658 results on '"William D. Chey"'
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2. Long-term safety of tenapanor in people with irritable bowel syndrome with constipation from the T3MPO-3 study: plain language summary of publication
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Anthony J. Lembo, Susan Edelstein, David P. Rosenbaum, Ceciel Rooker, Jeffrey D. Roberts, and William D. Chey
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Diseases of the digestive system. Gastroenterology ,RC799-869 - Abstract
Summary This document provides a short summary of the T3MPO-3 study, which was published in Neurogastroenterology and Motility in September 2023. At the end of this summary, there are links to websites where you can find more information about this study. Tenapanor (IBSRELA®) is a newly available medicine in the United States. It is used to treat irritable bowel syndrome with constipation (IBS-C) in people aged 18 years and older. In 2 large clinical trials, tenapanor was shown to improve the symptoms of IBS-C. People with IBS-C often need to take long-term medicines to keep their symptoms under control. As a result, this study, called T3MPO-3 , was undertaken to investigate whether there are any possible side effects associated with the long-term use of tenapanor in adults with IBS-C. There were 312 people who had taken part in either of the original 2 trials and took part in this study, with 90 receiving tenapanor for at least 1 year. Loose or watery stool (diarrhea) was the most common side effect, and most cases were mild or moderate. No people died in any of these studies. Who is this article for? This summary may help people with irritable bowel syndrome with constipation (IBS-C) and their family members and/or caregivers better understand the long-term safety of tenapanor for treating IBS-C. Two IBS-C patient advocates coauthored this summary. Where is the T3MPO-3 study in the medicine development timeline? The T3MPO-3 study was completed in 2018. In 2019, the Food and Drug Administration (FDA) approved tenapanor in the United States to treat IBS-C in adults. • The FDA is responsible for public health in the United States and makes sure that medicines are safe and effective. The medicine development process starts with laboratory and animal testing. Once a potential medicine has been identified and proven to be safe and effective in animals, it is tested in humans in phase I, phase II, and phase III studies. T3MPO-3 was a phase III study. What were the overall results? Diarrhea was the most common side effect in the three T3MPO studies. A side effect is something (expected or unexpected) that you feel was caused by a medicine or treatment you take. Side effects were similar to those reported by researchers in previous studies. No new safety issues were found with long-term use of tenapanor .
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- 2024
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3. Brief communication: global temporal trends in the efficacy of clarithromycin-based regimens for the treatment of infection
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Steven F. Moss, William D. Chey, Patrick Daniele, Corey Pelletier, Rinu Jacob, Gabriel Tremblay, Elizabeth Hubscher, Eckhard Leifke, and Peter Malfertheiner
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Diseases of the digestive system. Gastroenterology ,RC799-869 - Abstract
Background: Helicobacter pylori eradication rates achieved with clarithromycin-based triple therapies are declining due to antibiotic resistance, but data regarding temporal changes in efficacy with these eradication therapies are scarce. Objective: To evaluate the efficacy of clarithromycin-based triple eradication regimens over time. Design: A comprehensive literature review and time-trend analysis. Data sources and methods: Bibliographies of recently published systematic literature reviews were searched and supplemented with a targeted literature review conducted using Medline and Embase databases and ProQuest from conception to May 2021. Studies reporting H. pylori eradication rates of clarithromycin-based triple therapies were included and temporal trends were estimated using a random-effects model. Results: Eradication rates for triple therapies containing proton pump inhibitors (PPIs), clarithromycin, and amoxicillin showed a significant decline over the past 23 years ( p = 0.0315). However, this decline was not significant when eradication rates achieved with vonoprazan-based triple therapy were included ( p = 0.3910). Conclusion: Vonoprazan-based triple therapy partially mitigated the decline in eradication rates seen with PPI-based triple therapy, likely due to more powerful acid suppression of vonoprazan.
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- 2023
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4. A novel duodenal-release formulation of caraway oil and L-menthol is a safe, effective and well tolerated therapy for functional dyspepsia
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Brian E. Lacy, William D. Chey, Michael S. Epstein, Syed M. Shah, Patrick Corsino, Linda R. Zeitzoff, and Brooks D. Cash
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Abdominal pain ,Caraway oil ,Dyspepsia ,Functional dyspepsia ,L-menthol ,Diseases of the digestive system. Gastroenterology ,RC799-869 - Abstract
Abstract Background A randomized, placebo-controlled clinical trial (FDREST) of a novel formulation of caraway oil and L-menthol (COLM-SST) demonstrated symptom relief in patients with functional dyspepsia (FD). Two follow-up studies were conducted to evaluate patient satisfaction, self-regulated dosing, and long-term safety data: FDACT, Functional Dyspepsia Adherence and Compliance Trial, and FDSU36, Functional Dyspepsia Safety Update at 36 months. Methods A patient reported outcomes (PRO) questionnaire was designed and distributed online to assess real-world satisfaction and dosing frequency of open-label COLM-SST in patients with FD. A separate study analyzing voluntary safety surveillance data evaluated the frequency and severity of reported adverse events (AEs). Results A total of 600 FD patients were enrolled in the PRO study. Ninety five percent of respondents reported a major or moderate improvement in their FD symptoms and 91.7% indicated a major or moderate improvement in quality of life (QOL) using COLM-SST. Between 1 and 4 capsules were consumed daily by 91.2% of respondents, with 56.2% taking them before meals. Symptom relief was rapid, with 86.4% of respondents indicating relief within 2 h of taking COLM-SST. Few adverse events (AEs) were reported (0.0187%) by patients using COLM-SST. No serious AEs were identified. Conclusion COLM-SST is safe, well tolerated, and provides rapid relief of FD symptoms. These findings, demonstrated in the FDREST trial, were further supported by a large prospective PRO study evaluating self-regulated dosing frequency, symptom improvement, and QOL. COLM-SST was well-tolerated based on review of AE data at 36 months.
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- 2022
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5. Potassium-Competitive Acid Blocker and Proton Pump Inhibitor–Based Regimens for First-Line Helicobacter pylori Eradication: A Network Meta-Analysis
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Peter Malfertheiner, Steven F. Moss, Patrick Daniele, Corey Pelletier, Rinu Jacob, Gabriel Tremblay, Elizabeth Hubscher, Eckhard Leifke, and William D. Chey
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First-Line Regimens ,Empiric Therapy ,Network Meta-Analysis ,Diseases of the digestive system. Gastroenterology ,RC799-869 - Abstract
Background and Aims: Effective acid suppression is a crucial component of Helicobacter pylori (H. pylori) eradication regimens. Approved treatments include dual, triple, and quadruple therapies composed of certain antibiotics in combination with proton pump inhibitors (PPIs). Vonoprazan, a potassium-competitive acid blocker, provides more potent and durable acid suppression than PPIs. We compared the efficacy of vonoprazan-based therapies vs approved standard regimens using new evidence from the phase 3 pHalconHP trial in North America and Europe. Methods: Studies reporting first-line H. pylori eradication rates from empiric treatment with Food and Drug Administration–approved therapies and vonoprazan-containing therapies were identified via bibliographic searches of systematic literature reviews and a subsequent MEDLINE/Embase search using index terms for H. pylori and eradication. Randomized controlled trials comparing 2 or more relevant comparators were included in Bayesian network meta-analyses for grouped and distinct therapies. Results: Twenty-three distinct regimens from 42 trials including 12,773 patients were identified. Vonoprazan-based triple therapy showed the highest relative efficacy (odds ratio: 2.73, 95% credible interval 2.11, 3.54) and 72.1% probability of being the best. North American, Western, and global scenarios were largely consistent. Vonoprazan-based therapies demonstrated higher odds of H. pylori eradication than each PPI-based triple therapy. Furthermore, vonoprazan-based triple therapy was superior to bismuth subcitrate quadruple therapy (odds ratio: 1.60, 95% credible interval: 1.07, 2.38). Conclusion: Vonoprazan-based eradication regimens represent novel treatments for H. pylori infection on a global scale, offering efficacy that, in this analysis, is superior to PPI-based triple therapy and comparable or better than bismuth quadruple therapy.
