was undertaken and how it was conducted and analyzed . For example , a lack of adequately reported r and omization has been associated with bias in estimating the effectiveness of interventions ( 1 , 2 ) . To assess the strengths and limitations of an RCT , readers need and deserve to know the quality of its methods . Despite several decades of educational efforts , RCTs still are not being reported adequately ( 3 - 6 ) . For example , a review of 122 recently published RCTs that evaluated the effectiveness of selective serotonin-reuptake inhibitors as first-line management strategy for depression found that only 1 ( 0.8 % ) paper described r and omization adequately ( 5 ) . Inadequate reporting makes the interpretation of RCT results difficult if not impossible . Moreover , inadequate reporting borders on unethical practice when biased results receive false credibility . History of CONSORT In the mid-1990s , two independent initiatives to improve the quality of reports of RCTs led to the publication of the CONSORT ( Consoli date d St and ards of Reporting Trials ) statement ( 7 ) , which was developed by an international group of clinical trialists , statisticians , epidemiologists , and biomedical editors . CONSORT has been supported by a growing number of medical and health care journals ( 8 - 11 ) and editorial groups , including the International Committee of Medical Journal Editors ( ICMJE , also known as the Vancouver Group ) ( 12 ) , the Council of Science Editors ( CSE ) , and the World Association of Medical Editors ( WAME ) . CONSORT is also published in Dutch , English , French , German , Japanese , and Spanish . It can be accessed on the Internet , along with other information about the CONSORT group ( 13 ) . The CONSORT statement comprises a checklist and flow diagram for reporting an RCT . For convenience , the checklist and diagram together are called simply CONSORT . They are primarily intended for use in writing , review ing , or evaluating reports of simple two-group , parallel RCTs . Preliminary data indicate that the use of CONSORT does indeed help to improve the quality of reports of RCTs ( 14 , 15 ) . In an evaluation ( 14 ) of 71 RCTs published in three journals in 1994 , allocation concealment was not clearly reported in 43 ( 61 % ) of the RCTs . Four years later , after these three journals required that authors reporting an RCT use CONSORT , the proportion of papers in which allocation concealment was not clearly reported had dropped to 39 % ( 30 of 77 ; mean difference , 22 % [ 95 % CI of the difference , 38 % to 6 % ] ) . The usefulness of CONSORT is enhanced by continuous monitoring of the biomedical literature ; this monitoring allows CONSORT to be modified depending on the merits of maintaining or dropping current items and including new items . For example , when Meinert ( 16 ) observed that the flow diagram did not provide important information about the number of participants who entered each phase of an RCT ( enrollment , treatment allocation , follow-up , and data analysis ) , the diagram could be modified to accommo date the information . The checklist is similarly flexible . This iterative process makes the CONSORT statement a continually evolving instrument . While participants in the CON Output:	Efficacy and effectiveness research hypothetically use different method ologies , but the efficacy and effectiveness literature s in the treatment of depression were comparable for most of the coded characteristics .
MS21461	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: BACKGROUND : While surgery and perioperative smoking cessation interventions may motivate patients to quit smoking in the short term , it is unknown how often this translates into permanent cessation . In this study , we sought to determine the rates of long-term smoking cessation after a perioperative smoking cessation intervention and predictors of successful cessation at 1 year . METHODS : We previously reported short-term results from a perioperative r and omized controlled trial comparing usual care with an intervention involving ( 1 ) brief counseling by the preadmission nurse , ( 2 ) smoking cessation brochures , ( 3 ) referral to a telephone quitline , and ( 4 ) a free 6-week supply of transdermal nicotine replacement . We now report our 1-year follow-up outcomes . RESULTS : Between October 2010 and April 2012 , 168 patients were r and omized . At 1 year , 127 patients ( 76 % ) were available for follow-up telephone interview . Smoking cessation occurred in 8 % of control patients compared with 25 % of patients in the intervention group ( relative risk , 3.0 ; 95 % confidence interval [ CI ] , 1.2–7.8 ; P = 0.018 ) . The number needed-to-treat to achieve smoking cessation for 1 patient at 1 year postoperatively was 5.9 ( 95 % CI , 3.4–25.9 ) . Multivariable logistic regression modeling found that the intervention ( P = 0.020 ) and lower nicotine dependency at baseline ( P < 0.001 ) were predictive of success at smoking cessation at 1 year . Poisson regression showed that adjusted for nicotine dependency , those r and omized to the intervention group were 2.7 times ( 95 % CI , 1.1–6.7 ; P = 0.028 ) more likely to achieve long-term cessation than those in the control group . Adjusted for r and omization group , a low level of nicotine dependency result ed in a relative risk of quitting of 5.1 ( 95 % CI , 2.0–12.8 ; P = 0.001 ) . CONCLUSIONS : This study demonstrates that an intervention design ed for a busy preadmission clinic results in decreased smoking rates not only around the time of surgery but also continued benefit in smoking cessation at 1 year . Perioperative care providers have a unique opportunity to assist patients in smoking cessation and achieve long-lasting results Background Smoking is an important risk factor for cardiovascular disease ( CVD ) , and quitting is highly beneficial . Yet , less than 30 % of CVD patients stop smoking . Relapse-prevention strategies seem most effective when initiated during the exacerbation of the disease . Objective A nurse-delivered inpatient smoking cessation program based on the Transtheoretical Model with telephone follow-up tailored to levels of readiness to quit smoking was evaluated on smoking abstinence and progress to ulterior stages of change . Method Participants ( N = 168 ) were r and omly assigned by cohorts to inpatient counseling with telephone follow-up , inpatient counseling , and usual care . The inpatient intervention consisted of a 1-hr counseling session , and the telephone follow-up included 6 calls during the first 2 months after discharge . The nursing intervention was tailored to the individual 's stage of change . End points at 2 and 6 months included actual and continuous smoking cessation rates ( biochemical markers ) and increased motivation ( progress to ulterior stages of change ) . Results Assuming that surviving patients lost to follow-up were smokers , the 6-month smoking abstinence rate was 41.5 % in the inpatient counseling with telephone follow-up group , compared with 30.2 % and 20 % in the inpatient counseling and usual care groups , respectively ( p = .05 ) . Progress to ulterior stages of change was 43.3 % , 32.1 % , and 18.2 % , respectively ( p = .02 ) . Stage of change at baseline and intervention predicted smoking status at 6 months . Discussion This tailored smoking cessation program with telephone follow-up significantly increased smoking cessation at 6 months , and progression to ulterior stages of change . The telephone follow-up was an important adjunct . It is , therefore , recommended to include such comprehensive smoking cessation programs within hospital setting s for individuals with CVD OBJECTIVE To examine the effect of a nurse-delivered smoking cessation intervention on short-term smoking abstinence among hospitalized postoperative patients . DESIGN Prospect i ve , experimental , r and om assignment . SETTING Midwestern university-affiliated tertiary medical center . PATIENTS Postoperative smokers ( n = 80 ) from cardiovascular , oncology , and general surgical units . OUTCOME MEASURE Self-reported smoking status and saliva cotinine level at 5 to 6 weeks after hospitalization . INTERVENTION Three structured smoking cessation sessions during hospitalization , followed by phone calls once a week for 5 weeks after discharge . RESULTS Of the experimental group patients , 37.8 % were abstinent as compared to 25.6 % in the usual care group . Abstinence rates of experimental group patients from cardiovascular ( 40 % ) and oncology ( 64.3 % ) units were higher than that of GS ( 13.3 % ) unit patients . Regardless of group assignment , 100 % of cardiovascular and oncology patients abstained during hospitalization , compared to only 10.7 % of GS patients . CONCLUSIONS Preliminary results indicate that a nurse-delivered cessation intervention may be effective postoperatively among smokers with an identified smoking-related diagnosis This study examined the effectiveness of a nurse-managed minimal-contact smoking cessation intervention for patients hospitalized for cardiac disease . A pre-test-post-test quasi-experimental design was used . Patients who smoked prior to admission to cardiac wards of five hospitals ( n = 388 ) received the intervention , whereas smoking patients in six other hospitals were given usual care ( n = 401 ) . The intervention was initiated at the hospital and continued after discharge . The core elements were stop-smoking advice from the cardiologist , a short bedside consultation with a nurse , administration of self-help material s and aftercare by the cardiologist . Smoking cessation was assessed after 3 months by self-report . Logistic regression analysis excluding dropouts , controlling for covariates including baseline differences showed significant intervention effects ( one-tailed significance test ) on point prevalence abstinence ( OR = 2.11 ) and continuous abstinence ( OR = 1.41 ) . Intention-to-treat analysis including dropouts as smokers showed a significant effect on point prevalence abstinence ( OR 1.35 ) . We conclude that , compared to usual care , the low-intensity smoking cessation intervention for cardiac in patients was more effective in achieving smoking cessation . However , the small effects and the process evaluation suggest that improvements are needed OBJECTIVE To evaluate the effectiveness of a nurse-managed smoking cessation intervention in diabetic patients . RESEARCH DESIGN AND METHODS This r and omized controlled clinical trial involved 280 diabetic smokers ( age range 17 - 84 years ) who were r and omized either into control ( n = 133 ) or intervention ( n = 147 ) groups at 12 primary care centers and 2 hospitals located in Navarre , Spain . The intervention consisted of a 40-min nurse visit that included counseling , education , and contracting information ( a negotiated cessation date ) . The follow-up consisted of telephone calls , letters , and visits . The control group received the usual care for diabetic smokers . Baseline and 6-month follow-up measurements included smoking status ( self-reported cessation was verified by urine cotinine concentrations ) , mean number of cigarettes smoked per day , and stage of change . RESULTS At the 6-month follow-up , the smoking cessation incidence was 17.0 % in the intervention group compared with 2.3 % in the usual care group , which was a 14.7 % difference ( 95 % CI 8.2 - 21.3 % ) . Among participants who continued smoking , a significant reduction was evident in the average cigarette consumption at the 6-month follow-up . The mean number of cigarettes per day decreased from 20.0 at baseline to 15.5 at 6 months for the experimental group versus from 19.7 to 18.1 for the control group ( P < 0.01 ) . CONCLUSIONS A structured intervention managed by a single nurse was shown to be effective in changing the smoking behavior of diabetic patients STUDY OBJECTIVES Smoking cessation for current smokers is a health-care imperative . It is not clear which approaches to smoking cessation are the most effective in the hospital setting and which factors predict long-term abstinence . We hypothesized that a hospital-based smoking cessation program involving behavioral modification and support would provide an effective intervention for smoking cessation . DESIGN Prospect i ve cohort study . SETTING Smoking cessation clinics in a tertiary referral , cardiothoracic hospital . PATIENTS OR PARTICIPANTS Two hundred forty-three smokers and 187 never-smoker control subjects . INTERVENTIONS Smokers underwent specific sessions of individual counseling on behavioral modification , including written information , advice about quit aids , and support during the quit attempt . Abstinence was confirmed by exhaled carbon monoxide measurements . MEASUREMENTS AND RESULTS Compared to never-smoker control subjects , smokers were more likely to have grown up with a smoking father or siblings , and to currently live or socialize with other smokers . Two hundred sixteen smokers attended at least two sessions of the smoking cessation program . Of these , 25 % were unavailable for follow-up at 12 months and were assumed to be smoking . The point prevalence abstinence rate at 12 months was 32 % . Independent factors associated with abstinence at 12 months were self-belief in quitting ability , having a heart condition , growing up without siblings who smoked , and increasing number of pack-years . CONCLUSIONS This prospect i ve study has demonstrated that this hospital-based smoking cessation program was as effective as programs in other setting s. Social and psychological factors were associated with a greater chance of abstinence BACKGROUND Few research studies have evaluated the effectiveness of smoking interventions in hospitalized patients . This r and omized controlled trial compared the efficacy of 2 smoking cessation programs in patients hospitalized in 4 community hospitals in a large health maintenance organization within the San Francisco Bay Area in California . METHODS Patients were r and omly assigned to usual care ( n = 990 ) , nurse-mediated , behaviorally oriented inpatient counseling focused on relapse prevention with 1 postdischarge telephone contact ( minimal intervention , n = 473 ) , or the same inpatient counseling with 4 postdischarge telephone contacts ( intensive intervention , n = 561 ) . The main outcome measure , smoking cessation rate , was corroborated by plasma cotinine determination or family confirmation , 1 year after enrollment . RESULTS At 1 year smoking cessation rates were 27 % , 22 % , and 20 % for intensive intervention , minimal intervention , and usual care groups , respectively ( P = .009 for intensive vs usual care ) . Subgroup analyses by diagnosis revealed that the odds of cessation among patients with cardiovascular disease or other internal medical conditions were greater among those receiving the intensive intervention than among their counterparts receiving usual care ( odds ratios , 1.6 and 2.0 , respectively ) . CONCLUSIONS A multicomponent smoking cessation program consisting of physician advice ; in-hospital , nurse-mediated counseling ; and multiple postdischarge telephone contacts was effective in increasing smoking cessation rates among hospitalized smokers . Hospital-wide smoking cessation programs could substantially increase the effectiveness of hospital smoking bans PURPOSE / OBJECTIVES To determine the effectiveness of a nurse-managed minimal smoking-cessation intervention among hospitalized patients with cancer . DESIGN Prospect i ve , two-group , r and omized clinical trial . SETTING Urban , academic , tertiary-care setting . SAMPLE 28 adult male and female smokers with a diagnosis of cancer who are hospitalized for a surgical procedure . METHODS During hospitalization , subjects were assigned to a minimal smoking-cessation intervention group ( n = 14 ) or a usual care group ( n = 14 ) . Verification of smoking status was performed at a clinic visit six weeks postintervention . Nonsmoking status was defined as self-report of zero cigarettes/day during the prior week and confirmed by saliva cotinine analysis . MAIN RESEARCH VARIABLES One-time , Inpatient , nurse-managed , minimal smoking-cessation intervention , self-reported smoking status , and saliva cotinine level of < or = 14 ng/ml . FINDINGS Upon hospital admission , 64 % of the intervention group and 71 % of the usual care group reported their intention to quit smoking . At six weeks postintervention , only 21 % and 14 % of the intervention and usual care group , respectively , were classified as abstinent from smoking . More than 90 % of the intervention group members who resumed smoking did so within first week of discharge . IMPLICATION S FOR NURSING PRACTICE A more intensive intervention may be necessary to assist hospitalized surgical patients in achieving smoking Output:	Nurses ' interventions for smoking cessation play an important role in helping patients quit smoking successfully . There are a variety of interventions that nurses can employ according to the patient 's condition and diagnosis of different diseases . IMPLICATION FOR NURSING AND HEALTH POLICY Quitting smoking can reduce lung cancers and other health problems . Nurses play an important role in helping patients to quit smoking
MS21462	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: PURPOSE In metastatic colorectal cancer , phase III studies have demonstrated the superiority of fluorouracil ( FU ) with leucovorin ( LV ) in combination with irinotecan or oxaliplatin over FU + LV alone . This phase III study investigated two sequences : folinic acid , FU , and irinotecan ( FOLFIRI ) followed by folinic acid , FU , and oxaliplatin ( FOLFOX6 ; arm A ) , and FOLFOX6 followed by FOLFIRI ( arm B ) . PATIENTS AND METHODS Previously untreated patients with assessable disease were r and omly assigned to receive a 2-hour infusion of l-LV 200 mg/m(2 ) or dl-LV 400 mg/m(2 ) followed by a FU bolus 400 mg/m(2 ) and 46-hour infusion 2,400 to 3,000 mg/m(2 ) every 46 hours every 2 weeks , either with irinotecan 180 mg/m(2 ) or with oxaliplatin 100 mg/m(2 ) as a 2-hour infusion on day 1 . At progression , irinotecan was replaced by oxaliplatin ( arm A ) , or oxaliplatin by irinotecan ( arm B ) . RESULT Median survival was 21.5 months in 109 patients allocated to FOLFIRI then FOLFOX6 versus 20.6 months in 111 patients allocated to FOLFOX6 then FOLFIRI ( P = .99 ) . Median second progression-free survival ( PFS ) was 14.2 months in arm A versus 10.9 in arm B ( P = .64 ) . In first-line therapy , FOLFIRI achieved 56 % response rate ( RR ) and 8.5 months median PFS , versus FOLFOX6 which achieved 54 % RR and 8.0 months median PFS ( P = .26 ) . Second-line FOLFIRI achieved 4 % RR and 2.5 months median PFS , versus FOLFOX6 which achieved 15 % RR and 4.2 months PFS . In first-line therapy , National Cancer Institute Common Toxicity Criteria grade 3/4 mucositis , nausea/vomiting , and grade 2 alopecia were more frequent with FOLFIRI , and grade 3/4 neutropenia and neurosensory toxicity were more frequent with FOLFOX6 . CONCLUSION Both sequences achieved a prolonged survival and similar efficacy . The toxicity profiles were different Colorectal cancer continues to be an important public health concern , despite improvements in screening and better systemic chemotherapy . The integration of targeted therapies in the treatment of colon cancer has result ed in significant improvements in efficacy outcomes . Angiogenesis is important for tumor growth and metastasis and is an important target for new biological agents . Bevacizumab is a humanized recombinant antibody that prevents vascular endothelial growth factor ( VEGF ) receptor binding , and inhibits angiogenesis and tumor growth . The addition of bevacizumab to fluoropyrimidine-based chemotherapy , with or without irinotecan or oxaliplatin , in both the first- and second-line treatment of metastatic colorectal cancer , significantly increased median progression-free survival and overall survival in select r and omized phase III studies . Ongoing studies are evaluating the role of bevacizumab in the adjuvant treatment of colon cancer . Common toxicities associated with bevacizumab include hypertension , bleeding episodes , and thrombotic events . This review will focus on the integration of bevacizumab in the treatment paradigm of colon cancer and the management of its side effects Summary Background In the Medical Research Council ( MRC ) COIN trial , the epidermal growth factor receptor (EGFR)-targeted antibody cetuximab was added to st and ard chemotherapy in first-line treatment of advanced colorectal cancer with the aim of assessing effect on overall survival . Methods In this r and omised controlled trial , patients who were fit for but had not received previous chemotherapy for advanced colorectal cancer were r and omly assigned to oxaliplatin and fluoropyrimidine chemotherapy ( arm A ) , the same combination plus cetuximab ( arm B ) , or intermittent chemotherapy ( arm C ) . The choice of fluoropyrimidine therapy ( capecitabine or infused fluouroracil plus leucovorin ) was decided before r and omisation . R and omisation was done central ly ( via telephone ) by the MRC Clinical Trials Unit using minimisation . Treatment allocation was not masked . The comparison of arms A and C is described in a companion paper . Here , we present the comparison of arm A and B , for which the primary outcome was overall survival in patients with KRAS wild-type tumours . Analysis was by intention to treat . Further analyses with respect to NRAS , BRAF , and EGFR status were done . The trial is registered , IS RCT N27286448 . Findings 1630 patients were r and omly assigned to treatment groups ( 815 to st and ard therapy and 815 to addition of cetuximab ) . Tumour sample s from 1316 ( 81 % ) patients were used for somatic molecular analyses ; 565 ( 43 % ) had KRAS mutations . In patients with KRAS wild-type tumours ( arm A , n=367 ; arm B , n=362 ) , overall survival did not differ between treatment groups ( median survival 17·9 months [ IQR 10·3–29·2 ] in the control group vs 17·0 months [ 9·4–30·1 ] in the cetuximab group ; HR 1·04 , 95 % CI 0·87–1·23 , p=0·67 ) . Similarly , there was no effect on progression-free survival ( 8·6 months [ IQR 5·0–12·5 ] in the control group vs 8·6 months [ 5·1–13·8 ] in the cetuximab group ; HR 0·96 , 0·82–1·12 , p=0·60 ) . Overall response rate increased from 57 % ( n=209 ) with chemotherapy alone to 64 % ( n=232 ) with addition of cetuximab ( p=0·049 ) . Grade 3 and higher skin and gastrointestinal toxic effects were increased with cetuximab ( 14 vs 114 and 67 vs 97 patients in the control group vs the cetuximab group with KRAS wild-type tumours , respectively ) . Overall survival differs by somatic mutation status irrespective of treatment received : BRAF mutant , 8·8 months ( IQR 4·5–27·4 ) ; KRAS mutant , 14·4 months ( 8·5–24·0 ) ; all wild-type , 20·1 months ( 11·5–31·7 ) . Interpretation This trial has not confirmed a benefit of addition of cetuximab to oxaliplatin-based chemotherapy in first-line treatment of patients with advanced colorectal cancer . Cetuximab increases response rate , with no evidence of benefit in progression-free or overall survival in KRAS wild-type patients or even in patients selected by additional mutational analysis of their tumours . The use of cetuximab in combination with oxaliplatin and capecitabine in first-line chemotherapy in patients with widespread metastases can not be recommended . Funding Cancer Research UK , Cancer Research Wales , UK Medical Research Council , Merck BACKGROUND Patients with metastatic colorectal cancer that harbors KRAS mutations in exon 2 do not benefit from anti-epidermal growth factor receptor ( EGFR ) therapy . Other activating RAS mutations may also be negative predictive biomarkers for anti-EGFR therapy . METHODS In this prospect ive-retrospective analysis , we assessed the efficacy and safety of panitumumab plus oxaliplatin , fluorouracil , and leucovorin ( FOLFOX4 ) as compared with FOLFOX4 alone , according to RAS ( KRAS or NRAS ) or BRAF mutation status . A total of 639 patients who had metastatic colorectal cancer without KRAS mutations in exon 2 had results for at least one of the following : KRAS exon 3 or 4 ; NRAS exon 2 , 3 , or 4 ; or BRAF exon 15 . The overall rate of ascertainment of RAS status was 90 % . RESULTS Among 512 patients without RAS mutations , progression-free survival was 10.1 months with panitumumab-FOLFOX4 versus 7.9 months with FOLFOX4 alone ( hazard ratio for progression or death with combination therapy , 0.72 ; 95 % confidence interval [ CI ] , 0.58 to 0.90 ; P=0.004 ) . Overall survival was 26.0 months in the panitumumab-FOLFOX4 group versus 20.2 months in the FOLFOX4-alone group ( hazard ratio for death , 0.78 ; 95 % CI , 0.62 to 0.99 ; P=0.04 ) . A total of 108 patients ( 17 % ) with nonmutated KRAS exon 2 had other RAS mutations . These mutations were associated with inferior progression-free survival and overall survival with panitumumab-FOLFOX4 treatment , which was consistent with the findings in patients with KRAS mutations in exon 2 . BRAF mutations were a negative prognostic factor . No new safety signals were identified . CONCLUSIONS Additional RAS mutations predicted a lack of response in patients who received panitumumab-FOLFOX4 . In patients who had metastatic colorectal cancer without RAS mutations , improvements in overall survival were observed with panitumumab-FOLFOX4 therapy . ( Funded by Amgen and others ; PRIME Clinical Trials.gov number , NCT00364013 . ) PURPOSE The phase III CRYSTAL study demonstrated that addition of cetuximab to fluorouracil , leucovorin , and irinotecan ( FOLFIRI ) significantly improved overall survival , progression-free survival , and objective response in the first-line treatment of patients with KRAS codon 12/13 ( exon 2 ) wild-type metastatic colorectal cancer ( mCRC ) . Outcome was reassessed in subgroups defined by extended RAS mutation testing . PATIENTS AND METHODS Existing DNA sample s from KRAS exon 2 wild-type tumors from CRYSTAL study patients were reanalyzed for other RAS mutations in four additional KRAS codons ( exons 3 and 4 ) and six NRAS codons ( exons 2 , 3 , and 4 ) using beads , emulsion , amplification , and magnetics technology . No tissue microdissection was performed . A ≥ 5 % mutant allele cutoff was used to call mutations . RESULTS Mutation status was evaluable in 430 ( 64.6 % ) of 666 patients with KRAS exon 2 wild-type tumors . Other RAS mutations were detected in 63 ( 14.7 % ) of 430 patients . In those with RAS wild-type tumors , a significant benefit across all efficacy end points was associated with the addition of cetuximab to FOLFIRI . In patients with other RAS tumor mutations , no difference in efficacy outcomes between treatment groups was seen . The safety profile in RAS subgroups was similar and in line with expectations . CONCLUSION In the first-line treatment of mCRC , patients with RAS wild-type tumors derived a significant benefit from the addition of cetuximab to FOLFIRI ; patients with RAS tumor mutations did not . Molecular testing of tumors for all activating RAS mutations is essential before considering anti-epidermal growth factor receptor therapy , thereby allowing the further tailoring of cetuximab administration to maximize patient benefit PURPOSE We performed this phase III study to compare the irinotecan , leucovorin ( LV ) , and fluorouracil ( FU ) regimen ( FOLFIRI ) versus the oxaliplatin , LV , and FU regimen ( FOLFOX4 ) in previously untreated patients with advanced colorectal cancer . PATIENTS AND METHODS A total of 360 chemotherapy-naive patients were r and omly assigned to receive , every 2 weeks , either arm A ( FOLFIRI : irinotecan 180 mg/m(2 ) on day 1 with LV 100 mg/m(2 ) administered as a 2-hour infusion before FU 400 mg/m(2 ) administered as an intravenous bolus injection , and FU 600 mg/m(2 ) as a 22-hour infusion immediately after FU bolus injection on days 1 and 2 [ LV5FU2 ] ) or arm B ( FOLFOX4 : oxaliplatin 85 mg/m(2 ) on day 1 with LV5FU2 regimen ) . RESULTS One hundred sixty-four and 172 patients were assessable in arm A and B , respectively . Overall response rates ( ORR ) were 31 % in arm A ( 95 % CI , 24.6 % to 38.3 % ) and 34 % in arm B ( 95 % CI , 27.2 % to 41.5 % ; P = .60 ) . In both arms A and B , median time to progression ( TTP ; 7 v 7 months , respectively ) , duration of Output:	Finally , metastatic colorectal cancer patients progressing after all st and ard therapies ( maintaining a good ECOG performance status ) could be c and i date s for further therapies such as regorafenib and TAS-102 .
MS21463	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: OBJECTIVES To compare the sensitivity of 2 different non-endorectal coil strategies vs. endorectal coil ( ERC ) magnetic resonance imaging ( MRI ) for detection of prostate cancer ( PCa ) . METHODS In this prospect i ve , single-center , paired-patient , paired-reader study , 49 men with a clinical indication for MRI underwent non-ERC ( phased-array coil only ) T2-weighted imaging and diffusion-weighted imaging followed by the same sequences using both ERC and phased-array coils ( ERC Protocol ) . Patients were r and omized into 1 of 2 arms : st and ard non-ERC protocol and augmented non-ERC protocol . Lesions with Likert score≥3 were defined as suspicious for cancer . Radical prostatectomy specimen or combined systematic plus targeted biopsies served as the st and ard of reference . Cancers were stratified into risk groups according to the National Comprehensive Cancer Network guidelines . Generalized estimating equations with Bonferroni correction were used for comparisons . The level of reader confidence was inferred by the Likert scores assigned to index lesions . RESULTS The ERC protocol provided sensitivity ( 78 % ) superior to MRI without ERC for PCa detection , both with a st and ard ( 43 % ) ( P<0.0001 ) or augmented ( 60 % ) ( P<0.01 ) protocol . The ERC MRI missed less-intermediate or high-risk index lesions ( 4 % ) than st and ard non-ERC ( 42 % ) ( P = 0.02 ) and augmented non-ERC MRI ( 25 % ) , although the latter did not reach significance ( P = 0.09 ) . The ERC improved radiologist confidence for the detection of PCa ( average Likert score = 4.2±1.4 ) compared to st and ard ( 2.3±2.3 ) and augmented ( 2.9±2.1 ) non-ERC ( P = 0.001 ) . CONCLUSIONS The use of combined ERC and pelvic phased-array coil for T2-weighted imaging and diffusion-weighted imaging provides superior sensitivity for the detection of PCa compared to an examination performed without the ERC PURPOSE We determined the ability of combined endorectal magnetic resonance imaging ( MRI ) and magnetic resonance spectroscopic imaging ( MRSI ) to detect prostate cancer foci prospect ively in men with prior negative transrectal ultrasound ( TRUS ) prostate biopsy . MATERIAL S AND METHODS Endorectal MRI with spectroscopy was performed in 24 consecutive patients with 1 or more prior negative TRUS prostatic biopsies for persistently increased prostate specific antigen and /or abnormal digital rectal examination . All studies were interpreted by a dedicated radiologist who reported areas of interest in the peripheral zone as normal , equivocal or suspicious on MRI and MRSI separately . Equivocal and suspicious areas were then correlated with a 3-dimensional prostate model . All patients underwent a st and ard TRUS 10-core peripheral zone biopsy with up to 4 additional biopsies targeted at the equivocal or suspected sites . RESULTS Prostate cancer was detected in 7 of 24 subjects ( 29.2 % ) . Considering the equivocal category as test negative the sensitivity , specificity , positive and negative predictive values , and the accuracy of MRI , MRSI and combined MRI/MRSI for the detection of prostate cancer were 57.1 % , 57.1 % and 100.0 % , 88.2 % , 82.4 % and 70.6 % , 66.7 % , 57.1 % and 58.3 % , 83.3 % , 82.1 % and 100 % , and 79.2 % , 75.0 % and 79.2 % , respectively . The site of positive biopsy correlated correctly in 50 % and 28.6 % of MRI and MRSI labeled suspicious cores , respectively . CONCLUSIONS MRI and MRSI have the potential to identify cancer foci and direct TRUS in patients with a previous negative TRUS biopsy . Further , larger studies are required to quantify the amount of benefit A multichannel statistical classifier for detecting prostate cancer was developed and vali date d by combining information from three different magnetic resonance ( MR ) method ologies : T2-weighted , T2-mapping , and line scan diffusion imaging ( LSDI ) . From these MR sequences , four different sets of image intensities were obtained : T2-weighted ( T2W ) from T2-weighted imaging , Apparent Diffusion Coefficient ( ADC ) from LSDI , and proton density ( PD ) and T2 ( T2 Map ) from T2-mapping imaging . Manually segmented tumor labels from a radiologist , which were vali date d by biopsy results , served as tumor " ground truth . " Textural features were extracted from the images using co-occurrence matrix ( CM ) and discrete cosine transform ( DCT ) . Anatomical location of voxels was described by a cylindrical coordinate system . A statistical jack-knife approach was used to evaluate our classifiers . Single-channel maximum likelihood ( ML ) classifiers were based on 1 of the 4 basic image intensities . Our multichannel classifiers : support vector machine ( SVM ) and Fisher linear discriminant ( FLD ) , utilized five different sets of derived features . Each classifier generated a summary statistical map that indicated tumor likelihood in the peripheral zone ( PZ ) of the prostate gl and . To assess classifier accuracy , the average areas under the receiver operator characteristic ( ROC ) curves over all subjects were compared . Our best FLD classifier achieved an average ROC area of 0.839(+/-0.064 ) , and our best SVM classifier achieved an average ROC area of 0.761(+/-0.043 ) . The T2W ML classifier , our best single-channel classifier , only achieved an average ROC area of 0.599(+/-0.146 ) . Compared to the best single-channel ML classifier , our best multichannel FLD and SVM classifiers have statistically superior ROC performance ( P=0.0003 and 0.0017 , respectively ) from pairwise two-sided t-test . By integrating the information from multiple images and capturing the textural and anatomical features in tumor areas , summary statistical maps can potentially aid in image-guided prostate biopsy and assist in guiding and controlling delivery of localized therapy under image guidance PURPOSE To prospect ively evaluate the accuracy of transrectal ultrasonography (US)-guided biopsy directed with magnetic resonance ( MR ) spectroscopic imaging in patients with an elevated prostate specific antigen ( PSA ) level and negative findings at prior biopsy by using subsequent biopsy results as the reference st and ard . MATERIAL S AND METHODS The committee on human research approved this study , and written informed consent was obtained . MR imaging and MR spectroscopic imaging were performed in 42 men ( age range , 45 - 75 years ; average age , 63.3 years ; median age , 65 years ) with negative findings at two or more prostatic biopsies and at digital rectal examination . MR spectroscopic data were rated on a scale of 1 ( benign ) to 5 ( malignant ) on the basis of st and ardized metabolic criteria . Abnormal voxels were overlaid on the corresponding transverse transrectal US images and used to perform voxel-guided biopsy of the prostate . All patients subsequently received an extended-pattern biopsy scheme . RESULTS Thirty-one of 42 patients demonstrated metabolic abnormalities that were suspicious for cancer ( voxels with scores > or = 4 ) . Eleven patients with negative MR spectroscopic imaging results also had negative biopsy findings . Cancer was detected in 17 ( 55 % ) of 31 men with positive MR spectroscopic imaging findings ( voxels with scores > or = 4 ) with a sensitivity of 100 % , specificity of 44 % , positive predictive value of 55 % , negative predictive value of 100 % , and accuracy of 67 % . In men with at least one spectroscopic voxel with a score of 5 ( 12 of 17 men ) , the sensitivity , specificity , positive and negative predictive values , and accuracy were 71 % , 84 % , 75 % , 81 % , and 79 % , respectively . CONCLUSION Metabolic data from MR spectroscopic imaging can be transferred to transrectal US images and used to sample regions of cancer in men with rising PSA levels and negative findings at prior biopsy with good accuracy Purpose The purpose of this study was to evaluate the role of magnetic resonance spectroscopic imaging ( MRSI ) and dynamic contrast-enhanced magnetic resonance imaging ( DCE-MRI ) in detecting tumour foci in patients with elevated prostate-specific antigen ( PSA ) and negative transrectal ultrasonography (TRUS)-guided biopsy . Material s and methods This prospect i ve r and omised trial was conducted on 150 patients who underwent [1H]MRSI and DCE-MRI and targeted biopsies of suspicious areas on MRI associated with r and om biopsies . Results After the second biopsy , the diagnosis of prostate adenocarcinoma was made in 64/150 cases . On a perpatient basis , MRSI had 82.8 % sensitivity , 91.8 % specificity , 88.3 % positive predictive value ( PPV ) , 87.8 % negative predictive value ( NPV ) and 85.7 % diagnostic accuracy . The sensitivity , specificity , PPV , NPV and accuracy for DCE-MRI was 76.5 % , 89.5 % , 84.5 % , 83.7 % and 82 % , respectively . The combination of MRSI and DCE-MRI yielded 93.7 % sensitivity , 90.7 % specificity , 88.2 % PPV , 95.1 % NPV and 90.9 % accuracy in detecting prostate carcinoma . Conclusions The combined study with [1H]MRSI and DCE-MRI showed promising results in guiding the biopsy of cancer foci in patients with an initial negative TRUS-guided biopsy . RiassuntoObiettivoScopo del nostro lavoro è stato valutare il ruolo della risonanza magnetica ( RM ) con spettroscopia ( MRSI ) e studio dinamico ( DCEMR ) nell’individuazione di foci tumorali in pazienti con elevati valori di antigene prostatico specifico ( PSA ) e biopsia prostatica gui data tramite TRUS (trans-rectal-ultrasound)-gui data negativa . Material i e metodiLo studio è stato di tipo prospettico r and omizzato . Abbiamo esaminato 150 pazienti . Tutti sono stati sottoposti ad esame di 1H-MRSI e DCEMR ed a prelievi mirati nelle zone sospette alla RM , associate a biopsie r and om . RisultatiDopo la seconda biopsia , la diagnosi di adenocarcinoma prostatico è stata effettuata in 64/150 casi . Nella nostra popolazione , su una base patient by patient , l’MRSI ha mostrato i seguenti valori : sensibilità 82,8 % ; specificità 91,8 % ; valore predittivo positivo ( PPV ) 88,3 % ; valore predittivo negativo ( NPV ) 87,8 % ; accuratezza 85,7 % . La DCEMR ha mostrato i seguenti valori : sensibilità 76,5 % ; specificità 89,5 % ; PPV 84,5 % ; NPV 83,7 % ; accuratezza 82 % . L’associazione delle due metodiche , MRSI e DCEMR , aumenta la sensibilità ( 93,7 % ) , la specificità ( 90,7 % ) , il PPV ( 88,2 % ) , il PNV ( 95,1 % ) e l’accuratezza ( 90,9 % ) nel predire l’individuazione del carcinoma prostatico se paragonata alla sola metodica MRSI o DCEMR . Conclusion iLo studio combinato ha mostrato risultati promettenti nella guida alla biopsia dei foci tumorali in pazienti con prima biopsia TRUS-gui data negativa Purpose : This study aim ed to prospect ively analyze the role of magnetic resonance spectroscopy imaging ( MRSI ) and dynamic-contrast enhancement magnetic resonance ( DCEMR ) in the detection of prostate tumor foci in patients with persistently elevated prostate-specific antigen levels ( in the range of ≥4 ng/mL to < 10 ng/mL ) and prior negative r and om trans-rectal ultrasound (TRUS)-guided biopsy . Experimental Design : This was a prospect i ve r and omized single-center study . One hundred and eighty eligible cases were included in the study . Patients in group A were su bmi tted to a second r and om prostate biopsy , whereas patients in group B were su bmi tted to a 1H-MRSI-DCEMR examination and sample s targeted on suspicious areas were associated to the r and om biopsy . Results : At the second biopsy , a prostate adenocarcinoma histologic diagnosis was found in 22 of 90 cases ( 24.4 % ) in group A and in 41 of 90 cases ( 45.5 % ) in group B ( P = 0.01 ) . On a patient-by-patient basis , MRSI had 92.3 % sensitivity , 88.2 % specificity , 85.7 % positive predictive value ( PPV ) , 93.7 % negative predictive value ( NPV ) , Output:	Conclusions ERC use yielded no additional benefit in terms of prostate cancer detection accuracy compared to multi-channel PAC use ( 71 % versus 68 % ) while the use of additional functional imaging techniques ( DCE-MRI , DWI and MRSI ) in a multiparametric MRI protocol improves the accuracy of prostate cancer detection allowing both the early cure and the guidance of biopsy
MS21464	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: BACKGROUND A new class of monoclonal antibodies ( non-T-cell depleting ) has gained favor for induction therapy after transplantation . This study evaluated the non-T-cell depleting antibody to the CD25 cell , daclizumab , as a single-dose induction agent immediately after pediatric liver transplantation to spare the use of the calcineurin inhibitor , tacrolimus , for 7 days in respect to both efficacy and renal function . METHODS From January 1998 to November 2001 , 81 pediatric orthotopic liver transplant recipients receiving 89 liver grafts were evaluated . The treatment arm ( n=61 ) received daclizumab 1 mg/kg immediately after liver transplantation along with mycophenolate , steroids , and , on postoperative day 7 , tacrolimus . The control group did not receive induction therapy , whereas tacrolimus , mycophenolate , and steroids were started immediately after surgery . RESULTS The induction group had fewer patients with rejection within the first 30 days after liver transplantation ( 9 [ 14.8 % ] vs. 10 [ 50 % ] ; P=0.003 ) . The mean time to first rejection was similar between groups ( 12.1 [ + /-7.8 ] days vs. 18.5 [ + /-8.1 ] days ; P = not significant ) . There was a 3.39 increase in relative risk to develop rejection within the first 30 days after orthotopic liver transplantation if the patient did not receive induction therapy ( relative risk=3.39 ; 95 % confidence interval [ 1.61 , 7.14 ] ) . Two-year actuarial survival for the induction group was 93.2 % compared with 85 % in the control ; graft survival was also similar between groups ( 87.8 % vs. 72.7 % ) at 2 years . CONCLUSION Daclizumab 1 mg/kg given immediately after pediatric liver transplantation and withholding tacrolimus , is safe , efficacious , and reduces rejections within the first 30 days after surgery Meta- analysis plays an important role in the analysis and interpretation of clinical trials in medicine and of trials in the social sciences but is of importance in other fields ( e.g. , particle physics [ 1 ] ) as well . In 2001 , Hartung and Knapp [2],[3 ] introduced a new approach to test for a nonzero treatment effect in a meta- analysis of k studies . Hartung and Knapp [2],[3 ] suggest to use the r and om effects estimate according to DerSimonian and Laird [ 4 ] and propose a variance estimator q so that the test statistics for the treatment effect is t distributed with k − 1 degrees of freedom . In their paper on dichotomous endpoints , results of a simulation study with 6 and 12 studies illustrate for risk differences , log relative risks and log odds ratios , the excellent properties regarding control of the type I error , and the achieved power [ 2 ] . They investigate different sample sizes in each study , and different amounts of heterogeneity between studies and compare their new approach ( Hartung and Knapp approach ( HK ) ) with the fixed effects approach ( FE ) and the classical r and om effects approach by DerSimonian and Laird ( DL ) . It can be clearly seen that , with increasing heterogeneity , the FE as well as the DL does not control the type I error rate , while the HK keeps the type I error rate in nearly every situation and in every scale . Advantages and disadvantages of the two st and ard approaches and respective test statistics have been extensively discussed ( e.g. , [ 5–7 ] ) . While it is well known that the FE is too liberal in the presence of heterogeneity , the DL is often thought to be rather conservative because heterogeneity is incorporated into the st and ard error of the estimate for the treatment effect and this should lead to larger confidence intervals and smaller test statistics for the treatment effect ( [ 8 ] chapter 9.4.4.3 ) . This was disproved among others by Ziegler and Victor [ 7 ] , who observed in situations with increasing heterogeneity severe inflation of the type I error for the DerSimonian and Laird test statistic . Notably , the asymptotic properties of this approach will be valid , if both the number of studies and the number of patients per study are large enough ( [ 8 ] chapter 9.54 , [ 9,10 ] ) . Although power issues of meta- analysis tests have received some interest , comparisons between the approaches and the situation with two studies were not the main interest [ 11,12 ] . Borenstein et al. ( [ 10 ] , pp . 363/364 ) recommend the r and om effects approach in general for meta- analysis and do not recommend meta-analyses of small numbers of studies . However , meta-analyses of few and of even only two trials are of importance . In drug licensing in many instances , two successful phase III clinical trials have to be su bmi tted as pivotal evidence for drug licensing [ 13 ] , and summarizing the findings of these studies is required according to the International Conference on Harmonisation guidelines E9 and M4E ( [ 14,15 ] ) . It is stated that ‘ An overall summary and synthesis of the evidence on safety and efficacy from all the reported clinical trials is required for a marketing application [ ... ] . This may be accompanied , when appropriate , by a statistical combination of results ’ ( [ 14 ] , p. 31 ) . For the summary , ‘ The use of meta-analytic techniques to combine these estimates is often a useful addition , because it allows a more precise overall estimate of the size of the treatment effects to be generated , and provides a complete and concise summary of the results of the trials ’ ( [ 14 ] , p. 32 ) . While in st and ard drug development , this summary will include usually more than two studies ; in rare diseases for the same intervention , barely ever more than two studies are available because of the limited number of patients . Likewise , decision making in the context of health technology assessment is based on systematic review s and meta-analyses . Often in practice , only two studies are considered homogeneous enough from clinical grounds to be included into a meta- analysis and then form the basis for decision making about reimbursement [ 16 ] . Despite the fact that meta- analysis is non-experimental observational ( secondary ) research [ 17 ] and p-values should be interpreted with caution , meta-analyses of r and omized clinical trials are termed highest-level information in evidence -based medicine and are the recommended basis for decision making [ 18 ] . As statistical significance plays an important role in the assessment of the meta- analysis , it is m and atory to underst and the statistical properties of the relevant methodology also in a situation , where only two clinical trials are included into a meta- analysis . We found Cochrane review s including meta-analyses with two studies only , which are considered for evidence -based decision making even in the presence of a large amount of heterogeneity ( I2≈75 % ) [ 19–21 ] We repeated the simulation study for dichotomous endpoints of Hartung and Knapp [ 2 ] with programs written in R 3.1.0 [ 22 ] to compare the statistical properties of the FE , the DL , and the HK for testing the overall treatment effect θ ( H0 : θ = 0 ) in a situation with two to six clinical trials . We considered scenarios under the null and alternative hypothesis for the treatment effect with and without underlying heterogeneity . We present the findings for the odds ratio with pC=0.2 and did vary probability of success in the treatment group pT to investigate the type I error and the power characteristics . The total sample size per meta- analysis was kept constant in the different scenarios ( n = 480 ) and n/k number of patients per study to clearly demonstrate the effect of the number of included studies on power and type I error of the various approaches . Likewise , we attempted to avoid problems with zero cell counts or extremely low event rates that may impact on type I error and power as well . I2 was used to describe heterogeneity because thresholds have been published ( low : I2=25 % , moderate : I2=50 % , and high : I2=75 % ) [ 23 ] for the quantification of the degree of heterogeneity with this measure . We termed I2≤15 % negligible , and this refers to simulations assuming no heterogeneity ( i.e. , the fixed effects model ) . Table I summarizes the results of our simulation study . The well-known anticonservative behavior of the FE and the DL in the presence of even low heterogeneity is visible for small numbers of studies in the meta- analysis . Particularly for the FE , the increase in the type I error is pronounced . With more than four studies even in situations with substantial heterogeneity , the HK perfectly controls the type I error . There is almost no impact on the power of the test in situations with no or low heterogeneity , and overall , it seems as if the only price to be paid for an increased heterogeneity is a reduced power of the test . Table I Overview of the empirical type I error and power . This is in strong contrast to the situation with only two studies . Again , the HK perfectly controls the prespecified type I error . However , even in a homogeneous situation , the power of the meta- analysis test was lower than 15 % in situations where the power of the FE and the DL approximates 70 % and 60 % , respectively . In the presence of even low heterogeneity with the HK , there is not much chance to arrive at a positive conclusion even with substantial treatment effects . Figure 1 summarizes the main finding of our simulation study with k = 2 and 6 studies impressively . Figure 1 ( a – d ) : Influence of heterogeneity in meta- analysis with two and six studies on empirical power . FE , fixed effects approach ; DL , DerSimonian and Laird approach ; HK , Hartung and Knapp approach . In the left column , simulation results with two studies ... In the homogeneous situation with two studies , the DL and even better the FE can be used to efficiently base conclusions on a meta- analysis . In contrast , already with mild to moderate heterogeneity , both st and ard tests severely violate the prespecified type I error , and there is a high risk of false positive conclusion with the classical approaches . This has major implication s for decision making in drug licensing as well . We have noted previously that a meta- analysis can be confirmatory if a drug development program was design ed to include a preplanned meta- analysis of the two pivotal trials [ 24 ] . As an example , thrombosis prophylaxis was discussed in the paper by Koch and Rohmel [ 24 ] , where venous thromboembolism is accepted as primary endpoint in the pivotal trials . In case when both pivotal trials are successful , they can be combined to demonstrate a positive impact on , for example , mortality . This can be preplanned as a hierarchical testing procedure : first , both pivotal trials will be assessed individually before confirmatory conclusions will be based on the meta- analysis . As explained , neither the FE , nor the DL , nor the HK can be the methodology to be recommended for a priori planning in this sensitive area unless any indication for heterogeneity is taken as a trigger not to combine studies in a meta- analysis at all . It is our belief that not enough emphasis has been given to this finding in the original paper and the important role of heterogeneity is not acknowledged enough in the discussion of findings from meta-analyses , in general AIMS Immunosuppression therapy for the control of immunologic rejection is a key aspect in liver transplantation . The objective of this study was to evaluate induction therapy with daclizumab ( DAC ) in living donor liver transplantation ( LDLT ) in children . METHODS We compared 2 different immunosuppression protocol s in 30 children undergoing LDLT . The patients were divided into 2 groups : 12 patients received tacrolimus with mycophenolate mofetil ( TAC-MMF ) , and 18 patients received tacrolimus with MMF and DAC induction therapy at days 0 and 14 after LDLT ( DAC-TAC-MMF ) . Both groups were similar with regard to age , sex , weight , and indication for liver transplantation . The incidence of biopsy-proved rejection episodes , posttransplantation lymphoproliferative disease ( PTLD ) , and renal dysfunction were evaluated . Tacrolimus levels at posttransplantation day 14 and at 2 months after transplantation were compared in the 2 groups . RESULTS Acute rejection episodes were observed in 8 patients in the TAC-MMF group ( 66 % ) , and none in the DAC-TAC-MMF group ( 0 % ; P < .05 ) . Neither PTLD nor renal dysfunction was seen in any patient . Mean Tacrolimus level on posttransplantation day 14 was 10.67 + /- 5.4 ng/mL in the TAC-MMF group and 5.65 + /- 3.6 ng/mL in the DAC-TAC-MMF group ( P < .05 ) . After the second month the mean tacrolimus levels were 7.2 + /- 2.9 ng/mL and 6.8 + /- 3.5 ng/mL in the TAC-MMF and DAC-TAC-MMF groups , respectively . ( P = NS ) . CONCLUSION Induction therapy with DAC is safe and associated with a lower incidence of rejection episodes among children undergoing LDLT It has been shown that an induction therapy with the monoclonal anti-interleukin-2 receptor antibody basiliximab ( Simulect ) is capable to reduce the incidence of acute graft rejection in adult and pediatric liver transplantation ( Ltx ) . However , data on long-term results using basiliximab in children post-Ltx are still pending . Therefore , the objective of our study was to report on the long-term results of basiliximab induction therapy in pediatric liver transplant recipients . A total of 54 children received two single doses of basiliximab in addition to cyclosporine and prednisolone following Ltx . We analyzed the incidence of acute and chronic graft rejection that of post-transplant lymphoproliferative disease ( Output:	The Bayesian credibility intervals using weakly informative priors for the between‐trial heterogeneity exhibited coverage probabilities in excess of the nominal level for a range of scenarios considered . However , they tended to be shorter than those obtained by the Knapp – Hartung method , which were also conservative . In contrast , methods based on normal quantiles exhibited coverages well below the nominal levels in many scenarios . With very few studies , the performance of the Bayesian credibility intervals is of course sensitive to the specification of the prior for the between‐trial heterogeneity .
