human
***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 efficacy and safety of 4-g 5-aminosalicylic acid enemas were assessed in 153 patients with ulcerative colitis involving up to 50 cm of distal colon . Seventy-six patients received active medication and 77 received a placebo .  There were 20 dropouts ( 6 in the active group and 14 in the placebo group ) during the study because of insufficient efficacy . After 6 wk of therapy , 48 of the 76 patients ( 63 % ) receiving 5-aminosalicylic acid were considered to be " much improved " by the study physician compared to 22 of the 77 patients ( 29 % ) on placebo ( p = 0.001 ) . A disease activity index based on patient symptoms and sigmoidoscopic appearance was used to assess efficacy . Mean disease activity index declined 55 % for patients on 5-aminosalicylic acid and 24 % for patients on placebo ( p = 0.0001 ) . Analysis of subgroups indicated that patients most likely to respond were those with disease confined to the 20 - 40 cm from the anus . Response was not affected by concurrent sulfasalazine , but patients requiring concurrent oral steroids had a diminished response . Rapid onset of efficacy was shown by a significant reduction in rectal bleeding within 3 days of treatment initiation . 5-Aminosalicylic acid enemas are well tolerated and are of benefit in the treatment of ulcerative colitis confined to the distal colon Purpose Ulcerative colitis ( UC ) is associated with impaired health-related quality of life ( HRQL ) and work-related outcomes ( WRO ) . This analysis examined correspondences among measures of HRQL and WRO in patients with UC , as well as the magnitude of each measure ’s responsiveness to disease activity and treatment . Methods An open-label , prospect i ve trial of delayed-release mesalamine tablets formulated with MMX ® technology included 8 weeks of treatment for patients with active mild-to-moderate UC ( n = 137 ) and 12 months of maintenance treatment for patients with quiescent UC ( n = 206 ) . Spearman correlations ( ρ ) measured inter-domain associations across measures of generic HRQL [ 12-item Short-Form Health Survey ( SF-12v2 ) ] , disease-specific HRQL [ Short Inflammatory Bowel Disease Question naire ( SIBDQ ) ] , and disease-specific WRO [ Work Productivity and Activity Impairment for Specific Health Problems ( WPAI : SHP ) ] . Responsiveness to disease activity and treatment was assessed for each instrument . Results Changes in scores from baseline to week 8 were moderately correlated across all instrument domains : 65 of 80 ( 81 % ) between-instrument inter-domain correlations were of moderate magnitude ( 0.30 < ρ < 0.70 ) , with an average magnitude of 0.42 [ 95 % confidence interval ( CI ) 0.38–0.46 ] . Associations between symptom measures were stronger for SIBDQ ( |average ρ| = 0.41 ; 95 % CI 0.34–0.48 ) and WPAI : SHP ( 0.40 ; 0.30–0.47 ) than SF-12v2 ( 0.30 ; 0.27–0.34 ) . SIBDQ was most sensitive to treatment [ effect size ( dz ) for change from baseline to week 8 = 0.62 ; 95 % CI 0.35–0.89 ] , followed by WPAI : SHP ( dz = 0.43 ; 0.32–0.54 ) and SF-12v2 ( dz = 0.33 ; 0.27–0.39 ) . Conclusion While the SIBDQ showed the greatest overall responsiveness to disease activity and treatment , all three patient-reported outcomes instruments provided complementary interpretive information regarding the impact of UC treatment In recent years quality of life instruments have been featured as primary outcomes in many r and omized trials . One of the challenges facing the investigator using such measures is determining the significance of any differences observed , and communicating that significance to clinicians who will be applying the trial results . We have developed an approach to elucidating the significance of changes in score in quality of life instruments by comparing them to global ratings of change . Using this approach we have established a plausible range within which the minimal clinical ly important difference ( MCID ) falls . In three studies in which instruments measuring  dyspnea , fatigue , and emotional function in patients with chronic heart and lung disease were applied the MCID was represented by mean change in score of approximately 0.5 per item , when responses were presented on a seven point Likert scale . Furthermore , we have established ranges for changes in question naire scores that correspond to