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Background As severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transitions to endemicity and respiratory syncytial virus (RSV) and influenza reestablish their seasonal circulation patterns, understanding their comparative burden on infants and children can guide health system responses and funding priorities. Methods This was a population-based cohort study of children aged <5 years in Ontario, Canada, from September 2018 to August 2023 using linked health administrative databases. Results Seasonal cohorts comprised 731 838 to 763 660 children. RSV- and influenza-related hospital admission rates immediately decreased in March 2020. In 2021–2022, RSV-related admissions rebounded but remained 8%–11% lower than prepandemic seasons, whereas 2022–2023 RSV-related admissions increased 105%–113% versus prepandemic seasons and peak admissions occurred in November versus December. Influenza did not rebound until 2022–2023, when admissions were 28%–37% higher than prepandemic seasons. Coronavirus disease 2019 (COVID-19)–related admissions remained low until 2021–2022 and were lower than RSV-related admissions across all age groups during prepandemic and pandemic seasons. By contrast, 2021–2022 COVID-19-related admissions exceeded prepandemic influenza-related admissions by 30%–40% but decreased by 45% in 2022–2023 and were lower than prepandemic influenza-related admissions, except among infants aged <12 months who remained at highest risk. There was no distinct seasonal pattern for COVID-19–related admissions during the study. Conclusions RSV remains a major cause of childhood hospitalization. Although COVID-19 appears to be receding, its disease burden as it transitions to endemicity remains to be established. The unprecedented peaks in RSV-related hospital admissions during 2022–2023, together with the return of influenza and ongoing SARS-CoV-2 transmission, underscore the need to strengthen systems for real-time surveillance and to proactively prepare for critical healthcare scenarios. [ABSTRACT FROM AUTHOR]

Background Beyond clinical risk factors, little is known about the impact of social determinants on respiratory syncytial virus (RSV) burden. Our study aimed to estimate RSV-related hospitalization rates across sociodemographic and housing characteristics. Methods We conducted a population-based study of all RSV-related hospitalizations in Ontario, Canada, between September 1, 2016, and August 31, 2019, using validated hospital discharge codes and census data. Crude and age-standardized annualized RSV incidence rates and rate ratios (RRs) were estimated for a range of individual-level demographics and neighborhood-level measures of marginalization and housing characteristics. Results Overall, the annual RSV-related hospitalization rate was 27 per 100 000, with the highest rates observed in children age <12 months (1049 per 100 000) and 12–23 months (294 per 100 000) and adults age ≥85 years (155 per 100 000). Higher RSV-related hospitalization rates were associated with increasing marginalization quintile (Q) of material resources (RR, 1.4; Q5: 33 per 100 000 vs Q1: 24 per 100 000) and household instability (RR, 1.5; Q5: 31 per 100 000 vs Q1: 22 per 100 000). Conclusions The burden of RSV-related hospitalization was greatest in young children and older adults, with variation by sociodemographic and housing factors. Understanding the role of these social factors is crucial for informing equitable preventive program delivery. [ABSTRACT FROM AUTHOR]

• We evaluated people with suspected hypersensitivity after COVID-19 vaccination. • 92% of 180 referred for hypersensitivity reactions were recommended for revaccination. • 85% with physician-diagnosed hypersensitivity had no recurrent symptoms after revaccination. • Patients with COVID-19 vaccine hypersensitivity reactions can be safely revaccinated. COVID-19 vaccination has been associated with anaphylaxis and hypersensitivity reactions. Infectious disease physicians and allergists in the Canadian Special Immunization Clinic (SIC) Network developed guidance for evaluating patients with adverse events following immunization (AEFI) including suspected hypersensitivity. This study evaluated management and adverse event recurrence following subsequent COVID-19 vaccinations. Individuals aged 12 years and older enrolled at participating SICs before February 28, 2023 who were referred for suspected or diagnosed hypersensitivity reaction following COVID-19 vaccination, or for prevaccination assessment of suspected allergy to a COVID-19 vaccine component were included. De-identified clinical assessments and revaccination data, captured in a centralized database, were analyzed. The Brighton Collaboration case definition (BCCD) for anaphylaxis (2023 version) was applied. The analysis included 206 participants from 13 sites: 26 participants referred for pre-vaccination assessment and 180 participants referred for adverse events following COVID-19 vaccination (15/180 [8.3%] with BCCD confirmed anaphylaxis, 84 [46.7%] with immediate hypersensitivity symptoms not meeting BCCD, 33 [18.3%] with other diagnosed hypersensitivity reactions, and 48 [26.7%] participants with a final diagnosis of non-hypersensitivity AEFI). Among participants referred for AEFIs following COVID-19 vaccination, 166/180 (92.2%) were recommended for COVID-19 revaccination after risk assessment, of whom 158/166 (95.2%) were revaccinated (all with a COVID-19 mRNA vaccine). After revaccination, 1/15 (6.7%) participants with prior anaphylaxis, 1/77 (1.3%) with immediate hypersensitivity not meeting criteria for anaphylaxis and 1/24 (4.2%) with other physician diagnosed hypersensitivity developed recurrent AEFI symptoms that met the BCCD for anaphylaxis. All 26 participants referred pre-vaccination, including 9 (34.6%) with history of polyethylene glycol-asparaginase reactions, were vaccinated without occurrence of immediate hypersensitivity symptoms. Most individuals in this national cohort who experienced a hypersensitivity event following COVID-19 vaccination and were referred for specialist review were revaccinated without AEFI recurrence, suggesting that specialist evaluation can facilitate safe revaccination. [ABSTRACT FROM AUTHOR]

