Modelling mitigation strategies for pandemic (H1N1) 2009

Background

The 2009 influenza A (H1N1) pandemic has required decision-makers to act in the face of substantial uncertainties. Simulation models can be used to project the effectiveness of mitigation strategies, but the choice of the best scenario may change depending on model assumptions and uncertainties.

Methods

We developed a simulation model of a pandemic (H1N1) 2009 outbreak in a structured population using demographic data from a medium-sized city in Ontario and epidemiologic influenza pandemic data. We projected the attack rate under different combinations of vaccination, school closure and antiviral drug strategies (with corresponding “trigger” conditions). To assess the impact of epidemiologic and program uncertainty, we used “combinatorial uncertainty analysis.” This permitted us to identify the general features of public health response programs that resulted in the lowest attack rates.

Results

Delays in vaccination of 30 days or more reduced the effectiveness of vaccination in lowering the attack rate. However, pre-existing immunity in 15% or more of the population kept the attack rates low, even if the whole population was not vaccinated or vaccination was delayed. School closure was effective in reducing the attack rate, especially if applied early in the outbreak, but this is not necessary if vaccine is available early or if pre-existing immunity is strong.

Interpretation

Early action, especially rapid vaccine deployment, is disproportionately effective in reducing the attack rate. This finding is particularly important given the early appearance of pandemic (H1N1) 2009 in many schools in September 2009.Jurisdictions in the northern hemisphere are bracing for a “fall wave” of pandemic (H1N1) 2009.^1–3 Decision-makers face uncertainty, not just with respect to epidemiologic characteristics of the virus,⁴ but also program uncertainties related to feasibility, timeliness and effectiveness of mitigation strategies.⁵ Policy decisions must be made against this backdrop of uncertainty. However, the effectiveness of any mitigation strategy generally depends on the epidemiologic characteristics of the pathogen as well as the other mitigation strategies adopted. Mathematical models can project strategy effectiveness under hypothetical epidemiologic and program scenarios.^6–12 In the case of pandemic influenza, models have been used to assess the effectiveness of school closure⁷ and optimal use of antiviral drug^6,9,10 and vaccination strategies.⁸ However, model projections can be sensitive to input parameter values; thus, data uncertainty is an issue.¹³ Uncertainty analysis can help address the impact of uncertainties on model predictions but is often underutilized.¹³In this article, we present a simulation model of pandemic influenza transmission and mitigation in a population. This model projects the overall attack rate (percentage of people infected) during an outbreak. We introduce a formal method of uncertainty analysis that has not previously been applied to pandemic influenza, and we use this method to assess the impact of epidemiologic and program uncertainties. The model is intended to address the following policy questions that have been raised during the 2009 influenza pandemic: What is the impact of delayed vaccine delivery on attack rates? Can attack rates be substantially reduced without closing schools? What is the impact of pre-existing immunity from spring and summer 2009? We addressed these questions using a simulation model that projects the impact of vaccination, school closure and antiviral drug treatment strategies on attack rates.     

The responses of Aboriginal Canadians to adjuvanted pandemic (H1N1) 2009 influenza vaccine

Background:

Because many Aboriginal Canadians had severe cases of pandemic (H1N1) 2009 influenza, they were given priority access to vaccine. However, it was not known if the single recommended dose would adequately protect people at high risk, prompting our study to assess responses to the vaccine among Aboriginal Canadians.

Methods:

We enrolled First Nations and Métis adults aged 20–59 years in our prospective cohort study. Participants were given one 0.5-mL dose of ASO3-adjuvanted pandemic (H1N1) 2009 vaccine (Arepanrix, GlaxoSmithKline Canada). Blood samples were taken at baseline and 21–28 days after vaccination. Paired sera were tested for hemagglutination-inhibiting antibodies at a reference laboratory. To assess vaccine safety, we monitored the injection site symptoms of each participant for seven days. We also monitored patients for general symptoms within 7 days of vaccination and any use of the health care system for 21–28 days after vaccination.

Results:

We enrolled 138 participants in the study (95 First Nations, 43 Métis), 137 of whom provided all safety data and 136 of whom provided both blood samples. First Nations and Métis participants had similar characteristics, including high rates of chronic health conditions (74.4%–76.8%). Pre-existing antibody to the virus was detected in 34.3% of the participants, all of whom boosted strongly with vaccination (seroprotection rate [titre ≥ 40] 100%, geometric mean titre 531–667). Particpants with no pre-existing antibody also responded well. Fifty-eight of 59 (98.3%) First Nations participants showed seroprotection and a geometric mean titre of 353.6; all 30 Métis participants with no pre-existing antibody showed seroprotection and a geometric mean titre of 376.2. Pain at the injection site and general symptoms frequently occurred but were short-lived and generally not severe, although three participants (2.2%) sought medical attention for general symptoms.

Interpretation:

First Nations and Métis adults responded robustly to ASO3-adjuvanted pandemic (H1N1) 2009 vaccine. Virtually all participants showed protective titres, including those with chronic health conditions.

