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Background: Malignant brain tumours are rare, but are important to study because survival rates are low and few modifiable risk factors have been identified. Existing evidence suggests that outdoor ultrafine particles (UFPs; particulate matter < 100 nm; sometimes referred to as nanoparticles) can deposit in the brain and could encourage initiation and progression of cancerous tumours, but epidemiological data are limited., Methods: High-resolution estimates of outdoor UFP concentrations and size were linked to residential locations of approximately 1.5 million people in Montreal and Toronto, Canada from 2001 to 2015. Cox proportional hazards models were used to estimate associations between annual average outdoor UFPs and malignant brain tumour incidence while adjusting for potential confounding factors including other outdoor air pollutants., Findings: In total, 1365 incident brain tumour cases occurred during follow-up. Consistent positive associations were observed between long-term exposures to outdoor UFPs and brain tumour incidence with increased risk ranging from 10.5% (95% CI: -1.4, 24.0%) to 15.3% (95% CI: 0.4, 32.5%) per 10,000 particle/cm 3 increase. Long-term exposures to oxidant gases, black carbon, or fine particulate matter (PM 2.5 ) were not associated with increased brain tumour incidence., Interpretation: Our results suggest that long-term exposures to outdoor UFPs are associated with an increased risk of developing malignant brain tumours. On an absolute scale, the magnitude of this risk translates into approximately 24 additional cases per year per 10,000 particle/cm 3 increase in annual average outdoor UFPs in a hypothetical city of 3-million people., Funding: Canadian Institutes of Health Research (CIHR) Foundation Grant and The United States Health Effects Institute (HEI)., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [Scott Weichenthal reports financial support was provided by Canadian Institutes of Health Research. Scott Weichenthal reports financial support was provided by United States Health Effects Institute. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.]., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Outdoor fine particulate air pollution, <2.5 µm (PM 2.5 ) mass concentrations can be constructed through many different combinations of chemical components that have varying levels of toxicity. This poses a challenge for studies interested in estimating the health effects of total outdoor PM 2.5 (i.e., how much PM 2.5 mass is present in the air regardless of composition) because we must consider possible confounders of the version of treatment-outcome relationships., Methods: We evaluated the extent of possible bias in mortality hazard ratios for total outdoor PM 2.5 by examining models with and without adjustment for sulfate and nitrate in PM 2.5 as examples of potential confounders of version of treatment-outcome relationships. Our study included approximately 3 million Canadians and Cox proportional hazard models were used to estimate hazard ratios for total outdoor PM 2.5 adjusting for sulfate and/or nitrate and other relevant covariates., Results: Hazard ratios for total outdoor PM 2.5 and nonaccidental, cardiovascular, and respiratory mortality were overestimated due to the confounding version of treatment-outcome relationships, and associations for lung cancer mortality were underestimated. Sulfate was most strongly associated with nonaccidental, cardiovascular, and respiratory mortality suggesting that regulations targeting this specific component of outdoor PM 2.5 may have greater health benefits than interventions targeting total PM 2.5 ., Conclusions: Studies interested in estimating the health impacts of total outdoor PM 2.5 (i.e., how much PM 2.5 mass is present in the air) need to consider potential confounders of the version of treatment-outcome relationships. Otherwise, health risk estimates for total PM 2.5 will reflect some unknown combination of how much PM 2.5 mass is present in the air and the kind of PM 2.5 mass that is present., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The Environmental Epidemiology. All rights reserved.)

Introduction: Numerous studies support an important relationship between long-term exposure to outdoor fine particulate air pollution (PM 2.5 ) and both nonaccidental and cause-specific mortality. Less is known about the long-term health consequences of other traffic pollutants, including ultrafine particles (UFPs, <0.1 μm) and black carbon (BC), which are often present at elevated concentrations in urban areas but are not currently regulated. Knowledge is lacking largely because these pollutants generally are not monitored by governments and vary greatly over small spatial scales, hindering the evaluation of long-term exposures in population-based studies., Methods: We aimed to estimate associations between long-term exposures to outdoor UFPs and BC and nonaccidental and cause-specific mortality in Canada's two largest cities, Montreal and Toronto. We considered several approaches to exposure assessment: (1) land use regression (LUR) models based on large-scale year-long mobile monitoring campaigns combined with detailed land use and traffic information; (2) machine learning (i.e., convolutional neural networks [CNN]) models trained by combining mobile monitoring data with aerial images; and (3) the combined use of these two approaches. We also examined exposure models with and without backcasting based on historical trends in vehicle emissions (to capture potential trends in pollutant concentrations over time) and with and without accounting for neighborhood-level mobility patterns (based on travel demand surveys). These exposure models were linked to members of the Canadian Census Health and Environment Cohorts (CanCHEC) residing in Montreal or Toronto (including census years 1991, 1996, 2001, and 2006) with mortality follow-up from 2001 (or cohort entry for the 2006 cohort) to 2016. Cox proportional hazard models were used to estimate associations between long-term exposures to outdoor UFPs and BC, adjusting for sociodemographic factors and co-pollutants identified as potential confounding factors. Concentration-response relationships for outdoor UFPs and BC were also examined for nonaccidental and cause-specific mortality using smoothing splines., Results: Our cohort study included approximately 1.5 million people with 174,200 nonaccidental deaths observed during the follow-up period. Combined LUR and machine learning model predictions performed slightly better than LUR models alone and were used as the main exposure models in all epidemiological analyses. Long-term exposures to outdoor UFP number concentrations were consistently positively associated with nonaccidental and cause-specific mortality. Importantly, hazard ratios (HRs) for outdoor UFP number concentrations were sensitive to adjustment for UFP size: UFP size was inversely related to number concentrations and independently associated with mortality, resulting in underestimation of mortality risk for outdoor UFP number concentrations when UFP size was excluded. HRs for outdoor UFP number concentrations were robust to backcasting and mobility weighting but varied slightly in analyses using LUR and machine learning models alone, with stronger associations typically observed for the machine learning models. Associations between outdoor BC concentrations and mortality were generally weak or null, but a positive association was observed for cardiovascular mortality., Conclusions: Outdoor UFP number concentrations were consistently associated with increased risks of nonaccidental and cause-specific mortality in Montreal and Toronto. Our results suggest that UFP size should be considered in epidemiological analyses of outdoor UFP number concentrations, as excluding size can lead to an underestimation of health risks. Our results suggest that outdoor UFP number concentrations are positively associated with mortality independent of other outdoor air pollutants, including PM 2.5 mass concentrations and oxidant gases (i.e., nitrogen dioxide [NO 2 ] and ozone [O 3 ]). As outdoor UFPs are currently unregulated, interventions targeting these pollutants could significantly affect population health., (© 2024 Health Effects Institute. All rights reserved.)

