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Objective To examine the association between maternal mRNA covid-19 vaccination during the first trimester of pregnancy and the prevalence of major congenital anomalies in offspring.Design Population based cohort study with sibling matched analysis.Setting Multiple health administrative databases, linked and analysed at ICES, an independent, non-profit research institute that collects and analyses healthcare and demographic data, Ontario, Canada, from 16 October 2021 to 1 May 2023.Population 174 296 singleton live births >20 weeks' gestation with an expected birth date between 16 October 2021 and 1 May 2023: 34 181 (20%) born to mothers who received one or two doses of an mRNA covid-19 vaccine in the first trimester and 34 951 (20%) born to mothers who did not receive a vaccine before or during pregnancy. The sibling matched analysis included 13 312 infants exposed to a covid-19 vaccine in the first trimester and 15 089 matched older siblings with the same mother, with an expected birth date after 16 October 2016 and no reported in utero exposure to a covid-19 vaccine.Main outcome measures Major congenital anomalies, overall and grouped by specific organ systems, diagnosed within 28 days of birth.Results Major congenital anomalies were present in 832 (24.3 per 1000 live births) infants exposed to an mRNA covid-19 vaccine in the first trimester compared with 927 (26.5 per 1000 live births) infants not exposed to a vaccine, resulting in an adjusted prevalence ratio of 0.89 (95% confidence interval (CI) 0.79 to 1.01). Major congenital anomalies were present in 283 (21.3 per 1000 live births) and 343 (22.7 per 1000 live births) infants exposed to an mRNA covid-19 vaccine in the first trimester and their older siblings not exposed to a vaccine, respectively (adjusted prevalence ratio 0.91, 95% CI 0.77 to 1.07). First trimester vaccination was not associated with an increase in major congenital anomalies grouped by specific organ system in the primary or sibling matched analyses. Results were similar across a range of subgroup and sensitivity analyses.Conclusions In this large population based cohort study and sibling matched analysis, mRNA covid-19 vaccination during the first trimester of pregnancy was not associated with an increase in major congenital anomalies in offspring, overall or grouped by organ system.

Objective Health administrative data can support population-level research among people who inject drugs (PWID), however these data sources remain underutilized due to the difficulty in identifying drug use in routinely collected data. We validated case-ascertainment algorithms to identify PWID and tested their application in a hepatitis C (HCV) cohort in Ontario, Canada. Approach We conducted a validation study using reference standard cohorts of PWID recruited via community-based studies and population controls linked to health administrative data in Ontario, Canada (1992-2020). Tested case-ascertainment algorithms included combinations of hospitalizations/emergency department (ED) visits for drug use/poisoning, physician visits for drug use, opioid agonist treatment (OAT), or injecting-related infections. Sensitivity and specificity were estimated for lifetime history and recent injecting (past 1-5 years). We applied a high-performing algorithm among all Ontarians with laboratory-confirmed HCV between 1999-2018, to identify a sub-cohort of PWID with HCV. Results An algorithm including ≥1 hospitalization/ED visit or ≥1 physician visit for drug use or ≥1 OAT record had high accuracy for identifying IDU history (91.6% sensitivity, 94.2% specificity) and recent IDU (using 3 years lookback: 80.4% sensitivity, 99% specificity). When applied to a provincial cohort of 112,947 Ontarians diagnosed with HCV, this algorithm estimated 46% (N=52,248) had a history of IDU, of whom 52% (N=27,246) had an indication of recent IDU (within the past 3 years). Conclusion The methods developed in this study can enhance the capacity of population-level health research among people who inject drugs and support applied public health interventions towards hepatitis C elimination.

BackgroundSARS-CoV-2 variants of concern (VOCs) emerged and rapidly replaced the original strain worldwide. The increased transmissibility of these new variants led to increases in infections, hospitalizations, and mortality. However, there is a scarcity of retrospective investigations examining the severity of all the main VOCs in presence of key public health measures and within various social determinants of health (SDOHs). ObjectiveThis study aims to provide a retrospective assessment of the clinical severity of COVID-19 VOCs in the context of heterogenous SDOHs and vaccination rollout. MethodsWe used a population-based retrospective cohort design with data from the British Columbia COVID-19 Cohort, a linked provincial surveillance platform. To assess the relative severity (hospitalizations, intensive care unit [ICU] admissions, and deaths) of Gamma, Delta, and Omicron infections during 2021 relative to Alpha, we used inverse probability treatment weighted Cox proportional hazard modeling. We also conducted a subanalysis among unvaccinated individuals, as assessed severity differed across VOCs and SDOHs. ResultsWe included 91,964 individuals infected with a SARS-CoV-2 VOC (Alpha: n=20,487, 22.28%; Gamma: n=15,223, 16.55%; Delta: n=49,161, 53.46%; and Omicron: n=7093, 7.71%). Delta was associated with the most severe disease in terms of hospitalization, ICU admissions, and deaths (hospitalization: adjusted hazard ratio [aHR] 2.00, 95% CI 1.92-2.08; ICU: aHR 2.05, 95% CI 1.91-2.20; death: aHR 3.70, 95% CI 3.23-4.25 relative to Alpha), followed generally by Gamma and then Omicron and Alpha. The relative severity by VOC remained similar in the unvaccinated individual subanalysis, although the proportion of individuals infected with Delta and Omicron who were hospitalized was 2 times higher in those unvaccinated than in those fully vaccinated. Regarding SDOHs, the proportion of hospitalized individuals was higher in areas with lower income across all VOCs, whereas among Alpha and Gamma infections, 2 VOCs that cocirculated, differential distributions of hospitalizations were found among racially minoritized groups. ConclusionsOur study provides robust severity estimates for all VOCs during the COVID-19 pandemic in British Columbia, Canada. Relative to Alpha, we found Delta to be the most severe, followed by Gamma and Omicron. This study highlights the importance of targeted testing and sequencing to ensure timely detection and accurate estimation of severity in emerging variants. It further sheds light on the importance of vaccination coverage and SDOHs in the context of pandemic preparedness to support the prioritization of allocation for resource-constrained or minoritized groups.

BackgroundEvidence on protection of different patterns of infection- and vaccine-acquired immunity against Omicron-associated severe illness is useful in planning booster vaccination strategies. We examined protection of prior SARS-CoV-2 infection, a third or a fourth COVID-19 vaccine dose, and hybrid immunity against Omicron-associated severe illness.Methods and findingsThis population-based cohort study followed five million individuals with at least one SARS-CoV-2 RT-PCR test before November 21, 2021 until an Omicron-associatedhospitalization or death. We used Cox regression models to estimate risks of Omicron-associated hospitalization and a composite severe outcome (hospitalized and death), among individuals with infection- and/or vaccination-acquired immunity. Individuals who were unvaccinated and had no history of a prior infection severed as the reference group. Both adjusted hazard ratios (HR) and corresponding protection (one minus adjusted HR), with 95% confidence intervals (CIs), were reported. Three doses provided 94% (95%CI 93-95) and 93% (95%CI 91-94) protection against Omicron-associated hospitalization at 2-3 and ≥3 months post-vaccination respectively, similar to the protection conferred by three doses and a prior infection (2-3 months: 99%, 95%CI 97-100; ≥3 months: 97%, 95%CI 92-99) and four doses (1 month: 87%, 95%CI 79-92; 1-2 months: 96%, 95%CI 92-98). In individuals ≥65 years old, protection of four doses increased to 95% (95%CI 91-98) at 1-2 months, significantly higher than that of three doses over the follow-up period. Similar results were observed with the composite severe outcome.ConclusionAt least three antigenic exposures, achieved by vaccination or infection, confers significant protection against Omicron-associated hospitalization and death in all age groups. Our findings support a third dose for the overall population, regardless of prior infection status, and a fourth dose for the elderly to maintain high level of immunity and substantially reduce risk of severe illness at individual level.

