Comparative efficacy and safety of probiotics for the treatment of irritable bowel syndrome: a systematic review and network meta-analysis protocol.

INTRODUCTION: Irritable bowel syndrome (IBS) is a common chronic functional gastrointestinal disorder affecting approximately 10% to 25% of the adult population. A large number of clinical trials have been conducted to evaluate the efficacy of probiotics for IBS but the results were inconsistent. Previous meta-analyses have shown that probiotics are effective for IBS, but the comparative efficacy of individual species is unclear. In addition, evidence regarding the superiority of combination over single probiotic is still lacking. We, therefore, perform this study to evaluate the comparative efficacy and safety of various species of probiotics, and combination regimens for the treatment of IBS. METHODS AND ANALYSIS: This study is a systematic review with network meta-analysis. We will search PubMed, Scopus, The Cochrane Central Register of Controlled Trials and CINAHL for randomised controlled trials comparing probiotics with placebo or comparing different probiotics for IBS, with no language restrictions. The primary outcomes will be treatment response and global IBS-symptom score. We will initially combine included studies with traditional pairwise meta-analysis and then with random-effects network meta-analysis. We will quantify the effect of potential effect modifiers by meta-regression if appropriate. We will check the consistency assumption by testing the absolute difference between direct and indirect estimates for comparisons in closed loops. The quality of evidence will be evaluated according to the GRADE framework. ETHICS AND DISSEMINATION: Ethical approval is not required for literature-based studies. We will disseminate the findings through publications in peer-reviewed journals and relevant conferences.PROSPERO registration numberCRD42018102101.

Associations of anxiety with discomfort and tolerance in Chinese patients undergoing esophagogastroduodenoscopy.

OBJECTIVES: To evaluate the associations of pre-endoscopy anxiety with discomfort and tolerance in patients undergoing unsedated esophagogastroduodenoscopy (EGD). METHODS: This is a hospital-based cohort study of 348 patients undergoing routine, non-advanced EGD without sedation. The primary outcomes were discomfort and tolerance. The anxiety before endoscopy was evaluated with a 10-point visual analogue scale (VAS). The associations of pre-endoscopy anxiety with the outcomes were evaluated with logistic regression adjusting for potential confounders like age, sex, and body mass index. RESULTS: Seventy patients reported severe discomfort and 56 patients reported poor tolerance after endoscopy. The risk of severe discomfort increased with pre-endoscopy anxiety and reached a platform around 7-10 points. Compared with the participants with low pre-endoscopy anxiety, those with moderate (adjusted odds ratio [OR] 2.70, 95% confidence interval [CI] 1.17 to 6.22) and high level of anxiety (adjusted OR 6.87, 95% CI 2.16 to 21.79) were associated with a gradual increase in the risk of severe discomfort (P-trend < 0.001). The association between pre-endoscopy anxiety and tolerance was linear, with an adjusted OR of 1.67(95% CI 1.33 to 2.08) for a 1-score increase in pre-endoscopy anxiety VAS. The associations were not modified by age, sex, pharyngitis, duration of endoscopy, and diameter of the endoscope. CONCLUSIONS: Pre-endoscopy anxiety was an independent predictor of severe discomfort and poor tolerance in Chinese patients undergoing unsedated EGD. Our findings suggested the importance of the management of anxiety to reduce adverse endoscopic experience and taking high level of anxiety as an indication for sedation.

Proton pump inhibitors for preventing non-steroidal anti-inflammatory drug induced gastrointestinal toxicity: a systematic review.

OBJECTIVE: Proton pump inhibitors (PPIs) are recommended for preventing gastrointestinal lesions induced by non-steroidal anti-inflammatory drugs (NSAIDs). We performed this study: (1) to evaluate the effectiveness and safety of PPIs, (2) to explore the association between effectiveness and potential influential factors, and (3) to investigate the comparative effect of different PPIs. METHODS: MEDLINE, EMBASE, and the Cochrane Library were searched to identify randomized controlled trials comparing different classes of PPIs, or comparing PPIs with placebo, H2 receptor antagonists or misoprostol in NSAIDs users. Both pairwise meta-analysis and Bayesian network meta-analysis were performed. RESULTS: Analyses were based on 12,532 participants from 31 trials. PPIs were significantly more effective than placebo in reducing ulcer complications (relative risk [RR] = 0.29; 95% confidence interval [CI], 0.20 to 0.42) and endoscopic peptic ulcers (RR = 0.27; 95% CI, 0.22 to 0.33), with no subgroup differences according to class of NSAIDs, ulcer risk, history of previous ulcer disease, Helicobacter pylori infection, or age. To prevent one ulcer complication, 10 high risk patients and 268 moderate risk patients need PPI therapy. Network meta-analysis indicated that the effectiveness of different PPIs in reducing ulcer complications and endoscopic peptic ulcers is generally similar. PPIs significantly reduced gastrointestinal adverse events and the related withdrawals compared to placebo; there is no difference in safety between different PPIs. CONCLUSIONS: PPIs are effective and safe in preventing peptic ulcers and complications in a wide spectrum of patients requiring NSAID therapy. There is no major difference in the comparative effectiveness and safety between different PPIs.

Network Meta-Analysis Comparing Relatively Selective COX-2 Inhibitors Versus Coxibs for the Prevention of NSAID-Induced Gastrointestinal Injury.

Currently 2 difference classes of cyclooxygenase (COX)-2 inhibitors, coxibs and relatively selective COX-2 inhibitors, are available for patients requiring nonsteroidal anti-inflammatory drug (NSAID) therapy; their gastroprotective effect is hardly directly compared. The aim of this study was to compare the gastroprotective effect of relatively selective COX-2 inhibitors with coxibs. MEDLINE, EMBASE, and the Cochrane Library (from their inception to March 2015) were searched for potential eligible studies. We included randomized controlled trials comparing coxibs (celecoxib, etoricoxib, parecoxib, and lumiracoxib), relatively selective COX-2 inhibitors (nabumetone, meloxicam, and etodolac), and nonselective NSAIDs with a study duration ≥ 4 weeks. Comparative effectiveness and safety data were pooled by Bayesian network meta-analysis. The primary outcomes were ulcer complications and symptomatic ulcer. Summary effect-size was calculated as risk ratio (RR), together with the 95% confidence interval (CI). This study included 36 trials with a total of 112,351 participants. Network meta-analyses indicated no significant difference between relatively selective COX-2 inhibitors and coxibs regarding ulcer complications (RR, 1.38; 95% CI, 0.47-3.27), symptomatic ulcer (RR, 1.02; 95% CI, 0.09-3.92), and endoscopic ulcer (RR, 1.18; 95% CI, 0.37-2.96). Network meta-analyses adjusting potential influential factors (age, sex, previous ulcer disease, and follow-up time), and sensitivity analyses did not reveal any major change to the main results. Network meta-analyses suggested that relatively selective COX-2 inhibitors and coxibs were associated with comparable incidences of total adverse events (AEs) (RR, 1.09; 95% CI, 0.93-1.31), gastrointestinal AEs (RR, 1.04; 95% CI, 0.87-1.25), total withdrawals (RR, 1.00; 95% CI, 0.74-1.33), and gastrointestinal AE-related withdrawals (RR, 1.02; 95% CI, 0.57-1.74). Relatively selective COX-2 inhibitors appear to be associated with similar gastroprotective effect and tolerability as coxibs. Owing to the indirectness of the comparisons, future research is required to confirm the study conclusion.