The economic costs of orthopaedic services: a health system cost analysis of tertiary hospitals in a low-income country.

BACKGROUND: Traumatic injuries are rising globally, disproportionately affecting low- and middle-income countries, constituting 88% of the burden of surgically treatable conditions. While contributing to the highest burden, LMICs also have the least availability of resources to address this growing burden effectively. Studies on the cost-of-service provision in these settings have concentrated on the most common traumatic injuries, leaving an evidence gap on other traumatic injuries. This study aimed to address the gap in understanding the cost of orthopaedic services in low-income settings by conducting a comprehensive costing analysis in two tertiary-level hospitals in Malawi. METHODS: We used a mixed costing methodology, utilising both Top-Down and Time-Driven Activity-Based Costing approaches. Data on resource utilisation, personnel costs, medicines, supplies, capital costs, laboratory costs, radiology service costs, and overhead costs were collected for one year, from July 2021 to June 2022. We conducted a retrospective review of all the available patient files for the period under review. Assumptions on the intensity of service use were based on utilisation patterns observed in patient records. All costs were expressed in 2021 United States Dollars. RESULTS: We conducted a review of 2,372 patient files, 72% of which were male. The median length of stay for all patients was 9.5 days (8-11). The mean weighted cost of treatment across the entire pathway varied, ranging from $195 ($136-$235) for Supracondylar Fractures to $711 ($389-$931) for Proximal Ulna Fractures. The main cost components were personnel (30%) and medicines and supplies (23%). Within diagnosis-specific costs, the length of stay was the most significant cost driver, contributing to the substantial disparity in treatment costs between the two hospitals. CONCLUSION: This study underscores the critical role of orthopaedic care in LMICs and the need for context-specific cost data. It highlights the variation in cost drivers and resource utilisation patterns between hospitals, emphasising the importance of tailored healthcare planning and resource allocation approaches. Understanding the costs of surgical interventions in LMICs can inform policy decisions and improve access to essential orthopaedic services, potentially reducing the disease burden associated with trauma-related injuries. We recommend that future studies focus on evaluating the cost-effectiveness of orthopaedic interventions, particularly those that have not been analysed within the existing literature.

Premature Death as a Normative Concept.

The practical goal of preventing premature death seems uncontroversial. But the term 'premature death' is vague with several, sometimes conflicting definitions. This ambiguity results in several conceptions with which not all will agree. Moreover, the normative rationale behind the goal of preventing premature deaths is masked by the operational definition of existing measures. In this article, we argue that 'premature death' should be recognized as a normative concept. We propose that normative theories should be used to justify measures of premature death to provide them with normative validity and public legitimacy.

Criteria for the procedural fairness of health financing decisions: a scoping review.

Due to constraints on institutional capacity and financial resources, the road to universal health coverage (UHC) involves difficult policy choices. To assist with these choices, scholars and policy makers have done extensive work on criteria to assess the substantive fairness of health financing policies: their impact on the distribution of rights, duties, benefits and burdens on the path towards UHC. However, less attention has been paid to the procedural fairness of health financing decisions. The Accountability for Reasonableness Framework (A4R), which is widely applied to assess procedural fairness, has primarily been used in priority-setting for purchasing decisions, with revenue mobilization and pooling receiving limited attention. Furthermore, the sufficiency of the A4R framework's four criteria (publicity, relevance, revisions and appeals, and enforcement) has been questioned. Moreover, research in political theory and public administration (including deliberative democracy), public finance, environmental management, psychology, and health financing has examined the key features of procedural fairness, but these insights have not been synthesized into a comprehensive set of criteria for fair decision-making processes in health financing. A systematic study of how these criteria have been applied in decision-making situations related to health financing and in other areas is also lacking. This paper addresses these gaps through a scoping review. It argues that the literature across many disciplines can be synthesized into 10 core criteria with common philosophical foundations. These go beyond A4R and encompass equality, impartiality, consistency over time, reason-giving, transparency, accuracy of information, participation, inclusiveness, revisability and enforcement. These criteria can be used to evaluate and guide decision-making processes for financing UHC across different country income levels and health financing arrangements. The review also presents examples of how these criteria have been applied to decisions in health financing and other sectors.

The Role of HTA for Essential Health Benefit Package Design in Low or Middle-Income Countries.