Author(s): Anja Bilandzic 1, Tiffany Fitzpatrick 2, Laura Rosella 1,3,4, David Henry 1,4,5,* Introduction Well-conducted randomized controlled trials (RCTs) remain the gold standard for assessing medical interventions because their design [...], Background Systematic reviews of the effects of healthcare interventions frequently include non-randomized studies. These are subject to confounding and a range of other biases that are seldom considered in detail when synthesizing and interpreting the results. Our aims were to assess the reliability and usability of a new Cochrane risk of bias (RoB) tool for non-randomized studies of interventions and to determine whether restricting analysis to studies with low or moderate RoB made a material difference to the results of the reviews. Methods and Findings We selected two systematic reviews of population-based, controlled non-randomized studies of the relationship between the use of thiazolidinediones (TZDs) and cyclooxygenase-2 (COX-2) inhibitors and major cardiovascular events. Two epidemiologists applied the Cochrane RoB tool and made assessments across the seven specified domains of bias for each of 37 component studies. Inter-rater agreement was measured using the weighted Kappa statistic. We grouped studies according to overall RoB and performed statistical pooling for (a) all studies and (b) only studies with low or moderate RoB. Kappa scores across the seven bias domains ranged from 0.50 to 1.0. In the COX-2 inhibitor review, two studies had low overall RoB, 14 had moderate RoB, and five had serious RoB. In the TZD review, six studies had low RoB, four had moderate RoB, four had serious RoB, and two had critical RoB. The pooled odds ratios for myocardial infarction, heart failure, and death for rosiglitazone versus pioglitazone remained significantly elevated when analyses were confined to studies with low or moderate RoB. However, the estimate for myocardial infarction declined from 1.14 (95% CI 1.07-1.24) to 1.06 (95% CI 0.99-1.13) when analysis was confined to studies with low RoB. Estimates of pooled relative risks of cardiovascular events with COX-2 inhibitors compared with no nonsteroidal anti-inflammatory drug changed little when analyses were confined to studies with low or moderate RoB. The exception was a rise in the relative risk associated with ibuprofen from 1.07 (95% CI 0.97-1.18) to 1.14 (95% CI 1.03-1.26). The main limitation of our study was testing the instrument on a narrow range of pharmacoepidemiological studies; we cannot assume our findings extend to a broader range of interventions and settings. Conclusions The Cochrane RoB tool highlighted a wide range of risks of bias in studies included in two widely cited reviews and had the potential to change the conclusions of the reviews. Systematic reviews that incorporate non-randomized studies of medical interventions should include a detailed assessment of RoB for each included study.