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- 2022
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6. Polyethylene Glycol 3350 in the Treatment of Chronic Idiopathic Constipation: Post hoc Analysis Using FDA Endpoints
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Stacy B. Menees, Anthony J. Lembo, and William D. Chey
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Diseases of the digestive system. Gastroenterology ,RC799-869 - Abstract
Background & Aims. The efficacy and safety of polyethylene glycol 3350 for chronic idiopathic constipation have been demonstrated in randomized controlled trials. A new US Food and Drug Administration-recommended primary efficacy endpoint for evaluating chronic idiopathic constipation prompted our reevaluation of previously reported clinical data with polyethylene glycol 3350. Methods. This multicenter, double-blind, placebo-controlled, parallel-group trial included adults with chronic idiopathic constipation randomized to polyethylene glycol 3350 17 g (n = 204) or placebo (n = 100) once daily for 24 weeks. Post hoc analyses were performed using the US Food and Drug Administration endpoint (≥3 complete spontaneous bowel movements/week and an increase of ≥1 complete spontaneous bowel movement/week from baseline for ≥9/12 weeks, including 3 of the last 4 weeks) along with additional efficacy and safety outcomes. Results. The proportion of patients meeting the new endpoint was significantly higher with polyethylene glycol 3350 vs placebo (42% vs 13%; P
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- 2022
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7. Pharmacologic, Dietary, and Psychological Treatments for Irritable Bowel Syndrome With Constipation: Cost Utility Analysis
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Eric D. Shah, Jessica K. Salwen-Deremer, Peter R. Gibson, Jane G. Muir, Shanti Eswaran, and William D. Chey
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Medicine (General) ,R5-920 - Abstract
Introduction. Irritable bowel syndrome (IBS) is the most common gastroenterology referral and one of the most common gastrointestinal complaints in primary care. We performed a cost-utility analysis of the most common treatments available in general practice for IBS with constipation (IBS-C), the most expensive IBS subtype. Methods. We developed a decision analytic model evaluating guideline-recommended and Food and Drug Administration–approved drugs, supplements, and dietary/psychological interventions. Model inputs were derived from “global symptom improvement” outcomes in systematic reviews of clinical trials. Costs were derived from national datasets. Analysis was performed with a 1-year time horizon from patient and payer perspectives. We analyzed a prototypical managed-care health plan with no cost-sharing to the patient. Results. From a payer perspective, global IBS treatments (including low FODMAP, cognitive behavioral therapy [CBT], neuromodulators), which are not specific to the IBS-C bowel subtype were less expensive than on-label prescription drug treatments. From a patient perspective, on-label prescription drug treatment with linaclotide was the least expensive treatment strategy. Drug prices and costs to manage untreated IBS-C were most important determinants of payer treatment preferences. Effects of treatment on missed work-days and need for repeated appointments to complete treatment were the most important determinants of treatment preference to patients. Discussion. Due mostly to prescription drug prices, neuromodulators, low FODMAP, and CBT appear cost-effective compared to on-label drug treatments from a payer perspective in cost-utility analysis. These findings may explain common treatment barriers in clinical practice.
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- 2021
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8. A double-blind, 377-subject randomized study identifies Ruminococcus, Coprococcus, Christensenella, and Collinsella as long-term potential key players in the modulation of the gut microbiome of lactose intolerant individuals by galacto-oligosaccharides
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M. A. Azcarate-Peril, J. Roach, A. Marsh, William D. Chey, William J. Sandborn, Andrew J. Ritter, Dennis A. Savaiano, and T. R. Klaenhammer
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prebiotics ,microbiome modulation ,lactose intolerance ,human lactase ,bifidobacterium ,short chain fatty acids ,galacto-oligosaccharides ,gos ,Diseases of the digestive system. Gastroenterology ,RC799-869 - Abstract
Background. Our recent publication (Chey et al., Nutrients 2020) showed that a 30-day administration of pure galacto-oligosaccharides (GOS) significantly reduced symptoms and altered the fecal microbiome in patients with lactose intolerance (LI). Results. In this addendum, we performed an in-depth analysis of the fecal microbiome of the 377 LI patients randomized to one of two GOS doses (Low, 10–15 grams/day or High, 15–20 grams/day), or placebo in a multi-center, double-blinded, placebo-controlled trial. Sequencing of 16S rRNA amplicons was done on GOS or placebo groups at weeks zero (baseline), four (end of treatment), nine, 16 and 22. Taxa impacted by treatment and subsequent dairy consumption included lactose-fermenting species of Bifidobacterium, Lactobacillus, Lactococcus, and Streptococcus. Increased secondary fermentation microorganisms included Coprococcus and Ruminococcus species, Blautia producta, and Methanobrevibacterium. Finally, tertiary fermenters that use acetate to generate butyrate were also increased, including Faecalibacterium prausnitzii, Roseburia faecis, and C. eutactus. Conclusions. Results confirmed and expanded data on GOS microbiome modulation in LI individuals. Microbiome analysis at 16 and 22 weeks after treatment further suggested relatively long-term benefits when individuals continued consumption of dairy products.
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- 2021
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9. Comparison of anorectal function measured using wearable digital manometry and a high resolution manometry system
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Ali Attari, William D. Chey, Jason R. Baker, James A. Ashton-Miller, and Peter F. W. M. Rosier
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Medicine ,Science - Abstract
There is a need for a lower cost manometry system for assessing anorectal function in primary and secondary care settings. We developed an index finger-based system (termed “digital manometry”) and tested it in healthy volunteers, patients with chronic constipation, and fecal incontinence. Anorectal pressures were measured in 16 participants with the digital manometry system and a 23-channel high-resolution anorectal manometry system. The results were compared using a Bland-Altman analysis at rest as well as during maximum squeeze and simulated defecation maneuvers. Myoelectric activity of the puborectalis muscle was also quantified simultaneously using the digital manometry system. The limits of agreement between the two methods were -7.1 ± 25.7 mmHg for anal sphincter resting pressure, 0.4 ± 23.0 mmHg for the anal sphincter pressure change during simulated defecation, -37.6 ± 50.9 mmHg for rectal pressure changes during simulated defecation, and -20.6 ± 172.6 mmHg for anal sphincter pressure during the maximum squeeze maneuver. The change in the puborectalis myoelectric activity was proportional to the anal sphincter pressure increment during a maximum squeeze maneuver (slope = 0.6, R2 = 0.4). Digital manometry provided a similar evaluation of anorectal pressures and puborectalis myoelectric activity at an order of magnitude less cost than high-resolution manometry, and with a similar level of patient comfort. Digital Manometry provides a simple, inexpensive, point of service means of assessing anorectal function in patients with chronic constipation and fecal incontinence.
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- 2020
10. Mechanism of action and therapeutic benefit of rifaximin in patients with irritable bowel syndrome: a narrative review
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William D. Chey, Eric D. Shah, and Herbert L. DuPont
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Diseases of the digestive system. Gastroenterology ,RC799-869 - Abstract
Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder with a multifactorial pathophysiology. The gut microbiota differs between patients with IBS and healthy individuals. After a bout of acute gastroenteritis, postinfection IBS may result in up to approximately 10% of those affected. Small intestinal bacterial overgrowth (SIBO) is more common in patients with IBS than in healthy individuals, and eradication of SIBO with systemic antibiotics has decreased symptoms of IBS in some patients with IBS and SIBO. The nonsystemic (i.e. low oral bioavailability) antibiotic rifaximin is indicated in the United States and Canada for the treatment of adults with IBS with diarrhea (IBS-D). The efficacy and safety of 2-week single and repeat courses of rifaximin have been demonstrated in randomized, placebo-controlled studies of adults with IBS. Rifaximin is widely thought to exert its beneficial clinical effects in IBS-D through manipulation of the gut microbiota. However, current studies indicate that rifaximin induces only modest effects on the gut microbiota of patients with IBS-D, suggesting that the efficacy of rifaximin may involve other mechanisms. Indeed, preclinical data reveal a potential role for rifaximin in the modulation of inflammatory cytokines and intestinal permeability, but these two findings have not yet been examined in the context of clinical studies. The mechanism of action of rifaximin in IBS is likely multifactorial, and further study is needed.
