Lacy, Brian E.

OBJECTIVES: Prokinetics are recommended for the treatment of functional dyspepsia (FD) but systematic reviews give conflicting results on the efficacy of these agents. We have therefore conducted an updated systematic review to support the 2017 joint ACG/CAG dyspepsia guidelines. METHODS: Electronic databases, including MEDLINE, EMBASE, and CENTRAL, were searched until September 2017 for randomized controlled trials (RCTs) comparing either prokinetics and placebo or two types of prokinetics to improve FD symptoms. The primary outcome was absence or improvement of dyspeptic symptoms at the end of treatment. Double-blind eligibility assessment and data extraction was performed. Pooled risk ratios of symptoms persisting or adverse events occurring, and standardized mean difference of quality-of-life (QoL) scores with 95% CI, using a random effects model, were calculated. Quality of evidence was assessed using GRADE. RESULTS: The search identified 1388 citations; 38 studies in 35 papers were included. Of these, 29 trials comparing prokinetics with placebo were found. There was a statistically significant effect of prokinetic treatment in reducing global symptoms of FD (RR 0.81, 95% CI 0.74 to 0.89; I 2 91%; NNT 7), regardless of FD subtype or ethnicity. When comparing two types of prokinetic, the most commonly used comparator was domperidone. There was no difference in reducing global symptoms (RR 0.94, 95% CI 0.83 to 1.07). QoL was not improved with prokinetic treatment. The adverse events with individual prokinetics were not different from placebo, except for cisapride. The GRADE assessment rated the quality of the evidence in each outcome as very low. CONCLUSIONS: From the current evidence, prokinetics may be effective for the treatment in all subtypes of FD, with very low quality of evidence. There was no difference between prokinetics for dyspeptic symptom improvement. High-quality RCTs with large sample sizes of FD patients are needed to verify the efficacy of prokinetics.

Summary Background Irritable bowel syndrome ( IBS ) is a chronic functional bowel disorder. Disturbances in the gastrointestinal microbiome may be involved in its aetiology. Aim To perform a systematic review and meta‐analysis to examine the efficacy of prebiotics, probiotics, synbiotics and antibiotics in IBS . Methods MEDLINE , EMBASE , and the Cochrane Controlled Trials Register were searched (up to July 2017). Randomised controlled trials ( RCT s) recruiting adults with IBS , comparing prebiotics, probiotics, synbiotics or antibiotics with placebo or no therapy were eligible. Dichotomous symptom data were pooled to obtain a relative risk ( RR ) of remaining symptomatic after therapy, with a 95% confidence interval ( CI ). Continuous data were pooled using a standardised mean difference with a 95% CI . Results The search identified 4017 citations. Data for prebiotics and synbiotics were sparse. Fifty‐three RCT s of probiotics, involving 5545 patients, were eligible. Particular combinations of probiotics, or specific species and strains, appeared to have beneficial effects on global IBS symptoms and abdominal pain, but it was not possible to draw definitive conclusions about their efficacy. There were five trials of similar design that used rifaximin in non‐constipated IBS patients, which was more effective than placebo ( RR of symptoms persisting = 0.84; 95% CI 0.79‐0.90). Adverse events were no more common with probiotics or antibiotics. Conclusions Which particular combination, species or strains of probiotics are effective for IBS remains, for the most part, unclear. Rifaximin has modest efficacy in improving symptoms in non‐constipated IBS .

SummaryBackgroundIrritable bowel syndrome (IBS) is multifactorial in nature, and a wide range of therapies is available to manage symptoms of this common disorder.AimTo provide an overview of the safety of interventions that may be used to manage patients with diarrhoea‐predominant IBS (IBS‐D).MethodsMedline and Embase database searches (through 02 May 2018) to identify clinical studies that evaluated treatment safety and/or efficacy in adults with IBS‐D.ResultsIBS‐D treatments include dietary modification, probiotics, serotonin receptor antagonists, opioid receptor agonists and antagonists, nonsystemic antibiotics, bile acid sequestrants, antidepressants, and complementary and alternative therapies. These treatments vary in administration frequency (eg, daily; short‐course therapy) and target various pathophysiologic factors. Safety profiles vary considerably by treatment among IBS‐D therapies. The number needed to harm (defined as the number of patients treated to encounter an adverse event) was lowest (worse) for antidepressants (8.5) and highest (best) for probiotics (35), and the number needed to harm (defined as the number of patients who discontinued due to an adverse event) was lowest for tricyclic antidepressants (9) and highest for rifaximin (8971). Notable safety concerns with IBS‐D treatments include pancreatitis with eluxadoline, ischaemic colitis and serious complications of constipation with alosetron, and cardiac adverse events with loperamide and tricyclic antidepressants. Treatment decisions need to account for medication risks and adverse events for each patient.ConclusionsMultiple treatment options are now available for patients with IBS‐D. However, the safety profiles of these agents vary widely by number needed to harm value. Providers should consider both safety and efficacy of a specific intervention when determining how best to manage patients’ IBS‐D symptoms.

