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Background Repeated outbreaks of emerging pathogens underscore the need for preparedness plans to prevent, detect, and respond. As countries develop and improve National Action Plans for Health Security, addressing subnational variation in preparedness is increasingly important. One facet of preparedness and mitigating disease transmission is health facility accessibility, linking infected persons with health systems and vice versa. Where potential patients can access care, local facilities must ensure they can appropriately diagnose, treat, and contain disease spread to prevent secondary transmission; where patients cannot readily access facilities, alternate plans must be developed. Here, we use travel time to link facilities and populations at risk of viral hemorrhagic fevers (VHFs) and identify spatial variation in these respective preparedness demands. Methods and findings We used geospatial resources of travel friction, pathogen environmental suitability, and health facilities to determine facility accessibility of any at-risk location within a country. We considered in-country and cross-border movements of exposed populations and highlighted vulnerable populations where current facilities are inaccessible and new infrastructure would reduce travel times. We developed profiles for 43 African countries. Resulting maps demonstrate gaps in health facility accessibility and highlight facilities closest to areas at risk for VHF spillover. For instance, in the Central African Republic, we identified travel times of over 24 h to access a health facility. Some countries had more uniformly short travel times, such as Nigeria, although regional disparities exist. For some populations, including many in Botswana, access to areas at risk for VHF nationally was low but proximity to suitable spillover areas in bordering countries was high. Additional analyses provide insights for considering future resource allocation. We provide a contemporary use case for these analyses for the ongoing Ebola outbreak. Conclusions These maps demonstrate the use of geospatial analytics for subnational preparedness, identifying facilities close to at-risk populations for prioritizing readiness to detect, treat, and respond to cases and highlighting where gaps in health facility accessibility exist. We identified cross-border threats for VHF exposure and demonstrate an opportunity to improve preparedness activities through the use of precision public health methods and data-driven insights for resource allocation as part of a country’s preparedness plans.

Insecticide-treated nets (ITNs) are one of the most widespread and impactful malaria interventions in Africa, yet a spatially-resolved time series of ITN coverage has never been published. Using data from multiple sources, we generate high-resolution maps of ITN access, use, and nets-per-capita annually from 2000 to 2020 across the 40 highest-burden African countries. Our findings support several existing hypotheses: that use is high among those with access, that nets are discarded more quickly than official policy presumes, and that effectively distributing nets grows more difficult as coverage increases. The primary driving factors behind these findings are most likely strong cultural and social messaging around the importance of net use, low physical net durability, and a mixture of inherent commodity distribution challenges and less-than-optimal net allocation policies, respectively. These results can inform both policy decisions and downstream malaria analyses., Insecticide treated nets (ITNs) are an important part of malaria control in Africa and WHO targets aim for 80% coverage. This study estimates the spatio-temporal access and use of ITNs in Africa from 2000-2020, and shows that both metrics have improved over time but access remains below WHO targets.

As of June 19, 2020 there are more than 8.6 million COVID-19 cases worldwide with over 450,000 deaths. Providing obstetrical care in the setting of the pandemic poses challenges to the healthcare system in that, in comparison to many other medical specialties, obstetrical care cannot be deferred. Pregnant patients represent a high risk population for exposure and infection with respiratory pathogens and, as they require multiple points of contact with the healthcare system, are especially vulnerable. The purpose of this review is assess current epidemiology and outcomes research related to COVID-19 with a focus on obstetric patients. This review covers the global spread of the SARS-CoV-2 virus, symptomatology, modes of transmission, and current knowledge gaps related to epidemiology and outcomes for the obstetric population.

Maps of disease burden are a core tool needed for the control and elimination of malaria. Reliable routine surveillance data of malaria incidence, typically aggregated to administrative units, is becoming more widely available. Disaggregation regression is an important model framework for estimating high resolution risk maps from aggregated data. However, the aggregation of incidence over large, heterogeneous areas means that these data are underpowered for estimating complex, non-linear models. In contrast, prevalence point-surveys are directly linked to local environmental conditions but are not common in many areas of the world. Here, we train multiple non-linear, machine learning models on Plasmodium falciparum prevalence point-surveys. We then ensemble the predictions from these machine learning models with a disaggregation regression model that uses aggregated malaria incidences as response data. We find that using a disaggregation regression model to combine predictions from machine learning models improves model accuracy relative to a baseline model.

Summary:. Time-critical pathologies, such as the care of burn-injured patients, rely on accurate travel time data to plan high-quality service provision. Geospatial modeling, using data from the Malaria Atlas Project, together with census data, permits quantification of the huge global discrepancies in temporal access to burn care between high-income and low-resource settings. In this study, focusing on the United Kingdom and Ghana, we found that a 3-fold population difference exists with, respectively, 95.6% and 29.9% of the population that could access specialist burn care within 1-hour travel time. Solutions to such inequalities include upscaling of infrastructure and specialist personnel, but this is aspirational rather than feasible in most low- to middle-income countries. Mixed models of decentralization of care that leverage eHealth strategies, such as telemedicine, may enhance quality of local burns and reconstructive surgical care through skills transfer, capacity building, and expediting of urgent transfers, while empowering local healthcare communities. By extending specialist burn care coverage through eHealth to 8 district hospitals in rural Ghana, we demonstrate the potential to increase specialist population coverage within 1-hour travel time from 29.9% to 45.3%—equivalent to an additional 5.1 million people.

