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: BACKGROUND & AIMS Thiazolidinedione lig and s for the gamma subtype of peroxisome proliferator-activated receptors ( PPARgamma ) , widely used to treat type 2 diabetes mellitus , have been proposed as novel therapies for ulcerative colitis ( UC ) . METHODS This multicenter , r and omized , double-blind , placebo-controlled clinical trial compared the efficacy of rosiglitazone ( Av and ia ; GlaxoSmithKline , Philadelphia , PA ) 4 mg orally twice daily vs placebo twice daily for 12 weeks in 105 patients with mild to moderately active UC .  Disease activity was measured with the Mayo score . The primary end point was clinical response ( > /=2-point reduction ) at week 12 . Clinical remission ( Mayo score < /=2 ) , endoscopic remission , and quality of life were secondary outcomes . RESULTS After 12 weeks of therapy , 23 patients ( 44 % ) treated with rosiglitazone and 12 patients ( 23 % ) treated with placebo achieved clinical response ( P = .04 ) . Remission was achieved in 9 patients ( 17 % ) treated with rosiglitazone and 1 patient ( 2 % ) treated with placebo ( P = .01 ) . Endoscopic remission was uncommon in either treatment arm ( 8 % rosiglitazone vs 2 % placebo ; P = .34 ) . Clinical improvement was evident as early as 4 weeks after beginning treatment ( P = .049 ) . Quality of life was improved significantly at week 8 ( P = .01 ) , but not at week 4 ( P = .48 ) or week 12 ( P = .14 ) . Serious adverse events were rare . CONCLUSIONS Rosiglitazone was efficacious in the treatment of mild to moderately active UC OBJECTIVES : The impact of infliximab induction and maintenance therapy on health-related quality of life ( HRQL ) was evaluated in patients with ulcerative colitis ( UC ) . METHODS : In two placebo-controlled , double-blind studies ( the Active Ulcerative Colitis Trials 1 and 2 [ ACT 1 and 2 ] ) , 728 patients were r and omized to placebo or infliximab 5 mg/kg or 10 mg/kg . Infusions were administered at weeks 0 , 2 , 6 , and every 8 wk thereafter , up to week 22 ( ACT 2 ) or 46 ( ACT 1 ) . Changes in Inflammatory Bowel Disease Question naire ( IBDQ ) and Medical Outcomes Study 36-Item Short Form Health Survey physical and mental component summary ( PCS and MCS , respectively ) scores were analyzed . RESULTS : Baseline scores for the pooled patient population indicated substantial impairment in HRQL . Improvement at week 8 in the total IBDQ score was significantly greater in the infliximab 5-mg/kg ( 40 , P < 0.001 ) and 10-mg/kg ( 36 , P < 0.001 ) groups compared with the placebo group ( 28 ) . Improvement at week 8 was also significantly greater in the infliximab 5- and 10-mg/kg groups for the PCS ( 6.8 and 5.9 , respectively ) and MCS ( 5.9 and 6.4 , respectively ) compared with placebo ( PCS = 3.7 , MCS = 3.0 , P < 0.01 for all comparisons ) . Continued benefit was seen at weeks 30 and 54 with infliximab maintenance therapy ( P < 0.001 for all comparisons ) . Improvement in total IBDQ score correlated significantly ( P < 0.001 ) with improvement in both PCS and MCS scores , and Mayo score . CONCLUSIONS : Infliximab therapy substantially improved HRQL  in patients with UC . This benefit was sustained through 1 yr with maintenance infliximab therapy Background Placebo medications , by definition , are composed of inactive ingredients that have no physiological effect on symptoms . Nonetheless , administration of placebo in r and omized controlled trials ( RCTs ) and in clinical setting s has been demonstrated to have significant impact on many physical and psychological complaints . Until recently , conventional wisdom has suggested that patients must believe that placebo pills actually contain ( or , at least , might possibly contain ) active medication in order to elicit a response to placebo . However , several recent RCTs , including patients with irritable bowel syndrome ( IBS ) , chronic low back pain , and episodic migraine , have demonstrated that individuals receiving open-label placebo ( OLP )  can still experience symptomatic improvement and benefit from honestly described placebo treatment . Methods and design This paper describes an innovative multidisciplinary trial design ( n = 280 ) that attempts to replicate and exp and upon an earlier IBS OLP study . The current study will compare OLP to double-blind placebo ( DBP ) administration which is made possible by including a