Publications

BACKGROUND AND AIMS: Fecal microbiota transplantation (FMT) is a commonly used therapy for multiply recurrent Clostridioides difficile (mrCDI). By altering the gut microbiota, there is the potential for FMT to impact the risk for cardiometabolic, intestinal or immune-mediated conditions. Likewise, the microbiota disturbance associated with mrCDI could potentially lead to these conditions. We aimed to assess the associations of mrCDI and FMT with cardiometabolic, immune-mediated diseases, and irritable bowel syndrome.

METHODS: This retrospective cohort study using a United States commercial claims database included persons diagnosed with CDI or undergoing FMT. We created 2 pairwise comparisons: mrCDI vs non-mrCDI, and non-mrCDI or mrCDI treated with FMT vs mrCDI without FMT.

RESULTS: We found no significant association between mrCDI (vs non-mrCDI) and inflammatory bowel disease (adjusted hazard ratio (aHR) = 1.65; 95% confidence interval, 0.67-4.04), rheumatoid arthritis (HR = 0.86; 0.47-1.56), psoriasis (HR = 0.72; 0.23-2.27), diabetes (aHR = 0.97; 0.67-1.40), hypertension (aHR = 1.05; 0.76-1.44), myocardial infarction (aHR = 0.82; 0.63-1.06), stroke (aHR = 0.83; 0.62-1.12), or irritable bowel syndrome (HR = 0.94; 0.61-1.45). Similarly, we found no association of CDI with FMT (vs mrCDI without FMT) and diabetes (aHR = 0.92; 0.27-3.11), hypertension (aHR = 1.41; 0.64-3.15), stroke (aHR = 1.27; 0.69-2.34) or inflammatory bowel syndrome (aHR = 0.80; 0.26-2.46). However, the incidence of myocardial infarction was increased following FMT (aHR = 1.68; 1.01-2.81).

CONCLUSION: Relative to those with CDI, persons with mrCDI do not appear to be intrinsically at higher risk of cardiometabolic, immune-mediated diseases, or irritable bowel syndrome. However, those who underwent FMT for CDI had a higher incidence of myocardial infarction. Future studies should assess this association to assess reproducibility.

BACKGROUND: Delays in advancing to biologic therapies are associated with adverse outcomes in inflammatory bowel disease (IBD). Insurer-mandated prior authorizations have been linked to prolonged medication initiation times. We hypothesized that prior authorizations are associated with prolonged biologic initiation time and increased IBD-related healthcare utilization among children with IBD.

METHODS: We performed a retrospective cohort study of 190 pediatric patients with IBD initiating biologics at a tertiary care hospital to measure the association between prior authorization, biologic initiation time (physician recommendation to first dose), and healthcare utilization (hospitalization, surgery, or emergency department visit). Demographic, insurance, and disease severity-related covariables were collected. Multivariable linear regression was used to measure the association between prior authorization and biologic initiation time. Propensity score methods were used to measure the associations between prior authorization and IBD-related healthcare utilization within 180 days and corticosteroid dependence at 90 days, with adjustment for insurance type, demographics, and disease severity-related characteristics.

RESULTS: Median biologic initiation time was 21 days. Prior authorization and complicated prior authorizations (requiring appeal, step therapy, or peer-to-peer review) were associated with 10.2-day (95% confidence interval [CI] 8.2 to 12.3) and 24.6-day (95% CI 16.4 to 32.8) increases in biologic initiation time, respectively. Prior authorizations increased the likelihood of IBD-related healthcare utilization within 180 days by 12.9% (95% CI 2.5 to 23.4) and corticosteroid dependence at 90 days by 14.1% (95% CI 3.3 to 24.8).

CONCLUSIONS: Prior authorizations are associated with prolonged biologic initiation time and increased IBD-related healthcare utilization. Minimizing prior authorization-related delays may expedite biologic delivery and reduce the risk of IBD-related healthcare utilization.

BACKGROUND & AIMS: Laboratory studies have demonstrated that antibiotic use in conjunction with bowel purgatives causes alterations to the gut microbiota. Because gut microbiota changes may be a trigger for the development of irritable bowel syndrome (IBS), we sought to assess whether individuals who undergo bowel cleansing for colonoscopy and have concurrent antibiotic exposure develop IBS at higher rates than individuals who undergo colonoscopy without antibiotic exposure.

METHODS: We used data from Optum's de-identified Clinformatics Data Mart Database in the United States to study a cohort of 50- to 55-year-olds who underwent screening colonoscopy. Individuals exposed to antibiotics within 14 days of colonoscopy were propensity-score matched to individuals who were not exposed to antibiotics around colonoscopy. The primary outcome was a new IBS diagnosis, and the composite outcome was a new claim for IBS, IBS medications, or IBS symptoms. The association of antibiotic exposure and the outcomes was calculated using Cox proportional hazards regression.

