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Prashant Singh,1 Gregory S Sayuk,2 David P Rosenbaum,3 Susan Edelstein,3 Kenji Kozuka,3 Lin Chang4 1Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA; 2Department of Medicine, Washington University School of Medicine, St Louis, MO, USA; 3Ardelyx, Inc, Waltham, MA, USA; 4Department of Medicine, David Geffen School of Medicine, UCLA, Los Angeles, CA, USACorrespondence: Prashant Singh, Department of Internal Medicine, University of Michigan, 1500 East Medical Center Drive, Ann Arbor, MI, 48109, USA, Tel +1 734 647 9252, Fax +1 734 936 9849, Email singhpr@med.umich.eduBackground: Patients with irritable bowel syndrome with constipation (IBS-C) experience persistent abdominal pain, a common symptom leading to greater healthcare utilization and reports of treatment non-response. Clinically significant improvements in abdominal pain were observed in clinical trials of tenapanor, a first-in-class inhibitor of sodium/hydrogen exchanger isoform 3 (NHE3), for the treatment of IBS-C in adults.Aim: This narrative review reports the current knowledge about visceral hypersensitivity as a mechanism for abdominal pain in patients with IBS-C and explores the published evidence for hypothesized mechanisms by which tenapanor may reduce visceral hypersensitivity leading to the observed clinical response of decreased abdominal pain.Findings: Abdominal pain is experienced through activation and signaling of nociceptive dorsal root ganglia that innervate the gut. These sensory afferent neurons may become hypersensitized through signaling of transient receptor potential cation channel subfamily V member 1 (TRPV1), resulting in reduced action potential thresholds. TRPV1 signaling is also a key component of the proinflammatory cascade involving mast cell responses to macromolecule exposure following permeation through the intestinal epithelium. Indirect evidence of this pathway is supported by observations of higher pain in association with increased intestinal permeability in patients with IBS. Tenapanor reduces intestinal sodium absorption, leading to increased water retention in the intestinal lumen, thereby improving gastrointestinal motility. In animal models of visceral hypersensitivity, tenapanor normalized visceromotor responses and normalized TRPV1-mediated nociceptive signaling.Conclusion: By improving gastrointestinal motility, decreasing intestinal permeability and inflammation, and normalizing nociception through decreased TRPV1 signaling, tenapanor may reduce visceral hypersensitivity, leading to less abdominal pain in patients with IBS-C. Therapies that have demonstrated effects on visceral hypersensitivity may be the future direction for meaningful abdominal pain relief for patients with IBS-C.Keywords: IBS-C, NHE3, abdominal pain, TRPV1, sodium absorption, intestinal permeability

OBJECTIVE Initial treatment with antidepressant medication is insufficiently effective in some patients with type 2 diabetes, and factors predicting treatment outcome are poorly understood. RESEARCH DESIGN AND METHODS Aggregate data from two published trials were analyzed to determine the rates and predictors of response to antidepressant pharmacotherapy in adults with type 2 diabetes using conventional markers of initial treatment outcome (improvement, response, partial remission, and remission). Three hundred eighty-seven patients who received up to 16 weeks of open-label, acute-phase treatment using bupropion (n = 93) or sertraline (n = 294) were studied. Logistic regression was used to identify predictors of poor treatment outcome. Candidate predictors included age, race, sex, initial Beck Depression Inventory (iBDI) score, treatment received (sertraline or bupropion), family history of depression, extant diabetes complications (eDC), and A1C level. RESULTS Of 387 patients initiated on treatment, 330 (85.3%) met criteria for improvement, 232 (59.9%) for response, 207 (53.5%) for partial remission, and 179 (46.3%) for full remission. Significant independent predictors of poor outcome included eDC (for no improvement); sertraline treatment, eDC, and younger age (for nonresponse); sertraline treatment, eDC, and higher iBDI (for failure to partially remit); and younger age and higher iBDI (for failure to fully remit). Higher pain scores predicted three of the four markers of poor outcome in the subset with pain data. CONCLUSIONS In patients with type 2 diabetes, poor initial response to antidepressant medication is predicted by multiple factors. Auxiliary treatment of pain and impairment may be required to achieve better outcomes. [ABSTRACT FROM AUTHOR]

Background: Bloating is a bothersome symptom in irritable bowel syndrome with constipation (IBS-C)., Aim: To evaluate plecanatide efficacy in patients with IBS-C stratified by bloating intensity., Methods: Pooled phase 3 data (2 randomized, controlled IBS-C trials) from adults treated with plecanatide 3 mg or placebo for 12 weeks were analyzed. Patients were stratified post-hoc by baseline bloating severity (11-point scale: mild [≤ 5] and moderate-to-severe [> 5]). Assessments included change from baseline in bloating, abdominal pain, and complete spontaneous bowel movement (CSBM) frequency. Abdominal pain and bloating composite responders were defined as patients with ≥ 30% improvement from baseline in both bloating and abdominal pain at Week 12., Results: At baseline, 1104/1436 patients with IBS-C (76.9%) reported moderate-to-severe bloating. In the moderate-to-severe bloating subgroup, plecanatide significantly reduced bloating severity versus placebo (least-squares mean change [LSMC]: - 1.7 vs - 1.3; P = 0.002), reduced abdominal pain (- 1.7 vs - 1.3; P = 0.006), and increased CSBM frequency (1.4 vs 0.8; P < 0.0001). In the mild bloating subgroup, significant improvements were observed with plecanatide versus placebo for abdominal pain (LSMC: - 1.3 vs - 1.0; P = 0.046) and CSBM frequency (2.0 vs 1.2; P = 0.003) but not bloating (- 0.9 vs - 0.8; P = 0.28). A significantly greater percentage of patients were abdominal pain and bloating composite responders with plecanatide versus placebo (moderate-to-severe bloating: 33.6% vs 26.8% [P = 0.02]; mild bloating: 38.4% vs 27.2% [P = 0.03])., Conclusion: Plecanatide treatment improved IBS-C abdominal and bowel symptoms, including in those who present with moderate-to-severe bloating., (© 2024. The Author(s).)

