***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 Folic acid , vitamin B(6 ) , and vitamin B(12 ) act in concert in the one-carbon metabolism and may protect against colorectal neoplasia . We examined the effect of combined B-vitamin treatment on the occurrence of colorectal adenoma . METHODS The Women 's Antioxidant and Folic Acid Cardiovascular Study was a r and omized , double-blind , placebo-controlled trial of 5442 female health professionals at high risk for cardiovascular disease from April 1998 through July 2005 . Participants were r and omly assigned to receive a combination pill of folic acid ( 2.5 mg ) , vitamin B(6 ) ( 50 mg ) , and vitamin B(12 ) ( 1 mg ) or placebo . This study included 1470 participants who were followed up for as long as 9.2 years and underwent an endoscopy at any point during follow-up . We estimated relative risks using a generalized linear model with a natural logarithm link function and Poisson distributed errors . All statistical tests were two-sided . RESULTS The risk of colorectal adenoma was similar among participants receiving treatment ( 24.3 % , 180 of 741 participants ) vs placebo ( 24.0 % , 175 of 729 participants ) ( multivariable adjusted relative risk = 1.00 , 95 % confidence interval = 0.83 to 1.20 ) . Treatment was not associated with the risk of adenoma when data were analyzed by subsite , size , stage , and the number of adenomas . There was no statistically significant effect modification by alcohol intake , history of cancer or adenoma , or baseline plasma levels or intakes of folate , vitamin B(6 ) , or vitamin B(12 ) . CONCLUSION Our results indicate no statistically significant effect of combined folic acid , vitamin B(6 ) , and vitamin B(12 ) treatment on colorectal adenoma among women at high risk for cardiovascular disease CONTEXT Laboratory and epidemiological data suggest that folic acid may have an antineoplastic effect in the large intestine . OBJECTIVE To assess the safety and efficacy of folic acid supplementation for preventing colorectal adenomas . DESIGN , SETTING , AND PARTICIPANTS A double-blind , placebo-controlled , 2-factor , phase 3 , r and omized clinical trial conducted at 9 clinical centers between July 6 , 1994 , and October 1 , 2004 . Participants included 1021 men and women with a recent history of colorectal adenomas and no previous invasive large intestine carcinoma . INTERVENTION Participants were r and omly assigned in a 1:1 ratio to receive 1 mg/d of folic acid ( n = 516 ) or placebo ( n = 505 ) , and were separately r and omized to receive aspirin ( 81 or 325 mg/d ) or placebo . Follow-up consisted of 2 colonoscopic surveillance cycles ( the first interval was at 3 years and the second at 3 or 5 years later ) . MAIN OUTCOME MEASURES The primary outcome measure was occurrence of at least 1 colorectal adenoma . Secondary outcomes were the occurrence of advanced lesions ( > or = 25 % villous features , high- grade dysplasia , size > or = 1 cm , or invasive cancer ) and adenoma multiplicity ( 0 , 1 - 2 , or > or =3 adenomas ) . RESULTS During the first 3 years , 987 participants ( 96.7 % ) underwent colonoscopic follow-up , and the incidence of at least 1 colorectal adenoma was 44.1 % for folic acid ( n = 221 ) and 42.4 % for placebo ( n = 206 ) ( unadjusted risk ratio [ RR ] , 1.04 ; 95 % confidence interval [ CI ] , 0.90 - 1.20 ; P = .58 ) . Incidence of at least 1 advanced lesion was 11.4 % for folic acid ( n = 57 ) and 8.6 % for placebo ( n = 42 ) ( unadjusted RR , 1.32 ; 95 % CI , 0.90 - 1.92 ; P = .15 ) . A total of 607 participants ( 59.5 % ) underwent a second follow-up , and the incidence of at least 1 colorectal adenoma was 41.9 % for folic acid ( n = 127 ) and 37.2 % for placebo ( n = 113 ) ( unadjusted RR , 1.13 ; 95 % CI , 0.93 - 1.37 ; P = .23 ) ; and incidence of at least 1 advanced lesion was 11.6 % for folic acid ( n = 35 ) and 6.9 % for placebo ( n = 21 ) ( unadjusted RR , 1.67 ; 95 % CI , 1.00 - 2.80 ; P = .05 ) . Folic acid was associated with higher risks of having 3 or more adenomas and of noncolorectal cancers . There was no significant effect modification by sex , age , smoking , alcohol use , body mass index , baseline plasma folate , or aspirin allocation . CONCLUSIONS Folic acid at 1 mg/d does not reduce colorectal adenoma risk . Further research is needed to investigate the possibility that folic acid supplementation might increase the risk of colorectal neoplasia . