Paul Moayyedi

The efficacy of probiotics in the treatment of irritable bowel syndrome: a systematic review

Introduction Probiotics may benefit irritable bowel syndrome (IBS) symptoms, but randomised controlled trials (RCTs) have been conflicting; therefore a systematic review was conducted. Methods MEDLINE (1966 to May 2008), EMBASE (1988 to May 2008) and the Cochrane Controlled Trials Register (2008) electronic databases were searched, as were abstracts from DDW (Digestive Diseases Week) and UEGW (United European Gastroenterology Week), and authors were contacted for extra information. Only parallel group RCTs with at least 1 week of treatment comparing probiotics with placebo or no treatment in adults with IBS according to any acceptable definition were included. Studies had to provide improvement in abdominal pain or global IBS symptoms as an outcome. Eligibility assessment and data extraction were performed by two independent researchers. Data were synthesised using relative risk (RR) of symptoms not improving for dichotomous data and standardised mean difference (SMD) for continuous data using random effects models. Results 19 RCTs (18 papers) in 1650 patients with IBS were identified. Trial quality was generally good, with nine reporting adequate methods of randomisation and six a method of concealment of allocation. There were 10 RCTs involving 918 patients providing outcomes as a dichotomous variable. Probiotics were statistically significantly better than placebo (RR of IBS not improving=0.71; 95% CI 0.57 to 0.88) with a number needed to treat (NNT)=4 (95% CI 3 to 12.5). There was significant heterogeneity (χ2=28.3, p=0.001, I2=68%) and possible funnel plot asymmetry. Fifteen trials assessing 1351 patients reported on improvement in IBS score as a continuous outcome (SMD=−0.34; 95% CI −0.60 to −0.07). There was statistically significant heterogeneity (χ2=67.04, p<0.001, I2=79%), but this was explained by one outlying trial. Conclusion Probiotics appear to be efficacious in IBS, but the magnitude of benefit and the most effective species and strain are uncertain.

British Society of Gastroenterology guidelines on the diagnosis and management of Barrett's oesophagus

These guidelines provide a practical and evidence-based resource for the management of patients with Barretts oesophagus and related early neoplasia. The Appraisal of Guidelines for Research and Evaluation (AGREE II) instrument was followed to provide a methodological strategy for the guideline development. A systematic review of the literature was performed for English language articles published up until December 2012 in order to address controversial issues in Barretts oesophagus including definition, screening and diagnosis, surveillance, pathological grading for dysplasia, management of dysplasia, and early cancer including training requirements. The rigour and quality of the studies was evaluated using the SIGN checklist system. Recommendations on each topic were scored by each author using a five-tier system (A+, strong agreement, to D+, strongly disagree). Statements that failed to reach substantial agreement among authors, defined as >80% agreement (A or A+), were revisited and modified until substantial agreement (>80%) was reached. In formulating these guidelines, we took into consideration benefits and risks for the population and national health system, as well as patient perspectives. For the first time, we have suggested stratification of patients according to their estimated cancer risk based on clinical and histopathological criteria. In order to improve communication between clinicians, we recommend the use of minimum datasets for reporting endoscopic and pathological findings. We advocate endoscopic therapy for high-grade dysplasia and early cancer, which should be performed in high-volume centres. We hope that these guidelines will standardise and improve management for patients with Barretts oesophagus and related neoplasia.

An Evidence-Based Position Statement on the Management of Irritable Bowel Syndrome