Background & Aims: Anorectal manometry (ARM) is a comprehensive diagnostic tool for evaluating patients with constipation, fecal incontinence, or anorectal pain; however, it is not widely utilized for reasons that remain unclear. The aim of this roundtable discussion was to critically examine the current clinical practices of ARM and biofeedback therapy by physicians and surgeons in both academic and community settings., Methods: Leaders in medical and surgical gastroenterology and physical therapy with interest in anorectal disorders were surveyed regarding practice patterns and utilization of these technologies. Subsequently, a roundtable was held to discuss survey results, explore current diagnostic and therapeutic challenges with these technologies, review the literature, and generate consensus-based recommendations., Results: ARM identifies key pathophysiological abnormalities such as dyssynergic defecation, anal sphincter weakness, or rectal sensory dysfunction, and is a critical component of biofeedback therapy, an evidence-based treatment for patients with dyssynergic defecation and fecal incontinence. Additionally, ARM has the potential to enhance health-related quality of life and reduce healthcare costs. However, it has significant barriers that include a lack of education and training of healthcare providers regarding the utility and availability of ARM and biofeedback procedures, as well as challenges with condition-specific testing protocols and interpretation. Additional barriers include understanding when to perform, where to refer, and how to use these technologies, and confusion over billing practices., Conclusions: Overcoming these challenges with appropriate education, training, collaborative research, and evidence-based guidelines for ARM testing and biofeedback therapy could significantly enhance patient care of anorectal disorders., (Copyright © 2023 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Constipation is frequently encountered in hospital settings and can have potentially serious consequences yet is often underrecognized and undertreated. Opioid-induced constipation is a common cause of constipation in hospitalized patients. Opioids induce constipation through agonistic effects on enteric µ-opioid receptors. This review aims to provide insight on the identification and management of constipation in inpatient settings, with a particular focus on opioid-induced constipation. Constipation assessment should be routinely initiated at hospital admission and can be facilitated by thorough symptom assessments; relevant patient history, including recent medication use; physical examination; and patient assessment tools developed to evaluate the impact of constipation. Management of opioid-induced constipation should begin with ensuring adequate hydration and electrolyte balance and encouraging patient mobilization. Other treatments may include laxatives, enemas, intestinal secretagogues, peripherally acting µ-opioid receptor antagonists, and manual disimpaction. Surgical intervention may be required for some patients as a salvage therapy in severe, refractory cases.

Purpose: Rifaximin is indicated for the treatment of irritable bowel syndrome with diarrhea (IBS-D) in adults. The current aim was to evaluate rifaximin efficacy on individual and composite IBS-D symptoms using definitions not previously examined., Methods: Phase III post hoc analyses of two randomized, double-blind, placebo-controlled trials and the open-label phase of a randomized, double-blind, placebo-controlled trial were conducted. Adults with IBS-D received a 2-week course of rifaximin 550 mg TID. Individual and composite responses for abdominal pain (mean weekly improvements from baseline of ≥30%, ≥40%, or ≥50%), bloating (mean weekly improvements from baseline of ≥1 or ≥2 points; or ≥30%, ≥40%, or ≥50%), stool consistency (mean weekly average stool consistency score <3 or <4), and urgency (improvement from baseline of ≥30% or ≥40% in percentage of days with urgency) for ≥2 of the first 4 weeks after treatment, and weekly for 12 weeks, were assessed., Findings: Overall, 1258 patients from the double-blind trials (rifaximin [n = 624]; placebo [n = 634]) and 2438 from an open-label trial were analyzed. The percentage of bloating or urgency responders was significantly greater with double-blind rifaximin versus placebo (P ≤ 0.03). A significantly greater percentage of the double-blind group were composite abdominal pain and bloating responders versus placebo for all thresholds analyzed (P < 0.05). A significantly greater percentage of the double-blind group were tri-symptom composite end point responders (abdominal pain, bloating, and fecal urgency) versus placebo (P = 0.001). A significantly greater percentage of patients achieved response (≥30% composite tri-symptom threshold) with double-blind rifaximin versus placebo as early as 1 week posttreatment, with significance maintained through ≥5 weeks after treatment. Open-label results were consistent with those of the double-blind study., Implications: Rifaximin significantly improved multiple, concurrent IBS-D symptoms, using clinically relevant definitions of treatment response. Using a novel tri-symptom composite end point (ie, abdominal pain, bloating, fecal urgency), adults with IBS-D treated with a 2-week course of rifaximin were significantly more likely to be composite end point responders than those receiving placebo (≥30% or ≥40% threshold) for the three symptoms. Thus, rifaximin not only met current standard thresholds used for adjudication of responders in clinical trials but also achieved higher thresholds for many of these symptoms, suggesting potential for even more robust clinical improvements., Clinicaltrials: gov identifiers: NCT00731679, NCT00724126, and NCT01543178., Competing Interests: Declaration of Interest The study sponsor was involved in the study design and data collection. Dr Lacy reports serving as a scientific advisory board member for Allakos Inc, AlphaSigma USA, Inc, Arena Pharmaceuticals, Ironwood Pharmaceuticals, Inc, and Salix Pharmaceuticals. Dr Chang reports serving as an advisory board member or consultant for Ardelyx, Arena Pharmaceuticals, Bausch Health, Immunic, Ironwood Pharmaceuticals, Inc, Mauna Kea Technologies, and Trellus; and receiving grant support from AnX Robotica, Arena Pharmaceuticals, and Ironwood Pharmaceuticals. Dr Rao reports receiving research funding from Salix Pharmaceuticals. Dr Heimanson is an employee of Salix Pharmaceuticals. Dr Sayuk reports serving as a consultant for AbbVie and Ironwood Pharmaceuticals, Inc; and serving on the speakers’ bureau for AbbVie, Ironwood Pharmaceuticals, Inc, and Salix Pharmaceuticals., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background/aims: Cyclic vomiting syndrome (CVS) is characterized by episodes of nausea and vomiting, separated by symptom-free intervals. The pathogenesis of CVS is poorly understood. Limited data exist on evaluating impaired gastric accommodation as a mechanistic means for symptoms. We aim to determine if CVS patients demonstrate impaired gastric accommodation applying a nutrient drink test (NDT) protocol., Methods: Through this single-blinded pilot clinical trial, patients with CVS per Rome IV critera and healthy controls were assessed for presence of impaired gastric accommodation by administering an established NDT protocol. Statistical analysis was performed, with data presented as medians and interquartile range., Results: Eleven CVS patients and 15 healthy controls participated in the study between January 2018 and October 2018. Median age was 42.0 years and 37.0 years; majority of subjects were female, 72.7% and 73.3%, respectively. Demographics were similar between CVS and healthy controls. Almost all healthy controls (93.3%) ingested the complete 500 mL protocol, whereas a smaller proportion (72.7%) were able to complete all 4 doses in the CVS group ( P = 0.188). Post-prandial visual analogue scale scores of nausea and abdominal pain were found to be significantly higher in CVS patients compared to healthy controls., Conclusions: To our knowledge, this is the first NDT protocol in CVS evaluating the role of impaired gastric accommodation and hypersensitivity as a possible pathophysiologic mechanism. Findings from this study suggest the presence of gastric hypersensitivity in a subset of CVS patients. These results provide the foundational data necessary for future larger testing of NDT and diagnostic accuracy in CVS.