This Commentary explores the relationship between Health Technology Assessment (HTA) and Health Benefits Package (HBP) design to achieve Universal Health Coverage (UHC) in low- and middle-income countries. It emphasizes that while HTA evaluates individual healthcare interventions, HBP reform aims to create comprehensive service sets considering overall population health needs and available resources. Challenges in LMICs include limited local data and technical capacity, leading to reliance on cost-effectiveness estimates from other settings. We suggest a practical approach by combining HTA and HBP elements through a hybrid or compartmentalized method. This approach sets differentiated cost-effectiveness thresholds for specific healthcare platforms or programs (e.g., primary care or essential surgery), aligning priority-setting with organizational considerations, ethics, and implementation strategies. Strong institutions and academic support are vital for evidence-informed priority-setting processes. In summary, HTA can play a pivotal role in designing HBPs for UHC in LMICs, and a compartmentalized approach can enhance priority-setting while considering budget constraints and equity.

The use of cost-effectiveness analysis for health benefit package design - should countries follow a sectoral, incremental or hybrid approach?

BACKGROUND: Countries around the world are increasingly rethinking the design of their health benefit package to achieve universal health coverage. Countries can periodically revise their packages on the basis of sectoral cost-effectiveness analyses, i.e. by evaluating a broad set of services against a 'doing nothing' scenario using a budget constraint. Alternatively, they can use incremental cost-effectiveness analyses, i.e. to evaluate specific services against current practice using a threshold. In addition, countries may employ hybrid approaches which combines elements of sectoral and incremental cost-effectiveness analysis - a country may e.g. not evaluate the comprehensive set of all services but rather relatively small sets of services targeting a certain condition. However, there is little practical guidance for countries as to which kind of approach they should follow. METHODS: The present study was based on expert consultation. We refined the typology of approaches of cost-effectiveness analysis for benefit package design, identified factors that should be considered in the choice of approach, and developed recommendations. We reached consensus among experts over the course of several review rounds. RESULTS: Sectoral cost-effectiveness analysis is especially suited in contexts with large allocative inefficiencies in current service provision and can, in theory, realize large efficiency gains. However, it may be challenging to implement a comprehensive redesign of the package in practice. Incremental cost-effectiveness analysis is especially relevant in contexts where specific new services may impact the sustainability of the health system. It may potentially support efficiency improvement, but its focus has typically been on new services while existing inefficiencies remain unchallenged. The use of hybrid approach may be a way forward to address the strengths and weaknesses of sectoral and incremental analysis areas. Such analysis may be especially useful to target disease areas with suspected high inefficiencies in service provision, and would then make good use of the available research capacity and be politically rewarding. However, disease-specific analyses bear the risk of not addressing resource allocation inefficiencies across disease areas. CONCLUSIONS: Countries should carefully select their approach of cost-effectiveness analyses for benefit package design, based on their decision-making context.

Incidence and determinants of out-of-pocket health expenditure in Ethiopia 2012-16.

This study assesses the incidence of catastrophic health expenditure (CHE) and identifies the significant factors that expose households to higher levels of out-of-pocket (OOP) health expenditure. Data from the fifth and the sixth Ethiopian National Health Accounts household surveys, which were conducted in 2012-13 and 2015-16, respectively, are used. The incidence of CHE is estimated using both the capacity-to-pay and the budget share approaches. To ensure the robustness of our findings, both unconditional and conditional quantile estimators are adopted as multivariate regression techniques to estimate the impact of socio-economic variables on the distribution of households' OOP expenditure. Our findings show that the incidence of CHE in Ethiopia ranges from 1.7% to 4.7% depending on the approach and the threshold adopted. Larger families, the unemployed, the extremely poor, those who seek care at private-owned providers and families with members affected by chronic illness face higher OOP expenditure. Hence, policy should target those with these identified socio-economic characteristics in the provision of financial risk protection such as fee waiver systems and subsidies.

Can Geographically Targeted Vaccinations Be Ethically Justified? The Case of Norway During the COVID-19 Pandemic.