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00272324 BACKGROUND & AIMS Chemopreventive strategies might be used to reduce the recurrence of colorectal adenomas and the incidence of colorectal cancer . We performed a r and omized , double-blind , placebo-controlled trial to determine whether a combination of acetylsalicylic acid ( aspirin ) , calcitriol , and calcium carbonate could prevent colorectal adenoma recurrence . METHODS We included 1107 patients with 1 or more sporadic adenoma(s ) removed from the colon or rectum at centers in Europe , Russia , or the United States , from 2004 through 2010 . Inclusion criteria were 1 adenoma greater than 1 cm in diameter , more than 1 adenoma of any size , or an adenoma of any size and first-degree relatives with colorectal cancer . Subjects were assigned r and omly to groups given 0.5 μg calcitriol , 75 mg acetylsalicylic acid , and 1250 mg calcium carbonate ( n = 209 ) , or placebo ( n = 218 ) , each day for 3 years . The primary outcome was adenoma recurrence assessed by colonoscopy after 3 years . Secondary outcomes were the proportion of patients with advanced adenomas , the total number of colorectal adenomas , and adenoma size and features . RESULTS The trial was stopped in October 2010 because of futility . In this analysis , we found no differences between groups in the rate of recurrence ( odds ratio [ OR ] , 0.95 ; 95 % confidence interval [ CI ] , 0.61 - 1.48 ) , adverse effects , or secondary outcomes . Subgroup analyses indicated that the treatment effects may be influenced by smoking status ( nonsmokers OR , 0.65 ; 95 % CI , 0.26 - 1.22 vs current smokers OR , 1.70 ; 95 % CI , 0.70 - 4.09 ; P value interaction < .05 ) . However , the overall interaction was not significant . CONCLUSIONS In a prospect i ve study , the combination of calcitriol , aspirin , and calcium carbonate did not prevent recurrence of colorectal adenomas over a 3-year period . The negative results might be owing to the effects of smoking or low doses of the tested agents . Clinical trials.gov number : NCT00486512 Abstract Pre clinical studies of chemoprevention drugs given in combination at low doses show remarkable efficacy in preventing adenomas with little additional toxicities , suggesting a strategy to improve risk to benefit ratios for preventing recurrent adenomas . Three hundred seventy-five patients with history of resected ( ≥3 mm ) adenomas were r and omly assigned to receive oral difluoromethylornithine ( DFMO ) 500 mg and sulindac 150 mg once daily or matched placebos for 36 months , stratified by use of low-dose aspirin ( 81 mg ) at baseline and clinical site . Follow-up colonoscopy was done 3 years after r and omization or off- study . Colorectal adenoma recurrence was compared among the groups with log-binomial regression . Comparing the outcome in patients receiving placebos to those receiving active intervention , ( a ) the recurrence of one or more adenomas was 41.1 % and 12.3 % ( risk ratio , 0.30 ; 95 % confidence interval , 0.18 - 0.49 ; P < 0.001 ) ; ( b ) 8.5 % had one or more advanced adenomas , compared with 0.7 % of patients ( risk ratio , 0.085 ; 95 % confidence interval , 0.011 - 0.65 ; P < 0.001 ) ; and ( c ) 17 ( 13.2 % ) patients had multiple adenomas ( > 1 ) at the final colonoscopy , compared with 1 ( 0.7 % ; risk ratio , 0.055 ; 0.0074 - 0.41 ; P < 0.001 ) . Serious adverse events ( grade ≥3 ) occurred in 8.2 % of patients in the placebo group , compared with 11 % in the active intervention group ( P = 0.35 ) . There was no significant difference in the proportion