Antiviral drug treatment for nonsevere COVID-19: a systematic review and network meta-analysis

Background:Randomized trial evidence suggests that some antiviral drugs are effective in patients with COVID-19. However, the comparative effectiveness of antiviral drugs in nonsevere COVID-19 is unclear.Methods:We searched the Epistemonikos COVID-19 L·OVE (Living Overview of Evidence) database for randomized trials comparing antiviral treatments, standard care or placebo in adult patients with nonsevere COVID-19 up to Apr. 25, 2022. Reviewers extracted data and assessed risk of bias. We performed a frequentist network meta-analysis and assessed the certainty of evidence using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach.Results:We identified 41 trials, which included 18 568 patients. Compared with standard care or placebo, molnupiravir and nirmatrelvir–ritonavir each reduced risk of death with moderate certainty (10.9 fewer deaths per 1000, 95% confidence interval [CI] 12.6 to 4.5 fewer for molnupiravir; 11.7 fewer deaths per 1000, 95% CI 13.1 fewer to 2.6 more). Compared with molnupiravir, nirmatrelvir–ritonavir probably reduced risk of hospital admission (27.8 fewer admissions per 1000, 95% CI 32.8 to 18.3 fewer; moderate certainty). Remdesivir probably has no effect on risk of death, but may reduce hospital admissions (39.1 fewer admissions per 1000, 95% CI 48.7 to 13.7 fewer; low certainty).Interpretation:Molnupiravir and nirmatrelvir–ritonavir probably reduce risk of hospital admissions and death among patients with nonsevere COVID-19. Nirmatrelvir–ritonavir is probably more effective than molnupiravir for reducing risk of hospital admissions. Most trials were conducted with unvaccinated patients, before the emergence of the Omicron variant; the effectiveness of these drugs must thus be tested among vaccinated patients and against newer variants.

Most trials addressing the treatment of patients with COVID-19 have targeted patients admitted to hospital with severe or critical disease.¹ However, more recently, several treatments, including antiviral drugs, antidepressants, monoclonal antibodies and inhaled corticosteroids, have been studied for patients with nonsevere COVID-19.² Preliminary evidence from ongoing or recently completed trials suggests that 2 novel antiviral drugs — molnupiravir and nirmatrelvir–ritonavir (Paxlovid) — may be effective at reducing risk of hospital admission.^3–5 To date, evidence on antiviral drugs for nonsevere COVID-19 has not been systematically synthesized or appraised. Furthermore, although efficacy data from trials of molnupiravir, nirmatrelvir–ritonavir and remdesivir are promising, no head-to-head trials have compared these drugs.A network meta-analysis allows for comparison of treatments that have not been compared in randomized controlled trials (RCTs), using pooled estimates from direct and indirect evidence. They can provide guidance to clinicians and evidence users in determining which treatments are superior. This is particularly important as health care systems attempt to prioritize access to effective COVID-19 treatments in the early stages of the disease.We sought to compare the effectiveness of antiviral drugs for patients with nonsevere COVID-19.     

Geographic concentration of SARS-CoV-2 cases by social determinants of health in metropolitan areas in Canada: a cross-sectional study

Background:Understanding inequalities in SARS-CoV-2 transmission associated with the social determinants of health could help the development of effective mitigation strategies that are responsive to local transmission dynamics. This study aims to quantify social determinants of geographic concentration of SARS-CoV-2 cases across 16 census metropolitan areas (hereafter, cities) in 4 Canadian provinces, British Columbia, Manitoba, Ontario and Quebec.Methods:We used surveillance data on confirmed SARS-CoV-2 cases and census data for social determinants at the level of the dissemination area (DA). We calculated Gini coefficients to determine the overall geographic heterogeneity of confirmed cases of SARS-CoV-2 in each city, and calculated Gini covariance coefficients to determine each city’s heterogeneity by each social determinant (income, education, housing density and proportions of visible minorities, recent immigrants and essential workers). We visualized heterogeneity using Lorenz (concentration) curves.Results:We observed geographic concentration of SARS-CoV-2 cases in cities, as half of the cumulative cases were concentrated in DAs containing 21%–35% of their population, with the greatest geographic heterogeneity in Ontario cities (Gini coefficients 0.32–0.47), followed by British Columbia (0.23–0.36), Manitoba (0.32) and Quebec (0.28–0.37). Cases were disproportionately concentrated in areas with lower income and educational attainment, and in areas with a higher proportion of visible minorities, recent immigrants, high-density housing and essential workers. Although a consistent feature across cities was concentration by the proportion of visible minorities, the magnitude of concentration by social determinant varied across cities.Interpretation:Geographic concentration of SARS-CoV-2 cases was observed in all of the included cities, but the pattern by social determinants varied. Geographically prioritized allocation of resources and services should be tailored to the local drivers of inequalities in transmission in response to the resurgence of SARS-CoV-2.

The COVID-19 epidemic in Canada has varied in size and trajectory across provinces and large cities.^1,2 At the national level³ and within regions,^4,5 the burden of confirmed SARS-CoV-2 cases and severe COVID-19 outcomes has fallen disproportionately on socially and economically marginalized communities. ⁶ Social determinants of health refer to nonmedical factors influencing health outcomes, and structural determinants encompass cultural norms, policies and institutions that generate social stratification and determine socioeconomic position.^7,8 In Canada and elsewhere, data have consistently highlighted the importance of determinants such as household size and density, work in essential services and structural racism (measured by proxy) in the relative risk of COVID-19.^9–17Understanding the factors associated with geographic patterns of transmission within cities can help identify the populations and, specifically, the contexts with the greatest risks. Geographic analyses can enable better allocation of resources, tailoring of policies and implementation of context-specific strategies to more effectively and efficiently curb local transmission. ¹⁸ Although respiratory virus transmission is often geographically clustered within a city,¹⁹ the early public health response to SARS-CoV-2 transmission in Canada did little to take within-city clustering into account.^20,21 Similarly, few studies have quantified and compared the geographic concentration of SARS-CoV-2 cases by social determinants across Canada, and the extent to which the magnitude of inequalities might vary among cities and provinces.^19,22 We therefore sought to quantify and compare the magnitude of geographic concentration of SARS-CoV-2 cases by area-level social determinants of health across metropolitan areas in British Columbia, Manitoba, Ontario and Quebec, Canada.     

Association between virtual primary care and emergency department use during the first year of the COVID-19 pandemic in Ontario,Canada

Background:Uptake of virtual care increased substantially during the first year of the COVID-19 pandemic. The aim of this study was to evaluate whether a shift from in-person to virtual visits by primary care physicians was associated with increased use of emergency departments among their enrolled patients.Methods:We conducted an observational study of monthly virtual visits and emergency department visits from Apr. 1, 2020, to Mar. 31, 2021, using administrative data from Ontario, Canada. We used multivariable regression analysis to estimate the association between the proportion of a physician’s visits that were delivered virtually and the number of emergency department visits among their enrolled patients.Results:The proportion of virtual visits was higher among female, younger and urban physicians, and the number of emergency department visits was lower among patients of female and urban physicians. In an unadjusted analysis, a 1% increase in a physician’s proportion of virtual visits was found to be associated with 11.0 (95% confidence interval [CI] 10.1–11.8) fewer emergency department visits per 1000 rostered patients. After controlling for covariates, we observed no statistically significant change in emergency department visits per 1% increase in the proportion of virtual visits (0.2, 95% CI −0.5 to 0.9).Interpretation:We did not find evidence that patients substituted emergency department visits in the context of decreased availability of in-person care with their family physician during the first year of the COVID-19 pandemic. Future research should focus on the long-term impact of virtual care on access and quality of patient care.

