Search

Background and Aims Thromboprophylaxis use in paediatric inflammatory bowel disease [IBD] is inconsistent. Current guidelines only support treating children with acute severe colitis with risk factors. We convened an international RAND panel to explore thromboprophylaxis in paediatric IBD inpatients in the context of new evidence. Methods We convened a geographically diverse 14-person panel of paediatric gastroenterologists alongside supporting experts. An online survey was sent before an online meeting. Panellists were asked to rate the appropriateness of thromboprophylaxis in hospitalised paediatric IBD patients via 27 scenarios of varying ages, gender, and phenotype, with and without thrombotic risk factors. Anonymised results were presented at the meeting. A second modified survey was distributed to all panellists present at the meeting. Results from the second survey constitute the RAND panel results. The validated RAND disagreement index defined disagreement when ≥ 1. Results The combined outcome of thromboprophylaxis being considered appropriate until discharge and inappropriate to withhold was seen in 20 of 27 scenarios, including: all patients with new-onset acute severe colitis; all flares of known ulcerative colitis, irrespective of risk factors except in pre-pubescent patients with limited disease and no risk factors; and all Crohn’s patients with risk factors. Disagreement was seen in five scenarios regarding Crohn’s without risk factors, where outcomes were already uncertain. Conclusions RAND panels are an established method to assess expert opinion in areas of limited evidence. This work therefore constitutes neither a guideline nor a consensus; however, the findings suggest a need to re-evaluate the role of thromboprophylaxis in future guidelines.

Several studies have demonstrated higher rates of Clostridioides difficile infection (CDI) in adults with inflammatory bowel disease (IBD). We conducted a population-based study comparing the risk of hospitalization with CDI in children with and without IBD.Using health administrative data and validated algorithms, we identified all children (16 years) diagnosed with IBD in 5 Canadian provinces, then age and sex matched to 5 children without IBD. Province-specific 5-year incidence rates of hospitalization with CDI were pooled and generalized linear mixed-effects models were used to estimate the crude incidence rate ratio (IRR) comparing (1) children with and without IBD and (2) children with Crohn disease and ulcerative colitis. Hazard ratios (HR) from Cox proportional hazards models adjusting for age, sex, rural/urban household, and income were pooled using fixed-effects models.The incidence rate of CDI identified during hospitalization was 49.06 [95% confidence interval (CI), 39.40-61.08] per 10,000 person-years (PY) in 3593 children with IBD compared to 0.39 (95% CI, 0.13-1.21) per 10,000 PY in 16,284 children without IBD (crude IRR, 133.4, 95% CI, 42.1-422.7; adjusted HR, 68.2, 95% CI, 24.4-190.4). CDI was identified less often in children with Crohn disease than ulcerative colitis (crude IRR, 0.51, 95% CI, 0.32-0.82; adjusted HR, 0.69, 95% CI, 0.46-1.05).Children with IBD have a markedly higher incidence of CDI identified during a hospitalization relative to children without IBD. Consequently, symptomatic children with IBD who are hospitalized should be screened for CDI.

Pediatric inflammatory bowel disease (IBD) is becoming increasingly common around the world, rapidly accelerating in regions undergoing rapid economic development. IBD is more common among those living in cities, and the association between the urban environment and IBD incidence is strongest in children. The "urban exposome" is defined as the totality of environmental exposures associated with urban living: air pollution, water contamination, green and blue space, nighttime light, noise, and availability of pre-processed and packaged foods. Investigation of the role of the urban exposome and IBD is in its infancy. Existing research has reached heterogeneous conclusions, and most studies have focused specifically on adult-onset disease and environmental exposures in isolation rather than the interaction between exposures. By better understanding the impact of the urban exposome on pediatric IBD, we can work to minimize these exposures and decrease the future burden of IBD in children.

Background and Aims Age is a major prognostic factor for COVID-19 outcomes. The effect of inflammatory bowel disease [IBD] activity on COVID-19 is unclear. We examined the relationship between IBD activity and COVID-19 severity according to age. Methods We included IBD patients diagnosed with COVID-19, reported to SECURE-IBD between March 13, 2020 and August 3, 2021. Clinical IBD activity was measured by physician global assessment [PGA]. COVID-19-related outcomes were [1] intensive care unit [ICU] admission, ventilation or death, and [2] hospitalization. Using generalized estimating equations, we determined adjusted odds ratios [aOR, 95% confidence interval] for moderate and severe PGA vs clinical remission/mild PGA, controlling for demographics, medications and COVID-19 diagnosis period. We performed stratified analyses by age [≤50 vs >50 years]. Results Among 6078 patients, adverse COVID-19 outcomes were more common with active IBD: ICU/ventilation/death in 3.6% [175/4898] of remission/mild, 4.9% [45/920] of moderate and 8.8% [23/260] of severe [p < 0.001]; and hospitalization in 13% [649/4898] of remission/mild, 19% [178/920] of moderate and 38% [100/260] of severe [p < 0.001]. Stratified by decade, effect sizes were larger for younger patients. In patients ≤50 years, severe PGA was independently associated with ICU/ventilation/death (aOR 3.27 [1.15–9.30]) and hospitalization (aOR 4.62 [2.83–7.55]). In contrast, severe PGA was not independently associated with COVID-19 outcomes in those older than 50 years. Conclusions Clinically active IBD may be a risk factor for severe COVID-19, particularly in younger patients. IBD disease control, including through medication compliance, and strategies to mitigate the risk of COVID-19 infection amongst patients with active IBD [e.g. distancing, immunization] are key to limit adverse COVID-19 outcomes.

Inflammatory bowel diseases (IBDs), including Crohn's disease (CD) and ulcerative colitis, are chronic diseases of the gastrointestinal tract, with an unknown etiology, that affect over 6.8 million people worldwide. To characterize disease pathogenesis, proteomic and bioinformatic analyses were performed on colon biopsies collected during diagnostic endoscopy from 119 treatment-naïve pediatric patients, including from 78 IBD patients and 41 non-IBD patients who served as controls. Due to the presence of noninflamed and/or inflamed regions in IBD patients, up to two biopsies were obtained from IBD patients as compared to a single noninflamed biopsy from non-IBD pediatric control patients. Additional biopsies were obtained and analyzed from 33 of the IBD patients after IBD-directed therapeutic intervention for comparison of pre- and post-treatment proteomes. SuperSILAC was utilized to perform quantitative analysis of homogenized tissues, which were processed by filter-aided sample preparation. Hierarchical clustering and principal component analyses revealed proteomic patterns that distinguished inflamed from noninflamed tissues independent of therapy. Gene ontology revealed that proteins downregulated in inflammation are associated with metabolism, whereas upregulated proteins contribute to protein processing. A comparison of pre- and post-treatment proteomes from CD patients identified over 100 proteins that are significantly different between patients who responded and those who did not respond to therapy, including creatine kinase B and basigin.

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 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.

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 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.