This article discusses the fairness of geographically targeted vaccinations (GTVs). During the initial period of local and global vaccine scarcity, health authorities had to enact priority-setting strategies for mass vaccination campaigns against COVID-19. These strategies have in common that priority setting was based on personal characteristics, such as age, health status or profession. However, in 2021, an alternative to this strategy was employed in some countries, particularly Norway. In these countries, vaccine allocation was also based on the epidemiological situations in different regions, and vaccines were assigned based on local incidence rates. The aim of this article is to describe and examine how a geographical allocation mechanism may work by considering Norway as a case study and discuss what ethical issues may arise in this type of priority setting. We explain three core concepts: priority setting, geographical priority setting and GTVs. With a particular focus on Norway, we discuss the potential effects of GTV, the public perception of such a strategy, and if GTV can be considered a fair strategy. We conclude that the most reasonable defence of GTV seems to be through a consequentialist account that values both total health outcomes and more equal outcomes.

Distributional impact of infectious disease interventions in the Ethiopian Essential Health Service Package: a modelling study.

OBJECTIVES: Reducing inequalities in health and financial risk are key goals on the path toward universal health coverage, particularly in low-income and middle-income countries. The design of the health benefit package creates an opportunity to select interventions through established criteria. The aim of this study is to examine the health equity and financial protection impact of selected interventions, along with their costs, at the national level in Ethiopia. DESIGN: Distributional cost-effectiveness analysis. POPULATION: The eligible population for all selected interventions is assumed to be 10 million. DATA SOURCES: Data on disease prevalence and population size were gathered from the Global Burden of Disease database, and average health benefits and program costs are sourced from the Ethiopian Essential Health Service Package (EHSP) database, national surveys and other publicly available sources. INTERVENTION: A total of 30 interventions were selected from the latest EHSP revision and analysed over a 1-year period. OUTCOME MEASURES: Health benefits, social welfare indices and financial protection metrics across income quintiles were reported. RESULTS: We found 23 interventions that improve population health and reduce health inequality and four interventions reduce both population health and health inequality. Additionally, three interventions improve population health while increasing health inequality. Overall, the EHSP interventions provide a 0.021 improvement in health-adjusted life expectancy (HALE) per person, with a positive distributional equity impact: 0.029 (26.9%) HALE gained in the poorest and 0.015 (14.0%) in the richest quintile. Similarly, a total of 1 79 475 cases of catastrophic health expenditure were averted, including 82 100 (46.0%) cases in the poorest and 17 900 (10.0%) in the richest quintile. CONCLUSION: Increasing access to the EHSP improves health equity and financial protection. Improved access to selected EHSP interventions also has the potential to provide greater benefits to the poorest and thereby improve social welfare.

Cost of childhood cancer treatment in Ethiopia.

BACKGROUND: Despite the recent interest in expanding pediatric oncology units in Ethiopia, reflected in the National Childhood and Adolescent Cancer Control Plan (NCACCP), little is known about the cost of running a pediatric oncology unit and treating childhood cancers. METHODS: We collected historical cost data and quantity of services provided for the pediatric oncology unit and all other departments in Tikur Anbessa Specialized Hospital (TASH) from 8 July 2018 to 7 July 2019, using a provider perspective and mixed (top-down and bottom-up) costing approaches. Direct costs (human resources, drugs, supplies, medical equipment) of the pediatric oncology unit, costs at other relevant clinical departments, and overhead cost share are summed up to estimate the total annual cost of running the unit. Further, unit costs were estimated at specific childhood cancer levels. RESULTS: The estimated annual total cost of running a pediatric oncology unit was USD 776,060 (equivalent to USD 577 per treated child). The cost of running a pediatric oncology unit per treated child ranged from USD 469 to USD 1,085, on the scenario-based sensitivity analysis. Drugs and supplies, and human resources accounted for 33% and 27% of the total cost, respectively. Outpatient department and inpatient department shared 37% and 63% of the cost, respectively. For the pediatric oncology unit, the cost per OPD visit, cost per bed day, and cost per episode of hospital admission were USD 36.9, 39.9, and 373.3, respectively. The annual cost per treated child ranged from USD 322 to USD 1,313 for the specific childhood cancers. CONCLUSION: Running a pediatric oncology unit in Ethiopia is likely to be affordable. Further analysis of cost effectiveness, equity, and financial risk protection impacts of investing in childhood cancer programs could better inform the prioritization of childhood cancer control interventions in the Ethiopia Essential Health Service Package.

Fair pathways to net-zero healthcare.