MS21465	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: OBJECTIVES The authors used nationwide survey data to characterize current public conceptions related to recognition of mental illness and perceived causes , dangerousness , and desired social distance . METHODS Data were derived from a vignette experiment included in the 1996 General Social Survey . Respondents ( n = 1444 ) were r and omly assigned to 1 of 5 vignette conditions . Four vignettes described psychiatric disorders meeting diagnostic criteria , and the fifth depicted a " troubled person " with sub clinical problems and worries . RESULTS Results indicate that the majority of the public identifies schizophrenia ( 88 % ) and major depression ( 69 % ) as mental illnesses and that most report multicausal explanations combining stressful circumstances with biologic and genetic factors . Results also show , however , that smaller proportions associate alcohol ( 49 % ) or drug ( 44 % ) abuse with mental illness and that symptoms of mental illness remain strongly connected with public fears about potential violence and with a desire for limited social interaction . CONCLUSIONS While there is reason for optimism in the public 's recognition of mental illness and causal attributions , a strong stereotype of dangerousness and desire for social distance persist . These latter conceptions are likely to negatively affect people with mental illness This study explores the effect of classroom theory and contact with mentally ill patients on the attitudes of student nurses . The independent variables were ( a ) pre-class stage , ( b ) post-class stage , and ( c ) post- clinical placement stage . A total of 72 students took part in the study . While there were two significant changes in responses to specific attitudes at the post-class stage , there were three significant changes in responses to specific attitudes at the post- clinical stage on patients ' characteristics . However , when responses to all attitudes pertaining towards patients ' characteristics were grouped , there was no overall significant change at the post- clinical experience stage . Also , for attitudes towards patients ' treatment , there were significant changes in responses to two specific attitudes at the post-class stage and to three specific attitudes at the post- clinical experience stage . Furthermore , the highly significant positive change in attitudes towards patients ' treatment in the post-class stage remained highly significant at the post- clinical experience stage . This confirms that classroom theory , prior to clinical experience , can effect students ' attitudes towards patients treatment . In addition , students ' evaluative comments , while being critical of some aspects of their clinical placements , did not necessarily affect their attitudes towards the characteristics or treatment of the mentally ill OBJECTIVE This study evaluated a consumer delivered anti-stigma presentation , In Our Own Voice ( IOOV ) , with Masters of Social Work ( MSW ) students , replicating a previous study with undergraduates . METHODS Thirty MSW students completed pre and post surveys to measure changes in attitude , knowledge and social distance after the presentation . RESULTS Paired sample s t-tests showed increases in attitude ( p < .001 ) , knowledge ( p < .05 ) , and social distance ( p < .001 ) . Compared with previous research on undergraduate students , MSW students scored higher on all three pre-test measures ( all p < .001 ) . CONCLUSIONS The results further support the effectiveness of IOOV and indicate that graduate level helping professionals can benefit from anti-stigma programs . Future research should go beyond self-report knowledge and attitude evaluation , test the efficacy of the components of the IOOV program ( video , contact with presenters ) , and test the lasting effects of the program The profession of nursing is seeking to establish its unique professional identity by developing discipline-focused research and clinical practice supported by university education . However , according to refereed literature , educating undergraduate nurses in alcohol-related problems is lacking . The literature reveals that nurses in general lack the necessary knowledge , attitudes , and skills to work with problem drinkers . Alcohol early intervention is advocated as a strategy compatible with contemporary nursing practice . This paper reports a study that commenced with the development of a problem-based , five-week Alcohol Early Intervention Education Package ( AEIEP ) . This package became an intervention around which the knowledge and attitudes of a sample of 212 students of nursing were evaluated . A comprehensive instrument was developed to measure the respondent 's knowledge and attitude regarding alcohol-related problems in general and specifically in early intervention . The effects of the education intervention on the different strata of students , were examined in a quasi-experimental , pre-post test design . The findings demonstrated it had a significant effect on the knowledge and attitudes of students enrolled in an integrated bachelor of nursing curriculum Negative attitudes toward people experiencing mental illness and mental health nursing as a career option have been recognized as a major barrier to sustaining an adequate psychiatric nursing workforce . This article presents the findings from a prospect i ve observational study that explored the relationship between undergraduate nursing students ' ( n = 688 ) attitudes relevant to the mental health field , preparedness , and career preferences after they had completed a mental health placement . A comparison was also made between the self-reported attitudes , beliefs , and preferences of two groups of students , one with and one without relevant clinical experience . Finally , the psychometric properties of the clinical evaluation component of the survey were explored because the structure and composition of this component have not been assessed or reported previously . The findings have direct implication s for psychiatric-mental health education . They show a strong association between educational preparation , placement experiences , and students ' attitudes toward psychiatric nursing and consumers of mental health services . Findings also indicated that students with clinical experience felt significantly more prepared for employment in the mental health field and significantly less anxiety surrounding mental illness than did students without clinical experience The effects of three strategies for changing stigmatizing attitudes -- education ( which replaces myths about mental illness with accurate conceptions ) , contact ( which challenges public attitudes about mental illness through direct interactions with persons who have these disorders ) , and protest ( which seeks to suppress stigmatizing attitudes about mental illness)--were examined on attributions about schizophrenia and other severe mental illnesses . One hundred and fifty-two students at a community college were r and omly assigned to one of the three strategies or a control condition . They completed a question naire about attributions toward six groups -- depression , psychosis , cocaine addiction , mental retardation , cancer , and AIDS -- prior to and after completing the assigned condition . As expected , results showed that education had no effect on attributions about physical disabilities but led to improved attributions in all four psychiatric groups . Contact produced positive changes that exceeded education effects in attributions about targeted psychiatric disabilities : depression and psychosis . Protest yielded no significant changes in attributions about any group . This study also examined the effects of these strategies on processing information about mental illness Output:	MAIN RESULTS Both mental health-related theoretical education and clinical placement in mental health setting s are effective in changing the attitudes of health care students towards mental illness . CONCLUSIONS Theoretical education in the form of videos , lectures , presentations delivered by people with mental illness and coursework are effective stigma reduction interventions . Clinical placement is more effective when combined with theoretical education . However , the effect of educational interventions may be transient .
MS21466	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: STUDY QUESTION Does hormonal stimulation with corifollitropin alpha ( CFA ) only , mimicking a step down protocol , result in lower incidence of progesterone elevation on the day of hCGtrigger as compared to sustained stimulation with recombinant FSH ( rFSH ) ? SUMMARY ANSWER The current findings support the concept that sustained FSH stimulus contributes to premature progesterone elevation in stimulated IVF cycles . WHAT IS KNOWN ALREADY Serum progesterone rise during the follicular phase of ovarian stimulation for IVF treatment seems to be related to a poorer reproductive outcome . However , the mechanism by which the rise in progesterone is caused is not yet fully understood . STUDY DESIGN , SIZE , DURATION This study was a post hoc analysis of data from two multi-center , r and omized , double-blind , double-dummy , active-controlled , non-inferiority trials , ENGAGE and PURSUE , conducted from June 2006 to January 2008 and from July 2010 to October 2012 respectively . PARTICIPANTS / MATERIAL S , SETTING , METHODS In the ENGAGE- study , 1506 women , aged 18 - 36 years , were allocated to either a single injection of 150 mg CFA or daily injections of 200 IU rFSH in the first week of stimulation , using a st and ard GnRH antagonist protocol . In the PURSUE- study , a total of 1390 women , aged 35 - 42 years , were allocated to either a single injection of 150 mg of CFA or daily 300 IU of rFSH for the first week , again using a st and ard GnRH antagonist protocol . In both trials , daily rFSH was continued until three follicles reached > 17 mm in size . All women had a body weight of between 50 and 90 kg , regular menstrual cycles and an indication for ovarian stimulation before IVF . The incidence of progesterone elevation on day of hCG-trigger in patients with CFA only or rFSH stimulation , and triggered on Day 8 of stimulation , was analyzed . MAIN RESULTS AND THE ROLE OF CHANCE Of patients with CFA only stimulation , 5.4 % ( 13/239 patients ) showed a progesterone elevation above 1.5 ng/ml on day of hCG-trigger , whereas patients with rFSH stimulation had a significant higher incidence of progesterone elevation ( 18.3 % ; 62/339 patients ) ( P < 0.001 ) . LIMITATIONS , REASONS FOR CAUTION Post hoc analysis of data from previously published trials could be considered as a reason for caution . WIDER IMPLICATION S OF THE FINDINGS Future studies should evaluate whether it would be possible to prevent a premature progesterone rise in cycles stimulated with daily FSH by using a step down protocol towards the end of the follicular phase . STUDY FUNDING /COMPETING INTERESTS Financial/ Material Support was provided by Merck & Co. , Inc. , Kenilworth , NJ , USA . Davis Gates is an employee of Merck Sharp & Dohme Corp. , a subsidiary of Merck & Co. , Inc. , Kenilworth , NJ , USA and may own stock and /or hold stock options in the company . Fabiola Beligotti is an employee of MSD , Italy , a subsidiary of Merck & Co. , Inc. , Kenilworth , NJ , USA and may own stock and /or hold stock options in the company . Barbara Lawrenz , Nils Engelmann and Human M. Fatemi have no conflict of interest . TRIAL REGISTRATION NUMBER ENGAGE study : Clinical Trials.gov identifier NTC00696800 . PURSUE- study : NCT01144416 To evaluate the effects of high progesterone prior to oocyte retrieval on the genomic profile of peri-implantation endometrium , we conducted this single-center , prospect i ve cohort study . Depending on whether or not the progesterone level on the day of hCG administration and the day after hCG administration were elevated , a total of 20 women undergoing IVF treatment who did not have fresh embryo transfer were included : Group 1 refers to subjects with normal progesterone level on both days ; Group 2 refers to subjects with normal progesterone level on the day of hCG administration and high progesterone level on the day after hCG administration ; Group 3 refers to subjects with high progesterone level on the day of hCG administration and normal progesterone level on the day after hCG administration ; Group 4 refers to subjects with high progesterone level on both days . Five subjects were included in each group . Endometrial sample s were obtained 7days after hCG administration . We found that high progesterone level prior to oocyte retrieval predominantly affected components of the NK cell mediated cytotoxicity pathway in the endometrium and that significant differences were only seen when progesterone measurements on both the day of and day after hCG administration were considered together Recent studies suggest that elevated late follicular phase progesterone concentrations after ovarian stimulation for IVF may result in embryo-endometrial asynchrony , reducing the chance of successful implantation after fresh embryo transfer . It remains unclear to what extent elevated late follicular phase progesterone levels may occur in unstimulated cycles before frozen-thawed embryo transfer , or what affect they may have on outcomes . In this cohort study , 271 patients r and omized to the modified natural cycle arm of a r and omized controlled trial comparing two endometrial preparation regimens underwent late follicular phase progesterone and LH testing . A receiver operating characteristic curve was constructed to identify a progesterone cut-off level with the best predictive value for live birth ( progesterone level ≥4.6 nmol/l ) . A total of 24.4 % of patients revealed an isolated elevated serum progesterone of 4.6 nmol/l or greater , and 44.3 % showed an elevated progesterone level in association with a rise in LH . Neither endocrine disruption affected outcomes , with live birth rates of 12.9 % versus 10.6 % ( OR 0.6 , 95 % CI 0.19 to 1.9 ) and 11.9 % versus 17.5 % ( OR 1.6 , 95 % CI 0.79 to 3.1 ) , respectively . Whether monitoring of progesterone and LH in natural cycle frozen-thawed embryo transfer has added clinical value should studied further The impact of a premature elevation of serum progesterone level , the day of hCG administration in patients under controlled ovarian stimulation during IVF procedure , on human endometrial receptivity is still debated . In the present study , we investigated the endometrial gene expression profile shifts during the prereceptive and receptive secretory stage in patients with normal and elevated serum progesterone level on the day of hCG administration in fifteen patients under stimulated cycles . Then , specific biomarkers of endometrial receptivity in these two groups of patients were tested . Endometrial biopsies were performed on oocyte retrieval day and on day 3 of embryo transfer , respectively , for each patient . Sample s were analysed using DNA microarrays and qRT-PCR . The endometrial gene expression shift from the prereceptive to the receptive stage was altered in patients with high serum progesterone level ( > 1.5 ng/mL ) on hCG day , suggesting accelerated endometrial maturation during the periovulation period . This was confirmed by the functional annotation of the differentially expressed genes as it showed downregulation of cell cycle-related genes . Conversely , the profile of endometrial receptivity was comparable in both groups . Premature progesterone rise alters the endometrial gene expression shift between the prereceptive and the receptive stage but does not affect endometrial receptivity STUDY QUESTION Are there differences in estrogen and progesterone secretion in singleton pregnancies , up to Week 11 , between spontaneous pregnancies , after controlled ovarian hyperstimulation and fresh embryo transfer ( COH + ET ) and after frozen embryo transfer in a spontaneous cycle ( FET ) ? SUMMARY ANSWER Serum progesterone and estradiol ( E2 ) concentrations after COH + ET were higher in early pregnancy , lasting up to Week 7 - 8 , than FET and spontaneous pregnancies , while hormone levels after FET did not differ from spontaneous pregnancies . WHAT IS ALREADY KNOWN The risk of adverse perinatal outcomes after COH + ET seems to be increased when compared with spontaneous pregnancies . One of the reasons suggested for this is related to ovarian hyperstimulation . STUDY DESIGN , SIZE , DURATION This was a prospect i ve cohort study consisting of three different groups of pregnant women which were followed-up weekly until Week 11 of their pregnancies . The spontaneous pregnancy group consisted of 41 women , the COH + ET group consisted of 39 and the FET group consisted of 30 women . PARTICIPANTS / MATERIAL S , SETTING , METHODS Women in the control group with spontaneous conception were recruited from local prenatal clinics . Women in the COH + ET and FET groups were recruited from the Reproductive Unit of Oulu University Hospital . At each visit , a three-dimensional ultrasonography was performed to examine the ovarian volumes and vascularization . A blood sample was drawn to analyse progesterone and E2 levels . The pregnancy outcome was included in the analysis . MAIN RESULTS AND THE ROLE OF CHANCE At pregnancy Week 5 , the serum progesterone levels were higher after the COH + ET ( median 312 , inter-quartile range 183 - 480 nmol/l ) , when compared with the spontaneous ( 63 , 52 - 80 nmol/l ; P < 0.001 ) and FET ( 74 , 48 - 96 nmol/l ; P < 0.001 ) pregnancies . At Week 11 , the P ( 189 , 124 - 260 nmol/l ) was still higher in the COH + ET group ( FET 101 , 78 - 120 nmol/l , P < 0.001 ; spontaneous 115 , 80 - 139 nmol/l , P < 0.01 ) than the other two groups . The E2 levels at Week 5 were also significantly higher after COH + ET ( 4.1 , 2.2 - 6.6 nmol/l ) than in the spontaneous pregnancies ( 1.1 , 0.7 - 1.6 nmol/l , P < 0.001 ) or after FET ( 0.7 , 0.6 - 0.9 nmol/l , P < 0.001 ) . The volume of the ovaries and the intraovarian vasculature in the COH + ET group were significantly higher when compared with the other two groups ( P < 0.001 ) . The birthweight was negatively correlated with the serum P ( R -0.340 , P < 0.01 ) and E2 ( R= -0.275 , P < 0.05 ) in pregnancy Weeks 5 - 8 . In the multivariate analysis evaluating the factors affecting birthweight of the newborn , the significant factors were the length of gestation , maternal height and progesterone or E2 secretion during Weeks 5 - 8 . LIMITATIONS , REASONS FOR CAUTION Because of the low number of patients in this study , larger cohort studies are required to confirm the findings . WIDER IMPLICATION S OF THE FINDINGS The findings here indicate that COH-induced increased luteal activity should be evaluated by measuring steroid levels or the ovarian size or vascularity , rather than number of oocytes retrieved . If unphysiologically high steroid activity during pregnancy after COH contributes to the risk of adverse perinatal outcomes after fresh embryo transfer , milder stimulation protocol s or even freezing of all of the embryos should be considered . STUDY FUNDING /COMPETING INTERESTS This study was supported by a research grant from the Academy of Finl and . The authors declare no conflicts of interest Abstract This study analyzed the clinical outcomes of patients with elevated progesterone level on the HCG day in IVF/ICSI cycles , with different timing of embryo transfer . A total of 123 patients were involved in this prospect i ve r and omized clinical study . Group 1 : blastocyst transfer group , 38 cases ; Group 2 : frozen – thawed embryo transfer group ( first FET cycle ) , 42 cases ; Group 3 : fresh embryo transfer group , 43 cases . The basal FSH level was comparable among three groups ( 6.7 ± 3 versus 7.0 ± 2 versus 6.9 ± 2.4 , p = 0.897 ) . The clinical pregnancy rate was highest in group 2 , lowest in group 3 , with significantly difference ( 31.6 % versus 38.1 % versus 13.9 % , p = 0.037 ) . The implantation rate and live birth rate were still lowest in group 3 ( 21.9 % versus 19.8 % versus 6.7 % , p = 0.016 and 18.4 % versus 31 % versus 11.6 % , p = 0.081 ) . In conclusion , the elevated progesterone level will affect clinical pregnancy rate in fresh embryo transfer cycles . We suggest frozen-thawed embryo transfer for these patients . However , for those patients who expressed Output:	Up-to-the minute data show that , there is a different impact of elevated P4 in fresh , frozen and donor cycles , whereas there are plenty of reports pointing to a different endometrial gene expression on different P4 measurements . Our hypothesis states that the combination of P4 values and endometrial ultrasound parameters at the day of oocyte triggering can affect clinical pregnancy rates in normal responders undergoing ART
MS21467	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Background Repetitive Transcranial Magnetic Stimulation ( rTMS ) is an effective treatment for Major Depressive Disorder ( MDD ) , and is based upon delivery of focal high-energy pulses of electromagnetic stimulation . We postulated that delivery of rTMS at the subject ’s individual alpha frequency ( synchronized TMS , or sTMS ) would achieve efficacy with lower energy of stimulation . We developed a device that rotates neodymium cylindrical magnets at three locations along the midline above the subject ’s scalp to impart low-energy , sinusoidal-waveform magnetic brain stimulation over a broad area , and performed this efficacy study . Method Fifty-two subjects with MDD were enrolled in a r and omized , sham controlled , double-blind treatment study ( Trial Registration : NCT01683019 ) . Forty-six subjects were included in the final analysis . Most subjects received concurrent antidepressant medications that remained unchanged during the study . Subjects were r and omized to three treatment groups : 1 ) active sTMS with a fixed frequency at the subject ’s alpha frequency ; 2 ) active sTMS with a r and om stimulus frequency that varied between 8 Hz and 13 Hz ; and , 3 ) sham sTMS . 20 half-hour sTMS sessions were administered 5 days per week for 4 weeks . Results Subjects with either fixed or r and om frequency active sTMS had statistically significantly greater percentage reduction in depression severity compared to sham ( 48.5 % vs. 19.3 % , respectively ; p = 0.001 ) . No significant difference was found between fixed and r and om groups ( p = 0.30 ) . No significant side effects were reported . Conclusions These results suggest that sTMS may be an effective treatment for MDD BACKGROUND Theta-burst transcranial magnetic stimulation ( TBS ) has been shown to induce potent and long lasting effects on cortical excitability . In a previous open study , we demonstrated safety , tolerability and antidepressant properties of continuous TBS ( cTBS ) in major depression ( MD ) . The present study was aim ed to evaluate the therapeutic efficacy of cTBS in depressed patients using a double-blind , sham-controlled design . METHODS Twenty nine patients with MD were r and omized to receive either active cTBS to the right dorsolateral prefrontal cortex ( n=15 ) or sham cTBS ( n=14 ) for 10 consecutive work days . After the 10th session , patients who received sham TBS were crossed over to active cTBS which consisted of 10 daily sessions . Patients who received active cTBS continued with the same treatment protocol for additional 10 treatments . Each treatment session consisted of 3600 stimuli at an intensity of 100 % of the active motor threshold . Severity of depression was assessed weekly . RESULTS Overall , there was no significant difference in the degree of clinical improvement between active and sham cTBS groups . However , in patients whose medication status remained unchanged before the trial ( n=8 ) and in those who were medication-free ( n=3 ) , active cTBS result ed in a significantly greater reduction of Hamilton depression scores as compared to sham cTBS . LIMITATIONS A small sample size , confounding effect of medication and short treatment period . CONCLUSIONS Our results suggest that the antidepressant effect of cTBS is modest , yet it might be beneficial to patients nonresponsive to ongoing pharmacological treatment . A direct comparison between cTBS and conventional rTMS protocol s is warranted Objectives : Transcranial direct current stimulation ( tDCS ) has demonstrated some efficacy in treatment-resistant major depression ( TRD ) . The majority of previous controlled studies have used anodal stimulation to the left dorsolateral prefrontal cortex ( DLPFC ) and a control location such as the supraorbital region for the cathode . Several open-label studies have suggested effectiveness from anodal stimulation to the left DLPFC combined with cathodal stimulation to the right DLPFC . Thus , this study evaluated the efficacy of tDCS using anodal stimulation to the left DLPFC and cathodal stimulation to the right DLPFC compared to sham tDCS . Methods : Subjects between the ages of 18 and 65 were recruited from a tertiary care university hospital . Twenty-four subjects with TRD and a 17-item Hamilton Rating Scale for Depression greater than 21 were r and omized to receive tDCS or sham tDCS . The rates of remission were compared between the two treatment groups . Results : The remission rates did not differ significantly between the two groups using an intention to treat analysis . More subjects in the active tDCS group had failed a course of electroconvulsive therapy in the current depressive episode . Side effects did not differ between the two groups and in general the treatment was very well tolerated . Conclusion : Anodal stimulation to the left DLPFC and cathodal stimulation to the right DLPFC was not efficacious in TRD . However , a number of method ological limitations warrant caution in generalizing from this study . Ongoing , controlled studies should provide further clarification on the efficacy of this stimulation configuration in TRD . Clinical Trials.gov Identifier : NCT01078948 Although accelerated repetitive Transcranial Magnetic Stimulation ( rTMS ) paradigms and intermittent Theta-burst Stimulation ( iTBS ) may have the potency to result in superior clinical outcomes in Treatment Resistant Depression ( TRD ) , accelerated iTBS treatment has not yet been studied . In this registered r and omized double-blind sham-controlled crossover study , spread over four successive days , 50 TRD patients received 20 iTBS sessions applied to the left dorsolateral prefrontal cortex ( DLPFC ) . The accelerated iTBS treatment procedure was found to be safe and result ed in immediate statistically significant decreases in depressive symptoms regardless of order/type of stimulation ( real/sham ) . While only 28 % of the patients showed a 50 % reduction of their initial Hamilton Depression Rating Scale score at the end of the two-week procedure , this response rate increased to 38 % when assessed two weeks after the end of the sham-controlled iTBS protocol , indicating delayed clinical effects . Importantly , 30 % of the responders were considered in clinical remission . We found no demographic predictors for response . Our findings indicate that only four days of accelerated iTBS treatment applied to the left DLPFC in TRD may lead to meaningful clinical responses within two weeks post stimulation 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 Studies of repetitive transcranial magnetic stimulation ( rTMS ) in depression have mostly involved once-daily treatment , with positive but modest clinical results . This study tested the efficacy and safety of twice-daily rTMS over 2 weeks . METHOD Thirty-eight depressed subjects enrolled in a double-blind , sham-controlled trial of twice-daily rTMS ( left prefrontal cortex , 10 Hz , 110 % intensity , 1500 stimuli per session ) over 2 weeks . Mood and neuropsychological functioning were assessed weekly by blind raters , using the Montgomery-Asberg Depression Rating Scale ( MADRS ) as the primary outcome measure , plus the Hamilton Rating Scale for Depression ( HRSD ) and self-report measures . After the blind period , 22 subjects continued with once-daily rTMS to receive a total of 6 weeks of active rTMS . RESULTS Subjects were moderately treatment resistant . Active treatment result ed in significantly greater improvement than sham over the 2-week blind period on one outcome measure only ( MADRS p<0.05 ) . Subjects showed further improvement over the 6 weeks of active rTMS . Neuropsychological test scores did not change significantly . CONCLUSIONS rTMS given twice daily was effective and safe , with no adverse neuropsychological effects BACKGROUND We tested whether transcranial magnetic stimulation ( TMS ) over the left dorsolateral prefrontal cortex ( DLPFC ) is effective and safe in the acute treatment of major depression . METHODS In a double-blind , multisite study , 301 medication-free patients with major depression who had not benefited from prior treatment were r and omized to active ( n = 155 ) or sham TMS ( n = 146 ) conditions . Sessions were conducted five times per week with TMS at 10 pulses/sec , 120 % of motor threshold , 3000 pulses/session , for 4 - 6 weeks . Primary outcome was the symptom score change as assessed at week 4 with the Montgomery-Asberg Depression Rating Scale ( MADRS ) . Secondary outcomes included changes on the 17- and 24-item Hamilton Depression Rating Scale ( HAMD ) and response and remission rates with the MADRS and HAMD . RESULTS Active TMS was significantly superior to sham TMS on the MADRS at week 4 ( with a post hoc correction for ine quality in symptom severity between groups at baseline ) , as well as on the HAMD17 and HAMD24 scales at weeks 4 and 6 . Response rates were significantly higher with active TMS on all three scales at weeks 4 and 6 . Remission rates were approximately twofold higher with active TMS at week 6 and significant on the MADRS and HAMD24 scales ( but not the HAMD17 scale ) . Active TMS was well tolerated with a low dropout rate for adverse events ( 4.5 % ) that were generally mild and limited to transient scalp discomfort or pain . CONCLUSIONS Transcranial magnetic stimulation was effective in treating major depression with minimal side effects reported . It offers clinicians a novel alternative for the treatment of this disorder In previous studies , fast repetitive transcranial magnetic stimulation ( rTMS ) with a frequency > 1 Hz demonstrated substantial antidepressant effects compared to sham rTMS . However , it is not clear whether fast rTMS is superior to slow rTMS ( frequency < or = 1 Hz ) which is safe at therapeutically promising higher intensities . The aim of this double-blind study was to compare the action of fast , slow and sham rTMS . Eighteen patients with pharmacotherapy-resistant major depression were r and omized to receive fast ( 10 Hz ) , slow ( 0.3 Hz ) or sham rTMS with 250 stimuli/day for 5 successive days . rTMS was applied at 90 % motor threshold intensity to the left dorsolateral prefrontal cortex . Scores on the Hamilton Depression Rating Scale ( HDRS ) , but not on the Montgomery-Asberg Depression Rating Scale ( MADRS ) , showed a statistically significant time x group interaction with a reduction of 19 % after slow rTMS . However , the effect was clinical ly marginal and not reflected by self-rating scores . Verbal memory and reaction performance were not impaired after rTMS , and there was even a statistically significant time x group interaction with improvement of verbal memory performance after fast rTMS . In conclusion , this study further supported the safety of rTMS but does not show any clinical ly meaningful antidepressant efficacy of rTMS at 250 daily stimuli over 5 days in pharmacotherapy-refractory major depression It has been 30 years since the discovery that repeated electrical stimulation of neural pathways can lead to long-term potentiation in hippocampal slices . With its relevance to processes such as learning and memory , the technique has produced a vast literature on mechanisms of synaptic plasticity in animal models . To date , the most promising method for transferring these methods to humans is repetitive transcranial magnetic stimulation ( rTMS ) , a noninvasive method of stimulating neural pathways in the brain of conscious subjects through the intact scalp . However , effects on synaptic plasticity reported are often weak , highly variable between individuals , and rarely last longer than 30 min . Here we describe a very rapid method of conditioning the human motor cortex using rTMS that produces a controllable , consistent , long-lasting , and powerful effect on motor cortex physiology and behavior after an application period of only 20 - 190 OBJECTIVE High-frequency left-side repetitive transcranial magnetic stimulation ( rTMS ) and low-frequency stimulation to the right prefrontal cortex have both been shown to have antidepressant effects , but doubts remain about the magnitude of previously demonstrated treatment effects . The authors evaluated sequentially combined high-frequency left-side rTMS and low-frequency rTMS to the right prefrontal cortex for treatment-resistant depression . METHOD The authors conducted a 6-week double-blind , r and omized , sham-controlled trial in 50 patients with treatment-resistant depression . Three trains of low-frequency rTMS to the right prefrontal cortex of 140 seconds ' duration at 1 Hz were applied daily , followed immediately by 15 trains of 5 seconds ' duration of high-frequency left-side rTMS at 10 Hz . Sham stimulation was applied with the coil angled at 45 degrees from the scalp , resting on the side of one wing of the coil . The primary outcome variable was the score on the Montgomery-Asberg Depression Rating Scale . RESULTS There was a significantly greater response to active than sham stimulation at 2 weeks and across the full duration of the study . A significant proportion of the study group receiving active treatment met response ( 11 of 25 [ 44 % ] ) or remission ( nine of 25 [ 36 % ] ) criteria by study end compared to the sham stimulation group ( two of 25 [ 8 % ] and none of 25 respectively ) . CONCLUSIONS Sequentially applying both high-frequency left-side rTMS and low-frequency rTMS to the right prefrontal cortex , has substantial treatment efficacy in patients Output:	Several non‐invasive brain stimulation treatments seem efficacious across different outcome metrics . All‐cause discontinuation rates indicate no differences between sham and active treatment . There were no differences in all‐cause discontinuation rates . The strongest evidence was for high‐frequency rTMS over the left DLPFC . Intermittent TBS provides an advance in terms of reduced treatment duration . tDCS is a potential treatment for non‐treatment resistant depression . To date , there is not sufficient published data available to draw firm conclusions about the efficacy and acceptability of TBS and sTMS
MS21468	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: BACKGROUND The gastrointestinal microflora is an important constituent of the gut mucosal defense barrier . We have previously shown that a human intestinal floral strain , Lactobacillus GG ( ATCC 53103 ) , promotes local antigen-specific immune responses ( particularly in the IgA class ) , prevents permeability defects , and confers controlled antigen absorption . OBJECTIVE The aim of this study was to evaluate the clinical and immunologic effects of cow 's milk elimination without ( n = 14 ) and with ( n = 13 ) the addition of Lactobacillus GG ( 5 x 10(8 ) colony-forming units/gm formula ) in an extensively hydrolyzed whey formula in infants with atopic eczema and cow 's milk allergy . The second part of the study involved 10 breast-fed infants who had atopic eczema and cow 's milk allergy . In this group Lactobacillus GG was given to nursing mothers . METHODS The severity of atopic eczema was assessed by clinical scoring . The concentrations of fecal alpha 1- antitrypsin , tumor necrosis factor-alpha , and eosinophil cationic protein were determined as markers of intestinal inflammation before and after dietary intervention . RESULTS The clinical score of atopic dermatitis improved significantly during the 1-month study period in infants treated with the extensively hydrolyzed whey formula fortified with Lactobacillus GG . The concentration of alpha 1-antitrypsin decreased significantly in this group ( p = 0.03 ) but not in the group receiving the whey formula without Lactobacillus GG ( p = 0.68 ) . In parallel , the median ( lower quartile to upper quartile ) concentration of fecal tumor necrosis factor-alpha decreased significantly in this group , from 709 pg/gm ( 91 to 1131 pg/gm ) to 34 pg/gm ( 19 to 103 pg/gm ) ( p = 0.003 ) , but not in those receiving the extensively hydrolyzed whey formula only ( p = 0.38 ) . The concentration of fecal eosinophil cationic protein remained unaltered during therapy . CONCLUSION These results suggest that probiotic bacteria may promote endogenous barrier mechanisms in patients with atopic dermatitis and food allergy , and by alleviating intestinal inflammation , may act as a useful tool in the treatment of food allergy Objective . There is a growing body of clinical and laboratory evidence to support the notion that food allergy plays a role in the pathogenesis of atopic dermatitis ( AD ) . However , the incidence of IgE-mediated food allergy in children with AD is not well established . Design . A prospect i ve study to determine the prevalence of IgE-mediated food hypersensitivity among patients referred to a university-based dermatologist for evaluation of AD . Setting . University hospital pediatric dermatology clinic . Patients . A total of 63 patients with AD were recruited ( 35 male ; 32 white , 24 African-American , 7 Asian ) . Methods . Patients were assigned an AD symptom score ( SCORAD ) and were screened for food-specific serum IgE antibodies to six foods ( milk , egg , wheat , soy , peanut , fish ) known to be the most allergenic in children . The levels of food-specific serum IgE were determined by the CAP System fluoroscein-enzyme immunoassay ( CAP ) ; patients with a value ≥0.7 kIUa/L were invited for an additional allergy evaluation . Those with CAP values below the cutoff were considered not food allergic . Patients were considered to be allergic if they met one of the following criteria for at least one food : 1 ) reaction on food challenge ; 2 ) CAP value more than the 95 % confidence interval predictive for a reaction ; 3 ) convincing history of an acute significant ( hives , respiratory symptoms ) reaction after the isolated ingestion of a food to which there was a positive CAP or prick skin test . Results . A total of 63 patients ( median age , 2.8 years ; median SCORAD , 41.1 ) were recruited ; 22 had negative CAP values ( without a significant difference in age or SCORAD score , compared with the 41 with positive specific IgE values ) . Further allergy evaluation was offered to the 41 remaining patients ; 10 were lost to follow-up and 31 were evaluated further . Of these , 19 underwent a total of 50 food challenges ( 36 double-blind , placebo-controlled , and 14 open ) , with 11 patients experiencing 18 positive challenges ( 94 % with skin reactions ) . Additionally , 6 patients had a convincing history with a predictive level of IgE ; 5 had a convincing history with positive , indeterminate levels of IgE ; and 1 had predictive levels of IgE ( to egg and peanut ) without a history of an acute reaction . Overall , 23/63 ( 37 % ; 95 % confidence interval , 25 % to 50 % ) had clinical ly significant IgE-mediated food hypersensitivity without a significant difference in age or symptom score between those with or without food allergy . Conclusions . Approximately one third of children with refractory , moderate – severe AD have IgE-mediated clinical reactivity to food proteins . The prevalence of food allergy in this population is significantly higher than that in the general population , and an evaluation for food allergy should be considered in these patients Thirty seven breast fed infants with eczema were studied to see whether changes in their mothers ' diets affected their skin condition . Nineteen mothers and babies took part in a double blind crossover trial of exclusion of egg and cows ' milk , and 18 took part in open exclusion of 11 foods followed by double blind challenge to those mothers whose infants seemed to respond . Babies were examined at the beginning and end of each dietary period , and the extent and severity of the rash were given a numerical score . The eczema improved in six infants when their mothers avoided egg and cows ' milk and worsened again when these were reintroduced . Two infants suffered gastrointestinal reactions after maternal ingestion of egg and cows ' milk , one developing colitis . Maternal dietary exclusion seems to benefit some breast fed babies with eczema OBJECTIVE To evaluate the impact of childhood atopic eczema on families and assess the personal financial cost of its management . DESIGN Cross sectional survey . SETTING Paediatric dermatology and paediatric diabetology outpatient clinics . PATIENTS Parents of 48 r and omly selected children with atopic eczema and 46 with insulin dependent diabetes mellitus . MAIN OUTCOME MEASURES The impact on family score , the reported cost of relevant medical treatments , medical consultations , relevant hospitalisation , and income loss . RESULTS Families of children with moderate or severe atopic eczema had a significantly higher impact on family score than families of diabetic children . A conservative estimate of the annual personal financial cost of managing mild , moderate , and severe eczema was Aus$330 , 818 , and 1255 , respectively . The financial cost to the community for the management of atopic eczema in the study groups was greater . The personal financial cost of managing eczema was greater than for asthma . CONCLUSION Childhood atopic eczema has a profound impact on the social , personal , emotional , and financial perspectives of families Fifty‐three patients with atopic eczema took part in a double blind controlled cross‐over trial of an egg and cow 's milk exclusion diet . Response to the diet was assessed in terms of areas affected , day and night time itch , and topical steroid usage Over the last two decades the incidence of allergic diseases has increased in industrialized countries , and consequently new approaches have to be explored BACKGROUND The natural history of allergic disease and its potential for prevention merit close examination because of the explosive worldwide increase in the prevalence and morbidity of atopic disorders . This study examines the development of atopy at age 7 years in 165 children in a high-risk cohort , previously reported from birth to age 4 years . METHODS In this prospect i ve , r and omized , controlled study of food allergen avoidance in infancy , the prophylactic-treated group consisted of infants whose mothers avoided cow 's milk , egg , and peanut during the last trimester of pregnancy and lactation and who , themselves , avoided cow 's milk until age 1 year ( casein hydrolysate supplementation before age 1 ) , egg until age 2 years , and peanut and fish until age 3 years . The control group consisted of maternal/infant pairs who followed st and ard feeding practice s. RESULTS Despite a significant reduction in food allergy and milk sensitization before age 2 years , none of the following differed between the groups at age 7 years : food allergy , atopic dermatitis , allergic rhinitis , asthma , any atopic disease , lung function , food or aeroallergen sensitization , serum IgE level , or presence of nasal eosinophils or nasal basophilic cells . Children with food allergy by 4 years evidence d higher 7-year ( current ) prevalences of allergic rhinitis and asthma ( p < 0.01 ) . Atopic diseases/parameters at age 7 years were shown , by multivariate analysis ( p < 0.05 ) , to be associated with several genetic and environmental risk factors ( male gender , maternal nonwhite ethnicity and asthma , and household smoking ) , as well as predictive atopic markers during infancy ( elevated serum IgE level ; egg , cow 's milk , and peanut sensitization ; and nasal eosinophils and nasal basophilic cells ) . CONCLUSIONS These findings help to : ( 1 ) eluci date the natural history of atopic disease in high-risk children ; ( 2 ) document the progression of allergy from atopic dermatitis , food allergy , and food sensitization to respiratory allergy and aeroallergen sensitization despite food allergy prevention in infancy ; ( 3 ) identify allergy predictive markers ; and ( 4 ) exp and our appreciation of the interactions of genetic and environmental factors in the development of atopy While atopic dermatitis ( AD ) usually presents early in life , few prospect i ve studies focus on young children with AD . The objective of this study was to characterize , phenotypically and prospect ively , young children with AD . From a community birth cohort of 2,256 children , consecutive children with AD ( n = 221 ) were followed to 2 years of age , when they were re-examined and screened for atopic sensitization ( skin-prick test to foods ; Phadiatop ) . Ninety-nine controls were also examined . AD debuted during the first year in 88 % of cases . At the 2-year examination , when the children had already undergone topical treatment , 157/221 ( 71 % ) had ongoing eczema ranging among mild ( 45 % ) , moderate ( 53 % ) and severe ( 2 % ) . Airway problems indicating asthma had occurred in 9 % of cases and 6 % of controls ( not significant ) , and allergic rhinoconjunctivitis in 5 % and 0 % , respectively ( p<0.05 ) . The skin-prick test to common food allergens was positive in 27 % of cases and Phadiatop was positive in 15 % . In 67 % both tests were negative . Eczema severity did not differ between sensitized and non-sensitized children . Positive Phadiatop was more common in boys than in girls with ongoing AD ( 22 % vs 3 % , p<0.01 ) , and more boys than girls had ongoing AD ( 82 % vs 59 % , p<0.001 ) ; otherwise , no differences attributable to gender were found Cow 's milk and soy protein allergies are commonly associated with atopic dermatitis ( AD ) in young children . Amino acid (AA)-based elemental milk formula may improve AD control in these patients . This study investigates the efficacy of AA-based formula in treating young AD patients irrespective of their food allergy status . AD patients younger than 3 yr old were eligible . Sensitization to food allergens was ascertained by skin prick tests and allergen-specific immunoglobulin E ( IgE ) assay . Patients were then r and omly allocated to take either active treatment or pre-existing formulae ( placebo ) for 6 wk . They were allowed a 6-wk washout period before crossed over to the other intervention for another 6 wk . Fifteen AD patients , with median ( interquartile range , IQR ) age of 1.4 ( 0.6 - 2.6 ) yr , were recruited . Their median ( IQR ) SCORAD score was 23.9 ( 10.5 - 29.7 ) . Seven of them were sensitized to cow 's milk or soybean . Among 11 patients who completed the study , the median changes for all scores and urinary eosinophil protein X ( EPX ) concentration were not statistically significant . There was also no evidence of carry-over effects for SCORAD and its various components and global health score , except for urinary EPX concentration ( p = 0.05 ) . Our results do not support the use of AA-based elemental milk formula in treating young children with AD irrespective of their food allergy status BACKGROUND Little is known about the prevalence of atopic eczema outside Northern Europe . OBJECTIVES We sought to describe the magnitude and variation in the prevalence of atopic eczema symptoms throughout the world . METHODS A cross-sectional question naire survey was conducted on r and om sample s of schoolchildren aged 6 to 7 years Output:	There appears to be no benefit of an egg and milk free diet in unselected participants with atopic eczema . There is also no evidence of benefit in the use of an elemental or few-foods diet in unselected cases of atopic eczema . There may be some benefit in using an egg-free diet in infants with suspected egg allergy who have positive specific IgE to eggs . Little evidence supports the use of various exclusion diets in unselected people with atopic eczema , but that may be because they were not allergic to those substances in the first place .
MS21469	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Objectives The aim of this paper was to analyse the impact of obesity , in addition to known predictors , on disease outcome in early rheumatoid arthritis ( RA ) . Methods Body mass index ( BMI ) was available in 260 patients from the Swedish pharmacotherapy trial ( SWEFOT ) . Differences in disease activity ( DAS28 ) , functional impairment ( HAQ ) , pain ( Visual Analogue Scale , VAS-pain ) and radiographic damage were evaluated over 24 months between BMI categories ( obese BMI > 30 , n=43 ; overweight BMI = 25–29.9 , n=74 ; normal BMI < 25 , n=143 ) using non-parametric testing . Predictors of European League Against Rheumatism non-remission ( DAS28 ≥2.6 ) at 24 months of follow-up were evaluated using binary univariate and multivariate logistic regression . Results Obesity at baseline was associated with worse continuous-scale clinical outcomes over 24 months ( DAS28 , HAQ and VAS-pain at last visit : obese vs normal : p<0.001 ; obese vs overweight : p<0.05 ) . Furthermore , obese patients compared with non-obese patients had significantly greater odds of non-remission at 24 months ( adjusted OR ( aOR ) 5.2 ; 95 % CI 1.8 to 15.2 ) . Other independent predictors were female sex ( aOR 2.6 ; 95 % CI 1.1 to 5.8 ) , current smoking ( aOR 2.6 ; 95 % CI 1.1 to 6.3 ) and HAQ ( per-unit increase , aOR 1.9 ; 95 % CI 1.1 to 3.4 ) . The pattern was similar among seropositive and seronegative patients ; and in the subgroups of methotrexate responders and patients r and omised at 3 months to add-on of sulfasalazine+hydroxychloroquine , although not significant with add-on of infliximab . Obesity had no independent association to radiographic progression . Conclusions In this early RA trial reflecting today ’s st and ard treatment , obesity , in addition to sex , smoking and functional impairment strongly lowered the chance of attaining good clinical outcomes , including remission , today ’s treatment goal . This highlights the importance of considering lifestyle modification as one of the cornerstones of RA care . Trial registration number NCT00764725 ; Post- results . WHO data base at the Karolinska University Hospital : CT20080004 Objectives To evaluate prospect ively the effect of weight loss on the achievement of minimal disease activity ( MDA ) in overweight/obese patients with psoriatic arthritis ( PsA ) starting treatment with tumour necrosis factor α ( TNFα ) blockers . Methods Among subjects with PsA starting treatment with TNFα blockers , 138 overweight/obese patients received a concomitant dietary intervention ( 69 a hypocaloric diet ( HD ) and 69 a free-managed diet ( FD ) ) . Changes in metabolic variables were measured and a complete clinical rheumatological evaluation was made in all patients at baseline and after a 6-month follow-up to define the achievement of MDA . Results 126 subjects completed the study . MDA was more often achieved by HD than by FD subjects ( HR=1.85 , 95 % CI 1.019 to 3.345 , p=0.043 ) . A diet was successful ( ≥5 % weight loss ) in 74 ( 58.7 % ) patients . Regardless of the type of diet , after 6 months of treatment with TNFα blockers , ≥5 % of weight loss was a predictor of the achievement of MDA ( OR=4.20 , 95 % CI 1.82 to 9.66 , p<0.001 ) . For increasing weight-loss categories ( < 5 % , 5–10 % , > 10 % ) , MDA was achieved by 23.1 % , 44.8 % and 59.5 % , respectively . A higher rate of MDA achievement was found in subjects with 5–10 % ( OR=3.75 , 95 % CI 1.36 to 10.36 , p=0.011 ) and in those with > 10 % ( OR=6.67 , 95 % CI 2.41 to 18.41 , p<0.001 ) weight loss in comparison with those with < 5 % weight loss . Conclusions Regardless of the type of diet , a successful weight loss ( ≥5 % from baseline values ) is associated with a higher rate of achievement of MDA in overweight/obese patients with PsA who start treatment with TNFα blockers This post hoc analysis of ACQUIRE ( NCT00559585 ) explored the effect of baseline body mass index ( BMI ) on the pharmacokinetics of and clinical response to subcutaneous ( SC ) or intravenous ( IV ) abatacept in patients with rheumatoid arthritis ( RA ) . ACQUIRE was a phase 3b , 6-month , double-blind , double-dummy study in which patients with RA were r and omized ( 1:1 ) to SC ( fixed - dose ; 125 mg/week ) or IV ( weight-tiered ; ~ 10 mg/kg/month ) abatacept plus methotrexate . In this analysis , minimum abatacept plasma concentration ( Cmin ) was measured at 3 and 6 months , and clinical remission over 6 months was assessed by Disease Activity Score 28 ( C-reactive protein ; DAS28 [ CRP ] , < 2.6 ) , Simplified Disease Activity Index ( SDAI , ≤ 3.3 ) , and Clinical Disease Activity Index ( CDAI , ≤ 2.8 ) . Data were stratified by baseline BMI ( underweight/normal , < 25 kg/m2 ; overweight , 25 to < 30 kg/m2 ; obese , ≥ 30 kg/m2 ) and administration route . Of the 1456/1457 patients for whom baseline BMI s were available , 526 ( 36 % ; SC 265 , IV 261 ) patients were underweight/normal , 497 ( 34 % ; SC 249 , IV 248 ) were overweight , and 433 ( 30 % ; SC 221 , IV 212 ) were obese . Median Cmin abatacept concentration was ≥ 10 μg/mL ( efficacy threshold ) at 3 and 6 months in > 90 % of patients across BMI groups with both administration routes . DAS28 ( CRP ) , SDAI , and CDAI remission rates at 6 months were similar across BMI groups and 95 % confidence intervals overlapped at all time points in both separate and pooled SC/IV analyses . Therapeutic concentrations of abatacept and clinical remission rates using stringent criteria were similar across patient BMI s and administration routes Objective To evaluate the association between weight loss and rheumatoid arthritis ( RA ) disease activity . Methods We conducted a retrospective cohort study of RA patients seen at routine clinic visits at an academic medical center , 2012 - 2015 . We included patients who had ≥2 clinical disease activity index ( CDAI ) measures . We identified visits during follow-up where the maximum and minimum weights occurred and defined weight change and CDAI change as the differences of these measures at these visits . We defined disease activity improvement as CDAI decrease of ≥5 and clinical ly relevant weight loss as ≥5 kg . We performed logistic regression analyses to establish the association between improved disease activity and weight loss and baseline BMI category ( ≥25 kg/m2 or < 25 kg/m2 ) . We built linear regression models to investigate the association between continuous weight loss and CDAI change among patients who were overweight/obese at baseline and who lost weight during follow-up . Results We analyzed data from 174 RA patients with a median follow-up of 1.9 years ( IQR 1.3 - 2.4 ) ; 117 ( 67 % ) were overweight/obese at baseline , and 53 ( 31 % ) lost ≥5 kg during follow-up . Patients who were overweight/obese and lost ≥5 kg had three-fold increased odds of disease activity improvement compared to those who did not ( OR 3.03 , 95%CI 1.18 - 7.83 ) . Among those who were overweight/obese at baseline , each kilogram weight loss was associated with CDAI improvement of 1.15 ( 95%CI 0.42 - 1.88 ) . Our study was limited by using clinical data from a single center without fixed intervals for assessment s. Conclusion Clinical ly relevant weight loss ( ≥5 kg ) was associated with improved RA disease activity in the routine clinical setting . Further studies are needed for replication and to evaluate the effect of prospect i ve weight loss interventions on RA disease activity We prospect ively evaluated whether obesity impacts achievement of minimal disease activity ( MDA ) in subjects with psoriatic arthritis ( PsA ) Adalimumab is a fully human monoclonal antibody directed against tumor necrosis factor (TNF)-alpha , which is effective for the treatment of psoriasis and psoriatic arthritis ( PsA ) . The aim of this study is to determine whether the response of psoriasis to adalimumab treatment might be influenced by certain particular factors , such as body mass index ( BMI ) , history of biologic therapy , blood hypertension and metabolic comorbidities . For this reason , an exploratory analysis was conducted on 144 patients with psoriasis and concomitant PsA treated with adalimumab 40 mg every other week , evaluating the influence of such factors on the Psoriasis Area and Severity Index ( PASI ) response rate at week 12 . Our preliminary results suggest that the response rate at week 12 , in terms of both PASI-50 and PASI-75 , appeared to be independent of the presence of hypertension and /or metabolic comorbidities . The PASI-50 response was observed more frequently in patients with BMI less than 30 as compared to obese patients ( 79 % vs 58 % , p = 0.02 ) . Previous use of anti-TNF biologics did not appear to affect per se the rate of responders , although it was associated with a lower PASI-75 rate among responders OBJECTIVE Adipose tissue has immunomodulating effects in rheumatoid arthritis ( RA ) , although the exact role is , at present , unclear . The purpose of this study was to determine whether body mass index ( BMI ) affects response to infliximab in RA patients investigated prospect ively . METHODS In 89 patients with active RA , the BMI was calculated before initiation of infliximab treatment ( 3 mg/kg intravenously ) . After 16 weeks of treatment , changes in disease activity were assessed with the Disease Activity Score in 28 joints ( DAS28 ) . RESULTS The mean ± SD BMI was 26 ± 5 kg/m(2 ) ( range 17 - 42 ) . The BMI correlated positively with the DAS28 at baseline ( r = 0.34 , P = 0.001 ) . Since selection of study patients according to DAS28 values could influence the clinical response to tumor necrosis factor ( TNF ) blockade due to regression to the mean because the clinical response is itself based on the change in the DAS28 values , analysis of covariance was used to correct for the baseline DAS28 . A highly significant , negative association between the BMI and the absolute decrease in the DAS28 after 16 weeks ( P = 0.001 ) was found also when adjusted for anti-citrullinated protein antibodies . CONCLUSION Although the infliximab dosage is based on body weight , RA patients with a high BMI responded less well to infliximab , a finding that held true when adjusted for the baseline DAS28 or anti-citrullinated protein antibody status . These results support the notion that adipose tissue may be involved in the pathophysiology of RA and could have implication s for other immune-mediated inflammatory conditions treated with TNF antagonists OBJECTIVE To assess nutrient intakes and vitamin levels in 79 patients with rheumatoid arthritis participating in a trial and to determine whether changes in body mass index were associated with changes in disease activity . METHODS This study evaluated baseline vitamin levels , 1-day dietary intakes , and weight every 3 months for 1 year . Linear regression analysis was used to evaluate the relationship of time to body mass index . Analysis of covariance was used to determine if body mass index , time , or treatment had an effect on disease activity . RESULTS Deficient vitamin levels and poor nutrient intake patterns were prevalent in the study population . Changes in body mass index over time did not correlate with changes in disease activity . CONCLUSIONS Rheumatoid arthritis patients are at high risk of obesity , abnormal vitamin levels , and poor nutrient intakes . Changes in body mass index failed to correlate with changes in disease activity Introduction The excess of adipose tissue in obese individuals may have immunomodulating properties and pharmacokinetic consequences . The aim of this study was to determine whether body mass index ( BMI ) affects response to infliximab ( IFX ) in ankylosing spondylitis ( AS ) patients . Methods In 155 patients retrospectively included with active AS , the BMI was calculated before initiation of IFX treatment ( 5 mg/kg intravenously ) . After 6 months of treatment , changes from baseline in BASDAI , Visual Analogue Scale ( VAS Output:	Tumour necrosis factor-α inhibitors were mostly associated with negative outcomes .
