Faculty Bibliography

BACKGROUND & AIMS/OBJECTIVE:Disability in patients with medically refractory ulcerative colitis (UC) after total proctocolectomy (TPC) with ileal pouch anal anastomosis (IPAA) is not well understood. The aim of this study was to compare disability in patients with IPAA vs medically managed UC, and identify predictors of disability. METHODS:This was a multicenter cross-sectional study performed at 5 academic institutions in New York City. Patients with medically or surgically treated UC were recruited. Clinical and socioeconomic data were collected, and the Inflammatory Bowel Disease Disability Index (IBD-DI) was administered to eligible patients. Predictors of moderate-severe disability (IBD-DI ≥35) were assessed in univariable and multivariable models. RESULTS:A total of 94 patients with IPAA and 128 patients with medically managed UC completed the IBD-DI. Among patients with IPAA and UC, 35 (37.2%) and 30 (23.4%) had moderate-severe disability, respectively. Patients with IPAA had significantly greater IBD-DI scores compared with patients with medically managed UC (29.8 vs 17.9; P < .001). When stratified by disease activity, patients with active IPAA disease had significantly greater median IBD-DI scores compared with patients with active UC (44.2 vs 30.4; P = .01), and patients with inactive IPAA disease had significantly greater median IBD-DI scores compared with patients with inactive UC (23.1 vs 12.5; P < .001). Moderate-severe disability in patients with IPAA was associated with female sex, active disease, and public insurance. CONCLUSIONS:Patients with IPAA have higher disability scores than patients with UC, even after adjustment for disease activity. Female sex and public insurance are predictive of significant disability in patients with IPAA.

Evidence from recent epidemiological data suggests that the patient population with inflammatory bowel disease (IBD) is chronologically aging. As these individuals become older, cellular senescence leads to a state of chronic inflammation. This process, known as inflammaging, is thought to be closely linked with biological aging and may be upregulated within IBD. As a consequence, we see an increased risk of aging-related disorders within IBD. In addition, we see that frailty, which results from physiologic decline, is increasing in prevalence and is associated with adverse clinical outcomes in IBD. As such, in this review we explore the potential overlapping biology of IBD and aging, discuss the risk of aging-related disorders in IBD, and describe frailty and its relation to clinical outcomes within IBD. Finally, we discuss current considerations for clinical care and potential research avenues for further investigation.

Background: Older adults are the fastest growing subpopulation of patients with IBD, with approximately 15% diagnosed after 60 yearsof- age. Moreover, environmental exposures are thought to play a significant role in the development of older-onset IBD, given the lower genetic risk. Antibiotics have been associated with development of IBD in earlier generations, but the impact on IBD risk in older adults is uncertain. In this population-based cohort study, we assessed the impact of cumulative antibiotic use, the timing of antibiotic use, and the association between specific antibiotic classes and the development of older-onset IBD.
Method(s): Using Denmark nationwide registries, a cohort of residents >=60 years-of-age was established between 2000-2018. Information on exposure to antibiotics was retrieved from the Danish National Prescription Register. The number of courses of antibiotics (overall and specific classes) was considered a time-varying variable. The outcome, IBD, was identified based on ICD-10 codes in the Danish National Patient Register. Incidence rate ratios (IRRs) for IBD according to antibiotic use 1 to 5 years prior to IBD diagnosis were calculated by log-linear Poisson regression, and adjusted for age, sex, and calendar period.
Result(s): There were a total of 2,327,796 individuals aged 60 to 90 years included in the cohort, resulting in 22,670,484 personyears of follow-up. There were 10,773 new cases of ulcerative colitis (UC) and 3,825 new cases of Crohn's disease (CD). Overall, any antibiotic use was associated with an IRR for the development of IBD (IRR 1.64, 95%CI 1.58-1.71), with a positive dose response observed (1 course of antibiotics IRR 1.27 95%CI 1.21-1.33; 2 courses IRR 1.54 95%CI 1.46-1.63; 3 courses IRR 1.66 95%CI 1.67-1.77; 4 courses IRR 1.96 95%CI 1.83-2.09; 5+ courses IRR 2.35, 95%CI 2.24-2.47). A higher IRR was noted between the timeframe of 1-2 years before diagnosis (IRR 1.87, 95%CI 1.79-1.94) as compared to 2-5 years before diagnosis (IRR 1.42, 95%CI 1.36-1.48). Additionally, all antibiotic classes were associated with the development of IBD, including those not used to treat gastrointestinal infections. Antibiotics with the highest IRR were fluoroquinolones (IRR 2.27, 95%CI 2.08-2.48), nitroimidazoles (IRR 2.21, 95%CI 1.95-2.50), and macrolides (IRR 1.74, 95%CI 1.64-1.84). All results remained statistically significant when stratifying by UC and CD, with effect estimates slightly higher for CD as compared to UC.
Conclusion(s): Use of antibiotics, regardless of class studied, was associated with an increased risk of older-onset IBD. This risk was highest one to two years prior to diagnosis, but persisted even prior to that, suggesting a link between overall antibiotic use and development of older-onset IBD