Trial registration:

ClinicalTrials.gov trial register no. NCT.01001026.During the first wave of the H1N1 pandemic in Canada in 2009, some First Nations communities were severely affected, with younger adults and children most at risk for severe disease.^1,2 Whereas Aboriginal Canadians make up 3.4% of the population (with 1.14 million people), they accounted for 16% of admissions to hospital during the first wave of the pandemic, and 43% of Aboriginal patients had underlying medical conditions.³ The increased rate of severe disease might have resulted from residential crowding, prevalence of chronic health conditions, delayed access to health care or suboptimal immune responses to infection.⁴ When a federally funded, ASO3-adjuvanted (squalene/tocopherol) pandemic vaccine became available for Canadians later in 2009,⁵ Aboriginal people were given priority access to it.³ However, dosing requirements at the time were tentative. Previous studies of an ASO3-adjuvanted influenza A (H5N1) vaccine established that two doses were needed for immunity in adults.⁶ Because the 2009 influenza (H1N1) pandemic occurred without warning, no prepandemic studies had been done with vaccines based on this novel swine-derived virus.⁷The ASO3-adjuvanted pandemic (H1N1) 2009 vaccine manufactured in Canada (Arepanrix, GlaxoSmithKline, Laval, Quebec) was released for public use as soon as it was available, unstudied, to mitigate morbidity during the pandemic’s second wave, which was already in progress. A single 3.75-μg dose of hemagglutinin was recommended for adults using the preliminary results of a European trial of another ASO3-adjuvanted vaccine (Pandemrix, GlaxoSmithKline, Rixensart, Belgium) given to 65 adults aged 18–60 years.⁸ The European product was believed to be equivalent to the Canadian-made vaccine, but this had not yet been shown.We wondered if the recommended single dose would be adequate for Aboriginal Canadian adults given their heightened risk of severe influenza during the first wave. We were unable to identify any previous studies of influenza vaccines involving Aboriginal Canadians to determine if their responses would be similar to other Canadians or to the healthy European study participants on whom the dosing recommendation was based. Consequently, we undertook a study involving First Nations and Métis adults to assess their responses to the pandemic vaccine.     

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.     

Estimated cumulative incidence of pandemic (H1N1) influenza among pregnant women during the first wave of the 2009 pandemic

Background

Hospitalization and lab confirmed cases of H1N1 have been reported during the first wave of the 2009 pandemic but these are not accurate measures of influenza incidence in the population. We estimated the cumulative incidence of pandemic (H1N1) influenza among pregnant women in the province of Manitoba during the first wave of the 2009 pandemic.

Methods

Two panels of stored frozen serum specimens collected for routine prenatal screening were randomly selected for testing before (March 2009, n = 252) and after (August 2009, n = 296) the first wave of the pandemic. A standard hemagglutination inhibition assay was used to detect the presence of IgG antibodies against the pandemic (H1N1) 2009 virus. The cumulative incidence of pandemic (H1N1) influenza was calculated as the difference between the point prevalence rates in the first and second panels.

Results

Of the specimens collected in March, 7.1% were positive for the IgG antibodies (serum antibody titre ≥ 1:40). The corresponding prevalence was 15.7% among the specimens collected in August. The difference indicated a cumulative incidence of 8.6% (95% confidence interval [CI] 3.2%–13.7%). The rate differed geographically, the highest being in the northern regions (20.8%, 95% CI 7.9%–31.8%), as compared with 4.0% (95% CI 0.0%–11.9%) in Winnipeg and 8.9% (95% CI 0.0%–18.8%) in the rest of the province.

Interpretation

We estimated that the cumulative incidence of pandemic (H1N1) influenza among pregnant women in Manitoba during the first wave of the 2009 pandemic was 8.6%. It was 20.8% in the northern regions of the province.During the first wave of the pandemic (H1N1) 2009, the province of Manitoba was more severely affected than almost any other Canadian province.¹ Pregnant women in particular had higher rates of laboratory-confirmed infection and of severe illness.² However, the number of laboratory-confirmed cases is not an accurate measure of the incidence of influenza in the population. The number and geographic distribution of confirmed cases are influenced by differences in access to medical care, physicians’ practices and other factors.³We estimated the cumulative incidence of pandemic (H1N1) influenza among pregnant women in the province of Manitoba during the first wave of the 2009 pandemic. We did this by measuring the point seroprevalence in random samples of pregnant women presenting for routine prenatal screening before and after the first wave.     

Risk factors and outcomes among children admitted to hospital with pandemic H1N1 influenza

Background

Limited data are available on disease characteristics and outcomes of children with 2009 pandemic influenza A(H1N1) virus infection (pandemic H1N1 influenza) who have required hospital admission.

Methods

We reviewed the charts of 58 children with pandemic H1N1 influenza admitted to a large pediatric hospital in Ontario, Canada, between May 8 and July 22, 2009. We compared risk factors, severity indicators and outcomes of these children with those of 200 children admitted with seasonal influenza A during the previous 5 years (2004/05 to 2008/09).

Results

Children with pandemic H1N1 influenza were significantly older than those with seasonal influenza (median age 6.4 years v. 3.3 years). Forty-six (79%) of the children with pandemic H1N1 influenza had underlying medical conditions; of the other 12 who were previously healthy, 42% were under 2 years of age. Children admitted with pandemic H1N1 influenza were significantly more likely to have asthma than those with seasonal influenza (22% v. 6%). Two children had poorly controlled asthma, and 6 used inhaled medications only intermittently. The median length of stay in hospital was 4 days in both groups of children. Similar proportions of children required admission to the intensive care unit (21% of those with pandemic H1N1 influenza and 14% of those with seasonal influenza) and mechanical ventilation (12% and 10% respectively). None of the children admitted with pandemic H1N1 influenza died, as compared with 1 (0.4%) of those admitted with seasonal influenza.