MS21470	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: OBJECTIVE . Our goal was to test the effect of prenatal and infancy home visits by nurses on mothers ' fertility and children 's functioning 7 years after the program ended at child age 2 . METHODS . We conducted a r and omized , controlled trial in a public system of obstetric and pediatric care . A total of 743 primarily black women < 29 weeks ' gestation , with previous live births and at least 2 sociodemographic risk characteristics ( unmarried , < 12 years of education , unemployed ) , were r and omly assigned to receive nurse home visits or comparison services . Primary outcomes consisted of intervals between births of first and second children and number of children born per year ; mothers ' stability of relationships with partners and relationships with the biological father of the child ; mothers ' use of welfare , food stamps , and Medicaid ; mothers ' use of substances ; mothers ' arrests and incarcerations ; and children 's academic achievement , school conduct , and mental disorders . Secondary outcomes were the sequelae of subsequent pregnancies , women 's employment , experience of domestic violence , and children 's mortality . RESULTS . Nurse-visited women had longer intervals between births of first and second children , fewer cumulative subsequent births per year , and longer relationships with current partners . From birth through child age 9 , nurse-visited women used welfare and food stamps for fewer months . Nurse-visited children born to mothers with low psychological re sources , compared with control-group counterparts , had better grade -point averages and achievement test scores in math and reading in grade s 1 through 3 . Nurse-visited children , as a trend , were less likely to die from birth through age 9 , an effect accounted for by deaths that were attributable to potentially preventable causes . CONCLUSIONS . By child age 9 , the program reduced women 's rates of subsequent births , increased the intervals between the births of first and second children , increased the stability of their relationships with partners , facilitated children 's academic adjustment to elementary school , and seems to have reduced childhood mortality from preventable causes CONTEXT Home-visitation services have been promoted as a means of improving maternal and child health and functioning . However , long-term effects have not been examined . OBJECTIVE To examine the long-term effects of a program of prenatal and early childhood home visitation by nurses on women 's life course and child abuse and neglect . DESIGN R and omized trial . SETTING Semirural community in New York . PARTICIPANTS Of 400 consecutive pregnant women with no previous live births enrolled , 324 participated in a follow-up study when their children were 15 years old . INTERVENTION Families received a mean of 9 home visits during pregnancy and 23 home visits from the child 's birth through the second birthday . DATA SOURCES AND MEASURES : Women 's use of welfare and number of subsequent children were based on self-report ; their arrests and convictions were based on self-report and archived data from New York State . Verified reports of child abuse and neglect were abstract ed from state records . MAIN RESULTS During the 15-year period after the birth of their first child , in contrast to women in the comparison group , women who were visited by nurses during pregnancy and infancy were identified as perpetrators of child abuse and neglect in 0.29 vs 0.54 verified reports ( P<.001 ) . Among women who were unmarried and from households of low socioeconomic status at initial enrollment , in contrast to those in the comparison group , nurse-visited women had 1.3 vs 1.6 subsequent births ( P=.02 ) , 65 vs 37 months between the birth of the first and a second child ( P=.001 ) , 60 vs 90 months ' receiving Aid to Families With Dependent Children ( P=.005 ) , 0.41 vs 0.73 behavioral impairments due to use of alcohol and other drugs ( P=.03 ) , 0.18 vs 0.58 arrests by self-report ( P<.001 ) , and 0.16 vs 0.90 arrests disclosed by New York State records ( P<.001 ) . CONCLUSIONS This program of prenatal and early childhood home visitation by nurses can reduce the number of subsequent pregnancies , the use of welfare , child abuse and neglect , and criminal behavior on the part of low-income , unmarried mothers for up to 15 years after the birth of the first child OBJECTIVE The purpose of this study was to assess the contribution of depressive symptoms and poor contraceptive use early in the first postpartum year to the risk of unintended repeat pregnancy at the end of that year among adults with low educational status ( < 12th grade or equivalence ) . STUDY DESIGN This was a prospect i ve observational cohort study of 643 sexually active , low-income , inner-city adult women ( age > or = 19 ) who enrolled prenatally ( 14.7 + /- 6.9 weeks gestational age ) and were followed twice after delivery ( 3.3 + /- 1.3 months and 11.0 + /- 1.3 months ) . Associations were assessed by multivariate logistic regression . RESULTS Low educational status ( odds ratio , 2.32 ; 95 % CI , 1.25 - 4.33 ) and less effective contraceptive use ( odds ratio , 2.31 ; 95 % CI , 1.05 - 4.51 ) were associated with unintended pregnancy . Neither depressive symptoms nor contraceptive use reduced the risk of pregnancy that was associated with low educational status . CONCLUSION Low educational status was associated with more than twice the risk of unintended pregnancy 1 year after delivery . We found no evidence that depression or poor contraceptive use mediate this relationship OBJECTIVE To evaluate the efficacy and sustainability of a couple-focused human immunodeficiency virus ( HIV ) prevention intervention in reducing unprotected sex and increasing intent to use condoms and knowledge about AIDS . DESIGN R and omized controlled trial . SETTING Urban community setting s in Southern California . PARTICIPANTS Primarily Latino couples ( 168 couples ; 336 individuals ) who were aged 14 to 25 years , English or Spanish speaking , and coparenting a child at least 3 months of age . INTERVENTION A 12-hour theory-based , couple-focused HIV prevention program culturally tailored for young Latino parents , with emphasis on family protection , skill building , and issues related to gender and power . The 1½-hour control condition provided basic HIV-AIDS information . MAIN OUTCOME MEASURES Primary outcome measures included self-report of condom use during the past 3 months ; secondary , intent to use condoms and knowledge about AIDS . RESULTS The HIV prevention intervention reduced the proportion of unprotected sex episodes ( odds ratio , 0.87 per month from baseline to 6 months ; 95 % confidence interval [ CI ] , 0.82 - 0.93 ) and increased intent to use condoms ( slope increase , 0.20 ; 95 % CI , 0.04 - 0.37 ) at the 6-month follow-up ; however , these effects were not sustained at 12 months . Knowledge about AIDS was increased in both groups from baseline to 6 months ( slope estimate , 0.57 ; 95 % CI , 0.47 - 0.67 ) and was maintained in the intervention group only through 12 months . Female participants in both groups had higher intent to use condoms and knowledge about AIDS than male participants ( P ≤ .01 ) . CONCLUSIONS The couple-focused HIV prevention intervention reduced risky sexual behaviors and improved intent to use condoms among young Latino parents at the 6-month evaluation . A maintenance program is needed to improve the sustainability of effects over time CONTEXT Women with multiple pregnancies in adolescence may experience medical , psychological and social complications . Improved underst and ing of the individual- , dyad- , family- , peer/community- and social system-level risk factors for repeat pregnancy may lead to the development of more effective prevention strategies for adolescent mothers in a variety of setting s. METHODS Between 1993 and 1996 , white , black and Mexican American adolescent mothers at a labor and delivery unit in Texas were interviewed after delivery and completed written surveys prospect ively for up to 48 months . Logistic regression analyses were used to determine predictors of repeat pregnancy within 24 months , using social ecological theory as a guide . RESULTS Forty-two percent of adolescent mothers experienced a repeat pregnancy within 24 months ; 73 % of these delivered a second child . Individual-level predictors were planning to have another baby within five years ( odds ratio , 1.6 ) and not using long-acting contraceptives within three months of delivery ( 2.4 ) . Dyad-level predictors were not being in a relationship with the father of the first child three months after delivery ( 2.0 ) , being more than three years younger than the first child 's father ( 1.6 ) and experiencing intimate partner violence within three months after delivery ( 1.9 ) . Peer/community-level predictors were not being in school three months postpartum ( 1.8 ) and having many friends who were adolescent parents ( 1.5 ) . CONCLUSION Adolescent mothers are at high risk for a rapid subsequent pregnancy . Interventions that address the complex and multifaceted aspects of the lives of adolescent mothers are needed to prevent repeat pregnancy OBJECTIVE To examine the effectiveness of home visiting by paraprofessionals and by nurses as separate means of improving maternal and child health when both types of visitors are trained in a program model that has demonstrated effectiveness when delivered by nurses . METHODS A r and omized , controlled trial was conducted in public- and private-care setting s in Denver , Colorado . One thous and one hundred seventy-eight consecutive pregnant women with no previous live births who were eligible for Medicaid or who had no private health insurance were invited to participate . Seven hundred thirty-five women were r and omized to control , paraprofessional , or nurse conditions . Nurses completed an average of 6.5 home visits during pregnancy and 21 visits from birth to the children 's second birthdays . Paraprofessionals completed an average of 6.3 home visits during pregnancy and 16 visits from birth to the children 's second birthdays . The main outcomes consisted of changes in women 's urine cotinine over the course of pregnancy ; women 's use of ancillary services during pregnancy ; subsequent pregnancies and births , educational achievement , workforce participation , and use of welfare ; mother-infant responsive interaction ; families ' home environments ; infants ' emotional vulnerability in response to fear stimuli and low emotional vitality in response to joy and anger stimuli ; and children 's language and mental development , temperament , and behavioral problems . RESULTS Paraprofessional-visited mother-child pairs in which the mother had low psychological re sources interacted with one another more responsively than their control-group counterparts ( 99.45 vs 97.54 st and ard score points ) . There were no other statistically significant paraprofessional effects . In contrast to their control-group counterparts , nurse-visited smokers had greater reductions in cotinine levels from intake to the end of pregnancy ( 259.0 vs 12.32 ng/mL ) ; by the study child 's second birthday , women visited by nurses had fewer subsequent pregnancies ( 29 % vs 41 % ) and births ( 12 % vs 19 % ) ; they delayed subsequent pregnancies for longer intervals ; and during the second year after the birth of their first child , they worked more than women in the control group ( 6.83 vs 5.65 months ) . Nurse-visited mother-child pairs interacted with one another more responsively than those in the control group ( 100.31 vs 98.99 st and ard score points ) . At 6 months of age , nurse-visited infants , in contrast to their control-group counterparts , were less likely to exhibit emotional vulnerability in response to fear stimuli ( 16 % vs 25 % ) and nurse-visited infants born to women with low psychological re sources were less likely to exhibit low emotional vitality in response to joy and anger stimuli ( 24 % vs 40 % and 13 % vs 33 % ) . At 21 months , nurse-visited children born to women with low psychological re sources were less likely to exhibit language delays ( 7 % vs 18 % ) ; and at 24 months , they exhibited superior mental development ( 90.18 vs 86.20 Mental Development Index scores ) than their control-group counterparts . There were no statistically significant program effects for the nurses on women 's use of ancillary prenatal services , educational achievement , use of welfare , or their children 's temperament or behavior problems . For most outcomes on which either visitor produced significant effects , the paraprofessionals typically had effects that were about half the size of those produced by nurses . CONCLUSIONS When trained in a model program of prenatal and infancy home visiting , paraprofessionals produced small effects that rarely achieved statistical or clinical significance ; the absence of statistical significance for some outcomes is probably attributable to limited statistical power to detect small effects . Nurses produced significant effects on a wide range of maternal and child outcomes PURPOSE To compare effects of an early intervention program ( EIP ) of intense home visitation by public health nurses ( PHNs ) with effects of traditional public health nursing care ( TPHN ) on infant health and selected maternal outcomes of adolescent mothers . METHODS EIP adolescents ( N = 102 ) received preparation-for-motherhood classes and individual home visits ( from pregnancy through 1 year postpartum ) from PHNs employed in a county Output:	DISCUSSION Effective programs to support expectant and parenting teens have diverse characteristics , indicating there is no single approach for promoting teens ' education and healthy birth spacing .
MS21471	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Objective : For patients in intensive care units , sepsis is a common and potentially deadly complication and prompt initiation of appropriate antimicrobial therapy improves prognosis . The objective of this trial was to determine whether a strategy of antimicrobial spectrum escalation , guided by daily measurements of the biomarker procalcitonin , could reduce the time to appropriate therapy , thus improving survival . Design : R and omized controlled open-label trial . Setting : Nine multidisciplinary intensive care units across Denmark . Patients : A total of 1,200 critically ill patients were included after meeting the following eligibility requirements : expected intensive care unit stay of ≥24 hrs , nonpregnant , judged to not be harmed by blood sampling , bilirubin < 40 mg/dL , and triglycerides < 1000 mg/dL ( not suspensive ) . Interventions : Patients were r and omized either to the “ st and ard-of-care-only arm , ” receiving treatment according to the current international guidelines and blinded to procalcitonin levels , or to the “ procalcitonin arm , ” in which current guidelines were supplemented with a drug-escalation algorithm and intensified diagnostics based on daily procalcitonin measurements . Measurements and Main Results : The primary end point was death from any cause at day 28 ; this occurred for 31.5 % ( 190 of 604 ) patients in the procalcitonin arm and for 32.0 % ( 191 of 596 ) patients in the st and ard-of-care-only arm ( absolute risk reduction , 0.6 % ; 95 % confidence interval [ CI ] −4.7 % to 5.9 % ) . Length of stay in the intensive care unit was increased by one day ( p = .004 ) in the procalcitonin arm , the rate of mechanical ventilation per day in the intensive care unit increased 4.9 % ( 95 % CI , 3.0–6.7 % ) , and the relative risk of days with estimated glomerular filtration rate < 60 mL/min/1.73 m2 was 1.21 ( 95 % CI , 1.15–1.27 ) . Conclusions : Procalcitonin-guided antimicrobial escalation in the intensive care unit did not improve survival and did lead to organ-related harm and prolonged admission to the intensive care unit . The procalcitonin strategy like the one used in this trial can not be recommended IMPORTANCE Sepsis is considered to induce immune suppression , leading to increased susceptibility to secondary infections with associated late mortality . OBJECTIVE To determine the clinical and host genomic characteristics , incidence , and attributable mortality of intensive care unit (ICU)-acquired infections in patients admitted to the ICU with or without sepsis . DESIGN , SETTING , AND PARTICIPANTS Prospect i ve observational study comprising consecutive admissions of more than 48 hours in 2 ICUs in the Netherl and s from January 2011 to July 2013 stratified according to admission diagnosis ( sepsis or noninfectious ) . MAIN OUTCOMES AND MEASURES The primary outcome was ICU-acquired infection ( onset > 48 hours ) . Attributable mortality risk ( fraction of mortality that can be prevented by elimination of the risk factor , acquired infection ) was determined using time-to-event models accounting for competing risk . In a subset of sepsis admissions ( n = 461 ) , blood gene expression ( whole-genome transcriptome in leukocytes ) was analyzed at baseline and at onset of ICU-acquired infectious ( n = 19 ) and noninfectious ( n = 9 ) events . RESULTS The primary cohort included 1719 sepsis admissions ( 1504 patients ; median age , 62 years ; interquartile range [ IQR ] , 51 - 71 years ] ; 924 men [ 61.4 % ] ) . A comparative cohort included 1921 admissions ( 1825 patients , median age , 62 years ; IQR , 49 - 71 years ; 1128 men [ 61.8 % ] in whom infection was not present in the first 48 hours . Intensive care unit-acquired infections occurred in 13.5 % of sepsis ICU admissions ( n = 232 ) and 15.1 % of nonsepsis ICU admissions ( n = 291 ) . Patients with sepsis who developed an ICU-acquired infection had higher disease severity scores on admission than patients with sepsis who did not develop an ICU-acquired infection ( Acute Physiology and Chronic Health Evaluation IV [ APACHE IV ] median score , 90 [ IQR , 72 - 107 ] vs 79 [ IQR , 62 - 98 ] ; P < .001 ) and throughout their ICU stay but did not have differences in baseline gene expression . The population attributable mortality fraction of ICU-acquired infections in patients with sepsis was 10.9 % ( 95 % CI , 0.9%-20.6 % ) by day 60 ; the estimated difference between mortality in all patients with a sepsis admission diagnosis and mortality in those without ICU-acquired infection was 2.0 % ( 95 % CI , 0.2%-3.8 % ; P = .03 ) by day 60 . Among nonsepsis ICU admissions , ICU-acquired infections had a population attributable mortality fraction of 21.1 % ( 95 % CI , 0.6%-41.7 % ) by day 60 . Compared with baseline , blood gene expression at the onset of ICU-acquired infections showed reduced expression of genes involved in gluconeogenesis and glycolysis . CONCLUSIONS AND RELEVANCE Intensive care unit-acquired infections occurred more commonly in patients with sepsis with higher disease severity , but such infections contributed only modestly to overall mortality . The genomic response of patients with sepsis was consistent with immune suppression at the onset of secondary infection Purpose The optimal treatment duration for ventilator-associated pneumonia is based on one study dealing with late-onset of the condition . Shortening the length of antibiotic treatment remains a major prevention factor for the emergence of multiresistant bacteria . Objective To demonstrate that 2 different antibiotic treatment duration s ( 8 versus 15 days ) are equivalent in terms of clinical cure for early-onset ventilator-associated pneumonia . Methods R and omized , prospect i ve , open , multicenter trial carried out from 1998 to 2002 . Measurements The primary endpoint was the clinical cure rate at day 21 . The mortality rate was evaluated on days 21 and 90 . Results 225 patients were included in 13 centers . 191 ( 84.9 % ) patients were cured : 92 out of 109 ( 84.4 % ) in the 15 day cohort and 99 out of 116 ( 85.3 % ) in the 8 day cohort ( difference = 0.9 % , odds ratio = 0.929 ) . 95 % two-sided confidence intervals for difference and odds ratio were [ −8.4 % to 10.3 % ] and [ 0.448 to 1.928 ] respectively . Taking into account the limits of equivalence ( 10 % for difference and 2.25 for odds ratio ) , the objective of demonstrative equivalence between the 2 treatment duration s was fulfilled . Although the rate of secondary infection was greater in the 8 day than the 15 day cohort , the number of days of antibiotic treatment remained lower in the 8 day cohort . There was no difference in mortality rate between the 2 groups on days 21 and 90 . Conclusion Our results suggest that an 8-day course of antibiotic therapy is safe for early-onset ventilator-associated pneumonia in intubated patients . Trial Registration Clinical Trials.gov 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 Introduction The development of resistance by bacterial species is a compelling issue to reconsider indications and administration of antibiotic treatment . Adequate indications and duration of therapy are particularly important for the use of highly potent substances in the intensive care setting . Until recently , no laboratory marker has been available to differentiate bacterial infection from viral or non-infectious inflammatory reaction ; however , over the past years , procalcitonin ( PCT ) is the first among a large array of inflammatory variables that offers this possibility . The present study aim ed to investigate the clinical usefulness of PCT for guiding antibiotic therapy in surgical intensive care patients . Methods All patients requiring antibiotic therapy based on confirmed or highly suspected bacterial infections and at least two concomitant systemic inflammatory response syndrome criteria were eligible . Patients were r and omly assigned to either a PCT-guided ( study group ) or a st and ard ( control group ) antibiotic regimen . Antibiotic therapy in the PCT-guided group was discontinued , if clinical signs and symptoms of infection improved and PCT decreased to < 1 ng/ml or the PCT value was > 1 ng/ml , but had dropped to 25 to 35 % of the initial value over three days . In the control group antibiotic treatment was applied as st and ard regimen over eight days . Results A total of 110 surgical intensive care patients receiving antibiotic therapy after confirmed or high- grade suspected infections were enrolled in this study . In 57 patients antibiotic therapy was guided by daily PCT and clinical assessment and adjusted accordingly . The control group comprised 53 patients with a st and ardized duration of antibiotic therapy over eight days . Demographic and clinical data were comparable in both groups . However , in the PCT group the duration of antibiotic therapy was significantly shorter than compared to controls ( 5.9 + /- 1.7 versus 7.9 + /- 0.5 days , P < 0.001 ) without negative effects on clinical outcome . Conclusions Monitoring of PCT is a helpful tool for guiding antibiotic treatment in surgical intensive care patients . This may contribute to an optimized antibiotic regimen with beneficial effects on microbial resistance and costs in intensive care medicine . Annotation Results were previously published in German in Anaesthesist 2008 ; 57 : 571–577 ( PMID : 18463831).Trial registration IS RCT Objective : We sought to evaluate whether procalcitonin was superior to C-reactive protein in guiding antibiotic therapy in intensive care patients with sepsis . Design : R and omized open clinical trial . Setting : Two university hospitals in Brazil . Patients : Patients with severe sepsis or septic shock . Interventions : Patients were r and omized in two groups : the procalcitonin group and the C-reactive protein group . Antibiotic therapy was discontinued following a protocol based on serum levels of these markers , according to the allocation group . The procalcitonin group was considered superior if the duration of antibiotic therapy was at least 25 % shorter than in the C-reactive protein group . For both groups , at least seven full-days of antibiotic therapy were ensured in patients with Sequential Organ Failure Assessment greater than 10 and /or bacteremia at inclusion , and patients with evident resolution of the infectious process had antibiotics stopped after 7 days , despite biomarkers levels . Measurements and Main Results : Ninety-four patients were r and omized : 49 patients to the procalcitonin group and 45 patients to the C-reactive protein group . The mean age was 59.8 ( SD , 16.8 ) years . The median duration of antibiotic therapy for the first episode of infection was 7.0 ( Q1–Q3 , 6.0–8.5 ) days in the procalcitonin group and 6.0 ( Q1–Q3 , 5.0–7.0 ) days in the C-reactive protein group ( p = 0.13 ) , with a hazard ratio of 1.206 ( 95 % CI , 0.774–1.3 ; p = 0.13 ) . Overall , protocol overruling occurred in only 13 ( 13.8 % ) patients . Twenty-one patients died in each group ( p = 0.836 ) . Conclusions : C-reactive protein was as useful as procalcitonin in reducing antibiotic use in a predominantly medical population of septic patients , causing no apparent Objective Some patients with the phenotype of severe sepsis may have no overt source of infection or identified pathogen . We investigated whether a procalcitonin-based algorithm influenced antibiotic use in patients with non-microbiologically proven apparent severe sepsis . Design This multicentre , r and omised , controlled , single-blind trial was performed in two parallel groups . Setting Eight intensive care units in France . Participants Adults with the phenotype of severe sepsis and no overt source of infection , negative microbial cultures from multiple matrices and no antibiotic exposure shortly before intensive care unit admission . Intervention The initiation and duration of antibiotic therapy was based on procalcitonin levels in the experimental arm and on the intensive care unit physicians ’ clinical judgement without reference to procalcitonin values in the control arm . Main outcome measure The primary outcome was the proportion of patients on antibiotics on day 5 postr and omisation . Results Over a 3-year period Output:	Conclusions : Although the duration of antibiotic therapy is reduced with procalcitonin-guided therapy or prespecified limited duration , meta- analysis and trial sequential analyses are inconclusive for mortality benefit .
MS21472	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: BACKGROUND Since inflammation is believed to have a role in the pathogenesis of cardiovascular events , measurement of markers of inflammation has been proposed as a method to improve the prediction of the risk of these events . METHODS We conducted a prospect i ve , nested case-control study among 28,263 apparently healthy postmenopausal women over a mean follow-up period of three years to assess the risk of cardiovascular events associated with base-line levels of markers of inflammation . The markers included high-sensitivity C-reactive protein ( hs-CRP ) , serum amyloid A , interleukin-6 , and soluble intercellular adhesion molecule type 1 ( sICAM-1 ) . We also studied homocysteine and a variety of lipid and lipoprotein measurements . Cardiovascular events were defined as death from coronary heart disease , nonfatal myocardial infa rct ion or stroke , or the need for coronary-revascularization procedures . RESULTS Of the 12 markers measured , hs-CRP was the strongest univariate predictor of the risk of cardiovascular events ; the relative risk of events for women in the highest as compared with the lowest quartile for this marker was 4.4 ( 95 percent confidence interval , 2.2 to 8.9 ) . Other markers significantly associated with the risk of cardiovascular events were serum amyloid A ( relative risk for the highest as compared with the lowest quartile , 3.0 ) , sICAM-1 ( 2.6 ) , interleukin-6 ( 2.2 ) , homocysteine ( 2.0 ) , total cholesterol ( 2.4 ) , LDL cholesterol ( 2.4 ) , apolipoprotein B-100 ( 3.4 ) , HDL cholesterol ( 0.3 ) , and the ratio of total cholesterol to HDL cholesterol ( 3.4 ) . Prediction models that incorporated markers of inflammation in addition to lipids were significantly better at predicting risk than models based on lipid levels alone ( P<0.001 ) . The levels of hs-CRP and serum amyloid A were significant predictors of risk even in the subgroup of women with LDL cholesterol levels below 130 mg per deciliter ( 3.4 mmol per liter ) , the target for primary prevention established by the National Cholesterol Education Program . In multivariate analyses , the only plasma markers that independently predicted risk were hs-CRP ( relative risk for the highest as compared with the lowest quartile , 1.5 ; 95 percent confidence interval , 1.1 to 2.1 ) and the ratio of total cholesterol to HDL cholesterol ( relative risk , 1.4 ; 95 percent confidence interval , 1.1 to 1.9 ) . CONCLUSIONS The addition of the measurement of C-reactive protein to screening based on lipid levels may provide an improved method of identifying persons at risk for cardiovascular events One hundred fifteen college students were exposed to an evaluative speech task twice , separated by 2 weeks . At both sessions , we assessed cardiovascular , endocrine , immune , and psychological response at baseline and during the task . We found stability across sessions for stress-induced increases in anxiety and task engagement , heart rate , blood pressure , norpinephrine ( but not epinephrine ) , cortisol , natural killer cell cytotoxicity , and numbers of circulating CD3 + , CD8 + , and CD56 + ( but not CD4 + or CD19 + ) lymphocytes . The stable cardiovascular , immune , and endocrine reactivities were intercorrelated , providing evidence of a unified physiological stress response across these outcomes . Although stable stress-induced increases in task engagement were associated with the physiological stress responses , stress-induced anxiety was not Acute psychosocial stress stimulates transient increases in circulating pro-inflammatory plasma cytokines , but little is known about stress effects on anti-inflammatory cytokines or underlying mechanisms . We investigated the stress kinetics and interrelations of pro- and anti-inflammatory measures on the transcriptional and protein level . Forty-five healthy men were r and omly assigned to either a stress or control group . While the stress group underwent an acute psychosocial stress task , the second group participated in a non-stress control condition . We repeatedly measured before and up to 120min after stress DNA binding activity of the pro-inflammatory transcription factor NF-κB ( NF-κB-BA ) in peripheral blood mononuclear cells , whole-blood mRNA levels of NF-κB , its inhibitor IκBα , and of the pro-inflammatory cytokines interleukin (IL)-1ß and IL-6 , and the anti-inflammatory cytokine IL-10 . We also repeatedly measured plasma levels of IL-1ß , IL-6 , and IL-10 . Compared to non-stress , acute stress induced significant and rapid increases in NF-κB-BA and delayed increases in plasma IL-6 and mRNA of IL-1ß , IL-6 , and IκBα ( p's<.045 ) . In the stress group , significant increases over time were also observed for NF-κB mRNA and plasma IL-1ß and IL-10 ( p's<.055 ) . NF-κB-BA correlated significantly with mRNA of IL-1β ( r=.52 , p=.002 ) , NF-κB ( r=.48 , p=.004 ) , and IκBα ( r=.42 , p=.013 ) , and marginally with IL-6 mRNA ( r=.31 , p=.11 ) . Plasma cytokines did not relate to NF-κB-BA or mRNA levels of the respective cytokines . Our data suggest that stress induces increases in NF-κB-BA that relate to subsequent mRNA expression of pro-inflammatory , but not anti-inflammatory cytokines , and of regulatory-cytoplasmic-proteins . The stress-induced increases in plasma cytokines do not seem to derive from de novo synthesis in circulating blood cells Effects of three experimental manipulations : mental stress , relaxation , and a nociceptive inflammatory stimulus , capsaicin , on levels of interleukin-6 ( IL-6 ) were examined . Fifty subjects were pre-trained in relaxation and then r and omized to a stress ( Stroop test ) , relaxation ( tape ) , or control ( video ) manipulation . Subjects participated in an evening reactivity session including 20 min of stress , relaxation , or control followed by a capsaicin injection in the forearm . Cardiovascular variables and levels of IL-6 were measured before and after the manipulation , and at regular intervals up to 60 min post-capsaicin . Group assignment did not differentially affect change in IL-6 over time , either before or after capsaicin . Small but significant increases in IL-6 were seen at 60 min post-capsaicin . These findings suggest that an acute stress manipulation does not modulate IL-6 within this time frame . Although IL-6 did increase following a neurogenic inflammatory stimulus , it did so subsequent to the maximum flare , suggesting that flare mechanisms are independent of IL-6 The pathophysiological mechanisms underlying the association between psychological stress and cardiovascular disease are unclear . Interleukin-1beta ( IL-1beta ) and interleukin-6 ( IL-6 ) are inflammatory cytokines playing a pivotal role in atherosclerosis . IL-1beta activates IL-6 , and both cytokines are produced by peripheral blood mononuclear cells . One mechanism through which stress could promote atherosclerosis is by regulating mononuclear cell cytokine gene expression . We studied cardiovascular and cytokine responses in 32 healthy men participating in two 5-min mental tasks and in 10 controls . Blood pressure and heart rate , assessed using a Portapres-2 , increased significantly following tasks in all participants . Plasma IL-6 levels , determined by ELISA , also increased following tasks , with maximum levels detected 2h post-stress . Quantitative RT-PCR analysis showed that mononuclear cell IL-1beta gene expression rose significantly at 30 min post-stress and remained elevated at 75 and 120 min . Increases in IL-1beta gene expression correlated positively with plasma IL-6 responses , cardiovascular responses , subjective stress ratings , and anxiety symptoms . No changes were detected in controls . Stress-induced activation of mononuclear IL-1beta is a novel mechanism potentially linking stress and heart disease . This mechanism could also play a role in other inflammatory diseases exacerbated by stress The mechanisms of stress-related immune alterations have not been fully eluci date d. Cell-mediated immune responses as well as antibody and certain cytokines are reported as being suppressed during times of high stress . However , the role of suppression vs dysregulation has not been established in human stress models . The effect of exam stress on regulatory cytokines in 16 healthy medical students was assessed by measuring type-1 ( IFN-gamma ) and type-2 ( IL-10 ) cytokines from 72-h PHA/PMA-stimulated P BMC 4 weeks before and 48 h after exams . Results demonstrated decreased IFN-gamma accompanied by increased IL-10 during exam stress that result ed in a decreased IFN-gamma : IL-10 ratio . There was a significant correlation between the cytokine response to PHA/PMA and number and subjective adjustment to daily hassles . Additionally , students who reported greater levels of loneliness also reported greater numbers of and poorer subjective adjustment to hassles . The differences were consistent in both males and females but did not correlate with AM cortisol levels . Additionally , when individuals were grouped into high vs low preexam hassle levels , the type-1/type-2 shift in the IFN-gamma : IL-10 ratio occurred in the low hassles group only . These data suggest that psychologically stressful situations shift type-1/type-2 cytokine balance toward type-2 and result in an immune dysregulation rather than overall immunosuppression . This may partially explain the increased incidence of type-2-mediated conditions such as increased viral infections , latent viral expression , allergic/asthmatic reactions , and autoimmunity reported during periods of high stress Output:	These results extend findings from a prior meta- analysis ( Steptoe et al. , 2007 ) to show reliable increases in circulating IL-6 , IL-1β , IL-10 and TNF-α and stimulated IL-1β , IL-4 and interferon-γ in response to acute stress . It is possible that these responses contribute to associations between exposure to life challenges and vulnerability to inflammatory disease
MS21473	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: 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 Background Soil-transmitted helminth ( STH ) infections are a public health problem in re source -limited setting s worldwide . Chronic STH infection impairs optimum learning and productivity , contributing to the perpetuation of the poverty-disease cycle . Regular massive drug administration ( MDA ) is the cardinal recommendation for its control ; along with water , sanitation and hygiene ( WASH ) interventions . The impact of joint WASH interventions on STH infections has been reported ; studies on the independent effect of WASH components are needed to contribute with the improvement of current recommendations for the control of STH . The aim of this study is to assess the association of lacking access to water and sanitation with STH infections , taking into account the differences in route of infection among species and the availability of adequate water and sanitation at home . Methods and Findings Cross-sectional study , conducted in Salta province , Argentina . During a deworming program that enrolled 6957 individuals ; 771 were r and omly selected for stool/serum sampling for parasitological and serological diagnosis of STH . Bivariate stratified analysis was performed to explore significant correlations between risk factors and STH infections grouped by mechanism of entry as skin-penetrators ( hookworms and Strongyloides stercoralis ) vs. orally-ingested ( Ascaris lumbricoides and Trichuris trichiura ) . After controlling for potential confounders , unimproved sanitation was significantly associated with increased odds of infection of skin-penetrators ( adjusted odds ratio [ aOR ] = 3.9 ; 95 % CI : 2.6–5.9 ) . Unimproved drinking water was significantly associated with increased odds of infection of orally-ingested ( aOR = 2.2 ; 95 % CI : 1.3–3.7 ) . Conclusions Lack of safe water and proper sanitation pose a risk of STH infections that is distinct according to the route of entry to the human host used by each of the STH species . Interventions aim ed to improve water and sanitation access should be highlighted in the recommendations for the control of STH A water quality intervention that consists of water treatment , safe storage , and community education was field tested in Kitwe , Zambia . A total of 166 intervention households were r and omly selected from one community and 94 control households from another . Baseline surveys were conducted and the intervention was distributed . Weekly active diarrhea surveillance , biweekly water testing , and a follow-up survey were conducted . Compliance was high in intervention households : 97 % reported using disinfectant and 72 - 95 % had measurable chlorine in their water in biweekly testing . The percentage of intervention households storing water safely increased from 41.5 % to 89.2 % . Stored water in intervention households was significantly less contaminated with Escherichia coli than water in control households ( P < 0.001 ) . Diarrheal disease risk for individuals in intervention households was 48 % lower than for controls ( 95 % confidence interval = 0.3 , 0.9 ) . This intervention is a useful tool for preventing waterborne diseases in families in developing countries who lack access to potable water 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 ' In Indonesia , where diarrhea remains a major cause of mortality among children < 5 years , the government promotes boiling of drinking water . We assessed the impact of boiling on water quality in South Sulawesi . We surveyed r and omly selected households with at least one child < 5 years old in two rural districts and tested source and stored water sample s for Escherichia coli contamination . Among 242 households , 96 % of source and 51 % of stored water sample s yielded E. coli . Unboiled water sample s , obtained from 15 % of households , were more likely to yield E. coli than boiled sample s [ prevalence ratios ( PR ) = 2.0 , 95 % confidence interval ( CI ) 1.7 - 2.5 ] . Water stored in wide-mouthed ( PR = 1.4 , 95 % CI = 1.1 - 1.8 ) or uncovered ( PR = 1.8 , 95 % CI = 1.3 - 2.4 ) containers , or observed to be touched by the respondent 's h and s ( PR = 1.6 , 95 % CI = 1.3 - 2.1 ) was more likely to yield E. coli . A multivariable model showed that households that did not boil water were more likely to have contaminated stored water than households that did boil water ( PR = 1.9 , 95 % CI = 1.5 - 2.3 ) . Although this study demonstrated the effectiveness of boiling in reducing contamination , overall impact on water quality was suboptimal . Future studies are needed to identify factors behind the success of boiling water in Indonesia to inform efforts to scale up other effective water treatment practice 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 In response to a recorded increasing incidence of diarrhoea in Tumpat District , Malaysia , a case-control study was performed to identify modifiable risk factors for the transmission of diarrhoea , in children aged 4 - 59 months . Ninety-eight pairs of children , matched on age and sex , were recruited prospect ively from health centres . Exposure status was determined during a home visit . Interviewers were ' blinded ' as to the disease status of each child . Odds ratios were measured through matched pair analysis and conditional logistic regression . Risk factors for diarrhoea identified were : reported -- drinking of unboiled water , storage of cooked food before consumption and bottle feeding ; and observations -- animals inside the house and absence of washing water in latrines . Water quality , source of drinking water , reported h and washing behaviour , indiscriminate defecation by children , cup use and the absence of a functional latrine were not associated with diarrhoea . Nonsignificant associations were found for : accessibility of washing water source , type of water storage container and use of fly covers for food The risk factors for acquisition of cryptosporidial infection in re source -poor setting s are poorly understood . A nested case-control study was conducted to assess factors associated with childhood cryptosporidiosis ( detected by stool polymerase chain reaction ) in an endemic , Indian slum community using data from two community-based studies with 580 children followed prospect ively until their second birthday . Factors were assessed for overall cryptosporidiosis ( N = 406 ) , and for multiple ( N = 208 ) , asymptomatic ( N = 243 ) , and symptomatic ( N = 163 ) infections , respectively . Presence of older siblings ( odds ratio [ OR ] = 1.88 , P = 0.002 ) and stunting at 6 months of age ( OR = 1.74 , P = 0.019 ) were important risk factors for childhood cryptosporidiosis . Always boiling drinking water before consumption , the use of a toilet by all members of the family , and maternal age ≥ 23 years were protective . These results provide insights into acquisition of childhood cryptosporidiosis in setting s with poor environmental sanitation , contaminated public water supply systems , and close human-animal contact . Disease control strategies will require a multifaceted approach 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 ( Output:	Although our study was limited by the use of self-reported boiling and non-experimental design s , the evidence suggests that boiling provides measureable health benefits for pathogens whose transmission routes are primarily water based .
MS21474	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: BACKGROUND Multiple clinical , biologic , and pathologic factors are known to correlate with outcome in patients with invasive breast cancer . The utility of lymphovascular invasion as an additional useful prognostic indicator has been heretofore ill defined . The purpose of the current study was to determine whether the presence or absence of peritumoral lymphovascular invasion ( LVI ) contribute further significant information in assessing survival . METHODS Using a prospect i ve data base of 1,258 patients with invasive breast cancer followed up for as long as 12 years , eight factors were evaluated for their impact on patient survival : lymph node status , LVI , age at diagnosis , tumor size , tumor palpability , estrogen and progesterone receptor status , and nuclear grade . RESULTS Multivariate analysis revealed that both lymph node status and the presence or absence of LVI were highly significant independent predictors of outcome . CONCLUSIONS Knowledge of both lymph node status and the presence or absence of LVI can be used to predict which subset of patients will do extremely well ( node negative + LVI absent ) or extremely poorly ( node positive + LVI present ) . The combination of the two factors is most meaningful in patients with 1 to 3 positive nodes PURPOSE To prospect ively assess potential risk factors for relapse in clinical stage I nonseminomatous germ cell tumors of the testis ( CS I NSGCT ) . PATIENTS AND METHODS From September 1996 to May 2002 , 200 patients with CS I NSGCT were prospect ively assigned to retroperitoneal lymph node dissection ( RPLND ) , and risk factor assessment was performed within a multicenter protocol . One hundred sixty-five patients had an adequate minimum follow-up of 12 months ( mean , 34.5 months ) or had pathologic stage II . RESULTS Pathologic stage II disease was found in 27.9 % of patients . Only 0.6 % of patients relapsed in the retroperitoneum after confirmation of pathologic stage I disease . With reference pathology , vascular invasion ( VI ) was most predictive of stage in multifactorial analysis ( accuracy , 65.1 % ) . However , the positive predictive value ( PPV ) of VI to predict patients who have metastatic disease or relapse during follow-up was only 52.7 % . With absent VI , low-risk patients had a negative predictive value ( NPV ) of 76.9 % . With a combination of several risk factors , the PPV increased to 63.6 % and the negative predictive value increased to 86.5 % . CONCLUSION Even with an optimal combination of prognostic factors and reference pathology , more than one third of patients predicted to have pathologic stage II or relapse during follow-up will not harbor metastatic disease and , therefore , would be overtreated with adjuvant therapy . However , patients at low risk may be predicted at an 86.5 % level , and thus , surveillance in highly compliant patients would be a valuable option . For high-risk patients , further reduction of adjuvant treatment is necessary BACKGROUND Retrospective studies demonstrated that cell cycle-related and proliferation biomarkers add information to st and ard pathologic tumor features after radical cystectomy ( RC ) . There are no prospect i ve studies validating the clinical utility of markers in bladder cancer . OBJECTIVE To prospect ively determine whether a panel of biomarkers could identify patients with urothelial carcinoma of the bladder ( UCB ) who were likely to experience disease recurrence or mortality . DESIGN , SETTING , AND PARTICIPANTS Between January 2007 and January 2012 , every patient with high- grade bladder cancer , including 216 patients treated with RC and lymphadenectomy , underwent immunohistochemical staining for tumor protein p53 ( Tp53 ) ; cyclin-dependent kinase inhibitor 1A ( p21 , Cip1 ) ( CDKN1A ) ; cyclin-dependent kinase inhibitor 1B ( p27 , Kip1 ) ; antigen identified by monoclonal antibody Ki-67 ( MKI67 ) ; and cyclin E1 . INTERVENTION Every patient underwent RC and lymphadenectomy , and marker staining . OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Cox regression analyses tested the ability of the number of altered biomarkers to predict recurrence or cancer-specific mortality ( CSM ) . RESULTS AND LIMITATIONS Pathologic stage among the study population was pT0 ( 5 % ) , pT1 ( 35 % ) , pT2 ( 19 % ) , pT3 ( 29 % ) , and pT4 ( 13 % ) ; lymphovascular invasion ( LVI ) was seen in 34 % . The median number of removed lymph nodes was 23 , and 60 patients had lymph node involvement ( LNI ) . Median follow-up was 20 mo . Expression of p53 , p21 , p27 , cyclin E1 , and Ki-67 were altered in 54 % , 26 % , 46 % , 15 % , and 75 % patients , respectively . In univariable analyses , pT stage , LNI , LVI , perioperative chemotherapy ( CTx ) , margin status , and number of altered biomarkers predicted disease recurrence . In a multivariable model adjusting for pathologic stage , margins , LNI , and adjuvant CTx , only LVI and number of altered biomarkers were independent predictors of recurrence and CSM . The concordance index of a baseline model predicting CSM ( including pathologic stage , margins , LVI , LNI , and adjuvant CTx ) was 80 % and improved to 83 % with addition of the number of altered markers . CONCLUSIONS Molecular markers improve the prediction of recurrence and CSM after RC . They may identify patients who might benefit from additional treatments and closer surveillance after cystectomy BACKGROUND Some r and omised controlled trials ( RCTs ) done in German-speaking Europe are published in international English- language journals and others in national German- language journals . We assessed whether authors are more likely to report trials with statistically significant results in English than in German . METHODS We studied pairs of RCT reports , matched for first author and time of publication , with one report published in German and the other in English . Pairs were identified from reports round in a manual search of five leading German- language journals and from reports published by the same authors in English found on Medline . Quality of methods and reporting were assessed with two different scales by two investigators who were unaware of authors ' identities , affiliations , and other characteristics of trial reports . Main study endpoints were selected by two investigators who were unaware of trial results . Our main outcome was the number of pairs of studies in which the levels of significance ( shown by p values ) were discordant . FINDINGS 62 eligible pairs of reports were identified but 19 ( 31 % ) were excluded because they were duplicate publications . A further three pairs ( 5 % ) were excluded because no p values were given . The remaining 40 pairs were analysed . Design characteristics and quality features were similar for reports in both language s. Only 35 % of German- language articles , compared with 62 % of English- language articles , reported significant ( p < 0.05 ) differences in the main endpoint between study and control groups ( p = 0.002 by McNemar 's test ) . Logistic regression showed that the only characteristic that predicted publication in an English- language journal was a significant result . The odds ratio for publication of trials with significant results in English was 3.75 ( 95 % CI 1.25 - 11.3 ) . INTERPRETATION Authors were more likely to publish RCTs in an English- language journal if the results were statistically significant . English language bias may , therefore , be introduced in review s and meta-analyses if they include only trials reported in English . The effort of the Cochrane Collaboration to identify as many controlled trials as possible , through the manual search of many medical journals published in different language s will help to reduce such bias Despite years of research and hundreds of reports on tumour markers in oncology , the number of markers that have emerged as clinical ly useful is pitifully small . Often initially reported studies of a marker show great promise , but subsequent studies on the same or related markers yield inconsistent conclusions or st and in direct contradiction to the promising results . It is imperative that we attempt to underst and the reasons that multiple studies of the same marker lead to differing conclusions . A variety of method ologic problems have been cited to explain these discrepancies . Unfortunately , many tumour marker studies have not been reported in a rigorous fashion , and published articles often lack sufficient information to allow adequate assessment of the quality of the study or the generalisability of study results . The development of guidelines for the reporting of tumour marker studies was a major recommendation of the National Cancer Institute-European Organisation for Research and Treatment of Cancer ( NCI-EORTC ) First International Meeting on Cancer Diagnostics in 2000 . As for the successful CONSORT initiative for r and omised trials and for the STARD statement for diagnostic studies , we suggest guidelines to provide relevant information about the study design , pre-planned hypotheses , patient and specimen characteristics , assay methods , and statistical analysis methods . In addition , the guidelines suggest helpful presentations of data and important elements to include in discussion s. The goal of these guidelines is to encourage transparent and complete reporting so that the relevant information will be available to others to help them to judge the usefulness of the data and underst and the context in which the conclusions apply Output:	LVI was associated with higher pathological T stage and tumor grade , as well as lymph node metastasis . This meta- analysis indicates that LVI is significantly associated with poor outcome in patients with bladder cancer who underwent radical cystectomy .
MS21475	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: OBJECTIVE The objective of this study was to evaluate the effectiveness of a Self-Administered Behavioral Intervention using Tailored messages ( SEABIT ) for migraine . The primary measures were headache days , headache-related disability , behavioral/emotional factors , and headache-related beliefs . BACKGROUND Behavioral and cognitive-behavioral interventions for migraine treatment are well established and possess " Grade -A " evidence based on the U.S. Headache Consortium evidence -based guidelines . To increase the accessibility of behavioral interventions in primary and other setting s , treatment can be delivered in self-administered formats . Incorporating tailored health communication strategies ( via tailored messages ) into a self-administered format can help maintain a level of personalization without requiring regular visits to a behavioral specialist . Tailored messages are created using individual-level assessment data to educate and motivate the patient to develop behavioral skills and strategies for migraine prevention and management . METHODS Twenty-five individuals ( 95 % female , 90 % Caucasian , mean headache years = 21.0 ) began and 84 % ( 21/25 ) completed all phases of the 8-week SEABIT developed for migraine prevention ( preceded by a 1-month baseline phase and followed by a 1-month postintervention phase ) . RESULTS Overall , 62 % ( 13/21 ) reported at least a 50 % reduction in headache frequency , and mean headache frequency for the group was also significantly reduced from baseline to postintervention ( 16.9 vs. 10.7 , P < .001 ; eta2= .61 ) . Headache-related disability , behavioral/emotional factors , and headache-management self-efficacy also showed significant improvement . CONCLUSION The findings suggest that the SEABIT for migraine prevention is an effective behavioral intervention that potentially could be accessed and distributed in a variety of setting s including primary care Background : Chronic migraine ( CM ) is a debilitating neurological disorder with few treatment options . Peripheral nerve stimulation ( PNS ) of the occipital nerves is a potentially promising therapy for CM patients . Methods : In this r and omized , controlled multicenter study , patients diagnosed with CM were implanted with a neurostimulation device near the occipital nerves and r and omized 2:1 to active ( n = 105 ) or sham ( n = 52 ) stimulation . The primary endpoint was a difference in the percentage of responders ( defined as patients that achieved a ≥50 % reduction in mean daily visual analog scale scores ) in each group at 12 weeks . Results : There was not a significant difference in the percentage of responders in the Active compared with the Control group ( 95 % lower confidence bound ( LCB ) of −0.06 ; p = 0.55 ) . However , there was a significant difference in the percentage of patients that achieved a 30 % reduction ( p = 0.01 ) . Importantly , compared with sham-treated patients , there were also significant differences in reduction of number of headache days ( Active Group = 6.1 , baseline = 22.4 ; Control Group = 3.0 , baseline = 20.1 ; p = 0.008 ) , migraine-related disability ( p = 0.001 ) and direct reports of pain relief ( p = 0.001 ) . The most common adverse event was persistent implant site pain . Conclusion : Although this study failed to meet its primary endpoint , this is the first large-scale study of PNS of the occipital nerves in CM patients that showed significant reductions in pain , headache days , and migraine-related disability . Additional controlled studies using endpoints that have recently been identified and accepted as clinical ly meaningful are warranted in this highly disabled patient population with a large unmet medical need . Trial registration : Clinical trials.gov ( NCT00615342 ) Background and Purpose Behavioral medicine interventions that directly reduce arousal and negative emotions , such as relaxation training ( RT ) , are conceptually different from interventions that temporarily increase negative emotions , such as written emotional disclosure ( WED ) , but no studies have directly compared their efficacy . We compared the effects of RT and WED on people with tension or migraine headaches . Methods College students with either tension ( n = 51 ) or migraine ( n = 90 ) headaches were r and omized to one of three groups : RT , WED , or a neutral writing control condition ; four sessions were held over 2 weeks . Mood was measured before and after each session , and outcomes ( headache frequency , severity , disability , and general physical symptoms ) were assessed at baseline and at 1-month and 3-month follow-ups . Results As expected , RT led to an immediate increase in calmness , whereas WED led to an immediate increase in negative mood , for both headache sample s. Intent-to-treat analyses showed that , for the tension headache sample , RT led to improved headache frequency and disability compared to both WED and the control group , but WED had no effect . For migraine headaches , RT improved pain severity relative to the control group , but WED again had no effect . Conclusions A brief RT protocol was effective for tension headaches , but WED had no effect on health status for either tension or migraine headaches . Modifications to WED , such as targeting people with unresolved stress , providing guidance to enhance the potency of the writing , or including additional at-home writing and exposure exercises , may improve its efficacy for people with headaches and other health problems Background Modification of expectancies ( headache self-efficacy and headache locus of control ) is thought to be central to the success of psychological treatments for migraine . Purpose The purpose of this study is to examine expectancy changes with various combinations of Behavioral Migraine Management and migraine drug therapies . Methods Frequent migraine sufferers who failed to respond to 5 weeks of optimized acute migraine drug therapy were r and omized to a 2 ( Behavioral Migraine Management+ , Behavioral Migraine Management− ) × 2 ( β-blocker , placebo ) treatment design . Results Mixed models for repeated measures analyses ( N = 176 ) revealed large increases in headache self-efficacy and internal headache locus of control and large decreases in chance headache locus of control with Behavioral Migraine Management+ that were maintained over a 12-month evaluation period . Chance headache locus of control and socioeconomic status moderated changes in headache self-efficacy with Behavioral Migraine Management+ . Conclusions The “ deficiency ” hypothesis best explained how patient characteristics influenced changes in of headache self-efficacy with Behavioral Migraine Management In view of the association between chronic headaches and depression , this study compared a cognitive therapy package design ed for depression with a relatively st and ard behavioural treatment package design ed for headaches ( self-management training ) , in terms of their effects on headaches and depressive symptoms . Fifty-five subjects suffering from chronic headaches ( tension , migraine and combined ) were r and omly assigned to the two treatment conditions . Cognitive therapy and self-management training were equally effective at decreasing headaches and depressive symptoms on most measures . Changes in headaches and depressive symptoms were not significantly correlated in either condition , however . Greater headache improvement was associated with high pre-treatment headache activity for both conditions but , whilst self-management training was more effective for subjects low on depression , cognitive therapy was more effective for subjects high on chronicity . This suggests that the latter approach , or some variation of it , may be the treatment of choice for more chronic headache sufferers with depressive symptoms BACKGROUND Sleep problems have been linked with headaches for more than a century , but whether the headaches are the cause or the result of the disrupted sleep is unknown . OBJECTIVES We previously reported that nonrestorative sleep and poor sleep habits are almost universal in a referral population of women with transformed migraine ( TM ) . Since cognitive behavioral therapy is effective in improving sleep quality in individuals with poor sleep hygiene , we design ed a r and omized , placebo-controlled study to assess the impact of such treatment on TM . We hypothesized that behavioral sleep modification ( BSM ) would be associated with improvement in headache frequency and intensity and with reversion to episodic migraine . METHODS Subjects were 43 women with TM referred to an academic headache center . After obtaining informed consent , patients were r and omized to receive either behavioral sleep instructions or placebo behavioral instructions in addition to usual medical care . Subjects recorded headaches in st and ardized diaries . The first postintervention visit was scheduled at 6 weeks . At that visit , the blind was broken and all subjects received BSM instructions . A final visit was scheduled 6 weeks later . RESULTS Compared to the placebo behavioral group , the BSM group reported statistically significant reduction in headache frequency [ F ( 1 , 33 = 12.42 , P=.001 ) ] and headache intensity [ F(1 , 33 = 14.39 , P= .01 ) ] . They were more likely to revert to episodic migraine chi2 ( 2 , n = 43 ) = 7.06 , P= .029 . No member of the control group reverted to episodic migraine by the first postintervention visit . By the final visit , 48.5 % of those who had received BSM instructions had reverted to episodic migraine . CONCLUSIONS In this pilot study of women with TM , we found that a targeted behavioral sleep invention was associated with improvement in headache frequency , headache index , and with reversion to episodic migraine Abstract Introduction . Multimodal approaches in behavioral treatment have gained recent interest , with proven efficacy for migraine . The utility of the Internet has been demonstrated for behavioral treatment of headache disorders , but not specifically for migraine . The aim of the study was to develop and evaluate an Internet-based multimodal behavior treatment ( MBT ) program for migraine and to test h and massage treatment as an adjunct . Methods . Eighty-three adults , 58 women and 25 men , with at least two migraine attacks a month were recruited via advertisements . An MBT program aim ing at improvements in life-style and stress coping was developed for this study and , together with a diary , adapted for use over the Internet . Participants were r and omized to MBT with and without h and massage and to a control group , and were followed for 11 months . Question naires addressing issues of quality of life ( PQ23 ) and depressive symptoms ( MADRS-S ) were used . Results . A 50 % , or greater , reduction in migraine frequency was found in 40 % and 42 % of participants of the two groups receiving MBT ( with and without h and massage , respectively ) , who statistically were significantly more improved than participants in the control group . No effect of h and massage was detected , and gender did not show any independent contribution to the effect in a multivariate analysis . Conclusions . MBT administered over the Internet appears feasible and effective in the treatment of migraine , but no effect of h and massage was found . For increased knowledge on long-term effects and the modes of action of the present MBT program , further studies are needed BACKGROUND Chronic migraine ( CM ) and medication overuse headache ( MOH ) are disabling conditions that may be only partially managed with conservative treatments . Occipital nerve stimulation ( ONS ) is an innovative treatment for headache disorders . OBJECTIVES To investigate the safety and efficacy of ONS for CM and MOH patients and to evaluate changes in disability , quality of life , and drug intake in implanted patients . STUDY DESIGN Prospect i ve , r and omized cross-over study . METHODS Eligible patients who responded to a stimulation trial underwent device implantation and were r and omized to " Stimulation On " and " Stimulation Off " arms . Patients crossed over after one month , or when their headaches worsened . Stimulation was then switched On for all patients . Disability as measured by the Migraine Disability Assessment ( MIDAS ) , quality of life ( SF-36 ) , and drug intake ( patient 's diary ) were assessed over a one-year follow-up . RESULTS Thirty-four patients ( 76 % women , 34 % men , mean age : 46 ± 11 years ) were enrolled ; 30 were r and omized and 29 completed the study . Headache intensity and frequency were significantly lower in the On arm than in the Off arm ( p < 0.05 ) and decreased from the baseline to each follow-up visit in all patients with Stimulation On ( median MIDAS A and B scores : baseline = 70 and 8 ; one-year follow-up = 14 and 5 , p < 0.001 ) . Quality of life significantly improved ( p < 0.05 ) during the study . Triptans and nonsteroidal anti-inflammatory drug use fell dramatically from the baseline ( 20 and 25.5 doses/month ) to each follow-up visit ( 3 and 2 doses/month at one year , p < 0.001 ) . A total of 5 adverse events occurred : 2 infections and 3 lead migrations . LIMITATIONS Single-centre study , relatively small number of patients , absence of a control group . CONCLUSIONS According to the results obtained , ONS appears to be a safe and effective treatment for carefully selected CM and MOH patients Self-efficacy is posited in social cognitive theory as fundamental to behavior change . Few health behavior studies have examined self-efficacy prospect ively , viewed it as part of a reciprocal behavioral process , or compared self-efficacy beliefs in the same population across different behaviors . This article first discusses self efficacy in its theoretical context and review s the available prospect i ve studies . Second , it explores self-efficacy as a predictor of disease management behaviors in 570 older women with heart disease . Although the R 2 statistics in each case were modest , the construct is shown to be a statistically significant ( p < .05 ) predictor at both 4 and 12 months postbaseline of several disease management behaviors : using medicine as prescribed , getting adequate exercise , managing stress , and following a recommended diet . Building self- Output:	There was no evidence for either short-term or intermediate-term effectiveness of therapeutic patient education on self-efficacy or depressive symptoms . This systematic review revealed strong-moderate evidence for intermediate-term effectiveness of therapeutic patient education for migraine .