Over the past decade, it has become clear that the health sector is not only at risk from climate change but also a major polluter of greenhouse gases. In November 2021, the World Health Organization and partners launched the COP26 Health Programme for sustainable, climate-resilient and low-carbon health systems, and have since established the Alliance for Transformative Action on Climate and Health to support its implementation. Given the wide variation in health financing, carbon emissions and unmet health needs across the world, fair sharing of the remaining carbon budget and health gains will be critical. In this Perspective, we explore the challenges and opportunities of healthcare decarbonization, outlining the principles of fair pathways to net-zero healthcare that are attentive to health and socioeconomic inequalities within and between countries.

Cost-effectiveness of running a paediatric oncology unit in Ethiopia.

OBJECTIVE: To estimate the cost-effectiveness of running a paediatric oncology unit in Ethiopia to inform the revision of the Ethiopia Essential Health Service Package (EEHSP), which ranks the treatment of childhood cancers at a low and medium priority. METHODS: We built a decision analytical model-a decision tree-to estimate the cost-effectiveness of running a paediatric oncology unit compared with a do-nothing scenario (no paediatric oncology care) from a healthcare provider perspective. We used the recently (2018-2019) conducted costing estimate for running the paediatric oncology unit at Tikur Anbessa Specialized Hospital (TASH) and employed a mixed costing approach (top-down and bottom-up). We used data on health outcomes from other studies in similar settings to estimate the disability-adjusted life years (DALYs) averted of running a paediatric oncology unit compared with a do-nothing scenario over a lifetime horizon. Both costs and effects were discounted (3%) to the present value. The primary outcome was incremental cost in US dollars (USDs) per DALY averted, and we used a willingness-to-pay (WTP) threshold of 50% of the Ethiopian gross domestic product per capita (USD 477 in 2019). Uncertainty was tested using one-way and probabilistic sensitivity analyses. RESULTS: The incremental cost and DALYs averted per child treated in the paediatric oncology unit at TASH were USD 876 and 2.4, respectively, compared with no paediatric oncology care. The incremental cost-effectiveness ratio of running a paediatric oncology unit was USD 361 per DALY averted, and it was cost-effective in 90% of 100 000 Monte Carlo iterations at a USD 477 WTP threshold. CONCLUSIONS: The provision of paediatric cancer services using a specialised oncology unit is most likely cost-effective in Ethiopia, at least for easily treatable cancer types in centres with minimal to moderate capability. We recommend reassessing the priority-level decision of childhood cancer treatment in the current EEHSP.

Country readiness and prerequisites for successful design and transition to implementation of essential packages of health services: experience from six countries.

This paper reviews the experience of six low-income and lower middle-income countries in setting their own essential packages of health services (EPHS), with the purpose of identifying the key requirements for the successful design and transition to implementation of the packages in the context of accelerating progress towards universal health coverage (UHC). The analysis is based on input from three meetings of a knowledge network established by the Disease Control Priorities 3 Country Translation Project and working groups, supplemented by a survey of participating countries.All countries endorsed the Sustainable Development Goals target 3.8 on UHC for achievement by 2030. The assessment of country experiences found that health system strengthening and mobilising and sustaining health financing are major challenges. EPHS implementation is more likely when health system gaps are addressed and when there are realistic and sustainable financing prospects. However, health system assessments were inadequate and the government planning and finance sectors were not consistently engaged in setting the EPHS in most of the countries studied. There was also a need for greater engagement with community and civil society representatives, academia and the private sector in package design. Leadership and reinforcement of technical and managerial capacity are critical in the transition from EPHS design to sustained implementation, as are strong human resources and country ownership of the process. Political commitment beyond the health sector is key, particularly commitment from parliamentarians and policymakers in the planning and finance sectors. National ownership, institutionalisation of technical and managerial capacity and reinforcing human resources are critical for success.The review concludes that four prerequisites are crucial for a successful EPHS: (1) sustained high-level commitment, (2) sustainable financing, (3) health system readiness, and (4) institutionalisation.

Balancing the health benefits and climate mortality costs of haemodialysis.