Data on pediatric inflammatory bowel disease (IBD)-associated indirect and out-of-pocket (OOP) costs are limited. We aimed to estimate indirect (lost work hours and productivity) and OOP pediatric IBD-associated costs in Canada.In a nation-wide cross-sectional analysis, caregivers of children with IBD were invited to complete a questionnaire on lost work hours and OOP costs related to IBD in the 4 weeks prior to the survey. Participants were reinvited to periodically answer the same questionnaire every 3-9 months for 2 years. Lost productivity was calculated using the Human Capital method. Costs were reported in 2018 inflation-adjusted Canadian dollars. Predictors of high cost users (top 25%) were examined using binary logistic regression.Consecutive 243 (82 incident cases) of 262 (92.7%) approached participants completed the first survey with a total of 450 surveys longitudinally completed over 2 years. The median annual indirect cost per patient was $5966 (IQR $1809-$12,676), with $5721 (IQR $1366-$11,545) for Crohn's disease (CD) and $7007 (IQR $2428-$14,057) for ulcerative colitis (UC) ( P = 0.11). The annual median per patient OOP costs were $4550 with $4550 for CD and $5038 for UC ( P = 0.53). Longer travel distance to clinic was associated with higher OOP costs (odds ratio = 4.55; Plt; 0.0001; 95% confidence interval: 1.99-10.40).Indirect and OOP IBD-associated costs are substantial and more likely to affect families living in remote communities.

Background Transition in care is defined as the “purposeful and planned movement of adolescents and young adults with a chronic medical condition from pediatric to adult-oriented healthcare systems/care providers.” Currently, there are no Level 1 evidence-based interventions to improve the care of transitioning adolescents and young adults (AYAs) with inflammatory bowel disease (IBD). The development of a transition program using a biopsychosocial approach will improve the standards for healthcare delivery to transitioning IBD patients. This is a protocol for a structured randomized controlled trial (RCT) to assess the clinical and implementation effectiveness of a multimodal intervention focused on improving patient function, transition readiness and outcomes among AYA patients with IBD being cared for at pediatric centers in Canada. Methods This multi-center RCT is a type 1 hybrid effectiveness-implementation trial to evaluate effectiveness of the intervention and how it can be implemented more widely after the trial. We will include patients aged 16.0–17.5 years. The intervention program consists of 4 core components: (1) individualized assessment, (2) transition navigator, (3) virtual patient skills-building with a focus on building resilience, self-management and self-efficacy, and (4) a virtual structured education program. The control group will undergo standard-of-care defined by each participating center. The primary outcome will be the IBD Disability Index, a validated measure to assess patient functioning. Secondary outcomes include transition readiness and success, anxiety and depression scales, and health service utilization rates. Additionally, we will measure implementation outcomes and related barriers and facilitators for the intervention program. Discussion The type 1 hybrid effectiveness-implementation design will allow for the development of a feasible, sustainable, and acceptable final intervention model. The intervention will consist of modules that can be accessed in an online, virtual platform. The implementation will allow centralization of interventions and funding in order to minimize the impact on local clinical practice or hospital resources. The authors anticipate that the main study limitation will relate to study subjects not completely adhering to every component of the intervention, which will be evaluated and addressed using the implementation science approach. Trial registration NCT05221281. Registry: ClinicalTrials.gov. Date of registration: February 2, 2022. https://clinicaltrials.gov/ct2/show/NCT05221281.

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.

Background & aims: The incidence of inflammatory bowel disease (IBD) is increasing internationally, particularly in nations with historically low rates. Previous reports of the epidemiology of pediatric-onset IBD identified a paucity of data. We systematically reviewed the global trends in incidence and prevalence of IBD diagnosed in individuals Methods: We systematically reviewed studies indexed in MEDLINE, EMBASE, Airiti Library, and SciELO from January 2010 to February 2020 to identify population-based studies reporting the incidence and/or prevalence of IBD, Crohn's disease, ulcerative colitis, and/or IBD-unclassified. Data from studies published before 2000 were derived from a previously published systematic review. We described the geographic distribution and trends in children of all ages and limiting to very early onset (VEO) IBD.Results: A total of 131 studies from 48 countries were included. The incidence and prevalence of pediatric-onset IBD is highest in Northern Europe and North America and lowest in Southern Europe, Asia, and the Middle East. Among studies evaluating trends over time, most (31 of 37, 84%) studies reported significant increases in incidence and all (7 of 7) reported significant increases in prevalence. Data on the incidence and prevalence of VEO-IBD are limited to countries with historically high rates of IBD. Time trends in the incidence of VEO-IBD were visually heterogeneous.Conclusions: Rates of pediatric-onset IBD continue to rise around the world and data are emerging from regions where it was not previously reported; however, there remains a paucity of data on VEO-IBD and on pediatric IBD from developing and recently developed countries.

OBJECTIVES: To examine the four possible combinations of adherence to physical activity and screen time recommendations in adolescents and how the combinations relate to overweight and obesity. METHODS: A total of 9913 students in grades 7–12 were included in the present cross-sectional analyses. Moderate-to-vigorous physical activity (MVPA), screen time, and body mass index were self-reported. Multivariate logistic regression analysis was used to test the associations between combinations of MVPA (≥ 60 min/day [active] or 2 h/day [sedentary]) recommendations with overweight/obesity. RESULTS: We found that 53.1% of students in Ontario were considered “inactive+sedentary”, 23.7% were considered “inactive+not sedentary”, 12.1% were considered “active+sedentary”, and 11.1% were considered “active+not sedentary”. Some characteristics of “active+not sedentary” students (optimal category) included younger age, male gender, white ethnicity, higher socio-economic status, optimal sleep duration, and lower prevalence of cannabis use. After adjusting for relevant covariates, the “inactive+sedentary” group was more likely to report overweight/obesity than the “active+not sedentary” group (odds ratio [OR] = 1.71, 95% confidence interval [CI] = 1.26–2.32). The “inactive+not sedentary” group was also more likely to report overweight/obesity (OR = 1.54, 95% CI 1.20–1.97) while the “active+sedentary” group was not significantly associated with overweight/obesity (OR = 1.27, 95% CI 0.88–1.83). CONCLUSION: Children meeting both the physical activity and screen time recommendations are less likely to be classified as overweight/obese compared with any other combination. Future efforts are needed to target both MVPA and sedentary behaviour to address public health concerns such as excess weight.

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.

