ScISOr-ATAC reveals convergent and divergent splicing and chromatin specificities between matched cell types across cortical regions, evolution, and in Alzheimer's Disease.

Multimodal measurements have become widespread in genomics, however measuring open chromatin accessibility and splicing simultaneously in frozen brain tissues remains unconquered. Hence, we devised Single-Cell-ISOform-RNA sequencing coupled with the Assay-for-Transposase-Accessible-Chromatin (ScISOr-ATAC). We utilized ScISOr-ATAC to assess whether chromatin and splicing alterations in the brain convergently affect the same cell types or divergently different ones. We applied ScISOr-ATAC to three major conditions: comparing (i) the Rhesus macaque (Macaca mulatta) prefrontal cortex (PFC) and visual cortex (VIS), (ii) cross species divergence of Rhesus macaque versus human PFC, as well as (iii) dysregulation in Alzheimer's disease in human PFC. We found that among cortical-layer biased excitatory neuron subtypes, splicing is highly brain-region specific for L3-5/L6 IT_RORB neurons, moderately specific in L2-3 IT_CUX2.RORB neurons and unspecific in L2-3 IT_CUX2 neurons. In contrast, at the chromatin level, L2-3 IT_CUX2.RORB neurons show the highest brain-region specificity compared to other subtypes. Likewise, when comparing human and macaque PFC, strong evolutionary divergence on one molecular modality does not necessarily imply strong such divergence on another molecular level in the same cell type. Finally, in Alzheimer's disease, oligodendrocytes show convergently high dysregulation in both chromatin and splicing. However, chromatin and splicing dysregulation most strongly affect distinct oligodendrocyte subtypes. Overall, these results indicate that chromatin and splicing can show convergent or divergent results depending on the performed comparison, justifying the need for their concurrent measurement to investigate complex systems. Taken together, ScISOr-ATAC allows for the characterization of single-cell splicing and chromatin patterns and the comparison of sample groups in frozen brain samples.

A dominance approach to analyze the incidence of catastrophic health expenditures in Iran.

Financial protection is a health system goal for all countries. Assessing progress on this relies on measuring the incidence of catastrophic health expenditures (proportion of the population whose out-of-pocket (OOP) payments for health surpass a certain threshold of household resources). Standard approaches rely on selective thresholds, however this masks varying intensities of financial hardship and poses a measurement challenge as incidence is sensitive to the choice of the threshold. We address this problem by applying the dominance approach, which tests differences in catastrophic incidence curves over a continuous range of thresholds. Iran is an interesting country for empirical application of the dominance approach given its historically high reliance on OOP payments to finance its health system and its commitment to improving financial protection through several national health policies over the last two decades. Using data from annual Household Income and Expenditure Surveys from 2005 to 2017 (sample size: 26,851-39,088 households), incidence was analyzed following this novel approach. Distribution of incidence across socio-economic status was also analyzed by estimating concentration indices and across health services or products by estimating average shares of each item. Results showed that over time catastrophic health expenditures increased for thresholds lower than 25% and decreased for thresholds higher than 35%. Catastrophic health expenditures were more equally distributed across income levels at lower thresholds, becoming concentrated amongst the rich as the threshold rose. Medicines represented the largest share of catastrophic spending for the poorest; medicines, dentistry, inpatient and ancillary services for the richest. This is the first study to apply dominance methods to analyze catastrophic health expenditures in a country over time. The analysis provides a nuanced picture of who incurs catastrophic health expenditures, to what extent hardship is experienced and what were the drivers of these expenditures - thus providing a better basis for policy responses.

Characterization of the nanomechanical properties of the fission yeast (Schizosaccharomyces pombe) cell surface by atomic force microscopy.

Variations in cell wall composition and biomechanical properties can contribute to the cellular plasticity required during complex processes such as polarized growth and elongation in microbial cells. This study utilizes atomic force microscopy (AFM) to map the cell surface topography of fission yeast, Schizosaccharomyces pombe, at the pole regions and to characterize the biophysical properties within these regions under physiological, hydrated conditions. High-resolution images acquired from AFM topographic scanning reveal decreased surface roughness at the cell poles. Force extension curves acquired by nanoindentation probing with AFM cantilever tips under low applied force revealed increased cell wall deformation and decreased cellular stiffness (cellular spring constant) at cell poles (17 ± 4 mN/m) relative to the main body of the cell that is not undergoing growth and expansion (44 ± 10 mN/m). These findings suggest that the increased deformation and decreased stiffness at regions of polarized growth at fission yeast cell poles provide the plasticity necessary for cellular extension. This study provides a direct biophysical characterization of the S. pombe cell surface by AFM, and it provides a foundation for future investigation of how the surface topography and local nanomechanical properties vary during different cellular processes.

