Estimated Population-Level Impact of Pneumococcal Conjugate Vaccines Against All-Cause Pneumonia Mortality Among Unvaccinated in 5 Latin American Countries.

BACKGROUND: Pneumococcal conjugate vaccines (PCVs) provide strong direct protection in children, while limited data are available on their indirect effect on mortality among older age groups. This multicountry study aimed to assess the population-level impact of pediatric PCVs on all-cause pneumonia mortality among children ≥5 years of age, and invasive pneumococcal disease (IPD) cases in Chile. METHODS: Demographic and mortality data from Argentina, Brazil, Chile, Colombia, and Mexico were collected considering the ≥ 5-year-old population, from 2000 to 2019, with 1 795 789 deaths due to all-cause pneumonia. IPD cases in Chile were also evaluated. Time series models were employed to evaluate changes in all-cause pneumonia deaths during the postvaccination period, with other causes of death used as synthetic controls for unrelated temporal trends. RESULTS: No significant change in death rates due to all-cause pneumonia was detected following PCV introduction among most age groups and countries. The proportion of IPD cases caused by vaccine serotypes decreased from 29% (2012) to 6% (2022) among people aged ≥65 years in Chile. DISCUSSION: While an effect of PCV against pneumonia deaths (a broad clinical definition that may not be specific enough to measure indirect effects) was not detected, evidence of indirect PCV impact was observed among vaccine-type-specific IPD cases.

Phylogeographic Analysis of Mycobacterium kansasii Isolates from Patients with M. kansasii Lung Disease in Industrialized City, Taiwan.

Little is known about environmental transmission of Mycobacterium kansasii. We retrospectively investigated potential environmental acquisition, primarily water sources, of M. kansasii among 216 patients with pulmonary disease from an industrial city in Taiwan during 2015-2017. We analyzed sputum mycobacterial cultures using whole-genome sequencing and used hierarchical Bayesian spatial network methods to evaluate risk factors for genetic relatedness of M. kansasii strains. The mean age of participants was 67 years; 24.1% had previously had tuberculosis. We found that persons from districts served by 2 water purification plants were at higher risk of being infected with genetically related M. kansasii isolates. The adjusted odds ratios were 1.81 (1.25-2.60) for the Weng Park plant and 1.39 (1.12-1.71) for the Fongshan plant. Those findings unveiled the association between water purification plants and M. kansasii pulmonary disease, highlighting the need for further environmental investigations to evaluate the risk for M. kansasii transmission.

Exposure range matters: considering non-linear associations in the meta-analysis of environmental pollutant exposure using examples of per- and polyfluoroalkyl substances and birth outcomes.

Meta-analysis is a powerful analytic method for summarizing effect estimates across studies. However, conventional meta-analysis often assumes a linear exposure-outcome relationship and does not account for variability over the exposure ranges. In this work, we first used simulation techniques to illustrate that the linear-based meta-analytical approach may result in oversimplistic effect estimation based on three plausible non-linear exposure-outcome curves (S-shape, inverted U-shape, and M-shape). We showed that subgroup meta-analysis that stratifies on exposure levels can investigate non-linearity and identify the consistency of effect magnitudes in these simulated examples. Next, we examined the heterogeneity of effect estimates across exposure ranges in two published linear-based meta-analyses of prenatal exposure to per- and polyfluoroalkyl substances (PFAS) on changes in mean birth weight or risk of preterm birth. The re-analysis found some varying effect sizes and potential heterogeneity when restricting to different PFAS exposure ranges, but findings were sensitive to the cut-off choices used to rank the exposure levels. Finally, we discussed methodological challenges and recommendations for detecting and interpreting potential non-linear associations in meta-analysis. Using meta-analysis without accounting for exposure range could contribute to literature inconsistency for exposure-induced health effects and impede evidence-based policymaking. Therefore, investigating result heterogeneity by exposure range is recommended.

Incorporating Efficacy Data from Initial Trials Into Subsequent Evaluations: Application to Vaccines Against Respiratory Syncytial Virus.

