McCarty TR, Jirapinyo P, James LP, Gupta S, Chan WW, Thompson CC. Transoral incisionless fundoplication is cost-effective for treatment of gastroesophageal reflux disease. Endoscopy international open. 2022;10(7):E923-E932. doi:10.1055/a-1783-9378

Background and study aims  Given the sizable number of patients with symptomatic gastroesophageal reflux disease (GERD) despite proton pump inhibitor (PPI) therapy, non-pharmacologic treatment has become increasingly utilized. The aim of this study was to analyze the cost-effectiveness of medical, endoscopic, and surgical treatment of GERD. Patients and methods  A deterministic Markov cohort model was constructed from the US healthcare payer's perspective to evaluate the cost-effectiveness of three competing strategies: 1) omeprazole 20 mg twice daily; 2) transoral incisionless fundoplication (TIF 2.0); and 3) laparoscopic Nissen fundoplication [LNF]. Cost was reported in US dollars with health outcomes recorded in quality-adjusted life years (QALYs). Ten-year and lifetime time horizons were utilized with 3 % discount rate and half-cycle corrections applied. The main outcome was incremental cost-effectiveness ratio (ICER) with a willingness-to-pay threshold of $ 100,000 per QALY. Probabilistic sensitivity analyses were also performed. Results  In our base-case analysis, the average cost of TIF 2.0 was $ 13,978.63 versus $ 17,658.47 for LNF and $ 10,931.49 for PPI. Compared to the PPI strategy, TIF 2.0 was cost-effective with an incremental cost of $ 3,047 and incremental effectiveness of 0.29 QALYs, resulting in an ICER of $ 10,423.17 /QALY gained. LNF was strongly dominated by TIF 2.0. Over a lifetime horizon, TIF 2.0 remained the cost-effective strategy for patients with symptoms despite twice-daily 20-mg omeprazole. TIF 2.0 remained cost-effective after varying parameter inputs in deterministic and probabilistic sensitivity analyses and for scenario analyses in multiple age groups. Conclusions  Based upon this study, TIF 2.0 was cost-effective for patients with symptomatic GERD despite low-dose, twice-daily PPI.

Lodhia NA, Horton L, Thapa N, Goldin AH, Chan WW. Opioid-Associated Anorectal Dysfunction in Chronic Constipation. Digestive diseases and sciences. 2022;67(8):3904-3910. doi:10.1007/s10620-021-07288-5

INTRODUCTION: The role of anorectal and defecatory dysfunction in opioid-related constipation is unclear. We aimed to evaluate the relationship between opioid use and rectal sensation, defecatory function, and balloon expulsion on anorectal physiology testing.

METHODS: This was a retrospective cohort study of consecutive adults undergoing high-resolution anorectal manometry (HRAM) at a tertiary center for constipation. Clinical characteristics, medication use, and HRAM findings were obtained. Statistical analyses were performed using Fisher-exact/student t-test for univariate analyses and logistic/general linear regression for multivariable analyses to compare patients with no opioid use, recent (< 3 months) use, and distant (> 3 months) use.

RESULTS: 424 patients (49.8 ± 17.2 years; 85.6% female) were included. Compared to those without opioid history, patients with recent use had increased volumes for first rectal sensation (70.4 mL vs 59.4, p = 0.043), urge (120.5 mL vs 101.5, p = 0.017), and maximal tolerance (170.2 mL vs 147.2, p = 0.0018), but not patients with distant use. Recent opioid use was associated with increased risk of dyssynergic defecation (DD) (61.8% vs 46.4%, p = 0.035), but not failed balloon expulsion. On multivariable models controlling for potential confounders, recent opioid use, but not distant use, remained independently correlated with increased volumes for first rectal sensation (β-coefficient 9.78, p = 0.019), urge (β-coefficient 16.7, p = 0.0060), and maximal tolerance (β-coefficient 22.9, p = 0.0032), and higher risk for DD (aOR = 2.18, p = 0.026).

CONCLUSION: Recent opioid use was an independent risk factor for rectal hyposensitivity and DD on HRAM in patients with constipation, but that effect may decrease with discontinuation of use. Anorectal physiology testing should be considered in patients with opioid-associated constipation.

