Centrally Distributed Adiposity as a Modifiable Risk Factor for Fecal Incontinence: United States Population-based Analysis.

BACKGROUND AND AIMS: Fecal incontinence (FI) is highly prevalent with substantial impacts on quality of life and health care utilization. The impact of obesity on FI remains unclear, with differing conclusions using body mass index (BMI) as a risk factor. We aimed to determine the association between obesity and FI, and whether this relationship is dependent on the distribution of adiposity (waist circumference-to-height ratio [WHtR]). METHODS: This was a population-based analysis of the National Health and Nutrition Examination Survey, including participants who responded to the bowel health survey in 2005 to 2010. FI was defined by the accidental bowel leakage of solid stool, liquid, or mucus at least once in the past month. Stepwise multivariable logistic regression models were constructed to assess risk factors for FI. RESULTS: A total of 7606 participants were included, with an overall FI prevalence of 9.2%. When stratified by quartiles of body measurements, FI was increasingly prevalent from the 1st to the 4th quartile for both WHtR (range, 5.3%-12.5%) and BMI (range, 7.1%-10.5%). WHtR was associated with FI and was a stronger predictor than BMI in all quartiles of body measurement. On multivariable analysis, WHtR remained a significant predictor of FI comparing the 4th with the 1st quartile of body measurements (odds ratio [OR], 1.77; 95% confidence interval [CI], 1.11-2.80; P = .017), whereas BMI was not. A WHtR cutoff of >0.592 optimized the Youden index in prediction of FI in the overall sample. CONCLUSION: WHtR was independently associated with increased odds of FI in this nationally representative sample of United States adults, whereas BMI was not consistently correlated. This suggests bowel continence may depend more on how body mass is distributed.

Cost-Effectiveness Analysis of Current Treatment Options for Eosinophilic Esophagitis.

BACKGROUND AND AIMS: The management strategies for eosinophilic esophagitis (EoE) include proton pump inhibitors (PPI), swallowed topical steroids (tCS), elimination diets, and the biologic agent dupilumab, although there remains little guidance on the selection of initial treament. We performed cost-effectiveness analyses to compare these approaches of first-line therapy. METHODS: A Markov model was constructed from a payer perspective to evaluate the cost-effectiveness of first-line therapies for EoE, including PPI, tCS, and six-food elimination diet (SFED), with.crossover in treatments for primary and secondary non-response. The primary outcome was incremental cost-effectiveness ratio (ICER) at two- and five-year time horizons. Secondary analyses included modeling from a societal perspective that also accounted for patient-specific costs, as well as a separate simplified model comparing dupilumab to tCS and PPI. RESULTS: In the base-case scenario (five-year time horizon), the average costs were SFED:$15,296.81, PPI:$16,153.77, and tCS:$20,975.33 as initial therapy, with SFED being the dominant strategy (more effective/less costly), while PPI offered the lowest cost on a two-year time horizon. From a societal perspective, PPI was the dominant initial strategy on both two- and five-year time horizons. Amongst pharmacologic therapies, PPI was the most cost-effective first-line option. Dupilumab was not cost-effective relative to tCS, unless the quarterly cost is reduced from $7,311 to $2,038.50 per price threshold analysis under permissive modeling conditions. CONCLUSIONS: SFED was the most effective/least costly first-line therapy from payer perspective, while PPI was more cost-effective from societal perspective. PPI is also the most cost-effective pharmacologic strategy. Dupilumab requires substantial cost reductions to be considered cost-effective first-line pharmacotherapy.

Impact of Body Composition on Esophagogastric Junction Opening Measures: Discordant FLIP and Manometric Findings Are More Common With Increased Body Mass Index.