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- 2020
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11. In Memoriam: William Y. Chey, MD, DSc, AGAF, FACG
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William D. Chey
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Hepatology ,Gastroenterology - Published
- 2023
12. American Gastroenterological Association-American College of Gastroenterology Clinical Practice Guideline: Pharmacological Management of Chronic Idiopathic Constipation
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Lin Chang, William D. Chey, Aamer Imdad, Christopher V. Almario, Adil E. Bharucha, Susan Diem, Katarina B. Greer, Brian Hanson, Lucinda A. Harris, Cynthia Ko, M. Hassan Murad, Amit Patel, Eric D. Shah, Anthony J. Lembo, and Shahnaz Sultan
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Hepatology ,Gastroenterology - Published
- 2023
13. An Office-Based, Point-of-Care Test Predicts Treatment Outcomes With Community-Based Pelvic Floor Physical Therapy in Patients With Chronic Constipation
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Eric D. Shah, Elizabeth A. Pelletier, Carol Greeley, Emily E. Sieglinger, Jamie D. Sanchez, Kayla A. Northam, Jessica A. Perrone, Michael A. Curley, Christopher M. Navas, Tracy L. Ostler, Aimee R. Burnett Greeley, Pablo Martinez-Camblor, Jason R. Baker, Adrienne Harris, Corey A. Siegel, and William D. Chey
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Hepatology ,Gastroenterology - Abstract
Rectal evacuation disorders are common among constipated patients. We aimed to evaluate the accuracy of an investigational point-of-care test (rectal expulsion device [RED]) to predict outcomes with community-based pelvic floor physical therapy.We enrolled patients meeting Rome IV criteria for functional constipation failing fiber/laxatives for more than 2 weeks. RED was inserted and self-inflated, and then time-to-expel was measured in a left lateral position. All patients underwent empiric community-based pelvic floor physical therapy in routine care with outcomes measured at 12 weeks. The primary end point was global clinical response (Patient Assessment of Constipation Symptoms score reduction,0.75 vs baseline). Secondary end points included improvement in health-related quality-of-life (Patient Assessment of Constipation Quality of Life score reduction,1.0) and complete spontaneous bowel movement frequency (Food and Drug Administration complete spontaneous bowel movement responder definition).Thirty-nine patients enrolled in a feasibility phase to develop the use-case protocol. Sixty patients enrolled in a blinded validation phase; 52 patients (mean, 46.9 y; 94.2% women) were included in the intention-to-treat analysis. In the left lateral position, RED predicted global clinical response (generalized area under the curve [gAUC], 0.67; 95% CI, 0.58-0.76]), health-related quality-of-life response (gAUC, 0.67; 95% CI, 0.58-0.77; P.001), and complete spontaneous bowel movement response (gAUC, 0.63; 95% CI, 0.57-0.71; P.001). As a screening test, a normal RED effectively rules out evacuation disorders (expected clinical response, 8.9%; P = .042). Abnormal RED in the left lateral position (defined as expulsion within 5 seconds or120 seconds) predicted 48.9% clinical response to physical therapy. A seated maneuver enhanced the likelihood of clinical response (71.1% response with seated RED retained13 seconds) but likely is unnecessary in most settings.RED offers an opportunity to disrupt the paradigm by offering a personalized approach to managing chronic constipation in the community (Clinicaltrials.gov: NCT04159350).
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- 2023
14. Rare, Overlooked, or Underappreciated Causes of Recurrent Abdominal Pain: A Primer for Gastroenterologists
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Darren M, Brenner, Lawrence J, Brandt, Marc, Fenster, Matthew J, Hamilton, Amrit K, Kamboj, Amy S, Oxentenko, Bruce, Wang, and William D, Chey
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Hepatology ,Gastroenterology - Abstract
Recurrent abdominal pain is a common reason for repeated visits to outpatient clinics and emergency departments, reflecting a substantial unmet need for timely and accurate diagnosis. A lack of awareness of some of the rarer causes of recurrent abdominal pain may impede diagnosis and delay effective management. This article identifies some of the key rare but diagnosable causes that are frequently missed by gastroenterologists and provides expert recommendations to support recognition, diagnosis, and management with the ultimate aim of improving patient outcomes.
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- 2023
15. Age- and Gender-Based Differences in Anorectal Function, Gastrointestinal Symptoms, and Constipation-Specific Quality of Life in Patients with Chronic Constipation
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Borko Nojkov, Jason R. Baker, William D. Chey, Richard Saad, Lydia Watts, Moira Armstrong, Kristen Collins, Gabrielle Ezell, Cari Phillips, and Stacy Menees
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Physiology ,Gastroenterology - Abstract
The effect of age and gender differences on anorectal function, symptoms severity, and quality of life (QoL) in patients with chronic constipation (CC) is not well studied. This study examines the impact of age and gender on anorectal function testing (AFT) characteristics, symptoms burden, and QoL in patients with CC.This is a retrospective analysis of prospectively collected data from 2550 adults with CC who completed AFT. Collected data include demographics, sphincter response to simulated defecation during anorectal manometry (ARM), balloon expulsion testing (BET), and validated surveys assessing constipation symptoms and QoL. DD was defined as both the inability to relax the anal sphincter during simulated defecation and an abnormal BET.2550 subjects were included in the analysis (mean age = 48.6 years). Most patients were female (81.6%) and Caucasian (82%). 73% were 60 years old (mean = 41) vs. 27% ≥ 60 years old (mean = 69). The prevalence of impaired anal sphincter relaxation on ARM, abnormal BET, and DD in patients with CC was 48%, 42.1%, and 22.9%, respectively. Patients who were older and male were significantly more frequently diagnosed with DD and more frequently had impaired anal sphincter relaxation on ARM, compared to patients who were younger and female (p 0.05). Conversely, CC patients who were younger and female reported greater constipation symptoms severity and more impaired QoL (p ≤ 0.004).Among patients with CC referred for anorectal function testing, men and those older than 60 are more likely to have dyssynergic defecation, but women and patients younger than 60 experience worse constipation symptoms and QoL.
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- 2022
16. Overlap of disorders of gut–brain interaction: a systematic review and meta-analysis
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Thomas Fairlie, Ayesha Shah, Nicholas J Talley, William D Chey, Natasha Koloski, Yeong Yeh Lee, Kok-Ann Gwee, Michael P Jones, and Gerald Holtmann
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Hepatology ,Gastroenterology - Published
- 2023
17. Behavioral Health Digital Therapeutics for Patients With Irritable Bowel Syndrome: A Primer for Gastroenterologists
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Zachary M. Saleh, William D. Chey, and Sameer K. Berry
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Hepatology ,Gastroenterology - Published
- 2023
18. Up-Front Endoscopy Maximizes Cost-Effectiveness and Cost-Satisfaction in Uninvestigated Dyspepsia
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Emily V. Wechsler, Nitin K. Ahuja, Darren Brenner, Walter Chan, Lin Chang, William D. Chey, Anthony J. Lembo, Baha Moshiree, Judy Nee, Shailja C. Shah, Kyle Staller, and Eric D. Shah
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Hepatology ,Gastroenterology - Published
- 2023
19. Fecal Incontinence
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Stacy Menees and William D. Chey
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Gastroenterology - Published
- 2022
20. The low FODMAP diet for IBS; A multicentre UK study assessing long term follow up
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Imran Aziz, Anupam Rej, A Agrawal, Katie Sanders, Rupert Allen, Aimee Newton, Christian Charles Shaw, Nick Trott, Rachel Louise Buckle, David A Elphick, David S Sanders, Sophie Martin, Karen Mosey, William D. Chey, and Kelly Robinson
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Adult ,Male ,Pediatrics ,medicine.medical_specialty ,Long term follow up ,Nutritional composition ,Irritable Bowel Syndrome ,Diet, Carbohydrate-Restricted ,Diet, Gluten-Free ,03 medical and health sciences ,0302 clinical medicine ,Symptom relief ,Quality of life ,Surveys and Questionnaires ,medicine ,Humans ,Irritable bowel syndrome ,Aged ,chemistry.chemical_classification ,Hepatology ,business.industry ,Gastroenterology ,food and beverages ,Middle Aged ,medicine.disease ,Gluten ,United Kingdom ,chemistry ,030220 oncology & carcinogenesis ,Low fodmap diet ,Quality of Life ,Female ,030211 gastroenterology & hepatology ,Energy Intake ,business ,Follow-Up Studies - Abstract
Background The low FODMAP diet (LFD) is effective in managing irritable bowel syndrome (IBS) in the short term. This study assessed the long-term effect of the LFD on symptoms, nutritional composition and socialising. Methods Patients with IBS who received dietetic-led LFD advice were approached at long term follow up (>6 months post LFD advice) from six centres across the United Kingdom. Participants completed questionnaires assessing gastrointestinal symptoms, adherence, nutritional intake, dietary acceptability and food related quality of life (QOL). Results 205 participants completed the study, with a mean follow up of 44 months (3.7 years). Adequate symptom relief was noted in 60% of individuals at long term follow up, with 76% being on the personalisation phase of the LFD (pLFD). Mean nutritional intake did not differ between individuals on the pLFD versus habitual diet, with no difference in fructan intake (2.9 g/d vs 2.9 g/d, p = 0.96). The majority (80%) of individuals on the pLFD consumed specific ‘free-from’ products at the long term, with the purchase of gluten or wheat free products being the commonest (68%). Conclusion The majority of patients follow the pLFD in the long term, with a large proportion purchasing gluten or wheat free products to manage their symptoms.