moderate and large changes in the domains of interest . This information will be useful in interpreting question naire scores , both in individuals and in groups of patients participating in controlled trials , and in the planning of new trials Abstract Background and Aims R and omised trials have described the benefits of adalimumab [ ADA ] for ulcerative colitis [ UC ] ; however , few data are available on health-related quality of life [ HRQL ] and health care costs in clinical practice . Methods InspirADA , a multicentre , prospect i ve study , evaluated the effect of ADA in patients with moderate to severe UC treated according to usual clinical practice . Outcomes assessed were : Simple Clinical Colitis Activity Index [ SCCAI ] response/remission rates ; changes in HRQL ; all-cause direct costs ; and UC-related direct and indirect costs from baseline to Week 26 . Results Data from 463 patients were analysed . At Week 26 , 67 % ( 95 % confidence interval [ CI ] : 62 % , 71 % ) of patients achieved response ; 48 % [ 95 % CI : 44 % , 53 % ] were in remission . For the overall population , significant [ all p < 0.001 ] improvements from baseline to Week 26 were observed for the Short Inflammatory Bowel Disease Question naire [ SIBDQ ] ( mean change ± st and ard deviation [ SD ] : 17.4 ± 14.5 ) and the European Quality of Life—5 Dimensions—5 Level [ EQ-5D-5L ] ( index : 0.1 ± 0.2 ; visual analogue scale [ VAS ] : 19.5 ± 25.8 ) . Parallel improvements were seen in work productivity [ 11 % absolute decrease in absenteeism ; 25 % absolute decrease in impairment while working ; and 27 % absolute decrease in impairment of ability to perform daily activities , all p < 0.001 ] . Among study completers , cumulative all-cause medical costs and UC-related medical costs were significantly [ both p < 0.001 ] reduced by 59 % and 77 % , respectively , 6 months after initiation of therapy compared with the preceding 6 months . The safety profile  of ADA was consistent with that observed in previous clinical trials . Conclusions ADA therapy in usual clinical practice is effective at improving and maintaining symptomatic control , improving HRQL , and decreasing costs of medical care among patients with UC Background and Aims : This study assessed the efficacy of maintenance treatment with multimatrix mesalazine following achievement of complete or partial remission after induction treatment with high-dose multimatrix mesalazine . Methods : In this phase 3b/4 , open-label , multicentre , prospect i ve , single-arm study , patients with mild-to-moderate ulcerative colitis were treated with multimatrix mesalazine 4.8g/day once daily for 8 weeks [ induction phase ] . At Week 8 , those who achieved complete or partial remission , based on predefined clinical and endoscopic criteria , were eligible to receive 12 months of multimatrix mesalazine 2.4g/day once daily maintenance therapy . The primary endpoint was the proportion of patients in complete remission at Month 12 . Results : A total of 717 patients received induction treatment ; 25.9 % and 39.3 % of patients achieved complete and partial remission , respectively , at Week 8 . A total of 461 patients entered the maintenance phase . The likelihood of remaining in/achieving complete remission at Month 12 was higher for patients who entered the maintenance phase in complete remission compared with those who began maintenance in partial remission [ 47.8 % vs 26.0 % ; p < 0.001 ] . At Month 12 , mucosal healing [ endoscopy score ≤ 1 ] was demonstrated in 76.4 % [ 139/182 ] and 63.5 % [ 176/277 ] of those who were in complete and partial remission , respectively , at the end of induction . Conclusion : Patients achieving complete remission before dose reduction were more likely to remain in remission at Month 12 BACKGROUND Crohn 's disease ( CD ) is a chronic inflammatory bowel disease usually diagnosed in early adult life and characterized by unpredictable flares and debilitating symptoms such as diarrhea , abdominal pain , and fever , which can interfere with a patient 's ability to work and perform daily activities . OBJECTIVE The aim of this study was to assess the validity , reliability , and responsiveness of the Work Productivity and Activity Impairment question naire in CD ( WPAI : CD ) . METHODS The WPAI : CD was tested in CD patients enrolled in a 26-week r and omized clinical