Geography, generalisability, and susceptibility in clinical trials

This article is made available for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic

Workplace status and risk of hypertension among hourly and salaried aluminum manufacturing employees

An inverse relationship between workplace status and morbidity is well established; higher job status has been associated with reduced risks of heart disease, hypertension, and injury. Most research on job status, however, has focused on salaried populations, and it remains unclear whether job status operates similarly among hourly workers. Our objectives were to examine whether hourly status itself influences risk of hypertension after adjustment for socioeconomic confounders, and to explore the role of fine-scale job grade on hypertension incidence within hourly and salaried groups. We examined data for 14,999 aluminum manufacturing employees in 11 plants across the U.S., using logistic regression with adjustment for age, sex, race/ethnicity and other individual characteristics. Propensity score restriction was used to identify comparable groups of hourly and salaried employees, reducing confounding by sociodemographic characteristics. Job grade (coded 1 through 30, within hourly and salaried groups) was examined as a more refined measure of job status. Hourly status was associated with an increased risk of hypertension, after propensity restriction and adjustment for confounders. The observed effect of hourly status was stronger among women, although the propensity-restricted cohort was disproportionately male (96%). Among salaried workers, higher job grade was not consistently associated with decreased risk; among hourly employees, however, there was a significant trend, with higher job grades more protective against hypertension. Increasing the stringency of hypertension case criteria also increased the risk of severe or persistent hypertension for hourly employees.Hypertension Manufacturing employment Occupational status Job grade Propensity scores Salaried vs. hourly workers USA

Putting Co-Exposures on Equal Footing: An Ecological Analysis of Same-Scale Measures of Air Pollution and Social Factors on Cardiovascular Disease in New York City

Epidemiologic evidence consistently links urban air pollution exposures to health, even after adjustment for potential spatial confounding by socioeconomic position (SEP), given concerns that air pollution sources may be clustered in and around lower-SEP communities. SEP, however, is often measured with less spatial and temporal resolution than are air pollution exposures (i.e., census-tract socio-demographics vs. fine-scale spatio-temporal air pollution models). Although many questions remain regarding the most appropriate, meaningful scales for the measurement and evaluation of each type of exposure, we aimed to compare associations for multiple air pollutants and social factors against cardiovascular disease (CVD) event rates, with each exposure measured at equal spatial and temporal resolution. We found that, in multivariable census-tract-level models including both types of exposures, most pollutant–CVD associations were non-significant, while most social factors retained significance. Similarly, the magnitude of association was higher for an IQR-range difference in the social factors than in pollutant concentrations. We found that when offered equal spatial and temporal resolution, CVD was more strongly associated with social factors than with air pollutant exposures in census-tract-level analyses in New York City

Geocoding Error, Spatial Uncertainty, and Implications for Exposure Assessment and Environmental Epidemiology

Although environmental epidemiology studies often rely on geocoding procedures in the process of assigning spatial exposure estimates, geocoding methods are not commonly reported, nor are consequent errors in exposure assignment explored. Geocoding methods differ in accuracy, however, and, given the increasing refinement of available exposure models for air pollution and other exposures, geocoding error may account for an increasingly larger proportion of exposure misclassification. We used residential addresses from a reasonably large, dense dataset of asthma emergency department visits from all New York City hospitals (n = 21,183; 26.9 addresses/km2), and geocoded each using three methods (Address Point, Street Segment, Parcel Centroid). We compared missingness and spatial patterning therein, quantified distance and directional errors, and quantified impacts on pollution exposure estimates and assignment to Census areas for sociodemographic characterization. Parcel Centroids had the highest overall missingness rate (38.1%, Address Point = 9.6%, Street Segment = 6.1%), and spatial clustering in missingness was significant for all methods, though its spatial patterns differed. Street Segment geocodes had the largest mean distance error (µ = 29.2 (SD = 26.2) m; vs. µ = 15.9 (SD = 17.7) m for Parcel Centroids), and the strongest spatial patterns therein. We found substantial over- and under-estimation of pollution exposures, with greater error for higher pollutant concentrations, but minimal impact on Census area assignment. Finally, we developed surfaces of spatial patterns in errors in order to identify locations in the study area where exposures may be over-/under-estimated. Our observations provide insights towards refining geocoding methods for epidemiology, and suggest methods for quantifying and interpreting geocoding error with respect to exposure misclassification, towards understanding potential impacts on health effect estimates

