The Role of Neighborhood Air Pollution in Disparate Racial and Ethnic Asthma Acute Care Use.

Rationale: The share of Black or Latinx residents in a census tract remains associated with asthma-related emergency department (ED) visit rates after controlling for socioeconomic factors. The extent to which evident disparities relate to the within-city heterogeneity of long-term air pollution exposure remains unclear. Objectives: To investigate the role of intraurban spatial variability of air pollution in asthma acute care use disparity. Methods: An administrative database was used to define census tract population-based incidence rates of asthma-related ED visits. We estimate the associations between census tract incidence rates and 1) average fine and coarse particulate matter, nitrogen dioxide (NO2), and sulfur dioxide (SO2), and 2) racial and ethnic composition using generalized linear models controlling for socioeconomic and housing covariates. We also examine for the attenuation of incidence risk ratios (IRRs) associated with race/ethnicity when controlling for air pollution exposure. Measurements and Main Results: Fine and coarse particulate matter and SO2 are all associated with census tract-level incidence rates of asthma-related ED visits, and multipollutant models show evidence of independent risk associated with coarse particulate matter and SO2. The association between census tract incidence rate and Black resident share (IRR, 1.51 [credible interval (CI), 1.48-1.54]) is attenuated by 24% when accounting for air pollution (IRR, 1.39 [CI, 1.35-1.42]), and the association with Latinx resident share (IRR, 1.11 [CI, 1.09-1.13]) is attenuated by 32% (IRR, 1.08 [CI, 1.06-1.10]). Conclusions: Neighborhood-level rates of asthma acute care use are associated with local air pollution. Controlling for air pollution attenuates associations with census tract racial/ethnic composition, suggesting that intracity variability in air pollution could contribute to neighborhood-to-neighborhood asthma morbidity disparities.

Neighborhood-level variability in asthma-related emergency department visits in Central Texas.

BACKGROUND: The extent to which incidence rates of asthma-related emergency department (ED) visits vary from neighborhood to neighborhood and predictors of neighborhood-level asthma ED visit burden are not well understood. OBJECTIVE: We aimed to describe the census tract-level spatial distribution of asthma-related ED visits in Central Texas and identify neighborhood-level characteristics that explain variability in neighborhood-level asthma ED visit rates. METHODS: Conditional autoregressive models were used to examine the spatial distribution of asthma-related ED visit incidence rates across census tracts in Travis County, Texas, and assess the contribution of census tract characteristics to their distribution. RESULTS: There were distinct patterns in ED visit incidence rates at the census tract scale. These patterns were largely unexplained by socioeconomic or selected built environment neighborhood characteristics. However, racial and ethnic composition explained 33% of the variability of ED visit incidence rates across census tracts. The census tract predictors of ED visit incidence rates differed by racial and ethnic group. CONCLUSIONS: Variability in asthma ED visit incidence rates are apparent at smaller spatial scales. Most of the variability in census tract-level asthma ED visit rates in Central Texas is not explained by racial and ethnic composition or other neighborhood characteristics.

Causal Analysis of Air Pollution Mixtures: Estimands, Positivity, and Extrapolation.

Causal inference for air pollution mixtures is an increasingly important issue with appreciable challenges. When the exposure is a multivariate mixture, there are many exposure contrasts that may be of nominal interest for causal effect estimation, but the complex joint mixture distribution often renders observed data extremely limited in their ability to inform estimates of many commonly-defined causal effects. We use potential outcomes to 1) define causal effects of air pollution mixtures, 2) formalize the key assumption of mixture positivity required for estimation and 3) offer diagnostic metrics for positivity violations in the mixture setting that allow researchers to assess the extent to which data can actually support estimation of mixture effects of interest. For settings where there is limited empirical support, we redefine causal estimands that apportion causal effects according to whether they can be directly informed by observed data versus rely entirely on model extrapolation, isolating key sources of information on the causal effect of an air pollution mixture. The ideas are deployed to assess the ability of a national United States data set on the chemical components of ambient particulate matter air pollution to support estimation of a variety of causal mixture effects.

Pollen and viruses contribute to spatio-temporal variation in asthma-related emergency department visits.