Introduction The WHO has stated that vaccine hesitancy is a serious threat to overcoming COVID-19. Vaccine hesitancy among underserved and at-risk communities is an ongoing challenge in Canada. Public confidence in vaccine safety and effectiveness and the principles of equity need to be considered in vaccine distribution. In Canada, governments of each province or territory manage their own healthcare system, providing an opportunity to compare and contrast distribution strategies. The overarching objective of this study is to identify effective vaccine distribution approaches and advance knowledge on how to design and implement various strategies to meet the different needs of underserved communities.Methods and analysis Multiple case studies in seven Canadian provinces will be conducted using a mixed-methods design. The study will be informed by Experience-Based CoDesign techniques and theoretically guided by the Socio-Ecological Model and the Vaccine Hesitancy Matrix frameworks. Phase 1 will involve a policy document review to systematically explore the vaccine distribution strategy over time in each jurisdiction. This will inform the second phase, which will involve (2a) semistructured, in-depth interviews with policymakers, public health officials, researchers, providers, groups representing patients, researchers and stakeholders and (2b) an analysis of population-based administrative health data of vaccine administration. Integration of qualitative and quantitative data will inform the identification of effective vaccine distribution approaches for various populations. Informed by this evidence, phase 3 of the study will involve conducting focus groups with multiple stakeholders to codesign recommendations for the design and implementation of effective vaccine delivery strategies for equity-deserving and at-risk populations.Ethics and dissemination This study is approved by the University of Toronto’s Health Sciences Research Ethics Board (#42643), University of British Columbia Behavioural Research Ethics Board (#H22-01750-A002), Research Ethics Board of the Nova Scotia Health Authority (#48272), Newfoundland and Labrador Health Research Ethics Board (#2022.126), Conjoint Health Research Ethics Board, University of Calgary (REB22-0207), and University of Manitoba Health Research Board (H2022-239). The outcome of this study will be to produce a series of recommendations for implementing future vaccine distribution approaches from the perspective of various stakeholders, including equity-deserving and at-risk populations.

Objective To assess risk of adverse pregnancy, fetal, and neonatal outcomes after a third dose (first booster dose) of covid-19 vaccine during pregnancy among individuals who had completed both doses of primary covid-19 vaccine series before pregnancy.Design Population based, retrospective cohort study.Setting Ontario, Canada, from 20 December 2021 to 31 August 2022.Participants Individuals were included if they were pregnant with an expected date of delivery from 20 December 2021 (start date of third dose eligibility for everyone ≥18 years) to 31 August 2022, who had completed the two doses of primary covid-19 messenger RNA vaccine series before pregnancy, and became eligible for a third dose (≥six months since dose two) before the end of pregnancy.Main outcome measures Pregnancy outcomes included hypertensive disorders of pregnancy, placental abruption, caesarean delivery, chorioamnionitis, and postpartum hemorrhage. Fetal and neonatal outcomes included stillbirth, preterm birth, admission to neonatal intensive care unit for >24 h, newborn 5 min Apgar score

BackgroundWith the growing volume and complexity of laboratory repositories, it has become tedious to parse unstructured data into structured and tabulated formats for secondary uses such as decision support, quality assurance, and outcome analysis. However, advances in natural language processing (NLP) approaches have enabled efficient and automated extraction of clinically meaningful medical concepts from unstructured reports. ObjectiveIn this study, we aimed to determine the feasibility of using the NLP model for information extraction as an alternative approach to a time-consuming and operationally resource-intensive handcrafted rule-based tool. Therefore, we sought to develop and evaluate a deep learning–based NLP model to derive knowledge and extract information from text-based laboratory reports sourced from a provincial laboratory repository system. MethodsThe NLP model, a hierarchical multilabel classifier, was trained on a corpus of laboratory reports covering testing for 14 different respiratory viruses and viral subtypes. The corpus includes 87,500 unique laboratory reports annotated by 8 subject matter experts (SMEs). The classification task involved assigning the laboratory reports to labels at 2 levels: 24 fine-grained labels in level 1 and 6 coarse-grained labels in level 2. A “label” also refers to the status of a specific virus or strain being tested or detected (eg, influenza A is detected). The model’s performance stability and variation were analyzed across all labels in the classification task. Additionally, the model's generalizability was evaluated internally and externally on various test sets. ResultsOverall, the NLP model performed well on internal, out-of-time (pre–COVID-19), and external (different laboratories) test sets with microaveraged F1-scores >94% across all classes. Higher precision and recall scores with less variability were observed for the internal and pre–COVID-19 test sets. As expected, the model’s performance varied across categories and virus types due to the imbalanced nature of the corpus and sample sizes per class. There were intrinsically fewer classes of viruses being detected than those tested; therefore, the model's performance (lowest F1-score of 57%) was noticeably lower in the detected cases. ConclusionsWe demonstrated that deep learning–based NLP models are promising solutions for information extraction from text-based laboratory reports. These approaches enable scalable, timely, and practical access to high-quality and encoded laboratory data if integrated into laboratory information system repositories.

An underestimation of pertussis burden has impeded understanding of transmission and disallows effective policy and prevention to be prioritized and enacted. Capture-recapture analyses can improve burden estimates; however, uncertainty remains around incorporating health administrative data due to accuracy limitations. The aim of this study is to explore the impact of pertussis case definitions and data accuracy on capture-recapture estimates. We used a dataset from March 7, 2010 to December 31, 2017 comprised of pertussis case report, laboratory, and health administrative data. We compared Chao capture-recapture abundance estimates using prevalence, incidence, and adjusted false positive case definitions. The latter was developed by removing the proportion of false positive physician billing code-only case episodes after validation. We calculated sensitivity by dividing the number of observed cases by abundance. Abundance estimates demonstrated that a high proportion of cases were missed by all sources. Under the primary analysis, the highest sensitivity of 78.5% (95% CI 76.2-80.9%) for those less than one year of age was obtained using all sources after adjusting for false positives, which dropped to 43.1% (95% CI 42.4-43.8%) for those one year of age or older. Most code-only episodes were false positives (91.0%), leading to considerably lower abundance estimates and improvements in laboratory testing and case report sensitivity using this definition. Accuracy limitations can be accounted for in capture-recapture analyses using different case definitions and adjustment. The latter enhanced the validity of estimates, furthering the utility of capture-recapture methods to epidemiological research. Findings demonstrated that all sources consistently fail to detect pertussis cases. This is differential by age, suggesting ascertainment and testing bias. Results demonstrate the value of incorporating real time health administrative data into public health surveillance if accuracy limitations can be addressed.

BackgroundThe effects of the COVID-19 pandemic have been more pronounced for socially disadvantaged populations. We sought to determine how access to SARS-CoV-2 testing and the likelihood of testing positive for COVID-19 were associated with demographic factors, socioeconomic status (SES) and social determinants of health (SDH) in three Canadian provinces.MethodsAn observational population-based cross-sectional study was conducted for the provinces of Ontario, Manitoba and New Brunswick between March 1, 2020 and April 27, 2021, using provincial health administrative data. After excluding residents of long-term care homes, those without current provincial health insurance and those who were tested for COVID-19 out of province, records from provincial healthcare administrative databases were reviewed for 16,900,661 healthcare users. Data was modelled separately for each province in accordance to a prespecified protocol and follow-up consultations among provincial statisticians and collaborators. We employed univariate and multivariate regression models to examine determinants of testing and test results.ResultsAfter adjustment for other variables, female sex and urban residency were positively associated with testing, while female sex was negatively associated with test positivity. In New Brunswick and Ontario, individuals living in higher income areas were more likely to be tested, whereas in Manitoba higher income was negatively associated with both testing and positivity. High ethnocultural composition was associated with lower testing rates. Both high ethnocultural composition and high situational vulnerability increased the odds of testing positive for SARS-CoV-2.DiscussionWe observed that multiple demographic, income and SDH factors were associated with SARS-CoV-2 testing and test positivity. Barriers to healthcare access identified in this study specifically relate to COVID-19 testing but may reflect broader inequities for certain at-risk groups.

