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Background and aims: There is an incomplete understanding of the full safety profiles of repeated COVID-19 vaccinations in patients with inflammatory bowel disease (IBD). Among individuals with IBD, we assessed whether COVID-19 vaccines were associated with serious adverse events of special interest (AESI) and health care utilization [all-cause hospitalizations, Emergency Department (ED) visits, gastroenterology visits, IBD-related visits]. Methods: Using comprehensive administrative health data from Ontario, Canada, adults with IBD who received at least one COVID-19 vaccine from December 2020-January 2022 were included. Self-controlled case series analyses were conducted to evaluate the relative incidence rates of AESI and health care utilization outcomes across post-vaccination risk and control periods. Results: Among 88,407 IBD patients, 99.7% received mRNA vaccines and 75.9% received ≥ 3 doses. Relative to control periods, we did not detect an increase in AESI. IBD patients had fewer all-cause hospitalizations during post-vaccination risk periods. Patients experienced more all-cause ED visits after dose 2 [Relative Incidence (RI):1.08(95%CI:1.04–1.12)] but fewer visits after doses 3 [RI:0.85 (95%CI:0.81–0.90)] and 4 [RI:0.73 (95%CI:0.57–0.92)]. There was no increase in gastroenterologist visits or IBD-related health care utilization post-vaccination. There were fewer IBD-related hospitalizations after dose 1 [RI:0.84 (95%CI:0.72–0.98)] and 3 [RI:0.63 (95%CI:0.52–0.76)], fewer IBD-related ED visits after dose 3 [RI:0.81 (95%CI:0.71–0.91)] and 4 [RI:0.55 (95%CI:0.32–0.96)], and fewer outpatient visits after dose 2 [RI:0.91 (95%CI:0.90–0.93)] and 3 [RI:0.87 (95%CI:0.86–0.89)]. Conclusion: This population-based study did not detect increased AESI, all-cause or IBD-related health care utilization following COVID-19 vaccination, suggesting a lack of association between vaccination and increased disease activity. [ABSTRACT FROM AUTHOR]

Objectives Kawasaki disease (KD) is an immune-mediated vasculitis of childhood with multi-organ inflammation. We determined the risk of subsequent immune-mediated inflammatory disease (IMID), including arthritis, type 1 diabetes, IBD, autoimmune liver disease, primary sclerosing cholangitis and multiple sclerosis. Methods We conducted a matched population-based cohort study using health administrative data from Ontario, Canada. Children aged <18 years born between 1991 and 2016 diagnosed with KD (n  = 3753) were matched to 5 non-KD controls from the general population (n  = 18 749). We determined the incidence of IMIDs after resolution of KD. Three- and 12-month washout periods were used to exclude KD-related symptoms. Results There was an elevated risk of arthritis in KD patients compared with non-KD controls, starting 3 months after index date [103.0 vs 12.7 per 100 000 person-years (PYs); incidence rate ratio 8.07 (95% CI 4.95, 13.2); hazard ratio 8.08 (95% CI 4.95, 13.2), resulting in the overall incidence of IMIDs being elevated in KD patients (175.1 vs 68.0 per 100 000 PYs; incidence rate ratio 2.58 (95% CI 1.93, 3.43); hazard ratio 2.58, 95% CI 1.94, 3.43]. However, there was no increased risk for diabetes, IBD, autoimmune liver disease, primary sclerosing cholangitis or multiple sclerosis in KD patients. Similar results were observed using a 12-month washout period. Conclusion Children diagnosed with KD were at increased risk of arthritis following the acute KD event, but not other IMIDs. Health-care providers should monitor for arthritis in children following a diagnosis of KD. [ABSTRACT FROM AUTHOR]

