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We estimate that there will be 13·7 million new cases of childhood cancer globally between 2020 and 2050. At current levels of health system performance (including access and referral), 6·1 million (44·9%) of these children will be undiagnosed. Between 2020 and 2050, 11·1 million children will die from cancer if no additional investments are made to improve access to health-care services or childhood cancer treatment. Of this total, 9·3 million children (84·1%) will be in low-income and lower-middle-income countries. This burden could be vastly reduced with new funding to scale up cost-effective interventions. Simultaneous comprehensive scale-up of interventions could avert 6·2 million deaths in children with cancer in this period, more than half (56·1%) of the total number of deaths otherwise projected. Taking excess mortality risk into consideration, this reduction in the number of deaths is projected to produce a gain of 318 million life-years. In addition, the global lifetime productivity gains of US$2580 billion in 2020–50 would be four times greater than the cumulative treatment costs of $594 billion, producing a net benefit of $1986 billion on the global investment: a net return of $3 for every $1 invested. In sum, the burden of childhood cancer, which has been grossly underestimated in the past, can be effectively diminished to realise massive health and economic benefits and to avert millions of needless deaths.

The World Bank is publishing nine volumes of Disease Control Priorities, 3rd edition (DCP3) between 2015 and 2018. Volume 9, Improving Health and Reducing Poverty, summarises the main messages from all the volumes and contains cross-cutting analyses. This Review draws on all nine volumes to convey conclusions. The analysis in DCP3 is built around 21 essential packages that were developed in the nine volumes. Each essential package addresses the concerns of a major professional community (eg, child health or surgery) and contains a mix of intersectoral policies and health-sector interventions. 71 intersectoral prevention policies were identified in total, 29 of which are priorities for early introduction. Interventions within the health sector were grouped onto five platforms (population based, community level, health centre, first-level hospital, and referral hospital). DCP3 defines a model concept of essential universal health coverage (EUHC) with 218 interventions that provides a starting point for country-specific analysis of priorities. Assuming steady-state implementation by 2030, EUHC in lower-middle-income countries would reduce premature deaths by an estimated 4·2 million per year. Estimated total costs prove substantial: about 9·1% of (current) gross national income (GNI) in low-income countries and 5·2% of GNI in lower-middle-income countries. Financing provision of continuing intervention against chronic conditions accounts for about half of estimated incremental costs. For lower-middle-income countries, the mortality reduction from implementing the EUHC can only reach about half the mortality reduction in non-communicable diseases called for by the Sustainable Development Goals. Full achievement will require increased investment or sustained intersectoral action, and actions by finance ministries to tax smoking and polluting emissions and to reduce or eliminate (often large) subsidies on fossil fuels appear of central importance. DCP3 is intended to be a model starting point for analyses at the country level, but country-specific cost structures, epidemiological needs, and national priorities will generally lead to definitions of EUHC that differ from country to country and from the model in this Review. DCP3 is particularly relevant as achievement of EUHC relies increasingly on greater domestic finance, with global developmental assistance in health focusing more on global public goods. In addition to assessing effects on mortality, DCP3 looked at outcomes of EUHC not encompassed by the disability-adjusted life-year metric and related cost-effectiveness analyses. The other objectives included financial protection (potentially better provided upstream by keeping people out of the hospital rather than downstream by paying their hospital bills for them), stillbirths averted, palliative care, contraception, and child physical and intellectual growth. The first 1000 days after conception are highly important for child development, but the next 7000 days are likewise important and often neglected.

Summary Investments in cancer control—prevention, detection, diagnosis, surgery, other treatment, and palliative care—are increasingly needed in low-income and particularly in middle-income countries, where most of the world's cancer deaths occur without treatment or palliation. To help countries expand locally appropriate services, Cancer (the third volume of nine in Disease Control Priorities , 3rd edition) developed an essential package of potentially cost-effective measures for countries to consider and adapt. Interventions included in the package are: prevention of tobacco-related cancer and virus-related liver and cervical cancers; diagnosis and treatment of early breast cancer, cervical cancer, and selected childhood cancers; and widespread availability of palliative care, including opioids. These interventions would cost an additional US$20 billion per year worldwide, constituting 3% of total public spending on health in low-income and middle-income countries. With implementation of an appropriately tailored package, most countries could substantially reduce suffering and premature death from cancer before 2030, with even greater improvements in later decades.