Summary: Background: People experiencing homelessness face a high risk of SARS-CoV-2 infection and transmission, as well as health complications and death due to COVID-19. Despite being prioritised for receiving the COVID-19 vaccine in many regions, little data are available on vaccine uptake in this vulnerable population. Using population-based health-care administrative data from Ontario, Canada—a region with a universal, publicly funded health system—we aimed to describe COVID-19 vaccine coverage (ie, the estimated percentage of people who have received a vaccine) and determinants of vaccine receipt among individuals with a recent history of homelessness. Methods: We conducted a retrospective, population-based cohort study of adults (aged ≥18 years) with a recent experience of homelessness, inadequate housing, or shelter use as recorded in routinely collected health-care databases between June 14, 2020, and June 14, 2021 (a period within 6 months of Dec 14, 2020, when COVID-19 vaccine administration was initiated in Ontario). Participants were followed up from Dec 14, 2020, to Sept 30, 2021, for the receipt of one or two doses of a COVID-19 vaccine using the province's real-time centralised vaccine information system. We described COVID-19 vaccine coverage overall and within predefined subgroups. Using modified Poisson regression, we further identified sociodemographic factors, health-care usage, and clinical factors associated with receipt of at least one dose of a COVID-19 vaccine. Findings: 23 247 individuals with a recent history of homelessness were included in this study. Participants were predominantly male (14 752 [63·5%] of 23 247); nearly half were younger than 40 years (11 521 [49·6%]) and lived in large metropolitan regions (12 123 [52·2%]); and the majority (18 226 [78·4%]) visited a general practitioner for an in-person consultation during the observation period. By Sept 30, 2021, 14 271 (61·4%; 95% CI 60·8–62·0) individuals with a recent history of homelessness had received at least one dose of a COVID-19 vaccine and 11 082 (47·7%; 47·0–48·3) had received two doses; in comparison, over the same period, 86·6% of adults in the total Ontario population had received a first dose and 81·6% had received a second dose. In multivariable analysis, factors positively associated with COVID-19 uptake were one or more outpatient visits to a general practitioner (adjusted risk ratio [aRR] 1·37 [95% CI 1·31–1·42]), older age (50–59 years vs 18–29 years: 1·18 [1·14–1·22], ≥60 years vs 18–29 years: 1·27 [1·22–1·31]), receipt of an influenza vaccine in either of the two previous influenza seasons (1·25 [1·23–1·28]), being identified as homeless via a visit to a community health centre versus exclusively a hospital-based encounter (1·13 [1·10–1·15]), receipt of one or more SARS-CoV-2 tests between March 1, 2020, and Sept 30, 2021 (1·23 [1·20–1·26]), and the presence of chronic health conditions (one condition: 1·05 [1·03–1·08]; two or more conditions: 1·11 [1·08–1·14]). By contrast, living in a smaller metropolitan region (aRR 0·92 [95% CI 0·90–0·94]) or rural location (0·93 [0·90–0·97]) versus large metropolitan regions were associated with lower uptake. Interpretation: In Ontario, COVID-19 vaccine coverage among adults with a recent history of homelessness has lagged and, as of Sept 30, 2021, was 25 percentage points lower than that of the general adult population in Ontario for a first dose and 34 percentage points lower for a second dose. With high usage of outpatient health services among individuals with a recent history of homelessness, better utilisation of outpatient primary care structures might offer an opportunity to increase vaccine coverage in this population. Our findings underscore the importance of leveraging existing health and service organisations that are accessed and trusted by people who experience homelessness for targeted vaccine delivery. Funding: The Public Health Agency of Canada. Translation: For the French translation of the abstract see Supplementary Materials section.

Summary: Background: Cirrhosis is the result of advanced scarring (or fibrosis) of the liver, and is often diagnosed once decompensation with associated complications has occurred. Current non-invasive tests to detect advanced liver fibrosis have limited performance, with many indeterminate classifications. We aimed to identify patients with advanced liver fibrosis of all-causes using machine learning algorithms (MLAs). Methods: In this retrospective study of routinely collected laboratory, clinical, and demographic data, we trained six MLAs (support vector machine, random forest classifier, gradient boosting classifier, logistic regression, artificial neural network, and an ensemble of all these algorithms) to detect advanced fibrosis using 1703 liver biopsies from patients seen at the Toronto Liver Clinic (TLC) between Jan 1, 2000, and Dec 20, 2014. Performance was validated using five datasets derived from patient data provided by the TLC (n=104 patients with a biopsy sample taken between March 24, 2014, and Dec 31, 2017) and McGill University Health Centre (MUHC; n=404). Patients with decompensated cirrhosis were excluded. Performance was benchmarked against aspartate aminotransferase-to-platelet ratio index (APRI), fibrosis-4 index (FIB-4), non-alcoholic fatty liver disease fibrosis score (NFS), transient elastography, and an independent panel of five hepatology experts (MB, GS, HK, KP, and RSK). MLA performance was evaluated using the area under the receiver operating characteristic curve (AUROC) and the percentage of determinate classifications. Findings: The best MLA was an ensemble algorithm of support vector machine, random forest classifier, gradient boosting classifier, logistic regression, and neural network algorithms, which achieved 100% determinate classifications (95% CI 100·0–100·0), an AUROC score of 0·870 (95% CI 0·797–0·931) on the TLC validation set (fibrosis stages F0 and F1 vs F4), and an AUROC of 0·716 (95% CI 0·664–0·766) on the MUHC validation set (fibrosis stages F0, F1, and F2 vs F3 and F4). The ensemble MLA outperformed all routinely used biomarkers and achieved comparable performance to hepatologists as measured by AUROC and percentage of indeterminate classifications in both the TLC validation dataset (APRI AUROC score 0·719 [95% CI 0·611–0·820], 83·7% determinate [95% CI 76·0–90·4]; FIB-4 AUROC score 0·825 [95% CI 0·730–0·912], 72·1% determinate [95% CI 63·5–80·8]) and the MUHC validation dataset (APRI AUROC score 0·618 [95% CI 0·548–0·691], 75·5% determinate [95% CI 71·5–79·2]; FIB-4 AUROC score 0·717 (95% CI 0·652–0·776), 75·5% determinate [95% CI 0·713–0·797]), and achieving only slightly lower AUROC than transient elastography (0·773 [95% CI 0·699–0·834] vs 0·826 [95% CI 0·758–0·889]). Interpretation: We have shown that an ensemble MLA outperforms non-imaging-based methods in detecting advanced fibrosis across different causes of liver disease. Our MLA was superior to APRI, FIB-4, and NFS with no indeterminate classifications, while achieving performance comparable to an independent panel of experts. MLAs using routinely collected data could identify patients at high-risk of advanced hepatic fibrosis and cirrhosis among patients with chronic liver disease, allowing intervention before onset of decompensation. Funding: Toronto General Hospital Foundation.

Background There is a paucity of data on the burden of the full spectrum of community-acquired pneumonia (CAP) and acute otitis media (AOM) from outpatient and inpatient settings across the age spectrum.Methods We conducted a population-based retrospective study in Ontario and British Columbia (BC), Canada, to estimate the incidence rate of CAP and AOM in children and adults over a 14-year period using health administrative databases. CAP and AOM cases were identified from outpatient physician consultation and hospitalisation data in both provinces, and from emergency department visit data in Ontario.Results During 2005–2018, Ontario had 3 607 124 CAP, 172 290 bacterial CAP, 7814 pneumococcal pneumonia, and 8 026 971 AOM cases. The incidence rate of CAP declined from 3077/100 000 in 2005 to 2604/100 000 in 2010 before increasing to 2843/100 000 in 2018; bacterial CAP incidence rate also declined from 178/100 000 in 2005 to 112/100 000 in 2010 before increasing to 149/100 000 in 2018. The incidence rate of AOM decreased from 4192/100 000 in 2005 to 3178/100 000 in 2018. BC had 970 455 CAP, 317 913 bacterial CAP, 35 287 pneumococcal pneumonia and 2 022 871 AOM cases. The incidence rate of CAP in BC decreased from 2214/100 000 in 2005 to 1964/100 000 in 2010 before increasing to 2176/100 000 in 2018; bacterial CAP incidence rate increased from 442/100 000 in 2005 to 981/100 000 in 2018. The incidence rate of AOM decreased from 3684/100 000 in 2005 to 2398/100 000 in 2018. The incidence rate of bacterial CAP increased with age in older adults (≥65 years) with the highest burden in the oldest cohort aged ≥85 years both before and after 13-valent pneumococcal conjugate vaccine (PCV13) programme in both provinces. Hospitalised pneumococcal pneumonia decreased slightly but non-hospitalised pneumococcal pneumonia increased in BC during PCV13 period. No consistent direct benefit of PCV13 on CAP was observed in the paediatric population.Conclusions There is a substantial burden of CAP and AOM in Ontario and BC. Indirect benefits from childhood PCV vaccination and polysaccharide vaccination of older adults have not substantially decreased the burden of pneumococcal pneumonia in older adults.