nested , double-blind RCT comparing DBP and peppermint oil . The study also examines possible genetic and psychological predictors of OLP and seeks to better underst and participants ’ experiences with OLP and DBP through a series of extensive interviews with a r and omly selected subgroup . Discussion OLP treatment is a novel strategy for ethically harnessing placebo effects . It has potential to re-frame theories of placebo and to influence how physicians can optimize watch- and -wait strategies for common , subjective symptoms . The current study aims to dramatically exp and what we know about OLP by comparing , for the first time , OLP and DBP administration . Adopting a unique , multidisciplinary approach , the study also explores genetic , psychological and experiential dimensions of OLP . The paper ends with an extensive discussion of the “ culture ” of the trial as well as potential mechanisms of OLP and ethical implication s . Trial registration Clinical Trials.gov , identifier : NCT02802241 . Registered on 14 June 2016 UNLABELLED RATIONALE , AIMS & OBJECTIVE : Tools for the assessment of the quality of research studies tend to be specific to a particular research design ( e.g. r and omized controlled trials , or qualitative interviews ) . This makes it difficult to assess the quality of a body of research that addresses the same or a similar research question but using different approaches . The aim of this paper is to describe the development and preliminary evaluation of a  quality assessment tool that can be applied to a method ologically diverse set of research articles . METHODS The  16-item quality assessment tool ( QATSDD )  was assessed to determine its reliability and validity when used by health services research ers in the disciplines of psychology , sociology and nursing . Qualitative feedback was also gathered from mixed- methods health research ers regarding the comprehension , content , perceived value and usability of the tool . RESULTS Reference to existing widely used quality assessment tools and experts in systematic review confirmed that the components of the tool represented the construct of ' good research technique ' being assessed . Face validity was subsequently established through feedback from a sample of nine health research ers .  Inter-rater reliability was established through substantial agreement between three review ers when applying the tool to a set of three research papers ( κ = 71.5 % ) , and good to substantial agreement between their scores at time 1 and after a 6-week interval at time 2 confirmed test-retest reliability . CONCLUSIONS The QATSDD shows good reliability and validity for use in the quality assessment of a diversity of studies , and may be an extremely useful tool for review ers to st and ardize and increase the rigour of their assessment s in review s of the published papers which include qualitative and quantitative work Although the r and omized controlled trial has become the st and ard for regulatory approval of new drugs and devices in inflammatory bowel disease ( IBD ) , the components of effective trial design and implementation are still evolving . While induction and maintenance of remission are the ultimate goals in the treatment of IBD , the conduct of trials intended to measure these outcomes has varied substantially over time , as have the definitions of disease remission . Significant progress has been made in recent years towards underst and ing patient- and disease-related factors that are essential considerations in clinical trial design . However , questions remain regarding the best methods for assessing disease activity , and importantly for establishing trial end points that are clinical ly relevant and likely to affect meaningful long-term improvements in disease outcomes . This chapter will discuss the current ' best methods ' in IBD trial design and introduce potential future concepts for improving the efficiency of clinical trials as well as their utility to inform clinical practice management OBJECTIVES : We evaluated the effects of treatment on health-related quality of life ( HRQoL ) during a r and omized controlled trial of natalizumab maintenance therapy ( ENACT-2 ) using both disease-specific and generic measures . METHODS : Crohn 's disease patients who received natalizumab as induction therapy in ENACT-1 ( N = 724 ) and responded ( N = 339 ) were re-r and omized