- Published
- 2021
21. Reply
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William D. Chey and Colin W. Howden
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Hepatology ,Gastroenterology - Published
- 2022
22. Computer versus physician identification of gastrointestinal alarm features.
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Christopher V. Almario, William D. Chey, Sentia Iriana, Francis Dailey, Karen Robbins, Anish V. Patel, Mark Reid, Cynthia Whitman, Garth Fuller, Roger Bolus, Buddy Dennis, Rey Encarnacion, Bibiana Martínez, Jennifer Soares, Rushaba Modi, Nikhil Agarwal, Aaron Lee, Scott Kubomoto, Gobind Sharma, Sally Bolus, Lin Chang, and Brennan M. R. Spiegel
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- 2015
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23. Integrated Care for Irritable Bowel Syndrome
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Sameer K. Berry and William D. Chey
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medicine.medical_specialty ,business.industry ,Behavioral therapy ,Gastroenterology ,Psychological therapy ,medicine.disease ,Integrated care ,Pharmacotherapy ,Multidisciplinary approach ,medicine ,Behavioral interventions ,Intensive care medicine ,Clinical phenotype ,business ,Irritable bowel syndrome - Abstract
Irritable bowel syndrome (IBS) is a common symptom-based condition of heterogeneous pathogenesis and clinical phenotype. This heterogeneity and multidimensional nature creates significant diagnostic and treatment challenges. Recent evidence has documented the benefits of diet and behavioral interventions. These nonmedical strategies are causing a shift from the traditional care model to a multidisciplinary care model. Recent evidence suggests that collaborative, team-based integrated care leads to better clinical outcomes and reduced cost per cure compared with traditional care. Although it is growing increasingly clear that integrated care offers significant benefits to IBS patients, widespread dissemination will require solutions to structural, cultural, and financial barriers.
- Published
- 2021
24. Evaluating the Impact of Cost on the Treatment Algorithm for Chronic Idiopathic Constipation: Cost-Effectiveness Analysis
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William D. Chey, Anthony Lembo, Nitin K. Ahuja, Walter W. Chan, Corey A. Siegel, Kyle Staller, Darren M. Brenner, Judy Nee, and Eric D. Shah
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Prucalopride ,Hepatology ,business.industry ,Gastroenterology ,Cost-effectiveness analysis ,Clinical trial ,chemistry.chemical_compound ,Quality of life (healthcare) ,chemistry ,Tolerability ,medicine ,Plecanatide ,Medical prescription ,business ,Algorithm ,Linaclotide ,medicine.drug - Abstract
Introduction Chronic idiopathic constipation (CIC) is a common and burdensome illness. We performed a cost-effectiveness analysis of the US Food and Drug Administration-approved CIC drugs to evaluate and quantify treatment preferences compared with usual care from insurer and patient perspectives. Methods We evaluated the subset of patients with CIC and documented failure of over-the-counter (OTC) osmotic or bulk-forming laxatives. A RAND/UCLA consensus panel of 8 neurogastroenterologists informed model design. Treatment outcomes and costs were defined using integrated analyses of registered clinical trials and the US Centers for Medicare and Medicaid Services-supported cost databases. Quality-adjusted life years (QALYs) were calculated using health utilities derived from clinical trials. A 12-week time horizon was used. Results With continued OTC laxatives, CIC-related costs were $569 from an insurer perspective compared with $3,154 from a patient perspective (considering lost wages and out-of-pocket expenses). CIC prescription drugs increased insurer costs by $618-$1,015 but decreased patient costs by $327-$1,117. Effectiveness of CIC drugs was similar (0.02 QALY gained/12 weeks or ∼7 healthy days gained/year). From an insurer perspective, prescription drugs (linaclotide, prucalopride, and plecanatide) seemed less cost-effective than continued OTC laxatives (incremental cost-effectiveness ratio >$150,000/QALY gained). From a patient perspective, the cost-effective algorithm started with plecanatide, followed by choosing between prucalopride and linaclotide starting at the 145-μg dose (favoring prucalopride among patients whose disease affects their work productivity). The patient perspective was driven by drug tolerability and treatment effects on quality of life. Discussion Addressing costs at a policy level has the potential to enable patients and clinicians to move from navigating barriers in treatment access toward truly optimizing treatment choice.
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- 2021
25. Sucrase-Isomaltase Deficiency: Hiding in Plain Sight?
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Shanti Eswaran, William D. Chey, and Adrienne Lenhart
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medicine.medical_specialty ,Malabsorption ,business.industry ,Gastroenterology ,medicine.disease ,Osmotic diarrhea ,Sucrase-isomaltase deficiency ,Bloating ,Internal medicine ,medicine ,medicine.symptom ,Flatulence ,business ,Irritable bowel syndrome ,Pediatric population - Abstract
Our review focuses on the various presentations, diagnosis, and treatment of sucrose–isomaltase deficiency (SID), previously thought to be limited to the pediatric population with severe malabsorptive symptoms. Although sucrase–isomaltase deficiency is presumed to be a rare disorder, it is likely under recognized and more prevalent than is currently known. Congenital sucrase–isomaltase deficiency usually manifests early in life, but the phenotype may vary depending on the mutation(s) present. SID is characterized by dysfunction of the brush border enzyme, sucrase–isomaltase, with a subsequent inability to successfully digest sucrose and starch. This disorder can be further characterized as either a genetic (genetic/congenital sucrase–isomaltase deficiency) or a secondary condition. Sucrase–isomaltase deficiency can result in various clinical symptoms, ranging from mild bloating/flatulence to severe osmotic diarrhea with malabsorption. SID has been associated with irritable bowel syndrome, and further research is needed to further characterize this relationship.
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- 2021
26. Clinical History Does Not Reliably Predict Clinical Outcomes With Pelvic Floor Physical Therapy to Treat Chronic Constipation
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Eric D. Shah, Michael A. Curley, Tracy L. Ostler, Pablo Martinez-Camblor, and William D. Chey
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Hepatology ,Gastroenterology - Abstract
Chronic constipation affects 10%-20% of the population and impacts quality-of-life similarly to rheumatoid arthritis or congestive heart failure.