BackgroundAnecdotally there are reports of newly diagnosed SARS-CoV-2 infection shortly after vaccination. This has led some to speculate that vaccination itself might inadvertently increase the short-term risk of COVID potentially due to airborne spread at mass vaccination clinics or relaxation of precautions following vaccination. We explored whether receipt of vaccination was associated with a short-term increase in the risk of being diagnosed with COVID-19 and if differences exist between vaccination settings.MethodsWe conducted a cohort study in Ontario, Canada to compare the risk of SARS-CoV-2 infection within 21 days of receiving a first vaccination, according to the setting in which vaccines were administered between March 1, 2021 and May 6, 2021. We used linked population-wide vaccination, laboratory testing, and health administrative databases. We created a 1:1 matched comparison group of unexposed individuals. We reported the overall risk of infection calculated at 3, 7, 10, 14, 18, and 21 days. This was completed overall and by setting of vaccine receipt.ResultsWe identified 4,798,430 Ontario residents who received their first dose of a COVID-19 vaccine. In the primary analysis, the rate of SARS-CoV-2 infection was significantly lower among vaccine recipients vs non-recipients at all the post-vaccination time points. Analysis stratified by vaccination setting found that mass vaccination clinics, pharmacies, and physician offices were consistent with the main findings. Individuals who received their first vaccine dose in congregate residential settings had a higher rate of SARS-CoV-2 infection at 7 days (HR 1.35, 95% CI 1.00-1.83) and 10 days (HR 1.49, 95% CI 1.03-2.15).ConclusionIn this population-based cohort study, we found that there was no increased risk of SARS-CoV2 infection after vaccination suggesting no broad transmission of disease at time of vaccination. Some evidence of increased risk among those vaccinated in congregate settings, highlighting the need to consider opportunities for supporting safe vaccine administration in these settings. Given ongoing and future immunization programs, the results support the need for continued vigilance during any mass vaccination processes and education regarding the delayed nature of protection following vaccination.

Introduction Health care systems have faced unprecedented challenges due to the COVID-19 pandemic. Access to timely population-based data has been vital to informing public health policy and practice. Methods We describe how ICES, an independent not-for-profit research and analytic institute in Ontario, Canada, pivoted existing research infrastructure and engaged health system stakeholders to provide near real-time population-based data and analytics to support Ontario's COVID-19 pandemic response. Results Since April 2020, ICES provided the Ontario COVID-19 Provincial Command Table and public health partners with regular and ad hoc reports on SARS-CoV-2 testing and COVID-19 vaccine coverage. These reports: 1) helped identify congregate care/shared living settings that needed testing and prevention efforts early in the pandemic; 2) provided early indications of inequities in testing and infection in marginalized neighbourhoods, including areas with higher proportions of immigrants and visible minorities; 3) identified areas with high test positivity, which helped Public Health Units target and evaluate prevention efforts; and 4) contributed to altering the province's COVID-19 vaccine roll-out strategy to target high-risk neighbourhoods and helping Public Health Units and community organizations plan local vaccination programs. In addition, ICES is a key component of the Ontario Health Data Platform, which provides scientists with data access to conduct COVID-19 research and analyses. Discussion and Conclusion ICES was well-positioned to provide rapid analyses for decision-makers to respond to the evolving public health emergency, and continues to contribute to Ontario's pandemic response by providing timely, relevant reports to health system stakeholders and facilitating data access for externally-funded COVID-19 research.

ObjectiveRoutinely collected health administrative data can be used to efficiently assess disease burden in large populations, but it is important to evaluate the validity of these data. The objective of this study was to develop and validate International Classification of Disease 10th revision (ICD -10) algorithms that identify laboratory-confirmed influenza or laboratory-confirmed respiratory syncytial virus (RSV) hospitalizations using population-based health administrative data from Ontario, Canada.Study design and settingInfluenza and RSV laboratory data from the 2014-15, 2015-16, 2016-17 and 2017-18 respiratory virus seasons were obtained from the Ontario Laboratories Information System (OLIS) and were linked to hospital discharge abstract data to generate influenza and RSV reference cohorts. These reference cohorts were used to assess the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of the ICD-10 algorithms. To minimize misclassification in future studies, we prioritized specificity and PPV in selecting top-performing algorithms.Results83,638 and 61,117 hospitalized patients were included in the influenza and RSV reference cohorts, respectively. The best influenza algorithm had a sensitivity of 73% (95% CI 72% to 74%), specificity of 99% (95% CI 99% to 99%), PPV of 94% (95% CI 94% to 95%), and NPV of 94% (95% CI 94% to 95%). The best RSV algorithm had a sensitivity of 69% (95% CI 68% to 70%), specificity of 99% (95% CI 99% to 99%), PPV of 91% (95% CI 90% to 91%) and NPV of 97% (95% CI 97% to 97%).ConclusionWe identified two highly specific algorithms that best ascertain patients hospitalized with influenza or RSV. These algorithms may be applied to hospitalized patients if data on laboratory tests are not available, and will thereby improve the power of future epidemiologic studies of influenza, RSV, and potentially other severe acute respiratory infections.

IntroductionThere is an evidence gap regarding the duration of SARS-CoV-2 shedding and of its variability across different care settings and by age, sex, income, and co-morbidities. Such evidence is part of understanding of infectivity and reinfection. We examine direct measures of viral shedding using a linked population-based health administrative dataset.MethodsLaboratory and sociodemographic databases for Ontario, Canada were linked to identify those testing positive (RT-PCR) between Jan. 15 and April 30, 2020 who underwent subsequent testing by May 31, 2020. To maximise use of available data, we computed two shedding duration estimates defined as the time between initial positive and most recent positive (documented shedding) or second of two negative tests (documented resolution). We also report multivariable results using quantile regression to examine subgroup differences.ResultsIn Ontario, of the 16,595 who tested positive before April 30, 2020, 6604 had sufficient subsequent testing to allow shedding duration calculation. Documented shedding median duration calculated in 4,889 (29% of 16,595) patients was 19 days (IQR 12-28). Documented resolution median duration calculated in 3,219 (19% of the 16,595) patients was 25 days (IQR 18-34). Long-term care residents had 3-5 day longer shedding durations using both definitions. Shorter documented shedding durations of 2-4 days were observed in those living in higher income neighbourhoods. Shorter documented resolution durations of 2-3 days were observed at the 25th% of the distribution in those aged 20-49. Only 11.5% of those with definitive negative test results reverted to negative status by day 14.ConclusionsViral shedding continued well beyond 14 days among this large subset of a population-based group with COVID-19, and longer still for long-term care residents and those living in less affluent neighborhoods. Our findings do not speak to duration of infectivity but are useful for understanding the expected duration of RT-PCR positivity and for identifying reinfection.

ObjectiveTo determine 1-year attributable healthcare costs of bronchiolitis.MethodsUsing a population-based matched cohort and incidence-based cost analysis approach, we identified infants ResultsWe identified 58,375 infants with bronchiolitis (mean age 154±95 days, 61.3% males, 4.2% with comorbidities). Total 1-year mean bronchiolitis-attributable costs were $4,313 per patient (95%CI: $4,148-4,477), with $2,847 (95%CI: $2,712-2,982) spent on hospitalizations, $610 (95%CI: $594-627) on physician services, $562 (95%CI: $556-567)] on ED visits, $259 (95%CI: $222-297) on other healthcare costs and $35 ($27-42) on drugs. Attributable bronchiolitis costs were $2,765 (95%CI: $2735-2,794) vs $111 (95%CI: $102-121) in the initial 10 days post index date, $4,695 (95%CI: $4,589-4,800) vs $910 (95%CI: $847-973) in the initial 180 days and $1,158 (95%CI: $1,104-1213) vs $639 (95%CI: $599-679) during days 181-360. Mean 1-year bronchiolitis costs were higher in infants ConclusionsCompared to no bronchiolitis, bronchiolitis incurs five-time and two-time higher healthcare costs within the initial and subsequent six-months, respectively. Most expenses occur in the initial 10 days and relate to hospitalization.

BACKGROUND & OBJECTIVES:Vaccine safety signals require investigation, which may be done rapidly at the population level using ecological studies, before embarking on hypothesis-testing studies. Incidence rates were used to assess a signal of narcolepsy following AS03-adjuvanted monovalent pandemic H1N1 (pH1N1) influenza vaccination among children and adolescents in Sweden and Finland in 2010. We explored the utility of ecological data to assess incidence of narcolepsy following exposure to pandemic H1N1 virus or vaccination in 10 sites that used different vaccines, adjuvants, and had varying vaccine coverage. METHODS:We calculated incidence rates of diagnosed narcolepsy for periods defined by influenza virus circulation and vaccination campaign dates, and used Poisson regression to estimate incidence rate ratios (IRRs) comparing the periods during which wild-type virus circulated and after the start of vaccination campaigns vs. the period prior to pH1N1 virus circulation. We used electronic health care data from Sweden, Denmark, the United Kingdom, Canada (3 provinces), Taiwan, Netherlands, and Spain (2 regions) from 2003 to 2013. We investigated interactions between age group and adjuvant in European sites and conducted a simulation study to investigate how vaccine coverage, age, and the interval from onset to diagnosis may impact the ability to detect safety signals. RESULTS:Incidence rates of narcolepsy varied by age, continent, and period. Only in Taiwan and Sweden were significant time-period-by-age-group interactions observed. Associations were found for children in Taiwan (following pH1N1 virus circulation) and Sweden (following vaccination). Simulations showed that the individual-level relative risk of narcolepsy was underestimated using ecological methods comparing post- vs. pre-vaccination periods; this effect was attenuated with higher vaccine coverage and a shorter interval from disease onset to diagnosis. CONCLUSIONS:Ecological methods can be useful for vaccine safety assessment but the results are influenced by diagnostic delay and vaccine coverage. Because ecological methods assess risk at the population level, these methods should be treated as signal-generating methods and drawing conclusions regarding individual-level risk should be avoided.