Gallbladder dyskinesia is a functional disorder of the gastrointestinal tract, which can result in debilitating episodes of abdominal pain and associated symptoms. Key diagnostic criteria include a diminished gallbladder ejection fraction on scintigraphy and absence of other causes for the symptoms. Pathologic findings and follow-up suggest a distinct mechanistic basis for this condition. Unfortunately, the complexities of diagnosis and treatment combined with patient and provider preferences will likely continue to preclude randomized controlled studies to provide a clearer evidence-based management for this disorder. Patients meeting the clinical and diagnostic criteria for gallbladder dyskinesia should be referred for cholecystectomy, and most of these patients will have relief of their symptoms. A comprehensive preoperative discussion on expected outcomes needs to take place.

Objective: Posttraumatic stress symptoms (PTSS) have been associated with increased somatic symptom expression. Sleep concerns have been associated with PTSS and somatic symptoms. Previous research suggests that sleep affects multiple domains of functioning including comorbid psychological and physical health concerns. The current study examines whether perceived sleep quality or sleep efficiency/duration may be mediating the relationship between PTSS and somatic symptoms in a trauma-exposed sample., Method: The sample consisted of 864 students, recruited from a large Midwestern university and compensated with research participation credit. Data were collected online over approximately 39 months (October 2015 through January 2019), and the pertinent scales examined in this study included Pittsburgh Sleep Quality Index, Posttraumatic Stress Disorder Checklist for Diagnostic and Statistical Manual of Mental Disorders , fifth edition, and Screening for Somatoform Symptoms-7., Results: Of the 864 students, 668 participants identified as female (77.3%) and 540 identified as non-Hispanic White (62.5%), with an overall average age of 23.14 years ( SD = 6.64). Mediation analyses indicated that the overall model examining global sleep quality complaints as a mechanism of the relationship between PTSS and somatic symptoms was significant, F (3, 860) = 193.97, R ² = .40, p < .001, and that perceived sleep quality was found to be the only significant specific mediator (indirect effect = .21). Although females reported greater somatic severity, PTSS, and sleep concerns, models were significant, even after examining the influence of gender., Conclusions: Global sleep complaints are associated with both PTSS and somatic symptoms. Perceived sleep quality specifically mediated the relationship between PTSS and somatic symptoms, highlighting a potential intervention for improving physical health consequences in trauma-exposed individuals. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Irritable bowel syndrome with constipation (IBS-C) and chronic idiopathic constipation (CIC) are common gastrointestinal disorders imposing considerable impact on the quality of life and well-being of affected individuals. A paucity of evidence-based treatment options exist for CIC and IBS-C sufferers. Tegaserod, a 5-HT 4 agonist, has a substantial body of preclinical and clinical study evidence to support its beneficial role in modulating sensorimotor function of the luminal gastrointestinal tract. Tegaserod was first approved for use by the U.S. Food and Drug Administration for the management of IBS-C and CIC in 2002 and 2004, respectively. Tegaserod enjoyed a successful uptake in the management of these disorders during its first several years of availability in the United States, but was later withdrawn from the market in 2007 over concerns related to adverse cardiovascular events. Since then, additional safety data has been generated, and following a resubmission and review by the Food and Drug Administration, in April 2019, tegaserod was once again approved for use in IBS-C under a more restricted labeling, confining use to women under 65 years of age without heart disease or additional cardiovascular risk factors. This review summarizes the regulatory journey of tegaserod and details the existing pharmacokinetic, physiologic, clinical, and safety data of tegaserod generated over the last 2 decades. The discussion also examines the future of tegaserod in the treatment of these constipation disorders, as well as its potential role in other related disorders of brain-gut interaction., (Copyright © 2022 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Irritable bowel syndrome with diarrhea (IBS-D) is a chronic disorder of gut-brain interaction, characterized by recurrent abdominal pain in association with more frequent, loose stools. The pathophysiology of irritable bowel syndrome (IBS) includes disordered gut motility, alterations in gut microbiota, neural-hormonal system abnormalities, immune reactivity, and visceral hypersensitivity. Timely diagnosis of IBS-D can be achieved easily using clinical criteria. Formal IBS diagnosis is important for optimizing treatment and patient outcomes and facilitating patient access to appropriate educational resources. Yet, given the symptom overlap with other gastrointestinal conditions, diagnosis of IBS-D often is perceived to be challenging. Treatment of IBS includes both nonpharmacologic and pharmacologic options. Rifaximin, alosetron, and eluxadoline are effective treatments indicated for IBS-D, but have limited availability internationally. Dietary approaches may also be indicated for certain patients with IBS-D. Psychological interventions may be effective in treating abdominal pain alone and global symptoms in IBS. We describe use of these diverse therapies and provide an overview to facilitate the primary care provider's approach to distinguishing IBS-D from other conditions with symptom overlap., (© 2022. The Author(s).)

Objective: Some IBS patients possess detailed memories of the events surrounding their bowel symptom onset ("episodic memories"). In this exploratory study we sought to: (1) examine memory relationship with gastrointestinal (GI) symptom severity, extraintestinal symptoms, and mood; (2) qualitatively explore memory valence and content in IBS patients with or without episodic memories., Methods: Referral IBS patients n = 29; age 47.0± 2.2 years, 79.3% female) enrolled in this cross-sectional, mixed methods research study. Participants completed validated specific memory instruments [Autobiographical Memory Test (AMT), Sentence Completion for Events from the Past Test (SCEPT)] and relevant questionnaires [IBS symptoms 10-cm visual analog scale); SF-36 Health-related quality of life (HRQOL); Perley-Guze and PHQ-15/12: somatization; Beck Depression/Anxiety Inventories). Qualitative analysis examined the content and valence of general memories., Results: 14/29 (48.3%) of IBS subjects endorsed episodic memories of IBS symptom onset, often GI infections/enteritis (35.7%). Recall of the exact year (69%) and month (60%) of symptom onset were common. Episodic memories were associated with greater IBS symptom severity/bother, higher anxiety/depression, and poorer HRQOL. Though AMT and SCEPT memory specificity were not different based on episodic memories, overgeneralization to negatively-valenced cues in the AMT was associated with more severe IBS in those without episodic memory. Qualitative analysis revealed no observable differences in topic focus of IBS patients with and without episodic memories., Conclusions: IBS patients often endorse episodic memories associated with symptom onset, and this recall seems to associate with more severe symptoms. Overgeneralization responses to negative stimuli may lead to worse bowel symptoms in those without episodic memories. IBS memory specificity may associate with qualitative differences in processing psychosocial experiences and might be important to IBS pathophysiology., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Sayuk, North, Pollio, Gott and Alpers.)

