Early life exposures and risk of inflammatory bowel disease: A nested case-control study in Quebec, Canada.

BACKGROUND: Early life factors for inflammatory bowel disease are likely to impact the gut microbiota. AIM: We investigated the associations between early exposures and inflammatory bowel disease. METHODS: This case-control study was nested within the CO·MMUNITY cohort. Cases of Crohn's disease (CD) and ulcerative colitis (UC) were identified using validated algorithms. All cases and randomly selected controls were invited to complete a questionnaire including early life exposures. Analyses were conducted by logistic regression and causal mediation (direct/indirect effects for passive/active smoking). RESULTS: Early introduction of solid foods at 3-6 months tended to increase CD risk compared to later introduction (>6 months): OR = 1.23; 95 % CI: 0.96-1.56, but not of UC. Exclusive breastfeeding tended to decrease the risk of CD (OR = 0.77; 95 % CI: 0.55-1.08), less so for UC. Antibiotics tended to decrease CD (OR = 0.89; 95 % CI: 0.74-1.07) and UC (OR = 0.88; 95 % CI: 0.71-1.09). No association was found between pets and CD or UC. Passive smoking increased CD risk (OR = 1.23; 95 % CI: 1.00-1.51), 20 % of which was mediated by active smoking, but not UC. CONCLUSION: Differences were noticed in early risk factors for CD and UC. The impact of passive smoking was largely independent of active smoking, highlighting its importance for prevention.

Association between Bacillus Calmette-Guérin (BCG) vaccination and inflammatory bowel disease: A two-stage sampling design within the Quebec Birth Cohort on Immunity and Health (CO·MMUNITY).

BACKGROUND: Bacillus Calmette-Guérin (BCG) vaccination, primarily administered to prevent tuberculosis, exhibits nonspecific immune effects and could play a role in inflammatory bowel disease prevention. We investigated the associations of BCG with Crohn's disease and ulcerative colitis, and assessed sex-differences. METHODS: This two-stage study included 365,206 Canadians from the Quebec Birth Cohort on Immunity and Health (1970-2014; stage 1). Vaccination status was registry-based and inflammatory bowel disease cases were identified from health services with validated algorithms. We documented additional factors among 2644 participants in a nested case-control study in 2021 (stage 2). A two-stage logistic regression analysis was applied to estimate the odds ratios (OR), corrected for sampling fractions and adjusted for confounding factors. We used interaction terms to assess sex-differences on the multiplicative scale. RESULTS: In the stage 1 sample, 2419 cases of Crohn's disease and 1079 of ulcerative colitis were included. Forty-six percent of non-cases received the BCG vaccine as compared to 47% for Crohn's disease and 49% for ulcerative colitis. Associations differed by sex. BCG vaccination was not associated with Crohn's disease among men (OR = 0.91; 95% CI: 0.79-1.04) but was related to an increased risk among women (OR = 1.13; 95% CI: 1.00-1.28, P interaction: 0.001). For ulcerative colitis, there was a tendency toward a slightly elevated risk among men (OR = 1.09; 95%CI: 0.90-1.32), whereas the risk was more substantial for women (OR = 1.17; 95% CI:0.99-1.39, P interaction: <0.001). CONCLUSION: BCG vaccination does not play a preventive role in inflammatory bowel disease. Our results point to distinct associations between men and women.

Outcomes of Premature Infants With Type C Esophageal Atresia.