Background Substantial progress has been made in reducing the burden of malaria in Africa since 2000, but those gains could be jeopardised if the COVID-19 pandemic affects the availability of key malaria control interventions. The aim of this study was to evaluate plausible effects on malaria incidence and mortality under different levels of disruption to malaria control. Methods Using an established set of spatiotemporal Bayesian geostatistical models, we generated geospatial estimates across malaria-endemic African countries of the clinical case incidence and mortality of malaria, incorporating an updated database of parasite rate surveys, insecticide-treated net (ITN) coverage, and effective treatment rates. We established a baseline estimate for the anticipated malaria burden in Africa in the absence of COVID-19-related disruptions, and repeated the analysis for nine hypothetical scenarios in which effective treatment with an antimalarial drug and distribution of ITNs (both through routine channels and mass campaigns) were reduced to varying extents. Findings We estimated 215·2 (95% uncertainty interval 143·7–311·6) million cases and 386·4 (307·8–497·8) thousand deaths across malaria-endemic African countries in 2020 in our baseline scenario of undisrupted intervention coverage. With greater reductions in access to effective antimalarial drug treatment, our model predicted increasing numbers of cases and deaths: 224·1 (148·7–326·8) million cases and 487·9 (385·3–634·6) thousand deaths with a 25% reduction in antimalarial drug coverage; 233·1 (153·7–342·5) million cases and 597·4 (468·0–784·4) thousand deaths with a 50% reduction; and 242·3 (158·7–358·8) million cases and 715·2 (556·4–947·9) thousand deaths with a 75% reduction. Halting planned 2020 ITN mass distribution campaigns and reducing routine ITN distributions by 25%–75% also increased malaria burden to a total of 230·5 (151·6–343·3) million cases and 411·7 (322·8–545·5) thousand deaths with a 25% reduction; 232·8 (152·3–345·9) million cases and 415·5 (324·3–549·4) thousand deaths with a 50% reduction; and 234·0 (152·9–348·4) million cases and 417·6 (325·5–553·1) thousand deaths with a 75% reduction. When ITN coverage and antimalarial drug coverage were synchronously reduced, malaria burden increased to 240·5 (156·5–358·2) million cases and 520·9 (404·1–691·9) thousand deaths with a 25% reduction; 251·0 (162·2–377·0) million cases and 640·2 (492·0–856·7) thousand deaths with a 50% reduction; and 261·6 (167·7–396·8) million cases and 768·6 (586·1–1038·7) thousand deaths with a 75% reduction. Interpretation Under pessimistic scenarios, COVID-19-related disruption to malaria control in Africa could almost double malaria mortality in 2020, and potentially lead to even greater increases in subsequent years. To avoid a reversal of two decades of progress against malaria, averting this public health disaster must remain an integrated priority alongside the response to COVID-19. Funding Bill and Melinda Gates Foundation; Channel 7 Telethon Trust, Western Australia.

Access to healthcare is a requirement for human well-being that is constrained, in part, by the allocation of healthcare resources relative to the geographically dispersed human population(1-3). Quantifying access to care globally is challenging due to the absence of a comprehensive database of healthcare facilities. We harness major data collection efforts underway by OpenStreetMap, Google Maps and academic researchers to compile the most complete collection of facility locations to date. Leveraging the geographically variable strengths of our facility datasets, we use an established methodology(4)to characterize travel time to healthcare facilities in unprecedented detail. We produce maps of travel time with and without access to motorized transport, thus characterizing travel time to healthcare for populations distributed across the wealth spectrum. We find that just 8.9% of the global population (646 million people) cannot reach healthcare within one hour if they have access to motorized transport, and that 43.3% (3.16 billion people) cannot reach a healthcare facility by foot within one hour. Our maps highlight an additional vulnerability faced by poorer individuals in remote areas and can help to estimate whether individuals will seek healthcare when it is needed, as well as providing an evidence base for efficiently distributing limited healthcare and transportation resources to underserved populations both now and in the future. A global analysis generating high-resolution maps of travel time shows that 91.1% of the world's population can reach a hospital or clinic within an hour if they have access to motorized transportation, but only 56.7% can do so by walking, highlighting additional inequities for underserved populations accessing healthcare.

Background Mass drug administration (MDA) is a control and elimination tool for treating infectious diseases. For malaria, it is widely accepted that conducting MDA during the dry season results in the best outcomes. However, seasonal movement of populations into and out of MDA target areas is common in many places and could potentially fundamentally limit the ability of MDA campaigns to achieve elimination. Methods A mathematical model was used to simulate malaria transmission in two villages connected to a high-risk area into and out of which 10% of villagers traveled seasonally. MDA was given only in the villages. Prevalence reduction under various possible timings of MDA and seasonal travel was predicted. Results MDA is most successful when distributed outside the traveling season and during the village low-transmission season. MDA is least successful when distributed during the traveling season and when traveling overlaps with the peak transmission season in the high-risk area. Mistiming MDA relative to seasonal travel resulted in much poorer outcomes than mistiming MDA relative to the peak transmission season within the villages. Conclusions Seasonal movement patterns of high-risk groups should be taken into consideration when selecting the optimum timing of MDA campaigns.