to ENACT-2 in which they received natalizumab 300 mg ( N = 168 ) or placebo ( N = 171 ) every 4 wk for 48 additional wk . Outcome measures were the change from baseline on the inflammatory bowel disease question naire ( IBDQ ) , the short form-36 ( SF-36 ) , the EuroQol-5D ( EQ-5D ) , and a subject global assessment . RESULTS : At entry into ENACT-1 , scores indicated substantially impaired HRQoL for both the disease-specific and general measures . Natalizumab responders showed clinical ly meaningful improvement in HRQoL over the course of the ENACT-1 study . During maintenance therapy , IBDQ and SF-36 scale scores of patients who responded to natalizumab induction and were re-r and omized to receive the drug in ENACT-2 ( N = 168 ) remained stable , while those re-r and omized to placebo ( N = 171 ) worsened . At week 60 , 48 wk after the initiation of maintenance therapy , the mean change from ENACT-1 baseline of all scales of the IBDQ and the SF-36 was significantly higher for those who continued to receive natalizumab ( P < 0.001 for all scales ) . The scores of patients who received maintenance natalizumab treatment were not statistically different from those of a cross-section of the U.S. population for 6 of 8 scales of the SF-36 . CONCLUSIONS : The substantial improvement in HRQoL experienced by patients who responded to natalizumab induction therapy was maintained during an additional 48 wk of maintenance therapy Background Tofacitinib , a novel , oral Janus kinase inhibitor , demonstrated a dose-dependent efficacy for induction of clinical response and remission in patients with active ulcerative colitis ( UC ) . The objective of the current study was to determine the effect of tofacitinib on patient-reported outcomes ( PROs ) . Methods Eligible patients ( ≥18 years of age ) with a diagnosis of active UC ( total Mayo score of 6 - 12 points and moderately-to-severely active disease on sigmoidoscopy ) were r and omized in a 2:2:2:3:3 ratio to receive oral tofacitinib 0.5 mg , 3 mg , 10 mg , or 15 mg , or placebo twice daily ( BID ) for 8 weeks . PROs were assessed by the Inflammatory Bowel Disease Question naire ( IBDQ ) and the Inflammatory Bowel Disease Patient-Reported Treatment Impact ( IBD PRTI ) survey . Results At Week 8 , mean IBDQ total scores had improved relative to baseline across all five treatment groups ( baseline range 123.2 - 134.5 ; Week 8 range 149.6 - 175.4 ) . Improvement from baseline was significantly greater ( P = 0.001 ) for tofacitinib 15 mg BID versus placebo . For tofacitinib 15 mg BID , most patients reported satisfaction or extreme satisfaction , definite preference for tofacitinib , and definite willingness to use tofacitinib again on the IBD PRTI at week 8 . Patients achieving endoscopic remission ( Mayo endoscopy score of 0 ) had significantly higher IBDQ scores and favorable PRTI scores than those not achieving endoscopic remission . Conclusions Short-term treatment with tofacitinib BID was associated with dose-dependent improvement in health-related quality of life and patient preferences for tofacitinib . The results complement previously reported efficacy and safety data for the Phase II study . ( NCT 00787202 , November 6 , 2008 ) Background : The inflammatory bowel disease ( IBD ) disability index has recently been introduced to measure patients ' physical , psychological , familial , and social limitations associated with IBD . We assessed factors related to self-reported disability and the relationship between disability and direct health care costs . Methods : A large cohort of patients with Crohn 's disease ( CD ) and ulcerative colitis ( UC ) was prospect ively followed for 2 years by 3 monthly web-based question naires . At 2 years , patients completed the IBD disability index , with lower score indicating more disability . Linear regression analysis was used to examine the impact of demographics , clinical characteristics , and illness perceptions on self-reported disability . Trends in direct health care costs across the disability severity groups minimal , mild , moderate , and severe , were tested . Results : A total of 554 patients with CD and 424 patients with UC completed the IBD disability index ( response rate , 45 % ) . Both clinical characteristics and illness perceptions significantly contributed to self-reported disability ( 45%–47 % , P = 0.000 and 8%–12 % , P = 0.000 , 
    Output:
    