BACKGROUND: Asthma exacerbations are an important cause of emergency department visits but much remains unknown about the role of environmental triggers including viruses and allergenic pollen. A better understanding of spatio-temporal variation in exposure and risk posed by viruses and pollen types could help prioritize public health interventions. OBJECTIVE: Here we quantify the effects of regionally important Cupressaceae pollen, tree pollen, other pollen types, rhinovirus, seasonal coronavirus, respiratory syncytial virus, and influenza on asthma-related emergency department visits for people living near eight pollen monitoring stations in Texas. METHODS: We used age stratified Poisson regression analyses to quantify the effects of allergenic pollen and viruses on asthma-related emergency department visits. RESULTS: Young children (<5 years of age) had high asthma-related emergency department rates (24.1 visits/1,000,000 person-days), which were mainly attributed to viruses (51.2%). School-aged children also had high rates (20.7 visits/1,000,000 person-days), which were attributed to viruses (57.0%), Cupressaceae pollen (0.7%), and tree pollen (2.8%). Adults had lower rates (8.1 visits/1,000,000 person-days) which were attributed to viruses (25.4%), Cupressaceae pollen (0.8%), and tree pollen (2.3%). This risk was spread unevenly across space and time; for example, during peak Cuppressaceae season, this pollen accounted for 8.2% of adult emergency department visits near Austin where these plants are abundant, but 0.4% in cities like Houston where they are not; results for other age groups were similar. CONCLUSIONS: Although viruses are a major contributor to asthma-related emergency department visits, airborne pollen can explain a meaningful portion of visits during peak pollen season and this risk varies over both time and space because of differences in plant composition.

Bayesian nonparametric adjustment of confounding.

Analysis of observational studies increasingly confronts the challenge of determining which of a possibly high-dimensional set of available covariates are required to satisfy the assumption of ignorable treatment assignment for estimation of causal effects. We propose a Bayesian nonparametric approach that simultaneously (1) prioritizes inclusion of adjustment variables in accordance with existing principles of confounder selection; (2) estimates causal effects in a manner that permits complex relationships among confounders, exposures, and outcomes; and (3) provides causal estimates that account for uncertainty in the nature of confounding. The proposal relies on specification of multiple Bayesian additive regression trees models, linked together with a common prior distribution that accrues posterior selection probability to covariates on the basis of association with both the exposure and the outcome of interest. A set of extensive simulation studies demonstrates that the proposed method performs well relative to similarly-motivated methodologies in a variety of scenarios. We deploy the method to investigate the causal effect of emissions from coal-fired power plants on ambient air pollution concentrations, where the prospect of confounding due to local and regional meteorological factors introduces uncertainty around the confounding role of a high-dimensional set of measured variables. Ultimately, we show that the proposed method produces more efficient and more consistent results across adjacent years than alternative methods, lending strength to the evidence of the causal relationship between SO2 emissions and ambient particulate pollution.

Bayesian data fusion: Probabilistic sensitivity analysis for unmeasured confounding using informative priors based on secondary data.

Bayesian causal inference offers a principled approach to policy evaluation of proposed interventions on mediators or time-varying exposures. Building on the Bayesian g-formula method introduced by Keil et al., we outline a general approach for the estimation of population-level causal quantities involving dynamic and stochastic treatment regimes, including regimes related to mediation estimands such as natural direct and indirect effects. We further extend this approach to propose a Bayesian data fusion (BDF), an algorithm for performing probabilistic sensitivity analysis when a confounder unmeasured in a primary data set is available in an external data source. When the relevant relationships are causally transportable between the two source populations, BDF corrects confounding bias and supports causal inference and decision-making within the main study population without sharing of the individual-level external data set. We present results from a simulation study comparing BDF to two common frequentist correction methods for unmeasured mediator-outcome confounding bias in the mediation setting. We use these methods to analyze data on the role of stage at cancer diagnosis in contributing to Black-White colorectal cancer survival disparities.

Statistical considerations for the analysis of massively parallel reporter assays data.