McCarty TR, Chouairi F, Hathorn KE, Chan WW, Thompson CC. Trends and Socioeconomic Health Outcomes of Cannabis Use Among Patients With Gastroparesis: A United States Nationwide Inpatient Sample Analysis. Journal of clinical gastroenterology. 2022;56(4):324-330. doi:10.1097/MCG.0000000000001526

BACKGROUND: Although cannabis may worsen nausea and vomiting for patients with gastroparesis, it may also be an effective treatment for gastroparesis-related abdominal pain. Given conflicting data and a lack of current epidemiological evidence, we aimed to investigate the association of cannabis use on relevant clinical outcomes among hospitalized patients with gastroparesis.

MATERIALS AND METHODS: Patients with a diagnosis of gastroparesis were reviewed from the National Inpatient Sample (NIS) database between 2008 and 2014. Gastroparesis was identified by International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes with patients classified based on a diagnosis of cannabis use disorder. Demographics, comorbidities, socioeconomic status, and outcomes were compared between cohorts using χ2 and analysis of variance. Logistic regression was then performed and annual trends also evaluated.

RESULTS: A total of 1,473,363 patients with gastroparesis were analyzed [n=33,085 (2.25%) of patients with concomitant cannabis use disorder]. Patients with gastroparesis and cannabis use disorder were more likely to be younger and male gender compared with nonusers (36.7±18.8 vs. 51.9±16.8; P<0.001 and 52.9% vs. 33.5%; P<0.001, respectively). Race/ethnicity was different between groups (P<0.001). Cannabis users had a lower median household income and were more likely to have Medicaid payor status (all P<0.001). Controlling for confounders, length of stay, and mortality were significantly decreased for patients with gastroparesis and cannabis use (all P<0.001).

CONCLUSION: While patients with gastroparesis and cannabis use disorder were younger, with a lower socioeconomic status, and disproportionately affected by psychiatric diagnoses, these patients had better hospitalization outcomes, including decreased length of stay and improved in-hospital mortality.

Yadlapati R, Kaizer AM, Sikavi DR, et al. Distinct Clinical Physiologic Phenotypes of Patients With Laryngeal Symptoms Referred for Reflux Evaluation. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. 2022;20(4):776-786.e1. doi:10.1016/j.cgh.2021.05.025

BACKGROUND & AIMS: Heterogeneous presentations and disease mechanisms among patients with laryngeal symptoms account for misdiagnosis of laryngopharyngeal reflux (LPR), variations in testing, and suboptimal outcomes. We aimed to derive phenotypes of patients with laryngeal symptoms based on clinical and physiologic data and to compare characteristics across phenotypes.

METHODS: A total of 302 adult patients with chronic laryngeal symptoms were prospectively enrolled at 3 centers between January 2018 to October 2020 (age 57.2 ± 15.2 years; 30% male; body mass index 27.2 ± 6.0 kg/m2). Discriminant analysis of principal components (DAPC) was applied to 12 clinical and 11 physiologic variables collected in stable condition to derive phenotypic groups.

RESULTS: DAPC identified 5 groups, with significant differences across symptoms, hiatal hernia size, and number of reflux events (P < .01). Group A had the greatest hiatal hernia size (3.1 ± 1.0 cm; P < .001) and reflux events (37.5 ± 51; P < .001), with frequent cough, laryngeal symptoms, heartburn, and regurgitation. Group B had the highest body mass index (28.2 ± 4.6 kg/m2; P < .001) and salivary pepsin (150 ± 157 ng/mL; P = .03), with frequent cough, laryngeal symptoms, globus, heartburn, and regurgitation. Group C frequently reported laryngeal symptoms (93%; P < .001), and had fewest esophageal symptoms (9.6%; P < .001) and reflux events (10.7 ± 11.0; P < .001). Group D commonly reported cough (88%; P < .001) and heartburn. Group E (18%) was oldest (62.9 ± 14.3 years; P < .001) and distinguished by highest integrated relaxation pressure.

CONCLUSIONS: DAPC identified distinct clinicophysiologic phenotypes of patients with laryngeal symptoms referred for reflux evaluation: group A, LPR and gastroesophageal reflux disease (GERD) with hiatal hernia; group B, mild LPR/GERD; group C, no LPR/No GERD; group D, reflex cough; and group E, mixed/possible obstructive esophagogastric junction. Phenotypic differences may inform targeted clinical trials design and improve outcomes.