trial of cer-tolizumab pegol versus placebo . Discriminative validity of WPAI : CD absenteeism , presenteeism(reduced on-the-job effectiveness ) , overall work productivity loss ( absenteeism + presenteeism ) , and activity impairment scores was assessed relative to 5 measures of disease severity and health status : CD Activity Index ( CDAI ) , Short Form-36 physical component summary ( PCS ) and mental health component summary ( MCS ) scores , Inflammatory Bowel Disease Question naire ( IBDQ ) , and the 5-dimensional EuroQoL health-related quality -of-life visual analog scale ( EQ-VAS ) . Responsiveness was assessed by comparing changes in WPAI : CD scores from baseline to week 26 for patients in remission ( CDAI < 150 points ) versus no remission . St and ardized Response Means ( SRMs ) were calculated to evaluate the magnitude of the changes . RESULTS A total of 662 patients ( mean [ range ] age , 37.4 [ 18 - 77 ] years ; male , 288 [ 43.5 % ] ; white , 629 [ 95.0 % ] ) were enrolled in the study . Patients with CD of the worst severity ( CDAI > median ) showed significantly higher impairment in work ( + 10.5 % ) and activities ( + 10.4 % ) versus patients with " best health " ( no problems ) ( both , P < or = 0.001 ) . Patients with " worst " IBDQ , PCS , MCS , and EQ-VAS scores also showed significantly higher impairments in work ( IBDQ , VAS -24.2 % ; PCS , -24.1 % ; MCS , -15.9 % ; EQ-VAS , -16.5 % ) and activities ( IBDQ , -23.3 % ; PCS , -21.8 % ; MCS , -16.5 % ; EQ-VAS , -17.2 % ) versus " best " scores ( all , P < 0.05 ) . There were significant differences between WPAI : CD impairment scores for patients in remission versus patients failing to achieve remission ( P < 0.05 ) . SRMs were small ( ie , < 0.5 ) in the nonre-mission group , and moderate to large ( ie , > 0.5 ) for patients in remission . CONCLUSIONS The discriminative validity , reliability , and responsiveness of the WPAI : CD were demonstrated . The WPAI : CD may be useful for evaluating drug impact on CD OBJECTIVE Health-related quality of life ( HRQOL ) affects outcome in chronic diseases such as inflammatory bowel disease ( IBD ) . The inflammatory bowel disease question naire ( IBDQ ) , a disease-specific HRQOL question naire , can define changes in health status in IBD , but simple instruments are needed for daily application . The present study proposed to develop a short version of the IBDQ , the SIBDQ , for community physicians . METHODS Using data from a clinical trial in 149 patients with Crohn 's disease , 10 items were selected ( by forward stepwise regression ) that best explained the variance of the IBDQ or dimensional scores ( bowel , systemic , social , emotional ) . The validity , reliability , and responsiveness of the SIBDQ were then assessed in 150 different patients with Crohn 's disease and 45 with ulcerative colitis . All scores were reported with a 7-point scale ( 1 = poor HRQOL , 7 = optimum HRQOL ) . RESULTS Mean SIBDQ scores were similar ( p = 0.22 ) in Crohn 's patients among 14 participating centers at study entry . Mean scores were lower in active Crohn 's disease ( range 4.00 - 4.92 ) than inactive disease ( range 4.67 - 5.83 ; p = 0.0015 ) . In active ulcerative colitis , the mean SIBDQ was 4.79 + /- 1.17 compared to 5.90 + /- 0.80 ( p = 0.0006 ) in inactive disease . The SIBDQ explained 92 % and 90 % of the IBDQ variance in Crohn 's disease and ulcerative colitis , respectively . In patients with stable Crohn 's disease , the test-retest reliability coefficient was 0.65 and Crohnbach 's alpha was 0.78 , indicating good reliability . In patients with Crohn 's disease who relapsed during follow-up , 
    Output:
    
agent
The evidence supports the WPAI as having test-retest reliability ( reproducibility ) over time ; convergent validity , as indicated by moderate correlations with measures of quality of life and moderate-to-strong correlations with measures of disease activity ; known-groups validity , as indicated by differences in WPAI scores between patients with active and inactive disease ; ability ( sensitivity ) to detect change , as indicated by substantial improvement in scores for patients who achieve remission , accompanied by substantial worsening of scores for patients who relapse ; and , responsiveness to treatment , with improvements in scores following treatments that reduce disease activity .