OBJECTIVES The prevalence of inflammatory bowel disease (IBD) is increasing. The total direct costs of IBD have not been assessed on a population-wide level in the era of biologic therapy. DESIGN We identified all persons with IBD in Manitoba between 2005 and 2015, with each matched to 10 controls on age, sex, and area of residence. We enumerated all hospitalizations, outpatient visits and prescription medications including biologics, and their associated direct costs. Total and per capita annual IBD-attributable costs and health care utilization (HCU) were determined by taking the difference between the costs/HCU accrued by an IBD case and their controls. Generalized linear modeling was used to evaluate trends in direct costs and Poisson regression for trends in HCU. RESULTS The number of people with IBD in Manitoba increased from 6,323 to 7,603 between 2005 and 2015. The total per capita annual costs attributable to IBD rose from $3,354 in 2005 to $7,801 in 2015, primarily driven by an increase in per capita annual anti-tumor necrosis factor costs, which rose from $181 in 2005 to $5,270 in 2015. There was a significant decline in inpatient costs for CD ($99 ± 25/yr. P < 0.0001), but not for ulcerative colitis ($8 increase ±$18/yr, P = 0.63). DISCUSSION The direct health care costs attributable to IBD have more than doubled over the 10 years between 2005 and 2015, driven mostly by increasing expenditures on biological medications. IBD-attributable hospitalization costs have declined modestly over time for persons with CD, although no change was seen for patients with ulcerative colitis.

To evaluate for increased rectal bleeding following enoxaparin thromboprophylaxis in children hospitalized for ulcerative colitis (UC).Retrospective cohort study (2007--2016) of 218 inpatients with active UC. Patients receiving enoxaparin were compared with a nonenoxaparin-treated patient group. Severity of UC was determined using the Pediatric Ulcerative Colitis Activity Index (PUCAI). Hemoglobin (Hb) values and packed red blood cell (pRBC) transfusions were reviewed for a 7-day period following hospital admission. A linear mixed effect model was used to compare change in Hb values between the groups. Risk of pRBC transfusion was compared using a log-rank test and Cox proportional hazard regression. A sub-analysis was also conducted restricting to patients with severe UC to provide more generalizable insight into safety profile of enoxaparin.Children hospitalized for UC and receiving enoxaparin were more likely to have severe disease, received infliximab therapy and be admitted after 2010. Use of enoxaparin showed there was not a difference (P = 0.60) in the fall of Hb detected among those with acute severe colitis (initial PUCAI ≥65) during the week following admission. Moreover, there was no difference in the risk of requiring a pRBC transfusion with enoxaparin use (log-rank test all patients: P = 0.80; severe UC: P = 0.88; Cox proportional hazard regression all patients: P = 0.72; severe UC: 0.85).There was no difference in Hb levels or need for blood transfusions in children hospitalized for severe UC (PUCAI ≥65) whether or not they received enoxaparin for thromboembolism prophylaxis.

Background Advanced colorectal neoplasms (ACNs), including colorectal cancers (CRC) and high-risk adenomas (HRA), are detected in less than 20% of persons aged 50 years or older who undergo colonoscopy. We sought to derive personalized predictive models of risk of harbouring ACNs to improve colonoscopy wait times for high-risk patients and allocation of colonoscopy resources. Methods We characterized colonoscopy indications, neoplasia risk factors and colonoscopy findings through chart review for consecutive individuals aged 50 years or older who underwent outpatient colonoscopy at The Ottawa Hospital (Ottawa, Canada) between April 1, 2008 and March 31, 2012 for non-life threatening indications. We linked patients to population-level health administrative datasets to ascertain additional historical predictor variables and derive multivariable logistic regression models for risk of harboring ACNs at colonoscopy. We assessed model discriminatory capacity and calibration and the ability of the models to improve colonoscopy specificity while maintaining excellent sensitivity for ACN capture. Results We modelled 17 candidate predictors in 11,724 individuals who met eligibility criteria. The final CRC model comprised 8 variables and had a c-statistic value of 0.957 and a goodness-of-fit p-value of 0.527. Application of the models to our cohort permitted 100% sensitivity for identifying persons with CRC and > 90% sensitivity for identifying persons with HRA, while improving colonoscopy specificity for ACNs by 23.8%. Conclusions Our multivariable models show excellent discriminatory capacity for persons with ACNs and could significantly increase colonoscopy specificity without overly sacrificing sensitivity. If validated, these models could allow more efficient allocation of colonoscopy resources, potentially reducing wait times for those at higher risk while deferring unnecessary colonoscopies in low-risk individuals. Supplementary Information The online version contains supplementary material available at 10.1186/s12876-021-01965-5.

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.

Background Canadian-born children of South Asian [SA] ethnicity develop inflammatory bowel disease [IBD] at similar rates to those among Caucasian children. We evaluated the variation in phenotypic spectrum of IBD in SA and Caucasian children in a national paediatric inception cohort of new-onset IBD. Methods Patients aged Results Of 1156 children enrolled over 2014 to 2019, 623 were Caucasian [98% and 88% parents Canadian born] and 114 SA [79% Canadian born, 87% parents SA born]. Fewer SAs have a first-degree relative with IBD, 6% vs 19% in Caucasians, p = 0.002. SAs present at a younger age, median age 11.4 years (interquartile range [IQR] 9.2–14.3) vs 13 years [IQR 10.9-15 years], p = 0.03 and more commonly with a UC/IBD-U [ulcerative colitis/IBD-unclassified] subtype [ratio of UC/IBD-U to CD 1.2:1 vs 1:1.8 for Caucasians, p Conclusions The phenotypic spectrum of new-onset IBD in SA children differs from that of Caucasian children, but treatment and clinical course are similar within phenotypic subgroups.

Background and Aims The effectiveness and safety of vaccinations can be altered by immunosuppressive therapies, and perhaps by inflammatory bowel disease (IBD) itself. These recommendations developed by the Canadian Association of Gastroenterology and endorsed by the American Gastroenterological Association, aim to provide guidance on immunizations in adult and pediatric patients with IBD. This publication focused on inactivated vaccines. Methods Systematic reviews evaluating the efficacy, effectiveness, and safety of vaccines in patients with IBD, other immune-mediated inflammatory diseases, and the general population were performed. Critical outcomes included mortality, vaccine-preventable diseases, and serious adverse events. Immunogenicity was considered a surrogate outcome for vaccine efficacy. Certainty of evidence and strength of recommendations were rated according to the GRADE (Grading of Recommendation Assessment, Development, and Evaluation) approach. Key questions were developed through an iterative online platform, and voted on by a multidisciplinary group. Recommendations were formulated using the Evidence-to-Decision framework. Strong recommendation means that most patients should receive the recommended course of action, whereas a conditional recommendation means that different choices will be appropriate for different patients. Results Consensus was reached on 15 of 20 questions. Recommendations address the following vaccines: Haemophilus influenzae type b, recombinant zoster, hepatitis B, influenza, pneumococcus, meningococcus, tetanus-diphtheria-pertussis, and human papillomavirus. Most of the recommendations for patients with IBD are congruent with the current Centers for Disease Control and Prevention and Canada’s National Advisory Committee on Immunization recommendations for the general population, with the following exceptions. In patients with IBD, the panel suggested Haemophilus influenzae type b vaccine for patients older than 5 years of age, recombinant zoster vaccine for adults younger than 50 year of age, and hepatitis B vaccine for adults without a risk factor. Consensus was not reached, and recommendations were not made for 5 statements, due largely to lack of evidence, including double-dose hepatitis B vaccine, timing of influenza immunization in patients on biologics, pneumococcal and meningococcal vaccines in adult patients without risk factors, and human papillomavirus vaccine in patients aged 27–45 years. Conclusions Patients with IBD may be at increased risk of some vaccine-preventable diseases. Therefore, maintaining appropriate vaccination status in these patients is critical to optimize patient outcomes. In general, IBD is not a contraindication to the use of inactivated vaccines, but immunosuppressive therapy may reduce vaccine responses.