- Published
- 2022
27. Fishing for Irritable Bowel Syndrome: Which Alarm Features Weave the Best Net?
- Author
-
Justin Brandler and William D. Chey
- Subjects
medicine.medical_specialty ,Hepatology ,business.industry ,Fishing ,Gastroenterology ,MEDLINE ,medicine.disease ,Abdominal Pain ,Diagnosis, Differential ,Irritable Bowel Syndrome ,ALARM ,Emergency medicine ,medicine ,Humans ,Hunting ,business ,Irritable bowel syndrome - Published
- 2022
28. Randomized Placebo-Controlled Phase 3 Trial of Vibrating Capsule for Chronic Constipation
- Author
-
Satish S.C. Rao, Eamonn M.M. Quigley, William D. Chey, Amol Sharma, and Anthony J. Lembo
- Subjects
Hepatology ,Gastroenterology - Published
- 2023
29. Tegaserod for Irritable Bowel Syndrome With Constipation in Women Younger Than 65 Years Without Cardiovascular Disease: Pooled Analyses of 4 Controlled Trials
- Author
-
William D. Chey, Eric D. Shah, Brian E. Lacy, Darren M. Brenner, and Lin Chang
- Subjects
Adult ,medicine.medical_specialty ,Indoles ,Constipation ,Tegaserod ,Population ,Placebo ,Article ,Irritable Bowel Syndrome ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Clinical endpoint ,medicine ,Humans ,Functional GI Disorders ,Adverse effect ,education ,Irritable bowel syndrome ,Randomized Controlled Trials as Topic ,education.field_of_study ,Hepatology ,business.industry ,Gastroenterology ,Odds ratio ,Middle Aged ,medicine.disease ,Serotonin Receptor Agonists ,030220 oncology & carcinogenesis ,Female ,030211 gastroenterology & hepatology ,medicine.symptom ,business ,medicine.drug - Abstract
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
- Published
- 2021
30. S531 Safety and Tolerability of a Vibrating Capsule in Patients With Chronic Idiopathic Constipation
- Author
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William D Chey, Eamonn M. Quigley, Satish Rao, Bryan Curtin, Christine Frissora, Brennan Spiegel, Darren Brenner, and Anthony Lembo
- Subjects
Hepatology ,Gastroenterology - Published
- 2022
31. S562 Patient Compliance With Vibrating Capsule Predicts Outcome in Chronic Idiopathic Constipation (CIC)
- Author
-
Eamonn M. Quigley, Satish Rao, William D. Chey, Bryan F. Curtin, Christine Frissora, Brennan Spiegel, Darren Brenner, and Anthony Lembo
- Subjects
Hepatology ,Gastroenterology - Published
- 2022
32. S536 Prevalence of Disaccharidase Deficiencies in Adults With Irritable Bowel Syndrome and Functional Diarrhea: Interim Analysis From a Multicenter, Prospective U.S. Trial
- Author
-
Samuel W. Chey, William D. Chey, Brooks D. Cash, and Shanti L. Eswaran
- Subjects
Hepatology ,Gastroenterology - Published
- 2022
33. S521 IgG-based Elimination Diets for Patients with IBS: Results From a Prospective, Multi-Center, Double-Blind, Placebo-Controlled Trial
- Author
-
Anthony Lembo, William D. Chey, Brian E. Lacy, Charles W. Randall, Tisha Lundsford, Eamonn M. Quigley, Brooks D. Cash, and Elisabeth I. Laderman
- Subjects
Hepatology ,Gastroenterology - Published
- 2022
34. S525 The Low FODMAP Diet Improves Abdominal and Overall Symptoms in Patients With All Subtypes of Irritable Bowel Syndrome
- Author
-
Gregory Dean, Samuel W. Chey, and William D. Chey
- Subjects
Hepatology ,Gastroenterology - Published
- 2022
35. S541 Symptomatic Response to Antibiotics in Patients With Small Intestine Bacterial Overgrowth: A Systematic Review and Meta-Analysis
- Author
-
Will Takakura, Jiajing Wang, William D. Chey, Ali Rezaie, and Mark Pimentel
- Subjects
Hepatology ,Gastroenterology - Published
- 2022
36. Rates of Antimicrobial Resistance in Helicobacter pylori Isolates From Clinical Trial Patients Across the US and Europe
- Author
-
Francis Mégraud, David Y. Graham, Colin W. Howden, Ernest Trevino, Alice Weissfeld, Barbara Hunt, Neila Smith, Eckhard Leifke, and William D. Chey
- Subjects
Hepatology ,Gastroenterology - Abstract
Guidelines recommend that proton pump inhibitor-based triple regimens with clarithromycin not be used for Helicobacter pylori infection in areas where clarithromycin resistance is ≥15%, or in patients with prior macrolide use. Up-to-date information on local resistance patterns is limited, especially in the US. Here, we report resistance rates to antibiotics commonly used to treat H. pylori from a large study conducted in the US and Europe (pHalcon-HP).Gastric mucosal biopsies were collected from adult participants with H. pylori infection during screening. Minimum inhibitory concentrations were determined via agar dilution for clarithromycin, amoxicillin, and metronidazole, with breakpoints ≥1 μg/mL,0.125 μg/mL, and8 μg/mL, respectively. Resistance rates were obtained for the US and Europe, and also for US subregions and participating European countries.Resistance rates were established in isolates from 907 participants. Overall, 22.2% were resistant to clarithromycin, 1.2% to amoxicillin, and 69.2% to metronidazole. Resistance in the US and Europe was similar; metronidazole resistance was the most prevalent (50%-79%) and amoxicillin the least (≤5%). In all subregions, ≥15% of isolates were resistant to clarithromycin, except the UK (0/8 isolates). Among clarithromycin-resistant isolates, 75% were also metronidazole-resistant. Two US isolates were resistant to clarithromycin and amoxicillin; one of these was also metronidazole-resistant.The resistance rates observed in this study argue against the continued empiric use of proton pump inhibitor-based triple therapy containing clarithromycin, per treatment guidelines, and highlight the need for antibiotic resistance surveillance and novel treatment strategies for H. pylori infection in the US and Europe.
- Published
- 2022
37. Efficacy and safety of vibegron for the treatment of irritable bowel syndrome in women: Results of a randomized, double-blind, placebo-controlled phase 2 trial
- Author
-
Brian E. Lacy, Jennifer King, Denise Shortino, Chris Schaumburg, Cornelia Haag‐Molkenteller, and William D. Chey
- Subjects
Adult ,Irritable Bowel Syndrome ,Diarrhea ,Treatment Outcome ,Double-Blind Method ,Endocrine and Autonomic Systems ,Physiology ,Gastroenterology ,Humans ,Female ,Constipation ,Abdominal Pain - Abstract
Preclinical and clinical studies suggest that βAdult women with predominant-diarrhea IBS (IBS-D) or with mixed diarrhea/constipation (IBS-M), diagnosed using Rome IV criteria, were randomized 1:1 to receive once-daily vibegron 75 mg or placebo for 12 weeks. The primary endpoint was the percentage of patients with IBS-D considered abdominal pain intensity (API) weekly responders, defined as ≥30% reduction from baseline at week 12 in mean weekly worst abdominal pain over 24 hours using the API score. Patients completed a pain diary at baseline and at weeks 2, 4, 8, and 12. Safety was assessed by adverse events (AEs) in the overall IBS population.Of the 222 patients with IBS randomized (vibegron, N = 111; placebo, N = 111), 85% completed the trial. There was no significant difference in the percentage of patients with IBS-D (vibegron, N = 66; placebo, N = 63) considered API weekly responders with vibegron vs. placebo (p = 0.8222) after 12 weeks. The incidence of AEs was comparable between treatment groups (33.3% each), with equal rates of worsening IBS symptoms (2.7% each).In women with IBS-D, vibegron was not associated with significant improvement in the percentage of API weekly responders. Vibegron was generally safe and well tolerated and, in particular, did not worsen IBS symptoms vs. placebo.
- Published
- 2022
38. Abdominal Bloating in the United States: Results of a Survey of 88,795 Americans Examining Prevalence and Healthcare Seeking
- Author
-
Janice E. Oh, William D. Chey, and Brennan Spiegel
- Subjects
Hepatology ,Gastroenterology - Abstract
Although abdominal bloating is a common symptom, comparatively little is known about its prevalence in the community. This study aimed to examine the prevalence of bloating and assess related health care seeking using survey data from a nationally representative sample of nearly 89,000 Americans.Participants completed the National Gastrointestinal (GI) Survey II to measure the presence and severity of GI symptoms including bloating. We assessed the prevalence of bloating in the past 7 days, as well as severity and health care seeking for bloating. Multivariable regression was performed to identify associations between the outcomes and covariates.Of 88,795 survey completers, 12,324 (13.9%) reported bloating in the past 7 days. Women and those with comorbidities (eg, irritable bowel syndrome, chronic constipation, ulcerative colitis) and concomitant GI symptoms (eg, abdominal pain, excess gas) had higher odds for bloating (all P.001). These factors also predicted more severe bloating (all P.001). Among those who reported recent bloating, 58.5% never sought care for bloating-29% of whom were self-managing symptoms or were uncomfortable discussing symptoms with their providers.Bloating is common in the community because nearly 1 in 7 Americans have experienced this symptom in the past week. Women and those with certain comorbidities and concomitant GI symptoms are more likely to experience bloating and have more severe symptoms. Nearly one third of sufferers who have not sought care are managing symptoms on their own or are uncomfortable discussing it with their providers, emphasizing that efforts should be made to proactively inquire about bloating.
- Published
- 2022
39. Price Is Right: Exploring Prescription Drug Coverage Barriers for Irritable Bowel Syndrome Using Threshold Pricing Analysis
- Author
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William D. Chey, Anthony Lembo, Eric D. Shah, Lin Chang, Michael A Curley, and Kyle Staller
- Subjects
medicine.medical_specialty ,education.field_of_study ,Prescription drug ,Physiology ,Cost effectiveness ,business.industry ,Population ,Gastroenterology ,03 medical and health sciences ,0302 clinical medicine ,030220 oncology & carcinogenesis ,Health care ,Step therapy ,Medicine ,030211 gastroenterology & hepatology ,Prior authorization ,Disease management (health) ,Medical prescription ,business ,Intensive care medicine ,education ,health care economics and organizations - Abstract
Prescription drug costs exert profound effects on commercial insurance coverage and access to effective therapy. We aimed to assess threshold pricing to achieve budget neutrality of FDA-approved drugs treating irritable bowel syndrome from an insurance perspective, based on cost-savings resulting in decreased healthcare utilization through effective disease management. We constructed a decision-analytic model from an insurance perspective to assess the budget impact of IBS prescription drugs under usual insurance coverage levels in practice: (1) unrestricted drug access or (2) step therapy in a primary care population of middle-age, care-seeking IBS patients. Budget-neutral drug prices were then calculated which resulted in $0 budget impact to insurers with a short-term, one-year time horizon. If used according to FDA labeling, IBS-D drugs cost between $4778 and $16,844 per year and IBS-C drugs cost between $4319 and $4955 per year. These drug costs often exceed insurance expenditures of $6999 for IBS-D and $3929 for IBS-C if left untreated. Therefore, for drugs to have $0 budget impact to insurers, their prices would need to be discounted 36.7–74.2% for IBS-D drugs and 59.3–82.5% for IBS-C. IBS drugs are already priced to support step therapy “failing one of several common, inexpensive IBS treatments with a responder rate > 30–40%,” reflecting the subpopulation with more severe disease and greater healthcare costs. Broader prescription drug coverage for patients failing common, inexpensive IBS treatments to which at least 30–40% of patients would typically respond appears warranted to enable gastroenterologists to offer personalized approaches targeting specific mechanisms of this heterogeneous disease.