Interpretation

Pandemic H1N1 influenza did not appear to cause more severe disease than seasonal influenza A. Asthma appears to be a significant risk factor for severe disease, with no clear relation to severity of asthma. This finding should influence strategies for vaccination and pre-emptive antiviral therapy.Influenza causes significant morbidity and mortality in childhood.¹ Infants, young children and people 65 years of age and older account for the highest rates of influenza-related hospital admission.² Earlier case series of 2009 pandemic influenza A(H1N1) virus infection (pandemic H1N1 influenza) reported small numbers of children^3,4 or did not present data on children separately.⁵ A recently published series that included 122 children confirmed typical influenza-like presentation, reported a high prevalence of underlying medical conditions (60%, including asthma in 29%) and described the need for intensive care in 20% and mechanical ventilation in 10%.⁶ A previous comparison of children with pandemic H1N1 influenza and those in previous years with seasonal influenza included only children considered to have died of influenza.⁷In this article, we present our experience with children admitted to hospital with pandemic H1N1 influenza. Our primary goal was to describe the demographic characteristics, clinical features and markers of severity of illness of these children. Our secondary goal was to identify risk factors for severe disease or poor outcome by comparing these children with those who had been admitted in previous years with seasonal influenza.     

Correlates of severe disease in patients with 2009 pandemic influenza (H1N1) virus infection

Background

In the context of 2009 pandemic influenza (H1N1) virus infection (pandemic H1N1 influenza), identifying correlates of the severity of disease is critical to guiding the implementation of antiviral strategies, prioritization of vaccination efforts and planning of health infrastructure. The objective of this study was to identify factors correlated with severity of disease in confirmed cases of pandemic H1N1 influenza.

Methods

This cumulative case–control study included all laboratory-confirmed cases of pandemic H1N1 influenza among residents of the province of Manitoba, Canada, for whom the final location of treatment was known. Severe cases were defined by admission to a provincial intensive care unit (ICU). Factors associated with severe disease necessitating admission to the ICU were determined by comparing ICU cases with two control groups: patients who were admitted to hospital but not to an ICU and those who remained in the community.

Results

As of Sept. 5, 2009, there had been 795 confirmed cases of pandemic H1N1 influenza in Manitoba for which the final treatment location could be determined. The mean age of individuals with laboratory-confirmed infection was 25.3 (standard deviation 18.8) years. More than half of the patients (417 or 52%) were female, and 215 (37%) of 588 confirmed infections for which ethnicity was known occurred in First Nations residents. The proportion of First Nations residents increased with increasing severity of disease (116 [28%] of 410 community cases, 74 [54%] of 136 admitted to hospital and 25 [60%] of 42 admitted to an ICU; p < 0.001), as did the presence of an underlying comorbidity (201 [35%] of 569 community cases, 103 [57%] of 181 admitted to hospital and 34 [76%] of 45 admitted to an ICU; p < 0.001). The median interval from onset of symptoms to initiation of antiviral therapy was 2 days (interquartile range, IQR 1–3) for community cases, 4 days (IQR 2–6) for patients admitted to hospital and 6 days (IQR 4–9) for those admitted to an ICU (p < 0.001). In a multivariable logistic model, the interval from onset of symptoms to initiation of antiviral therapy (odds ratio [OR] 8.24, 95% confidence interval [CI] 2.82–24.1), First Nations ethnicity (OR 6.52, 95% CI 2.04–20.8) and presence of an underlying comorbidity (OR 3.19, 95% CI 1.07–9.52) were associated with increased odds of admission to the ICU (i.e., severe disease) relative to community cases. In an analysis of ICU cases compared with patients admitted to hospital, First Nations ethnicity (OR 3.23, 95% CI 1.04–10.1) was associated with increased severity of disease.

Interpretation

Severe pandemic H1N1 influenza necessitating admission to the ICU was associated with a longer interval from onset of symptoms to treatment with antiviral therapy and with the presence of an underlying comorbidity. First Nations ethnicity appeared to be an independent determinant of severe infection. Despite these associations, the cause and outcomes of pandemic HINI influenza may involve many complex and interrelated factors, all of which require further research and analysis.In April 2009, Canada’s first wave of pandemic influenza (H1N1) virus infections (pandemic H1N1 influenza) began. The highest burden of severe illness in Canada occurred in the province of Manitoba, where 45 Manitobans and 9 out-of-province patients were admitted to an intensive care unit (ICU). In this first wave, ICU staff and equipment were mobilized to expand bed capacity and ventilator capabilities to accommodate clinical need.Although many individuals presented with mild, self-limited symptoms and no sign of pulmonary involvement, some people required admission to an ICU and received maximal life support measures.^1–3 Predicting disease and mitigating hazard in at-risk populations is an important aim of public heath epidemiology, and in preparation for future waves of pandemic H1N1 influenza, determining correlates of the severity of disease may be very important. Initial reports have suggested that, in addition to many of the previously known risk factors for complications of seasonal influenza, obesity⁴ and other underlying comorbidities^3,5 may be risk factors for severe disease. The interval from onset of symptoms to initiation of antiviral therapy or other treatment and supportive care was also associated with adverse outcome in a recent case series.⁶ In a Canadian study of severe pandemic H1N1 influenza, First Nations people were proportionally overrepresented among patients in the ICU.² However, it is unclear if this association was independent of potential confounding factors. The ability to determine correlates of severe pandemic H1N1 disease and subsequent need for ICU resources in at-risk populations would provide opportunities for public and population health analysis and action, public education, strategic prioritization of vaccination efforts, efficient and equitable allocation and use of antiviral drugs, and development of infrastructure within the health system.The objectives of this study were to identify factors that were correlated with severity of disease in confirmed cases of pandemic H1N1 influenza. Our hypothesis, which was based on existing literature, was that obesity, First Nations ethnicity and longer interval from onset of symptoms to treatment would be important determinants of the severity of disease.     

