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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. [ABSTRACT FROM AUTHOR]

Background Modern, specialised care for children with inflammatory bowel disease [IBD] may have resulted in changes in health services use. We report trends over time in health services utilisation and surgery for children with IBD and children without IBD. Methods Children aged <18 years, diagnosed with IBD between 1994 and 2013 [ n = 5518] and followed until 2015 in Ontario, Canada, were identified from health administrative data and matched to children without IBD on age, sex, rural/urban household, and income [ n = 26,677]. We report the annual percentage change [APC] with 95% confidence intervals [CI] in the rate of outpatient visits, emergency department [ED] visits, and hospitalisations, using negative binomial regression for events within 5 years from the diagnosis/index date. We used Cox proportional hazards regression models to report APC in hazards of intestinal resection [Crohn's disease; CD] and colectomy [ulcerative colitis; UC]. Results IBD-specific hospitalisation rates decreased by 2.5% [95% CI 1.8–3.2%] annually, and all-cause hospitalisation rates in children without IBD decreased by 4.3% [95% CI 3.5–5.1%] annually. Intestinal resection risk in CD decreased by 6.0% [95% CI 4.6–7.3%] annually and colectomy risk in UC decreased by 3.0% [95% CI 0.7–5.2%] annually. In contrast, IBD-specific outpatient visit rates increased after 2005 by 4.0% [95% CI 3.1–4.9%] annually. Similar trends in outpatient visits were not observed in children without IBD. Conclusions Hospitalisations and surgeries decreased over time while outpatient visits increased after 2005. Decreasing hospitalisations were mirrored in children without IBD, likely resulting from a combination of changes in disease management and health system factors. [ABSTRACT FROM AUTHOR]

Background and Aims The combination of infliximab and azathioprine is more efficacious than either therapy alone for Crohn's disease [CD] and ulcerative colitis [UC]. However, it is uncertain whether these benefits extend to real-world clinical practice and to other combinations of biologics and immunomodulators. Methods We collected health administrative data from four Canadian provinces representing 78 413 patients with inflammatory bowel disease [IBD] of whom 11 244 were prescribed anti-tumour necrosis factor [anti-TNF] agents. The outcome of interest was the first occurrence of treatment failure: an unplanned IBD-related hospitalization, IBD-related resective surgery, new/recurrent corticosteroid use or anti-TNF switch. Multivariable Cox proportional hazards modelling was used to assess the association between the outcome of interest and receiving combination therapy vs anti-TNF monotherapy. Multivariable regression models were used to assess the impact of choice of immunomodulator or biologic on reaching the composite outcome, and random effects generic inverse variance meta-analysis of deterministically linked data was used to pool the results from the four provinces to obtain aggregate estimates of effect. Results In comparison with anti-TNF monotherapy, combination therapy was associated with a significant decrease in treatment ineffectiveness for both CD and UC (CD: adjusted hazard ratio [aHR] 0.77, 95% confidence interval [CI] 0.66–0.90; UC: aHR 0.72, 95% CI 0.62–0.84). Combination therapy was equally effective for adalimumab and infliximab in CD. In UC azathioprine was superior to methotrexate as the immunomodulatory agent (aHR = 1.52 [95% CI 1.02–2.28]) but not CD (aHR = 1.22 [95% CI 0.96–1.54]). Conclusion In an analysis of a database of real-world patients with IBD, combination therapy decreased the likelihood of treatment failure in both CD and UC. [ABSTRACT FROM AUTHOR]

Background: Studies examining the association between smoking and the need for surgery in patients with Crohn's disease and ulcerative colitis have reached inconsistent conclusions. These studies often do not differentiate between patients undergoing early surgery and patients having surgery later in their disease course. Our study examined the association between smoking status and time to first bowel resection in patients with Crohn's disease and ulcerative colitis.Methods: We searched MEDLINE and EMBASE for studies (n = 12) reporting on the association between smoking status (current, former, and never) and surgery in IBD, and incorporated disease duration in the analysis. Hazard ratios (HR) with 95% confidence intervals (CI) were pooled across studies using random effects models.Results: Current smokers with Crohn's disease were at increased risk of intestinal resection compared to never smokers (HR 1.27, 95% CI 1.08 to 1.49); however, there was no difference in the need for surgery when comparing former and never smokers (HR 1.11, 95% CI 0.95 to 1.30). In patients with ulcerative colitis, there was no difference in the need for colectomy when comparing current smokers to never smokers (HR 0.98, 95% CI 0.67 to 1.44). Former smokers with ulcerative colitis were at increased risk of colectomy (HR 1.38, 95% CI 1.04 to 1.83) compared to never smokers.Conclusions: Current smokers with Crohn's disease are at increased risk of surgery, while former smokers with ulcerative colitis have increased risk of colectomy. [ABSTRACT FROM AUTHOR]