Rationale: Outdoor fine particulate air pollution (PM2.5) contributes to millions of deaths around the world each year, but much less is known about the long-term health impacts of other particulate air pollutants including ultrafine particles (a.k.a. nanoparticles) which are in the nanometer size range (<100 nm), widespread in urban environments, and not currently regulated., Objectives: Estimate the associations between long-term exposure to outdoor ultrafine particles and mortality., Methods: Outdoor air pollution levels were linked to the residential addresses of a large, population-based cohort from 2001 - 2016. Associations between long-term exposure to outdoor ultrafine particles and nonaccidental and cause-specific mortality were estimated using Cox proportional hazards models., Measurements: An increase in long-term exposure to outdoor ultrafine particles was associated with an increased risk of nonaccidental mortality (Hazard Ratio = 1. 073, 95% Confidence Interval = 1. 061, 1. 085) and cause-specific mortality, the strongest of which was respiratory mortality (Hazard Ratio = 1.174, 95% Confidence Interval = 1.130, 1.220)., Main Results: Long-term exposure to outdoor ultrafine particles was associated with increased risk of mortality. We estimated the mortality burden for outdoor ultrafine particles in Montreal and Toronto, Canada to be approximately 1100 additional nonaccidental deaths every year. Furthermore, we observed possible confounding by particle size which suggests that previous studies may have underestimated or missed important health risks associated with ultrafine particles., Conclusions: As outdoor ultrafine particles are not currently regulated, there is great potential for future regulatory interventions to improve population health by targeting these common outdoor air pollutants.

Recent studies have identified inequality in the distribution of air pollution attributable health impacts, but to our knowledge this has not been examined in Canadian cities. We evaluated the extent and sources of inequality in air pollution attributable mortality at the census tract (CT) level in seven of Canada's largest cities. We first regressed fine particulate matter (PM 2.5 ) and nitrogen dioxide (NO 2 ) attributable mortality against the neighborhood (CT) level prevalence of age 65 and older, low income, low educational attainment, and identification as an Indigenous (First Nations, Métis, Inuit) or Black person, accounting for spatial autocorrelation. We next examined the distribution of baseline mortality rates, PM 2.5 and NO 2 concentrations, and attributable mortality by neighborhood (CT) level prevalence of these characteristics, calculating the concentration index, Atkinson index, and Gini coefficient. Finally, we conducted a counterfactual analysis of the impact of reducing baseline mortality rates and air pollution concentrations on inequality in air pollution attributable mortality. Regression results indicated that CTs with a higher prevalence of low income and Indigenous identity had significantly higher air pollution attributable mortality. Concentration index, Atkinson index, and Gini coefficient values revealed different degrees of inequality among the cities. Counterfactual analysis indicated that inequality in air pollution attributable mortality tended to be driven more by baseline mortality inequalities than exposure inequalities. Reducing inequality in air pollution attributable mortality requires reducing disparities in both baseline mortality and air pollution exposure., Competing Interests: The authors declare no conflicts of interest relevant to this study., (© 2023 His Majesty the King in Right of Canada and The Authors. Reproduced with the permission of the Minister of Health Canada.)

Background: Household air conditioning is one of the most effective approaches for reducing the health impacts of heat exposure; however, few studies have measured the prevalence of household air conditioning in Canada., Data and Methods: Data were obtained from the 2017 Canadian Community Health Survey and the 2017 Households and the Environment Survey. Statistics Canada linked the survey respondents and created survey weights. Four heat-vulnerable populations were defined: older adults, older adults living alone, older adults with at least one health condition associated with reduced thermoregulation and older adults living alone and with a health condition associated with reduced thermoregulation. Weighted ratios and logistic regression models were used to analyze person-level air conditioning rates for national, regional and heat-vulnerable populations., Results: Approximately 61% of the national population had household air conditioning. Regional rates ranged between 32% in British Columbia and 85% in Ontario. People living alone and people who did not own a home were significantly less likely to have air conditioning in Canada and in most regions. One heat vulnerable group, older adults living alone, had significantly lower air conditioning rates compared with the national and Ontario averages, at 56% and 81%, respectively., Interpretation: This study is the first to quantify air conditioning prevalence in Canada at the person-level. The results of this study may inform heat-health policies and climate change adaptation strategies that aim to identify populations with high risks of heat-related mortality or morbidity and low access to household air conditioning.