Background: Inflammatory bowel disease (IBD) may be life-threatening and often reduces quality of life. We determined trends in life expectancy and health-adjusted life expectancy in people with and without IBD.Methods: We conducted a retrospective cohort study of population-level health administrative, demographic and health survey data available from databases in Ontario. We matched people with a diagnosis of IBD to those without a diagnosis of IBD. We used period life tables that were generated using age- and sex-specific 5-year mortality rates to calculate life expectancy (for 1996, 2000, 2008 and 2011). We incorporated the Health Utility Index (National Population Health Study; Canadian Community Health Survey) to estimate health-adjusted life expectancy (for 1996, 2000 and 2008).Results: Life expectancy in patients with IBD increased between 1996 and 2011 (females: from 75.5 to 78.4 yr, difference: 2.9 yr [95% confidence interval (CI) 1.3 to 4.5]; males: from 72.2 to 75.5 yr, difference: 3.2 yr [95% CI 2.1 to 4.4]). Between 1996 and 2008, health-adjusted life expectancy decreased among males by 3.9 years (95% CI 1.2 to 6.6). There was no statistically significant change in health-adjusted life expectancy among females with IBD (difference: 2.0 yr, 95% CI -1.6 to 5.7). Life expectancy and health-adjusted life expectancy were lower in people with IBD compared with those without IBD. Differences in life expectancy in people with and without IBD ranged from 6.6 to 8.1 years in females and 5.0 to 6.1 years in males, depending on the year. Differences in health-adjusted life expectancy for people with and without IBD ranged from 9.5 to 13.5 years in females and 2.6 to 6.7 years in males.Interpretation: Whilst life expectancy has increased among people with IBD, a gap in life expectancy between those with and without IBD remains, and the effect of pain on daily functioning contributes substantially to reduced health-adjusted life expectancy, suggesting that improved pain mitigation strategies should be implemented. [ABSTRACT FROM AUTHOR]

Background and aims: Canada's large geographic area and low population density pose challenges in access to specialized health care for remote and rural residents. We compared health services use, surgical rate, and specialist gastroenterologist care in rural and urban inflammatory bowel disease (IBD) patients in Canada.Methods: We used validated algorithms that were applied to population-based health administrative data to identify all people living with the following three Canadian provinces: Alberta, Manitoba, and Ontario (ON). We compared rural residents with urban residents for time to diagnosis, hospitalizations, outpatient visits, emergency department (ED) use, surgical rate, and gastroenterologist care. Multivariable regression compared the outcomes in rural/urban patients, controlling for confounders. Provincial results were meta-analyzed using random-effects models to produce overall estimates.Results: A total of 36,656 urban and 5,223 rural residents with incident IBD were included. Outpatient physician visit rate was similar in rural and urban patients. IBD-specific and IBD-related hospitalization rates were higher in rural patients (incidence rate ratio [IRR] 1.17, 95% CI 1.02–1.34, and IRR 1.27, 95% CI 1.04–1.56, respectively). The rate of ED visits in ON were similarly elevated for rural patients (IRR 1.53, 95% CI 1.42–1.65, and IRR 1.33, 95% CI 1.25–1.40). There were no differences in surgical rates or prediagnosis lag time between rural and urban patients. Rural patients had fewer IBD-specific gastroenterologist visits (IRR 0.79, 95% CI 0.73–0.84) and a smaller proportion of their IBD-specific care was provided by gastroenterologists (28.3% vs 55.2%, P [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]