Compare meta-analysis in a distributed network to individual-level analysis for assessment of time trends of health services utilization with health administrative data.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.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).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.

Background & AimsWe aim to provide guidance for medical treatment of luminal Crohn’s disease in children.MethodsWe performed a systematic search of publication databases to identify studies of medical management of pediatric Crohn’s disease. Quality of evidence and strength of recommendations were rated according to the GRADE (Grading of Recommendation Assessment, Development, and Evaluation) approach. We developed statements through an iterative online platform and then finalized and voted on them.ResultsThe consensus includes 25 statements focused on medical treatment options. Consensus was not reached, and no recommendations were made, for 14 additional statements, largely due to lack of evidence. The group suggested corticosteroid therapies (including budesonide for mild to moderate disease). The group suggested exclusive enteral nutrition for induction therapy and biologic tumor necrosis factor antagonists for induction and maintenance therapy at diagnosis or at early stages of severe disease, and for patients failed by steroid and immunosuppressant induction therapies. The group recommended against the use of oral 5-aminosalicylate for induction or maintenance therapy in patients with moderate disease, and recommended against thiopurines for induction therapy, corticosteroids for maintenance therapy, and cannabis in any role. The group was unable to clearly define the role of concomitant immunosuppressants during initiation therapy with a biologic agent, although thiopurine combinations are not recommended for male patients. No consensus was reached on the role of aminosalicylates in treatment of patients with mild disease, antibiotics or vedolizumab for induction or maintenance therapy, or methotrexate for induction therapy. Patients in clinical remission who are receiving immunomodulators should be assessed for mucosal healing within 1 year of treatment initiation.ConclusionsEvidence-based medical treatment of Crohn’s disease in children is recommended, with thorough ongoing assessments to define treatment success.

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.

Background Anti–tumor necrosis factor (anti-TNF) drugs are highly effective in the treatment of moderate-to-severe Crohn’s disease (CD) and ulcerative colitis (UC), but they are very costly. Due to their effectiveness, they could potentially reduce future health care spending on other medical therapies, hospitalization, and surgery. The impact of downstream costs has not previously been quantified in a real-world population-based setting. Methods We used the University of Manitoba IBD Database to identify all persons in a Canadian province with CD or UC who received anti-TNF therapy between 2004 and 2016. All inpatient, outpatient, and drug costs were enumerated both in the year before anti-TNF initiation and for up to 5 years after anti-TNF initiation. Costs before and after anti-TNF initiation were compared, and multivariate linear regression analyses were performed to look for predictors of higher costs after anti-TNF initiation. Results A total of 928 people with IBD (676 CD, 252 UC) were included for analyses. The median cost of health care in the year before anti-TNF therapy was $4698 for CD vs $6364 for UC. The median cost rose to $39,749 and $49,327, respectively, in the year after anti-TNF initiation, and to $210,956 and $245,260 in the 5 years after initiation for continuous anti-TNF users. Inpatient and outpatient costs decreased in the year after anti-TNF initiation by 12% and 7%, respectively, when excluding the cost of anti-TNFs. Conclusions Direct health care expenditures markedly increase after anti-TNF initiation and continue to stay elevated over pre-initiation costs for up to 5 years, with only small reductions in the direct costs of non-drug-related health care.

Objective The adult INTERMED is used to determine case complexity and psychosocial needs. We developed and validated a pediatric version of the INTERMED for children and adolescents with inflammatory bowel disease (IBD) and assessed its utility in predicting healthcare utilization. Methods We performed a cross-sectional study of children (aged 8–17 y) with IBD (n = 148) and their parents, seen in a hospital-based clinic. Subjects completed semi-structured interviews that were scored on the 34 pIBD-INTERMED items. To assess inter-rater reliability, 40 interviews were videotaped and scored by a second assessor. Convergent and predictive validity were assessed by examining the relation of the pIBD-INTERMED to standardized measures of psychological, social, and family functioning, disease activity, and healthcare utilization. Results Correlational analyses supported the validity of all five pIBD-INTERMED domains with very good inter-rater reliability (median r = 0.87) and internal consistency (α = 0.91) for the total complexity index. Ratings of 2–3 on the pIBD-INTERMED “mental health/cognitive threat” item were associated with greater odds of behavior and social problems (CBCL-Internalizing scale OR = 7.27, 95% CI 2.17–24.36); CBCL-Externalizing scale OR = 24.79, 95% CI 5.00–122.84), depression (Children's Depression Inventory OR = 8.52, 95% CI 1.70–43.02) and anxiety (Multidimensional Anxiety for Children OR = 11.57, 95% CI 3.00–45.37). The pIBD-INTERMED complexity index added significantly to the prediction of healthcare utilization, beyond the contribution of disease severity. Conclusions The pIBD-INTERMED is a reliable and valid tool for identifying psychosocial risks and needs of children with IBD. It can be used to guide planning of individualized care and enhance interdisciplinary pediatric IBD care.

ObjectivePatients 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.DesignThis 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.ResultsAbout 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.ConclusionWomen 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.

Surgery for inflammatory bowel disease (IBD) is associated with an increased risk of venous thromboembolism (VTE) during hospitalization. It is unclear whether this association persists after hospital discharge.We assessed the association between surgery and VTE following hospital discharge in IBD.We conducted a population-based cohort study between 2002 and 2016 in Ontario, Canada. Adults with IBD hospitalized for ≥ 72 h who underwent an intra-abdominal surgery were compared to hospitalized, nonsurgical IBD patients. Multivariable Cox proportional hazard models were used to compare VTE risk within 12 months of discharge.A total of 80,445 hospital discharges were analyzed: 60% Crohn's disease (CD) and 40% ulcerative colitis (UC). The median time to VTE was three times longer for nonsurgical patients with CD and 1.6 times longer for nonsurgical patients with UC. Compared with nonsurgical patients, surgery for CD was associated with a lower cumulative risk of VTE in the 2 weeks after discharge and persisted through to 12 months after discharge (adjusted HR 0.24; 95% CI 0.15-0.40). In contrast, urgent surgery for UC was associated with an increased risk of VTE. The increased risk was greatest at 2 weeks after discharge (aHR, 1.80; 95% CI 1.26-2.57) and declined progressively over the course of 12 months.Surgery was associated with a greater risk of VTE after hospital discharge in UC but not CD. In patients with UC who have undergone urgent surgery, healthcare providers should consider an extended period of prophylaxis after hospital discharge.

