Search

M Ellen Kuenzig,1,2 Therese A Stukel,3,4 Matthew W Carroll,5 Gilaad G Kaplan,6 Anthony R Otley,7 Harminder Singh,8– 10 Alain Bitton,11 Stephen G Fung,12,13 Sarah Spruin,3,14 Stephanie Coward,6 Yunsong Cui,15 Zoann Nugent,8 Anne M Griffiths,1,2,16 David R Mack,12,13,17 Kevan Jacobson,18 Geoffrey C Nguyen,3,4,19 Laura E Targownik,19 Wael El-Matary,20 Charles N Bernstein,8,9 Trevor J B Dummer,21 Jennifer L Jones,15 Lisa M Lix,22 Sanjay K Murthy,14,23– 25 Juan Nicolás Peña-Sánchez,26 Soheila Nasiri,12,13 Eric I Benchimol1– 4,16 On behalf of the Canadian Gastro-Intestinal Epidemiology Consortium1SickKids Inflammatory Bowel Disease Centre, Division of Gastroenterology, Hepatology and Nutrition, The Hospital for Sick Children (Sickkids), Toronto, Ontario, Canada; 2Child Health Evaluative Sciences, SickKids Research Institute, The Hospital for Sick Children, Toronto, Ontario, Canada; 3ICES, Toronto, Ontario, Canada; 4Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Ontario, Canada; 5Division of Pediatric Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada; 6Departments of Medicine & Community Health Sciences, University of Calgary, Calgary, Alberta, Canada; 7Department of Pediatrics, Dalhousie University, Halifax, Nova Scotia, Canada; 8Univeristy of Manitoba IBD Clinical and Research Centre, University of Manitoba, Winnipeg, Manitoba, Canada; 9Department of Internal Medicine, Max Rady College of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada; 10Research Institute at CancerCare Manitoba, Winnipeg, Manitoba, Canada; 11McGill University Health Centre, Division of Gastroenterology and Hepatology, Montreal, Québec, Canada; 12CHEO Inflammatory Bowel Disease Centre, Division of Gastroenterology, Hepatology and Nutrition, CHEO, Ottawa, Ontario, Canada; 13CHEO Research Institute, Ottawa, Ontario, Canada; 14Ottawa Hospital Research Institute, Ottawa, Ontario, Canada; 15Department of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada; 16Department of Paediatrics, University of Toronto, Toronto, Ontario, Canada; 17Department of Pediatrics, University of Ottawa, Ottawa, Ontario, Canada; 18Department of Pediatrics, BC Children’s Hospital Research Institute, University of British Columbia, Vancouver, British Columbia, Canada; 19Mount Sinai Hospital Centre for Inflammatory Bowel Disease, Department of Medicine, University of Toronto, Toronto, Ontario, Canada; 20Department of Pediatrics, University of Manitoba, Winnipeg, Manitoba, Canada; 21School of Population and Public Health, University of British Columbia, Vancouver, BC, Canada; 22Department of Community Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada; 23Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada; 24Division of Gastroenterology, The Ottawa Hospital IBD Centre, Ottawa, Ontario, Canada; 25School of Epidemiology and Public Health, University of Ottawa, Ottawa, Ontario, Canada; 26Department of Community Health & Epidemiology, College of Medicine, University of Saskatchewan, Saskatoon, Saskatchewan, CanadaCorrespondence: Eric I Benchimol, The Hospital for Sick Children Division of Gastroenterology, Hepatology and Nutrition 555 University Avenue, Toronto, ON, M5G 1X8, Canada, Fax +1-416-813-4972, Email eric.benchimol@sickkids.caPurpose: The incidence of childhood-onset inflammatory bowel disease (IBD) is rising. We described variation in health services utilization and need for surgery among children with IBD between six and 60 months following IBD diagnosis across Canadian pediatric centers and evaluated the associations between care provided at diagnosis at each center and the variation in these outcomes.Patients and Methods: Using population-based deterministically-linked health administrative data from four Canadian provinces (Alberta, Manitoba, Nova Scotia, Ontario) we identified children diagnosed with IBD < 16 years of age using validated algorithms. Children were assigned to a pediatric center of care using a hierarchical approach based on where they received their initial care. Outcomes included IBD-related hospitalizations, emergency department (ED) visits, and IBD-related abdominal surgery occurring between 6 and sixty months after diagnosis. Mixed-effects meta-analysis was used to pool results and examine the association between center-level care provision and outcomes.Results: We identified 3784 incident cases of pediatric IBD, of whom 2937 (77.6%) were treated at pediatric centers. Almost a third (31.4%) of children had ≥ 1 IBD-related