- Published
- 2021
40. Efficacy of Tenapanor in Treating Patients With Irritable Bowel Syndrome With Constipation: A 26-Week, Placebo-Controlled Phase 3 Trial (T3MPO-2)
- Author
-
David P. Rosenbaum, William D. Chey, Yang Yang, and Anthony Lembo
- Subjects
Male ,medicine.medical_specialty ,Abdominal pain ,Constipation ,Placebo ,Gastroenterology ,Article ,Irritable Bowel Syndrome ,03 medical and health sciences ,0302 clinical medicine ,Double-Blind Method ,Internal medicine ,medicine ,Clinical endpoint ,Humans ,Adverse effect ,Functional GI Disorders ,Irritable bowel syndrome ,Sulfonamides ,Hepatology ,business.industry ,Middle Aged ,medicine.disease ,Isoquinolines ,Discontinuation ,Abdominal Pain ,Intention to Treat Analysis ,030220 oncology & carcinogenesis ,Defecation ,030211 gastroenterology & hepatology ,Female ,medicine.symptom ,business - Abstract
INTRODUCTION: Tenapanor is a first-in-class, minimally absorbed, small-molecule inhibitor of the gastrointestinal sodium/hydrogen exchanger isoform 3. This phase 3 trial assessed the long-term efficacy and safety of tenapanor 50 mg b.i.d. for the treatment of patients with irritable bowel syndrome with constipation (IBS-C). METHODS: In this randomized double-blind study (ClinicalTrials.gov identifier: NCT02686138), patients with IBS-C received tenapanor 50 mg b.i.d. or placebo b.i.d. for 26 weeks. The primary endpoint was the proportion of patients who had a reduction of ≥30.0% in average weekly worst abdominal pain and an increase of ≥1 weekly complete spontaneous bowel movement from baseline, both in the same week, for ≥6 of the first 12 treatment weeks (6/12-week combined responder). RESULTS: Of the 620 randomized patients with IBS-C, 593 (95.6%) were included in the intention-to-treat analysis set (tenapanor: n = 293; placebo: n = 300) and 481 patients (77.6%) completed the 26-week treatment period. In the intention-to-treat analysis set (mean age: 45.4 years; 82.1% women), a significantly greater proportion of patients treated with tenapanor were 6/12-week combined responders than those treated with placebo (36.5% vs 23.7%; P < 0.001). Abdominal symptoms and global symptoms of IBS were significantly improved with tenapanor compared with placebo. Diarrhea, the most common adverse event, was typically transient and mild to moderate in severity. Diarrhea led to study drug discontinuation for 19 (6.5%) and 2 patients (0.7%) receiving tenapanor and placebo, respectively. DISCUSSION: Tenapanor 50 mg b.i.d. improved IBS-C symptoms over 26 weeks and was generally well tolerated, offering a potential new long-term treatment option for patients with IBS-C (see Visual abstract, Supplementary Digital Content 1, http://links.lww.com/AJG/B797).
- Published
- 2020
41. Contrasting Clinician and Insurer Perspectives to Managing Irritable Bowel Syndrome: Multilevel Modeling Analysis
- Author
-
Jessica K. Salwen-Deremer, Laurie Keefer, Lin Chang, Shanti Eswaran, Eric D. Shah, Jane G. Muir, Peter R. Gibson, and William D. Chey
- Subjects
medicine.medical_specialty ,Eluxadoline ,Prescription drug ,Cost-Benefit Analysis ,medicine.medical_treatment ,Insurance Carriers ,Insurance Coverage ,Irritable Bowel Syndrome ,03 medical and health sciences ,0302 clinical medicine ,Humans ,Medicine ,Disease management (health) ,Medical prescription ,Intensive care medicine ,health care economics and organizations ,Irritable bowel syndrome ,Hepatology ,business.industry ,Gastroenterology ,Disease Management ,medicine.disease ,Cognitive behavioral therapy ,Alosetron ,030220 oncology & carcinogenesis ,Quality of Life ,Plecanatide ,030211 gastroenterology & hepatology ,business ,medicine.drug - Abstract
Introduction Insurance coverage is an important determinant of treatment choice in irritable bowel syndrome (IBS), often taking precedence over desired mechanisms of action or patient goals/values. We aimed to determine whether routine and algorithmic coverage restrictions are cost-effective from a commercial insurer perspective. Methods A multilevel microsimulation tracking costs and outcomes among 10 million hypothetical moderate-to-severe patients with IBS was developed to model all possible algorithms including common global IBS treatments (neuromodulators; low fermentable oligo-, di-, and mono-saccharides, and polyols; and cognitive behavioral therapy) and prescription drugs treating diarrhea-predominant IBS (IBS-D) or constipation-predominant IBS (IBS-C) over 1 year. Results Routinely using global IBS treatments (central neuromodulator; low fermentable oligo-, di-, and mono-saccharides, and polyols; and cognitive behavioral therapy) before US Food and Drug Administration-approved drug therapies resulted in per-patient cost savings of $9,034.59 for IBS-D and $2,972.83 for IBS-C over 1 year to insurers, compared with patients starting with on-label drug therapy. Health outcomes were similar, regardless of treatment sequence. Costs varied less than $200 per year, regardless of the global IBS treatment order. The most cost-saving and cost-effective IBS-D algorithm was rifaximin, then eluxadoline, followed by alosetron. The most cost-saving and cost-effective IBS-C algorithm was linaclotide, followed by either plecanatide or lubiprostone. In no scenario were prescription drugs routinely more cost-effective than global IBS treatments, despite a stronger level of evidence with prescription drugs. These findings were driven by higher prescription drug prices as compared to lower costs with global IBS treatments. Discussion From an insurer perspective, routine and algorithmic prescription drug coverage restrictions requiring failure of low-cost behavioral, dietary, and off-label treatments appear cost-effective. Efforts to address insurance coverage and drug pricing are needed so that healthcare providers can optimally care for patients with this common, heterogenous disorder.
- Published
- 2020
42. Randomized Trial of 2 Delayed-Release Formulations of Linaclotide in Patients With Irritable Bowel Syndrome With Constipation
- Author
-
David S. Reasner, Gregory S. Sayuk, Niels Borgstein, Elizabeth P. Shea, William D. Chey, Susan M. Fox, Ramesh Boinpally, Wieslaw Bochenek, Wilmin Bartolini, and Kenneth Tripp
- Subjects
Adult ,Diarrhea ,Male ,Abdominal pain ,medicine.medical_specialty ,Constipation ,Placebo ,Gastroenterology ,Article ,law.invention ,Irritable Bowel Syndrome ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Randomized controlled trial ,Double-Blind Method ,law ,Internal medicine ,medicine ,Humans ,Adverse effect ,Functional GI Disorders ,Defecation ,Linaclotide ,Irritable bowel syndrome ,Hepatology ,business.industry ,Guanylyl Cyclase C Agonists ,Middle Aged ,medicine.disease ,Abdominal Pain ,chemistry ,030220 oncology & carcinogenesis ,Delayed-Action Preparations ,030211 gastroenterology & hepatology ,Female ,medicine.symptom ,business ,Peptides - Abstract
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.
