Quantifying the Cost of Shigella Diarrhea in the Enterics for Global Health (EFGH) Shigella Surveillance Study.

Background: Comparative costs of public health interventions provide valuable data for decision making. However, the availability of comprehensive and context-specific costs is often limited. The Enterics for Global Health (EFGH) Shigella surveillance study-a facility-based diarrhea surveillance study across 7 countries-aims to generate evidence on health system and household costs associated with medically attended Shigella diarrhea in children. Methods: EFGH working groups comprising representatives from each country (Bangladesh, Kenya, Malawi, Mali, Pakistan, Peru, and The Gambia) developed the study methods. Over a 24-month surveillance period, facility-based surveys will collect data on resource use for the medical treatment of an estimated 9800 children aged 6-35 months with diarrhea. Through these surveys, we will describe and quantify medical resources used in the treatment of diarrhea (eg, medication, supplies, and provider salaries), nonmedical resources (eg, travel costs to the facility), and the amount of caregiver time lost from work to care for their sick child. To assign costs to each identified resource, we will use a combination of caregiver interviews, national medical price lists, and databases from the World Health Organization and the International Labor Organization. Our primary outcome will be the estimated cost per inpatient and outpatient episode of medically attended Shigella diarrhea treatment across countries, levels of care, and illness severity. We will conduct sensitivity and scenario analysis to determine how unit costs vary across scenarios. Conclusions: Results from this study will contribute to the existing body of literature on diarrhea costing and inform future policy decisions related to investments in preventive strategies for Shigella.

Identifying opportunities to optimize mass drug administration for soil-transmitted helminths: A visualization and descriptive analysis using process mapping.

BACKGROUND: The control of soil-transmitted helminths (STH) is achieved through mass drug administration (MDA) with deworming medications targeting children and other high-risk groups. Recent evidence suggests that it may be possible to interrupt STH transmission by deworming individuals of all ages via community-wide MDA (cMDA). However, a change in delivery platforms will require altering implementation processes. METHODS: We used process mapping, an operational research methodology, to describe the activities required for effective implementation of school-based and cMDA in 18 heterogenous areas and over three years in Benin, India, and Malawi. Planned activities were identified during workshops prior to initiation of a large cMDA trial (the DeWorm3 trial). The process maps were updated annually post-implementation, including adding or removing activities (e.g., adaptations) and determining whether activities occurred according to plan. Descriptive analyses were performed to quantify differences and similarities at baseline and over three implementation years. Comparative analyses were also conducted between study sites and areas implementing school-based vs. cMDA. Digitized process maps were developed to provide a visualization of MDA processes and inspected to identify implementation bottlenecks and inefficient activity flows. RESULTS: Across three years and all clusters, implementation of cMDA required an average of 13 additional distinct activities and was adapted more often (5.2 adaptations per year) than school-based MDA. An average of 41% of activities across both MDA platforms did not occur according to planned timelines; however, deviations were often purposeful to improve implementation efficiency or effectiveness. Visualized process maps demonstrated that receipt of drugs at the local level may be an implementation bottleneck. Many activities rely on the effective setting of MDA dates and estimating quantity of drugs, suggesting that the timing of these activities is important to meet planned programmatic outcomes. CONCLUSION: Implementation processes were heterogenous across settings, suggesting that MDA is highly context and resource dependent and that there are many viable ways to implement MDA. Process mapping could be deployed to support a transition from a school-based control program to community-wide STH transmission interruption program and potentially to enable integration with other community-based campaigns. TRIAL REGISTRATION: NCT03014167.

Overestimation of school-based deworming coverage resulting from school-based reporting.

