Redefining pandemic preparedness: Multidisciplinary insights from the CERP modelling workshop in infectious diseases, workshop report.

In July 2023, the Center of Excellence in Respiratory Pathogens organized a two-day workshop on infectious diseases modelling and the lessons learnt from the Covid-19 pandemic. This report summarizes the rich discussions that occurred during the workshop. The workshop participants discussed multisource data integration and highlighted the benefits of combining traditional surveillance with more novel data sources like mobility data, social media, and wastewater monitoring. Significant advancements were noted in the development of predictive models, with examples from various countries showcasing the use of machine learning and artificial intelligence in detecting and monitoring disease trends. The role of open collaboration between various stakeholders in modelling was stressed, advocating for the continuation of such partnerships beyond the pandemic. A major gap identified was the absence of a common international framework for data sharing, which is crucial for global pandemic preparedness. Overall, the workshop underscored the need for robust, adaptable modelling frameworks and the integration of different data sources and collaboration across sectors, as key elements in enhancing future pandemic response and preparedness.

Mortality risk from United States coal electricity generation.

Policy-makers seeking to limit the impact of coal electricity-generating units (EGUs, also known as power plants) on air quality and climate justify regulations by quantifying the health burden attributable to exposure from these sources. We defined "coal PM2.5" as fine particulate matter associated with coal EGU sulfur dioxide emissions and estimated annual exposure to coal PM2.5 from 480 EGUs in the US. We estimated the number of deaths attributable to coal PM2.5 from 1999 to 2020 using individual-level Medicare death records representing 650 million person-years. Exposure to coal PM2.5 was associated with 2.1 times greater mortality risk than exposure to PM2.5 from all sources. A total of 460,000 deaths were attributable to coal PM2.5, representing 25% of all PM2.5-related Medicare deaths before 2009 and 7% after 2012. Here, we quantify and visualize the contribution of individual EGUs to mortality.

[Epidemic forecasting and COVID-19]. / Prévisions épidémiques et Covid-19.

Since December 2019, the COVID-19 pandemic has had a major impact on global health and the economy. Epidemiological forecasts are crucial for governmental decisions, healthcare officials, and the general public. A collaboration between the Institute of Global Health at the University of Geneva and the Swiss Data Science Center created an interactive dashboard providing forecasts for over 200 countries and territories. This dashboard has been a valuable tool for the public and authorities alike. The pandemic has highlighted the importance of international collaborations and a robust national surveillance system. Data collection systems, pathogen-agnostic models, and communication tools need to be consolidated and maintained in operation.

Depuis décembre 2019, la pandémie de Covid-19 a eu un impact majeur sur la santé et l'économie mondiales. Les prévisions épidémiques sont essentielles pour les décisions gouvernementales, les responsables de la santé et le public. Un projet entre l'Institut de santé globale de l'Université de Genève et le Swiss Data Science Center a créé un tableau de bord interactif fournissant des prévisions pour plus de 200 pays et territoires, qui fut un outil précieux pour le public et les autorités. La pandémie a souligné l'importance des collaborations internationales et d'un système de surveillance national solide. Les systèmes de collecte de données, les modèles agnostiques aux pathogènes et les outils de communication doivent être consolidés et maintenus en fonctionnement.

Inequitable Exposures to U.S. Coal Power Plant-Related PM2.5: 22 Years and Counting.