Access and continuity are important health system characteristics for the prevention and management of chronic diseases and treatment of nonurgent acute concerns.^1,2 Virtual care has the potential to improve both of these characteristics. It has also been associated with improved therapeutic effects, efficiency gains, patient satisfaction and compliance.³ Despite these potential benefits, virtual care was not widely adopted in Canada before the COVID-19 pandemic. In 2018, only 4% of family physicians in Canada were offering video visits.⁴ Some prepandemic studies found reduced quality and inconsistent results regarding patient experiences with virtual care, even with improved access.^3,5 The pandemic pushed health care systems to rapidly implement virtual primary care; physicians in Canada were directed to restrict in-office visits and provide care virtually whenever possible.⁶ One Ontario-based study found a 5600% increase in virtual visits early in the pandemic, while in-office visits decreased by 79%, compared with the same period in 2019.⁷ Several Canadian studies also reported that emergency department visits declined during the first wave of the pandemic, possibly owing to avoidance of in-person urgent care from fear of contracting SARS-CoV-2.^8–10In later stages of the pandemic, questions arose about the quality of virtual care and the broader system effects of reduced access to in-person care, such as patients substituting emergency department visits when in-person care options were unavailable.^11–13 The impact of virtual care on emergency department use has been studied elsewhere, but we are not aware of published studies in the context of the COVID-19 pandemic in Ontario. Six studies found that virtual care had no impact on use of emergency departments, as described in a review article, but 1 study reported that nurse consultations via telephone were associated with increased emergency department visits.¹⁴ Observational studies found no association between virtual care and subsequent or reduced emergency department use.^15,16 Several studies found that patients self-reported that they would use the emergency department 4%–12% of the time if no virtual care options were available.^15,17,18We aimed to evaluate whether a shift from in-person to virtual visits by primary care physicians in patient enrolment practices was associated with increased use of emergency departments among their enrolled patients during the first year of the COVID-19 pandemic.     

Outcomes in patients with and without disability admitted to hospital with COVID-19: a retrospective cohort study

Background:Disability-related considerations have largely been absent from the COVID-19 response, despite evidence that people with disabilities are at elevated risk for acquiring COVID-19. We evaluated clinical outcomes in patients who were admitted to hospital with COVID-19 with a disability compared with patients without a disability.Methods:We conducted a retrospective cohort study that included adults with COVID-19 who were admitted to hospital and discharged between Jan. 1, 2020, and Nov. 30, 2020, at 7 hospitals in Ontario, Canada. We compared in-hospital death, admission to the intensive care unit (ICU), hospital length of stay and unplanned 30-day readmission among patients with and without a physical disability, hearing or vision impairment, traumatic brain injury, or intellectual or developmental disability, overall and stratified by age (≤ 64 and ≥ 65 yr) using multivariable regression, controlling for sex, residence in a long-term care facility and comorbidity.Results:Among 1279 admissions to hospital for COVID-19, 22.3% had a disability. We found that patients with a disability were more likely to die than those without a disability (28.1% v. 17.6%), had longer hospital stays (median 13.9 v. 7.8 d) and more readmissions (17.6% v. 7.9%), but had lower ICU admission rates (22.5% v. 28.3%). After adjustment, there were no statistically significant differences between those with and without disabilities for in-hospital death or admission to ICU. After adjustment, patients with a disability had longer hospital stays (rate ratio 1.36, 95% confidence interval [CI] 1.19–1.56) and greater risk of readmission (relative risk 1.77, 95% CI 1.14–2.75). In age-stratified analyses, we observed longer hospital stays among patients with a disability than in those without, in both younger and older subgroups; readmission risk was driven by younger patients with a disability.Interpretation:Patients with a disability who were admitted to hospital with COVID-19 had longer stays and elevated readmission risk than those without disabilities. Disability-related needs should be addressed to support these patients in hospital and after discharge.

A successful public health response to the COVID-19 pandemic requires accurate and timely identification of, and support for, high-risk groups. There is increasing recognition that marginalized groups, including congregate care residents, racial and ethnic minorities, and people experiencing poverty, have elevated incidence of COVID-19.^1,2 Older age and comorbidities such as diabetes are also risk factors for severe COVID-19 outcomes.^3,4 One potential high-risk group that has received relatively little attention is people with disabilities.The World Health Organization estimates there are 1 billion people with disabilities globally.⁵ In North America, the prevalence of disability is 20%, with one-third of people older than 65 years having a disability.⁶ Disabilities include physical disabilities, hearing and vision impairments, traumatic brain injury and intellectual or developmental disabilities.^5,6 Although activity limitations experienced by people with disabilities are heterogeneous,^5,6 people with disabilities share high rates of risk factors for acquiring COVID-19, including poverty, residence in congregate care and being members of racialized communities.^7–9 People with disabilities may be more reliant on close contact with others to meet their daily needs, and some people with disabilities, especially intellectual developmental disabilities, may have difficulty following public health rules. Once they acquire SARS-CoV-2 infection, people with disabilities may be at risk for severe outcomes because they have elevated rates of comorbidities.¹⁰ Some disabilities (e.g., spinal cord injuries and neurologic disabilities) result in physiologic changes that increase vulnerability to respiratory diseases and may mask symptoms of acute respiratory disease, which may delay diagnosis.^11–13 There have also been reports of barriers to high-quality hospital care for patients with disabilities who have COVID-19, including communication issues caused by the use of masks and restricted access to support persons.^14–17Some studies have suggested that patients with disabilities and COVID-19 are at elevated risk for severe disease and death, with most evaluating intellectual or developmental disability.^13,18–26 Yet, consideration of disability-related needs has largely been absent from the COVID-19 response, with vaccine eligibility driven primarily by age and medical comorbidity, limited accommodations made for patients with disabilities who are in hospital, and disability data often not being captured in surveillance programs.^14–17 To inform equitable pandemic supports, there is a need for data on patients with a broad range of disabilities who have COVID-19. We sought to evaluate standard clinical outcomes in patients admitted to hospital with COVID-19²⁷ (i.e., in-hospital death, intensive care unit [ICU] admission, hospital length of stay and unplanned 30-d readmission) for patients with and without a disability, overall and stratified by age. We hypothesized that patients with a disability would have worse outcomes because of a greater prevalence of comorbidities,¹⁰ physiologic characteristics that increase morbidity risk^11–13 and barriers to high-quality hospital care.^14–17     

Risk of interpersonal violence during and after pregnancy among people with schizophrenia: a population-based cohort study

Background:Schizophrenia is associated with increased risk of experiencing interpersonal violence. Little is known about risk specifically around the time of pregnancy.Methods:This population-based cohort study included all individuals (aged 15–49 yr) listed as female on their health cards who had a singleton birth in Ontario, Canada, between 2004 and 2018. We compared those with and without schizophrenia on their risk of an emergency department (ED) visit for interpersonal violence in pregnancy or within 1 year postpartum. We adjusted relative risks (RRs) for demographics, prepregnancy history of substance use disorder and history of interpersonal violence. In a subcohort analysis, we used linked clinical registry data to evaluate interpersonal violence screening and self-reported interpersonal violence during pregnancy.Results:We included 1 802 645 pregnant people, 4470 of whom had a diagnosis of schizophrenia. Overall, 137 (3.1%) of those with schizophrenia had a perinatal ED visit for interpersonal violence, compared with 7598 (0.4%) of those without schizophrenia, for an RR of 6.88 (95% confidence interval [CI] 5.66–8.37) and an adjusted RR of 3.44 (95% CI 2.86–4.15). Results were similar when calculated separately for the pregnancy (adjusted RR 3.47, 95% CI 2.68–4.51) period and the first year postpartum (adjusted RR 3.45, 95% CI 2.75–4.33). Pregnant people with schizophrenia were equally likely to be screened for interpersonal violence (74.3% v. 73.8%; adjusted RR 0.99, 95% CI 0.95–1.04), but more likely to self-report it (10.2% v. 2.4%; adjusted RR 3.38, 95% CI 2.61–4.38), compared with those without schizophrenia. Among patients who did not self-report interpersonal violence, schizophrenia was associated with an increased risk for a perinatal ED visit for interpersonal violence (4.0% v. 0.4%; adjusted RR 6.28, 95% CI 3.94–10.00).Interpretation:Pregnancy and postpartum are periods of higher risk for interpersonal violence among people with schizophrenia compared with those without schizophrenia. Pregnancy is a key period for implementing violence prevention strategies in this population.

