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: Objective The aim of the study was to compare azathioprine versus mesalazine tablets for the prevention of clinical recurrence in patients with postoperative Crohn 's disease ( CD ) with moderate or severe endoscopic recurrence . Methods This was a 1 year , double-blind , double-dummy , r and omised study which took place in 21 gastroenterology centres in Austria , the Czech Republic , Germany and Israel . The study participants were 78 adults with CD who had undergone resection with ileocolonic anastomosis in the preceding 6–24 months without subsequent clinical recurrence and with a Crohn 's disease activity index ( CDAI ) score < 200 , but with moderate or severe endoscopic recurrence . The study drugs were azathioprine 2.0–2.5 mg/kg/day or mesalazine 4 g/day over 1 year . The primary end point was therapeutic failure during 1 year , defined as a CDAI score ≥200 and an increase of ≥60 points from baseline , or study drug discontinuation due to lack of efficacy or intolerable adverse drug reaction . Results Treatment failure occurred in 22.0 % ( 9/41 ) of azathioprine-treated patients and 10.8 % ( 4/37 ) of mesalazine-treated patients , a difference of 11.1 % ( 95 % CI −5.0 % to 27.3 % , p=0.19 ) . Clinical recurrence was significantly less frequent with azathioprine versus mesalazine ( 0/41 ( 0 % ) vs 4/37 ( 10.8 % ) , p=0.031 ) , whereas study drug discontinuation due to adverse drug reactions only occurred in azathioprine-treated patients ( 9/41 ( 22.0 % ) vs 0 % , p=0.002 ) . The proportion of patients showing ≥1 point reduction in Rutgeerts score between baseline and month 12 was 63.3 % ( 19/30 ) and 34.4 % ( 11/32 ) in the azathioprine and mesalazine groups , respectively ( p=0.023 ) . Conclusions In this population of patients with postoperative CD at high risk of clinical recurrence , superiority for azathioprine versus mesalazine could not be demonstrated for therapeutic failure . Clinical trial registration number NCT00946946 BACKGROUND & AIMS The aim of this study was to evaluate the usefulness of short-term infliximab combined with azathioprine ( AZA ) or 6-mercaptopurine ( 6-MP ) in steroid-dependent Crohn 's disease patients . METHODS Patients with active disease despite prednisone given for more than 6 months were eligible and were stratified as follows : the failure stratum consisted of patients receiving AZA/6-MP at a stable dose for more than 6 months , and the naive stratum consisted of patients not treated previously with AZA/6-MP . Patients were r and omized to infliximab 5 mg/kg or placebo at weeks 0 , 2 , and 6 . All patients were treated with AZA/6-MP maintained at a stable dose throughout the 52 weeks of the study . The primary end point was remission off steroids at week 24 . RESULTS Among the 113 enrolled patients ( 55 in the failure stratum ) , 57 were assigned to infliximab . At week 24 , the success rate ( intent-to-treat analysis ) was higher in the infliximab group than in the placebo group ( 57 % vs 29 % ; P = .003 ) ; at weeks 12 and 52 , the corresponding rates were 75 % vs 38 % ( P < .001 ) and 40 % vs 22 % ( P = .04 ) , respectively . In each stratum , the success rate was significantly higher in the infliximab group at weeks 12 and 24 , and a trend was found at week 52 . In the failure stratum , only 27 % of the patients in the infliximab group were still in remission off steroids , compared with 52 % in the naive stratum . Steroid resistance was less common and the cumulative dose of prednisone was lower in the infliximab group . CONCLUSIONS Infliximab plus AZA/6-MP is more effective than AZA/6-MP alone in steroid-dependent Crohn 's disease patients The effect of azathioprine in patients with active Crohn 's disease has been evaluated in a double-blind cross-over trial . Fifteen patients were treated with both azathioprine and placebo : only two improved while on azathioprine , six got worse , and in seven there was no change . The drug seemed to be the cause of deterioration in two of the patients . Although the drug may be of some value in a few patients , it should be used with caution and only when other measures have failed A system has been constructed to evaluate the design , implementation , and analysis of  r and omized control trials ( RCT ) . The degree of quadruple blinding ( the r and omization process , the physicians and patients as to therapy , and the physicians as to ongoing results ) is considered to be the most important aspect of any trial . The analytic techniques are scored with the same emphasis as is placed on the control of bias in the planning and implementation of the studies . Description of the patient and treatment material s and the measurement of various controls of quality have less weight . An index of quality of a RCT is proposed with its pros and cons . If published