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.     

Association between exposure to suicide and suicidality outcomes in youth

Background:

Ecological studies support the hypothesis that suicide may be “contagious” (i.e., exposure to suicide may increase the risk of suicide and related outcomes). However, this association has not been adequately assessed in prospective studies. We sought to determine the association between exposure to suicide and suicidality outcomes in Canadian youth.

Methods:

We used baseline information from the Canadian National Longitudinal Survey of Children and Youth between 1998/99 and 2006/07 with follow-up assessments 2 years later. We included all respondents aged 12–17 years in cycles 3–7 with reported measures of exposure to suicide.

Results:

We included 8766 youth aged 12–13 years, 7802 aged 14–15 years and 5496 aged 16–17 years. Exposure to a schoolmate’s suicide was associated with ideation at baseline among respondents aged 12–13 years (odds ratio [OR] 5.06, 95% confidence interval [CI] 3.04–8.40), 14–15 years (OR 2.93, 95% CI 2.02–4.24) and 16–17 years (OR 2.23, 95% CI 1.43–3.48). Such exposure was associated with attempts among respondents aged 12–13 years (OR 4.57, 95% CI 2.39–8.71), 14–15 years (OR 3.99, 95% CI 2.46–6.45) and 16–17 years (OR 3.22, 95% CI 1.62–6.41). Personally knowing someone who died by suicide was associated with suicidality outcomes for all age groups. We also assessed 2-year outcomes among respondents aged 12–15 years: a schoolmate’s suicide predicted suicide attempts among participants aged 12–13 years (OR 3.07, 95% CI 1.05–8.96) and 14–15 years (OR 2.72, 95% CI 1.47–5.04). Among those who reported a schoolmate’s suicide, personally knowing the decedent did not alter the risk of suicidality.

Interpretation:

We found that exposure to suicide predicts suicide ideation and attempts. Our results support school-wide interventions over current targeted interventions, particularly over strategies that target interventions toward children closest to the decedent.Suicidal thoughts and behaviours are prevalent^1–3 and severe^4–7 among adolescents. One hypothesized cause of suicidality is “suicide contagion” (i.e., exposure to suicide or related behaviours influences others to contemplate, attempt or die by suicide).⁸ Ecological studies support this theory: suicide and suspected suicide rates increase following a highly publicized suicide.^9–11 However, such studies are prone to ecological fallacy and do not allow for detailed understanding of who may be most vulnerable.Adolescents may be particularly susceptible to this contagion effect. More than 13% of adolescent suicides are potentially explained by clustering;^12–14 clustering may explain an even larger proportion of suicide attempts.^15,16 Many local,^17,18 national^8,19 and international²⁰ institutions recommend school- or community-level postvention strategies in the aftermath of a suicide to help prevent further suicides and suicidality. These postvention strategies typically focus on a short interval following the death (e.g., months) with services targeted toward the most at-risk individuals (e.g., those with depression).¹⁹In this study, we assessed the association between exposure to suicide and suicidal thoughts and attempts among youth, using both cross-sectional and prospective (2-yr follow-up) analyses in a population-based cohort of Canadian youth.     

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.     

Enteric absorption and pharmacokinetics of oseltamivir in critically ill patients with pandemic (H1N1) influenza

Background

Whether the enteric absorption of the neuraminidase inhibitor oseltamivir is impaired in critically ill patients is unknown. We documented the pharmacokinetic profile of oseltamivir in patients admitted to intensive care units (ICUs) with suspected or confirmed pandemic (H1N1) influenza.

Methods

We included 41 patients 18 years of age and older with suspected or confirmed pandemic (H1N1) influenza who were admitted for ventilatory support to nine ICUs in three cities in Canada and Spain. Using tandem mass spectrometry, we assessed plasma levels of oseltamivir free base and its active metabolite carboxylate at baseline (before gastric administration of the drug) and at 2, 4, 6, 9 and 12 hours after the fourth or later dose.

Results

Among the 36 patients who did not require dialysis, the median concentration of oseltamivir free base was 10.4 (interquartile range [IQR] 4.8–14.9) μg/L; the median concentration of the carboxylate metabolite was 404 (IQR 257–900) μg/L. The volume of distribution of the carboxylate metabolite did not increase with increasing body weight (R² = 0.00, p = 0.87). The rate of elimination of oseltamivir carboxylate was modestly correlated with estimations of creatinine clearance (R² = 0.27, p < 0.001). Drug clearance in the five patients who required continuous renal replacement therapy was about one-sixth that in the 36 patients with relatively normal renal function.