INTRODUCTION: Increased intra-abdominal pressure in patients with elevated body mass index (BMI) may affect measurements of esophagogastric junction (EGJ) opening. METHODS: Findings from adult patients who underwent both impedance planimetry with functional luminal imaging probe (FLIP) and high-resolution manometry (HRM) were compared by BMI. RESULTS: Among patients with no EGJ outflow obstruction on HRM, abnormal EGJ classifications on FLIP were more common among those with elevated than normal BMI (61.1% vs 31.6%, P = 0.037). DISCUSSION: Discordant results between FLIP and HRM on EGJ opening are more common in patients with elevated BMI. Body composition may impact EGJ function and measures on current testing modalities.

Quantified Metrics of Gastric Emptying Delay by Glucagon-Like Peptide-1 Agonists: A Systematic Review and Meta-Analysis With Insights for Periprocedural Management.

INTRODUCTION: Divergent recommendations for periprocedural management of glucagon-like peptide-1 (GLP-1) receptor agonist (GLP-1 RA) medications rely on limited evidence. We performed a systematic review and meta-analysis to provide quantitative measures of gastric emptying relevant to mechanisms of weight loss and to periprocedural management of GLP-1 RA. We hypothesized that the magnitude of gastric emptying delay would be low and of limited clinical significance to procedural sedation risks. METHODS: A protocolized search identified studies on GLP-1 RA that quantified gastric emptying measures. Pooled estimates using random effects were presented as a weighted mean difference with 95% confidence intervals (CIs). Univariate meta-regression was performed to assess the influence of GLP-1 RA type, short-acting vs long-acting mechanism of action, and duration of treatment on gastric emptying. RESULTS: Fifteen studies met the inclusion criteria. Five studies (n = 247) utilized gastric emptying scintigraphy. Mean T 1/2 was 138.4 minutes (95% CI 74.5-202.3) for GLP-1 RA vs 95.0 minutes (95% CI 54.9-135.0) for placebo, with a pooled mean difference of 36.0 minutes (95% CI 17.0-55.0, P < 0.01, I2 = 79.4%). Ten studies (n = 411) utilized the acetaminophen absorption test, with no significant delay in gastric emptying measured by T max , area under the curve (AUC) 4hr , and AUC 5hr with GLP-1 RA ( P > 0.05). On meta-regression, the type of GLP-1 RA, mechanism of action, and treatment duration did not impact gastric emptying ( P > 0.05). DISCUSSION: While a gastric emptying delay of ∼36 minutes is quantifiable on GLP-1 RA medications, it is of limited magnitude relative to standard periprocedural fasting periods. There were no substantial differences in gastric emptying on modalities reflective of liquid emptying (acetaminophen absorption test), particularly at time points relevant to periprocedural care.

Allergic phenotype identified on allergen testing is associated with proton pump inhibitor nonresponse in eosinophilic esophagitis.

BACKGROUND AND AIM: Food/environmental allergens have been associated with eosinophilic esophagitis (EoE); however, the correlation between allergy profiles and disease responsiveness to proton pump inhibitor (PPI) therapy remains unclear. We aimed to assess the association between food/environmental allergies identified on allergen testing and histologic response to PPI in patients with treatment-naive EoE. METHODS: Adults with newly diagnosed EoE who underwent formal testing for food/environmental allergies at a tertiary center were included. All patients underwent twice-daily PPI for 8 weeks with subsequent repeat endoscopy and biopsy to assess histologic response. Patients with <15 eosinophils/hpf on post-PPI mucosal biopsies were classified as responders (PPI-r-EoE), while those with ≥15 eosinophils/hpf were nonresponders (PPI-nr-EoE). RESULTS: Sixty-one patients met inclusion criteria (21 PPI-r-EoE vs 40 PPI-nr-EoE). Demographic, clinical, and endoscopic finding variables were similar between groups. Positive food allergen test was more prevalent among PPI-nr-EoE patients (82.5% vs 42.9%, P = 0.003). On multivariable analysis, positive food allergen testing remained an independent predictor for PPI nonresponse (aOR 0.15, CI: 0.04-0.58, P = 0.0006). Positive environmental allergen testing was highly prevalent, with no significant differences between groups (77.5% vs 95.2%, P = 0.14). However, higher number of positive environmental allergens (23.3% [≥5 allergens] vs 73.3% [<5 allergens], P = 0.003) and specific aeroallergens correlated with PPI-nr-EoE. CONCLUSION: Positive food allergy testing and increased environmental allergens predicted lower likelihood of histologic response to PPI in EoE. Our findings support an allergic phenotype of EoE that may less likely respond to PPI therapy. Formal allergen testing may play a role in therapy selection and tailored management in EoE.