An analysis of financial protection before and after the Iranian Health Transformation Plan.

BACKGROUND: Protecting people against the financial consequences of health-care payments is a key objective of health systems. AIMS: We carried out a descriptive analysis of changes in health spending associated with the implementation of the latest health sector reform in the Islamic Republic of Iran, the Health Transformation Plan (HTP). METHODS: The study relied on 2 rounds of data from the Household Expenditure and Income Survey (2014 and 2015). Key indicators of financial protection in health expenditure were estimated. The Kakwani index was used for out-of-pocket (OOP) health expenditure to measure the degree of progressivity in the distribution of such payments. RESULTS: Total OOP per capita health expenditure showed a 2.5% relative decrease in real terms in 2015 compared to 2014. Estimation of the Kakwani index suggested OOP spending became slightly more progressive over the time period of HTP reform. The share of the population facing catastrophic health expenditure also decreased significantly from 2.9% to 2.1% at the national level. However, the incidence of impoverishment due to OOP payments increased slightly between preand post-HTP, from 0.2% to 0.5%. CONCLUSION: Our findings suggest that the new policies have a positive association in improving financial protection against health costs among Iranians, albeit slightly less so for the poor. Future efforts to increase public spending for financial protection would be challenging and should rely on efficiency gains such as a move from fee-for-service to performance- based payment systems and more organized OOP collection mechanisms involving prepayment and risk pooling.

Correction to: What has been the progress in addressing financial risk in Uganda? Analysis of catastrophe and impoverishment due to health payments.

An amendment to this paper has been published and can be accessed via the original article.

What has been the progress in addressing financial risk in Uganda? Analysis of catastrophe and impoverishment due to health payments.

BACKGROUND: Monitoring progress towards Universal Health Coverage (UHC) requires an assessment of progress in coverage of health services and protection of households from the impact of direct out-of-pocket payments (i.e. financial risk protection). Although Uganda has expressed aspirations for attaining UHC, out-of-pocket payments remain a major contributor to total health expenditure. The aim of this study is to monitor progress in financial risk protection in Uganda. METHODS: This study uses data from the Uganda National Household Surveys for 2005/06, 2009/10, 2012/13 and 2016/17. We measure financial risk protection using catastrophic health care payments and impoverishment indicators. Health care payments are catastrophic if they exceed a set threshold (i.e. 10 and 25%) of the total household consumption expenditure. Health payments are impoverishing if they push the household below the poverty line (the US$1.90/day and Uganda's national poverty lines). A logistic regression model is used to assess the factors associated with household financial risk. RESULTS: The results show that while progress has been made in reducing financial risk, this progress remains minimal, and there is still a risk of a reversal of this trend. We find that although catastrophic health payments at the 10% threshold decreased from 22.4% in 2005/06 to 13.8% in 2012/13, it increased to 14.2% in 2016/17. The percentage of Ugandans pushed below the national poverty line (US$1.90/day) has decreased from 5.2% in 2005/06 to 2.7% in 2016/17. The distribution of both catastrophic health payments and impoverishment varies across socio-economic status, location and residence. In addition, certain household characteristics (poverty, having a child below 5 years and an adult above 60 years) are more associated with the lack of financial risk protection. CONCLUSION: There is need for targeted interventions to reduce OOP, especially among those affected so as to increase financial risk protection. In the short-term, it is important to ensure that public health services are funded adequately to enable effective coverage with quality health care. In the medium-term, increased reliance on mandatory prepayment will reduce the burden of OOP health spending further.

Impact of out of pocket payments on financial risk protection indicators in a setting with no user fees: the case of Mauritius.