Background: Detection and removal of colonic adenomatous polyps (CAP) decreases colorectal cancer (CRC) development, particularly with more or larger polyps or polyps with advanced villous/dysplastic histology. Immunosuppression following solid organ transplantation (SOT) may accelerate CAP development and progression compared to average-risk population but the benefit of earlier colonoscopic surveillance is unclear., Aims: Study the impact of maintenance immunosuppression post-SOT on developmental timing, multiplicity and pathological features of CAP, by measuring incidence of advanced CAP (villous histology, size ≥ 10 mm, ≥ 3 polyps, presence of dysplasia) post-SOT and the incidence of newly diagnosed CRC compared to average-risk age-matched population., Methods: Single-center retrospective cohort study of SOT recipients., Results: 295 SOT recipients were included and were compared with 291 age-matched average-risk controls. The mean interval between screening and surveillance colonoscopies between SOT and control groups was 6.3 years vs 5.9 years (p = 0.13). Post-SOT maintenance immunosuppression mean duration averaged 59.9 months at surveillance colonoscopy. On surveillance examinations, SOT recipients exhibited more advanced (≥ 10 mm) adenomas compared to matched controls (9.2% vs. 3.8%, p = 0.034; adjusted OR 2.38; 95% CI 1.07-5.30)., Conclusion: SOT recipients appear at higher risk for developing advanced CAP, suggesting that earlier surveillance should be considered., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Chronic idiopathic constipation and irritable bowel syndrome with constipation are complex, overlapping conditions. Although multiple guidelines have informed healthcare providers on appropriate treatment options for patients with chronic idiopathic constipation and irritable bowel syndrome with constipation, little direction is offered on treatment selection. First-line treatment options usually include fiber and over-the-counter osmotic laxatives; however, these are insufficient for many individuals. When these options fail, prescription secretagogues (plecanatide, linaclotide, lubiprostone, and tenapanor [pending commercial availability]), or serotonergic agents (prucalopride and tegaserod) are generally preferred. Individuals experiencing concurrent abdominal pain and/or bloating may experience greater overall improvements from prescription therapies because these agents have been proven to reduce concurrent abdominal and bowel symptoms. Should initial prescription treatments fail, retrying past treatment options (if not adequately trialed initially), combining agents from alternative classes, or use of adjunctive therapies may be considered. Given the broad spectrum of available agents, therapy should be tailored by mutual decision-making between the patient and practitioner. Overall, patients need to be actively monitored and managed to maximize clinical outcomes., (Copyright © 2022 by The American College of Gastroenterology.)

Multiple therapeutic agents are currently available for the treatment of chronic idiopathic constipation and irritable bowel syndrome with constipation. A better understanding of the mechanism of action of each treatment provides important insights into expected responses and is key to optimizing treatment outcomes. Some constipation treatments, such as stimulant laxatives, may increase bowel movement frequency but are ineffective at relieving, and may even exacerbate, abdominal symptoms. On the contrary, prescription treatments, such as the guanylyl cyclase-C agonists, for example, may improve bowel symptoms and reduce visceral hypersensitivity. This review summarizes the mechanisms of action of commonly used over-the-counter and prescription therapies for chronic idiopathic constipation and irritable bowel syndrome with constipation, outlining how these mechanisms contribute to the efficacy and safety of each treatment option., (Copyright © 2022 by The American College of Gastroenterology.)

Disorders of defecation, including constipation and fecal incontinence, are very common. The digital rectal examination (DRE) is a key component in the early evaluation of patients with these complaints. Confident performance of a DRE requires dedicated training for the clinician and hands-on experience with the technique. DRE can yield a diagnostic accuracy comparable to specialized physiologic tests, including anorectal manometry. This review will describe in detail the steps required to perform a thorough DRE evaluation, as well as the proper interpretation of observations. Thereafter, the current evidence-based findings supporting the value of DRE in defecatory disorders will be summarized., (Published by Elsevier Inc.)

Introduction: Irritable bowel syndrome (IBS) is a symptom-based disorder of chronic abdominal pain and altered bowel habits. The pathogenesis of IBS is multifactorial, leading to the potential for the development of diverse treatment strategies. This mechanistic heterogeneity suggests that available therapies will only prove effective in a subset of IBS sufferers. Current US Food and Drug Administration (FDA) approved therapies for IBS with diarrhea (IBS-D) and IBS with constipation (IBS-C) are reviewed. Limited symptom responses and side effect experiences lead to considerable patient dissatisfaction with currently available IBS treatments. Only a small percentage of IBS patients are on prescription therapies underscoring the potential market and need for additional therapeutic options., Areas Covered: Expanding on currently available therapies, the serotonergic and endogenous opioid receptor systems continue to be a focus of future IBS treatment development. Additional novel emerging therapies include the endogenous cannabinoid system, bile acid secretion and sequestration, and exploit our enhanced understanding of visceral sensory signaling and intestinal secretomotor function., Expert Opinion: While challenges remain for the future development of IBS therapies, the diverse etiologies underlying the disorder present an opportunity for novel therapies. Hence, great potential is anticipated for future IBS treatment options.

Diarrhea-predominant irritable bowel syndrome is a common functional gastrointestinal disorder that manifests with abdominal pain and diarrheal bowel patterns, without structural explanation. Diarrhea-predominant irritable bowel syndrome is a heterogeneous condition resulting from diverse pathophysiologic processes. Treatment strategies with varied mechanisms of action are beneficial in its management. The clinician must become familiar with a multi-dimensional approach to irritable bowel syndrome. The 3 approved medications are central to disease management. Effective treatment uses off-label medications and emerging therapies and a growing number of over-the-counter and supplemental agents to optimize symptom improvement for the patient with diarrhea-predominant irritable bowel syndrome., Competing Interests: Disclosure Dr G.S. Sayuk is a speaker and consultant for Salix, Allergan, Ironwood, and Alnylam, and is a speaker for the GI Health Foundation., (Copyright © 2021 Elsevier Inc. All rights reserved.)