papers were to approximate these principles , there would be a marked improvement in the quality of r and omized control trials . Finally , a reasonable st and ard design and conduct of trials will facilitate the interpretation of those with conflicting results and help in making valid combinations of undersized trials Background Although the cost of Crohn ’s disease ( CD ) treatment differs considerably , hospitalization and surgery costs account for most of the total treatment cost . Decreasing hospitalization and surgery rates are pivotal issues in reducing health-care costs . Material / Methods We evaluated the effect of azathioprine ( AZA ) compared with mesalazine on incidence of re-hospitalizations due to all causes and for CD-related surgeries . In this controlled , r and omized study , 72 subjects with sub-occlusive ileocecal CD were r and omized for AZA ( 2–3 mg/kg per day ) or mesalazine ( 3.2 g per day ) therapy during a 3-year period . The primary end point was the re-hospitalization proportion due to all causes , as well as for surgical procedures during this period evaluated between the groups . Results On an intention-to-treat basis , the proportion of patients re-hospitalized within 36 months due to all causes was lower in patients treated with AZA compared to those on mesalazine ( 0.39 vs. 0.83 , respectively ; p=0.035 ) . The AZA group had also significantly lower proportions of re-hospitalization for surgical intervention ( 0.25 vs. 0.56 , respectively ; p=0.011 ) . The number of admissions ( 0.70 vs. 1.41 , p=0.001 ) and the length of re-hospitalization ( 3.8 vs. 7.7 days ; p=0.002 ) were both lower in AZA patients . Conclusions Patients with sub-occlusive ileocecal CD treated with AZA had lower re-hospitalization rates due to all causes and for surgical management of CD compared to those treated with mesalazine during a 3-year period . The long-term use of AZA in ileocecal CD patients recovering from a sub-occlusion episode can save healthcare costs BACKGROUND & AIMS Immunomodulator therapy is effective for patients with Crohn 's disease ( CD ) but has not been shown to affect disease progression , presumably because it is given too late after diagnosis . We compared the efficacy of early treatment ( within 6 months after diagnosis ) with azathioprine versus conventional management of patients at high risk for disabling disease . METHODS We performed an open-label trial of adults with a diagnosis of CD for less than 6 months who were at risk for disabling disease . From July 2005 to November 2010 , patients at 24 French centers were r and omly assigned to treatment with azathioprine ( 2.5 mg ∙ kg(-1 ) ∙ day(-1 ) , n = 65 ) or conventional management ( azathioprine only in cases of corticosteroid dependency , chronic active disease with frequent flares , poor response to corticosteroids , or development of severe perianal disease ) ( n = 67 ) . The primary end point was the proportion of trimesters spent in corticosteroid-free and anti-tumor necrosis factor (TNF)-free remission during the first 3 years after inclusion . RESULTS During the 3-year follow-up period , 16 patients in the azathioprine group were switched to mercaptopurine or methotrexate therapy because of intolerance or poor efficacy . Forty-one patients in the conventional management  group required immunosuppressant therapy  ( 61 % ; median time to first prescription , 11 months ) . In the azathioprine group , a median 67 % of trimesters were spent in remission ( interquartile range , 11%-85 % ) compared with 56 % in the conventional management group ( interquartile range , 29%-73 % ) ( P = .69 ) . Among secondary outcomes , a higher cumulative proportion of patients in the azathioprine group were free of perianal surgery than in the conventional management group ( 96 % ± 3 % and 82 % ± 6 % at month 36 , respectively ; P = .036 ) . The cumulative proportion of patients free of intestinal surgery and anti-TNF therapy did not differ between groups . CONCLUSIONS Based on results from a clinical trial , administration of azathioprine within 6 months of diagnosis of CD was no more effective than conventional management in increasing time of clinical remission . Clinical trials.gov , Number NCT00546546 BACKGROUND & AIMS No therapy has been shown to reliably prevent the evolution of postoperative recurrence of Crohn 's disease . The aim of the current trial was to compare 6-mercaptopurine ( 6-MP ) and mesalamine with placebo for the prevention of clinical , endoscopic , and radiographic recurrence of Crohn 's disease after resection and ileocolic anastomosis . METHODS Five centers r and omized 131 patients to receive 6-MP ( 50 mg ) , mesalamine  ( 3 g ) , or placebo daily in a double-blind , double-dummy trial . Patients had clinical assessment s at 7 weeks and then every 3 months ; colonoscopy at 6 , 12 , and 24 months ; and small bowel series at 12 and 24 months . End points were clinical , endoscopic , and radiographic recurrence rates at 24 months . RESULTS Clinical recurrence rates ( intent to treat ) by life-table analysis at 24 months were 50 % ( 95 % confidence interval [ CI ] , 34%-68 % ) , 58 % ( 95 % CI , 41%-75 % ) , and 77 % ( 95 % CI , 61%-91 % ) in patients receiving 6-MP , mesalamine , and placebo , respectively . Endoscopic recurrence rates were 43 % ( 95 % CI , 28%-63 % ) , 63 % ( 95 % CI , 47%-79 % ) , and 64 % ( 95 % CI , 46%-81 % ) , and radiographic recurrence rates were 33 % ( 95 % CI , 19%-54 % ) , 46 % ( 95 % CI , 29%-66 % ) , and 49 % ( 95 % CI , 30%-72 % ) , respectively . 