Background Paediatric data on the association between diagnostic delay and inflammatory bowel disease [IBD] complications are lacking. We aimed to determine the effect of diagnostic delay on stricturing/fistulising complications, surgery, and growth impairment in a large paediatric cohort, and to identify predictors of diagnostic delay. Methods We conducted a national, prospective, multicentre IBD inception cohort study including 1399 children. Diagnostic delay was defined as time from symptom onset to diagnosis >75th percentile. Multivariable proportional hazards [PH] regression was used to examine the association between diagnostic delay and stricturing/fistulising complications and surgery, and multivariable linear regression to examine the association between diagnostic delay and growth. Predictors of diagnostic delay were identified using Cox PH regression. Results Overall (64% Crohn’s disease [CD]; 36% ulcerative colitis/IBD unclassified [UC/IBD-U]; 57% male]), median time to diagnosis was 4.2 (interquartile range [IQR] 2.0–9.2) months. For the overall cohort, diagnostic delay was >9.2 months; in CD, >10.8 months and in UC/IBD-U, >6.6 months. In CD, diagnostic delay was associated with a 2.5-fold higher rate of strictures/internal fistulae (hazard ratio [HR] 2.53, 95% confidence interval [CI] 1.41–4.56). Every additional month of diagnostic delay was associated with a decrease in height-for-age z-score of 0.013 standard deviations [95% CI 0.005–0.021]. Associations persisted after adjusting for disease location and therapy. No independent association was observed between diagnostic delay and surgery in CD or UC/IBD-U. Diagnostic delay was more common in CD, particularly small bowel CD. Abdominal pain, including isolated abdominal pain in CD, was associated with diagnostic delay. Conclusions Diagnostic delay represents a risk factor for stricturing/internal fistulising complications and growth impairment in paediatric CD. Podcast This article has an associated podcast which can be accessed at https://academic.oup.com/ecco-jcc/pages/podcast

Randomised controlled trials are increasingly conducted as embedded, nested, or using cohorts or routinely collected data, including registries, electronic health records, and administrative databases, to assess if participants are eligible for the trial and to facilitate recruitment, to deliver an embedded intervention, to collect trial outcome data, or a combination of these purposes. This report presents the Consolidated Standards of Reporting Trials (CONSORT) extension for randomised controlled trials conducted using cohorts and routinely collected data (CONSORT-ROUTINE). The extension was developed to look at the unique characteristics of trials conducted with these types of data with the goal of improving reporting quality in the long term by setting standards early in the process of uptake of these trial designs. The extension was developed with a sequential approach, including a Delphi survey, a consensus meeting, and piloting of the checklist. The checklist was informed by the CONSORT 2010 statement and two reporting guidelines for observational studies, the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement and the REporting of studies Conducted using Observational Routinely collected Data (RECORD) statement. The extension includes eight items modified from the CONSORT 2010 statement and five new items. Reporting items with explanations and examples are provided, including key aspects of trials conducted using cohorts or routinely collected data that require specific reporting considerations.

South Asian (SA) Canadian immigrants have a higher risk of developing certain immune-mediated inflammatory diseases compared to non-migrant SAs. We sought to investigate the effect of migration on the gut metagenome and to identify microbiological associations between migration and conditions that may influence the development of immune-mediated inflammatory diseases. Metagenomic analysis of 58 first-generation (GEN1) SA immigrants and 38 unrelated Canadian born children-of-immigrants (GEN2) determined that the time lived in Canada was associated with continued changes in gut microbial communities. Migration of GEN1 to Canada early in life results in a gut community with similarities to GEN2 SA Canadians and non-SA North Americans. Conversely, GEN1 immigrants who arrived recently to Canada exhibited pronounced differences from GEN2, while displaying microbial similarities to a non-migrating SA cohort. Multivariate analysis identified that community composition was primarily influenced by high abundance taxa. Prevotella copri dominated in GEN1 and non-migrant SAs. Clostridia and functionally related Bacteroidia spp. replaced P. copri dominance over generations in Canada. Mutually exclusive Dialister species occurred at differing relative abundances over time and generations in Canada. This shift in species composition is accompanied by a change in genes associated with carbohydrate utilization and short-chain fatty acid production. Total energy derived from carbohydrates compared to protein consumption was significantly higher for GEN1 recent immigrants, which may influence the functional requirements of the gut community. This study demonstrates the associations between migration and the gut microbiome, which may be further associated with the altered risk of immune-mediated inflammatory diseases observed for SA Canadians.

Background Pregnant women with inflammatory bowel disease (IBD) are at increased risk of developing complications from vaccine-preventable infections. We investigated the factors influencing vaccine administration in pregnant women with IBD and their infants, in addition to the safety of vaccination in the infants. Methods This retrospective cohort study identified individuals from a tertiary referral clinic whose records were linked to a provincial vaccine database. We conducted χ 2 tests, Fisher exact tests, and logistic regression adjusting for age and disease duration to compare vaccine administration by medication class. Potential rotavirus vaccine adverse events were determined in infants of women with IBD. Results We included 303 pregnant women and 262 infants. Vaccines were administered to women on biologic therapy as follows: hepatitis B virus (82.9%), diphtheria-tetanus-pertussis (82.1%), and hepatitis A virus (49.3%). The influenza vaccination was provided peripartum in 50.7% of patients. The measles-mumps-rubella-varicella vaccine was provided to 89.3% of women before biologic initiation. Women treated with a biologic (adjusted odds ratio, 2.50; 95% confidence interval, 1.39-4.35) or immunomodulator (adjusted odds ratio, 4.00; 95% confidence interval, 2.22-7.69) were more likely to receive the Prevnar 13 and Pneumovax 23 vaccines than were unexposed individuals, but the overall proportion vaccinated was low (Prevnar 13, 35.7%; Pneumovax 23, 39.3%). At least 90% of infants received the measles-mumps-rubella-varicella vaccine and inactivated vaccines. Fourteen biologic-exposed children (19.2%) received the live rotavirus vaccine with no significant differences in adverse events compared with biologic-unexposed infants (7.1% vs 8.2%, P = 0.99). Conclusions Better education surrounding vaccine recommendations is required for both health care providers and individuals with IBD given poor pneumococcal, hepatitis A virus, and influenza vaccination rates. Inadvertent administration of the rotavirus vaccine in biologic-exposed infants did not result in more adverse events, raising the possibility of safety.