Interpretation

Oseltamivir was well absorbed enterically in critically ill patients admitted to the ICU with suspected or confirmed pandemic (H1N1) influenza. The dosage of 75 mg twice daily achieved plasma levels that were comparable to those in ambulatory patients and were far in excess of concentrations required to maximally inhibit neuraminidase activity of the virus. Adjustment of the dosage in patients with renal dysfunction requiring continuous renal replacement therapy is appropriate; adjustment for obesity does not appear to be necessary.A substantial number of cases of pandemic (H1N1) influenza have involved young adults and adolescents without serious comorbidities who present with severe viral pneumonia complicated by acute respiratory distress syndrome, rhabdomyolysis, renal failure and, occasionally, shock.^1,2 Antiviral therapy in such critically ill patients typically requires oral or nasogastric administration of the neuraminidase inhibitor oseltamivir. Current guidelines from the World Health Organization for the pharmacologic management of progressive or severe pandemic (H1N1) influenza recommend the consideration of high-dose therapy (≥ 150 mg twice daily).^3,4 Critically ill patients exhibit defects in gastrointestinal absorption because of impaired gut perfusion, edema of the bowel wall and ileus as a consequence of critical illness and shock.⁵ Whether the enteric absorption of oseltamivir is impaired in such patients is unknown.We undertook this study to document the pharmacokinetic profile of oseltamivir administered orally or by nasogastric tube in patients admitted to intensive care units (ICUs) with respiratory failure due to suspected or confirmed pandemic (H1N1) influenza.     

Effect of ambient air pollution on the incidence of appendicitis

Background

The pathogenesis of appendicitis is unclear. We evaluated whether exposure to air pollution was associated with an increased incidence of appendicitis.

Methods

We identified 5191 adults who had been admitted to hospital with appendicitis between Apr. 1, 1999, and Dec. 31, 2006. The air pollutants studied were ozone, nitrogen dioxide, sulfur dioxide, carbon monoxide, and suspended particulate matter of less than 10 μ and less than 2.5 μ in diameter. We estimated the odds of appendicitis relative to short-term increases in concentrations of selected pollutants, alone and in combination, after controlling for temperature and relative humidity as well as the effects of age, sex and season.

Results

An increase in the interquartile range of the 5-day average of ozone was associated with appendicitis (odds ratio [OR] 1.14, 95% confidence interval [CI] 1.03–1.25). In summer (July–August), the effects were most pronounced for ozone (OR 1.32, 95% CI 1.10–1.57), sulfur dioxide (OR 1.30, 95% CI 1.03–1.63), nitrogen dioxide (OR 1.76, 95% CI 1.20–2.58), carbon monoxide (OR 1.35, 95% CI 1.01–1.80) and particulate matter less than 10 μ in diameter (OR 1.20, 95% CI 1.05–1.38). We observed a significant effect of the air pollutants in the summer months among men but not among women (e.g., OR for increase in the 5-day average of nitrogen dioxide 2.05, 95% CI 1.21–3.47, among men and 1.48, 95% CI 0.85–2.59, among women). The double-pollutant model of exposure to ozone and nitrogen dioxide in the summer months was associated with attenuation of the effects of ozone (OR 1.22, 95% CI 1.01–1.48) and nitrogen dioxide (OR 1.48, 95% CI 0.97–2.24).

Interpretation

Our findings suggest that some cases of appendicitis may be triggered by short-term exposure to air pollution. If these findings are confirmed, measures to improve air quality may help to decrease rates of appendicitis.Appendicitis was introduced into the medical vernacular in 1886.¹ Since then, the prevailing theory of its pathogenesis implicated an obstruction of the appendiceal orifice by a fecalith or lymphoid hyperplasia.² However, this notion does not completely account for variations in incidence observed by age,^3,4 sex,^3,4 ethnic background,^3,4 family history,⁵ temporal–spatial clustering⁶ and seasonality,^3,4 nor does it completely explain the trends in incidence of appendicitis in developed and developing nations.^3,7,8The incidence of appendicitis increased dramatically in industrialized nations in the 19th century and in the early part of the 20th century.¹ Without explanation, it decreased in the middle and latter part of the 20th century.³ The decrease coincided with legislation to improve air quality. For example, after the United States Clean Air Act was passed in 1970,⁹ the incidence of appendicitis decreased by 14.6% from 1970 to 1984.³ Likewise, a 36% drop in incidence was reported in the United Kingdom between 1975 and 1994¹⁰ after legislation was passed in 1956 and 1968 to improve air quality and in the 1970s to control industrial sources of air pollution. Furthermore, appendicitis is less common in developing nations; however, as these countries become more industrialized, the incidence of appendicitis has been increasing.⁷Air pollution is known to be a risk factor for multiple conditions, to exacerbate disease states and to increase all-cause mortality.¹¹ It has a direct effect on pulmonary diseases such as asthma¹¹ and on nonpulmonary diseases including myocardial infarction, stroke and cancer.^11–13 Inflammation induced by exposure to air pollution contributes to some adverse health effects.^14–17 Similar to the effects of air pollution, a proinflammatory response has been associated with appendicitis.^18–20We conducted a case–crossover study involving a population-based cohort of patients admitted to hospital with appendicitis to determine whether short-term increases in concentrations of selected air pollutants were associated with hospital admission because of appendicitis.     

Likelihood of coronary angiography among First Nations patients with acute myocardial infarction

Background:

Morbidity due to cardiovascular disease is high among First Nations people. The extent to which this may be related to the likelihood of coronary angiography is unclear. We examined the likelihood of coronary angiography after acute myocardial infarction (MI) among First Nations and non–First Nations patients.

Methods:

Our study included adults with incident acute MI between 1997 and 2008 in Alberta. We determined the likelihood of angiography among First Nations and non–First Nations patients, adjusted for important confounders, using the Alberta Provincial Project for Outcome Assessment in Coronary Heart Disease (APPROACH) database.

