***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 Few treatments have demonstrated efficacy and safety for diarrhea-predominant irritable bowel syndrome ( IBS-D ) . A phase 3 , r and omized , double-blind , placebo-controlled trial was performed to evaluate the safety and efficacy of repeat treatment with the nonsystemic antibiotic rifaximin . METHODS The trial included adults with IBS-D , mean abdominal pain and bloating scores of 3 or more , and loose stool , located at 270 centers in the United States and Europe from February 2012 through June 2014 . Those responding to a 2-week course of open-label rifaximin  550 mg 3 times daily , who then relapsed during an observation phase ( up to 18 weeks ) , were r and omly assigned to groups given repeat treatments of rifaximin 550 mg or placebo 3 times daily for 2 weeks . The primary end point was percentage of responders after first repeat treatment , defined as a decrease in abdominal pain of ≥30 % from baseline and a decrease in frequency of loose stools of ≥50 % from baseline , for 2 or more weeks during a 4-week post-treatment period . RESULTS Of 1074 patients ( 44.1 % ) who responded to open-label rifaximin , 382 ( 35.6 % ) did not relapse and 692 ( 64.4 % ) did ; of these , 636 were r and omly assigned to receive repeat treatment with rifaximin ( n = 328 ) or placebo ( n = 308 ) . The percentage of responders was significantly greater with rifaximin than placebo ( 38.1 % vs 31.5 % ; P = .03 ) . The percentage of responders for abdominal pain ( 50.6 % vs 42.2 % ; P = .018 ) was significantly greater with rifaximin than placebo , but not stool consistency ( 51.8 % vs 50.0 % ; P = .42 ) . Significant improvements were also noted for prevention of recurrence , durable response , and bowel movement urgency . Adverse event rates were low and similar between groups . CONCLUSIONS In a phase 3 study of patients with relapsing symptoms of IBS-D , repeat rifaximin treatment was efficacious and well tolerated . Clinical Trials.gov ID : NCT01543178 BACKGROUND & AIMS Eluxadoline is approved by the Food and Drug Administration for the treatment of adults with irritable bowel syndrome with diarrhea ( IBS‐D ) .  Eluxadoline is a locally acting mixed & mgr;‐opiod and & kgr;‐opioid receptor agonist and & dgr;‐opioid receptor antagonist . The abuse potential of eluxadoline was evaluated as part of the Phase 2 and 3 clinical trials assessing the efficacy , safety , and tolerability of the drug . METHODS One Phase 2 ( IBS‐2001 ) and two Phase 3 ( IBS‐3001 and IBS‐3002 ) r and omized controlled trials enrolled patients meeting Rome III criteria for IBS‐D. Patients received oral twice‐daily double‐blind treatment with eluxadoline or placebo for 12 , 26 , or 52 weeks . The primary end point of these studies was the proportion of patients who had a composite response of decrease in abdominal pain and improvement in stool consistency on the same day for at least 50 % of days . Safety data were pooled , and specific adverse event terms potentially related to abuse were assessed descriptively . Adverse events reported during a 2‐week post‐treatment period ( IBS‐3001 ) and a 4‐week single‐blind washout period ( IBS‐3002 ) were assessed for signs of opioid withdrawal . Potential withdrawal effects were assessed by using the Subjective Opiate Withdrawal Scale . RESULTS Overall , 807 and 1032 patients received 1 or more doses of eluxadoline  ( 75 or 100 mg , respectively ) , and 975 patients received placebo  . The overall incidence of adverse events potentially related to abuse did not differ significantly among the groups given placebo , eluxadoline 75 mg , or eluxadoline 100 mg ( 2.8 % , 2.7 % , and 4.3 % , respectively ) . The most common adverse events potentially related to abuse were anxiety and somnolence , which occurred in less than 2 % of patients in each group . Median overall Subjective Opiate Withdrawal Scale scores did not differ significantly among the groups given placebo , eluxadoline 75 mg , or eluxadoline 100 mg ( 3.0 , 2.0 , and 3.0 , respectively ) . CONCLUSIONS In an analysis of data from Phase 2 and Phase 3 trials of eluxadoline ( 75 or 100 mg ) for patients with IBS‐D , data revealed no signs of abuse potential for eluxadoline . Clinical Trials.gov numbers : NCT01130272 , NCT01553591 , NCT01553747 BACKGROUND Evidence suggests that gut flora may play an important role in the pathophysiology of the irritable bowel syndrome ( IBS ) . We evaluated rifaximin , a minimally absorbed antibiotic , as treatment for IBS . METHODS In two identically design ed , phase 3 , double-blind , placebo-controlled trials ( TARGET 1 and TARGET 2 ) , patients who had IBS without constipation were r and omly assigned to either rifaximin at a dose of 550 mg or placebo , three times daily for 2 weeks , and were followed for an additional 10 weeks . The primary end point , the proportion of patients who had adequate relief of global IBS symptoms , and the key secondary end point , the proportion of patients who had adequate relief of IBS-related bloating , were assessed weekly . Adequate relief was defined as self-reported relief of symptoms for at least 2 of the first 4 weeks after treatment . Other secondary end points included the percentage of patients who had a response to treatment as assessed by daily self-ratings of global IBS symptoms and individual symptoms of bloating , abdominal pain , and stool consistency during the 4 weeks after treatment and during the entire 3 months of the study . RESULTS Significantly more patients in the rifaximin group than in the placebo group had adequate relief of global IBS symptoms during the first 4 weeks after treatment ( 40.8 % vs. 31.2 % , P=0.01 , in TARGET 1 ; 40.6 % vs. 32.2 % , P=0.03 , in TARGET 2 ; 40.7 % vs. 31.7 % , P<0.001 , in the two studies combined ) . Similarly , more patients in the rifaximin group than in the placebo group had adequate relief of bloating ( 39.5 % vs. 28.7 % , P=0.005 , in TARGET 1 ; 41.0 % vs. 31.9 % , P=0.02 , in TARGET 2 ; 40.2 % vs. 30.3 % , P<0.001 , in the two studies combined ) . In addition , significantly more patients in the rifaximin group had a response to treatment as assessed by daily ratings of IBS symptoms , bloating , abdominal pain , and stool consistency . The incidence of adverse events was similar in the two groups . CONCLUSIONS Among patients who had IBS without constipation , treatment with rifaximin for 2 weeks provided significant relief of IBS symptoms , bloating , abdominal pain , and loose or watery stools . ( Funded by Salix Pharmaceuticals ; Clinical Trials.gov numbers , NCT00731679 and NCT00724126 . ) 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 Objectives : Eluxadoline is a mixed μ-opioid receptor ( OR ) and κ-OR agonist and δ-OR antagonist , approved for the treatment of irritable bowel syndrome with diarrhea ( IBS-D ) . This analysis evaluated the safety and tolerability of eluxadoline 75 and 100 mg twice daily ( BID ) in one Phase 2 ( IBS-2001 ) and two Phase 3 ( IBS-3001 and IBS-3002 ) studies . Methods : Adults with IBS-D ( Rome III criteria ) were r and omized to placebo or eluxadoline ( 75 or 100 mg ) BID for 12 ( IBS-2001 ) , 26 ( IBS-3002 ) , or 52 ( IBS-3001 ) weeks . Safety data were pooled . Adverse events ( AEs ) were assessed , with special focus on opioid-related AEs , including suspected sphincter of Oddi spasm ( SOS ) events . Results : 2,776 patients were included in the enrolled set ; the safety set comprised 2,814 patients , based on actual treatments received . The most frequent AEs in the placebo and eluxadoline 75 and 100 mg groups were constipation ( 2.5 , 7.4 , and 8.1 % , respectively ) and nausea ( 5.0 , 8.1 , and 7.1 % , respectively ) ; discontinuation due to constipation was uncommon ( 0.3 , 1.1 , and 1.5 % , respectively ) . Ten SOS events ( 10/1,839 ; 0.5 % ) occurred in eluxadoline-treated patients , manifesting as acute abdominal pain with elevated aminotransferases or lipase , or pancreatitis ; all occurred in patients without a gallbladder . Eight of these events occurred with the higher dose of eluxadoline , within 1 week of initiation of therapy , and all resolved with eluxadoline discontinuation . There were five events independently adjudicated as pancreatitis not associated with SOS , three of which were associated with heavy alcohol use . Conclusions : Eluxadoline was well tolerated in Phase 2 and 3 trials , with constipation and nausea the most common AEs . Consistent with the known adverse effects of opioid agonists , clinical ly apparent SOS events were observed in eluxadoline-treated patients . All occurred in patients without a gallbladder and the majority were observed in patients on the higher dose of eluxadoline , suggesting a possible association OBJECTIVE : There has been growing interest in the investigation of health-related quality of life ( HRQOL ) among patients with gastrointestinal ( GI ) disorders . We recently reported on the development and preliminary validation of the IBS-QOL , a specific quality -of-life measure for irritable bowel syndrome ( IBS ) . The aim of this study was to determine the longitudinal construct validity ( responsiveness ) of the IBS-QOL . METHODS : Female patients enrolled in a multicenter treatment trial for functional bowel disorders were studied pre- and posttreatment with the IBS-QOL and other health status measures . Based on the response to treatment for several variables ( pain/14-day score , daily function , and days in bed/3 months ) , patients were stratified into Responders , Partial Responders , and Nonresponders . Change scores in the IBS-QOL were then statistically compared with changes in the other variables to determine their correlation and whether Responders were significantly different from non- and Partial Responders on the IBS-QOL . RESULTS : There was a significant correlation between change scores on the IBS-QOL and the other measures of treatment effect ( Pain/14 days , r = 0.25 , p < 0.002 ; Sickness Impact Profile [ SIP ] Total Score , r = 0.28 , p < 0.0004 ) . In addition , the IBS-QOL scores significantly differentiated Responders from Nonresponders for most of the variables tested ( regression trend test for Pain/14 days , p < 0.04 ; SIP Total , p < 0.0001 ; SIP Physical , p < 0.0001 ; SIP Psychosocial , p < 0.002 , and SIP Eating , p < 0.04 ) . CONCLUSION : The IBS-QOL is responsive to treatment in a referral-based clinical population of patients with functional bowel disorders The mixed μ‐ and κ‐opioid receptor agonist and δ‐opioid receptor antagonist , eluxadoline , is licensed in the USA for the treatment of irritable bowel syndrome  with diarrhoea ( IBS‐D ) , based on the results of two large Phase 3 clinical trials Effects of the currently marketed form of loperamide ( Imodium capsules ) that might relate to abuse potential were examined . Study I was a double‐blind “ dose run‐up ” in adult male subjects with a history of illicit drug use but no history of opioid addiction . Subjective responses to doses of loperamide ranging from 12 to 60 mg were compared with responses to 120 mg codeine sulfate ( 96 mg base ) and to placebo . Based on study I , loperamide ( 60 mg ) was used in study II and its effects were compared with those of codeine ( 96 mg base ) and placebo in an exaddict subject group . Study II subjects had had extensive opioid experience but were not actively addicted at the time of this double‐blind , inpatient study . In study II , as in 
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It also improved IBS severity and other abdominal symptoms such as bloating , discomfort , and risk of urgency and fecal incontinence .
Conclusion Eluxadoline ’s place in clinical practice might prove useful since the pharmacological options of IBS-D are limited and eluxadoline showed a positive effect in treating the symptoms of