OBJECTIVES:We sought to determine predictors of hospitalization for children presenting with croup to emergency departments (EDs), as well as predictors of repeat ED presentation and of hospital readmissions within 18 months of index admission. We also aimed to develop a practical tool to predict hospitalization risk upon ED presentation.METHODS:Multiple deterministically linked health administrative data sets from Ontario, Canada, were used to conduct this population-based cohort study between April 1, 2006 and March 31, 2017. Children born between April 1, 2006, and March 31, 2011, were eligible if they had 1 ED visit with a croup diagnosis. Multivariable logistic regression was used to determine factors associated with hospitalization, subsequent ED visits, and subsequent croup hospitalizations. A multivariable prediction tool and associated scoring system were created to predict hospitalization risk within 7 days of ED presentation.RESULTS:Overall, 1811 (3.3%) of the 54 981 eligible children who presented to an Ontario ED were hospitalized. Significant hospitalization predictors included age, sex, Canadian Triage and Acuity Scale score, gestational age at birth, and newborn distress. Younger patients and boys were more likely to revisit the ED for croup. Our multivariable prediction tool could forecast hospitalization up to a 32% probability for a given patient.CONCLUSIONS:This study is the first population-based study in which predictors of hospitalization for croup based on demographic and historical factors are identified. Our prediction tool emphasized the importance of symptom severity on ED presentation but will require refinement before clinical implementation.

Kawasaki disease (KD) is a childhood vasculitis with conflicting reported North American trends in incidence and patient characteristics.(1) determine KD incidence between 1995 and 2017; (2) compare patient characteristics by era and age group; (3) determine complication and cardiovascular follow-up rates.We used population-based health administrative data to identify children (0-18 yr) hospitalized with KD in Ontario, Canada between 1995 and 2017. We excluded children with prior KD diagnosis or incomplete records. We determined the annualized incidence and follow-up trends.KD was diagnosed in 4,346 children between 1995 and 2017. Annual KD incidence was 22.0 (5 yr), 6.1 (5-9 yr), and 0.6 (10-18 yr) per 100,000 children. KD incidence increased significantly for all age groups, including from 18.4 to 25.0 cases per 100,000 children5 yr. Ninety-day mortality occurred in ≤5 children (≤0.1%). Coronary artery aneurysm (CAA) occurred in 106 children (2.4%, 95% confidence interval 2.0-2.9) during admission and 151 (3.5%, 95% confidence interval 3.0-4.1) during 11-year median follow-up. Children 10-18 yr had longer hospitalizations (4.3 vs. 3.5 days, p = 0.003) and more CAA (7.4% vs. 3.4%, p = 0.007). By 1-year post-diagnosis, 3970 (91.3%) and 2576 (59.3%) children had echocardiography and cardiology follow-up, respectively.KD incidence is increasing in Ontario, with greater healthcare utilization from hospitalizations and subsequent follow-up.4346 children were hospitalized for Kawasaki disease over 22 years in Ontario, and Kawasaki disease incidence increased significantly for all age groups, males and females. Older children (10-18 years) had longer hospital length of stay, more PICU admissions and more frequent coronary artery aneurysms. Nearly all children with Kawasaki disease had follow-up echocardiography within 1 year.

Background There are currently no nationwide data on the epidemiology of inflammatory bowel diseases (IBD) in Israel. We aimed to determine the population-based epidemiological trends of IBD in the diverse Israeli population. Methods Health-administrative data were retrieved from all 4 Israeli health maintenance organizations, insuring 98% of the population, using validated identification algorithms. National trends were determined using Joinpoint regression analysis calculating annual percent change and average annual percent change (AAPC). Results By 2019, there were 46,074 patients with IBD in Israel, corresponding to a national prevalence of 519/100,000 (0.52%), of whom 54.1% had Crohn disease (CD) and 45.9% had ulcerative colitis (UC). The number of Jewish patients doubled from 18,701 in 2005 (354/100,000) to 38,950 (589/100,000) in 2018 (AAPC, +4.0%; P < 0.05), and the number of Arab patients increased 3-fold from 1096 (102.1/100,000) to 3534 (240.7/100,000; AAPC, +6.8%; P < 0.05) during the same years. However, the increase rate has gradually decelerated over time (annual percent change during 2005-2008, 2009-2014, and 2005-2018 was +6.7%, +4.2%, and +2.3%, respectively; P < 0.05). Pediatric prevalence increased from 37.4 to 52.2/100,000, with CD predominating in both Jews and Arabs. The incidence of CD remained stable (from 15.9/100,000 to 14.9/100,000) and the incidence of UC decreased (15.4/100,000 to 10.5/100,000 (AAPC, –3.2%; P < 0.001)). In contrast, pediatric incidence of CD increased from 7.3/100,000 to 8.3/100,000 (AAPC, +1.9%; P < 0.05) and that of UC increased from 2.6 to 4.4/100,000 (AAPC, +5.8%; P < 0.05). Conclusions The IBD prevalence rate in Israel is still increasing but gradually decelerating, probably due to the decreasing overall IBD incidence. Nonetheless, incidence rate in children is still increasing. Ongoing narrowing in the rates between Jews and Arabs over time may indicate shared environmental factors.

Background & AimsPatients with inflammatory bowel disease (IBD) may be at increased risk of some vaccine-preventable diseases. The effectiveness and safety of vaccinations may be altered by immunosuppressive therapies or IBD itself. These recommendations, developed by the Canadian Association of Gastroenterology and endorsed by the American Gastroenterological Association, aim to provide guidance on immunizations in patients with inflammatory bowel disease. This publication focused on live vaccines.MethodsSystematic reviews evaluating the efficacy, effectiveness, and safety of vaccines in patients with IBD, other immune-mediated inflammatory diseases, and the general population were performed. Critical outcomes included mortality, vaccine-preventable diseases, and serious adverse events. Immunogenicity was considered a surrogate outcome for vaccine efficacy. Certainty of evidence and strength of recommendations were rated according to the GRADE (Grading of Recommendation Assessment, Development, and Evaluation) approach. Key questions were developed through an iterative process and voted on by a multidisciplinary panel. Recommendations were formulated using the Evidence-to-Decision framework. Strong recommendation means that most patients should receive the recommended course of action, whereas a conditional recommendation means that different choices will be appropriate for different patients.ResultsThree good practice statements included reviewing a patient’s vaccination status at diagnosis and at regular intervals, giving appropriate vaccinations as soon as possible, and not delaying urgently needed immunosuppressive therapy to provide vaccinations. There are 4 recommendations on the use of live vaccines. Measles, mumps, rubella vaccine is recommended for both adult and pediatric patients with IBD not on immunosuppressive therapy, but not for those using immunosuppressive medications (conditional). Varicella vaccine is recommended for pediatric patients with IBD not on immunosuppressive therapy, but not for those using immunosuppressive medications (conditional). For adults, recommendations are conditionally in favor of varicella vaccine for those not on immunosuppressive therapy, and against for those on therapy. No recommendation was made regarding the use of live vaccines in infants born to mothers using biologics because the desirable and undesirable effects were closely balanced and the evidence was insufficient.ConclusionsMaintaining appropriate vaccination status in patients with IBD is critical to optimize patient outcomes. In general, live vaccines are recommended in patients not on immunosuppressive therapy, but not for those using immunosuppressive medications. Additional studies are needed to evaluate the safety and efficacy of live vaccines in patients on immunosuppressive therapy.