Background: Numerous epidemiological studies have documented the adverse health impact of long-term exposure to fine particulate matter [particulate matter ≤ 2.5 μ m in aerodynamic diameter ( PM 2.5 )] on mortality even at relatively low levels. However, methodological challenges remain to consider potential regulatory intervention's complexity and provide actionable evidence on the predicted benefits of interventions. We propose the parametric g-computation as an alternative analytical approach to such challenges., Method: We applied the parametric g-computation to estimate the cumulative risks of nonaccidental death under different hypothetical intervention strategies targeting long-term exposure to PM 2.5 in the Canadian Community Health Survey cohort from 2005 to 2015. On both relative and absolute scales, we explored the benefits of hypothetical intervention strategies compared with the natural course that a ) set the simulated exposure value at each follow-up year to a threshold value if exposure was above the threshold ( 8.8   μ g / m 3 , 7.04   μ g / m 3 , 5   μ g / m 3 , and 4   μ g / m 3 ), and b ) reduced the simulated exposure value by a percentage (5% and 10%) at each follow-up year. We used the 3-y average PM 2.5 concentration with 1-y lag at the postal code of respondents' annual mailing addresses as their long-term exposure to PM 2.5 . We considered baseline and time-varying confounders, including demographics, behavior characteristics, income level, and neighborhood socioeconomic status. We also included the R syntax for reproducibility and replication., Results: All hypothetical intervention strategies explored led to lower 11-y cumulative mortality risks than the estimated value under the natural course without intervention, with the smallest reduction of 0.20 per 1,000 participants (95% CI: 0.06, 0.34) under the threshold of 8.8   μ g / m 3 , and the largest reduction of 3.40 per 1,000 participants (95% CI: - 0.23 , 7.03) under the relative reduction of 10% per interval. The reductions in cumulative risk, or numbers of deaths that would have been prevented if the intervention was employed instead of maintaining the status quo, increased over time but flattened toward the end of the follow-up period. Estimates among those ≥ 65 years of age were greater with a similar pattern. Our estimates were robust to different model specifications., Discussion: We found evidence that any intervention further reducing the long-term exposure to PM 2.5 would reduce the cumulative mortality risk, with greater benefits in the older population, even in a population already exposed to low levels of ambient PM 2.5 . The parametric g-computation used in this study provides flexibilities in simulating real-world interventions, accommodates time-varying exposure and confounders, and estimates adjusted survival curves with clearer interpretation and more information than a single hazard ratio, making it a valuable analytical alternative in air pollution epidemiological research. https://doi.org/10.1289/EHP11095.

Background: Mortality rates in Canada have been shown to vary by population group (e.g., Indigenous peoples, immigrants) and social economic status (e.g., income levels). Mortality patterns for some groups, including Black individuals, are not as well known. The objective of this study was to assess cause-specific mortality for Black adults living in Canada., Methods: Mortality inequalities between Black and White cohort members were estimated by sex using Cox proportional hazard models, based on data from the 2001, 2006 and 2011 Canadian Census Health and Environment Cohorts (CanCHECs). The CanCHEC cycles were combined and followed for mortality between Census Day and December 31, 2016 or 2019, resulting in a follow-up period of 15.6, 13.6 or 8.6 years, depending on the CanCHEC cycle., Results: Ischemic heart disease mortality was the leading cause of death among adult Black males (12.9%) and females (9.8%), as it is for adult White males (16.4%) and females (12.4%). Despite reduced risk of all-cause mortality among Black males and females, compared with White cohort members, there was notable increased risk for some cause-specific mortality. For instance, in the age-adjusted model, among the 25 causes of death examined, Black males had an increased risk of dying from four causes (HIV/AIDS, prostate cancer, diabetes mellitus and cerebrovascular disease), compared with White males. Similarly, Black females were at an increased risk for 6 causes of death (HIV/AIDS, stomach cancer, corpus uteri cancer, lymphomas and multiple myeloma, diabetes mellitus, and endocrine disorders) out of the 27 causes of death examined. These relative increased risks persisted for most causes of death after adjustment for differences in important social determinants of health., Interpretation: Results showed substantial variability in the risk of dying by cause of death between Black and White cohort members. An important step in reducing health inequities is the routine identification and surveillance of different health outcomes by population groups. This study helps fill that information gap.

Emissions of fine particulate matter (PM 2.5 ) from human activities have been linked to substantial disease burdens, but evidence regarding how reducing PM 2.5 at its sources would improve public health is sparse. We followed a population-based cohort of 2.7 million adults across Canada from 2007 through 2016. For each participant, we estimated annual mean concentrations of PM 2.5 and the fractional contributions to PM 2.5 from the five leading anthropogenic sources at their residential address using satellite observations in combination with a global atmospheric chemistry transport model. For each source, we estimated the causal effects of six hypothetical interventions on 10-y nonaccidental mortality risk using the parametric g-formula, a structural causal model. We conducted stratified analyses by age, sex, and income. This cohort would have experienced tangible health gains had contributions to PM 2.5 from any of the five sources been reduced. Compared with no intervention, a 10% annual reduction in PM 2.5 contributions from transportation and power generation, Canada's largest and fifth-largest anthropogenic sources, would have prevented approximately 175 (95%CI: 123-226) and 90 (95%CI: 63-117) deaths per million by 2016, respectively. A more intensive 50% reduction per year in PM 2.5 contributions from the two sources would have averted 360 and 185 deaths per million, respectively, by 2016. The potential health benefits were greater among men, older adults, and low-income earners. In Canada, where PM 2.5 levels are among the lowest worldwide, reducing PM 2.5 contributions from anthropogenic sources by as little as 10% annually would yield meaningful health gains.