BACKGROUND: Mauritius embraces principles of a welfare state with free health care at point of use in any public facilities. However, the health financing landscape changed in 2007 when Private Health Expenditure (PvtHE) surpassed General Government Health Expenditure. PvtHE is predominately out of pocket (OOP) with only 3.4% related to premiums for private insurance. In 2014, Household OOP Expenditure on health accounted for 52.8% of total health expenditure. OOP is known to be regressive and to impact negatively on households' living standards. OBJECTIVES: This paper aims to examine trends in OOP in Mauritius, to assess its impacts through an analysis of key indicators of financial protection, namely catastrophic health expenditure (CHE) and impoverishment due to OOP health expenditure. It also aims to predict core determinants of CHEs. METHODS: Household Budget Surveys (HBS) of 2001/2002, 2006/2007 and 2012 were the primary source data. CHE and impoverishment were used to assess financial hardships resulting from OOP health payments. The incidence of CHE was estimated at three threshold levels (10,25 and 40%), using the budget share and the capacity to pay approaches. Impoverishment due to OOP was measured by changes in the incidence of poverty and intensity of poverty using the US$ 3.1 international poverty line. Logistic regression analysis was used to identify determinants of CHE. FINDINGS: Household CHE increased from 5.78% in 2001/02 to 8.85% in 2012 and 0.61% in 2001/02 to 1.25% in 2012, for 10 and 40% thresholds, respectively. The incidence of CHE was significantly higher in urban areas compared to rural areas. The highest levels of CHEs were among households' heads, who are retired rising from 1.62% in 2001/02 to 3.71% in 2012, followed by households' head who are widowed from 2.29% in 2001/02 to 2.63% in 2012 and homemakers from 2.12% in 2001/02 to 2.57% in 2012 at the 40% threshold. The share of households pushed below the poverty line due to OOP dropped from 0.4% in 2001/02 to 0.2% in 2006/07 before rising to 0.34% in 2012. In 2012, poverty gap occurred only among households under poorest quintile 1 (0.24%) and quintile 2 (0.03%). Overall poverty gap dropped from 0.08% in 2001/02 to 0.05% in 2012. Logistic regression analysis revealed that the odds ratio of facing CHE were significant only among households with heads being retired and with a presence of an elderly member in the household. CONCLUSION: Despite the rise in incidence of CHE between 2001 and 2012 the impact of OOP on the level of impoverishment and poverty gap has not been significant.

Measuring financial protection against catastrophic health expenditures: methodological challenges for global monitoring.

BACKGROUND: Monitoring financial protection against catastrophic health expenditures is important to understand how health financing arrangements in a country protect its population against high costs associated with accessing health services. While catastrophic health expenditures are generally defined to be when household expenditures for health exceed a given threshold of household resources, there is no gold standard with several methods applied to define the threshold and household resources. These different approaches to constructing the indicator might give different pictures of a country's progress towards financial protection. In order for monitoring to effectively provide policy insight, it is critical to understand the sensitivity of measurement to these choices. METHODS: This paper examines the impact of varying two methodological choices by analysing household expenditure data from a sample of 47 countries. We assess sensitivity of cross-country comparisons to a range of thresholds by testing for restricted dominance. We further assess sensitivity of comparisons to different methods for defining household resources (i.e. total expenditure, non-food expenditure and non-subsistence expenditure) by conducting correlation tests of country rankings. RESULTS: We found country rankings are robust to the choice of threshold in a tenth to a quarter of comparisons within the 5-85% threshold range and this increases to half of comparisons if the threshold is restricted to 5-40%, following those commonly used in the literature. Furthermore, correlations of country rankings using different methods to define household resources were moderate to high; thus, this choice makes less difference from a measurement perspective than from an ethical perspective as different definitions of available household resources reflect varying concerns for equity. CONCLUSIONS: Interpreting comparisons from global monitoring based on a single threshold should be done with caution as these may not provide reliable insight into relative country progress. We therefore recommend financial protection against catastrophic health expenditures be measured across a range of thresholds using a catastrophic incidence curve as shown in this paper. We further recommend evaluating financial protection in relation to a country's health financing system arrangements in order to better understand the extent of protection and better inform future policy changes.

Progress on impoverishing health spending in 122 countries: a retrospective observational study.