***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 efficacy and safety of 4-g 5-aminosalicylic acid enemas were assessed in 153 patients with ulcerative colitis involving up to 50 cm of distal colon . Seventy-six patients received active medication and 77 received a placebo .  There were 20 dropouts ( 6 in the active group and 14 in the placebo group ) during the study because of insufficient efficacy . After 6 wk of therapy , 48 of the 76 patients ( 63 % ) receiving 5-aminosalicylic acid were considered to be " much improved " by the study physician compared to 22 of the 77 patients ( 29 % ) on placebo ( p = 0.001 ) . A disease activity index based on patient symptoms and sigmoidoscopic appearance was used to assess efficacy . Mean disease activity index declined 55 % for patients on 5-aminosalicylic acid and 24 % for patients on placebo ( p = 0.0001 ) . Analysis of subgroups indicated that patients most likely to respond were those with disease confined to the 20 - 40 cm from the anus . Response was not affected by concurrent sulfasalazine , but patients requiring concurrent oral steroids had a diminished response . Rapid onset of efficacy was shown by a significant reduction in rectal bleeding within 3 days of treatment initiation . 5-Aminosalicylic acid enemas are well tolerated and are of benefit in the treatment of ulcerative colitis confined to the distal colon Purpose Ulcerative colitis ( UC ) is associated with impaired health-related quality of life ( HRQL ) and work-related outcomes ( WRO ) . This analysis examined correspondences among measures of HRQL and WRO in patients with UC , as well as the magnitude of each measure ’s responsiveness to disease activity and treatment . Methods An open-label , prospect i ve trial of delayed-release mesalamine tablets formulated with MMX ® technology included 8 weeks of treatment for patients with active mild-to-moderate UC ( n = 137 ) and 12 months of maintenance treatment for patients with quiescent UC ( n = 206 ) . Spearman correlations ( ρ ) measured inter-domain associations across measures of generic HRQL [ 12-item Short-Form Health Survey ( SF-12v2 ) ] , disease-specific HRQL [ Short Inflammatory Bowel Disease Question naire ( SIBDQ ) ] , and disease-specific WRO [ Work Productivity and Activity Impairment for Specific Health Problems ( WPAI : SHP ) ] . Responsiveness to disease activity and treatment was assessed for each instrument . Results Changes in scores from baseline to week 8 were moderately correlated across all instrument domains : 65 of 80 ( 81 % ) between-instrument inter-domain correlations were of moderate magnitude ( 0.30 < ρ < 0.70 ) , with an average magnitude of 0.42 [ 95 % confidence interval ( CI ) 0.38–0.46 ] . Associations between symptom measures were stronger for SIBDQ ( |average ρ| = 0.41 ; 95 % CI 0.34–0.48 ) and WPAI : SHP ( 0.40 ; 0.30–0.47 ) than SF-12v2 ( 0.30 ; 0.27–0.34 ) . SIBDQ was most sensitive to treatment [ effect size ( dz ) for change from baseline to week 8 = 0.62 ; 95 % CI 0.35–0.89 ] , followed by WPAI : SHP ( dz = 0.43 ; 0.32–0.54 ) and SF-12v2 ( dz = 0.33 ; 0.27–0.39 ) . Conclusion While the SIBDQ showed the greatest overall responsiveness to disease activity and treatment , all three patient-reported outcomes instruments provided complementary interpretive information regarding the impact of UC treatment In recent years quality of life instruments have been featured as primary outcomes in many r and omized trials . One of the challenges facing the investigator using such measures is determining the significance of any differences observed , and communicating that significance to clinicians who will be applying the trial results . We have developed an approach to elucidating the significance of changes in score in quality of life instruments by comparing them to global ratings of change . Using this approach we have established a plausible range within which the minimal clinical ly important difference ( MCID ) falls . In three studies in which instruments measuring  dyspnea , fatigue , and emotional function in patients with chronic heart and lung disease were applied the MCID