Background: Populations are simultaneously exposed to outdoor concentrations of oxidant gases (i.e., O 3 and NO 2 ) and fine particulate air pollution (PM 2.5 ). Since oxidative stress is thought to be an important mechanism explaining air pollution health effects, the adverse health impacts of oxidant gases may be greater in locations where PM 2.5 is more capable of causing oxidative stress., Methods: We conducted a cohort study of 2 million adults in Canada between 2001 and 2016 living within 10 km of ground-level monitoring sites for outdoor PM 2.5 components and oxidative potential. O x exposures (i.e., the redox-weighted average of O 3 and NO 2 ) were estimated using a combination of chemical transport models, land use regression models, and ground-level data. Cox proportional hazards models were used to estimate associations between 3-year moving average O x and mortality outcomes across strata of transition metals and sulfur in PM 2.5 and three measures of PM 2.5 oxidative potential adjusting for possible confounding factors., Results: Associations between O x and mortality were consistently stronger in regions with elevated PM 2.5 transition metal/sulfur content and oxidative potential. For example, each interquartile increase (6.27 ppb) in O x was associated with a 14.9% (95% CI = 13.0, 16.9) increased risk of nonaccidental mortality in locations with glutathione-related oxidative potential (OP GSH ) above the median whereas a 2.50% (95% CI = 0.600, 4.40) increase was observed in regions with OP GSH levels below the median (interaction P value <0.001)., Conclusion: Spatial variations in PM 2.5 composition and oxidative potential may contribute to heterogeneity in the observed health impacts of long-term exposures to oxidant gases., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.)

The World Health Organization (WHO) recently released new guidelines for outdoor fine particulate air pollution (PM 2.5 ) recommending an annual average concentration of 5 μg/m 3 . Yet, our understanding of the concentration-response relationship between outdoor PM 2.5 and mortality in this range of near-background concentrations remains incomplete. To address this uncertainty, we conducted a population-based cohort study of 7.1 million adults in one of the world's lowest exposure environments. Our findings reveal a supralinear concentration-response relationship between outdoor PM 2.5 and mortality at very low (<5 μg/m 3 ) concentrations. Our updated global concentration-response function incorporating this new information suggests an additional 1.5 million deaths globally attributable to outdoor PM 2.5 annually compared to previous estimates. The global health benefits of meeting the new WHO guideline for outdoor PM 2.5 are greater than previously assumed and indicate a need for continued reductions in outdoor air pollution around the world.