BACKGROUND: Emissions from coal power plants have decreased over recent decades due to regulations and economics affecting costs of providing electricity generated by coal vis-à-vis its alternatives. These changes have improved regional air quality, but questions remain about whether benefits have accrued equitably across population groups. OBJECTIVES: We aimed to quantify nationwide long-term changes in exposure to particulate matter (PM) with an aerodynamic diameter ≤2.5µm (PM2.5) associated with coal power plant SO2 emissions. We linked exposure reductions with three specific actions taken at individual power plants: scrubber installations, reduced operations, and retirements. We assessed how emissions changes in different locations have influenced exposure inequities, extending previous source-specific environmental justice analyses by accounting for location-specific differences in racial/ethnic population distributions. METHODS: We developed a data set of annual PM2.5 source impacts ("coal PM2.5") associated with SO2 emissions at each of 1,237 U.S. coal-fired power plants across 1999-2020. We linked population-weighted exposure with information about each coal unit's operational and emissions-control status. We calculate changes in both relative and absolute exposure differences across demographic groups. RESULTS: Nationwide population-weighted coal PM2.5 declined from 1.96µg/m3 in 1999 to 0.06 µg/m3 in 2020. Between 2007 and 2010, most of the exposure reduction is attributable to SO2 scrubber installations, and after 2010 most of the decrease is attributable to retirements. Black populations in the South and North Central United States and Native American populations in the western United States were inequitably exposed early in the study period. Although inequities decreased with falling emissions, facilities in states across the North Central United States continue to inequitably expose Black populations, and Native populations are inequitably exposed to emissions from facilities in the West. DISCUSSION: We show that air quality controls, operational adjustments, and retirements since 1999 led to reduced exposure to coal power plant related PM2.5. Reduced exposure improved equity overall, but some populations continue to be inequitably exposed to PM2.5 associated with facilities in the North Central and western United States. https://doi.org/10.1289/EHP11605.

Trend estimation and short-term forecasting of COVID-19 cases and deaths worldwide.

Since the beginning of the COVID-19 pandemic, many dashboards have emerged as useful tools to monitor its evolution, inform the public, and assist governments in decision-making. Here, we present a globally applicable method, integrated in a daily updated dashboard that provides an estimate of the trend in the evolution of the number of cases and deaths from reported data of more than 200 countries and territories, as well as 7-d forecasts. One of the significant difficulties in managing a quickly propagating epidemic is that the details of the dynamic needed to forecast its evolution are obscured by the delays in the identification of cases and deaths and by irregular reporting. Our forecasting methodology substantially relies on estimating the underlying trend in the observed time series using robust seasonal trend decomposition techniques. This allows us to obtain forecasts with simple yet effective extrapolation methods in linear or log scale. We present the results of an assessment of our forecasting methodology and discuss its application to the production of global and regional risk maps.

Multi-syndrome, multi-gene risk modeling for individuals with a family history of cancer with the novel R package PanelPRO.

Identifying individuals who are at high risk of cancer due to inherited germline mutations is critical for effective implementation of personalized prevention strategies. Most existing models focus on a few specific syndromes; however, recent evidence from multi-gene panel testing shows that many syndromes are overlapping, motivating the development of models that incorporate family history on several cancers and predict mutations for a comprehensive panel of genes.We present PanelPRO, a new, open-source R package providing a fast, flexible back-end for multi-gene, multi-cancer risk modeling with pedigree data. It includes a customizable database with default parameter values estimated from published studies and allows users to select any combinations of genes and cancers for their models, including well-established single syndrome BayesMendel models (BRCAPRO and MMRPRO). This leads to more accurate risk predictions and ultimately has a high impact on prevention strategies for cancer and clinical decision making. The package is available for download for research purposes at https://projects.iq.harvard.edu/bayesmendel/panelpro.