hospitalization and there were 0.66 hospitalizations per person during follow-up. More than half (55.8%) of children had ≥ 1 ED visit and there were 1.64 ED visits per person. Between-center heterogeneity was high for both outcomes; centers where more children visited the ED at diagnosis had more IBD-related hospitalizations and more ED visits during follow-up. Between-center heterogeneity was high for intestinal resection in Crohn’s disease but not colectomy in ulcerative colitis.Conclusion: There is variation in health services utilization among children with IBD and risk of undergoing intestinal resection in those with Crohn’s disease, but not colectomy among children with ulcerative colitis, across Canadian pediatric tertiary-care centers. Improvements in clinical care pathways are needed to ensure all children have equitable and timely access to high quality care.Plain Language Summary: Inflammatory bowel disease (IBD) is a chronic health condition of the gastrointestinal system, which is becoming more common in children. They require lifelong treatment and receiving high quality care is important for preventing complications. We determined if outcomes of children with IBD was different across Canada. We also tested if differences in care at diagnosis was related to outcomes. More than three-quarters of children with IBD were treated at pediatric hospitals. Children treated at some hospitals were more likely to be hospitalized and visit the emergency room when compared to children treated at other hospitals. Children with Crohn’s disease (one type of IBD) were more likely to have surgery at some hospitals when compared to children treated at other hospitals. We should improve care to make sure children living with IBD have timely access to high quality specialist care.Keywords: Crohn’s disease, ulcerative colitis, health administrative data, variation in care, health services utilization, surgery

Eric I Benchimol,1–5 M Ellen Kuenzig,1,2,5 Charles N Bernstein,6,7 Geoffrey C Nguyen,5,8 Astrid Guttmann,5,9 Jennifer L Jones,10 Beth K Potter,4 Laura E Targownik,6,7 Christina A Catley,5 Zoann J Nugent,6,11 Divine Tanyingoh,12,13 Nassim Mojaverian,5 Fox E Underwood,12,13 Shabnaz Siddiq,1,2 Anthony R Otley,14 Alain Bitton,15 Matthew W Carroll,16 Jennifer C deBruyn,17 Trevor JB Dummer,18 Wael El-Matary,19 Anne M Griffiths,9 Kevan Jacobson,20,21 Desmond Leddin,10 Lisa M Lix,22 David R Mack,1–3 Sanjay K Murthy,4,23 Juan Nicolás Peña-Sánchez,24 Harminder Singh,6,7 Gilaad G Kaplan12,13 On behalf of the Canadian Gastro-Intestinal Epidemiology Consortium 1Children’s Hospital of Eastern Ontario IBD Centre, Division of Gastroenterology, Hepatology and Nutrition, Children’s Hospital of Eastern Ontario, Ottawa, Canada; 2Children’s Hospital of Eastern Ontario Research Institute, Ottawa, Canada; 3Department of Pediatrics, University of Ottawa, Ottawa, Canada; 4School of Epidemiology and Public Health, University of Ottawa, Ottawa, Canada; 5ICES, Toronto, Canada; 6University of Manitoba IBD Clinical and Research Centre, University of Manitoba, Winnipeg, Canada; 7Department of Internal Medicine, University of Manitoba, Winnipeg, Canada; 8Department of Medicine, Mount Sinai Hospital Centre for Inflammatory Bowel Disease, University of Toronto, Toronto, Canada; 9Department of Paediatrics, University of Toronto, Toronto, Canada; 10Department of Medicine, Dalhousie University, Halifax, Canada; 11CancerCare Manitoba, Winnipeg, Canada; 12Department of Medicine, University of Calgary, Calgary, Alberta, Canada; 13Department of Community Health Sciences, University of Calgary, Calgary, Alberta, Canada; 14Department of Pediatrics, Dalhousie University, Halifax, Canada; 15Division of Gastroenterology, McGill University Health Centre, Montreal, Canada; 16Division of Pediatric Gastroenterology and Nutrition, Department of Pediatrics, University of Alberta, Edmonton, Canada; 17Division of Gastroenterology, Department of Pediatrics, University of Calgary, Calgary, Canada; 18School of Population and Public Health, University of British Columbia, British Columbia, Canada; 19Department of Pediatrics, University of Manitoba, Winnipeg, Canada; 20Department of Pediatrics, The University of British Columbia, British Columbia, Canada; 21Child and Family Research Institute, The University of British Columbia, British Columbia, Canada; 22Department of Community Health Sciences, University of Manitoba, Winnipeg, Canada; 23The Ottawa Hospital IBD