Examining the Nocebo Effect in Trials of Neuromodulators for Use in Disorders of Gut-Brain Interaction.

INTRODUCTION: Nocebo effects are believed to influence the rate of reported adverse events (AE) and subject withdrawal in both the treatment and placebo groups of randomized clinical trials (RCT). Neuromodulators are commonly prescribed to treat disorders of gut-brain interaction (DGBI), but adherence to these medications is often limited by side effects such as headache, dry mouth, fatigue, and altered bowel habits. We performed a systematic review and meta-analysis to assess the proportion and risk difference of patients who experienced side effects leading to withdrawal in the placebo arm vs the treatment arm of RCT of neuromodulators for DGBI. We also sought to estimate the risk of developing any AE in the placebo arm of these studies and the rate of specific individual AEs. METHODS: We searched MEDLINE, Embase, Web of Science Core Collection, and the Cochrane Central Register of Controlled Trials Searches to identify RCT that included terms for DGBI and for commonly prescribed neuromodulators. We calculated pooled proportions of patients experiencing an AE leading to withdrawal in the active treatment group vs the placebo group with 95% confidence intervals (CI), the pooled proportions of patients experiencing any AE, the pooled proportions of patients experiencing specific AE such as dizziness and headache, the pooled proportions of patients experiencing severe AE, and corresponding pooled risk differences with 95% CI. RESULTS: There were 30 RCT included representing 2,284 patients with DGBI. Twenty-seven RCT reported data on AE leading to withdrawal. The pooled proportion of total patients with AE leading to withdrawal in the placebo group was 4% (95% CI 0.02-0.04). The pooled proportion of patients with AE leading to withdrawal who received neuromodulators was 9% (95% CI 0.06-0.13). In the 12 studies reporting data on patients experiencing at least 1 AE, the pooled proportion of patients experiencing any AE in the placebo group was 18% (95% CI 0.08-0.30), compared with 43% (95% CI 0.24-0.63) in the neuromodulator group. Thus, approximately 44% of the rate of withdrawal (0.04/0.09) and 42% of the rate reporting any side effects (0.18/0.43) in the neuromodulator group may be attributed to nocebo effects in the right context. Subgroup analysis by sex, medication class, risk of bias, and specific DGBI revealed differing withdrawal rates. There was no statistically significant difference in patients experiencing individual AE of dizziness, headache, or diarrhea. Rates of dry mouth, fatigue, and constipation were higher in treatment groups compared with those in placebo groups. DISCUSSION: Patients with DGBI in RCT randomized to placebo groups frequently experience AE and AE that lead to withdrawal consistent with a strong nocebo effect. Nonspecific AE such as dizziness, headaches, and diarrhea occurred similarly in patients receiving placebo compared with those receiving neuromodulators.

The effect of geographic origin and destination on congenital heart disease outcomes: a retrospective cohort study.