Importance: Immune-mediated inflammatory diseases (IMIDs) and COVID-19 are independently associated with venous thromboembolisms (VTEs)., Objective: To determine if individuals with IMIDs are at higher risk of VTE following COVID-19 infection compared with individuals without IMIDs., Design, Setting, and Participants: Population-based matched cohort study using multiple deterministically linked health administrative databases from Ontario, Canada, and including patients testing positive for COVID-19 between January 1, 2020, and December 30, 2021, and followed up until March 31, 2022. Individuals with IMIDs (n = 28 440) who tested positive for COVID-19 were matched with up to 5 individuals without an IMID (n = 126 437) who tested positive for COVID-19. Matching was based on year of birth, sex, neighborhood income, and rural/urban residence. Data analysis was performed from August 6, 2022, to August 21, 2023., Exposure: Diagnosis of an IMID, identified using algorithms based on diagnostic codes, procedures, and specialist visits., Main Outcome and Measure: The main outcome was estimated age- and sex-standardized incidence of VTE. Proportional cause-specific hazard models compared the risk of VTE in people with and without IMIDs. Death was a competing risk. Models adjusted for history of VTE, 2 or more doses of a COVID-19 vaccine 14 or more days prior to COVID-19 diagnosis, and the Charlson Comorbidity Index. Routinely collected health data were used, so the hypothesis tested was formulated after data collection but prior to being granted access to data., Results: The study included 28 440 individuals (16 741 [58.9%] female; 11 699 [41.1%] male) with an IMID diagnosed prior to first COVID-19 diagnosis, with a mean (SD) age of 52.1 (18.8) years at COVID-19 diagnosis. These individuals were matched to 126 437 controls without IMIDs. The incidence of VTE within 6 months of COVID-19 diagnosis among 28 440 individuals with an IMID was 2.64 (95% CI, 2.23-3.10) per 100 000 person-days compared with 2.18 (95% CI, 1.99-2.38) per 100 000 person-days among 126 437 matched individuals without IMIDs. The VTE risk was not statistically significantly different among those with vs without IMIDs (adjusted hazard ratio, 1.12; 95% CI, 0.95-1.32)., Conclusions and Relevance: In this retrospective population-based cohort study of individuals with IMIDs following COVID-19, individuals with IMIDs did not have a higher risk of VTE compared with individuals without an IMID. These data provide reassurance to clinicians caring for individuals with IMIDs and COVID-19.

Background and Objectives: Compare meta-analysis in a distributed network to individual-level analysis for assessment of time trends of health services utilization with health administrative data., Methods: We used administrative data from Ontario, Canada to analyze temporal trends in pediatric inflammatory bowel disease health services use. Beta coefficients were obtained using negative binomial, logistic, and Cox proportional hazards regression models. We replicated the individual-level analyses in each Ontario Local Health Integration Network (LHIN), then meta-analyzed aggregate trends using both fixed and random effects meta-analysis. We compared the pooled estimates of effect with individual-level analysis., Results: Beta coefficients, summary effect estimates, and 95% confidence intervals (CIs) from the meta-analysis of data from distributed networks were not different than those from individual-level data, regardless of meta-analytic approach used. For example, the 5-year odds ratio of colectomy in ulcerative colitis using individual-level analysis was 0.978 (95% CI 0.950 to 1.007) compared to distributed network fixed effects meta-analysis: 0.982 (95% CI 0.950 to 1.015), and random effects meta-analysis: 0.982 (95% CI 0.950 to 1.015)., Conclusion: Meta-analysis of multi-jurisdictional estimates were similar to estimates obtained from individual-level analysis. This method is a valid alternative for analysis of multi-jurisdictional data when individual-level data cannot be shared., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

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., (© The Author(s) 2021. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation.)

Introduction: Environmental factors related to urbanization and industrialization are believed to be involved in inflammatory bowel disease (IBD) development, but no study has looked at the association between greenspace and IBD., Methods: We conducted a retrospective cohort study using linked population-based health administrative and environmental data sets. The study population comprised 2,715,318 mother-infant pairs from hospital births in Ontario, Canada, between April 1, 1991, and March 31, 2014. We measured the exposure to residential greenspace using the normalized difference vegetation index derived using remote-sensing methods. Average greenspace was estimated for the pregnancy and childhood periods. We used mixed-effects Cox proportional hazard models to assess potential associations between residential greenspace and the risk of developing IBD before 18 years while adjusting for covariates including sex, maternal IBD, rural/urban residence at birth, and neighborhood income., Results: There were 3,444 IBD diagnoses that occurred during follow-up. An increase in the interquartile range of residential greenspace during the childhood period was associated with a lower risk of developing pediatric-onset IBD (hazard ratio [HR] 0.77, 95% confidence interval [CI] 0.74-0.81). This relationship was significant for both ulcerative colitis (HR 0.72 95% CI 0.67-0.78) and Crohn's disease (HR 0.81, 95% CI 0.76-0.87). There was a linear dose response across increasing quartiles of greenspace (P < 0.0001). No consistent association was detected between maternal intrapartum greenspace exposure and pediatric-onset IBD., Discussion: Higher exposure to residential greenspace during childhood was associated with a reduced risk of IBD, suggesting a novel avenue to prevent IBD in children., (Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