MS21476	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Background — The antiplatelet effects of the Platelet Inhibition and Patient Outcomes ( PLATO ) trial dose of ticagrelor in patients nonresponsive to clopidogrel and after they switch agents are unknown . Methods and Results — Patients with stable coronary artery disease on aspirin therapy received a 300-mg clopidogrel load ; nonresponders were identified by light transmittance aggregometry . In a 2-way crossover design , nonresponders ( n=41 ) and responders ( n=57 ) r and omly received clopidogrel ( 600 mg/75 mg once daily ) or ticagrelor ( 180 mg/90 mg twice daily ) for 14 days during period 1 . In period 2 , all nonresponders switched treatment ; half of the responders continued the same treatment , whereas the others switched treatment . Inhibition of platelet aggregation was higher in nonresponders treated with ticagrelor compared with clopidogrel ( P<0.05 ) . Treatment with ticagrelor among nonresponders result ed in a > 10 % , > 30 % , and > 50 % decrease in platelet aggregation from baseline in 100 % , 75 % , and 13 % of patients , respectively . Platelet aggregation fell from 59±9 % to 35±11 % in patients switched from clopidogrel to ticagrelor and increased from 36±14 % to 56±9 % in patients switched from ticagrelor to clopidogrel ( P<0.0001 for both ) . Platelet reactivity was below the cut points previously associated with ischemic risk measured by light transmittance aggregometry , VerifyNow P2Y12 assay , and vasodilator-stimulated phosphoprotein phosphorylation in 98 % to 100 % of patients after ticagrelor therapy versus 44 % to 76 % of patients after clopidogrel therapy . Conclusions — Ticagrelor therapy overcomes nonresponsiveness to clopidogrel , and its antiplatelet effect is the same in responders and nonresponders . Nearly all clopidogrel nonresponders and responders treated with ticagrelor will have platelet reactivity below the cut points associated with ischemic risk . Clinical Trial Registration — http://www . clinical trials.gov . Unique Identifier : NCT00642811 Aims Patients with diabetes mellitus ( DM ) have increased platelet reactivity and reduced platelet response to clopidogrel compared with patients without DM . Prasugrel , a more potent antiplatelet agent , is associated with greater reductions in ischaemic events compared with clopidogrel , particularly in patients with DM . The aim of this study was to perform serial pharmacodynamic assessment s of prasugrel with high-dose clopidogrel in patients with DM . Methods and results Optimizing anti-Platelet Therapy In diabetes MellitUS (OPTIMUS)-3 was a prospect i ve , r and omized , double-blind , crossover study in patients with type 2 DM and coronary artery disease ( CAD ) . Patients ( n= 35 ) were r and omly assigned to either prasugrel 60 mg loading dose (LD)/10 mg maintenance dose ( MD ) or clopidogrel 600 mg LD/150 mg MD over two 1-week treatment periods separated by a 2-week washout period . Platelet function was assessed by VerifyNow ® P2Y12 assay , light transmission aggregometry , and vasodilator-stimulated phosphoprotein phosphorylation at 0 , 1 , 4 , and 24 h and 7 days . Greater platelet inhibition by VerifyNow ® P2Y12 was achieved by prasugrel compared with clopidogrel at 4 h post-LD ( least squares mean , 89.3 vs. 27.7 % , P < 0.0001 ; primary endpoint ) . The difference in platelet inhibition between prasugrel and clopidogrel was significant from 1 h through 7 days ( P < 0.0001 ) . Similar results were obtained using all other platelet function measures . Prasugrel result ed in fewer poor responders at all time points irrespective of definition used . Conclusion In patients with type 2 DM and CAD , st and ard-dose prasugrel is associated with greater platelet inhibition and better response profiles during both the loading and maintenance periods when compared with double-dose clopidogrel . Clinical trial identifier : www . clinical trials.gov — Background —Ticagrelor and prasugrel provide stronger platelet inhibition compared with clopidogrel . Direct pharmacodynamic comparison between them has not yet been reported in ST-segment – elevation myocardial infa rct ion patients . Methods and Results —In a prospect i ve , single-center , single-blind study , 55 out of 117 ( 47 % ) screened consecutive ST-segment – elevation myocardial infa rct ion patients undergoing primary percutaneous coronary intervention were r and omized to either ticagrelor 180 mg loading followed by 90 mg bid , or prasugrel 60 mg loading followed by 10 mg od for 5 days . Platelet reactivity ( PR ) was assessed with the VerifyNow P2Y12 function assay and the Multiplate Analyzer at 0 , 1 , 2 , 6 , 24 hours , and 5 days postr and omization . The primary end point , PR with VerifyNow at hour 1 , did not differ significantly between patients r and omized to ticagrelor versus prasugrel ( 257.3 P2Y12 reaction unit [ PRU ] , 95 % CI 230.8–283.8 versus 231.3 PRU , 95 % CI 205.3–257.4 ; P=0.2 ) . PR did not differ at 2 , 6 , and 24 hours , although at day 5 it was lower with ticagrelor than prasugrel ( 25.6 PRU , 95 % CI 12.3–38.9 versus 50.3 PRU , 95 % CI 36.4–64.1 ; P=0.01 ) . At hour 2 , high on-treatment PR rates ( cutoff 208 PRU ) were 46.2 % and 34.6 % for ticagrelor and prasugrel , respectively , decreased significantly thereafter , whereas did not differ significantly between the 2 agents at all the time points of the study . Conclusions —In patients with ST-segment – elevation myocardial infa rct ion undergoing primary percutaneous coronary intervention , both ticagrelor and prasugrel exhibit an initial delay in the onset of their antiplatelet action . Ticagrelor did not appear superior to prasugrel in reducing PR during the first 24 hours of ST-segment – elevation myocardial infa rct ion . Clinical Trial Registration —URL : http://www . clinical trials.gov . Unique identifier : NCT01463163 Background — The increasing use of higher-than-approved doses of clopidogrel in clinical practice is based in part on the desire for greater levels of inhibition of platelet aggregation ( IPA ) . Prasugrel is a new thienopyridine that is more potent than st and ard-dose clopidogrel in healthy subjects and patients with stable coronary artery disease . The relative antiplatelet effects of prasugrel versus high-dose clopidogrel in percutaneous coronary intervention patients are unknown . Methods and Results — Prasugrel in Comparison to Clopidogrel for Inhibition of Platelet Activation and Aggregation – Thrombolysis in Myocardial Infa rct ion 44 ( PRINCIPLE-TIMI 44 ) was a r and omized , double-blind , 2-phase crossover study of prasugrel compared with high-dose clopidogrel in patients undergoing cardiac catheterization for planned percutaneous coronary intervention . The primary end point of the loading-dose phase ( prasugrel 60 mg versus clopidogrel 600 mg ) was IPA with 20 & mgr;mol/L ADP at 6 hours . Patients with percutaneous coronary intervention entered the maintenance-dose phase , a 28-day crossover comparison of prasugrel 10 mg/d versus clopidogrel 150 mg/d with a primary end point of IPA after 14 days of either drug . In this study , 201 subjects were r and omized . IPA at 6 hours was significantly higher in subjects receiving prasugrel ( mean±SD , 74.8±13.0 % ) compared with clopidogrel ( 31.8±21.1 % ; P<0.0001 ) . During the maintenance-dose phase , IPA with 20 & mgr;mol/L ADP was higher in subjects receiving prasugrel ( 61.3±17.8 % ) compared with clopidogrel ( 46.1±21.3 % ; P<0.0001 ) . Results were consistent across all key secondary end points ; significant differences emerged by 30 minutes and persisted across all time points . Conclusions — Among patients undergoing cardiac catheterization with planned percutaneous coronary intervention , loading with 60 mg prasugrel result ed in greater platelet inhibition than a 600-mg clopidogrel loading dose . Maintenance therapy with prasugrel 10 mg/d result ed in a greater antiplatelet effect than 150 mg/d clopidogrel OBJECTIVES Our goal was to compare the safety and initial efficacy of AZD6140 , the first reversible oral adenosine diphosphate receptor antagonist , with clopidogrel in patients with non-ST-segment elevation acute coronary syndromes ( NSTE-ACS ) . BACKGROUND AZD6140 achieves higher mean levels of platelet inhibition than clopidogrel in patients with stable coronary artery disease . METHODS A total of 990 patients with NSTE-ACS , treated with aspirin and st and ard therapy for ACS , were r and omized in a 1:1:1 double-blind fashion to receive either twice-daily AZD6140 90 mg , AZD6140 180 mg , or clopidogrel 300-mg loading dose plus 75 mg once daily for up to 12 weeks . RESULTS The primary end point , the Kaplan-Meier rate of major or minor bleeding through 4 weeks , was 8.1 % in the clopidogrel group , 9.8 % in the AZD6140 90-mg group , and 8.0 % in the AZD6140 180-mg group ( p = 0.43 and p = 0.96 , respectively , vs. clopidogrel ) ; the major bleeding rates were 6.9 % , 7.1 % , and 5.1 % , respectively ( p = 0.91 and p = 0.35 , respectively , vs. clopidogrel ) . Although not statistically significant , favorable trends were seen in the Kaplan-Meier rates of myocardial infa rct ion ( MI ) over the entire study period ( MI : 5.6 % , 3.8 % , and 2.5 % , respectively ; p = 0.41 and p = 0.06 , respectively , vs. clopidogrel ) . In a post-hoc analysis of continuous electrocardiograms , mostly asymptomatic ventricular pauses > 2.5 s were more common , especially in the AZD6140 180-mg group ( 4.3 % , 5.5 % , and 9.9 % , respectively ; p = 0.58 and p = 0.01 , respectively , vs. clopidogrel ) . CONCLUSIONS This initial experience with AZD6140 in patients with ACS showed no difference in major bleeding but an increase in minor bleeding at the higher dose with encouraging results on the secondary end point of MI . This agent is currently being studied in a large outcomes trial in 18,000 patients with ACS 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 Output:	Our results suggest that ticagrelor allows a higher platelet reactivity inhibition as compared with prasugrel and leads to a further decrease in the rate of HTPR
MS21477	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Cardiopulmonary bypass ( CPB ) contributes to the secretion of anti-inflammatory cytokines that mediate the inflammatory response observed during open heart surgery . In addition to many factors , type of anesthesia management affects immune response and central nervous system in cardiac surgery . The aim of this study was to assess the effect of propofol versus desflurane anesthesia on systemic immune modulation and central nervous system on patients undergoing coronary artery bypass grafting . Forty patients undergoing elective coronary artery bypass graft surgery with CPB were included in this prospect i ve r and omized study . Patients were allocated to receive propofol ( n = 20 ) or desflurane ( n = 20 ) for maintenance of anesthesia . The blood sample s for IL-6 , IL-8 , TNF-α , and S100β were drawn just prior to the operation before the induction of anesthesia , second before cardiopulmonary bypass , third after CPB , fourth 4 h postoperatively at the ICU . Major finding in our study is that S100β levels were lower in propofol group when compared to desflurane anesthesia . And also immune reaction was less in patients exposed to desflurane anesthesia when compared to propofol anesthesia as indicated by lower plasma concentrations of IL-8 and IL-6 . Propofol is more preferable in terms of S100β for anesthetic management for CABG OBJECTIVES Neuropsychological disorders are some of the most common complications of coronary artery bypass graft ( CABG ) surgery . The early diagnosis of postoperative brain damage is difficult and mainly based on the observation of specific brain injury markers . The aim of this study was to analyze the effects of volatile anesthesia ( VA ) on plasma total and ionized arteriovenous magnesium concentrations in the brain circulation ( a-vtMg and a-viMg ) , plasma matrix metalloproteinase-9 ( MMP-9 ) , and glial fibrillary acidic protein ( GFAP ) in adult patients undergoing CABG surgery . DESIGN An observational study . SETTING The Department of Cardiac Surgery in a Medical University Hospital . PATIENTS AND METHODS Studied parameters were measured during surgery and in the early postoperative period . Patients were assigned to 3 groups : group O , patients who did not receive VA ; group ISO , patients who received isoflurane ; and group SEV , patients who received sevoflurane . RESULTS Ninety-two patients were examined . CABG surgery increased MMP-9 and GFAP . The highest MMP-9 , GFAP , and the most dramatic disorders in a-vtMg and a-viMg were noted in group O. CONCLUSIONS Cardiac surgery increased plasma MMP-9 and GFAP concentrations . Changes in MMP-9 , GFAP , and arteriovenous tMg and iMg were significantly higher in group O. Volatile anesthetics , such as ISO or SEV , reduced plasma MMP-9 , GFAP concentrations , and disturbances in a-vtMg and a-viMg We investigated the long-term effects of sevoflurane on histopathologic injury and key proteins of apoptosis in a rat hemispheric ischemia/reperfusion model . Sixty-four male Sprague-Dawley rats were r and omly assigned to Group 1 ( fentanyl and N2O/O2 ; control ) and Group 2 ( 2.0 vol% sevoflurane and O2/air ) . Ischemia ( 45 min ) was produced by unilateral common carotid artery occlusion plus hemorrhagic hypotension ( mean arterial blood pressure 40 mm Hg ) . Animals were killed after 1 , 3 , 7 , and 28 days . In hematoxylin and eosin-stained brain sections eosinophilic hippocampal neurons were counted . Activated caspase-3 and the apoptosis-regulating proteins Bax , Bcl-2 , Mdm-2 , and p53 were analyzed by immunostaining . No eosinophilic neurons were detected in sevoflurane-anesthetized rats over time , whereas 9%–38 % of the hippocampal neurons were eosinophilic ( days 1–28 ) in control animals . On days 1 and 3 , the concentration of Bax was 140%–200 % larger in fentanyl/N2O-anesthetized animals compared with sevoflurane . Bcl-2 was 100 % less in control animals during the first 3 days . Activated caspase-3 was detected in neurons of both groups ( 0.75%–2.2 % ) . These data support a sustained neuroprotective potency of sevoflurane related to reduced eosinophilic injury after cerebral ischemia/reperfusion BACKGROUND A recent study demonstrated that almost 75 % of strokes after coronary artery revascularization surgery occur in patients classified preoperatively as low to medium risk . Thus , despite the use of risk classification , most strokes can occur when not expected . We hypothesized that optimization of cerebral oxygen delivery variables by using noninvasive cerebral oximetry could reduce the incidence of stroke . METHODS Cerebral oximetry was used by all surgeons to monitor cerebral oxygen saturation in all cardiac surgery patients from January 1 , 2002 , until June 30 , 2003 ( n = 1034 ; 18 months , treatment group ) . Cerebral oxygen delivery was optimized during surgery by modifying oxygen delivery and consumption variables to maintain oximetry values at or near the patient 's preinduction baseline . Stroke was defined according to guidelines of the Society of Thoracic Surgeons . The incidence of stroke in the treatment group was compared with that for patients who underwent cardiac surgery between July 1 , 2000 , and December 31 , 2001 , ( n = 1245 ; 18 months , control group ) before cerebral oximetry was incorporated . RESULTS Age and sex distribution were similar in the 2 groups . The study group had significantly more patients in New York Heart Association ( NYHA ) classes III and IV than the control group , and patients in the study group were sicker overall . Despite this difference , the study group overall had fewer permanent strokes ( 10 [ 0.97 % ] versus 25 [ 2.5 % ] ; P < .044 ) . This difference remained significant when the results were controlled for NYHA class and on-pump or off-pump surgery . When the patients were examined by NYHA class , the proportion of patients requiring prolonged ventilation was significantly smaller in the study group ( 6.8 % versus 10.6 % ; P < .0014 ) , as was the length of hospital stay ( P < .046 ) . CONCLUSIONS The treatment group , which underwent all cardiac surgeries with optimized cerebral oxygen delivery using cerebral oximetry monitoring , demonstrated a significantly lower incidence of permanent stroke . Because our study is retrospective , a prospect i ve r and omized trial is warranted BACKGROUND Previously , we reported that there was no significant difference at 30 days in the rate of a primary composite outcome of death , myocardial infa rct ion , stroke , or new renal failure requiring dialysis between patients who underwent coronary-artery bypass grafting ( CABG ) performed with a beating-heart technique ( off-pump ) and those who underwent CABG performed with cardiopulmonary bypass ( on-pump ) . We now report results on quality of life and cognitive function and on clinical outcomes at 1 year . METHODS We enrolled 4752 patients with coronary artery disease who were scheduled to undergo CABG and r and omly assigned them to undergo the procedure off-pump or on-pump . Patients were enrolled at 79 centers in 19 countries . We assessed quality of life and cognitive function at discharge , at 30 days , and at 1 year and clinical outcomes at 1 year . RESULTS At 1 year , there was no significant difference in the rate of the primary composite outcome between off-pump and on-pump CABG ( 12.1 % and 13.3 % , respectively ; hazard ratio with off-pump CABG , 0.91 ; 95 % confidence interval [ CI ] , 0.77 to 1.07 ; P=0.24 ) . The rate of the primary outcome was also similar in the two groups in the period between 31 days and 1 year ( hazard ratio , 0.79 ; 95 % CI , 0.55 to 1.13 ; P=0.19 ) . The rate of repeat coronary revascularization at 1 year was 1.4 % in the off-pump group and 0.8 % in the on-pump group ( hazard ratio , 1.66 ; 95 % CI , 0.95 to 2.89 ; P=0.07 ) . There were no significant differences between the two groups at 1 year in measures of quality of life or neurocognitive function . CONCLUSIONS At 1 year after CABG , there was no significant difference between off-pump and on-pump CABG with respect to the primary composite outcome , the rate of repeat coronary revascularization , quality of life , or neurocognitive function . ( Funded by the Canadian Institutes of Health Research ; CORONARY Clinical Trials.gov number , NCT00463294 . ) In this study , we examined the cerebral oxygenation effects of two methods of pharmacologic burst suppression during cardiopulmonary bypass ( CPB ) in valvular heart surgery patients . Patients were r and omly entered into one of three groups : control ( n = 13 , fentanyl and midazolam ) , control plus burst suppression doses of thiopental ( n = 15 ) , or control plus burst suppression doses of isoflurane ( n = 16 ) . Burst suppression ( 80 % suppression ) was accomplished in the thiopental and isoflurane groups 15 min before aortic cannulation and was maintained through aortic decannulation . Cerebral physiologic measurements were made during hypothermia ( 27 - 28[degree sign]C ) and on rewarming to 36[degree sign]C. During hypothermia , burst suppression produced significant ( P < 0.005 ) differences with regard to cerebral vascular resistance ( P = 0.003 ) , cerebral arterial venous oxygen difference [ C(a-v)O2 ] ( P = 0.032 ) , cerebral blood flow ( CBF ) ( P = 0.009 ) , and cerebral oxygen delivery ( P = 0.027 ) . There was a similar pattern on rewarming , with groups differing significantly ( P < 0.05 ) with respect to CBF ( P = 0.016 ) , cerebral vascular resistance ( P = 0.008 ) , oxygen delivery ( P = 0.004 ) , C(a-v)O2 ( P = 0.043 ) , and cerebral oxygen extraction ( P = 0.046 ) . Rewarming rates were similar among groups . There was no difference in neurologic outcome or requirement for inotropic support among groups . The time to awakening was increased ( P = 0.0005 ) in the thiopental group . The thiopental group had lower cerebral oxygen delivery , but not lower cerebral metabolic rate of oxygen consumption , compared with the control group , result ing in widening C(a-v)O2 during CPB . This lack of coupling of oxygen delivery and consumption suggests that pharmacologic neuroprotective mechanisms are complex and involve more than an improvement in the ratio of global cerebral oxygen supply to dem and . Implication s : This study demonstrates that the balance of cerebral oxygen delivery to consumption during cardiopulmonary bypass is altered differently by thiopental and isoflurane . As others have noted , it seems that cerebral protection is more complex than a simple improvement in the balance of oxygen delivery and consumption . ( Anesth Analg 1998;86:246 - 51 BACKGROUND Because the time available for cooling and rewarming during deliberate mild hypothermia is limited , studies of the rate of the cooling and rewarming are useful . The decrease in core hypothermia caused by heat redistribution depends on the anaesthetic agent used . We therefore investigated possible differences between sevoflurane and propofol on the decrease and recovery of core temperature during deliberate mild hypothermia for neurosurgery . METHODS After institutional approval and informed consent , 26 patients were assigned r and omly to maintenance of anaesthesia with propofol or sevoflurane . Patients in the propofol group ( n=13 ) received propofol induction followed by a continuous infusion of propofol 3 - 5 mg kg(-1 ) h(-1 ) . Patients in the sevoflurane group ( n=13 ) received propofol induction followed by sevoflurane 1 - 2 % . Nitrous oxide and fentanyl were also used for anaesthetic maintenance . After induction of anaesthesia , patients were cooled and tympanic membrane temperature was maintained at 34.5 degrees C. After surgery , patients were actively rewarmed . RESULTS There was no difference in the rate of decrease and recovery of core temperature between the groups . There was also no difference in skin surface temperature gradient ( forearm to fingertip ) , heart rate and mean arterial blood pressure between the groups . CONCLUSIONS Sevoflurane-based anaesthesia did not affect cooling and rewarming for deliber Output:	Among secondary outcome variables , mini-mental state examination scores of the inhalation anaesthesia group were significantly higher than those of the TIVA group 24 hours after operation ( WMD ( 95 % CI ) : 1.87 ( 0.82 to 2.92 ) ) , but no significant difference was found in arteriovenous oxygen content difference , cerebral oxygen extraction ratio and jugular bulb venous oxygen saturation , which were assessed at cooling and rewarming during CPB . This study demonstrates that anaesthesia with volatile agents appears to provide better cerebral protection than TIVA for patients undergoing cardiac surgery with CPB , suggesting that inhalation anaesthesia may be more suitable for patients undergoing cardiac surgery
MS21478	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: The article presents final analyses of overall survival from a phase III trial of lapatinib and capecitabine in patients with human epidermal growth factor receptor 2–positive locally advanced or metastatic breast cancer that progressed following prior therapy including trastuzumab PURPOSE To test whether combining bevacizumab , an anti-vascular endothelial growth factor treatment , with endocrine therapy ( ET ) could potentially delay the emergence of resistance to ET . PATIENTS AND METHODS A multicenter , r and omized , open-label , phase III , binational ( Spain and Germany ) study added bevacizumab ( 15 mg/kg every 3 weeks ) to ET ( ET-B ; letrozole or fulvestrant ) as first-line therapy in postmenopausal patients with human epidermal growth factor receptor 2 ( HER2 ) -negative and hormone receptor-positive advanced breast cancer . We compared progression-free survival ( PFS ) , overall survival ( OS ) , overall response rate ( ORR ) , response duration ( RD ) , time to treatment failure ( TTF ) , clinical benefit rate ( CBR ) , and safety . RESULTS From 380 patients recruited ( 2007 to 2011 ) , 374 were analyzed by intent to-treat ( 184 patients on ET and 190 patients on ET-B ) . Median age was 65 years , 270 patients ( 72 % ) had Eastern Cooperative Oncology Group performance status of 0 , 178 patients ( 48 % ) had visceral metastases , and 171 patients ( 46 % ) and 195 patients ( 52 % ) had received prior chemotherapy or ET , respectively . Median PFS was 14.4 months in the ET arm and 19.3 months in the ET-B arm ( hazard ratio , 0.83 ; 95 % CI , 0.65 to 1.06 ; P = .126 ) . ORR , CBR , and RD with ET versus ET-B were 22 % versus 41 % ( P < .001 ) , 67 % versus 77 % ( P = .041 ) , and 13.3 months versus 17.6 months ( P = .434 ) , respectively . TTF and OS were comparable in both arms . Grade 3 to 4 hypertension , aminotransferase elevation , and proteinuria were significantly higher in the ET-B arm . Eight patients ( 4.2 % ) receiving ET-B died during study or within 30 days of end of treatment . CONCLUSION The addition of bevacizumab to ET in first-line treatment failed to produce a statistically significant increase in PFS or OS in women with HER2-negative/hormone receptor-positive advanced breast cancer BACKGROUND The BOLERO-2 study previously demonstrated that adding everolimus ( EVE ) to exemestane ( EXE ) significantly improved progression-free survival ( PFS ) by more than twofold in patients with hormone-receptor-positive ( HR(+ ) ) , HER2-negative advanced breast cancer that recurred or progressed during/after treatment with nonsteroidal aromatase inhibitors ( NSAIs ) . The overall survival ( OS ) analysis is presented here . PATIENTS AND METHODS BOLERO-2 is a phase III , double-blind , r and omized international trial comparing EVE 10 mg/day plus EXE 25 mg/day versus placebo ( PBO ) + EXE 25 mg/day in postmenopausal women with HR(+ ) advanced breast cancer with prior exposure to NSAIs . The primary end point was PFS by local investigator assessment ; OS was a key secondary end point . RESULTS At the time of data cutoff ( 3 October 2013 ) , 410 deaths had occurred and 13 patients remained on treatment . Median OS in patients receiving EVE + EXE was 31.0 months [ 95 % confidence interval ( CI ) 28.0 - 34.6 months ] compared with 26.6 months ( 95 % CI 22.6 - 33.1 months ) in patients receiving PBO + EXE ( hazard ratio = 0.89 ; 95 % CI 0.73 - 1.10 ; log-rank P = 0.14 ) . Post study treatments were received by 84 % of patients in the EVE + EXE arm versus 90 % of patients in the PBO + EXE arm . Types of post study therapies were balanced across arms , except for chemotherapy ( 53 % EVE + EXE versus 63 % PBO + EXE ) . No new safety concerns were identified . CONCLUSIONS In BOLERO-2 , adding EVE to EXE did not confer a statistically significant improvement in the secondary end point OS despite producing a clinical ly meaningful and statistically significant improvement in the primary end point , PFS ( 4.6-months prolongation in median PFS ; P < 0.0001 ) . Ongoing translational research should further refine the benefit of mTOR inhibition and related pathways in this treatment setting . TRIAL REGISTRATION NUMBER NCT00863655 Introduction Effective treatments for hormone-receptor-positive ( HR+ ) breast cancer ( BC ) following relapse/progression on nonsteroidal aromatase inhibitor ( NSAI ) therapy are needed . Initial Breast Cancer Trials of OraL EveROlimus-2 ( BOLERO-2 ) trial data demonstrated that everolimus and exemestane significantly prolonged progression-free survival ( PFS ) versus placebo plus exemestane alone in this patient population . Methods BOLERO-2 is a phase 3 , double-blind , r and omized , international trial comparing everolimus ( 10 mg/day ) plus exemestane ( 25 mg/day ) versus placebo plus exemestane in postmenopausal women with HR+ advanced BC with recurrence/progression during or after NSAIs . The primary endpoint was PFS by local investigator review , and was confirmed by independent central radiology review . Overall survival , response rate , and clinical benefit rate were secondary endpoints . Results Final study results with median 18-month follow-up show that median PFS remained significantly longer with everolimus plus exemestane versus placebo plus exemestane [ investigator review : 7.8 versus 3.2 months , respectively ; hazard ratio = 0.45 ( 95 % confidence interval 0.38–0.54 ) ; log-rank P < 0.0001 ; central review : 11.0 versus 4.1 months , respectively ; hazard ratio = 0.38 ( 95 % confidence interval 0.31–0.48 ) ; log-rank P < 0.0001 ] in the overall population and in all prospect ively defined subgroups , including patients with visceral metastases , patients with recurrence during or within 12 months of completion of adjuvant therapy , and irrespective of age . The incidence and severity of adverse events were consistent with those reported at the interim analysis and in other everolimus trials . Conclusion The addition of everolimus to exemestane markedly prolonged PFS in patients with HR+ advanced BC with disease recurrence/progression following prior NSAIs . These results further support the use of everolimus plus exemestane in this patient population . Clinical Trials.gov # NCT00863655 Background A r and omized Phase II study evaluated the activity of weekly paclitaxel versus its combination with trastuzumab for treatment of patients with advanced breast cancer overexpressing HER-2 . Patients and methods Among 124 patients r and omized , 123 are assessable for toxicity and 118 for response . Patients received weekly paclitaxel single agent ( 80 mg/m2 ) or combined with trastuzumab ( 4 mg/kg loading dose , then weekly 2 mg/kg ) . HER-2 overexpression was determined by immunohistochemistry ( IHC ) . Patients with 2+/3 + IHC scores were eligible . IHC was compared with HER-2 serum extracellular domain ( ECD ) . Results Patient characteristics were similar in the two arms . Both treatments were feasible and well tolerated with no grade 4 hematologic toxicity . No patient developed cardiac toxicity . The combined treatment was statistically significant superior for overall response rate ( ORR ) ( 75 % vs. 56.9 % ; P = 0.037 ) , particularly in the subset of IHC 3 + patients ( 84.5 % vs. 47.5 % ; P = 0.00050 ) . A statistically significant better median time to progression was seen in the subgroup with IHC 3 + ( 369 vs. 272 days ; P = 0.030 ) and visceral disease ( 301 vs. 183 days ; P = 0.0080 ) treated with combination . Multivariable analysis of predictive factors showed that only IHC score retained statistically significant value for ORR ( P = 0.0035 ) . Conclusion Weekly paclitaxel plus trastuzumab is highly active and safe and it is superior to paclitaxel alone in patients with IHC score of 3 + BACKGROUND mTOR inhibition reverses trastuzumab resistance via the hyperactivated PIK/AKT/mTOR pathway due to PTEN loss , by sensitising PTEN-deficient tumours to trastuzumab . The BOLERO-1 study assessed the efficacy and safety of adding everolimus to trastuzumab and paclitaxel as first-line treatment for patients with HER2-positive advanced breast cancer . METHODS In this phase 3 , r and omised , double-blind trial , patients were enrolled across 141 sites in 28 countries . Eligible patients were aged 18 years or older , with locally assessed HER2-positive advanced breast cancer , with Eastern Cooperative Oncology Group ( ECOG ) performance status of 0 - 1 , who had not received previous trastuzumab or chemotherapy for advanced breast cancer within 12 months of r and omisation , had measurable disease as per Response Evaluation Criteria in Solid Tumors ( RECIST ) or bone lesions in the absence of measurable disease , without previous systemic treatment for advanced disease except endocrine therapy . Patients were r and omly assigned ( 2:1 ) with an interactive voice and web response system to receive either 10 mg everolimus once a day orally or placebo plus weekly trastuzumab intravenously at 4 mg/kg loading dose on day 1 with subsequent weekly doses of 2 mg/kg of each 4 week cycle plus paclitaxel intravenously at a dose of 80 mg/m(2 ) on days 1 , 8 , and 15 of each 4 week cycle . R and omisation was stratified according to previous use of trastuzumab and visceral metastasis . Patients and investigators were masked to the assigned treatments . Identity of experimental treatments was concealed by use of everolimus and placebo that were identical in packaging , labelling , appearance , and administration schedule . The two primary objectives were investigator-assessed progression-free survival in the full study population and in the subset of patients with hormone receptor-negative breast cancer at baseline ; the latter was added during the course of the study , before unmasking based on new clinical and biological findings from other studies . All efficacy analyses were based on the intention-to-treat population . Enrolment for this trial is closed and results of the final progression-free survival analyses are presented here . This trial is registered with Clinical Trials.gov , number NCT00876395 . FINDINGS Between Sept 10 , 2009 , and Dec 16 , 2012 , 719 patients were r and omly assigned to receive everolimus ( n=480 ) or placebo ( n=239 ) . Median follow-up was 41·3 months ( IQR 35·4 - 46·6 ) . In the full population , median progression-free survival was 14·95 months ( 95 % CI 14·55 - 17·91 ) with everolimus versus 14·49 months ( 12·29 - 17·08 ) with placebo ( hazard ratio 0·89 , 95 % CI 0·73 - 1·08 ; p=0·1166 ) . In the HR-negative sub population ( n=311 ) , median progression-free survival with everolimus was 20·27 months ( 95 % CI 14·95 - 24·08 ) versus 13·08 months ( 10·05 - 16·56 ) with placebo ( hazard ratio 0·66 , 95 % CI 0·48 - 0·91 ; p=0·0049 ) ; however , the protocol -specified significance threshold ( p=0·0044 ) was not crossed . The most common adverse events with everolimus were stomatitis ( 314 [ 67 % ] of 472 patients in the everolimus group vs 77 [ 32 % ] of 238 patients in the placebo group ) , diarrhoea ( 267 [ 57 % ] vs 111 [ 47 % ] patients ) , and alopecia ( 221 [ 47 % ] vs 125 [ 53 % ] ) . The most frequently reported grade 3 or 4 adverse events in the everolimus group versus the placebo group were neutropenia ( 117 [ 25 % ] vs 35 [ 15 % ] ) , stomatitis ( 59 [ 13 % ] vs three [ 1 % ] ) , anaemia ( Output:	Albeit small , the gain in months of median PFS and median OS was significant . Importantly , the results reported show large variation , and thus routinely applying a personalized approach seems warranted
MS21479	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Background : The frequency of HIV dementia in a recent study of HIV+ individuals at the Infectious Disease Institute in Kampala , Ug and a , was 31 % . Coformulated generic drugs , which include stavudine , are the most common regimens to treat HIV infection in Ug and a and many other parts of Africa . Objective : To evaluate the benefits and risks of stavudine-based highly active antiretroviral therapy ( HAART ) for HIV-associated cognitive impairment and distal sensory neuropathy . The study compared neuropsychological performance changes in HIV+ individuals initiating HAART for 6 months and HIV− individuals receiving no treatment for 6 months . The risk of antiretroviral toxic neuropathy as a result of the initiation of stavudine-based HAART was also examined . Methods : At baseline , 102 HIV+ individuals in Ug and a received neurologic , neuropsychological , and functional assessment s ; began HAART ; and were followed up for 6 months . Twenty-five HIV− individuals received identical clinical assessment s and were followed up for 6 months . Results : In HIV+ individuals , there was improvement in verbal memory , motor and psychomotor speed , executive thinking , and verbal fluency . After adjusting for differences in sex , HIV+ individuals demonstrated significant improvement in the Color Trails 2 test ( p = 0.025 ) compared with HIV− individuals . Symptoms of neuropathy developed in 38 % of previously asymptomatic HIV+ patients after initiation of the stavudine-based HAART . Conclusions : After the initiation of highly active antiretroviral therapy ( HAART ) including stavudine , HIV+ individuals with cognitive impairment improve significantly as demonstrated by improved performance on a test of executive function . However , peripheral neurotoxicity occurred in 30 patients , presumably because of stavudine-based HAART , suggesting the need for less toxic therapy A study of neuropsychological performance was conducted in 33 HIV+ patients initiating highly active antiretroviral therapy ( HAART ) . Grooved Pegboard ( GP ) non-dominant h and performance improved in 23/33 ( 70 % ) subjects ( P=0.002 ) . Among 23 patients with motor slowing ( GP non-dominant h and z score < -1.0 ) at baseline , 18 ( 78 % ) improved on the GP non-dominant h and test after initiating HAART ( P=0.001 ) . GP non-dominant h and performance improved longitudinally in HIV+ patients initiating HAART , while matched HIV+ controls not on HAART did not change ( P=0.045 ) . Significant improvement in motor performance can occur after HAART in HIV+ patients with impairment Objectives To delineate and compare the nature and frequency of mutations known to confer resistance to HIV-1 nucleoside reverse transcriptase inhibitors in the cerebrospinal fluid ( CSF ) and blood compartments . Methods Fifty-three paired CSF and plasma specimens had been prospect ively collected and stored from 49 HIV-1 infected patients . These were tested using a commercially available line probe assay which allows the simultaneous detection of wild-type and drug selected variants conferring resistance to one or more drugs : zidovudine , didanosine , zalcitabine , and lamivudine . Results Of the 53 ( 58 % ) paired sample s , 31 could be amplified by nested PCR . The current assay 's limitation for use with CSF is highlighted as 91 % of blood sample s amplified compared with 60 % of CSF sample s showing the assays inability to amplify viral loads below 1000 copies/ml . Of the 31 patients 21 ( 68 % ) had identical resistance patterns in the CSF and plasma ; the other 10 ( 32 % ) patients had a resistance profile in the CSF that was different from that in their plasma . Of these , three sample s demonstrated amino acid changes associated with high level zidovudine resistance in the CSF but the blood sample remained genotypically sensitive . Nine sample s demonstrated resistance in blood but remained wild-type in the CSF . Resistant genotypes were detected in CSF for all nucleosides except didanosine . Conclusions Differences in the positions and frequencies of wild-type and drug selected variants in specimens derived from the CSF and blood compartments were detected in a significant number of patients ; this argues for the independent development of drug resistance in the CNS in some patients . These findings may have important implication s in guiding antiretroviral therapy in HIV-1 infection Objectives : This study examined the effects of HAART on neurocognitive functioning in persons with hepatitis C virus ( HCV ) and HIV co-infection . Design : A prospect i ve study examining neurocognitive performance before and after HAART initiation . Method : Participant groups included a mono-infected group ( 45 HIV+/HCV− participants ) and a co-infected group ( 20 HIV+/HCV+ participants ) . A neuropsychological battery ( attention/concentration , psychomotor speed , executive functioning , verbal memory , visual memory , fine motor , and gross motor functioning ) was used to evaluate all participants . After 6 months of HAART , 31 HIV+ mono-infected and 13 HCV+/HIV+ co-infected participants were reevaluated . Results : Neurocognitive functioning by domain revealed significantly worse performance in the co-infected group when compared to the monoinfected group on domains of visual memory and fine motor functioning . Assessment of neurocognitive functioning after antiretroviral therapy revealed that the co-infected group was no longer performing worse than the monoinfected group . Conclusions : The findings of the current study suggest that persons with HCV+/HIV+ co-infection may have greater neurocognitive declines than persons with HIV infection alone . HCV+/HIV+ co-infection may accelerate the progression of HIV related neurocognitive decline Objectives : HAART suppresses HIV viral replication and restores immune function . The effects of HAART on neurological disease are less well understood . The aim of this study was to assess the prevalence and incidence of neurocognitive impairment in individuals who initiated HAART as part of an AIDS clinical trial . Design : A prospect i ve cohort study of HIV-positive patients enrolled in r and omized antiretroviral trials , the AIDS Clinical Trials Group ( ACTG ) Longitudinal Linked R and omized Trials ( ALLRT ) study . Methods : We examined the association between baseline and demographic characteristics and neurocognitive impairment among 1160 subjects enrolled in the ALLRT study . Results : A history of immunosuppression ( nadir CD4 cell count < 200 cells/μl ) was associated with an increase in prevalent neurocognitive impairment . There were no significant virological and immunological predictors of incident neurocognitive impairment . Current immune status ( low CD4 cell count ) was associated with sustained prevalent impairment . Conclusion : The association of previous advanced immunosuppression with prevalent and sustained impairment suggests that there is a non-reversible component of neural injury that tracks with a history of disease progression . The association of sustained impairment with worse current immune status ( low CD4 cell count ) suggests that restoring immunocompetence increases the likelihood of neurocognitive recovery . Finally , the lack of association between incident neurocognitive impairment and virological and immunological indicators implies that neural injury continues in some patients regardless of the success of antiretroviral therapy on these laboratory measures Objective : To rigorously evaluate the time course of cognitive change in a cohort of individuals with HIV-associated neurocognitive disorders ( H AND ) initiating combination antiretroviral therapy ( CART ) , and to investigate which demographic , laboratory , and treatment factors are associated with neuropsychological ( NP ) outcome ( or “ any NP improvement ” ) . Methods : Study participants included 37 HIV+ individuals with mild to moderate NP impairment who initiated CART and underwent NP testing at 12 , 24 , 36 , and 48 weeks thereafter . NP change was assessed using a regression-based change score that was normed on a separate NP-stable group thereby controlling for regression toward the mean and practice effect . Mixed-effect regression models adjusting for loss to follow-up were used to evaluate the time course of cognitive change and its association with baseline and time-varying predictors . Results : In persons with H AND initiating CART , cognitive improvement happens soon after initiation ( 13 % at week 12 ) , but more often 24 , 36 , and up to 48 weeks after initiation ( up to 41 % ) , with fewer than 5 % demonstrating significant worsening . In multivariate analyses , unique predictors of NP improvement included more severe baseline NP impairment and higher CART CNS penetration index . Greater viral load decrease was associated with NP improvement only in univariate analyses . Conclusion : Clinical ly meaningful neuropsychological improvement seemed to peak around 24–36 weeks after combination antiretroviral therapy initiation and was prolonged over the 1-year study period . This study also provides new evidence that benefit may be maximized by choosing antiretroviral medications that reach therapeutic concentrations in the CNS At least 10 different genetic human immunodeficiency virus type 1 ( HIV-1 ) subtypes ( A-J ) are responsible for the AIDS p and emic . Much of the underst and ing of HIV-1 disease progression derives from studies in the developed world where HIV infection is almost exclusively subtype B. This has led many to question whether the properties and consequences of HIV-1 infection can be generalized across subtypes that afflict the majority of infected persons in the developing world . From 1985 to 1997 , a prospect i ve study of registered female sex workers in Senegal tracked the introduction and spread of HIV-1 subtypes A , C , D , and G. In clinical follow-up , the AIDS-free survival curves differed by HIV-1 subtype . Women infected with a non-A subtype were 8 times more likely to develop AIDS than were those infected with subtype A ( hazard ratio=8.23 ; P=. 009 ) , the predominant subtype in the study . These data suggest that HIV-1 subtypes may differ in rates of progression to AIDS Summary : Although the effects of highly active antiretroviral therapy ( HAART ) have result ed in substantial improvements in the systemic health of patients with HIV infection , concerns remain that these medications , which cross the blood – brain barrier poorly , may have a less beneficial effect on nervous system function . This raises the possibility that there may be a progressive long-term decline in neurologic function in patients with adequate systemic response . In a prospect i ve longitudinal study , subjects were evaluated immediately before instituting HAART . Forty-eight subjects underwent ultrasensitive HIV RNA quantitative evaluation of both plasma and cerebrospinal fluid as well as neurologic and neuropsychological examinations . They were reevaluated 6 months after treatment initiation while receiving stable HAART . Both plasma and cerebrospinal fluid viral levels significantly declined after treatment . There was significant improvement in neurologic and neuropsychological functioning after HAART . These results indicate that despite the poor central nervous system penetration of most of these agents , there is satisfactory short-term improvement in both central nervous system viral burden and nervous system function with HAART . However , because treatment failure is increasingly likely over time , continued longitudinal evaluation of this group of subjects is required Interpretations of longitudinal studies of cognitive aging are misleading unless effects of practice and selective drop-out are considered . A r and om effects model taking practice and drop-out into account analyzed data from four successive presentations of each of two intelligence tests , two vocabulary tests , and two verbal memory tests during a 17-year longitudinal study of 5,899 community residents whose ages ranged from 49 to 92 years . On intelligence tests , substantial practice effects counteracted true declines observed over 3 to 5 years of aging and remained significant even with intervals of 7 years between successive assessment s. Adjustment for practice and drop-out revealed accelerating declines in fluid intelligence and cumulative learning , linear declines in verbal free recall , and no substantial change in vocabulary . Socioeconomic status and basal levels of general fluid ability did not affect rates of decline . After further adjustment for demographics , variability between individuals was seen to increase as the sample aged Nucleoside reverse transcriptase inhibitors ( NRTIs ) suppress human immunodeficiency virus ( HIV ) replication , but are often associated with mitochondrial toxicity . Although well studied outside of the central nervous system , no investigation has examined the effects of these drugs on brain mitochondria of individuals living with HIV . The authors used proton magnetic resonance spectroscopy to evaluate NRTI-related changes in brain mitochondria . N-acetylaspartate ( NAA ; sensitive to alterations in mitochondrial integrity ) was measured in frontal lobe white and gray matter of 18 HIV+ individuals taking didanosine and /or stavudine ( two NRTIs likely to cause mitochondrial toxicity ) , 14 HIV+ individuals taking zidovudine and lamivudine , 16 HIV+ individuals not currently taking antiretrovirals , and 17 HIV− controls . The HIV+ groups were comparable on demographic measures , estimates of illness severity , and estimated length of HIV infection . Those taking didanosine and /or stavudine had a significant 11.4 % decrease in concentrations of frontal white matter NAA compared to HIV− controls , whereas NAA levels of the other HIV+ groups were intermediate . Group differences in metabolites were not found in front Output:	The results show that although HAART does improve cognition , it does not appear to fully eradicate impairments .