BACKGROUND: To review the outcomes of premature patients with type C esophageal atresia (EA). METHODS: In this retrospective cohort study, charts of patients of type C EA patients were reviewed from 1992 to 2022. Outcomes of premature patients were compared to term patients. Preterm patients were analyzed to compare outcomes of infants with very low birth weights (VLBW) to patients >1,500 g as well as primary versus delayed anastomosis. RESULTS: Among 192 type C EA, 67 were premature. Median and interquartile range (IQR) gestational age and birth weight of preterm patients were 34 [33-36] weeks and 1965 [1740-2290] g. Delayed anastomosis was performed in 12 (18%) preterm vs. 3 (2%) term patients (p = 0.0003). Short-term postoperative outcomes were similar between preterm and term patients, except for recurrent fistula (16% vs. 6%, p = 0.01). Prematurity was associated with an increased need for long-term enteral tube feeding (56% vs. 10%, p = 0.0001) and parenteral nutrition (10 days vs. 0 days, p = 0.0004). The length of stay was 3 times longer when patients were premature (50 days vs. 17 days, p = 0.002). Delayed surgery in preterm patients was associated with post-operative leaks, strictures, recurrent fistula, prolonged enteral tube feeding, and gastrostomy insertion. Patients with very low birth weight (VLBW) were compared to other preterm patients and showed no difference in terms of rate of delayed surgery, and post-operative outcomes. CONCLUSION: Despite increased prematurity-related comorbidities and low birth weight, premature infants with type C EA/TEF have similar post-operative outcomes to term patients though recurrent fistula was more frequent with prematurity. TYPE OF STUDY: Retrospective cohort study. LEVEL OF EVIDENCE: III.

Effects of polyphenol supplementation on hepatic steatosis, intima-media thickness and non-invasive vascular elastography in obese adolescents: a pilot study protocol.

INTRODUCTION: Non-alcoholic fatty liver disease (NAFLD) is increasingly prevalent in obese adolescents. Increased systemic inflammation and decreased gut microbial diversity linked to obesity affect the liver and are also associated with cardiovascular diseases in adulthood. However, NAFLD and vascular alterations are reversible. METHODS AND ANALYSIS: This pilot study evaluated the feasibility of a prospective open-label randomised controlled trial evaluating the effects of polyphenols on NAFLD and vascular parameters in obese adolescents. Children aged 12-18 years with hepatic steatosis (n=60) will be recruited. The participants will be randomised with a 1:1 allocation ratio to receive polyphenol supplementation one time per day for 8 weeks along with the clinician-prescribed treatment (group B, n=30) or to continue the prescribed treatment without taking any polyphenols (group A, n=30). The outcome measures will be collected from both the groups at day 1 before starting polyphenol supplementation, at day 60 after 8 weeks of supplementation and at day 120, that is, 60 days after supplementation. The changes in hepatic steatosis and vascular parameters will be measured using liver and vascular imaging. Furthermore, anthropometric measures, blood tests and stool samples for gut microbiome analysis will be collected. After evaluating the study's feasibility, we hypothesise that, as a secondary outcome, compared with group A, the adolescents in group B will have improved NAFLD, vascular parameters, systemic inflammation and gut microbiome. ETHICS AND DISSEMINATION: This study is approved by Health Canada and the hospital ethics. Participants and their parents/tutors will both provide consent. Trial results will be communicated to the collaborating gastroenterologists who follow the enrolled participants. Abstracts and scientific articles will be submitted to high-impact radiological societies and journals. CLINICALTRIALS: gov ID: NCT03994029. Health Canada authorisation referral number: 250 811. Protocole version 13, 2 June 2023. TRIAL REGISTRATION NUMBER: NCT03994029.

ADALIMUMAB VERSUS INFLIXIMAB IN LUMINAL PEDIATRIC CROHN'S DISEASE: COMPARABLE OUTCOMES IN A PROSPECTIVE MULTICENTER COHORT STUDY.

BACKGROUND: This study compared real-world effectiveness between adalimumab (ADA) and infliximab (IFX) in children with Crohn's disease (CD). METHODS: Children enrolled into the prospective Canadian Children Inflammatory Bowel Disease Network (CIDsCaNN) National Inception Cohort between 2014 and 2020 who commenced ADA or IFX as first anti-tumor necrosis factor (antiTNF) agent for luminal CD were included. Multivariate logistic regression modelled the propensity of commencing ADA; propensity score matching was used to match IFX-treated children to ADA-treated children. The primary outcome at one year was steroid-free clinical remission (SFCR). Secondary outcomes at one year were I) combined SFCR and c-reactive protein (CRP) remission; II) treatment intensification; and III) antiTNF durability. Odds ratios (aOR) and hazard ratio (aHR) adjusted for concomitant immunomodulator use with 95% confidence interval (CI) are reported. RESULTS: In the propensity score matched cohort of 147 ADA-treated and 147 IFX-treated children, 92 (63%) ADA- and 87 (59%) IFX-treated children achieved SFCR at one year (aOR: 1.4, 95% CI 0.9-2.4); 75 of 140 (54%) ADA- and 85 of 144 (59%) IFX-treated children achieved combined SFCR and CRP remission (aOR: 1.0, 95% CI 0.6-1.6). ADA-treated children less frequently underwent treatment intensification (21 [14%]) compared to IFX-treated children (69 [47%]) (P<0.0001). Discontinuation of antiTNF occurred in 18 (12%) ADA-treated and 15 (10%) IFX-treated children (aHR: 1.2, 95% CI 0.6-2.2). CONCLUSION: Children with Crohn's disease achieved favourable outcomes at one year with either ADA or IFX as first antiTNF agents. Those receiving IFX did not have significantly superior outcomes compared to clinically similar children receiving ADA.

