Chapel Hill, NC, United States
Chapel Hill, NC, United States

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Long M.D.,University of North Carolina at Chapel Hill | Long M.D.,Center for Gastrointestinal Biology and Disease | Kappelman M.D.,Center for Gastrointestinal Biology and Disease | Kappelman M.D.,University of North Carolina at Chapel Hill | And 7 more authors.
Inflammatory Bowel Diseases | Year: 2012

Background: The widespread use of the Internet allows for unique research opportunities. We aimed to develop and follow an Internet-based cohort (e-cohort) of patients with self-reported inflammatory bowel diseases (IBD) over time. Methods: We established an e-cohort of adults with IBD (CCFA Partners) by recruiting through Crohn's and Colitis Foundation of America (CCFA) email rosters, CCFA Website promotion, social media, and other publicity mechanisms. The baseline survey included modules on disease course and activity, diet and exercise, and patient-reported outcomes (PROs). Baseline characteristics of the cohort are summarized using descriptive statistics. Results: A total of 7819 adults with IBD joined CCFA Partners through August, 2011. The median age was 42 years (interquartile range [IQR] 30-54), 5074 (72.3%) were female. A total of 4933 (63.1%) had Crohn's disease (CD), 2675 (34.2%) had ulcerative colitis (UC), and 211 (2.7%) had IBD unspecified. For CD, the mean short CD Activity Index (CDAI) was 151.9 (standard deviation [SD] 106.4), with 2274 (59.4%) in remission. For UC, the mean simple clinical colitis activity index (SCCAI) was 3.6 (SD 2.8), with 937 (42.9%) in remission. The mean short IBD questionnaire (SIBDQ) score was 48.7 (SD 11.8). SIBDQ was inversely correlated with disease activity (P < 0.01). The mean Morisky medication adherence score (MMAS) was 5.7 (SD 2.0). MMAS scores were inversely correlated with disease activity (P < 0.01). Conclusions: CCFA Partners is a novel e-cohort. Enrollment is ongoing, with surveys twice yearly. CCFA Partners represents a unique resource to study PROs and changes in disease management over time. (Inflamm Bowel Dis 2012;) Copyright © 2012 Crohn's & Colitis Foundation of America, Inc.


Nighot P.,North Carolina State University | Nighot P.,University of New Mexico | Young K.,North Carolina State University | Nighot M.,North Carolina State University | And 8 more authors.
Inflammatory Bowel Diseases | Year: 2013

Background: Previously, it was shown that the chloride channel ClC-2 modulates intestinal tight junction (TJ) barrier function. The aim of the present study was to investigate the role of ClC-2 in epithelial barrier function and recovery in the event of epithelial injury. Methods: The role of ClC-2 was investigated in TJ barrier function in dextran sodium sulfate (DSS)-induced colitis in ClC-2 knockout mice and ClC-2 knockdown intestinal Caco-2 cells. Barrier function was measured electrophysiologically and by transepithelial mannitol fluxes. Selected TJ and associated proteins were Western blotted, cytokines were measured using quantitative PCR, and human colonic biopsies were examined with immunohistochemistry. Results: ClC-2-/- mice had a higher disease activity index, higher histological scores, and increased paracellular permeability compared with wild-type mice when treated with DSS. DSS-treated ClC-2-/- mice had increased claudin-2 expression, greater loss of occludin in the membrane, increased association of occludin with caveolin-1, and significantly increased tumor necrosis factor-a and interleukin-1β messenger RNA. ClC-2 knockdown in human intestinal Caco-2 cells resulted in a greater loss of epithelial resistance in the event of epithelial injury. The restoration of colonic barrier function after DSS colitis was delayed in ClC-2-/- mice. In human colonic biopsies, the protein and messenger RNA expression of ClC-2 was found to be reduced in patients with ulcerative colitis. Conclusions: ClC-2 plays a critical role in experimental colitis in that its absence increases disease activity, reduces barrier function and recovery, and perturbs TJs. Furthermore, ClC-2 expression is markedly reduced in the colon of human patients with ulcerative colitis. Copyright © 2013 Crohn's & Colitis Foundation of America, Inc.