agent
***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 & AIMS Thiazolidinedione lig and s for the gamma subtype of peroxisome proliferator-activated receptors ( PPARgamma ) , widely used to treat type 2 diabetes mellitus , have been proposed as novel therapies for ulcerative colitis ( UC ) . METHODS This multicenter , r and omized , double-blind , placebo-controlled clinical trial compared the efficacy of rosiglitazone ( Av and ia ; GlaxoSmithKline , Philadelphia , PA ) 4 mg orally twice daily vs placebo twice daily for 12 weeks in 105 patients with mild to moderately active UC .  Disease activity was measured with the Mayo score . The primary end point was clinical response ( > /=2-point reduction ) at week 12 . Clinical remission ( Mayo score < /=2 ) , endoscopic remission , and quality of life were secondary outcomes . RESULTS After 12 weeks of therapy , 23 patients ( 44 % ) treated with rosiglitazone and 12 patients ( 23 % ) treated with placebo achieved clinical response ( P = .04 ) . Remission was achieved in 9 patients ( 17 % ) treated with rosiglitazone and 1 patient ( 2 % ) treated with placebo ( P = .01 ) . Endoscopic remission was uncommon in either treatment arm ( 8 % rosiglitazone vs 2 % placebo ; P = .34 ) . Clinical improvement was evident as early as 4 weeks after beginning treatment ( P = .049 ) . Quality of life was improved significantly at week 8 ( P = .01 ) , but not at week 4 ( P = .48 ) or week 12 ( P = .14 ) . Serious adverse events were rare . CONCLUSIONS Rosiglitazone was efficacious in the treatment of mild to moderately active UC OBJECTIVES : The impact of infliximab induction and maintenance therapy on health-related quality of life ( HRQL ) was evaluated in patients with ulcerative colitis ( UC ) . METHODS : In two placebo-controlled , double-blind studies ( the Active Ulcerative Colitis Trials 1 and 2 [ ACT 1 and 2 ] ) , 728 patients were r and omized to placebo or infliximab 5 mg/kg or 10 mg/kg . Infusions were administered at weeks 0 , 2 , 6 , and every 8 wk thereafter , up to week 22 ( ACT 2 ) or 46 ( ACT 1 ) . Changes in Inflammatory Bowel Disease Question naire ( IBDQ ) and Medical Outcomes Study 36-Item Short Form Health Survey physical and mental component summary ( PCS and MCS , respectively ) scores were analyzed . RESULTS : Baseline scores for the pooled patient population indicated substantial impairment in HRQL . Improvement at week 8 in the total IBDQ score was significantly greater in the infliximab 5-mg/kg ( 40 , P < 0.001 ) and 10-mg/kg ( 36 , P < 0.001 ) groups compared with the placebo group ( 28 ) . Improvement at week 8 was also significantly greater in the infliximab 5- and 10-mg/kg groups for the PCS ( 6.8 and 5.9 , respectively ) and MCS ( 5.9 and 6.4 , respectively ) compared with placebo ( PCS = 3.7 , MCS = 3.0 , P < 0.01 for all comparisons ) . Continued benefit was seen at weeks 30 and 54 with infliximab maintenance therapy ( P < 0.001 for all comparisons ) . Improvement in total IBDQ score correlated significantly ( P < 0.001 ) with improvement in both PCS and MCS scores , and Mayo score . CONCLUSIONS : Infliximab therapy substantially improved HRQL  in patients with UC . This benefit was sustained through 1 yr with maintenance infliximab therapy Background Placebo medications , by definition , are composed of inactive ingredients that have no physiological effect on symptoms . Nonetheless , administration of placebo in r and omized controlled trials ( RCTs ) and in clinical setting s has been demonstrated to have significant impact on many physical and psychological complaints . Until recently , conventional wisdom has suggested that patients must believe that placebo pills actually contain ( or , at least , might possibly contain ) active medication in order to elicit a response to placebo . However , several recent RCTs , including patients with irritable bowel syndrome ( IBS ) , chronic low back pain , and episodic migraine , have demonstrated that individuals receiving open-label placebo ( OLP )  can still experience symptomatic improvement and benefit from honestly described placebo treatment . Methods and design This paper describes an innovative multidisciplinary trial design ( n = 280 ) that attempts to replicate and exp and upon an earlier IBS OLP study . The current study will compare OLP to double-blind placebo ( DBP ) administration which is made possible by including a