Phenotype and outcomes of very early onset and early onset inflammatory bowel diseases in a Montreal pediatric cohort.

Objectives: The incidence of very-early-onset inflammatory bowel disease (VEO-IBD) and early-onset IBD (EO-IBD) is increasing. Here, we report their phenotype and outcomes in a Montreal pediatric cohort. Methods: We analyzed data from patients diagnosed with IBD between January 2014 and December 2018 from the CHU Sainte-Justine. The primary endpoint was to compare the phenotypes of VEO-IBD and EO-IBD. The secondary endpoints involved comparing outcomes and rates of steroid-free clinical remission (SFCR) at 12 (±2) months (m) post-diagnosis and at last follow-up. Results: 28 (14 males) and 67 (34 males) patients were diagnosed with VEO-IBD and EO-IBD, respectively. Crohn's disease (CD) was more prevalent in EO-IBD (64.2% vs. 39.3%), whereas unclassified colitis (IBD-U) was diagnosed in 28.6% of VEO-IBD vs. 10.4% of EO-IBD (p < 0.03). Ulcerative colitis (UC) and IBD-U predominantly presented as pancolitis in both groups (VEO-IBD: 76.5% vs. EO-IBD: 70.8%). Combining all disease subtypes, histological upper GI lesions were found in 57.2% of VEO-IBD vs. 83.6% of EO-IBD (p < 0.009). In each subtype, no differential histological signature (activity, eosinophils, apoptotic bodies, granulomas) was observed between both groups. At 12 m post-diagnosis, 60.8% of VEO-IBD and 62.7% of EO-IBD patients were in SFCR. At a median follow-up of 56 m, SFCR was observed in 85.7% of VEO-IBD vs. 85.0% of EO-IBD patients. Conclusion: The rate of patients in SFCR at 1-year post-diagnosis and at the end of follow-up did not significantly differ between both groups.

Inflammatory Bowel Disease Among Canadian Children: Comparison Between Children of Non-European Descent and Children of European Descent.

BACKGROUND: Inflammatory bowel disease (IBD) phenotypes may differ between countries and ancestral groups. The study aim was to examine ancestry and subtype variations of children newly diagnosed with IBD. METHODS: Children newly diagnosed with IBD enrolled into the Canadian Children Inflammatory Bowel Disease Network inception cohort study were categorized into 8 ancestral groups. Prospectively collected data at diagnosis and follow-up were compared between ancestral groups. RESULTS: Among 1447 children (63.2% Crohn's disease, 30.7% ulcerative colitis), 67.8% were European, 9.4% were South Asian, 3.8% were West Central Asian and Middle Eastern, 2.3% were African, 2.2% were East/South East Asian, 2.0% were Caribbean/Latin/Central/South American, 9.9% were mixed, and 2.6% were other. Children of African descent with ulcerative colitis had an older age of diagnosis compared with children of European descent (median 15.6 years vs 13.3 years; P = .02). Children of European descent had a higher proportion of positive family history with IBD (19.3% vs 12.1%; P = .001) compared with children of non-European descent. Children of European descent also had a lower proportion of immigrants and children of immigrants compared with children of non-European descent (9.8% vs 35.9%; P < .0001; and 3.6% vs 27.2%; P < .0001, respectively) . CONCLUSIONS: Important differences exist between different ancestral groups in pediatric patients with IBD with regard to age of diagnosis, family history, and immigrant status. Our study adds to the knowledge of the impact of ancestry on IBD pathogenesis.