Results:

Of the 46 764 people with acute MI, 1043 (2.2%) were First Nations. First Nations patients were less likely to receive angiography within 1 day after acute MI (adjusted odds ratio [OR] 0.73, 95% confidence interval [CI] 0.62–0.87). Among First Nations and non–First Nations patients who underwent angiography (64.9%), there was no difference in the likelihood of percutaneous coronary intervention (PCI) (adjusted hazard ratio [HR] 0.92, 95% CI 0.83–1.02) or coronary artery bypass grafting (CABG) (adjusted HR 1.03, 95% CI 0.85–1.25). First Nations people had worse survival if they received medical management alone (adjusted HR 1.38, 95% CI 1.07–1.77) or if they underwent PCI (adjusted HR 1.38, 95% CI 1.06–1.80), whereas survival was similar among First Nations and non–First Nations patients who received CABG.

Interpretation:

First Nations people were less likely to undergo angiography after acute MI and experienced worse long-term survival compared with non–First Nations people. Efforts to improve access to angiography for First Nations people may improve outcomes.Although cardiovascular disease has been decreasing in Canada,¹ First Nations people have a disproportionate burden of the disease. First Nations people in Canada have a 2.5-fold higher prevalence of cardiovascular disease than non–First Nations people,² with hospital admissions for cardiovascular-related events also increasing.³The prevalence of cardiovascular disease in First Nations populations is presumed to be reflective of the prevalence of cardiovascular risk factors.^4–7 However, the disproportionate increase in rates of hospital admission suggests that suboptimal management of cardiovascular disease or its risk factors may also influence patient outcomes.^2,3 Racial disparities in the quality of cardiovascular care resulting in adverse outcomes have been documented, although most studies have focused on African-American, Hispanic and Asian populations.^8,9 As a result, it is unclear whether suboptimal delivery of guideline-recommended treatment contributes to increased cardiovascular morbidity and mortality among First Nations people.^10–12We undertook a population-based study involving adults with incident acute myocardial infarction (MI) to examine the receipt of guideline-recommended coronary angiography among First Nations and non–First Nations patients.^10–12 Among patients who underwent angiography, we sought to determine whether there were differences between First Nations and non–First Nations patients in the likelihood of revascularization and long-term survival.     

Relation between fractures and mortality: results from the Canadian Multicentre Osteoporosis Study

Background

Fractures have largely been assessed by their impact on quality of life or health care costs. We conducted this study to evaluate the relation between fractures and mortality.

Methods

A total of 7753 randomly selected people (2187 men and 5566 women) aged 50 years and older from across Canada participated in a 5-year observational cohort study. Incident fractures were identified on the basis of validated self-report and were classified by type (vertebral, pelvic, forearm or wrist, rib, hip and “other”). We subdivided fracture groups by the year in which the fracture occurred during follow-up; those occurring in the fourth and fifth years were grouped together. We examined the relation between the time of the incident fracture and death.

Results

Compared with participants who had no fracture during follow-up, those who had a vertebral fracture in the second year were at increased risk of death (adjusted hazard ratio [HR] 2.7, 95% confidence interval [CI] 1.1–6.6); also at risk were those who had a hip fracture during the first year (adjusted HR 3.2, 95% CI 1.4–7.4). Among women, the risk of death was increased for those with a vertebral fracture during the first year (adjusted HR 3.7, 95% CI 1.1–12.8) or the second year of follow-up (adjusted HR 3.2, 95% CI 1.2–8.1). The risk of death was also increased among women with hip fracture during the first year of follow-up (adjusted HR 3.0, 95% CI 1.0–8.7).

Interpretation

Vertebral and hip fractures are associated with an increased risk of death. Interventions that reduce the incidence of these fractures need to be implemented to improve survival.Osteoporosis-related fractures are a major health concern, affecting a growing number of individuals worldwide. The burden of fracture has largely been assessed by the impact on health-related quality of life and health care costs.^1,2 Fractures can also be associated with death. However, trials that have examined the relation between fractures and mortality have had limitations that may influence their results and the generalizability of the studies, including small samples,^3,4 the examination of only 1 type of fracture,^4–10 the inclusion of only women,^8,11 the enrolment of participants from specific areas (i.e., hospitals or certain geographic regions),^{3,4,7,8,10,12} the nonrandom selection of participants^3–11 and the lack of statistical adjustment for confounding factors that may influence mortality.^3,5–7,12We evaluated the relation between incident fractures and mortality over a 5-year period in a cohort of men and women 50 years of age and older. In addition, we examined whether other characteristics of participants were risk factors for death.     

Effectiveness of training family physicians to deliver a brief intervention to address excessive substance use among young patients: a cluster randomized controlled trial

Background:

Brief interventions delivered by family physicians to address excessive alcohol use among adult patients are effective. We conducted a study to determine whether such an intervention would be similarly effective in reducing binge drinking and excessive cannabis use among young people.

Methods:

We conducted a cluster randomized controlled trial involving 33 family physicians in Switzerland. Physicians in the intervention group received training in delivering a brief intervention to young people during the consultation in addition to usual care. Physicians in the control group delivered usual care only. Consecutive patients aged 15–24 years were recruited from each practice and, before the consultation, completed a confidential questionnaire about their general health and substance use. Patients were followed up at 3, 6 and 12 months after the consultation. The primary outcome measure was self-reported excessive substance use (≥ 1 episode of binge drinking, or ≥ 1 joint of cannabis per week, or both) in the past 30 days.