BACKGROUND: When a randomized controlled trial fails to demonstrate statistically significant efficacy against the primary endpoint, a potentially costly new trial would need to be conducted to receive licensure. Incorporating data from previous trials might allow for more efficient follow-up trials to demonstrate efficacy, speeding the availability of effective vaccines. METHODS: Based on the outcomes from a failed trial of a maternal vaccine against respiratory syncytial virus (RSV), we simulated data for a new Bayesian group-sequential trial. We analyzed the data either ignoring data from the previous trial (i.e., weakly informative prior distributions) or using prior distributions incorporating the historical data into the analysis. We evaluated scenarios where efficacy in the new trial was the same, greater than, or less than that in the original trial. For each scenario, we evaluated the statistical power and type I error rate for estimating the vaccine effect following interim analyses. RESULTS: When we used a stringent threshold to control the type I error rate, analyses incorporating historical data had a small advantage over trials that did not. If control of type I error is less important (e.g., in a postlicensure evaluation), the incorporation of historical data can provide a substantial boost in efficiency. CONCLUSIONS: Due to the need to control the type I error rate in trials used to license a vaccine, incorporating historical data provides little additional benefit in terms of stopping the trial early. However, these statistical approaches could be promising in evaluations that use real-world evidence following licensure.

Disparities in Colorectal Cancer Screening Before and After the Onset of the COVID Pandemic.

BACKGROUND: Colorectal cancer (CRC) screening is underutilized among those with lower socioeconomic status and in racial and ethnic minoritized populations who have been disproportionately impacted by COVID. OBJECTIVE: To compare disparities in CRC screening before and after the onset of the COVID pandemic among privately insured individuals. DESIGN: Retrospective cohort study using deidentified claims data from the USA between January 1, 2017, and December 31, 2022. PARTICIPANTS: Blue Cross Blue Shield beneficiaries aged 50-75 years with average risk of CRC. MAIN MEASURE(S): Mean screening use was compared by demographic and area-level socioeconomic factors between the periods preceding (January 1, 2017 to February 28, 2020) and following (July 1, 2020 to December 31, 2022) the onset of the COVID pandemic. Difference-in-differences analysis was used to evaluate changes in screening differences. RESULTS: Our study included 21,724,223 beneficiaries. Compared to males, females had higher screening in both periods (p < 0.05), and this sex difference in screening increased 1.63% (95% confidence interval [CI]: 1.32%, 1.94%) following the onset of the pandemic. Compared to residents in areas with high socioeconomic status (SES), low SES area residents had lower screening (p < 0.001) during both periods. Furthermore, this difference grew 4.32% (95% CI, 3.76%, 4.88%) during the post-onset period. Metropolitan area residents had higher screening than non-metropolitan area residents during both periods (p < 0.001); however, this difference decreased 0.77% (95% CI, 0.34%, 1.20%) during the post-onset period. Among beneficiaries with high risk of CRC, the difference in screening based on social deprivation index and metropolitan area status increased 6.99% (95% CI, 5.77%, 8.20%) and 1.82% (95% CI, 0.88%, 2.74%), respectively. CONCLUSIONS: Among privately insured individuals, CRC screening after the COVID pandemic recovered unevenly based on sex, area-level socioeconomic measures, and metropolitan area status, with pre-pandemic disparities persisting and even worsening for some of the factors.

A scalar-on-quantile-function approach for estimating short-term health effects of environmental exposures.

Environmental epidemiologic studies routinely utilize aggregate health outcomes to estimate effects of short-term (eg, daily) exposures that are available at increasingly fine spatial resolutions. However, areal averages are typically used to derive population-level exposure, which cannot capture the spatial variation and individual heterogeneity in exposures that may occur within the spatial and temporal unit of interest (eg, within a day or ZIP code). We propose a general modeling approach to incorporate within-unit exposure heterogeneity in health analyses via exposure quantile functions. Furthermore, by viewing the exposure quantile function as a functional covariate, our approach provides additional flexibility in characterizing associations at different quantile levels. We apply the proposed approach to an analysis of air pollution and emergency department (ED) visits in Atlanta over 4 years. The analysis utilizes daily ZIP code-level distributions of personal exposures to 4 traffic-related ambient air pollutants simulated from the Stochastic Human Exposure and Dose Simulator. Our analyses find that effects of carbon monoxide on respiratory and cardiovascular disease ED visits are more pronounced with changes in lower quantiles of the population's exposure. Software for implement is provided in the R package nbRegQF.

A scaled kernel density estimation prior for dynamic borrowing of historical information with application to clinical trial design.