BACKGROUND: The goal of universal health coverage (UHC) requires that families who get needed health care do not suffer financial hardship as a result. This can be measured by instances of impoverishment, when a household's consumption including out-of-pocket spending on health is more than the poverty line but its consumption, excluding out-of-pocket spending, is less than the poverty line. This links UHC directly to the policy goal of reducing poverty. METHODS: We measure the incidence and depth of impoverishment as the difference in the poverty head count and poverty gap with and without out-of-pocket spending included in household total consumption. We use three poverty lines: the US$1·90 per day and $3·10 per day international poverty lines and a relative poverty line of 50% of median consumption per capita. We estimate impoverishment in 122 countries using 516 surveys between 1984 and 2015. We estimate the global incidence of impoverishment due to out-of-pocket payments by aggregating up from each country, using a survey for the year in question when available, and interpolation and model-based estimates otherwise. We do not derive global estimates to measure the depth of impoverishment but focus on the median depth for the 122 countries in our sample, accounting for 90% of the world's population. FINDINGS: We find impoverishment due to out-of-pocket spending even in countries where the entire population is officially covered by a health insurance scheme or by national or subnational health services. Incidence is negatively correlated with the share of total health spending channelled through social security funds and other government agencies. Across countries, the population-weighted median annual rate of change of impoverishment is negative at the $1·90 per day poverty line but positive at the $3·10 per day and relative poverty lines. We estimate that at the $1·90 per day poverty line, the worldwide incidence of impoverishment decreased between 2000 and 2010, from 131 million people (2·1% of the world's population) to 97 million people (1·4%). The population-weighted median of the poverty gap increase attributable to out-of-pocket health expenditures among the 122 countries in our sample are ¢1·22 per capita at the $1·90 per day poverty line and ¢3·74 per capita at the $3·10 per day poverty line. In all countries, out-of-pocket spending can be both catastrophic and impoverishing at all income levels, but this partly depends on the choice of the poverty line. INTERPRETATION: Out-of-pocket spending on health can add to the poverty head count and the depth of poverty by diverting household spending from non-health budget items. The scale of such impoverishment varies between countries and depends on the poverty line but might in some low-income countries account for as much as four percentage points of the poverty head count. Increasing the share of total health expenditure that is prepaid, especially through taxes and mandatory contributions, can help reduce impoverishment. FUNDING: Rockefeller Foundation, Ministry of Health of Japan, and UK Department for International Development.

Progress on catastrophic health spending in 133 countries: a retrospective observational study.

BACKGROUND: The goal of universal health coverage (UHC) requires inter alia that families who get needed health care do not suffer undue financial hardship as a result. This can be measured by the percentage of people in households whose out-of-pocket health expenditures are large relative to their income or consumption. We aimed to estimate the global incidence of catastrophic health spending, trends between 2000 and 2010, and associations between catastrophic health spending and macroeconomic and health system variables at the country level. METHODS: We did a retrospective observational study of health spending using data obtained from household surveys. Of 1566 potentially suitable household surveys, 553 passed quality checks, covering 133 countries between 1984 and 2015. We defined health spending as catastrophic when it exceeded 10% or 25% of household consumption. We estimated global incidence by aggregating up from every country, using a survey for the year in question when available, and interpolation and model-based estimates otherwise. We used multiple regression to explore the relation between a country's incidence of catastrophic spending and gross domestic product (GDP) per person, the Gini coefficient for income inequality, and the share of total health expenditure spent by social security funds, other government agencies, private insurance schemes, and non-profit institutions. FINDINGS: The global incidence of catastrophic spending at the 10% threshold was estimated as 9·7% in 2000, 11·4% in 2005, and 11·7% in 2010. Globally, 808 million people in 2010 incurred catastrophic health spending. Across 94 countries with two or more survey datapoints, the population-weighted median annual rate of change of catastrophic payment incidence was positive whatever catastrophic payment incidence measure was used. Incidence of catastrophic payments was correlated positively with GDP per person and the share of GDP spent on health, and incidence correlated negatively with the share of total health spending channelled through social security funds and other government agencies. INTERPRETATION: The proportion of the population that is supposed to be covered by health insurance schemes or by national or subnational health services is a poor indicator of financial protection. Increasing the share of GDP spent on health is not sufficient to reduce catastrophic payment incidence; rather, what is required is increasing the share of total health expenditure that is prepaid, particularly through taxes and mandatory contributions. FUNDING: Rockefeller Foundation, Ministry of Health of Japan, UK Department for International Development (DFID).