The timing of initiating biologic therapy in persons with Crohn's disease (CD) and ulcerative colitis (UC) is an area of ongoing controversy. In particular, there is concern that delaying the initiation of biologic therapy may lead to more treatment-resistant disease, which can result in more complications and hospitalizations. We used health administrative data from Manitoba, Canada to identify all persons with a new diagnosis of inflammatory bowel disease (IBD) between 2001 and 2018 who received tumor necrosis factor antagonists (anti-TNF) therapy and had at least 1 year of post anti-TNF initiation follow-up. We measured the rates of hospitalization, surgery, and outpatient visits, prior to and for up to 5 years following anti-TNF initiation. We compared the rates of these health care utilization outcomes between persons receiving anti-TNFs within 2 years following diagnosis and those receiving anti-TNFs more than 2 years following IBD diagnosis. We used inverse probability treatment weighting to adjust for baseline differences in risk between the 2 groups. Among 742 persons with CD, early anti-TNF initiators had fewer IBD-specific and overall hospitalizations over the 5 years following the start of therapy. Incidence of resective surgery was also lower in earlier anti-TNF initiators with CD if the first year following initiation was excluded from the analysis. In 318 cases of UC, there was no impact of the timing of anti-TNF therapy on the rates of hospitalization and surgery. Earlier administration of anti-TNF therapy is associated with reduced downstream health care resource utilization in CD, though these impacts are not evident in UC. [ABSTRACT FROM AUTHOR]

Objective: To determine the frequency with which inflammatory bowel disease (IBD) is diagnosed in persons with Hirschsprung disease in population-based datasets from 3 Canadian provinces.Study Design: In study I, Ontario data were used to assess the incidence of IBD in a birth cohort of children with Hirschsprung disease relative to children without Hirschsprung disease. In study II, a case-control design was used in Alberta and Manitoba to determine the frequency of previously diagnosed Hirschsprung disease in persons with IBD, compared with the frequency of Hirschsprung disease in matched controls. Validated algorithms for Hirschsprung disease and IBD were applied to each provincial health registry.Results: In study I, of the 716 children diagnosed with Hirschsprung disease in Ontario since 1991, 18 (2.5%) ultimately developed IBD (168.8 per 100 000 person-years), compared with 7109 of 3 377 394 children without Hirschsprung disease (0.2%, 14.2 per 100 000 person-years). The percentage of males with post-Hirschsprung disease IBD was 77.8%. The incidence rate ratio was 11.9 (95% CI, 7.5-18.8). In study II, the OR of having had Hirschsprung disease before a diagnosis of IBD compared with controls was 74.9 (95% CI, 17.1-328.7) in Alberta and 23.8 (95% CI, 4.6-123) in Manitoba. Crohn's disease was more common after Hirschsprung disease than ulcerative colitis.Conclusions: IBD can emerge in more than 2% of patients with Hirschsprung disease and, like Hirschsprung disease itself, is more common in males. IBD is much more common after a diagnosis of Hirschsprung disease than in the general population. [ABSTRACT FROM AUTHOR]

• High-income nations have the highest rates of inflammatory bowel disease. • Exposure to O x during childhood was associated with IBD < 18 years. • Ambient air pollution is suspected to be associated with risk of IBD. High-income nations have the highest rates of inflammatory bowel disease (IBD). The incidence of pediatric-onset IBD is increasing faster than IBD diagnosed in older individuals. Previous epidemiological studies have shown that air pollution might be a risk factor for development of earlier-onset IBD, but results remain mixed. The objective of this study was to evaluate the associations between maternal and early-life exposures to nitrogen dioxide (NO 2), fine particulate matter (PM 2.5), ozone (O 3 ,) and oxidant capacity (O x) and risk of pediatric-onset IBD diagnosis. We conducted a retrospective cohort study using linked population-based health administrative data. Singleton livebirths in Ontario, Canada between April 1st, 1991 and March 31st, 2014 were included. We investigated the association between weekly exposures during pregnancy and annual exposures from birth until the age of 18 years, and IBD diagnosed <18 years of age using Cox proportional hazards models. We reported hazard ratios (HR) and 95% confidence intervals (CI) for an associated increase in the interquartile range (IQR) of each pollutant. Models were mutually adjusted for exposures in both prenatal and postnatal periods, as well as for sex, rurality of residence at birth, maternal IBD, and neighborhood income. 2,218,789 newborns were included in this study, of whom 2491 developed IBD during follow-up. Increased associations with pediatric-onset IBD were noted for childhood exposure to O x (HR 1.08, 95% CI 1.01–1.16). IBD development was also associated with O x during the second trimester (HR 1.21, 95% CI 1.03–1.42), but not the overall pregnancy period (HR 1.12, 95% CI 0.79–1.59). There were no associations of IBD with exposure to NO 2 , PM 2.5 , or O 3. Exposure to O x during childhood was associated with IBD < 18 years. This suggests that air pollution may impact the developing child physiology in such a way that leads to early onset of IBD. [ABSTRACT FROM AUTHOR]