Incidence and prevalence of paediatric-onset multiple sclerosis in two Canadian provinces: a population-based study representing over half of Canada's population.

BACKGROUND: Population-based studies estimating the epidemiology of paediatric-onset multiple sclerosis (PoMS) are scarce. METHODS: We accessed population-based health administrative data from two provinces in Canada, Ontario and British Columbia (BC). Individuals with PoMS were identified via a validated case definition. The index date ('MS onset') was the first demyelinating or MS specific claim recorded ≤18 years of age. We estimated the age-standardised annual incidence and prevalence of PoMS, and 95% CIs between 2003 and 2019. We used negative binomial regression models to assess the temporal changes in the annual crude incidence and prevalence of PoMS, and the ratios comparing sex groups. RESULTS: From 2003 to 2019, a total of 148 incident PoMS cases were identified in BC, and 672 in Ontario. The age-standardised annual incidence of PoMS was stable in both provinces, averaging 0.95 (95% CI 0.79 to 1.13) in BC and 0.98 (95%CI 0.84 to 1.12) in Ontario per 100 000 person-years. The incidence ratio by sex (female vs male) was also stable over the study period, averaging 1.5:1 (95% CI 1.06 to 2.08, BC) and 2.0:1 (95% CI 1.61 to 2.59, Ontario). The age-standardised prevalence per 100 000 people rose from 4.75 (2003) to 5.52 (2019) in BC and from 2.93 (2003) to 4.07 (2019) in Ontario, and the increase was statistically significant in Ontario (p=0.002). There were more female prevalent PoMS cases than males in both provinces. CONCLUSIONS: Canada has one of the highest rates of PoMS globally, and the prevalence, but not incidence, has increased over time. Allocation of resources to support the growing youth population with MS should be a priority.

Oral Antibiotics and Risk of Serious Cutaneous Adverse Drug Reactions.

Importance: Serious cutaneous adverse drug reactions (cADRs) are potentially life-threatening drug hypersensitivity reactions involving the skin and internal organs. Antibiotics are a recognized cause of these reactions, but no studies have compared relative risks across antibiotic classes. Objectives: To explore the risk of serious cADRs associated with commonly prescribed oral antibiotics, and to characterize outcomes of patients hospitalized for them. Design, Setting, and Participants: Nested case-control study using population-based linked administrative datasets among adults aged 66 years or older who received at least 1 oral antibiotic between 2002 and 2022 in Ontario, Canada. Cases were those who had an emergency department (ED) visit or hospitalization for serious cADRs within 60 days of the prescription, and each case was matched with up to 4 controls who did not. Exposure: Various classes of oral antibiotics. Main Outcomes and Measures: Conditional logistic regression estimate of the association between different classes of oral antibiotics and serious cADRs, using macrolides as the reference group. Results: During the 20-year study period, we identified 21 758 older adults (median age, 75 years; 64.1% female) who had an ED visit or hospitalization for serious cADRs following antibiotic therapy and 87 025 matched controls who did not. In the primary analysis, sulfonamide antibiotics (adjusted odds ratio [aOR], 2.9; 95% CI, 2.7-3.1) and cephalosporins (aOR, 2.6; 95% CI, 2.5-2.8) were most strongly associated with serious cADRs relative to macrolides. Additional associations were evident with nitrofurantoin (aOR, 2.2; 95% CI, 2.1-2.4), penicillins (aOR, 1.4; 95% CI, 1.3-1.5), and fluoroquinolones (aOR, 1.3; 95% CI, 1.2-1.4). The crude rate of ED visits or hospitalization for cADRs was highest for cephalosporins (4.92 per 1000 prescriptions; 95% CI, 4.86-4.99) and sulfonamide antibiotics (3.22 per 1000 prescriptions; 95% CI, 3.15-3.28). Among the 2852 case patients hospitalized for cADRs, the median length of stay was 6 days (IQR, 3-13 days), 9.6% required transfer to a critical care unit, and 5.3% died in the hospital. Conclusion and Relevance: Commonly prescribed oral antibiotics are associated with an increased risk of serious cADRs compared with macrolides, with sulfonamides and cephalosporins carrying the highest risk. Prescribers should preferentially use lower-risk antibiotics when clinically appropriate.

Long-term Neurobehavioral and Metabolic Outcomes in Offspring of Mothers With Diabetes During Pregnancy: A Large, Population-Based Cohort Study in Ontario, Canada.