Introduction: Mortality is associated with long-term exposure to fine particulate matter (particulate matter ≤2.5 μm in aerodynamic diameter; PM 2.5 ), although the magnitude and form of these associations remain poorly understood at lower concentrations. Knowledge gaps include the shape of concentration-response curves and the lowest levels of exposure at which increased risks are evident and the occurrence and extent of associations with specific causes of death. Here, we applied improved estimates of exposure to ambient PM 2.5 to national population-based cohorts in Canada, including a stacked cohort of 7.1 million people who responded to census year 1991, 1996, or 2001. The characterization of the shape of the concentration-response relationship for nonaccidental mortality and several specific causes of death at low levels of exposure was the focus of the Mortality-Air Pollution Associations in Low Exposure Environments (MAPLE) Phase 1 report. In the Phase 1 report we reported that associations between outdoor PM 2.5 concentrations and nonaccidental mortality were attenuated with the addition of ozone (O 3 ) or a measure of gaseous pollutant oxidant capacity (O x ), which was estimated from O 3 and nitrogen dioxide (NO 2 ) concentrations. This was motivated by our interests in understanding both the effects air pollutant mixtures may have on mortality and also the role of O 3 as a copollutant that shares common sources and precursor emissions with those of PM 2.5 . In this Phase 2 report, we further explore the sensitivity of these associations with O 3 and O x , evaluate sensitivity to other factors, such as regional variation, and present ambient PM 2.5 concentration-response relationships for specific causes of death., Methods: PM 2.5 concentrations were estimated at 1 km 2 spatial resolution across North America using remote sensing of aerosol optical depth (AOD) combined with chemical transport model (GEOS-Chem) simulations of the AOD:surface PM 2.5 mass concentration relationship, land use information, and ground monitoring. These estimates were informed and further refined with collocated measurements of PM 2.5 and AOD, including targeted measurements in areas of low PM 2.5 concentrations collected at five locations across Canada. Ground measurements of PM 2.5 and total suspended particulate matter (TSP) mass concentrations from 1981 to 1999 were used to backcast remote-sensing-based estimates over that same time period, resulting in modeled annual surfaces from 1981 to 2016., Annual exposures to PM 2.5 were then estimated for subjects in several national population-based Canadian cohorts using residential histories derived from annual postal code entries in income tax files. These cohorts included three census-based cohorts: the 1991 Canadian Census Health and Environment Cohort (CanCHEC; 2.5 million respondents), the 1996 CanCHEC (3 million respondents), the 2001 CanCHEC (3 million respondents), and a Stacked CanCHEC where duplicate records of respondents were excluded (Stacked CanCHEC; 7.1 million respondents). The Canadian Community Health Survey (CCHS) mortality cohort (mCCHS), derived from several pooled cycles of the CCHS (540,900 respondents), included additional individual information about health behaviors. Follow-up periods were completed to the end of 2016 for all cohorts. Cox proportional hazard ratios (HRs) were estimated for nonaccidental and other major causes of death using a 10-year moving average exposure and 1-year lag. All models were stratified by age, sex, immigrant status, and where appropriate, census year or survey cycle. Models were further adjusted for income adequacy quintile, visible minority status, Indigenous identity, educational attainment, labor-force status, marital status, occupation, and ecological covariates of community size, airshed, urban form, and four dimensions of the Canadian Marginalization Index (Can-Marg; instability, deprivation, dependency, and ethnic concentration). The mCCHS analyses were also adjusted for individual-level measures of smoking, alcohol consumption, fruit and vegetable consumption, body mass index (BMI), and exercise behavior., In addition to linear models, the shape of the concentration-response function was investigated using restricted cubic splines (RCS). The number of knots were selected by minimizing the Bayesian Information Criterion (BIC). Two additional models were used to examine the association between nonaccidental mortality and PM 2.5 . The first is the standard threshold model defined by a transformation of concentration equaling zero if the concentration was less than a specific threshold value and concentration minus the threshold value for concentrations above the threshold. The second additional model was an extension of the Shape Constrained Health Impact Function (SCHIF), the eSCHIF, which converts RCS predictions into functions potentially more suitable for use in health impact assessments. Given the RCS parameter estimates and their covariance matrix, 1,000 realizations of the RCS were simulated at concentrations from the minimum to the maximum concentration, by increments of 0.1 μg/m 3 . An eSCHIF was then fit to each of these RCS realizations. Thus, 1,000 eSCHIF predictions and uncertainty intervals were determined at each concentration within the total range., Sensitivity analyses were conducted to examine associations between PM 2.5 and mortality when in the presence of, or stratified by tertile of, O 3 or O x . Additionally, associations between PM 2.5 and mortality were assessed for sensitivity to lower concentration thresholds, where person-years below a threshold value were assigned the mean exposure within that group. We also examined the sensitivity of the shape of the nonaccidental mortality-PM 2.5 association to removal of person-years at or above 12 μg/m 3 (the current U.S. National Ambient Air Quality Standard) and 10 μg/m 3 (the current Canadian and former [2005] World Health Organization [WHO] guideline, and current WHO Interim Target-4). Finally, differences in the shapes of PM 2.5 -mortality associations were assessed across broad geographic regions (airsheds) within Canada., Results: The refined PM 2.5 exposure estimates demonstrated improved performance relative to estimates applied previously and in the MAPLE Phase 1 report, with slightly reduced errors, including at lower ranges of concentrations (e.g., for PM 2.5 <10 μg/m 3 )., Positive associations between outdoor PM 2.5 concentrations and nonaccidental mortality were consistently observed in all cohorts. In the Stacked CanCHEC analyses (1.3 million deaths), each 10-μg/m 3 increase in outdoor PM 2.5 concentration corresponded to an HR of 1.084 (95% confidence interval [CI]: 1.073 to 1.096) for nonaccidental mortality. For an interquartile range (IQR) increase in PM 2.5 mass concentration of 4.16 μg/m 3 and for a mean annual nonaccidental death rate of 92.8 per 10,000 persons (over the 1991-2016 period for cohort participants ages 25-90), this HR corresponds to an additional 31.62 deaths per 100,000 people, which is equivalent to an additional 7,848 deaths per year in Canada, based on the 2016 population. In RCS models, mean HR predictions increased from the minimum concentration of 2.5 μg/m 3 to 4.5 μg/m 3 , flattened from 4.5 μg/m 3 to 8.0 μg/m 3 , then increased for concentrations above 8.0 μg/m 3 . The threshold model results reflected this pattern with -2 log-likelihood values being equal at 2.5 μg/m 3 and 8.0 μg/m 3 . However, mean threshold model predictions monotonically increased over the concentration range with the lower 95% CI equal to one from 2.5 μg/m 3 to 8.0 μg/m 3 . The RCS model was a superior predictor compared with any of the threshold models, including the linear model., In the mCCHS cohort analyses inclusion of behavioral covariates did not substantially change the results for both linear and nonlinear models. We examined the sensitivity of the shape of the nonaccidental mortality-PM 2.5 association to removal of person-years at or above the current U.S. and Canadian standards of 12 μg/m 3 and 10 μg/m 3 , respectively. In the full cohort and in both restricted cohorts, a steep increase was observed from the minimum concentration of 2.5 μg/m 3 to 5 μg/m 3 . For the full cohort and the <12 μg/m 3 cohort the relationship flattened over the 5 to 9 μg/m 3 range and then increased above 9 μg/m 3 . A similar increase was observed for the <10 μg/m 3 cohort followed by a clear decline in the magnitude of predictions over the 5 to 9 μg/m 3 range and an increase above 9 μg/m 3 . Together these results suggest that a positive association exists for concentrations >9 μg/m 3 with indications of adverse effects on mortality at concentrations as low as 2.5 μg/m 3 ., Among the other causes of death examined, PM 2.5 exposures were consistently associated with an increased hazard of mortality due to ischemic heart disease, respiratory disease, cardiovascular disease, and diabetes across all cohorts. Associations were observed in the Stacked CanCHEC but not in all other cohorts for cerebrovascular disease, pneumonia, and chronic obstructive pulmonary disease (COPD) mortality. No significant associations were observed between mortality and exposure to PM 2.5 for heart failure, lung cancer, and kidney failure., In sensitivity analyses, the addition of O 3 and O x attenuated associations between PM 2.5 and mortality. When analyses were stratified by tertiles of copollutants, associations between PM 2.5 and mortality were only observed in the highest tertile of O 3 or O x . Across broad regions of Canada, linear HR estimates and the shape of the eSCHIF varied substantially, possibly reflecting underlying differences in air pollutant mixtures not characterized by PM 2.5 mass concentrations or the included gaseous pollutants. Sensitivity analyses to assess regional variation in population characteristics and access to healthcare indicated that the observed regional differences in concentration-mortality relationships, specifically the flattening of the concentration-mortality relationship over the 5 to 9 μg/m 3 range, was not likely related to variation in the makeup of the cohort or its access to healthcare, lending support to the potential role of spatially varying air pollutant mixtures not sufficiently characterized by PM 2.5 mass concentrations., Conclusions: In several large, national Canadian cohorts, including a cohort of 7.1 million unique census respondents, associations were observed between exposure to PM 2.5 with nonaccidental mortality and several specific causes of death. Associations with nonaccidental mortality were observed using the eSCHIF methodology at concentrations as low as 2.5 μg/m 3 , and there was no clear evidence in the observed data of a lower threshold, below which PM 2.5 was not associated with nonaccidental mortality., (© 2022 Health Effects Institute. All rights reserved.)