Centre, Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada; 24Department of Community Health and Epidemiology, University of Saskatchewan, Saskatoon, Canada Background and aims: Canada’s large geographic area and low population density pose challenges in access to specialized health care for remote and rural residents. We compared health services use, surgical rate, and specialist gastroenterologist care in rural and urban inflammatory bowel disease (IBD) patients in Canada.Methods: We used validated algorithms that were applied to population-based health administrative data to identify all people living with the following three Canadian provinces: Alberta, Manitoba, and Ontario (ON). We compared rural residents with urban residents for time to diagnosis, hospitalizations, outpatient visits, emergency department (ED) use, surgical rate, and gastroenterologist care. Multivariable regression compared the outcomes in rural/urban patients, controlling for confounders. Provincial results were meta-analyzed using random-effects models to produce overall estimates.Results: A total of 36,656 urban and 5,223 rural residents with incident IBD were included. Outpatient physician visit rate was similar in rural and urban patients. IBD-specific and IBD-related hospitalization rates were higher in rural patients (incidence rate ratio [IRR] 1.17, 95% CI 1.02–1.34, and IRR 1.27, 95% CI 1.04–1.56, respectively). The rate of ED visits in ON were similarly elevated for rural patients (IRR 1.53, 95% CI 1.42–1.65, and IRR 1.33, 95% CI 1.25–1.40). There were no differences in surgical rates or prediagnosis lag time between rural and urban patients. Rural patients had fewer IBD-specific gastroenterologist visits (IRR 0.79, 95% CI 0.73–0.84) and a smaller proportion of their IBD-specific care was provided by gastroenterologists (28.3% vs 55.2%, P65 years (33.0% vs 59.2%, P

BackgroundPatients with inflammatory bowel disease (IBD) have a high prevalence of osteoporosis. A number of studies have found that corticosteroid use is associated with the development of osteoporosis in these patients. Calcium supplementation may be of benefit in corticosteroid-induced osteoporosis and calcium may be a nutrient that patients with IBD lack.AimTo test the benefit of calcium supplementation on bone density in a pilot study over a 1-year period, in a group of corticosteroid-using patients with IBD, in a randomized, double-blind, placebo-controlled treatment study.MethodsCorticosteroid-using patients with IBD including males over the age of 18 years and premenopausal females, were randomized to receive either calcium carbonate 1000 mg plus vitamin D 250 IU (Oscal) or an identically matched placebo. Dual energy X-ray absorptiometry measurements of bone density were obtained at entry and at 1 year. At entry, and every 3 months thereafter, serum was collected for the measurement of haemoglobin, biochemistry and bone hormones. Simultaneously a 24-h urine collection was analysed for calcium excretion and creatinine clearance, and a 4-day food record was collected to document dietary calcium and vitamin D ingestion.ResultsWe found a high prevalence of moderately severe decreased bone density in corticosteroid-using patients with IBD. The dose of prednisone in the year prior to study entry was inversely correlated with bone density at the hip (R = -0.67, P = 0.004). At study entry serum osteocalcin was inversely correlated with corticosteroid dose in the year prior to the study (R = -0.64, P = 0.02) and at study end, directly correlated with the percentage change in spine bone density (R = 0.59, P = 0.01). The dietary calcium intake of these patients was close to the current RDA (recommended daily intake) for premenopausal, post-adolescent adults. Calcium supplementation with small extra doses of vitamin D conferred no obvious benefit to bone density at the end of 1 year. There was no correlation between oral calcium ingestion and bone mass measurements. Both the treatment and placebo groups' bone density remained relatively stable at 1 year, suggesting that bone loss in corticosteroid-using patients may peak early into the use of the corticosteroids.ConclusionsCalcium supplementation (1000 mg/day) conferred no significant benefit to bone density at 1 year in patients with corticosteroid-using IBD patients with osteoporosis. Future investigations should explore other therapeutic avenues that may have greater effects on increasing bone density in patients who already have considerable osteoporosis.