Crohn's disease (CD) and ulcerative colitis (UC) are relapsing and remitting chronic inflammatory diseases of the gastrointestinal tract. Although surgery for UC can provide a cure, surgery for CD is rarely curative. In the past few decades, research has identified risk factors for postsurgical CD recurrence, enabling patient risk stratification to guide monitoring and prophylactic treatment to prevent CD recurrence. A MEDLINE literature review identified articles regarding post-operative monitoring of CD recurrence after resection surgery. In this review, we discuss the evidence on risk factors for post-operative CD recurrence as well as suggestions on post-operative management.

BACKGROUND:Gastrointestinal symptoms are common in patients with COVID-19, but prevalence of co-infection with enteric pathogens is unknown. AIMS/OBJECTIVE:This study assessed the prevalence of enteric infections among hospitalized patients with COVID-19. METHODS:We evaluated 4973 hospitalized patients ≥ 18 years of age tested for COVID-19 from March 11 through April 28, 2020, at two academic hospitals. The primary exposure was a positive COVID-19 test. The primary outcome was detection of a gastrointestinal pathogen by PCR stool testing. RESULTS:Among 4973 hospitalized individuals, 311 were tested for gastrointestinal infections (204 COVID-19 positive, 107 COVID-19 negative). Patients with COVID-19 were less likely to test positive compared to patients without COVID-19 (10% vs 22%, p < 0.01). This trend was driven by lower rates of non-C.difficile infections (11% vs 22% in COVID-19 positive vs. negative, respectively, p = 0.04), but not C. difficile infection (5.1% vs. 8.2%, p = 0.33). On multivariable analysis, infection with COVID-19 remained significantly associated with lower odds of concurrent GI infection (aOR 0.49, 95% CI 0.24-0.97), again driven by reduced non-C.difficile infection. Testing for both C.difficile and non-C.difficile enteric infection decreased dramatically during the pandemic. CONCLUSIONS:Pathogens aside from C.difficile do not appear to be a significant contributor to diarrhea in COVID-19 positive patients.

BACKGROUND:Although age is often used as a clinical risk stratification tool, recent data have suggested that adverse outcomes are driven by frailty rather than chronological age. AIMS/OBJECTIVE:In this nationwide cohort study, we assessed the prevalence of frailty, and factors associated with 30-day readmission and mortality among hospitalized IBD patients. METHODS:Using the Nationwide Readmission Database, we examined all patients with IBD hospitalized from 2010 to 2014. Based on index admission, we defined IBD and frailty using previously validated ICD codes. We used univariable and multivariable regression to assess risk factors associated with all-cause 30-day readmission and 30-day readmission mortality. RESULTS:From 2010 to 2014, 1,405,529 IBD index admissions were identified, with 152,974 (10.9%) categorized as frail. Over this time period, the prevalence of frailty increased each year from 10.20% (27,594) in 2010 to 11.45% (33,507) in 2014. On multivariable analysis, frailty was an independent predictor of readmission (aRR 1.16, 95% CI: 1.14-1.17), as well as readmission mortality (aRR 1.12, 95% CI 1.02-1.23) after adjusting for relevant clinical factors. Frailty also remained associated with readmission after stratification by IBD subtype, admission characteristics (surgical vs. non-surgical), age (patients ≥ 60 years old), and when excluding malnutrition, weight loss, and fecal incontinence as frailty indicators. Conversely, we found older age to be associated with a lower risk of readmission. CONCLUSIONS:Frailty, independent of age, comorbidities, and severity of admission, is associated with a higher risk of readmission and mortality among IBD patients, and is increasing in prevalence. Given frailty is a potentially modifiable risk factor, future studies prospectively assessing frailty within the IBD patient population are needed.