BACKGROUND: Soil Transmitted Helminths (STH) infect over 1.5 billion people globally and are associated with anemia and stunting, resulting in an annual toll of 1.9 million Disability-Adjusted Life Years (DALYs). School-based deworming (SBD), via mass drug administration (MDA) campaigns with albendazole or mebendazole, has been recommended by the World Health Organization to reduce levels of morbidity due to STH in endemic areas. DeWorm3 is a cluster-randomized trial, conducted in three study sites in Benin, India, and Malawi, designed to assess the feasibility of interrupting STH transmission with community-wide MDA as a potential strategy to replace SBD. This analysis examines data from the DeWorm3 trial to quantify discrepancies between school-level reporting of SBD and gold standard individual-level survey reporting of SBD. METHODOLOGY/PRINCIPAL FINDINGS: Population-weighted averages of school-level SBD calculated at the cluster level were compared to aggregated individual-level SBD estimates to produce a Mean Squared Error (MSE) estimate for each study site. In order to estimate individual-level SBD coverage, these MSE values were applied to SBD estimates from the control arm of the DeWorm3 trial, where only school-level reporting of SBD coverage had been collected. In each study site, SBD coverage in the school-level datasets was substantially higher than that obtained from individual-level datasets, indicating possible overestimation of school-level SBD coverage. When applying observed MSE to project expected coverages in the control arm, SBD coverage dropped from 89.1% to 70.5% (p-value < 0.001) in Benin, from 97.7% to 84.5% (p-value < 0.001) in India, and from 41.5% to 37.5% (p-value < 0.001) in Malawi. CONCLUSIONS/SIGNIFICANCE: These estimates indicate that school-level SBD reporting is likely to significantly overestimate program coverage. These findings suggest that current SBD coverage estimates derived from school-based program data may substantially overestimate true pediatric deworming coverage within targeted communities. TRIAL REGISTRATION: NCT03014167.

Introduction of the Ellavi uterine balloon tamponade into the Kenyan and Ghanaian maternal healthcare package for improved postpartum haemorrhage management: an implementation research study.

OBJECTIVES: Use of intrauterine balloon tamponades for refractory postpartum haemorrhage (PPH) management has triggered recent debate since effectiveness studies have yielded conflicting results. Implementation research is needed to identify factors influencing successful integration into maternal healthcare packages. The Ellavi uterine balloon tamponade (UBT) (Ellavi) is a new low-cost, preassembled device for treating refractory PPH. DESIGN: A mixed-methods, prospective, implementation research study examining the adoption, sustainability, fidelity, acceptability and feasibility of introducing a newly registered UBT. Cross-sectional surveys were administered post-training and post-use over 10 months. SETTING: Three Ghanaian (district, regional) and three Kenyan (levels 4-6) healthcare facilities. PARTICIPANTS: Obstetric staff (n=451) working within participating facilities. INTERVENTION: PPH management training courses were conducted with obstetric staff. PRIMARY AND SECONDARY OUTCOME MEASURES: Facility measures of adoption, sustainability and fidelity and individual measures of acceptability and feasibility. RESULTS: All participating hospitals adopted the device during the study period and the majority (52%-62%) of the employed obstetric staff were trained on the Ellavi; sustainability and fidelity to training content were moderate. The Ellavi was suited for this context due to high delivery and PPH burden. Dynamic training curriculums led by local UBT champions and clear instructions on the packaging yielded positive attitudes and perceptions, and high user confidence, resulting in overall high acceptability. Post-training and post-use, ≥79% of the trainees reported that the Ellavi was easy to use. Potential barriers to use included the lack of adjustable drip stands and difficulties calculating bag height according to blood pressure. Overall, the Ellavi can be feasibly integrated into PPH care and was preferred over condom catheters. CONCLUSIONS: The training package and time saving Ellavi design facilitated its adoption, acceptability and feasibility. The Ellavi is appropriate and feasible for use among obstetric staff and can be successfully integrated into the Kenyan and Ghanaian maternal healthcare package. TRIAL REGISTRATION NUMBERS: NCT04502173; NCT05340777.

Contraceptive self-injection through routine service delivery: Health worker perspectives from Uganda.