MS21480	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: There are no data on the prevalence and other epidemiologic characteristics of chronic symmetric polyneuropathy ( CSP ) in the community . This study was design ed to assess the prevalence and risk factors of CSP in well-defined elderly ( 55 years and older ) population s from two separate areas in Italy . Thirty-five general practitioners working in the two areas were invited to interview a r and om sample of patients requesting consultation . They used a pretested question naire which focused on selected symptoms of polyneuropathy , common risk factors for CSP , and current drug treatments . Patients giving affirmative answers to the questions on screening symptoms received a further clinical evaluation by a neurologist . Details are given of the general characteristics of the study areas and population s , the methods of case ascertainment , the validation of the screening instruments , and the results of a pilot study Objective This project evaluated the utility of quantitative sensory techniques in predicting the development of neuropathy for subjects participating in a prospect i ve study . Research Design and Methods Distal symmetric polyneuropathy was evaluated in 77 insulin-dependent diabetes mellitus individuals via quantitative sensory testing , nerve conduction studies , and clinical examination . Results Although the specificity and positive predictive value were low for the quantitative sensory techniques as predictors of neuropathy diagnosed on clinical exam ∼2 yr later , the sensitivity for vibratory thresholds was high ( 100 % ) . Variability over the 2-yr interval was shown on follow-up testing for each of the objective assessment modalities and it was not explained by differences for potential risk factors measured at baseline . Conclusion Despite a cross-sectional relationship between the assessment modalities and clinical ly overt neuropathy at baseline , these follow-up data suggest that the potential for the objective modalities as predictors of clinical ly diagnosed neuropathy may be limited Article abstract -Despite prominent symptoms of neuropathic pain , patients with small-fiber sensory neuropathies have few objective abnormalities on clinical examination and routine electrodiagnostic studies . We quantified intraepidermal nerve fiber ( IENF ) density in sections of skin obtained by punch skin biopsy , and found it to be significantly reduced in patients with painful sensory neuropathies compared with age-matched control subjects . In addition , IENF density correlated with clinical estimates of neuropathy severity , as judged by the extent of clinical ly identifiable sensory abnormalities . IENF density at the calf was lower than that obtained from skin at more proximal sites , indicating the length dependency of small-fiber loss in these neuropathies . NEUROLOGY 1997;48 : 708 - We assessed the involvement of somatic unmyelinated fibers in sensory ganglionopathies by skin biopsy and quantitative sensory testing ( QST ) . Sixteen patients with ganglionopathy , 16 with axonal neuropathy , and 15 normal controls underwent skin biopsy at the proximal thigh and the distal leg . Intraepidermal nerve fibers ( IENF ) were immunostained by antiprotein gene product 9.5 , and their linear density was quantified under light microscopy . Confocal microscopy studies with double staining of nerve fibers and basement membrane were also performed . Healthy subjects and neuropathy patients showed the typical proximodistal gradient of IENF density ; in neuropathies , values were significantly lower at the distal site of the leg , confirming the length-dependent loss of cutaneous innervation . Conversely , ganglionopathy patients with hyperalgesic symptoms did not show any change of IENF density between the proximal thigh and the distal leg . The distinct pattern of epidermal denervation seen in sensory ganglionopathy reflected the degeneration of somatic unmyelinated fibers in a fashion that was not length-dependent , which was consistent with both clinical and neurophysiologic observations and supported the diagnosis Output:	The literature indicates that symptoms alone have relatively poor diagnostic accuracy in predicting the presence of polyneuropathy ; signs are better predictors of polyneuropathy than symptoms ; and single abnormalities on examination are less sensitive than multiple abnormalities in predicting the presence of polyneuropathy . The combination of neuropathic symptoms , signs , and electrodiagnostic findings provides the most accurate diagnosis of distal symmetrical polyneuropathy . The highest likelihood of polyneuropathy ( useful for clinical trials ) occurs with a combination of multiple symptoms , multiple signs , and abnormal electrodiagnostic studies . A modest likelihood of polyneuropathy ( useful for field or epidemiological studies ) occurs with a combination of multiple symptoms and multiple signs when the results of electrodiagnostic studies are not available . A lower likelihood of polyneuropathy occurs when electrodiagnostic studies and signs are discordant . The inclusion of this formalized case definition in clinical and epidemiological research studies will ensure greater consistency of case selection
MS21481	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Purpose Ulinastatin , a serine protease inhibitor , inhibits several pro-inflammatory proteases and decreases inflammatory cytokine levels and mortality in experimental sepsis . We studied the effect of ulinastatin on 28-day all-cause mortality in a double-blind trial in patients with severe sepsis in seven Indian hospitals . Methods Patients with sepsis were r and omized within 48 h of onset of one or more organ failures to receive intravenous administration of ulinastatin ( 200,000 IU ) or placebo 12 hourly for 5 days . Results Of 122 r and omized subjects , 114 completed the study ( 55 receiving ulinastatin , 59 receiving placebo ) . At baseline , the mean APACHE II score was 13.4 ( SD = 4.4 ) , 48 ( 42 % ) patients were receiving mechanical ventilation , 58 ( 51 % ) were on vasopressors , and 35 % had multiple organ failure . In the modified intention-to-treat analysis ( patients receiving six or more doses of study drugs ) , 28-day all-cause mortality was 7.3 % with ulinastatin ( 4 deaths ) versus 20.3 % ( 12 deaths ) with placebo ( p = 0.045 ) . On multivariate analysis too , treatment with ulinastatin ( odds ratio 0.26 , 95 % CI 0.07–0.95 ; p = 0.042 ) independently decreased 28-day all-cause mortality . However , the mortality difference did not reach statistical significance in the intention-to-treat analysis [ 10.2 % ( 6/59 deaths ) with ulinastatin versus 20.6 % ( 13/63 deaths ) in the placebo group ; p = 0.11 ] . The ulinastatin group had lower incidence of new-onset organ failure ( 10 vs. 26 patients , p = 0.003 ) , more ventilator-free days ( mean ± SD 19.4 ± 10.6 days vs. 10.2 ± 12.5 days , p = 0.019 ) , and shorter hospital stay ( 11.8 ± 7.1 days vs. 24.2 ± 7.2 days , p < 0.001 ) . Conclusions In this pilot study , intravenous administration of ulinastatin reduced mortality in patients with severe sepsis in the modified intention-to-treat analysis , but not in the intention-to-treat analysis Introduction Severe sepsis is associated with a high mortality rate despite implementation of guideline recommendations . Adjunctive treatment may be efficient and require further investigation . In light of the crucial role of immunologic derangement in severe sepsis , thymosin alpha 1 ( Tα1 ) is considered as a promising beneficial immunomodulatory drug . The trial is to evaluate whether Tα1 improves 28-day all-cause mortality rates and immunofunction in patients with severe sepsis . Methods We performed a multicenter r and omized controlled trial in six tertiary , teaching hospitals in China between May 12 , 2008 and Dec 22 , 2010 . Eligible patients admitted in ICU with severe sepsis were r and omly allocated by a central r and omization center to the control group or Tα1 group ( 1:1 ratio ) . The primary outcome was death from any cause and was assessed 28 days after enrollment . Secondary outcomes included dynamic changes of Sequential Organ Failure Assessment ( SOFA ) and monocyte human leukocyte antigen-DR ( mHLA-DR ) on day 0 , 3 , 7 in both groups . All analyses were done on an intention-to-treat basis . Results A total of 361 patients were allocated to either the control group ( n = 180 ) or Tα1 ( n = 181 ) group . The mortalities from any cause within 28 days in the Tα1 group and control group were 26.0 % and 35.0 % respectively with a marginal P value ( nonstratified analysis , P = 0.062 ; log rank , P = 0.049 ) ; the relative risk of death in the Tα1 group as compared to the control group was 0.74 ( 95 % CI 0.54 to 1.02 ) . Greater improvement of mHLA-DR was observed in the Tα1 group on day 3 ( mean difference in mHLA-DR changes between the two groups was 3.9 % , 95 % CI 0.2 to 7.6 % , P = 0.037 ) and day 7 ( mean difference in mHLA-DR changes between the two groups was 5.8 % , 95 % CI 1.0 to 10.5 % , P = 0.017 ) than in the control group . No serious drug-related adverse event was recorded . Conclusions The use of Tα1 therapy in combination with conventional medical therapies may be effective in improving clinical outcomes in a targeted population of severe sepsis . Trial registration Clinical Trials.gov NCT00711620 OBJECTIVE The aim of this study was to evaluate the potential efficacy of therapy with thymosin alpha(1 ) and ulinastatin for patients with sepsis due to carbapenem-resistant bacteria . DESIGN Prospect i ve , r and omized , parallel controlled clinical study . METHODS A total of 120 patients received a diagnosis of sepsis caused by infection with carbapenem-resistant bacteria and satisfied the study enrollment criteria . Sixty patients received carbapenems combined with thymosin alpha(1 ) and ulinastatin ( the CTU group ) , and the other 60 patients were treated with carbapenems and placebo ( the CP group ) . For both groups , flow cytometry was used to enumerate lymphocyte subsets , and ELISA was used to determine cytokine concentrations . RESULTS When the 2 groups were compared , the CTU group exhibited a better performance with respect to organ failure scores such as the Acute Physiology and Chronic Health Evaluation II score , the Multiple Organ Failure Score , and the Glasgow Coma Scale . The CTU group also showed significant improvements in CD4(+)CD8(+ ) count after initiation of treatment . In addition , compared with the CP group , in the CTU group the balance between proinflammatory mediators ( such as tumor necrosis factor-alpha , interleukin [IL]-1beta , IL-6 , and IL-8 ) and anti-inflammatory cytokines ( including IL-4 and IL-10 ) was better modulated , and the cumulative survival rate of the CTU group exceeded that of the CP group by 17.8 % at day 28 , 25.9 % at day 60 , and 27.4 % at day 90 . CONCLUSION Immunomodulatory therapy that combines thymosin alpha(1 ) and ulinastatin appears to improve the survival rate for patients infected with carbapenem-resistant bacteria . The number of patients in this study was relatively small , and although the same number of patients was initially enrolled in each study group , the groups were not the same size at the end of the study . Therefore , a larger clinical trial should be conducted to vali date this conclusion . TRIAL REGISTRATION The trial was registered with the Chinese State Food and Drug Administration ( Peking Science and Technology Development Plan , 2002[641 ] ) , ( registration number 2007Y0211 ) Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more OBJECTIVE To investigate the immune and inflammation confusion state in severe sepsis and the effects of two way immunomodulation therapy with continuous blood purification ( CBP ) , thymosin alpha1 , and combined therapy of CBP and thymosin alpha(1 ) . METHODS 91 Patients with severe sepsis aged > 18 , with Marshall score>5 . were r and omly divided into 4 groups : CBP Group ( n = 22 ) undergoing continuous renal replacement therapy ( CRRT ) or molecular adsorbents recirculating system ( MARS ) therapy once a day for 3 days in addition to classical Surviving Sepsis Campaign ( SSC ) therapy , Thymosin alpha(1 ) Group ( n = 23 ) undergoing subcutaneous injection of thymosin alpha(1 ) 1.6 mg once a day for 7 days in addition to SSC therapy , Combined Therapy Group ( n = 22 ) undergoing CBP combined with thymosin alpha(1 ) treatment in addition to SSC therapy , and SSC Group ( treatment control group , n = 24 ) undergoing SSC therapy only . Peripheral blood sample s were collected before treatment , and 3 and 7 days after the beginning of treatment ( days 4 and 8) to detect the serum interleukin (IL)-6 , IL-10 , and tumor necrosis factor (TNF)-alpha . The levels of CD(14)(+ ) monocyte human leucocyte antigen (HLA)-DR and T lymphocytes were monitored . The mechanical ventilation time , ICU stay length , and mortality within 28 d and mortality within 90 d were observed . Ten healthy persons were used as healthy control group . RESULTS Thirty-four of the 91 patients died within 28 d with a mortality of 77.4 % ( Death Group ) and other 57 patients were put in Survival Group . The levels of serum IL-6 , IL-10 , and TNFalpha , and IL-6/IL-10 at different time points of both Death and Survival Groups were all significantly higher , and the HLA-DR level , and CD(3)(+ ) , CD(4)(+ ) , and CD(8)(+ ) T lymphocyte numbers at different time points of both Death and Survival Groups were all significantly lower than those of the healthy controls ( P < 0.05 or < 0.01 ) . The levels of serum IL-6 , IL-6/IL-10 , TNFalpha , HLA-DR , and CD(3)(+ ) , CD(4)(+ ) , and CD(8)(+ ) T lymphocyte at different time points of Death Group were all significantly higher than those of Survival Group ( P < 0.05 or < 0.01 ) . The CD(3)(+ ) T lymphocyte number on day 8 of Thymosin Group was significantly higher than that of SSC Group ( all P < 0.05 ) . The serum IL-6 and TNFalpha and IL-6/IL-10 were decreased , and HLA-DR , and CD(3)(+ ) , CD(4)(+ ) , and CD(8)(+ ) were increased significantly on day 8 in CBP and Combined Therapy Groups . The level of TNFalpha decreased , and the numbers of CD(3)(+ ) and CD(4)(+ ) T lymphocytes increased significantly on day 4 in Combined Therapy Group ( P < 0.05 or P < 0.01 ) . Compared with Thymosin Group , almost all the indexes of CBP and Combined Therapy Groups were improved , only the CD(3)(+ ) T lymphocyte level on day 4 increased and the IL-6/IL-10 ratio on day 8 was decreased significantly in Combined Therapy Group ( both P < 0.05 ) . Compared with those of SSC Group , the mechanical ventilation time , length of ICU stay within 28 days , and 28 days mortality and 90 days mortality of the 3 treatment groups were all decreased , and there were statistical differences in the length of ICU stay of CBP Group and in the mechanical ventilation time and length of ICU stay within 28 days of Combined Therapy Group ( both P < 0.05 ) . CONCLUSION Systemic inflammatory response and immunodepression exist simultaneously in severe sepsis . Thymosin alpha(1 ) increases the cellular immunity , and CBP bi-modulates the immune turbulence , reduces the inflammatory mediators , and ameliorates the immune homeostasis . These 2 therapies also improve the clinical prognosis and the combination of both would be more effective Objectives : To study the effect of immunomodulatory therapy with ulinastatin plus thymosin α 1 on septic patients . Method : A total of 56 sepsis patients were r and omized into a treatment group , receiving immunomodulatory therapy , and a placebo group , a placebo . Acute Physiology and Chronic Health Evaluation II scores , clinical data , lymphocyte subsets , immunological indexes , and coagulation parameters were determined before admission and on the 3rd , 8th , and 28th day after admission to the Intensive Care Unit . Results : The treatment group experienced a 78 % cumulative survival , the placebo group experienced a 60 % cumulative survival ; the survival difference was mirrored by Acute Physiology and Chronic Health Evaluation II scores and more quickly improved leukocyte counts , lymphocyte counts , coagulation parameters , and cytokine levels in the treatment . Conclusions : Combined immunomodulatory therapy with ulinastatin plus thymosin α1 appears to yield improved survival for patients with sepsis ; this finding should be verified in larger clinical trials OBJECTIVE To investigate the effect of ulinastatin ( UTI ) on the levels of immune regulatory cells , pro-inflammatory mediators , and the expression of human leukocyte antigen-DR ( HLA-DR ) in CD14⁺ monocytes . METHODS A total of sixty patients with severe sepsis who were admitted to intensive care unit Output:	Treatment of severe sepsis with UCT reduced both the 28-day and the 90-day mortality , whereas treatment with TA reduced only the 28-day mortality . The effects of UCT , UA , and TA on intensive care unit stay , mechanical ventilation , antibiotics and vasopressor use , and 28-day APACHE II scores of septic patients are still unclear .
MS21482	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Abstract Conclusion : Patients operated with tonsillar surgery report a high degree of symptom relief 6 months after surgery . Objective : The purpose of this study was to analyze symptom relief 6 months after tonsil surgery in relation to age , indication , surgical procedure , primary bleeding and unplanned postoperative visits . The National Tonsil Surgery Register in Sweden offers data from 54 696 patients registered during 1997–2008 . Methods : This was a prospect i ve assessment by question naire . Data were collected using three question naires , two completed by professionals and one 6 months postoperatively by the parents/ patients . Results : Among 54 696 patients , the most common surgical indications were obstruction ( 49.7 % ) , followed by recurrent tonsillitis ( 35.2 % ) . Symptom relief 6 months after surgery was high in all indication groups ( > 92 % ) , and highest for patients operated on the indication peritonsillitis ( > 98 % ) . The indications obstruction , recurrent tonsillitis or chronic tonsillitis reported a high degree ( > 96 % ) of symptom relief . Of the patients who underwent tonsillectomy with adenoidectomy , 97.5 % were symptom-free compared to 96 % of patients who had tonsillectomy alone and 96.1 % who underwent tonsillotomy ( p < 0.0001 ) . In all , 13.9 % of patients required an unplanned visit to the clinic postoperatively . Only 148 of 54 696 patients reported worsening of symptoms after surgery OBJECTIVE To assess the effectiveness of adenotonsillectomy in children with mild symptoms of throat infections or adenotonsillar hypertrophy . DESIGN Open , r and omised controlled trial . SETTING 21 general hospitals and three academic centres in the Netherl and s. PARTICIPANTS 300 children aged 2 - 8 years requiring adenotonsillectomy . INTERVENTION Adenotonsillectomy compared with watchful waiting . MAIN OUTCOME MEASURES Episodes of fever , throat infections , upper respiratory tract infections , and health related quality of life . RESULTS During the median follow up period of 22 months , children in the adenotonsillectomy group had 2.97 episodes of fever per person year compared with 3.18 in the watchful waiting group ( difference -0.21 , 95 % confidence interval -0.54 to 0.12 ) , 0.56 throat infections per person year compared with 0.77 ( -0.21 , -0.36 to -0.06 ) , and 5.47 upper respiratory tract infections per person year compared with 6.00 ( -0.53 , -0.97 to -0.08 ) . No clinical ly relevant differences were found for health related quality of life . Adenotonsillectomy was more effective in children with a history of three to six throat infections than in those with none to two . 12 children had complications related to surgery . CONCLUSION Adenotonsillectomy has no major clinical benefits over watchful waiting in children with mild symptoms of throat infections or adenotonsillar hypertrophy OBJECTIVE To compare the estimated cost-effectiveness of childhood (adeno)tonsillectomy vs medical therapy for recurrent sore throats from the intention-to-treat ( ITT ) analysis of a r and omized controlled trial ( RCT ) with that modeled on the recorded timing of surgical interventions as observed in all participants irrespective of their original group allocation . STUDY DESIGN A pragmatic RCT ( trial ) with a parallel nonr and omized patient preference group ( cohort ) of (adeno)tonsillectomy vs medical therapy . SETTING Five secondary care UK otolaryngology departments . SUBJECTS AND METHODS Eligible children , aged 4 to 15 years , were enrolled to the trial ( 268 ) or cohort ( 461 ) groups . Outcomes included sore throat diaries , quality of life , and general practice consultations . The RCT protocol ITT analysis was compared with an as-treated analysis incorporating the cohort group , modeled to reflect the timing of tonsillectomy and the differential switch rates among the original groups . RESULTS In the RCT ITT analysis , tonsillectomy saved 3.5 sore throats , whereas the as-treated model suggested an average reduction of more than 8 sore throats in 2 years for surgery within 10 weeks of consultation , falling to only 3.5 twelve months later due to the spontaneous improvement in the medical therapy group . CONCLUSION In eligible UK school-age children , tonsillectomy can save up to 8 sore throats at a reasonable cost , if performed promptly . Further prospect i ve data collection , accounting for baseline and per-trial preferences and choice , is urgently needed Abstract Objective To assess the effectiveness of adenotonsillectomy in children with mild symptoms of throat infections or adenotonsillar hypertrophy . Design Open , r and omised controlled trial . Setting 21 general hospitals and three academic centres in the Netherl and s. Participants 300 children aged 2 - 8 years requiring adenotonsillectomy . Intervention Adenotonsillectomy compared with watchful waiting . Main outcome measures Episodes of fever , throat infections , upper respiratory tract infections , and health related quality of life . Results During the median follow up period of 22 months , children in the adenotonsillectomy group had 2.97 episodes of fever per person year compared with 3.18 in the watchful waiting group ( difference −0.21 , 95 % confidence interval −0.54 to 0.12 ) , 0.56 throat infections per person year compared with 0.77 ( −0.21 , −0.36 to −0.06 ) , and 5.47 upper respiratory tract infections per person year compared with 6.00 ( −0.53 , −0.97 to −0.08 ) . No clinical ly relevant differences were found for health related quality of life . Adenotonsillectomy was more effective in children with a history of three to six throat infections than in those with none to two . 12 children had complications related to surgery . Conclusion Adenotonsillectomy has no major clinical benefits over watchful waiting in children with mild symptoms of throat infections or adenotonsillar hypertrophy We studied the efficacy of tonsillectomy , or tonsillectomy with adenoidectomy , in 187 children severely affected with recurrent throat infection . Ninety-one of the children were assigned r and omly to either surgical or nonsurgical treatment groups , and 96 were assigned according to parental preference . In both the r and omized and nonr and omized trials , the effects of tonsillectomy and of tonsillectomy with adenoidectomy were similar . By various measures , the incidence of throat infection during the first two years of follow-up was significantly lower ( P less than or equal to 0.05 ) in the surgical groups than in the corresponding nonsurgical groups . Third-year differences , although in most cases not significant , also consistently favored the surgical groups . On the other h and , in each follow-up year many subjects in the nonsurgical groups had fewer than three episodes of infection , and most episodes among subjects in the nonsurgical groups were mild . Of the 95 subjects treated with surgery , 13 ( 14 per cent ) had surgery-related complications , all of which were readily managed or self-limited . These results warrant the election of tonsillectomy for children meeting the trials ' stringent eligibility criteria , but also provide support for nonsurgical management . Treatment for such children must therefore be individualized A clinical trial to study the effects of adenotonsillectomy showed that children with a marked susceptibility to respiratory tract infection benefited from the operation , especially by a reduction in throat illness . They did not reach the state of health of the " normal " child so far as respiratory tract and nonrespiratory diseases were concerned even after two years , but the difference was lessened in the second year as the first-year improvement was increased in the second year . The difference between the hospitalized and the normal children could be due to an immunological defect in the former . The decision to operate should be made in the light of a documented history of the child 's illnesses following a vigorous course of nasal hygiene which can alter the clinical state due to the removal of a source of infection OBJECTIVES To examine the clinical effectiveness and cost-effectiveness of tonsillectomy/adeno-tonsillectomy in children aged 4 - 15 years with recurrent sore throats in comparison with st and ard non-surgical management . DESIGN A pragmatic r and omised controlled trial with economic analysis comparing surgical intervention with conventional medical treatment in children with recurrent sore throats ( trial ) and a parallel non-r and omised cohort study ( cohort study ) . SETTING Five secondary care otolaryngology departments located in the north of Engl and or west of Scotl and . PARTICIPANTS 268 ( trial : 131 allocated to surgical management ; 137 allocated to medical management ) and 461 ( cohort study : 387 elected to have surgical management ; 74 elected to have medical management ) children aged between 4 and 15 years on their last birthday with recurrent sore throats . Participants were stratified by age ( 4 - 7 years , 8 - 11 years , 12 - 15 years ) . INTERVENTIONS Treatment was tonsillectomy and adeno-tonsillectomy with adenoid curettage and tonsillectomy by dissection or bipolar diathermy according to surgical preference within 12 weeks of r and omisation . The control was non-surgical conventional medical treatment only . MAIN OUTCOME MEASURES The primary clinical outcome was the reported number of episodes of sore throat in the 2 years after entry into the study . Secondary clinical outcomes included : the reported number of episodes of sore throat ; number of sore throat-related GP consultations ; reported number of symptom-free days ; reported severity of sore throats ; and surgical and anaesthetic morbidity . In addition to the measurement of these clinical outcomes , the impact of the treatment on costs and quality of life was assessed . RESULTS Of the 1546 children assessed for eligibility , 817 were excluded ( 531 not meeting inclusion criteria , 286 refused ) and 729 enrolled to the trial ( 268 ) or cohort study ( 461 ) . The mean ( st and ard deviation ) episode of sore throats per month was in year 1 - cohort medical 0.59 ( 0.44 ) , cohort surgical 0.71 ( 0.50 ) , trial medical 0.64 ( 0.49 ) , trial surgical 0.50 ( 0.43 ) ; and in year 2 - cohort medical 0.38 ( 0.34 ) , cohort surgical 0.19 ( 0.36 ) , trial medical 0.33 ( 0.43 ) , trial surgical 0.13 ( 0.21 ) . During both years of follow-up , children r and omised to surgical management were less likely to record episodes of sore throat than those r and omised to medical management ; the incidence rate ratios in years 1 and 2 were 0.70 [ 95 % confidence interval ( CI ) 0.61 to 0.80 ] and 0.54 ( 95 % CI 0.42 to 0.70 ) respectively . The incremental cost-effectiveness ratio was estimated as 261 pounds per sore throat avoided ( 95 % confidence interval 161 pounds to 586 pounds ) . Parents were willing to pay for the successful treatment of their child 's recurrent sore throat ( mean 8059 pounds ) . The estimated incremental cost per quality -adjusted life-year ( QALY ) ranged from 3129 pounds to 6904 pounds per QALY gained . CONCLUSIONS Children and parents exhibited strong preferences for the surgical management of recurrent sore throats . The health of all children with recurrent sore throat improves over time , but trial participants r and omised to surgical management tended to experience better outcomes than those r and omised to medical management . The limitations of the study due to poor response at follow-up support the continuing careful use of ' watchful waiting ' and medical management in both primary and secondary care in line with current clinical guidelines until clear-cut evidence of clinical effectiveness and cost-effectiveness is available . TRIAL REGISTRATION Current Controlled Trials IS RCT N47891548 OBJECTIVE In previous clinical trials involving children severely affected with recurrent throat infection ( 7 or more well-documented , clinical ly important , adequately treated episodes of throat infection in the preceding year , or 5 or more such episodes in each of the 2 preceding years , or 3 or more such episodes in each of the 3 preceding years ) , we found tonsillectomy efficacious in reducing the number and severity of subsequent episodes of throat infection for at least 2 years . The results seemed to warrant the election of tonsillectomy in children meeting the trials ' stringent eligibility criteria but also provided support for nonsurgical management . We undertook the present trials to determine 1 ) whether tonsillectomy would afford equivalent benefit in children who were less severely affected than those in our earlier trials but who nonetheless had indications for tonsillectomy comparable to those in general use , and 2 ) whether , in such children , the addition of adenoidectomy would confer additional benefit . METHODS We conducted 2 parallel r and omized , controlled trials in the Ambulatory Care Center of Children 's Hospital of Pittsburgh . To be eligible , children were required to have had a history of recurrent episodes of Output:	We found no evidence for prescription of antibiotics . Adeno-/tonsillectomy leads to a reduction in the number of episodes of sore throat and days with sore throat in children in the first year after surgery compared to ( initial ) non-surgical treatment . Children who were more severely affected were more likely to benefit as they had a small reduction in moderate/severe sore throat episodes . The size of the effect is very modest , but there may be a benefit to knowing the precise timing of one episode of pain lasting several days - it occurs immediately after surgery as a direct consequence of the procedure . It is clear that some children get better without any surgery , and that whilst removing the tonsils will always prevent ' tonsillitis ' , the impact of the procedure on ' sore throats ' due to pharyngitis is much less predictable . Insufficient information is available on the effectiveness of adeno-/tonsillectomy versus non-surgical treatment in adults to draw a firm conclusion .The impact of surgery , as demonstrated in the included studies , is modest . Many participants in the non-surgical group improve spontaneously ( although some people r and omised to this group do in fact undergo surgery ) . The potential ' benefit ' of surgery must be weighed against the risks of the procedure as adeno-/tonsillectomy is associated with a small but significant degree of morbidity in the form of primary and secondary haemorrhage and , even with good analgesia , is particularly uncomfortable for adults
MS21483	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: ABSTRACT . Examined is the relationship of patient-reported health-related quality of life ( HRQOL ) to the mode of survey administration in the Hemodialysis Study . In addition to self-administered surveys to assess HRQOL , interviewer-administered surveys were made available to include patients with poor vision , decreased manual dexterity , or strong preference . For examining the predictors of participation by self-administration of the survey , multiple logistic regression was performed . For examining the relationship of HRQOL results to mode of survey administration , adjusted differences between the self-administered and interviewer-administered groups were obtained from multiple linear regression models accounting for sociodemographic and case-mix factors . A total of 978 of the first 1000 subjects in the Hemodialysis Study completed the survey by interview ( n = 427 ) or by self-administration ( n = 551 ) . The interviewer-administered group was older , was more likely black , had longer duration of ESRD , had a higher prevalence of diabetes , and had more severe comorbidity ( all P < 0.01 ) . After adjustment for these differences , patients in the interviewer-administered group had higher scores on scales that measured Role-Physical , Role-Emotional , and Effects of Kidney Disease ( all P < 0.001 ) . Dialysis studies that restrict HRQOL measurement to patients who are able to complete surveys without assistance will not accurately represent the health of the overall hemodialysis population . Clinical studies and clinical practice s using HRQOL as an outcome should include interviewer administration or risk a selection bias against subjects with older age , minority status , and higher level of comorbidity . Future investigation should include research of survey modalities with a low response burden such as telephone interview , computer-assisted interview , and proxy administration Because of its sound psychometric properties the SF-36 General Health Question naire is used throughout the world , yet it is difficult to analyse and score . Using a newly developed software package , onto which any question naire can be loaded , we developed an electronic version of the SF-36 General Health Question naire . The purpose of this study is test the effect of the electronic mode of administration on the measurement properties of the SF-36 . In a r and omised cross-over design study 79 healthy individuals and 36 chronic pain patients completed both electronic and paper versions of the SF-36 . Seventy-one percent preferred the electronic SF-36 , 7 % stated no preference , and 22 % preferred the paper version . Completion time for the electronic SF-36 was slightly less , and there were no missing or problematical responses , whereas 44 % of participants had at least one missing or problematical response in the paper version . Data entry and auditing time was 8 hours . There was less than 4 % inter-version difference for any of the SF-36 sub-scales . The electronic SF-36 was well accepted and slightly quicker to complete than the paper version . We conclude that the electronic SF-36 is equivalent in performance and more effective than the paper version Background The Internet has tremendous appeal for conducting r and omized clinical trials and may be especially applicable to trials requiring frequent participant contact . Trials of cold sore remedies , for example , often require daily clinic visits during outbreaks , imposing substantial burden on participants . An Internet-based r and omized clinical trial design may reduce this burden , permitting frequent symptom reports with considerably less effort . Objective To evaluate the feasibility of a Web-based r and omized clinical trial requiring frequent participant interaction , using a 6-month , double-blind , r and omized , placebo-controlled pilot trial of a topical ointment containing dioctyl sodium sulfosuccinate ( DSS ) ( Zilex ; Meditech Pharmaceuticals , Inc , Scottsdale , Arizona , USA ) intended for treatment of recurrent herpes labialis . A secondary objective was to obtain preliminary data on effectiveness outcomes , to assist in planning a fully-powered trial of DSS . Methods Adults with physician-confirmed herpes labialis were recruited to apply to the trial . Eligible applicants were r and omized to DSS or placebo , mailed to them upon enrolment with instructions to apply topically every 2 hours for the duration of every cold sore outbreak . Participants were instructed to complete online question naires at 2-week intervals and , at the initiation of a cold sore , daily " outbreak question naires " until outbreak termination . Feasibility outcome measures included trial participant characteristics , frequency of cold sores , participant retention and adherence ( to study medication ) , and data completeness . Treatment effectiveness outcome measures included outbreak duration , days to crust formation , and pain . Results Of the 292 individuals applying , 182 screened eligible ; 32 participants with confirmed herpes labialis enrolled in the trial . 16 were r and omized into the verum group and 16 into the placebo group . 29 ( 91 % ) participants completed the trial . During the trial , 34 outbreaks were reported among 23 ( 72 % ) participants , result ing in a cold sore incidence rate of 19.8 per 100 person-months of observation . Online data were available for 32 outbreaks ; the absence of a resolution date made it impossible to accurately calculate the duration of 12 ( 38 % ) outbreaks . Although the DSS treatment group had a shorter mean outbreak duration ( 6.6 vs 7.7 days , P= .2 ) and fewer mean days to crust formation ( 3.5 vs 4.9 , P= .1 ) , these differences did not reach statistical significance . The DSS group has statistically significant lower mean pain scores ( 3.1 vs 7.6 , P= .04 ) , but participants in this group also consumed more acetaminophen tablets than the placebo group ( 1.1 versus 0.5 , P=.55 ) . Adherence to medication was similar in both groups : 7 ( 50 % ) of the verum group reported using the cream as directed compared to 6 ( 46.2 % ) in the placebo group ; ( P= .8 ) . Conclusions We efficiently recruited participants and achieved high overall retention rates . However , participant adherence to the daily outbreak visit schedules was low and only 7 ( 50 % ) participants used the cream as directed . These limitations could be addressed in future Internet-based studies by using Personal Digital Assistants ( PDAs ) , using reminder devices , and providing incentives . By enhancing participant adherence , clinical trials requiring frequent participant contact may be feasible over the Internet Background Measurement of socioeconomic position ( SEP ) over the life course in population health surveillance systems is important for examining differences in health and illness between different population groups and for monitoring the impact of policies and interventions aim ed at reducing health inequities and intergenerational disadvantage over time . While face-to-face surveys are considered the gold st and ard of interviewing techniques , computer-assisted telephone interviewing is often preferred for cost and convenience . This study compared recall of parents ' highest level of education in telephone and face-to-face surveys . Methods Questions about father 's and mother 's highest education level were included in two representative population health surveys of South Australians aged 18 years and over in Spring 2004 . A r and om sample selected from the electronic white pages ( EWP ) responded to a computer-assisted telephone interview ( n = 2999 ) , and a multistage clustered area sample responded to a face-to-face interview ( n = 2893 ) . A sub sample of respondents in the face-to-face sample who owned a telephone that was listed in the EWP ( n = 2206 ) was also compared to the telephone interview sample . Results The proportion of respondents who provided information about their father 's and mother 's highest education level was significantly higher in the face-to-face interview ( 86.3 % and 87.8 % , respectively ) than in the telephone interview ( 80.4 % and 79.9 % , respectively ) . Recall was also significantly higher in the sub sample of respondents in the face-to-face interview who had a telephone that was listed in the EWP . Those with missing data for parents ' education were more likely to be socioeconomically disadvantaged regardless of the survey mode . Conclusion While face-to-face interviewing obtained higher item response rates for questions about parents ' education , survey mode did not appear to influence the factors associated with having missing data on father 's or mother 's highest education level Can r and omised controlled trials be successfully conducted over the internet ? The authors report a feasibility study of such a trial in patients with osteoarthritis of the knee The possibility of conducting clinical trials entirely on line is an enticing but relatively unexplored medical application of the internet . The penetrance of the internet in the population offers the possibility of rapid recruitment of participants , and technological advances enable instant collection of data in a secure and confidential manner.1 These attributes could theoretically accelerate the evaluation of many compounds by cutting costs and reducing the duration of each study . Many components of an online trial , such as recruitment websites and electronic data capture technologies , have been separately described,2–4 but few attempts have been made to integrate these into a single process , and no study has evaluated the performance of such an endeavour . We set out to explore these issues by attempting a prototype double blind r and omised placebo controlled trial in people recruited and followed entirely over the internet . The underlying intention in the design was to translate , as far as possible , all elements of a rigorous r and omised placebo controlled trial into the virtual domain . To maximise the chance of success we chose to test glucosamine , a safe nutritional product popularly taken for symptoms of osteoarthritis of the knee,5 by using a trial design appropriate for this purpose . We design ed a 14 week ( 2 week run-in , 12 week intervention ) internet based placebo controlled r and omised trial of glucosamine with biweekly scheduled online assessment s of knee pain with the Western Ontario and McMaster Universities osteoarthritis index ( WOMAC ) as the primary outcome measure.6 The WOMAC was developed and vali date d as a self report question naire , can be used on a computer screen , and is recommended as a primary outcome for osteoarthritis BACKGROUND Previous research suggests that people respond differently to health status measures when data are collected by interview or self completion of a question naire . The objective of this study was to determine whether SF-36 health status scores differ systematic ally by method of administration . METHOD A r and omized cross-over study was carried out on 210 new attenders at general medicine , endocrinology , gastroenterology and urological out-patient departments . The outcome was the difference in SF-36 profiles comparing clinic based interviews with self completion at home by the same subjects . RESULTS For seven of the eight variables of the SF-36 scores were lower in the self assessment , the differences being statistically significant in four of the eight comparisons . The largest differences were in role limitations due to emotional problems ( difference 14.74 , 95 per cent confidence interval ( CI ) 7.76 - 21.7 ) and social function ( difference 7.21 , 95 per cent CI 3.19 - 11.23 ) . CONCLUSIONS Clinic based interviews systematic ally exaggerate health status compared with self assessment . The difference is sufficiently large to underestimate the effectiveness of health service interventions when a clinic based pre-intervention and postal self completed follow-up design is used , unless adjustment is made for this systematic bias Surveys of risk behaviors have been hobbled by their reliance on respondents to report accurately about engaging in behaviors that are highly sensitive and may be illegal . An audio computer-assisted self-interviewing ( audio-CASI ) technology for measuring those behaviors was tested with 1690 respondents in the 1995 National Survey of Adolescent Males . The respondents were r and omly assigned to answer questions using either audio-CASI or a more traditional self-administered question naire . Estimates of the prevalence of male-male sex , injection drug use , and sexual contact with intravenous drug users were higher by factors of 3 or more when audio-CASI was used . Increased reporting was also found for several other risk behaviors OBJECTIVE : To test the feasibility of creating a valid and reliable checklist with the following features : appropriate for assessing both r and omised and non-r and omised studies ; provision of both an overall score for study quality and a profile of scores not only for the quality of reporting , internal validity ( bias and confounding ) and power , but also for external validity . DESIGN : A pilot version was first developed , based on epidemiological principles , review s , and existing checklists for r and omised studies . Face and content validity were assessed by three experienced review ers and reliability was determined using two raters assessing 10 r and omised and 10 non-r and omised studies . Using different raters , the checklist was revised and tested for internal consistency ( Kuder-Richardson 20 ) , test-retest and inter-rater reliability ( Spearman correlation coefficient and sign rank test ; kappa statistics ) , criterion validity , and respondent burden . MAIN RESULTS : The performance of the checklist improved considerably after revision of a pilot version . The Quality Index had high internal consistency ( KR-20 : 0.89 ) as did the subscales apart from external validity ( KR-20 : 0.54 ) . Test-retest ( r 0.88 ) and inter-rater ( r 0.75 ) reliability of the Quality Index were good . Reliability of the subscales varied from good ( bias ) to poor ( external validity ) . The Quality Index correlated highly with an existing , established instrument for assessing r and omised studies ( r 0.90 ) . There was little difference between its performance with non-r and omised and with r and omised studies . Raters took about 20 minutes to assess each paper ( range 10 to 45 minutes ) . CONCLUSIONS : This study has shown that it is feasible to develop a checklist that can be used to assess the method ological quality not only of r and omised controlled trials but also non-r and omised studies . It has also shown that it is possible to produce a check Output:	Two features of mode were clearly associated with bias in response ; however , none of the features of mode was associated with changes in precision . In terms of mediating factors , there was some suggestion that there was an interaction between both telephone and computer for data collection and date of publication , supporting the theory that differences disappear as new technologies become commonplace . Individual analysis of the Short Form question naire-36 items and Minnesota Multiphasic Personality Inventory ( MMPI ) showed a varied pattern across the different subscales , with conflicting results between the two types of study . None of the MMPI measures used to detect deviant responding showed a relationship with the mode features tested .
MS21484	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: BACKGROUND In an era of cost containment and outcome -based medicine , bariatric surgeons are attempting to decrease perioperative morbidity and streamline care . One way of accomplishing this is by decreasing opioid use and hospital stay . Several studies of nonbariatric open procedures have shown that continuous infusion catheters ( CIC ) are beneficial . Bariatric surgeons frequently utilize CIC , but the data is sparse for the clinical efficacy in laparoscopic procedures . OBJECTIVE Evaluate the efficacy of CIC in laparoscopic sleeve gastrectomy . SETTING military teaching hospital . METHODS In this single institution prospect i ve r and omized double-blind controlled study , 82 patients undergoing laparoscopic sleeve gastrectomy ( LSG ) received either .2 % ropivacaine or .9 % normal saline ( placebo ) via CIC . After discharge , total narcotic usage , total antiemetic usage , pain scores , and hospital length of stay were evaluated . A one-way ANOVA was used to assess statistical significance . Power was 80 % to detect 52 mg morphine equivalent difference . RESULTS A total of 82 patients were enrolled , 39 received ropivacaine , and 43 received placebo . There was no statistically significant difference in narcotic usage between the ropivacaine group and placebo group , 51.9 mg versus 55.2 mg , respectively ( P = .63 ) . Ondansetron usage was 10.7 mg and 10.6 mg for ropivacaine and placebo groups . ( P = .98 ) . Average pain score was 3.0 for each group ( P = .632 ) . Total hospital length of stay was 37.5 hours for ropivacaine group and 38.1 hours for placebo group ( P = .768 ) . CONCLUSIONS We found no difference in narcotic usage , antiemetic usage , pain scores , or hospital length of stay between ropivacaine and placebo groups . We conclude there is no utility of CIC in LSG BACKGROUND Postoperative pain can be prevented . Gabapentin may be effective in this role . Our primary objective was to test the hypothesis that a prophylactic administration of gabapentin in obese patients before surgery has an opioid-sparing effect and reduces postoperative oxycodone consumption more efficiently than placebo . METHODS The study enrolled 113 patients undergoing laparoscopic sleeve-gastrectomy under general anesthesia . The patients were r and omly allocated to the control or gabapentin group and received a single oral dose of gabapentin 1200 mg or a matching placebo 1 h before surgery . RESULTS The mean time from the end of anesthesia to the commencement of analgesic therapy was 74.3±37.8 minutes in the placebo group and 110.4±65.4 minutes with gabapentin ( mean difference : -36 , 95 % CI : 12 to 40 , P=0.0004 ) . The mean 12-hour oxycodone consumption was 31.5±10 mg with placebo and 26.3±10 mg with gabapentin ( mean difference : -5.2 mg , 95 % CI : -9.08 to -1.35 , P=0.0085 ) . The mean NRS pain intensity at 12 hours was 2±0.9 in the placebo group and 1.5±0.9 with gabapentin ( mean difference : -0.5 , 95 % CI : 0.15 to 0.81 , P=0.003 ) . CONCLUSIONS The dem and for oxycodone was delayed in the gabapentin group ; also , the total 12-hour dose requirement of oxycodone was lower in the gabapentin group Purpose The transversus abdominis plane ( TAP ) block is a technique increasingly used for analgesia after surgery on the anterior abdominal wall . We undertook this study to determine the feasibility and analgesic efficacy of ultrasound-guided TAP blocks in morbidly obese patients . We describe the dermatomal spread of local anesthetic in TAP blocks administered , and test the hypothesis that TAP blocks decrease visual analog scale ( VAS ) scores . Patients and methods After ethics committee approval and informed consent , 35 patients with body mass index > 35 undergoing single-port sleeve gastrectomy ( SPSG ) were enrolled . All patients received balanced general anesthesia , followed by intravenous patient-controlled analgesia ( IV-PCA ; hydromorphone ) postoperatively ; all reported VAS > 3 upon arrival to the recovery room . From the cohort of 35 patients having single-port laparoscopy ( SPL ) , a sealed envelope method was used to r and omly select ten patients to the TAP group and 25 patients to the control group . The ten patients in the TAP group received ultrasound-guided TAP blocks with 30 mL of 0.2 % Ropivacaine injected bilaterally . The dermatomal distribution of the sensory block ( by pinprick test ) was recorded . VAS scores for the first 24 hours after surgery and opioid use were compared between the IV-PCA+TAP block and IV-PCA only groups . Results Sensory block ranged from T5–L1 . Mean VAS pain scores decreased from 8 ± 2 to 4 ± 3 ( P=0.04 ) within 30 minutes of TAP block administration . Compared with patients given IV-PCA only , significantly fewer patients who received TAP block had moderate or severe pain ( VAS 4–10 ) after block administration at 6 hours and 12 hours post-surgery . However , cumulative consumption of hydromorphone at 24 hours after SPSG surgery was similar for both groups . Conclusion Ultrasound-guided TAP blocks in morbidly obese patients are feasible and result in satisfactory analgesia following SPSG in the immediate postoperative period BACKGROUND OFIRMEV is an intravenous form of acetaminophen approved by the Food and Drug Administration for use as an antipyretic and treatment of mild to moderate pain alone or in conjunction with opioid medications . Intravenous APAP use in postsurgical pain management has been reported to decrease opioid usage , time to rescue dose , and subjective pain . OBJECTIVES We used a placebo-controlled , r and omized double-blind study to test the efficacy of OFIRMEV in decreasing opioid use and subjective pain after laparoscopic sleeve gastrectomy . SETTING U.S. military training hospital . METHODS Thirty-four patients who met criteria were enrolled and r and omly assigned to 2 separate limbs of the study . The OFIRMEV and placebo groups had similar mean age ranges ( 48±11 and 50±11 yr ) and a female/male ratio of 5:1 and 6:1 , respectively . The patients received an intraoperative dose and then postoperative administration of intravenous OFIRMEV 1 g or placebo every 6 hours for 24 hours in addition to fentanyl via patient-controlled analgesia . Subjective pain scores , the total amount of fentanyl used , time to rescue of first narcotic dose , and total postanesthesia care unit ( PACU ) narcotic use were measured during the first 24 hours after surgery . RESULTS Subjective pain score was significantly decreased compared with baseline at 12 , 16 , and 20 hours after surgery in OFIRMEV-treated patients but not in the placebo group . However , total narcotic use , time to rescue of first narcotic dose , and total PACU narcotic dose were not statistically different between the 2 groups . CONCLUSION Intravenous OFIRMEV use caused a modest but statistically significant decrease in subjective pain without affecting narcotic use after laparoscopic sleeve gastrectomy . ( Surg Obes Relat Dis 2015;0:000 - 00 . ) © 2015 American Society for Metabolic and Bariatric Surgery . All rights reserved BACKGROUND AND OBJECTIVE Postoperative nausea and vomiting ( PONV ) occur frequently after laparoscopic bariatric surgery . The combination of haloperidol , dexamethasone , and ondansetron may reduce these undesirable events . The aim of this study was to evaluate the intensity of nausea and pain , the number of vomiting episodes , and morphine consumption in postoperative ( PO ) obese patients undergoing laparoscopic sleeve gastrectomy ( LSG ) . METHOD A clinical , r and omized , controlled , double-blind study conducted with 90 patients with body mass index ≥ 35 kg.cm(-2 ) . Patients were divided into three groups of 30 individuals to receive ondansetron 8 mg ( Group O ) ; ondansetron 8 mg and dexamethasone 8 mg ( Group OD ) ; and ondansetron 8 mg , dexamethasone 8 mg , and haloperidol 2 mg ( Group HDO ) . We evaluated the intensity of nausea and pain using the verbal numeric scale , cumulative number of vomiting episodes , and morphine consumption in the period of 0 - 2 , 2 - 12 , 12 - 24 , and 24 - 36 hours postoperatively . RESULTS Nausea intensity was lower in Group HDO compared to Group O ( p = 0.001 ) , pain intensity was lower in Group HDO compared to Group O ( p = 0.046 ) , and morphine consumption was lower in Group HDO compared to Group O ( p = 0.037 ) . There was no difference between groups regarding the number of vomiting episodes ( p = 0.052 ) . CONCLUSION The combination of haloperidol , ondansetron , and dexamethasone reduced nausea and pain intensity and morphine consumption in postoperative obese patients undergoing LSG Background : The use of opioids in surgeries for morbidly obese patients could cause respiratory depression . Therefore , alternative analgesics are needed to improve anesthetic management for obese patients . The objective of this study was to compare the effect of dexmedetomidine and clonidine on pain as well as analgesic consumption at 24 h postoperatively in patients undergoing laparoscopic gastric sleeve . The secondary objective was to compare patients ’ and surgeons ’ satisfaction . Material s and Methods : A total of 60 obese and morbidly obese patients scheduled to undergo laparoscopic gastric sleeve were r and omly assigned into two groups . 10 min after induction of general anesthesia , one group received 0.8 - 1.2 μg/kg/30 min intravenous ( IV ) clonidine through 500 mL lactated Ringer 's solution and placebo ( normal saline solution ) through syringe pump . The second group received IV dexmedetomidine through syringe pump at a rate 0.5 - 0.8 μg/kg/h and placebo through 500 mL lactated Ringer 's solution . Data on pain , analgesic consumption , and return to normal activity in addition to patients ’ and surgeons ’ satisfaction were collected . Results : Both groups were similar with respect to demographic and intraoperative hemodynamic characteristics . Fentanyl consumption , surgery duration and hospital stay were similar for the two groups . Pain scores on walking were significantly lower in the clonidine group at 12 h postoperatively ( P = 0.014 ) compared with dexmedetomidine group . The number of patients who consumed pethidine was significantly lower in the clonidine group at 12 h postoperatively ( P = 0.045 ) . Conclusion : This study concluded that clonidine and dexmedetomidine yielded similar outcomes with a difference in pain and analgesic consumption at 12 h postoperatively Introduction Although bariatric surgery is actually mainly performed laparoscopically , analgesic optimization continues being essential to reduce complications and to improve the patients ’ comfort . The aim of this study is to evaluate the postoperative pain after analgesia iv exclusively , or associated with epidural analgesia or port-sites infiltration with bupivacaine . Patients and methods A prospect i ve r and omized study of patients undergoing laparoscopic sleeve gastrectomy between 2012 and 2014 was performed . Patients were divided into three groups : Analgesia iv exclusively ( Group 1 ) , epidural analgesia + analgesia iv ( Group 2 ) and port-sites infiltration + analgesia iv ( Group 3 ) . Pain was quantified by means of a Visual Analogic Scale , and morphine rescue needs were determined 24 h after surgery . Results A total of 147 were included . Groups were comparable in age , gender and BMI . There were no differences in operation time , complications , mortality or hospital stay between groups . Median pain 24 h after surgery was 5 in Group 1 , 2.5 in Group 2 and 2 in Group 3 ( P = 0.01 ) , without statistically significant differences between Groups 2 and 3 . In Group 1 , morphine rescue was necessary in 16.3 % of the cases , 2 % in Group 2 and 2 % in Group 3 ( P = 0.014 ) , without statistically significant differences between Groups 2 and 3 . Conclusion Epidural analgesia and port-sites infiltration with bupivacaine , associated with analgesia iv , reduce the postoperative pain , when compared with analgesia iv exclusively . Clinical trials Clinical Trials.gov Identifier : NCT02662660 Background The treatment of pain in obese patients is always a challenge . These patients have low pain thresholds , and the use of opioids can be especially harmful . Intraoperative nervous fiber section and the high temper Output:	Gabapentinoids and transversus abdominis plane blocks reduced LSG postoperative pain . There was limited procedure-specific evidence of analgesic effects for acetaminophen , non-steroidal anti-inflammatory drugs , dexamethasone , magnesium , and tramadol in this setting . Inconsistent evidence was found in the studies investigating alpha-2-agonists . No evidence was found for intraperitoneal local anesthetic administration or single-port laparoscopy .