OBJECTIVES: Irritable bowel syndrome (IBS) is a chronic functional bowel disorder that is thought to be due to a disorder of brain–gut function. Drugs acting centrally, such as antidepressants, and psychological therapies may, therefore, be effective. METHODS: We updated a previous systematic review and meta-analysis of randomized controlled trials (RCTs). MEDLINE, EMBASE, PsychINFO, and the Cochrane Controlled Trials Register were searched (up to July 2017). Trials recruiting adults with IBS, which compared antidepressants versus placebo, or psychological therapies versus control therapy or “usual management” were eligible. Dichotomous symptom data were pooled to obtain a relative risk (RR) of remaining symptomatic after therapy, with a 95% confidence interval (CI). RESULTS: The search strategy identified 5316 citations. Fifty-three RCTs, reported in 51 separate articles, were eligible for inclusion: 17 compared antidepressants with placebo, 35 compared psychological therapies with control therapy or “usual management”, and one compared both psychological therapy and antidepressants with placebo. Four of the trials of psychological therapies, and one of the RCTs of antidepressants, were identified since our previous meta-analysis. The RR of IBS symptoms not improving with antidepressants versus placebo was 0.66 (95% CI 0.57–0.76), with similar treatment effects for both tricyclic antidepressants and SSRIs, although with heterogeneity between RCTs of the latter ( I 2 = 49%, P = 0.07). The RR of symptoms not improving with psychological therapies was 0.69 (95% CI 0.62–0.76). Cognitive behavioral therapy, relaxation therapy, multi-component psychological therapy, hypnotherapy, and dynamic psychotherapy were all beneficial when data from two or more RCTs were pooled. There was significant heterogeneity between studies ( I 2 = 69%, P < 0.001) and significant funnel plot asymmetry. There were also issues regarding trial design, including lack of blinding. CONCLUSIONS: Antidepressants are efficacious in reducing symptoms in IBS patients. Psychological therapies also appear to be effective treatments for IBS, although there are limitations in the quality of the evidence, and treatment effects may be overestimated as a result.

Background: Alosetron is approved to treat women with severe IBS and diarrhea (IBS-D) who have failed standard therapy. In our study, we aimed to evaluate alosetron efficacy using new US Food and Drug Administration (FDA) endpoints and utilization in clinical practice. Methods: This prospective, open-label, multicenter, observational 12-week study evaluated women with severe IBS-D enrolled in the alosetron prescribing program. The coprimary FDA endpoints were changes from baseline in stool consistency and abdominal pain severity. Responders achieved a 30% decrease compared with baseline in weekly average of the worst abdominal pain in the past 24 h, and a 50% or greater reduction from baseline in the number of days/week with at least one stool of type 6 (mushy) or type 7 (watery) consistency. Secondary endpoints included changes from baseline in stool frequency, fecal urgency and fecal incontinence. Results: Enrolled patients ( n = 192) were primarily White (90.6%), with a mean age of 44.5 years. Patient and physician rating of IBS severity was between moderate and severe (85.9% concordance, Spearman coefficient 0.429, p < 0.0001). Alosetron 0.5 mg twice daily (82.8%) was the most common dosing regimen. A total of 152 alosetron-treated patients completed the study. Of 105 fully evaluable patients, 45% met the FDA composite endpoint responder criteria for ⩾50% of the study period. Improvements in all individual symptoms were statistically significant compared with baseline. There were no serious adverse events, cases of colonic ischemia, or complications of constipation. Conclusion: In a clinical practice setting study, alosetron demonstrated treatment success using a rigorous FDA composite endpoint and also improved multiple other IBS symptoms, including fecal urgency and incontinence in women with severe IBS-D [ ClinicalTrials.gov identifier: NCT01257477].