BACKGROUND: Irritable bowel syndrome with diarrhea (IBS-D) is a chronic disorder of gut-brain interaction that negatively affects work productivity and health-related quality of life (HRQOL). IBS-D therapeutic options are limited and include loperamide, an over-the-counter μ-opioid receptor agonist commonly used as an antidiarrheal agent, and eluxadoline, a mixed μ- and κ-opioid receptor agonist and δ-opioid receptor antagonist approved in the United States for the treatment of IBS-D in adults. OBJECTIVE: To characterize the effect of eluxadoline on work productivity and HRQOL in patients with IBS-D with previous inadequate response to loperamide. METHODS: The Work Productivity and Activity Impairment Questionnaire for IBS-D (WPAI:IBS-D), Centers for Disease Control and Prevention Healthy Days Core Module (CDC HRQOL-4), and EuroQoL-5 Dimension (EQ-5D) instruments were administered at baseline and week 12 of a phase 4 clinical trial (RELIEF), assessing the efficacy and safety of eluxadoline treatment in adults with IBS-D reporting previous inadequate response to loperamide. Changes from baseline to week 12 for each assessment were evaluated using an analysis of covariance model. Indirect costs were calculated by converting overall work productivity losses into monetary values. RESULTS: A total of 346 patients were randomized to either eluxadoline (n = 172) or placebo (n = 174). From baseline to week 12, compared with placebo, twice-daily treatment with eluxadoline resulted in significantly greater reductions in absenteeism (2.6%; P = 0.046). Numerically greater decreases in presenteeism, overall work productivity loss, and daily activity impairment were also observed in patients receiving eluxadoline compared with those receiving placebo ( P = not significant for each). Numerical reductions in overall work productivity loss from baseline to week 12 translate to approximately 2.4 hours per patient per week (123 hours annually) and correspond to an avoided overall work loss of $4,503 annually for an employee with IBS-D treated with eluxadoline. In addition, from baseline to week 12, treatment with eluxadoline led to a significantly greater reduction in the number of unhealthy days experienced (-1.7 days; P = 0.042), as well as numerical improvements in EQ-5D measures in comparison with placebo ( P = not significant for each). CONCLUSIONS: In patients with IBS-D reporting inadequate response to loperamide, eluxadoline treatment was associated with significant reductions in absenteeism and the number of unhealthy days experienced. Eluxadoline treatment of IBS-D may lead to significant cost savings via mitigation of losses in work productivity. DISCLOSURES: This study was sponsored by Allergan plc (before acquisition by AbbVie, Inc.). Allergan plc and/or AbbVie, Inc., was involved in the study design, collection, analysis, interpretation of the data, writing of the report, and the decision to submit the report for publication. Abel and Burslem are employees of AbbVie, Inc., and own stock/stock options. Brenner has served as a consultant, speaker, and/or advisor for Allergan plc (before acquisition by AbbVie, Inc.), Alnylam, Alpha Sigma, Arena, Bayer, Ironwood Pharmaceuticals, Salix Pharmaceuticals, Shire, Synergy, and Takeda Pharmaceuticals. He is also supported in research by an unrestricted gift from the Irene D. Pritzker Foundation. Sayuk has served as a consultant and speaker for Allergan plc (before acquisition by AbbVie, Inc.), Gi Health Foundation, Ironwood Pharmaceuticals, Salix Pharmaceuticals, and Synergy. Portions of the current work were presented at AMCP Nexus; October 22-25, 2018; Orlando, FL.

Functional gastrointestinal disorders (FGIDs), characterized by chronic abdominal complaints without a structural or biochemical cause, are common diseases that are frequently encountered by specialists in internal medicine. Collectively, irritable bowel syndrome (IBS) and functional dyspepsia are estimated to affect up to 22% of the population, and are often associated with additional somatic and pain complaints, all without an obvious structural source [1,2]. An appreciation of the current understanding of the mechanistic basis for these disorders is key to developing treatment goals and optimization of patient management strategies. In recent years, the brain-gut axis increasingly has been recognized as a central factor in the experience of functional abdominal pain disorders, including the most recent Rome IV guidelines which identify FGIDs as disorders of gut-brain interaction [3]. The brain-gut axis (BGA), simply defined, is a complex network of bidirectional communication between the central and enteric nervous systems. This axis broadly includes all the systems involved with communication between the GI tract and central nervous system (CNS), with principle inputs into this network occurring between the CNS, enteric nervous system (ENS), and autonomic nervous systems (ANS), but also includes interfaces with numerous other factors, including endocrine hormones and immune effector cells as well as interactions with the gut microbiota. Perturbances to this system have been found to play a critical role in the development of visceral hypersensitivity, bowel dysregulation, and mood. This review will summarize the principle processes involved in the neurologic and biologic function of the brain-gut axis, our current understanding of its role in functional GI disorders, and potential targets for therapeutic intervention., (Published by Elsevier B.V.)

Introduction: Immediate-release (IR) formulation of linaclotide 290 μg improves abdominal pain and constipation (APC) in patients with irritable bowel syndrome (IBS) with constipation. Delayed-release (DR) formulations were developed on the premise that targeting the ileum (delayed-release formulation 1 [DR1]) or ileocecal junction and cecum (MD-7246, formerly DR2) would modulate linaclotide's secretory effects while preserving pain relief effects., Methods: This phase 2b study randomized patients with IBS with constipation to placebo or 1 of 7 once-daily linaclotide doses (DR1 30, 100, or 300 μg; MD-7246 30, 100, or 300 μg; or IR 290 μg) for 12 weeks. Key efficacy endpoints were change from baseline in abdominal pain and complete spontaneous bowel movement frequency, and 6/12-week combined APC+1 responder rate., Results: Overall, 532 patients were randomized; mean age was 45.1 years, and most were women (83.3%) and White (64.7%). All linaclotide DR1 and MD-7246 groups experienced greater improvements in abdominal pain from baseline and vs placebo throughout treatment. Linaclotide DR1 and IR led to numerically greater improvements from baseline in complete spontaneous bowel movement frequency and higher APC+1 responder rates compared with placebo; MD-7246 results were similar to placebo. Diarrhea was the most common adverse event with DR1 and IR; rates were similar between MD-7246 and placebo., Discussion: Altering the site of drug delivery in the intestine might uncouple linaclotide's pain relief from secretory effects. Persistent, modest abdominal pain improvement with limited impact on bowel symptom parameters, as seen across MD-7246 doses, warrants further study of MD-7246 as a novel treatment for abdominal pain, regardless of IBS subtype., (Copyright © 2020 by The American College of Gastroenterology.)

Introduction: Text message-based interventions reduce colonoscopy no-show rates and improve bowel preparation scores. In this non-randomized study, we assessed whether an interactive text messaging system could improve colonoscopy outcomes., Methods: Colonoscopy pre-procedural instructions were programmed into a dedicated software platform created for this study. In the intervention arm, text messages were sent to veterans during a 4-week study period. Validated pre-procedural satisfaction questionnaires were completed by patients during standard protocol and intervention periods. Demographics and colonoscopy outcomes data were compared between the standard protocol and intervention arms, including procedure completion rate on scheduled date, Boston bowel preparation score (BPPS), adenoma detection rate, and satisfaction., Results: Of 241 patients, 128 were in the standard protocol arm and 113 in the intervention arm. Higher proportions of patients receiving text messages underwent colonoscopy on their scheduled date (69.9%) compared to the ones in the standard protocol (50.8%, p = 0.015). Patients with ≥3 interactions with the system had 80.6% likelihood of completing colonoscopy on the scheduled date compared to 56.9% with <3 interactions and 50.8% with standard protocol (p < 0.001). Frequency of interaction with the system was similar between older (>65 years) and younger patients (p = 1.0). Among older patients, colonoscopy was completed successfully in 84.2% when alert-based human interactions occurred compared to 65.6% in those without and 47.9% with standard protocol (p = 0.018). More than 90% indicated they would recommend the system to patients undergoing future colonoscopy., Conclusion: An interactive text messaging system improves successful colonoscopy rates in a VA setting, with greatest impact in older patients., (© 2020 S. Karger AG, Basel.)