MS21485	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Study Design . Two abdominal muscle patterns were tested in the same group of individuals , and their effects were compared in relation to sacroiliac joint laxity . One pattern was contraction of the transversus abdominis , independently of the other abdominals ; the other was a bracing action that used all the lateral abdominal muscles . Objectives . To demonstrate the biomechanical effect of the exercise for the transversus abdominis known to be effective in low back pain . Summary of Background Data . Drawing in the abdominal wall is a specific exercise for the transversus abdominis muscle ( in cocontraction with the multifidus ) , which is used in the treatment of back pain . Clinical effectiveness has been demonstrated to be a reduction of 3-year recurrence from 75 % to 35 % . To the authors ’ best knowledge , there is not yet in vivo proof of the biomechanical effect of this specific exercise . This study of a biomechanical model on the mechanics of the sacroiliac joint , however , predicted a significant effect of transversus abdominis muscle force . Methods . Thirteen healthy individuals who could perform the test patterns were included . Sacroiliac joint laxity values were recorded with study participants in the prone position during the two abdominal muscle patterns . The values were recorded by means of Doppler imaging of vibrations . Simultaneous electromyographic recordings and ultrasound imaging were used to verify the two muscle patterns . Results . The range of sacroiliac joint laxity values observed in this study was comparable with levels found in earlier studies of healthy individuals . These values decreased significantly in all individuals during both muscle patterns ( P < 0.001 ) . The independent transversus abdominis contraction decreased sacroiliac joint laxity ( or rather increased sacroiliac joint stiffness ) to a significantly greater degree than the general abdominal exercise pattern ( P < 0.0260 ) . Conclusions . Contraction of the transversus abdominis significantly decreases the laxity of the sacroiliac joint . This decrease in laxity is larger than that caused by a bracing action using all the lateral abdominal muscles . These findings are in line with the authors ’ biomechanical model predictions and support the use of independent transversus abdominis contractions for the treatment of low back pain Stability ball training ( SBT ) is believed to improve spinal stability ( SS ) and could reduce the risk of back pain in sedentary individuals . The purpose of this study was to examine the effects of SBT on SS . Twenty sedentary individuals were r and omly assigned to either an experimental group that performed SBT twice per week for 10 weeks or to a control group . Differences between groups were assessed by analysis of variance ( ANOVA ) with repeated measures . The experimental group improved significantly ( p < 0.05 ) on the static back-endurance test from pretest ( 149.3 ± 72.3 seconds ) to posttest ( 194.6 ± 56.7 seconds ) and the side bridge test from pretest ( 45.4 ± 39.4 seconds ) to posttest ( 71.3 ± 59.7 seconds ) . Back endurance for the control group did not change from pretest ( 123.4 ± 64.9 seconds ) to posttest ( 87.5 ± 40.2 seconds ) , nor did the results of the side bridge test change for this group from pretest ( 41.8 ± 26.4 seconds ) to posttest ( 51.6 ± 35.9 seconds ) . These findings illustrate that SBT may provide improvements in SS within this population . Practitioners might use SBT exercises where the position of the spine is maintained during the early phases of back-pain prevention programs . This type of programming might be beneficial to individuals who spend a good deal of time sitting ( i.e. , in corporate fitness programs ) or for individuals who are prone to back pain and have been cleared to exercise . Also , the side bridge and static back endurance assessment s may be good choices for measuring SS in field setting Methods of exercise such as Pilates and taiji quan , which have been shown to have beneficial effects on physical and mental characteristics , have been studied more often in sample s of older participants . The purpose of this investigation was to examine the effects of a semester of either Pilates or taiji quan training on perceived self-efficacy , sleep quality and mood , as well as strength and balance in college-age individuals . Self-efficacy was found to be improved in the Pilates and taiji quan groups and there was a trend towards improvement in sleep quality . Mood was found to be improved significantly in the Pilates group while the taiji group showed a trend towards improvement . There were no changes or group differences in the strength or balance measures . Pilates and taiji quan are effective exercise modes to improve mental parameters in college-age individuals STUDY DESIGN R and omized pretest-posttest control group design . OBJECTIVES To determine the intratester and intertester reliability of a modified isometric stability test and to use this test to evaluate the effects of practice following a 4-week stabilization exercise program with weekly reinstruction . BACKGROUND Although " stabilization " exercise programs are commonplace in the clinic , the reliability to a tool capable of measuring changes in the ability to perform increasingly difficult stabilization exercises has not , to our knowledge , been reported . In addition , it is not clear if practice improves the ability to perform stabilization exercises . METHODS AND MEASURES A convenience sample of 44 asymptomatic subjects was pretested using a pressure transducer placed beneath the lumbar spine to detect motion ( + /- 4 mm Hg ) . A series of 7 exercises was attempted , which required increasing levels of muscular control of the lumbar spine for stability . Subjects received a pass or fail for each exercise level based on the pressure gauge readings and the absence of movement compensations . Subjects were assigned r and omly to exercise and nonexercise groups , and posttest measurements were taken after 4 weeks . The control group did not receive additional instruction . RESULTS The weighted kappa coefficient of 0.61 for intratester and 0.62 for intertester represents good agreement . The median level of exercise attainment increased for the exercise group but not for the nonexercise group . CONCLUSION These results suggest that the modified isometric stability test was reliable and that a 4-week lumbar stabilization exercise program , with weekly intervals of reinstruction and testing , improves the ability to perform progressively difficult lumbar stabilization exercises OBJECTIVE To evaluate the influence of pain on vertical ground-reaction force ( VGRF ) in patients with low back problems and the effect of the Pilates method on the gait of these patients . DESIGN A single-blind r and omized controlled trial . PARTICIPANTS 28 individuals assigned to a control group ( n = 11 ) and a low-back group ( n = 17 ) , the latter of which was subdivided into a Pilates group ( n = 8) and a no-Pilates group ( n = 9 ) . INTERVENTION The Pilates group undertook 15 sessions of Pilates . MAIN OUTCOME MEASURES The VGRF parameters were recorded during preferred and faster walking speeds . The data were collected before and after the intervention . RESULTS The weight-acceptance rate and push-off rate were significantly less in the right lower limb of low-back group than of the control group at preferred speed . Improvements were seen in the Pilates group postintervention , with increased middle-support force for the left lower limb at faster walking speed and decreased pain ; this did not occur in the no-Pilates group . CONCLUSIONS These results suggest that patients with low back pain use strategies to attenuate the amount of force imposed on their body . The Pilates method can improve weight discharge in gait and reduce pain compared with no intervention OBJECTIVE To determine whether the abdominal hollowing technique is more effective for lumbar spine stabilization than a full abdominal muscle cocontraction . DESIGN Within-subject , repeated- measures analysis of variance was used to examine the effect of combining each of 4 loading conditions with either the hollow or brace condition on the dependent variables of stability and compression . A simulation was also conducted to assess the outcome of a person activating just the transversus abdominis during the hollow . SETTING Laboratory . PARTICIPANTS Eight healthy men ( age range , 20 - 33y ) . INTERVENTIONS Electromyography and spine kinematics were recorded during an abdominal brace and a hollow while supporting either a bilateral or asymmetric weight in the h and s. MAIN OUTCOME MEASURES Spine stability index and lumbar compression were calculated . RESULTS In the simulation " ideal case , " the brace technique improved stability by 32 % , with a 15 % increase in lumbar compression . The transversus abdominis contributed .14 % of stability to the brace pattern with a less than 0.1 % decrease in compression . CONCLUSIONS Whatever the benefit underlying low-load transversus abdominis activation training , it is unlikely to be mechanical . There seems to be no mechanical rationale for using an abdominal hollow , or the transversus abdominis , to enhance stability . Bracing creates patterns that better enhance stability Study Design . A r and omized , controlled trial , test‐retest design , with a 3‐ , 6‐ , and 30‐month postal question naire follow‐up . Objective . To determine the efficacy of a specific exercise intervention in the treatment of patients with chronic low back pain and a radiologic diagnosis of spondylolysis or spondylolisthesis . Summary of Background Data . A recent focus in the physiotherapy management of patients with back pain has been the specific training of muscles surrounding the spine ( deep abdominal muscles and lumbar multifidus ) , considered to provide dynamic stability and fine control to the lumbar spine . In no study have research ers evaluated the efficacy of this intervention in a population with chronic low back pain where the anatomic stability of the spine was compromised . Methods . Forty‐four patients with this condition were assigned r and omly to two treatment groups . The first group underwent a 10‐week specific exercise treatment program involving the specific training of the deep abdominal muscles , with co‐activation of the lumbar multifidus proximal to the pars defects . The activation of these muscles was incorporated into previously aggravating static postures and functional tasks . The control group underwent treatment as directed by their treating practitioner . Results . After intervention , the specific exercise group showed a statistically significant reduction in pain intensity and functional disability levels , which was maintained at a 30‐month follow‐up . The control group showed no significant change in these parameters after intervention or at follow‐up . Summary . A " specific exercise " treatment approach appears more effective than other commonly prescribed conservative treatment programs in patients with chronically symptomatic spondylolysis or spondylolisthesis STUDY DESIGN A r and omized controlled trial , prestest-posttest design , with a 3- , 6- , and 12-month follow-up . OBJECTIVES To investigate the efficacy of a therapeutic exercise approach in a population with chronic low back pain ( LBP ) . BACKGROUND Therapeutic approaches developed from the Pilates method are becoming increasingly popular ; however , there have been no reports on their efficacy . METHODS AND MEASURES Thirty-nine physically active subjects between 20 and 55 years old with chronic LBP were r and omly assigned to 1 of 2 groups . The specific-exercise-training group participated in a 4-week program consisting of training on specialized ( Pilates ) exercise equipment , while the control group received the usual care , defined as consultation with a physician and other specialists and healthcare professionals , as necessary . Treatment sessions were design ed to train the activation of specific muscles thought to stabilize the lumbar-pelvic region . Functional disability outcomes were measured with The Rol and Morris Disability Question naire ( RMQ/RMDQ-HK ) and average pain intensity using a 101-point numerical rating scale . RESULTS There was a significantly lower level of functional disability ( P = .023 ) and average pain intensity ( P = .002 ) in the specific-exercise-training group than in the control group following the treatment intervention period . The posttest adjusted mean in functional disability level in the specific-exercise-training group was 2.0 ( 95 % CI , 1.3 to 2.7 ) RMQ/RMDQ-HK points compared to a posttest adjusted mean in the control group of 3.2 ( 95 % CI , 2.5 to 4.0 ) RMQ/RMDQ-HK points . The posttest adjusted mean in pain intensity in the specific-exercise-training group was 18.3 ( 95 % CI , 11.8 to 24.8 ) , as compared to 33.9 ( 95 % CI , 26.9 to 41.0 ) in the control group . Improved disability scores in the specific-exercise-training group were maintained for up to 12 months following treatment intervention . CONCLUSIONS The individuals in the specific-exercise-training group reported a significant decrease in LBP and disability , which was maintained over a 12-month follow-up period . Treatment with a modified Pilates-based approach was more efficacious than usual care in a population with chronic , unresolved LBP Mirrors are often used in an instructional environment where precise movements must be learned ( e.g. , martial arts , Pilates , dance ) . The potential for mirrors in the learning environment of a Pilates class , to affect the subsequent performance of a Pilates star movement when mirrors are not present , was examined . Twenty subjects learned the Pilates star movement over seven weeks , either with ( n=11 ) or without ( n=9 ) , mirrors present in the Pilates studio . Performance of the star without mirrors present was assessed quantitatively before and after the training , by video analysis of the degree of lateral straightness of the subject 's body at the start , middle , and end of the star movement . Performance of the star movement without a mirror present improved similarly for both the group that learned with , and the group that learned without , mirrors present ( p<0.05 ) . These results indicate that the inclusion of mirrors in a learning environment , to provide immediate visual feedback during learning , does not necessarily enhance the subsequent performance of a skill when mirrors are not present Study Design . Intrasubject controls with r Output:	Conclusion : There is a scientific basis for the effectiveness of Pilates exercise , with limited evidence to support it as a rehabilitative intervention
MS21486	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: AIM The purpose of this study was to examine the effects of a 10-week aerobic games programme on physical fitness . METHODS One hundred eleven children , aged 3 to 6 years , participated in this study ; 60 children were male ( age : 4.28 ± 0.61 years old ) , and 51 were female ( age 4.59 ± 0.49 years old ) . Participants were r and omly assigned to an experimental group ( EG ; n = 56 ) and a control group ( CG ; n = 55 ) . A fitness test battery previously vali date d for preschoolers was used . The children in the EG performed 3 weekly training sessions of physical activity in a classroom during a 10-week period . Every EG session lasted about 30 min . RESULTS There were no significant differences in any variable in the pretest between groups . In the posttest , the EG achieved better results in horizontal jump and sprint . In relation to posttest-pretest differences , the EG showed a greater increase in horizontal jump , sprint , and endurance . CONCLUSION An aerobic games programme in the school setting improved physical fitness in preschool children OBJECTIVES The aims were to examine the relationship between children 's motor skill levels and types of physical activities performed during preschool attendance , and to examine the relationship between motor skill performance and parent perception of athletic competence . DESIGN Cross-sectional . METHODS Participants were 264 , 3- , 4- , and 5-year-old children from 22 preschools . Locomotor and object control skills were assessed with a st and ardized motor skill protocol . Direct observation ( OSRAC-P ) was used to record activity types : walk , run , jump/skip , dance , and throw . Parents rated their child 's athletic competence . Children were categorized into tertiles for locomotor and object control scores . Mixed models were used to test for differences across motor skill tertiles for each aim . Models controlled for sex , age , race/ethnicity , body mass index , and parent education , with preschool as a r and om variable . RESULTS Children in the highest locomotor tertile engaged in more dancing than children in the lowest tertile ( p = 0.04 ) . Children in the highest object control tertile engaged in throwing more frequently than children in lower tertiles ( p < 0.05 ) . Parents of children in the highest locomotor tertile perceived their children 's competence as higher than parents of children in lower tertiles ( p < 0.05 ) . Parents of children in the lowest object control tertile perceived their children 's competence as significantly lower than parents of children in higher tertiles ( p < 0.05 ) . CONCLUSIONS These findings point to the need for policy and practice research to help parents and child care professionals provide opportunities for young children to learn and practice motor skills OBJECTIVE To prospect ively examine the effects of a r and omized school-based intervention on nutrition and physical activity knowledge and preferences , anthropometric measures , and fitness in low socioeconomic kindergarten children . STUDY DESIGN A total of 376 children completed a school-year combined dietary-behavioral-physical activity intervention and were compared with 349 control subjects ( age 3.8 to 6.8 years ) . RESULTS The prevalence of overweight and obesity among the kindergarten children was 27.7 % . Even though the intervention was not associated with between group differences in body mass index changes , it was associated with significantly ( P < .05 ) greater increase in nutrition knowledge and preferences , physical activity knowledge and preferences , and improvement in fitness . There was a greater ( P < .05 ) decrease in the number of overweight children in the intervention group ( -31.9 % ) compared with the controls ( -17.5 % ) . CONCLUSIONS A kindergarten dietary-physical activity intervention applied by the kindergarten teachers , had no effect on body mass index changes between the groups , but improved nutrition and physical activity knowledge and preferences , improved fitness , and decreased the percent of overweight children . This intervention may play an important role in health promotion , prevention and treatment of childhood obesity Background Obesity is the most common chronic pediatric disease in westernized , especially low socioeconomic societies . We previously demonstrated the beneficial effects of a r and omized prospect i ve school-based health education program for low socioeconomic status Arab-Israeli kindergarten children . Methods To examine whether the effects of our program on nutrition and physical activity knowledge and preferences , anthropometric measures , and fitness persisted one year after the end of intervention . We were able to perform the one year follow-up in 203 kindergarten children ( 59 % of our 342 original cohort ; 85 control , 118 intervention ) . Results At one year following the intervention BMI and BMI percentiles approached baseline level in both the intervention ( 16.4±0.2 kg/m2 and 61.5±2.4 % , respectively ) and control group participants ( 16.5±0.2 kg/m2 and 58.5±3.3 % , respectively ) . Yet , a year after the end of the intervention , the decrease in BMI % ile from baseline was significantly greater in the intervention group ( -7.8±1.5 vs. -1.9±1.9 , p<0.012 ) . Nutritional and physical activity knowledge and preferences , and physical fitness remained significantly elevated in the intervention compared to the control group participants . Conclusions The beneficial effects of a kindergarten dietary-physical activity intervention applied by the kindergarten teachers , on nutrition and physical activity knowledge and preferences , fitness , and BMI percentile were evident one year after the end of intervention . This promising program may play a role in health promotion , prevention and treatment of childhood obesity Background Physical activity interventions targeting children and adolescents ( ≤18 years ) often focus on complex intra- and inter-personal behavioral constructs , social-ecological frameworks , or some combination of both . Recently published meta-analytical review s and large-scale r and omized controlled trials have demonstrated that these intervention approaches have largely produced minimal or no improvements in young people ’s physical activity levels . Discussion In this paper , we propose that the main reason for previous studies ’ limited effects is that fundamental mechanisms that lead to change in youth physical activity have often been overlooked or misunderstood . Evidence from observational and experimental studies is presented to support the development of a new theory positing that the primary mechanisms of change in many youth physical activity interventions are approaches that fall into one of the following three categories : ( a ) the expansion of opportunities for youth to be active by the inclusion of a new occasion to be active , ( b ) the extension of an existing physical activity opportunity by increasing the amount of time allocated for that opportunity , and /or ( c ) the enhancement of existing physical activity opportunities through strategies design ed to increase physical activity above routine practice . Their application and considerations for intervention design and interpretation are presented . Summary The utility of these mechanisms , referred to as the Theory of Exp and ed , Extended , and Enhanced Opportunities ( TEO ) , is demonstrated in their parsimony , logical appeal , support with empirical evidence , and the direct and immediate application to numerous setting s and context s. The TEO offers a new way to underst and youth physical activity behaviors and provides a common taxonomy by which interventionists can identify appropriate targets for interventions across different setting s and context s. We believe the formalization of the TEO concepts will propel them to the forefront in the design of future intervention studies and through their use , lead to a greater impact on youth activity behaviors than what has been demonstrated in previous studies 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 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 of obesity increased while certain measures of physical fitness deteriorated in preschool children in China over the past decade . This study tested the effectiveness of a multifaceted intervention that integrated childcare center , families , and community to promote healthy growth and physical fitness in preschool Chinese children . Methods This 12-month study was conducted using a quasi-experimental pretest/posttest design with comparison group . The participants were 357 children ( mean age = 4.5 year ) enrolled in three grade levels in two childcare centers in Beijing , China . The intervention included : 1 ) childcare center intervention ( physical activity policy changes , teacher training , physical education curriculum and food services training ) , 2 ) family intervention ( parent education , internet website for support , and family events ) , and 3 ) community intervention ( playground renovation and community health promotion events ) . The study outcome measures included body composition ( percent body fat , fat mass , and muscle mass ) , Body Mass Index ( BMI ) and BMI z-score and physical fitness scores in 20- Output:	Preliminary evidence suggests that ECEC-based interventions to increase CVF are highly effective at improving preschool children 's exercise test scores .
MS21487	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Objective : The underlying changes in biological processes that are associated with reported changes in mental and physical health in response to meditation have not been systematic ally explored . We performed a r and omized , controlled study on the effects on brain and immune function of a well‐known and widely used 8‐week clinical training program in mindfulness meditation applied in a work environment with healthy employees . Methods : We measured brain electrical activity before and immediately after , and then 4 months after an 8‐week training program in mindfulness meditation . Twenty‐five subjects were tested in the meditation group . A wait‐list control group ( N = 16 ) was tested at the same points in time as the meditators . At the end of the 8‐week period , subjects in both groups were vaccinated with influenza vaccine . Results : We report for the first time significant increases in left‐sided anterior activation , a pattern previously associated with positive affect , in the meditators compared with the nonmeditators . We also found significant increases in antibody titers to influenza vaccine among subjects in the meditation compared with those in the wait‐list control group . Finally , the magnitude of increase in left‐sided activation predicted the magnitude of antibody titer rise to the vaccine . Conclusions : These findings demonstrate that a short program in mindfulness meditation produces demonstrable effects on brain and immune function . These findings suggest that meditation may change brain and immune function in positive ways and underscore the need for additional research Objectives : This r and omized controlled trial was conducted to examine immune recovery following breast cancer ( BC ) therapy and evaluate the effect of mindfulness-based stress reduction therapy ( MBSR ) on immune recovery with emphasis on lymphocyte subsets , T cell activation , and production of T-helper 1 ( Th1 ; interferon [IFN]-γ ) and T-helper 2 ( Th2 ; interleukin-4 [ IL-4 ] ) cytokines . Method : Participants who completed the study consisted of 82 patients diagnosed with Stage 0–III BC , who received lumpectomy and adjuvant radiation ± chemotherapy . Patients were r and omized into an MBSR(BC ) intervention program or a control ( usual care ) group . Immune cell measures were assessed at baseline and within 2 weeks after the 6-week intervention . The numbers and percentages of lymphocyte subsets , activated T cells , and Th1 and Th2 cells in peripheral blood sample s were determined by immunostaining and flow cytometry . Results : Immune subset recovery after cancer treatment showed positive associations with time since treatment completion . The B and natural killer ( NK ) cells were more susceptible than T cells in being suppressed by cancer treatment . Women who received MBSR(BC ) had T cells more readily activated by the mitogen phytohemagglutinin ( PHA ) and an increase in the Th1/Th2 ratio . Activation was also higher for the MBSR(BC ) group if < 12 weeks from the end of treatment and women in MBSR(BC ) < 12 weeks had higher T cell count for CD4 + . Conclusion : MBSR(BC ) promotes a more rapid recovery of functional T cells capable of being activated by a mitogen with the Th1 phenotype , whereas substantial recovery of B and NK cells after completion of cancer treatment appears to occur independent of stress-reducing interventions We propose a model wherein chronic stress results in glucocorticoid receptor resistance ( GCR ) that , in turn , results in failure to down-regulate inflammatory response . Here we test the model in two viral-challenge studies . In study 1 , we assessed stressful life events , GCR , and control variables including baseline antibody to the challenge virus , age , body mass index ( BMI ) , season , race , sex , education , and virus type in 276 healthy adult volunteers . The volunteers were subsequently quarantined , exposed to one of two rhinoviruses , and followed for 5 d with nasal washes for viral isolation and assessment of signs/symptoms of a common cold . In study 2 , we assessed the same control variables and GCR in 79 subjects who were subsequently exposed to a rhinovirus and monitored at baseline and for 5 d after viral challenge for the production of local ( in nasal secretions ) proinflammatory cytokines ( IL-1β , TNF-α , and IL-6 ) . Study 1 : After covarying the control variables , those with recent exposure to a long-term threatening stressful experience demonstrated GCR ; and those with GCR were at higher risk of subsequently developing a cold . Study 2 : With the same controls used in study 1 , greater GCR predicted the production of more local proinflammatory cytokines among infected subjects . These data provide support for a model suggesting that prolonged stressors result in GCR , which , in turn , interferes with appropriate regulation of inflammation . Because inflammation plays an important role in the onset and progression of a wide range of diseases , this model may have broad implication s for underst and ing the role of stress in health The aim of the study was to determine changes in the rate of decline of immunological parameters after psychosocial group intervention . Subjects were 26 asymptomatic HIV-infected homosexual men who participated in a cognitive-behavioral group therapy ( CBT ; n = 14 ) , or an experiential group therapy program ( ET ; n = 12 ) , both of 15 weeks duration . The outcome measures were changes in the decline of CD4 cell counts , and T cell proliferative responses to anti-CD3 monoclonal antibodies from preintervention to 24 months postintervention . No differences in the rate of decline of CD4 cells or T cell responses between the CBT and ET condition were found , and there were no significant changes in CD4 cell count from pre- to postintervention . However , those subjects who showed larger decreases in distress showed a smaller decline in CD4 cell counts . While the rate of decline in T cell responses was significantly less after both interventions , a similar positive change in T cell responses was found in a comparison group of 149 HIV-infected men with similar demographic , psychosocial and immunological characteristics who did not participate in one of the interventions . We conclude that the psychosocial intervention programs tested here did not cause changes in CD4 cell decline or T cell responses and that decreases in distress were related to increases in CD4 cell counts This article presents the results of two investigations , each measuring cellular immune function on 3 investigation days 1 week apart in 15 high and 15 low hypnotizable healthy subjects r and omly selected for three groups : ( 1 ) a guided imagery group receiving instructions to enhance cellular immune function : ( 2 ) a relaxation group which did not receive instructions regarding the immune system , and ( 3 ) a control group . Study 1 investigated changes in monocyte chemotaxis ( MC ) and lymphocyte proliferative response ( LPR ) to three mitogens , while natural killer cell activity ( NKCA ) was measured in study 2 . The results show similar patterns of brief decreases in LPR and NKCA immediately after intervention on all investigation days in both the imagery and relaxation groups . Increases in MC were found in both intervention groups on day 1 . On a follow-up investigation day in study 2 , a brief stress task yielded a slight increase in NKCA . In study 2 , the control group showed decreases in NKCA similar to those observed in the two intervention groups . In general there were no significant changes in preintervention immune function throughout the investigation period . When comparing the effects in high and low hypnotizable subjects , we found that high hypnotizables showed greater decreases in LPR and NKCA than low hypnotizables . There are several inconsistencies between the results of the limited number of investigations study ing the effects of guided imagery and relaxation on immune function . These differences may in part be explained by differences in methodology , time intervals between blood sampling , and subject characteristics such as age , health status and hypnotizability . The inconsistent results make it premature to make inferences about possible benefits of the application of these techniques in the treatment of immune related diseases , and further investigations are needed Background Previous research has provided evidence for the link between psychological processes and psychophysiological health outcomes . Psychological interventions , such as face-to-face or online cognitive behavioral therapy ( CBT ) and serious games aim ed at improving health , have shown promising results in promoting health outcomes . Few studies so far , however , have examined whether Internet-based CBT combined with serious gaming elements is effective in modulating health outcomes . Moreover , studies often did not incorporate psychophysiological or immunological challenges in order to gain insight into physiological responses to real-life challenges after psychological interventions . The overall aim of this study is to investigate the effects of a psychological intervention on self-reported and physiological health outcomes in response to immune and psychophysiological challenges . Methods / design In a r and omized controlled trial , 60 healthy men are r and omly assigned to either an experimental condition , receiving guided Internet-based ( e-health ) CBT combined with health-related serious gaming elements for 6 weeks , or a control condition receiving no intervention . After the psychological intervention , self-reported vitality is measured , and participants are given an immunological challenge in the form of a Mycobacterium bovis Bacillus Calmette-Guérin ( BCG ) vaccination . One day after the vaccination , participants are asked to perform several psychophysiological tasks in order to explore the effects of the psychological intervention on participants ’ stress response following the immune challenge . To assess the delayed effects of vaccination on self-reported and physiological health outcomes , a follow-up visit is planned 4 weeks later . Total study duration is approximately 14 weeks . The primary outcome measure is self-reported vitality measured directly after the intervention . Secondary outcome measures include inflammatory and endocrine markers , as well as psychophysiological measures of heart rate and skin conductance in response to the psychophysiological tasks after the BCG vaccination . Discussion The innovative design features of this study – e.g. , combining guided e-health CBT with health-related serious gaming elements and incorporating immunological and psychophysiological challenges – will provide valuable information on the effects of a psychological intervention on both self-reported and physiological health outcomes . This study will offer further insights into the mechanisms underlying the link between psychological factors and health outcomes and is anticipated to contribute to the optimization of health care strategies . Trial registration Nederl and s Trial Register , NTR5610 . Registered on 4 January 2016 Background : Although mindfulness meditation interventions have recently shown benefits for reducing stress in various population s , little is known about their relative efficacy compared with relaxation interventions . Purpose : This r and omized controlled trial examines the effects of a 1-month mindfulness meditation versus somatic relaxation training as compared to a control group in 83 students ( M age=25 ; 16 men and 67 women ) reporting distress . Method : Psychological distress , positive states of mind , distractive and ruminative thoughts and behaviors , and spiritual experience were measured , while controlling for social desirability . Results : Hierarchical linear modeling reveals that both meditation and relaxation groups experienced significant decreases in distress as well as increases in positive mood states over time , compared with the control group ( p<.05 in all cases ) . There were no significant differences between meditation and relaxation on distress and positive mood states over time . Effect sizes for distress were large for both meditation and relaxation ( Cohen ’s d=1.36 and .91 , respectively ) , whereas the meditation group showed a larger effect size for positive states of mind than relaxation ( Cohen ’s d=.71 and .25 , respectively ) . The meditation group also demonstrated significant pre-post decreases in both distractive and ruminative thoughts/behaviors compared with the control group ( p<.04 in all cases ; Cohen ’s d=.57 for rumination and .25 for distraction for the meditation group ) , with mediation models suggesting that mindfulness meditation ’s effects on reducing distress were partially mediated by reducing rumination . No significant effects were found for spiritual experience . Conclusions : The data suggest that compared with a no-treatment control , brief training in mindfulness meditation or somatic relaxation reduces distress and improves positive mood states . However , mindfulness meditation may be specific in its ability to reduce distractive and ruminative thoughts and behaviors , and this ability may provide a unique mechanism by which mindfulness meditation reduces distress Meditation practice s may impact physiological pathways that are modulated by stress and relevant to disease . While much attention has been paid to meditation practice s that emphasize calming the mind , improving focused attention , or developing mindfulness , less is known about meditation practice s that foster compassion . Accordingly , the current study examined the effect of compassion meditation on innate immune , neuroendocrine and behavioral responses to psychosocial stress and evaluated the degree to which engagement in meditation practice influenced stress reactivity . Sixty-one healthy adults were r and omized to 6 weeks of training in compassion meditation ( n=33 ) or participation in a health discussion control group ( n=28 ) followed by exposure to a st and ardized laboratory stressor ( Trier social stress test [ TSST ] ) . Physiologic and behavioral responses to the TSST were determined by repeated assessment s of plasma concentrations of interleukin (IL)-6 and cortisol as well as total distress scores on the Profile of Mood States ( POMS ) . No main effect of group assignment on TSST responses was found for IL-6 , cortisol or POMS scores . However , within the meditation group , increased meditation practice was correlated with decreased TSST-induced IL-6 ( r(p)=-0.46 , p=0.008 ) and POMS distress scores ( r(p)=-0.43 , p=0.014 ) . Moreover , individuals with meditation practice times above the median exhibited lower TSST-induced IL-6 and POMS distress scores compared to individuals below the median , who did not differ from controls . These data suggest that engagement in compassion meditation may reduce stress-induced immune and behavioral responses , although future studies are required to determine whether individuals who engage in compassion meditation techniques are more likely to exhibit reduced stress reactivity In a prospect i ve r and omised Output:	This is also relevant for clinical practice , as psychological interventions can possibly supplement , or at least partially replace , current drug treatments in various somatic conditions to reduce side effects
MS21488	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: In a prospect i ve r and omized study the efficiacy of physical therapy in female stress incontinence could be verified . The greatest success rate was achieved by medical gymnastics , whereas the perineal electrical stimulation should be used as supporting measure like a biofeedback mechanism because of its low effective intensity . Despite of the good therapeutic success ( 51.5 % ) with lasting effects no objective criteria to the use of physical therapy in female stress incontinence were found OBJECTIVE To investigate associations between diet and non-dietary lifestyle factors and the onset of overactive bladder ( OAB ) in men . SUBJECTS R and om sample of community-dwelling men aged 40 years plus . DESIGN AND METHODS Baseline data on urinary symptoms and diet were collected from 5454 men using a postal question naire and a food-frequency question naire . Follow-up data on urinary symptoms were collected from 4887 men in a postal survey one year later . Logistic regression analysis was used to investigate diet and lifestyle factors associated with onset of OAB in the men without OAB at baseline . RESULTS There was a highly significant negative association between beer intake at baseline and subsequent OAB onset ( P=0.001 ) , with reduced risk at all levels of intake compared with those who seldom/never drank beer . Adjustment for total alcohol intake ( g ethanol day(-1 ) ) reduced the significance of the association ( P=0.02 ) . None of the food groups studied was associated with OAB onset , with the possible exception of potatoes ( P=0.05 ) , which showed an increased risk of onset at the highest level of consumption . Physical activity , smoking and obesity were not significantly associated . CONCLUSIONS While most diet and lifestyle factors were not associated with OAB onset , the evidence from this prospect i ve longitudinal study suggests that beer may have a protective role in the development of OAB . This could be due to a non-alcoholic ingredient as well as the alcohol content Abstract : The aim of this study was to evaluate the effect of weight reduction on urinary incontinence in moderately obese women . This prospect i ve cohort study enrolled moderately obese women experiencing four or more incontinence episodes per week . BMI and a 7-day urinary diary were collected at baseline and on the completion of weight reduction . The study included 10 women with a mean ( þSD ) baseline BMI of 38.3 ( þ10.1 ) kg/m2 and 13 ( þ10 ) incontinent episodes per week . Participants had a mean BMI reduction of 5.3 ( þ6.2 ) kg/m2 ( P<0.03 ) . Among women achieving a weight loss of ≥5 % , 6/6 had ≥50 % reduction in incontinence frequency compared to 1 in 4 women with < 5 % weight loss ( P<0.03 ) . Incontinence episodes decreased to 8 ( þ10 ) per week following weight reduction ( P<0.07 ) . The study demonstrated an association between weight reduction and improved urinary incontinence . Weight reduction should be considered for moderately obese women as part of non-surgical therapy for incontinence Patients with symptoms of frequency and urgency often complain that their symptoms are exacerbated by tea or coffee . A series of 20 women with confirmed detrusor instability and 10 asymptomatic women were given 200 mg of caffeine citrate and urodynamic studies were performed . In the group with detrusor instability there was a statistically significant increase in detrusor pressure on bladder filling following administration of caffeine , but no difference in volume at first contraction , height of contraction or bladder capacity . Normal women had no abnormality on cystometry Background Both maternal pre-pregnancy obesity and excessive gestational weight gain are increasing in prevalence and associated with a number of adverse pregnancy outcomes for both mother and child . Observational studies regarding physical activity in pregnancy have found reduced weight gain in active mothers , as well as reduced risk of adverse pregnancy outcomes . There is however a lack of high quality , r and omized controlled trials on the effects of regular exercise training in pregnancy , especially those with a pre-pregnancy body mass index ( BMI ) at or above 30 kg/m2 . Methods We are conducting a r and omised , controlled trial in Norway with two parallel arms ; one intervention group and one control group . We will enroll 150 previously sedentary , pregnant women with a pre-pregnancy BMI at or above 30 kg/m2 . The intervention group will meet for organized exercise training three times per week , starting in gestation week 14 ( range 12 - 16 ) . The control group will get st and ard antenatal care . The main outcome measure will be weight gain from baseline to delivery . Among the secondary outcome measures are changes in exercise capacity , endothelial function , physical activity level , body composition , serum markers of cardiovascular risk , incontinence , lumbopelvic pain and cardiac function from baseline to gestation week 37 ( range 36 - 38 ) . Offspring outcome measures include anthropometric variables at birth , Apgar score , as well as serum markers of inflammation and metabolism in cord blood . Discussion The results of this trial will provide knowledge about effects of regular exercise training in previously sedentary , obese pregnant women . If the program proves effective in reducing gestational weight gain and adverse pregnancy outcomes , such programs should be considered as part of routine pregnancy care for obese women . Trial Registration Clinical Trials.gov : OBJECTIVE : To estimate the effect of a decrease in urinary incontinence ( UI ) frequency on UI management costs among women enrolled in a clinical trial of a weight loss intervention and to identify factors that predict change in cost . METHODS : This is a secondary cohort analysis of 338 obese and overweight women with 10 or more weekly episodes of UI enrolled in an 18-month r and omized clinical trial of a weight loss intervention compared with a structured education program to treat UI . Quantities of re sources used for incontinence management , including pads , additional laundry , and dry cleaning , were reported by participants . Direct costs for UI management ( “ cost ” ) were calculated by multiplying re sources used by national re source costs ( in 2006 U.S. dollars ) . R and omized groups were combined to examine the effects of change in incontinence frequency on cost . Possible predictors of change in cost were examined using generalized estimating equations controlling for factors associated with change in cost in univariable analyses . RESULTS : Mean age±st and ard deviation was 53±10 years and baseline weight was 97±17 kg . Mean weekly UI frequency was 24±18 at baseline and decreased by 37 % at 6 months and 60 % at 18 months ' follow-up ( both P<.001 ) . At baseline , adjusted mean cost was $ 7.76±$14 per week , with costs increasing significantly with greater incontinence frequency . Mean cost decreased by 54 % at 6 months and 81 % at 18 months ( both P<.001 ) . In multivariable analyses , cost independently decreased by 23 % for each decrease of seven UI episodes per week and 21 % for each 5 kg of weight lost ( P<.001 for both ) . CONCLUSION : In obese and overweight women enrolled in a clinical trial of weight loss for UI , incontinence management cost decreased by 81 % at 18 months ( $ 327 per woman per year ) and was strongly and independently associated with decreasing incontinence frequency . LEVEL OF EVIDENCE : Objective To evaluate the effectiveness of self management as a first line intervention for men with lower urinary tract symptoms . Design R and omised controlled trial . Setting A teaching hospital and a district general hospital in London . Participants 140 men ( mean age 63 ( SD 10.7 ) years ) , recruited between January 2003 and April 2004 , referred by general practitioners to urological outpatient departments with uncomplicated lower urinary tract symptoms . Interventions Self management and st and ard care ( n=73 ) or st and ard care alone ( n=67 ) . The self management group took part in three small group sessions comprising education , lifestyle advice , and training in problem solving and goal setting skills . Main outcome measures The primary outcome measure was treatment failure measured at 3 , 6 , and 12 months . Symptom severity ( international prostate symptom score ; higher scores represent a poorer outcome ) was used as a secondary outcome . Results At three months , treatment failure had occurred in 7 ( 10 % ) of the self management group and in 27 ( 42 % ) of the st and ard care group ( difference=32 % , 95 % confidence interval 18 % to 46 % ) . Corresponding differences in the frequency of treatment failure were 42 % ( 27 % to 57 % ) at six months and 48 % ( 32 % to 64 % ) at 12 months . At three months , the mean international prostate symptom score was 10.7 in the self management group and 16.4 in the st and ard care group ( difference=5.7 , 3.7 to 7.7 ) . Corresponding differences in score were 6.5 ( 4.3 to 8.7 ) at six months and 5.1 ( 2.7 to 7.6 ) at 12 months . Conclusions Self management significantly reduced the frequency of treatment failure and reduced urinary symptoms . Because of the large observed benefit of self management , the results of this study support the case for a large multicentre trial to confirm whether self management could be considered as first line treatment for men with lower urinary tract symptoms . Trial registration National Research Register N0263115137 ; Clinical trials NCT00270309 PURPOSE We determined the effect of caffeine restriction and fluid manipulation in the treatment of patients with urodynamic stress incontinence and detrusor overactivity . MATERIAL S AND METHODS This was a 4-week r and omized , prospect i ve , observational crossover study in 110 women with urodynamic stress incontinence ( USI ) or idiopathic detrusor overactivity ( IDO ) to determine the effect of caffeine restriction , and of increasing and decreasing fluid intake on urinary symptoms . Data were recorded in a urinary diary for the entire study period on urgency episodes , frequency , pad weight increase , wetting episodes and quality of life . RESULTS A total of 69 women with a mean age of 54.8 years completed the study , including 39 with USI and 30 with IDO . In the IDO group decreasing fluid intake significantly decreased voiding frequency , urgency and wetting episodes with improved quality of life . In the USI group there was a significant decrease in wetting episodes when fluid intake was decreased . Changing from caffeine containing to decaffeinated drinks produced no improvement in symptoms . CONCLUSIONS Conservative and life-style interventions are first line treatments in the management of incontinence and storage lower urinary tract symptoms . This study shows that a decrease in fluid intake improves some of these symptoms in patients with USI and IDO and , therefore , it should be considered when treating such patients This study was design ed to determine whether a 6-month Tai Chi exercise program can improve self-reported physical functioning limitations among healthy , physically inactive older individuals . Ninety-four community residents ages 65 to 96 ( M age = 72.8 years , SD = 5.1 ) volunteered to participate in the study . Participants were r and omly assigned to either a 6-month experimental ( Tai Chi ) group ( n = 49 ) , which exercised twice per week for 60 min , or a wait-list control group ( n = 45 ) . A 6-item self-report physical functioning scale , assessing the extent of behavioral dysfunction caused by health problems , was used to evaluate change in physical functioning limitations as a result of Tai Chi intervention . Results indicated that compared to the control group , participants in the Tai Chi group experienced significant improvements in all aspects of physical functioning over the course of the 6-month intervention . Overall , the experimental group had 65 % improvement across all 6 functional status measures ranging from daily activities such as walking and lifting to moderate-vigorous activities such as running . It was concluded that the 6-month Tai Chi exercise program was effective for improving functional status in healthy , physically inactive older adults . A self-paced and self-controlled activity such as Tai Chi has the potential to be an effective , low-cost means of improving functional status in older persons Objective : Maintaining weight loss is a major challenge in obesity treatment . Individuals often indicate that waning motivation prompts cessation of effective weight management behaviors . Therefore , a novel weight loss maintenance program that specifically targets motivational factors was evaluated . Design : Overweight women ( N=338 ; 19 % African American ) with urinary incontinence were r and omized to lifestyle obesity treatment or control and followed for 18 months . All participants in lifestyle ( N=226 ) received the same initial 6-month group behavioral obesity treatment and were then r and omized to ( 1 ) a novel motivation-focused maintenance program ( N=113 ) or ( 2 ) a st and ard skill-based maintenance approach (N=113).Main Outcome Measure : Weight assessed at baseline , 6 and 18 months . Results : Both treatment groups ( motivation-focused and skill-based ) achieved comparable 18-month weight losses ( −5.48 % for motivation-focused vs −5.55 % in skill-based , P=0.98 ) , and both groups lost significantly more than controls ( −1.51 % ; P=0.0012 in motivation-focused and P=0.0021 in skill-based ) . Conclusions : A motivation-focused maintenance program offers an alternative , effective approach to weight maintenance exp and ing available evidence -based interventions beyond traditional skill-based programs . Trial Registration : clinical trials. Output:	However , it was not possible to reach any conclusions about the effects of these changes , due to method ological limitations , that result ed in very low quality evidence .Adverse effects appeared relatively uncommon for all interventions studied . Generally , there was insufficient evidence to inform practice reliably about whether lifestyle interventions are helpful in the treatment of urinary incontinence
MS21489	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: STUDY OBJECTIVE To compare the renal , hemodynamic , and pulmonary effects of a 6-hour infusion of furosemide versus conventional bolus administration in premature infants . DESIGN Prospect i ve , blinded , placebo-controlled , r and omized study . SETTING Two level III , university-based neonatal intensive care units . PATIENTS Thirty premature infants with significant lung disease , requiring furosemide after a red cell infusion . INTERVENTIONS Infants received furosemide 1 mg/kg over 2 minutes , followed by a 6-hour placebo infusion , or a small loading dose of 0.1 mg/kg , followed by a slow infusion of 0.9 mg/kg over 6 hours . Serum and urine were collected to determine percentage fractional excretion of sodium ( FENa ) . MEASUREMENTS AND MAIN RESULTS Urine output and blood pressure were measured every 2 hours after furosemide administration . Percentage FENa was measured immediately before furosemide and compared with pooled urine from an 8-hour collection after furosemide administration . Serum sodium , creatinine , and calcium were measured before and 24 hours after drug administration . Mean airway pressure and percentage inspired oxygen were compared before , 1 - 4 hours after , and 4 - 12 hours after drug administration . No significant differences were detected between the two methods of drug administration . CONCLUSION Our data suggest that a 6-hour infusion of furosemide does not offer substantial clinical advantage over conventional bolus administration in premature infants when focusing on urine output , blood pressure , FENa , or pulmonary effect BACKGROUND Transfusion-associated circulatory overload ( TACO ) is a frequent complication of blood transfusion . Investigations identifying risk factors for TACO in critically ill patients are lacking . STUDY DESIGN AND METHODS We performed a 2-year prospect i ve cohort study of consecutive patients receiving blood product transfusion in the medical intensive care unit ( ICU ) of the tertiary care institution . Patients were followed for development of transfusion-related complications . TACO was defined as acute hydrostatic pulmonary edema occurring within 6 hours of transfusion . In a nested case-control design , transfusion characteristics were compared between cases ( TACO ) and controls after matching by age , sex , and ICU admission diagnostic category . In a secondary analysis , patient characteristics before transfusion were compared between cases ( TACO ) and r and omly selected controls . RESULTS Fifty-one of 901 ( 6 % ) transfused patients developed TACO . Compared with matched controls , TACO cases had a more positive fluid balance ( 1.4 L vs. 0.8 L , p = 0.003 ) , larger amount of plasma transfused ( 0.4 L vs. 0.07 L , p = 0.007 ) , and faster rate of blood component transfusion ( 225 mL/hr vs. 168 mL/hr , p = 0.031 ) . In a secondary analysis comparing TACO cases and r and om controls , left ventricular dysfunction before transfusion ( odds ratio [ OR ] , 8.23 ; 95 % confidence interval [ CI ] , 3.36 - 21.97 ) and plasma ordered for the reversal of anticoagulant ( OR , 4.31 ; 95 % CI , 1.45 - 14.30 ) were significantly related to the development of TACO . CONCLUSION Volume of transfused plasma and the rate of transfusion were identified as transfusion-specific risk factors for TACO . Left ventricular dysfunction and fresh-frozen plasma ordered for the reversal of anticoagulant were strong predictors of TACO before the onset of transfusion Left ventricular filling pressure ( LVFP ) as reflected by pulmonary capillary wedge pressure ( PCWP ) was measured in 40 adult cases of chronic severe anemia ( CSA ) before and after transfusion of 1 unit of whole citrated blood , using Swan-Ganz monitoring catheters . The cases were r and omized into 4 groups of 10 each . Blood was transfused at a rate of 2 ml , 5 ml and 10 ml/min in groups A , B and C , respectively . In group D , blood transfusion ( BT ) was given at 5 ml/min but this group received , in addition , 40 mg furosemide intravenously just prior to the transfusion . Pretransfusion PCWP was normal in all the cases . Following BT the " wedge " pressure increased significantly in the first 3 groups , the rise being proportionately greater with faster transfusions ( 15.8 , 20.9 and 32.2 % in groups A , B and C , respectively ) . In group D , however , PCWP actually decreased by 21.7 % ( p less than 0.001 ) . As far as we know , this is the first study in which a definite and significant rise in PCWP has been documented following transfusion of blood even at conventional speed ( group A ) . The implication s of such an increase in " wedge " pressure as well as the observation that it can be completely blocked by furosemide are discussed . On the basis of these observations it is recommended that intravenous furosemide should be administered routinely before any BT in cases of CSA . Such practice will also permit blood to be transfused at a comparatively faster speed , without jeopardizing patient safety BACKGROUND The use of premedication to prevent acute transfusion reactions has been estimated to occur in 50 % to 80 % of transfusions . While this practice has some biologic rationale , few clinical studies have been performed to assess the efficacy of this practice , and the method ologic quality of these studies is variable . The primary objective of this study was to describe current practice s regarding transfusion premedication to prevent febrile nonhemolytic transfusion reactions , mild allergic transfusion reactions , and transfusion-associated circulatory overload . STUDY DESIGN AND METHODS We conducted an observational retrospective chart review of a stratified r and om sample of 324 transfusions that took place over a 6-month period . Data were abstract ed from medical records and then scanned into a data base for analysis . We calculated inter- and intraobserver agreement on key abstract ed data to estimate assessment error . A two-phase adjudication process was used to determine whether or not medications given before the time of each transfusion were intended as premedications . RESULTS Of the transfusions sample d , 1.6 % ( 95 % confidence interval , 0.4 - 3.9 ) were associated with premedication medications to prevent an acute transfusion reaction . Inter- and intraobserver reliability in the abstract ion of key data points was good . Good agreement in adjudicator classification of outcomes was achieved only when adjudicators were provided with patient source documents . CONCLUSIONS Premedication use was infrequent and much less common than previously reported . Improved methods of capturing transfusion premedication , which likely require prospect i ve assessment s , are needed for future research studies Summary An investigation was planned to establish whether direct transfusion of packed cells with added ethacrynic acid was as safe and effective as exchange transfusion in the management of severe an˦mia in pregnancy , when cardiac failure caused by an˦mia is either present or imminent . 93 pregnant Nigerian women with h˦matocrit readings between 5 % and 13 % were allocated at r and om to two treatment groups . One group received exchange transfusion and the other was managed by direct transfusion of packed cells to which ethacrynic acid had been added . Subsequent treatment was the same for both groups . Analysis of maternal and fetal outcome showed that the results achieved by the two methods of treatment was similar . In the 46 patients treated by exchange transfusion 1 mother and 12 fetuses were lost , compared with no maternal death and the loss of 11 fetuses in the 47 treated by direct transfusion and ethacrynic acid . Apart from its simplicity , the ethacrynic acid technique has the advantage that less donor blood is required . Direct blood-transfusion combined with ethacrynic acid is , therefore , recommended for the initial treatment of very severe an˦mia in pregnancy , except for patients who require emergency surgery and those in advanced labour , for whom exchange transfusion is still preferred Pulmonary capillary ' wedge ' pressures ( PCWP ) were measured in 20 adult cases of chronic severe anemia ( CSA ) before and after transfusion of 700 ml of whole blood at a rate of 5 ml/min . The cases were r and omly divided into 2 groups of 10 cases each . Group II also received 40 mg of furosemide immediately before the start of transfusion . The majority of the cases had hemoglobin values less than 4 g% and serum albumin values less than 2.5 g% . Pretransfusion intracardiac pressures were normal in all the cases . Following blood transfusion ( BT ) , appreciable rises ( p less than 0.001 ) in hemoglobin and arterial and venous oxygen saturation were observed . PCWP increased significantly after BT in Group I ( p less than 0.001 ) . Although it decreased by 3.75 % in Group II , this was not statistically significant ( p greater than 0.05 ) . This study implies that a blood transfusion of 700 ml , given at a speed of 5 ml/min in patients with CSA , results in sufficient hemodynamic stress to cause a significant rise in PCWP , and that this is completely prevented by simultaneous administration of 40 mg of furosemide OBJECTIVE To assess the effect of furosemide administered with packed red blood cell transfusion on cardiopulmonary variables of hemodynamically stable , electively transfused preterm infants beyond the first week of life . STUDY DESIGN A r and omized , stratified , double-blind , placebo-controlled trial of intravenous furosemide ( 1 mg/kg ) versus placebo ( normal saline ) just before " top-up " packed red blood cell transfusion ( 20 mL/kg over 4 hours ) in a tertiary neonatal intensive care unit . RESULTS The primary outcome was a change in fraction of inspired oxygen ( FiO(2 ) ) during the 24 hours posttransfusion compared with the 6-hour pretransfusion period . Secondary outcomes were functional echocardiographic and clinical /biochemical variables . Of 51 consecutive preterm infants with mean ( ± SD ) birth weights of 900 g ( ± 28 ) ; enrollment weights of 1342 g ( ± 432 ) ; birth gestation of 27 weeks ( ± 1 ) ; and postmenstrual age of 32 weeks ( ± 4 ) , 40 completed the study . Pretransfusion variables were comparable between the furosemide ( n = 21 ) and placebo ( n = 19 ) groups . There was a small but significant increase ( P < .05 ) in posttransfusion FiO(2 ) in placebo ( relative increase of 7 % , equivalent to an absolute increase from 0.27 to 0.29 ) compared with the furosemide group . Other variables were similar . No infant received open-label furosemide . CONCLUSIONS Routine furosemide in electively transfused preterm infants confers minimal clinical benefits . Prevention of a clinical ly insignificant FiO(2 ) rise needs to be balanced against potential adverse effects Output:	There was insufficient evidence to determine whether premedicating people undergoing blood transfusion with loop diuretics prevents clinical ly important transfusion-related morbidity .
