***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: OBJECTIVES : Though the greatest proportion of irritable bowel syndrome ( IBS ) patients report a mixed bowel pattern ( IBS-Mixed ) , no available therapies have been rigorously evaluated in this subgroup . This study aim ed to evaluate the efficacy and safety of the 5-HT4 agonist tegaserod in women with IBS-Mixed and IBS with constipation ( IBS-C ) . METHODS : This prospect i ve , double-blind , r and omized , placebo-controlled , multicenter study was conducted in 100 centers in North America , South America , and Europe . Women with IBS-Mixed or IBS-C received tegaserod 6 mg or placebo twice daily . The primary efficacy variable was the patient 's assessment of satisfactory relief over the 4-wk treatment period . The proportion of patients reporting satisfactory relief for ≥3 of 4 treatment weeks ( 75 % rule ) and individual IBS symptoms were assessed . RESULTS : In total , 661 women were r and omized ( IBS-Mixed 324 , IBS-C 337 ) . Baseline symptom assessment s identified clear differences between the two cohorts . Tegaserod provided significant improvement in satisfactory relief of IBS symptoms over 4 wk ( OR 1.75 , 95 % CI 1.35–2.25 , P < 0.001 ) in both IBS-Mixed and IBS-C patients . Using the 75 % rule , 52.3 % of tegaserod-receiving IBS-M patients and 43.3 % of IBS-C patients were responders ( vs 36.3 , OR 1.88 , 95 % CI 1.16–3.04 , P < 0.010 ; and 28.9 , OR 1.90 , 95 % CI 1.19–3.05 , P < 0.008 for placebo , respectively ) . The most frequent adverse events leading to study discontinuation in tegaserod-treated patients were diarrhea ( 1.5 % ) and abdominal pain ( 0.9 % ) . Overall 7 % of IBS-C patients reported diarrhea compared to 12 % of IBS-Mixed ( placebo 2.4 % , 1.8 % , respectively ) . CONCLUSIONS : Tegaserod is effective in treating overall IBS symptoms in patients with IBS-Mixed and OBJECTIVES : To assess long-term safety and efficacy of alosetron in women with severe , chronic diarrhea-predominant IBS and in a subset having more frequent urgency ( i.e. , bowel urgency at least 10 of 14 days during screening ) . METHODS : R and omized patients received either alosetron 1 mg ( n = 351 ) or placebo ( n = 363 ) twice daily during a 48-wk , double-blind study . The primary endpoint was the 48-wk average rate of adequate relief of IBS pain and discomfort . Secondary endpoints included 48-wk average satisfactory control rates of urgency , stool frequency , stool consistency , and bloating . Other efficacy endpoints were average monthly adequate relief and urgency control rates and impact of provided rescue medication . RESULTS : Alosetron-treated patients had significantly greater 48-wk average adequate relief ( p = 0.01 ) and urgency control ( p < 0.001 ) rates , regardless of rescue medication use , compared with placebo . Results in subjects with more frequent urgency were more robust than those in the overall population ( p = 0.005 ) . In weeks without rescue medication use , satisfactory control rates for stool frequency and stool consistency were significantly greater in alosetron-treated patients than placebo . Alosetron-treated patients had significantly greater adequate relief than placebo-treated patients ( p < 0.05 ) in 9 of 12 months and significantly greater urgency control ( p < 0.001 ) in all months . Adequate relief and urgency control were maintained throughout the treatment . Adverse events and serious adverse events were similar between treatment groups , except for constipation . Neither ischemic colitis nor serious events related to bowel motor dysfunction was reported . CONCLUSIONS : Long-term use of alosetron is effective and well-tolerated in women with chronic , diarrhea-predominant IBS , including those with more frequent urgency : No currently available treatment provides consistent relief of irritable bowel syndrome . Colonic sensory and motor function are modulated partly through 5HT3‐receptors Herbal remedies , particularly peppermint , have been reported to be helpful in controlling symptoms of irritable bowel syndrome ( IBS ) . We conducted a r and omized double-blind placebo-controlled study on 90 out patients with IBS . Subjects took one capsule of enteric-coated , delayed-release peppermint oil ( Colpermin ) or placebo three times daily for 8 weeks . We visited patients after the first , fourth , and eighth weeks and evaluated their symptoms and quality of life . The number of subjects free from abdominal pain or discomfort changed from 0 at week 0 to 14 at week 8 in the Colpermin group and from 0 to 6 in controls ( P < 0.001 ) . The severity of abdominal pain was also reduced significantly in the Colpermin group as compared to controls . Furthermore , Colpermin significantly improved the quality of life . There was no significant adverse reaction .  