Introduction Corticosteroids are effective for inducing clinical remission in inflammatory bowel disease (IBD), but not for maintaining remission. Reducing corticosteroid use and dependence is an important treatment goal since their use is associated with adverse events. The extent to which the improvements in IBD therapy have led to less corticosteroid use in the modern era remains unclear. Methods We used the University of Manitoba Inflammatory Bowel Disease Epidemiologic Database to assess the cumulative annual dosing of corticosteroids on a per-patient basis for all persons with IBD in the province of Manitoba between 1997 and 2017. Joinpoint analysis was used to assess for trends in corticosteroid use and to look at variation in the trends over time. Results The mean annual exposure to corticosteroids decreased from 419 mg/yr (1997) to 169 mg/yr (2017) for Crohn's disease (CD) (annual decline: 3.8% per year, 95% confidence interval 3.1-4.6) and from 380 to 240 mg/yr in ulcerative colitis (UC) (annual decline: 2.5% per year, 95% confidence interval 2.1-2.8). In CD, there was an acceleration in the rate of decline after 2007 (pre-2007, 1.9% decline per year; after 2007, 5.7% per year); there was no corresponding acceleration in the rate of decline in UC. Discussion Corticosteroid use has decreased in both CD and UC over the past 2 decades, becoming more pronounced after 2007 in CD. Potential explanations include introduction and increasing penetrance of biologic therapy in CD and greater awareness of corticosteroid-related adverse events in IBD. Further work is required understand the drivers of persistent corticosteroid use in IBD and how this can be further reduced.

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.

BACKGROUND: The requirement for a tracheostomy in children is associated with significant morbidity, mortality, and healthcare utilization. Easy identification of children with tracheostomies would facilitate important research on this population and provide quality improvement initiatives. AIM: The purpose of this study is to determine whether an algorithm of diagnostic and procedural codes can accurately identify children hospitalized with a tracheostomy using routinely collected health data. METHODS: Chart reviews were performed at the Children's Hospital of Eastern Ontario (CHEO) and the London Health Sciences Center (LHSC) to establish a true positive cohort of pediatric patients with tracheostomies admitted between 2008 and 2016. A multidisciplinary team developed algorithms of diagnostic and procedural codes contained within the Canadian Institute for Health Information Discharge Abstract Database. Algorithms were tested and refined against the true-positive and true-negative cohort. The accuracy of the diagnostic codes related to tracheostomy complications was also evaluated. RESULTS: A chart review identified 158 unique children with tracheostomies (77 at CHEO, 81 at LHSC) with 901 individual admissions (401 at CHEO, 507 at LHSC). The best algorithms for identifying children with a tracheostomy had a sensitivity and specificity of more than 99%, a positive predictive value (PPV) of 94.0% and negative predictive value (NPV) of 100%. The algorithm for the identification of tracheostomy-related complications had a sensitivity of 76.7%, a specificity of 65%, PPV of 52.3%, and an NPV of 84.7%. CONCLUSIONS: This study provides an algorithm for the accurate identification of children hospitalized in Canada with a tracheostomy, facilitating population-level epidemiological research and quality improvement initiatives.

Background The incidence of very early onset inflammatory bowel disease (VEOIBD) is increasing, yet the phenotype and natural history of VEOIBD are not well described. Methods We performed a retrospective cohort study of patients diagnosed with VEOIBD (6 years of age and younger) between 2008 and 2013 at 25 North American centers. Eligible patients at each center were randomly selected for chart review. We abstracted data at diagnosis and at 1, 3, and 5 years after diagnosis. We compared the clinical features and outcomes with VEOIBD diagnosed younger than 3 years of age with children diagnosed with VEOIBD at age 3 to 6 years. Results The study population included 269 children (105 [39%] Crohn’s disease, 106 [39%] ulcerative colitis, and 58 [22%] IBD unclassified). The median age of diagnosis was 4.2 years (interquartile range 2.9–5.2). Most (94%) Crohn’s disease patients had inflammatory disease behavior (B1). Isolated colitis (L2) was the most common disease location (70% of children diagnosed younger than 3 years vs 43% of children diagnosed 3 years and older; P = 0.10). By the end of follow-up, stricturing/penetrating occurred in 7 (6.6%) children. The risk of any bowel surgery in Crohn’s disease was 3% by 1 year, 12% by 3 years, and 15% by 5 years and did not differ by age at diagnosis. Most ulcerative colitis patients had pancolitis (57% of children diagnosed younger than 3 years vs 45% of children diagnosed 3 years and older; P = 0.18). The risk of colectomy in ulcerative colitis/IBD unclassified was 0% by 1 year, 3% by 3 years, and 14% by 5 years and did not differ by age of diagnosis. Conclusions Very early onset inflammatory bowel disease has a distinct phenotype with predominantly colonic involvement and infrequent stricturing/penetrating disease. The cumulative risk of bowel surgery in children with VEOIBD was approximately 14%–15% by 5 years. These data can be used to provide anticipatory guidance in this emerging patient population.

Background Respiratory syncytial virus (RSV) infection is a major cause of hospitalization in young children in Canada, despite routine immunoprophylaxis in those with medical risk factors. We aimed to determine if cold temperatures are associated with RSV hospitalization. Methods We conducted a population-based nested case–control study of children in Ontario, Canada, using health administrative data. We compared children hospitalized for RSV between September 1, 2011 and August 31, 2012 to age and sex matched controls. We used multivariable logistic regression to identify associations between minimum daily temperature and RSV hospitalizations with adjustment for sociodemographic and environmental factors. Results We identified 1670 children with RSV hospitalizations during the study period and 6680 matched controls. Warmer temperatures (OR = 0.94, 95%CI: 0.93, 0.95) were associated with lower odds of RSV hospitalization. Southern ecozone (OR = 1.6, 95%CI: 1.2, 2.1), increased ozone concentration (OR = 1.03, 95%CI: 1.01, 1.06) and living in a lower income neighbourhood (OR = 1.3, 95%CI: 1.1, 1.5) significantly increased the odds of RSV hospitalization, as did living in a household with a larger number of siblings in a sub-cohort of children (OR = 1.34, 95%CI: 1.26, 1.41). Conclusions In Ontario, the likelihood of having an RSV hospitalization is associated with colder temperature exposures and socioeconomic factors.