Shen X.J.,Center for Gastrointestinal Biology and Disease
Gut microbes | Year: 2010

The human large bowel is colonized by complex and diverse bacterial communities. However, the relationship between commensal bowel bacteria and adenomas (colorectal cancer precursors) is unclear. This study aimed to characterize adherent bacteria in normal colon and evaluate differences in community composition associated with colorectal adenomas. We evaluated adherent bacteria in normal colonic mucosa of 21 adenoma and 23 non-adenoma subjects enrolled in a cross sectional study. Terminal restriction fragment length polymorphism, clone sequencing and fluorescent in-situ hybridization analysis of the 16S rRNA genes were used to characterize adherent bacteria. A total of 335 clones were sequenced and processed for phylogenetic and taxonomic analysis. Differences in bacterial composition between cases and controls were evaluated by UniFrac and analysis of similarity matrix. Overall, Firmicutes (62%), Bacteroidetes (26%) and Proteobacteria (11%) were the most dominant phyla. The bacterial composition differed significantly between cases and controls (UniFrac p < 0.001). We observed significantly higher abundance of Proteobacteria (p < 0.05) and lower abundance of Bacteroidetes (p < 0.05) in cases compared to controls. At the genus level, case subjects showed increased abundance of Dorea spp. (p < 0.005), Faecalibacterium spp. (p < 0.05) and lower proportions of Bacteroides spp. (p < 0.03) and Coprococcus spp. (p < 0.05) than controls. Cases had higher bacterial diversity and richness than controls. These findings reveal that alterations in bacterial community composition associated with adenomas may contribute to the etiology of colorectal cancer. Extension of these findings could lead to strategies to manipulate the microbiota to prevent colorectal adenomas and cancer as well as to identify individuals at high risk.


Long M.D.,University of North Carolina at Chapel Hill | Long M.D.,Center for Gastrointestinal Biology and Disease | Farraye F.A.,Boston University | Okafor P.N.,Boston University | And 6 more authors.
Inflammatory Bowel Diseases | Year: 2013

Objectives: Patients with inflammatory bowel disease (IBD) may be at increased risk for pneumocystis jiroveci pneumonia (PCP). Our aims were (1) to determine the incidence and relative risk of PCP in IBD and (2) to describe medication exposures in patients with IBD with PCP. Methods: We performed a retrospective cohort study and a case series using administrative data from IMS Health Inc, LifeLink Health Plan Claims Database. In the cohort, patients with IBD were matched to 4 individuals with no IBD claims. PCP risk was evaluated by incidence rate ratio and adjusted Cox proportional hazards modeling. The demographics and medication histories of the 38 cases of PCP in patients with IBD were extracted. Results: The cohort included 50,932 patients with Crohn's disease, 56,403 patients with ulcerative colitis, and 1269 patients with unspecified IBD; matched to 434,416 individuals without IBD. The crude incidence of PCP was higher in the IBD cohort (10.6/100,000) than in the non-IBD cohort (3.0/ 100,000). In the adjusted analyses, PCP risk was higher in the IBD versus non-IBD cohort (hazard ratio, 2.96; 95% confidence interval, 1.75-4.29), with the greatest risk in Crohn's disease compared with non-IBD (hazard ratio, 4.01; 95% confidence interval, 1.88-8.56). In the IBD case series of PCP cases (n = 38), the median age was 49 (interquartile range, 43-57). A total of 20 individuals (53%) were on corticosteroids alone or in combination with other immunosuppression. Conclusions: Although the overall incidence of PCP is low, patients with IBD are at increased risk. Patients with IBD with PCP are predominantly on corticosteroids alone or in combination before PCP diagnosis. Copyright © 2013 Crohn's & Colitis Foundation of America, Inc.


Jensen E.T.,Center for Esophageal Diseases and Swallowing | Martin C.F.,Center for Gastrointestinal Biology and Disease | Kappelman M.D.,University of North Carolina at Chapel Hill | Dellon E.S.,Center for Esophageal Diseases and Swallowing
Journal of Pediatric Gastroenterology and Nutrition | Year: 2016

Objectives: Eosinophilic esophagitis (EoE) is becoming increasingly more common, but the prevalence of other eosinophilic gastrointestinal disorders (EGIDs) is unknown. Our objective was to estimate the prevalence of eosinophilic gastritis, gastroenteritis, and colitis in the United States. Methods: We used the IMS Health LifeLink PharMetrics Plus Claims Database, data representative of a US national commercially insured population containing medical and pharmaceutical claims for >75 million individuals. We restricted our sample to patients ages 0 to 64 with continuous enrollment between July 1, 2009, and June 30, 2011. We identified patients with eosinophilic gastritis, gastroenteritis, and colitis as defined by ≥1 instance of the International Classification of Diseases, Ninth Revision codes 535.70, 558.41, and 558.42, respectively. Wecalculated the prevalence of the codes in the database and then standardized the estimates to the US population by age and sex. © 2015 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.