Background and Aims: Gastroparesis (GP) patients suffer from recurrent symptoms of nausea, vomiting, early satiety, and abdominal pain. The impact of GP on quality of life (QoL), health care utilization and daily activities is not well understood. Materials and Methods: Part 1: 398 adult patients (≥18 y) with documented GP (symptoms >6 mo) were surveyed to assess QoL and pain using the Short Form 36 and McGill pain questionnaires. Part 2: 491 adult GP patients were surveyed to evaluate employment status, work and daily activities, medication use, physician visits, diagnostic testing, emergency room visits, and hospitalizations related to their GP symptoms. Both protocols received Institutional Review Board approval. Results: Part 1: 250 fully evaluable surveys were returned (63%). The mean age was 46.8 years (range, 18 to 84 y); 78% were women. Mean Short Form 36 scores for mental health (56.9) and social functioning (68.1) were analogous to scores for patients with serious chronic medical disorders and depression. Pain scores were lower in patients with idiopathic GP compared with diabetic GP. Part 2: 228 evaluable surveys were analyzed (58.3% response rate). The mean age was 49.6 (19 to 86 y); 77.2% were women. GP symptoms reduced daily activities in 67.5% and lowered annual income in 28.5%. In total, 11% were disabled due to GP symptoms. Conclusions: GP reduces patients’ QoL and places a significant financial burden on the health care system. Treatment strategies for GP patients should be broad based and incorporate pain management, psychological evaluation and management, and strategies to improve overall well-being with a return to work and daily activities.

SummaryBackgroundObesity is associated with increased oesophageal acid exposure time (AET) in patients with gastro‐oesophageal reflux (GER), and may decrease the effects of proton pump inhibitors (PPIs).AimTo evaluate the effects of increased body mass on the ability of PPI therapy to decrease AET in patients with reflux symptoms.MethodsAcid exposure time profiles collected from adult patients using wireless pH‐metry while on or off PPI therapy was retrospectively reviewed. Patients were separated into five body mass index (BMI) categories as defined by the World Health Organization. A multivariable logistic regression evaluated the association between abnormal AET and BMI groups while controlling for age, gender and pH capsule placement methods.ResultsThe study group comprised 968 patients with 336 (34.7%) studied on a PPI and 632 (65.3%) studied off PPI therapy. AET (total greater than 5.3%) was found more frequently in the overweight (67%) and obese classes (74–80%) compared to those who were normal weight (40%) while off acid‐suppressing medications (P < 0.001). No significant differences were found between these groups when studied on acid‐suppressing medications, and the proportion of patients with abnormal AET across BMI classes was similar regardless of taking a PPI either once or twice daily.ConclusionsThis is the largest study to report on the relationship between BMI and oesophageal acid exposure time in patients with GER on and off PPI therapy. We conclude that obesity is related to increased acid exposure time, but with no significant difference in acid exposure time among different weight‐based groups when taking a once or twice‐daily PPI.

SummaryBackgroundFunctional dyspepsia (FD), a common functional gastrointestinal disorder, is defined by the Rome III criteria as symptoms of epigastric pain or discomfort (prevalence in FD of 89–90%), postprandial fullness (75–88%), and early satiety (50–82%) within the last 3 months with symptom onset at least 6 months earlier. Patients cannot have any evidence of structural disease to explain symptoms and predominant symptoms of gastroesophageal reflux are exclusionary. Symptoms of FD are non‐specific and the pathophysiology is diverse, which explains in part why a universally effective treatment for FD remains elusive.AimTo present current management options for the treatment of FD (therapeutic gain/response rate noted when available).ResultsThe utility of Helicobacter pylori eradication for the treatment of FD is modest (6–14% therapeutic gain), while the therapeutic efficacy of proton pump inhibitors (PPI) (7–10% therapeutic gain), histamine‐type‐2‐receptor antagonists (8–35% therapeutic gain), prokinetic agents (18–45%), tricyclic antidepressants (TCA) (response rates of 64–70%), serotonin reuptake inhibitors (no better than placebo) is limited and hampered by inadequate data. This review discusses dietary interventions and analyses studies involving complementary and alternative medications, and psychological therapies.ConclusionsA reasonable treatment approach based on current evidence is to initiate therapy with a daily PPI in H. pylori‐negative FD patients. If symptoms persist, a therapeutic trial with a tricyclic antidepressant may be initiated. If symptoms continue, the clinician can possibly initiate therapy with an anti‐nociceptive agent, a prokinetic agent, or some form of complementary and alternative medications, although evidence from prospective studies to support this approach is limited.