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"Chey, William D."
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ACG Clinical Guideline: Management of Irritable Bowel Syndrome
2021
Irritable bowel syndrome (IBS) is a highly prevalent, chronic disorder that significantly reduces patients' quality of life. Advances in diagnostic testing and in therapeutic options for patients with IBS led to the development of this first-ever American College of Gastroenterology clinical guideline for the management of IBS using Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology. Twenty-five clinically important questions were assessed after a comprehensive literature search; 9 questions focused on diagnostic testing; 16 questions focused on therapeutic options. Consensus was obtained using a modified Delphi approach, and based on GRADE methodology, we endorse the followingWe suggest that a positive diagnostic strategy as compared to a diagnostic strategy of exclusion be used to improve time to initiating appropriate therapy. We suggest that serologic testing be performed to rule out celiac disease in patients with IBS and diarrhea symptoms. We suggest that fecal calprotectin be checked in patients with suspected IBS and diarrhea symptoms to rule out inflammatory bowel disease. We recommend a limited trial of a low fermentable oligosaccharides, disacchardies, monosaccharides, polyols (FODMAP) diet in patients with IBS to improve global symptoms. We recommend the use of chloride channel activators and guanylate cyclase activators to treat global IBS with constipation symptoms. We recommend the use of rifaximin to treat global IBS with diarrhea symptoms. We suggest that gut-directed psychotherapy be used to treat global IBS symptoms. Additional statements and information regarding diagnostic strategies, specific drugs, doses, and duration of therapy can be found in the guideline.
Journal Article
Fiber and Functional Gastrointestinal Disorders
by
Chey, William D
,
Muir, Jane
,
Eswaran, Shanti
in
Abdominal Pain - etiology
,
Constipation - diet therapy
,
Constipation - etiology
2013
Despite years of advising patients to alter their dietary and supplementary fiber intake, the evidence surrounding the use of fiber for functional bowel disease is limited. This paper outlines the organization of fiber types and highlights the importance of assessing the fermentation characteristics of each fiber type when choosing a suitable strategy for patients. Fiber undergoes partial or total fermentation in the distal small bowel and colon leading to the production of short-chain fatty acids and gas, thereby affecting gastrointestinal function and sensation. When fiber is recommended for functional bowel disease, use of a soluble supplement such as ispaghula/psyllium is best supported by the available evidence. Even when used judiciously, fiber can exacerbate abdominal distension, flatulence, constipation, and diarrhea.
Journal Article
Increased Risk of COVID-19 Among Users of Proton Pump Inhibitors
by
Spiegel, Brennan M.R.
,
Almario, Christopher V.
,
Chey, William D.
in
Abdomen
,
Adolescent
,
Adult
2020
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.
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).
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.
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.
Journal Article
Transient Lymphocytic Colitis After SARS-CoV2 mRNA Vaccine
by
Chey, Samuel W.
,
Westerhoff, Maria
,
Chey, William D.
in
Abdomen
,
Biopsy
,
Colitis, Lymphocytic - diagnosis
2022
This is the first scientific report describing lymphocytic colitis after administration of the Pfizer severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) messenger RNA (mRNA) vaccine. The patient developed liquid stools, abdominal pain, and nausea within 24 hours of receiving the second dose. Symptoms were persistent for 3 months but improved 113 days after onset. Laboratory profiles and gastrointestinal polymerase chain reaction were normal. Esophagogastroduodenoscopy and colonoscopy performed 98 days after onset revealed patchy erythema in the descending colon and rectosigmoid. Mucosal evaluation revealed lymphocytic colitis. Review of the Vaccine Adverse Event Reporting System revealed 5 cases of microscopic colitis after the second mRNA dose. This report and Vaccine Adverse Event Reporting System cases suggest providers should consider microscopic colitis in the differential diagnosis of patients with severe, persistent diarrhea after the SARS-CoV2 mRNA vaccine.
Journal Article
American College of Gastroenterology Guideline on the Management of Helicobacter pylori Infection
by
Chey, William D.
,
Wong, Benjamin C.Y.
in
Amoxicillin
,
Gastroenterology
,
Helicobacter Infections - diagnosis
2007
Helicobacter pylori (H. pylori) remains a prevalent, worldwide, chronic infection. Though the prevalence of this infection appears to be decreasing in many parts of the world, H. pylori remains an important factor linked to the development of peptic ulcer disease, gastric malignanc and dyspeptic symptoms. Whether to test for H. pylori in patients with functional dyspepsia, gastroesophageal reflux disease (GERD), patients taking nonsteroidal antiinflammatory drugs, with iron deficiency anemia, or who are at greater risk of developing gastric cancer remains controversial. H. pylori can be diagnosed by endoscopic or nonendoscopic methods. A variety of factors including the need for endoscopy, pretest probability of infection, local availability, and an understanding of the performance characteristics and cost of the individual tests influences choice of evaluation in a given patient. Testing to prove eradication should be performed in patients who receive treatment of H. pylori for peptic ulcer disease, individuals with persistent dyspeptic symptoms despite the test-and-treat strategy, those with H. pylori-associated MALT lymphoma, and individuals who have undergone resection of early gastric cancer. Recent studies suggest that eradication rates achieved by first-line treatment with a proton pump inhibitor (PPI), clarithromycin, and amoxicillin have decreased to 70-85%, in part due to increasing clarithromycin resistance. Eradication rates may also be lower with 7 versus 14-day regimens. Bismuth-containing quadruple regimens for 7-14 days are another first-line treatment option. Sequential therapy for 10 days has shown promise in Europe but requires validation in North America. The most commonly used salvage regimen in patients with persistent H. pylori is bismuth quadruple therapy. Recent data suggest that a PPI, levofloxacin, and amoxicillin for 10 days is more effective and better tolerated than bismuth quadruple therapy for persistent H. pylori infection, though this needs to be validated in the United States.