Stress is a known trigger for flares of inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS); however, this process is not well understood. Here, we find that restraint stress in mice leads to signs of diarrhea, fecal dysbiosis, and a barrier defect via the opening of goblet-cell associated passages. Notably, stress increases host immunity to gut bacteria as assessed by immunoglobulin A (IgA)-bound gut bacteria. Stress-induced microbial changes are necessary and sufficient to elicit these effects. Moreover, similar to mice, many diarrhea-predominant IBS (IBS-D) patients from two cohorts display increased antibacterial immunity as assessed by IgA-bound fecal bacteria. This antibacterial IgA response in IBS-D correlates with somatic symptom severity and was distinct from healthy controls or IBD patients. These findings suggest that stress may play an important role in patients with IgA-associated IBS-D by disrupting the intestinal microbial community that alters gastrointestinal function and host immunity to commensal bacteria., Competing Interests: DECLARATION OF INTERESTS The authors declare no competing interests. D.K. serves as Senior Scientific Advisor to Diversigen, a company involved in the commercialization of microbiome analysis. Diversigen is now a wholly owned subsidiary of OraSure. P.C.K. is on the advisory board of Novome Biotechnologies and is an ad hoc consultant for Pendulum Therapeutics, IP Group, and Otsuka Pharmaceuticals. These interests have been reviewed and managed by the respective institutions in accordance with their conflict-of-interest policies.

Functional dyspepsia is a common functional gastrointestinal (GI) disorder of gastroduodenal origin, diagnosed clinically in the presence of prototypical symptoms of epigastric pain and meal-related symptoms, and without structural explanation. The most recent diagnostic criteria provide for two functional dyspepsia subtypes, epigastric pain syndrome (EPS) and post-prandial distress syndrome (PDS) based on the predominant symptom pattern. The evaluation of dyspepsia should keep laboratory, imaging, and invasive testing to a minimum, as extensive or repetitive investigations are of rather low diagnostic yield in the absence of localizing symptoms or alarm features. Factors with etiopathologic relationships to functional dyspepsia include micro-inflammation, GI infections, abnormalities of gastroduodenal motility, visceral hypersensitivity, disturbances along the brain-gut axis, and psychological factors; all of these causative mechanisms have potential to partially explain symptoms in some functional dyspepsia patients, thus providing a rationale for the efficacy of a diversity of therapeutic approaches to functional dyspepsia. Management of dyspepsia symptoms relies upon both pharmacologic treatments and non-pharmacologic approaches, including psychological and complementary interventions. The evidence in support of established functional dyspepsia therapies is reviewed, and forms the basis for an effective functional dyspepsia treatment strategy emphasizing the patient's current symptom severity, pattern, and impact on the function and quality of life of the individual.

Background & Aims: Esophageal motor disorders (EMD) and pathologic reflux are often identified in obese individuals, but it is not clear how obesity contributes to these symptoms. We examined the relationships among symptom burden, EMD, acid exposure time (AET), symptom association probability, and body mass index (BMI)., Methods: We performed a retrospective study of 1089 consecutive patients who underwent high-resolution manometry, of which 426 patients also underwent reflux monitoring off acid suppression, over a 2-year period at a tertiary referral center. Symptom burden was assessed by questionnaires to determine dominant symptom intensity (DSI; product of symptom severity, and frequency, on 5-point Likert scales) and global symptom severity (GSS; global esophageal symptoms on 10-cm visual analog scales) at the time of esophageal testing; BMIs were recorded. We compared proportions of patients with EMD and abnormal reflux burden among BMI categories and correlated them with symptom burden., Results: Four-hundred thirty-three patients (39.8%) met the criteria for EMD. Esophageal outflow obstruction was observed in higher proportions of patients with low BMIs (underweight, 25.9%; normal, 14.1%; overweight, 13.9%; and obese, 9.8%; P = .037), but EMDs were less frequent in obese patients (P = .047), despite higher symptom burden compared with non-obese patients (DSI, 10.5 ± 0.3 vs 9.7 ± 0.2; P = .03 and GSS, 6.5 ± 1 vs 5.9 ± 1; P = .01). Among the 426 patients who underwent reflux monitoring, the proportions with total AET (P = .02), and upright AET (P < .001) increased among BMI categories, supine AET trended strongly (P = .06), in combination with increasing DSI and GSS (P ≤ .001 for each comparison). BMI correlated with symptom burden, higher AET, and positive symptom association probability (P < .01 for each analysis)., Conclusions: Increased symptom burden in obese individuals correlates with esophageal acid burden but not with motor disorders., (Copyright © 2020 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background: Many communities face a shortage of qualified endoscopists. Training physician assistants (PAs) to perform colonoscopies can expand the availability of colorectal cancer screening. This study examined screening colonoscopy metrics and quality indicators among gastroenterologists, supervised PAs, and gastroenterology fellows., Methods: Consecutive patients undergoing average-risk screening colonoscopy were stratified into one of three groups by endoscopist type. Procedure and pathology reports were reviewed for the technical performance and quality metrics of the providers., Results: PAs performed comparably to gastroenterologists in technical performance and quality metrics, and demonstrated higher cecal intubation rates than their gastroenterologist colleagues. Comparisons of attending physicians and PAs grouped by years of experience also did not show notable differences in performance., Conclusions: In a supervised practice, PAs performed on par with their gastroenterology colleagues on established colonoscopy quality indicators. Following proper training, PAs can be employed in the provision of screening colonoscopy.