Rangan V, Borges LF, Lo WK, et al. Novel Advanced Impedance Metrics on Impedance-pH Testing Predict Lung Function Decline in Idiopathic Pulmonary Fibrosis. The American journal of gastroenterology. 2022;117(3):405-412. doi:10.14309/ajg.0000000000001577

INTRODUCTION: Gastroesophageal reflux has been associated with idiopathic pulmonary fibrosis (IPF). Mean nocturnal baseline impedance (MNBI) is a marker of esophageal mucosal integrity, whereas postreflux swallow-induced peristaltic wave (PSPW) index reflects esophageal chemical clearance. Both metrics offer novel ways to assess reflux burden on multichannel intraluminal impedance-pH testing (MII-pH), but their role in extraesophageal reflux remains unclear. We aimed to evaluate the relationship between these novel metrics and lung function decline in patients with IPF.

METHODS: Adults with IPF undergoing prelung transplant MII-pH were enrolled. All patients completed pulmonary function testing (PFT) at the time of MII-pH and at the 1-year follow-up. MNBI was calculated by averaging baseline impedance at three 10-minute intervals (1 AM/2 AM/3 AM). PSPW index was the proportion of all reflux episodes, followed by a peristaltic swallow within 30 seconds. Univariate (Student t-test/Pearson correlation) and multivariable (general linear regression) analyses were performed.

RESULTS: One hundred twenty-five subjects (mean age = 61.7 years, 62% men) were included. Forced expiratory volume in one second and forced vital capacity declined more significantly over 12 months in subjects with lower distal MNBI, proximal MNBI, and PSPW index (all P < 0.05). On multivariable analyses adjusting for age, sex, proton pump inhibitor use, and baseline lung function, distal MNBI (β = -10.86, P = 0.024; β = -8.03, P = 0.045), proximal MNBI (β = -13.5, P = 0.0068; β = -9.80, P = 0.025), and PSPW index (β = -18.1, P = 0.010; β = -12.55, P = 0.050) remained predictive of greater forced expiratory volume in one second and forced vital capacity decline.

DISCUSSION: Low distal MNBI, proximal MNBI, and PSPW index independently predicted more severe lung function decline over 1 year in patients with IPF. These impedance metrics may have prognostic value and support a role for reflux in IPF pathogenesis.

Cai JX, Wong D, Lee DJH, Chan WW. Eating and Psychiatric Disorders Are Independent Risk Factors for Rumination Syndrome. Journal of clinical gastroenterology. 2022;56(3):228-233. doi:10.1097/MCG.0000000000001510

GOAL: The goal of this study was to evaluate whether a history of eating disorders (EDs) or psychiatric disorders (PDs) are risk factors for rumination syndrome (RS).

BACKGROUND: RS is a disorder of gut-brain interaction characterized by an effortless postprandial retrograde flow of ingested contents. Disorder of gut-brain interactions have been associated with psychiatric and behavioral comorbidities. No prior comparative study has assessed the relationship between RS and ED or PD.

METHODS: This was a case-control study of adults with RS at a tertiary center in January 2013 to January 2018. Two age-matched/gender-matched controls per RS case were identified. The Fisher exact test (categorical)/Student t test (continuous) and forward stepwise logistic regression were performed for univariate and multivariable analyses, respectively.

RESULTS: Seventy-two patients (24 cases/48 controls) were included. Baseline demographics and characteristics were similar between cases and controls. Among RS patients, 9 (37.5%) had a history of ED, including 3 (12.5%) anorexia nervosa and 4 (16.7%) bulimia nervosa; and 20 (83.3%) had a PD, including 9 (37.5%) anxiety and 7 (29.2%) depression. Prevalence of ED (37.5% vs. 4.2%, P=0.0002) and PD (83.3% vs. 50.0%, P=0.0062) were higher among RS patients than controls. Specifically, the risks of anorexia nervosa (16.7% vs. 0%, P=0.005) and bulimia nervosa (21.1% vs. 0%, P=0.001) were both increased in RS patients. On multivariable analysis, ED (adjusted odds ratio=16.4, P=0.0033) and PD (adjusted odds ratio=4.47, P=0.029) remained independent predictors for RS.

CONCLUSIONS: A history of ED and PD were independent risk factors for RS. Abnormal eating behaviors and psychiatric comorbidities may contribute to the pathogenesis of RS. Evaluation of RS should include a detailed history for ED and PD.

Derousseau T, Chan WW, Cangemi D, Kaza V, Lo WK, Gavini S. Delayed Gastric Emptying in Prelung Transplant Patients Is Associated With Posttransplant Acute Cellular Rejection Independent of Reflux. Journal of clinical gastroenterology. 2022;56(2):e121-e125. doi:10.1097/MCG.0000000000001502

GOAL: The goal of this study was to evaluate the relationship between pretransplant delayed gastric emptying (DGE) and posttransplant acute cellular rejection (ACR) in lung transplant recipients.