BACKGROUND: Congenital heart disease (CHD) is a common and significant birth defect, frequently requiring surgical intervention. For beneficiaries of the Department of Defense, a new diagnosis of CHD may occur while living at rural duty stations. Choice of tertiary care center becomes a function of geography, referring provider recommendations, and patient preference. METHODS: Using billing data from the Military Health System over a 5-year period, outcomes for beneficiaries age < 10 years undergoing CHD surgery were compared by patient origin (rural versus urban residence) and the distance to treatment (patient's home and the treating tertiary care center). These beneficiaries include children of active duty, activated reserves, and federally activated National Guard service members. Analysis of the outcomes were adjusted for procedure complexity risk. Treatment centers were further stratified by annual case volume and whether they publicly reported results in the society of thoracic surgery (STS) outcomes database. RESULTS: While increasing distance was associated with the cost of admission, there was no associated risk of inpatient mortality, one year mortality, or increased length of stay. Likewise, rural origination was not significantly associated with target outcomes. Patients traveled farther for STS-reporting centers (STS-pr), particularly high-volume centers. Such high-volume centers (> 50 high complexity cases annually) demonstrated decreased one year mortality, but increased cost and length of stay. CONCLUSIONS: Together, these findings contribute to the national conversation of rural community medicine versus regionalized subspecialty care; separation of patients between rural areas and more urban locations for initial CHD surgical care does not increase their mortality risk. In fact, traveling to high volume centers may have an associated mortality benefit.

A Nationwide Survey of Gastroenterology Program Leadership Regarding Implementation of the GI Hospitalist Model.

BACKGROUND: Academic gastroenterology (GI) hospitalists are increasing, however the impacts on fellowship training and clinical care are unclear. Motivations for implementation of the GI hospitalist model are uninvestigated. AIMS: We aimed to determine the prevalence of GI hospitalists, explore motivations for and against adoption of a GIH model, and investigate the model's effects on fellowship training. METHODS: Leadership at current general GI fellowships were surveyed about current staffing models, as well as effects and perceptions of the hospitalist model. RESULTS: There was a total of 52 (26%) respondents and 12 (23%) reported having a GI hospitalist at their institution. A majority of respondents stated burnout and reduced time on service for other faculty was a primary reason for hiring a GI hospitalist. DISCUSSION: The largest perceived benefit of a hospitalist is reduced burnout and time on service for outpatient GI faculty. Many respondents also believed a GIH would improve fellowship education and quality of inpatient care.

Utilizing Google Trends to Assess Worldwide Interest in Irritable Bowel Syndrome and Commonly Associated Treatments.

BACKGROUND: Examining the prevalence of irritable bowel syndrome (IBS) across regions has been challenging given significant methodological heterogeneity. AIMS: We aimed to perform a uniform assessment of the global burden of IBS using data from Google Trends, a novel, online tool. METHODS: Google Trends measures popularity of a search term in a given week compared to popularity of all search terms in that week, calculated as relative search volume (RSV). We compiled data on the popularity of IBS and its treatments across 173 countries between 2014 and 2018. We compared Google Trends popularity for IBS with prior epidemiological prevalence data, while controlling for gross domestic product (GDP) per capita and physician density. RESULTS: Of the 173 countries with Google Trends data, 137 countries also had data for GDP per capita and physician density. Worldwide popularity of IBS as a search topic increased from 79 to 89 (13% increase by RSV) over the 5-year period between 2014 and 2018. Country-specific change in IBS RSV ranged from - 35% (Nigeria) to + 64% (Pakistan). There was poor correlation between the Google Trends data and prior epidemiological data (0.08, Pearson correlation, p = 0.64). Popularity of the low-FODMAP diet increased the most among 8 common therapies (RSV 41 to 89, 117% increase). CONCLUSIONS: Google Trends is a novel tool that can complement traditional epidemiological methods in gastrointestinal disease. Future research is needed to assess its utility and accuracy as a measure of disease burden across different gastrointestinal diseases.

Increased Internet Search Interest for GI Symptoms May Predict COVID-19 Cases in US Hotspots.

Google Trends is an online tool that allows measurement of search term popularity on Google, spatially and temporally. While not an epidemiological tool for determining incidence, it can estimate the popularity of a certain disease by search volume over time.1,2 It has previously correlated well with infectious disease incidence and has demonstrated utility in disease forecasting, especially with influenza data.3 We utilized Google Trends to investigate whether search interest in common gastrointestinal (GI) symptoms would correlate with coronavirus disease 2019 (COVID-19) incidence data.

