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      Inflammatory Bowel Disease Increases the Risk of Venous Thromboembolism in Children: A Population-Based Matched Cohort Study

      research-article
      1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 1 , 13 , 10 , 12 , 11 , 14 , 10 , 15 , 16 , 17 , 18 , 15 , 16 , 17 , 7 , 8 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 10 , 23 , 24 , 10 , 7 , 5 , 14 , 28 , 5 , 10 , 23 , 24 , 1 , 2 , 10 , 13 , 22 , 23 , 24
      Journal of Crohn's & Colitis
      Oxford University Press
      Venous thromboembolism, inflammatory bowel disease, paediatrics, epidemiology, complications, health administrative data, routinely collected health data

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          Abstract

          Background and Aims

          Although venous thromboembolism [VTE] is a well-known complication of inflammatory bowel disease [IBD] in adults, limited data exist on the risk in children. We report the incidence of VTE among children with and without IBD.

          Methods

          We conducted a matched cohort study within a distributed network of population-based Canadian provincial health administrative databases. Children <16 years diagnosed with IBD were identified using validated algorithms from administrative data in Alberta, Manitoba, Nova Scotia, Ontario and Québec and compared to age- and sex-matched children without IBD. Hospitalizations for VTE within 5 years of IBD diagnosis were identified. Generalized linear mixed-effects models were used to pool province-specific incidence rates and incidence rate ratios [IRR] with 95% confidence intervals [CI]. Hazard ratios [HR] from Cox proportional hazards models were pooled with fixed-effects meta-analysis.

          Results

          The 5-year incidence of VTE among 3593 children with IBD was 31.2 [95% CI 23.7–41.0] per 10 000 person-years [PY] compared to 0.8 [95% CI 0.4–1.7] per 10 000 PY among 16 289 children without IBD [unadjusted IRR 38.84, 95% CI 16.59–90.83; adjusted HR 22.91, 95% CI 11.50–45.63]. VTE was less common in Crohn’s disease than ulcerative colitis [unadjusted IRR 0.47, 95% CI 0.27–0.83; adjusted HR 0.52, 95% CI 0.29–0.94]. The findings were similar for deep vein thrombosis and pulmonary embolism when comparing children with and without IBD.

          Conclusions

          The risk of VTE is much higher in children with IBD than controls without IBD. While the absolute risk is low, we found a higher incidence rate than previously described in the pediatric literature.

          Conference Presentation: An abstract based on the data included in this paper was presented at Canadian Digestive Diseases Week [Montréal, Canada] in March 2020.

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          Most cited references36

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          Conducting Meta-Analyses inRwith themetaforPackage

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            A modified poisson regression approach to prospective studies with binary data.

            G Zou (2004)
            Relative risk is usually the parameter of interest in epidemiologic and medical studies. In this paper, the author proposes a modified Poisson regression approach (i.e., Poisson regression with a robust error variance) to estimate this effect measure directly. A simple 2-by-2 table is used to justify the validity of this approach. Results from a limited simulation study indicate that this approach is very reliable even with total sample sizes as small as 100. The method is illustrated with two data sets.
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              Conducting meta-analyses in R with the metafor package

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                Author and article information