OBJECTIVE: Offspring of women with diabetes are at increased risk of developing neurobehavioral and cardiometabolic disorders, but there is scant evidence regarding the association between glycemic level during pregnancy and these long-term offspring outcomes. RESEARCH DESIGN AND METHODS: We conducted a population-based, cohort study of deliveries in Ontario between April 1991 and March 2018. Women had preexisting diabetes, gestational diabetes, or no diabetes. We applied a Cox proportional hazard model to examine the risk of developing attention deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and cardiometabolic outcomes in offspring and assessed the association between pregnancy HbA1c levels and risk of outcomes, adjusting for confounders. RESULTS: A total of 3,407,961 mother-infant pairs were followed up to 29 years. Using a Cox proportional hazard model, offspring of women with type 1 diabetes had the highest risk of ADHD (adjusted hazard ratio [aHR] 1.43 [95% CI 1.36-1.49]), ASD (aHR 1.94 [1.80-2.09]), diabetes (aHR 4.73 [4.34-5.16]), hypertension (aHR 2.32 [2.07-2.61]), and cardiovascular disease (CVD) (aHR 1.72 [1.56-1.90]), followed by offspring of women with type 2 diabetes and gestational diabetes compared with those unexposed. Among women with preexisting diabetes, there was an association between level of pregnancy HbA1c and offspring diabetes (aHR 1.22 [95% CI 1.12-1.32]), hypertension (aHR 1.42 [1.29-1.57]), and CVD (aHR 1.20 [1.11-1.29]) but no statistically significant association with neurobehavioral outcomes. CONCLUSIONS: In utero exposure to maternal diabetes was associated with an increase in ADHD, ASD, and cardiometabolic outcomes in offspring, with differences seen across diabetes subtypes. Pregnancy glycemia was associated with cardiometabolic outcomes, but not neurobehavioral outcomes, and provides a potentially modifiable risk factor to decrease cardiometabolic outcomes in offspring.

Validity of diagnoses of SARS-CoV-2 infection in Canadian administrative health data: a multiprovince, population-based cohort study.

BACKGROUND: Accurate coding of diagnoses of SARS-CoV-2 infection in administrative data benefits population-based studies about the epidemiology, treatment and outcomes of COVID-19. We describe the validity of diagnoses of SARS-CoV-2 infection recorded in hospital discharge abstracts, emergency department records and outpatient physician service claims from 3 Canadian provinces. METHODS: In this cohort study, population-based inpatient, emergency department and outpatient records were linked to SARS-CoV-2 polymerase chain reaction (PCR; reference standard) test results from British Columbia, Manitoba and Ontario for Apr. 1, 2020, to Mar. 31, 2021. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of diagnoses of SARS-CoV-2 infection were estimated for each quarter in the study period, overall and by province, age group and sex. RESULTS: Our study encompassed more than 13 million SARS-CoV-2 PCR test results. Specificity and NPV of diagnoses of SARS-CoV-2 infection were consistently high (i.e., most estimates were > 95%). Overall sensitivity estimates were 86.2%, 60.4% and 20.3% in the first quarter for inpatient, emergency department and outpatient cohorts, and 66.2%, 47.5% and 25.0% in the last quarter, respectively. For inpatients, overall PPV estimates ranged from 50.0% to 66.4%. For emergency department patients, overall PPV estimates were 76.9% and 68.3% in the first and last quarters, respectively. For outpatients, PPV estimates were 6.8% and 29.1% in the first and last quarters, respectively. INTERPRETATION: We found variations in the validity of diagnoses for SARS-CoV-2 infection recorded in different health care settings, geographic areas and over time. Our multiprovince validation study provides evidence about the potential use of inpatient and emergency department records as an alternative to population-based laboratory data for identification of patients with SARS-CoV-2 infection, but does not support the use of outpatient claims for this purpose.

Delivery Strategies Supporting School-Age Child Health: A Systematic Review.

CONTEXT: School-aged children (SAC; 5-9 years) remain understudied in global efforts to examine intervention effectiveness and scale up evidence-based interventions. OBJECTIVE: This review summarizes the available evidence describing the effectiveness of key strategies to deliver school-age interventions. DATA SOURCES: We searched Medline, PsycINFO, Campbell Collaboration, and The Cochrane Library during November 2020. STUDY SELECTION: Systematic reviews and meta-analyses that: target SAC, examine effective delivery of well-established interventions, focus on low- and middle-income countries (LMICs), were published after 2010, and focus on generalizable, rather than special, populations. DATA EXTRACTION: Two reviewers conducted title and abstract screening, full-text screening, data extraction, and quality assessments. RESULTS: Sixty reviews met the selection criteria, with 35 containing evidence from LMICs. The outcomes assessed and the reported effectiveness of interventions varied within and across delivery strategies. Overall, community, school, and financial strategies improved several child health outcomes. The greatest evidence was found for the use of community-based interventions to improve infectious disease outcomes, such as malaria control and prevention. School-based interventions improved child development and infectious disease-related outcomes. Financial strategies improved school enrollment, food security, and dietary diversity. LIMITATIONS: Relatively few LMIC studies examined facility, digital, and self-management strategies. Additionally, we found considerable heterogeneity within and across delivery strategies and review authors reported methodological limitations within the studies. CONCLUSIONS: Despite limited research, available information suggests community-based strategies can be effective for the introduction of a range of interventions to support healthy growth and development in SAC. These also have the potential to reduce disparities and reach at-risk and marginalized populations.