Genetic mutations that increase cancer risk can be passed down from parents to their children, which can affect families across many generations. In these families, multiple members may be affected by different types of cancer, and these cancers often develop at an early age. Unaffected family members are often referred to genetic counselling, where they can explore their own risk of cancer. Clinicians and genetic counselors can provide recommendations to minimize cancer risk and inform personal choices on how to manage that risk, such as opting for preventative surgeries or participating in regular screening. In genetic counselling sessions, highly trained clinicians and specialists use software that takes an individual's family history of cancer and uses it to estimate their individual risk of carrying certain genetic mutations. These estimates can in turn help to predict their future risk of cancer. Many existing software packages are limited to estimating risks based on mutations in well-known cancer-related genes, such as BRCA1 and BRCA2 in breast and ovarian cancer. However, emerging evidence suggests that many of the genes associated with cancer risk work as part of a complex and overlapping network. Since current risk-profiling software packages are only designed to consider such genes in isolation, they cannot generate the most robust, accurate or comprehensive cancer risk profiles. To address this challenge, Lee, Liang et al. have developed a new risk-profiling software that can integrate a large number of gene mutations and a wide range of potential cancer types to provide more accurate estimates of individual cancer risk. This software, called PanelPRO, uses evidence identified from extensive literature reviews to model the complex interplay between genes and cancer risk. The software not only calculates risks based on known genes, but also allows other developers to integrate new cancer-related genes that may be identified in the future. Importantly, the software is compatible with genetic counselling applications, since it returns answers within seconds when reasonable family and gene database sizes are used. PanelPRO is a new, modern, flexible and efficient software package that provides an important advance towards modelling the vast genetic and biological complexity that contributes to inherited cancer risk. This software is designed to provide a more accurate and comprehensive estimate of cancer risk for individuals with family histories of cancer. As an open-source software, it is freely available for research purposes, and can be licensed by software companies and healthcare organizations to integrate electronic patient records and rapidly identify at-risk individuals across larger patient groups. Ultimately, this software has the potential to improve cancer prevention strategies and optimize the personalized decision-making processes around cancer risk.

Disconnectomics of the Rich Club Impacts Motor Recovery After Stroke.

BACKGROUND AND PURPOSE: Structural brain networks possess a few hubs, which are not only highly connected to the rest of the brain but are also highly connected to each other. These hubs, which form a rich-club, play a central role in global brain organization. To investigate whether the concept of rich-club sheds new light on poststroke recovery, we applied a novel network-theoretical quantification of lesions to patients with stroke and compared the outcomes with what lesion size alone would indicate. METHODS: Whole-brain structural networks of 73 patients with ischemic stroke were reconstructed using diffusion-weighted imaging data. Disconnectomes, a new type of network analyses, were constructed using only those fibers that pass through the lesion. Fugl-Meyer upper extremity scores and their changes were used to determine whether the patients show natural recovery or not. RESULTS: Cluster analysis revealed 3 patient clusters: small-lesion-good-recovery, midsized-lesion-poor-recovery (MLPR), and large-lesion-poor-recovery (LLPR). The small-lesion-good-recovery consisted of subjects whose lesions were small, and whose prospects for recovery were relatively good. To explain the nondifference in recovery between the MLPR and LLPR clusters despite the difference (LLPR>MLPR) in lesion volume, we defined the [Formula: see text] metric to be the sum of the entries in the disconnectome and, more importantly, the [Formula: see text] to be the sum of all entries in the disconnectome corresponding to edges with at least one node in the rich-club. Unlike lesion volume and corticospinal tract damage (MLPRLLPR) or showed no difference for [Formula: see text]. CONCLUSIONS: Smaller lesions that focus on the rich-club can be just as devastating as much larger lesions that do not focus on the rich-club, pointing to the role of the rich-club as a backbone for functional communication within brain networks and for recovery from stroke.

[Swiss Precision and Global Predictions]. / Covid-19 : précision suisse et prévisions globales.

A consortium of Swiss universities has set up a dashboard providing daily 7-day epidemic forecasting for 209 countries and territories around the world. Relayed on social networks, international media, and the sites of major public health agencies, these forecasts can help guiding public policy. However, the time horizon of these forecasts is limited and their accuracy is sometimes questionable, even at 7 days. Interdisciplinary research aimed at increasing the complexity of mathematical models can improve the accuracy of the forecasts provided.