was represented by mean change in score of approximately 0.5 per item , when responses were presented on a seven point Likert scale . Furthermore , we have established ranges for changes in question naire scores that correspond to moderate and large changes in the domains of interest . This information will be useful in interpreting question naire scores , both in individuals and in groups of patients participating in controlled trials , and in the planning of new trials Abstract Background and Aims R and omised trials have described the benefits of adalimumab [ ADA ] for ulcerative colitis [ UC ] ; however , few data are available on health-related quality of life [ HRQL ] and health care costs in clinical practice . Methods InspirADA , a multicentre , prospect i ve study , evaluated the effect of ADA in patients with moderate to severe UC treated according to usual clinical practice . Outcomes assessed were : Simple Clinical Colitis Activity Index [ SCCAI ] response/remission rates ; changes in HRQL ; all-cause direct costs ; and UC-related direct and indirect costs from baseline to Week 26 . Results Data from 463 patients were analysed . At Week 26 , 67 % ( 95 % confidence interval [ CI ] : 62 % , 71 % ) of patients achieved response ; 48 % [ 95 % CI : 44 % , 53 % ] were in remission . For the overall population , significant [ all p < 0.001 ] improvements from baseline to Week 26 were observed for the Short Inflammatory Bowel Disease Question naire [ SIBDQ ] ( mean change ± st and ard deviation [ SD ] : 17.4 ± 14.5 ) and the European Quality of Life—5 Dimensions—5 Level [ EQ-5D-5L ] ( index : 0.1 ± 0.2 ; visual analogue scale [ VAS ] : 19.5 ± 25.8 ) . Parallel improvements were seen in work productivity [ 11 % absolute decrease in absenteeism ; 25 % absolute decrease in impairment while working ; and 27 % absolute decrease in impairment of ability to perform daily activities , all p < 0.001 ] . Among study completers , cumulative all-cause medical costs and UC-related medical costs were significantly [ both p < 0.001 ] reduced by 59 % and 77 % , respectively , 6 months after initiation of therapy compared with the preceding 6 months . The safety profile  of ADA was consistent with that observed in previous clinical trials . Conclusions ADA therapy in usual clinical practice is effective at improving and maintaining symptomatic control , improving HRQL , and decreasing costs of medical care among patients with UC Background and Aims : This study assessed the efficacy of maintenance treatment with multimatrix mesalazine following achievement of complete or partial remission after induction treatment with high-dose multimatrix mesalazine . Methods : In this phase 3b/4 , open-label , multicentre , prospect i ve , single-arm study , patients with mild-to-moderate ulcerative colitis were treated with multimatrix mesalazine 4.8g/day once daily for 8 weeks [ induction phase ] . At Week 8 , those who achieved complete or partial remission , based on predefined clinical and endoscopic criteria , were eligible to receive 12 months of multimatrix mesalazine 2.4g/day once daily maintenance therapy . The primary endpoint was the proportion of patients in complete remission at Month 12 . Results : A total of 717 patients received induction treatment ; 25.9 % and 39.3 % of patients achieved complete and partial remission , respectively , at Week 8 . A total of 461 patients entered the maintenance phase . The likelihood of remaining in/achieving complete remission at Month 12 was higher for patients who entered the maintenance phase in complete remission compared with those who began maintenance in partial remission [ 47.8 % vs 26.0 % ; p < 0.001 ] . At Month 12 , mucosal healing [ endoscopy score ≤ 1 ] was demonstrated in 76.4 % [ 139/182 ] and 63.5 % [ 176/277 ] of those who were in complete and partial remission , respectively , at the end of induction . Conclusion : Patients achieving complete remission before dose reduction were more likely to remain in remission at Month 12 BACKGROUND Crohn 's disease ( CD ) is a chronic inflammatory bowel disease usually diagnosed in early adult life and