Fine-Scale Source Apportionment Including Diesel-Related Elemental and Organic Constituents of PM2.5 across Downtown Pittsburgh

Health effects of fine particulate matter (PM2.5) may vary by composition, and the characterization of constituents may help to identify key PM2.5 sources, such as diesel, distributed across an urban area. The composition of diesel particulate matter (DPM) is complicated, and elemental and organic carbon are often used as surrogates. Examining multiple elemental and organic constituents across urban sites, however, may better capture variation in diesel-related impacts, and help to more clearly separate diesel from other sources. We designed a “super-saturation” monitoring campaign of 36 sites to capture spatial variance in PM2.5 and elemental and organic constituents across the downtown Pittsburgh core (~2.8 km2). Elemental composition was assessed via inductively-coupled plasma mass spectrometry (ICP-MS), organic and elemental carbon via thermal-optical reflectance, and organic compounds via thermal desorption gas-chromatography mass-spectrometry (TD-GCMS). Factor analysis was performed including all constituents—both stratified by, and merged across, seasons. Spatial patterning in the resultant factors was examined using land use regression (LUR) modelling to corroborate factor interpretations. We identified diesel-related factors in both seasons; for winter, we identified a five-factor solution, describing a bus and truck-related factor [black carbon (BC), fluoranthene, nitrogen dioxide (NO2), pyrene, total carbon] and a fuel oil combustion factor (nickel, vanadium). For summer, we identified a nine-factor solution, which included a bus-related factor (benzo[ghi]fluoranthene, chromium, chrysene, fluoranthene, manganese, pyrene, total carbon, total elemental carbon, zinc) and a truck-related factor (benz[a]anthracene, BC, hopanes, NO2, total PAHs, total steranes). Geographic information system (GIS)-based emissions source covariates identified via LUR modelling roughly corroborated factor interpretations

Spatial Patterns in Rush-Hour vs. Work-Week Diesel-Related Pollution across a Downtown Core

Despite advances in monitoring and modelling of intra-urban variation in multiple pollutants, few studies have attempted to separate spatial patterns by time of day, or incorporated organic tracers into spatial monitoring studies. Due to varying emissions sources from diesel and gasoline vehicular traffic, as well as within-day temporal variation in source mix and intensity (e.g., rush-hours vs. full-day measures), accurately assessing diesel-related air pollution within an urban core can be challenging. We allocated 24 sampling sites across downtown Pittsburgh, Pennsylvania (2.8 km2) to capture fine-scale variation in diesel-related pollutants, and to compare these patterns by sampling interval (i.e., “rush-hours” vs. “work-week” concentrations), and by season. Using geographic information system (GIS)-based methods, we allocated sampling sites to capture spatial variation in key traffic-related pollution sources (i.e., truck, bus, overall traffic densities). Programmable monitors were used to collect integrated work-week and rush-hour samples of fine particulate matter (PM2.5), black carbon (BC), trace elements, and diesel-related organics (polycyclic aromatic hydrocarbons (PAHs), hopanes, steranes), in summer and winter 2014. Land use regression (LUR) models were created for PM2.5, BC, total elemental carbon (EC), total organic carbon (OC), elemental (Al, Ca, Fe), and organic constituents (total PAHs, total hopanes), and compared by sampling interval and season. We hypothesized higher pollution concentrations and greater spatial contrast in rush-hour, compared to full work-week samples, with variation by season and pollutant. Rush-hour sampling produced slightly higher total PM2.5 and BC concentrations in both seasons, compared to work-week sampling, but no evident difference in spatial patterns. We also found substantial spatial variability in most trace elements and organic compounds, with comparable spatial patterns using both sampling paradigms. Overall, we found higher concentrations of traffic-related trace elements and organic compounds in rush-hour samples, and higher concentrations of coal-related elements (e.g., As, Se) in work-week samples. Mean bus density was the strongest LUR predictor in most models, in both seasons, under each sampling paradigm. Within each season and constituent, the bus-related terms explained similar proportions of variance in the rush-hour and work-week samples. Rush-hour and work-week LUR models explained similar proportions of spatial variation in pollutants, suggesting that the majority of emissions may be produced during rush-hour traffic across downtown. Results suggest that rush-hour emissions may predominantly shape overall spatial variance in diesel-related pollutants