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ObjectiveTo compare efficacy of pharmacotherapies for chronic idiopathic constipation (CIC) based on comparisons to placebo using Bayesian network meta-analysis.Data sourcesWe conducted searches (inception to May 2015) of MEDLINE, EMBASE, Scopus and Cochrane Central, as well as original data from authors or drug companies for the medications used for CIC.Study selectionPhase IIB and phase III randomised, placebo-controlled trials (RCT) of ≥4 weeks' treatment for CIC in adults with Rome II or III criteria for functional constipation; trials included at least one of four end points.Data extraction and synthesisTwo investigators independently evaluated all full-text articles that met inclusion criteria and extracted data for primary and secondary end points, risk of bias and quality of evidence.OutcomesPrimary end points were ≥3 complete spontaneous bowel movements (CSBM)/week and increase over baseline by ≥1 CSBM/week. Secondary end points were change from baseline (Δb) in the number of SBM/week and Δb CSBM/week.ResultsTwenty-one RCTs (9189 patients) met inclusion and end point criteria: 9 prucalopride, 3 lubiprostone, 3 linaclotide, 2 tegaserod, 1 each velusetrag, elobixibat, bisacodyl and sodium picosulphate (NaP). All prespecified end points were unavailable in four polyethylene glycol studies. Bisacodyl, NaP, prucalopride and velusetrag were superior to placebo for the ≥3 CSBM/week end point. No drug was superior at improving the primary end points on network meta-analysis. Bisacodyl appeared superior to the other drugs for the secondary end point, Δb in number of SBM/week.ConclusionsCurrent drugs for CIC show similar efficacy. Bisacodyl may be superior to prescription medications for Δb in the number of SBM/week in CIC.

There is no universally available laboratory test to diagnose bile acid diarrhoea (BAD). ObjectiveTo conduct a systematic review and meta-analysis to identify a biomarker for idiopathic BAD in patients with functional bowel disorder (FBD) with diarrhoea.DesignWe searched multiple databases through 15 May 2015. Data were only available to estimate the diagnostic yield of each test (the prevalence of a positive test). Estimates were pooled across studies using the random effects model.ResultsWe included 36 studies, enrolling 5028 patients (24 using 75selenium homotaurocholic acid test (75SeHCAT) retention of <10%, 6 using fasting serum C4, 3 using fasting serum fibroblast growth factor 19 (FGF19) and 2 based on total faecal bile acid (BA) excretion over 48 h). The diagnostic yields (and 95% CI) of abnormal tests were: 0.308 (0.247 to 0.377) for 75SeHCAT retention (<10%), 0.171 (0.134 to 0.217) for serum C4, 0.248 (0.147 to 0.385) for serum FGF19 and 0.255 (0.071 to 0.606) for total faecal BA excretion over 48 h. The majority of the analyses were associated with substantial heterogeneity. Performance characteristics relative to a gold standard test could not be estimated.ConclusionsOverall, the test with the highest diagnostic yield conducted in the largest number of studies was 75SeHCAT retention, which is not widely available in many countries outside Europe and Canada. Using different diagnostic tests, 25% (average) of patients with lower FBD with diarrhoea has evidence of idiopathic BAD. These tests serve to identify idiopathic BAD among patients with FBD with diarrhoea. Further studies are required to appraise the performance characteristics of tests for idiopathic BAD.

Currently opioids are the most frequently used medications for chronic noncancer pain. Opioid-induced constipation is the most common adverse effect associated with prolonged use of opioids, having a major impact on quality of life. There is an increasing need to treat opioid-induced constipation. With the recent approval of medications for the treatment of opioid-induced constipation, there are several therapeutic approaches. This review addresses the clinical presentation and diagnosis of opioid-induced constipation, barriers to its diagnosis, effects of opioids in the gastrointestinal tract, differential tolerance to opiates in different gastrointestinal organs, medications approved and in development for the treatment of opioid-induced constipation, and a proposed clinical management algorithm for treating opioid-induced constipation in patients with noncancer pain.

Abstract Malnutrition is a very common and often underrecognized condition among patients with inflammatory bowel diseases (IBD). This is most commonly due to increased nutritional requirements and gastrointestinal losses, along with reduced oral intake. Screening for malnutrition is an essential component of managing both inpatients and outpatients with IBD. Although enteral nutrition is the preferred route of supplementation, parenteral nutrition (PN) remains an important strategy and should be considered in certain situations, such as cases with short-bowel syndrome, high-output intestinal fistula, prolonged ileus, or small-bowel obstruction. Appropriate use of PN is critical in order to prevent associated complications. This review addresses the common indications for use of PN, the composition of PN, and the possible complications encountered with PN use, as well as scenarios of inappropriate PN use among patients with IBD. A clinical management algorithm for utilizing PN among patients with IBD is proposed in this review. Lay Summary Malnutrition is common and underrecognized among patients with inflammatory bowel diseases (IBD). Screening for malnutrition is an essential component of IBD management. Although enteral nutrition is the preferred route of supplementation, parenteral nutrition (PN) should be considered in certain situations. Appropriate use of PN is critical to prevent associated complications.