Journal Article
The Efficacy and Safety of Rifaximin for the Irritable Bowel Syndrome: A Systematic Review and Meta-Analysis
by
Chey, William D
,
Menees, Stacy B
,
Maneerattannaporn, Monthira
in
Anti-Infective Agents - therapeutic use
,
Antibacterial agents
,
Antibiotics. Antiinfectious agents. Antiparasitic agents
2012
Irritable bowel syndrome (IBS) affects 10-15% of the population, and treatment options are limited. Rifaximin is a minimally absorbed antibiotic that has shown efficacy in IBS patients. The objective of our study was to perform a meta-analysis and systematic review of available randomized, placebo controlled trials evaluating the efficacy and tolerability of rifaximin in patients with IBS.
We performed a systematic literature search of multiple online electronic databases regardless of language. Inclusion criteria entailed randomized, placebo controlled trials and IBS defined by accepted symptom-based criteria. Meta-analysis was conducted to evaluate the summary odds ratios (ORs) and 95% confidence intervals (CIs) of combined studies for the primary and secondary outcomes using a random-effects model based on the DerSimonian and Laird method to reflect both within- and between study variability. We assessed heterogeneity using χ(2) test and the inconsistency index statistic (I(2)). Significant heterogeneity was defined as I(2) ≥25%. Meta-regression was performed using generalized linear mixed-effects model and study as random effects to estimate the summary OR adjusting for covariate differences across studies and treatment group. Publication bias was assessed by funnel plot analysis.
Systematic review identified 13,700 citations. Eighteen were deemed to be potentially relevant, of which five articles met eligibility. Meta-analysis found rifaximin to be more efficacious than placebo for global IBS symptom improvement (OR=1.57; 95% CI=1.22, 2.01; therapeutic gain=9.8%; number needed to treat (NNT)=10.2), with mild heterogeneity (P=0.25, I(2)=26%). For the key secondary outcome of bloating, raw data were available for four studies. Rifaximin was significantly more likely to improve bloating than placebo (OR=1.55; 95% CI=1.23-1.96; therapeutic gain=9.9%; NNT=10.1), with no significant heterogeneity (P=0.27, I(2)=23%). We found that studies with older patients and more females demonstrated higher response rates, which was consistent regardless of treatment group. In addition, studies with higher cumulative dose tended to report a higher response rate. Of the covariates evaluated, we found age to be most predictive of response, with a correlation coefficient of 0.97 between aggregate response rate and mean age in the placebo groups. Although studies with higher cumulative dose tended to show increased response rates, this was also seen consistently in both the treated and placebo groups. Adverse effects were similar among patients receiving rifaximin or placebo in all studies. The most common adverse events (AEs) (≤10%) with rifaximin were headache, upper respiratory infection, nausea, nasopharygitis, diarrhea, and abdominal pain. Serious AEs were rare (<1%) and similar with rifaximin and placebo.
Rifaximin proved more effective than placebo for global symptoms and bloating in IBS patients. The modest therapeutic gain was similar to that yielded by other currently available therapies for IBS. AEs were similar between rifaximin and placebo.
Journal Article
The Spectrum of Constipation-Predominant Irritable Bowel Syndrome and Chronic Idiopathic Constipation: US Survey Assessing Symptoms, Care Seeking, and Disease Burden
2015
The irritable bowel syndrome with constipation (IBS-C) and chronic idiopathic constipation (CIC) are associated with substantial symptom and disease burden. Although typically classified as distinct diseases, symptoms frequently overlap.
The objective of this study was to characterize symptom and disease burden in IBS-C and CIC sufferers and examine a subset of CIC sufferers with abdominal symptoms.
In a US population-based survey, respondents meeting the Rome III criteria for IBS-C or CIC rated symptom frequency and bothersomeness, missed work and disrupted productivity, and degree of obtaining and satisfaction with physician care. CIC respondents were analyzed in two subgroups: those with abdominal symptoms ≥once weekly (CIC-A) and those without (CIC-NA).