Colpermin is effective and safe as a therapeutic agent in patients with IBS suffering from abdominal pain or discomfort OBJECTIVES : Bowel urgency is one of the most bothersome symptoms for nonconstipated IBS patients . The efficacy of alosetron in control of bowel urgency and Global Improvement of IBS symptoms were evaluated in a multicenter double-blind , r and omized , placebo-controlled study . METHODS : Female IBS patients with lack of satisfactory control of bowel urgency were r and omized 2:1 to alosetron 1 mg twice daily or placebo  treatment groups . The primary endpoint was the proportion of days with satisfactory control of bowel urgency during the 12-wk treatment period and 2-wk follow-up period . Secondary endpoints included IBS Global Improvement ( responder defined as patient-reported moderate or substantial improvement in IBS symptoms ) and improvements in bowel function ( stool frequency , consistency , and sensation of incomplete evacuation ) . RESULTS : A total of 801 women were r and omized to the  alosetron ( n = 532 ) or placebo groups ( n = 269 ) . Physicians classified 98 % of patients with diarrhea-predominant IBS . Patients treated with alosetron had a significantly greater proportion of days with satisfactory control of urgency compared to placebo for the treatment period ( 73 % vs 57 % , p < 0.001 ) . A significantly greater number of patients treated with alosetron were IBS Global Improvement responders compared to placebo at week 12 ( 76 % vs 44 % , p < 0.001 ) . IBS Global Improvement responders had more days with satisfactory control of urgency at week 12 ( 88 % vs 48 % ) as well as firmer stools , fewer stools/day , and fewer days with incomplete evacuation compared with nonresponders . Alosetron-treated patients showed improvements in bowel functions compared to placebo-treated patients . Constipation was the most commonly reported adverse event . CONCLUSIONS : Alosetron is effective at managing bowel urgency in women with diarrhea-predominant IBS . The IBS Global Improvement assessment correlated with improvements in bowel function and may be a useful tool in future IBS clinical trials Are meta-analyses the brave new world , or are the critics of such combined analyses right to say that the biases inherent in clinical trials make them uncombinable ? Negative trials are often unreported , and hence can be missed by meta-analysts . And how much heterogeneity between trials is acceptable ? A recent major criticism is that large r and omised trials do not always agree with a prior meta- analysis . Neither individual trials nor meta-analyses , reporting as they do on population effects , tell how to treat the individual patient . Here we take a more rounded approach to meta-analyses , arguing that their strengths outweigh their weaknesses , although the latter must not be brushed aside A double-blind controlled therapeutic trial of factorial design was used to study the therapeutic effects of lorazepam , hyoscine butylbromide , and ispaghula husk in 12 r and omised blocks of eight patients with the irritable bowel syndrome ( IBS ) . Each of the three agents caused a sustained symptomatic improvement in some of the patients , although only with ispaghula was the difference between the real and dummy preparation statistically significant . When the eight possible combinations of treatment were analysed none of the 12 patients who received only dummy preparations of the three agents had maintained any improvement over the three months of the trial . Seven patients improved among the 12 who received potent preparations of all three agents , and between four and six patients improved in the groups receiving one or two of the potent preparations . These therapeutic results , though far from perfect , show that the types of drug commonly used to treat IBS are of some value and may be additive in their effects . Similar combinations of other therapeutic agents may be more effective , but it will be possible to determine this only by