Results:

Of the 33 participating physicians, 17 were randomly allocated to the intervention group and 16 to the control group. Of the 594 participating patients, 279 (47.0%) identified themselves as binge drinkers or excessive cannabis users, or both, at baseline. Excessive substance use did not differ significantly between patients whose physicians were in the intervention group and those whose physicians were in the control group at any of the follow-up points (odds ratio [OR] and 95% confidence interval [CI] at 3 months: 0.9 [0.6–1.4]; at 6 mo: 1.0 [0.6–1.6]; and at 12 mo: 1.1 [0.7–1.8]). The differences between groups were also nonsignificant after we re stricted the analysis to patients who reported excessive substance use at baseline (OR 1.6, 95% CI 0.9–2.8, at 3 mo; OR 1.7, 95% CI 0.9–3.2, at 6 mo; and OR 1.9, 95% CI 0.9–4.0, at 12 mo).

Interpretation:

Training family physicians to use a brief intervention to address excessive substance use among young people was not effective in reducing binge drinking and excessive cannabis use in this patient population. Trial registration: Australian New Zealand Clinical Trials Registry, no. ACTRN12608000432314.Most health-compromising behaviours begin in adolescence.¹ Interventions to address these behaviours early are likely to bring long-lasting benefits.² Harmful use of alcohol is a leading factor associated with premature death and disability worldwide, with a disproportionally high impact on young people (aged 10–24 yr).^3,4 Similarly, early cannabis use can have adverse consequences that extend into adulthood.^5–8In adolescence and early adulthood, binge drinking on at least a monthly basis is associated with an increased risk of adverse outcomes later in life.^9–12 Although any cannabis use is potentially harmful, weekly use represents a threshold in adolescence related to an increased risk of cannabis (and tobacco) dependence in adulthood.¹³ Binge drinking affects 30%–50% and excessive cannabis use about 10% of the adolescent and young adult population in Europe and the United States.^10,14,15Reducing substance-related harm involves multisectoral approaches, including promotion of healthy child and adolescent development, regulatory policies and early treatment interventions.¹⁶ Family physicians can add to the public health messages by personalizing their content within brief interventions.^17,18 There is evidence that brief interventions can encourage young people to reduce substance use, yet most studies have been conducted in community settings (mainly educational), emergency services or specialized addiction clinics.^1,16 Studies aimed at adult populations have shown favourable effects of brief alcohol interventions, and to some extent brief cannabis interventions, in primary care.^19–22 These interventions have been recommended for adolescent populations.^4,5,16 Yet young people have different modes of substance use and communication styles that may limit the extent to which evidence from adult studies can apply to them.Recently, a systematic review of brief interventions to reduce alcohol use in adolescents identified only 1 randomized controlled trial in primary care.²³ The tested intervention, not provided by family physicians but involving audio self-assessment, was ineffective in reducing alcohol use in exposed adolescents.²⁴ Sanci and colleagues showed that training family physicians to address health-risk behaviours among adolescents was effective in improving provider performance, but the extent to which this translates into improved outcomes remains unknown.^25,26 Two nonrandomized studies suggested screening for substance use and brief advice by family physicians could favour reduced alcohol and cannabis use among adolescents,^27,28 but evidence from randomized trials is lacking.²⁹We conducted the PRISM-Ado (Primary care Intervention Addressing Substance Misuse in Adolescents) trial, a cluster randomized controlled trial of the effectiveness of training family physicians to deliver a brief intervention to address binge drinking and excessive cannabis use among young people.     

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.     

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.     

Rates and determinants of seasonal influenza vaccination in pregnancy and association with neonatal outcomes

Background:

There is growing evidence that seasonal influenza vaccination in pregnancy has benefits for mother and baby. We determined influenza vaccination rates among pregnant women during the 2 nonpandemic influenza seasons following the 2009 H1N1 pandemic, explored maternal factors as predictors of influenza vaccination status and evaluated the association between maternal influenza vaccination and neonatal outcomes.

Methods:

We used a population-based perinatal database in the province of Nova Scotia, Canada, to examine maternal vaccination rates, determinants of vaccination status and neonatal outcomes. Our cohort included women who gave birth between Nov. 1, 2010, and Mar. 31, 2012. We compared neonatal outcomes between vaccinated and unvaccinated women using logistic regression analysis.

Results:

Overall, 1958 (16.0%) of 12 223 women in our cohort received the influenza vaccine during their pregnancy. Marital status, parity, location of residence (rural v. urban), smoking during pregnancy and maternal influenza risk status were determinants of maternal vaccine receipt. The odds of preterm birth was lower among infants of vaccinated women than among those of nonvaccinated women (adjusted odds ratio [OR] 0.75, 95% confidence interval [CI] 0.60–0.94). The rate of low-birth-weight infants was also lower among vaccinated women (adjusted OR 0.73, 95% CI 0.56–0.95).