Incorporating historical data into a current data analysis can improve estimation of parameters shared across both datasets and increase the power to detect associations of interest while reducing the time and cost of new data collection. Several methods for prior distribution elicitation have been introduced to allow for the data-driven borrowing of historical information within a Bayesian analysis of the current data. We propose scaled Gaussian kernel density estimation (SGKDE) prior distributions as potentially more flexible alternatives. SGKDE priors directly use posterior samples collected from a historical data analysis to approximate probability density functions, whose variances depend on the degree of similarity between the historical and current datasets, which are used as prior distributions in the current data analysis. We compare the performances of the SGKDE priors with some existing approaches using a simulation study. Data from a recently completed phase III clinical trial of a maternal vaccine for respiratory syncytial virus are used to further explore the properties of SGKDE priors when designing a new clinical trial while incorporating historical data. Overall, both studies suggest that the new approach results in improved parameter estimation and power in the current data analysis compared to the considered existing methods.

Hierarchical Bayesian modeling of heterogeneous outcome variance in cluster randomized trials.

BACKGROUND: Heterogeneous outcome correlations across treatment arms and clusters have been increasingly acknowledged in cluster randomized trials with binary endpoints, where analytical methods have been developed to study such heterogeneity. However, cluster-specific outcome variances and correlations have yet to be studied for cluster randomized trials with continuous outcomes. METHODS: This article proposes models fitted in the Bayesian setting with hierarchical variance structure to quantify heterogeneous variances across clusters and explain it with cluster-level covariates when the outcome is continuous. The models can also be extended to analyzing heterogeneous variances in individually randomized group treatment trials, with arm-specific cluster-level covariates, or in partially nested designs. Simulation studies are carried out to validate the performance of the newly introduced models across different settings. RESULTS: Simulations showed that overall the newly introduced models have good performance, reporting low bias and approximately 95% coverage for the intraclass correlation coefficients and regression parameters in the variance model. When variances are heterogeneous, our proposed models had improved model fit over models with homogeneous variances. When used to analyze data from the Kerala Diabetes Prevention Program study, our models identified heterogeneous variances and intraclass correlation coefficients across clusters and examined cluster-level characteristics associated with such heterogeneity. CONCLUSION: We proposed new hierarchical Bayesian variance models to accommodate cluster-specific variances in cluster randomized trials. The newly developed methods inform the understanding of how an intervention strategy is implemented and disseminated differently across clusters and can help improve future trial design.

Mapping partner drug resistance to guide antimalarial combination therapy policies in sub-Saharan Africa.

Resistance to artemisinin-based combination therapies (ACTs) threatens the global control of Plasmodium falciparum malaria. ACTs combine artemisinin-derived compounds with partner drugs to enable multiple mechanisms of clearance. Although ACTs remain widely effective in sub-Saharan Africa, long-standing circulation of parasite alleles associated with reduced partner drug susceptibility may contribute to the development of clinical resistance. We fitted a hierarchical Bayesian spatial model to data from over 500 molecular surveys to predict the prevalence and frequency of four key markers in transporter genes (pfcrt 76T and pfmdr1 86Y, 184F, and 1246Y) in first-level administrative divisions in sub-Saharan Africa from the uptake of ACTs (2004 to 2009) to their widespread usage (2010 to 2018). Our models estimated that the pfcrt 76T mutation decreased in prevalence in 90% of regions; the pfmdr1 N86 and D1246 wild-type genotypes increased in prevalence in 96% and 82% of regions, respectively; and there was no significant directional selection at the pfmdr1 Y184F locus. Rainfall seasonality was the strongest predictor of the prevalence of wild-type genotypes, with other covariates, including first-line drug policy and transmission intensity more weakly associated. We lastly identified regions of high priority for enhanced surveillance that could signify decreased susceptibility to the local first-line ACT. Our results can be used to infer the degree of molecular resistance and magnitude of wild-type reversion in regions without survey data to inform therapeutic policy decisions.

Associations Between Long-Term Air Pollutant Exposure and 30-Day All-Cause Hospital Readmissions in US Patients With Stroke.