Self-care reproductive health innovations are increasingly valued as practices that enable women to manage their fertility with greater autonomy. While self-care, by definition, takes place beyond the clinic walls, many self-care practices nonetheless require initial or follow up visits to a health worker. Access to self-care hinges on the extent to which health care workers who serve as gatekeepers find the innovation appropriate and practical. Self-injection of subcutaneous depot medroxyprogesterone acetate (DMPA-SC) is being introduced and scaled in many countries. In late 2018, health workers in Uganda began offering self-injection of DMPA-SC in the public sector, and this study examines health workers' views on the acceptability and feasibility of training women to self-inject. We conducted in-person interviews with 120 health workers active in the self-injection program to better understand provider practices, program satisfaction, and their views on feasibility. A subset of 77 health workers participated in in-depth interviews. Quantitative data was analyzed using Stata (v14) software, and chi square and student t tests used to measure between group differences. Qualitative data was analyzed using Atlas.ti, employing an iterative coding process, to identify key themes that resonated. The majority of health workers were very satisfied with the self-injection program and reported it was moderately easy to integrate self-injection training into routine service delivery. They identified lack of time to train clients in the clinic setting, lack of materials among community health workers, and client fear of self-injection as key challenges. Community health workers were less likely to report time challenges and indicated higher levels of satisfaction and greater ease in offering self-injection services. The relatively high acceptability of the self-injection program among health workers is promising; however, strategies to overcome feasibility challenges, such as workload constraints that limit the ability to offer self-injection training, are needed to expand service delivery to more women interested in this new self-care innovation. As self-injection programs are introduced and scaled across settings, there is a need for evidence regarding how self-care innovations can be designed and implemented in ways that are practical for health workers, while optimizing women's successful adoption and use.

Contraceptive self-injection through routine service delivery: Experiences of Ugandan women in the public health system.

Contraceptive self-injection (SI) is a new self-care practice with potential to transform women's family planning access by putting a popular method, injectable contraception, directly into the hands of users. Research shows that SI is feasible and acceptable; evidence regarding how to design and implement SI programs under real-world conditions is still needed. This evaluation examined women's experiences when self-injection of subcutaneous depot medroxyprogesterone acetate (DMPA-SC) was introduced in Uganda alongside other contraceptive options in the context of informed choice. We conducted structured survey interviews with 958 randomly selected SI clients trained in three districts in 2019. SI clients demonstrated their injection technique on a model to permit an assessment of injection proficiency. A randomly selected subset of 200 were re-interviewed 10-17 months post-training to understand resupply experiences, waste disposal practices and continuation. Finally, we conducted survey interviews with a random sample of 200 clients who participated in training but declined to self-inject. Data were analyzed using Stata IC/14.2. Differences between groups were measured using chi square and t-tests. Multivariate analyses predicting injection proficiency and SI adoption employed mixed effects logistic regression. Nearly three quarters of SI clients (73%) were able to demonstrate injection proficiency without additional instruction from a provider. Years of education, having received a complete training, practicing, and taking home a job aid were associated with higher odds of proficiency. Self-reported satisfaction and continuation were high, with 93% reinjecting independently 3 months post-training. However, a substantial share of those trained opted not to self-inject. Being single, having a partner supportive of family planning use, training with a job aid, practicing, witnessing a demonstration and exposure to a full training were associated with higher odds of becoming an SI client; conversely, those trained in a group had reduced odds of becoming an SI client. The self-care program was successful for the majority of women who became self-injectors, enabling most women to demonstrate SI proficiency. Nearly all those who opted to self-inject reinjected independently, and the majority continued self-injecting for at least 1 year. Additional research should identify strategies to facilitate adoption by women who wish to self-inject but face challenges.

Costs of community-wide mass drug administration and school-based deworming for soil-transmitted helminths: evidence from a randomised controlled trial in Benin, India and Malawi.

OBJECTIVES: Current guidelines for the control of soil-transmitted helminths (STH) recommend deworming children and other high-risk groups, primarily using school-based deworming (SBD) programmes. However, targeting individuals of all ages through community-wide mass drug administration (cMDA) may interrupt STH transmission in some settings. We compared the costs of cMDA to SBD to inform decision-making about future updates to STH policy. DESIGN: We conducted activity-based microcosting of cMDA and SBD for 2 years in Benin, India and Malawi within an ongoing cMDA trial. SETTING: Field sites and collaborating research institutions. PRIMARY AND SECONDARY OUTCOMES: We calculated total financial and opportunity costs and costs per treatment administered (unit costs in 2019 USD ($)) from the service provider perspective, including costs related to community drug distributors and other volunteers. RESULTS: On average, cMDA unit costs were more expensive than SBD in India ($1.17 vs $0.72) and Malawi ($2.26 vs $1.69), and comparable in Benin ($2.45 vs $2.47). cMDA was more expensive than SBD in part because most costs (~60%) were 'supportive costs' needed to deliver treatment with high coverage, such as additional supervision and electronic data capture. A smaller fraction of cMDA costs (~30%) was routine expenditures (eg, drug distributor allowances). The remaining cMDA costs (~10%) were opportunity costs of staff and volunteer time. A larger percentage of SBD costs was opportunity costs for teachers and other government staff (between ~25% and 75%). Unit costs varied over time and were sensitive to the number of treatments administered. CONCLUSIONS: cMDA was generally more expensive than SBD. Accounting for local staff time (volunteers, teachers, health workers) in community programmes is important and drives higher cost estimates than commonly recognised in the literature. Costs may be lower outside of a trial setting, given a reduction in supportive costs used to drive higher treatment coverage and economies of scale. TRIAL REGISTRATION NUMBER: NCT03014167.