Interpersonal violence is defined as the intentional use of force or power against others, including physical, sexual and psychological abuse perpetrated by strangers, acquaintances, family members or intimate partners.^1–5 Around the time of pregnancy, interpersonal violence affects not only the person experiencing it, but also the developing fetus or infant.⁶ Maternal consequences include acute injuries, chronic pain and psychiatric disorders.^7,8 Interpersonal violence is also associated with absent or delayed prenatal care, preterm birth, poor fetal growth, difficulties in maternal–child attachment, and maternal, fetal and neonatal death.^9–14Women with schizophrenia are at high risk of experiencing interpersonal violence during their lifetime from known and unknown perpetrators.^15–17 The lifetime prevalence of physical or sexual assault in this population is 20.7%, about 9 times the risk of those without serious mental illness.¹⁸ Many women with schizophrenia become pregnant, but little is known about their risk of experiencing interpersonal violence around this time.^19,20 In 2 small clinical studies, rates of self-reported interpersonal violence in pregnancy were upward of 20%.^21,22 However, these studies had no comparator groups without schizophrenia, included only self-reported risk and did not evaluate postpartum risk.We sought to compare the risk of an emergency department (ED) visit for interpersonal violence during pregnancy and until 1 year postpartum among people with and without schizophrenia in Ontario. We also sought to compare rates of interpersonal violence screening and disclosure in response to screening in these 2 groups, as well as risk for an ED visit for interpersonal violence in pregnancy or within the first year postpartum among those who did not self-report interpersonal violence. The latter question is important given that people with schizophrenia report being concerned that disclosure of any social issues during the perinatal period could possibly lead to undesirable consequences, such as child apprehension.^23,24     

Illuminating and mitigating the evolving impacts of COVID-19 on ethnocultural communities: a participatory action mixed-methods study

BACKGROUND:The COVID-19 pandemic has exacerbated disparities in poverty and illness for people in vulnerable circumstances in ethnocultural communities. We sought to understand the evolving impacts of COVID-19 on ethnocultural communities to inform intersectoral advocacy and community action.METHODS:The Illuminate Project used participatory action research, with cultural health brokers as peer researchers, from Sept. 21 to Dec. 31, 2020, in Edmonton, Alberta. Twenty-one peer researchers collected narratives from members of ethnocultural communities and self-interpreted them as they entered the narratives into the SenseMaker platform, a mixed-method data collection tool. The entire research team analyzed real-time, aggregate, quantitative and qualitative data to identify emerging thematic domains, then visualized these domains with social network analysis.RESULTS:Brokers serving diverse communities collected 773 narratives. Identified domains illuminate the evolving and entangled impacts of COVID-19 including the following: COVID-19 prevention and management; care of acute, chronic and serious illnesses other than COVID-19; maternal care; mental health and triggers of past trauma; financial insecurity; impact on children and youth and seniors; and legal concerns. We identified that community social capital and cultural brokering are key assets that facilitate access to formal health and social system supports.INTERPRETATION:The Illuminate Project has illustrated the entangled, systemic issues that result in poor health among vulnerable members of ethnocultural communities, and the exacerbating effects of COVID-19, which also increased barriers to mitigation. Cultural brokering and community social capital are key supports for people during the COVID-19 pandemic. These findings can inform policy to reduce harm and support community resiliency.

Mahatma Gandhi observed that “the true measure of any society can be found in how it treats its most vulnerable members.” Ethnocultural communities, defined by their unique shared characteristics (e.g., cultural traditions, language, country of origin),¹ face greater challenges and have higher rates of poverty and illness than the general Canadian population. Migration results in conditions that affect all social determinants of health and disproportionally affect health outcomes, herein referred to as vulnerable circumstances.^2,3 The emergence of major outbreaks of SARS-CoV-2 infections in ethnocultural communities highlights both the vulnerable circumstances of these communities and the disparities they face in accessing high-quality, culturally appropriate information and support.^4–7 Studies have shown substantial variation in deaths attributed to COVID-19 based on factors such as age, sex, ethnicity, length of time in Canada, income and education.^8–11 However, given the well-known gap in reporting comprehensive COVID-19 data in relation to race and ethnicity, efforts to measure its impact are hampered.^8–12 There is an urgent need to understand the evolving challenges of COVID-19 to inform action and public policy that can mitigate these challenges.To understand evolving situations of complexity and crisis, sensemaking, defined as “a continuous process to establish situational awareness,”¹³ is a crucial undertaking.¹⁴ Using participatory action research,^15–18 we sought to understand the evolving impacts of COVID-19 on ethnocultural communities to inform broader national efforts to migitate the impacts of COVID-19. Particularly, we sought to understand how the challenges of COVID-19 are entangled with contextual factors at multiple levels, how families and communities are leveraging strengths and social capital to adapt, and the role of cultural brokers in managing the crisis.     

Association between long-term exposure to ambient air pollution and COVID-19 severity: a prospective cohort study

Background:The tremendous global health burden related to COVID-19 means that identifying determinants of COVID-19 severity is important for prevention and intervention. We aimed to explore long-term exposure to ambient air pollution as a potential contributor to COVID-19 severity, given its known impact on the respiratory system.Methods:We used a cohort of all people with confirmed SARS-CoV-2 infection, aged 20 years and older and not residing in a long-term care facility in Ontario, Canada, during 2020. We evaluated the association between long-term exposure to fine particulate matter (PM_2.5), nitrogen dioxide (NO₂) and ground-level ozone (O₃), and risk of COVID-19-related hospital admission, intensive care unit (ICU) admission and death. We ascertained individuals’ long-term exposures to each air pollutant based on their residence from 2015 to 2019. We used logistic regression and adjusted for confounders and selection bias using various individual and contextual covariates obtained through data linkage.Results:Among the 151 105 people with confirmed SARS-CoV-2 infection in Ontario in 2020, we observed 8630 hospital admissions, 1912 ICU admissions and 2137 deaths related to COVID-19. For each interquartile range increase in exposure to PM_2.5 (1.70 μg/m³), we estimated odds ratios of 1.06 (95% confidence interval [CI] 1.01–1.12), 1.09 (95% CI 0.98–1.21) and 1.00 (95% CI 0.90–1.11) for hospital admission, ICU admission and death, respectively. Estimates were smaller for NO₂. We also estimated odds ratios of 1.15 (95% CI 1.06–1.23), 1.30 (95% CI 1.12–1.50) and 1.18 (95% CI 1.02–1.36) per interquartile range increase of 5.14 ppb in O₃ for hospital admission, ICU admission and death, respectively.Interpretation:Chronic exposure to air pollution may contribute to severe outcomes after SARS-CoV-2 infection, particularly exposure to O₃.