Summary The importance of breastfeeding in low-income and middle-income countries is well recognised, but less consensus exists about its importance in high-income countries. In low-income and middle-income countries, only 37% of children younger than 6 months of age are exclusively breastfed. With few exceptions, breastfeeding duration is shorter in high-income countries than in those that are resource-poor. Our meta-analyses indicate protection against child infections and malocclusion, increases in intelligence, and probable reductions in overweight and diabetes. We did not find associations with allergic disorders such as asthma or with blood pressure or cholesterol, and we noted an increase in tooth decay with longer periods of breastfeeding. For nursing women, breastfeeding gave protection against breast cancer and it improved birth spacing, and it might also protect against ovarian cancer and type 2 diabetes. The scaling up of breastfeeding to a near universal level could prevent 823 000 annual deaths in children younger than 5 years and 20 000 annual deaths from breast cancer. Recent epidemiological and biological findings from during the past decade expand on the known benefits of breastfeeding for women and children, whether they are rich or poor.

Background: Mass deworming affects millions of children afflicted by intestinal parasites.We aimed to assess differences in effects of deworming on nutritional and cognitive outcomes across potential effect modifiers. Methods: For this systematic review and network meta-analysis of individual participant data (IPD), we searched MEDLINE, CINAHL, LILACS, EMBASE, the Cochrane Library, Econlit, Internet Documents in Economics Access Service, Public Affairs Information Service, Social Services Abstracts, Global Health CABI and CAB Abstracts to March 27, 2018. We searched grey literature, contacted authors and screened reviews. We included randomized and quasi randomized trials of deworming children compared to placebo or other nutritional or deworming interventions with data on baseline infection. We used a frequentist approach for random-effects network meta-analysis with IPD using General Linear Mixed Models, assessed Cochrane Risk of Bias and GRADE for overall quality, following a pre-specified protocol. The main outcomes were weight, height, haemoglobin and cognition. Findings: We received IPD from 19 RCTs of STH deworming with 31,945 participants. For deworming for schistosomiasis alone, we received too few studies. Overall risk of bias was low. STH deworming vs. placebo effect on weight was 0.01 kg (95%CI: -0.08 to 0.11), height 0.09 cm (95%CI: -0.08, to 0.27) (moderate certainty), and haemoglobin 0.32 g/L (95%CI: -0.63 to 1.26) (low certainty). No study showed important effects on cognition (low certainty). There were no statistically significant subgroup effects across age, sex, nutritional status or infection intensity. Confidence limits included important effects on weight and haemoglobin for children with higher intensity infections. Interpretation: Deworming for STH alone is insufficient to improve child nutrition and cognition at population level in areas with light intensity infections. Funding Statement: Bill and Melinda Gates Foundation Declaration of Interests: Dr. Friis reports grants from ARLA Food for Health Center, grants from Danish Dairy Research Foundation, grants from Nutriset, outside the submitted work. Dr. Elliott reports grants from Wellcome Trust, during the conduct of the study. Dr. King reports grants from World Health Organization for work included in the study. Dr. LIU reports grants from International Initiative for Impact Evaluation, grants from National Natural Science Foundation of China, during the conduct of the study. All other authors state they have nothing to disclose. Ethics Approval Statement: This study was approved by the Bruyere Research Institute and SickKids research ethics boards.