Background: 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. Objectives: The objective of this study was to evaluate the associations between maternal and early-life exposures to nitrogen dioxide (NO2), fine particulate matter (PM2.5), ozone (O3,) and oxidant capacity (Ox) and risk of pediatric-onset IBD diagnosis. Methods: 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

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

To appraise the reporting quality of studies which concerned linezolid-related thrombocytopenia referring to REporting of studies Conducted using Observational Routinely collected health Data (RECORD) statement.Medline, Embase, Cochrane library and clinicaltrial.gov were searched for observational studies concerning linezolid-related thrombocytopenia using routinely collected health data from 2000 to 2017. Two reviewers screened potential eligible articles and extracted data independently. Finally, reporting quality assessment was performed by two senior researchers using RECORD statement.Of 25 included studies, 11 (44.0%) mentioned the type of data in the title and/or abstract. In 38 items derived from RECORD statement, the median number of items reported in the included studies was 22 (inter-quartile range 18-27). Inadequate reporting issues were discovered in the following aspects: validation studies of the codes or algorithms, study size estimation, quantitative variables, subgroup statistical methods, missing data, follow-up/matching or sampling strategy, sensitivity analysis and cleaning methods, funding and role of funders and accessibility of protocol, raw data.This study provides the evidence that the reporting quality of post-marketing safety evaluation studies conducted using routinely collected health data was often insufficient. Future stakeholders are encouraged to endorse the RECORD guidelines in pharmacovigilance.

The incidence and prevalence of childhood-onset inflammatory bowel diseases (IBD), including subtypes Crohn's disease and ulcerative colitis, have risen dramatically in recent years, and have emerged globally as important pediatric chronic diseases. Therefore, health care providers are more frequently encountering very young children with IBD, a chronic and incurable condition requiring life-long therapy. These children are living long lives with IBD and therefore knowledge of long-term outcomes is increasingly important to better counsel families and determine the best course of treatment. This review summarizes the current knowledge and literature surrounding long-term outcomes of pediatric IBD, with emphasis on the following areas: need for surgery due to complicated disease behavior, risk of disease remission and recurrence, mental health and psychosocial well-being, educational outcomes, linear growth impairment, cancer risk, and mortality. In addition, we review recent research about predicting negative long-term outcomes in children with IBD.

Importance Seasonal influenza vaccination in pregnancy can reduce influenza illness among pregnant women and newborns. Evidence is limited on whether seasonal influenza vaccination in pregnancy is associated with adverse childhood health outcomes. Objective To assess the association between maternal influenza vaccination during pregnancy and early childhood health outcomes. Design, Setting, and Participants Retrospective cohort study, using a birth registry linked with health administrative data. All live births in Nova Scotia, Canada, between October 1, 2010, and March 31, 2014, were included, with follow-up until March 31, 2016. Adjusted hazard ratios (HRs) and incidence rate ratios (IRRs) with 95% confidence intervals were estimated while controlling for maternal medical history and other potential confounders using inverse probability of treatment weighting. Exposures Seasonal influenza vaccination during pregnancy. Main Outcomes and Measures Childhood outcomes studied were immune-related (eg, asthma, infections), non–immune-related (eg, neoplasms, sensory impairment), and nonspecific (eg, urgent or inpatient health care utilization), measured from emergency department and hospitalization databases. Results Among 28 255 children (49% female, 92% born at ≥37 weeks’ gestation), 10 227 (36.2%) were born to women who received seasonal influenza vaccination during pregnancy. During a mean follow-up of 3.6 years, there was no significant association between maternal influenza vaccination and childhood asthma (incidence rate, 3.0 vs 2.5 per 1000 person-years; difference, 0.53 per 1000 person-years [95% CI, −0.15 to 1.21]; adjusted HR, 1.22 [95% CI, 0.94 to 1.59]), neoplasms (0.32 vs 0.26 per 1000 person-years; difference, 0.06 per 1000 person-years [95% CI, −0.16 to 0.28]; adjusted HR, 1.26 [95% CI, 0.57 to 2.78]), or sensory impairment (0.80 vs 0.97 per 1000 person-years; difference, −0.17 per 1000 person-years [95% CI, −0.54 to 0.21]; adjusted HR, 0.82 [95% CI, 0.49 to 1.37]). Maternal influenza vaccination in pregnancy was not significantly associated with infections in early childhood (incidence rate, 184.6 vs 179.1 per 1000 person-years; difference, 5.44 per 1000 person-years [95% CI, 0.01 to 10.9]; adjusted IRR, 1.07 [95% CI, 0.99 to 1.15]) or with urgent and inpatient health services utilization (511.7 vs 477.8 per 1000 person-years; difference, 33.9 per 1000 person-years [95% CI, 24.9 to 42.9]; adjusted IRR, 1.05 [95% CI, 0.99 to 1.16]). Conclusions and Relevance In this population-based cohort study with mean follow-up duration of 3.6 years, maternal influenza vaccination during pregnancy was not significantly associated with an increased risk of adverse early childhood health outcomes.

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.

Background Patients diagnosed with inflammatory bowel disease (IBD) during childhood require transfer to an adult gastroenterologist, in Ontario usually just before their 18th birthday. Pediatric onset IBD is a complex phenotype with demonstrated noncompliance risk that may require targeted measures to optimize health care outcomes in the adult care setting. Purpose The purpose of this study was to determine the impact of posttransfer health care setting (academic versus community gastroenterologist) on emergent health resource utilization. Methods This was a population-based retrospective cohort study using health care administrative data from Ontario, Canada. A cohort of patients with Pediatric onset IBD was identified and health resource utilization during a 2-year pretransfer period, transfer of care period and 2-year posttransfer period was analyzed. Posttransfer health care setting was defined as academic (i.e., gastroenterologists providing care in a university affiliated tertiary care center) versus community. A third comparator group, loss to follow-up, was also identified. The primary outcome of this study comprised emergency department utilization. Secondary outcomes included hospitalizations, surgeries, ambulatory visits, endoscopic investigations, and radiological investigations. Results Overall, there were no significant differences found in emergency department use, ambulatory care visits (aside from the expected drop in the lost to follow-up group), hospitalizations, endoscopic procedures, or radiological procedures between exposure groups. Conclusions Posttransfer health care setting does not seem to significantly impact emergent health resource utilization in the posttransfer period.

Objectives: The incidence of pediatric-onset inflammatory bowel disease (IBD) is increasing worldwide. We used population-based health administrative data to determine national Canadian IBD incidence, prevalence, and trends over time of childhood-onset IBD. Methods: We identified children

Background: Intussusception has been identified as a rare adverse event following rotavirus immunization. We sought to determine the incidence of intussusception among infants in Canada both before and after introduction of rotavirus immunization programs. Methods: We used Canadian Institute for Health Information (CIHI) Discharge Abstract Database (DAD) to identify infants under 1 y of age who were admitted to a Canadian hospital, which the exception of Quebec, which does not submit data to CIHI, with a diagnosis of intussusception (ICD-10 code K56.1, and ICD-9 code 560) between January 1st, 2003 and December 31, 2013. We compared rates of intussusception hospitalization before and after rotavirus vaccine program introduction. Rates were adjusted for calendar year, age (in months), sex and region using Poisson regression models. Denominator data for infants under 1 year, stratified by age in months, were obtained from Statistics Canada. Results: Annual intussusception hospitalization rates ranged from 20-30 per 100,000 infants over the study period, with no evidence of a trend over time. Intussusception hospitalization rates were highest in infants 4 to