***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 Aims Smoking affects the course of inflammatory bowel disease [ IBD ] . We aim ed to study the impact of smoking on IBD-specific costs and health-related quality -of-life [ HrQoL ] among adults with Crohn 's disease [ CD ] and ulcerative colitis [ UC ] . Methods A large cohort of IBD patients was prospect ively followed during 1 year using 3-monthly question naires on smoking status , health re sources , disease activity and HrQoL. Costs were calculated by multiplying used re sources with corresponding unit prices . Healthcare costs , patient costs , productivity losses , disease course items and HrQoL were compared between smokers , never-smokers and ex-smokers , adjusted for potential confounders . Results In total , 3030 patients [ 1558 CD , 1054 UC , 418 IBD-unknown ] were enrolled ; 16 % smoked at baseline . In CD ,  disease course was more severe among smokers . Smoking was associated with > 30 % higher annual societal costs in IBD ( € 7,905 [ 95 % confidence interval € 6,234 - € 9,864 ] vs € 6,017 [ € 5,186 - € 6,946 ] in never-smokers and € 5,710 [ € 4,687 - € 6,878 ] in ex-smokers , p = 0.06 and p = 0.04 , respectively ) . In CD , smoking patients generated the highest societal costs , primarily driven by the use of anti-tumour necrosis factor compounds . In UC , societal costs of smoking patients were comparable to those of non-smokers . Societal costs of IBD patients who quitted smoking > 5 years before inclusion were lower than in patients who quitted within the past 5 years ( € 5,135 [ 95 % CI € 4,122 - € 6,303 ] vs € 9,342 [ € 6,010 - € 12,788 ] , p = 0.01 ) . In both CD and UC , smoking was associated with a lower HrQoL. Conclusions Smoking is associated with higher societal costs and lower HrQoL  in IBD patients . Smoking cessation may result in considerably lower societal costs The clinical course of perianal fistulas and associated abscesses was evaluated prospect ively in 90 patients with Crohn 's disease . Fistula type , rectal disease , faecal diversion , and immunosuppression were examined as prognostic indicators for fistula healing and recurrence . Median follow up was 22 months . The outcome was evaluated with life table analysis . Prognostic factors were analysed by multiple regression . Inactivation was achieved in all patients . The risks of recurrent fistula activity were 48 % at one year and 59 % at two years . Fistulas were healed in 51 % after two years but reopened in 44 % within 18 months of healing . Faecal diversion and absence of rectal disease decreased recurrence rates ( p = 0.019/0.04 ) and increased healing rates ( p = 0.005/0.017 ) . The outcome in patients with trans-sphincteric fistulas  was better than that in those with ischiorectal fistulas but worse than in patients with subcutaneous fistulas ( p = 0.015 for healing ; p = 0.007 for recurrent fistula activity ) . After initial treatment about 20 % of the patients were symptomatic and about 10 % had painful events per six month period . Incontinence was rare and did not increase during the study period . Perianal fistulas and associated abscesses can be controlled safely by simple drainage of pus collection s. Frequent reinfection and re-opening after healing of fistulas are characteristic . Fistula type , rectal disease , and stool contamination influence the clinical course . Only a few patients , however , have continuous symptoms from perianal fistulas Aliment Pharmacol Ther 2010 ; 32 : 1228–1239 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 OBJECTIVES : Given the importance of tobacco smoking ( TS ) as the only environmental factor repeatedly linked to the development of the Crohn ’s disease ( CD ) , it is surprising that very few prospect i ve studies have assessed whether TS is associated with an increased frequency of clinical relapse . Our aim was to evaluate the current impact of TS on disease relapse and the clinical benefit of quitting smoking in the present era of widespread use of anti-TNF drugs and immunosuppressants . METHODS : This was a multicenter prospect i ve cohort study , which included 573 CD patients in clinical remission with various smoking habits . All smokers were advised to quit . Patients not exposed to tobacco before inclusion ( non- and former smokers ) , continuing smokers , and quitters were compared regarding differences in disease outcomes during a follow-up of 4 years . RESULTS : A total of 148 continuing smokers , 190 nonsmokers , 160 former smokers , and 75 quitters were included . In comparison with nonsmokers , continuing smokers relapsed more frequently with an incidence rate ratio of 1.53 ( 95 % confidence interval ( CI ) : 1.10–2.17 ) . Former smokers and quitters had similar relapse incidences compared with nonsmokers . Smoking was an independent predictor for disease relapse in the multivariate analysis ( hazard ratio : 1.58 ( 95 % CI 1.20–2.09 ) . In the time-dependent analysis , continuing smokers had earlier relapse , regardless of anti-TNF or immunosuppressant use . CONCLUSIONS : Continuing smokers have more disease relapses , and patients who quit smoking have a similar relapse incidence compared with nonsmokers OBJECTIVE To evaluate the efficacy and toxicity of infliximab for the treatment of fistulizing Crohn 's disease . METHODS Consecutive