Summary Background Health outcomes are known to vary at both the country and local levels, but trends in mortality across a detailed and comprehensive set of causes have not been previously described at a very local level. Life expectancy in King County, WA, USA, is in the 95th percentile among all counties in the USA. However, little is known about how life expectancy and mortality from different causes of death vary at a local, neighbourhood level within this county. In this analysis, we estimated life expectancy and cause-specific mortality within King County to describe spatial trends, quantify disparities in mortality, and assess the contribution of each cause of death to overall disparities in all-cause mortality. Methods We applied established so-called garbage code redistribution algorithms and small area estimation methods to death registration data for King County to estimate life expectancy, cause-specific mortality rates, and years of life lost (YLL) rates from 152 causes of death for 397 census tracts from Jan 1, 1990, to Dec 31, 2014. We used the cause list developed for the Global Burden of Disease 2015 study for this analysis. Deaths were tabulated by age group, sex, census tract, and cause of death. We used Bayesian mixed-effects regression models to estimate mortality overall and from each cause. Findings Between 1990 and 2014, life expectancy in King County increased by 5·4 years (95% uncertainty interval [UI] 5·0–5·7) among men (from 74·0 years [73·7–74·3] to 79·3 years [79·1–79·6]) and by 3·4 years (3·0–3·7) among women (from 80·0 years [79·7–80·2] to 83·3 years [83·1–83·5]). In 2014, life expectancy ranged from 68·4 years (95% UI 66·9–70·1) to 86·7 years (85·0–88·2) for men and from 73·6 years (71·6–75·5) to 88·4 years (86·9–89·9) for women among census tracts within King County. Rates of YLL by cause also varied substantially among census tracts for each cause of death. Geographical areas with relatively high and relatively low YLL rates differed by cause. In general, causes of death responsible for more YLLs overall also contributed more significantly to geographical inequality within King County. However, certain causes contributed more to inequality than to overall YLLs. Interpretation This census tract-level analysis of life expectancy and cause-specific YLL rates highlights important differences in health among neighbourhoods in King County that are masked by county-level estimates. Efforts to improve population health in King County should focus on reducing geographical inequality, by targeting those health conditions that contribute the most to overall YLLs and to inequality. This analysis should be replicated in other locations to more fully describe fine-grained local-level variation in population health and contribute to efforts to improve health while reducing inequalities. Funding John W Stanton and Theresa E Gillespie.

Malaria transmission in Madagascar is highly heterogeneous, exhibiting spatial, seasonal and long-term trends. Previous efforts to map malaria risk in Madagascar used prevalence data from Malaria Indicator Surveys. These cross-sectional surveys, conducted during the high transmission season most recently in 2013 and 2016, provide nationally representative prevalence data but cover relatively short time frames. Conversely, monthly case data are collected at health facilities but suffer from biases, including incomplete reporting and low rates of treatment seeking. We combined survey and case data to make monthly maps of prevalence between 2013 and 2016. Health facility catchment populations were estimated to produce incidence rates from the case data. Smoothed incidence surfaces, environmental and socioeconomic covariates, and survey data informed a Bayesian prevalence model, in which a flexible incidence-to-prevalence relationship was learned. Modelled spatial trends were consistent over time, with highest prevalence in the coastal regions and low prevalence in the highlands and desert south. Prevalence was lowest in 2014 and peaked in 2015 and seasonality was widely observed, including in some lower transmission regions. These trends highlight the utility of monthly prevalence estimates over the four year period. By combining survey and case data using this two-step modelling approach, we were able to take advantage of the relative strengths of each metric while accounting for potential bias in the case data. Similar modelling approaches combining large datasets of different malaria metrics may be applicable across sub-Saharan Africa.

BACKGROUND: The fifth Millennium Development Goal (MDG 5) established the goal of a 75% reduction in the maternal mortality ratio (MMR; number of maternal deaths per 100,000 livebirths) between 1990 and 2015. We aimed to measure levels and track trends in maternal mortality, the key causes contributing to maternal death, and timing of maternal death with respect to delivery.METHODS: We used robust statistical methods including the Cause of Death Ensemble model (CODEm) to analyse a database of data for 7065 site-years and estimate the number of maternal deaths from all causes in 188 countries between 1990 and 2013. We estimated the number of pregnancy-related deaths caused by HIV on the basis of a systematic review of the relative risk of dying during pregnancy for HIV-positive women compared with HIV-negative women. We also estimated the fraction of these deaths aggravated by pregnancy on the basis of a systematic review. To estimate the numbers of maternal deaths due to nine different causes, we identified 61 sources from a systematic review and 943 site-years of vital registration data. We also did a systematic review of reports about the timing of maternal death, identifying 142 sources to use in our analysis. We developed estimates for each country for 1990-2013 using Bayesian meta-regression. We estimated 95% uncertainty intervals (UIs) for all values.FINDINGS: 292,982 (95% UI 261,017-327,792) maternal deaths occurred in 2013, compared with 376,034 (343,483-407,574) in 1990. The global annual rate of change in the MMR was -0·3% (-1·1 to 0·6) from 1990 to 2003, and -2·7% (-3·9 to -1·5) from 2003 to 2013, with evidence of continued acceleration. MMRs reduced consistently in south, east, and southeast Asia between 1990 and 2013, but maternal deaths increased in much of sub-Saharan Africa during the 1990s. 2070 (1290-2866) maternal deaths were related to HIV in 2013, 0·4% (0·2-0·6) of the global total. MMR was highest in the oldest age groups in both 1990 and 2013. In 2013, most deaths occurred intrapartum or postpartum. Causes varied by region and between 1990 and 2013. We recorded substantial variation in the MMR by country in 2013, from 956·8 (685·1-1262·8) in South Sudan to 2·4 (1·6-3·6) in Iceland.INTERPRETATION: Global rates of change suggest that only 16 countries will achieve the MDG 5 target by 2015. Accelerated reductions since the Millennium Declaration in 2000 coincide with increased development assistance for maternal, newborn, and child health. Setting of targets and associated interventions for after 2015 will need careful consideration of regions that are making slow progress, such as west and central Africa.FUNDING: Bill & Melinda Gates Foundation.