- Published
- 2020
43. Utility of Anorectal Testing to Predict Outcomes With Pelvic Floor Physical Therapy in Chronic Constipation: Pragmatic Trial
- Author
-
Eric D. Shah, Elizabeth A. Pelletier, Carol Greeley, Emily E. Sieglinger, Jamie D. Sanchez, Kayla A. Northam, Jessica A. Perrone, Michael A. Curley, Christopher M. Navas, Tracy L. Ostler, Aimee R. Burnett Greeley, Pablo Martinez-Camblor, Jason R. Baker, and William D. Chey
- Subjects
Hepatology ,Gastroenterology - Abstract
We performed a clinical trial that aimed to inform the clinical utility of anorectal manometry (ARM) and balloon expulsion time (BET) as up-front tests to predict outcomes with community-based pelvic floor physical therapy as the next best step to address chronic constipation after failing an empiric trial of soluble fiber supplementation or osmotic laxatives.We enrolled 60 treatment-naïve patients with Rome IV functional constipation failing 2 weeks of soluble fiber supplementation or osmotic laxatives. All patients underwent ARM/BET (London protocol) followed by community-based pelvic floor physical therapy. Outcomes were assessed at baseline and 12 weeks. The primary end point was clinical response (Patient Assessment of Constipation-Symptoms instrument).Fifty-three patients completed pelvic rehabilitation and the post-treatment questionnaire. Contemporary frameworks define dyssynergia on balloon expulsion time and dyssynergic patterns (ARM), but these parameters did not inform clinical outcomes (area under the curve [AUC],0.6). Squeeze pressure (192.5 mm Hg on at least 1 of 3 attempts; sensitivity, 47.6%; specificity, 83.9%) and limited squeeze duration (inability to sustain 50% of squeeze pressure for20 seconds; sensitivity, 71.4%; specificity, 58.1%) were the strongest predictors of clinical outcomes. Combining BET with squeeze duration (BET less than 6.5 seconds and/or limited squeeze duration) improved predictive accuracy (AUC, 0.75; 95% CI, 0.59-0.90). BET poorly predicted outcomes as a single test (AUC, 0.54; 95% CI, 0.38-0.69).Using ARM to evaluate squeeze profiles, rather than dyssynergia, appears useful to screen patients with chronic constipation for up-front pelvic floor physical therapy based on likelihood of response. BET appears noninformative as a single screening test (ClinicalTrials.gov: NCT04159350).
- Published
- 2022
44. Video-Based Deep Learning to Detect Dyssynergic Defecation with 3D High-Definition Anorectal Manometry
- Author
-
Joshua J, Levy, Christopher M, Navas, Joan A, Chandra, Brock C, Christensen, Louis J, Vaickus, Michael, Curley, William D, Chey, Jason R, Baker, and Eric D, Shah
- Abstract
We developed a deep learning algorithm to evaluate defecatory patterns to identify dyssynergic defecation using 3-dimensional high definition anal manometry (3D-HDAM).We developed a 3D-HDAM deep learning algorithm to evaluate for dyssynergia.Spatial-temporal data were extracted from consecutive 3D-HDAM studies performed between 2018 and 2020 at Dartmouth-Hitchcock Health. The technical procedure and gold standard definition of dyssynergia were based on the London consensus, adapted to the needs of 3D-HDAM technology. Three machine learning models were generated: (1) traditional machine learning informed by conventional anorectal function metrics, (2) deep learning, and (3) a hybrid approach. Diagnostic accuracy was evaluated using bootstrap sampling to calculate area-under-the-curve (AUC). To evaluate overfitting, models were validated by adding 502 simulated defecation maneuvers with diagnostic ambiguity.302 3D-HDAM studies representing 1208 simulated defecation maneuvers were included (average age 55.2 years; 80.5% women). The deep learning model had comparable diagnostic accuracy [AUC 0.91 (95% confidence interval 0.89-0.93)] to traditional [AUC 0.93(0.92-0.95)] and hybrid [AUC 0.96(0.94-0.97)] predictive models in training cohorts. However, the deep learning model handled ambiguous tests more cautiously than other models; the deep learning model was more likely to designate an ambiguous test as inconclusive [odds ratio 4.21(2.78-6.38)] versus traditional/hybrid approaches.Deep learning is capable of considering complex spatial-temporal information on 3D-HDAM technology. Future studies are needed to evaluate the clinical context of these preliminary findings.
- Published
- 2022
45. Vonoprazan Triple and Dual Therapy for Helicobacter pylori Infection in the United States and Europe: Randomized Clinical Trial
- Author
-
William D. Chey, Francis Mégraud, Loren Laine, Luis J. López, Barbara J. Hunt, and Colin W. Howden
- Subjects
Adult ,Sulfonamides ,Hepatology ,Helicobacter pylori ,Gastroenterology ,Amoxicillin ,Proton Pump Inhibitors ,United States ,Anti-Bacterial Agents ,Helicobacter Infections ,Treatment Outcome ,Clarithromycin ,Humans ,Drug Therapy, Combination ,Lansoprazole ,Pyrroles - Abstract
Novel, effective treatments for Helicobacter pylori infection are needed. This study evaluated the efficacy of vonoprazan, a potassium-competitive acid blocker, vs standard treatment on H pylori eradication in the United States and Europe.In a randomized, controlled, phase 3 trial, treatment-naïve adults with H pylori infection were randomized 1:1:1 to open-label vonoprazan dual therapy (20 mg vonoprazan twice daily; 1 g amoxicillin 3 times daily), or double-blind triple therapy twice a day (vonoprazan 20 mg or lansoprazole 30 mg; amoxicillin 1 g; clarithromycin 500 mg) for 14 days. The primary outcome was noninferiority in eradication rates in patients without clarithromycin- and amoxicillin-resistant strains (noninferiority margin = 10%). Secondary outcomes assessed superiority in eradication rates in clarithromycin-resistant infections, and in all patients.A total of 1046 patients were randomized. Primary outcome eradication rates (nonresistant strains): vonoprazan triple therapy 84.7%, dual therapy 78.5%, vs lansoprazole triple therapy 78.8% (both noninferior; difference 5.9%; 95% confidence interval [CI], -0.8 to 12.6; P.001; difference -0.3%; 95% CI, -7.4 to 6.8; P = .007, respectively). Eradication rates in clarithromycin-resistant infections: vonoprazan triple therapy 65.8%, dual therapy 69.6%, vs lansoprazole triple therapy 31.9% (both superior; difference 33.9%; 95% CI, 17.7-48.1; P .001; difference 37.7%; 95% CI, 20.5-52.6; P.001, respectively). In all patients, vonoprazan triple and dual therapy were superior to lansoprazole triple therapy (80.8% and 77.2%, respectively, vs 68.5%, difference 12.3%; 95% CI, 5.7-18.8; P .001; difference 8.7%; 95% CI, 1.9-15.4; P = .013). Overall frequency of treatment-emergent adverse events was similar between vonoprazan and lansoprazole regimens (P.05).Both vonoprazan-based regimens were superior to proton pump inhibitor-based triple therapy in clarithromycin-resistant strains and in the overall study population.gov; NCT04167670.
- Published
- 2022
46. Fecal Incontinence: Pathogenesis, Diagnosis, and Updated Treatment Strategies
- Author
-
Stacy, Menees and William D, Chey
- Subjects
Diarrhea ,Male ,Anal Canal ,Humans ,Female ,Fecal Incontinence - Abstract
Fecal incontinence (FI) is defined as the involuntary loss or passage of solid or liquid stool in patients. FI is a common and debilitating condition in men and women. The incidence increases with age and also often goes unreported to health care providers. It is crucial that providers ask at-risk patients about possible symptoms. Evaluation and management is tailored to specific symptoms and characteristics of the incontinence. If conservative methods fail to improve symptoms, then other surgical options are considered, such as sacral nerve stimulation and anal sphincter augmentation. This review provides an update on current and future therapies.
- Published
- 2022
47. Small Intestinal Bacterial Overgrowth
- Author
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William D. Chey, Brian Ginnebaugh, and Richard J. Saad
- Subjects
0301 basic medicine ,medicine.medical_specialty ,Diagnostic methods ,business.industry ,medicine.drug_class ,Antibiotics ,Gastroenterology ,Gold standard (test) ,medicine.disease ,Asymptomatic ,Steatorrhea ,03 medical and health sciences ,Malnutrition ,030104 developmental biology ,0302 clinical medicine ,Small intestinal bacterial overgrowth ,medicine ,030211 gastroenterology & hepatology ,medicine.symptom ,Intensive care medicine ,business ,Dietary modifications - Abstract
Small intestinal bacterial overgrowth (SIBO) is a condition with presentation that can vary from asymptomatic to steatorrhea and malnutrition. Small bowel aspiration and culture is the current gold standard of diagnosis; however, this is invasive and is not without risk to the patient. Breath testing is a noninvasive and less expensive alternative method; however, it lacks diagnostic sensitivity and specificity. Novel diagnostic methods being studied include gas-sensing capsules. The mainstay of treatment is antibiotics; alternative therapies include herbal medications, dietary modifications, and prokinetic agents. Further investigation into less invasive and less harmful diagnostic methods and treatment options is warranted.