MS21490	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Background : The number of Mendelian r and omization analyses including large numbers of genetic variants is rapidly increasing . This is due to the proliferation of genome-wide association studies , and the desire to obtain more precise estimates of causal effects . However , some genetic variants may not be valid instrumental variables , in particular due to them having more than one proximal phenotypic correlate ( pleiotropy ) . Methods : We view Mendelian r and omization with multiple instruments as a meta- analysis , and show that bias caused by pleiotropy can be regarded as analogous to small study bias . Causal estimates using each instrument can be displayed visually by a funnel plot to assess potential asymmetry . Egger regression , a tool to detect small study bias in meta- analysis , can be adapted to test for bias from pleiotropy , and the slope coefficient from Egger regression provides an estimate of the causal effect . Under the assumption that the association of each genetic variant with the exposure is independent of the pleiotropic effect of the variant ( not via the exposure ) , Egger ’s test gives a valid test of the null causal hypothesis and a consistent causal effect estimate even when all the genetic variants are invalid instrumental variables . Results : We illustrate the use of this approach by re-analysing two published Mendelian r and omization studies of the causal effect of height on lung function , and the causal effect of blood pressure on coronary artery disease risk . The conservative nature of this approach is illustrated with these examples . Conclusions : An adaption of Egger regression ( which we call MR-Egger ) can detect some violations of the st and ard instrumental variable assumptions , and provide an effect estimate which is not subject to these violations . The approach provides a sensitivity analysis for the robustness of the findings from a Mendelian r and omization investigation Adult height has been found in some but not all studies to be associated positively with overall cancer incidence as well as several site-specific cancers . The Physicians ' Health Study ( PHS ) , a r and omized trial of beta-carotene and aspirin in the primary prevention of cancer and cardiovascular disease in men , provided an opportunity to examine the association between height and total malignant neoplasms ( excluding non-melanoma skin cancer ) , as well as site-specific cancers including prostate , colorectal , and lung cancer . The PHS is comprised of 22,071 US male physicians in the United States , a population homogeneous for adult socioeconomic status , aged 40 to 84 years in 1982 . Participants were classified into five height categories at study entry . After an average follow-up of over 12 years , there were 2,566 cases of incident total malignant neoplasms , including 1,047 prostate , 341 colorectal , and 170 lung cancer cases . Height was associated positively with both total malignant neoplasms and prostate cancer . Compared with men in the shortest category(≤ 67 inches ) , relative risks and 95 percent confidence intervals (CI)for total malignant neoplasms for men whose height ( in inches ) was 68 - 69,70 - 71 , 72 , and 73 + were , respectively : 1.13 ( CI = 0.99 - 1.28 ) , 1.15 ( CI = 1.02 - 1.30 ) , 1.29 ( CI = 1.12 - 1.49 ) , and 1.21 ( CI = 1.05 - 1.39 ) , P trend 0.001,adjusted for age , r and omized treatment assignments , body mass index ( wt/ht2 ) , cigarette smoking , alcohol use , and exercise frequency . For prostatecancer , the corresponding RR values were 1.23 ( CI = 1.00 - 1.51 ) , 1.26 ( CI = 1.04 - 1.54 ) , 1.59 ( CI = 1.27 - 1.98 ) , and 1.26 ( CI = 1.00 - 1.59 ) , P trend 0.005.For colorectal cancer , in some but not all height categories compared with the shortest , there were elevated RRs without a significant linear trend : RR= 1.51 ( CI = 1.06 - 2.14 ) , 1.14 ( CI = 0.80 - 1.62 ) , 1.19 ( CI = 0.79 - 1.80 ) , and 1.53 ( CI = 1.04 - 2.25 ) , P trend 0.23 . In contrast , there was no evidence of an association of height with lung cancer . These data indicate a positive association between height and risk of total malignant neoplasms , as well as of prostate cancer and , possibly , colorectal cancer Objectives : Few risk factors for prostate cancer are known , but both endocrine changes and dietary factors have been implicated in the etiology of the disease . Anthropometry may therefore provide a tool in the search for carcinogenic mechanisms connected to these suggested causal components . Methods : We have studied the association between body size and prostate cancer risk in a prospect i ve study of 22,248 Norwegian men . During 12 years of follow-up , 642 men developed cancer of the prostate . A possible association between anthropometry ( height , weight , body mass index ( BMI ) , and lean body mass ( LBM ) ) and prostate cancer risk was assessed using Cox regression analysis . Results : Overall , we observed no significant trend for any of the variables studied , although an excess risk of prostate cancer with increasing height was suggested by an age-adjusted relative risk of 1.2 ( 95 % CI=0.9–1.6 ) for the tallest compared to the shortest quintile of men . None of the other three variables ( weight , BMI , and LBM ) displayed any consistent relation with the risk of prostate cancer . Conclusions : We conclude that these results do not indicate a strong association between anthropometric factors and risk of prostate cancer Background High cholesterol may be a modifiable risk factor for prostate cancer but results have been inconsistent and subject to potential " reverse causality " where undetected disease modifies cholesterol prior to diagnosis . Methods We conducted a prospect i ve cohort study of 12,926 men who were enrolled in the Midspan studies between 1970 and 1976 and followed up to 31st December 2007 . We used Cox-Proportional Hazards Models to evaluate the association between baseline plasma cholesterol and Gleason grade -specific prostate cancer incidence . We excluded cancers detected within at least 5 years of cholesterol assay . Results 650 men developed prostate cancer in up to 37 years ' follow-up . Baseline plasma cholesterol was positively associated with hazard of high grade ( Gleason score≥8 ) prostate cancer incidence ( n = 119 ) . The association was greatest among men in the 2nd highest quintile for cholesterol , 6.1 to < 6.69 mmol/l , Hazard Ratio 2.28 , 95 % CI 1.27 to 4.10 , compared with the baseline of < 5.05 mmol/l . This association remained significant after adjustment for body mass index , smoking and socioeconomic status . Conclusions Men with higher cholesterol are at greater risk of developing high- grade prostate cancer but not overall risk of prostate cancer . Interventions to minimise metabolic risk factors may have a role in reducing incidence of aggressive prostate cancer Most common human traits and diseases have a polygenic pattern of inheritance : DNA sequence variants at many genetic loci influence the phenotype . Genome-wide association ( GWA ) studies have identified more than 600 variants associated with human traits , but these typically explain small fractions of phenotypic variation , raising questions about the use of further studies . Here , using 183,727 individuals , we show that hundreds of genetic variants , in at least 180 loci , influence adult height , a highly heritable and classic polygenic trait . The large number of loci reveals patterns with important implication s for genetic studies of common human diseases and traits . First , the 180 loci are not r and om , but instead are enriched for genes that are connected in biological pathways ( P = 0.016 ) and that underlie skeletal growth defects ( P < 0.001 ) . Second , the likely causal gene is often located near the most strongly associated variant : in 13 of 21 loci containing a known skeletal growth gene , that gene was closest to the associated variant . Third , at least 19 loci have multiple independently associated variants , suggesting that allelic heterogeneity is a frequent feature of polygenic traits , that comprehensive explorations of already-discovered loci should discover additional variants and that an appreciable fraction of associated loci may have been identified . Fourth , associated variants are enriched for likely functional effects on genes , being over-represented among variants that alter amino-acid structure of proteins and expression levels of nearby genes . Our data explain approximately 10 % of the phenotypic variation in height , and we estimate that unidentified common variants of similar effect sizes would increase this figure to approximately 16 % of phenotypic variation ( approximately 20 % of heritable variation ) . Although additional approaches are needed to dissect the genetic architecture of polygenic human traits fully , our findings indicate that GWA studies can identify large numbers of loci that implicate biologically relevant genes and pathways As with other instrumental variable ( IV ) analyses , Mendelian r and omization ( MR ) studies rest on strong assumptions . These assumptions are not routinely systematic ally evaluated in MR applications , although such evaluation could add to the credibility of MR analyses . In this article , the authors present several methods that are useful for evaluating the validity of an MR study . They apply these methods to a recent MR study that used fat mass and obesity-associated ( FTO ) genotype as an IV to estimate the effect of obesity on mental disorder . These approaches to evaluating assumptions for valid IV analyses are not fail-safe , in that there are situations where the approaches might either fail to identify a biased IV or inappropriately suggest that a valid IV is biased . Therefore , the authors describe the assumptions upon which the IV assessment s rely . The methods they describe are relevant to any IV analysis , regardless of whether it is based on a genetic IV or other possible sources of exogenous variation . Methods that assess the IV assumptions are generally not conclusive , but routinely applying such methods is nonetheless likely to improve the scientific contributions of MR studies Purpose To assess the association between height and risk of cancer and cancer death . Methods The metabolic syndrome and cancer project is a prospect i ve pooled cohort study of 585,928 participants from seven cohorts in Austria , Norway , and Sweden . Hazard ratios ( HRs ) and 95 % confidence intervals ( CIs ) for cancer incidence and death were estimated in height categories and per 5-cm increment for each cancer site using Cox proportional hazards model . Results During a mean follow-up of 12.7 years ( SD = 7.2 ) , 38,862 participants were diagnosed with cancer and 13,547 participants died of cancer . Increased height ( per 5-cm increment ) was associated with an increased overall cancer risk in women , HR 1.07 ( 95 % CI 1.06–1.09 ) , and in men , HR 1.04 ( 95 % CI 1.03–1.06 ) . The highest HR was seen for malignant melanoma in women , HR 1.17 ( 95 % CI 1.11–1.24 ) , and in men HR 1.12 ( 95 % CI 1.08–1.19 ) . Height was also associated with increased risk of cancer death in women , HR 1.03 ( 95 % CI 1.01–1.16 ) , and in men , HR 1.03 ( 95 % CI 1.01–1.05 ) . The highest HR was observed for breast cancer death in postmenopausal women ( > 60 years ) , HR 1.10 ( 95 % CI 1.00–1.21 ) , and death from renal cell carcinoma in men , HR 1.18 ( 95 % CI 1.07–1.30 ) . All these associations were independent of body mass index . Conclusion Height was associated with risk of cancer and cancer death indicating that factors related to height such as hormonal and genetic factors stimulate both cancer development and progression Background : The relationship between prostate cancer and height is uncertain . Methods : We prospect ively examined the association of height with prostate cancer among 34268 men in the prostate , lung , colorectal , and ovarian cancer trial . Anthropometry was assessed at baseline and 2144 incident prostate cancer cases were identified upto 8.9 years of follow-up . Results : Overall , tallness was not associated with the risk of prostate cancer or with the risk of non-aggressive disease , but the risk for aggressive prostate cancer tended to be greater in taller men ( Gleason score ⩾7 or stage ⩾III ; P trend=0.05 ; relative risk ( RR ) for 190 cm+ vs ⩽170 cm=1.39 , 95 % confidence interval ( 95 % CI ) : 0.96–2.01 ) . This association was largely limited to men below the age of 65 years ( P trend=0.008 ; RR for 190 cm+ vs ⩽170 cm=1.76 , 95 % CI : 1.06–2.93 ; P for interaction=0.009 ) , although the number of cases was small and risk estimates were somewhat unstable . Conclusion : The results of this large prospect i ve prostate cancer screening trial suggest that tallness is associated with increased risk for younger onset aggressive prostate cancer Studies of colon cancer risk in males have reported strong positive associations with obesity , particularly with central adiposity . The association has been weaker and less consistent for women . Output:	Our study provides evidence for a potential causal association of adult height with the risk of colorectal and lung cancers and suggests that certain genetic factors and biological pathways affecting adult height may also affect the risk of these cancers
MS21491	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: BACKGROUND A range of health care practitioners use cranial techniques . Palpation of a cranial rhythmic impulse ( CRI ) is a fundamental clinical skill used in diagnosis and treatment with these techniques . There has been little research establishing the reliability of CRI rate palpation . OBJECTIVE This study aim ed to establish the intraexaminer and interexaminer reliability of CRI rate palpation and to investigate the " core-link " hypothesis of craniosacral interaction that is used to explain simultaneous motion at the cranium and sacrum . DESIGN Within-subjects , repeated- measures design . SUBJECTS Two registered osteopaths , both with postgraduate training in diagnosis and treatment , using cranial techniques , palpated 11 normal healthy subjects . METHODS Examiners simultaneously palpated for the CRI at the head and the sacrum of each subject . Examiners indicated the " full flexion " phase of the CRI by activating silent foot switches that were interfaced with a computer . Subject arousal was monitored using heart rate . Examiners were blind to each other 's results and could not communicate during data collection . RESULTS Reliability was estimated from calculation of intraclass correlation coefficients ( 2,1 ) . Intrarater reliability for examiners at either the head or the sacrum was fair to good , significant intraclass correlation coefficients ranging from + 0.52 to + 0.73 . Interexaminer reliability for simultaneous palpation at the head and the sacrum was poor to nonexistent , ICCs ranging from -0.09 to + 0.31 . There were significant differences between rates of CRI palpated simultaneously at the head and the sacrum . CONCLUSIONS The results fail to support the construct validity of the " core-link " hypothesis as it is traditionally held by proponents of craniosacral therapy and osteopathy in the cranial field Objectives : With growing evidence for the effectiveness of craniosacral therapy ( CST ) for pain management , the efficacy of CST remains unclear . This study therefore aim ed at investigating CST in comparison with sham treatment in chronic nonspecific neck pain patients . Material s and Methods : A total of 54 blinded patients were r and omized into either 8 weekly units of CST or light-touch sham treatment . Outcomes were assessed before and after treatment ( week 8) and again 3 months later ( week 20 ) . The primary outcome was the pain intensity on a visual analog scale at week 8 ; secondary outcomes included pain on movement , pressure pain sensitivity , functional disability , health-related quality of life , well-being , anxiety , depression , stress perception , pain acceptance , body awareness , patients ’ global impression of improvement , and safety . Results : In comparison with sham , CST patients reported significant and clinical ly relevant effects on pain intensity at week 8 ( −21 mm group difference ; 95 % confidence interval , −32.6 to −9.4 ; P=0.001 ; d=1.02 ) and at week 20 ( −16.8 mm group difference ; 95 % confidence interval , −27.5 to −6.1 ; P=0.003 ; d=0.88 ) . Minimal clinical ly important differences in pain intensity at week 20 were reported by 78 % within the CST group , whereas 48 % even had substantial clinical benefit . Significant between-group differences at week 20 were also found for pain on movement , functional disability , physical quality of life , anxiety and patients ’ global improvement . Pressure pain sensitivity and body awareness were significantly improved only at week 8 . No serious adverse events were reported . Discussion : CST was both specifically effective and safe in reducing neck pain intensity and may improve functional disability and the quality of life up to 3 months after intervention Background To determine whether the complementary approach of visceral manipulative osteopathic treatment accelerates complete meconium excretion and improves feeding tolerance in very low birth weight infants . Methods This study was a prospect i ve , r and omized , controlled trial in premature infants with a birth weight < 1500 g and a gestational age < 32 weeks who received a visceral osteopathic treatment 3 times during their first week of life or no treatment . Results Passage of the last meconium occurred after a median of 7.5 days ( 95 % confidence interval : 6–9 days , n = 21 ) in the intervention group and after 6 days ( 95 % confidence interval : 5 - 9 days , n = 20 , ) in the control group ( p = 0.11 ) . However , osteopathic treatment was associated with a 8 day longer time to full enteral feedings ( p = 0.02 ) , and a 34 day longer hospital stay ( Median = 66 vs. 100 days i.e. ; p=0.14 ) . Osteopathic treatment was tolerated well and no adverse events were observed . Conclusions Visceral osteopathic treatment of the abdomen did not accelerate meconium excretion in VLBW ( very low birth weight)-infants . However infants in the osteopathic group had a longer time to full enteral feedings and a longer hospital stay , which could represent adverse effects . Based on our trial results , we can not recommend visceral osteopathic techniques in VLBW-infants . Trial registration Clinical trials.gov : Inevitable subjectivity makes interexaminer reliability of manual assessment procedures a special matter of concern . The cranial concept ( CC ) , one aspect of osteopathy , deals with very subtle changes that have to be palpated . One of the main principles of the CC is the primary respiratory mechanism ( PRM ) , which is hypothesized to be a palpable physiological phenomenon that occurs in rhythmic cycles , called flexion- and extension-phase , which are independent from cardiac and respiratory rates . Palpation of the PRM is one of the first steps in assessment within the CC . An inter- and intraexaminer reliability study design for repeated measures was used in this study . Forty nine healthy subjects were palpated simultaneously twice , once at the head and once at the pelvis . PRM-frequency ( f ) , the mean duration of the flexion phase and the mean ratio of flexion- to extension-phase were used as the main outcome measures . Inter- and intraexaminer reliability and correlations to the respiratory rates were analysed for all three parameters . Inter- as well as intraexaminer agreement could not be described beyond chance agreement , as the range within the 95 % limits of agreement ( e.g. for f=6.6 cycles/90 s ) for all cases resembled the total range of values ( e.g. for f=7 cycles/90 s ) that were produced . A significant effect of the examiners ' respiration was found for both examiners at the pelvis ( P=0.004 for one examiner , P < 0.0001 for the other examiner ) , and for one examiner only at the head ( P=0.0017 ) . No correlation could be found for the subjects ' respiratory rates . In conclusion , PRM-rates could not be palpated reliably and under certain conditions were influenced by the examiners ' respiratory rates . These results do not support the hypotheses behind the PRM . The role of PRM palpation for clinical decision making and the models explaining the PRM should therefore be rethought BACKGROUND The efficacy of osteopathic manual therapy ( OMT ) applications on chronic nonspecific low back pain ( LBP ) has been demonstrated . However , visceral applications , which are an important part of OMT techniques , have not been included in those studies . OBJECTIVE The study 's objective was to determine the effect of OMT including visceral applications on the function and quality of life ( QoL ) in patients with chronic nonspecific LBP . DESIGN The study was design ed with a simple method of block r and omization . METHODS Thirty-nine patients with chronic nonspecific LBP were included in the study . OMT group consisted of 19 patients to whom OMT and exercise methods were applied . The visceral osteopathic manual therapy ( vOMT ) group consisted of 20 patients to whom visceral applications were applied in addition to the applications carried out in the other group . Ten sessions were performed over a two-week period . Pain ( VAS ) , function ( Oswestry Index ) and QoL ( SF-36 ) assessment s were carried out before the treatment and on the sixth week of treatment . RESULTS Both of the treatments were found to be effective on pain and function , physical function , pain , general health , social function of the QoL sub-parameter . vOMT was effective on all sub-QoL parameters ( p<0.05 ) . Comparing the groups , it was determined that the energy and physical limitations of the QoL scores in vOMT were higher ( p < 0.05 ) . CONCLUSION Visceral applications on patients with non-specific LBP gave positive results together with OMT and exercise methods . We believe that visceral fascial limitations , which we think cause limitations and pain in the lumbar segment , should be taken into consideration BACKGROUND This study aim ed to investigate whether the addition of visceral manipulation , to a st and ard physiotherapy algorithm , improved outcomes in patients with low back pain . METHODS Sixty-four patients with low back pain who presented for treatment at a private physiotherapy clinic were r and omized to one of two groups : st and ard physiotherapy plus visceral manipulation ( n = 32 ) or st and ard physiotherapy plus placebo visceral manipulation ( n = 32 ) . The primary outcome was pain ( measured with the 0 - 10 Numerical Pain Rating Scale ) at 6 weeks . Secondary outcomes were pain at 2 and 52 weeks , disability ( measured with the Rol and -Morris Disability Question naire ) at 2 , 6 and 52 weeks and function ( measured with the Patient-Specific Functional Scale ) at 2 , 6 and 52 weeks . This trial was registered with the Australia and New Zeal and Clinical Trials Registry ( ACTRN12611000757910 ) . RESULTS The addition of visceral manipulation did not affect the primary outcome of pain at 6 weeks ( -0.12 , 95 % CI = -1.45 to 1.21 ) . There were no significant between-group differences for the secondary outcomes of pain at 2 weeks or disability and function at 2 , 6 or 52 weeks . The group receiving addition of visceral manipulation had less pain than the placebo group at 52 weeks ( mean 1.57 , 95 % CI = 0.32 to 2.82 ) . Participants were adequately blinded to group status and there were no adverse effects reported in either group . CONCLUSIONS Our study suggests that visceral manipulation in addition to st and ard care is not effective in changing short-term outcomes but may produce clinical ly worthwhile improvements in pain at 1 year STUDY OBJECTIVE To estimate the feasibility of preoperative ultrasound evaluation of the umbilical region in patients undergoing laparoscopy with a previous history of abdominal surgery . DESIGN Prospect i ve study ( Canadian Task Force Classification II-1 ) . SETTING Department of Obstetrics and Gynecology Fatebenefratelli Isola Tiberina Hospital . PATIENTS Twenty-five women with a previous history of open abdominal surgery ( group A ) and a group of 22 women with no previous history of surgery ( group B ) underwent dynamic ultrasound evaluation of the umbilical field . INTERVENTION Ultrasound Slide-By test . RESULTS Patients were asked to take a deep inspiratory breath , which accentuated respiratory excursion . The movement of the intraabdominal contents in a vertical fashion in relation to the abdominal wall , referred to as the " viscera slide , " between the bowel and peritoneum was evaluated . Abdominal wall tissue thickness , Uracus to peritoneum thickness ( UTP , mm ) were also evaluated . Non parametric Mann-Whitney testing was used . No major demographic differences between the 2 study groups was noted . The abdominal wall tissue thickness was not significantly different between the 2 groups . The UTP was shorter in A group than in B group ( 1.5 + /- 0.3 mm vs 3.5 + /- 0.9 mm , p = .002 ) . Absence of the " sliding viscera " sign was observed in 16 patients in group A and in 1 patient in group B. Patients with an absence of the sliding viscera sign were found to have subumbilical fibrous adhesions during laparoscopy . CONCLUSIONS Evaluation of trocar insertion sites may be difficult and remains a challenge for peritoneal endosurgical access . We have shown that absence of the " sliding viscera " sign is more likely to be linked to subumbilical adhesions and represents a quick method for preoperative assessment . The UTP may also be a useful measurement , which requires further validation Output:	The analysis of reliability studies shows that the diagnostic techniques used in visceral osteopathy are unreliable . Conclusions The results of the systematic review lead us to conclude that well-conducted and sound evidence on the reliability and the efficacy of techniques in visceral osteopathy is absent .
MS21492	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Background Development of longer term stroke rehabilitation services is limited by lack of evidence of effectiveness for specific interventions and service models . We describe the protocol for a multicentre r and omised controlled trial which is evaluating an extended stroke rehabilitation service . The extended service commences when routine ‘ organised stroke care ’ ( stroke unit and early supported discharge ( ESD ) ) ends . Methods / design This study is a multicentre r and omised controlled trial with health economic and process evaluations . It is set within NHS stroke services which provide ESD . Participants are adults who have experienced a new stroke ( and carer if appropriate ) , discharged from hospital under the care of an ESD team . The intervention group receives an extended stroke rehabilitation service provided for 18 months following completion of ESD . The extended rehabilitation service involves regular contact with a senior ESD team member who leads and coordinates further rehabilitation . Contact is usually by telephone . The control group receives usual stroke care post-ESD . Usual care may involve referral of patients to a range of rehabilitation services upon completion of ESD in accordance with local clinical practice . R and omisation is via a central independent web-based service . The primary outcome is extended activities of daily living ( Nottingham Extended Activities of Daily Living Scale ) at 24 months post-r and omisation . Secondary outcomes ( at 12 and 24 months post-r and omisation ) are health status , quality of life , mood and experience of services for patients , and quality of life , experience of services and carer stress for carers . Re source use and adverse events are also collected . Outcomes are undertaken by a blinded assessor . Implementation and delivery of the extended stroke rehabilitation service will also be described . Semi-structured interviews will be conducted with a sub sample of participants and staff to gain insight into perceptions and experiences of rehabilitation services delivered or received . Allowing for 25 % attrition , 510 participants are needed to provide 90 % power to detect a difference in mean Nottingham Extended Activities of Daily Living Scale score of 6 with a 5 % significance level . Discussion The provision of longer term support for stroke survivors is currently limited . The results from this trial will inform future stroke service planning and configuration . Trial registration This trial was registered with IS RCT N ( identifier : IS RCT N45203373 ) on 9 August 2012 Objective : To investigate the effect of community-based ambulation training on walking function of patients with post-stroke hemiparesis . Design : R and omized , single-blind , controlled pilot study . Setting : Inpatient rehabilitation hospital . Subjects : Twenty-five subjects were r and omly assigned to either the experimental group or the control group , with 13 and 12 subjects , respectively . Interventions : All subjects received a routine physical therapy . The subjects in the experimental group also received community-based ambulation training , which was performed for an hour , once a day , three times a week for a four-week period . Main measures : Ten-metre walk test , 6-minute walk test , community walk test , walking ability question naire and activities-specific balance confidence scale before and after the intervention . Results : The change values of the 10-m walk test ( 0.21 ± 0.12 m/s versus 0.07 ± 0.10 m/s ) , community walk test ( −13.61 ± 10.31 minutes versus −3.27 ± 11.99 minutes ) , walking ability question naire ( 6.15 ± 3.60 score versus 2.75 ± 2.38 score ) and activities-specific balance confidence scale ( 17.45 ± 11.55 score versus 2.55 ± 10.14 score ) were significantly higher in the experimental group than in the control group ( P < 0.05 ) . At post-test , the 10-m walk test was significantly higher in the experimental group than in the control group ( 0.72 ± 0.24 m/s versus 0.50 ± 0.23 m/s ) ( P < 0.05 ) . In the experimental group , there were significant differences for all variables between pre-test and post-test ( P < 0.01 ) , whereas the subjects of the control group showed a significant difference in only the walking ability question naire ( P < 0.01 ) . Conclusions : The findings demonstrate that community-based ambulation training can be helpful in improving walking ability of patients with post-stroke hemiparesis and may be used as a practical adjunct to routine rehabilitation therapy Objectives The objective of this study was to test the feasibility of conducting a r and omised controlled trial ( RCT ) of an intervention targeted at activities of daily living ( ADL ) , delivered by an occupational therapist , in homecare reablement . Design Feasibility parallel group RCT . Setting Single-site local authority homecare reablement service . Participants People referred for homecare reablement with ability to consent . Exclusion criteria were as follows : inability to speak English , receiving other community therapy services , needing two or more to assist transfer and receiving end-of-life care . Control ‘ Usual care ’ was 6 weeks of homecare reablement delivered by social care workers ( no routine health professional input ) . Intervention A targeted ADL programme , delivered by an occupational therapist incorporating goal setting , teaching/practising techniques , equipment/adaptations and provision of advice/support . This was in addition to usual care . Outcome measures Aspects of feasibility including eligibility , recruitment , intervention delivery , attrition and suitability and sensitivity of outcome measures . Participant outcomes were personal and extended ADL , quality of life , falls and use of health and social care services . Results 30 participants were recruited , 15 to each arm , which was 60 % of those eligible . Data from 22 ( 73 % ) were analysed at 6 months . Of the 15 participants , 13 ( 86 % ) received the intervention and were able to set one or more ADL goals . There were improvements from baseline in both groups , although overall improvements were greater in the occupational therapy ( OT ) intervention group . The biggest threat to feasibility was a change in service configuration during the trial , involving additional occupational therapy input , affecting usual care and recruitment . Conclusions Despite the service reconfiguration , it was feasible to recruit and retain participants , deliver the intervention and collect outcome data that were responsive to change . The choice of primary outcome measure remains unclear . A further powered study is feasible and warranted ; however , the design will require careful consideration because of ongoing national changes in service configurations . Trial registration number IS RCT N21710246 ; Results Background and Purpose — Current theories of motor control in rehabilitation focus on how the nervous system responds to many types of external and internal constraints to execute motor behavior to accomplish a task . However , the dynamic interplay between these 2 constraints remains unclear . This study examined the impact of some aspects of internal and external constraints on motor performance in persons with stroke . Methods — Twenty-seven persons with stroke used the uninvolved arms to perform an upper-extremity reaching task under 4 experimental conditions , formed by the crossing of functional goals and personal preferences . For the higher level of a functional goal , subjects took a drink from a can of beverage . For the lower level of a functional goal , subjects brought the can to the mouth without drinking . The level of personal preferences was determined , by interview , by the degree of predilection for particular beverages . Results — Significant and large effects of functional goals and personal preference were found in the variables of movement time and reaction time . However , the data trend of the 4 testing conditions varied according to presence of visuospatial neglect and side of lesion . Conclusions — Offering choices for the treatment activities and incorporating functional goals to therapeutic tasks might enhance response rate or movement efficiency , depending on the side of the lesion and presence of visuospatial neglect . The findings suggest that the consideration of the neglect phenomenon is a necessity when rehabilitative treatment planning incorporates constraint factors OBJECTIVE The purpose of this study was to examine the effect of presence or absence of an object ( goal -directed action vs. rote exercise ) and the effect of functional specificity of the object on the organization of reaching movements of persons who have had a stroke . METHOD A repeated-measure counterbalanced design was used in each of two experiments . Eighteen persons who had been hospitalized after stroke were recruited from the roster of a rehabilitation hospital and through stroke clubs and volunteered to participate . Fourteen of these became the data -producing sample . In Experiment 1 , the OPTO-TRAK/3020 motion analysis system was used to record movement when the participants reached for preferred food ( goal -directed action ) or to a spatial location ( rote exercise ) . In Experiment 2 , the system recorded movement when participants reached to pick up the receiver of an active telephone ( natural context ) , a detached receiver ( partial context ) , and a stick ( simulated context ) . The organization of the reach movement was described kinematically as the number of zero crossings of the acceleration profile ( smoothness ) , movement time ( speed ) , displacement , peak velocity ( an indication of force ) , and location of peak velocity in the velocity profile ( planning strategy ) . RESULTS Goal -directed action produced significantly smoother , faster , more forceful , and more preplanned movement than did the rote exercise condition . Functional specificity of the context did not significantly affect organization of the reach . CONCLUSION Goal -directed reach enabled persons with stroke to display characteristics typical of reach to a target by persons who have not had a stroke better than reaching out in space . These findings support the occupational therapy practice of using objects in a functional context to improve coordinated movement . However , the nature of the objects to be used requires further study OBJECTIVES To compare the benefits of a short-term occupational therapy intervention ( OTI ) when added to the conventional treatment model ( CTM ) in the functional recovery of patients admitted to an acute geriatric unit ( AGU ) . STUDY DESIGN Non-pharmacological r and omized clinical trial . 400 patients were r and omized to OTI ( n = 198 ) or CTM ( n = 202 ) group . Mean age 83.5 . Interventions included needs assessment , iatrogenic prevention , retraining in activities of daily living , and instructions for caregivers in three groups of patients defined a priori ( cardiopulmonary disease , stroke , other conditions ) 5 days a week , 30 - 45 min a day . MAIN OUTCOME MEASURE Recovery of ≥ 10 Barthel index points by discharge . Secondary outcome was the reduction in confusional episodes . RESULTS The adjusted relative risk ( RR ) of functional recovery in the OTI group was 1.16 ( 95%CI 0.91 - 1.47 ) . In participants with cardiopulmonary disease was 1.57 ( 95%CI 1.06 - 2.32 ) , number needed to treat ( NNT ) 5 . Participants with other conditions assigned to OTI had a reduction in acute confusional episodes ; RR 0.48 ( 95 % CI 0.26 - 0.87 ) , NNT 7 . CONCLUSIONS Although overall there were no significant differences , patients with cardiopulmonary disease or non-stroke pathologies admitted to an AGU , may benefit from a short-term OTI The objective of this study was to develop and examine the effectiveness of an individual home rehabilitation program for patients with ischemic stroke . This was a r and omized controlled trial in 60 patients with recent middle cerebral artery infa rct ion . After hospital discharge for acute stroke care , they were r and omly assigned to receive either a home rehabilitation program for three months ( intervention group ) or usual care ( control group ) . We collected outcome data over three months after their discharge from the hospital . The Barthel Index ( BI ) , the Modified Rankin Scale ( MRS ) , the health-related quality -of-life index ( EQ-5D ) , the Hospital Anxiety and Depression score ( HADs ) , and the Thai Mental State Examination ( TMSE ) were used to analyze the outcomes . In the intervention group , all outcomes were significantly better ( p<0.05 ) than in the control group , except in the case of TMSE . A favorable outcome , which was defined as minimal or no disability as measured by BI ( score 95–100 ) , was achieved by 93.33 % of patients in the intervention group , and 90 % had favorable scores ( 0 or 1 ) on the MRS . This showed a benefit in reducing disability , with two being the number of patients considered as needed-to-treat ( NNT ) ( 95 % CI , 1.0–1.2 ) . All dimensions of EQ-5D in the intervention group were significantly better for quality of life and generic health status than in the control group ( p=0.001 ) . Depression was found in one patient ( 3.33 % ) in the intervention group and in two patients ( 6.67 % ) in the control group . Dementia was found in three patients ( 10 % ) in the intervention group and in four patients ( 13.33 % ) in the control group . We concluded that an early home rehabilitation program for patients with ischemic stroke in the first three-month period provides significantly better outcomes in improving function , reducing disability , increasing quality of life , and reducing depression than a program of usual care does Objective : To assess the effectiveness of community-based rehabilitation for stroke patients who were not admitted to hospital in South London . Design : R and omized controlled trial . Setting : Patients ' homes in South London . Subjects : Stroke patients not admitted to hospital after a stroke . Intervention : Rehabilitation at home by rehabilitation team for up to three months or usual care . Main outcome measures : The primary outcome measure was the Barthel score . Secondary measures included the Motricity Index , Rivermead ADL , Hospital Anxiety and Depression score and Nottingham Health Profile . Results : Forty-three patients who remained at home were r and omized to rehabilitation team ( 23 ) or ‘ usual ’ care ( 20 ) . The mean number of physiotherapy sessions was three ( range 1–14 ) for the rehabilitation team group and two for the usual care group . Patients ( with a deficit ) in the rehabilitation arm of the trial were more likely to receive occupational , physical and speech therapy than those Output:	We found low- quality evidence that occupational therapy targeted towards activities of daily living after stroke can improve performance in activities of daily living and reduce the risk of deterioration in these abilities . Because the included studies had method ological flaws , this research does not provide a reliable indication of the likely effect of occupational therapy for adults with stroke
MS21493	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Background : Intimate partner violence ( IPV ) is associated with a wide range of negative outcomes , including sexual risk behavior . This cross-sectional study explored mediators of the relationship between IPV and risky sexual behavior in 717 women recruited from a sexually transmitted disease ( STD ) clinic . Methods : Participants were recruited from a public STD clinic in upstate New York as part of a r and omized controlled trial that was design ed to evaluate several sexual risk reduction interventions . They completed an audio computer-assisted self-interview in a private room . Results : Among these women , 18 % reported IPV in the past 3 months and 57 % reported lifetime experience of IPV . Recent IPV was associated with greater sexual risk , as measured by more episodes of unprotected sex ( overall and with a steady partner ) . Although IPV was associated with depressive symptoms and drug use before sex , these variables did not mediate the relationship between IPV and sexual risk behavior . Conclusions : The results indicate that IPV is common among women who attend an STD clinic and warrants increased attention . Research is needed to better underst and the pathways linking IPV and HIV risk in women , to optimize the design of effective interventions In a sample of 810 women residing in shelters and low-income housing , this 6-month prospect i ve study investigated associations of recent violence and substance use withHIV-related sexual behaviors and cognitions . Controlling for baseline sexual behavior , partner violence at baseline was associated with less sexual activity and unprotected sex at follow-up . Non-partner violence at baseline was associated with a higher likelihood of being sexually active at follow-up ( housed women ) , but less frequent sexual activity . Drinking to intoxication at baseline was associated with less ability to refuse unwanted sex ( sheltered women ) and higher perceived susceptibility to HIV at follow-up , whereas baseline drug use was associated with greater perceived ability to refuse unwanted sex and condom use self-efficacy . These findings differed in important ways from cross-sectional associations , emphasizing the need for additional prospect i ve research to fully underst and the impact of violence and substance use on women ’s HIV-related behaviors and cognitions Abstract Objective : The relationship between condom use and 2 less visible categories of intimate partner violence ( IPV ) , sexual coercion and verbal aggression , was examined among college students . Methods : In March 2007 a r and om cross-sectional sample of undergraduates from the southeast region of the United States was taken to collect information about sexual coercion and verbal aggression , in addition to condom use consistency . Alcohol use was also assessed . Results : Of the 142 participants , 31.7 % reported being victims of sexual coercion , and 78 % reported having verbally aggressive partners . Participants who reported experiencing sexual coercion in their relationship were significantly less likely to consistently use condoms . Additionally , alcohol use before or during episodes of verbal aggression was negatively associated with condom use . Alcohol use was also significantly associated with heightened incidents of coercion and aggression . Conclusions : Results indicate that among college students , the presence of sexual coercion adversely affects condom use , as does alcohol use Background : Intimate partner violence ( IPV ) is common among young adult relationships , and is associated with significant morbidity , including sexually transmitted infections ( STI ) . This study measured the association between IPV victimization and perpetration and prevalent STIs and STI-risk behaviors among a sample of young women . Methods : This analysis uses wave 3 of the National Longitudinal Study of Adolescent Health and was restricted to the 3548 women who reported on a sexual relationship that occurred in the previous 3 months and agreed to STI testing . A multivariate r and om effects model was used to determine associations between STI and STI-risk behaviors and IPV . Results : The IPV prevalence over the past year was 32%—3 % victim-only , 12 % perpetrator-only , and 17 % reciprocal . The STI prevalence was 7.1 % . Overall , 17 % of participants reported partner concurrency and 32 % reported condom use at last vaginal intercourse . In multivariate analysis , victim-only and reciprocal IPV were associated with not reporting condom use at last vaginal intercourse . Perpetrator-only , victim-only , and reciprocal IPV were associated with partner concurrency . Victim-only IPV was associated with a higher likelihood of having a prevalent STI ( odds ratio : 2.1 ; 95 % confidence interval : 1.0–4.2 ) . Conclusions : This analysis adds to the growing body of literature that suggests that female IPV victims have a higher STI prevalence , as well as a higher prevalence of STI-risk behaviors , compared with women in nonviolent relationships . Women in violent relationships should be considered for STI screening in clinics , and IPV issues should be addressed in STI prevention messages , given its impact on risk for STI acquisition Output:	CONCLUSIONS Quantitative , qualitative , and mixed methods research has demonstrated the linkages between female IPV victimization/male IPV perpetration and condom or oral contraceptive use .
MS21494	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Study Design . This study evaluated clinical and magnetic resonance imaging differences of patients treated surgically for lumbar disc herniation . Clinical follow-up and magnetic resonance imaging evaluation of epidural fibrosis were used to assess patient outcome . Objectives . The purpose of this study was to evaluate the difference in clinical outcome with either free-fat graft , Golfoam , or no interposition membrane placed in the laminectomy defect after nerve root decompression . Summary of Background Data . Epidural fibrosis has been considered a cause of recurrent symptoms after lumbar laminectomy , and numerous material s have been evaluated for prophylaxis of the “ laminectomy membrane . ” These have been mainly histologic and animal studies with no data correlating clinical symptoms and postoperative epidural scar formation . Methods . One hundred fifty-six patients who were treated surgically for lumbar disc herniation were r and omly assigned to one of three groups and followed prospect ively for at least 1 year . Thirty-three of these patients were received magnetic resonance imaging evaluations after 6 months by an idependent radiologist who grade d the amount of epidural scar formation . The patients were assessed at 1 year and given a rating of excellent , good , fair , or poor , and the scar was grade d as none , minimal , or moderate . Results . Although 97 % of all patients improved , 83 % were rated excellent or good . There were no statistical differences between the three groups clinical ly and radiographically . Patients with workers compensation had a statistically significant lower success rate ( P < 0.001 ) . Conclusions . Clinical outcome after lumbar disc surgery does not correlate with the use or type of interposition membrane used to prevent epidural fibrosis Abstract This single-blind r and omised clinical trial compared osteopathic manipulative treatment with chemonucleolysis ( used as a control of known efficacy ) for symptomatic lumbar disc herniation . Forty patients with sciatica due to this diagnosis ( confirmed by imaging ) were treated either by chemonucleolysis or manipulation . Outcomes ( leg pain , back pain and self-reported disability ) were measured at 2 weeks , 6 weeks and 12 months . The mean values for all outcomes improved in both groups . By 12 months , there was no statistically significant difference in outcome between the treatments , but manipulation produced a statistically significant greater improvement for back pain and disability in the first few weeks . A similar number from both groups required additional orthopaedic intervention ; there were no serious complications . Crude cost analysis suggested an overall financial advantage from manipulation . Because osteopathic manipulation produced a 12-month outcome that was equivalent to chemonucleolysis , it can be considered as an option for the treatment of symptomatic lumbar disc herniation , at least in the absence of clear indications for surgery . Further study into the value of manipulation at a more acute stage is warranted OBJECT The authors of clinical studies have demonstrated a significant association between the presence of extensive post-lumbar discectomy peridural scar formation and the recurrence of low-back and radicular pain . Low-dose perioperative radiotherapy has been demonstrated to inhibit peridural fibrosis after laminectomy in animal models . The present study was design ed to evaluate the clinical efficacy of preoperative irradiation in patients with failed-back surgery syndrome due to peridural fibrosis who underwent reexploration and nerve root decompression . METHODS Ten patients with symptomatic post-discectomy peridural fibrosis were r and omized . Half of the patients underwent 700-cGy external-beam irradiation to the operative site 24 hours prior to reexploration and decompressive treatment of their symptomatic nerve root(s ) ( treatment group ) and the other half underwent reexploration and decompressive treatment without preoperative irradiation ( control group ) . All patients underwent simulated irradiation so neither patient nor surgeon was aware of the patient 's group . In all patients the antiadhesion product ADCON-L was placed over the affected nerve root at the time of surgery . Clinical outcome was assessed using the American Association of Neurological Surgeons/Congress of Neurological Surgeons Joint Section Lumbar Disc Herniation Study Question naire at baseline , 6 weeks , 3 months , and 1 year follow up . Five men and five women ( mean age 42 years ) underwent r and omization and surgery . Three patients underwent reexploration at L4 - 5 , four at L5-S1 , and three at both levels . No complication was associated with irradiation , and no new neurological deficits occurred . At 1-year follow-up examination , three irradiation-treated patients were pain free and two experienced improvement . In the control group , three patients experienced improved pain relief and two were unchanged . There was a trend toward better outcome at 1 year in the radiotherapy-treated group ( p = 0.056 ) . CONCLUSIONS Preoperative low-dose external-beam irradiation improved clinical outcomes after reexploration and decompression of nerve roots affected by postlaminectomy peridural fibrosis causing radicular pain . The addition of preoperative irradiation may improve outcome in patients who undergo reoperation for recurrent radicular pain associated with a significant amount of peridural fibrosis , particularly now that no antiadhesion product is available for clinical use Objective : To determine the efficacy of epidural corticosteroid injections for sciatica . Methods : Three epidural injections ( two day intervals ) of 2 ml prednisolone acetate ( 50 mg ) or 2 ml isotonic saline were administered to patients with sciatica presumably due to a disk herniation lasting 15–180 days . Self evaluation was the main judgment criterion at day 20 . Patients who recovered or showed marked improvement were considered as success . Pain measured by VAS , the SLR test , Schober ’s test , Dallas pain question naire , and the Rol and -Morris index were evaluated at days 0 , 5 , 20 , and 35 . Only analgesics were authorised , patients requiring non-steroidal anti-inflammatory drugs ( NSAIDs ) before day 20 were considered as failure . Results : 42 patients were included in the control group ( CG ) , 43 in the steroid group ( SG ) . On an intention to treat analysis 15/42 ( 36 % ) in the CG and 22/43 ( 51 % ) in the SG ( p=0.15 ) were considered as success ( difference 15.5 % , 95 % CI ( −5.4 to 36.3 ) ) . Among the 48 failures , 14 patients ( 6 CG , 8 SG ) required NSAIDs , 3 ( 2 CG , 1 SG ) required surgery , and 7 ( 3 CG , 4 SG ) other treatments . On analysis according to protocol , in 74 remaining patients 12/35 ( 34 % ) in the CG and 22/39 ( 56 % ) in the SG ( p=0.057 ) were considered as success ( difference 22.1 % , 95 % CI ( 0.0 to 44.2 ) ) . For all secondary end points intragroup improvement with time was significant , but intergroup differences were not . Conclusion : The efficacy of isotonic saline administered epidurally for sciatica can not be excluded , but epidural steroid injections provide no additional improvement CONTEXT Lumbar diskectomy is the most common surgical procedure performed for back and leg symptoms in US patients , but the efficacy of the procedure relative to nonoperative care remains controversial . OBJECTIVE To assess the efficacy of surgery for lumbar intervertebral disk herniation . DESIGN , SETTING , AND PATIENTS The Spine Patient Outcomes Research Trial , a r and omized clinical trial enrolling patients between March 2000 and November 2004 from 13 multidisciplinary spine clinics in 11 US states . Patients were 501 surgical c and i date s ( mean age , 42 years ; 42 % women ) with imaging-confirmed lumbar intervertebral disk herniation and persistent signs and symptoms of radiculopathy for at least 6 weeks . INTERVENTIONS St and ard open diskectomy vs nonoperative treatment individualized to the patient . MAIN OUTCOME MEASURES Primary outcomes were changes from baseline for the Medical Outcomes Study 36-item Short-Form Health Survey bodily pain and physical function scales and the modified Oswestry Disability Index ( American Academy of Orthopaedic Surgeons MODEMS version ) at 6 weeks , 3 months , 6 months , and 1 and 2 years from enrollment . Secondary outcomes included sciatica severity as measured by the Sciatica Bothersomeness Index , satisfaction with symptoms , self-reported improvement , and employment status . RESULTS Adherence to assigned treatment was limited : 50 % of patients assigned to surgery received surgery within 3 months of enrollment , while 30 % of those assigned to nonoperative treatment received surgery in the same period . Intent-to-treat analyses demonstrated substantial improvements for all primary and secondary outcomes in both treatment groups . Between-group differences in improvements were consistently in favor of surgery for all periods but were small and not statistically significant for the primary outcomes . CONCLUSIONS Patients in both the surgery and the nonoperative treatment groups improved substantially over a 2-year period . Because of the large numbers of patients who crossed over in both directions , conclusions about the superiority or equivalence of the treatments are not warranted based on the intent-to-treat analysis . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00000410 BACKGROUND Lumbar-disk surgery often is performed in patients who have sciatica that does not resolve within 6 weeks , but the optimal timing of surgery is not known . METHODS We r and omly assigned 283 patients who had had severe sciatica for 6 to 12 weeks to early surgery or to prolonged conservative treatment with surgery if needed . The primary outcomes were the score on the Rol and Disability Question naire , the score on the visual-analogue scale for leg pain , and the patient 's report of perceived recovery during the first year after r and omization . Repeated- measures analysis according to the intention-to-treat principle was used to estimate the outcome curves for both groups . RESULTS Of 141 patients assigned to undergo early surgery , 125 ( 89 % ) underwent microdiskectomy after a mean of 2.2 weeks . Of 142 patients design ated for conservative treatment , 55 ( 39 % ) were treated surgically after a mean of 18.7 weeks . There was no significant overall difference in disability scores during the first year ( P=0.13 ) . Relief of leg pain was faster for patients assigned to early surgery ( P<0.001 ) . Patients assigned to early surgery also reported a faster rate of perceived recovery ( hazard ratio , 1.97 ; 95 % confidence interval , 1.72 to 2.22 ; P<0.001 ) . In both groups , however , the probability of perceived recovery after 1 year of follow-up was 95 % . CONCLUSIONS The 1-year outcomes were similar for patients assigned to early surgery and those assigned to conservative treatment with eventual surgery if needed , but the rates of pain relief and of perceived recovery were faster for those assigned to early surgery . ( Current Controlled Trials number , IS RCT N26872154 [ controlled-trials.com ] . ) Study Design . We r and omized 200 patients after lumbar discectomy to receive epidural steroid or none with a 2-year follow-up . Objective . To evaluate the outcome , neurologic impairment and safety of epidural steroid following lumbar discectomy for herniated disc disease . Summary of Background Data . Convalescence after discectomy for herniated disc disease is dependent on pain and the inflammatory response . Previous studies in arthroscopic and abdominal surgery demonstrate steroids , which reduce the inflammatory response and enhance recovery . Here we report a 2-year follow-up of a r and omized trial of epidural steroid following lumbar discectomy . Methods . Through 2001 and 2003 200 patients undergoing discectomy for herniated disc disease were r and omly allocated to receive epidural methylprednisolone 40 mg or none . In the control group ( 62 males and 38 females , median age 41 years , 18–66 ) 48 L5 , 50 L4 , and 6 L3 discectomies were performed and in the intervention group ( 60 males and 40 females , median age 45 years , 15–53 ) 56 L5 , 46 L4 , and 3 L3 discectomies . Contemporary with r and omization to epidural steroid or none both groups received preoperative prophylactic antibiotics and the same multimodal pain treatment . Results . Hospital stay was reduced from 8 to 6 days ( P = 0.0001 ) and the number of patients with neurologic signs were reduced more ( 70 % vs. 44 % , P = 0.0004 ) by epidural steroid . Incidence of reoperation at 1 year was 6 % in both groups and 8 % in the control group and 7 % in the intervention group after 2 years . No infections were registered . Conclusion . Epidural methylprednisolone enhances recovery after discectomy for herniated disc disease without apparent side effects The management of sciatica due to lumbar nerve root compromise remains controversial , probably because few well-controlled studies of conservative management have been performed . This preliminary study assesses the efficacy of epidural injections of 80 mg triamcinolone acetonide plus 0.5 % procaine hydrochloride in saline , administered via the caudal route , in a double-blind , placebo controlled trial with 1 year follow- Output:	For overall recovery as the outcome , compared with inactive control or conventional care , there was a statistically significant improvement following disc surgery , epidural injections , nonopioid analgesia , manipulation , and acupuncture . Traction , percutaneous discectomy , and exercise therapy were significantly inferior to epidural injections or surgery . For pain as the outcome , epidural injections and biological agents were significantly better than inactive control , but similar findings for disc surgery were not statistically significant . Biological agents were significantly better for pain reduction than bed rest , nonopioids , and opioids . Opioids , education/advice alone , bed rest , and percutaneous discectomy were inferior to most other treatment strategies ; although these findings represented large effects , they were statistically equivocal . The findings support the effectiveness of nonopioid medication , epidural injections , and disc surgery . They also suggest that spinal manipulation , acupuncture , and experimental treatments , such as anti-inflammatory biological agents , may be considered . The findings do not provide support for the effectiveness of opioid analgesia , bed rest , exercise therapy , education/advice ( when used alone ) , percutaneous discectomy , or traction .
