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Emerging evidence suggests that living near major roads might adversely affect cognition. However, little is known about its relationship with the incidence of dementia, Parkinson's disease, and multiple sclerosis. We aimed to investigate the association between residential proximity to major roadways and the incidence of these three neurological diseases in Ontario, Canada. In this population-based cohort study, we assembled two population-based cohorts including all adults aged 20–50 years (about 4·4 million; multiple sclerosis cohort) and all adults aged 55–85 years (about 2·2 million; dementia or Parkinson's disease cohort) who resided in Ontario, Canada on April 1, 2001. Eligible patients were free of these neurological diseases, Ontario residents for 5 years or longer, and Canadian-born. We ascertained the individual's proximity to major roadways based on their residential postal-code address in 1996, 5 years before cohort inception. Incident diagnoses of dementia, Parkinson's disease, and multiple sclerosis were ascertained from provincial health administrative databases with validated algorithms. We assessed the associations between traffic proximity and incident dementia, Parkinson's disease, and multiple sclerosis using Cox proportional hazards models, adjusting for individual and contextual factors such as diabetes, brain injury, and neighbourhood income. We did various sensitivity analyses, such as adjusting for access to neurologists and exposure to selected air pollutants, and restricting to never movers and urban dwellers. Between 2001, and 2012, we identified 243 611 incident cases of dementia, 31 577 cases of Parkinson's disease, and 9247 cases of multiple sclerosis. The adjusted hazard ratio (HR) of incident dementia was 1·07 for people living less than 50 m from a major traffic road (95% CI 1·06–1·08), 1·04 (1·02–1·05) for 50–100 m, 1·02 (1·01–1·03) for 101–200 m, and 1·00 (0·99–1·01) for 201–300 m versus further than 300 m (p for trend=0·0349). The associations were robust to sensitivity analyses and seemed stronger among urban residents, especially those who lived in major cities (HR 1·12, 95% CI 1·10–1·14 for people living <50 m from a major traffic road), and who never moved (1·12, 1·10–1·14 for people living <50 m from a major traffic road). No association was found with Parkinson's disease or multiple sclerosis. In this large population-based cohort, living close to heavy traffic was associated with a higher incidence of dementia, but not with Parkinson's disease or multiple sclerosis. Health Canada (MOA-4500314182).

Globally, primary care changed dramatically as a result of the coronavirus disease 2019 (COVID-19) pandemic. We aimed to understand the degree to which office and virtual primary care changed, and for which patients and physicians, during the initial months of the pandemic in Ontario, Canada. This population-based study compared comprehensive, linked primary care physician billing data from Jan. 1 to July 28, 2020, with the same period in 2019. We identified Ontario residents with at least 1 office or virtual (telephone or video) visit during the study period. We compared trends in total physician visits, office visits and virtual visits before COVID-19 with trends after pandemic-related public health measures changed the delivery of care, according to various patient and physician characteristics. We used interrupted time series analysis to compare trends in the early and later halves of the COVID-19 period. Compared with 2019, total primary care visits between March and July 2020 decreased by 28.0%, from 7.66 to 5.51 per 1000 people/day. The smallest declines were among patients with the highest expected health care use (8.3%), those who could not be attributed to a primary care physician (10.2%), and older adults (19.1%). In contrast, total visits in rural areas increased by 6.4%. Office visits declined by 79.1% and virtual care increased 56-fold, comprising 71.1% of primary care physician visits. The lowest uptake of virtual care was among children (57.6%), rural residents (60.6%) and physicians with panels of ≥ 2500 patients (66.0%). Primary care in Ontario saw large shifts from office to virtual care over the first 4 months of the COVID-19 pandemic. Total visits declined least among those with higher health care needs. The determinants and consequences of these major shifts in care require further study.