RESULTS: There were 408,714 individuals who met criteria for the screening colonoscopy cohort. Of these, 24,617 (6.0%) were exposed to antibiotics around the time of colonoscopy, and they were propensity-score matched to 24,617 individuals not exposed to antibiotics. There was no statistically significant association between antibiotic use and IBS (hazard ratio, 1.11; 95% confidence interval, 0.89-1.39), but there was a weak association between antibiotic use and the composite outcome (hazard ratio, 1.12; 95% confidence interval, 1.02-1.24; number needed to harm, 94).

CONCLUSIONS: Individuals concurrently exposed to antibiotics and bowel purgative had slightly higher rates of surrogate IBS outcomes compared with matched controls who did not receive antibiotics concurrently with bowel purgative.

BACKGROUND: Patients with recent hematopoietic cell transplantation (HCT) are considered high risk for gastrointestinal endoscopy due to the potential for procedural bacterial translocation. Prior studies investigating these risks do not account for the higher baseline rate of infectious complications among those who are immunocompromised. We performed a retrospective cohort study of patients with recent HCT who underwent endoscopy and their matched controls who did not undergo endoscopy.

METHODS: We identified patients who underwent HCT followed by upper and/or lower endoscopy at the University of Pennsylvania from 2000 to 2018. Individuals were matched 1:1 by age, sex, and type of HCT to controls who underwent HCT without subsequent endoscopy. Infectious adverse events were assessed by Sepsis-3 and Sepsis-2 criteria. Factors associated with infectious adverse events after endoscopy/index date were assessed using multivariable conditional logistic regression.

RESULTS: We identified 149 patients who underwent HCT and endoscopy and 149 matched controls who underwent HCT without endoscopy. Sepsis-3 infectious adverse events occurred in 3.4% of patients in each group. Sepsis-2 infectious adverse events occurred in 20.1% of patients who underwent endoscopy compared to 19.5% of controls. There was no association between endoscopy and Sepsis-2 infectious adverse events in the multivariable regression analysis (adjusted odds ratio 1.65, 95% CI 0.51-5.26).

CONCLUSIONS: When compared to controls with similar immune statuses, patients who underwent endoscopy after HCT did not have a higher risk of infectious adverse events. These results may inform clinical decision making regarding the risks and benefits of endoscopic management after HCT.

BACKGROUND AND AIMS: Barrett's esophagus (BE) screening is not highly utilized in the United States, and there are few data describing providers' approach to screening. To fill this gap and guide the implementation of future BE screening strategies, we studied evaluation practice patterns for gastroesophageal reflux disease (GERD) by nongastroenterologists.

METHODS: We performed a retrospective cohort study of patients with chronic GERD using health claims data from the United States between 2005 and 2019. We used up to 5 years of data after the diagnosis of chronic GERD to determine patient factors associated with completion of a gastroenterology encounter. We also identified patient factors associated with whether the first gastroenterology encounter was a direct-access upper endoscopy or an office visit.

RESULTS: We identified 484,023 patients diagnosed with chronic GERD by a nongastroenterology provider. The cumulative incidence of completing a gastroenterology encounter within 5 years was 38.7%. Gastrointestinal symptoms, such as dysphagia (adjusted hazard ratio [aHR] = 2.11, 95% confidence interval [CI] = 1.94-2.30), abdominal pain (aHR = 1.89, 95% CI = 1.85-1.94), and melena (aHR = 1.73, 95% CI = 1.65-1.82), were strongly associated with completion of a gastroenterology encounter. The patient factors strongly associated with direct-access upper endoscopy included dysphagia (aHR = 1.68, 95% CI = 1.52-1.85), weight loss (aHR = 1.46, 95% CI = 1.28-1.63), and melena (aHR = 1.42, 95% CI = 1.28-1.56).

CONCLUSION: A total of 38.7% of patients with chronic GERD complete a gastroenterology encounter within 5 years of diagnosis, and gastrointestinal alarm symptoms are the most strongly associated factors for receiving gastroenterology care. These findings highlight the importance of incorporating primary care providers in the development of new BE screening programs.

BACKGROUND & AIMS: Efforts to assess and improve the effectiveness of Barrett's esophagus (BE) screening and surveillance are ongoing in the United States. Currently, there are limited population-based data in the United States to guide these efforts.

METHODS: We performed a retrospective cohort study using data from large commercial and Medicare Advantage health plans in the United States from 2004 - 2019. We identified individuals with BE and analyzed the proportion who developed EAC. EACs were classified as prevalent EAC (diagnosed within 30 days of index endoscopy), post-endoscopy esophageal adenocarcinoma (PEEC, diagnosed 30 - 365 days after index endoscopy), and incident EAC (diagnosed 365 days or more after index endoscopy). Using this cohort, we performed a nested case-control study to identify factors associated with prevalent EAC at BE diagnosis and study healthcare utilization prior to BE diagnosis.