Importance Examining life expectancy by county allows for tracking geographic disparities over time and assessing factors related to these disparities. This information is potentially useful for policy makers, clinicians, and researchers seeking to reduce disparities and increase longevity. Objective To estimate annual life tables by county from 1980 to 2014; describe trends in geographic inequalities in life expectancy and age-specific risk of death; and assess the proportion of variation in life expectancy explained by variation in socioeconomic and race/ethnicity factors, behavioral and metabolic risk factors, and health care factors. Design, Setting, and Participants Annual county-level life tables were constructed using small area estimation methods from deidentified death records from the National Center for Health Statistics (NCHS), and population counts from the US Census Bureau, NCHS, and the Human Mortality Database. Measures of geographic inequality in life expectancy and age-specific mortality risk were calculated. Principal component analysis and ordinary least squares regression were used to examine the county-level association between life expectancy and socioeconomic and race/ethnicity factors, behavioral and metabolic risk factors, and health care factors. Exposures County of residence. Main Outcomes and Measures Life expectancy at birth and age-specific mortality risk. Results Counties were combined as needed to create stable units of analysis over the period 1980 to 2014, reducing the number of areas analyzed from 3142 to 3110. In 2014, life expectancy at birth for both sexes combined was 79.1 (95% uncertainty interval [UI], 79.0-79.1) years overall, but differed by 20.1 (95% UI, 19.1-21.3) years between the counties with the lowest and highest life expectancy. Absolute geographic inequality in life expectancy increased between 1980 and 2014. Over the same period, absolute geographic inequality in the risk of death decreased among children and adolescents, but increased among older adults. Socioeconomic and race/ethnicity factors, behavioral and metabolic risk factors, and health care factors explained 60%, 74%, and 27% of county-level variation in life expectancy, respectively. Combined, these factors explained 74% of this variation. Most of the association between socioeconomic and race/ethnicity factors and life expectancy was mediated through behavioral and metabolic risk factors. Conclusions and Relevance Geographic disparities in life expectancy among US counties are large and increasing. Much of the variation in life expectancy among counties can be explained by a combination of socioeconomic and race/ethnicity factors, behavioral and metabolic risk factors, and health care factors. Policy action targeting socioeconomic factors and behavioral and metabolic risk factors may help reverse the trend of increasing disparities in life expectancy in the United States.

Background: We describe challenges associated with incorporating knowledge assessment into an educational game on a sensitive topic and discuss possible motivations for, and solutions to, these challenges. Methods: The My Future Family Game (MFF) is a tool for collecting data about family planning intentions. The game was expanded to include information about human anatomy and sexual reproduction. To assess the efficacy of the game as a tool for teaching sexual education, we designed a pre-post study with assessments before and after the game which was deployed in three schools in and around Chennai, India in summer of 2018. Results: The pre-post process did not effectively assess knowledge gain and made the game less enjoyable. Although all participants completed the pre-test because it was required to access the main game, many did not complete the post test. As a result, the post-test scores are of limited use in assessing the efficacy of the intervention as an educational tool. This deployment demonstrated that pre-post testing has to be integrated in a way that motivates players to improve their scores in the post-test. The pre-test results did provide useful information about players’ knowledge of human anatomy and mechanisms of human reproduction prior to gameplay and validated the tool as a means of data collection. Conclusion: Adding outcomes assessment required asking players questions about sexual anatomy and function with little or no introduction. This process undermined elements of the initial game design and made the process less enjoyable for participants. Understanding these failures has been a vital step in the process of iterative game design. Modifications were made to the pre-post test process for future deployments so that the process of assessment does not diminish enthusiasm for game play or enjoyment and motivates completion of the post-test as part of gameplay.

Background: Since 2000, the scale-up of malaria control interventions has substantially reduced morbidity and mortality caused by the disease globally, fuelling bold aims for disease elimination. In tandem with increased availability of geospatially resolved data, malaria control programmes increasingly use high-resolution maps to characterise spatially heterogeneous patterns of disease risk and thus efficiently target areas of high burden. Methods: We updated and refined the Plasmodium falciparum parasite rate and clinical incidence models for sub-Saharan Africa, which rely on cross-sectional survey data for parasite rate and intervention coverage. For malaria endemic countries outside of sub-Saharan Africa, we produced estimates of parasite rate and incidence by applying an ecological downscaling approach to malaria incidence data acquired via routine surveillance. Mortality estimates were derived by linking incidence to systematically derived vital registration and verbal autopsy data. Informed by high-resolution covariate surfaces, we estimated P falciparum parasite rate, clinical incidence, and mortality at national, subnational, and 5 × 5 km pixel scales with corresponding uncertainty metrics. Findings: We present the first global, high-resolution map of P falciparum malaria mortality and the first global prevalence and incidence maps since 2010. These results are combined with those for Plasmodium vivax (published separately) to form the malaria estimates for the Global Burden of Disease 2017 study. The P falciparum estimates span the period 2000–17, and illustrate the rapid decline in burden between 2005 and 2017, with incidence declining by 27·9% and mortality declining by 42·5%. Despite a growing population in endemic regions, P falciparum cases declined between 2005 and 2017, from 232·3 million (95% uncertainty interval 198·8–277·7) to 193·9 million (156·6–240·2) and deaths declined from 925 800 (596 900–1 341 100) to 618 700 (368 600–952 200). Despite the declines in burden, 90·1% of people within sub-Saharan Africa continue to reside in endemic areas, and this region accounted for 79·4% of cases and 87·6% of deaths in 2017. Interpretation: High-resolution maps of P falciparum provide a contemporary resource for informing global policy and malaria control planning, programme implementation, and monitoring initiatives. Amid progress in reducing global malaria burden, areas where incidence trends have plateaued or increased in the past 5 years underscore the fragility of hard-won gains against malaria. Efforts towards elimination should be strengthened in such areas, and those where burden remained high throughout the study period.

Background: In response to a Grand Challenges in Global Health call for action to collect data about family planning intentions and increase the uptake of family planning methods in India, our team designed, developed, and piloted the My Future Family video game in Karnataka Province. The game educates adolescents about human sexuality and reproduction while asking players when they would like to achieve five important family planning milestones. Participants were also asked to report who influences them the most when making family planning decisions. Methods: Focus groups were conducted and the resulting data used to design the game which was iteratively tested and then piloted in 11 schools in rural and urban areas of southern India. Data was collected throughout gameplay and cross-checked with paper questionnaires. Results: In August 2017, we successfully piloted the game with 382 adolescents and validated its efficacy both as an educational tool and as an innovative means of accurate data collection. Conclusion: It has historically been problematic to gather accurate data about adolescents in India on this culturally sensitive topic for a variety of reasons. These include difficulties obtaining consent, developing appropriate survey methods, and framing questions in language that young people can understand. Our game met these challenges by working within a single school system with approval from senior administration, delivering information via a game environment which freed players from societal constraints, and communicating information via images and audio in addition to text in both English and Kannada (the local language).