© 2015 Elsevier Ltd. The World Bank will publish the nine volumes of Disease Control Priorities, 3rd edition, in 2015-16. Volume 1-. Essential Surgery-identifies 44 surgical procedures as essential on the basis that they address substantial needs, are cost effective, and are feasible to implement. This report summarises and critically assesses the volume's five key findings. First, provision of essential surgical procedures would avert about 1·5 million deaths a year, or 6-7% of all avertable deaths in low-income and middle-income countries. Second, essential surgical procedures rank among the most cost effective of all health interventions. The surgical platform of the first-level hospital delivers 28 of the 44 essential procedures, making investment in this platform also highly cost effective. Third, measures to expand access to surgery, such as task sharing, have been shown to be safe and effective while countries make long-term investments in building surgical and anaesthesia workforces. Because emergency procedures constitute 23 of the 28 procedures provided at first-level hospitals, expansion of access requires that such facilities be widely geographically diffused. Fourth, substantial disparities remain in the safety of surgical care, driven by high perioperative mortality rates including anaesthesia-related deaths in low-income and middle-income countries. Feasible measures, such as WHO's Surgical Safety Checklist, have led to improvements in safety and quality. Fifth, the large burden of surgical disorders, cost-effectiveness of essential surgery, and strong public demand for surgical services suggest that universal coverage of essential surgery should be financed early on the path to universal health coverage. We point to estimates that full coverage of the component of universal coverage of essential surgery applicable to first-level hospitals would require just over US$3 billion annually of additional spending and yield a benefit-cost ratio of more than 10:1. It would efficiently and equitably provide health benefits, financial protection, and contributions to stronger health systems.

Maternal undernutrition contributes to 800,000 neonatal deaths annually through small for gestational age births; stunting, wasting, and micronutrient deficiencies are estimated to underlie nearly 3·1 million child deaths annually. Progress has been made with many interventions implemented at scale and the evidence for effectiveness of nutrition interventions and delivery strategies has grown since The Lancet Series on Maternal and Child Undernutrition in 2008. We did a comprehensive update of interventions to address undernutrition and micronutrient deficiencies in women and children and used standard methods to assess emerging new evidence for delivery platforms. We modelled the effect on lives saved and cost of these interventions in the 34 countries that have 90% of the world's children with stunted growth. We also examined the effect of various delivery platforms and delivery options using community health workers to engage poor populations and promote behaviour change, access and uptake of interventions. Our analysis suggests the current total of deaths in children younger than 5 years can be reduced by 15% if populations can access ten evidence-based nutrition interventions at 90% coverage. Additionally, access to and uptake of iodised salt can alleviate iodine deficiency and improve health outcomes. Accelerated gains are possible and about a fifth of the existing burden of stunting can be averted using these approaches, if access is improved in this way. The estimated total additional annual cost involved for scaling up access to these ten direct nutrition interventions in the 34 focus countries is Int$9·6 billion per year. Continued investments in nutrition-specific interventions to avert maternal and child undernutrition and micronutrient deficiencies through community engagement and delivery strategies that can reach poor segments of the population at greatest risk can make a great difference. If this improved access is linked to nutrition-sensitive approaches--ie, women's empowerment, agriculture, food systems, education, employment, social protection, and safety nets--they can greatly accelerate progress in countries with the highest burden of maternal and child undernutrition and mortality.

The fragile histidine triad protein, Fhit, has a number of reported tumor suppressive functions which include signaling of apoptosis in cancer cells in vitro and in vivo, modulation of the DNA damage response, down-regulation of target oncogene expression, suppression of tumor growth in vivo, and suppression of cancer cell invasion and metastasis. Most of these functions of Fhit have been observed on exogenous re-expression of Fhit in Fhit-negative cancer cells. However, little is known about the tumorigenic changes that occur in normal or precancerous cells following loss of Fhit expression. Recently, we have shown that shortly after loss of Fhit expression, cells exhibit signs of DNA replication stress-induced DNA damage and develop genomic instability. Here, we extend these findings through investigation of different factors that affect Fhit function to prevent DNA damage. We found that Fhit activity is dependent upon a functional HIT domain and the tyrosine-114 residue, previously shown to be required for tumor suppression by Fhit. Furthermore, Fhit function was shown to be independent of exogenous and endogenous sources of oxidative stress. Finally, Fhit function was shown to be dependent upon Chk1 kinase activity, but independent of Atr or Atm kinases. Evidence suggests that Fhit and Chk1 kinase cooperate to prevent replication stress-induced DNA damage. These findings provide important and unexpected insights into the mechanism whereby loss of Fhit expression contributes to cell transformation.