6-MP was more effective than placebo ( P < 0.05 ) at preventing clinical and endoscopic recurrence over 2 years . Patient withdrawals result ed in 69 % of the study population evaluable for the clinical recurrence end point . CONCLUSIONS 6-MP , 50 mg daily , was more effective than placebo at preventing postoperative recurrence of Crohn 's disease and should be considered as a maintenance therapy after ileocolic resection Introduction : Azathioprine is effective for maintenance of remission in Crohn 's disease , however , duration of efficacy and the dose response relationship has not been fully evaluated BACKGROUND & AIMS More than 80 % of Crohn 's disease ( CD ) patients undergoing resection suffer recurrence of their disease . Therapy with aminosalicylates , antimetabolites , or antibiotics leads to a modest reduction in the incidence of recurrence . GOAL We sought to examine whether metronidazole for 3 months together with azathioprine ( AZA ) for 12 months is superior to metronidazole alone to reduce recurrence of postoperative CD in " high-risk " patients . METHODS CD patients undergoing curative ileocecal resection with > or=1 risk factor for recurrence received metronidazole ( 3 months ) and AZA/placebo ( 12 months ) . The primary end point was the proportion of patients with significant endoscopic recurrence 3 and 12 months after surgery . Secondary end points included clinical recurrence , safety , and tolerability of treatment . RESULTS Eighty-one patients were r and omized ; 19 discontinued the study early .  Significant endoscopic recurrence was observed in 14 of 32 ( 43.7 % ) patients in the AZA group and in 20 of 29 ( 69.0 % ) patients in the placebo group at 12 months postsurgery ( 
    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: Objective The aim of the study was to compare azathioprine versus mesalazine tablets for the prevention of clinical recurrence in patients with postoperative Crohn 's disease ( CD ) with moderate or severe endoscopic recurrence . Methods This was a 1 year , double-blind , double-dummy , r and omised study which took place in 21 gastroenterology centres in Austria , the Czech Republic , Germany and Israel . The study participants were 78 adults with CD who had undergone resection with ileocolonic anastomosis in the preceding 6–24 months without subsequent clinical recurrence and with a Crohn 's disease activity index ( CDAI ) score < 200 , but with moderate or severe endoscopic recurrence . The study drugs were azathioprine 2.0–2.5 mg/kg/day or mesalazine 4 g/day over 1 year . The primary end point was therapeutic failure during 1 year , defined as a CDAI score ≥200 and an increase of ≥60 points from baseline , or study drug discontinuation due to lack of efficacy or intolerable adverse drug reaction . Results Treatment failure occurred in 22.0 % ( 9/41 ) of azathioprine-treated patients and 10.8 % ( 4/37 ) of mesalazine-treated patients , a difference of 11.1 % ( 95 % CI −5.0 % to 27.3 % , p=0.19 ) . Clinical recurrence was significantly less frequent with azathioprine versus mesalazine ( 0/41 ( 0 % ) vs 4/37 ( 10.8 % ) , p=0.031 ) , whereas study drug discontinuation due to adverse drug reactions only occurred in azathioprine-treated patients ( 9/41 ( 22.0 % ) vs 0 % , p=0.002 ) . The proportion of patients showing ≥1 point reduction in Rutgeerts score between baseline and month 12 was 63.3 % ( 19/30 ) and 34.4 % ( 11/32 ) in the azathioprine and mesalazine groups , respectively ( p=0.023 ) . Conclusions In this population of patients with postoperative CD at high risk of clinical recurrence , superiority for azathioprine versus mesalazine could not be demonstrated for therapeutic failure . Clinical trial registration number NCT00946946 BACKGROUND & AIMS The aim of this study was to evaluate the usefulness of short-term infliximab combined with azathioprine ( AZA ) or 6-mercaptopurine ( 6-MP ) in steroid-dependent Crohn 's disease patients . METHODS Patients with active disease despite prednisone given for more than 6 months were eligible and were stratified as follows : the failure stratum consisted of patients receiving AZA/6-MP at a stable dose