Importance Substance use disorders, including alcohol use disorders and drug use disorders, and intentional injuries, including self-harm and interpersonal violence, are important causes of early death and disability in the United States. Objective To estimate age-standardized mortality rates by county from alcohol use disorders, drug use disorders, self-harm, and interpersonal violence in the United States. Design and Setting Validated small-area estimation models were applied to deidentified death records from the National Center for Health Statistics (NCHS) and population counts from the US Census Bureau, NCHS, and the Human Mortality Database to estimate county-level mortality rates from 1980 to 2014 for alcohol use disorders, drug use disorders, self-harm, and interpersonal violence. Exposures County of residence. Main Outcomes and Measures Age-standardized mortality rates by US county (N = 3110), year, sex, and cause. Results Between 1980 and 2014, there were 2 848 768 deaths due to substance use disorders and intentional injuries recorded in the United States. Mortality rates from alcohol use disorders (n = 256 432), drug use disorders (n = 542 501), self-harm (n = 1 289 086), and interpersonal violence (n = 760 749) varied widely among counties. Mortality rates decreased for alcohol use disorders, self-harm, and interpersonal violence at the national level between 1980 and 2014; however, over the same period, the percentage of counties in which mortality rates increased for these causes was 65.4% for alcohol use disorders, 74.6% for self-harm, and 6.6% for interpersonal violence. Mortality rates from drug use disorders increased nationally and in every county between 1980 and 2014, but the relative increase varied from 8.2% to 8369.7%. Relative and absolute geographic inequalities in mortality, as measured by comparing the 90th and 10th percentile among counties, decreased for alcohol use disorders and interpersonal violence but increased substantially for drug use disorders and self-harm between 1980 and 2014. Conclusions and Relevance Mortality due to alcohol use disorders, drug use disorders, self-harm, and interpersonal violence varied widely among US counties, both in terms of levels of mortality and trends. These estimates may be useful to inform efforts to target prevention, diagnosis, and treatment to improve health and reduce inequalities.

Objective. The University of Chicago Medicine (UCM) led the Expanded Testing and Linkage to Care (X-TLC) program for disproportionately affected populations on the South Side of Chicago. The X-TLC program aimed to expand routine HIV testing to high-prevalence communities with disproportionately affected populations (i.e., minority men and women, men who have sex with men, and intravenous drug users) according to CDC guidelines at multiple clinical sites. Methods. The X-TLC program used standard blood-based laboratory testing vs. point-of-care rapid testing or rapid laboratory testing with point-of-care results notification. Site coordinators and the linkage-to-care coordinator at UCM oversaw testing, test notification, and linkage to care. Results. From February 1, 2011, through December 31, 2013, the X-TLC program completed 75,345 HIV tests on 67,153 unique patients. Of the total tests, 48,044 (63.8%) were performed on patients who self-identified as African American and 6,606 (8.8%) were performed on patients who self-identified as Hispanic. Of the 67,153 patients tested, 395 (0.6%) tested positive and 176 (0.3%) were previously unaware of their HIV-positive status. Seroprevalence was even higher for EDs, where 127 of 12,957 patients tested positive for HIV (1.0% seroprevalence), than for other patient care sites, including for new diagnoses, where 50 of 12,957 patients tested positive for HIV (0.4% seroprevalence). Of the 176 newly diagnosed patients, 166 of 173 (96.0%) patients who were still alive when testing was complete received their test results, and 148 of the 166 patients who were eligible for care (89.0%) were linked to care. Patients linked to X-TLC physicians did well with respect to the continuum of care: 77 of 123 (62.6%) patients achieved HIV viral load of Conclusion. Lead organizations such as UCM were able to assist and oversee HIV screening and linkage to care for HIV patients diagnosed at community sites. HIV screening and linkage to care can be accomplished by incorporating standard testing for HIV into routine medical care.