BACKGROUND: Long-term exposure to air pollutants is associated with increased stroke incidence, morbidity, and mortality; however, research on the association of pollutant exposure with poststroke hospital readmissions is lacking. METHODS: We assessed associations between average annual carbon monoxide (CO), nitrogen dioxide (NO2), ozone (O3), particulate matter 2.5, and sulfur dioxide (SO2) exposure and 30-day all-cause hospital readmission in US fee-for-service Medicare beneficiaries age ≥65 years hospitalized for ischemic stroke in 2014 to 2015. We fit Cox models to assess 30-day readmissions as a function of these pollutants, adjusted for patient and hospital characteristics and ambient temperature. Analyses were then stratified by treating hospital performance on the Centers for Medicare and Medicaid Services risk-standardized 30-day poststroke all-cause readmission measure to determine if the results were independent of performance: low (Centers for Medicare and Medicaid Services rate for hospital <25th percentile of national rate), high (>75th percentile), and intermediate (all others). RESULTS: Of 448 148 patients with stroke, 12.5% were readmitted within 30 days. Except for tropospheric NO2 (no national standard), average 2-year CO, O3, particulate matter 2.5, and SO2 values were below national limits. Each one SD increase in average annual CO, NO2, particulate matter 2.5, and SO2 exposure was associated with an adjusted 1.1% (95% CI, 0.4-1.9%), 3.6% (95% CI, 2.9%-4.4%), 1.2% (95% CI, 0.2%-2.3%), and 2.0% (95% CI, 1.1%-3.0%) increased risk of 30-day readmission, respectively, and O3 with a 0.7% (95% CI, 0.0%-1.5%) decrease. Associations between long-term air pollutant exposure and increased readmissions persisted across hospital performance categories. CONCLUSIONS: Long-term air pollutant exposure below national limits was associated with increased 30-day readmissions after stroke, regardless of hospital performance category. Whether air quality improvements lead to reductions in poststroke readmissions requires further research.

Patterns of Infectious Disease Associated With Injection Drug Use in Massachusetts.

BACKGROUND: Since 2014, multiple outbreaks of human immunodeficiency virus (HIV) among people who inject drugs have occurred across the United States along with hepatitis C virus (HCV), skin and soft tissue infections (SSTIs), and infective endocarditis (IE), creating a converging public health crisis. METHODS: We analyzed the temporal patterns of infectious disease and overdose using a hierarchical Bayesian distributed lag logistic regression model examining the probability that a given geographic area experienced at least 1 HIV case in a given month as a function of the counts/rates of overdose, HCV, SSTI, and IE and associated medical procedures at different lagged time periods. RESULTS: Current-month HIV is associated with increasing HCV cases, abscess incision and drainage, and SSTI cases, in distinct temporal patterns. For example, 1 additional HCV case occurring 5 and 7 months previously is associated with a 4% increase in the odds of observing at least 1 current-month HIV case in a given locale (odds ratios, 1.04 [90% credible interval {CrI}: 1.01-1.10] and 1.04 [90% CrI: 1.00-1.09]). No such associations were observed for echocardiograms, IE, or overdose. CONCLUSIONS: Lagged associations in other infections preceding rises in current-month HIV counts cannot be described as predictive of HIV outbreaks but may point toward newly discovered epidemics of injection drug use and associated clinical sequalae, prompting clinicians to screen patients more carefully for substance use disorder and associated infections.

A Bayesian framework for incorporating exposure uncertainty into health analyses with application to air pollution and stillbirth.

Studies of the relationships between environmental exposures and adverse health outcomes often rely on a two-stage statistical modeling approach, where exposure is modeled/predicted in the first stage and used as input to a separately fit health outcome analysis in the second stage. Uncertainty in these predictions is frequently ignored, or accounted for in an overly simplistic manner when estimating the associations of interest. Working in the Bayesian setting, we propose a flexible kernel density estimation (KDE) approach for fully utilizing posterior output from the first stage modeling/prediction to make accurate inference on the association between exposure and health in the second stage, derive the full conditional distributions needed for efficient model fitting, detail its connections with existing approaches, and compare its performance through simulation. Our KDE approach is shown to generally have improved performance across several settings and model comparison metrics. Using competing approaches, we investigate the association between lagged daily ambient fine particulate matter levels and stillbirth counts in New Jersey (2011-2015), observing an increase in risk with elevated exposure 3 days prior to delivery. The newly developed methods are available in the R package KDExp.