Frequency of Eating Disorder Pathology Among Patients With Chronic Constipation and Contribution of Gastrointestinal-Specific Anxiety.

BACKGROUND & AIMS: Individuals with eating disorders (EDs) frequently have constipation-related symptoms, although the mechanisms of this relationship are not clear. We examined the frequency of and relation between EDs and constipation in patients with chronic constipation referred for anorectal manometry. METHODS: We analyzed data from 279 patients with chronic constipation (79.2% female) evaluated at a tertiary center from June 2017 through September 2018. Participants completed a standardized psychometric assessment (patient assessment of constipation symptoms questionnaire and hospital anxiety and depression scale and visceral sensitivity index analyses) and anorectal manometry. A subset of patients completed colonic transit testing. Participants with clinically significant ED pathology were identified based on scores of 20 or higher on the Eating Attitudes Test-26. We performed a logistic regression analysis to examine factors associated with the likelihood of having ED pathology. Odds ratios were calculated based on continuous variables. We examined the contribution of anxiety to the relationship between severity of ED pathology and symptoms of constipation (such as abdominal pain) using a regression-based bootstrapping approach. RESULTS: Of the study participants, 53 (19.0%) had clinically significant ED pathology. The presence of ED pathology was associated with greater general anxiety scores, based on the hospital anxiety and depression scale (odds ratio, 1.20; 95% CI, 1.05-1.38), and greater gastrointestinal-specific anxiety scores, based on the visceral sensitivity index (odds ratio, 1.06; 95% CI, 1.03-1.09). Gastrointestinal-specific anxiety fully mediated the relationship between the severity of ED pathology and constipation (standardized ß, 0.11-0.16; P = .026-.024). We found no differences in anorectal manometry or colonic transit between patients with vs without ED pathology. CONCLUSIONS: In an analysis of patients with chronic constipation, we found that 19% had clinically significant ED pathology. Our preliminary finding indicated that ED pathology might contribute to constipation via gastrointestinal-specific anxiety. Clinicians should consider screening patients with chronic constipation for EDs-especially patients who report symptoms such as bloating and abdominal pain.

Jackhammer Esophagus After Lung Transplantation: Results of a Retrospective Multicenter Study.

GOALS: We sought to determine the incidence of jackhammer esophagus (JE) after lung transplantation (LT) and identify potential risk factors for the development of JE after LT. BACKGROUND: JE is a rare esophageal motility disorder, and its pathophysiology remains unclear. Lung transplantation has been implicated as a potential risk factor for JE, but the incidence of JE after LT is unknown. STUDY: A retrospective cohort of adult patients who underwent LT at 2 tertiary care centers over 7.5 years was reviewed. Analysis was performed on patients who underwent a high-resolution esophageal manometry (EM) study before and after LT. JE was defined according to the latest Chicago classification, version 3.0. RESULTS: A total of 57 patients without JE identified on pre-LT EM also underwent an EM study after LT. Fifteen (25.4%) were found to have new JE after LT. Patients with newly diagnosed JE after LT were older (61.3±5.3 y vs. 51.6±15.6 y; P=0.02) and more often had chronic obstructive pulmonary disease (COPD; 47.6% vs. 16.6%; P=0.03) compared with those without COPD. There was a trend toward increased risk for JE among female individuals (60% vs. 33.3%; P=0.07) and those with shorter surgical anastomosis times (75.8±12.2 min vs. 84.4±14.3; P=0.06). There was no significant difference between body mass index, opioid use, pretransplant EM findings, surgical ischemic time, occurrence of gastroparesis, or measured post-LT outcomes between the 2 groups. CONCLUSIONS: JE occurs not uncommonly in patients after LT. Older age and COPD pre-LT may be significant risk factors.

Colonic Stool Burden a Useful Surrogate for Slow Transit Constipation as Determined by a Radiopaque Transit Study.