Importance In the United States, regional variation in cardiovascular mortality is well-known but county-level estimates for all major cardiovascular conditions have not been produced. Objective To estimate age-standardized mortality rates from cardiovascular diseases by county. Design and Setting Deidentified death records from the National Center for Health Statistics and population counts from the US Census Bureau, the National Center for Health Statistics, and the Human Mortality Database from 1980 through 2014 were used. Validated small area estimation models were used to estimate county-level mortality rates from all cardiovascular diseases, including ischemic heart disease, cerebrovascular disease, ischemic stroke, hemorrhagic stroke, hypertensive heart disease, cardiomyopathy, atrial fibrillation and flutter, rheumatic heart disease, aortic aneurysm, peripheral arterial disease, endocarditis, and all other cardiovascular diseases combined. Exposures The 3110 counties of residence. Main Outcomes and Measures Age-standardized cardiovascular disease mortality rates by county, year, sex, and cause. Results From 1980 to 2014, cardiovascular diseases were the leading cause of death in the United States, although the mortality rate declined from 507.4 deaths per 100 000 persons in 1980 to 252.7 deaths per 100 000 persons in 2014, a relative decline of 50.2% (95% uncertainty interval [UI], 49.5%-50.8%). In 2014, cardiovascular diseases accounted for more than 846 000 deaths (95% UI, 827-865 thousand deaths) and 11.7 million years of life lost (95% UI, 11.6-11.9 million years of life lost). The gap in age-standardized cardiovascular disease mortality rates between counties at the 10th and 90th percentile declined 14.6% from 172.1 deaths per 100 000 persons in 1980 to 147.0 deaths per 100 000 persons in 2014 (posterior probability of decline >99.9%). In 2014, the ratio between counties at the 90th and 10th percentile was 2.0 for ischemic heart disease (119.1 vs 235.7 deaths per 100 000 persons) and 1.7 for cerebrovascular disease (40.3 vs 68.1 deaths per 100 000 persons). For other cardiovascular disease causes, the ratio ranged from 1.4 (aortic aneurysm: 3.5 vs 5.1 deaths per 100 000 persons) to 4.2 (hypertensive heart disease: 4.3 vs 17.9 deaths per 100 000 persons). The largest concentration of counties with high cardiovascular disease mortality extended from southeastern Oklahoma along the Mississippi River Valley to eastern Kentucky. Several cardiovascular disease conditions were clustered substantially outside the South, including atrial fibrillation (Northwest), aortic aneurysm (Midwest), and endocarditis (Mountain West and Alaska). The lowest cardiovascular mortality rates were found in the counties surrounding San Francisco, California, central Colorado, northern Nebraska, central Minnesota, northeastern Virginia, and southern Florida. Conclusions and Relevance Substantial differences exist between county ischemic heart disease and stroke mortality rates. Smaller differences exist for diseases of the myocardium, atrial fibrillation, aortic and peripheral arterial disease, rheumatic heart disease, and endocarditis.

Introduction Cancer is a leading cause of morbidity and mortality in the United States and results in a high economic burden. Objective To estimate age-standardized mortality rates by US county from 29 cancers. Design and Setting Deidentified death records from the National Center for Health Statistics (NCHS) and population counts from the Census Bureau, the NCHS, and the Human Mortality Database from 1980 to 2014 were used. Validated small area estimation models were used to estimate county-level mortality rates from 29 cancers: lip and oral cavity; nasopharynx; other pharynx; esophageal; stomach; colon and rectum; liver; gallbladder and biliary; pancreatic; larynx; tracheal, bronchus, and lung; malignant skin melanoma; nonmelanoma skin cancer; breast; cervical; uterine; ovarian; prostate; testicular; kidney; bladder; brain and nervous system; thyroid; mesothelioma; Hodgkin lymphoma; non-Hodgkin lymphoma; multiple myeloma; leukemia; and all other cancers combined. Exposure County of residence. Main Outcomes and Measures Age-standardized cancer mortality rates by county, year, sex, and cancer type. Results A total of 19 511 910 cancer deaths were recorded in the United States between 1980 and 2014, including 5 656 423 due to tracheal, bronchus, and lung cancer; 2 484 476 due to colon and rectum cancer; 1 573 593 due to breast cancer; 1 077 030 due to prostate cancer; 1 157 878 due to pancreatic cancer; 209 314 due to uterine cancer; 421 628 due to kidney cancer; 487 518 due to liver cancer; 13 927 due to testicular cancer; and 829 396 due to non-Hodgkin lymphoma. Cancer mortality decreased by 20.1% (95% uncertainty interval [UI], 18.2%-21.4%) between 1980 and 2014, from 240.2 (95% UI, 235.8-244.1) to 192.0 (95% UI, 188.6-197.7) deaths per 100 000 population. There were large differences in the mortality rate among counties throughout the period: in 1980, cancer mortality ranged from 130.6 (95% UI, 114.7-146.0) per 100 000 population in Summit County, Colorado, to 386.9 (95% UI, 330.5-450.7) in North Slope Borough, Alaska, and in 2014 from 70.7 (95% UI, 63.2-79.0) in Summit County, Colorado, to 503.1 (95% UI, 464.9-545.4) in Union County, Florida. For many cancers, there were distinct clusters of counties with especially high mortality. The location of these clusters varied by type of cancer and were spread in different regions of the United States. Clusters of breast cancer were present in the southern belt and along the Mississippi River, while liver cancer was high along the Texas-Mexico border, and clusters of kidney cancer were observed in North and South Dakota and counties in West Virginia, Ohio, Indiana, Louisiana, Oklahoma, Texas, Alaska, and Illinois. Conclusions and Relevance Cancer mortality declined overall in the United States between 1980 and 2014. Over this same period, there were important changes in trends, patterns, and differences in cancer mortality among US counties. These patterns may inform further research into improving prevention and treatment.

BACKGROUND: This paper investigates trends in suicide rate, the reasons for and means of suicide and the occupation of deceased, to prioritize suicide prevention activities in India and to highlight the limitations to data quality for surveillance. METHODS: Data available in the public domain from the National Crimes Record Bureau (NCRB) were analysed from 2001 to 2010 at the national and sub-national levels, split by age groups and sex for ages 15 years and above. RESULTS: The reported suicide rate was 14.9 and 15.4 suicides per 100 000 population in 2001 and 2010, respectively. More developed states reported significantly higher suicide rates than the less developed (mean 20.5 versus 8.16), but neither experienced large changes over time. Among males, the reported suicide rate changed slightly (17.8 to 19.5); it remained almost similar for females (11.9 to 11.1). Housewives accounted for the highest proportion of suicide deaths over the decade. Distribution of the reasons for suicide remained almost constant over time; most suicides (33.7%) were due to personal/social reasons, followed by health at 24.3% and unknown reasons at 16.4%; differences were observed between the more and less developed states. Marriage-related suicides were higher for females, and health reasons increased with increasing age. Nationally, poison/overdose with drugs/pesticides was the leading means of suicide through the decade, although the gap between this and hanging decreased over time. The state level data showed considerable heterogeneity in the quality of data across the indicators assessed. CONCLUSIONS: These data provide a range of information to identify vulnerable groups, to formulate appropriate suicide prevention strategies. Addressing the limitations in data quality would facilitate further utility of surveillance data to prevent suicides.© The Author 2016; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association. Language: en