IBS is characterized by abdominal discomfort associated with altered bowel function; structural and biochemical abnormalities are absent. e pathophysiology of IBS is multifactorial and of intense recent interest, largely because of the possibility of developing targeted therapies. As IBS is one of the most common disorders managed by gastroenterologists and primary care physicians, this monograph was developed to educate physicians about its epidemiology, diagnostic approach, and treatments. e American College of Gastroenterology (ACG) IBS Task Force updated the 2002 monograph because new evidence has emerged on the bene* t and risks of drugs used for IBS. Furthermore, new drugs also have been developed and the evidence for e+ cacy of these drugs needed to be assessed. To critically evaluate the rapidly expanding research about IBS, a series of systematic reviews were performed. Standard criteria for systematic reviews were met, including comprehensive literature searching, use of prespeci* ed study selection criteria, and use of a standardized and transparent process to extract and analyze data from studies. Evidence-based statements were developed from these data by the entire ACG IBS Task Force. Recommendations were graded using a formalized system that quanti* es the strength of evidence. Each recommendation was classi* ed as strong (grade 1) or weak (grade 2) and the strength of evidence classi* ed as strong (level A), moderate (level B), or weak (level C). Recommendations in this position statement may be crossreferenced with the supporting evidence in the accompanying article, “ An Evidenced Based Review on the Management of Irritable Bowel Syndrome ” .

Efficacy of Antidepressants and Psychological Therapies in Irritable Bowel Syndrome: Systematic Review and Meta-analysis.

Objective: Irritable bowel syndrome (IBS) is a chronic functional gastrointestinal disorder. Evidence for treatment of the condition with antidepressants and psychological therapies is conflicting. Design: Systematic review and meta-analysis of randomised controlled trials (RCTs). MEDLINE, EMBASE and the Cochrane Controlled Trials Register were searched (up to May 2008). Setting: RCTs based in primary, secondary and tertiary care. Patients: Adults with IBS. Interventions: Antidepressants versus placebo, and psychological therapies versus control therapy or “usual management”. Main outcome measures: Dichotomous symptom data were pooled to obtain a relative risk (RR) of remaining symptomatic after therapy, with a 95% confidence interval (CI). The number needed to treat (NNT) was calculated from the reciprocal of the risk difference. Results: The search strategy identified 571 citations. Thirty-two RCTs were eligible for inclusion: 19 compared psychological therapies with control therapy or “usual management”, 12 compared antidepressants with placebo, and one compared both psychological therapy and antidepressants with placebo. Study quality was generally good for antidepressant but poor for psychological therapy trials. The RR of IBS symptoms persisting with antidepressants versus placebo was 0.66 (95% CI, 0.57 to 0.78), with similar treatment effects for both tricyclic antidepressants and selective serotonin reuptake inhibitors. The RR of symptoms persisting with psychological therapies was 0.67 (95% CI, 0.57 to 0.79). The NNT was 4 for both interventions. Conclusions: Antidepressants are effective in the treatment of IBS. There is less high-quality evidence for routine use of psychological therapies in IBS, but available data suggest these may be of comparable efficacy.

Systematic Review of the Risk of Enteric Infection in Patients Taking Acid Suppression

CONTEXT:Proton pump inhibitors (PPIs) and H2 receptor antagonists (H2RAs) have become the mainstay of therapy in acid-related upper gastrointestinal disorders. There have been concerns raised about the possible association of PPIs with enteric infections.OBJECTIVE: We conducted a systematic review to evaluate any association between acid suppression and enteric infection. We also assessed differences between types of enteric infections and the type of acid suppression.DATA SOURCES:Electronic searches of MEDLINE (1966–2005), EMBASE (1988–2005), and CINAHL (1982–2005) were undertaken using a combination of subject headings and text words related to PPI therapy, H2RAs, and enteric infections.STUDY SELECTION:All observational studies were eligible, including cross-sectional, case control, and cohort studies that evaluated risk of enteric infection associated with antisecretory therapy. Eligibility assessment was made by two independent researchers.DATA EXTRACTION:Information on study design, patient population, type of acid suppression, type of infection, and outcomes was collected. The odds ratio (OR) of taking acid suppression therapy in cases and controls was calculated and results were synthesized using a random effects model (DerSimonian and Laird, Stats direct version 2.4.4).DATA SYNTHESIS:A total of 12 papers evaluating 2,948 patients with Clostridium difficile were included in the review. There was an increased risk of taking antisecretory therapy in those infected with C. difficile (pooled OR 1.94, 95% CI 1.37–2.75). There was significant heterogeneity between the studies (P = 0.0006) that was not explained by planned subgroup analysis. The association was greater for PPI use (OR 1.96, 95% CI 1.28–3.00) compared with H2RA use (OR 1.40, 95% CI 0.85–2.29). A total of six studies evaluated Salmonella, Campylobacter, and other enteric infections in 11,280 patients. There was an increased risk of taking acid suppression in those with enteric infections (OR 2.55, 95% CI 1.53–4.26). There was significant heterogeneity between the studies (P < 0.0001) that was not explained by subgroup analysis. The association was greater for PPI use (OR 3.33, 95% CI 1.84–6.02) compared with H2RA use (OR 2.03, 95% CI 1.05–3.92).CONCLUSION: There is an association between acid suppression and an increased risk of enteric infection. Further prospective studies on patients taking long-term acid suppression are needed to establish whether this association is causal.