for more than 6 months , and the naive stratum consisted of patients not treated previously with AZA/6-MP . Patients were r and omized to infliximab 5 mg/kg or placebo at weeks 0 , 2 , and 6 . All patients were treated with AZA/6-MP maintained at a stable dose throughout the 52 weeks of the study . The primary end point was remission off steroids at week 24 . RESULTS Among the 113 enrolled patients ( 55 in the failure stratum ) , 57 were assigned to infliximab . At week 24 , the success rate ( intent-to-treat analysis ) was higher in the infliximab group than in the placebo group ( 57 % vs 29 % ; P = .003 ) ; at weeks 12 and 52 , the corresponding rates were 75 % vs 38 % ( P < .001 ) and 40 % vs 22 % ( P = .04 ) , respectively . In each stratum , the success rate was significantly higher in the infliximab group at weeks 12 and 24 , and a trend was found at week 52 . In the failure stratum , only 27 % of the patients in the infliximab group were still in remission off steroids , compared with 52 % in the naive stratum . Steroid resistance was less common and the cumulative dose of prednisone was lower in the infliximab group . CONCLUSIONS Infliximab plus AZA/6-MP is more effective than AZA/6-MP alone in steroid-dependent Crohn 's disease patients The effect of azathioprine in patients with active Crohn 's disease has been evaluated in a double-blind cross-over trial . Fifteen patients were treated with both azathioprine and placebo : only two improved while on azathioprine , six got worse , and in seven there was no change . The drug seemed to be the cause of deterioration in two of the patients . Although the drug may be of some value in a few patients , it should be used with caution and only when other measures have failed A system has been constructed to evaluate the design , implementation , and analysis of  r and omized control trials ( RCT ) . The degree of quadruple blinding ( the r and omization process , the physicians and patients as to therapy , and the physicians as to ongoing results ) is considered to be the most important aspect of any trial . The analytic techniques are scored with the same emphasis as is placed on the control of bias in the planning and implementation of the studies . Description of the patient and treatment material s and the measurement of various controls of quality have less weight . An index of quality of a RCT is proposed with its pros and cons . If published papers were to approximate these principles , there would be a marked improvement in the quality of r and omized control trials . Finally , a reasonable st and ard design and conduct of trials will facilitate the interpretation of those with conflicting results and help in making valid combinations of undersized trials Background Although the cost of Crohn ’s disease ( CD ) treatment differs considerably , hospitalization and surgery costs account for most of the total treatment cost . Decreasing hospitalization and surgery rates are pivotal issues in reducing health-care costs . Material / Methods We evaluated the effect of azathioprine ( AZA ) compared with mesalazine on incidence of re-hospitalizations due to all causes and for CD-related surgeries . In this controlled , r and omized study , 72 subjects with sub-occlusive ileocecal CD were r and omized for AZA ( 2–3 mg/kg per day ) or mesalazine ( 3.2 g per day ) therapy during a 3-year period . The primary end point was the re-hospitalization proportion due to all causes , as well as for surgical procedures during this period evaluated between the groups . Results On an intention-to-treat basis , the proportion of patients re-hospitalized within 36 months due to all causes was lower in patients treated with AZA compared to those on mesalazine ( 0.39 vs. 0.83 , respectively ; p=0.035 ) . The AZA group had also significantly lower proportions of re-hospitalization for surgical intervention ( 0.25 vs. 0.56 , respectively ; p=0.011 ) . The number of admissions ( 0.70 vs. 1.41 , p=0.001 ) and the length of re-hospitalization ( 3.8 vs. 7.7 days ; p=0.002 ) were both lower in AZA patients . Conclusions Patients with sub-occlusive ileocecal CD treated with AZA had lower re-hospitalization rates due to all causes and for surgical management of CD compared to those treated with mesalazine during a 3-year period . The long-term use of AZA in ileocecal CD patients recovering from a sub-occlusion episode can save healthcare costs BACKGROUND & AIMS Immunomodulator therapy is effective for patients with Crohn 's disease ( CD ) but has not been shown to affect disease progression , presumably because it is given too late after diagnosis . We compared the efficacy of early treatment ( within 6 months after diagnosis ) with azathioprine versus conventional management of patients at high risk for disabling disease . METHODS We performed an open-label trial of adults