We used a large national cohort in Canada to assess the incidence of acute myocardial infarction (AMI) and stroke hospitalizations in association with long-term exposure to fine particulate matter (PM 2.5 ), nitrogen dioxide (NO 2 ), and ozone (O 3 ). The study population comprised 2.7 million respondents from the 2006 Canadian Census Health and Environment Cohort (CanCHEC), followed for incident hospitalizations of AMI or stroke between 2006 and 2016. We estimated 10-year moving average estimates of PM 2.5 , NO 2 , and O 3 , annually. We used Cox proportional hazards models to examine the associations adjusting for various covariates. For AMI, each interquartile range (IQR) increase in exposure was found to be associated with a hazard ratio of 1.026 (95% CI: 1.007-1.046) for PM 2.5 , 1.025 (95% CI: 1.001-1.050) for NO 2 , and 1.062 (95% CI: 1.041-1.084) for O 3 , respectively. Similarly, for stroke, an IQR increase in exposure was associated with a hazard ratio of 1.078 (95% CI: 1.052-1.105) for PM 2.5 , 0.995 (95% CI: 0.965-1.030) for NO 2 , and 1.055 (95% CI: 1.028-1.082) for O 3 , respectively. We found consistent evidence of positive associations between long-term exposures to PM 2.5 , and O 3 , and to a lesser degree NO 2 , with incident AMI and stroke hospitalizations., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Using a nationally representative cohort of Canadian adults, we assessed associations between neighbourhood walkability and cause-specific mortality and investigated whether they differed by socioeconomic status., Methods: The study population was drawn from the 2001 Canadian Census Health and Environment Cohort, which contains individual-level data from a random sample of 20% of Canadian households mandated to complete the long-form census. We included those aged ≥ 25 years at baseline who lived in urban and suburban areas. The national death registry was used to ascertain annual vital status. Linkages to annual income tax data provided place of residence. The Canadian Active Living Environments, a national index that summarizes walkability across Canadian neighbourhoods, was assigned to individuals' residential history. The Cox proportional hazards model was used to assess associations between walkability and cause-specific mortality., Results: A total of 1.8 million participants (52.5% female) accrued 27.3 million person-years and 265 710 deaths during the 15-year follow-up. The adjusted hazard ratio (HR) for living in a highly walkable neighbourhood relative to living in the least walkable neighbourhoods was associated with a 9% (HR: 0.91 [0.88, 0.95]) and 3% (HR: 0.97 [0.94, 0.99]) reduced risk of cardiovascular and all non-accidental mortality, respectively. The strongest benefits of walkability were found among individuals within the lowest education and household income categories, and who lived in the most deprived neighbourhoods. There were no significant associations (most [class 5] versus least [class 1] walkable HR: 0.84 [0.61-1.16]) seen for accidental traffic mortality., Conclusions: Canadian adults who live in walkable neighbourhoods have lower rates of cardiovascular and non-accidental mortality, with the greatest benefits seen in those from the lowest socioeconomic groups., (Crown Copyright © 2022. Published by Elsevier Ltd. All rights reserved.)

Background: Over the last decade, several studies have reported that residential proximity to vegetation, or 'greenness', is associated with improved birth outcomes, including for term birth weight (TBW), preterm birth (PTB), and small for gestational age (SGA). However, there remain several uncertainties about these possible benefits including the role of air pollution, and the extent to they are influenced socioeconomic status., Methods: We addressed these gaps using a national population-based study of 2.2 million singleton live births in Canadian metropolitan areas between 1999 and 2008. Exposures to greenness, fine particulate matter (PM 2.5 ), and nitrogen dioxide (NO 2 ) were assigned to infants using the postal code of their mother's residence at the time of birth. The Normalized Difference Vegetation Index (NDVI) was used to characterize greenness, while estimates of ambient PM 2.5 and NO 2 were estimated using remote sensing, and a national land-use regression surface, respectively. Multivariable regression analysis was performed to describe associations between residential greenness and the birth outcomes. Stratified analyses explored whether these associations were modified by neighbourhood measures of socioeconomic status., Results: Mothers who lived in greener areas had a lower risk of low TBW, PTB, and SGA babies. These associations persisted after adjustment for ambient NO 2 and PM 2.5. Specifically, in fully adjusted models, an interquartile range (IQR = 0.16) increase in the NDVI within a residential buffer of 250 m yielded odds ratios of 0.93 (95% confidence interval (CI): 0.92, 0.94), 0.94 (95% CI: 0.92, 0.95), and 0.94 (95% CI: 0.93, 0.95) for the outcomes of PTB, low TBW, and SGA, respectively. Similarly, an IQR increase in greenness was associated with a 16.3 g (95% CI: 15.3, 17.4) increase in TBW. We found inverse associations between greenness and the occurrence of adverse birth outcomes regardless of the socioeconomic status of the neighbourhood., Interpretation: Our findings support the hypothesis that residential greenness contributes to healthier pregnancies, that these associations are independent from exposure to air pollution. , and that proximity to greenness benefits all mothers regardless of socioeconomic status., (Copyright © 2021 Elsevier Inc. All rights reserved.)