                Journal
                J Crohns Colitis
                J Crohns Colitis
                eccojc
                Journal of Crohn's & Colitis
                Oxford University Press (UK )
                1873-9946
                1876-4479
                December 2021
                27 June 2021
                27 June 2021
                : 15
                : 12
                : 2031-2040
                Affiliations
                [1 ] SickKids Inflammatory Bowel Disease Centre, Division of Gastroenterology, Hepatology and Nutrition, The Hospital for Sick Children , Toronto, Ontario, Canada
                [2 ] Child Health Evaluative Sciences, SickKids Research Institute , Toronto, Ontario, Canada
                [3 ] McGill University Health Centre, Division of Gastroenterology and Hepatology , Montreal, Québec, Canada
                [4 ] Division of Pediatric Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, University of Alberta , Edmonton, Alberta, Canada
                [5 ] Departments of Medicine and Community Health Sciences, University of Calgary , Calgary, Alberta, Canada
                [6 ] Department of Pediatrics, Dalhousie University , Halifax, Nova Scotia, Canada
                [7 ] Univeristy of Manitoba IBD Clinical and Research Centre, University of Manitoba , Winnipeg, Manitoba, Canada
                [8 ] Department of Internal Medicine, Max Rady College of Medicine, University of Manitoba , Winnipeg, Manitoba, Canada
                [9 ] Research Institute at CancerCare Manitoba , Winnipeg, Manitoba, Canada
                [10 ] ICES , Toronto, Ontario, Canada
                [11 ] Mount Sinai Hospital Centre for Inflammatory Bowel Disease, Department of Medicine, University of Toronto , Toronto, Ontario, Canada
                [12 ] Institute of Health Policy, Management and Evaluation, University of Toronto , Toronto, Ontario, Canada
                [13 ] Department of Paediatrics, and Institute of Health Policy, Management and Evaluation University of Toronto , Toronto, Ontario, Canada
                [14 ] Department of Medicine, Dalhousie University , Halifax, Nova Scotia, Canada
                [15 ] Department of Medicine, University of Ottawa , Ottawa, Ontario, Canada
                [16 ] Ottawa Hospital Research Institute , Ottawa, Ontario, Canada
                [17 ] Division of Gastroenterology, The Ottawa Hospital IBD Centre , Ottawa, Ontario, Canada
                [18 ] School of Epidemiology and Public Health, University of Ottawa , Ottawa, Ontario, Canada
                [19 ] Department of Community Health Sciences, Rady Faculty of Health Sciences, University of Manitoba , Winnipeg, Manitoba, Canada
                [20 ] George & Fay Yee Centre for Healthcare Innovation, University of Manitoba , Winnipeg, Manitoba, Canada
                [21 ] Department of Community Health & Epidemiology, College of Medicine, University of Saskatchewan , Saskatoon, Saskatchewan, Canada
                [22 ] Department of Pediatrics, University of Ottawa , Ottawa, Ontario, Canada
                [23 ] CHEO Inflammatory Bowel Disease Centre, Division of Gastroenterology, Hepatology and Nutrition, CHEO , Ottawa, Ontario, Canada
                [24 ] CHEO Research Institute , Ottawa, Ontario, Canada
                [25 ] Department of Pediatrics, BC Children’s Hospital Research Institute, University of British Columbia , Vancouver, British Columbia, Canada
                [26 ] Department of Pediatrics, University of Manitoba , Winnipeg, Manitoba, Canada
                [27 ] School of Population and Public Health, University of British Columbia , Vancouver, British Columbia, Canada
                [28 ] Lady Davis Institute of Medical Research, Jewish General Hospital , Montreal, Québec, Canada
                Author notes
                Corresponding author: Eric Benchimol, MD, PhD, FRCPC, The Hospital for Sick Children, Division of Gastroenterology, Hepatology and Nutrition, 555 University Avenue, Toronto, ON, M5G 1X8, Canada. Tel: (416]813-1500 ext. 308179; Fax: (416]813-4972; Email: eric.benchimol@ 123456sickkids.ca
                Author information
                https://orcid.org/0000-0002-3984-8426
                https://orcid.org/0000-0001-7083-7429
                https://orcid.org/0000-0001-8041-3574
                https://orcid.org/0000-0002-4653-525X
                https://orcid.org/0000-0001-7269-8557
                https://orcid.org/0000-0001-6417-7583
                https://orcid.org/0000-0001-8855-3598
                Article
                jjab113
                10.1093/ecco-jcc/jjab113
                8684458
                34175936
                69936f8a-7c19-4d14-b0ed-dcde1807c8c5
                © The Author(s) 2021. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License ( https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com

                History
                : 20 July 2021
                Page count
                Pages: 10
                Funding
                Funded by: Crohn's and Colitis Canada, DOI 10.13039/501100007658;
                Funded by: Canadian Institutes of Health Research, DOI 10.13039/501100000024;
                Award ID: 201409FDN-333131-FDN-CECC-164898
                Categories
                Original Articles
                AcademicSubjects/MED00260

                venous thromboembolism,inflammatory bowel disease,paediatrics,epidemiology,complications,health administrative data,routinely collected health data

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