Noncoding DNA contains gene regulatory elements that alter gene expression, and the function of these elements can be modified by genetic variation. Massively parallel reporter assays (MPRA) enable high-throughput identification and characterization of functional genetic variants, but the statistical methods to identify allelic effects in MPRA data have not been fully developed. In this study, we demonstrate how the baseline allelic imbalance in MPRA libraries can produce biased results, and we propose a novel, nonparametric, adaptive testing method that is robust to this bias. We compare the performance of this method with other commonly used methods, and we demonstrate that our novel adaptive method controls Type I error in a wide range of scenarios while maintaining excellent power. We have implemented these tests along with routines for simulating MPRA data in the Analysis Toolset for MPRA (@MPRA), an R package for the design and analyses of MPRA experiments. It is publicly available at http://github.com/redaq/atMPRA.

Invited Commentary: The Promise and Pitfalls of Causal Inference With Multivariate Environmental Exposures.

The accompanying article by Keil et al. (Am J Epidemiol. 2021;190(12):2647-2657) deploys Bayesian g-computation to investigate the causal effect of 6 airborne metal exposures linked to power-plant emissions on birth weight. In so doing, it articulates the potential value of framing the analysis of environmental mixtures as an explicit contrast between exposure distributions that might arise in response to a well-defined intervention-here, the decommissioning of coal plants. Framing the mixture analysis as that of an approximate "target trial" is an important approach that deserves incorporation into the already rich literature on the analysis of environmental mixtures. However, its deployment in the power plant example highlights challenges that can arise when the target trial is at odds with the exposure distribution observed in the data, a discordance that seems particularly difficult in studies of environmental mixtures. Bayesian methodology such as model averaging and informative priors can help, but they are ultimately limited for overcoming this salient challenge.

Bipartite Causal Inference with Interference.

Statistical methods to evaluate the effectiveness of interventions are increasingly challenged by the inherent interconnectedness of units. Specifically, a recent flurry of methods research has addressed the problem of interference between observations, which arises when one observational unit's outcome depends not only on its treatment but also the treatment assigned to other units. We introduce the setting of bipartite causal inference with interference, which arises when 1) treatments are defined on observational units that are distinct from those at which outcomes are measured and 2) there is interference between units in the sense that outcomes for some units depend on the treatments assigned to many other units. The focus of this work is to formulate definitions and several possible causal estimands for this setting, highlighting similarities and differences with more commonly considered settings of causal inference with interference. Towards an empirical illustration, an inverse probability of treatment weighted estimator is adapted from existing literature to estimate a subset of simplified, but interesting, estimands. The estimators are deployed to evaluate how interventions to reduce air pollution from 473 power plants in the U.S. causally affect cardiovascular hospitalization among Medicare beneficiaries residing at 18,807 zip code locations.

Four Decades of United States Mobile Source Pollutants: Spatial-Temporal Trends Assessed by Ground-Based Monitors, Air Quality Models, and Satellites.

On-road emissions sources degrade air quality, and these sources have been highly regulated. Epidemiological and environmental justice studies often use road proximity as a proxy for traffic-related air pollution (TRAP) exposure, and other studies employ air quality models or satellite observations. To assess these metrics' abilities to reproduce observed near-road concentration gradients and changes over time, we apply a hierarchical linear regression to ground-based observations, long-term air quality model simulations using Community Multiscale Air Quality (CMAQ), and satellite products. Across 1980-2019, observed TRAP concentrations decreased, and road proximity was positively correlated with TRAP. For all pollutants, concentrations decreased fastest at locations with higher road proximity, resulting in "flatter" concentration fields in recent years. This flattening unfolded at a relatively constant rate for NOx, whereas the flattening of CO concentration fields has slowed. CMAQ largely captures observed spatial-temporal NO2 trends across 2002-2010 but overstates the relationships between CO and elemental carbon fine particulate matter (EC) road proximity. Satellite NOx measures overstate concentration reductions near roads. We show how this perspective provides evidence that California's on-road vehicle regulations led to substantial decreases in NO2, NOx, and EC in California, with other states that adopted California's light-duty automobile standards showing mixed benefits over states that did not adopt these standards.

