Chang, Lin

Abstract Transition services—programs that support adolescents and young adults (AYAs) as they move from a child‐centered to a more autonomous, adult‐orientated healthcare system—have been associated with improved short‐ and long‐term healthcare outcomes. Unfortunately, there is a paucity of evidence exploring transition services within the neurogastroenterology and motility (NGM) field. The overall aim of this article, endorsed by the American Neurogastroenterology and Motility Society and European Society of Neurogastroenterology and Motility, is to promote a discussion about the role of transition services for patients with NGM disorders. The AYAs addressed herein are those who have: (a) a ROME positive disorder of gut–brain interaction (DGBI), (b) a primary or secondary motility disorder (including those with motility disorders that have been surgically managed), or (c) an artificial feeding requirement (parenteral or enteral tube feeding) to manage malnutrition secondary to categories (a) or (b). The issues explored in this position paper include the specific physical and psychological healthcare needs of patients with NGM disorders; key healthcare professionals who should form part of a secondary care NGM transition service; the triadic relationship between healthcare professionals, caregivers, and patients; approaches to selecting patients who may benefit most from transition care; methods to assess transition readiness; and strategies with which to facilitate transfer of care between healthcare professionals. Key areas for future research are also addressed, including the construction of NGM‐specific transition readiness questionnaires, tools to assess post‐transfer healthcare outcomes, and educational programs to train healthcare professionals about transition care in NGM.

INTRODUCTION: This post hoc analysis evaluated the efficacy of tenapanor on abdominal symptoms in patients with irritable bowel syndrome with constipation. Abdominal symptoms assessed included pain, discomfort, bloating, cramping, and fullness. METHODS: The abdominal symptom data were pooled from 3 randomized controlled trials (NCT01923428, T3MPO-1 [NCT02621892], and T3MPO-2 [NCT02686138]). Weekly scores were calculated for each abdominal symptom, and the Abdominal Score (AS) was derived as the average of weekly scores for abdominal pain, discomfort, and bloating. The overall change from baseline during the 12 weeks was assessed for each symptom weekly score and the AS. The AS 6/12-week and 9/12-week response rates (AS improvement of ≥2 points for ≥6/12- or ≥9/12-week) were also evaluated. The association of weekly AS response status (reduction of ≥30%) with weekly complete spontaneous bowel movement (CSBM) status (=0 and >0) was assessed. RESULTS: Among 1,372 patients (684 tenapanor [50 mg twice a day] and 688 placebo), the least squares mean change from baseline in AS was −2.66 for tenapanor vs −2.09 for placebo ( P < 0.0001). The 6/12-week AS response rate was 44.4% for tenapanor vs 32.4% for placebo ( P < 0.0001), and for 9/12-week AS, 30.6% for tenapanor vs 20.5% for placebo ( P < 0.0001). A significant association between weekly CSBM status and weekly AS response status was observed each week ( P < 0.0001), with a greater proportion achieving an AS reduction in patients with >0 CSBMs in a week. DISCUSSION: Tenapanor significantly reduced abdominal symptoms in patients with irritable bowel syndrome with constipation, particularly pain, discomfort, and bloating measured by AS, compared with placebo.

INTRODUCTION: Chronic idiopathic constipation (CIC) is a common disorder associated with significant impairment in quality of life. This clinical practice guideline, jointly developed by the American Gastroenterological Association and the American College of Gastroenterology, aims to inform clinicians and patients by providing evidence-based practice recommendations for the pharmacological treatment of CIC in adults. METHODS: The American Gastroenterological Association and the American College of Gastroenterology formed a multidisciplinary guideline panel that conducted systematic reviews of the following agents: fiber, osmotic laxatives (polyethylene glycol, magnesium oxide, lactulose), stimulant laxatives (bisacodyl, sodium picosulfate, senna), secretagogues (lubiprostone, linaclotide, plecanatide), and serotonin type 4 agonist (prucalopride). The panel prioritized clinical questions and outcomes and used the Grading of Recommendations Assessment, Development, and Evaluation framework to assess the certainty of evidence for each intervention. The Evidence to Decision framework was used to develop clinical recommendations based on the balance between the desirable and undesirable effects, patient values, costs, and health equity considerations. RESULTS: The panel agreed on 10 recommendations for the pharmacological management of CIC in adults. Based on available evidence, the panel made strong recommendations for the use of polyethylene glycol, sodium picosulfate, linaclotide, plecanatide, and prucalopride for CIC in adults. Conditional recommendations were made for the use of fiber, lactulose, senna, magnesium oxide, and lubiprostone. DISCUSSION: This document provides a comprehensive outline of the various over-the-counter and prescription pharmacological agents available for the treatment of CIC. The guidelines are meant to provide a framework for approaching the management of CIC; clinical providers should engage in shared decision making based on patient preferences as well as medication cost and availability. Limitations and gaps in the evidence are highlighted to help guide future research opportunities and enhance the care of patients with chronic constipation.