BACKGROUND: DGE is very prevalent (23% to 91%) after lung transplantation but pretransplant prevalence has not been well studied. DGE may lead to poor posttransplant outcomes by predisposing to microaspiration. Pretransplant testing for DGE may help identify patients at risk for negative posttransplant outcomes including ACR.

MATERIALS AND METHODS: A retrospective review of a prospectively collected database of consecutive patients undergoing prelung transplant evaluation at a tertiary referral center from 2010 to 2015 was performed. Patients with pretransplant gastric emptying scintigraphy were included in the study. ACR diagnosis was made using International Society for Heart and Lung Transplantation (ISHLT) histologic criteria. Typical gastroparesis symptoms at the time of gastric emptying scintigraphy and pretransplant 24-hour pH impedance monitoring (MII-pH) data was collected. Logistic regression was used for multivariate analysis. Subgroup analyses were performed to account for gastroesophageal reflux (GER).

RESULTS: A total of 83 subjects (18 with DGE, 51.8% male, mean age: 53.6 y) met the criteria for inclusion. Patients with DGE were more likely to have typical symptoms of gastroparesis, though 61.1% of DGE patients were asymptomatic. ACR was more prevalent in patients with DGE (33.3% vs. 12.3%, P=0.04). This correlation was independent of GER as measured by MII-pH on subgroup analysis (75% vs. 14.3%, n=0.02).

DISCUSSION: Lung transplant recipients with pretransplant DGE have a higher incidence of ACR, independent of GER. Routine pretransplant testing for DGE may help identify patients at greater risk for adverse posttransplant outcomes as the majority of patients with DGE are asymptomatic.


Shah ED, Staller K, Nee J, et al. Evaluating the Impact of Cost on the Treatment Algorithm for Chronic Idiopathic Constipation: Cost-Effectiveness Analysis. The American journal of gastroenterology. 2021;116(10):2118-2127. doi:10.14309/ajg.0000000000001403

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.

Sikavi DR, Cai JX, Leung R, Carroll TL, Chan WW. Impaired Proximal Esophageal Contractility Predicts Pharyngeal Reflux in Patients With Laryngopharyngeal Reflux Symptoms. Clinical and translational gastroenterology. 2021;12(10):e00408. doi:10.14309/ctg.0000000000000408

OBJECTIVES: The pathophysiology of laryngopharyngeal reflux (LPR) remains incompletely understood. Proximal esophageal motor dysfunction may impair bolus clearance, increasing the risk of pharyngeal refluxate exposure. We aimed to evaluate the association of proximal esophageal contractility with objective reflux metrics.

METHODS: We evaluated adults with LPR symptoms undergoing high-resolution manometry (HRM) and combined hypopharyngeal-esophageal multichannel intraluminal impedance-pH testing at a tertiary center between March 2018 and August 2019. Routine parameters per Chicago classification were obtained on HRM. Proximal esophageal contractility was evaluated using proximal contractile integral (PCI), which quantifies contractile pressure >20 mm Hg for the region spanning the distal margin of the upper esophageal sphincter and transition zone. Univariate (Kendall correlation and Student t test) and multivariable (general linear regression and logistic regression) analyses were performed.

RESULTS: We enrolled 138 patients (66.7% women, mean age 57.1 years) in this study. Lower PCI was associated with an elevated risk of increased pharyngeal reflux (adjusted odds ratio 0.83 per 100 mm Hg-s-cm change in PCI, 95% confidence interval: 0.69-0.98), with a trend toward increased bolus exposure time and total reflux events, after multivariable adjustment. The relationship between PCI and pharyngeal reflux was strongest among participants without a primary motility disorder on HRM (adjusted odds ratio 0.63, 95% confidence interval: 0.42-0.85, P interaction = 0.04). Among continuously expressed reflux parameters, lower PCI was significantly associated with more distal acid reflux events (β = -0.0094, P = 0.03) and total reflux events (β = -0.0172, P = 0.05), after adjusting for confounders.

DISCUSSION: Reduced proximal esophageal contractility as assessed by decreased PCI on HRM independently predicted increased pharyngeal reflux in patients with LPR symptoms, particularly among those without a coexisting motility disorder.