Fecal Microbiota Transplantation Induces Remission in Patients With Active Ulcerative Colitis in a Randomized Controlled Trial

BACKGROUND & AIMS Ulcerative colitis (UC) is difficult to treat, and standard therapy does not always induce remission. Fecal microbiota transplantation (FMT) is an alternative approach that induced remission in small series of patients with active UC. We investigated its safety and efficacy in a placebo-controlled randomized trial. METHODS We performed a parallel study of patients with active UC without infectious diarrhea. Participants were examined by flexible sigmoidoscopy when the study began and then were randomly assigned to groups that received FMT (50 mL, via enema, from healthy anonymous donors; n = 38) or placebo (50 mL water enema; n = 37) once weekly for 6 weeks. Patients, clinicians, and investigators were blinded to the groups. The primary outcome was remission of UC, defined as a Mayo score ≤2 with an endoscopic Mayo score of 0, at week 7. Patients provided stool samples when the study began and during each week of FMT for microbiome analysis. The trial was stopped early for futility by the Data Monitoring and Safety Committee, but all patients already enrolled in the trial were allowed to complete the study. RESULTS Seventy patients completed the trial (3 dropped out from the placebo group and 2 from the FMT group). Nine patients who received FMT (24%) and 2 who received placebo (5%) were in remission at 7 weeks (a statistically significant difference in risk of 17%; 95% confidence interval, 2%-33%). There was no significant difference in adverse events between groups. Seven of the 9 patients in remission after FMT received fecal material from a single donor. Three of the 4 patients with UC ≤1 year entered remission, compared with 6 of 34 of those with UC >1 year (P = .04, Fishers exact test). Stool from patients receiving FMT had greater microbial diversity, compared with baseline, than that of patients given the placebo (P = .02, Mann-Whitney U test). CONCLUSIONS FMT induces remission in a significantly greater percentage of patients with active UC than placebo, with no difference in adverse events. Fecal donor and time of UC appear to affect outcomes. ClinicalTrials.gov Number: NCT01545908.

Gastro-oesophageal reflux disease.

Gastro-oesophageal reflux disease refers to reflux of gastric contents into the oesophagus leading to oesophagitis, reflux symptoms sufficient to impair quality of life, or long-term complications. Transient relaxation of the lower oesophageal sphincter is believed to be the primary mechanism of the disease although the underlying cause remains uncertain. Obesity and smoking are weakly associated with the disease and genetic factors might be important. A negative association with Helicobacter pylori exists, but eradication of H pylori does not seem to cause reflux disease. Diagnosis is imprecise as there is no gold standard. Reflux symptoms are helpful in diagnosis but they lack sensitivity. Ambulatory oesophageal pH monitoring also seems to be insensitive despite high specificity. Empirical acid suppression with a proton-pump inhibitor (PPI) has reasonable sensitivity but poor specificity. Some evidence suggests that once patients develop the disease, severity is determined early and patients seem to continue with that phenotype long term. Unfortunately, most patients do not respond to life-style advice and require further therapy. H2 receptor antagonists and PPIs are better than placebo in oesophagitis, with a number needed to treat of five and two, respectively. In non-erosive reflux disease, acid suppression is better than placebo but the response rate is lower. Most patients need long-term treatment because the disease usually relapses. The role of endoscopic therapy is uncertain. Anti-reflux surgery is probably as effective as PPI therapy although there is a low operative mortality and morbidity.