Long M.D.,University of North Carolina at Chapel Hill | Long M.D.,Center for Gastrointestinal Biology and Disease | Kappelman M.D.,Center for Gastrointestinal Biology and Disease | Kappelman M.D.,University of North Carolina at Chapel Hill | And 6 more authors.
Journal of Crohn's and Colitis | Year: 2014

Background and aims: Little is known about depression in elderly individuals with inflammatory bowel diseases (IBD). We assessed the point prevalence of depression and determined associations with disease activity, quality of life, and medication adherence in elderly patients with IBD. Methods: We identified elderly (≥ 65. years) individuals within Crohn's and Colitis Foundation of America Partners, an online IBD cohort. Individuals completed the short geriatric depression scale (GDS). We used bivariate statistics to determine whether demographic or disease-related factors, disease activity, quality of life or medication adherence was associated with depression. We used logistic regression to estimate independent effects of depression on medication adherence. Results: A total of 359 elderly individuals with IBD completed the GDS. The mean age was 70.2 years (SD 4.7); mean disease duration was 25.6. years (SD 17.6), and 62.6% had Crohn's disease (CD). The point prevalence of depression was 22.6%. Lower education levels (p= 0.001), higher corticosteroid use (< 0.01) and lower exercise levels (< 0.001) were associated with depression. For both CD and ulcerative colitis (UC), those with depression had increased disease activity (short Crohn's disease activity index 52.5 versus 29, p= 0.005, and simple clinical colitis activity index 5 versus 2, p= 0.003). Depressed patients had lower quality of life (short IBD questionnaire 4.6 versus 5.7, p< 0.001). Depressed individuals had reduced medication adherence (adjusted OR 2.18; 95% CI 1.04-4.57). Conclusions: Depression is common in this geriatric IBD cohort. Depression is independently associated with reduced medication adherence. Recognition and treatment of depression in elderly patients with IBD could improve outcomes. © 2013 European Crohn's and Colitis Organisation.


Long M.D.,University of North Carolina at Chapel Hill | Long M.D.,Center for Gastrointestinal Biology and Disease | Martin C.,University of North Carolina at Chapel Hill | Martin C.,Center for Gastrointestinal Biology and Disease | And 4 more authors.
American Journal of Gastroenterology | Year: 2013

OBJECTIVES:Patients with inflammatory bowel disease (IBD) may be at increased risk for infections. We aimed to determine the pneumonia risk in IBD and how specific medications affect this risk.METHODS:We performed a retrospective cohort and a nested case-control study using administrative data from IMS Health Inc., LifeLink Health Plan Claims Database. Limitations to this data set include lack of clinical details to validate exposures and outcomes. In the cohort, IBD patients were matched to four individuals without IBD. Pneumonia risk was evaluated by incidence rate ratio (IRR) and adjusted Cox proportional hazards models (hazard ratio (HR)). In the nested case-control, 4,856 IBD patients with pneumonia were matched to four IBD patients without pneumonia by incidence density sampling. We used conditional logistic regression to determine the associations between medications and pneumonia.RESULTS:The cohort included 50,932 patients with Crohn's disease (CD), 56,403 patients with ulcerative colitis (UC), and 1,269 with unspecified IBD; matched to 434,416 individuals without IBD. Median follow-up within the cohort was 24 months. The IBD cohort had an increased pneumonia risk when compared with non-IBD (IRR 1.82, 95% confidence interval (CI) 1.75-1.88). In adjusted Cox analysis, pneumonia risk remained increased for the IBD vs. non-IBD cohort (HR 1.54, 95% CI 1.49-1.60), with increased risk in both CD (HR 1.71, 95% CI 1.62-1.80) and UC (HR 1.41, 95% CI 1.34-1.48). In the nested case-control analysis, use of biologic medications (odds ratio (OR) 1.32, 95% CI 1.11-1.57), corticosteroids (OR 1.91, 95% CI 1.72-2.12), thiopurines (OR 1.13, 95% CI 1.00-1.27), proton-pump inhibitors (PPIs) (OR 1.15, 95% CI 1.04-1.26), or narcotics (2.28, 95% CI 2.09-2.48) was independently associated with pneumonia.CONCLUSIONS: Patients with IBD are at increased risk for pneumonia. Medications such as corticosteroids and narcotics are particularly associated with pneumonia in this population. An emphasis upon primary prevention of pneumonia through vaccination and reduction of risk factors is warranted. © 2013 by the American College of Gastroenterology.