Trends and patterns of disparities in diabetes and chronic kidney disease mortality among US counties, 1980-2014.

INTRODUCTION: Diabetes and chronic kidney diseases are associated with a large health burden in the USA and globally. OBJECTIVE: To estimate age-standardized mortality rates by county from diabetes mellitus and chronic kidney disease. DESIGN AND SETTING: Validated small area estimation models were applied to de-identified death records from the National Center for Health Statistics (NCHS) and population counts from the census bureau, NCHS, and the Human Mortality Database to estimate county-level mortality rates from 1980 to 2014 from diabetes mellitus and chronic kidney disease (CKD). EXPOSURES: County of residence. MAIN OUTCOMES AND MEASURES: Age-standardized mortality rates by county, year, sex, and cause. RESULTS: Between 1980 and 2014, 2,067,805 deaths due to diabetes were recorded in the USA. The mortality rate due to diabetes increased by 33.6% (95% UI: 26.5%-41.3%) between 1980 and 2000 and then declined by 26.4% (95% UI: 22.8%-30.0%) between 2000 and 2014. Counties with very high mortality rates were found along the southern half of the Mississippi river and in parts of South and North Dakota, while very low rates were observed in central Colorado, and select counties in the Midwest, California, and southern Florida. A total of 1,659,045 deaths due to CKD were recorded between 1980 and 2014 (477,332 due to diabetes mellitus, 1,056,150 due to hypertension, 122,795 due to glomerulonephritis, and 2,768 due to other causes). CKD mortality varied among counties with very low mortality rates observed in central Colorado as well as some counties in southern Florida, California, and Great Plains states. High mortality rates from CKD were observed in counties throughout much of the Deep South, and a cluster of counties with particularly high rates was observed around the Mississippi river. CONCLUSIONS AND RELEVANCE: This study found large inequalities in diabetes and CKD mortality among US counties. The findings provide insights into the root causes of this variation and call for improvements in risk factors, access to medical care, and quality of medical care.

Costing interventions in the field: preliminary cost estimates and lessons learned from an evaluation of community-wide mass drug administration for elimination of soil-transmitted helminths in the DeWorm3 trial.

OBJECTIVE: To present a costing study integrated within the DeWorm3 multi-country field trial of community-wide mass drug administration (cMDA) for elimination of soil-transmitted helminths. DESIGN: Tailored data collection instruments covering resource use, expenditure and operational details were developed for each site. These were populated alongside field activities by on-site staff. Data quality control and validation processes were established. Programmed routines were used to clean, standardise and analyse data to derive costs of cMDA and supportive activities. SETTING: Field site and collaborating research institutions. PRIMARY AND SECONDARY OUTCOME MEASURES: A strategy for costing interventions in parallel with field activities was discussed. Interim estimates of cMDA costs obtained with the strategy were presented for one of the trial sites. RESULTS: The study demonstrated that it was both feasible and advantageous to collect data alongside field activities. Practical decisions on implementing the strategy and the trade-offs involved varied by site; trialists and local partners were key to tailoring data collection to the technical and operational realities in the field. The strategy capitalised on the established processes for routine financial reporting at sites, benefitted from high recall and gathered operational insight that facilitated interpretation of the estimates derived. The methodology produced granular costs that aligned with the literature and allowed exploration of relevant scenarios. In the first year of the trial, net of drugs, the incremental financial cost of extending deworming of school-aged children to the whole community in India site averaged US$1.14 (USD, 2018) per person per round. A hypothesised at-scale routine implementation scenario yielded a much lower estimate of US$0.11 per person treated per round. CONCLUSIONS: We showed that costing interventions alongside field activities offers unique opportunities for collecting rich data to inform policy toward optimising health interventions and for facilitating transfer of economic evidence from the field to the programme. TRIAL REGISTRATION NUMBER: NCT03014167; Pre-results.