By November 2021, COVID-19 had caused more than 5 million deaths globally¹ and more than 29 400 in Canada.² The clinical manifestations of SARS-CoV-2 infection range from being asymptomatic to multiple organ failure and death. Identifying risk factors for COVID-19 severity is important to better understand etiological mechanisms and identify populations to prioritize for screening, vaccination and medical treatment. Risk factors for severity of COVID-19 include male sex, older age, pre-existing medical conditions and being from racialized communities.^3–5 More recently, ambient air pollution has been implicated as a potential driver of COVID-19 severity.^6–10Long-term exposure to ambient air pollution, a major contributor to global disease burden,¹¹ could increase the risk of severe COVID-19 outcomes by several mechanisms. Air pollutants can reduce individuals’ pulmonary immune responses and antimicrobial activities, boosting viral loads.⁸ Air pollution can also induce chronic inflammation and overexpression of the alveolar angiotensin-converting enzyme 2 (ACE) receptor,⁷ the key receptor that facilitates SARS-CoV-2 entry into cells.^12,13 Exposure to air pollution contributes to chronic conditions, such as cardiovascular disease, that are associated with unfavourable COVID-19 prognosis, possibly owing to persistent immune activation and excessive amplification of cytokine development.¹⁰ Thus, greater exposure to long-term air pollution may lead to severe COVID-19 outcomes.Reports exist of positive associations between long-term exposure to particulate matter with diameters equal to or smaller than 2.5 or 10 μm (PM_2.5 and PM₁₀), ground-level ozone (O₃) and nitrogen dioxide (NO₂), and metrics of COVID-19 severity (e.g., mortality and case fatality rate).^8–10 However, most studies to date have used ecological and cross-sectional designs, owing to limited access to individual data, which leads to ambiguity in interpreting the results, thus hindering their influence on policy. ^6,14 Ecological designs do not allow for disentangling the relative impacts of air pollution on individual susceptibility to infection and disease severity.¹⁴ Residual confounding by factors such as population mobility and social interactions is also problematic. Therefore, a cohort study with data on individuals with SARS-CoV-2 is a more appropriate design.^6,14 Studies that have used individual data were conducted in specific subpopulations^15,16 or populations with few severe cases,¹⁷ or had limited data on individual exposure to air pollutants.¹⁸ In Canada, 1 ecological study found a positive association between long-term exposure to PM_2.5 and COVID-19 incidence,¹⁹ but no published study has explored the association between air pollution and COVID-19 severity.We aimed to examine the associations between long-term exposure to 3 common air pollutants (PM_2.5, NO₂ and O₃) and key indicators of COVID-19 severity, including hospital admission, intensive care unit (ICU) admission and death, using a large prospective cohort of people with confirmed SARS-CoV-2 infection in Ontario, Canada, in 2020. The air contaminants PM_2.5, NO₂ and O₃ are regularly monitored by the Canadian government, and are key pollutants that are considered when setting air-quality policies. They originate from varying sources (NO₂ is primarily emitted during combustion of fuel, O₃ is primarily formed in air by chemical reactions of nitrogen oxides and volatile organic compounds, and PM_2.5 can be emitted during combustion or formed by reactions of chemicals like sulphur dioxide and nitrogen oxides in air) and they may affect human health differently.^20,21,22     

Parents’ perspectives on SARS-CoV-2 vaccinations for children: a qualitative analysis

Background:Uptake of the SARS-CoV-2 vaccine for children aged 5–11 years has been lower than anticipated in Canada. Although research has explored parental intentions toward SARS-CoV-2 vaccination for children, parental decisions regarding vaccinations have not been studied in-depth. We sought to explore reasons why parents chose to vaccinate or not vaccinate their children against SARS-CoV-2 to better understand their decisions.Methods:We conducted a qualitative study involving in-depth individual interviews with a purposive sample of parents in the Greater Toronto Area, Ontario, Canada. We conducted interviews via telephone or video call from February to April 2022 and analyzed the data using reflexive thematic analysis.Results:We interviewed 20 parents. We found that parental attitudes toward SARS-CoV-2 vaccinations for their children represented a complex continuum of concern. We identified 4 cross-cutting themes: the newness of SARS-CoV-2 vaccines and the evidence supporting their use; the perceived politicization of guidance for SARS-CoV-2 vaccination; the social pressure surrounding SARS-CoV-2 vaccinations; and the weighing of individual versus collective benefits of vaccination. Parents found making a decision about vaccinating their child challenging and expressed difficulty sourcing and evaluating evidence, determining the trustworthiness of guidance, and balancing their own conceptions of health care decisions with societal expectations and political messaging.Interpretation:Parents’ experiences making decisions regarding SARS-CoV-2 vaccination for their children were complex, even for those who were supportive of SARS-CoV-2 vaccinations. These findings provide some explanation for the current patterns of uptake of SARS-CoV-2 vaccination among children in Canada; health care providers and public health authorities can consider these insights when planning future vaccine rollouts.

In November 2021, children aged 5–11 years became eligible to receive the SARS-CoV-2 vaccine in Canada.¹ Before regulatory approval of SARS-CoV-2 vaccines for children, about two-thirds of parents in Canada reported a willingness to have their child receive the vaccine.^2–4 However, uptake of the vaccine for this age group has been lower than initial evidence of parental intent suggested. As of October 2022, only 47% of 5- to 11-year-old children in Canada had received at least 1 dose of the SARS-CoV-2 vaccine, and 42% had completed their primary series, compared with 90% and 88%, respectively, of people aged 12 years and older; rates in Ontario were similar.⁵Considerable research has evaluated parental intention to vaccinate their children against SARS-CoV-2 in Canada^2–4,6–8 and internationally,^9–16 but few studies have explored parents’ decisions to have their children vaccinated or not, once eligible.¹⁷ Given the observed discrepancy between parental intention and decision to seek vaccination for their children against SARS-CoV-2, it is critical to investigate how and why parents make their decisions. Understanding the factors that influence parents to seek vaccination against SARS-CoV-2 for their children, or not, would help inform policies and interventions focused on this population and would help health care professionals understand parents’ perspectives and concerns.Vaccine hesitancy is defined by the World Health Organization as a “delay in acceptance or refusal of vaccines despite availability of vaccination services.”¹⁸ This definition is often used to describe individuals who have apprehension about vaccination, choose to delay vaccination or refuse vaccines entirely.¹⁹ Attitudes toward SARS-CoV-2 vaccination for children have received much attention in the literature, but most studies have used quantitative surveys to measure vaccine hesitancy; in-depth qualitative evidence on the reasons underlying those attitudes and decisions is needed. Although the spectrum of hesitancy for SARS-CoV-2 vaccination is acknowledged in the literature;^20–22 the full range and nature of these perspectives, and the experiences of parents related to SARS-CoV-2 vaccination decisions for their children, has not yet been explored. We sought to understand why parents chose to seek vaccination against SARS-CoV-2 for their children or not, and to capture the nuances of these decisions.     

SARS-CoV-2 seroprevalence in health care workers from 10 hospitals in Quebec,Canada: a cross-sectional study

Background:The COVID-19 pandemic has disproportionately affected health care workers. We sought to estimate SARS-CoV-2 seroprevalence among hospital health care workers in Quebec, Canada, after the first wave of the pandemic and to explore factors associated with SARS-CoV-2 seropositivity.Methods:Between July 6 and Sept. 24, 2020, we enrolled health care workers from 10 hospitals, including 8 from a region with a high incidence of COVID-19 (the Montréal area) and 2 from low-incidence regions of Quebec. Eligible health care workers were physicians, nurses, orderlies and cleaning staff working in 4 types of care units (emergency department, intensive care unit, COVID-19 inpatient unit and non-COVID-19 inpatient unit). Participants completed a questionnaire and underwent SARS-CoV-2 serology testing. We identified factors independently associated with higher seroprevalence.Results:Among 2056 enrolled health care workers, 241 (11.7%) had positive SARS-CoV-2 serology. Of these, 171 (71.0%) had been previously diagnosed with COVID-19. Seroprevalence varied among hospitals, from 2.4% to 3.7% in low-incidence regions to 17.9% to 32.0% in hospitals with outbreaks involving 5 or more health care workers. Higher seroprevalence was associated with working in a hospital where outbreaks occurred (adjusted prevalence ratio 4.16, 95% confidence interval [CI] 2.63–6.57), being a nurse or nursing assistant (adjusted prevalence ratio 1.34, 95% CI 1.03–1.74) or an orderly (adjusted prevalence ratio 1.49, 95% CI 1.12–1.97), and Black or Hispanic ethnicity (adjusted prevalence ratio 1.41, 95% CI 1.13–1.76). Lower seroprevalence was associated with working in the intensive care unit (adjusted prevalence ratio 0.47, 95% CI 0.30–0.71) or the emergency department (adjusted prevalence ratio 0.61, 95% CI 0.39–0.98).Interpretation:Health care workers in Quebec hospitals were at high risk of SARS-CoV-2 infection, particularly in outbreak settings. More work is needed to better understand SARS-CoV-2 transmission dynamics in health care settings.

