An Evidence-Based Systematic Review on the Management of Irritable Bowel Syndrome

Section 2.1 Methodology for systematic reviews of irritable bowel syndrome therapy, levels of evidence, and grading of recommendations We have conducted a series of systematic reviews on the diagnostic criteria, the value of diagnostic tests, and the efficacy of therapy in IBS. We also performed a narrative review of the epidemiology of IBS. There have been several systematic reviews of therapy for IBS (1-5), but these either have not quantitatively combined the data into meta-analyses (1-3) or have inaccuracies in applying eligibility criteria and data extraction (4,5). We have, therefore, repeated all systematic reviews of IBS and synthesized the data where appropriate. Systematic review methodology For all reviews, we evaluated manuscripts that studied adults using any definition of IBS. This included a clinician-defined diagnosis, Manning criteria (6), the Kruis score (7), or Rome I (8), II (9), or III (10) criteria. For reviews of diagnostic tests, we included case series and case-control studies that evaluated serologic tests for celiac sprue (anti-gliadin, anti-endomysial, and tissue transglutaminase antibodies), lactose hydrogen breath tests, and tests for small bowel bacterial overgrowth (lactulose and glucose hydrogen breath test or jejunal aspirates). For reviews of therapies of IBS, we included only parallel group RCTs comparing active intervention with either placebo or no therapy. The following treatments were considered: Diet Fiber, bulking agents, and laxatives Antispasmodics and Peppermint Oil Antidiarrheal agents Antibiotic therapy Probiotic therapy 5HT3 antagonists 5HT4 agonists Selective C-2 chloride channel activators (Lubiprostone) Antidepressants Psychological therapies Herbal therapies and acupuncture Emerging therapies Subjects needed to be followed up for at least one week. The trial needed to include one or more of the following outcome measures: Global assessment of IBS cure or improvement Abdominal pain cure or improvement Global IBS symptom or abdominal pain scores Search strategy for identification of studies Medline (1966-June 2008), Embase (1988-June 2008), and the Cochrane Controlled Trials Register (Issue 2, 2008) electronic databases were searched. An example of the Medline search is given below. IBS patients were identified with the terms irritable bowel syndrome and functional diseases, colon (both as medical subject heading (MeSH) and free text terms), and IBS, spastic colon, irritable colon, and functional adj5 (adj5 is a term used by Medline for words that appear within 5 adjectives of each other) bowel (as free text terms). Studies identified from this search were combined with the following terms used to identify therapies for IBS: dietary fiber, cereals, psyllium, sterculia, karaya gum, parasympatholytics, scopolamine, trimebutine, muscarinic antagonists, and the following free text terms: bulking agent, psyllium fiber, fiber, husk, bran, ispaghula, wheat bran, spasmolytics, spasmolytic agents, antispasmodics, mebeverine, alverine, pinaverium bromide, otilonium bromide, cimetropium bromide, hyoscine butyl bromide, butylscopolamine, peppermint oil, loperamide and colpermin, serotonin antagonists, serotonin agonists, cisapride, receptors (serotonin, 5-HT3), and receptors (serotonin, 5-HT4; both as MeSH terms and free text terms), and the following free text terms: 5-HT3, 5-HT4, alosetron, cilansetron, tegaserod, and renzapride, psychotropic drugs, antidepressive agents, antidepressive agents (tricyclic), desipramine, imipramine, trimipramine, doxepin, dothiepin, nortriptyline, amitriptyline, selective serotonin re-uptake inhibitors, paroxetine, sertraline, fluoxetine, citalopram, venlafaxine, cognitive therapy, psychotherapy, behaviour therapy, relaxation techniques, and hypnosis (both as MeSH terms and free text terms), and the following free text terms: behavioral therapy, relaxation therapy, and hypnotherapy. Saccharomyces, Lactobacillus, Bifidobacterium, Escherichia coli or probiotics (MeSH and free text terms). An RCT filter was applied to the electronic searches. The searches were limited to humans. A recursive search of the bibliography of relevant articles also was conducted. DDW abstract books were hand searched between 2000 and 2008; UEGW abstract books were hand searched between 2000 and 2007. Authors of trial reports that did not give enough detail for adequate data extraction were contacted and asked to contribute full datasets. Experts in the field were contacted for leads on unpublished studies and no language restrictions were applied. Trials were assessed for risk of bias according to three characteristics: method of randomization, method of concealment of treatment allocation, and implementation of masking. 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There have been RCTs patients that evaluated the of loperamide in the treatment of IBS with There were no of loperamide on with placebo risk of IBS not were but adequate of adequate concealment of The of in each trial was used a of IBS by to the that of the group with of The of that the risk of not with loperamide was There were no in one and in each of the trial Section of in the of irritable bowel syndrome A of a is more placebo for improvement of IBS and for There no data to the and of for the of IBS a efficacy in three RCTs IBS patients of these RCTs were all criteria for RCTs studies with concealment of treatment allocation, implementation of of and and criteria of the Rome for of treatment of functional patients Rome criteria for IBS, no placebo of patients to IBS and outcome is improvement in IBS of these RCTs improvement in with and patients were more to improvement in IBS or both with is not for treatment of IBS, is for treatment of at the of for three IBS of for three for for and for The RCT only and in this patients improvement in with patients on these is to be in patients or IBS patients with a symptom of and the is for In the patients were to for followed by placebo for placebo for In this patients to adequate of IBS in of the three to be as a patients were more to be of the improvement was not of the of In a RCT IBS patients were to three for or placebo with a In this of IBS was on a symptom and patients to a improvement in IBS from to one of to be as a on assessment of the patients were more patients to improvement in abdominal pain and a of the data did not improvement for the of abdominal or RCT patients with a of of Rome II criteria for IBS. IBS patients were more patients to that have the of treatment but the of patients to that have the of treatment in both This that of IBS not be of RCTs have that IBS symptom improvement for at least patients with hydrogen breath tests, were with three for patients breath tests at and tests in a of patients at three and and of breath tests were with in abdominal and on on one IBS patients with to repeated of a RCT of patients that patients were more to improvement in IBS with patients trial of did not efficacy of for IBS as a In this a of to was for was for and or for one week. of this patients also symptom at and and IBS was as of three or more Manning criteria.

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