carrying out factorial therapeutic trials Background / objective In order to follow the most recent developments and recommendations in trial methodology for drug evaluation in patients with irritable bowel syndrome , we performed an extended analysis of a large clinical trial from a previously published study of otilonium bromide , using an assessment that integrates the key symptoms of irritable bowel syndrome . Material s and methods A large-scale clinical trial with a double-blind , placebo-controlled , parallel-group study design was conducted in 378 patients , treated for 15 weeks with the recommended st and ard dose of 40 mg otilonium bromide or placebo three times daily . The study was based on the collection of 12 single efficacy endpoints . The new efficacy assessment was based on the data reported by the patients . Rather than demonstrating score differences between the treatment groups of the study , we carried out an assessment that integrates the most frequent symptoms reported ( pain frequency and intensity , presence of meteorism and distension ) by the patient . Results The rate of response to treatment within 2–4 months ( the primary efficacy outcome measure ) was significantly higher in the otilonium bromide group ( 36.9 % ) than in the placebo group ( 22.5 % ; P = 0.007 ) . In each month of treatment , the rate of monthly response was higher in the otilonium bromide group as compared to the placebo group ( P < 0.05 ) . The total monthly and weekly responses to the single endpoints ( intensity and frequency of pain and discomfort , meteorism/abdominal distension , severity of diarrhoea or constipation and mucus in the stool ) were significantly more frequent in the group treated with otilonium bromide than in the placebo-treated group , with differences ranging from 10 % to 20 % . The subgroup analysis of the intestinal habits endpoint indicates that patients with diarrhoea have an additional benefit . Conclusion The present re-evaluation of a previously published study confirms that otilonium bromide is more effective than placebo for the treatment of irritable bowel syndrome , being very efficient in relieving pain and discomfort BACKGROUND AND AIM Previous studies with cisapride reported conflicting results in patients with constipation-predominant irritable bowel syndrome ( IBS ) . To gain further evidence , this r and omized double-blind study was carried out . METHODS Eighty-two symptomatic out patients were r and omized to receive either 5 mg oral cisapride or placebo three times daily for a period of 12 weeks . In patients without satisfactory improvement after 4 weeks , the dose was doubled . Symptom evaluation used visual analog scales ( VAS ) and the investigators ' global assessment . RESULTS After 4 weeks , in 18 ( 45 % ) cisapride and 24 ( 57 % ) placebo patients the dose was doubled because of insufficient improvement of symptoms . The mean VAS score for patients ' global rating of IBS symptoms at baseline was 67.5 mm for cisapride versus 70.7 mm for placebo , and improved to 38.4 mm versus 44.5 mm after 12 weeks of treatment . Investigators rated the overall effect of therapy as good or excellent in 70 % of the cisapride and 50 % of the placebo group . Neither these nor further efficacy parameter differences reached statistical significance . CONCLUSIONS These results indicate that the effect of 15 - 30 mg cisapride daily on symptoms of constipation-predominant IBS is not significantly superior to placebo . During the 12 week treatment of this trial cisapride proved to be safe and tolerable BACKGROUND : A r and omized , double blind , placebo-controlled dose-ranging study was conducted to assess the efficacy of alosetron in men with diarrhea-predominant irritable bowel syndrome ( IBS ) . METHODS : Six hundred and sixty-two men were r and omized to treatment with alosetron 0.5 , 1.0 , 2.0 , 4.0 mg , or placebo twice daily for 12 wk , followed by a 4-wk posttreatment period . Adequate relief of IBS pain and discomfort during week 5–12 of the treatment phase was the primary endpoint ; secondary endpoints included bowel urgency , stool frequency , and consistency , incomplete evacuation , bloating , and abdominal pain or discomfort . RESULTS : Subjects ranked urgency and abdominal pain as their most bothersome IBS symptoms . 
    Output:
    
Placebo response rates across RCTs of pharmacological therapies in IBS were high .