The COVID-19 pandemic has disproportionately affected health care workers. In France, Spain, Italy, Germany and the United States, at least 10% of cases reported in spring 2020 were in health care workers.¹ In Quebec, 25% (14 177 of 56 565) of all cases declared during the first wave of the pandemic, from March to July 2020, were in health care workers,² about one-third of whom were working in acute care hospitals.¹ The Montréal area was the most affected region in Quebec and Canada during the first wave, reaching a COVID-19 incidence rate of 1336 per 100 000 population.²The number of COVID-19 cases reported among health care workers underestimated the number of those infected with SARS-CoV-2 during that period, given limited testing leading to undiagnosed asymptomatic or paucisymptomatic infections.³ Seroprevalence studies are an important tool to determine the proportion of people infected with SARS-CoV-2, both in the general population and among health care workers.⁴ After the first wave in Quebec, SARS-CoV-2 seroprevalence in adults aged 18–69 years was found to be low (3.1% in Montréal and 1.3% in less affected regions), but this proportion could be much higher among health care workers who had to work despite the general shutdown of social and economic activities, especially if they were exposed to major outbreaks.⁵Only 2 other Canadian studies provide SARS-CoV-2 seroprevalence estimates among health care workers, and both studies were from a single centre.^6,7 Outside Canada, most seroprevalence studies among health care workers include a single site and do not provide a representative estimate for a defined region.⁸ Several studies have reported a higher seroprevalence among health care workers from units treating patients with COVID-19 (COVID-19 units) compared with other units (non–COVID-19 units), emergency departments or intensive care units.^9,10 Other studies have not identified such associations.^11,12 In this study, we aimed to assess the seroprevalence of SARS-CoV-2 antibody among hospital health care workers from a variety of settings after the first pandemic wave in Quebec, and to explore factors associated with SARS-CoV-2 seropositivity.     

Preterm birth and stillbirth rates during the COVID-19 pandemic: a population-based cohort study

BACKGROUND:Conflicting reports have emerged for rates of preterm births and stillbirths during the COVID-19 pandemic. Most of these reports did not account for natural variation in these rates. We aimed to evaluate variations in preterm birth and stillbirth rates before and during the COVID-19 pandemic in Ontario, Canada.METHODS:We conducted a retrospective cohort study using linked population health administrative databases of pregnant people giving birth in any hospital in Ontario between July 2002 and December 2020. We calculated preterm birth and stillbirth rates. We assessed preterm birth at 22–28, 29–32 and 33–36 weeks’ gestation, and stillbirths at term and preterm gestation. We used Laney control P′ charts for the 18-year study period (6-mo observation periods) and interrupted time-series analyses for monthly rates for the most recent 4 years.RESULTS:We evaluated 2 465 387 pregnancies, including 13 781 that resulted in stillbirth. The mean preterm birth rate for our cohort was 7.96% (range 7.32%–8.59%). From January to December 2020, we determined that the preterm birth rate in Ontario was 7.87%, with no special cause variation. The mean stillbirth rate for the cohort was 0.56% (range 0.48%–0.70%). From January to December 2020, the stillbirth rate was 0.53%, with no special cause variation. We did not find any special cause variation for preterm birth or stillbirth subgroups. We found no changes in slope or gap between prepandemic and pandemic periods using interrupted time-series analyses.INTERPRETATION:In Ontario, Canada, we found no special cause variation (unusual change) in preterm birth or stillbirth rates, overall or by subgroups, during the first 12 months of the COVID-19 pandemic compared with the previous 17.5 years.

Preterm birth (birth before 37 weeks’ gestation) is a leading cause of mortality and morbidities in the neonatal period,¹ childhood and adulthood.² Stillbirth has devastating consequences for families.³ The causes of both preterm birth and stillbirth are multifactorial. During the pandemic, reports described reductions in preterm birth rates in Denmark,⁴ the Netherlands,⁵ Ireland⁶ and the United States.⁷ At the same time, increases in stillbirth rates were reported from the United Kingdom,⁸ Italy,⁹ Nepal¹⁰ and India,¹¹ with or without changes in rates of preterm births. Meta-analyses have emerged with differing conclusions.^12,13 Some speculated reasons for reductions in preterm births included reductions in physical activity during pregnancy, reduced stress related to work–life balance, less exposure to infection, fewer medical interventions, reduced travel and pollution,¹⁴ and improved hygiene and rest. Proposed reasons for increases in preterm birth rates include higher stress due to worry about the pandemic, employment or financial challenges, home schooling and reduced maternity services.¹⁵ Less stringent fetal surveillance from reduced attendance at medical appointments for fear of infection, cancellation of face-to-face appointments and reduced staffing for maternity services are possible reasons for increased rates of stillbirths. Thus, it is important to evaluate preterm births and stillbirths simultaneously to understand the true impact.¹⁶Some previous reports compared preterm birth and stillbirth rates during the pandemic to similar time periods in the past few years. However, within a jurisdiction, these rates are known to fluctuate between epochs¹⁷ and, thus, it is preferable to evaluate rates over longer periods to establish whether observed variations are usual (common cause variation) or unusual (special cause variation). Our objective was to evaluate whether the COVID-19 pandemic affected preterm birth or stillbirth rates in Ontario by comparing rates for the early COVID-19 pandemic time period with rates from the previous 17.5 years to identify patterns of variation.     

Hospital factors associated with maternal and neonatal outcomes of deliveries to patients with a previous cesarean delivery: an ecological study

Background:Recommendations for deliveries of pregnant patients with a previous cesarean delivery and the type of hospitals deemed safe for these deliveries have evolved in recent years, although no studies have examined hospital factors and associated safety. We sought to evaluate maternal and neonatal outcomes among patients with a previous cesarean delivery by hospital tier and volume.Methods:We carried out an ecological study of singleton live births delivered at term gestation to patients with a previous cesarean delivery in all Canadian hospitals (excluding Quebec), 2013–2019. We obtained data from the Discharge Abstract Database of the Canadian Institute for Health Information. The primary outcomes were severe maternal morbidity or mortality (SMMM), and serious neonatal morbidity or mortality (SNMM). We used regression modelling to examine hospital tier (tier 4 hospitals being those that provide the highest level of care) and volume; we also identified hospitals with high rates of SMMM and SNMM using within-tier comparisons and comparisons with the overall rate.Results:We included 235 442 deliveries to patients with a previous cesarean delivery; SMMM and SNMM rates were 14.6 per 1000 deliveries and 4.6 per 1000 live births, respectively. Among patients with a parity of 1, SMMM rates were lower in tier 1 hospitals (adjusted incidence rate ratio [IRR] 0.68, 95% confidence interval [CI] 0.52–0.89) and higher in tier 4 hospitals (adjusted IRR 1.41, 95% CI 1.05–1.91) than in tier 2 hospitals; SNMM rates did not differ by hospital tier. Rates of SNMM increased with increasing hospital volume (adjusted IRR 1.02, 95% CI 1.00–1.04) and increasing rates of vaginal birth after cesarean delivery (adjusted IRR 1.02, 95% CI 1.01–1.04). Most hospitals had relatively low SMMM and SNMM rates, although a few hospitals in each tier and volume category had significantly higher rates than others.Interpretation:Adverse maternal and neonatal outcomes among patients with a previous cesarean delivery showed no clear pattern of decreasing SMMM and SNMM with increasing tiers of service and hospital volume. All hospitals, irrespective of tier or size, should continually review their rates of adverse maternal and neonatal outcomes.