Un consortium émanant de hautes écoles suisses a mis en place un tableau de bord fournissant quotidiennement des prévisions épidémiologiques à 7 jours pour 209 pays et territoires dans le monde. Relayées sur les réseaux sociaux, les médias internationaux et les sites des grandes agences de sécurité sanitaire, ces prévisions peuvent aider au guidage des politiques publiques. Cependant l'horizon de temps de ces prévisions est limité et leur précision parfois questionnable, même à 7 jours. Des pistes sont proposées à travers une recherche interdisciplinaire visant à complexifier les modèles mathématiques pour améliorer la précision des prévisions fournies.

Comparisons of simple and complex methods for quantifying exposure to individual point source air pollution emissions.

Expanded use of reduced complexity approaches in epidemiology and environmental justice investigations motivates detailed evaluation of these modeling approaches. Chemical transport models (CTMs) remain the most complete representation of atmospheric processes but are limited in applications that require large numbers of runs, such as those that evaluate individual impacts from large numbers of sources. This limitation motivates comparisons between modern CTM-derived techniques and intentionally simpler alternatives. We model population-weighted PM2.5 source impacts from each of greater than 1100 coal power plants operating in the United States in 2006 and 2011 using three approaches: (1) adjoint PM2.5 sensitivities calculated by the GEOS-Chem CTM; (2) a wind field-based Lagrangian model called HyADS; and (3) a simple calculation based on emissions and inverse source-receptor distance. Annual individual power plants' nationwide population-weighted PM2.5 source impacts calculated by HyADS and the inverse distance approach have normalized mean errors between 20 and 28% and root mean square error ranges between 0.0003 and 0.0005 µg m-3 compared with adjoint sensitivities. Reduced complexity approaches are most similar to the GEOS-Chem adjoint sensitivities nearby and downwind of sources, with degrading performance farther from and upwind of sources particularly when wind fields are not accounted for.

Embedding Mobile Health Technology into the Nurses' Health Study 3 to Study Behavioral Risk Factors for Cancer.

BACKGROUND: Physical activity and sleep are behavioral risk factors for cancer that may be influenced by environmental exposures, including built and natural environments. However, many studies in this area are limited by residence-based exposure assessment and/or self-reported, time-aggregated measures of behavior. METHODS: The Nurses' Health Study 3 (NHS3) Mobile Health Substudy is a pilot study of 500 participants in the prospective NHS3 cohort who use a smartphone application and a Fitbit for seven-day periods, four times over a year, to measure minute-level location, physical activity, heart rate, and sleep. RESULTS: We have collected data on 435 participants, comprising over 6 million participant-minutes of heart rate, step, sleep, and location. Over 90% of participants had five days of ≥600 minutes of Fitbit wear-time in their first sampling week, and this percentage dropped to 70% for weeks 2 to 4. Over 819 sampling weeks, we observed an average of 7,581 minutes of heart rate and step data [interquartile range (IQR): 6,651-9,645] per participant-week, and >2 million minutes of sleep in over 5,700 sleep bouts. We have recorded location data for 5,237 unique participant-days, averaging 104 location observations per participant-day (IQR: 103-107). CONCLUSIONS: This study describes a protocol to incorporate mobile health technology into a nationwide prospective cohort to measure high-resolution objective data on environment and behavior. IMPACT: This project could provide translational insights into interventions for urban planning to optimize opportunities for physical activity and healthy sleep patterns to reduce cancer risk.See all articles in this CEBP Focus section, "Modernizing Population Science."

Assessing NO2 Concentration and Model Uncertainty with High Spatiotemporal Resolution across the Contiguous United States Using Ensemble Model Averaging.

NO2 is a combustion byproduct that has been associated with multiple adverse health outcomes. To assess NO2 levels with high accuracy, we propose the use of an ensemble model to integrate multiple machine learning algorithms, including neural network, random forest, and gradient boosting, with a variety of predictor variables, including chemical transport models. This NO2 model covers the entire contiguous U.S. with daily predictions on 1-km-level grid cells from 2000 to 2016. The ensemble produced a cross-validated R2 of 0.788 overall, a spatial R2 of 0.844, and a temporal R2 of 0.729. The relationship between daily monitored and predicted NO2 is almost linear. We also estimated the associated monthly uncertainty level for the predictions and address-specific NO2 levels. This NO2 estimation has a very high spatiotemporal resolution and allows the examination of the health effects of NO2 in unmonitored areas. We found the highest NO2 levels along highways and in cities. We also observed that nationwide NO2 levels declined in early years and stagnated after 2007, in contrast to the trend at monitoring sites in urban areas, where the decline continued. Our research indicates that the integration of different predictor variables and fitting algorithms can achieve an improved air pollution modeling framework.