Of the 10,030 respondents, 328 met the criteria for IBS-C and 552 for CIC (363 CIC-A; 189 CIC-NA). All symptoms were significantly more frequent in IBS-C vs. CIC respondents (P<0.0001). Constipation was extremely/very bothersome in 72% of IBS-C respondents, 62% of CIC-A, and 40% of CIC-NA (P<0.01 all pairs). All 11 other measured symptoms were significantly more bothersome in IBS-C and CIC-A vs. CIC-NA respondents. In IBS-C vs. CIC-A, abdominal discomfort, bloating, straining, and pellet-like stools were also significantly more bothersome, with other remaining symptoms similar. Gastrointestinal symptoms disrupted productivity a mean of 4.9 days per month in IBS-C respondents, 3.2 in CIC-A, and 1.2 in CIC-NA (P<0.001 all pairs); missed days were similar in IBS-C and CIC-A respondents.
CIC respondents with abdominal symptoms experience greater disease burden compared with CIC respondents without frequent abdominal symptoms and have a disease burden profile that is similar to IBS-C respondents.
Journal Article
A Randomized Placebo-Controlled Phase IIb Trial of A3309, A Bile Acid Transporter Inhibitor, for Chronic Idiopathic Constipation
by
Chey, William D
,
Camilleri, Michael
,
Graffner, Hans
in
Abdominal Pain - chemically induced
,
Adult
,
Aged
2011
A3309 is a minimally absorbed ileal bile acid (BA) transporter (IBAT) inhibitor. We conducted an 8-week, multicenter, randomized, double-blind, placebo-controlled, parallel group, phase IIb study, which evaluated A3309 in patients with chronic idiopathic constipation (CIC).
Patients with CIC (modified Rome III criteria and <3 complete (CSBM) spontaneous bowel movements (SBMs)/week during the 2-week baseline) were randomized to 5, 10, or 15 mg A3309 or placebo once daily. The primary end point was change in SBM number during week 1 compared with baseline. Other bowel and abdominal symptoms were assessed as secondary end points. Serum 7αC4 and lipids were evaluated as biomarkers of BA synthesis/loss.
In all, 190 patients (mean 48 years, 90% female) were randomized. Mean increase (95% confidence interval) in SBM for week 1 were 1.7 (0.7-2.8) for placebo vs. 2.5 (1.5-3.5), 4.0 (2.9-5.0), and 5.4 (4.4-6.4) for 5 mg, 10 mg (P<0.002), and 15 mg (P<0.001) A3309, respectively. Increased stool frequency was maintained over 8 weeks. Time to first SBM and CSBM were significantly reduced in the 10- and 15-mg A3309 groups compared with placebo. Straining and bloating decreased with A3309 compared with placebo (P<0.05). Increased 7αC4 and reduced low-density lipoprotein cholesterol with A3309 suggested increased BA synthesis and BA loss. The most common adverse events (AEs) were abdominal pain and diarrhea, which occurred most commonly in the 15-mg A3309 group. No drug-related serious AEs were observed.
A3309 increased stool frequency and improved constipation-related symptoms in CIC; effects were maintained over 8 weeks of treatment.
Journal Article
The Utility of Probiotics in the Treatment of Irritable Bowel Syndrome: A Systematic Review
by
Chey, William D
,
Brenner, Darren M
,
Moeller, Matthew J
in
Bifidobacterium
,
Bifidobacterium infantis
,
Biological and medical sciences
2009
Irritable bowel syndrome (IBS) is a common disorder and available therapies have limited efficacy. Mucosal inflammation and alterations in gut microflora may contribute to the development of IBS symptoms, and researchers have hypothesized that probiotics might improve these symptoms. The aim of this study was to perform a systematic review of randomized controlled trials (RCTs) evaluating the efficacy, safety, and tolerability of probiotics in the treatment of IBS.
Comprehensive literature searches of multiple databases were performed. Study selection criteria were as follows: (i) RCTs, (ii) adults with IBS defined by Manning or Rome II criteria, (iii) single or combination probiotic vs. placebo, and (iv) improvement in IBS symptoms and/or decrease in frequency of adverse events reported. Data about study design and results were extracted in duplicate using standardized data extraction forms. Owing to variability in outcome measures, quantitative pooling of data was not feasible.
A total of 16 RCTs met selection criteria. Of those, 11 studies showed suboptimal study design with inadequate blinding, inadequate trial length, inadequate sample size, and/or lack of intention-to-treat analysis. None of the studies provided quantifiable data about both tolerability and adverse events. Bifidobacterium infantis 35624 showed significant improvement in the composite score for abdominal pain/discomfort, bloating/distention, and/or bowel movement difficulty compared with placebo (P<0.05) in two appropriately designed studies. No other probiotic showed significant improvement in IBS symptoms in an appropriately designed study.
B. infantis 35624 has shown efficacy for improvement of IBS symptoms. Most RCTs about the utility of probiotics in IBS have not used an appropriate study design and do not adequately report adverse events. Therefore, there is inadequate data to comment on the efficacy of other probiotics. Future probiotic studies should follow Rome II recommendations for appropriate design of an RCT.
Journal Article
Evaluating the Impact of Cost on the Treatment Algorithm for Chronic Idiopathic Constipation: Cost-Effectiveness Analysis
2021
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.
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.
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.
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.
Journal Article