Cost-effectiveness of self-injected DMPA-SC compared with health-worker-injected DMPA-IM in Senegal.

OBJECTIVES: To evaluate the cost-effectiveness of self-injected subcutaneous depot medroxyprogesterone acetate (DMPA-SC) compared to health-worker-administered intramuscular DMPA (DMPA-IM) in Senegal and to assess how including practice or demonstration injections in client self-injection training affects estimates. STUDY DESIGN: We developed a decision-tree model with a 12-month time horizon for a hypothetical cohort of 100,000 injectable contraceptive users in Senegal. We used the model to estimate incremental costs per disability-adjusted life year (DALY) averted. The analysis derived model inputs from DMPA-SC self-injection continuation and costing research studies and peer-reviewed literature. We evaluated the cost-effectiveness from societal and health system perspectives and conducted one-way and probabilistic sensitivity analyses to test the robustness of results. RESULTS: Compared to health-worker-administered DMPA-IM, self-injected DMPA-SC could prevent 1402 additional unintended pregnancies and avert 204 maternal DALYs per year for this hypothetical cohort. From a societal perspective, self-injection costs less than health worker administration regardless of the training approach and is therefore dominant. From the health system perspective, self-injection is dominant compared to health worker administration if a one-page instruction sheet is used and one additional DMPA-SC unit is used for training and is cost-effective at $208 per DALY averted when two additional DMPA-SC units are used. Sensitivity analysis showed estimates were robust. CONCLUSIONS: Self-injected DMPA-SC averted more pregnancies and DALYs and cost less from the societal perspective compared to health-worker-administered DMPA-IM and hence is dominant. Using fewer DMPA-SC units for practice or demonstration improves cost-effectiveness of self-injection from the health system perspective. IMPLICATIONS: Evidence from Senegal shows that self-injection of DMPA-SC can be dominant or cost-effective from both health system and societal perspectives relative to DMPA-IM from health workers even if women practice injecting or health workers demonstrate with one or two DMPA-SC units. Evidence on whether practice or demonstration is required for client training would be useful.

Is contraceptive self-injection cost-effective compared to contraceptive injections from facility-based health workers? Evidence from Uganda.

OBJECTIVE: To assess the cost-effectiveness of self-injected subcutaneous depot medroxyprogesterone acetate (DMPA-SC) compared to health-worker-administered intramuscular DMPA (DMPA-IM) in Uganda. STUDY DESIGN: We developed a decision-tree model with a 12-month time horizon for a hypothetical cohort of approximately 1 million injectable contraceptive users in Uganda to estimate the incremental costs per pregnancy averted and per disability-adjusted life year (DALY) averted. The study design derived model inputs from DMPA-SC self-injection continuation and costing research studies and peer-reviewed literature. We calculated incremental cost-effectiveness ratios from societal and health system perspectives and conducted one-way and probabilistic sensitivity analyses to test the robustness of results. RESULTS: Self-injected DMPA-SC could prevent 10,827 additional unintended pregnancies and 1620 maternal DALYs per year for this hypothetical cohort compared to DMPA-IM administered by facility-based health workers. Due to savings in women's time and travel costs, under a societal perspective, self-injection could save approximately US$1 million or $84,000 per year, depending on the self-injection training aid used. From a health system perspective, self-injection would avert more pregnancies but incur additional costs. A training approach using a one-page client instruction sheet would make self-injection cost-effective compared to DMPA-IM, with incremental costs per pregnancy averted of $15 and per maternal DALY averted of $98. Sensitivity analysis showed that the estimates were robust. The one-way and probabilistic sensitivity analyses showed that the costs of the first visit for self-injection (which include training costs) were an important variable impacting the cost-effectiveness estimates. CONCLUSIONS: Under a societal perspective, self-injected DMPA-SC averted more pregnancies and cost less compared to health-worker-administered DMPA-IM. Under a health system perspective, self-injected DMPA-SC can be cost-effective relative to DMPA-IM when a lower-cost visual aid for client training is used. IMPLICATIONS: Self-injection has economic benefits for women through savings in time and travel costs, and it averts additional pregnancies and maternal disability-adjusted life years compared to health-worker-administered injectable DMPA-IM. Implementing lower-cost approaches to client training can help ensure that self-injection is also cost-effective from a health system perspective.