Irritable bowel syndrome with diarrhea (IBS-D) and NAFLD are both common conditions that may be influenced by shared pathways of altered bile acid (BA) signaling and homeostatic regulation. Pathophysiological links between IBS-D and altered BA metabolism include altered signaling through the ileal enterokine and fibroblast growth factor 19 (FGF19) as well as increased circulating levels of 7α-hydroxy-4-cholesten-3-one, a metabolic intermediate that denotes increased hepatic BA production from cholesterol. Defective production or release of FGF19 is associated with increased BA production and BA diarrhea in some IBS-D patients. FGF19 functions as a negative regulator of hepatic cholesterol 7α-hydroxylase; therefore, reduced serum FGF19 effectively de-represses hepatic BA production in a subset of IBS-D patients, causing BA diarrhea. In addition, FGF19 modulates hepatic metabolic homeostatic response signaling by means of the fibroblast growth factor receptor 4/klotho beta receptor to activate cascades involved in hepatic lipogenesis, fatty acid oxidation, and insulin sensitivity. Emerging evidence of low circulating FGF19 levels in subsets of patients with pediatric and adult NAFLD demonstrates altered enterohepatic BA homeostasis in NAFLD. Conclusion: Here we outline how understanding of shared pathways of aberrant BA homeostatic signaling may guide targeted therapies in some patients with IBS-D and subsets of patients with NAFLD., (© 2020 The Authors. Hepatology Communications published by Wiley Periodicals, Inc., on behalf of the American Association for the Study of Liver Diseases.)

Sleep disturbance and fatigue are commonly reported among patients with Crohn's disease (CD). In this prospective study, we aimed to define sleep quality in CD patients at various disease activity states and compare to healthy controls using objective and subjective measures. A prospective observational cohort study of CD patients seen at a tertiary academic inflammatory bowel diseases (IBD) clinic was compared to healthy volunteers. CD activity was assessed using the Harvey-Bradshaw Index (HBI). Sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI) and Epworth Sleepiness Scale (ESS) and objectively over 1-week using actigraphy (motion-based) and morning urinary melatonin metabolite. 121 subjects (CD patients N = 61; controls N = 60) completed the study. 34 had active CD (HBI > 4). Sleep disturbance was more frequently reported by CD subjects than controls (PSQI: 57% vs. 35%, p = 0.02) and in patients with active CD versus in remission state (PSQI 75.8% vs. 33.3%, p < 0.01; ESS: 45.5% vs. 19%, p = 0.03). Sleep parameters as measured by actigraphy and urine melatonin metabolite did not vary by group. Crohn's patients report significantly more disturbed sleep than controls. However, poor sleep was not confirmed by objective measures of sleep quality. Excessive daytime sleepiness in CD patients may be driven by factors beyond objectively measured poor sleep.

Irritable bowel syndrome (IBS) is a functional bowel disorder characterized by abdominal pain and alterations in stool form and/or frequency, leading to reduced quality of life. Pharmacologic agents currently approved by the US Food and Drug Administration for treatment of IBS with diarrhea (IBS-D) in adults are the nonsystemic antibiotic rifaximin, the mixed µ- and κ-opioid receptor agonist/δ-opioid antagonist eluxadoline, and the selective serotonin 5-HT 3 antagonist alosetron (the last of which is indicated only in women with severe IBS-D refractory to conventional therapy). Both eluxadoline and alosetron are administered as chronic daily therapies; rifaximin is given as a 2-week course of treatment with repeat courses administered as needed for symptom recurrence. Presumed mechanisms of action of rifaximin include modulation of the gut microbiota, anti-inflammatory activity, normalization of visceral hypersensitivity, and reduction in intestinal permeability. Eluxadoline targets opioid receptors in the gastrointestinal (GI) tract, resulting in decreased GI motility, fluid secretion, and visceral pain perception. Alosetron antagonizes serotonergic afferent neural signals and also slows GI motility. The efficacy and safety of these agents have been investigated in several rigorous clinical trials, and it has been demonstrated that they improve global and individual IBS symptoms. This review highlights the pivotal efficacy and safety data of the three pharmacologic agents currently indicated in the USA for the management of IBS-D in adults.Funding: Salix Pharmaceuticals.

Background: Spontaneous bacterial peritonitis (SBP) is common in hospitalized cirrhotic patients with ascites and carries high mortality. This study aimed to determine whether early diagnostic paracentesis (EDP) <12 h of hospitalization conveys an intermediate-term (6-month) survival benefit in cirrhotic patients diagnosed with SBP., Methods: Consecutive US veterans with cirrhosis diagnosed with SBP over 13 years at a single VA medical center were reviewed retrospectively. Kaplan-Meyer analyses assessed the effects of EDP on survival., Results: A total of 79 cirrhotic patients were diagnosed with SBP (61.8 ± 8.8 years, n = 77 male, n = 52 [66.8%] Caucasian, n = 23 [29.1%] African-American). Underlying liver diseases included hepatitis c viral infection (HCV) (17.5%), alcohol (28.6%), alcohol and HCV (30.1%), and cryptogenic/metabolic (15.9%). Median baseline model for end-stage liver disease (MELD) was 12 (range 6-34), and median MELD at presentation was 18. Seven subjects had a history of hepatocellular carcinoma (11.1%), and 26 (41.3%) presented with sepsis. Thirty-three (52.4%) subjects died within 6 months after the SBP admission. Of the subjects, 41 (65.1%) underwent EDP, of which 23 (56.0%) survived at least 6 months, compared to only 7 of the 22 patients (31.8%) undergoing paracentesis >12 h from presentation ( P = 0.057). The maximal benefit of EDP on survival was observed beyond days 14 and 30; at these time points, no statistical difference in mortality was discernable ( P = 0.55 and 0.71). In a multivariate model including age, MELD at admission, hepatocellular cancer, and sepsis criteria, EDP (p 0.034) positively impacted patient survival at 6 months., Conclusions: EDP is associated with improved 6-month mortality in cirrhotic patients with ascites. In this veteran cohort, EDP was as important as MELD as a predictor of intermediate-term survival., (© 2019 The Authors. JGH Open: An open access journal of gastroenterology and hepatology published by Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Although common, little is known about the characteristics and management of undifferentiated abdominal pain (UAP) in the pediatric emergency department (ED). This study was a 12-month retrospective study for "abdominal pain" ED visits. Patients without an identifiable diagnosis were categorized as "UAP," while others with identified disease processes were categorized as "structural gastrointestinal diagnosis (SGID)." We included 2383 (72%) visits with 869 (36.5%) UAP visits and 1514 (63.5%) SGID visits. SGID patients had more laboratory tests (811 [53.6%] vs 422 [48.6%], P = .0186), and often had multiple tests performed (565 [69.7%] vs 264 [62.6%], P = .0116). Computed tomography and ultrasound scans were more common in SGID (computed tomography: 108 [7.1%] vs 27 [3.1%], P = .0004; ultrasound: 377 [24.9%] vs 172 [19.9%], P = .0044), and laboratory results (white blood cell count, hemoglobin, albumin, C-reactive protein) were abnormal at significantly higher rates. Analyses revealed the duration of pain as primary covariate in variance of pain etiology. Clinical features, such as duration of pain, may be augmented by laboratory tests to facilitate recognition of UAP in the ED.