Effect of fibre, antispasmodics, and peppermint oil in the treatment of irritable bowel syndrome: systematic review and meta-analysis.

Objective To determine the effect of fibre, antispasmodics, and peppermint oil in the treatment of irritable bowel syndrome. Design Systematic review and meta-analysis of randomised controlled trials. Data sources Medline, Embase, and the Cochrane controlled trials register up to April 2008. Review methods Randomised controlled trials comparing fibre, antispasmodics, and peppermint oil with placebo or no treatment in adults with irritable bowel syndrome were eligible for inclusion. The minimum duration of therapy considered was one week, and studies had to report either a global assessment of cure or improvement in symptoms, or cure of or improvement in abdominal pain, after treatment. A random effects model was used to pool data on symptoms, and the effect of therapy compared with placebo or no treatment was reported as the relative risk (95% confidence interval) of symptoms persisting. Results 12 studies compared fibre with placebo or no treatment in 591 patients (relative risk of persistent symptoms 0.87, 95% confidence interval 0.76 to 1.00). This effect was limited to ispaghula (0.78, 0.63 to 0.96). Twenty two trials compared antispasmodics with placebo in 1778 patients (0.68, 0.57 to 0.81). Various antispasmodics were studied, but otilonium (four trials, 435 patients, relative risk of persistent symptoms 0.55, 0.31 to 0.97) and hyoscine (three trials, 426 patients, 0.63, 0.51 to 0.78) showed consistent evidence of efficacy. Four trials compared peppermint oil with placebo in 392 patients (0.43, 0.32 to 0.59). Conclusion Fibre, antispasmodics, and peppermint oil were all more effective than placebo in the treatment of irritable bowel syndrome.

Efficacy of Biological Therapies in Inflammatory Bowel Disease: Systematic Review and Meta-Analysis

OBJECTIVES:Crohns disease (CD) and ulcerative colitis (UC) are inflammatory disorders of the gastrointestinal tract of unknown etiology. Evidence for treatment of the condition with biological therapies exists, but no systematic review and meta-analysis has examined this issue in its entirety.METHODS:MEDLINE, EMBASE, and the Cochrane central register of controlled trials were searched (through to December 2010). Trials recruiting adults with active or quiescent CD or UC and comparing biological therapies (anti-tumor necrosis factor-α (TNFα) antibodies or natalizumab) with placebo were eligible. Dichotomous symptom data were pooled to obtain relative risk (RR) of failure to achieve remission in active disease and RR of relapse of activity in quiescent disease once remission had occurred, with a 95% confidence interval (CI).RESULTS:The search strategy identified 3,061 citations, 27 of which were eligible. Anti-TNFα antibodies and natalizumab were both superior to placebo in inducing remission of luminal CD (RR of no remission=0.87; 95% CI 0.80–0.94 and RR=0.88; 95% CI 0.83–0.94, respectively). Anti-TNFα antibodies were also superior to placebo in preventing relapse of luminal CD (RR of relapse=0.71; 95% CI 0.65–0.76). Infliximab was superior to placebo in inducing remission of moderate to severely active UC (RR=0.72; 95% CI 0.57–0.91).CONCLUSIONS:Biological therapies were superior to placebo in inducing remission of active CD and UC, and in preventing relapse of quiescent CD.

Management of Helicobacter pylori infection—the Maastricht V/Florence Consensus Report

Important progress has been made in the management of Helicobacter pylori infection and in this fifth edition of the Maastricht Consensus Report, key aspects related to the clinical role of H. pylori were re-evaluated in 2015. In the Maastricht V/Florence Consensus Conference, 43 experts from 24 countries examined new data related to H. pylori in five subdivided workshops: (1) Indications/Associations, (2) Diagnosis, (3) Treatment, (4) Prevention/Public Health, (5) H. pylori and the Gastric Microbiota. The results of the individual workshops were presented to a final consensus voting that included all participants. Recommendations are provided on the basis of the best available evidence and relevance to the management of H. pylori infection in the various clinical scenarios.