The aim of this study was to assess the accuracy and utility of administrative health data in identifying persons with inflammatory bowel disease on a population basis and to determine the incidence and prevalence of this disease in the Canadian province of Manitoba. The data from Manitoba Health (the province's single insurer) were used to identify residents with physician and/or hospital contacts for Crohn's disease or ulcerative colitis based on International Classification of Diseases, Ninth Revision, Clinical Modification, codes between 1984 and 1995. Of 5,182 eligible individuals, 4,514 were mailed questionnaires and 2,725 responded. Cases were defined as individuals with five or more separate medical contacts with one of these diagnoses or three or more such contacts if they were resident for less than 2 years. The accuracy of the study case definitions was high when compared with either self-report or chart review. The 1989-1994 age- and sex-adjusted annual incidence was 14.6/100,000 for Crohn's disease and 14.3/100,000 for ulcerative colitis. The prevalence of Crohn's disease in 1994 was 198.5/100,000, and that of ulcerative colitis was 169.7/100,000. In conclusion, the authors have successfully established and validated a population-based database of inflammatory bowel disease based on administrative data. The high incidence rates and dynamic epidemiology of inflammatory bowel disease in Manitoba indicate the presence of important environmental risk factors, which warrants further investigation. [ABSTRACT FROM AUTHOR]

The recommended approach to the increased risk of colorectal carcinoma in ulcerative colitis has been colonoscopic surveillance rather than prophylactic colectomy. This strategy is based on the assumption that dysplastic lesions can be detected before invasive cancer has developed. We have analysed published reports on dysplasia surveillance to find out whether this assumption is valid. Ten prospective studies (1225 patients) satisfied our criteria. Of 40 patients with dysplasia-associated mass or lesion (DALM) detected, 17 (43%) already had cancer at immediate colectomy. The risks of cancer at immediate colectomy were 42% (10 of 24 patients) for high-grade and 19% (3 of 16) for low-grade dysplasia. Of 47 patients found to have high-grade dysplasia after the initial colonoscopy, 15 (32%) had cancer. 16-29% of patients with untreated low-grade dysplasia progressed to DALM, high-grade dysplasia, or cancer. Of patients with indefinite results, 28% progressed to high-grade dysplasia and 9% to cancer, so continued surveillance is essential. The risk of progression to dysplasia was only 2.4% for patients whose initial result was negative, so surveillance could perhaps be less frequent for these patients. Immediate colectomy is essential for all patients diagnosed with high-grade or low-grade dysplasia. A diagnosis of dysplasia does not preclude the presence of invasive cancer. We believe that patients should be informed about the limitations of colonoscopic surveillance so that they can take part rationally in decision-making about their management. [ABSTRACT FROM AUTHOR]

Despite recent progress in our understanding of the association between the gut microbiome and inflammatory bowel disease (IBD), the role of microbiome biomarkers in IBD diagnosis remains underexplored. Here we developed a microbiome-based diagnostic test for IBD. By utilization of metagenomic data from 5,979 fecal samples with and without IBD from different geographies and ethnicities, we identified microbiota alterations in IBD and selected ten and nine bacterial species for construction of diagnostic models for ulcerative colitis and Crohn's disease, respectively. These diagnostic models achieved areas under the curve >0.90 for distinguishing IBD from controls in the discovery cohort, and maintained satisfactory performance in transethnic validation cohorts from eight populations. We further developed a multiplex droplet digital polymerase chain reaction test targeting selected IBD-associated bacterial species, and models based on this test showed numerically higher performance than fecal calprotectin in discriminating ulcerative colitis and Crohn's disease from controls. Here we discovered universal IBD-associated bacteria and show the potential applicability of a multibacteria biomarker panel as a noninvasive tool for IBD diagnosis., (© 2024. The Author(s).)