This study explores the ancestral and phenotypic variation of Canadian children newly diagnosed with inflammatory bowel disease. It identifies differences between children of European and non-European descent in phenotypes of inflammatory bowel disease, disease location and behavior, family history, and immigrant status.

Epstein-Barr virus seroprevalence and viral load at disease onset in children with inflammatory bowel disease.

Background and Aim: Patients with inflammatory bowel disease (IBD) are at increased risk for life-threatening complications of Epstein-Barr virus (EBV), including lymphoproliferative diseases. These complications are likely related to inherent immune dysfunction and immunomodulating therapies often used. We aimed to determine the seroprevalence of EBV at diagnosis in our population, its impact on disease at onset, and the risk of active EBV infection. Methods: We included patients newly diagnosed with IBD for whom an EBV serology was performed over a 2-year period. Demographic information and data on disease characteristics were collected retrospectively. Stored serum from the time of diagnosis was retrieved when available for the patients with positive EBV serology, and quantitative polymerase chain reaction testing was performed to assess the pre-treatment viral load of EBV. Results: One hundred twenty patients were included in the study. Fifty-three patients (44.2%) had positive EBV serology at diagnosis. Stratified by age group, the prevalence of seropositive patients was for 0 to <10 years 35%, 10 to <17 years 46%, and ≥17 years 50%. Overall, therapies started within 6 months of diagnosis were similar in both the seropositive and seronegative groups. Within the seropositive group, 66% received systemic corticosteroids, 32.1% infliximab, 5.7% adalimumab, and 5.7% azathioprine. Conclusion: EBV seroprevalence is high in pediatric patients with IBD. EBV seropositivity did not seem to influence the severity of disease at onset or initial choice of therapy.

Appendectomy and risk for inflammatory bowel disease: effect of age and time post appendectomy - a cohort study.

BACKGROUND AND OBJECTIVE: Appendectomy may modulate the risk of inflammatory bowel disease through an effect on the gut microbiota. This study investigated the associations between appendectomy and incidence of Crohn's disease (CD) or ulcerative colitis (UC), with an emphasis on the influence of age and time post appendectomy. METHODS: This cohort study included 400 520 subjects born in Québec in 1970-1974 and followed until 2014. Administrative health data were used to ascertain appendectomy and cases of CD and UC. Cox proportional hazards models with time-dependent variables (appendectomy and time elapsed post appendectomy) allowed for the estimation of HRs and 95% CIs. RESULTS: A total of 2545 (0.6%) CD cases and 1134 (0.3%) UC cases were identified during follow-up. Appendectomy increased the risk of CD (HR=2.02; 95% CI: 1.66 to 2.44), especially when performed at 18-29 years of age. The risk of CD was increased in the first 2 years, and decreased significantly after ≥15 years post appendectomy. Appendectomy appeared to protect against UC (HR=0.39; 95% CI: 0.22 to 0.71). The risk of UC was not associated with age at appendectomy, but decreased with time elapsed post appendectomy (HR=0.21; 95% CI: 0.06 to 0.72, comparing ≥5 with 0-4 years after appendectomy). CONCLUSIONS: The increased risk of CD related to appendectomy in young adults may result from detection bias, but physicians should have a low threshold for suspicion of CD in young symptomatic adults with a history of appendectomy. A strong protective effect of appendectomy against UC was observed after 5 years.

Canadian Consensus Statements on the Transition of Adolescents and Young Adults with Inflammatory Bowel Disease from Pediatric to Adult Care: A Collaborative Initiative Between the Canadian IBD Transition Network and Crohn's and Colitis Canada.