- Published
- 2020
48. Increased Risk of COVID-19 Among Users of Proton Pump Inhibitors
- Author
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Christopher V. Almario, William D. Chey, and Brennan Spiegel
- Subjects
Adult ,medicine.medical_specialty ,Adolescent ,Pneumonia, Viral ,Logistic regression ,Drug Prescriptions ,Article ,Odds ,Gastric Acid ,Betacoronavirus ,Young Adult ,03 medical and health sciences ,COVID-19 Testing ,0302 clinical medicine ,Heartburn ,Internal medicine ,medicine ,Humans ,Medical prescription ,Young adult ,Pandemics ,Hepatology ,Clinical Laboratory Techniques ,SARS-CoV-2 ,business.industry ,Confounding ,Gastroenterology ,COVID-19 ,Confounding Factors, Epidemiologic ,Proton Pump Inhibitors ,Odds ratio ,Hydrogen-Ion Concentration ,Middle Aged ,Health Surveys ,Effective dose (pharmacology) ,Confidence interval ,Gastrointestinal Microbiome ,Editorial ,Gastric Mucosa ,030220 oncology & carcinogenesis ,Gastroesophageal Reflux ,Female ,030211 gastroenterology & hepatology ,Coronavirus Infections ,business - Abstract
Introduction Proton pump inhibitors (PPIs) increase the risk for enteric infections that is likely related to PPI-induced hypochlorhydria. Although the impact of acid suppression on severe acute respiratory syndrome coronavirus 2 is unknown thus far, previous data revealed that pH ≤3 impairs the infectivity of the similar severe acute respiratory syndrome coronavirus 1. Thus, we aimed to determine whether use of PPIs increases the odds for acquiring coronavirus disease 2019 (COVID-19) among community-dwelling Americans. Methods From May 3 to June 24, 2020, we performed an online survey described to participating adults as a "national health survey." A multivariable logistic regression was performed on reporting a positive COVID-19 test to adjust for a wide range of confounding factors and to calculate adjusted odds ratios (aORs) and 95% confidence intervals (CIs). Results Of 53,130 participants, 3,386 (6.4%) reported a positive COVID-19 test. In regression analysis, individuals using PPIs up to once daily (aOR 2.15; 95% CI, 1.90-2.44) or twice daily (aOR 3.67; 95% CI, 2.93-4.60) had significantly increased odds for reporting a positive COVID-19 test when compared with those not taking PPIs. Individuals taking histamine-2 receptor antagonists were not at elevated risk. Discussion We found evidence of an independent, dose-response relationship between the use of antisecretory medications and COVID-19 positivity; individuals taking PPIs twice daily have higher odds for reporting a positive test when compared with those using lower-dose PPIs up to once daily, and those taking the less potent histamine-2 receptor antagonists are not at increased risk. These findings emphasize good clinical practice that PPIs should only be used when indicated at the lowest effective dose, such as the approved once-daily label dosage of over-the-counter and prescription PPIs. Further studies examining the association between PPIs and COVID-19 are needed.
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- 2020
49. Evidence of Duodenal Epithelial Barrier Impairment and Increased Pyroptosis in Patients With Functional Dyspepsia on Confocal Laser Endomicroscopy and 'Ex Vivo' Mucosa Analysis
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Elisabeth M. Davis, Chung Owyang, William D. Chey, Shi-Yi Zhou, Russell D. Dolan, Thomas D. Wang, Xueyan Guo, Borko Nojkov, Kenya Jackson, Julia J. Liu, Henry D. Appelman, and Matthew B. Sturm
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Adult ,Male ,Pathology ,medicine.medical_specialty ,Duodenum ,Biopsy ,Epithelium ,Pathogenesis ,Young Adult ,Claudin-1 ,Cell Adhesion ,Electric Impedance ,Pyroptosis ,medicine ,Humans ,Endoscopy, Digestive System ,Dyspepsia ,Intestinal Mucosa ,Aged ,Microscopy, Confocal ,Hepatology ,medicine.diagnostic_test ,Interleukin-6 ,Esophagogastroduodenoscopy ,business.industry ,Caspase 1 ,Gastroenterology ,Histology ,Middle Aged ,medicine.anatomical_structure ,Case-Control Studies ,Immunohistochemistry ,Female ,business - Abstract
Introduction Duodenal epithelial barrier impairment and immune activation may play a role in the pathogenesis of functional dyspepsia (FD). This study was aimed to evaluate the duodenal epithelium of patients with FD and healthy individuals for detectable microscopic structural abnormalities. Methods This is a prospective study using esophagogastroduodenoscopy enhanced with duodenal confocal laser endomicroscopy (CLE) and mucosal biopsies in patients with FD (n = 16) and healthy controls (n = 18). Blinded CLE images analysis evaluated the density of epithelial gaps (cell extrusion zones), a validated endoscopic measure of the intestinal barrier status. Analyses of the biopsied duodenal mucosa included standard histology, quantification of mucosal immune cells/cytokines, and immunohistochemistry for inflammatory epithelial cell death called pyroptosis. Transepithelial electrical resistance (TEER) was measured using Ussing chambers. Epithelial cell-to-cell adhesion proteins expression was assessed by real-time polymerase chain reaction. Results Patients with FD had significantly higher epithelial gap density on CLE in the distal duodenum than that of controls (P = 0.002). These mucosal abnormalities corresponded to significant changes in the duodenal biopsy samples of patients with FD, compared with controls, including impaired mucosal integrity by TEER (P = 0.009) and increased number of epithelial cells undergoing pyroptosis (P = 0.04). Reduced TEER inversely correlated with the severity of certain dyspeptic symptoms. Furthermore, patients with FD demonstrated altered duodenal expression of claudin-1 and interleukin-6. No differences in standard histology were found between the groups. Discussion This is the first report of duodenal CLE abnormalities in patients with FD, corroborated by biopsy findings of epithelial barrier impairment and increased cell death, implicating that duodenal barrier disruption is a pathogenesis factor in FD and introducing CLE a potential diagnostic biomarker in FD.
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- 2020
50. Efficacy of Tenapanor in Treating Patients With Irritable Bowel Syndrome With Constipation: A 12-Week, Placebo-Controlled Phase 3 Trial (T3MPO-1)
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William D. Chey, David P. Rosenbaum, and Anthony Lembo
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Adult ,Diarrhea ,Male ,medicine.medical_specialty ,Constipation ,Treatment outcome ,Placebo ,Gastroenterology ,law.invention ,Irritable Bowel Syndrome ,chemistry.chemical_compound ,Deprescriptions ,Double-Blind Method ,Randomized controlled trial ,law ,Internal medicine ,medicine ,Humans ,ARTICLE ,Functional GI Disorders ,Tenapanor ,Irritable bowel syndrome ,Sulfonamides ,Hepatology ,Sodium-Hydrogen Exchanger 3 ,business.industry ,Middle Aged ,Isoquinolines ,medicine.disease ,Abdominal Pain ,Clinical trial ,Treatment Outcome ,chemistry ,Female ,medicine.symptom ,business - Abstract
OBJECTIVES: Tenapanor is a first-in-class, minimally absorbed, small-molecule inhibitor of the gastrointestinal sodium/hydrogen exchanger isoform 3. This phase 3 trial assessed the efficacy and safety of tenapanor 50 mg b.i.d. for the treatment of patients with constipation-predominant irritable bowel syndrome (IBS-C). METHODS: In this phase 3, double-blind study (ClinicalTrials.gov identifier NCT02621892), patients with IBS-C were randomized to tenapanor 50 mg b.i.d. or placebo b.i.d. for 12 weeks followed by a 4-week randomized withdrawal period. The primary efficacy variable was the proportion of patients who reported a reduction in average weekly worst abdominal pain of ≥30.0% and an increase of ≥1 complete spontaneous bowel movement from baseline, both in the same week, for ≥6 weeks of the 12-week treatment period. RESULTS: Of the 629 randomized patients with IBS-C, 606 (96.3%) were included in the intention-to-treat analysis set (tenapanor: n = 307; placebo: n = 299) and 533 (84.7%) completed the 12-week treatment period. In the intention-to-treat analysis set (mean age 45 years, 81.4% women), a significantly greater proportion of patients treated with tenapanor met the primary endpoint than patients treated with placebo (27.0% vs 18.7%, P = 0.020). Abdominal symptoms and global symptoms of IBS also improved with tenapanor (P < 0.05 vs placebo). Diarrhea was the most commonly reported adverse event, resulting in study drug discontinuation in 6.5% and 0.7% of patients receiving tenapanor and placebo, respectively, during the 12-week treatment period. DISCUSSION: Tenapanor 50 mg b.i.d. improved IBS-C symptoms and was generally well tolerated, offering a potential new treatment option for patients with IBS-C.
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- 2020
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