***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 : Despite potent drugs and surgical techniques , the treatment of perianal fistulizing Crohn 's disease ( CD ) remains challenging . We assessed treatment strategies for perianal fistulizing CD and their effect on remission , response , and relapse . Methods : Patients with perianal fistulizing CD visiting the Erasmus MC between January 1 , 1980 and January 1 , 2000 were identified . Demographics , fistula characteristics , and received treatments aim ed at the outcome of these strategies were noted . Results : In total , 232 patients were identified ( 98 male ; 42.2 % ) . Median follow-up was 10.0 years ( range , 0.5–37.5 yr ) . Complex fistulas were present in 78.0 % . Medical treatment ( antibiotics , steroids , immunosuppressants , and anti-tumor necrosis factor ) commenced in 79.7 % of the patients and in 53.2 % , surgery ( colectomy , fistulectomy , stoma , and rectum amputation ) was performed . Simple fistulas healed more often than complex fistulas ( 88.2 % versus 64.6 % ; P < 0.001 ) . Rectum involvement was not associated with a lower remission rate , and anti-tumor necrosis factor therapy did not increase complete fistula healing rates in simple and complex fistula . Initially , healed fistulas recurred in 26.7 % in case of simple fistulas and in 41.9 % in case of complex fistulas ( P = 0.051 ) . Only 37.0 % of the complex fistulas were in remission at the end of follow-up compared with 66.7 % of the simple fistulas ( P < 0.001 ) . Conclusions : Only the minority of CD complex perianal fistulas were in remission after conventional treatment strategies after a median follow-up of 10 years . Simple fistulas were more likely to heal than complex fistulas , and less of these healed fistulas relapsed . However , more than 3 quarters of the patients had complex perianal fistulas Introduction Crohn ’s disease ( CD ) and ulcerative colitis ( UC ) , the main forms of inflammatory bowel disease ( IBD ) , are chronic , progressive and disabling disorders of the gastrointestinal tract . Although data from r and omised controlled trials ( RCTs ) provide the foundation of evidence that vali date s medical therapy for IBD , considerable heterogeneity exists in the measured outcomes used in these studies . Furthermore , in recent years , there has been a paradigm shift in IBD treatment targets , moving from symptom-based scoring to improvement or normalisation of objective measures of inflammation such as endoscopic appearance , inflammatory biomarkers and histological and radiographic end points . The abundance of new treatment options and evolving end points poses opportunities and challenges for all stakeholders involved in drug development . Accordingly , there exists a need to harmonise measures used in clinical trials through the development of a core outcome set ( COS ) . Methods and analysis The development of an IBD-specific COS includes four steps . First , a systematic literature review is performed to identify outcomes previously used in IBD RCTs . Second , semistructured qualitative interviews are conducted with key stakeholders , including patients , clinicians , research ers , pharmaceutical industry representatives , healthcare payers and regulators to identify additional outcomes of importance . Using the outcomes generated from literature review and stakeholder interviews , an international two-round Delphi survey is conducted to prioritise outcomes for inclusion in the COS . Finally , a consensus meeting is held to ratify the COS and disseminate findings for application in future IBD trials . Ethics and dissemination Given that over 30 novel therapeutic compounds are in development for IBD treatment , the design of robust clinical trials measuring relevant and st and ardised outcomes is crucial . St and ardising outcomes through a COS will reduce heterogeneity in trial reporting , facilitate valid comparisons of new therapies and improve clinical trial quality BACKGROUND & AIMS This study determined the effectiveness of tacrolimus for the treatment of Crohn 's disease fistulas . METHODS The study was a r and omized , double-blind , placebo-controlled , multicenter clinical trial . Forty-eight patients with Crohn 's disease and draining perianal or enterocutaneous fistulas were r and omized to treatment with oral tacrolimus 0.2 mg . kg(-1 ) . day(-1 ) or placebo for 10 weeks . The primary outcome measure was fistula improvement as defined by closure of > /=50 % of particular fistulas that were draining at baseline and maintenance of that closure for at least 4 weeks . A secondary outcome measure was fistula remission as defined by closure of all fistulas and maintenance of that closure for at least 4 weeks . RESULTS Forty-three percent of tacrolimus-treated patients had fistula improvement compared with 8 % of placebo-treated patients ( P = 0.004 ) . Ten percent of tacrolimus-treated patients had fistula remission compared with 8 % of placebo-treated patients ( P = 0.86 ) . Adverse events significantly associated with tacrolimus , including headache , increased serum creatinine level , insomnia , leg cramps , paresthesias , and tremor , were managed with dose reduction . CONCLUSIONS Oral tacrolimus 0.2 mg . kg(-1 ) . day(-1 ) is effective for fistula improvement , but not fistula remission , in patients with perianal Crohn 's disease . Adverse events associated with tacrolimus can be managed by dose reduction . Lower doses of tacrolimus should be evaluated Background : Although metronidazole and ciprofloxacin are used to treat perianal Crohn 's disease ( CD ) , no placebo‐controlled trials have been performed . Methods : We performed a placebo‐controlled pilot trial to evaluate the efficacy and safety of metronidazole and ciprofloxacin in patients with perianal CD . Twenty‐five patients with CD and actively draining perianal fistulas were r and omized to receive ciprofloxacin 500 mg , metronidazole 500 mg , or placebo twice daily for 10 weeks . Remission and response of perianal fistulas were defined as closure of all fistulas and closure of at least 50 % of fistulas that were draining at baseline , respectively . The primary endpoint was remission at 10 weeks . Results : Ten patients were r and omized to ciprofloxacin , 7 to metronidazole , and 8 to placebo . Remission at week 10 occurred in 3 patients ( 30 % ) treated with ciprofloxacin , no patients ( 0 % ) treated with metronidazole , and 1 patient ( 12.5 % ) treated with placebo ( P = 0.41 ) . Response at week 10 occurred in 4 patients ( 40 % ) treated with ciprofloxacin , 1 patient ( 14.3 % ) treated with metronidazole , and 1 patient ( 12.5 % ) treated with placebo ( P = 0.43 ) . Termination of the trial prior to week 10 occurred in 1 patient ( 10 % ) treated with ciprofloxacin , 5 patients ( 71.4 % ) treated with metronidazole , and 1 patient ( 12.5 % ) treated with  placebo  ( P < 0.02 ) . No serious adverse events occurred . Conclusion : Remission and response occurred more frequently in patients treated with ciprofloxacin but the differences were not significant in this pilot study . Ciprofloxacin was well tolerated Objective To assess whether a combination of adalimumab and ciprofloxacin is superior to adalimumab alone in the treatment of perianal fistulising Crohn 's disease ( CD ) . Design R and omised , double-blind , placebo controlled trial in eight Dutch hospitals . In total , 76 CD patients with active perianal fistulising disease were enrolled . After adalimumab induction therapy ( 160/80 mg week 0 , 2 ) , patients received 40 mg every other week together with ciprofloxacin 500 mg or placebo twice daily for 12 weeks . After 12 weeks , adalimumab was continued . Follow-up was 24 weeks . Primary endpoint ( clinical response ) was defined as 50 % reduction of fistulas from baseline to week 12 . Secondary endpoints included remission ( closure of all fistulas ) , Perianal Crohn 's Disease Activity Index , Crohn 's Disease Activity Index ( CDAI ) and Inflammatory Bowel Disease Question naire ( IBDQ ) . Results Clinical response was observed in 71 % of patients treated with adalimumab plus ciprofloxacin and in 47 % treated with adalimumab plus placebo ( p=0.047 ) . Likewise , remission rate at week 12 was significantly higher ( p=0.009 ) in the combination group ( 65 % ) compared with adalimumab plus