Importance Infectious diseases are mostly preventable but still pose a public health threat in the United States, where estimates of infectious diseases mortality are not available at the county level. Objective To estimate age-standardized mortality rates and trends by county from 1980 to 2014 from lower respiratory infections, diarrheal diseases, HIV/AIDS, meningitis, hepatitis, and tuberculosis. Design and Setting This study used deidentified death records from the National Center for Health Statistics (NCHS) and population counts from the US Census Bureau, NCHS, and the Human Mortality Database. Validated small-area estimation models were applied to these data to estimate county-level infectious disease mortality rates. Exposures County of residence. Main Outcomes and Measures Age-standardized mortality rates of lower respiratory infections, diarrheal diseases, HIV/AIDS, meningitis, hepatitis, and tuberculosis by county, year, and sex. Results Between 1980 and 2014, there were 4 081 546 deaths due to infectious diseases recorded in the United States. In 2014, a total of 113 650 (95% uncertainty interval [UI], 108 764-117 942) deaths or a rate of 34.10 (95% UI, 32.63-35.38) deaths per 100 000 persons were due to infectious diseases in the United States compared to a total of 72 220 (95% UI, 69 887-74 712) deaths or a rate of 41.95 (95% UI, 40.52-43.42) deaths per 100 000 persons in 1980, an overall decrease of 18.73% (95% UI, 14.95%-23.33%). Lower respiratory infections were the leading cause of infectious diseases mortality in 2014 accounting for 26.87 (95% UI, 25.79-28.05) deaths per 100 000 persons (78.80% of total infectious diseases deaths). There were substantial differences among counties in death rates from all infectious diseases. Lower respiratory infection had the largest absolute mortality inequality among counties (difference between the 10th and 90th percentile of the distribution, 24.5 deaths per 100 000 persons). However, HIV/AIDS had the highest relative mortality inequality between counties (10.0 as the ratio of mortality rate in the 90th and 10th percentile of the distribution). Mortality from meningitis and tuberculosis decreased over the study period in all US counties. However, diarrheal diseases were the only cause of infectious diseases mortality to increase from 2000 to 2014, reaching a rate of 2.41 (95% UI, 0.86-2.67) deaths per 100 000 persons, with many counties of high mortality extending from Missouri to the northeastern region of the United States. Conclusions and Relevance Between 1980 and 2014, there were declines in mortality from most categories of infectious diseases, with large differences among US counties. However, over this time there was an increase in mortality for diarrheal diseases.

Importance County-level patterns in mortality rates by cause have not been systematically described but are potentially useful for public health officials, clinicians, and researchers seeking to improve health and reduce geographic disparities. Objectives To demonstrate the use of a novel method for county-level estimation and to estimate annual mortality rates by US county for 21 mutually exclusive causes of death from 1980 through 2014. Design, Setting, and Participants Redistribution methods for garbage codes (implausible or insufficiently specific cause of death codes) and small area estimation methods (statistical methods for estimating rates in small subpopulations) were applied to death registration data from the National Vital Statistics System to estimate annual county-level mortality rates for 21 causes of death. These estimates were raked (scaled along multiple dimensions) to ensure consistency between causes and with existing national-level estimates. Geographic patterns in the age-standardized mortality rates in 2014 and in the change in the age-standardized mortality rates between 1980 and 2014 for the 10 highest-burden causes were determined. Exposure County of residence. Main Outcomes and Measures Cause-specific age-standardized mortality rates. Results A total of 80 412 524 deaths were recorded from January 1, 1980, through December 31, 2014, in the United States. Of these, 19.4 million deaths were assigned garbage codes. Mortality rates were analyzed for 3110 counties or groups of counties. Large between-county disparities were evident for every cause, with the gap in age-standardized mortality rates between counties in the 90th and 10th percentiles varying from 14.0 deaths per 100 000 population (cirrhosis and chronic liver diseases) to 147.0 deaths per 100 000 population (cardiovascular diseases). Geographic regions with elevated mortality rates differed among causes: for example, cardiovascular disease mortality tended to be highest along the southern half of the Mississippi River, while mortality rates from self-harm and interpersonal violence were elevated in southwestern counties, and mortality rates from chronic respiratory disease were highest in counties in eastern Kentucky and western West Virginia. Counties also varied widely in terms of the change in cause-specific mortality rates between 1980 and 2014. For most causes (eg, neoplasms, neurological disorders, and self-harm and interpersonal violence), both increases and decreases in county-level mortality rates were observed. Conclusions and Relevance In this analysis of US cause-specific county-level mortality rates from 1980 through 2014, there were large between-county differences for every cause of death, although geographic patterns varied substantially by cause of death. The approach to county-level analyses with small area models used in this study has the potential to provide novel insights into US disease-specific mortality time trends and their differences across geographic regions.