Extensive work is underway to quantify the carbon footprint of specific healthcare interventions and identify ways to minimise healthcare-related emissions; however, it remains unclear how to balance the relative benefits from delivering healthcare with the harm from the associated carbon footprint. To estimate emissions-related harms, we used the Mortality Cost of Carbon, a recently developed metric from environmental economics, which presents the impacts of carbon emissions in the form of excess deaths. We convert deaths into years of life lost and compare this with the healthy life years gained, under two temperature scenarios: 'Dynamic Integrated Climate Economy Model with an Endogenous Mortality Response' (DICE-EMR) (2.4°C) and 'DICE-Baseline' (4.1°C). As a case study, we use haemodialysis, a life-prolonging intervention with a large carbon footprint. We estimate that 19-53 and 10-25 healthy life years are gained from haemodialysis per year of life lost from the associated emissions in the DICE-EMR and DICE-Baseline scenarios, respectively, depending on the country and treatment regimen. This brings the distribution of harms, benefits and tradeoffs inherent to the decarbonisation of healthcare into sharper focus. More fully accounting for the harm imposed by carbon emissions could result in better value investments to lower the carbon footprint of interventions and support the implementation of the net-zero healthcare agenda.

Effect of kangaroo mother care initiated in community settings on financial risk protection of low-income households: a randomised controlled trial in Haryana, India.

INTRODUCTION: Many families in low-income and middle-income countries have high out-of-pocket expenditures (OOPE) for healthcare, and some face impoverishment. We aimed to assess the effect of Kangaroo Mother Care initiated in community setting (ciKMC) on financial risk protection estimated by healthcare OOPE, catastrophic healthcare expenditure (CHE) and impoverishment due to healthcare seeking for low birthweight infants, using a randomised controlled trial design. METHODS: We included 4475 low birthweight infants randomised to a ciKMC (2491 infants) and a control (1984 infants) arm, in a large trial conducted between 2017 and 2018 in Haryana, India. We used generalised linear models of the Gaussian family with an identity link to estimate the mean difference in healthcare OOPE, and Cox regression to estimate the HRs for CHE and impoverishment, between the trial arms. RESULTS: Overall, in the 8-week observation period, the mean healthcare OOPE per infant was lower (US$20.0) in the ciKMC arm compared with the control arm (US$25.6) that is, difference of -US$5.5, 95% CI -US$11.4 to US$0.3, p=0.06). Among infants who sought care it was US$8.5 (95% CI -US$17.0 to -US$0.03, p=0.03) lower in the ciKMC arm compared with the control arm. The HR for impoverishment due to healthcare seeking was 0.56 (95% CI 0.36 to 0.89, p=0.01) and it was 0.91 (95% CI 0.74 to 1.12, p=0.37) for CHE. CONCLUSION: ciKMC can substantially reduce the cost of care seeking and the risk of impoverishment for households. Our findings show that supporting mothers to provide KMC to low birthweight infants at home, in addition to reducing early infant mortality, may provide financial risk protection. TRIAL REGISTRATION NUMBER: CTRI/2017/10/010114.

The global temperature-related mortality impact of earlier decarbonization for the Australian health sector and economy: A modelling study.

BACKGROUND: Sustained elevated concentration of GHGs is predicted to increase global mortality. With the Australian health sector responsible for 7% of the nation's GHG emissions, the benefits and costs of various decarbonisation trajectories are currently being investigated. To assist with this effort, we model the impact earlier decarbonisation has on temperature-related mortality. DESIGN: We used DICE-EMR, an Integrated Assessment Model with an endogenous mortality response, to simulate Australian GHG trajectories and estimate the temperature-related mortality impact of early decarbonisation. We modelled a linear decline of the Australian health sector's and economy's GHG annual emissions to net-zero targets of 2040 and 2050. MAIN OUTCOME MEASURE: Deaths averted and monetary-equivalent welfare gain. RESULTS: Decarbonisation of the Australian health sector by 2050 and 2040 is projected to avert an estimated 69,000 and 77,000 global temperature-related deaths respectively in a Baseline global emissions scenario. Australian economy decarbonisation by 2050 and 2040 is projected to avert an estimated 988,000 and 1,101,000 global deaths respectively. Assuming a low discount rate and high global emissions trajectory, we estimate a monetary equivalent welfare gain of $151 billion if the Australian health sector decarbonises by 2040, only accounting for the benefits in reducing temperature-related mortality. CONCLUSIONS: Earlier decarbonisation has a significant impact on temperature-related mortality. Many uncertainties exist and health impacts other than temperature-related mortality are not captured by this analysis. Nevertheless, such models can help communicate the health risk of climate change and improve climate policy decision making.