Objectives: Irritable bowel syndrome with diarrhea (IBS-D) is a functional gastrointestinal disorder with limited effective treatment options. We evaluated the efficacy and safety of eluxadoline in patients with IBS-D who reported inadequate symptom control with prior loperamide., Methods: Three hundred forty-six adults with IBS-D (Rome III criteria) were randomly assigned to placebo or eluxadoline 100 mg twice daily for 12 weeks. Patients recorded daily IBS-D symptoms, including worst abdominal pain (WAP) and stool consistency (through Bristol Stool Scale). The primary endpoint was proportion of composite responders, defined as patients who met daily composite response criteria (≥40% WAP improvement and <5 Bristol Stool Scale score) for at least 50% of treatment days, and recorded ≥60 days of diary entries over the 12-week period., Results: Over 12 weeks, a significantly greater proportion of eluxadoline patients achieved the primary composite responder endpoint compared to placebo (22.7% vs 10.3%, P = 0.002), and component endpoints of improvements in stool consistency (27.9% vs 16.7%, P = 0.01) and WAP (43.6% vs 31.0%, P = 0.02). Additionally, a greater proportion of eluxadoline patients met the composite responder endpoint assessed at monthly intervals compared to placebo (weeks 1-4: 14.0% vs 6.9%, P = 0.03; weeks 5-8: 26.7% vs 14.9%, P = 0.006; weeks 9-12: 30.8% vs 16.7%, P = 0.002). Rates of adverse events were comparable in both groups (37.4% vs 35.3%); no treatment-related serious adverse event, cases of sphincter of Oddi spasm, or pancreatitis were reported., Discussion: Eluxadoline appears safe and effective for treating IBS-D symptoms in patients with an intact gallbladder reporting inadequate relief with prior loperamide use.

Background and Aim: Walled-off pancreatic necrosis (WON) frequently develops after necrotizing pancreatitis. Endoscopic drainage has become the preferred modality for symptomatic or infected WON. The aim of the present study was to assess health-related quality of life (HR-QOL) and long-term outcomes in patients undergoing endoscopic drainage for WON., Methods: Patients undergoing endoscopic drainage of WON from January 2006 to May 2016 were identified. Data recorded included demographic information, and the incidence of long-term sequelae including pancreatic endocrine and exocrine insufficiency. Attempts were made to contact all patients. HR-QOL was assessed using the SF-36 questionnaire., Results: Eighty patients were analyzed, 41 (51.3%) of whom completed the SF-36. One-year all-cause mortality was 6.2%, and disease-related mortality was 3.7%. A notable proportion of patients developed exocrine insufficiency (32.5%), endocrine insufficiency (27.7%), and long-term opiate use (42.5%). Development of exocrine insufficiency was predictive of lower total SF-36 scores (P = 0.016). Patients with WON had better HR-QOL compared with cohorts of irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD). In patients developing exocrine insufficiency versus healthy controls, poorer scores in the physical role (P < 0.001), general health (P < 0.001), vitality (P = 0.001), and emotional role (P = 0.029) domains were observed. Exocrine insufficiency patients had better HR-QOL than the IBS and IBD cohorts, although these differences were less pronounced., Conclusion: After undergoing endoscopic drainage for WON, patients have relatively preserved HR-QOL. The subset of patients that develop exocrine insufficiency have significantly poorer HR-QOL compared to healthy controls, although not to the degree of chronic gastrointestinal disorders such as IBS and IBD., (© 2018 Japan Gastroenterological Endoscopy Society.)

Background/aims: Breaks in the peristaltic contour on esophageal high-resolution manometry (HRM) may be associated with bolus retention in the esophagus. We evaluated the relationship between peristaltic breaks and esophageal symptoms, reflux exposure, and symptom outcomes in a prospective patient cohort., Methods: Two hundred and eighteen patients (53.2 ± 0.9 years, 68.3% female) undergoing both pH-impedance testing and HRM over a 5-year period were prospectively evaluated. Demographics, symptom presentation, acid exposure time, symptom association probability, and symptom burden scores were collected. Outcomes were assessed on follow-up using changes in symptom scores. Presence of long breaks (≥ 5 cm) on HRM was assessed by a blinded author. Relationships between breaks, reflux parameters, presenting symptoms, and outcomes were assessed., Results: Patients with long breaks were more likely to have cough as a presenting symptom than those without (43.4% vs 28.6%, P = 0.024); statistical differences were not demonstrated with other symptoms ( P ≥ 0.3). Numbers of swallows with long breaks were higher in patients with cough compared to those without (2.4 ± 0.3 vs 1.6 ± 0.2, P = 0.021); differences were not found with other symptoms ( P ≥ 0.4). Long breaks were not associated with age, gender, race, reflux burden, symptom association, or changes in symptom metrics ( P ≥ 0.1 for all comparisons). Among patients with cough, the presence of long breaks predicted suboptimal symptom improvement with antireflux therapy ( P = 0.018); this difference did not hold true for other symptoms ( P ≥ 0.2)., Conclusions: Long breaks in esophageal peristaltic integrity are associated with cough. The presence of long breaks is associated with suboptimal benefit from antireflux therapy.

Background: While opioid prescriptions have increased alarmingly in the United States (US), their use for unexplained chronic gastrointestinal (GI) pain (eg, irritable bowel syndrome) carries an especially high risk for adverse effects and questionable benefit., Aim: To compare opioid use among US veterans with structural GI diagnoses (SGID) and those with unexplained GI symptoms or functional GI diagnoses (FGID), a group for whom opioids have no accepted role., Methods: Veterans Health Administration (VHA) administrative data from fiscal year 2012 were used to identify veterans with diagnostic codes recorded for SGID and FGID. This cohort study examined VHA pharmacy data to compare groups receiving ≥ 1 opioid prescription during the year and number of prescriptions filled. Bivariate and multiple logistic regression analyses adjusted for potential confounding factors (demographics, medical diagnoses, social factors) and identified potential mediators (service use, psychiatric comorbidity) of opioid use in these groups., Results: A greater proportion of veterans with FGID received an opioid prescription during fiscal year 2012 (36.0% of 272 431) compared to only 28.9% of 1 223 744 in the SGID group (Relative Risk [RR] = 1.25). In multivariate logistic regression, personality disorders and drug abuse (OR 1.23 for each group), recent homelessness (OR 1.22), psychotropic medication fills (OR 1.55) and emergency department encounters (OR 1.21) were independently associated with opioid prescription use., Conclusions: Despite the potential for adverse consequences, opioids more often are prescribed for veterans with chronic, unexplained GI symptoms compared to those with structural diagnoses. Psychiatric comorbidities and frequent healthcare encounters mediate some of the opioid use risk., (© 2018 John Wiley & Sons Ltd.)