OBJECTIVES: Plain film abdominal x-ray (AXR) is frequently used in the evaluation of constipation, but studies assessing the association between stool burden on AXR and colonic transit have been limited. We sought to investigate the relationship between colonic stool burden and slow transit constipation, as determined by a radiopaque marker (ROM) transit study. METHODS: A retrospective cohort population was assembled, consisting of adult patients with chronic constipation who underwent testing with both a ROM study and anorectal manometry at 2 tertiary care centers over 5 years. Stool burden was graded by 2 independent observers, with colonic transit being assessed by the Hinton method. RESULTS: Of 361 patients, 145 (40.3%) had slow transit constipation, and women were more likely than men to have slow transit constipation (42.3% vs 26.5%, P = 0.04). The mean stool burden scores by observer 1 and observer 2 for patients with slow transit constipation were significantly higher than the mean stool burden scores for patients with normal transit constipation (8.1 ± 1.6 vs 6.9 ± 1.9, P < 0.0001; 8.5 ± 1.5 vs 5.8 ± 1.6, P < 0.0001). The Pearson correlation coefficient for the stool burden score and number of remaining ROMs was 0.31 (moderate) for observer 1 (P < 0.0001) and 0.62 (strong) for observer 2 (P < 0.0001), whereas the Pearson correlation coefficient for interrater reliability of the stool burden score was 0.58 (P < 0.0001), indicating a strong correlation. The ideal score cutoff for both observers was 7, with moderate agreement by Cohen's kappa (0.43, P < 0.0001). CONCLUSIONS: Stool burden assessment on AXR may be a reliable alternative ROM study in the assessment of colonic transit.

Relationship Between Recreational Marijuana Use and Bowel Function in a Nationwide Cohort Study.

OBJECTIVES: Although the endogenous cannabinoid system modulates bowel function, our understanding of the impact of recreational marijuana (MJ) use on bowel motility is limited. This study examines the effect of MJ on self-reported bowel function among a large cohort of US adults. METHODS: We identified adults (age: 20-59 years) who completed both the drug use and bowel health questionnaires in the National Health and Nutrition Examination Survey over a 6-year period from 2005 to 2010 (n = 9,645). Constipation and diarrhea were defined according to stool form (Bristol Stool Form Scale) and/or frequency criteria. Adjusted odds ratios (AORs) for likelihood of constipation or diarrhea were estimated in a multinomial logistic model according to MJ use status. RESULTS: Overall, constipation prevalence was lower among those with recent MJ use compared with those with past/never use (7.5% vs 10.2%, P = 0.03). Recent MJ use was associated with a 30% decreased odds of constipation (crude odds ratio: 0.71 [0.56-0.98], P = 0.005), which persisted after stepwise adjustment for age and other demographic factors including sex, ethnicity, education, body mass index, and socioeconomic status (AOR: 0.64 [0.49-0.83], P = 0.001); comorbidities, substance use (alcohol, tobacco, heroin, and cocaine), constipating medications, general health condition, rigorous physical activity, and emotional disturbances (AOR: 0.68 [0.48-0.93], P = 0.016); and diet (AOR: 0.68 [0.52-0.89], P = 0.006). There was no association between recent MJ use and diarrhea. DISCUSSION: In a nationally representative sample of community-dwelling US adults, recent MJ use was associated with decreased odds of constipation, counter to the known physiologic effects of cannabinoids on colonic motility.

The Epistemological Weight of Randomized-Controlled Trials Depends on Their Results.

When evaluating the internal validity of clinical trials, physicians and medical researchers place substantial importance on factors such as blinding and randomization. For a particular randomized-controlled trial (RCT), causal inference and explanation require additional contextual considerations, to which we assign the term "epistemological weight." We argue that one component of epistemological weight, epistemological function, depends on a trial's results. We further note that discordant RCTs often lead to hypothesis generation, an epistemological function that is rare among concordant studies. As an example of methodologically sound but discordant studies, we explore the issue of hormone-replacement therapy and cardiovascular outcomes.