Developing a dataset to track aid for reproductive, maternal, newborn and child health, 2003-2013.

We created a dataset to generate estimates of donor-reported 'official development assistance' and private grants (ODA+) to reproductive, maternal, newborn and child health (RMNCH) by donor, recipient country and activity type over the period 2003-2013. We collected disbursement information from the Organisation for Economic Co-operation and Development Creditor Reporting System (CRS) in January 2015. All 2.1 million records across all sectors were coded based on donor name, project title, short and long descriptions, and CRS code describing the purpose of the disbursement. We classified records according to the degree to which they would promote attainment of Millennium Development Goals 4 and 5 (reproductive and sexual health, maternal and newborn health, and child health). We also classified records according to whether they supported prenatal and neonatal health (PNH). The dataset includes project funding as well as allocating shares of general budget support, health sector support and basket funding. The data can be used to analyse resource flows to RMNCH or to other purposes or beneficiaries of ODA+.

Countdown to 2015: changes in official development assistance to reproductive, maternal, newborn, and child health, and assessment of progress between 2003 and 2012.

BACKGROUND: Tracking of aid resources to reproductive, maternal, newborn, and child health (RMNCH) provides timely and crucial information to hold donors accountable. For the first time, we examine flows in official development assistance (ODA) and grants from the Bill & Melinda Gates Foundation (collectively termed ODA+) in relation to the continuum of care for RMNCH and assess progress since 2003. METHODS: We coded and analysed financial disbursements for maternal, newborn, and child health (MNCH) and for reproductive health (R*) to all recipient countries worldwide from all donors reporting to the creditor reporting system database for the years 2011-12. We also included grants from the Bill & Melinda Gates Foundation. We analysed trends for MNCH for the period 2003-12 and for R* for the period 2009-12. FINDINGS: ODA+ to RMNCH from all donors to all countries worldwide amounted to US$12·2 billion in 2011 (an 11·8% increase relative to 2010) and $12·8 billion in 2012 (a 5·0% increase relative to 2011). ODA+ to MNCH represents more than 60% of all aid to RMNCH. ODA+ to projects that have newborns as part of the target population has increased 34-fold since 2003. ODA to RMNCH from the 31 donors, which have reported consistently since 2003, to the 75 Countdown priority countries, saw a 3·2% increase in 2011 relative to 2010 ($8·3 billion in 2011), and an 11·8% increase in 2012 relative to 2011 ($9·3 billion in 2012). ODA to RMNCH projects has increased with time, whereas general budget support has continuously declined. Bilateral agencies are still the predominant source of ODA to RMNCH. Increased funding to family planning, nutrition, and immunisation projects were noted in 2011 and 2012. ODA+ has been targeted to RMNCH during the period 2005-12, although there is no evidence of improvements in targeting over time. INTERPRETATION: Despite a reduction in ODA+ in 2011, ODA+ to RMNCH increased in both 2011 and 2012. The increase in funding is encouraging, but continued increases are needed to accelerate progress towards achieving MDGs 4 and 5 and beyond. FUNDING: Bill & Melinda Gates Foundation.

Financial risk protection and universal health coverage: evidence and measurement challenges.

Financial risk protection is a key component of universal health coverage (UHC), which is defined as access to all needed quality health services without financial hardship. As part of the PLOS Medicine Collection on measurement of UHC, the aim of this paper is to examine and to compare and contrast existing measures of financial risk protection. The paper presents the rationale behind the methodologies for measuring financial risk protection and how this relates to UHC as well as some empirical examples of the types of measures. Additionally, the specific challenges related to monitoring inequalities in financial risk protection are discussed. The paper then goes on to examine and document the practical challenges associated with measurement of financial risk protection. This paper summarizes current thinking on the area of financial risk protection, provides novel insights, and suggests future developments that could be valuable in the context of monitoring progress towards UHC.

Reproductive health priorities: evidence from a resource tracking analysis of official development assistance in 2009 and 2010.