Short term exposure to fine particulate matter and hospital admission risks and costs in the Medicare population: time stratified, case crossover study.

OBJECTIVE: To assess risks and costs of hospital admission associated with short term exposure to fine particulate matter with diameter less than 2.5 µm (PM2.5) for 214 mutually exclusive disease groups. DESIGN: Time stratified, case crossover analyses with conditional logistic regressions adjusted for non-linear confounding effects of meteorological variables. SETTING: Medicare inpatient hospital claims in the United States, 2000-12 (n=95 277 169). PARTICIPANTS: All Medicare fee-for-service beneficiaries aged 65 or older admitted to hospital. MAIN OUTCOME MEASURES: Risk of hospital admission, number of admissions, days in hospital, inpatient and post-acute care costs, and value of statistical life (that is, the economic value used to measure the cost of avoiding a death) due to the lives lost at discharge for 214 disease groups. RESULTS: Positive associations between short term exposure to PM2.5 and risk of hospital admission were found for several prevalent but rarely studied diseases, such as septicemia, fluid and electrolyte disorders, and acute and unspecified renal failure. Positive associations were also found between risk of hospital admission and cardiovascular and respiratory diseases, Parkinson's disease, diabetes, phlebitis, thrombophlebitis, and thromboembolism, confirming previously published results. These associations remained consistent when restricted to days with a daily PM2.5 concentration below the WHO air quality guideline for the 24 hour average exposure to PM2.5. For the rarely studied diseases, each 1 µg/m3 increase in short term PM2.5 was associated with an annual increase of 2050 hospital admissions (95% confidence interval 1914 to 2187 admissions), 12 216 days in hospital (11 358 to 13 075), US$31m (£24m, €28m; $29m to $34m) in inpatient and post-acute care costs, and $2.5bn ($2.0bn to $2.9bn) in value of statistical life. For diseases with a previously known association, each 1 µg/m3 increase in short term exposure to PM2.5 was associated with an annual increase of 3642 hospital admissions (3434 to 3851), 20 098 days in hospital (18 950 to 21 247), $69m ($65m to $73m) in inpatient and post-acute care costs, and $4.1bn ($3.5bn to $4.7bn) in value of statistical life. CONCLUSIONS: New causes and previously identified causes of hospital admission associated with short term exposure to PM2.5 were found. These associations remained even at a daily PM2.5 concentration below the WHO 24 hour guideline. Substantial economic costs were linked to a small increase in short term PM2.5.

Data Science in Environmental Health Research.

PURPOSE OF REVIEW: Data science is an exploding trans-disciplinary field that aims to harness the power of data to gain information or insights on researcher-defined topics of interest. In this paper we review how data science can help advance environmental health research. RECENT FINDINGS: We discuss the concepts computationally scalable handling of Big Data and the design of efficient research data platforms, and how data science can provide solutions for methodological challenges in environmental health research, such as high-dimensional outcomes and exposures, and prediction models. Finally, we discuss tools for reproducible research. SUMMARY: In this paper we present opportunities to improve environmental research capabilities by embracing data science, and the pitfalls that environmental health researchers should avoid when employing data scientific approaches. Throughout the paper, we emphasize the need for environmental health researchers to collaborate more closely with biostatisticians and data scientists to ensure robust and interpretable results.

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.

Relative Effects of the Hospital Readmissions Reduction Program on Hospitals That Serve Poorer Patients.