Canada's experience with the coronavirus disease-2019 (COVID-19) pandemic has been characterized by considerable regional variation, as would be expected in a highly decentralized federation. Yet, the country has been beset by challenges, similar to many of those documented in the severe acute respiratory syndrome outbreak of 2003. Despite a high degree of pandemic preparedness, the relative success with flattening the curve during the first wave of the pandemic was not matched in much of Canada during the second wave. This paper critically reviews Canada's response to the COVID-19 pandemic with a focus on the role of the federal government in this public health emergency, considering areas within its jurisdiction (international borders), areas where an increased federal role may be warranted (long-term care), as well as its technical role in terms of generating evidence and supporting public health surveillance, and its convening role to support collaboration across the country. This accounting of the first 12 months of the pandemic highlights opportunities for a strengthened federal role in the short term, and some important lessons to be applied in preparing for future pandemics. [ABSTRACT FROM AUTHOR]

Abstract Background The potential benefits of coordinating infectious disease eradication programs that use campaigns such as supplementary immunization activities (SIAs) should not be over-looked. One example of a coordinated approach is an adaptive "sequential strategy": first, all annual SIA budget is dedicated to the eradication of a single infectious disease; once that disease is eradicated, the annual SIA budget is re-focussed on eradicating a second disease, etc. Herd immunity suggests that a sequential strategy may eradicate several infectious diseases faster than a non-adaptive "simultaneous strategy" of dividing annual budget equally among eradication programs for those diseases. However, mathematical modeling is required to understand the potential extent of this effect. Methods Our objective was to illustrate how budget allocation strategies can interact with the nonlinear nature of disease transmission to determine time to eradication of several infectious diseases under different budget allocation strategies. Using a mathematical transmission model, we analyzed three hypothetical vaccine-preventable infectious diseases in three different countries. A central decision-maker can distribute funding among SIA programs for these three diseases according to either a sequential strategy or a simultaneous strategy. We explored the time to eradication under these two strategies under a range of scenarios. Results For a certain range of annual budgets, all three diseases can be eradicated relatively quickly under the sequential strategy, whereas eradication never occurs under the simultaneous strategy. However, moderate changes to total SIA budget, SIA frequency, order of eradication, or funding disruptions can create disproportionately large differences in the time and budget required for eradication under the sequential strategy. We find that the predicted time to eradication can be very sensitive to small differences in the rate of case importation between the countries. We also find that the time to eradication of all three diseases is not necessarily lowest when the least transmissible disease is targeted first. Conclusions Relatively modest differences in budget allocation strategies in the near-term can result in surprisingly large long-term differences in time required to eradicate, as a result of the amplifying effects of herd immunity and the nonlinearities of disease transmission. More sophisticated versions of such models may be useful to large international donors or other organizations as a planning or portfolio optimization tool, where choices must be made regarding how much funding to dedicate to different infectious disease eradication efforts.

Background Inappropriate antibiotic prescribing, such as for viral illness, remains common in primary care. The objective of this study was to estimate the proportion of community-prescribed antibiotics to children aged less than 5 years attributable to common respiratory viruses. Methods We fitted time-series negative binomial models to predict weekly antibiotic prescribing rates from positive viral pathogen tests for the period 1 April 2009 through 27 December 2017 using comprehensive, population-based administrative data for all children (<5 years) living in Scotland. Multiple respiratory viral pathogens were considered, including respiratory syncytial virus (RSV), influenza, human metapneumovirus (HMPV), rhinovirus, and human parainfluenza (HPIV) types 1–4. We estimated the proportion of antibiotic prescriptions explained by virus circulation according to type of virus, by age group, presence of high-risk chronic conditions, and antibiotic class. Results We included data on 6 066 492 antibiotic prescriptions among 452 877 children. The antibiotic-prescribing rate among all Scottish children (<5 years) was 609.7 per 1000 child-years. Our final model included RSV, influenza, HMPV, HPIV-1, and HPIV-3. An estimated 6.9% (95% confidence interval, 5.6–8.3%), 2.4% (1.7–3.1%), and 2.3% (.8–3.9%) of antibiotics were attributable to RSV, influenza, and HMPV, respectively. RSV was consistently associated with the highest proportion of prescribed antibiotics, particularly among children without chronic conditions and for amoxicillin and macrolide prescriptions. Conclusions Nearly 14% of antibiotics prescribed to children in this study were estimated to be attributable to common viruses for which antibiotics are not recommended. A future RSV vaccine could substantially reduce unnecessary antibiotic prescribing among children. [ABSTRACT FROM AUTHOR]