of patients reporting hearing changes from baseline . Recurrent adenomatous polyps can be markedly reduced by a combination of low oral doses of DFMO and sulindac and with few side effects Objective To evaluate the influence of low-dose , enteric-coated aspirin tablets ( 100 mg/day for 2 years ) on colorectal tumour recurrence in Asian patients with single/multiple colorectal tumours excised by endoscopy . Design A double-blinded , r and omised , placebo-controlled multicentre clinical trial was conducted . Participants 311 subjects with single/multiple colorectal adenomas and adenocarcinomas excised by endoscopy were enrolled in the study ( 152 patients in the aspirin group and 159 patients in the placebo group ) . Enrolment began at the hospitals ( n=19 ) in 2007 and was completed in 2009 . Results The subjects treated with aspirin displayed reduced colorectal tumourigenesis and primary endpoints with an adjusted OR of 0.60 ( 95 % CI 0.36 to 0.98 ) compared with the subjects in the placebo group . Subgroup analysis revealed that subjects who were non-smokers , defined as those who had smoked in the past or who had never smoked , had a marked reduction in the number of recurrent tumours in the aspirin-treated group . The adjusted OR for aspirin treatment in non-smokers was 0.37 ( CI 0.21 to 0.68 , p<0.05 ) . Interestingly , the use of aspirin in smokers result ed in an increased risk , with an OR of 3.44 . In addition , no severe adverse effects were observed in either group . Conclusions Low-dose , enteric-coated aspirin tablets reduced colorectal tumour recurrence in an Asian population . The results are consistent with those obtained from other r and omised controlled trials in Western countries . The clinical trial registry website and the clinical trial number http://www.umin.ac.jp ( number UMIN000000697 ) BACKGROUND AND METHODS Laboratory , clinical , and epidemiologic evidence suggests that calcium may help prevent colorectal adenomas . We conducted a r and omized , double-blind trial of the effect of supplementation with calcium carbonate on the recurrence of colorectal adenomas . We r and omly assigned 930 subjects ( mean age , 61 years ; 72 percent men ) with a recent history of colorectal adenomas to receive either calcium carbonate ( 3 g [ 1200 mg of elemental calcium ] daily ) or placebo , with follow-up colonoscopies one and four years after the qualifying examination . The primary end point was the proportion of subjects in whom at least one adenoma was detected after the first follow-up endoscopy but up to ( and including ) the second follow-up examination . Risk ratios for the recurrence of adenomas were adjusted for age , sex , lifetime number of adenomas before the study , clinical center , and length of the surveillance period . RESULTS The subjects in the calcium group had a lower risk of recurrent adenomas . Among the 913 subjects who underwent at least one study colonoscopy , the adjusted risk ratio for any recurrence of adenoma with calcium as compared with placebo was 0.85 ( 95 percent confidence interval , 0.74 to 0.98 ; P=0.03 ) . The main analysis was based on the 832 subjects ( 409 in the calcium group and 423 in the placebo group ) who completed both follow-up examinations . At least one adenoma was diagnosed between the first and second follow-up endoscopies in 127 subjects in the calcium 
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Kappelman MD , Rifas-Shiman SL , Porter CQ , et al. Direct health care costs of Crohn ’s disease and ulcerative colitis in US children and adults .
S and born WJ , Rutgeerts P , Feagan BG , et al. Colectomy rate comparison after treatment of ulcerative colitis with placebo or infliximab .
Lichtenstein GR , Yan S , Bala M , et al. Remission in patients with Crohn ’s disease is associated with improvement in employment and quality of life and a decrease in hospitalizations and surgeries .
Lee JK , Tang DH , Mollon L , et al. Cost-effectiveness of biological agents used in ulcerative colitis .