Adjusting for unmeasured spatial confounding with distance adjusted propensity score matching.

Propensity score matching is a common tool for adjusting for observed confounding in observational studies, but is known to have limitations in the presence of unmeasured confounding. In many settings, researchers are confronted with spatially-indexed data where the relative locations of the observational units may serve as a useful proxy for unmeasured confounding that varies according to a spatial pattern. We develop a new method, termed distance adjusted propensity score matching (DAPSm) that incorporates information on units' spatial proximity into a propensity score matching procedure. We show that DAPSm can adjust for both observed and some forms of unobserved confounding and evaluate its performance relative to several other reasonable alternatives for incorporating spatial information into propensity score adjustment. The method is motivated by and applied to a comparative effectiveness investigation of power plant emission reduction technologies designed to reduce population exposure to ambient ozone pollution. Ultimately, DAPSm provides a framework for augmenting a "standard" propensity score analysis with information on spatial proximity and provides a transparent and principled way to assess the relative trade-offs of prioritizing observed confounding adjustment versus spatial proximity adjustment.

Uncertainty in the design stage of two-stage Bayesian propensity score analysis.

The two-stage process of propensity score analysis (PSA) includes a design stage where propensity scores (PSs) are estimated and implemented to approximate a randomized experiment and an analysis stage where treatment effects are estimated conditional on the design. This article considers how uncertainty associated with the design stage impacts estimation of causal effects in the analysis stage. Such design uncertainty can derive from the fact that the PS itself is an estimated quantity, but also from other features of the design stage tied to choice of PS implementation. This article offers a procedure for obtaining the posterior distribution of causal effects after marginalizing over a distribution of design-stage outputs, lending a degree of formality to Bayesian methods for PSA that have gained attention in recent literature. Formulation of a probability distribution for the design-stage output depends on how the PS is implemented in the design stage, and propagation of uncertainty into causal estimates depends on how the treatment effect is estimated in the analysis stage. We explore these differences within a sample of commonly used PS implementations (quantile stratification, nearest-neighbor matching, caliper matching, inverse probability of treatment weighting, and doubly robust estimation) and investigate in a simulation study the impact of statistician choice in PS model and implementation on the degree of between- and within-design variability in the estimated treatment effect. The methods are then deployed in an investigation of the association between levels of fine particulate air pollution and elevated exposure to emissions from coal-fired power plants.

Causal inference with interfering units for cluster and population level treatment allocation programs.

Interference arises when an individual's potential outcome depends on the individual treatment level, but also on the treatment level of others. A common assumption in the causal inference literature in the presence of interference is partial interference, implying that the population can be partitioned in clusters of individuals whose potential outcomes only depend on the treatment of units within the same cluster. Previous literature has defined average potential outcomes under counterfactual scenarios where treatments are randomly allocated to units within a cluster. However, within clusters there may be units that are more or less likely to receive treatment based on covariates or neighbors' treatment. We define new estimands that describe average potential outcomes for realistic counterfactual treatment allocation programs, extending existing estimands to take into consideration the units' covariates and dependence between units' treatment assignment. We further propose entirely new estimands for population-level interventions over the collection of clusters, which correspond in the motivating setting to regulations at the federal (vs. cluster or regional) level. We discuss these estimands, propose unbiased estimators and derive asymptotic results as the number of clusters grows. For a small number of observed clusters, a bootstrap approach for confidence intervals is proposed. Finally, we estimate effects in a comparative effectiveness study of power plant emission reduction technologies on ambient ozone pollution.

Approaches to treatment effect heterogeneity in the presence of confounding.

The literature on causal effect estimation tends to focus on the population mean estimand, which is less informative as medical treatments are becoming more personalized and there is increasing awareness that subpopulations of individuals may experience a group-specific effect that differs from the population average. In fact, it is possible that there is underlying systematic effect heterogeneity that is obscured by focusing on the population mean estimand. In this context, understanding which covariates contribute to this treatment effect heterogeneity (TEH) and how these covariates determine the differential treatment effect (TE) is an important consideration. Towards such an understanding, this paper briefly reviews three approaches used in making causal inferences and conducts a simulation study to compare these approaches according to their performance in an exploratory evaluation of TEH when the heterogeneous subgroups are not known a priori. Performance metrics include the detection of any heterogeneity, the identification and characterization of heterogeneous subgroups, and unconfounded estimation of the TE within subgroups. The methods are then deployed in a comparative effectiveness evaluation of drug-eluting versus bare-metal stents among 54 099 Medicare beneficiaries in the continental United States admitted to a hospital with acute myocardial infarction in 2008.

