Prospective Cohort Study

Urban populations are often simultaneously exposed to air pollution and environmental noise, which are independently associated with cardiovascular disease. Few studies have examined acute physiologic responses to both air and noise pollution using personal exposure measures. We conducted a repeated measures panel study of air pollution and noise in 46 non-smoking adults in Toronto, Canada. Data were analyzed using linear mixed-effects models and weighted cumulative exposure modeling of recent exposure. We examined acute changes in cardiovascular health effects of personal (ultrafine particles, black carbon) and regional (PM2.5, NO2, O3, Ox) measurements of air pollution and the role of personal noise exposure as a confounder of these associations. We observed adverse changes in subclinical cardiovascular outcomes in response to both air pollution and noise, including changes in endothelial function and heart rate variability (HRV). Our findings show that personal noise exposures can confound associations for air pollutants, particularly with HRV, and that impacts of air pollution and noise on HRV occur soon after exposure. Thus, both noise and air pollution have a measurable impact on cardiovascular physiology. Noise should be considered alongside air pollution in future studies to elucidate the combined impacts of these exposures in urban environments.

/pdf/acute-cardiovascular-health-effects-in-a-panel-study-of-3d8l4zvqwl.pdf

Acute cardiovascular health effects in a panel study of personal exposure to traffic-related air pollutants and noise in Toronto, Canada.

Introduction The impact of traffic-related pollution around schools on student health has attracted increased attention in recent years. As students are exposed to pollutants around schools during their daily commute, the effect of pollutant exposure on students is substantial. Methods A literature review of the effects of traffic-related pollution around schools on student health and mitigation measures was conducted. A simple meta-analysis on the effects of PM2.5 and PM10 on respiratory health was also performed. Results Traffic-related pollutants have a great impact on student health. For example, NO2, elemental carbon, and particulate matter have a significant impact on the cognition and developmental nervous systems and respiratory system of students. When concentrations are high, the prevalence of respiratory infection, asthma, tracheitis, and other diseases in children increases. Traffic-related pollutants around schools affect the cardiovascular system and are associated with allergic symptoms. To reduce the effect of traffic-related pollution on student health, some mitigation measures are suggested. Suitable transport routes and walking routes to and from school should be planned based on the pollution levels around the school. Trees and hedges could be set up on the roads around the school to prevent the diffusion of PM. The influence of street form and building layout on pollutant diffusion should be considered in urban planning. In heavily polluted areas, pollutant filters can be used to clean the air. The government should actively reduce the number of vehicles near schools, strengthen infrastructure construction, and reduce congestion. At the social level, idle running time should be reduced. Conclusions We have a relatively strong understanding of the traffic pollution around schools and its impact on student health. The mitigation measures for reducing the effect of traffic pollution on student health were summarized. Future government policies and social initiatives that could be taken were proposed.

A review of the effect of traffic-related air pollution around schools on student health and its mitigation

A higher-than-usual resistance to standard sedation regimens in COVID-19 patients suffering from acute respiratory distress syndrome (ARDS) has led to the frequent use of the second-line anaesthetic agent ketamine. Simultaneously, an increased incidence of cholangiopathies in mechanically ventilated patients receiving prolonged infusion of high-dose ketamine has been noted. Therefore, the objective of this study was to investigate a potential dose-response relationship between ketamine and bilirubin levels.Post hoc analysis of a prospective observational cohort of patients suffering from COVID-19-associated ARDS between March 2020 and August 2021. A time-varying, multivariable adjusted, cumulative weighted exposure mixed-effects model was employed to analyse the exposure-effect relationship between ketamine infusion and total bilirubin levels.Two-hundred forty-three critically ill patients were included into the analysis. Ketamine was infused to 170 (70%) patients at a rate of 1.4 [0.9-2.0] mg/kg/h for 9 [4-18] days. The mixed-effects model revealed a positively correlated infusion duration-effect as well as dose-effect relationship between ketamine infusion and rising bilirubin levels (p < 0.0001). In comparison, long-term infusion of propofol and sufentanil, even at high doses, was not associated with increasing bilirubin levels (p = 0.421, p = 0.258). Patients having received ketamine infusion had a multivariable adjusted competing risk hazard of developing a cholestatic liver injury during their ICU stay of 3.2 [95% confidence interval, 1.3-7.8] (p = 0.01).A causally plausible, dose-effect relationship between long-term infusion of ketamine and rising total bilirubin levels, as well as an augmented, ketamine-associated, hazard of cholestatic liver injury in critically ill COVID-19 patients could be shown. High-dose ketamine should be refrained from whenever possible for the long-term analgosedation of mechanically ventilated COVID-19 patients. 