nested , double-blind RCT comparing DBP and peppermint oil . The study also examines possible genetic and psychological predictors of OLP and seeks to better underst and participants ’ experiences with OLP and DBP through a series of extensive interviews with a r and omly selected subgroup . Discussion OLP treatment is a novel strategy for ethically harnessing placebo effects . It has potential to re-frame theories of placebo and to influence how physicians can optimize watch- and -wait strategies for common , subjective symptoms . The current study aims to dramatically exp and what we know about OLP by comparing , for the first time , OLP and DBP administration . Adopting a unique , multidisciplinary approach , the study also explores genetic , psychological and experiential dimensions of OLP . The paper ends with an extensive discussion of the “ culture ” of the trial as well as potential mechanisms of OLP and ethical implication s . Trial registration Clinical Trials.gov , identifier : NCT02802241 . Registered on 14 June 2016 UNLABELLED RATIONALE , AIMS & OBJECTIVE : Tools for the assessment of the quality of research studies tend to be specific to a particular research design ( e.g. r and omized controlled trials , or qualitative interviews ) . This makes it difficult to assess the quality of a body of research that addresses the same or a similar research question but using different approaches . The aim of this paper is to describe the development and preliminary evaluation of a  quality assessment tool that can be applied to a method ologically diverse set of research articles . METHODS The  16-item quality assessment tool ( QATSDD )  was assessed to determine its reliability and validity when used by health services research ers in the disciplines of psychology , sociology and nursing . Qualitative feedback was also gathered from mixed- methods health research ers regarding the comprehension , content , perceived value and usability of the tool . RESULTS Reference to existing widely used quality assessment tools and experts in systematic review confirmed that the components of the tool represented the construct of ' good research technique ' being assessed . Face validity was subsequently established through feedback from a sample of nine health research ers .  Inter-rater reliability was established through substantial agreement between three review ers when applying the tool to a set of three research papers ( κ = 71.5 % ) , and good to substantial agreement between their scores at time 1 and after a 6-week interval at time 2 confirmed test-retest reliability . CONCLUSIONS The QATSDD shows good reliability and validity for use in the quality assessment of a diversity of studies , and may be an extremely useful tool for review ers to st and ardize and increase the rigour of their assessment s in review s of the published papers which include qualitative and quantitative work Although the r and omized controlled trial has become the st and ard for regulatory approval of new drugs and devices in inflammatory bowel disease ( IBD ) , the components of effective trial design and implementation are still evolving . While induction and maintenance of remission are the ultimate goals in the treatment of IBD , the conduct of trials intended to measure these outcomes has varied substantially over time , as have the definitions of disease remission . Significant progress has been made in recent years towards underst and ing patient- and disease-related factors that are essential considerations in clinical trial design . However , questions remain regarding the best methods for assessing disease activity , and importantly for establishing trial end points that are clinical ly relevant and likely to affect meaningful long-term improvements in disease outcomes . This chapter will discuss the current ' best methods ' in IBD trial design and introduce potential future concepts for improving the efficiency of clinical trials as well as their utility to inform clinical practice management OBJECTIVES : We evaluated the effects of treatment on health-related quality of life ( HRQoL ) during a r and omized controlled trial of natalizumab maintenance therapy ( ENACT-2 ) using both disease-specific and generic measures . METHODS : Crohn 's disease patients who received natalizumab as induction therapy in ENACT-1 ( N = 724 ) and responded ( N = 339 ) were re-r and omized