A global perspective on coal-fired power plants and burden of lung cancer.

BACKGROUND: Exposure to ambient particulate matter generated from coal-fired power plants induces long-term health consequences. However, epidemiologic studies have not yet focused on attributing these health burdens specifically to energy consumption, impeding targeted intervention policies. We hypothesize that the generating capacity of coal-fired power plants may be associated with lung cancer incidence at the national level. METHODS: Age- and sex-adjusted lung cancer incidence from every country with electrical plants using coal as primary energy supply were followed from 2000 to 2016. We applied a Poisson regression longitudinal model, fitted using generalized estimating equations, to estimate the association between lung cancer incidence and per capita coal capacity, adjusting for various behavioral and demographic determinants and lag periods. RESULTS: The average coal capacity increased by 1.43 times from 16.01 gigawatts (GW) (2000~2004) to 22.82 GW (2010~2016). With 1 kW (KW) increase of coal capacity per person in a country, the relative risk of lung cancer increases by a factor of 59% (95% CI = 7.0%~ 135%) among males and 85% (95% CI = 22%~ 182%) among females. Based on the model, we estimate a total of 1.37 (range = 1.34 ~ 1.40) million standardized incident cases from lung cancer will be associated with coal-fired power plants in 2025. CONCLUSIONS: These analyses suggest an association between lung cancer incidence and increased reliance on coal for energy generation. Such data may be helpful in addressing a key policy question about the externality costs and estimates of the global disease burden from preventable lung cancer attributable to coal-fired power plants at the national level.

Characterizing population exposure to coal emissions sources in the United States using the HyADS model.

In anticipation of the expanding appreciation for air quality models in health outcomes studies, we develop and evaluate a reduced-complexity model for pollution transport that intentionally sacrifices some of the sophistication of full-scale chemical transport models in order to support applicability to a wider range of health studies. Specifically, we introduce the HYSPLIT average dispersion model, HyADS, which combines the HYSPLIT trajectory dispersion model with modern advances in parallel computing to estimate ZIP code level exposure to emissions from individual coal-powered electricity generating units in the United States. Importantly, the method is not designed to reproduce ambient concentrations of any particular air pollutant; rather, the primary goal is to characterize each ZIP code's exposure to these coal power plants specifically. We show adequate performance towards this goal against observed annual average air pollutant concentrations (nationwide Pearson correlations of 0.88 and 0.73 with SO 4 2 - and PM2.5, respectively) and coal-combustion impacts simulated with a full-scale chemical transport model and adjusted to observations using a hybrid direct sensitivities approach (correlation of 0.90). We proceed to provide multiple examples of HyADS's single-source applicability, including to show that 22% of the population-weighted coal exposure comes from 30 coal-powered electricity generating units.

Are per capita carbon emissions predictable across countries?

BACKGROUND: China and other developing countries in Asia follow similar economic growth patterns described by the flying geese (FG) model, which explains the "catching-up" process of industrialization in latecomer economies. Japan, newly industrialized economies, and China have followed this path, with similar economic development trajectories. Based on the FG model, we postulated a "flying S" hypothesis stating that if a country is located within an FG region and its energy matrix is relatively constant, its per capita CO2 emission curve will mirror that of "leading geese" countries in the same FG group. METHOD: Historical CO2 emissions data were obtained from literature review and national reports and were calculated using bottom-up methods. A sigmoid-shaped, non-linear mixed effect model was applied to examine ex post data with 1000 simulated predictions to construct 95% empirical bands from these fits. By multiplying by estimated population, we predicted total emissions of selected FG countries. RESULTS: Per capita CO2 emissions from the same FG group mirror each other, especially among second and third industrial sectors. We estimated an annual 18,252.24 million tons of CO2 emissions (MtCO2) (95% CI = 9458.88-23,972.88) in China and 8281.76 MtCO2 (95% CI = 2765.68-14,959.12) in India in 2030. CONCLUSION: This study bridges the macroeconomic FG paradigm to study climate change and proposes a "flying S" hypothesis to predict greenhouse gas emissions in East Asia. By applying our theory to empirical data, we provide an alternative framework to predict CO2 emissions in 2030 and beyond.

