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 & 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 & 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 & AIMS: Identification of postendoscopy esophageal adenocarcinoma (PEEC) among Barrett's esophagus (BE) patients presents an opportunity to improve survival of esophageal adenocarcinoma (EAC). We aimed to estimate the proportion of PEEC within the first year after BE diagnosis.

METHODS: Multiple databases (Medline, Embase, Scopus, and Cochrane databases) were searched until September 2020 for original studies with at least 1-year follow-up evaluation that reported EAC and/or high-grade dysplasia (HGD) in the first year after index endoscopy in nondysplastic BE, low-grade dysplasia, or indefinite dysplasia. The proportions of PEEC defined using EAC alone and EAC+HGD were calculated by dividing EAC or EAC+HGD in the first year over the total number of EAC or EAC+HGD, respectively.

RESULTS: We included 52 studies with 145,726 patients and a median follow-up period of 4.8 years. The proportion of PEEC (EAC) was 21% (95% CI, 13-31) and PEEC (EAC+HGD) was 26% (95% CI, 19-34). Among studies with nondysplastic BE only, the PEEC (EAC) proportion was 17% (95% CI, 11-23) and PEEC (EAC+HGD) was 14% (95% CI, 8-19). Among studies with 5 or more years of follow-up evaluation, the PEEC (EAC) proportion was 10% and PEEC (EAC+HGD) was 19%. Meta-regression analysis showed a strong inverse relationship between PEEC and incident EAC (P < .001). The PEEC (EAC) proportion increased from 5% in studies published before 2000 to 30% after 2015. Substantial heterogeneity was observed for most analyses.

CONCLUSIONS: PEEC accounts for a high proportion of HGD/EACs and is proportional to reduction in incident EAC. Using best endoscopic techniques now and performing future research on improving neoplasia detection through implementation of quality measures and educational tools is needed to reduce PEEC.

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: 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 & 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.