Objectives: With the increased prevalence of childhood-onset inflammatory bowel disease (IBD), there is a greater need for a planned transition process for adolescents and young adults (AYA). The Canadian IBD Transition Network and Crohn's and Colitis Canada joined in collaborative efforts to describe a set of care consensus statements to provide a framework for transitioning AYA from pediatric to adult care. Methods: Consensus statements were drafted after focus group meetings and literature reviews. An expert panel consisting of 20 IBD physicians, nurses, surgeon, adolescent medicine physician, as well as patient and caregiver representatives met, discussed and systematically voted. The consensus was reached when greater than 75% of members voted in agreement. When greater than 75% of members rated strong support, the statement was rendered a strong recommendation, suggesting that a clinician should implement the statement for all or most of their clinical practice. Results: The Canadian expert panel generated 15 consensus statements (9 strong and 6 weak recommendations). Areas of focus of the statements included: transition program implementation, key stakeholders, areas of potential need and gaps in the research. Conclusions: These consensus statements provide a framework for the transition process. The quality of evidence for these statements was generally low, highlighting the need for further controlled studies to investigate and better define effective strategies for transition in pediatric to adult IBD care.

Meat Intake Is Associated with a Higher Risk of Ulcerative Colitis in a Large European Prospective Cohort Studyø.

BACKGROUND AND AIMS: We aimed to investigate the association between protein intake and risk of inflammatory bowel disease [IBD] in the European Prospective Investigation into Cancer and Nutrition. METHODS: A total of 413 593 participants from eight European countries were included. Dietary data were collected at baseline from validated food frequency questionnaires. Dietary data were calibrated to correct errors in measures related to each country-specific questionnaire. Associations between proteins [total, animal, and vegetable] or food sources of animal proteins, and IBD risk were estimated by Cox proportional hazard models. RESULTS: After a mean follow-up of 16 years, 177 patients with Crohn's disease [CD] and 418 with ulcerative colitis [UC], were identified. There was no association between total protein, animal protein, or vegetable protein intakes and CD or UC risks. Total meat and red meat intakes were associated with UC risk (hazard ratio [HR] for the 4th vs 1st quartile = 1.40, 95% confidence interval [CI] = 0.99-1.98, p-trend = 0.01; and 1.61, 95% CI = 1.10-2.36, p-trend = 0.007, respectively]. There was no association between other food sources of animal protein [processed meat, fish, shellfish, eggs, poultry] and UC. We found no association between food sources of animal proteins and CD risk. CONCLUSIONS: Meat and red meat consumptions are associated with higher risks of UC. These results support dietary counselling of low meat intake in people at high-risk of IBD.

A qualitative study of adolescents and young adults' experience and perceived needs during the first wave of the COVID-19 pandemic.

AIMS: COVID-19 has led to unprecedented public health measures such as school and university closures across the world. While initial surveys show an increase in anxiety, we have little information on the subjective experience of adolescents and young adults (AYAs). The aims of this study were to understand the lived experience and needs of AYAs related to home confinement and preventive measures due to COVID-19. DEMOGRAPHICS AND SETTINGS: A total of 25 AYAs (13-24 years old) with diverse gender, age, or health conditions, living in Québec (Canada), were interviewed in May 2020, during the COVID-19 home confinement period. METHODOLOGY: Four virtual focus groups were held via a virtual video-conferencing platform (Zoom©). Thematic analysis was conducted. RESULTS: Thematic analysis revealed five main themes: (1) challenges and opportunities related to the experience of home confinement; (2) variable risk perception of COVID-19 infection; (3) development of coping strategies to maintain well-being; (4) need for information and accompaniment; (5) apprehensions related to perceptions of the future. CONCLUSION: AYAs did not feel considered in public health decisions, fostering an increase in anxiety, especially in more vulnerable AYAs living with chronic diseases.

Benchmark of Data Processing Methods and Machine Learning Models for Gut Microbiome-Based Diagnosis of Inflammatory Bowel Disease.