Costs of administering injectable contraceptives through health workers and self-injection: evidence from Burkina Faso, Uganda, and Senegal.

OBJECTIVE: To evaluate the 12-month total direct costs (medical and nonmedical) of delivering subcutaneous depot medroxyprogesterone acetate (DMPA-SC) under three strategies - facility-based administration, community-based administration and self-injection - compared to the costs of delivering intramuscular DMPA (DMPA-IM) via facility- and community-based administration. STUDY DESIGN: We conducted four cross-sectional microcosting studies in three countries from December 2015 to January 2017. We estimated direct medical costs (i.e., costs to health systems) using primary data collected from 95 health facilities on the resources used for injectable contraceptive service delivery. For self-injection, we included both costs of the actual research intervention and adjusted programmatic costs reflecting a lower-cost training aid. Direct nonmedical costs (i.e., client travel and time costs) came from client interviews conducted during injectable continuation studies. All costs were estimated for one couple year of protection. One-way sensitivity analyses identified the largest cost drivers. RESULTS: Total costs were lowest for community-based distribution of DMPA-SC (US$7.69) and DMPA-IM ($7.71) in Uganda. Total costs for self-injection before adjustment of the training aid were $9.73 (Uganda) and $10.28 (Senegal). After adjustment, costs decreased to $7.83 (Uganda) and $8.38 (Senegal) and were lower than the costs of facility-based administration of DMPA-IM ($10.12 Uganda, $9.46 Senegal). Costs were highest for facility-based administration of DMPA-SC ($12.14) and DMPA-IM ($11.60) in Burkina Faso. Across all studies, direct nonmedical costs were lowest for self-injecting women. CONCLUSIONS: Community-based distribution and self-injection may be promising channels for reducing injectable contraception delivery costs. We observed no major differences in costs when administering DMPA-SC and DMPA-IM under the same strategy. IMPLICATIONS: Designing interventions to bring contraceptive service delivery closer to women may reduce barriers to contraceptive access. Community-based distribution of injectable contraception reduces direct costs of service delivery. Compared to facility-based health worker administration, self-injection brings economic benefits for women and health systems, especially with a lower-cost client training aid.

Trends and Patterns of Geographic Variation in Mortality From Substance Use Disorders and Intentional Injuries Among US Counties, 1980-2014.

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.

Trends and Patterns of Differences in Infectious Disease Mortality Among US Counties, 1980-2014.

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.

Variation in life expectancy and mortality by cause among neighbourhoods in King County, WA, USA, 1990-2014: a census tract-level analysis for the Global Burden of Disease Study 2015.

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.

Local, national, and regional viral haemorrhagic fever pandemic potential in Africa: a multistage analysis.