Although growing evidence links air pollution to stroke incidence, less is known about the effect of air pollution on atrial fibrillation (AF), an important risk factor for stroke. We assessed the associations between air pollution and incidence of AF and stroke. We also sought to characterize the shape of pollutant-disease relationships. The population-based cohort comprised 5,071,956 Ontario residents, age 35–85 y and without the diagnoses of both outcomes on 1 April 2001 and was followed up until 31 March 2015. AF and stroke cases were ascertained using health administrative databases with validated algorithms. Based on annual residential postal codes, we assigned 5-y running average concentrations of fine particulate matter ([Formula: see text]), nitrogen dioxide ([Formula: see text]), and ozone ([Formula: see text]) from satellite-derived data, a land-use regression model, and a fusion-based method, respectively, as well as redox-weighted averages of [Formula: see text] and [Formula: see text] ([Formula: see text]) for each year. Using Cox proportional hazards models, we estimated the hazard ratios (HRs) and 95% confidence intervals (95% CIs) of AF and stroke with each of these pollutants, adjusting for individual- and neighborhood-level variables. We used newly developed nonlinear risk models to characterize the shape of pollutant–disease relationships. Between 2001 and 2015, we identified 313,157 incident cases of AF and 122,545 cases of stroke. Interquartile range increments of [Formula: see text], [Formula: see text], [Formula: see text], and [Formula: see text] were associated with increases in the incidence of AF [HRs (95% CIs): 1.03 (1.01, 1.04), 1.02 (1.01, 1.03), 1.01 (1.00, 1.02), and 1.01 (1.01, 1.02), respectively] and the incidence of stroke [HRs (95% CIs): 1.05 (1.03, 1.07), 1.04 (1.01, 1.06), 1.05 (1.03, 1.06), and 1.05 (1.04, 1.06), respectively]. Associations of similar magnitude were found in various sensitivity analyses. Furthermore, we found a near-linear association for stroke with [Formula: see text], whereas [Formula: see text], [Formula: see text]-, and [Formula: see text] relationships exhibited sublinear shapes. Air pollution was associated with stroke and AF onset, even at very low concentrations. https://doi.org/10.1289/EHP4883.

Epidemiological evidence for the association between traffic-related noise and the incidence of major cardiovascular events such as acute myocardial infarction (AMI) and congestive heart failure (CHF) is inconclusive, especially in North America. We evaluated the associations between long-term exposure to road traffic noise and the incidence of AMI and CHF. Our study population comprised people 30-100 years of age who lived in Toronto, Canada, from 2001 to 2015 and were free of AMI (referred to as the AMI cohort) or CHF (the CHF cohort) at baseline. Outcomes were ascertained from health administrative databases using validated algorithms. Annual average noise levels were estimated as the A-weighted equivalent sound pressure level over the 24-h period (LAeq24) and during nighttime (LAeqNight), respectively, using propagation modeling, and assigned to participants' annual six-digit postal code addresses during follow-up. We calculated hazard ratios (HRs) and 95% confidence intervals (CIs) for incident AMI and CHF in relation to LAeq24 and LAeqNight using random-effects Cox proportional hazards models adjusting for individual- and census tract-level covariates, including traffic-related air pollutants [e.g., ultrafine particles (UFPs) and nitrogen dioxide]. During follow-up, there were 37,441 AMI incident cases and 95,138 CHF incident cases. Each interquartile range change in LAeq24 was associated with an increased risk of incident AMI ( ; 95% CI: 1.06, 1.08) and CHF ( ; 95% CI: 1.06, 1.09). Similarly, LAeqNight was associated with incident AMI ( ; 95% CI: 1.05, 1.08) and CHF ( ; 95% CI: 1.05, 1.07). These results were robust to various sensitivity analyses and remained elevated after controlling for long-term exposure to UFPs and nitrogen dioxide. We found near-linear relationships between noise and the incidence of AMI and CHF with no evidence of threshold values. In this large cohort study in Toronto, Canada, chronic exposure to road traffic noise was associated with elevated risks for AMI and CHF incidence. https://doi.org/10.1289/EHP5809.