IMPORTANCE: Hospitals that serve poorer populations have higher readmission rates. It is unknown whether these hospitals effectively lowered readmission rates in response to the Hospital Readmissions Reduction Program (HRRP). OBJECTIVE: To compare pre-post differences in readmission rates among hospitals with different proportion of dual-eligible patients both generally and among the most highly penalized (ie, low performing) hospitals. DESIGN: Retrospective cohort study using piecewise linear model with estimated hospital-level risk-standardized readmission rates (RSRRs) as the dependent variable and a change point at HRRP passage (2010). Economic burden was assessed by proportion of dual-eligibles served. SETTING: Acute care hospitals within the United States. PARTICIPANTS: Medicare fee-for-service beneficiaries aged 65 years or older discharged alive from January 1, 2003 to November 30, 2014 with a principal discharge diagnosis of acute myocardial infarction (AMI), congestive heart failure (CHF), and pneumonia. MAIN OUTCOME AND MEASURE: Decrease in hospital-level RSRRs in the post-law period, after controlling for the pre-law trend. RESULTS: For AMI, the pre-post difference between hospitals that service high and low proportion of dual-eligibles was not significant (-65 vs. -64 risk-standardized readmissions per 10000 discharges per year, P=0.0678). For CHF, RSRRs declined more at high than low dual-eligible hospitals (-79 vs. -75 risk-standardized readmissions per 10000 discharges per year, P=0.0006). For pneumonia, RSRRs declined less at high than low dual-eligible hospitals (-44 vs. -47 risk-standardized readmissions per 10000 discharges per year, P=0.0003). Among the 742 highest penalized hospitals and all conditions, the pre-post decline in rate of change of RSRRs was less for high dual-eligible hospitals than low dual-eligible hospitals (-68 vs. -74 risk-standardized readmissions per 10000 discharges per year for AMI, -88 vs. -97 for CHF, and -47 vs. -56 for pneumonia, P<0.0001 for all). CONCLUSIONS AND RELEVANCE: For all hospitals, differences in pre-post trends in RSRRs varied with disease conditions. However, for the highest-penalized hospitals, the pre-post decline in RSRRs was greater for low than high dual-eligible hospitals for all penalized conditions. These results suggest that high penalty, high dual-eligible hospitals may be less able to improve performance on readmission metrics.

CAUSAL INFERENCE IN THE CONTEXT OF AN ERROR PRONE EXPOSURE: AIR POLLUTION AND MORTALITY.

We propose a new approach for estimating causal effects when the exposure is measured with error and confounding adjustment is performed via a generalized propensity score (GPS). Using validation data, we propose a regression calibration (RC)-based adjustment for a continuous error-prone exposure combined with GPS to adjust for confounding (RC-GPS). The outcome analysis is conducted after transforming the corrected continuous exposure into a categorical exposure. We consider confounding adjustment in the context of GPS subclassification, inverse probability treatment weighting (IPTW) and matching. In simulations with varying degrees of exposure error and confounding bias, RC-GPS eliminates bias from exposure error and confounding compared to standard approaches that rely on the error-prone exposure. We applied RC-GPS to a rich data platform to estimate the causal effect of long-term exposure to fine particles (PM2.5) on mortality in New England for the period from 2000 to 2012. The main study consists of 2202 zip codes covered by 217,660 1 km × 1 km grid cells with yearly mortality rates, yearly PM2.5 averages estimated from a spatio-temporal model (error-prone exposure) and several potential confounders. The internal validation study includes a subset of 83 1 km × 1 km grid cells within 75 zip codes from the main study with error-free yearly PM2.5 exposures obtained from monitor stations. Under assumptions of noninterference and weak unconfoundedness, using matching we found that exposure to moderate levels of PM2.5 (8 < PM2.5 ≤ 10 µg/m3) causes a 2.8% (95% CI: 0.6%, 3.6%) increase in all-cause mortality compared to low exposure (PM2.5 ≤ 8 µg/m3).