Objectives: Adverse childhood experiences (ACE) are associated with immune-mediated inflammatory diseases (IMID). We evaluated whether: (i) ACE associate with psychiatric comorbidity among individuals with IMID, including rheumatoid arthritis (RA), multiple sclerosis (MS), and inflammatory bowel disease (IBD); (ii) whether psychiatric disorders mediate the relationship between ACE and IMID; and (iii) whether these findings differ from those in individuals with other chronic physical disorders., Methods: Using data from the Canadian Longitudinal Study on Aging (CLSA) we performed a retrospective case-control study of participants aged 45-85 years recruited between 2010 and 2015. ACE were queried using questions derived from the Childhood Experiences of Violence Questionnaire-Short Form and the National Longitudinal Study of Adolescent to Adult Health Wave III questionnaire. We used multivariable logistic regression and causal mediation analysis to address our objectives., Results: We included 13,977 CLSA participants. Among the 31 % of IMID participants who reported a comorbid psychiatric disorder, 79 % reported a history of ACE. ACE associated with increased odds (OR [95 % CI]) of a psychiatric disorder (2.55 [1.02-6.35]) among participants with IMID; this did not differ across IMID. The total effect (OR [95 % CI]) of ACE on IMID was 1.11 (1.07-1.16), of which 10.60 % (8.04-17.47) was mediated by psychiatric disorders. We found similar associations among participants with other chronic physical disorders., Conclusion: Our findings suggest that psychiatric disorders partially mediate the association between ACE and IMID. Most participants with IMID and comorbid psychiatric disorders report a history of ACE and may benefit from trauma-informed mental health care., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background & Aims: Unaffected first-degree relatives (FDRs) from families with ≥2 affected FDRs with Crohn's disease (CD, multiplex families) have a high risk of developing CD, although the underlying mechanisms driving this risk are poorly understood. We aimed to identify differences in biomarkers between FDRs from multiplex vs simplex families and investigate the risk of future CD onset accounting for potential confounders., Methods: We assessed the Crohn's and Colitis Canada Genetic Environmental Microbial cohort of healthy FDRs of patients with CD. Genome-wide CD-polygenic risk scores, urinary fractional excretion of lactulose-to-mannitol ratio, fecal calprotectin (FCP), and fecal 16S ribosomal RNA microbiome were measured at recruitment. Associations between CD multiplex status and baseline biomarkers were determined using generalized estimating equations models. Cox models were used to assess the risk of future CD onset., Results: There were 4051 participants from simplex families and 334 from CD multiplex families. CD multiplex status was significantly associated with higher baseline FCP (P = .026) but not with baseline CD-polygenic risk scores or the lactulose-to-mannitol ratio. Three bacterial genera were found to be differentially abundant between both groups. CD multiplex status at recruitment was independently associated with an increased risk of developing CD (adjusted hazard ratio, 3.65; 95% confidence interval, 2.18-6.11, P < .001)., Conclusion: Within FDRs of patients with CD, participants from multiplex families had a 3-fold increased risk of CD onset, a higher FCP, and an altered bacterial composition, but not genetic burden or altered gut permeability. These results suggest that putative environmental factors might be enriched in FDRs from multiplex families., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Little is known about patterns of opioid prescribing in inflammatory bowel disease (IBD), but pain is common in persons with IBD. We estimated the incidence and prevalence of opioid use in adults with IBD and an unaffected reference cohort and assessed factors that modified opioid use., Methods: Using population-based health administrative data from Manitoba, Canada, we identified 5233 persons with incident IBD and 26 150 persons without IBD matched 5:1 on sex, birth year, and region from 1997 to 2016. New and prevalent opioid prescription dispensations were quantified, and patterns related to duration of use were identified. Generalized linear models were used to test the association between IBD, psychiatric comorbidity, and opioid use adjusting for sociodemographic characteristics, physical comorbidities, and healthcare