Patients with inflammatory bowel disease (IBD) wait months and undergo numerous invasive procedures between the initial appearance of symptoms and receiving a diagnosis. In order to reduce time until diagnosis and improve patient wellbeing, machine learning algorithms capable of diagnosing IBD from the gut microbiome's composition are currently being explored. To date, these models have had limited clinical application due to decreased performance when applied to a new cohort of patient samples. Various methods have been developed to analyze microbiome data which may improve the generalizability of machine learning IBD diagnostic tests. With an abundance of methods, there is a need to benchmark the performance and generalizability of various machine learning pipelines (from data processing to training a machine learning model) for microbiome-based IBD diagnostic tools. We collected fifteen 16S rRNA microbiome datasets (7,707 samples) from North America to benchmark combinations of gut microbiome features, data normalization and transformation methods, batch effect correction methods, and machine learning models. Pipeline generalizability to new cohorts of patients was evaluated with two binary classification metrics following leave-one-dataset-out cross (LODO) validation, where all samples from one study were left out of the training set and tested upon. We demonstrate that taxonomic features processed with a compositional transformation method and batch effect correction with the naive zero-centering method attain the best classification performance. In addition, machine learning models that identify non-linear decision boundaries between labels are more generalizable than those that are linearly constrained. Lastly, we illustrate the importance of generating a curated training dataset to ensure similar performance across patient demographics. These findings will help improve the generalizability of machine learning models as we move towards non-invasive diagnostic and disease management tools for patients with IBD.

Risk Factors of Clinical Relapses in Pediatric Luminal Crohn's Disease: A Retrospective Cohort Study.

INTRODUCTION: There is currently little knowledge on factors associated with the relapse of Crohn's disease (CD) in children. The aims of this study were to describe the risk factors associated with relapse in pediatric CD and the changes in the relapse rate over the past decade. METHODS: Patients younger than 18 years and diagnosed between 2009 and 2019 were included in this retrospective cohort study. Clinical, endoscopic, histological, and laboratory data, as well as induction and maintenance treatments, were collected from the medical records. Survival analyses and Cox regression models were used to assess the impact of these risk factors on relapse. RESULTS: Six hundred thirty-nine patients were included. There was a decrease in the clinical relapse rate over the past decade: 70.9% of the patients diagnosed between 2009 and 2014 relapsed as compared with 49.1% of the patients diagnosed between 2015 and 2019 (P < 0.0001). The following variables were associated with clinical relapse: female sex (adjusted hazard ratio [aHR] = 1.52, P = 0.0007), exposure to oral 5-ASA (aHR = 1.44, P = 0.04), use of immunomodulatory agents compared with tumor necrosis factor-alpha inhibitors (methotrexate aHR = 1.73, P = 0.003; thiopurines aHR = 1.63, P = 0.002), presence of granulomas (aHR = 1.34, P = 0.02) and increased eosinophils on intestinal biopsies (aHR = 1.36, P = 0.02), high levels of C-reactive protein (aHR = 1.01, P < 0.0001) and fecal calprotectin (aHR = 1.08, P < 0.0001), and low serum infliximab levels (aHR = 2.32, P = 0.001). DISCUSSION: Relapse of pediatric CD has decreased in the past decade. The risk of relapse is significantly associated with clinical, endoscopic, histological, and laboratory variables and treatment strategies.

Current applications for measuring pediatric intima-media thickness.

Intima-media thickness is a known subclinical radiologic marker of the early manifestations of atherosclerotic disease. It is the thickness of the vessel wall, most often the carotid artery. Intima-media thickness is measured on conventional US manually or automatically. Other measurement techniques include radiofrequency US. Because there is variation in its measurement, especially in children, several recommendations have been set to increase the measurement's validity and comparability among studies. Despite these recommendations, several pitfalls should be avoided, and quality control should be performed to avoid erroneous interpretation. This article summarizes current literature in relation to the clinical applications for intima-media thickness measurement in children with known risk factors such as obesity, liver steatosis, hypercholesterolemia, diabetes, hypertension, systemic inflammatory diseases, cancer survival, kidney and liver transplant, and sickle cell disease or beta thalassemia major. Most potential indications for intima-media thickness measurement remain in the research domain and should be interpreted combined with other markers. The objective of diagnosing an increased intima-media thickness is to start a multidisciplinary treatment approach to prevent disease progression and its sequelae in adulthood.

Changes in the clinical phenotype and behavior of pediatric luminal Crohn's disease at diagnosis in the last decade.