characterized by unpredictable flares and debilitating symptoms such as diarrhea , abdominal pain , and fever , which can interfere with a patient 's ability to work and perform daily activities . OBJECTIVE The aim of this study was to assess the validity , reliability , and responsiveness of the Work Productivity and Activity Impairment question naire in CD ( WPAI : CD ) . METHODS The WPAI : CD was tested in CD patients enrolled in a 26-week r and omized clinical trial of cer-tolizumab pegol versus placebo . Discriminative validity of WPAI : CD absenteeism , presenteeism(reduced on-the-job effectiveness ) , overall work productivity loss ( absenteeism + presenteeism ) , and activity impairment scores was assessed relative to 5 measures of disease severity and health status : CD Activity Index ( CDAI ) , Short Form-36 physical component summary ( PCS ) and mental health component summary ( MCS ) scores , Inflammatory Bowel Disease Question naire ( IBDQ ) , and the 5-dimensional EuroQoL health-related quality -of-life visual analog scale ( EQ-VAS ) . Responsiveness was assessed by comparing changes in WPAI : CD scores from baseline to week 26 for patients in remission ( CDAI < 150 points ) versus no remission . St and ardized Response Means ( SRMs ) were calculated to evaluate the magnitude of the changes . RESULTS A total of 662 patients ( mean [ range ] age , 37.4 [ 18 - 77 ] years ; male , 288 [ 43.5 % ] ; white , 629 [ 95.0 % ] ) were enrolled in the study . Patients with CD of the worst severity ( CDAI > median ) showed significantly higher impairment in work ( + 10.5 % ) and activities ( + 10.4 % ) versus patients with " best health " ( no problems ) ( both , P < or = 0.001 ) . Patients with " worst " IBDQ , PCS , MCS , and EQ-VAS scores also showed significantly higher impairments in work ( IBDQ , VAS -24.2 % ; PCS , -24.1 % ; MCS , -15.9 % ; EQ-VAS , -16.5 % ) and activities ( IBDQ , -23.3 % ; PCS , -21.8 % ; MCS , -16.5 % ; EQ-VAS , -17.2 % ) versus " best " scores ( all , P < 0.05 ) . There were significant differences between WPAI : CD impairment scores for patients in remission versus patients failing to achieve remission ( P < 0.05 ) . SRMs were small ( ie , < 0.5 ) in the nonre-mission group , and moderate to large ( ie , > 0.5 ) for patients in remission . CONCLUSIONS The discriminative validity , reliability , and responsiveness of the WPAI : CD were demonstrated . The WPAI : CD may be useful for evaluating drug impact on CD OBJECTIVE Health-related quality of life ( HRQOL ) affects outcome in chronic diseases such as inflammatory bowel disease ( IBD ) . The inflammatory bowel disease question naire ( IBDQ ) , a disease-specific HRQOL question naire , can define changes in health status in IBD , but simple instruments are needed for daily application . The present study proposed to develop a short version of the IBDQ , the SIBDQ , for community physicians . METHODS Using data from a clinical trial in 149 patients with Crohn 's disease , 10 items were selected ( by forward stepwise regression ) that best explained the variance of the IBDQ or dimensional scores ( bowel , systemic , social , emotional ) . The validity , reliability , and responsiveness of the SIBDQ were then assessed in 150 different patients with Crohn 's disease and 45 with ulcerative colitis . All scores were reported with a 7-point scale ( 1 = poor HRQOL , 7 = optimum HRQOL ) . RESULTS Mean SIBDQ scores were similar ( p = 0.22 ) in Crohn 's patients among 14 participating centers at study entry . Mean scores were lower in active Crohn 's disease ( range 4.00 - 4.92 ) than inactive disease ( range 4.67 - 5.83 ; p = 0.0015 ) . In active ulcerative colitis , the mean SIBDQ was 4.79 + /- 1.17 compared to 5.90 + /- 0.80 ( p = 0.0006 ) in inactive disease . The SIBDQ explained 92 % and 90 % of the IBDQ variance in Crohn 's disease and ulcerative colitis , respectively . In patients with stable Crohn 's disease , the test-retest reliability coefficient was 0.65 and Crohnbach 's alpha was 0.78 , indicating good reliability . In patients with Crohn 's disease who relapsed during follow-up , 
    Output:
    