RESULTS: We identified 50,817 individuals with incident BE. Of the 366 who developed EAC, 67.2%, 13.7%, and 19.1% were diagnosed with prevalent EAC, PEEC, and incident EAC respectively. Factors positively associated with prevalent EAC versus BE without prevalent EAC included male sex, dysphagia, weight loss, and Charlson-Deyo comorbidity score. In those with prevalent EAC, most patients with dysphagia or weight loss had their symptoms first recorded within three months of EAC diagnosis. Healthcare utilization rates were similar between those with and without prevalent EAC.

CONCLUSIONS: Two-thirds of EACs among individuals with BE are diagnosed at the time of BE diagnosis. Additionally, PEEC accounts for 14% of these EACs. These results may guide future research studies that investigate novel BE diagnostic strategies that reduce the morbidity and mortality of EAC.

BACKGROUND: Acute coronary syndrome (ACS)-related readmission is an important hospital quality measure. Medication management therapy, especially adherence to antiplatelet agents post discharge, could play an important role in reducing readmission rates. Newer agents such as ticagrelor and prasugrel have been shown, in randomized control trials, to have superior effectiveness to cardiovascular outcomes compared to clopidogrel, but they are more expensive and have more common adverse events such as bleeding and dyspnea.

OBJECTIVE: We compared real-world readmission rates and adherence to antiplatelet agents among patients who initiated these agents post discharge.

METHODS: This was a retrospective cohortstudy of patients with an index ACS-related hospitalization between 1 July 2017 and 31 December 2018. Using integrated pharmacy and medical claims data from a large national pharmacy benefits manager for commercially insured adults aged ≥ 18 years, we compared ACS-related readmission and medication adherence (as medication possession ratio (MPR)) among the three agents. ANOVA and logistic regression, controlling for demographics such as age, gender, and Charlson Comorbidity Index, were used to estimate any association between the agents and 365-day readmission rates.

RESULTS: Of the 948 eligible patients, 86, 342, and 520 were initiated on prasugrel, ticagrelor, and clopidogrel (PTC), respectively. There were 4.7%, 5.3%, and 8.5% readmissions rates in the PTC cohorts, respectively, but these were not statistically significant in either the ANOVA or the logistic regression analyses. MPR was highest in the ticagrelor (88.1%) cohort, followed by the prasugrel (79.1%) and clopidogrel (76.4%) cohorts.

CONCLUSION: Ticagrelor cohort had the highest medication adherence. Clopidogrel cohort had the highest readmission rate but the difference with the other cohorts was statistically insignificant.

BACKGROUND: For atrial fibrillation (AF) patients, oral anticoagulants (OACs) can reduce the risk of stroke by 60%; however, nearly 50% of patients recommended to receive OACs do not receive therapy. Integrated insurers that cover pharmacy and medical benefits may be incentivized to improve OAC use and adherence because they benefit from offsets in medical costs associated with prevented strokes. OBJECTIVE: To compare OAC use and adherence between AF patients enrolled in Medicare stand-alone prescription drug plans (PDPs), which only cover pharmacy benefits, and those enrolled in Medicare Advantage prescription drug (MAPD) plans, which cover medical and pharmacy benefits. METHODS: This was a retrospective cohort study, conducted using 2014-2016 Medicare claims data from the Centers for Medicare & Medicaid Services and a large regional health plan in Pennsylvania. Primary outcomes included OAC use and OAC adherence. OAC use was measured as filling at least 1 prescription for an OAC after AF diagnosis. OAC adherence was defined as having greater than or equal to 80% of days covered with an OAC. We constructed conditional logistic regression models in propensity score-matched samples to test the association between enrollment in PDPs or MAPD plans and outcomes. RESULTS: There were 2,551 AF patients enrolled in PDPs and 4,502 in MAPD plans before propensity score matching. The propensity score-matched sample included 2,537 patients in each group. OAC use was higher among MAPD beneficiaries (74%-76%) compared with PDP beneficiaries (70%; P < 0.001), and 41%-42% of MAPD beneficiaries were adherent to OACs, compared with 34% of PDP beneficiaries (P < 0.001). In adjusted analyses among propensity score-matched samples, PDP enrollment was associated with lower odds of OAC use (OR = 0.67, 95% CI = 0.56-0.81) and adherence (OR = 0.68, 95% CI = 0.59-0.78) compared with MAPD enrollment. CONCLUSIONS: AF patients enrolled in MAPD plans were more likely to use and adhere to OACs compared with PDP enrollees. These results may reflect the financial incentives of MAPD plans to improve guideline-recommended OAC use, since MAPD insurers bear the risk of pharmacy and medical costs and thus may benefit from cost savings associated with averted stroke events. As efforts to improve use and adherence of OACs in AF patients increase, focus should be given to how insurance benefit designs can affect medication use. DISCLOSURES: No outside funding supported this study. Hernandez has received personal fees from BMS and Pfizer, unrelated to this study. The other authors have nothing to disclose.