IntroductionIrritable bowel syndrome (IBS) is the most prevalent of the functional gastrointestinal disorders (FGIDs). Current estimates are that IBS affects up to 10-12% of adults in North America (1,2). Although it can affect all individuals regardless of age, creed, or gender, IBS is more common among women and is most commonly diagnosed in younger individuals (< age 50) (2, 3). IBS is characterized by recurrent abdominal pain and altered bowel habits; bloating and distention frequently coexist. The diagnosis of IBS is made by taking a careful history, eliciting key symptoms, as well as performing a physical examination and limited diagnostic testing (4-6). IBS is categorized into four main subtypes based on the predominant bowel habit: IBS with constipation (IBC-C); IBS with diarrhea (IBS-D); IBS with mixed symptomology (IBS-M); and unclassified IBS (5).IBS imposes a significant burden to the health care system and to individuals.Direct medical costs attributed to IBS in the US, excluding prescription and over-thecounter medicines, were estimated at $1.5-$10 billion per year in 2005 (7). Patients with IBS enrolled in a large Health Maintenance Organization (HMO) had significantly more outpatient visits and incurred nearly 50% more in total costs than individuals without IBS (8). A retrospective case-control study from another large HMO reported that patients with IBS had significantly more diagnostic tests, imaging, and surgery compared with patients without a diagnosis of IBS (9). Significant variations in care across the United States related to the diagnosis and treatment of IBS also play a role in excessive health care costs (10). The burden of IBS on individuals can be measured in a number of ways. Studies have demonstrated consistently that IBS impairs work-related activities (e.g., lost work time, reduced productivity while at work) and also reduces quality of life (11,12). The development Ford et al.Page 3 of 91 of effective and efficient treatment strategies for IBS assumes considerable importance, therefore, not just for the individual sufferer, but for society at large.Given the clinical heterogeneity that is a hallmark of the disorder and the absence of a single effective therapy for all sufferers, available therapies tend to focus on predominant symptomatology at presentation (i.e., altered bowel habits, abdominal pain, or bloating) (4-6). Based on their purported mode of action, many pharmacological therapies for IBS developed in recent decades have been directed towards those with a particular bowel habit, whether diarrhea or constipation.However, treating IBS patients can be difficult as no validated treatment algorithm exists, not all patients respond to treatment, and patients with similar symptoms frequently respond to the same treatment differently. Fortunately, a variety of novel therapeutic strategies are being explored and new compounds have appeared since the last iteration of the ACG monograph on IBS (4). The goal of this document, therefore, is to provide an updated, evidence-based d...

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 (RCTs) 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 RCTs 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.

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 & AIMS It is not clear whether symptoms alone can be used to estimate the biologic activity of eosinophilic esophagitis (EoE). We aimed to evaluate whether symptoms can be used to identify patients with endoscopic and histologic features of remission. METHODS Between April 2011 and June 2014, we performed a prospective, observational study and recruited 269 consecutive adults with EoE (67% male; median age, 39 years old) in Switzerland and the United States. Patients first completed the validated symptom-based EoE activity index patient-reported outcome instrument and then underwent esophagogastroduodenoscopy with esophageal biopsy collection. Endoscopic and histologic findings were evaluated with a validated grading system and standardized instrument, respectively. Clinical remission was defined as symptom score <20 (range, 0 100); histologic remission was defined as a peak count of <20 eosinophils/ mm2 in a high-power field (corresponds to approximately <5 eosinophils/median high-power field); and endoscopic remission as absence of white exudates, moderate or severe rings, strictures, or combination of furrows and edema. We used receiver operating characteristic analysis to determine the best symptom score cutoff values for detection of remission. RESULTS Of the study subjects, 111 were in clinical remission (41.3%), 79 were in endoscopic remission (29.7%), and 75 were in histologic remission (27.9%). When the symptom score was used as a continuous variable, patients in endoscopic, histologic, and combined (endoscopic and histologic remission) remission were detected with area under the curve values of 0.67, 0.60, and 0.67, respectively. A symptom score of 20 identified patients in endoscopic remission with 65.1% accuracy and histologic remission with 62.1% accuracy; a symptom score of 15 identified patients with both types of remission with 67.7% accuracy. CONCLUSIONS In patients with EoE, endoscopic or histologic remission can be identified with only modest accuracy based on symptoms alone. At any given time, physicians cannot rely on lack of symptoms to make assumptions about lack of biologic disease activity in adults with EoE. ClinicalTrials.gov, Number: NCT00939263.