/pdf/long-term-ketamine-infusion-induced-cholestatic-liver-injury-13pu1a2a.pdf

Long-term ketamine infusion-induced cholestatic liver injury in COVID-19-associated acute respiratory distress syndrome

Short-term effects of ultrafine particles on heart rate variability: A systematic review and meta-analysis.

An accurate assessment of the safety or effectiveness of drugs in pharmaco-epidemiological studies requires defining an etiologically correct time-varying exposure model, which specifies how previous drug use affects the outcome of interest. To address this issue, we develop, and validate in simulations, a new approach for flexible modeling of the cumulative effects of time-varying exposures on repeated measures of a continuous response variable, such as a quantitative surrogate outcome, or a biomarker. Specifically, we extend the linear mixed effects modeling to estimate how past and recent drug exposure affects the way individual values of the outcome change throughout the follow-up. To account for the dosage, duration and timing of past exposures, we rely on a flexible weighted cumulative exposure methodology to model the cumulative effects of past drug use, as the weighted sum of past doses. Weights, modeled with unpenalized cubic regression B-splines, reflect the relative importance of doses taken at different times in the past. In simulations, we evaluate the performance of the model under different assumptions concerning (i) the shape of the weight function, (ii) the sample size, (iii) the number of the longitudinal observations and (iv) the intra-individual variance. Results demonstrate the accuracy of our estimates of the weight function and of the between- and within-patients variances, and good correlation between the observed and predicted longitudinal changes in the outcome. We then apply the proposed method to re-assess the association between time-varying glucocorticoid exposure and weight gain in people living with rheumatoid arthritis.

Modeling of cumulative effects of time-varying drug exposures on within-subject changes in a continuous outcome.

Objectives People with HIV are exposed to a higher risk of coronary artery disease (CAD) compared with the general population. Epicardial fat may play a unique role in promoting coronary atherosclerosis. We measured epicardial fat in participants living with HIV and controls and investigated its association with coronary plaque volume and low attenuation plaque, a marker of plaque vulnerability. Design This is a cross-sectional study, nested in the Canadian HIV and Aging Cohort Study, a large prospective cohort actively following participants with HIV and controls. Participants with low/intermediate cardiovascular risk without symptoms/history of CAD were invited to undergo cardiac computed tomography (CT). Methods Volume of epicardial fat, coronary plaque and low attenuation component of the plaque were measured. Association between epicardial fat, coronary plaque volume and low attenuation component was tested using adjusted regression analysis. Results A total of 169 participants with HIV and 81 controls underwent cardiac CT. Participants with HIV had a greater epicardial fat volume compared with controls (P = 0.019). In participants with HIV, epicardial fat volume was positively associated with duration of nonnucleoside reverse transcriptase inhibitors (NNRTI) (β=2.19, P = 0.004). After adjustment for cardiovascular risk factors, epicardial fat volume was positively associated to noncalcified plaque volume [odds ratio (OR) = 1.09, P = 0.028] and to the low-attenuation plaque component portion (β=0.38, P = 0.026). Conclusion The association of epicardial fat volume to noncalcified plaque volume and to low attenuation component plaque may suggest a potential mechanism by which epicardial fat could be a silent driver of CAD in the HIV population.

Coraline Danieli

Papers

Acute cardiovascular health effects in a panel study of personal exposure to traffic-related air pollutants and noise in Toronto, Canada.

Modeling of cumulative effects of time-varying drug exposures on within-subject changes in a continuous outcome.

Association of epicardial fat with noncalcified coronary plaque volume and with low attenuation plaque in people with HIV.