Under-reporting of pertussis cases is a longstanding challenge. We estimated the true number of pertussis cases in Ontario using multiple data sources, and evaluated the completeness of each source.We linked data from multiple sources for the period 2009 to 2015: public health reportable disease surveillance data, public health laboratory data, and health administrative data (hospitalizations, emergency department visits, and physician office visits). To estimate the total number of pertussis cases in Ontario, we used a three-source capture-recapture analysis stratified by age (infants, or aged one year and older) and adjusting for dependency between sources. We used the Bayesian Information Criterion to compare models.Using probable and confirmed reported cases, laboratory data, and combined hospitalizations/emergency department visits, the estimated total number of cases during the six-year period amongst infants was 924, compared with 545 unique observed cases from all sources. Using the same sources, the estimated total for those aged 1 year and older was 12,883, compared with 3,304 observed cases from all sources. Only 37% of infants and 11% for those aged 1 year and over admitted to hospital or seen in an emergency department for pertussis were reported to public health. Public health reporting sensitivity varied from 2% to 68% depending on age group and the combination of data sources included. Sensitivity of combined hospitalizations and emergency department visits varied from 37% to 49% and of laboratory data from 1% to 50%.All data sources contribute cases and are complementary, suggesting that the incidence of pertussis is substantially higher than suggested by routine reports. The sensitivity of different data sources varies. Better case identification is required to improve pertussis control in Ontario.

In August 2011, Ontario, Canada introduced a rotavirus immunization program using Rotarix™ vaccine. No assessments of rotavirus vaccine coverage have been previously conducted in Ontario.We assessed vaccine coverage (series initiation and completion) and factors associated with uptake using the Electronic Medical Record Administrative data Linked Database (EMRALD), a collection of family physician electronic medical records (EMR) linked to health administrative data. Series initiation (1 dose) and series completion (2 doses) before and after the program's introduction were calculated. To identify factors associated with series initiation and completion, adjusted odds ratios (aOR) and 95% confidence intervals (95%CI) were calculated using logistic regression.A total of 12,525 children were included. Series completion increased each year of the program (73%, 79% and 84%, respectively). Factors associated with series initiation included high continuity of care (aOR = 2.15; 95%CI, 1.61-2.87), maternal influenza vaccination (aOR = 1.55; 95%CI,1.24-1.93), maternal immmigration to Canada in the last five years (aOR = 1.47; 95% CI, 1.05-2.04), and having no siblings (aOR = 1.62; 95%CI,1.30-2.03). Relative to the first program year, infants were more likely to initiate the series in the second year (aOR = 1.71; 95% CI 1.39-2.10) and third year (aOR = 2.02; 95% CI 1.56-2.61) of the program. Infants receiving care from physicians with large practices were less likely to initiate the series (aOR 0.91; 95%CI, 0.88-0.94, per 100 patients rostered) and less likely to complete the series (aOR 0.94; 95%CI, 0.91-0.97, per 100 patients rostered). Additional associations were identified for series completion.Family physician delivery achieved moderately high coverage in the program's first three years. This assessment demonstrates the usefulness of EMR data for evaluating vaccine coverage. Important insights into factors associated with initiation or completion (i.e. high continuity of care, smaller roster sizes, rural practice location) suggest areas for research and potential program supports.

BACKGROUND:To evaluate screening and treatment strategies, large-scale real-world data on liver disease-related outcomes are needed. We sought to validate health administrative data for identification of cirrhosis, decompensated cirrhosis and hepatocellular carcinoma among patients with known liver disease. METHODS:Primary patient data were abstracted from patients of the Toronto Center for Liver Disease with viral hepatitis (2006-2014), and all patients with liver disease from the Kingston Health Sciences Centre Hepatology Clinic (2013). We linked clinical information to health administrative data and tested a range of coding algorithms against the clinical reference standard. RESULTS:A total of 6,714 patients had primary chart data abstracted. A single physician visit code for cirrhosis was sensitive (98-99%), and a single hospital diagnostic code for cirrhosis was specific (91-96%). The most sensitive algorithm for decompensated cirrhosis was one cirrhosis code with any of: a hospital diagnostic code, death code, or procedure code for decompensation (range 88-99% across groups). The most specific was one cirrhosis code and one hospital diagnostic code (range 89-98% across groups). Two physician visit codes or a single hospital diagnostic code, death code, or procedure code combined with a code for cirrhosis were sensitive and specific for hepatocellular carcinoma (sensitivity 94-96%, specificity 93-98%). CONCLUSION:These sensitive and specific algorithms can be used to define patient cohorts or detect clinical outcomes using health administrative data. Our results will facilitate research into the adequacy of screening and treatment for patients with chronic viral hepatitis or other liver diseases.

While medical records have detailed information, they are limited in reach to the availability and accessibility of those records. On the other hand, administrative data while limited in scope, have a much further reach in coverage of an entire population. However, few studies have validated the use of administrative data for identifying infections in pediatric populations. Pediatric patients from Ontario, Canada aged

Uncertainty remains regarding the magnitude of effectiveness of influenza vaccines for preventing serious outcomes, especially among young children. We estimated vaccine effectiveness (VE) against laboratory-confirmed influenza hospitalizations among children aged 6-59 months. We used the test-negative design in hospitalized children in Ontario, Canada during the 2010-11 to 2013-14 influenza seasons. We used logistic regression models adjusted for age, season, and time within season to calculate VE estimates by vaccination status (full vs. partial), age group, and influenza season. We also assessed VE incorporating prior history of influenza vaccination. We included specimens from 9,982 patient hospitalization episodes over four seasons, with 12.8% testing positive for influenza. We observed variation in VE by vaccination status, age group, and influenza season. For the four seasons combined, VE was 60% (95%CI, 44%-72%) for full vaccination and 39% (95%CI, 17%-56%) for partial vaccination. VE for full vaccination was 67% (95%CI, 48%-79%) for children aged 24-59 months, 48% (95%CI, 12%-69%) for children aged 6-23 months, 77% (95%CI, 47%-90%) for 2010-11, 59% (95%CI, 13%-81%) for 2011-12, 33% (95%CI, -18% to 62%) for 2012-13, and 72% (95%CI, 42%-86%) for 2013-14. VE in children aged 24-59 months appeared similar between those vaccinated in both the current and previous seasons and those vaccinated in the current season only, with the exception of 2012-13, when VE was lower for those vaccinated in the current season only. Influenza vaccination is effective in preventing pediatric laboratory-confirmed influenza hospitalizations during most seasons.

Few studies have evaluated the mortality or quantified the economic burden of community-onset Clostridium difficile infection (CDI). We estimated the attributable mortality and costs of community-onset CDI. We conducted a population-based matched cohort study. We identified incident subjects with community-onset CDI using health administrative data (emergency department visits and hospital admissions) in Ontario, Canada between January 1, 2003 and December 31, 2010. We propensity-score matched each infected subject to one uninfected subject and followed subjects in the cohort until December 31, 2011. We evaluated all-cause mortality and costs (unadjusted and adjusted for survival) from the healthcare payer perspective (2014 Canadian dollars). During our study period, we identified 7,950 infected subjects. The mean age was 63.5 years (standard deviation = 22.0), 62.7% were female, and 45.0% were very high users of the healthcare system. The relative risk for 30-day, 180-day, and 1-year mortality were 7.32 (95% confidence interval [CI], 5.94-9.02), 3.55 (95%CI, 3.17-3.97), and 2.59 (95%CI, 2.37-2.83), respectively. Mean attributable cumulative 30-day, 180-day, and 1-year costs (unadjusted for survival) were $7,434 (95%CI, $7,122-$7,762), $12,517 (95%CI, $11,687-$13,366), and $13,217 (95%CI, $12,062-$14,388). Mean attributable cumulative 1-, 2-, and 3-year costs (adjusted for survival) were $10,700 (95%CI, $9,811-$11,645), $13,312 (95%CI, $12,024-$14,682), and $15,812 (95%CI, $14,159-$17,571). Infected subjects had considerably higher risk of all-cause mortality and costs compared with uninfected subjects. This study provides insight on an understudied patient group. Our study findings will facilitate assessment of interventions to prevent community-onset CDI.