BACKGROUND: Information is scarce about the extent to which official development assistance (ODA) is spent on reproductive health to provide childbirth care; support family planning; address sexual health; and prevent, treat, and care for sexually transmitted infections, including HIV. We analysed flows of ODA to reproductive health for 2009 and 2010, assessed their distribution by donor type and purpose, and investigated the extent to which disbursements respond to need. We aimed to provide global estimates of aid to reproductive health, to assess the allocation of resources across reproductive health activities, and to encourage donor accountability in targeting aid flows to those most in need. METHODS: We applied a standard definition of reproductive health across all donors, including a portion of disease-specific activities and health systems development. We analysed disbursements to reproductive health by donor type and purpose (eg, family planning). We also reported on an indicator to monitor donor disbursements: ODA to reproductive health per woman aged 15-49 years. We analysed the extent to which funding is targeted to countries most in need, proxied by female life expectancy at birth and prevalence of HIV infection in adults. FINDINGS: Donor disbursements to reproductive health activities in all countries amounted to US$5579 million in 2009 and US$5637 million in 2010-an increase of 1.0%. ODA for such activities in the 74 Countdown priority countries increased more rapidly at 5.3%. More than half of the funding was directed towards prevention, treatment, and care of HIV infection for women of reproductive age (15-49 years of age). On average, ODA to general reproductive health activities amounted to 15.9% and ODA to family planning 7.2%. Aid to reproductive health was heavily dependent on the USA, the Global Fund, the UK, the United Nations Population Fund, and the World Bank. INTERPRETATION: Donors are prioritising reproductive health, and the slight increase in funding in 2009-10 is welcome, especially in the present economic climate. The large share of such funding for activities related to HIV infection in women of reproductive age affects the amount of ODA received by priority countries. It should thus be distinguished from resources directed to other reproductive health activities, such as family planning, which has been the focus of recent worldwide advocacy efforts. Tracking of donor aid to reproductive health should continue to allow investigation of the allocation of resources across reproductive health activities, and to encourage donor accountability in targeting aid flows to those most in need. FUNDING: Bill & Melinda Gates Foundation, World Bank, and the Governments of Australia, Canada, Norway, Sweden, and the UK.

Comparative costs and cost-effectiveness of behavioural interventions as part of HIV prevention strategies.

BACKGROUND: Behavioural interventions have been widely integrated in HIV/AIDS social marketing prevention strategies and are considered valuable in settings with high levels of risk behaviours and low levels of HIV/AIDS awareness. Despite their widespread application, there is a lack of economic evaluations comparing different behaviour change communication methods. This paper analyses the costs to increase awareness and the cost-effectiveness to influence behaviour change for five interventions in Benin. METHODS: Cost and cost-effectiveness analyses used economic costs and primary effectiveness data drawn from surveys. Costs were collected for provider inputs required to implement the interventions in 2009 and analysed by 'person reached'. Cost-effectiveness was analysed by 'person reporting systematic condom use'. Sensitivity analyses were performed on all uncertain variables and major assumptions. RESULTS: Cost-per-person reached varies by method, with public outreach events the least costly (US$2.29) and billboards the most costly (US$25.07). Influence on reported behaviour was limited: only three of the five interventions were found to have a significant statistical correlation with reported condom use (i.e. magazines, radio broadcasts, public outreach events). Cost-effectiveness ratios per person reporting systematic condom use resulted in the following ranking: magazines, radio and public outreach events. Sensitivity analyses indicate rankings are insensitive to variation of key parameters although ratios must be interpreted with caution. CONCLUSION: This analysis suggests that while individual interventions are an attractive use of resources to raise awareness, this may not translate into a cost-effective impact on behaviour change. The study found that the extensive reach of public outreach events did not seem to influence behaviour change as cost-effectively when compared with magazines or radio broadcasts. Behavioural interventions are context-specific and their effectiveness influenced by a multitude of factors. Further analyses using a quasi-experimental design would be useful to programme implementers and policy makers as they face decisions regarding which HIV prevention activities to prioritize.

Evaluating health systems strengthening interventions in low-income and middle-income countries: are we asking the right questions?