INTRODUCTION: Linaclotide improves abdominal pain and constipation in patients with constipation-predominant irritable bowel syndrome (IBS-C). Patients report additional bothersome abdominal symptoms of bloating and discomfort. The intention of this study was to evaluate linaclotide's efficacy in relieving IBS-C-related abdominal symptoms (bloating, discomfort, and pain) using a novel multi-item Abdominal Score (AS). METHODS: Patients with IBS-C with abdominal pain ≥3 (0–10 scale) were randomized to linaclotide 290 μg or placebo daily for 12 weeks. The AS, derived from the Diary for IBS Symptoms-Constipation, is the average of abdominal bloating, discomfort, and pain at their worst (0 = none, 10 = worst possible). The primary end point was overall change from baseline (CFB) in AS. Secondary end points included CFB in 12-week AS evaluated using cumulative distribution function and 6-week/12-week AS responder (AS improvement ≥2 points for ≥6-week/12-week). RESULTS: Overall, 614 patients (mean age 46.7 years; 81% female) were randomized. All prespecified end points showed significant benefit of linaclotide vs placebo. The mean overall CFB AS reduction for linaclotide was −1.9 vs −1.2 for placebo ( P < 0.0001); the 6-week/12-week AS responder rate was 40.5% for linaclotide vs 23.4% for placebo (odds ratio = 2.2 [95% confidence interval, 1.55–3.12; P < 0.0001]). Diarrhea was the most common treatment-emergent adverse event (linaclotide = 4.6%, placebo = 1.6%). DISCUSSION: Linaclotide significantly reduced multiple abdominal symptoms important to patients with IBS-C (bloating, discomfort, and pain) compared with placebo, as measured by a novel multi-item AS. The AS, derived from the Diary for IBS Symptoms-Constipation, should be considered for use in future IBS-C clinical studies to measure clinically meaningful improvements beyond traditional end points.

INTRODUCTION: Tegaserod was the first US Food and Drug Administration–approved drug for irritable bowel syndrome with constipation (IBS-C) in women and was recently reapproved for use. Recognizing that clinical trials were performed almost 20 years ago, we performed an integrated analysis on patient-reported outcomes relevant to current practice including previously unpublished data. METHODS: Data from 4 12-week, randomized, placebo-controlled trials evaluating tegaserod 6 mg b.i.d. in patients with IBS-C were pooled. We analyzed 2 groups: all women (overall population) and women younger than 65 years without a history of cardiovascular ischemic events (indicated population). The primary end point was subjective global assessment of IBS-C symptom relief. Responders rated themselves as “considerably” or “completely” relieved ≥50% of the time or at least “somewhat relieved” 100% of the time over the last 4 weeks. RESULTS: The overall and indicated populations included 2,939 (tegaserod [n = 1,478]; placebo [n = 1,461]) and 2,752 (tegaserod [n = 1,386]; placebo [n = 1,366]) participants, respectively. The pooled odds ratios (95% confidence interval) for clinical response during the last 4 weeks in the overall and indicated populations with tegaserod were 1.37 (1.18, 1.59; P < 0.001) and 1.38 (1.18, 1.61; P < 0.001). In the overall and indicated populations, clinical response rates for tegaserod during the last 4 weeks were 43.3% and 44.1% versus 35.9% and 36.5% with placebo ( P < 0.001). Adverse events were similar between groups. No significant cardiovascular events related to tegaserod were observed in patients with ≤1 cardiac risk factor. DISCUSSION: Tegaserod 6 mg b.i.d. reduced IBS-C symptoms in overall and US Food and Drug Administration–indicated populations (women aged <65 years with no history of cardiovascular ischemic events).

Background: Irritable bowel syndrome with diarrhea (IBS-D) is a prevalent gastrointestinal (GI) disorder with a varied presentation, often overlapping with other GI and non-GI disorders. Eluxadoline is a locally active mixed µ- and κ-opioid receptor agonist and δ-opioid receptor antagonist approved for the treatment of IBS-D in adults. As IBS-D is a heterogeneous disease, factors such as patient demographics, symptom severity, and symptom pattern history can potentially inform treatment selection. Methods: Here, we report additional prospectively planned analyses of two large double-blind, placebo-controlled studies (IBS-3001 and IBS-3002) enrolling patients meeting Rome III criteria for IBS-D. Patients were randomized 1:1:1 to receive placebo or eluxadoline 75 mg or 100 mg twice daily. Efficacy (abdominal pain, stool consistency, and composite, simultaneous improvement in both) and safety were assessed for prospectively defined patient subgroups stratified by age, sex, race, presence of comorbidities, and baseline disease characteristics. Results: Across all age, sex, race, comorbidity, and disease characteristic subgroups, a greater proportion of patients were composite responders with both eluxadoline doses as compared with placebo, including patients with a history of depression or a history of gastroesophageal reflux disease. Among patients aged ⩾65 years, a greater proportion of patients receiving eluxadoline 75 mg were composite, abdominal pain, and stool consistency responders compared with those receiving 100 mg. The proportion of patients with at least one adverse event was slightly higher in patients aged ⩾65 years and also in female patients. Conclusions: This analysis suggests that eluxadoline is effective in treating IBS-D across a range of commonly encountered patient types. In contrast to the overall population, patients aged ⩾65 years demonstrated a greater proportion of responders at the lower approved 75 mg eluxadoline dose.