Background: Originally used for screening of inborn errors of metabolism, routine metabolite profiles of newborns have also been associated with prematurity and some childhood diseases. We sought to determine whether metabolites measured during routine newborn screening could identify infants who develop inflammatory bowel disease (IBD) in childhood., Methods: We conducted a population-based matched case-control study using health administrative data from Ontario, Canada. Children born 2006 to 2015 with IBD were identified using a validated algorithm and matched to 5 controls based on birth date, sex, rural/urban household, and mean neighborhood income quintile at birth. Cases and controls were linked deterministically to metabolic profiles from Newborn Screening Ontario. We fit a lasso penalized logistic regression model and used 10-fold cross-validation to obtain internally valid performance measures. Models included metabolites, amino acids, and endocrine markers. Models also included ratios of metabolites, gestational age, birth weight, mode of delivery, age at serum collection, maternal age at delivery, maternal history of IBD, and parity., Results: Three hundred eight cases of IBD, diagnosed at 5.5 ± 2.8 years, were matched to 1540 controls. No individual metabolites were associated with IBD. The c-statistic was 0.50 for the training data. After 10-fold cross-validation the C statistic was 0.50, indicating no significant association between metabolites and IBD diagnosis., Conclusions: Newborn screening serum metabolites could not identify children who will develop IBD in this population-based cohort. Future studies with an expanded panel of metabolites may provide improved prediction of IBD., (© 2019 Crohn’s & Colitis Foundation. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Inflammatory bowel disease (IBD) is associated with a high risk of venous thromboembolism (VTE) during hospitalization. It is unclear if this association persists after discharge. We aimed to assess the incidence of postdischarge VTE in IBD patients and to determine if IBD is associated with increased VTE risk., Methods: We performed a population-based cohort study between 2002 and 2016 using Ontario health administrative data sets. Hospitalized (≥72 hours) adults with IBD were stratified into nonsurgical and surgical cohorts and matched on propensity score to non-IBD controls. Time to postdischarge VTE was assessed by Kaplan-Meier methods, and VTE risk was assessed by Cox proportional hazard models., Results: A total of 81,900 IBD discharges (62,848 nonsurgical and 19,052 surgical) were matched to non-IBD controls. The cumulative incidence of VTE at 12 months after discharge was 2.3% for nonsurgical IBD patients and 1.6% for surgical IBD patients. The incidence increased in the nonsurgical IBD cohort by 4% per year (incidence rate ratio, 1.04; 95% CI, 1.02-1.05). In our propensity score-matched analysis, the risk of VTE at 1-month postdischarge was greater in nonsurgical IBD patients (hazard ratio [HR], 1.72; 95% CI, 1.51-1.96) and surgical patients with ulcerative colitis (HR, 1.68; 95% CI, 1.16-2.45) but not surgical patients with Crohn's disease. These trends persisted through 12 months., Conclusions: Nonsurgical IBD patients and surgical patients with ulcerative colitis are 1.7-fold more likely to develop postdischarge VTE than non-IBD patients. These findings support the need for increased vigilance and consideration of thromboprophylaxis in this population., (© 2020 Crohn’s & Colitis Foundation. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: Biliary atresia (BA) is the most common reason for liver transplant in childhood, and outcomes worsen with older age at hepatoportoenterostomy (HPE). We determined direct health care costs in children with BA, compared to controls in a population-based cohort of children in Ontario, Canada., Methods: We used health administrative data to identify all children diagnosed with BA between 2002 and 2016 (n = 121) and matched controls (n = 602). We determined annual direct healthcare costs, and rates of health services utilization, liver transplantation, death, portal hypertension, cirrhosis, esophageal varices, and major upper gastrointestinal bleeding requiring hospitalization. Multivariable regression models determined the association between age at HPE, risk of liver transplant, and direct costs., Results: Incidence of BA was 6.07 (4.99-7.15) per 100,000 live births. The annual median (interquartile range) direct health care costs were higher in BA cases ($4210; interquartile range $1091-$16,765) compared to controls ($283; $112-$634). Compared to age at HPE <45 days, there was no significant association between direct costs and HPE ≥90 days (rate ratio 1.24, 95% confidence interval [CI] 0.78-1.97) or 45 to 90 days (rate ratio 1.05, 95% CI 0.73-1.50). Age at HPE ≥90 days was significantly associated with risk of undergoing liver transplant compared to age <45 days (hazard ratio 5.27, 95% CI 2.45-11.34). Direct costs were higher in patients with BA who underwent liver transplantation compared to those who did not ($39,476±$84,367 vs $22,579 ± $67,913)., Conclusions: Direct ealth care costs were high in patients with BA, especially in those who underwent liver transplantation. Age at HPE was associated with risk of liver transplantation, but not direct health care costs, utilization, or other risk outcomes.