Confounding by Conception Seasonality in Studies of Temperature and Preterm Birth: A Simulation Study.

BACKGROUND: Seasonal patterns of conception may confound acute associations between birth outcomes and seasonally varying exposures. We aim to evaluate four epidemiologic designs (time-stratified case-crossover, time-series, pair-matched case-control, and time-to-event) commonly used to study acute associations between ambient temperature and preterm births. METHODS: We conducted simulations assuming no effect of temperature on preterm birth. We generated pseudo-birth data from the observed seasonal patterns of birth in the United States and analyzed them in relation to observed temperatures using design-specific seasonality adjustments. RESULTS: Using the case-crossover approach (time-stratified by calendar month), we observed a bias (among 1,000 replicates) = 0.016 (Monte-Carlo standard error 95% CI: 0.015-0.018) in the regression coefficient for every 10°C increase in mean temperature in the warm season (May-September). Unbiased estimates obtained using the time-series approach required accounting for both the pregnancies-at-risk and their weighted probability of birth. Notably, adding the daily weighted probability of birth from the time-series models to the case-crossover models corrected the bias in the case-crossover approach. In the pair-matched case-control design, where the exposure period was matched on gestational window, we observed no bias. The time-to-event approach was also unbiased but was more computationally intensive than others. CONCLUSIONS: Most designs can be implemented in a way that yields estimates unbiased by conception seasonality. The time-stratified case-crossover design exhibited a small positive bias, which could contribute to, but not fully explain, previously reported associations.

Reconstructing the course of the COVID-19 epidemic over 2020 for US states and counties: Results of a Bayesian evidence synthesis model.

Reported COVID-19 cases and deaths provide a delayed and incomplete picture of SARS-CoV-2 infections in the United States (US). Accurate estimates of both the timing and magnitude of infections are needed to characterize viral transmission dynamics and better understand COVID-19 disease burden. We estimated time trends in SARS-CoV-2 transmission and other COVID-19 outcomes for every county in the US, from the first reported COVID-19 case in January 13, 2020 through January 1, 2021. To do so we employed a Bayesian modeling approach that explicitly accounts for reporting delays and variation in case ascertainment, and generates daily estimates of incident SARS-CoV-2 infections on the basis of reported COVID-19 cases and deaths. The model is freely available as the covidestim R package. Nationally, we estimated there had been 49 million symptomatic COVID-19 cases and 404,214 COVID-19 deaths by the end of 2020, and that 28% of the US population had been infected. There was county-level variability in the timing and magnitude of incidence, with local epidemiological trends differing substantially from state or regional averages, leading to large differences in the estimated proportion of the population infected by the end of 2020. Our estimates of true COVID-19 related deaths are consistent with independent estimates of excess mortality, and our estimated trends in cumulative incidence of SARS-CoV-2 infection are consistent with trends in seroprevalence estimates from available antibody testing studies. Reconstructing the underlying incidence of SARS-CoV-2 infections across US counties allows for a more granular understanding of disease trends and the potential impact of epidemiological drivers.

Spatial modeling of Mycobacterium tuberculosis transmission with dyadic genetic relatedness data.

Understanding factors that contribute to the increased likelihood of pathogen transmission between two individuals is important for infection control. However, analyzing measures of pathogen relatedness to estimate these associations is complicated due to correlation arising from the presence of the same individual across multiple dyadic outcomes, potential spatial correlation caused by unmeasured transmission dynamics, and the distinctive distributional characteristics of some of the outcomes. We develop two novel hierarchical Bayesian spatial methods for analyzing dyadic pathogen genetic relatedness data, in the form of patristic distances and transmission probabilities, that simultaneously address each of these complications. Using individual-level spatially correlated random effect parameters, we account for multiple sources of correlation between the outcomes as well as other important features of their distribution. Through simulation, we show the limitations of existing approaches in terms of estimating key associations of interest, and the ability of the new methodology to correct for these issues across datasets with different levels of correlation. All methods are applied to Mycobacterium tuberculosis data from the Republic of Moldova, where we identify previously unknown factors associated with disease transmission and, through analysis of the random effect parameters, key individuals, and areas with increased transmission activity. Model comparisons show the importance of the new methodology in this setting. The methods are implemented in the R package GenePair.

Investigation of Sources of Fluorinated Compounds in Private Water Supplies in an Oil and Gas-Producing Region of Northern West Virginia.