to ENACT-2 in which they received natalizumab 300 mg ( N = 168 ) or placebo ( N = 171 ) every 4 wk for 48 additional wk . Outcome measures were the change from baseline on the inflammatory bowel disease question naire ( IBDQ ) , the short form-36 ( SF-36 ) , the EuroQol-5D ( EQ-5D ) , and a subject global assessment . RESULTS : At entry into ENACT-1 , scores indicated substantially impaired HRQoL for both the disease-specific and general measures . Natalizumab responders showed clinical ly meaningful improvement in HRQoL over the course of the ENACT-1 study . During maintenance therapy , IBDQ and SF-36 scale scores of patients who responded to natalizumab induction and were re-r and omized to receive the drug in ENACT-2 ( N = 168 ) remained stable , while those re-r and omized to placebo ( N = 171 ) worsened . At week 60 , 48 wk after the initiation of maintenance therapy , the mean change from ENACT-1 baseline of all scales of the IBDQ and the SF-36 was significantly higher for those who continued to receive natalizumab ( P < 0.001 for all scales ) . The scores of patients who received maintenance natalizumab treatment were not statistically different from those of a cross-section of the U.S. population for 6 of 8 scales of the SF-36 . CONCLUSIONS : The substantial improvement in HRQoL experienced by patients who responded to natalizumab induction therapy was maintained during an additional 48 wk of maintenance therapy Background Tofacitinib , a novel , oral Janus kinase inhibitor , demonstrated a dose-dependent efficacy for induction of clinical response and remission in patients with active ulcerative colitis ( UC ) . The objective of the current study was to determine the effect of tofacitinib on patient-reported outcomes ( PROs ) . Methods Eligible patients ( ≥18 years of age ) with a diagnosis of active UC ( total Mayo score of 6 - 12 points and moderately-to-severely active disease on sigmoidoscopy ) were r and omized in a 2:2:2:3:3 ratio to receive oral tofacitinib 0.5 mg , 3 mg , 10 mg , or 15 mg , or placebo twice daily ( BID ) for 8 weeks . PROs were assessed by the Inflammatory Bowel Disease Question naire ( IBDQ ) and the Inflammatory Bowel Disease Patient-Reported Treatment Impact ( IBD PRTI ) survey . Results At Week 8 , mean IBDQ total scores had improved relative to baseline across all five treatment groups ( baseline range 123.2 - 134.5 ; Week 8 range 149.6 - 175.4 ) . Improvement from baseline was significantly greater ( P = 0.001 ) for tofacitinib 15 mg BID versus placebo . For tofacitinib 15 mg BID , most patients reported satisfaction or extreme satisfaction , definite preference for tofacitinib , and definite willingness to use tofacitinib again on the IBD PRTI at week 8 . Patients achieving endoscopic remission ( Mayo endoscopy score of 0 ) had significantly higher IBDQ scores and favorable PRTI scores than those not achieving endoscopic remission . Conclusions Short-term treatment with tofacitinib BID was associated with dose-dependent improvement in health-related quality of life and patient preferences for tofacitinib . The results complement previously reported efficacy and safety data for the Phase II study . ( NCT 00787202 , November 6 , 2008 ) Background : The inflammatory bowel disease ( IBD ) disability index has recently been introduced to measure patients ' physical , psychological , familial , and social limitations associated with IBD . We assessed factors related to self-reported disability and the relationship between disability and direct health care costs . Methods : A large cohort of patients with Crohn 's disease ( CD ) and ulcerative colitis ( UC ) was prospect ively followed for 2 years by 3 monthly web-based question naires . At 2 years , patients completed the IBD disability index , with lower score indicating more disability . Linear regression analysis was used to examine the impact of demographics , clinical characteristics , and illness perceptions on self-reported disability . Trends in direct health care costs across the disability severity groups minimal , mild , moderate , and severe , were tested . Results : A total of 554 patients with CD and 424 patients with UC completed the IBD disability index ( response rate , 45 % ) . Both clinical characteristics and illness perceptions significantly contributed to self-reported disability ( 45%–47 % , P = 0.000 and 8%–12 % , P = 0.000 , 
    Output:
    