MS21495	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: There is a burgeoning literature on communication in general practice . It is often assumed that trained GPs know and practice the techniques described , but that time is a major constraint . In two experimental studies patients were given shorter or longer appointments , and the doctors ' use of different verbal interventions was measured . Our analysis focused on how individual doctors varied in their use of interviewing techniques according to the time available . When more time was available some interventions were used more frequently by all doctors , but for other interventions the response was variable . For example , GPs who normally used facilitation frequently used it more often when greater time was available , whereas doctors who used this technique less frequently tended not to change when more time was available . This suggests that , at least in the short term , there is a differential response to changes in the time available in the consultation , with increased time being a necessary but not sufficient condition to promote the greater use of the communication techniques which doctors use less frequently Abstract Objectives : To measure quality of care at general practice consultations in diverse geographical areas , and to determine the principal correlates associated with enablement as an outcome measure . Design : Cross sectional multi practice question naire based study . Setting : R and om sample of practice s in four participating regions : Lothian , Coventry , Oxfordshire , and west London . Participants : 25 994 adults attending 53 practice s over two weeks in March and April 1998 . Main outcome measures : Patient enablement , duration of consultation , how well patients know their doctor , and the size of the practice list . Results : A hierarchy of needs or reasons for consultation was created . Similar overall enablement scores were achieved for most casemix presentations ( mean 3.1 , 95 % confidence interval 3.1 to 3.1 ) . Mean duration of consultation for all patients was 8.0 minutes ( 8.0 to 8.1 ) ; however , duration of consultation increased for patients with psychological problems or where psychological and social problems coexisted ( mean 9.1 , 9.0 to 9.2 ) . The 2195 patients who spoke language s other than English at home were analysed separately as they had generally higher enablement scores ( mean 4.5 , 4.3 to 4.7 ) than those patients who spoke English only despite having shorter consultations ( mean 7.1 ( 6.9 to 7.3 ) minutes . At individual consultations , enablement score was most closely correlated with duration of consultation and knowing the doctor well . Individual doctors had a wide range of mean enablement scores ( 1.1 - 5.3 ) and mean duration s of consultation ( 3.8 - 14.4 minutes ) . Doctors ' ability to enable was linked to the duration of their consultation and the percentage of their patients who knew them well and was inversely related to the size of their practice . At practice level , mean enablement scores ranged from 2.3 to 4.4 and duration of consultation ranged from 4.9 to 12.2 minutes . Correlations between ranks at practice level were not significant . Conclusions : It may be time to reward doctors who have longer consultations , provide greater continuity of care , and both enable more patients and enable patients more . Key messages 38 % of practice s approached on a r and om basis in four areas of the United Kingdom collected data for 2 weeks showing the feasibility of surveying the content and outcome of routine consultations in general practice At consultation level , enablement correlates best with the duration of consultations and how well the patient knows the doctor These correlates apply at doctor level as well — more enabling doctors work in smaller practice s than less enabling doctors Case mix does not seem to be a determinant of enablement scores , but patients with more complex problems require longer consultations to achieve equal enablement Patterns of duration of consultation and enablement in patients who speak language s other than English are different and require further A controlled trial was carried out to determine whether longer booking intervals at surgeries affected general practitioners ' self-assessed levels of stress and arousal . Sixteen general practitioners from 10 practice s took part . Surgery sessions with patients booked at 10 minute intervals ( experimental sessions ) were compared with the doctors ' usual booking intervals of between 7.5 and 5.0 minutes ( control sessions ) . Stress and arousal were assessed by the general practitioner before and after each surgery session using a mood adjective check list . The study included 109 experimental and 184 control sessions . The median consultation length increased from six minutes in the control sessions to seven minutes in the experimental sessions . At the end of the experimental sessions , stress scores were lower , and arousal scores higher than at the end of the control sessions ( P less than 0.001 ) . There were no significant differences between experimental and control sessions in stress or arousal at the start of the sessions . Favourable mood changes were seen more consistently in the experimental sessions than control sessions , with less than a quarter of doctors showing increased stress or decreased arousal after sessions relative to before . It is concluded that longer booking intervals are of psychological advantage to general practitioners Intermittent acute inflammation of aural , nasal , and articular cartilage is typical of relapsing polychondritis.1 Laboratory tests are unhelpful , though a raised erythrocyte sedimentation rate and mild leucocytosis are usually present . ' Definitive diagnosis was made by the histological appearance of affected cartilage . Audiovestibular damage may occur as the presenting symptom , ' and in our patient deafness may have been the first manifestation of the disease . Difficulty with intubation many years later suggests that tracheal cartilage was affected . Hashimoto 's thyroiditis with myxoedema,5 goitre , l and diabetes mellitus3 5 have been associated with relapsing polychondritis and often precede the cartilaginous manifestations by many years . To our knowledge there has been no report of Graves 's disease , diabetes mellitus , and vitiligo occurring in a patient with relapsing polychondritis and gastric parietal cell and intrinsic factor antibodies . We postulate that the associated widespread autoimmune disease in this case of relapsing -polychondritis suggests an organ-specific autoimmune aetiology for the condition . The presence of circulating specific antihuman cartilage antibodies supports this view , though the antigen is unidentified . The finding of anticartilage antibodies in two out of three cases led to a similar conclusion .2 The relation between clinical disease of cartilage and circulating anticartilage antibodies is at present unknown . Cell-mediated immunity to cartilage has also been reported in polychondritis.3 4 A search for anticartilage antibodies together with clinical and immunological evidence of other autoimmune disease should be made in all suspected cases OBJECTIVE --To see whether extending appointment length from seven and a half minutes or less to 10 minutes per patient would increase health promotion in general practice consultations . DESIGN --Controlled trial of 10 minute appointments . Consultations were compared with control surgeries in which the same doctors booked patients at their normal rate ( median six minutes per patient ) . SETTING --10 general practice s in Nottinghamshire . SUBJECTS--16 general practitioners were recruited . Entry criteria were a booking rate of eight or more patients an hour , a wish for longer consultations , and plans to increase appointment length . MAIN OUTCOME MEASURES -- Duration of consultations ; recording of blood pressure , weight , and cervical cytology in the medical record ; recording of advice about smoking , alcohol , diet , exercise , and immunisation in the medical record ; reporting of the above activities by patients . RESULTS --Mean consultation times were 8.25 minutes in the experimental sessions and 7.04 and 7.16 minutes in the control sessions . Recording of blood pressure , smoking , alcohol consumption , and advice about immunisation was significantly more frequent in the experimental sessions , and the proportion of consultations in which one or more items of health education were recorded in the medical notes increased by an average of over 6 % in these sessions . Patients more often reported discussion of smoking and alcohol consumption and coverage of previous health problems in the experimental sessions . There was little change in discussion of exercise , diet , and weight or cervical cytology activity . CONCLUSIONS --Shortage of time is a major factor in general practitioners ' failure to realise their potential in health promotion . General practice should be organised so that doctors can run 10 minute appointment sessions In a study in which patients were allocated non- systematic ally to surgeries booked at 5 , 7.5 , and 10 minute intervals 623 consultations were taperecorded . In surgeries booked at longer intervals doctors used the extra time to take a fuller history from their patients . In surgeries booked at 10 minute intervals doctors spent more time explaining the patient 's problem , explaining the proposed management , and in discussing prevention and health education , these increases not being evident in surgeries booked at 7.5 minute intervals An experiment was carried out in which patients who were seeking appointments for a consultation in a general practice in south London attended consulting sessions booked at 5 , 7.5 , or 10 minute intervals . The particular session that the patient attended was determined non- systematic ally . The clinical content of the consultation was recorded on an encounter sheet and on audio-tape . At the end of each consultation patients were invited to complete a question naire design ed to measure satisfaction with the consultation . The stress engendered in doctors carrying out surgery sessions booked at different intervals of time was also measured . At surgery sessions booked at 5 minute intervals , compared with 7.5 and 10 minute intervals , the doctors spent less time with the patients and identified fewer problems , and the patients were less satisfied with the consultation . Blood pressure was recorded twice as often in surgery sessions that were booked at 10 minute intervals compared with those booked at 5 minute intervals . There was no evidence that patients who attended sessions booked at shorter intervals received more prescriptions , were investigated or referred more often to hospital specialists , or returned more often for further consultations within four weeks . There was no evidence that the doctors experienced more stress in dealing with consultations that were booked at 5 minute intervals than at consultations booked at 7.5 and 10 minute intervals , though they complained of shortage of time more often in surgery sessions that were booked at shorter intervals BACKGROUND Shared decision-making ( SDM ) between professionals and patients is increasingly advocated from ethical principles . Some data are accruing about the effects of such approaches on health or other patient-based outcomes . These effects often vary substantially between studies . OBJECTIVE Our aim was to evaluate the effects of training GPs in SDM , and the use of simple risk communication aids in general practice , on patient-based outcomes . METHODS A cluster r and omized trial with crossover was carried out with the participation of 20 recently qualified GPs in urban and rural general practice s in Gwent , South Wales . A total of 747 patients with known atrial fibrillation , prostatism , menorrhagia or menopausal symptoms were invited to a consultation to review their condition or treatments . After baseline , participating doctors were r and omized to receive training in ( i ) SDM skills ; or ( ii ) the use of simple risk communication aids , using simulated patients . The alternative training was then provided for the final study phase . Patients were r and omly allocated to a consultation during baseline or intervention 1 ( SDM or risk communication aids ) or intervention 2 phases . A r and omly selected half of the consultations took place in ' research clinics ' to evaluate the effects of more time for consultations , compared with usual surgery time . Patient-based outcomes were assessed at exit from consultation and 1 month follow-up . These were : COMRADE instrument ( principal measures ; subscales of risk communication and confidence in decision ) , and a range of secondary measures ( anxiety , patient enablement , intention to adhere to chosen treatment , satisfaction with decision , support in decision making and SF-12 health status measure ) . Multilevel modelling was carried out with outcome score as the dependent variable , and follow-up point ( i.e. exit or 1 month later for each patient ) , patient and doctor levels of explanatory variables . RESULTS No statistically significant changes in patient-based outcomes due to the training interventions were found : COMRADE risk communication score increased 0.7 [ 95 % confidence interval ( CI ) -0.92 to 2.32 ] after risk communication training and 0.9 ( 95 % CI -0.89 to 2.35 ) after SDM training ; and COMRADE satisfaction with communication score increased by 1.0 ( 95 % CI -1.1 to 3.1 ) after risk communication , and decreased by 0.6 ( 95 % CI 2.7 to -1.5 ) after SDM training . Patients ' confidence in the decision ( 2.1 increase , 95 % CI 0.7 - 3.5 , P < 0.01 ) and expectation to adhere to chosen treatments ( 0.7 increase , 95 % CI 0.04 - 1.36 , P < 0.05 ) were significantly greater among patients seen in the research clinics ( when more time was available ) compared with usual surgery time . Most outcomes deteriorated between exit and 1 month later . There was no interaction between intervention effects . CONCLUSION Patients can be more involved in treatment decisions , and risks and benefits of treatment options can be explained in more detail , without adversely affecting patient-based outcomes . SDM and risk communication may be advocated from values and ethical principles even without evidence of health gain or improvement in patient-based outcomes , but the re sources required to enhance these professional skills must also be taken into consideration . These data also indicate the benefits of extra consultation time Output:	Altering appointment length result ed in modest changes in average length of consultation . There were no consistent differences in problem recognition , examination , prescribing , referral or investigation rates . There was some evidence that blood pressure was checked and smoking discussed more often when more time was available . None of the interventions were associated with differences in patient satisfaction . AUTHORS ' CONCLUSIONS The findings of this review do not provide sufficient evidence to support or resist a policy of altering the lengths of primary care physicians ' consultations .
MS21496	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: OBJECTIVES The objectives of this study were to evaluate the efficacy , safety , and tolerability of quetiapine for treating psychosis in patients with probable/possible Alzheimer disease and assess its impact on other psychopathology and social and daily functioning . METHOD The authors conducted a multicenter , double-blind , placebo-controlled , r and omized trial of flexibly dosed quetiapine and haloperidol . Primary outcomes were change in total Brief Psychiatric Rating Scale ( BPRS ) and Clinical Global Impressions-Severity of Illness ( CGI-S ) scores at week 10 . Secondary outcomes included BPRS factors , Neuropsychiatric Inventory ( NPI ) , Multidimensional Observation Scale for Elderly Subjects ( MOSES ) , and Physical Self-Maintenance Scale ( PSMS ) . RESULTS Two hundred eighty-four participants ( mean age : 83.2 years ) were r and omized ; 63.4 % completed ; and mean Mini-Mental State Examination score was 12.8 . Median of the mean daily dose was 96.9 mg for quetiapine and 1.9 mg for haloperidol . No differential benefit was seen on any psychosis measure . BPRS agitation factor scores improved with quetiapine versus placebo and not quetiapine versus haloperidol . BPRS anergia scores worsened with haloperidol versus quetiapine but not quetiapine versus placebo . No NPI factors showed change , including the agitation factor . MOSES Withdrawal Subscale and PSMS total scores worsened with haloperidol versus quetiapine . Somnolence occurred in 25.3 % , 36.2 % , and 4.1 % of the quetiapine , haloperidol , and placebo groups , respectively ; parkinsonism was most prevalent in the haloperidol group ; other safety and tolerability measures differed little among groups . CONCLUSION All treatment groups showed improvement in measures of psychosis without significant differences between them when planned comparisons were performed . Participants treated with quetiapine or haloperidol showed inconsistent evidence of improvement in agitation . Tolerability was better with quetiapine compared with haloperidol Introduction : Psychosis ( delusions and /or hallucinations ) is a well-recognized complication of treatment of Parkinson ’s disease ( PD ) . Quetiapine is a currently favored treatment , but data on its efficacy are equivocal . This trial aim ed to provide further evidence on the efficacy of quetiapine in PD psychosis . Methods : We conducted a 12 week double blind r and omized placebo-controlled trial . Time to dropout due to lack of improvement of psychosis was the primary outcome measure . Other important secondary outcomes were evaluated using st and ard rating scales for PD and psychiatric symptoms . Results : Twenty-four eligible subjects gave consent . The primary outcome , time to dropout , was examined using survival analysis . It was shown that patients in the quetiapine group dropped out earlier than those in the placebo group , but this difference was not significant ( p = 0.68 ) . No significant changes were found for any of the secondary outcome measures in either group . Conclusions : In this study , quetiapine at doses of up to 150 mg/day failed to significantly improve psychosis compared to placebo , however the small sample size does not allow any conclusive interpretation of the results . Quetiapine did not appear to worsen PD motor functioning , but its use was limited by a faster drop out compared with placebo . Significant impediments were difficulty with recruitment and natural fluctuation in symptoms during the trial BACKGROUND To evaluate the antipsychotic efficacy of olanzapine ( OLZ ) in patients with Parkinson 's disease ( PD ) and drug-induced psychosis ( DIP ) and its repercussion on the motor function . METHODS Ten patients ( 5 women and 5 men ) diagnosed of PD and DIP , aged 67 years ( range : 50 - 81 ) , with PD duration of 11.1 years ( range : 6 - 23 ) , treated chronically with levodopa per day , received a dose of 2.5 or 5.0 mg OLZ daily . Data concerning improvement of psychosis and worsening of motor function was based on Positive And Negative Symptoms Scale ( PANSS ) and Unified Parkinsons Disease Rating Scale ( UPDRS ) motor . RESULTS Psychotic symptoms were improved in all patients . In most of them the improvement was almost total . Seven patients increased levodopa dose on OLZ , but significant worsening of motor function was reported just in one patient . None of the patients had agranulocytosis in the blood monitoring . Two patients presented weight gain . Seven patients improved their cognitive status . CONCLUSIONS We conclude that OLZ at the doses studied may have efficacy for DIP which appears in PD and does not induce worsening of motor function in most of the patients Objective : To compare the efficacy and safety of clozapine in drug induced psychosis in Parkinson ’s disease ( PD ) . Methods : A four week , r and omised , double blind , parallel comparison of clozapine and placebo , followed by a 12 week clozapine open period , plus a one month period after drug discontinuation , in 60 patients with PD . The primary efficacy outcome was the “ clinical global impression scale ” ( CGI ) ; the positive subscore of the “ positive and negative syndrome scale ” ( PANSS ) was used as the secondary efficacy parameter and the “ unified Parkinson ’s disease rating scale ” ( UPDRS ) and the “ mini mental test examination ” ( MMSE ) as safety outcomes . Results : The mean ( SD ) dosage of clozapine was 35.8 ( 12.5–50 ) mg at the end of the double blind period . The mean ( SD ) scores on the CGI improved by 1.8 ( 1.5 ) for the clozapine group compared with 0.6 ( 1.1 ) for the placebo group ( p = 0.001 ) . The mean ( SD ) positive subscore of PANSS improved by 5.6 ( 3.9 ) for the clozapine group ( 0.8 ( 2.8 ) for the placebo group ; p < 0.0001 ) . At the end of the open period , 25 patients had completely recovered from delusions and hallucinations , and 19 experienced a relapse within one month after the clozapine washout period . The UPDRS motor and MMSE mean scores did not change significantly in either group . Somnolence was more frequent with clozapine than with placebo . Conclusions : Clozapine at a mean dose lower than 50 mg/day improves drug induced psychosis in PD without significant worsening of motor function , and the effect wears off once the treatment stops 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 In a double-blind placebo-controlled study , we evaluated the effects of clozapine ( 75 to 250 mg/day , mean 170.8 ) on dopaminomimetic psychosis and parkinsonian disability . Clozapine prevented deterioration of psychosis during the increase of dopaminomimetics in the 3 patients who completed the study . Worsening of parkinsonism occurred in 3 of the 6 patients . In the dosage used , clozapine 's usefulness was limited by its propensity to produce sedation , confusion , and increased parkinsonism BACKGROUND Parkinson 's disease psychosis , which includes hallucinations and delusions , is frequent and debilitating in people with Parkinson 's disease . We aim ed to assess safety and efficacy of pimavanserin , a selective serotonin 5-HT2A inverse agonist , in this population . METHODS In our 6 week , r and omised , double-blind , placebo-controlled study , we enrolled adults ( aged ≥40 years ) with Parkinson 's disease psychosis . Antipsychotic treatments were not permitted during the study , but controlled antiparkinsonian medication or deep brain stimulation was allowed . Eligible participants entered a 2 week non-pharmacological lead-in phase to limit the placebo response , after which they were r and omly allocated ( 1:1 ) to receive pimavanserin 40 mg per day or matched placebo . The primary outcome was antipsychotic benefit as assessed by central , independent raters with the Parkinson 's disease-adapted scale for assessment of positive symptoms ( SAPS-PD ) in all patients who received at least one dose of study drug and had a SAPS assessment at baseline and at least one follow-up . We assessed safety and tolerability in all patients who received at least one dose of study drug . This study is registered with Clinical Trials.gov , number NCT01174004 . FINDINGS Between Aug 11 , 2010 , and Aug 29 , 2012 , we r and omly allocated 199 patients to treatment groups . For 90 recipients of placebo and 95 recipients of pimavanserin included in the primary analysis , pimavanserin was associated with a -5·79 decrease in SAPS-PD scores compared with -2·73 for placebo ( difference -3·06 , 95 % CI -4·91 to -1·20 ; p=0·001 ; Cohen 's d 0·50 ) . Ten patients in the pimavanserin group discontinued because of an adverse event ( four due to psychotic disorder or hallucination within 10 days of start of the study drug ) compared with two in the placebo group . Overall , pimavanserin was well tolerated with no significant safety concerns or worsening of motor function . INTERPRETATION Pimavanserin may benefit patients with Parkinson 's disease psychosis for whom few other treatment options exist . The trial design used in this study to manage placebo response could have applicability to other studies in neuropsychiatric disease . FUNDING ACADIA Pharmaceuticals Objective : To compare olanzapine and clozapine for safety and efficacy measures of psychosis and motor function in patients with PD and chronic hallucinations . Background : Hallucinations occur in approximately one third of patients with PD treated chronically with dopaminergic drugs . Although clozapine is known to be an effective antipsychotic agent that does not significantly exacerbate parkinsonism , its use requires frequent blood count assessment . Olanzapine is another novel antipsychotic that is not associated with blood dyscrasia , and if equally effective could become the preferred drug for treating hallucinations in subjects with PD . Methods : A r and omized , double-blind , parallel comparison of olanzapine and clozapine in patients with PD with chronic hallucinations was conducted . The primary outcome measure was the Scale for the Assessment of Positive Symptoms ( SAPS ) for psychotic symptoms . The Unified Parkinson ’s Disease Rating Scale ( UPDRS ) motor subscale was used as a secondary outcome measure and as a safety monitoring tool . Results : After 15 patients had completed the study , safety stopping rules were invoked because of exacerbated parkinsonism in olanzapine-treated subjects . UPDRS motor impairment scores from baseline to study end significantly increased with olanzapine treatment , and change scores between the olanzapine and clozapine groups significantly differed . The primary clinical domains responsible for the motor decline were gait and bradykinesia . Even with a smaller patient number than originally anticipated , clozapine significantly improved hallucinations and overall behavioral assessment , whereas olanzapine had no effect . Conclusions : At the doses studied , olanzapine aggravates parkinsonism in comparison with clozapine and should not be regularly used in the management of hallucinations in patients with PD Objective : To assess the efficacy and tolerability of quetiapine for agitation or psychosis in patients with dementia and parkinsonism . Methods : Multicenter r and omized , double-blind , placebo-controlled parallel groups clinical trial involving 40 patients with dementia with Lewy bodies ( n = 23 ) , Parkinson disease ( PD ) with dementia ( n = 9 ) , or Alzheimer disease with parkinsonian features ( n = 8) . The main outcome measure for efficacy was change in the Brief Psychiatric Rating Scale ( BPRS ) from baseline to 10 weeks of therapy . For tolerability it was change in the Unified PD Rating Scale ( UPDRS ) motor section over the same time period . The trial was confounded by the need for a design change and incomplete recruitment . Results : No significant differences in the primary or secondary outcome measures of efficacy were observed . An unexpectedly large placebo effect , inadequate dosage ( mean 120 mg/day ) , and inadequate power may have contributed to lack of demonstrable benefit . Quetiapine was generally well-tolerated and did not worsen parkinsonism , but was associated with a trend toward a decline on a measure of daily functioning . Conclusions : Quetiapine was well-tolerated and did not worsen parkinsonism . Although conclusions about efficacy may be limited , the drug in the dosages used did not show demonstrable benefit for treating agitation or psychosis in patients with dementia and parkinsonism . These findings are in keeping with prior studies reporting limited efficacy of various medications for reducing behavioral problems in demented patients Polysomnographic studies of Parkinson 's disease ( PD ) patients with visual hallucinations ( VH ) usually reveal short , fragmented rapid eye movement ( REM ) sleep , with lower sleep efficiency and reduced total REM sleep . Quetiapine has been demonstrated in open-label trials to be effective for the treatment of insomnia and VH in PD . To confirm quetiapine 's efficacy in improving VH , and to determine whether the mechanism was due to its effect on REM sleep architecture , we performed a pilot , Output:	Although clozapine had an effective and relatively safe profile , all atypical antipsychotics included in the present study may be unsafe , as they may worsen motor function when compared to placebo
MS21497	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: OBJECTIVE To evaluate effectiveness of the Adolescent Coping With Depression ( CWD-A ) course , a cognitive-behavioral group intervention for depressed adolescents with comorbid conduct disorder . METHOD Between 1998 and 2001 , 93 nonincarcerated adolescents ( ages 13 - 17 years ) meeting criteria for major depressive disorder and conduct disorder were recruited from a county juvenile justice department and r and omly assigned to the CWD-A or a life skills/tutoring control condition . Participants were assessed post-treatment and at 6- and 12-month follow-up . Dichotomous outcomes were analyzed with logistic regression ; dimensional measures were analyzed using r and om effects regression . RESULTS Major depressive disorder recovery rates post-treatment were greater in CWD-A ( 39 % ) compared with life skills/tutoring control ( 19 % ) ( odds ratio 2.66 , 95 % confidence interval = 1.03 - 6.85 ) . CWD-A participants reported greater reductions in Beck Depression Inventory-II ( r2 = 0.055 , p = .033 ) and Hamilton Depression Rating Scale ( r2 = 0.047 , p = .039 ) scores and improved social functioning ( r2 = 0.064 , p = .019 ) post-treatment . Group differences in major depressive disorder recovery rates at 6- and 12-month follow-up were nonsignificant , as were differences in conduct disorder both post-treatment and during follow-up . CONCLUSIONS This is the first r and omized , controlled trial of a psychosocial intervention with adolescents with major depressive disorder and conduct disorder . Although the CWD-A appears to be an effective acute treatment for depression in adolescents with multiple disorders , findings emphasize the need to improve long-term outcomes for depressed adolescents with psychiatric comorbidity and imply that interventions for comorbid population s focus directly on each specific disorder AIM The aim of the present study was to examine the intervention effects of intensive interpersonal psychotherapy for depressed adolescents with suicidal risk ( IPT-A-IN ) by comparison with treatment as usual ( TAU ) at schools . METHODS A total of 347 students from one-fifth of the classes of a high school in southern Taiwan completed the Beck Depression Inventory-II , the Beck Scale for Suicide Ideation , the Beck Anxiety Inventory and the Beck Hopelessness Scale for screening for suicidal risk . Of them , 73 depressed students who had suicidal risk on screening were r and omly assigned to the IPT-A-IN or TAU group . Analysis of covariance ( ANCOVA ) was performed to examine the effect of IPT-A-IN on reducing the severity of depression , suicidal ideation , anxiety and hopelessness . RESULTS Using the pre-intervention scores as covariates , the IPT-A-IN group had lower post-intervention severity of depression , suicidal ideation , anxiety and hopelessness than the TAU group . CONCLUSION Intensive school-based IPT-A-IN is effective in reducing the severity of depression , suicidal ideation , anxiety and hopelessness in depressed adolescents with suicidal risk The efficacy of Structured Learning Therapy ( SLT ) in treating adolescent depression was evaluated . SLT treatment focuses on developing social competencies , self-evaluation skills , and appropriate affective expression . Eighteen adolescents , aged 14 - 19 years , prescreened for depression were r and omly assigned to the SLT treatment or control group . All subjects participated in six biweekly 60-minute sessions . Pre- , post , and follow-up assessment s on depression , self-esteem , and personality measures were conducted . Results suggest that SLT reliably reduced depression in males ( p < .05 ) and maintained their improved level of functioning ( p < .02 ) . Female treatment subjects did not improve significantly . Results suggest differential effectiveness of treatment across gender OBJECTIVE To design a treatment manual and adherence measure for attachment-based family therapy ( ABFT ) for adolescent depression and to collect pilot data on the treatment 's efficacy . METHOD Over a period of 2 years , 32 adolescents meeting criteria for major depressive disorder ( MDD ) were r and omly assigned to 12 weeks of ABFT or a 6-week , minimal-contact , waitlist control group . The sample was 78 % female and 69 % African American ; 69 % were from low-income , inner-city communities . RESULTS At post-treatment , 81 % of the patients treated with ABFT no longer met criteria for MDD , in contrast with 47 % of patients in the waitlist group . Mixed factorial analyses of variance revealed that , compared with the waitlist group , patients treated with ABFT showed a significantly greater reduction in both depressive and anxiety symptoms and family conflict . Of the 15 treated cases assessed at the follow-up , 13 patients ( 87 % ) continued to not meet criteria for MDD 6 months after treatment ended . CONCLUSIONS ABFT appears to be a promising treatment and worthy of further development BACKGROUND Although considered clinical ly effective , there is little systematic research confirming the use of Individual Psychodynamic Psychotherapy or Family Therapy as treatments for depression in children and young adolescents . AIMS A clinical trial assessed the effectiveness of these two forms of psychotherapy in treating moderate and severe depression in this age group . METHODS A r and omised control trial was conducted with 72 patients aged 9 - 15 years allocated to one of two treatment groups . RESULTS Significant reductions in disorder rates were seen for both Individual Therapy and Family Therapy . A total of 74.3 % of cases were no longer clinical ly depressed following Individual Therapy and 75.7 % of cases were no longer clinical ly depressed following Family Therapy . This included cases of Dysthymia and " Double Depression " ( co-existing Major Depressive Disorder and Dysthymia ) . There was also an overall reduction in co-morbid conditions across the study . The changes in both treatment groups were persistent and there was ongoing improvement . At follow up six months after treatment had ended , 100 % of cases in the Individual Therapy group , and 81 % of cases in the Family Therapy group were no longer clinical ly depressed . CONCLUSIONS This study provides evidence supporting the use of focused forms of both Individual Psychodynamic Therapy and Family Therapy for moderate to severe depression in children and young adolescents OBJECTIVE Aspects of depressed adolescents ' perceived interpersonal functioning were examined as moderators of response to treatment among adolescents treated with interpersonal psychotherapy for depressed adolescents ( IPT-A ; Mufson , Dorta , Moreau , & Weissman , 2004 ) or treatment as usual ( TAU ) in school-based health clinics . METHOD Sixty-three adolescents ( 12 - 18 years of age ) participated in a clinical trial examining the effectiveness of IPT-A ( Mufson , Dorta , Wickramaratne , et al. , 2004 ) . The sample was 84.1 % female and 15.9 % male ( mean age = 14.67 years ) . Adolescents were 74.6 % Latino , 14.3 % African American , 1.6 % Asian American , and 9.5 % other . They came primarily from low-income families . Adolescents were r and omly assigned to receive IPT-A or TAU delivered by school-based mental health clinicians . Assessment s , completed at baseline and at Weeks 4 , 8 , and 12 ( or at early termination ) , included the Hamilton Rating Scale for Depression ( Hamilton , 1967 ) , the Conflict Behavior Question naire ( Robin & Foster , 1989 ) , and the Social Adjustment Scale-Self-Report ( Weissman & Bothwell , 1976 ) . RESULTS Multilevel modeling indicated that treatment condition interacted with adolescents ' baseline reports of conflict with their mothers and social dysfunction with friends to predict the trajectory of adolescents ' depressive symptoms over the course of treatment , controlling for baseline levels of depression . The benefits of IPT-A over TAU were particularly strong for the adolescents who reported high levels of conflict with their mothers and social dysfunction with friends . CONCLUSIONS Replication with larger sample s would suggest that IPT-A may be particularly helpful for depressed adolescents who are reporting high levels of conflict with their mothers or interpersonal difficulties with friends Nine-month outcome data of a r and omized controlled out-patient trial of cognitive-behavioural treatment ( CBT ) for children and adolescents with depression are presented . CBT was compared with a non-focussed intervention ( NFI ) in 56 subjects . At 9 months after thr termination of the trial , 21 children ( 37.5 % ) fulfilled criteria for a psychiatric disorder ( DSM-III-R ) , out of whom 15 ( 26.8 % ) had a depressive illness . However , 25 subjects ( 45 % ) reported depressive symptoms of significant severity to suggest a depressive episode during the previous 9-month period . Both treatment groups maintained a significant improvement on all psychosocial measures since the post-treatment assessment . No significant treatment effect was established . Low self-esteem at the time of referral , predicted presence of psychiatric disorder , and child-reported scores of depressive symptoms and low self-esteem at follow-up . The research and clinical implication s for the treatment of depressive disorders in young life are discussed A controlled trial was conducted to evaluate a prevention program aim ed at reducing depressive and anxious symptoms in rural school children . Seventh- grade children with elevated depression were selected . Nine primary schools ( n = 90 ) were r and omly assigned to receive the program , and 9 control schools ( n = 99 ) received their usual health education classes . Children completed question naires on depression , anxiety , explanatory style , and social skills . Parents completed the Child Behavior Checklist ( T. M. Achenbach , 1991 ) . No intervention effects were found for depression . Intervention group children reported less anxiety than the control group after the program and at 6-month follow-up and more optimistic explanations at postintervention . Intervention group parents reported fewer child internalizing and externalizing symptoms at postintervention only BACKGROUND Previous studies in non clinical sample s have shown psychosocial treatments to be efficacious in the treatment of adolescent depression , but few psychotherapy treatment studies have been conducted in clinical ly referred , depressed adolescents . METHODS One hundred seven adolescent patients with DSM-III-R major depressive disorder ( MDD ) were r and omly assigned to 1 of 3 treatments : individual cognitive behavior therapy , systemic behavior family therapy ( SBFT ) , or individual nondirective supportive therapy ( NST ) . Treatments were 12 to 16 sessions provided in as many weeks . Intent-to-treat analyses were conducted using all follow-up data . RESULTS Of the 107 patients enrolled in the study , 78 ( 72.9 % ) completed the study , 4 ( 3.7 % ) never initiated treatment , 10 ( 9.3 % ) had exclusionary criteria that were undetected at entry , 8 ( 7.5 % ) dropped out , and 7 ( 6.5 % ) were removed for clinical reasons . Cognitive behavior therapy showed a lower rate of MDD at the end of treatment compared with NST ( 17.1 % vs 42.4 % ; P = .02 ) , and result ed in a higher rate of remission ( 64.7 % , defined as absence of MDD and at least 3 consecutive Beck Depression Inventory scores < 9 ) than SBFT ( 37.9 % ; P = .03 ) or NST ( 39.4 % ; p = .04 ) . Cognitive behavior therapy result ed in more rapid relief in interviewer-rated ( vs both treatments , P = .03 ) and self-reported depression ( vs SBFT , P = .02 ) . All 3 treatments showed significant and similar reductions in suicidality and functional impairment . Parents ' views of the credibility of cognitive behavior therapy improved compared with parents ' views of both SBFT ( P = .01 ) and NST ( P = .05 ) . CONCLUSIONS Cognitive behavior therapy is more efficacious than SBFT or NST for adolescent MDD in clinical setting s , result ing in more rapid and complete treatment response Les auteurs ont trouve une efficacite semblable pour la therapie cognitivo-comportementale et pour la relaxation , dans le traitement de la depression chez 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 OBJECTIVE A r and omized , Output:	In addition , IPT and CBT were more beneficial than problem-solving therapy . Waitlist was significantly inferior to other control conditions . These data suggest that IPT and CBT should be considered as the best available psychotherapies for depression in children and adolescents . Waitlist may inflate the effect of psychotherapies , so that psychological placebo or treatment-as-usual may be preferable as a control condition in psychotherapy trials
MS21498	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: STUDY OBJECTIVE --The aim was to examine social and physical correlates of blood pressure in 15 year olds . DESIGN --This was the first , baseline , sweep of a longitudinal survey of 15 year olds based on a two stage stratified clustered r and om sample . SETTING --The Central Clydeside Conurbation , in the West of Scotl and . In 1981 this had a population of 1.7 million and a st and ardised mortality ratio ( relative to Scotl and as a whole ) of 109 . SUBJECTS -- A r and om sample of households containing 15 year olds were approached by Strathclyde Regional Council ; 70 % agreed to have their names passed on to the MRC ( 15 % refused , 10 % could not be contacted , and 5 % had moved ) . Of these 1177 , 11 % refused to participate , 3 % were not contactable/had moved , and 4 % did not provide full data . Complete blood pressure data are available for 959 15 year olds ( 464 males and 495 females ) . MEASUREMENTS AND MAIN RESULTS --Blood pressure , pulse rate , height , weight , and room temperature were measured by nurses in the subjects ' homes . Smoking , drinking , and frequency of vigorous exercise were self reported . Maternal height , birthweight , occupation of head of household , and housing tenure were reported by parents . After controlling for the other variables , systolic blood pressure was significantly associated with weight , pulse rate , and room temperature in males and with weight , pulse rate , housing tenure , smoking , and exercise in females . Diastolic blood pressure was associated with room temperature in males and with mother 's height , pulse rate , and housing tenure in females . Controlling for current weight , birthweight was inversely related to systolic blood pressure in males and positively associated in females , though in neither case were these associations statistically significant . CONCLUSIONS --In males , blood pressure was mainly related to anthropometric factors whereas in females it was additionally related to socioeconomic and behavioural variables . Although not reaching significance , the weight st and ardised relationship between birthweight and systolic blood pressure was consistent for males , but not females , with those reported by recent British studies of children and adults . The longitudinal design of this study will allow us to examine correlates of blood pressure in the same individuals as they reach social and physical maturity STUDY OBJECTIVE : To examine the relation between birth weight and blood pressure at 5 years in a cohort of South African children . DESIGN : Prospect i ve cohort study . PARTICIPANTS : 849 five year old children . SETTING : Soweto , a sprawling urban area close to Johannesburg , South Africa , which was a design ated residential area for people classified as " black " under apartheid legislation . MAIN RESULTS : Systolic blood pressure at 5 years was inversely related to birthweight ( r = -0.05 , p = 0.0007 ) , independent of current weight , height , gestational age , maternal age or socioeconomic status at 5 years . There was no relation between birth weight and diastolic blood pressure . After adjusting for current weight and height , there was a mean decline in systolic blood pressure of 3.4 mm Hg ( 95 % confidence intervals 1.4 , 5.3 mm Hg ) for every 1000 g increase in birth weight . CONCLUSIONS : These data from a disadvantaged urbanised community in Southern Africa extend the reported observations of an inverse relation between birth weight and systolic blood pressure . The study adds to the evidence that influences in fetal life and early childhood influence systolic blood pressure . Further research is required to assess whether efforts to reduce the incidence of low birthweight babies will attenuate the prevalence of hypertension in future generations This study aims to determine whether variables reflecting an adverse intrauterine environment are associated with childhood blood pressure . The authors conducted a secondary analysis of data from a prospect i ve cohort of children born to healthy , nulliparous women enrolled in a r and omized controlled trial . A total of 518 children were traced in 1995 - 1996 from 614 eligible children born in a clinic in Rosario , Argentina . The outcome was systolic blood pressure at 5 - 9 years . Hemoglobin during pregnancy was positively associated with children 's pressure . Other maternal characteristics during pregnancy ( blood pressure , smoking , weight gain , weight at 20 weeks ' gestation , and glycemia ) and size at birth ( birth weight , ponderal index , head circumference/length ratio , and small for gestational age ) were not associated with children 's pressure . Among children in the upper quartile of body mass index , there was a weak inverse correlation between birth weight and systolic pressure , and systolic pressure was 14.8 mmHg ( 95 percent confidence interval : 3.3 , 26.4 ) higher in low birth weight children than in others . The main predictors of childhood pressure were childhood body mass index and maternal pressure outside pregnancy . In this healthy population , the authors found weak support for an association between variables reflecting an adverse fetal environment and childhood blood pressure . Low birth weight was a risk factor for high blood pressure only in overweight children BACKGROUND Many studies have shown that low birth weight is associated with high blood pressure . The composition of the diet of pregnant women has also been found to affect blood pressure in their children . We assessed the effect of prenatal exposure to the Dutch famine of 1944 - 1945 , during which the caloric intake from protein , fat and carbohydrate was proportionally reduced , on blood pressures in adults now aged about 50 years . METHODS AND RESULTS We measured blood pressures at home and in the clinic among people born at term in one hospital in Amsterdam , The Netherl and s , between November 1 1943 and February 28 1947 , for whom we had detailed birth records . Blood pressures of people exposed to famine during late ( n = 120 ) , mid-(n = 109 ) or early gestation ( n = 68 ) were compared with those of people born in the year before or conceived in the year after the famine ( unexposed subjects , n = 442 ) . No effect of prenatal exposure on systolic and diastolic blood pressure was observed . The mean systolic blood pressure taken in the clinic in those exposed in late gestation , and adjusted for sex and age , was 1.3 mmHg higher than in the unexposed group ( 95 % confidence interval -1.9 to 4.4 ) . The mean systolic blood pressure differed by -0.6 mmHg ( 95 % confidence interval -3.9 to 2.7 ) for those exposed in mid-gestation and -1.7 mmHg ( 95 % confidence interval -5.6 to 2.2 ) for those exposed in early gestation . People who were small at birth had higher blood pressures . A 1 kg increase in birth weight was associated with a decrease of 2.7 mmHg ( 95 % confidence interval 0.3 to 5.1 ) in systolic blood pressure . Analyses of blood pressures measured at home gave similar results . CONCLUSION High blood pressure was not linked to prenatal exposure to a balanced reduction of macronutrients in the maternal diet . However , it was linked to reduced fetal growth . We postulate that it might be the composition rather than the quantity of a pregnant woman 's diet that affects her child 's blood pressure in later life BACKGROUND Several studies have found a relation ship between small size at birth and high blood pressure ( HBP ) . However , this association has not been fully evaluated in adolescence . The aim of the present study was to evaluate the relation of birth weight ( BW ) to BP in adolescence , controlling for factors related to BP , to extrauterine environment , and to maternal risk of fetal distress . METHODS In 1310 adolescents ( ages 12 - 14 years ) , r and omly selected from Turin school children , we evaluated BP , heart rate ( HR ) , weight , height , familial risk of hypertension , parental cultural level , BW , and maternal history of diseases during pregnancy . The BW-BP association was tested by using multiple regression analysis and adjusting for the other variables mentioned above . The same analysis was done for the subgroup at high risk of fetal distress . RESULTS The association between BW and BP was negative but weak when we adjusted for all confounders (= -0.07 in males ; = -0.27 in females ) . The association was negative and became stronger after the inclusion of all confounders , particularly HR (= -3.92 ) , in the group of children at high risk of fetal distress . CONCLUSIONS Intrauterine environment , as reflected by BW , has little effect on BP in early adolescence without concomitant maternal diseases or environmental conditions leading to severe placental hypoperfusion OBJECTIVES To determine the association between birth weight and systolic blood pressure ( SBP ) in male adolescents at the age of 18 years . DESIGN A prospect i ve study by means of a register linkage between the Swedish Medical Birth Register and the national register for conscript testing before military service . METHODS From the birth registry we collected data on birth weight , gestational age , maternal age and parity for 149378 individuals . At conscript testing , subjects were given a physical examination , and weight , height , and mean blood pressure were recorded after 5 - 10 min rest . RESULTS Mean+/-SD birth weight was 3543+/-551 g after a mean of 39.7+/-2.0 gestational weeks . Mean+/-SD blood pressure at the conscript testing was 128.8+/-10.9/65.2+/-10.6 mmHg . SBP , but not diastolic blood pressure , differed significantly ( test for trend , P < 0.001 ) between birth weight strata ( deciles ) , with a higher SBP in strata with lower birth weight . A difference in birth weight of 1000 g decreased SBP by 0.8 mmHg . This was most pronounced in subjects with a rapid growth development ( n = 1057 ) , coming from the lowest decile of birth weight and reaching to the highest decile of body mass index , in a very consistent manner . The odds ratio for being in the top decile of SBP was 1.55 ( 95 % confidence interval 1.32 - 1.81 ) for this growth ' catch-up ' group compared with the rest of the cohort . CONCLUSIONS Birth weight was inversely associated with SBP in a large cohort of young men in their late teens . This supports the notion of a programming effect of fetal growth retardation in utero on haemodynamic regulation in early adult life In a retrospective survey , 487 research projects approved by the Central Oxford Research Ethics Committee between 1984 and 1987 , were studied for evidence of publication bias . As of May , 1990 , 285 of the studies had been analysed by the investigators , and 52 % of these had been published . Studies with statistically significant results were more likely to be published than those finding no difference between the study groups ( adjusted odds ratio [ OR ] 2.32 ; 95 % confidence interval [ Cl ] 1.25 - 4.28 ) . Studies with significant results were also more likely to lead to a greater number of publications and presentations and to be published in journals with a high citation impact factor . An increased likelihood of publication was also associated with a high rating by the investigator of the importance of the study results , and with increasing sample size . The tendency towards publication bias was greater with observational and laboratory-based experimental studies ( OR = 3.79 ; 95 % Cl = 1.47 - 9.76 ) than with r and omised clinical trials ( OR = 0.84 ; 95 % Cl = 0.34 - 2.09 ) . We have confirmed the presence of publication bias in a cohort of clinical research studies . These findings suggest that conclusions based only on a review of published data should be interpreted cautiously , especially for observational studies . Improved strategies are needed to identify the results of unpublished as well as published studies Output:	This analysis strongly suggests , but does not prove , that publication bias is present when systematic ally examining the relationship between blood pressure and birth weight . Controlling for publication bias lessens the apparent relationship between the regression coefficient and age of the study population
MS21499	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: BACKGROUND The comparative effectiveness of treatments for prostate cancer that is detected by prostate-specific antigen ( PSA ) testing remains uncertain . METHODS We compared active monitoring , radical prostatectomy , and external-beam radiotherapy for the treatment of clinical ly localized prostate cancer . Between 1999 and 2009 , a total of 82,429 men 50 to 69 years of age received a PSA test ; 2664 received a diagnosis of localized prostate cancer , and 1643 agreed to undergo r and omization to active monitoring ( 545 men ) , surgery ( 553 ) , or radiotherapy ( 545 ) . The primary outcome was prostate-cancer mortality at a median of 10 years of follow-up . Secondary outcomes included the rates of disease progression , metastases , and all-cause deaths . RESULTS There were 17 prostate-cancer-specific deaths overall : 8 in the active-monitoring group ( 1.5 deaths per 1000 person-years ; 95 % confidence interval [ CI ] , 0.7 to 3.0 ) , 5 in the surgery group ( 0.9 per 1000 person-years ; 95 % CI , 0.4 to 2.2 ) , and 4 in the radiotherapy group ( 0.7 per 1000 person-years ; 95 % CI , 0.3 to 2.0 ) ; the difference among the groups was not significant ( P=0.48 for the overall comparison ) . In addition , no significant difference was seen among the groups in the number of deaths from any cause ( 169 deaths overall ; P=0.87 for the comparison among the three groups ) . Metastases developed in more men in the active-monitoring group ( 33 men ; 6.3 events per 1000 person-years ; 95 % CI , 4.5 to 8.8 ) than in the surgery group ( 13 men ; 2.4 per 1000 person-years ; 95 % CI , 1.4 to 4.2 ) or the radiotherapy group ( 16 men ; 3.0 per 1000 person-years ; 95 % CI , 1.9 to 4.9 ) ( P=0.004 for the overall comparison ) . Higher rates of disease progression were seen in the active-monitoring group ( 112 men ; 22.9 events per 1000 person-years ; 95 % CI , 19.0 to 27.5 ) than in the surgery group ( 46 men ; 8.9 events per 1000 person-years ; 95 % CI , 6.7 to 11.9 ) or the radiotherapy group ( 46 men ; 9.0 events per 1000 person-years ; 95 % CI , 6.7 to 12.0 ) ( P<0.001 for the overall comparison ) . CONCLUSIONS At a median of 10 years , prostate-cancer-specific mortality was low irrespective of the treatment assigned , with no significant difference among treatments . Surgery and radiotherapy were associated with lower incidences of disease progression and metastases than was active monitoring . ( Funded by the National Institute for Health Research ; ProtecT Current Controlled Trials number , IS RCT N20141297 ; Clinical Trials.gov number , NCT02044172 . ) BACKGROUND The Prostate Cancer Research International Active Surveillance ( PRIAS ) study was initiated a decade ago to study the most optimal selection and follow-up of men on active surveillance ( AS ) . OBJECTIVE We report on 10 yr of follow-up of men on AS in the PRIAS study and evaluate if criteria used to recommend a switch to active treatment truly predict unfavorable outcome on subsequent radical prostatectomy ( RP ) . DESIGN , SETTING , AND PARTICIPANTS Men with low-risk prostate cancer were included and followed prospect ively on AS . Follow-up consisted of regular prostate-specific antigen ( PSA ) tests , digital rectal examinations , and biopsies . Men with Gleason > 3 + 3 , more than two positive biopsy cores , or stage higher than cT2 were advised to switch to active treatment ( until 2014 , a PSA doubling time [ PSA DT ] of 0 - 3 yr was also used ) . OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Reclassification rates , treatment after discontinuation , and outcome on RP after discontinuing AS were reported . Regression analysis on the outcome of RP was used to evaluate the predictive value of criteria currently used to recommend a switch to active treatment . Kaplan-Meier and competing risk analysis were used to report discontinuation rates over time and long-term oncologic end points . RESULTS AND LIMITATIONS A total of 5302 men were included in PRIAS across 18 countries . Reclassification rates remained stable on all subsequent biopsies , with 22 - 33 % of men having either Gleason > 3 + 3 or more than two positive cores on any repeat biopsy . At 5 and 10 yr of follow-up , 52 % and 73 % of men , respectively , had discontinued AS , most of them because of protocol -based reclassification . A third of men undergoing subsequent RP had favorable pathologic tumor features ( Gleason 3 + 3 and pT2 ) . Of the criteria used to recommend a switch to active treatment , more than two positive cores and a PSA DT of 0 - 3 yr were not predictive of unfavorable pathologic outcome on RP . CONCLUSIONS A substantial group of men discontinued AS without subsequent unfavorable tumor features on RP ; therefore , we propose Gleason upgrading and cT3 as the only indicators for an immediate switch to active treatment . Surrogate indicators ( eg , more than two positive cores and a fast-rising PSA ) should not trigger immediate active treatment but rather further investigation to confirm the suspicion of higher risk disease . PATIENT SUMMARY We confirmed the safety of active surveillance as a treatment option for men with low-risk prostate cancer ; however , some changes could be made to the follow-up protocol to safely increase the number of men who remain on active surveillance OBJECTIVE To develop nomograms that predict the probability of overall prostate cancer ( PCa ) and clinical ly significant PCa ( Gleason ≥7 ) on magnetic resonance imaging (MRI)-targeted , and combined MRI-targeted and systematic , prostate biopsy . MATERIAL S AND METHODS From June 2012 to August 2014 , magnetic resonance imaging to ultrasound fusion-targeted prostate biopsy was performed on 464 men with suspicious regions identified on pre-biopsy 3 T MRI along with systematic 12 core biopsy . Logistic regression modeling was used to evaluate predictors of overall and clinical ly significant PCa , and corresponding nomograms were generated for men who were not previously biopsied or had 1 or more prior negative biopsies . Models were created with 70 % of a r and omly selected training sample and bias-corrected using bootstrap resampling . The models were then vali date d with the remaining 30 % testing sample pool . RESULTS A total of 459 patients were included for analysis ( median age 66 years , prostate-specific antigen [ PSA ] 5.2 ng/mL , prostate volume 49 cc ) . Independent predictors of PCa on targeted and systematic prostate biopsy were PSA density , age , and MRI suspicion score . PCa probability nomograms were generated for each cohort using the predictors . Bias-corrected areas under the receiver-operating characteristic curves for overall and clinical ly significant PCa detection were 0.82 ( 0.78 ) and 0.91 ( 0.84 ) for men without prior biopsy and 0.76 ( 0.65 ) and 0.86 ( 0.87 ) for men with a prior negative biopsy in the training ( testing ) sample s. CONCLUSION PSA density , age , and MRI suspicion score predict PCa on combined MRI-targeted and systematic biopsy . Our generated nomograms demonstrate high diagnostic accuracy and may further aid in the decision to perform biopsy in men with clinical suspicion of PCa BACKGROUND Prostate Imaging-Reporting and Data System v. 2 ( PI-RADSv2 ) provides st and ardized nomenclature for interpretation of prostate multiparametric MRI ( mpMRI ) . Inclusion of additional features for categorization may provide benefit to stratification of disease . PURPOSE To prospect ively compare PI-RADSv2 to a qualitative in-house system for detecting prostate cancer on mpMRI . STUDY TYPE Prospect i ve . POPULATION In all , 338 patients who underwent mpMRI May 2015-May 2016 , with subsequent MRI/transrectal ultrasound fusion-guided biopsy . FIELD STRENGTH 3 T mpMRI ( T2 W , diffusion-weighted [ DW ] , apparent diffusion coefficient [ ADC ] map , b-2000 DWI acquisition , and dynamic contrast-enhanced [ DCE ] MRI ) . ASSESSMENT One genitourinary radiologist prospect ively read mpMRIs using both in-house and PI-RADSv2 5-category systems . STATISTICAL TEST In lesion-based analysis , overall and clinical ly significant ( CS ) tumor detection rates ( TDR ) were calculated for all PI-RADSv2 and in-house categories . The ability of each scoring system to detect cancer was assessed by area under receiver operator characteristic curve ( AUC ) . Within each PI-RADSv2 category , lesions were further stratified by their in-house categories to determine if TDRs can be increased by combining features of both systems . RESULTS In 338 patients ( median prostate-specific antigen [ PSA ] 6.5 [ 0.6 - 113.6 ] ng/mL ; age 64 [ 44 - 84 ] years ) , 733 lesions were identified ( 47 % tumor-positive ) . Predictive abilities of both systems were comparable for all ( AUC 76 - 78 % ) and CS cancers ( AUCs 79 % ) . The in-house system had higher overall and CS TDRs than PI-RADSv2 for categories 3 and 4 ( P < 0.01 for both ) , with the greatest difference between the scoring systems seen in lesions scored category 4 ( CS TDRs : in-house 65 % , PI-RADSv2 22.1 % ) . For lesions categorized as PI-RADSv2 = 4 , characterization of suspicious/indeterminate extraprostatic extension ( EPE ) and equivocal findings across all mpMRI sequences contributed to significantly different TDRs for both systems ( TDR range 19 - 75 % , P < 0.05 ) . DATA CONCLUSION PI-RADSv2 behaves similarly to an existing vali date d system that relies on the number of sequences on which a lesion is seen . This prospect i ve evaluation suggests that sequence positivity and suspicion of EPE can enhance PI-RADSv2 category 4 cancer detection . LEVEL OF EVIDENCE 1 Technical Efficacy : Stage 3 J. Magn . Reson . Imaging 2018;47:1326 - 1335 Purpose : We sought to determine whether saturation of the index lesion during magnetic resonance imaging‐transrectal ultrasound fusion guided biopsy would decrease the rate of pathological upgrading from biopsy to radical prostatectomy . Material s and Methods : We analyzed a prospect ively maintained , single institution data base for patients who underwent fusion and systematic biopsy followed by radical prostatectomy in 2010 to 2016 . Index lesion was defined as the lesion with largest diameter on T2‐weighted magnetic resonance imaging . In patients with a saturated index lesion transrectal fusion biopsy targets were obtained at 6 mm intervals along the long axis of the index lesion . In patients with a nonsaturated index lesion only 1 target was obtained from the lesion . Gleason 6 , 7 and 8‐10 were defined as low , intermediate and high risk , respectively . Results : Included in the study were 208 consecutive patients , including 86 with a saturated and 122 with a nonsaturated lesion . Median patient age was 62.0 years ( IQR 10.0 ) and median prostate specific antigen was 7.1 ng/ml ( IQR 8.0 ) . The median number of biopsy cores per index lesion was higher in the saturated lesion group ( 4 vs 2 , p < 0.001 ) . The risk category up grade rate from systematic only , fusion only , and combined fusion and systematic biopsy results to prostatectomy was 40.9 % , 23.6 % and 13.8 % , respectively . The risk category up grade from combined fusion and systematic biopsy results was lower in the saturated than in the nonsaturated lesion group ( 7 % vs 18 % , p = 0.021 ) . There was no difference in the up grade rate based on systematic biopsy between the 2 groups . However , fusion biopsy results were significantly less up grade d in the saturated lesion group ( Gleason up grade 20.9 % vs 36.9 % , p = 0.014 and risk category up grade 14 % vs 30.3 % , p = 0.006 ) . Conclusions : Our results demonstrate that saturation of the index lesion significantly decreases the risk of upgrading on radical prostatectomy by minimizing the impact of tumor heterogeneity Purpose To vali date the dominant pulse sequence paradigm and limited role of dynamic contrast material -enhanced magnetic resonance ( MR ) imaging in the Prostate Imaging Reporting and Data System ( PI Output:	EVIDENCE SYNTHESIS It has been shown that the test performance of PI-RADS v2 in research and clinical practice retains higher accuracy over systematic transrectal ultrasound ( TRUS ) biopsies for PCa diagnosis . PI-RADS v2 fails to detect all cancers but does detect the majority of tumors capable of causing patient harm , which should not be missed . Test performance depends on the definition and prevalence of clinical ly significant disease . It has been shown that the test performance of PI-RADS v2 in research and clinical practice is improved , retaining higher accuracy over systematic TRUS biopsies for PCa diagnosis . PATIENT SUMMARY Multiparametric magnetic resonance imaging ( MRI ) and MRI-directed biopsies using the Prostate Imaging-Reporting and Data System improves the detection of prostate cancers likely to cause harm , and at the same time decreases the detection of disease that does not lead to harms if left untreated .

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