use., Results: Opioids were dispensed to 27% of persons with IBD and to 12.9% of the unaffected reference cohort. The unadjusted crude incidence per 1000 person-years of opioid use was nearly twice as high for the IBD cohort (88.63; 95% CI, 82.73-91.99) vs the reference cohort (45.02; 95% CI, 43.49-45.82; relative risk 1.97; 95% CI, 1.86-2.08). The incidence rate per 1000 person-years was highest in those 18-44 years at diagnosis (98.01; 95% CI, 91.45-104.57). The relative increase in opioid use by persons with IBD compared to reference cohort was lower among persons with psychiatric comorbidity relative to the increased opioid use among persons with IBD and reference cohort without psychiatric comorbidity., Discussion: The use of opioids is more common in people with IBD than in people without IBD. This does not appear to be driven by psychiatric comorbidity., (© 2024 Crohn’s & Colitis Foundation. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation.)

Background & Aims: To date, it is unclear how environmental factors influence Crohn's disease (CD) risk and how they interact with biological processes. This study investigates the association between environmental exposures and CD risk and evaluates their association with pre-disease biomarkers., Methods: We studied 4289 healthy first-degree relatives (FDRs) of patients with CD from the Crohn's and Colitis Canada - Genetic, Environmental, Microbial (CCC-GEM) project. Regression models identified environmental factors associated with future CD onset and their association with pre-disease biological factors, including altered intestinal permeability measured by urinary fractional excretion of lactulose to mannitol ratio (LMR); gut inflammation via fecal calprotectin (FCP) levels; and fecal microbiome composition through 16S rRNA sequencing., Results: Over a 5.62-year median follow-up, 86 FDRs developed CD. Living with a dog between ages 5 and 15 (hazard ratio [HR], 0.62; 95% confidence interval [CI], 0.40-0.96; P = .034), and living with a large family size in the first year of life (HR, 0.43; 95% CI, 0.21-0.85; P = .016) were associated with decreased CD risk, whereas having a bird at the time of recruitment (HR, 2.78; 95% CI, 1.36-5.68; P = .005) was associated with an increased CD risk. Furthermore, living with a dog was associated with reduced LMR, altered relative abundance of multiple bacterial genera, and increased Chao1 diversity, whereas bird owners had higher FCP levels. Large family during participants' first year of life was associated with altered microbiota composition without affecting FCP or LMR., Conclusion: This study identifies environmental variables associated with CD risk. These variables were also associated with altered barrier function, subclinical inflammation, and gut microbiome composition shifts, suggesting potential roles in CD pathogenesis., (Copyright © 2024 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Introduction: Canada has a high burden of inflammatory bowel disease (IBD). Historical trends of IBD incidence and prevalence were analyzed to forecast the Canadian burden over the next decade., Methods: Population-based surveillance cohorts in 8 provinces derived from health administrative data assessed the national incidence (2007-2014) and prevalence (2002-2014) of IBD. Autoregressive integrated moving average models were used to forecast incidence and prevalence, stratified by age, with 95% prediction intervals (PI), to 2035. The average annual percentage change (AAPC) with 95% confidence interval (CI) was calculated for the forecasted incidence and prevalence., Results: The national incidence of IBD is estimated to be 29.9 per 100,000 (95% PI 28.3-31.5) in 2023. With a stable AAPC of 0.36% (95% CI -0.05 to 0.72), the incidence of IBD is forecasted to be 31.2 per 100,000 (95% PI 28.1-34.3) in 2035. The incidence in pediatric patients (younger than 18 years) is increasing (AAPC 1.27%; 95% CI 0.82-1.67), but it is stable in adults (AAPC 0.26%; 95% CI -0.42 to 0.82). The prevalence of IBD in Canada was 843 per 100,000 (95% PI 716-735) in 2023 and is expected to steadily climb (AAPC 2.43%; 95% CI 2.32-2.54) to 1,098 per 100,000 (95% PI 1,068-1,127) by 2035. The highest prevalence is in seniors with IBD (1,174 per 100,000 in 2023; AAPC 2.78%; 95% CI 2.75-2.81)., Discussion: Over the next decade, the Canadian health care systems will contend with the juxtaposition of rising incidence of pediatric IBD and a rising prevalence of overall IBD driven by the aging population., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