Iron deficiency is very widespread, with adverse consequences for health and cognition. Iron supplementation is not popular for long-term use, and cereal fortification is not feasible where milling occurs locally. Double-fortified salt (DFS: using both iron and iodine) is an alternative. The study undertakes a literature survey to find the effect of DFS on hemoglobin, and then uses a previous algorithm to make calculations for India. The benefit:cost ratio was estimated as 2.4:1 if only the benefits to children and women were included, and between 4:1 and 5:1 if anemia levels for men also decreased. This is just a little lower than the median ratio estimated for iron fortification of cereal staples (6.7:1), for home fortification for children less than two (37:1), and for biofortification – breeding for high iron – of cereals (high, but no exact figure available). Double-fortified salt is therefore a good alternative for improving iron status in populations where fortification of other staple foods does not achieve desired coverage.

Background Using twice-yearly campaigns such as Child Health Days to deliver vitamin A supplements has been a key strategy over the last 2 decades, and was an important component in helping reach the Millennium Development Goals in child health. As countries move to strengthen their routine health services under the Sustainable Development Goals, efforts are underway to shift supplementation from campaign to routine delivery. Objective The aim of this study was to compare cost, coverage, and user satisfaction between twice-yearly campaigns and routine delivery of vitamin A supplements in Senegal. Methods Information was collected on cost, coverage, and user satisfaction with both types of delivery, using administrative data, interviews at various levels in the health system, and focus group discussions with caregivers. Both qualitative and quantitative information were obtained, for 2 regions using routine delivery and 2 regions using campaign delivery. Results Routine delivery receives fewer dedicated resources. Coverage is lower, especially of children >12 mo of age. Districts undertake outreach (“mini-campaigns”) to try to improve coverage in regions using routine delivery, in effect using a hybrid approach. Some mothers prefer the administration of supplements at a health facility as it is perceived as more hygienic and involving professional health workers, but others, especially those living further away, prefer house-to-house delivery which was the norm for the campaign mode. Conclusions Advance planning for the shift to routine delivery is important in maintaining coverage, as is strengthening the primary health care system by having an appropriate ratio of salaried workers to population. When the system relies heavily on volunteers, and the small incentive payments to volunteers are discontinued, coverage suffers. Routine delivery also relies on good record-keeping and hence literacy. Community understanding of, and support for, supplementation are even more important for routine than for campaign delivery.

This paper examines the evidence for a causal relationship between iron deficiency and a variety of functional consequences with economic implications (motor and mental impairment in children and low work productivity in adults). To the extent that we can be confident that iron deficiency does cause a consequence with economic implications, this effect is quantified in economic terms. Illustrative calculations for 10 developing countries suggest that the median value of annual physical productivity losses due to iron deficiency is around $2.32 per capita, or 0.57% of GDP. Median total losses (physical and cognitive combined) are $16.78 per capita, 4.05% of GDP. Using a cost of $1.33 per case of anemia prevented, from one of the few effectiveness studies of national fortification, allows us to calculate the benefit-cost ratio for long-term iron fortification programs. The median value is 6:1 for the 10 countries examined and rises to 36:1 including the discounted future benefits attributable to cognitive improvements. This paper improves on previous work by including a much more thorough survey of the quantitative magnitudes involved, and by incorporating effects of iron deficiency on cognition. However, more research is needed to verify the accuracy of the assumptions needed for this type of analysis.

This commentary assesses the strength of the causal evidence presented by Haas and Brownlie in this supplement and examines the potential magnitude of iron-deficiency anemia on welfare. From both the laboratory and field experiments, the evidence is strong and suggests that the potential magnitude of the effect of iron-deficiency anemia on work productivity is substantial. This commentary briefly discusses some of the limitations of using the estimates of effects on physiological capacity for measuring the effect on the social and economic well-being of individuals and society. Biological data are relevant to social and economic development, but additional field studies may be as important as the laboratory experiments to answer questions that also affect work productivity, household maintenance and child raising activities, and hence affect social and economic development. We extend the critical evidence review of human field studies that received disproportionately less attention than the laboratory studies in Haas and Brownlie. We provide some estimates of the magnitude of effects on well-being based on how this information has been used. Future field studies that examine the effect of iron-deficiency anemia and work output in an economic sense should measure increases in productivity but should complement this information with data on wages, income or some measure of profits to derive a money metric measure of increased productivity. Additional information on individual time allocation in household work, child care and leisure may also be required to capture social benefits deriving from improved work capacity.