Interpretation:

Despite current guidelines advising all pregnant women to receive the seasonal influenza vaccine, influenza vaccination rates among pregnant women in our cohort were low in the aftermath of the 2009 H1N1 pandemic. This study and others have shown an association between maternal influenza vaccination and improved neonatal outcomes, which supports stronger initiatives to promote vaccination during pregnancy.Influenza viruses are the leading cause of serious wintertime respiratory morbidity worldwide. Several studies investigating the effects of influenza-related illness during pregnancy have shown a strong impact on the health of pregnant women in terms of increased rates of hospital admission because of respiratory illness.^1–3 Schanzer and colleagues² found that pregnant women in Canada were at increased risk of influenza-related hospital admission when compared with nonpregnant women of similar age and health status. In addition, influenza-related illness during pregnancy may have a negative impact on neonatal outcomes. A study in Nova Scotia, Canada, showed that infants whose mothers were admitted to hospital because of respiratory illness during influenza season while pregnant were more likely to be small for gestational age and to have lower mean birth weight.⁴By 2007, the cumulative evidence from these and other studies was compelling enough for advisory boards in Canada to recommend routine influenza vaccination for all pregnant women, including those without medical comorbidities.⁵ Despite these recommendations, seasonal vaccination rates among pregnant women have remained low. In a cohort of pregnant women who delivered at the IWK Health Centre, Halifax, from 2006 to 2009, only 20% had received the vaccine during their pregnancy.⁶ Increased vaccination rates among pregnant women were reported for the 2009 H1N1 pandemic year,⁷ but it is unknown whether this has translated into higher rates of seasonal influenza vaccination since then. Studies have shown that concern about vaccine safety is the most commonly cited reason for refusing the vaccine,^8,9 despite much evidence showing it to be safe in pregnancy.¹⁰ A recommendation from a maternity care provider has been shown to be a key factor in increasing vaccination rates.^11,12In light of the growing evidence that influenza vaccination during pregnancy has benefits for both the mother and the infant,^13–18 we evaluated rates of seasonal influenza vaccination among pregnant women in the 2 nonpandemic influenza seasons (2010/11 and 2011/12) following the 2009 H1N1 pandemic. We also assessed whether neonatal outcomes differed between women who received the vaccine during pregnancy and those who did not.     

Self-harm and risk of motor vehicle crashes among young drivers: findings from the DRIVE Study

Background

Some motor vehicle crashes, particularly single-vehicle crashes, may result from intentional self-harm. We conducted a prospective cohort study to assess the risk that intentional self-harm poses for motor vehicle crashes among young drivers.

Methods

We prospectively linked survey data from newly licensed drivers aged 17–24 years to data on licensing attempts and police-reported motor vehicle crashes during the follow-up period. We investigated the role of recent engagement in self-harm on the risk of a crash. We took into account potential confounders, including number of hours of driving per week, psychological symptoms and substance abuse.

Results

We included 18 871 drivers who participated in the DRIVE Study for whom data on self-harm and motor vehicle crashes were available. The mean follow-up was 2 years. Overall, 1495 drivers had 1 or more crashes during the follow-up period. A total of 871 drivers (4.6%) reported that they had engaged in self-harm in the year before the survey. These drivers were at significantly increased risk of a motor vehicle crash compared with drivers who reported no self-harm (relative risk [RR] 1.42, 95% confidence interval [CI] 1.15–1.76). The risk remained significant, even after adjustment for age, sex, average hours of driving per week, previous crash, psychological distress, duration of sleep, risky driving behaviour, substance use, remoteness of residence and socio-economic status (RR 1.37, 95% CI 1.09–1.72). Most of the drivers who reported self-harm and had a subsequent crash were involved in a multiple-vehicle crash (84.1% [74/88]).

Interpretation

Engagement in self-harm behaviour was an independent risk factor for subsequent motor vehicle crash among young drivers, with most crashes involving multiple vehicles.Globally, poor mental health and injuries (including suicide) are ranked as the first and second highest contributors of lost disability-adjusted life-years among young people.¹ Self-harm and suicide attempts are reported by 5%–17% of people aged 14–25 years and may be increasing in prevalence.^2–5 Self-harm refers to the deliberate injuring of oneself through such methods as superficial cutting, attempted hanging and poisoning.⁶ Self-harm is performed most often by people with mental health problems and is a risk factor for suicide and other causes of death.^6–8 Reasons for this behaviour are not well known. They may include coping with feelings of distress, suicidal intent, crying out for attention, addictive self-mutilation, impulsive behaviour, self-loathing and punishment, and attempting to feel in control. A recent study found the rate ratio of self-harm to suicide to be 36 (95% confidence interval [CI] 34.9–37.1).⁹The rate of death from motor vehicle crashes is hypothesized to be increased among individuals who have previously attempted suicide, and crashes are implicated as a mode of self-harm.^8,10,11 There are several possible reasons for this increased risk of crash-related injury and death. For example, individuals who self-harm may deliberately attempt to injure or kill themselves using a motor vehicle. Alternatively, an increased risk of crash may occur through an indirect association of self-harm with other risk factors associated with crashes. Poor mental health for example is associated with self-harm and has been linked to higher rates of crashes.⁸ Common symptoms of poor mental health include depressed or anxious mood, disturbed sleep and poor concentration, all of which may impair cognitive and psychomotor function and thereby impair a person’s ability to drive.¹² Self-harm is also commonly associated with alcohol and other substance use, which are also risk factors for motor vehicle crashes.^2,13,14 Finally, developmentally young adults and people who self-harm have poor impulse control, which suggests that they may be particularly vulnerable to a range of health risks, including accidental injury.^6,15,16Most studies of motor vehicle crashes among people who self-harm recruited patients seeking health services and used linked data from death registers to examine fatal outcomes. We conducted a prospective study to examine self-harm as a risk factor for nonfatal motor vehicle crashes. We used a cohort of young drivers of whom a subset engaged in self-harm. We also explored the role of associated risk factors, including symptoms of mental disorder and substance use, in explaining any difference in rates of crash.