BackgroundInflammatory bowel disease (IBD) has been associated with an increased risk of thromboembolic vascular complications. Although studies from the National Inpatient Sample (NIS) examined this association to some extent, sub-stratification for Crohn’s disease (CD) and ulcerative colitis (UC) in larger studies is lacking. The aims of this study were to utilize the NIS to determine the prevalence of thromboembolic events in inpatients with IBD compared to in patients without IBD and to explore the inpatient outcomes like morbidity, mortality, and resource utilization in patients with IBD and thromboembolic events as stratified by disease subtype.MethodsThis was a retrospective observational study using the NIS 2016. All patients with ICD10-CM codes for IBD were included. Patients with thromboembolic events were identified using diagnostic ICD codes and stratified into 4 categories: (1) Deep vein thrombosis (DVT), (2) Pulmonary embolism (PE), (3) Portal vein thrombosis (PVT), and (4) Mesenteric ischemia, which were then sub-stratified for CD and UC. The primary outcome was the inpatient prevalence and odds of thromboembolic events in patients with IBD compared to without IBD. Secondary outcomes were inpatient morbidity, mortality, resource utilization, colectomy rates, hospital length of stay (LOS), and total hospital costs and charges compared to patients with IBD and thromboembolic events.ResultsA total of 331,950 patients with IBD were identified, of who 12,719 (3.8%) had an associated thromboembolic event. For the primary outcome, after adjusting for confounders, inpatients with IBD had higher adjusted odds of DVT (aOR 1.59, p < 0.001), PE (aOR 1.20, p < 0.001), PVT (aOR 3.18, p < 0.001) and mesenteric ischemia (aOR 2.49, p < 0.001) compared to inpatients without IBD, an observation which was confirmed for both patients with CD and UC. Inpatients with IBD and associated DVT, PE and mesenteric ischemia had higher morbidity, mortality, odds of colectomy, cost, and charges.ConclusionsInpatients with IBD have higher odds of associated thromboembolic disorders compared to patients without IBD. Furthermore, inpatients with IBD and thromboembolic events have significantly higher mortality, morbidity, colectomy rates and resource utilization. For these reasons, increased awareness and specialized strategies for the prevention and management of thromboembolic events should be considered in inpatients with IBD.

Background The pentapeptide ghrelin agonist, relamorelin, accelerates colonic transit in patients with chronic constipation (CC). In a murine model, relamorelin decreased excitability of colonic circular smooth muscle cells and colonic intraluminal pressure. Aim To determine short-term effects of relamorelin on colonic motility measured by barostat and multilumen manometry in CC. Methods In a placebo-controlled, single-dose, double-blind, randomized study in patients with CC, we investigated the motor effects of relamorelin, 100 μg, SQ (12 patients) compared to placebo SQ (six patients). A motility-barostat balloon assembly was used to measure colonic compliance; tone and phasic pressure activity were measured before and after a 1000-kcal milkshake meal (administered ~60 min post-medication). Overall “background” phasic pressure activity was assessed by: average amplitude and motility index (MI = ln[sum amplitudes × #contractions + 1]) over defined periods. High-amplitude propagating contractions (HAPCs) were characterized by amplitude >75 mmHg and propagating contractions >50 mmHg; both were propagated over at least 10 cm. Postprandial HAPCs were the primary end point. The study sample had 80 % power to detect an increase of 3.3 HAPCs in the hour post-meal. Results Relamorelin, 100 μg, significantly induced more pre-meal propagated contractions [PCs of either >50 or >75 mmHg] compared to placebo ( p  < 0.05). Relamorelin also induced more post-meal PCs >50 or >75 mmHg than placebo. Relamorelin did not significantly alter colonic compliance, fasting or postprandial phasic pressure activity (20 min pre-meal fasting MI) or tone, and 60 min postprandial phasic pressure amplitude or MI, or tone. Conclusions Relamorelin stimulates propagated colonic contractions without alteration of background irregular contractions in CC. ClinicalTrial.Gov registration number: NCT 01781104.

ObjectiveNGM282 is an analog of fibroblast growth factor 19 (FGF19), a potent inhibitor of bile acid (BA) synthesis in animals and humans. In phase 2 trials in type 2 diabetes and primary biliary cholangitis, NGM282 was associated with dose-related abdominal cramping and diarrhea. We aimed to examine effects of NGM282 on colonic transit, stool frequency and consistency, hepatic BA synthesis (fasting serum C4), fecal fat, and BA in functional constipation (FC).MethodsTwo-dose NGM282 (1 and 6 mg, subcutaneously daily), parallel-group, randomized, placebo-controlled, 14-day study in patients with FC (Rome III criteria) and baseline colonic transit 24 h geometric center (GC) <3.0. We explored treatment interaction with SNPs in genes KLB, FGFR4, and TGR5 (GPBAR1). Statistical analysis: overall ANCOVA at α = 0.025 (baseline as covariate where available), with three pairwise comparisons among the three groups (α = 0.008).ResultsOverall, NGM282 altered bowel function (number of bowel movements, looser stool form, and increased ease of passage) and significantly accelerated gastric and colonic transit. Dose-related effects were seen with GC 24 h, but not with gastric emptying (GE) and GC 48 h. There were no differences in fecal fat or weight, but there was reduced fecal total BA excretion with NGM282. The most common adverse events were increased appetite (n = 0 with placebo, 2 with 1 mg, 9 with 6 mg), injection site reaction (n = 2 placebo, 4 with 1 mg, 8 with 6 mg), and diarrhea (n = 1 with 1 mg and 4 with 6 mg NGM282). There was treatment interaction with KLB SNP, with greater increase in colonic transit in participants with the minor A allele (p = 0.056).ConclusionNGM282 significantly impacts GE and colonic transit, consistent with the observed clinical symptoms. The specific mechanism of prokinetic activity requires further research.

H. pylori is the most common infection in the world and is associated with gastrointestinal and extra-gastrointestinal manifestations, including peptic ulcer disease, gastrointestinal bleeding, and lymphoproliferative disorders. Despite being discovered less than half a century ago, antibiotic resistance, exacerbated by medication non-adherence and inefficacy of proton pump inhibitors, has grown substantially, explaining the rising incidence of refractory H. pylori infection. In this review, we discuss risk factors, treatment options, surveillance and follow-up, as well as emerging therapies for refractory H. pylori.