Infants are at high risk for influenza illness, but are ineligible for vaccination before 6 months. Transfer of maternal antibodies to the fetus has been demonstrated for 2009 A/H1N1 pandemic vaccines; however, clinical effectiveness is unknown. Our objective was to evaluate the association between 2009 A/H1N1 pandemic vaccination during pregnancy and rates of infant influenza and pneumonia.We linked a population-based birth cohort to administrative databases to measure rates of influenza and pneumonia diagnosed during ambulatory physician visits, hospitalizations and emergency department visits during one year of follow-up. We estimated incidence rate ratios and 95% confidence intervals (95% CI) using Poisson regression, comparing infants born to A/H1N1-vaccinated women (vaccine-exposed infants) with unexposed infants, adjusted for confounding using high-dimensional propensity scores.Among 117,335 infants in the study, 36,033 (31%) were born to A/H1N1-vaccinated women. Crude rates of influenza during the pandemic (per 100,000 infant-days) for vaccine-exposed and unexposed infants were similar (2.19, 95% CI: 1.27-3.76 and 3.60, 95% CI: 2.51-5.14, respectively), as were crude rates of influenza and pneumonia combined. We did not observe any significant differences in rates of study outcomes between study groups during the second wave of the 2009 A/H1N1 pandemic, nor during any post-pandemic time period.We observed no difference in rates of study outcomes among infants born to A/H1N1-vaccinated mothers relative to unexposed infants born during the second A/H1N1 pandemic wave; however, due to late availability of the pandemic vaccine, the available follow-up time during the pandemic time period was very limited.

BackgroundThe aim of this study was to understand online public perceptions of the debate surrounding the choice of annual influenza vaccinations or wearing masks as a condition of employment for healthcare workers, such as the one enacted in British Columbia in August 2012.MethodsFour national and 82 local (British Columbia) Canadian online news sites were searched for articles posted between August 2012 and May 2013 containing the words "healthcare workers" and "mandatory influenza vaccinations/immunizations" or "mandatory flu shots and healthcare workers." We included articles from sources that predominantly concerned our topic of interest and that generated reader comments. Two researchers coded the unedited comments using thematic analysis, categorizing codes to allow themes to emerge. In addition to themes, the comments were categorized by: 1) sentiment towards influenza vaccines; 2) support for mandatory vaccination policies; 3) citing of reference materials or statistics; 4) self-identified health-care worker status; and 5) sharing of a personal story.Results1163 comments made by 648 commenters responding to 36 articles were analyzed. Popular themes included concerns about freedom of choice, vaccine effectiveness, patient safety, and distrust in government, public health, and the pharmaceutical industry. Almost half (48%) of commenters expressed a negative sentiment toward the influenza vaccine, 28% were positive, 20% were neutral, and 4% expressed mixed sentiment. Of those who commented on the policy, 75% did not support the condition to work policy, while 25% were in favour. Of the commenters, 11% self-identified as healthcare workers, 13% shared personal stories, and 18% cited a reference or statistic.InterpretationThe perception of the influenza vaccine in the comment sections of online news sites is fairly poor. Public health agencies should consider including online forums, comment sections, and social media sites as part of their communication channels to correct misinformation regarding the benefits of HCW influenza immunization and the effectiveness of the vaccine.

Given the variation in human papillomavirus (HPV) vaccine coverage across Canada, and debate regarding delivery of HPV vaccines in Catholic schools, we studied online comments on Canadian news websites to understand public perceptions of HPV and HPV vaccine.We searched English- and French-language Canadian news websites for 2012 articles that contained the terms "HPV" or "human papillomavirus." Articles about HPV vaccinations that contained at least one comment were included. Two researchers independently coded comments, analyzing them for emerging themes.We identified 3073 comments from 1198 individuals in response to 71 news articles; 630 (52.6%) individuals expressed positive sentiments about HPV vaccination (2.5 comments/individual), 404 (33.7%) were negative (3.0 comments/individual), 34 (2.8%) were mixed (1.5 comments/individual) and 130 (10.8%) were neutral (1.6 comments/individual). Vaccine-supportive commenters believed the vaccine is safe and effective. Common themes in negative comments included concerns regarding HPV vaccine safety and efficacy, distrust of pharmaceutical companies and government, and belief that school-age children are too young for HPV vaccine. Many comments focused on whether the Catholic Church has the right to inform health policy for students, and discussion often evolved into debates regarding HPV and sexual behaviour. We noted that many individuals doubted the credibility of vaccine safety information.The majority of commenters do not appear to be against HPV vaccination, but public health messaging that focuses on both the vaccine's safety profile, and its use as a means to prevent cancer rather than sexually transmitted HPV infection may facilitate its acceptance.

To determine if reductions in medically-attended pediatric varicella and herpes zoster occurred in Ontario, Canada, after publicly-funded varicella immunization was implemented in 2004.For fiscal years (FY) 1992-2011, we examined data on varicella and herpes zoster physician office visits, emergency department (ED) visits, hospitalizations (including for varicella-associated skin and soft tissue infections [SSTI]), and intensive care unit (ICU) admissions, among those aged

BACKGROUND: Estimates of the effectiveness of influenza vaccines in older adults may be biased because of difficulties identifying and adjusting for confounders of the vaccine-outcome association. We estimated vaccine effectiveness for prevention of serious influenza complications among older persons by using methods to account for underlying differences in risk for these complications. METHODS: We conducted a retrospective cohort study among Ontario residents aged ≥ 65 years from September 1993 through September 2008. We linked weekly vaccination, hospitalization, and death records for 1.4 million community-dwelling persons aged ≥ 65 years. Vaccine effectiveness was estimated by comparing ratios of outcome rates during weeks of high versus low influenza activity (defined by viral surveillance data) among vaccinated and unvaccinated subjects by using log-linear regression models that accounted for temperature and time trends with natural spline functions. Effectiveness was estimated for three influenza-associated outcomes: all-cause deaths, deaths occurring within 30 days of pneumonia/influenza hospitalizations, and pneumonia/influenza hospitalizations. RESULTS: During weeks when 5% of respiratory specimens tested positive for influenza A, vaccine effectiveness among persons aged ≥ 65 years was 22% (95% confidence interval [CI], -6%-42%) for all influenza-associated deaths, 25% (95% CI, 13%-37%) for deaths occurring within 30 days after an influenza-associated pneumonia/influenza hospitalization, and 19% (95% CI, 4%-31%) for influenza-associated pneumonia/influenza hospitalizations. Because small proportions of deaths, deaths after pneumonia/influenza hospitalizations, and pneumonia/influenza hospitalizations were associated with influenza virus circulation, we estimated that vaccination prevented 1.6%, 4.8%, and 4.1% of these outcomes, respectively. CONCLUSIONS: By using confounding-reducing techniques with 15 years of provincial-level data including vaccination and health outcomes, we estimated that influenza vaccination prevented ~4% of influenza-associated hospitalizations and deaths occurring after hospitalizations among older adults in Ontario.

OBJECTIVE: We investigated the association between a child's birth order and emergency room (ER) visits and hospital admissions following 2-,4-,6- and 12-month pediatric vaccinations. METHODS: We included all children born in Ontario between April 1(st), 2006 and March 31(st), 2009 who received a qualifying vaccination. We identified vaccinations, ER visits and admissions using health administrative data housed at the Institute for Clinical Evaluative Sciences. We used the self-controlled case series design to compare the relative incidence (RI) of events among 1(st)-born and later-born children using relative incidence ratios (RIR). RESULTS: For the 2-month vaccination, the RIR for 1(st)-borns versus later-born children was 1.37 (95% CI: 1.19-1.57), which translates to 112 additional events/100,000 vaccinated. For the 4-month vaccination, the RIR for 1(st)-borns vs. later-borns was 1.70 (95% CI: 1.45-1.99), representing 157 additional events/100,000 vaccinated. At 6 months, the RIR for 1(st) vs. later-borns was 1.27 (95% CI: 1.09-1.48), or 77 excess events/100,000 vaccinated. At the 12-month vaccination, the RIR was 1.11 (95% CI: 1.02-1.21), or 249 excess events/100,000 vaccinated. CONCLUSIONS: Birth order is associated with increased incidence of ER visits and hospitalizations following vaccination in infancy. 1(st)-born children had significantly higher relative incidence of events compared to later-born children.