Objective: Patients with inflammatory bowel disease (IBD) have an elevated risk of mental illness. We determined the incidence and correlates of new-onset mental illness associated with IBD during pregnancy and post partum., Design: This cohort study using population-based health administrative data included all women with a singleton live birth in Ontario, Canada (2002-2014). The incidence of new-onset mental illness from conception to 1-year post partum was compared between 3721 women with and 798 908 without IBD, generating adjusted HRs (aHR). Logistic regression was used to identify correlates of new-onset mental illness in the IBD group., Results: About 22.7% of women with IBD had new-onset mental illness versus 20.4% without, corresponding to incidence rates of 150.2 and 132.8 per 1000 patient-years (aHR 1.12, 95% CI 1.05 to 1.20), or one extra case of new-onset mental illness per 43 pregnant women with IBD. The risk was elevated in the post partum (aHR 1.20, 95% CI 1.09 to 1.31), but not during pregnancy, and for Crohn's disease (aHR 1.12, 95% CI 1.02 to 1.23), but not ulcerative colitis. The risk was specifically elevated for a new-onset mood or anxiety disorder (aHR 1.14, 95% CI 1.04 to 1.26) and alcohol or substance use disorders (aHR 2.73, 95% CI 1.42 to 5.26). Predictors of a mental illness diagnosis were maternal age, delivery year, medical comorbidity, number of prenatal visits, family physician obstetrical care and infant mortality., Conclusion: Women with IBD were at an increased risk of new-onset psychiatric diagnosis in the postpartum period, but not during pregnancy. Providers should look to increase opportunities for prevention, early identification and treatment accordingly., Competing Interests: Competing interests: SNV: receives royalties from UpToDate Inc for authorship of topics focused on depression and antidepressant medication use in pregnancy. LET: received investigator-initiated funding from Janssen Canada and served on advisory boards for AbbVie Canada, Takeda Canada, Merck Canada, Pfizer Canada and Mallinckrodt USA. CHS: serves on advisory boards and as a speaker for Janssen Canada, Abbvie Canada, Shire Canada, Takeda Canada, Ferring Canada and received educational grants from Janssen Canada., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Canada has one of the highest rates of inflammatory bowel disease (IBD) in the world, with 1 in 140 Canadians currently living with the disease. IBD occurs less often among individuals living in rural households. This protective effect is particularly pronounced in young children, and early-life exposure to the rural environment greatly reduces the risk. However, individuals living in rural areas who have IBD have decreased access to specialist gastroenterology care., (Copyright © 2019 Longwoods Publishing.)