BACKGROUND AND AIMS: The aims of this study were to describe the trends in the behavior of pediatric CD during the last decade and to describe the seasonal variation of disease presentation. METHODS: Patients under 18 years old and diagnosed between 2009 and 2019 were included. The clinical, endoscopic, histological, and laboratory data were collected from the medical records. We analyzed the trends of these parameters according to the year and season of diagnosis. RESULTS: 654 patients were included in the study. The number of incident CD cases increased yearly. Patients diagnosed between 2015 and 2019 were younger at diagnosis (OR 2.53, p = 0.02), had more perianal diseases (OR: 2.30, p < 0.0001) and more granulomas (OR: 1.61, p = 0.003), but fewer eosinophils (OR: 0.35, p < 0.0001) and less chronic lymphoplasmacytic infiltrate (OR: 0.56, p = 0.008) as compared to the 2009-2014 cohort. There was fewer CD diagnosis during winter. Patients diagnosed in the fall had lower PCDAIs, less failure to thrive and less extensive digestive involvement. Colonic disease was significantly more frequent during summer and fall. CONCLUSION: The clinical and histological phenotype of CD has changed over time and there are important seasonal trends in the frequency and severity on disease behavior suggesting possible disease triggers.

Factors associated with time to clinical remission in pediatric luminal Crohn's disease: A retrospective cohort study.

BACKGROUND AND AIM: Data on factors influencing time to remission in pediatric Crohn's disease (CD) are very limited in the literature. The aim of this retrospective cohort study was to describe the trends of time to clinical remission over the past decade and to identify factors associated with time to clinical remission in children with luminal CD. METHODS: Patients under 18 years old diagnosed between 2009 and 2019 were included. All data were collected from the patients' medical records. Survival analyses and linear regression models were used to assess the impact of clinical, laboratory, endoscopic, histological, and therapeutic factors on time to clinical remission. RESULTS: A total of 654 patients were included in the study. There was no change in the time to clinical remission over the decade. Female sex in adolescents (adjusted bêta regression coefficient [aß] = 31.8 days, P = 0.02), upper digestive tract involvement (aß = 46.4 days, P = 0.04) perianal disease (aß = 32.2 days, P = 0.04), presence of active inflammation on biopsies at diagnosis (aß = 46.7 days, P = 0.01) and oral 5-aminosalicylates (5-ASA) exposure (aß = 56.6 days, P = 0.002) were associated with longer time to clinical remission. Antibiotic exposure (aß = -29.3 days, P = 0.04), increased eosinophils (aß = -29.6 days, P = 0.008) and combination of exclusive enteral nutrition with tumor-necrosis-factor-alpha (TNF-alpha) inhibitors as induction therapy (aß = -36.8 days, P = 0.04) were associated with shorter time to clinical remission. CONCLUSION: In children with newly diagnosed Crohn's disease, time to clinical remission did not shorten during the decade. It was associated with baseline clinical and histological data and treatment strategies. Combination of enteral nutrition and TNF-alpha inhibitors was associated with faster clinical remission.

Diagnostic Delay Is Associated With Complicated Disease and Growth Impairment in Paediatric Crohn's Disease.

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.

Risk Perception of COVID-19 Infection and Adherence to Preventive Measures among Adolescents and Young Adults.

To explore factors influencing adolescents and young adults' (AYAs) risk perception of COVID-19 and adherence to public health measures, we conducted a cross-sectional online survey of AYAs (14-22 years old) from Quebec (Canada) recruited through school and community partners in April 2020 during the first wave of the COVID-19 pandemic. The study included 3037 participants (mean age = 17.7 years, 74.6% female). AYAs had higher mean (standard deviation (SD)) risk perception of COVID-19 for their relatives (8.2 (1.9)) than for themselves (5.6 (2.6)) (p < 0.001). Factors associated with higher risk perception included higher disease knowledge (adjusted odds ratio (aOR) 1.06, 95% CI 1.01-1.11), presence of chronic disease (aOR 2.31, 95%CI 1.82-2.93) and use of immunosuppressants (aOR 2.53, 95%CI 1.67-3.87). AYAs with a higher risk perception (aOR 1.06, 95%CI 1.02-1.10) those wishing to help flatten the disease curve (aOR 1.18, 95%CI 1.12-1.25) or to protect their family/friends (aOR 1.14, 95%CI 1.05-1.24) were more likely to engage in preventive behaviors. Self-perceived risk and desire to protect others were significantly associated with adherence to preventive measures among youth. These findings may help inform public health messaging to AYAs in the current and future pandemics.