One possible side effect of thrombopoietin receptor agonists in immune thrombocytopenia is thrombosis. Our aim is to systematically review whether patients with ITP that were treated with a TPO-RA have an increased risk for thrombosis as compared to ITP patients without TPO-RA. Patients in the intervention group were required to receive TPO-RA therapy. The primary outcome was the incidence of thromboembolic events. Eleven studies were included in the pooled analysis. More thromboembolic events were noted in the TPO-RA group than in the control group: 25 compared to 4. Ten out of 11 studies showed a relative risk greater than 1. However, none of these individual risk ratios was statistically significant. The meta-analysis showed a RR of 1.82 [95 % CI 0.78-4.24]. Our findings indicate there is a non-significant higher chance of thrombosis in ITP patients with TPO-RA treatments versus ITP patients without TPO-RA treatment., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Associations between mortality and exposure to ambient air pollution are usually explored using concentrations of residential outdoor fine particulate matter (PM 2.5 ) to estimate individual exposure. Such studies all have an important limitation in that they do not capture data on individual mobility throughout the day to areas where concentrations may be substantially different, leading to possible exposure misclassification. We examine the possible role of outdoor PM 2.5 concentrations at work for a large population-based mortality cohort., Methods: Using the 2001 Canadian Census Health and Environment Cohort (CanCHEC), we created a time-weighted average that incorporates employment hours worked in the past week and outdoor PM 2.5 concentration at work and home. We used a Cox proportional hazard model with a 15-year follow-up (2001 to 2016) to explore whether inclusion of workplace estimates had an impact on hazard ratios for mortality for this cohort., Results: Hazard ratios relying on outdoor PM 2.5 concentration at home were not significantly different from those using a time-weighted estimate, for the full cohort, nor for those who commute to a regular workplace. When exploring cohort subgroups according to neighborhood type and commute distance, there was a notable but insignificant change in risk of nonaccidental death for those living in car-oriented neighborhoods, and with commutes greater than 10 km., Conclusions: Risk analyses performed with large cohorts in low-pollution environments do not seem to be biased if relying solely on outdoor PM 2.5 concentrations at home to estimate exposure., Competing Interests: The authors declare that they have no conflicts of interest with regard to the content of this report., (Copyright © 2021 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The Environmental Epidemiology. All rights reserved.)

Background: There is increasing interest in the health effects of air pollution. However, the relationships between ozone exposure and mortality attributable to neurological diseases remain unclear., Objectives: To assess associations of long-term exposure to ozone with death from Parkinson's disease, dementia, stroke, and multiple sclerosis., Methods: Our analyses were based on the 2001 Canadian Census Health and Environment Cohort. Census participants were linked with vital statistics records through 2016, resulting in a cohort of 3.5 million adults/51,045,700 person-years, with 8,500/51,300/43,300/1,300 deaths from Parkinson's/dementia/stroke/multiple sclerosis, respectively. Ten-year average ozone concentrations estimated by chemical transport models and adjusted by ground measurements were assigned to subjects based on postal codes. Cox proportional hazards models were used to calculate hazard ratios (HRs) for deaths from the four neurological diseases, adjusting for eight common demographic and socioeconomic factors, seven environmental indexes, and six contextual covariates., Results: The fully adjusted HRs for Parkinson's, dementia, stroke, and multiple sclerosis mortalities related to one interquartile range increase in ozone (10.1 ppb), were 1.09 (95% confidence interval 1.04-1.14), 1.08 (1.06-1.10), 1.06 (1.04-1.09), and 1.35 (1.20-1.51), respectively. The covariates did not influence significance of the ozone-mortality associations, except airshed (i.e., broad region of Canada). During the period of 2001-2016, 5.66%/5.01%/ 3.77%/19.11% of deaths from Parkinson's/dementia/stroke/multiple sclerosis, respectively, were attributable to ozone exposure., Conclusions: We found positive associations between ozone exposure and mortality due to Parkinson's, dementia, stroke, and multiple sclerosis., (Crown Copyright © 2021. Published by Elsevier Ltd. All rights reserved.)