A substantial literature argues that women have been left out of economic development, but evidence from labor force surveys in middle-income developing countries suggests otherwise. Women's participation rates in the market labor force have been increasing, women have shifted into white-collar occupations, and certain previously male-dominated occupations have become female-dominated (clerical work in Asia, for example). Women's relative pay has risen somewhat faster in Asia and Latin America than occurred during industrialization in the United States. Although inequalities remain, there is no evidence that women on average are being marginalized.

This article summarizes available information on costs of feeding and food subsidy programmes, comparing unit costs, share of non-food costs and cost-effectiveness. The effects of programme scale, operating agency (NGO versus government) and geographical location are examined for feeding programmes, both for unit costs and the non-food cost share. Two of the very few cost-effectiveness studies of nutrition interventions estimate cost per death averted to be around $1500, higher than some basic health interventions. There are, however, methodological problems with using this particular cost-effectiveness measure for nutrition interventions.

This paper uses cross-country data from 34 developing countries to examine the correlation between the real cereal price paid by consumers, aggregate calorie intake, and the infant mortality rate. The results suggest that higher cereal prices across countries are associated with higher infant mortality (the elasticity is between 0.2 and 0.6). However this correlation does not exist using time series data for individual countries. The results require further investigation: nevertheless they suggest that although the short-run costs of higher farm prices may not immediately be evident, there may be important long-run social costs.

This study compares the cost-effectiveness of three services for the treatment of diarrhea, in a rural area of Bangladesh. It also examines patterns of user composition, and how these depend on factors other than disease severity and incidence. The three services are a large hospital-style treatment center, an ambulance system bringing patients from greater distances, and a small treatment center staffed by paramedics. The results show that the long run average cost per patient is about +16 at the large center, with an additional +13 if the patient came by ambulance, compared to +3 at the small center. Corresponding costs per death averted were +1300, an additional +360, and +190 respectively. Previous studies have suggested that there is no more cost-effective alternative for the prevention of diarrhea, although in future home-based oral rehydration therapy may be a potential alternative. Each service exhibits use patterns suggesting that males and especially small boys receive preferential access to treatment. This bias is exacerbated as distance from the center increases, or if a fee is charged. The study concludes firstly that diarrhea treatment costs in clinics are relatively high, and secondly that unintended biases in service use should be an important consideration in service design.

Economic events of the 1970s and early 1980s (world recession and disruption of international trade and finance) hit sub-Saharan Africa particularly badly. There has been heated debate as to the role of additional external resources and domestic adjustment measures in economic recovery. This paper uses a supply constrained macroeconometric model of the Tanzanian economy to simulate the effects of several alternative strategies. The results highlight the problems of either a strategy of devaluation or of more external aid alone. One inexpensive policy advocated is that of freeing project aid for general balance of payments support.

This paper presents and tests a model of the determinants of nutrient intake. The model is based on an identity whereby calorie intake per adult equivalent can be expressed as a function of total expenditure, the share of food in the budget, a unit value index, an expenditure efficiency index, and household composition. These endogenous variables are in turn expressed as a function of exogenous variables such as assets, demographic factors and agricultural technology. The results help to explain the large variance in calorie intake at a given level of income, and suggest that interesting compensatory behavior occurs by households.

This paper presents a detailed description of a macroeconometric model of Tanzania, a small open economy at an early stage of economic development. In this economy, imports are a crucial constraint on sectoral output. Since exports are a main source of finance for imports, the export sector is modelled in some detail. The paper describes the theoretical structure of the model, provides a complete list of equations, and briefly discusses its forecasting properties.

This paper uses household data from the Philippines to examine jointly household decisions on family size and child quality, using nutritional status as a measure of quality. The results suggest that there are significant substitutions away from larger families and towards higher quality children with higher maternal and paternal education. Similar but less significant substitutions occur with higher maternal occupational status, and lower child mortality in the locality. However the paper finds only limited support for the idea that parents are concerned about average child quality, since the results show that there are strong birth order effects on nutritional status.