In recent years, there have been several calls for rigorous health policy and systems research to inform efforts to strengthen health systems (HS) in low- and middle-income countries (LMICs), including the use of systems thinking concepts in designing and evaluating HS strengthening interventions. The objectives of this paper are to assess recent evaluations of HS strengthening interventions to examine the extent to which they ask a broader set of questions, and provide an appropriately comprehensive assessment of the effects of these interventions across the health system. A review of evaluations conducted in 2009-10 was performed to answer these questions. Out of 106 evaluations, less than half (43%) asked broad research questions to allow for a comprehensive assessment of the intervention's effects across multiple HS building blocks. Only half of the evaluations referred to a conceptual framework to guide their impact assessment. Overall, 24% and 9% conducted process and context evaluations, respectively, to answer the question of whether the intervention worked as intended, and if so, for whom, and under what circumstances. Almost half of the evaluations considered HS impact on one building block, while most interventions were complex targeting two or more building blocks. None incorporated evaluation designs that took into account the characteristics of complex adaptive systems such as non-linearity of effects or interactions between the HS building blocks. While we do not argue that all evaluations should be comprehensive, there is a need for more comprehensive evaluations of the wider range of the intervention's effects, when appropriate. Our findings suggest that the full range of barriers to more comprehensive evaluations need to be examined and, where appropriate, addressed. Possible barriers may include limited capacity, lack of funding, inadequate time frames, lack of demand from both researchers and research funders, or difficulties in undertaking this type of evaluation.

Countdown to 2015: changes in official development assistance to maternal, newborn, and child health in 2009-10, and assessment of progress since 2003.

BACKGROUND: Tracking of financial resources to maternal, newborn, and child health provides crucial information to assess accountability of donors. We analysed official development assistance (ODA) flows to maternal, newborn, and child health for 2009 and 2010, and assessed progress since our monitoring began in 2003. METHODS: We coded and analysed all 2009 and 2010 aid activities from the database of the Organisation for Economic Co-operation and Development, according to a functional classification of activities and whether all or a proportion of the value of the disbursement contributed towards maternal, newborn, and child health. We analysed trends since 2003, and reported two indicators for monitoring donor disbursements: ODA to child health per child and ODA to maternal and newborn health per livebirth. We analysed the degree to which donors allocated ODA to 74 countries with the highest maternal and child mortality rates (Countdown priority countries) with time and by type of donor. FINDINGS: Donor disbursements to maternal, newborn, and child health activities in all countries continued to increase, to $6511 million in 2009, but slightly decreased for the first time since our monitoring started, to $6480 million in 2010. ODA for such activities to the 74 Countdown priority countries continued to increase in real terms, but its rate of increase has been slowing since 2008. We identified strong evidence that targeting of ODA to countries with high rates of maternal mortality improved from 2005 to 2010. Targeting of ODA to child health also improved but to a lesser degree. The share of multilateral funding continued to decrease but, relative to bilaterals and global health initiatives, was better targeted. INTERPRETATION: The recent slowdown in the rate of funding increases is worrying and likely to partly result from the present financial crisis. Tracking of donor aid should continue, to encourage donor accountability and to monitor performance in targeting aid flows to those in most need. FUNDING: Bill & Melinda Gates Foundation; World Bank; Governments of Australia, Canada, Norway, Sweden, and the UK.

Prevention and management of chronic disease: a litmus test for health-systems strengthening in low-income and middle-income countries.

National health systems need strengthening if they are to meet the growing challenge of chronic diseases in low-income and middle-income countries. By application of an accepted health-systems framework to the evidence, we report that the factors that limit countries' capacity to implement proven strategies for chronic diseases relate to the way in which health systems are designed and function. Substantial constraints are apparent across each of the six key health-systems components of health financing, governance, health workforce, health information, medical products and technologies, and health-service delivery. These constraints have become more evident as development partners have accelerated efforts to respond to HIV, tuberculosis, malaria, and vaccine-preventable diseases. A new global agenda for health-systems strengthening is arising from the urgent need to scale up and sustain these priority interventions. Most chronic diseases are neglected in this dialogue about health systems, despite the fact that non-communicable diseases (most of which are chronic) will account for 69% of all global deaths by 2030 with 80% of these deaths in low-income and middle-income countries. At the same time, advocates for action against chronic diseases are not paying enough attention to health systems as part of an effective response. Efforts to scale up interventions for management of common chronic diseases in these countries tend to focus on one disease and its causes, and are often fragmented and vertical. Evidence is emerging that chronic disease interventions could contribute to strengthening the capacity of health systems to deliver a comprehensive range of services-provided that such investments are planned to include these broad objectives. Because effective chronic disease programmes are highly dependent on well-functioning national health systems, chronic diseases should be a litmus test for health-systems strengthening.