Gestational age is often incompletely recorded in administrative records, despite being critical to paediatric and maternal health research. Several algorithms exist to estimate gestational age using administrative databases; however, many have not been validated or use complicated methods that are not readily adaptable. We developed a simple algorithm to estimate common gestational age categories from routine administrative data. We leveraged a population-based registry of all hospital births occurring in Ontario, Canada over 2002-2016 including 1.8 million birth records. In this sample, this simple algorithm had excellent performance compared to a verified measure of gestational age; 87.61% agreement (95% CI: 87.49, 87.74). The accuracy of the algorithm exceeded 98% for all of the gestational age categories. Agreement notably increased over time and was greatest among singleton births and infants born at 2500-2999 g. This study provides a straight-forward algorithm for accurately estimating common gestational age categories that is easily adaptable for use in other countries.Impact StatementWhat is already known on this subject? Gestational age is often incompletely or inaccurately recorded in administrative health databases, despite being critical to the study of many paediatric and maternal health outcomes. Consequently, researchers must rely on various methods to estimate gestational age, many of these methods are either overly simple (i.e. assuming a uniform duration) or analytically complicated and difficult to adapt for new populations (e.g. regression-based approaches).What the results of this study add? This study, based on a population-based registry of all 1.8 million births occurring in Ontario, Canada 2003-2016, found that a simple, sex-specific algorithm using three commonly recorded birth record characteristics performs almost perfectly compared to a clinical estimate recorded near birth.What the implications are of these findings for clinical practice and/or further research? This study suggests that a straight-forward, sex-specific algorithm based on routinely collected birth record data is able to accurately estimate common gestational age categories (i.e. extreme preterm, <28 weeks; very preterm, 28-32 weeks; moderate-to-late preterm, 33-26 weeks; and term, 37 weeks of completed gestational age). This work will be of greatest interest to perinatal researchers using routinely collected health administrative data. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the effectiveness of two palivizumab programmes targeting high-risk infants, defined by prematurity, diagnosis of comorbidities and geography, and assess potential disparities by neighbourhood income.Design: Controlled, interrupted time series.Setting: Ontario, Canada.Patients: We used linked health and demographic administrative databases to identify all children born in hospitals 1 January 1993 through 31 December 2016. Follow-up ended at the earliest of second birthday or 30 June 2017.Intervention: Palivizumab-eligibility: child was born very preterm and ≤6 months old during respiratory syncytial virus (RSV) season; <24 months old with significant chronic lung or congenital heart disease; or ≤6 months, born preterm or residents of remote regions.Main Outcome: Severe RSV-related illness, defined as hospitalisation or death with a diagnosis of bronchiolitis, RSV pneumonia or RSV.Results: 3 million births and 87 000 RSV-related events were identified. Over the study period, rates of severe RSV-related illness declined 65.4% among the highest risk group, eligible infants <6 months (230.6 to 79.8 admissions per 1000 child-years). Relative to changes among ineligible infants <6 months, rates dropped 10.4% (95% CI -18.6% to 39.4%) among eligible infants immediately following introduction of a national palivizumab programme in 1998. Initially, rates were considerably higher among infants from low-income neighbourhoods, but income-specific rates converged over time among eligible infants <6 months; such convergence was not seen among other children.Conclusions: Incidence of severe RSV-related illness declined over the study period. While we cannot attribute causality, the timing and magnitude of these declines suggest impact of palivizumab in reducing RSV burden and diminishing social inequities among palivizumab-eligible infants. [ABSTRACT FROM AUTHOR]

Aim: To determine factors associated with a serious outcome (hospital admission or severe outcome: critical care or death) and associated with illness caused by laboratory‐confirmed influenza, with a specific interest in low‐ and middle‐income countries (LMIC). Method: Databases were searched on 11 March 2016 for reports of influenza and factors associated with mortality or morbidity in humans, with no language restrictions. Pooled risks were estimated using random‐effects models. Results: Despite the heterogeneity of results across studies, known risk factors for serious disease were associated with both hospital admission and severe outcomes (critical care and/or death). In LMIC, but not in high income countries (HIC), pregnant women, people with HIV/AIDS and children < 5 years old (compared with older children) were at increased risk of a severe outcome. Also, although all patients with neurological conditions were at higher risk of severe outcomes than those without, children were at higher risk than adults and children who lived in a LMIC were at significantly higher risk than those living in HIC. Adults were more likely than children to suffer a severe outcome if they had diabetes or a hematologic condition, were obese or had liver disease. Asthma is a risk factor for hospital admission but not for severe outcomes. Conclusion: Known risk factors for serious disease remain important predictors of hospital admission and severe outcomes with few differences between HIC and LMIC countries. These differences likely reflect differences in health‐seeking behaviours and health services, but high heterogeneity between studies limits conclusions about the effect size. [ABSTRACT FROM AUTHOR]