The approach to delivery for patients with a previous cesarean delivery has undergone substantial changes over the last few decades in Canada, the United States and elsewhere. Rates of vaginal birth after cesarean delivery (VBAC) in Canada increased rapidly, from less than 5% of deliveries in the late 1970s to peak at more than 35% in the mid-1990s.^1–4 However, this trend reversed sharply after studies in the mid-1990s showed that attempted VBAC (as opposed to elective repeat cesarean delivery) was associated with higher rates of severe maternal morbidity and of fetal and infant morbidity and mortality.^5–9 The decline has partly reversed after the release of a guideline from the Society of Obstetricians and Gynaecologists of Canada (SOGC) in 2005, and the National Institutes of Health Consensus Development Conference in 2010, which affirmed that patients with 1 previous transverse lower-segment cesarean section and no contraindications could be offered a trial of labour with appropriate discussion of risks and benefits.^10,11Recommendations regarding hospitals deemed safe for delivering patients with a previous cesarean delivery have also evolved. The 1998 and 1999 guidelines of the American College of Obstetricians and Gynecologists (ACOG) required hospitals attempting trials of labour to have “ready availability of emergency care” or “immediate availability of emergency care.”^12,13 After the publication of these guidelines, about 30% of hospitals in the US stopped offering trial-of-labour services to patients with a previous cesarean delivery because they could not provide immediate surgical and anesthesia services, which compelled many patients who had opted for a trial of labour to travel to hospitals far from their homes and families.^14–16 More recently, guidelines have attempted to balance clinical safety with the challenges associated with such social disruption. The current ACOG guideline states that a trial of labour can be attempted in a level 1 maternity care facility (i.e., a hospital providing basic obstetric services), which has “the ability to begin emergency cesarean delivery within a time interval that best incorporates maternal and fetal risks and benefits.”¹⁷ Similarly, the current SOGC guideline states that hospitals providing trial-of-labour services should have “the resources to perform an emergency cesarean section.”¹⁸ This change in recommendations has led to an increase in the number of hospitals that offer trials of labour, though concerns about inadequate access to such delivery options persist.^19,20Although clinical guidelines regarding hospitals deemed safe for delivering patients with a previous cesarean delivery have changed in recent years, to our knowledge, no studies have evaluated hospital factors and associated safety issues. We sought to evaluate maternal and infant outcomes of deliveries to patients with a previous cesarean delivery by tier of obstetric service and hospital delivery volume.     

Maternal cardiovascular disease after twin pregnancies complicated by hypertensive disorders of pregnancy: a population-based cohort study

Background:People whose singleton pregnancy is affected by hypertensive disorders of pregnancy (HDP) are at risk of future cardiovascular disease. It is unclear, however, whether this association can be extrapolated to twin pregnancies. We aimed to compare the association between HDP and future cardiovascular disease after twin and singleton pregnancies.Methods:We conducted a population-based retrospective cohort study that included nulliparous people in Ontario, Canada, 1992–2017. We compared the future risk of cardiovascular disease among pregnant people from the following 4 groups: those who delivered a singleton without HDP (referent) and with HDP, and those who delivered twins either with or without HDP.Results:The populations of the 4 groups were as follows: 1 431 651 pregnant people in the singleton birth without HDP group; 98 631 singleton birth with HDP; 21 046 twin birth without HDP; and 4283 twin birth with HDP. The median duration of follow-up was 13 (interquartile range 7–20) years. The incidence rate of cardiovascular disease was lowest among those with a singleton or twin birth without HDP (0.72 and 0.74 per 1000 person-years, respectively). Compared with people with a singleton birth without HDP, the risk of cardiovascular disease was highest among those with a singleton birth and HDP (1.47 per 1000 person-years; adjusted hazard ratio [HR] 1.81 [95% confidence interval (CI) 1.72–1.90]), followed by people with a twin pregnancy and HDP (1.07 per 1000 person-years; adjusted HR 1.36 [95% CI 1.04–1.77]). The risk of the primary outcome after a twin pregnancy with HDP was lower than that after a singleton pregnancy with HDP (adjusted HR 0.74 [95% CI 0.57–0.97]), when compared directly.Interpretation:In a twin pregnancy, HDP are weaker risk factors for postpartum cardiovascular disease than in a singleton pregnancy.

Cardiovascular disease has been shown to be the leading cause of death among women.^1–3 Classic risk factors for cardiovascular disease include obesity, diabetes mellitus, hypertension and family history of cardiovascular disease. ³ More recently, an association has been established between a history of hypertensive disorders of pregnancy (HDP) — gestational hypertension and pre-eclampsia — and future risk of cardiovascular disease.^1,4–11 Consequently, some recommend using a history of HDP for cardiovascular disease risk stratification in women.^3,12The leading hypothesis for the pathogenesis of HDP is that it results from abnormal placentation due to impaired trophoblast invasion,^13–16 resulting in reduced placental perfusion.^17–19 This, in turn, leads to abnormal secretion of the angiogenic factors soluble FMS-like tyrosine kinase 1 (sFlt1) and soluble endoglin (sEng),²⁰ which induce endothelial dysfunction and the clinical manifestations of HDP.^19,21–24 The mechanisms underlying the association between HDP and future cardiovascular disease are under debate.²⁵ One hypothesis is that HDP are merely a marker of underlying subclinical or clinical vascular risk factors that predispose a person to both HDP and future cardiovascular disease.A person who is pregnant with twins is at about 3–4 times higher risk of HDP than a person with a singleton pregnancy,^26–33 with rates of 14% and 5%, respectively.³⁴ The higher risk of HDP in twin pregnancies may be due to higher circulating sFlt1 and sEng owing to greater placental mass in twin pregnancies, ^35–37 and less related to the classic vascular risk factors for HDP in a singleton pregnancy. Therefore, a logical question is whether the established higher risk of future cardiovascular disease after singleton pregnancies with HDP also occurs in twin pregnancies with HDP. Limited data are available to answer this question.³⁸ In the current study, we aimed to test the hypothesis that the association between HDP and future cardiovascular disease is less pronounced in twin versus singleton pregnancies.     