Per- and polyfluoroalkyl substances (PFASs) are a class of toxic organic compounds that have been widely used in consumer applications and industrial activities, including oil and gas production. We measured PFAS concentrations in 45 private wells and 8 surface water sources in the oil and gas-producing Doddridge, Marshall, Ritchie, Tyler, and Wetzel Counties of northern West Virginia and investigated relationships between potential PFAS sources and drinking water receptors. All surface water samples and 60% of the water wells sampled contained quantifiable levels of at least one targeted PFAS compound, and four wells (8%) had concentrations above the proposed maximum contaminant level (MCL) for perfluorooctanoic acid (PFOA). Individual concentrations of PFOA and perfluorobutanesulfonic acid exceeded those measured in finished public water supplies. Total targeted PFAS concentrations ranged from nondetect to 36.8 ng/L, with surface water concentrations averaging 4-fold greater than groundwater. Semiquantitative, nontargeted analysis showed concentrations of emergent PFAS that were potentially higher than targeted PFAS. Results from a multivariate latent variable hierarchical Bayesian model were combined with insights from analyses of groundwater chemistry, topographic characteristics, and proximity to potential PFAS point sources to elucidate predictors of PFAS concentrations in private wells. Model results reveal (i) an increased vulnerability to contamination in upland recharge zones, (ii) geochemical controls on PFAS transport likely driven by adsorption, and (iii) possible influence from nearby point sources.

Using multi-sourced big data to correlate sleep deprivation and road traffic noise: A US county-level ecological study.

BACKGROUND: Road traffic noise is a serious public health problem globally as it has adverse psychological and physiologic effects (i.e., sleep). Since previous studies mainly focused on individual levels, we aim to examine associations between road traffic noise and sleep deprivation on a large scale; namely, the US at county level. METHODS: Information from a large-scale sleep survey and national traffic noise map, both obtained from government's open data, were utilized and processed with Geographic Information System (GIS) techniques. To examine the associations between traffic noise and sleep deprivation, we used a hierarchical Bayesian spatial modelling framework to simultaneously adjust for multiple socioeconomic factors while accounting for spatial correlation. FINDINGS: With 62.90% of people not getting enough sleep, a 10 dBA increase in average sound-pressure level (SPL) or Ls10 (SPL of the relatively noisy area) in a county, was associated with a 49% (OR: 1.49; 95% CrIs:1.19-1.86) or 8% (1.08; 1.00-1.16) increase in the odds of a person in a particular county not getting enough sleep. No significant association was observed for Ls90 (SPL of the relatively quiet area). A 10% increase in noise exposure area or population ratio was associated with a 3% (1.03; 1.01-1.06) or 4% (1.04; 1.02-1.06) increase in the odds of a person within a county not getting enough sleep. INTERPRETATION: Traffic noise can contribute to variations in sleep deprivation among counties. This study suggests that policymakers could set up different noise-management strategies for relatively quiet and noisy areas and incorporate geospatial noise indicators, such as exposure population or area ratio. Furthermore, urban planners should consider urban sprawl patterns differently in terms of noise-induced sleep problems.

Phylogeography and transmission of M. tuberculosis in Moldova: A prospective genomic analysis.

BACKGROUND: The incidence of multidrug-resistant tuberculosis (MDR-TB) remains critically high in countries of the former Soviet Union, where >20% of new cases and >50% of previously treated cases have resistance to rifampin and isoniazid. Transmission of resistant strains, as opposed to resistance selected through inadequate treatment of drug-susceptible tuberculosis (TB), is the main driver of incident MDR-TB in these countries. METHODS AND FINDINGS: We conducted a prospective, genomic analysis of all culture-positive TB cases diagnosed in 2018 and 2019 in the Republic of Moldova. We used phylogenetic methods to identify putative transmission clusters; spatial and demographic data were analyzed to further describe local transmission of Mycobacterium tuberculosis. Of 2,236 participants, 779 (36%) had MDR-TB, of whom 386 (50%) had never been treated previously for TB. Moreover, 92% of multidrug-resistant M. tuberculosis strains belonged to putative transmission clusters. Phylogenetic reconstruction identified 3 large clades that were comprised nearly uniformly of MDR-TB: 2 of these clades were of Beijing lineage, and 1 of Ural lineage, and each had additional distinct clade-specific second-line drug resistance mutations and geographic distributions. Spatial and temporal proximity between pairs of cases within a cluster was associated with greater genomic similarity. Our study lasted for only 2 years, a relatively short duration compared with the natural history of TB, and, thus, the ability to infer the full extent of transmission is limited. CONCLUSIONS: The MDR-TB epidemic in Moldova is associated with the local transmission of multiple M. tuberculosis strains, including distinct clades of highly drug-resistant M. tuberculosis with varying geographic distributions and drug resistance profiles. This study demonstrates the role of comprehensive genomic surveillance for understanding the transmission of M. tuberculosis and highlights the urgency of interventions to interrupt transmission of highly drug-resistant M. tuberculosis.