The magnitude and perceived reasons for childhood cancer treatment abandonment in Ethiopia: from health care providers' perspective.

BACKGROUND: Treatment abandonment is one of major reasons for childhood cancer treatment failure and low survival rate in low- and middle-income countries. Ethiopia plans to reduce abandonment rate by 60% (2019-2023), but baseline data and information about the contextual risk factors that influence treatment abandonment are scarce. METHODS: This cross-sectional study was conducted from September 5 to 22, 2021, on the three major pediatric oncology centers in Ethiopia. Data on the incidence and reasons for treatment abandonment were obtained from healthcare professionals. We were unable to obtain data about the patients' or guardians' perspective because the information available in the cancer registry was incomplete to contact adequate number of respondents. We used a validated, semi-structured questionnaire developed by the International Society of Pediatric Oncology Abandonment Technical Working Group. We included all (N = 38) health care professionals (physicians, nurses, and social workers) working at these centers who had more than one year of experience in childhood cancer service provision (a universal sampling and 100% response rate). RESULTS: The perceived mean abandonment rate in Ethiopia is 34% (SE 2.5%). The risk of treatment abandonment is dependent on the type of cancer (high for bone sarcoma and brain tumor), the phase of treatment and treatment outcome. The highest risk is during maintenance and treatment failure or relapse for acute lymphoblastic leukemia, and during pre- or post-surgical phase for Wilms tumor and bone sarcoma. The major influencing risk factors in Ethiopia includes high cost of care, low economic status, long travel time to treatment centers, long waiting time, belief in the incurability of cancer and poor public awareness about childhood cancer. CONCLUSIONS: The perceived abandonment rate in Ethiopia is high, and the risk of abandonment varies according to the type of cancer, phase of treatment or treatment outcome. Therefore, mitigation strategies to reduce the abandonment rate should include identifying specific risk factors and prioritizing strategies based on their level of influence, effectiveness, feasibility, and affordability.

Changes in life expectancy and disease burden in Norway, 1990-2019: an analysis of the Global Burden of Disease Study 2019.

BACKGROUND: Geographical differences in health outcomes are reported in many countries. Norway has led an active policy aiming for regional balance since the 1970s. Using data from the Global Burden of Disease Study (GBD) 2019, we examined regional differences in development and current state of health across Norwegian counties. METHODS: Data for life expectancy, healthy life expectancy (HALE), years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life-years (DALYs) in Norway and its 11 counties from 1990 to 2019 were extracted from GBD 2019. County-specific contributors to changes in life expectancy were compared. Inequality in disease burden was examined by use of the Gini coefficient. FINDINGS: Life expectancy and HALE improved in all Norwegian counties from 1990 to 2019. Improvements in life expectancy and HALE were greatest in the two counties with the lowest values in 1990: Oslo, in which life expectancy and HALE increased from 71·9 years (95% uncertainty interval 71·4-72·4) and 63·0 years (60·5-65·4) in 1990 to 81·3 years (80·0-82·7) and 70·6 years (67·4-73·6) in 2019, respectively; and Troms og Finnmark, in which life expectancy and HALE increased from 71·9 years (71·5-72·4) and 63·5 years (60·9-65·6) in 1990 to 80·3 years (79·4-81·2) and 70·0 years (66·8-72·2) in 2019, respectively. Increased life expectancy was mainly due to reductions in cardiovascular disease, neoplasms, and respiratory infections. No significant differences between the national YLD or DALY rates and the corresponding age-standardised rates were reported in any of the counties in 2019; however, Troms og Finnmark had a higher age-standardised YLL rate than the national rate (8394 per 100 000 [95% UI 7801-8944] vs 7536 per 100 000 [7391-7691]). Low inequality between counties was shown for life expectancy, HALE, all level-1 causes of DALYs, and exposure to level-1 risk factors. INTERPRETATION: Over the past 30 years, Norway has reduced inequality in disease burden between counties. However, inequalities still exist at a within-county level and along other sociodemographic gradients. Because of insufficient Norwegian primary data, there remains substantial uncertainty associated with regional estimates for non-fatal disease burden and exposure to risk factors. FUNDING: Bill & Melinda Gates Foundation, Research Council of Norway, and Norwegian Institute of Public Health.