patients with fistulizing Crohn 's disease receiving infliximab were prospect ively enrolled . Partial response was defined as a reduction of 50 % or more from base-line in the number of draining fistulae . Complete response was defined as the closure of all fistulae . The influence of different variables on the efficacy of infliximab was evaluated . RESULTS 108 patients were included . The disease was inflammatory plus fistulizing in 18 % and only fistulizing in 82 % . After the third infusion of infliximab the response was partial in 26 % and complete in 57 % . Response ( % ) rates ( partial/complete ) depending on fistula location were : enterocutaneous ( 25/68 % ) , perianal ( 35/60 % ) , rectovaginal ( 36/64 % ) , and enterovesical ( 20/40 % ) . None of the studied variables ( including concomitant immunosuppressive therapy ) correlated with efficacy of infliximab in the multivariate analysis . Incidence of adverse effects ( 21 % ) depending on the dose of infliximab was : first dose ( 5.6 % ) , second ( 7.4 % ) , and third ( 11.1 % ) . CONCLUSIONS Infliximab is an efficacious treatment for fistulizing Crohn 's disease . Partial response was achieved in approximately one third of the patients , and complete response in more than half . No studied variable was predictive of response . Adverse effects were relatively infrequent and mild Background Due to the considerable variety in the clinical presentation of anorectal and rectovaginal fistulas in Crohn ’s disease , data on treatment results for each type of fistula are limited . The aim of this study was to summarize the results after surgical treatment of such fistulas in a large consecutive series of patients . Patients and methods All patients with anorectal or rectovaginal fistula due to Crohn ’s disease requiring surgery in our institution between 1991 and 2001 were extracted from a prospect i ve data base . A st and ardized telephone interview was conducted and patients were followed in our outpatient clinic , the department of internal medicine , or at their gastroenterologist . Type of fistula and interventions were classified and analyzed . Recurrence-free time intervals were estimated for each type of fistula and for the different surgical procedures . The influence of the surgical procedure , the number of operations performed , and the correlation to other localizations of the disease were analyzed in regard to the recurrence rate . Results From 777 patients with Crohn ’s disease undergoing surgery between 1991 and 2001 , 147 had anorectal or rectovaginal fistula ( 292 operations ) . Ninety-eight percent of them also had Crohn ’s disease in the colon or rectum compared to only 21 % of patients without a fistula ( p value < 0.001 ) . Over long-term follow-up , 29 patients ( 20 % ) required proctectomy . Submucosal fistulas needed major surgery in only 14 % of cases compared to 56 % of cases with rectovaginal fistulas . After 5 years , complex fistulas showed a strong trend towards a higher recurrence rate after surgery than simple submucosal fistulas ( 45.6 % vs. 18.8 % , p = 0.079 ) . Whereas recurrences occurred over the whole observation period in the group of patients with complex fistulas , there was no further recurrence in patients with submucosal fistulas 13 months after surgery . In rectovaginal fistulas , additional levatorplasty showed no advantage over st and ard endorectal advancement flap . Conclusions Long-term follow-up demonstrates that recurrence rates after repair of complex fistulas for Crohn ’s disease are high and continuously increase over time . Submucosal fistulas have the best outcome ; after 13 months without recurrence , definite cure can be expected BACKGROUND The purpose of our study was to eluci date features , surgical procedures , and long-term results in patients with anorectal complications of Crohn 's disease . METHODS Physical findings , surgical treatment , and long-term outcome were recorded prospect ively for 224 patients who had anorectal complications of Crohn 's disease between October 1984 and May 1999 . RESULTS Presenting complications included abscess ( n = 36 ) , fistula-in-ano ( n = 51 ) , rectovaginal fistula ( n = 20 ) , anal stenosis ( n = 40 ) , anal incontinence ( n = 11 ) , or a combination of features ( n = 66 ) . Twenty-four patients did not undergo surgical treatment ; the remaining 200 patients underwent 284 procedures . Ultimately , 139 patients ( 62 % ) retained anorectal function ; reasons for proctectomy in the remaining 85 patients included disease ( n = 66 ) , extensive fistular disease ( n = 15 ) , fecal incontinence ( n = 2 ) , and tight anal stenosis ( n = 1 ) . Patients with rectal disease had a significantly higher rate of proctectomy than patients with rectal sparing ( 77.6 % vs. 13.6 % , respectively , P<.0001 ) . In the absence of rectal involvement , patients with multiple complications had a significantly higher rate of proctectomy than patients with single complications ( 23 % vs. 10 % , P<.05 ) . CONCLUSIONS A wide spectrum of surgical techniques is required for the management of the diverse anorectal complications of Crohn 's disease . Complete healing and control of seps 
    Output:
    
Conclusions This systematic review has identified potential prognostic markers , including genetic factors and disease behaviour .