Inflammatory Bowel Disease in Appalachian Kentucky: An Investigation of Outcomes and Health Care Utilization.

BACKGROUND: Rural residence has been associated with a lower incidence of inflammatory bowel disease (IBD) but higher health care utilization and worse outcomes. Socioeconomic status is intrinsically tied to both IBD incidence and outcomes. Inflammatory bowel disease outcomes have not been investigated in Appalachia: a rural, economically distressed region rife with risk factors for both increased incidence and unfavorable outcomes. METHODS: Hospital inpatient discharge and outpatient services databases were utilized to assess outcomes in patients diagnosed with either Crohn's disease (CD) or ulcerative colitis (UC) in Kentucky. Encounters were classified by patient residence in Appalachian or non-Appalachian counties. Data were reported as crude and age-adjusted rates of visits per 100,000 population per year collected in 2016 to 2019. National inpatient discharge data from 2019, stratified by rural and urban classification codes, were utilized to compare Kentucky to national trends. RESULTS: Crude and age-adjusted rates of inpatient, emergency department and outpatient encounters were higher in the Appalachian cohort for all 4 years observed. Appalachian inpatient encounters are more frequently associated with a surgical procedure (Appalachian, 676, 24.7% vs non-Appalachian, 1408, 22.2%; P = .0091). In 2019, the Kentucky Appalachian cohort had significantly higher crude and age-adjusted rates of inpatient discharges for all IBD diagnoses compared with national rural and nonrural populations (crude 55.2; 95% CI, 50.9-59.5; age-adjusted 56.7; 95% CI, 52.1-61.3). CONCLUSIONS: There is disproportionately higher IBD health care utilization in Appalachian Kentucky compared with all cohorts, including the national rural population. There is a need for aggressive investigation into root causes of these disparate outcomes and identification of barriers to appropriate IBD care.

The Kentucky Appalachian IBD population experiences increased health care utilization, with increased rates of inpatient admissions, emergency department, and outpatient visits compared with non-Appalachian Kentuckians. Kentucky Appalachian rates of inpatient admissions are higher compared with national rates, controlling for rural residence.

Chronic opioid use is associated with early biologic discontinuation in inflammatory bowel disease.

BACKGROUND: Chronic opioid use is associated with poorer clinical outcomes in inflammatory bowel disease. AIMS: To investigate an association between chronic opioid use and persistence with biologic agents in management of inflammatory bowel disease. METHODS: A total of 16 624 patients diagnosed with inflammatory bowel disease and receiving a first-time biologic prescription from 2011 to 2016 were identified retrospectively from the Truven MarketScan Database. A cohort of 1768 patients were identified as chronic opioid users utilising outpatient prescription claims. Utilisation patterns of biologic therapies were assessed from inpatient administration and outpatient claims data, including persistence calculations. Information on healthcare utilisation and common comorbidities was also collected. A Cox regression model was constructed to assess the hazard of chronic opioid use on early discontinuation of biologic therapy controlling for disease severity. RESULTS: A mean 1.5 different biologic agents were utilised by inflammatory bowel disease patients with chronic opioid use (vs 1.37 in the comparator group; P < 0.0001). A lower proportion of the chronic opioid use cohort persisted on biologic therapies to the end of the study period (16.2% vs 33.5% P < 0.0001). Inflammatory bowel disease patients with chronic opioid use utilised more healthcare resources and had a higher rate of comorbidities than the reference cohort. Patients with chronic opioid use were 23% more likely (hazard ratio 1.23; 95% CI [1.16-1.31]) to be non-persistent with biologic therapy while accounting for relevant markers of disease acuity. CONCLUSIONS: Chronic opioid use is associated with increased hazard of biologic discontinuation in inflammatory bowel disease. Symptoms of opioid withdrawal may mimic IBD flares thereby leading providers to inappropriately switch biologic therapies and compromise disease control.

SIRT2 Contributes to the Regulation of Intestinal Cell Proliferation and Differentiation.

BACKGROUND AND AIMS: Intestinal mucosa undergoes a continual process of proliferation, differentiation, and apoptosis. Disruption of this homeostasis is associated with disorders such as inflammatory bowel disease (IBD). We investigated the role of Sirtuin 2 (SIRT2), a NAD-dependent protein deacetylase, in intestinal epithelial cell (IEC) proliferation and differentiation and the mechanism by which SIRT2 contributes to maintenance of intestinal cell homeostasis. METHODS: IECs were collected from SIRT2-deficient mice and patients with IBD. Expression of SIRT2, differentiation markers (mucin2, intestinal alkaline phosphatase, villin, Na,K-ATPase, and lysozyme) and Wnt target genes (EPHB2, AXIN2, and cyclin D1) was determined by western blot, real-time RT-PCR, or immunohistochemical (IHC) staining. IECs were treated with TNF or transfected with siRNA targeting SIRT2. Proliferation was determined by villus height and crypt depth, and Ki67 and cyclin D1 IHC staining. For studies using organoids, intestinal crypts were isolated. RESULTS: Increased SIRT2 expression was localized to the more differentiated region of the intestine. In contrast, SIRT2 deficiency impaired proliferation and differentiation and altered stemness in the small intestinal epithelium ex vivo and in vivo. SIRT2-deficient mice showed decreased intestinal enterocyte and goblet cell differentiation but increased the Paneth cell lineage and increased proliferation of IECs. Moreover, we found that SIRT2 inhibits Wnt/ß-catenin signaling, which critically regulates IEC proliferation and differentiation. Consistent with a distinct role for SIRT2 in maintenance of gut homeostasis, intestinal mucosa from IBD patients exhibited decreased SIRT2 expression. CONCLUSION: We demonstrate that SIRT2, which is decreased in intestinal tissues from IBD patients, regulates Wnt-ß-catenin signaling and is important for maintenance of IEC proliferation and differentiation.