Background: Vascular disease and cognitive impairment have been increasingly documented in inflammatory bowel disease (IBD), and both have been individually correlated with changes in brain structure. This study aimed to determine if both macro- and microstructural brain changes are prevalent in IBD and whether alterations in brain structure mediate the relationship between vascular disease and cognitive functioning., Methods: Eighty-four IBD participants underwent multimodal magnetic resonance imaging. Volumetric and mean diffusivity measures of the thalamus, hippocampus, normal-appearing white matter, and white matter lesions were converted to age- and sex-adjusted z scores. Vascular comorbidity was assessed using a modified Framingham Risk Score and cognition was assessed using a battery of neuropsychological tests. Test scores were standardized using local regression-based norms. We generated summary statistics for the magnetic resonance imaging metrics and cognitive tests, and these were examined using canonical correlation analysis and linear regression modeling., Results: Greater vascular comorbidity was negatively correlated with thalamic, normal-appearing white matter, and white matter lesion volumes. Higher Framingham Risk Score were also correlated with lower processing speed, learning and memory, and verbal fluency. Increased vascular comorbidity was predictive of poorer cognitive functioning, and this effect was almost entirely mediated (94.76%) by differences in brain structure., Conclusions: Vascular comorbidity is associated with deleterious effects on brain structure and lower cognitive functioning in IBD. These findings suggest that proper identification and treatment of vascular disease is essential to the overall management of IBD, and that certain brain areas may serve as critical targets for predicting the response to therapeutic interventions., (© The Author(s) 2023. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background & Aims: Colonoscopic surveillance is recommended in patients with colonic inflammatory bowel disease (IBD) given their increased risk of colorectal cancer (CRC). We aimed to develop and validate a dynamic prediction model for the occurrence of advanced colorectal neoplasia (aCRN, including high-grade dysplasia and CRC) in IBD., Methods: We pooled data from 6 existing cohort studies from Canada, The Netherlands, the United Kingdom, and the United States. Patients with IBD and an indication for CRC surveillance were included if they underwent at least 1 follow-up procedure. Exclusion criteria included prior aCRN, prior colectomy, or an unclear indication for surveillance. Predictor variables were selected based on the literature. A dynamic prediction model was developed using a landmarking approach based on Cox proportional hazard modeling. Model performance was assessed with Harrell's concordance-statistic (discrimination) and by calibration curves. Generalizability across surveillance cohorts was evaluated by internal-external cross-validation., Results: The surveillance cohorts comprised 3731 patients, enrolled and followed-up in the time period from 1973 to 2021, with a median follow-up period of 5.7 years (26,336 patient-years of follow-up evaluation); 146 individuals were diagnosed with aCRN. The model contained 8 predictors, with a cross-validation median concordance statistic of 0.74 and 0.75 for a 5- and 10-year prediction window, respectively. Calibration plots showed good calibration. Internal-external cross-validation results showed medium discrimination and reasonable to good calibration., Conclusions: The new prediction model showed good discrimination and calibration, however, generalizability results varied. Future research should focus on formal external validation and relate predicted aCRN risks to surveillance intervals before clinical application., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: The incidence of pediatric-onset inflammatory bowel disease (IBD) and the costs of caring for individuals with IBD are both increasing. We calculated the direct healthcare costs of pediatric IBD in the first year after diagnosis and developed a model to predict children who would have high costs (top 25th percentile)., Methods: Using data from the Canadian Children IBD Network inception cohort (≤16 years of age, diagnosed between 2013 and 2019) deterministically linked to health administrative data from Ontario, Canada, we estimated direct healthcare