placebo ( 33 % ) . Combination treatment was associated with a higher mean CDAI change and mean IBDQ change at week 12 ( p=0.005 and p=0.009 , respectively ) . At week 24 , no difference in clinical response between the two treatment groups was observed ( p=0.22 ) . No difference in safety issues was observed . Conclusions Combination therapy of adalimumab and ciprofloxacin is more effective than adalimumab monotherapy to achieve fistula closure in CD . However , after discontinuation of antibiotic therapy , the beneficial effect of initial coadministration is not maintained . Trial registration Clinical Trials.gov Identifier : NCT00736983 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 Ustekinumab , a monoclonal antibody to the p40 subunit of interleukin-12 and interleukin-23 , was evaluated as an intravenous induction therapy in two population s with moderately to severely active Crohn 's disease .  Ustekinumab was also evaluated as subcutaneous maintenance therapy . METHODS We r and omly assigned patients to receive a single intravenous dose of ustekinumab ( either 130 mg or approximately 6 mg per kilogram of body weight ) or placebo in two induction trials . The UNITI-1 trial included 741 patients who met the criteria for primary or secondary nonresponse to tumor necrosis factor ( TNF ) antagonists or had unacceptable side effects . The UNITI-2 trial included 628 patients in whom conventional therapy failed or unacceptable side effects occurred . Patients who completed these induction trials then participated in IM-UNITI , in which the 397 patients who had a response to ustekinumab  were r and omly assigned to receive subcutaneous maintenance injections of 90 mg of ustekinumab ( either every 8 weeks or every 12 weeks ) or placebo . The primary end point for the induction trials was a clinical response at week 6 ( defined as a decrease from baseline in the Crohn 's Disease Activity Index [ CDAI ] score of ≥100 points or a CDAI score < 150 ) . The primary end point for the maintenance trial was remission at week 44 ( CDAI score < 150 ) . RESULTS The rates of response at week 6 among patients receiving intravenous ustekinumab at a dose of either 130 mg or approximately 6 mg per kilogram were significantly higher than the rates among patients receiving placebo ( in UNITI-1 , 34.3 % , 33.7 % , and 21.5 % , respectively , with P≤0.003 for both comparisons with placebo ; in UNITI-2 , 51.7 % , 55.5 % , and 28.7 % , respectively , with P<0.001 for both doses ) . In the groups receiving maintenance doses of ustekinumab every 8 weeks or every 12 weeks , 53.1 % and 48.8 % , respectively , were in remission at week 44 , as compared with 35.9 % of those receiving placebo ( P=0.005 and P=0.04 , respectively ) . Within each trial , adverse-event rates were similar among treatment groups . CONCLUSIONS Among patients with moderately to severely active Crohn 's disease , those receiving intravenous ustekinumab had a significantly higher rate of response than did those receiving placebo . Subcutaneous ustekinumab maintained remission in patients who had a clinical response to induction therapy . ( Funded by Janssen Research and Development ; Clinical Trials.gov numbers , NCT01369329 , NCT01369342 , and NCT01369355 . ) In this study we aim ed to determine the microorganisms found in perianal fistulas in Crohn ’s disease and whether treatment with ciprofloxacin affects these microorganisms . Thirteen patients ( males/females , 7/6 ; median age , 34 years ; range , 18–61 years ) with fistulas were treated with infliximab  , 5 mg/kg intravenously , at weeks 6 , 8 , and 12 and r and omized to double-blind treatment with ciprofloxacin , 500 mg bd ( n = 6 ) , or placebo ( n = 7 ) for 12 weeks . Sample s 
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There was also low‐ quality evidence to support the efficacy of combination therapy with TNF antagonists and antibiotics vs a TNF antagonist alone .
: In a systematic review and meta‐ analysis of 27 controlled trials , we found TNF antagonists to be effective for induction and maintenance of perianal fistula response and remission .
There are few data on the effects on internal fistulae .