Suicidality among sexual minority and transgender adolescents: a nationally representative population-based study of youth in Canada

Background:Very little research has described risk of suicidal ideation and suicide attempt among transgender youth using high-quality, nationally representative data. We aimed to assess risk of suicidality among transgender and sexual minority adolescents in Canada.Methods:We analyzed a subsample of adolescents aged 15–17 years from the 2019 Canadian Health Survey on Children and Youth, a nationally representative, cross-sectional survey. We defined participants’ transgender identity (self-reported gender different from sex assigned at birth) and sexual minority status (self-reported attraction to people of the same gender) as exposures, and their self-reported previous-year suicidal ideation and lifetime suicide attempt as outcomes.Results:We included 6800 adolescents aged 15–17 years, including 1130 (16.5%) who indicated some degree of same-gender attraction, 265 (4.3%) who were unsure of their attraction and 50 (0.6%) who reported a transgender identity. Compared with cisgender, heterosexual adolescents, transgender adolescents showed 5 times the risk of suicidal ideation (95% confidence interval [CI] 3.63 to 6.75; 58% v. 10%) and 7.6 times the risk of suicide attempt (95% CI 4.76 to 12.10; 40% v. 5%). Among cisgender adolescents, girls attracted to girls had 3.6 times the risk of previous-year suicidal ideation (95% CI 2.59 to 5.08) and 3.3 times the risk of having ever attempted suicide (95% CI 1.81 to 6.06), compared with their heterosexual peers. Adolescents attracted to multiple genders had 2.5 times the risk of suicidal ideation (95% CI 2.12 to 2.98) and 2.8 times the risk of suicide attempt (95% CI 2.18 to 3.68). Youth questioning their sexual orientation had twice the risk of having attempted suicide in their lifetime (95% CI 1.23 to 3.36).Interpretation:We observed that transgender and sexual minority adolescents were at increased risk of suicidal ideation and attempt compared with their cisgender and heterosexual peers. These findings highlight the need for inclusive prevention approaches to address suicidality among Canada’s diverse youth population.

Suicide is the second leading cause of death among adolescents and young adults aged 15–24 years in Canada.^1,2 Suicidal ideation and suicide attempt are common among adolescents³ and are risk factors for death by suicide.⁴ Sexual minority youth (i.e., youth who are attracted to the same gender or multiple genders, or who identify as lesbian, gay, bisexual or queer)⁵ are known to be at increased risk of poor mental health,^6–8 including suicidal ideation and attempt.^5–10 Over the previous 2 decades, stigma around identifying as a sexual minority has reduced;⁷ however, the risk of poor mental health and of suicidality remains high among sexual minority youth.^7,11 This population is still more likely to experience bullying and peer victimization,^9,12,13 which is associated with suicidality among sexual minority adolescents.⁵Transgender youth are those whose gender identity does not match their sex assigned at birth.¹⁴ Among other terms, gender-nonconforming, nonbinary, genderqueer and genderfluid are used to describe the gender identity of a subset of young people who identify outside the gender binary (i.e., as neither male nor female) or who experience fluidity between genders.⁹ Suicidality among transgender and gender-nonconforming adolescents is not as well studied. In a Canadian survey of transgender and gender-nonconforming youth aged 14–25 years, 64% of participants reported that they had seriously considered suicide in the previous 12 months.¹⁵ Transgender and gender-nonconforming youth seem to have a higher probability of many risk factors for suicidality, including peer victimization,^8,16 family dysfunction^7,17 and barriers to accessing mental health care.¹⁸ However, the epidemiology of suicidality among transgender and gender-nonconforming youth remains understudied in population-based samples; most research on the mental health of transgender youth comes from small community samples of help-seeking youth or targeted surveys of transgender adolescents.^5,19,20 Two population-based studies from California²¹ and New Zealand²² suggested that transgender youth are at increased risk of suicidal ideation and suicide attempt. However, only the New Zealand study²² used the gold-standard measure of gender identity, contrasting adolescents’ sex assigned at birth with their self-identified gender.²³Further epidemiological research employing large, representative samples and adequate measures of gender identity is needed to understand the burden of suicidality among lesbian, gay, bisexual, transgender and queer youth. We sought to build on existing evidence to assess risk of suicidal ideation and attempt among transgender and sexual minority adolescents in Canada, as compared with their cisgender and heterosexual peers, as well as to explore the relation between suicidality and experience of bullying.     

Reasons for cannabis use during pregnancy and lactation: a qualitative study

Background:Cannabis use among pregnant and lactating people is increasing, despite clinical evidence showing that cannabis use may be associated with low birth weight and childhood developmental deficits. Our objective was to understand why pregnant and lactating people use cannabis and how these motivations change across perinatal stages.Methods:Using qualitative, constructivist grounded theory methodology, we conducted telephone and virtual interviews with 52 individuals from across Canada. We selected participants using maximum variation and theoretical sampling. They were eligible if they had been pregnant or lactating within the past year and had decided to continue, cease or decrease their cannabis use during the perinatal period.Results:We identified 3 categories of reasons that people use cannabis during pregnancy and lactation: sensation-seeking for fun and enjoyment; symptom management of chronic conditions and conditions related to pregnancy; and coping with the unpleasant, but nonpathologized, experiences of life. Before pregnancy, participants endorsed reasons for using cannabis in these 3 categories in similar proportions, with many offering multiple reasons for use. During pregnancy, reasons for use shifted primarily to symptom management. During lactation, reasons returned to resemble those expressed before pregnancy.Interpretation:In this study, we showed that pregnant and lactating people use cannabis for many reasons, particularly for symptom management. Reasons for cannabis use changed across reproductive stages. The dynamic nature of the reasons for use across stages speaks to participant perception of benefits and risks, and perhaps a desire to cast cannabis use during pregnancy as therapeutic because of perceived stigma.

Cannabis use by pregnant and lactating people is increasing, though it is difficult to establish the prevalence of cannabis use in pregnancy. Reported prevalence varies from 2% to 36%, depending on the methodology used to detect use, the population studied and the definition of use.^1–12 Pregnant people have reported using cannabis to manage pregnancy-related conditions (e.g., nausea, weight gain, sleep difficulty)^13–19 and pre-existing conditions (e.g., mental health, insomnia, chronic pain),^13,14,18 as well as to improve mood, mental, physical and spiritual well-being,^16,18 provide pleasure and manage stress.^13–16 Recent systematic reviews have not found empirical data on reasons for cannabis use during lactation.^20,21Evidence is still emerging about clinical outcomes related to cannabis use during pregnancy and lactation, and well-controlled studies are lacking.^22–24 The available evidence is limited by reliance on self-reported data about dose, composition and timing of exposure, the changing nature of tetrahydrocannabinol levels in cannabis over time, and a lack of studies that control for known confounders such as polysubstance and tobacco use.^25–31 The available evidence does suggest that cannabis use during pregnancy may be associated with complications such as low birth weight, childhood neurodevelopmental outcomes and preterm birth.^{22–24,32,33} Very few studies have analyzed the outcomes associated with cannabis exposure through breastmilk, with 1 study suggesting decreased infant motor development and another showing no effects on developmental outcomes.^34–36 Given the potential harms identified, and in the absence of high-quality evidence available to guide practice, most clinical guidelines recommend abstinence from cannabis during pregnancy and lactation.^37–39People who perceive benefits from cannabis may wish to or may be motivated to continue using it through pregnancy and lactation, however. Counselling that explores the reasons patients are considering cannabis use and suggests related alternatives or harm reduction strategies has been identified as a helpful strategy to minimize potential harm.^13,40,41,42 Such an approach requires that clinicians understand the motivations to use cannabis before pregnancy, during pregnancy and during lactation. We sought to explore why people use cannabis during pregnancy and lactation.     

Comparison of black–white disparities in preterm birth between Canada and the United States

Background:

A higher risk of preterm birth among black women than among white women is well established in the United States. We compared differences in preterm birth between non-Hispanic black and white women in Canada and the US, hypothesizing that disparities would be less extreme in Canada given the different historical experiences of black populations and Canada’s universal health care system.

Methods:

Using data on singleton live births in Canada and the US for 2004–2006, we estimated crude and adjusted risk ratios and risk differences in preterm birth (< 37 wk) and very preterm birth (< 32 wk) among non-Hispanic black versus non-Hispanic white women in each country. Adjusted models for the US were standardized to the covariate distribution of the Canadian cohort.