and medication costs accrued between 31 and 365 days after diagnosis. Candidate predictors included age at diagnosis, sex, rural/urban residence location, distance to pediatric center, neighborhood income quintile, IBD type, initial therapy, disease activity, diagnostic delay, health services utilization or surgery around diagnosis, regular primary care provider, and receipt of mental health care. Logistic regression with stepwise elimination was used for model building; 5-fold nested cross-validation optimized and improved model accuracy while limiting overfitting., Results: The mean cost among 487 children with IBD was CA$15 168 ± 15 305. Initial treatment (anti-tumor necrosis factor therapy, aminosalicylates, or systemic steroids), having a mental health care encounter, undergoing surgery, emergency department visit at diagnosis, sex, and age were predictors of increased costs, while having a regular primary care provider was a predictor of decreased costs. The C-statistic for our model was 0.71., Conclusions: The cost of caring for children with IBD in the first year after diagnosis is immense and can be predicted based on characteristics at diagnosis. Efforts that mitigate rising costs without compromising quality of care are needed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: The interplay between diet and the gut microbiota in multiple sclerosis (MS) is poorly understood. We aimed to assess the interrelationship between diet, the gut microbiota, and MS., Methods: We conducted a case-control study including 95 participants (44 pediatric-onset MS cases, 51 unaffected controls) enrolled from the Canadian Pediatric Demyelinating Disease Network study. All had completed a food frequency questionnaire ≤21-years of age, and 59 also provided a stool sample., Results: Here we show that a 1-point increase in a Mediterranean diet score is associated with 37% reduced MS odds (95%CI: 10%-53%). Higher fiber and iron intakes are also associated with reduced MS odds. Diet, not MS, explains inter-individual gut microbiota variation. Several gut microbes abundances are associated with both the Mediterranean diet score and having MS, and these microbes are potential mediators of the protective associations of a healthier diet., Conclusions: Our findings suggest that the potential interaction between diet and the gut microbiota is relevant in MS., (© 2024. The Author(s).)

Objective: To determine how serologic responses to coronavirus disease 2019 (COVID-19) vaccination and infection in immune-mediated inflammatory disease (IMID) are affected by time since last vaccination and other factors., Methods: Post-COVID-19 vaccination, data, and dried blood spots or sera were collected from adults with rheumatoid arthritis, inflammatory bowel disease, systemic lupus erythematosus, ankylosing spondylitis and spondylarthritis, and psoriasis and psoriatic arthritis. The first sample was collected at enrollment, then at 2 to 4 weeks and 3, 6, and 12 months after the latest vaccine dose. Multivariate generalized estimating equation regressions (including medications, demographics, and vaccination history) evaluated serologic response, based on log-transformed anti-receptor-binding domain (RBD) IgG titers; we also measured antinucleocapsid (anti-N) IgG., Results: Positive associations for log-transformed anti-RBD titers were seen with female sex, number of doses, and self-reported COVID-19 infections in 2021 to 2023. Negative associations were seen with prednisone, anti-tumor necrosis factor agents, and rituximab. Over the 2021-2023 period, most (94%) of anti-N positivity was associated with a self-reported infection in the 3 months prior to testing. From March 2021 to February 2022, anti-N positivity was present in 5% to 15% of samples and was highest in the post-Omicron era, with antinucleocapsid positivity trending to 30% to 35% or higher as of March 2023. Anti-N positivity in IMID remained lower than Canada's general population seroprevalence (> 50% in 2022 and > 75% in 2023). Time since last vaccination was negatively associated with log-transformed anti-RBD titers, particularly after 210 days., Conclusion: Ours is the first pan-Canadian IMID assessment of how vaccine history and other factors affect serologic COVID-19 vaccine responses. These findings may help individuals personalize vaccination decisions, including consideration of additional vaccination when > 6 months has elapsed since last COVID-19 vaccination/infection., (Copyright © 2024 by the Journal of Rheumatology.)