Long M.D.,University of North Carolina at Chapel Hill | Long M.D.,Center for Gastrointestinal Biology and Disease | Martin C.F.,University of North Carolina at Chapel Hill | Martin C.F.,Center for Gastrointestinal Biology and Disease | And 7 more authors.
Gastroenterology | Year: 2012

Background & Aims: Patients with inflammatory bowel disease (IBD) are at risk for certain malignancies. We aimed to determine the risk of melanoma and nonmelanoma skin cancer (NMSC) in patients with IBD and how medications affect these risks. Methods: We performed retrospective cohort and nested case-control studies using administrative data from the LifeLink Health Plan Claims Database from 1997 to 2009. The cohort comprised 108,579 patients with IBD, and each was matched to 4 individuals without IBD. The risk of melanoma and NMSC was evaluated by incidence rate ratio (IRR) and by adjusted Cox proportional hazard ratio (HR) modeling. In nested case-control studies, patients with melanoma or NMSC were matched to 4 patients with IBD without melanoma or NMSC. Conditional logistic regression was used to determine associations between medications and both skin cancers. Results: In the cohort, IBD was associated with an increased incidence of melanoma (IRR, 1.29; 95% confidence interval [CI], 1.09-1.53). Risk was greatest among individuals with Crohn's disease (IRR, 1.45; 95% CI, 1.13-1.85; adjusted HR, 1.28; 95% CI, 1.00-1.64). The incidence of NMSC also increased among patients with IBD (IRR, 1.46; 95% CI, 1.40-1.53) and was greatest among those with CD (IRR, 1.64; 95% CI, 1.54-1.74). In the nested case-control studies, therapy with biologics increased the risk of melanoma (odds ratio [OR], 1.88; 95% CI, 1.08-3.29). Patients who had been treated with thiopurines had an increased risk of NMSC (OR, 1.85; 95% CI, 1.66-2.05). Conclusions: Immunosuppression increases the risk of melanoma and NMSC among patients with IBD. The risk of melanoma is increased by use of biologics, and the risk of NMSC is increased by use of thiopurines. Patients with IBD should be counseled and monitored for skin cancer. © 2012 AGA Institute.


Long M.D.,University of North Carolina at Chapel Hill | Long M.D.,Center for Gastrointestinal Biology and Disease | Martin C.,University of North Carolina at Chapel Hill | Martin C.,Center for Gastrointestinal Biology and Disease | And 4 more authors.
Alimentary Pharmacology and Therapeutics | Year: 2013

Background Patients with inflammatory bowel disease (IBD) on certain immunosuppressants have increased herpes zoster (HZ) risk. Aim To determine the risk of HZ in IBD and how antitumour necrosis factor-alpha (anti-TNF) agents affect this risk. Methods We performed a retrospective cohort and nested case-control study using administrative data from IMS LifeLink® Information Assets-Health Plan Claims Database. In the cohort, we identified IBD patients


Carroll I.M.,Center for Gastrointestinal Biology and Disease | Ringel-Kulka T.,University of North Carolina at Chapel Hill | Keku T.O.,Center for Gastrointestinal Biology and Disease | Chang Y.-H.,Korea Research Institute of Bioscience and Biotechnology | And 3 more authors.
American Journal of Physiology - Gastrointestinal and Liver Physiology | Year: 2011

Alterations in the intestinal microbiota have been suggested as an etiological factor in the pathogenesis of irritable bowel syndrome (IBS). This study used a molecular fingerprinting technique to compare the composition and biodiversity of the microbiota within fecal and mucosal niches between patients with diarrhea-predominant IBS (D-IBS) and healthy controls. Terminal-restriction fragment (T-RF) length polymorphism (T-RFLP) fingerprinting of the bacterial 16S rRNA gene was used to perform microbial community composition analyses on fecal and mucosal samples from patients with D-IBS (n = 16) and healthy controls (n = 21). Molecular fingerprinting of the microbiota from fecal and colonic mucosal samples revealed differences in the contribution of T-RFs to the microbiota between D-IBS patients and healthy controls. Further analysis revealed a significantly lower (1.2-fold) biodiversity of microbes within fecal samples from D-IBS patients than healthy controls (P = 0.008). No difference in biodiversity in mucosal samples was detected between D-IBS patients and healthy controls. Multivariate analysis of T-RFLP profiles demonstrated distinct microbial communities between luminal and mucosal niches in all samples. Our findings of compositional differences in the luminal- and mucosal-associated microbiota between D-IBS patients and healthy controls and diminished microbial biodiversity in D-IBS fecal samples further support the hypothesis that alterations in the intestinal microbiota may have an etiological role in the pathogenesis of D-IBS and suggest that luminal and mucosal niches need to be investigated. © 2011 the American Physiological Society.

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