Quality of Care at Hospitals Identified as Outliers in Publicly Reported Mortality Statistics for Percutaneous Coronary Intervention.

BACKGROUND: Public reporting of percutaneous coronary intervention (PCI) outcomes may create disincentives for physicians to provide care for critically ill patients, particularly at institutions with worse clinical outcomes. We thus sought to evaluate the procedural management and in-hospital outcomes of patients treated for acute myocardial infarction before and after a hospital had been publicly identified as a negative outlier. METHODS: Using state reports, we identified hospitals that were recognized as negative PCI outliers in 2 states (Massachusetts and New York) from 2002 to 2012. State hospitalization files were used to identify all patients with an acute myocardial infarction within these states. Procedural management and in-hospital outcomes were compared among patients treated at outlier hospitals before and after public report of outlier status. Patients at nonoutlier institutions were used to control for temporal trends. RESULTS: Among 86 hospitals, 31 were reported as outliers for excess mortality. Outlier facilities were larger, treating more patients with acute myocardial infarction and performing more PCIs than nonoutlier hospitals (P<0.05 for each). Among 507 672 patients with acute myocardial infarction hospitalized at these institutions, 108 428 (21%) were treated at an outlier hospital after public report. The likelihood of PCI at outlier (relative risk [RR], 1.13; 95% confidence interval [CI], 1.12-1.15) and nonoutlier institutions (RR, 1.13; 95% CI, 1.11-1.14) increased in a similar fashion (interaction P=0.50) after public report of outlier status. The likelihood of in-hospital mortality decreased at outlier institutions (RR, 0.83; 95% CI, 0.81-0.85) after public report, and to a lesser degree at nonoutlier institutions (RR, 0.90; 95% CI, 0.87-0.92; interaction P<0.001). Among patients that underwent PCI, in-hospital mortality decreased at outlier institutions after public recognition of outlier status in comparison with prior (RR, 0.72; 9% CI, 0.66-0.79), a decline that exceeded the reduction at nonoutlier institutions (RR, 0.87; 95% CI, 0.80-0.96; interaction P<0.001). CONCLUSIONS: Large hospitals with higher clinical volume are more likely to be designated as negative outliers. The rates of percutaneous revascularization increased similarly at outlier and nonoutlier institutions after report of outlier status. After outlier designation, in-hospital mortality declined at outlier institutions to a greater extent than was observed at nonoutlier facilities.

Guided Bayesian imputation to adjust for confounding when combining heterogeneous data sources in comparative effectiveness research.

In comparative effectiveness research, we are often interested in the estimation of an average causal effect from large observational data (the main study). Often this data does not measure all the necessary confounders. In many occasions, an extensive set of additional covariates is measured for a smaller and non-representative population (the validation study). In this setting, standard approaches for missing data imputation might not be adequate due to the large number of missing covariates in the main data relative to the smaller sample size of the validation data. We propose a Bayesian approach to estimate the average causal effect in the main study that borrows information from the validation study to improve confounding adjustment. Our approach combines ideas of Bayesian model averaging, confounder selection, and missing data imputation into a single framework. It allows for different treatment effects in the main study and in the validation study, and propagates the uncertainty due to the missing data imputation and confounder selection when estimating the average causal effect (ACE) in the main study. We compare our method to several existing approaches via simulation. We apply our method to a study examining the effect of surgical resection on survival among 10 396 Medicare beneficiaries with a brain tumor when additional covariate information is available on 2220 patients in SEER-Medicare. We find that the estimated ACE decreases by 30% when incorporating additional information from SEER-Medicare.