Objective: To investigate the association between changes in long term residential exposure to ambient fine particulate matter (PM 2.5 ) and premature mortality in Canada., Design: Population based quasi-experimental study., Setting: Canada., Participants: 663 100 respondents to the 1996, 2001, and 2006 Canadian censuses aged 25-89 years who had consistently lived in areas with either high or low PM 2.5 levels over five years preceding census day and moved during the ensuing five years., Interventions: Changes in long term exposure to PM 2.5 arising from residential mobility., Main Outcome Measures: The primary outcome was deaths from natural causes. Secondary outcomes were deaths from any cardiometabolic cause, any respiratory cause, and any cancer cause. All outcomes were obtained from the national vital statistics database., Results: Using a propensity score matching technique with numerous personal, socioeconomic, health, and environment related covariates, each participant who moved to a different PM 2.5 area was matched with up to three participants who moved within the same PM 2.5 area. In the matched groups that moved from high to intermediate or low PM 2.5 areas, residential mobility was associated with a decline in annual PM 2.5 exposure from 10.6 μg/m 3 to 7.4 and 5.0 μg/m 3 , respectively. Conversely, in the matched groups that moved from low to intermediate or high PM 2.5 areas, annual PM 2.5 increased from 4.6 μg/m 3 to 6.7 and 9.2 μg/m 3 . Five years after moving, individuals who experienced a reduction in exposure to PM 2.5 from high to intermediate levels showed a 6.8% (95% confidence interval 1.7% to 11.7%) reduction in mortality (2510 deaths in 56 025 v 4925 deaths in 101 960). A greater decline in mortality occurred among those exposed to a larger reduction in PM 2.5 . Increased mortality was found with exposure to PM 2.5 from low to high levels, and to a lesser degree from low to intermediate levels. Furthermore, the decreases in PM 2.5 exposure were most strongly associated with reductions in cardiometabolic deaths, whereas the increases in PM 2.5 exposure were mostly related to respiratory deaths. No strong evidence was found for the changes in PM 2.5 exposure with cancer related deaths., Conclusions: In Canada, decreases in PM 2.5 were associated with lower mortality, whereas increases in PM 2.5 were associated with higher mortality. These results were observed at PM 2.5 levels considerably lower than many other countries, providing support for continuously improving air quality., Competing Interests: Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/disclosure-of-interest/ and declare: support from funded by Health Canada for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Individual and neighbourhood-scale socioeconomic characteristics modify associations between exposure to air pollution and mortality. The role of stress, which may integrate effects of social and environmental exposures on health, is unknown. We examined whether an individual's perspective on their own well-being, as assessed using self-rated measures of stress and health, modifies the pollutant-mortality relationship., Methods: The Canadian Community Health Survey (CCHS)-mortality cohort includes respondents from surveys administered between 2001 and 2012 linked to vital statistics and postal codes from 1981 until 2016. Annual fine particulate matter (PM 2.5 ), nitrogen dioxide (NO 2 ), and ozone (O 3 ) exposure estimates were attached to a sample of cohort members aged 30-89 years (n = 398,300 respondents/3,848,400 person-years). We examined whether self-rated stress, distress, mental health, and general health modified associations between long-term exposure to each pollutant (three-year moving average with one-year lag) and non-accidental mortality using Cox survival models, adjusted for individual- (i.e. socioeconomic and behavioural) and neighbourhood-scale covariates., Results: In fully-adjusted models, the relationship between exposure to pollutants and mortality was stronger among those with poor self-rated mental health, including a significant difference for NO 2 (hazard ratio (HR) = 1.15, 95% CI 1.06-1.25 per IQR) compared to those with very good/excellent mental health (HR = 1.05, 95% CI 1.01-1.08; Cochran's Q = 4.01; p < 0.05). Poor self-rated health was similarly associated with higher pollutant-associated HRs, but only in unadjusted models. Stress and distress did not modify pollutant-mortality associations., Conclusions: Poor self-rated mental and general health were associated with increased mortality attributed to exposure to ambient pollutants., (Crown Copyright © 2020. Published by Elsevier Inc. All rights reserved.)

Background: A growing number of epidemiological studies have linked air pollution exposure to psychological conditions. Laboratory studies indicate that air pollutants can activate the neuroendocrine stress axis and modulate stress hormone levels, which could contribute to the development or exacerbation of psychological distress. The present study examined the spatial associations between air pollutants (fine particulate matter [PM 2.5 ], nitrogen dioxide [NO 2 ] and ground-level ozone [O 3 ]) and psychological distress among subjects in the most populous provinces in Canada., Data and Methods: Subjects were sampled from the Canadian Community Health Survey in three regions (Quebec in 2005 [n=25,800], British Columbia and Alberta in 2005 [n=23,000], and Ontario in 2011 [n=36,000]), and were assigned estimates of annual exposure to three ambient air pollutants (PM 2.5 , NO 2 and O 3 ) for the same years. Individual psychological distress was assessed using the Kessler Psychological Distress Scale (K10), based on anxiety and depressive symptoms in the past month. Regression models (both ordinary least squares and simultaneous autoregressive models) were applied to estimate associations between K10 distress scores and each air pollutant, after adjusting for individual (demographic, socioeconomic and behavioural) and neighbourhood covariates.., Results: Psychological distress was positively associated with PM 2.5 and NO 2 in all three regions, and with O 3 in Quebec. However, after further adjusting for individual and neighbourhood covariates, the associations between distress and air pollution remained statistically significant only in Quebec., Discussion: Some evidence for positive associations between psychological distress and ambient air pollution after adjusting for spatial autocorrelation was found.

Background: Immigrants make up 20% of the Canadian population; however, little is known about the mortality impacts of fine particulate matter (PM 2.5 ) air pollution on immigrants compared with non-immigrants, or about how impacts may change with duration in Canada., Data and Methods: This study used the 2001 Canadian Census Health and Environment Cohort, a longitudinal cohort of 3.5 million individuals, of which 764,000 were classified as immigrants (foreign-born). Postal codes from annual income tax files were used to account for mobility among respondents and to assign annual PM 2.5 concentrations from 1998 to 2016. Exposures were estimated as a three-year moving average prior to the follow-up year. Cox survival models were used to determine hazard ratios (HRs) for cause-specific mortality, comparing the Canadian and foreign-born populations, with further stratification by year of immigration grouped into 10-year cohorts., Results: Differences in urban-rural settlement patterns resulted in greater exposure to PM 2.5 for immigrants compared with non-immigrants (mean = 9.3 vs. 7.5 μg/m 3 ), with higher exposures among more recent immigrants. In fully adjusted models, immigrants had higher HRs per 10 μg/m 3 increase in PM 2.5 concentration compared with Canadian-born individuals for cardiovascular mortality (HR [95% confidence interval] = 1.22 [1.12 to 1.34] vs. 1.12 [1.07 to 1.18]) and cerebrovascular mortality (HR = 1.25 [1.03 to 1.52] vs. 1.03 [0.93 to 1.15]), respectively. However, tests for differences between the two groups were not significant when Cochran's Q test was used. No significant associations were found for respiratory outcomes, except for lung cancer in non-immigrants (HR = 1.10 [1.02 to 1.18]). When stratified by year of immigration, differences in HRs across varied by cause of death., Discussion: In Canada, PM 2.5 is an equal-opportunity risk factor, with immigrants experiencing similar if not higher mortality risks compared with non-immigrants for cardiovascular-related causes of death. Some notable differences also existed with cerebrovascular and lung cancer deaths. Continued reductions in air pollution, particularly in urban areas, will improve the health of the Canadian population as a whole.