Importance Chronic respiratory diseases are an important cause of death and disability in the United States. Objective To estimate age-standardized mortality rates by county from chronic respiratory diseases. Design, Setting, and Participants Validated small area estimation models were applied to deidentified death records from the National Center for Health Statistics and population counts from the US Census Bureau, National Center for Health Statistics, and Human Mortality Database to estimate county-level mortality rates from 1980 to 2014 for chronic respiratory diseases. Exposure County of residence. Main Outcomes and Measures Age-standardized mortality rates by county, year, sex, and cause. Results A total of 4 616 711 deaths due to chronic respiratory diseases were recorded in the United States from January 1, 1980, through December 31, 2014. Nationally, the mortality rate from chronic respiratory diseases increased from 40.8 (95% uncertainty interval [UI], 39.8-41.8) deaths per 100 000 population in 1980 to a peak of 55.4 (95% UI, 54.1-56.5) deaths per 100 000 population in 2002 and then declined to 52.9 (95% UI, 51.6-54.4) deaths per 100 000 population in 2014. This overall 29.7% (95% UI, 25.5%-33.8%) increase in chronic respiratory disease mortality from 1980 to 2014 reflected increases in the mortality rate from chronic obstructive pulmonary disease (by 30.8% [95% UI, 25.2%-39.0%], from 34.5 [95% UI, 33.0-35.5] to 45.1 [95% UI, 43.7-46.9] deaths per 100 000 population), interstitial lung disease and pulmonary sarcoidosis (by 100.5% [95% UI, 5.8%-155.2%], from 2.7 [95% UI, 2.3-4.2] to 5.5 [95% UI, 3.5-6.1] deaths per 100 000 population), and all other chronic respiratory diseases (by 42.3% [95% UI, 32.4%-63.8%], from 0.51 [95% UI, 0.48-0.54] to 0.73 [95% UI, 0.69-0.78] deaths per 100 000 population). There were substantial differences in mortality rates and changes in mortality rates over time among counties, and geographic patterns differed by cause. Counties with the highest mortality rates were found primarily in central Appalachia for chronic obstructive pulmonary disease and pneumoconiosis; widely dispersed throughout the Southwest, northern Great Plains, New England, and South Atlantic for interstitial lung disease; along the southern half of the Mississippi River and in Georgia and South Carolina for asthma; and in southern states from Mississippi to South Carolina for other chronic respiratory diseases. Conclusions and Relevance Despite recent declines in mortality from chronic respiratory diseases, mortality rates in 2014 remained significantly higher than in 1980. Between 1980 and 2014, there were important differences in mortality rates and changes in mortality by county, sex, and particular chronic respiratory disease type. These estimates may be helpful for informing efforts to improve prevention, diagnosis, and treatment.

Importance The literature focuses on mortality among children younger than 5 years. Comparable information on nonfatal health outcomes among these children and the fatal and nonfatal burden of diseases and injuries among older children and adolescents is scarce.Objective To determine levels and trends in the fatal and nonfatal burden of diseases and injuries among younger children (aged Evidence Review Data from vital registration, verbal autopsy studies, maternal and child death surveillance, and other sources covering 14 244 site-years (ie, years of cause of death data by geography) from 1980 through 2013 were used to estimate cause-specific mortality. Data from 35 620 epidemiological sources were used to estimate the prevalence of the diseases and sequelae in the GBD 2013 study. Cause-specific mortality for most causes was estimated using the Cause of Death Ensemble Model strategy. For some infectious diseases (eg, HIV infection/AIDS, measles, hepatitis B) where the disease process is complex or the cause of death data were insufficient or unavailable, we used natural history models. For most nonfatal health outcomes, DisMod-MR 2.0, a Bayesian metaregression tool, was used to meta-analyze the epidemiological data to generate prevalence estimates.Findings Of the 7.7 (95% uncertainty interval [UI], 7.4-8.1) million deaths among children and adolescents globally in 2013, 6.28 million occurred among younger children, 0.48 million among older children, and 0.97 million among adolescents. In 2013, the leading causes of death were lower respiratory tract infections among younger children (905 059 deaths; 95% UI, 810 304-998 125), diarrheal diseases among older children (38 325 deaths; 95% UI, 30 365-47 678), and road injuries among adolescents (115 186 deaths; 95% UI, 105 185-124 870). Iron deficiency anemia was the leading cause of years lived with disability among children and adolescents, affecting 619 (95% UI, 618-621) million in 2013. Large between-country variations exist in mortality from leading causes among children and adolescents. Countries with rapid declines in all-cause mortality between 1990 and 2013 also experienced large declines in most leading causes of death, whereas countries with the slowest declines had stagnant or increasing trends in the leading causes of death. In 2013, Nigeria had a 12% global share of deaths from lower respiratory tract infections and a 38% global share of deaths from malaria. India had 33% of the world’s deaths from neonatal encephalopathy. Half of the world’s diarrheal deaths among children and adolescents occurred in just 5 countries: India, Democratic Republic of the Congo, Pakistan, Nigeria, and Ethiopia.Conclusions and Relevance Understanding the levels and trends of the leading causes of death and disability among children and adolescents is critical to guide investment and inform policies. Monitoring these trends over time is also key to understanding where interventions are having an impact. Proven interventions exist to prevent or treat the leading causes of unnecessary death and disability among children and adolescents. The findings presented here show that these are underused and give guidance to policy makers in countries where more attention is needed.

The differentiation of several T- and B-cell effector programs in the immune system is directed by signature transcription factors that induce rapid epigenetic remodelling. Here we report that promyelocytic leukaemia zinc finger (PLZF), the BTB-zinc finger (BTB-ZF) transcription factor directing the innate-like effector program of natural killer T-cell thymocytes, is prominently associated with cullin 3 (CUL3), an E3 ubiquitin ligase previously shown to use BTB domain-containing proteins as adaptors for substrate binding. PLZF transports CUL3 to the nucleus, where the two proteins are associated within a chromatin-modifying complex. Furthermore, PLZF expression results in selective ubiquitination changes of several components of this complex. CUL3 was also found associated with the BTB-ZF transcription factor BCL6, which directs the germinal-centre B cell and follicular T-helper cell programs. Conditional CUL3 deletion in mice demonstrated an essential role for CUL3 in the development of PLZF- and BCL6-dependent lineages. We conclude that distinct lineage-specific BTB-ZF transcription factors recruit CUL3 to alter the ubiquitination pattern of their associated chromatin-modifying complex. We propose that this new function is essential to direct the differentiation of several T- and B-cell effector programs, and may also be involved in the oncogenic role of PLZF and BCL6 in leukaemias and lymphomas.