Where Is Air Quality Improving, and Who Benefits? A Study of PM2.5 and Ozone Over 15 Years.

In the United States, concentrations of criteria air pollutants have declined in recent decades. Questions remain regarding whether improvements in air quality are equitably distributed across subpopulations. We assessed spatial variability and temporal trends in concentrations of particulate matter with an aerodynamic diameter ≤2.5 µm (PM2.5) and ozone (O3) across North Carolina from 2002-2016, and associations with community characteristics. Estimated daily PM2.5 and O3 concentrations at 2010 Census tracts were obtained from the Fused Air Quality Surface Using Downscaling archive and averaged to create tract-level annual PM2.5 and O3 estimates. We calculated tract-level measures of: racial isolation of non-Hispanic Black individuals, educational isolation of non-college educated individuals, the neighborhood deprivation index (NDI), and percentage of the population in urban areas. We fitted hierarchical Bayesian space-time models to estimate baseline concentrations of and time trends in PM2.5 and O3 for each tract, accounting for spatial between-tract correlation. Concentrations of PM2.5 and O3 declined by 6.4 µg/m3 and 13.5 ppb, respectively. Tracts with lower educational isolation and higher urbanicity had higher PM2.5 and more pronounced declines in PM2.5. Racial isolation was associated with higher PM2.5 but not with the rate of decline in PM2.5. Despite declines in pollutant concentrations, over time, disparities in exposure increased for racially and educationally isolated communities.

Geographic Variation in the Utilization of and Mortality After Emergency General Surgery Operations in the Northeastern and Southeastern United States.

OBJECTIVE: To define geographic variations in emergency general surgery (EGS) care, we sought to determine how much variability exists in the rates of EGS operations and subsequent mortality in the Northeastern and Southeastern United States (US). SUMMARY BACKGROUND DATA: While some geographic variations in healthcare are normal, unwarranted variations raise questions about the quality, appropriateness, and cost-effectiveness of care in different areas. METHODS: Patients ≥18 years who underwent 1 of 10 common EGS operations were identified using the State Inpatient Databases (2011-2012) for 6 states, representing Northeastern (New York) and Southeastern (Florida, Georgia, Kentucky, North Carolina, Mississippi) US. Geographic unit of analysis was the hospital service area (HSA). Age-standardized rates of operations and in-hospital mortality were calculated and mapped. Differences in rates across geographic areas were compared using the Kruskal-Wallis test, and variance quantified using linear random-effects models. Variation profiles were tabulated via standardized rates of utilization and mortality to compare geographically heterogenous areas. RESULTS: 227,109 EGS operations were geospatially analyzed across the 6 states. Age-standardized EGS operation rates varied significantly by region (Northeast rate of 22.7 EGS operations per 10,000 in population versus Southeast 21.9; P < 0.001), state (ranging from 9.9 to 29.1; P < 0.001), and HSA (1.9-56.7; P < 0.001). The geographic variability in age-standardized EGS mortality rates was also significant at the region level (Northeast mortality rate 7.2 per 1000 operations vs Southeast 7.4; P < 0.001), state-level (ranging from 5.9 to 9.0 deaths per 1000 EGS operations; P < 0.001), and HSA-level (0.0-77.3; P < 0.001). Maps and variation profiles visually exhibited widespread and substantial differences in EGS use and morality. CONCLUSIONS: Wide geographic variations exist across 6 Northeastern and Southeastern US states in the rates of EGS operations and subsequent mortality. More detailed geographic analyses are needed to determine the basis of these variations and how they can be minimized.