Background and Aim-Eosinophilic esophagitis (EoE) is characterized by medically/surgicallyresistant gastroesophageal reflux symptoms and dense squamous eosinophilia. Studies suggest that histological assessment of esophageal eosinophilia alone cannot reliably separate patients with EoE from those with gastroesophageal reflux disease (GERD). Our goal was to develop an assay to identify EoE patients and perhaps differentiate EoE from other causes of esophageal eosinophilia.

OBJECTIVES:In patients with celiac disease, enteropathy is caused by the entry of gluten peptides into the lamina propria of the intestine, in which their immunogenicity is potentiated by tissue transglutaminase (tTG) and T-helper type 1–mediated immune responses are triggered. Tight junction disassembly and paracellular permeability are believed to have an important role in the transport of gluten peptides to the lamina propria. Larazotide acetate is a tight-junction regulator peptide that, in vitro, prevents the opening of intestinal epithelial tight junctions. The aim of this study was to evaluate the efficacy and tolerability of larazotide acetate in protecting against gluten-induced intestinal permeability and gastrointestinal symptom severity in patients with celiac disease.METHODS:In this dose-ranging, placebo-controlled study, 86 patients with celiac disease controlled through diet were randomly assigned to larazotide acetate (0.25, 1, 4, or 8 mg) or placebo three times per day with or without gluten challenge (2.4 g/day) for 14 days. The primary efficacy outcome was the urinary lactulose/mannitol (LAMA) fractional excretion ratio. Secondary endpoints included gastrointestinal symptom severity, quality-of-life measures, and antibodies to tTG.RESULTS:LAMA measurements were highly variable in the outpatient setting. The increase in LAMA ratio associated with the gluten challenge was not statistically significantly greater than the increase in the gluten-free control. Among patients receiving the gluten challenge, the difference in the LAMA ratios for the larazotide acetate and placebo groups was not statistically significant. However, larazotide acetate appeared to limit gluten-induced worsening of gastrointestinal symptom severity as measured by the Gastrointestinal Symptom Rating Scale at some lower doses but not at the higher dose. Symptoms worsened significantly in the gluten challenge–placebo arm compared with the placebo–placebo arm, suggesting that 2.4 g of gluten per day is sufficient to induce reproducible gluten toxicity. Larazotide acetate was generally well tolerated. No serious adverse events were observed. The most common adverse events were headache and urinary tract infection.CONCLUSIONS:LAMA variability in the outpatient setting precluded accurate assessment of the effect of larazotide acetate on intestinal permeability. However, some lower doses of larazotide acetate appeared to prevent the increase in gastrointestinal symptom severity induced by gluten challenge.

The incidence of ischemic colitis and serious complications of constipation is very low and is rarely associated with long-term sequelae or serious morbidity.

Introduction There is limited literature comparing the experiences and attitudes of patients with chronic idiopathic constipation (CIC) to those of healthcare professionals (HCPs) treating CIC patients. The BURDEN-CIC study was conducted to better understand the experiences and ongoing needs of CIC patients and to assess their alignment versus disconnection with the perceptions and needs of HCPs who treat CIC patients.MethodsThe BURDEN-CIC study was an author-developed, online questionnaire that used KnowledgePanel® to survey individuals with CIC (n = 1223). HCPs who treat CIC patients were recruited separately and participated in a complementary online questionnaire (n = 331).ResultsMost patients had used (58%) or were using (51%) over-the-counter treatments for their CIC, with only 16% currently on prescription therapy. More than half (59%) of current CIC prescription users were not satisfied/completely satisfied with their current chronic treatment. Many patients (42%) felt frustrated regarding their CIC, and a similar percentage (40%) expressed acceptance that CIC was part of their daily life. The majority of HCPs agreed that CIC patients were frustrated (72%), stressed (50%), or fed up (43%) with current treatment options but were relatively unaware (21%) that patients were accepting of their CIC. HCPs reported the greatest challenges in treating CIC patients as response rates to current therapies (55%), treatment adherence (55%), management of treatment-related diarrhea (34%), and lack of treatment options (34%).ConclusionBURDEN-CIC identified that many patients and HCPs are frustrated and not satisfied with current CIC treatments due to lack of efficacy and side effects, such as diarrhea. The survey identified that many patients are “accepting” of their disease, potentially compromising treatment outcomes. More dialogue is needed between HCPs and CIC patients, especially regarding management of treatment expectations and side effects. Further, additional treatment options would be useful for both patients and HCPs.FundingSynergy Pharmaceuticals Inc.