Results:

In Canada, 8.9% and 5.9% of infants born to black and white mothers, respectively, were preterm; the corresponding figures in the US were 12.7% and 8.0%. Crude risk ratios for preterm birth among black women relative to white women were 1.49 (95% confidence interval [CI] 1.32 to 1.66) in Canada and 1.57 (95% CI 1.56 to 1.58) in the US (p value for heterogeneity [p_H] = 0.3). The crude risk differences for preterm birth were 2.94 (95% CI 1.91 to 3.96) in Canada and 4.63 (95% CI 4.56 to 4.70) in the US (p_H = 0.003). Adjusted risk ratios for preterm birth (p_H = 0.1) were slightly higher in Canada than in the US, whereas adjusted risk differences were similar in both countries. Similar patterns were observed for racial disparities in very preterm birth.

Interpretation:

Relative disparities in preterm birth and very preterm birth between non-Hispanic black and white women were similar in magnitude in Canada and the US. Absolute disparities were smaller in Canada, which reflects a lower overall risk of preterm birth in Canada than in the US in both black and white populations.In the United States, a higher risk of preterm birth among black women than among white women is well established.^1–3 This racial disparity is of great concern because preterm birth is a leading cause of perinatal mortality and is predictive of developmental problems and adverse health outcomes later in life.⁴ The underlying causes of the racial disparity in preterm birth in the US are not well understood, although research has suggested contributing roles for a wide range of factors, including socioeconomic disadvantage,⁵ poor neighbourhood conditions (e.g., poverty, crime),^5,6 lack of access to health care,⁷ psychosocial stress,⁸ racial discrimination⁹ and adverse health behaviours.¹⁰Rates of preterm birth have consistently been lower in Canada than in the US.^11,12 However, in contrast to the US, little is known about differences in rates by race or ethnicity in Canada. There is evidence that African-born and Caribbean-born women in the provinces of Quebec and Ontario have higher rates of preterm birth than Canadian-born women.^13–15 Although the magnitude of these differences is smaller than the disparity in preterm births between black and white women in the US,¹⁶ foreign-born black women in the US have been found to be at lower risk of preterm birth than US-born black women.^17,18In both Canada and the US, socioeconomic conditions at both individual and neighbourhood levels are important predictors of preterm birth.^19–21 Although the income gap between black and white people is markedly smaller in Canada than in the US,²² black populations in both countries have lower education levels, higher unemployment rates and a greater likelihood of living in low-quality neighbourhoods compared with white populations.²³ Canada and the US share similar social and economic influences, yet the historical experiences of black populations and the social welfare systems (e.g., universal health care) are quite different in the 2 countries. Black people constitute about 13% of the total US population, but only about 3% of the Canadian population.^24,25 The overwhelming majority of Canada’s black population are immigrants who entered the country after 1960 and their descendants, whereas more than 85% of black Americans can trace their ancestry 3 or more generations in the US, with most being descendants of slaves.²²The objectives of our study are twofold. First, using data from a new cohort linking birth registrations with information from the 2006 Canadian long-form census, we present Canada-wide estimates of differences in preterm birth rates between black and white populations. Second, we use comparable methodology to compare racial differences in preterm birth rates between Canada and the US. Given different historical experiences of black populations in the 2 countries, as well as Canada’s commitment to universal health care and its general perception as a more egalitarian society than the US,²² we hypothesized that we would observe smaller racial disparities in the rates in Canada than in the US.     

Incidence of childhood cancer in Canada during the COVID-19 pandemic

Background:The COVID-19 pandemic has had a major impact on access to health care resources. Our objective was to estimate the impact of the COVID-19 pandemic on the incidence of childhood cancer in Canada. We also aimed to compare the proportion of patients who enrolled in clinical trials at diagnosis, presented with metastatic disease or had an early death during the first 9 months of the COVID-19 pandemic compared with previous years.Methods:We conducted an observational study that included children younger than 15 years with a new diagnosis of cancer between March 2016 and November 2020 at 1 of 17 Canadian pediatric oncology centres. Our primary outcome was the monthly age-standardized incidence rates (ASIRs) of cancers. We evaluated level and trend changes using interventional autoregressive integrated moving average models. Secondary outcomes were the proportion of patients who were enrolled in a clinical trial, who had metastatic or advanced disease and who died within 30 days. We compared the baseline and pandemic periods using rate ratios (RRs) and 95% confidence intervals (CIs).Results:Age-standardized incidence rates during COVID-19 quarters were 157.7, 164.6, and 148.0 per million, respectively, whereas quarterly baseline ASIRs ranged between 150.3 and 175.1 per million (incidence RR 0.93 [95% CI 0.78 to 1.12] to incidence RR 1.04 [95% CI 0.87 to 1.24]). We found no statistically significant level or slope changes between the projected and observed ASIRs for all new cancers (parameter estimate [β], level 4.98, 95% CI −15.1 to 25.04, p = 0.25), or when stratified by cancer type or by geographic area. Clinical trial enrolment rate was stable or increased during the pandemic compared with baseline (RR 1.22 [95% CI 0.70 to 2.13] to RR 1.71 [95% CI 1.01 to 2.89]). There was no difference in the proportion of patients with metastatic disease (RR 0.84 [95% CI 0.55 to 1.29] to RR 1.22 [0.84 to 1.79]), or who died within 30 days (RR 0.16 [95% CI 0.01 to 3.04] to RR 1.73 [95% CI 0.38 to 15.2]).Interpretation:We did not observe a statistically significant change in the incidence of childhood cancer, or in the proportion of children enrolling in a clinical trial, presenting with metastatic disease or who died early during the first 9 months of the COVID-19 pandemic, which suggests that access to health care in pediatric oncology was not reduced substantially in Canada.

Concerns have been raised that the COVID-19 pandemic disrupted health care–seeking behaviours and access to health care, affecting the diagnosis and management of other conditions such as cancer. Studies conducted in the Netherlands and United Kingdom using administrative data have shown as much as a 50% reduction in cancer incidence in adults after March 2020.^1,2 Other studies in adult populations thus far have shown a decrease in the number of new cancer diagnoses, and cancer-related medical visits, therapies and surgeries, ^1,3–5 raising concerns about potential excess cancer mortality in the upcoming years.⁶ This may be explained partly by the suspension or reduction of cancer-screening procedures, such as mammography, colonoscopy and cervical cytology by up to 90%,^3,5,7 because these screening initiatives play a critical role in the detection of cancers in adults. A 2020 retrospective single-centre cohort study in Japan that involved 123 patients with colorectal cancer reported that significantly more of these patients presented with complete intestinal obstruction, which suggests that detection delays might have contributed to diagnosis at later stages of the disease.⁸ It is unclear whether these findings apply to childhood cancer because cancer screening is not part of routine pediatric care, and early detection may not be as important in childhood cancer than in its adult counterpart.⁹In children, case series and single-centre retrospective cohort studies, notably from Italy and the United States, suggested a marked reduction in incident cancers, along with high acuity of care at presentation.^10–13 Similar concerns of delayed clinical presentation were raised in other pediatric patient populations, with reports of children presenting at late stages of sepsis or diabetic ketoacidosis, which suggests a delay in seeking care.^14,15It is possible that fear of COVID-19 dissuaded families with children from seeking care for nonspecific symptoms such as pain, headache or fatigue, which are typical triggers leading to a pediatric cancer diagnosis. Understanding the indirect effects of health policies during the COVID-19 pandemic is important to guide policy-making and mitigate barriers to essential health care in future public health crises.Our objective was to measure the impact of the COVID-19 pandemic and associated restrictions on the incidence of childhood cancer in Canada. We also aimed to compare the proportion of patients who enrolled in clinical trials at diagnosis, presented with metastatic disease or died during the first 9 months of the COVID-19 pandemic compared with previous years.