Introduction: Crohn's disease (CD) carries a major healthcare burden, costing over $10 billion a year in the United States. Strictures are a common complication of CD, emerging in over half of patients after 20 years from diagnosis, and requiring invasive interventions such as surgery which further increases healthcare costs. Endoscopic balloon dilation (EBD) has emerged as an alternative intervention in managing CD strictures. We determined the cost-effectiveness of EBD versus resection surgery for patients with short (<4-5cm) anastomotic or primary small or large bowel strictures.
Method(s): A microsimulation state-transition model simulated the benefits and risks of EBD and bowel resection surgery for patients with primary or anastomotic strictures due to CD. Our base case was a 40-year-old patient with CD who developed a stricture. Strategies included EBD or surgery as a patient's first procedure, after which they were allowed to receive either procedure based on probabilities of subsequent intervention derived from the literature. Our primary outcome was qualityadjusted life years (QALYs) over ten years, and strategies were compared using a willingness to pay of $100,000/QALY from a societal perspective. Costs (in 2021 $US) and incremental cost-effectiveness ratios (ICER) were calculated. Deterministic 1-way and probabilistic analyses assessed model uncertainty.
Result(s): The EBD strategy cost $19,822 and resulted in 6.18 QALYs while the surgery strategy cost $41,358 and resulted in 6.37 QALYs. Surgery had an ICER of $113,332 per QALY, making EBD a cost-effective strategy. The median number of EBDs was 6 in the EBD strategy and 0 in the surgery strategy. The median number of surgeries was 2 in the surgery strategy and 1 in the EBD strategy. Of individuals who initially received EBD, 50.4% underwent subsequent surgery. One-way sensitivity analyses showed that the probabilities of requiring repeated interventions, surgery mortality (, 0.6%), and quality of life after interventions were the most influential parameters in our model. Probabilistic sensitivity analyses favored EBD in 50.9% of iterations.
Conclusion(s): EBD, when feasible, is a cost-effective strategy for managing CD primary or anastomotic strictures. Sensitivity analyses show that differences in patient risk and quality of life after intervention can impact cost-effectiveness. The decision between EBD or surgery should be made considering cost-effectiveness, patient risks, and quality of life preferences

Introduction: Patients with inflammatory bowel disease (IBD) have a 2-to 3-fold greater risk of venous thromboembolism (VTE) than the general population, with increased risk during hospitalization. However, recent evidence suggests that this increased risk persists post-discharge. As such, we aimed to determine the cost-effectiveness of post-discharge VTE prophylaxis among hospitalized patients with IBD.
Method(s): A decision tree was used to compare inpatient prophylaxis alone versus 4 weeks of postdischarge VTE prophylaxis with rivaroxaban 10 mg/day. Our primary outcome was quality-adjusted life years (QALYs) over one year, and strategies were compared using a willingness to pay of $100,000/QALY from a societal perspective. Costs (in 2020 $US), incremental cost-effectiveness ratios (ICERs), and number needed to treat (NNT) to prevent one VTE and VTE death were calculated. Deterministic 1-way and probabilistic analyses were performed to assess uncertainty within the model.
Result(s): Four-week post-discharge prophylaxis with rivaroxaban resulted in 1.68 higher QALYs per 1000 persons and an incremental cost of $185,778 per QALY as compared to no postdischarge prophylaxis (see Table). The NNT to prevent a single VTE was 78 individuals, while the NNT to prevent a single VTE-related death was 3190 individuals. One-way sensitivity analyses showed that higher baseline VTE risk>4.5% or decreased cost of rivaroxaban <=$280 can reduce the ICER to<$100,000/QALY (see Figure, Tornado Diagram showing main drivers of the ICER). Probabilistic sensitivity analyses favored post-discharge prophylaxis in 30.5% of iterations
Conclusion(s): Four weeks of post-discharge VTE prophylaxis results in higher QALYs as compared to inpatient prophylaxis alone, and can prevent one post-discharge VTE among 78 patients with IBD. As such, post-discharge VTE prophylaxis in patients with IBD should be considered in a case-by-case scenario considering VTE risk profile, costs, and patient preference