BACKGROUND: Although interruption of endemic measles was achieved in the Americas in 2002, Quebec experienced an outbreak in 2011 of 776 reported cases; 80% of these individuals had not been fully vaccinated. We analyzed readers' online responses to Canadian news articles regarding the outbreak to better understand public perceptions of measles and vaccination. METHODS: We searched Canadian online English and French news sites for articles posted between April 2011 and March 2012 containing the words "measles" and "Quebec". We included articles that i) concerned the outbreak or related vaccination strategies; and ii) generated at least ten comments. Two English and two bilingual researchers coded the unedited comments, categorizing codes to allow themes to emerge. RESULTS: We analyzed 448 comments from 188 individuals, in response to three French articles and six English articles; 112 individuals expressed positive perceptions of measles vaccination (2.2 comments/person), 38 were negative (4.2 comments/person), 11 had mixed feelings (1.5 comments/person), and 27 expressed no opinion (1.1 comments/person). Vaccine-supportive themes involved the success of vaccination in preventing disease spread, societal responsibility to vaccinate for herd immunity, and refutation of the autism link. Those against measles vaccination felt it was a personal rather than societal choice, and conveyed a distrust of vaccine manufacturers, believing that measles infection is not only safe but safer than vaccination. Commenters with mixed feelings expressed uncertainty of the infection's severity, and varied in support of all vaccines based on perceived risk/benefit ratios. CONCLUSION: The anti-vaccine minority's volume of comments translates to a disproportionately high representation on online boards. Public health messages should address concerns by emphasizing that immunization is always a personal choice in Canada, and that the pharmaceutical industry is strictly controlled. Illustrating the dangers of measles through personal stories, rather than scientific data only, may also serve to strengthen messaging.

Although the benefits of physical activity in preventing chronic medical conditions are well established, its impacts on infectious diseases, and seasonal influenza in particular, are less clearly defined. We examined the association between physical activity and influenza-coded outpatient visits, as a proxy for influenza infection.We conducted a cohort study of Ontario respondents to Statistics Canada's population health surveys over 12 influenza seasons. We assessed physical activity levels through survey responses, and influenza-coded physician office and emergency department visits through physician billing claims. We used logistic regression to estimate the risk of influenza-coded outpatient visits during influenza seasons. The cohort comprised 114,364 survey respondents who contributed 357,466 person-influenza seasons of observation. Compared to inactive individuals, moderately active (OR 0.83; 95% CI 0.74-0.94) and active (OR 0.87; 95% CI 0.77-0.98) individuals were less likely to experience an influenza-coded visit. Stratifying by age, the protective effect of physical activity remained significant for individuals

Individual-level immunization data captured electronically can facilitate evidence-based decision-making and planning. Populating individual-level records through manual data entry is time-consuming. An alternative is to use scannable forms, completed at the point of vaccination and subsequently scanned and exported to a database or registry. To explore the suitability of this approach for collecting immunization data, we conducted a feasibility study in two settings in Ontario, Canada.Prior to the 2011-2012 influenza vaccination campaign, we developed a scannable form template and a corresponding database that captured required demographic and clinical data elements. We examined efficiency, data quality, and usability through time observations, record audits, staff interviews, and client surveys. The mean time required to scan and verify forms (62.3 s) was significantly shorter than manual data entry (69.5 s) in one organization, whereas there was no difference (36.6 s vs. 35.4 s) in a second organization. Record audits revealed no differences in data quality between records populated by scanning versus manual data entry. Data processing personnel and immunized clients found the processes involved to be straightforward, while nurses and managers had mixed perceptions regarding the ease and merit of using scannable forms. Printing quality and other factors rendered some forms unscannable, necessitating manual entry.Scannable forms can facilitate efficient data entry, but certain features of the forms, as well as the workflow and infrastructure into which they are incorporated, should be evaluated and adapted if scannable forms are to be a meaningful alternative to manual data entry.

Evidence-based priority setting is increasingly important for rationally distributing scarce health resources and for guiding future health research. We sought to quantify the contribution of a wide range of infectious diseases to the overall infectious disease burden in a high-income setting.We used health-adjusted life years (HALYs), a composite measure comprising premature mortality and reduced functioning due to disease, to estimate the burden of 51 infectious diseases and associated syndromes in Ontario using 2005-2007 data. Deaths were estimated from vital statistics data and disease incidence was estimated from reportable disease, healthcare utilization, and cancer registry data, supplemented by local modeling studies and national and international epidemiologic studies. The 51 infectious agents and associated syndromes accounted for 729 lost HALYs, 44.2 deaths, and 58,987 incident cases per 100,000 population annually. The most burdensome infectious agents were: hepatitis C virus, Streptococcus pneumoniae, Escherichia coli, human papillomavirus, hepatitis B virus, human immunodeficiency virus, Staphylococcus aureus, influenza virus, Clostridium difficile, and rhinovirus. The top five, ten, and 20 pathogens accounted for 46%, 67%, and 75% of the total infectious disease burden, respectively. Marked sex-specific differences in disease burden were observed for some pathogens. The main limitations of this study were the exclusion of certain infectious diseases due to data availability issues, not considering the impact of co-infections and co-morbidity, and the inability to assess the burden of milder infections that do not result in healthcare utilization.Infectious diseases continue to cause a substantial health burden in high-income settings such as Ontario. Most of this burden is attributable to a relatively small number of infectious agents, for which many effective interventions have been previously identified. Therefore, these findings should be used to guide public health policy, planning, and research.

The wintertime co-occurrence of peaks in influenza and invasive pneumococcal disease (IPD) is well documented, but how and whether wintertime peaks caused by these two pathogens are causally related is still uncertain. We aimed to investigate the relationship between influenza infection and IPD in Ontario, Canada, using several complementary methodological tools.We evaluated a total number of 38,501 positive influenza tests in Central Ontario and 6,191 episodes of IPD in the Toronto/Peel area, Ontario, Canada, between 1 January 1995 and 3 October 2009, reported through population-based surveillance. We assessed the relationship between the seasonal wave forms for influenza and IPD using fast Fourier transforms in order to examine the relationship between these two pathogens over yearly timescales. We also used three complementary statistical methods (time-series methods, negative binomial regression, and case-crossover methods) to evaluate the short-term effect of influenza dynamics on pneumococcal risk. Annual periodicity with wintertime peaks could be demonstrated for IPD, whereas periodicity for influenza was less regular. As for long-term effects, phase and amplitude terms of pneumococcal and influenza seasonal sine waves were not correlated and meta-analysis confirmed significant heterogeneity of influenza, but not pneumococcal phase terms. In contrast, influenza was shown to Granger-cause pneumococcal disease. A short-term association between IPD and influenza could be demonstrated for 1-week lags in both case-crossover (odds ratio [95% confidence interval] for one case of IPD per 100 influenza cases = 1.10 [1.02-1.18]) and negative binomial regression analysis (incidence rate ratio [95% confidence interval] for one case of IPD per 100 influenza cases = 1.09 [1.05-1.14]).Our data support the hypothesis that influenza influences bacterial disease incidence by enhancing short-term risk of invasion in colonized individuals. The absence of correlation between seasonal waveforms, on the other hand, suggests that bacterial disease transmission is affected to a lesser extent. Please see later in the article for the Editors' Summary.

BACKGROUND: Live vaccines have distinct safety profiles, potentially causing systemic reactions one to 2 weeks after administration. In the province of Ontario, Canada, live MMR vaccine is currently recommended at age 12 months and 18 months. METHODS: Using the self-controlled case series design we examined 271,495 12 month vaccinations and 184,312 18 month vaccinations to examine the relative incidence of the composite endpoint of emergency room visits or hospital admissions in consecutive one day intervals following vaccination. These were compared to a control period 20 to 28 days later. In a post-hoc analysis we examined the reasons for emergency room visits and the average acuity score at presentation for children during the at-risk period following the 12 month vaccine. RESULTS: Four to 12 days post 12 month vaccination, children had a 1.33 (1.29-1.38) increased relative incidence of the combined endpoint compared to the control period, or at least one event during the risk interval for every 168 children vaccinated. Ten to 12 days post 18 month vaccination, the relative incidence was 1.25 (95%, 1.17-1.33) which represented at least one excess event for every 730 children vaccinated. The primary reason for increased events was statistically significant elevations in emergency room visits following all vaccinations. There were non-significant increases in hospital admissions. There were an additional 20 febrile seizures for every 100,000 vaccinated at 12 months. CONCLUSIONS: There are significantly elevated risks of primarily emergency room visits approximately one to two weeks following 12 and 18 month vaccination. Future studies should examine whether these events could be predicted or prevented.