with a diagnosis of CD for less than 6 months who were at risk for disabling disease . From July 2005 to November 2010 , patients at 24 French centers were r and omly assigned to treatment with azathioprine ( 2.5 mg ∙ kg(-1 ) ∙ day(-1 ) , n = 65 ) or conventional management ( azathioprine only in cases of corticosteroid dependency , chronic active disease with frequent flares , poor response to corticosteroids , or development of severe perianal disease ) ( n = 67 ) . The primary end point was the proportion of trimesters spent in corticosteroid-free and anti-tumor necrosis factor (TNF)-free remission during the first 3 years after inclusion . RESULTS During the 3-year follow-up period , 16 patients in the azathioprine group were switched to mercaptopurine or methotrexate therapy because of intolerance or poor efficacy . Forty-one patients in the conventional management  group required immunosuppressant therapy  ( 61 % ; median time to first prescription , 11 months ) . In the azathioprine group , a median 67 % of trimesters were spent in remission ( interquartile range , 11%-85 % ) compared with 56 % in the conventional management group ( interquartile range , 29%-73 % ) ( P = .69 ) . Among secondary outcomes , a higher cumulative proportion of patients in the azathioprine group were free of perianal surgery than in the conventional management group ( 96 % ± 3 % and 82 % ± 6 % at month 36 , respectively ; P = .036 ) . The cumulative proportion of patients free of intestinal surgery and anti-TNF therapy did not differ between groups . CONCLUSIONS Based on results from a clinical trial , administration of azathioprine within 6 months of diagnosis of CD was no more effective than conventional management in increasing time of clinical remission . Clinical trials.gov , Number NCT00546546 BACKGROUND & AIMS No therapy has been shown to reliably prevent the evolution of postoperative recurrence of Crohn 's disease . The aim of the current trial was to compare 6-mercaptopurine ( 6-MP ) and mesalamine with placebo for the prevention of clinical , endoscopic , and radiographic recurrence of Crohn 's disease after resection and ileocolic anastomosis . METHODS Five centers r and omized 131 patients to receive 6-MP ( 50 mg ) , mesalamine  ( 3 g ) , or placebo daily in a double-blind , double-dummy trial . Patients had clinical assessment s at 7 weeks and then every 3 months ; colonoscopy at 6 , 12 , and 24 months ; and small bowel series at 12 and 24 months . End points were clinical , endoscopic , and radiographic recurrence rates at 24 months . RESULTS Clinical recurrence rates ( intent to treat ) by life-table analysis at 24 months were 50 % ( 95 % confidence interval [ CI ] , 34%-68 % ) , 58 % ( 95 % CI , 41%-75 % ) , and 77 % ( 95 % CI , 61%-91 % ) in patients receiving 6-MP , mesalamine , and placebo , respectively . Endoscopic recurrence rates were 43 % ( 95 % CI , 28%-63 % ) , 63 % ( 95 % CI , 47%-79 % ) , and 64 % ( 95 % CI , 46%-81 % ) , and radiographic recurrence rates were 33 % ( 95 % CI , 19%-54 % ) , 46 % ( 95 % CI , 29%-66 % ) , and 49 % ( 95 % CI , 30%-72 % ) , respectively . 6-MP was more effective than placebo ( P < 0.05 ) at preventing clinical and endoscopic recurrence over 2 years . Patient withdrawals result ed in 69 % of the study population evaluable for the clinical recurrence end point . CONCLUSIONS 6-MP , 50 mg daily , was more effective than placebo at preventing postoperative recurrence of Crohn 's disease and should be considered as a maintenance therapy after ileocolic resection Introduction : Azathioprine is effective for maintenance of remission in Crohn 's disease , however , duration of efficacy and the dose response relationship has not been fully evaluated BACKGROUND & AIMS More than 80 % of Crohn 's disease ( CD ) patients undergoing resection suffer recurrence of their disease . Therapy with aminosalicylates , antimetabolites , or antibiotics leads to a modest reduction in the incidence of recurrence . GOAL We sought to examine whether metronidazole for 3 months together with azathioprine ( AZA ) for 12 months is superior to metronidazole alone to reduce recurrence of postoperative CD in " high-risk " patients . METHODS CD patients undergoing curative ileocecal resection with > or=1 risk factor for recurrence received metronidazole ( 3 months ) and AZA/placebo ( 12 months ) . The primary end point was the proportion of patients with significant endoscopic recurrence 3 and 12 months after surgery . Secondary end points included clinical recurrence , safety , and tolerability of treatment . RESULTS Eighty-one patients were r and omized ; 19 discontinued the study early .  Significant endoscopic recurrence was observed in 14 of 32 ( 43.7 % ) patients in the AZA group and in 20 of 29 ( 69.0 % ) patients in the placebo group at 12 months postsurgery ( 
    Output:
    