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Ulcerative Colitis Patients With Clostridium difficile are at Increased Risk of Death, Colectomy, and Postoperative Complications: A Population-Based Inception Cohort Study

Negrón, María E DVM, PhD1,2; Rezaie, Ali MD, MSc3; Barkema, Herman W DVM, PhD2; Rioux, Kevin MD, PhD4; De Buck, Jeroen PhD2; Checkley, Sylvia DVM, PhD5; Beck, Paul L MD, PhD4; Carroll, Matthew BMed, MHSc6; Fedorak, Richard N MD7; Dieleman, Levinus MD7; Panaccione, Remo MD4; Ghosh, Subrata MD4; Kaplan, Gilaad G MD, MPH, FRCPC1,4

American Journal of Gastroenterology: May 2016 - Volume 111 - Issue 5 - p 691–704
doi: 10.1038/ajg.2016.106
ORIGINAL CONTRIBUTIONS: INFLAMMATORY BOWEL DISEASE
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Objectives: Clostridium difficile(C. difficile) may worsen the prognosis of ulcerative colitis (UC). The objectives of this study were to: (i) validate the International Classification of Diseases-10 (ICD-10) code forC. difficile; (ii) determine the risk ofC. difficileinfection after diagnosis of UC; (iii) evaluate the effect ofC. difficileinfection on the risk of colectomy; and (iv) assess the association betweenC. difficileand postoperative complications.

Methods: The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated by comparing ICD-10 codes forC. difficilewith stool toxin tests. A population-based surveillance cohort of newly diagnosed UC patients living in Alberta, Canada were identified from 2003 to 2009 (n=1,754). The effect of aC. difficileinfection on colectomy was modeled using competing risk survival regression after adjusting for covariates. The effect of aC. difficileinfection on postoperative complications was assessed using a mixed effects logistic regression model.

Results: The sensitivity, specificity, PPV, and NPV of the ICD-10 code forC. difficilewere 82.1%, 99.4%, 88.4%, and 99.1%, respectively. The risk ofC. difficileinfection within 5 years of diagnosis with UC was 3.4% (95% confidence interval (CI): 2.5–4.6%). The risk of colectomy was higher among UC patients diagnosed withC. difficile(sub-hazard ratio (sHR)=2.36; 95% CI: 1.47–3.80).C. difficileincreased the risk of postoperative complications (odds ratio=4.84; 95% CI: 1.28–18.35).C. difficilewas associated with mortality (sHR=2.56 times; 95% CI: 1.28–5.10).

Conclusions: C. difficilediagnosis worsens the prognosis of newly diagnosed patients with UC by increasing the risk of colectomy, postoperative complications, and death.

1Department of Community Health Sciences, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada

2Departments of Production Animal Health, Faculty of Veterinary Medicine, University of Calgary, Calgary, Alberta, Canada

3Cedars-Sinai Medical Center, Los Angeles, California, USA

4Department of Medicine, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada

5Ecosystem and Public Health, Faculty of Veterinary Medicine, University of Calgary, Calgary, Alberta, Canada

6Department of Pediatrics, University of Alberta

7Department of Medicine, Division of Gastroenterology & Nutrition, University of Alberta, Edmonton, Alberta, Canada

Correspondence: Gilaad G. Kaplan, MD, MPH, FRCPC, Teaching Research and Wellness Center, 3280 Hospital Drive NW, 6D56, Calgary, Alberta T2N 4N1, Canada. E-mail: ggkaplan@ucalgary.ca

Received 03 September 2015; accepted 01 January 2016

Guarantor of the article: Gilaad G. Kaplan, MD, MPH, FRCPC.

Specific author contributions: Study concept and design: MEN, HWB, AR, KR, JDB, SC, GGK. Data acquisition: MEN, AR, GGK. Interpretation of the data: MEN, HWB, AR, KR, JDB, SC, PLB, MC, RF, LD, RP, SG, GGK. Statistical analysis: MEN, AR, GGK. Drafting of the manuscript: MEN, HWB, GGK. Critical revision of the manuscript for important intellectual content: AR, KR, JDB, SC, PLB, MC, RNF, LD, RP, SG. Final approval of the manuscript: MEN, HWB, AR, KR, JDB, SC, PLB, MC, RNF, LD, RP, SG, GGK. Writing Assistance: None.

Financial support: This project was funded by the Alberta Inflammatory Bowel Disease Consortium, which is funded by an AHFMR Interdisciplinary Team Grant. AHFMR is now Alberta Innovates—Health Solutions. This project was also funded by a CIHR Team Grant (Health Challenges in Chronic Inflammation). Dr Kaplan was supported by a New Investigator Award from the Canadian Institute of Health Research and a Population Health Investigator Award from Alberta Innovates—Health Solutions.

Potential competing interests: The authors declare no conflict of interest.

© The American College of Gastroenterology 2016. All Rights Reserved.
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