BackgroundThe world is currently confronting the first influenza pandemic of the 21(st) century. Influenza vaccination is an effective preventive measure, but the unique epidemiological features of swine-origin influenza A (H1N1) (pH1N1) introduce uncertainty as to the best strategy for prioritization of vaccine allocation. We sought to determine optimal prioritization of vaccine distribution among different age and risk groups within the Canadian population, to minimize influenza-attributable morbidity and mortality.Methodology/principal findingsWe developed a deterministic, age-structured compartmental model of influenza transmission, with key parameter values estimated from data collected during the initial phase of the epidemic in Ontario, Canada. We examined the effect of different vaccination strategies on attack rates, hospitalizations, intensive care unit admissions, and mortality. In all scenarios, prioritization of high-risk individuals (those with underlying chronic conditions and pregnant women), regardless of age, markedly decreased the frequency of severe outcomes. When individuals with underlying medical conditions were not prioritized and an age group-based approach was used, preferential vaccination of age groups at increased risk of severe outcomes following infection generally resulted in decreased mortality compared to targeting vaccine to age groups with higher transmission, at a cost of higher population-level attack rates. All simulations were sensitive to the timing of the epidemic peak in relation to vaccine availability, with vaccination having the greatest impact when it was implemented well in advance of the epidemic peak.Conclusions/significanceOur model simulations suggest that vaccine should be allocated to high-risk groups, regardless of age, followed by age groups at increased risk of severe outcomes. Vaccination may significantly reduce influenza-attributable morbidity and mortality, but the benefits are dependent on epidemic dynamics, time for program roll-out, and vaccine uptake.

BackgroundIn July 2000, the province of Ontario, Canada, initiated a universal influenza immunization program (UIIP) to provide free seasonal influenza vaccines for the entire population. This is the first large-scale program of its kind worldwide. The objective of this study was to conduct an economic appraisal of Ontario's UIIP compared to a targeted influenza immunization program (TIIP).Methods and findingsA cost-utility analysis using Ontario health administrative data was performed. The study was informed by a companion ecological study comparing physician visits, emergency department visits, hospitalizations, and deaths between 1997 and 2004 in Ontario and nine other Canadian provinces offering targeted immunization programs. The relative change estimates from pre-2000 to post-2000 as observed in other provinces were applied to pre-UIIP Ontario event rates to calculate the expected number of events had Ontario continued to offer targeted immunization. Main outcome measures were quality-adjusted life years (QALYs), costs in 2006 Canadian dollars, and incremental cost-utility ratios (incremental cost per QALY gained). Program and other costs were drawn from Ontario sources. Utility weights were obtained from the literature. The incremental cost of the program per QALY gained was calculated from the health care payer perspective. Ontario's UIIP costs approximately twice as much as a targeted program but reduces influenza cases by 61% and mortality by 28%, saving an estimated 1,134 QALYs per season overall. Reducing influenza cases decreases health care services cost by 52%. Most cost savings can be attributed to hospitalizations avoided. The incremental cost-effectiveness ratio is Can$10,797/QALY gained. Results are most sensitive to immunization cost and number of deaths averted.ConclusionsUniversal immunization against seasonal influenza was estimated to be an economically attractive intervention.

BACKGROUND: In temperate climates, invasive meningococcal disease (IMD) incidence tends to coincide with or closely follow peak incidence of influenza virus infection; at a seasonal level, increased influenza activity frequently correlates with increased seasonal risk of IMD. METHODS: We evaluated 240 cases of IMD reported in central Ontario, Canada, from 2000 to 2006. Associations between environmental and virological (influenza A, influenza B and respiratory syncytial virus (RSV)) exposures and IMD incidence were evaluated using negative binomial regression models controlling for seasonal oscillation. Acute effects of weekly respiratory virus activity on IMD risk were evaluated using a matched-period case-crossover design with random directionality of control selection. Effects were estimated using conditional logistic regression. RESULTS: Multivariable negative binomial regression identified elevated IMD risk with increasing influenza A activity (per 100 case increase, incidence rate ratio = 1.18, 95% confidence interval (CI): 1.06, 1.31). In case-crossover models, increasing weekly influenza A activity was associated with an acute increase in the risk of IMD (per 100 case increase, odds ratio (OR) = 2.03, 95% CI: 1.28 to 3.23). Increasing weekly RSV activity was associated with increased risk of IMD after adjusting for RSV activity in the previous 3 weeks (per 100 case increase, OR = 4.31, 95% CI: 1.14, 16.32). No change in disease risk was seen with increasing influenza B activity. CONCLUSIONS: We have identified an acute effect of influenza A and RSV activity on IMD risk. If confirmed, these finding suggest that influenza vaccination may have the indirect benefit of reducing IMD risk.

Statins possess immunomodulatory properties and have been proposed for reducing morbidity during an influenza pandemic. We sought to evaluate the effect of statins on hospitalizations and deaths related to seasonal influenza outbreaks.We conducted a population-based cohort study over 10 influenza seasons (1996 to 2006) using linked administrative databases in Ontario, Canada. We identified all adults older than 65 years who had received an influenza vaccination prior to the start of influenza season and distinguished those also prescribed statins (23%) from those not also prescribed statins (77%). Propensity-based matching, which accounted for each individual's likelihood of receiving a statin, yielded a final cohort of 2,240,638 patients, exactly half of whom received statins. Statins were associated with small protective effects against pneumonia hospitalization (odds ratio [OR] 0.92; 95% CI 0.89-0.95), 30-day pneumonia mortality (0.84; 95% CI 0.77-0.91), and all-cause mortality (0.87; 95% CI 0.84-0.89). These protective effects attenuated substantially after multivariate adjustment and when we excluded multiple observations for each individual, declined over time, differed across propensity score quintiles and risk groups, and were unchanged during post-influenza season periods. The main limitations of this study were the observational study design, the non-specific outcomes, and the lack of information on medications while hospitalized.Statin use is associated with a statistically significant but minimal protective effect against influenza morbidity that can easily be attributed to residual confounding. Public health officials and clinicians should focus on other measures to reduce morbidity and mortality from the next influenza pandemic.

BACKGROUND: In 2000, Ontario, Canada, initiated a universal influenza immunization program (UIIP) to provide free influenza vaccines for the entire population aged 6 mo or older. Influenza immunization increased more rapidly in younger age groups in Ontario compared to other Canadian provinces, which all maintained targeted immunization programs. We evaluated the effect of Ontario's UIIP on influenza-associated mortality, hospitalizations, emergency department (ED) use, and visits to doctors' offices. METHODS AND FINDINGS: Mortality and hospitalization data from 1997 to 2004 for all ten Canadian provinces were obtained from national datasets. Physician billing claims for visits to EDs and doctors' offices were obtained from provincial administrative datasets for four provinces with comprehensive data. Since outcomes coded as influenza are known to underestimate the true burden of influenza, we studied more broadly defined conditions. Hospitalizations, ED use, doctors' office visits for pneumonia and influenza, and all-cause mortality from 1997 to 2004 were modelled using Poisson regression, controlling for age, sex, province, influenza surveillance data, and temporal trends, and used to estimate the expected baseline outcome rates in the absence of influenza activity. The primary outcome was then defined as influenza-associated events, or the difference between the observed events and the expected baseline events. Changes in influenza-associated outcome rates before and after UIIP introduction in Ontario were compared to the corresponding changes in other provinces. After UIIP introduction, influenza-associated mortality decreased more in Ontario (relative rate [RR] = 0.26) than in other provinces (RR = 0.43) (ratio of RRs = 0.61, p = 0.002). Similar differences between Ontario and other provinces were observed for influenza-associated hospitalizations (RR = 0.25 versus 0.44, ratio of RRs = 0.58, p < 0.001), ED use (RR = 0.31 versus 0.69, ratio of RRs = 0.45, p < 0.001), and doctors' office visits (RR = 0.21 versus 0.52, ratio of RRs = 0.41, p < 0.001). Sensitivity analyses were carried out to assess consistency, specificity, and the presence of a dose-response relationship. Limitations of this study include the ecological study design, the nonspecific outcomes, difficulty in modeling baseline events, data quality and availability, and the inability to control for potentially important confounders. CONCLUSIONS: Compared to targeted programs in other provinces, introduction of universal vaccination in Ontario in 2000 was associated with relative reductions in influenza-associated mortality and health care use. The results of this large-scale natural experiment suggest that universal vaccination may be an effective public health measure for reducing the annual burden of influenza.