Introduction Bioresorbable implants significantly advance orthopedics and regenerative medicine, offering advantages over permanent implants for bone regeneration. They eliminate the need for secondary surgery and reduce long-term risks associated with permanent implants. Magnesium-based alloys are particularly promising, as their biocompatibility and mechanical properties are similar to bone. However, the degradation of magnesium is associated with physiological challenges that need to be better understood. Objective The primary focus of this in vitro study was to investigate the osteogenic and immunomodulatory potential of WE43, a promising magnesium alloy tailored for clinical applications, and to test its osteogenic effect when a plasma electrolytic oxidation (PEO) surface modification is added. Results The present data revealed that WE43 implants show excellent biocompatibility and bioactivity, promoting the viability of osteoblasts and enhancing the expression of osteogenic genes, specially Alpl and Tnfrsf11b. PEO surface modification did not further enhance osteogenic differentiation. Notably, WE43 implants elicited a minimal inflammatory response in RAW264.7 murine macrophages, indicating good biocompatibility. Furthermore, supernatant collected from RAW264.7 murine macrophages cultured with WE43 implants stimulated the Alpl expression in MC3T3-E1 murine osteoblasts, demonstrating their potential osteoimmune effect. Conclusion The present findings highlight the promising potential of WE43 alloy as a biocompatible and osteoinductive biomaterial for bone regeneration applications. Their osteoimmune modulation further demonstrates the advantages of using this alloy system. Specifically, a minimal, well-controlled inflammatory response can promote a faster transition to the bone remodeling phase, leading to quicker and more effective bone regeneration. Methodology A comprehensive in vitro investigation was conducted to assess the impact of both WE43 and WE43 PEO on the viability, Alkaline Phosphatase (ALP) expression, osteogenic gene expression (Alpl, Tnfrsf11b, and Bglap), and mineralization of MC3T3-E1 murine osteoblasts. The osteoimmunomodulatory response to WE43 was evaluated using RAW264.7 murine macrophages by assessing their response to direct contact with the alloy.

Background Lung cancer is one of the most common cancers and causes of cancer death in Canada. Some previous literature suggests that socioeconomic inequalities in lung cancer screening, treatment and survival may exist. The objective of this study was to compare overall survival for immigrants versus long-term residents of Ontario, Canada among patients diagnosed with lung cancer. Methods This population-based retrospective cohort study utilized linked health administrative databases and identified all individuals (immigrants and long-term residents) aged 40 + years diagnosed with incident lung cancer between April 1, 2012 and March 31, 2017. The primary outcome was 5-year overall survival with December 31, 2019 as the end of the follow-up period. We implemented adjusted Cox proportional hazards models stratified by age at diagnosis, sex, and cancer stage at diagnosis to examine survival. Results Thirty-eight thousand seven hundred eighty-eight individuals diagnosed with lung cancer were included in our cohort including 7% who were immigrants. Immigrants were younger at diagnosis and were more likely to reside in the lowest neighbourhood income quintile (30.6% versus 24.5%) than long-term residents. After adjusting for age at diagnosis, neighbourhood income quintile, comorbidities, visits to primary care in the 6 to 30 months before diagnosis, continuity of care, cancer type and cancer stage at diagnosis, immigrant status was associated with a lower hazard of dying 5-years post-diagnosis for both females (0.7; 95% CI 0.6–0.8) and males (0.7; 95% CI 0.6–0.7) in comparison to long-term residents. This trend held in adjusted models stratified by cancer stage at diagnosis. For example, female immigrants diagnosed with early stage lung cancer had a hazard ratio of 0.5 (95% CI 0.4–0.7) in comparison to long-term residents. Conclusion Overall survival post diagnosis with lung cancer was better among Ontario immigrants versus long-term residents. Additional research, potentially on the protective effects of immigrant enclave and the intersection of immigrant status with racial/ethnic identity, is needed to further explore why better overall survival for immigrants remained.