BACKGROUND: Predicting when and where pathogens will emerge is difficult, yet, as shown by the recent Ebola and Zika epidemics, effective and timely responses are key. It is therefore crucial to transition from reactive to proactive responses for these pathogens. To better identify priorities for outbreak mitigation and prevention, we developed a cohesive framework combining disparate methods and data sources, and assessed subnational pandemic potential for four viral haemorrhagic fevers in Africa, Crimean-Congo haemorrhagic fever, Ebola virus disease, Lassa fever, and Marburg virus disease. METHODS: In this multistage analysis, we quantified three stages underlying the potential of widespread viral haemorrhagic fever epidemics. Environmental suitability maps were used to define stage 1, index-case potential, which assesses populations at risk of infection due to spillover from zoonotic hosts or vectors, identifying where index cases could present. Stage 2, outbreak potential, iterates upon an existing framework, the Index for Risk Management, to measure potential for secondary spread in people within specific communities. For stage 3, epidemic potential, we combined local and international scale connectivity assessments with stage 2 to evaluate possible spread of local outbreaks nationally, regionally, and internationally. FINDINGS: We found epidemic potential to vary within Africa, with regions where viral haemorrhagic fever outbreaks have previously occurred (eg, western Africa) and areas currently considered non-endemic (eg, Cameroon and Ethiopia) both ranking highly. Tracking transitions between stages showed how an index case can escalate into a widespread epidemic in the absence of intervention (eg, Nigeria and Guinea). Our analysis showed Chad, Somalia, and South Sudan to be highly susceptible to any outbreak at subnational levels. INTERPRETATION: Our analysis provides a unified assessment of potential epidemic trajectories, with the aim of allowing national and international agencies to pre-emptively evaluate needs and target resources. Within each country, our framework identifies at-risk subnational locations in which to improve surveillance, diagnostic capabilities, and health systems in parallel with the design of policies for optimal responses at each stage. In conjunction with pandemic preparedness activities, assessments such as ours can identify regions where needs and provisions do not align, and thus should be targeted for future strengthening and support. FUNDING: Paul G Allen Family Foundation, Bill & Melinda Gates Foundation, Wellcome Trust, UK Department for International Development.

Trends and Patterns of Differences in Chronic Respiratory Disease Mortality Among US Counties, 1980-2014.

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.

Mapping under-5 and neonatal mortality in Africa, 2000-15: a baseline analysis for the Sustainable Development Goals.

BACKGROUND: During the Millennium Development Goal (MDG) era, many countries in Africa achieved marked reductions in under-5 and neonatal mortality. Yet the pace of progress toward these goals substantially varied at the national level, demonstrating an essential need for tracking even more local trends in child mortality. With the adoption of the Sustainable Development Goals (SDGs) in 2015, which established ambitious targets for improving child survival by 2030, optimal intervention planning and targeting will require understanding of trends and rates of progress at a higher spatial resolution. In this study, we aimed to generate high-resolution estimates of under-5 and neonatal all-cause mortality across 46 countries in Africa. METHODS: We assembled 235 geographically resolved household survey and census data sources on child deaths to produce estimates of under-5 and neonatal mortality at a resolution of 5 × 5 km grid cells across 46 African countries for 2000, 2005, 2010, and 2015. We used a Bayesian geostatistical analytical framework to generate these estimates, and implemented predictive validity tests. In addition to reporting 5 × 5 km estimates, we also aggregated results obtained from these estimates into three different levels-national, and subnational administrative levels 1 and 2-to provide the full range of geospatial resolution that local, national, and global decision makers might require. FINDINGS: Amid improving child survival in Africa, there was substantial heterogeneity in absolute levels of under-5 and neonatal mortality in 2015, as well as the annualised rates of decline achieved from 2000 to 2015. Subnational areas in countries such as Botswana, Rwanda, and Ethiopia recorded some of the largest decreases in child mortality rates since 2000, positioning them well to achieve SDG targets by 2030 or earlier. Yet these places were the exception for Africa, since many areas, particularly in central and western Africa, must reduce under-5 mortality rates by at least 8·8% per year, between 2015 and 2030, to achieve the SDG 3.2 target for under-5 mortality by 2030. INTERPRETATION: In the absence of unprecedented political commitment, financial support, and medical advances, the viability of SDG 3.2 achievement in Africa is precarious at best. By producing under-5 and neonatal mortality rates at multiple levels of geospatial resolution over time, this study provides key information for decision makers to target interventions at populations in the greatest need. In an era when precision public health increasingly has the potential to transform the design, implementation, and impact of health programmes, our 5 × 5 km estimates of child mortality in Africa provide a baseline against which local, national, and global stakeholders can map the pathways for ending preventable child deaths by 2030. FUNDING: Bill & Melinda Gates Foundation.

Trends and Patterns of Geographic Variation in Cardiovascular Mortality Among US Counties, 1980-2014.

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.

Inequalities in Life Expectancy Among US Counties, 1980 to 2014: Temporal Trends and Key Drivers.

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.