Additively manufactured scaffolds offer significant potential for treating bone defects, owing to their porous, customizable architecture and functionalization capabilities. Although various biomaterials have been investigated, metals – the most successful orthopedic material – have yet to yield satisfactory results. Conventional bio‐inert metals, such as titanium (Ti) and its alloys, are widely used for fixation devices and reconstructive implants, but their non‐bioresorbable nature and the mechanical property mismatch with human bones limit their application as porous scaffolds for bone regeneration. Advancements in additive manufacturing have facilitated the use of bioresorbable metals, including magnesium (Mg), zinc (Zn), and their alloys, as porous scaffolds via Laser Powder Bed Fusion (L‐PBF) technology. This in vivo study presents a comprehensive, side‐by‐side comparative analysis of the interactions between bone regeneration and additively manufactured bio‐inert/bioresorbable metal scaffolds, as well as their therapeutic outcomes. The research offers an in‐depth understanding of the metal scaffold‐assisted bone healing process, illustrating that Mg and Zn scaffolds contribute to the bone healing process in distinct ways, but ultimately deliver superior therapeutic outcomes compared to Ti scaffolds. These findings suggest that bioresorbable metal scaffolds hold considerable promise for the clinical treatment of bone defects in the near future.

Gatifloxacin has been associated with both hypoglycemia and hyperglycemia. This study examined dysglycemia-related health outcomes associated with the use of various antibiotics in adults 66 years of age or older in Ontario, Canada. As compared with the use of other broad-spectrum oral antibiotics, including other fluoroquinolones, gatifloxacin use among outpatients appears to be clearly associated with both subsequent hypoglycemia and subsequent hyperglycemia. This study examined dysglycemia-related health outcomes associated with the use of various antibiotics. Gatifloxacin use among outpatients appears to be clearly associated with both subsequent hypoglycemia and subsequent hyperglycemia. Fluoroquinolones, broad-spectrum antibiotics that are widely perceived to have favorable adverse-effect profiles, have become the most prescribed antibiotics in the United States. 1 From 1995 to 2002, the number of fluoroquinolone prescriptions in the United States increased by a factor of more than three, reaching about 22 million prescriptions per year. 1 The available fluoroquinolones have well-established differences in antimicrobial activity, but their disparate adverse-effect profiles are increasingly being recognized. Serious adverse events have led to the withdrawal or restriction of several fluoroquinolones in recent years, 2 including temafloxacin (because of hemolysis, renal failure, and hypoglycemia), 3 , 4 grepafloxacin and sparfloxacin (because of QT-interval . . .

The COVID-19 pandemic disrupted progress towards global HCV elimination goals by interrupting essential health services in Canada and globally. We aimed to evaluate the effect of the pandemic on hepatitis C virus (HCV) testing rates in a population-based cohort study in Ontario using health administrative data. All residents with records of either HCV antibody or ribonucleic acid (RNA) tests were included. Monthly testing rate per 1000 population were compared during the pre-pandemic (01/01/2015–29/02/2020) and pandemic (01/03/2020–31/12/2022) periods using interrupted time series models, stratified by sex, homelessness, human immunodeficiency virus (HIV), and immigration status, and people who inject drugs (PWID). The HCV testing rate followed a statistically significant upward trend before the pandemic, dropping at its onset with 1.38/1000 fewer individuals initiating testing monthly. Compared to counterfactual estimates, the observed monthly number of people tested per 1000 population was lower by 1.41 (95% CI: 1.18–1.64) in 2020 (May–Dec), 1.17 (95% CI: 0.99–1.36) in 2021, and 1.41 (95% CI: 1.22–1.59) in 2022, corresponding to relative reductions of 47%, 34%, and 41%, respectively. Testing rates remained below expected levels across all subgroups throughout 2020–2022, with the greatest absolute declines observed among people co-infected with HIV, people experiencing homelessness, and PWID. Tailored, equity-focused interventions are needed to address these persistent gaps in HCV testing, without which Canada’s progress toward its 2030 elimination targets remains at risk.