In 2005, WHO set a global goal to reduce rates of death from chronic (non-communicable) disease by an additional 2% every year. To this end, we investigated how many deaths could potentially be averted over 10 years by implementation of selected population-based interventions, and calculated the financial costs of their implementation. We selected two interventions: to reduce salt intake in the population by 15% and to implement four key elements of the WHO Framework Convention on Tobacco Control (FCTC). We used methods from the WHO Comparative Risk Assessment project to estimate shifts in the distribution of risk factors associated with salt intake and tobacco use, and to model the effects on chronic disease mortality for 23 countries that account for 80% of chronic disease burden in the developing world. We showed that, over 10 years (2006-2015), 13.8 million deaths could be averted by implementation of these interventions, at a cost of less than US$0.40 per person per year in low-income and lower middle-income countries, and US$0.50-1.00 per person per year in upper middle-income countries (as of 2005). These two population-based intervention strategies could therefore substantially reduce mortality from chronic diseases, and make a major (and affordable) contribution towards achievement of the global goal to prevent and control chronic diseases.

Chronic (non-communicable) diseases--principally cardiovascular diseases, cancer, chronic respiratory diseases, and diabetes--are leading causes of death and disability but are surprisingly neglected elements of the global-health agenda. They are underappreciated as development issues and underestimated as diseases with profound economic effects. Achievement of the global goal for prevention and control of chronic diseases would avert 36 million deaths by 2015 and would have major economic benefits. The main challenge for achievement of the global goal is to show that it can be reached in a cost-effective manner with existing interventions. This series of papers in The Lancet provides evidence that this goal is not only possible but also realistic with a small set of interventions directed towards whole populations and individuals who are at high risk. The total yearly cost of the interventions in 23 low-income and middle-income countries is about US$5.8 billion (as of 2005). In this final paper in the Series we call for a serious and sustained worldwide effort to prevent and control chronic diseases in the context of a general strengthening of health systems. Urgent action is needed by WHO, the World Bank, regional banks and development agencies, foundations, national governments, civil society, non-governmental organisations, the private sector including the pharmaceutical industry, and academics. We have established the Chronic Disease Action Group to encourage, support, and monitor action on the implementation of evidence-based efforts to promote global, regional, and national action to prevent and control chronic diseases.

In 2005, a global goal of reducing chronic disease death rates by an additional 2% per year was established. Scaling up coverage of evidence-based interventions to prevent cardiovascular disease in high-risk individuals in low-income and middle-income countries could play a major part in reaching this goal. We aimed to estimate the number of deaths that could be averted and the financial cost of scaling up, above current coverage levels, a multidrug regimen for prevention of cardiovascular disease (a statin, aspirin, and two blood-pressure-lowering medicines) in 23 such countries. Identification of individuals was limited to those already accessing health services, and treatment eligibility was based on the presence of existing cardiovascular disease or absolute risk of cardiovascular disease by use of easily measurable risk factors. Over a 10-year period, scaling up this multidrug regimen could avert 17.9 million deaths from cardiovascular disease (95% uncertainty interval 7.4 million-25.7 million). 56% of deaths averted would be in those younger than 70 years, with more deaths averted in women than in men owing to larger absolute numbers of women at older ages. The 10-year financial cost would be US$47 billion ($33 billion-$61 billion) or an average yearly cost per head of $1.08 ($0.75-1.40), ranging from $0.43 to $0.90 across low-income countries and from $0.54 to $2.93 across middle-income countries. This package could effectively meet three-quarters of the proposed global goal with a moderate increase in health expenditure.

Since the discovery of the haemochromatosis gene (HFE; chromosome 6p21.3) associated with haemochromatosis in 1996, many studies about diverse aspects of this common genetic disorder have been done. Some patients present with cirrhosis and show high mortality, whereas many asymptomatic homozygotes for the C282Y mutation in the haemochromatosis gene identified in population screening studies, who have been followed up for many years, do not develop iron overload. Studies described the usefulness of transferrin saturation and serum ferritin tests, and the acceptability of genetic testing for haemochromatosis. Phlebotomy therapy improves hepatic fibrosis. Here, we summarise some new findings in haemochromatosis, a disorder first described in 1865.

Age, sex, and blood pressure could modify the associations of total cholesterol (and its main two fractions, HDL and LDL cholesterol) with vascular mortality. This meta-analysis combined prospective studies of vascular mortality that recorded both blood pressure and total cholesterol at baseline, to determine the joint relevance of these two risk factors.

In the UK, about one in 200 infants is stillborn, and rates of stillbirth have recently slightly increased. This recent rise might reflect increasing frequency of some important maternal risk factors for stillbirth, including nulliparity, advanced age, and obesity. Most stillbirths are related to placental dysfunction, which in many women is evident from the first half of pregnancy and is associated with fetal growth restriction. There is no effective screening test that has clearly shown a reduction in stillbirth rates in the general population. However, assessments of novel screening methods have generally failed to distinguish between effective identification of high-risk women and successful intervention for such women. Future research into stillbirth will probably focus on understanding the pathophysiology of impaired placentation to establish screening tests for stillbirth, and assessment of interventions to prevent stillbirth in women who screen positive.

Since the prevalence of obesity continues to increase, there is a demand for effective and safe anti-obesity agents that can produce and maintain weight loss and improve comorbidity. We did a meta-analysis of all published randomised controlled trials to assess the efficacy and safety of the newly approved anti-obesity agent rimonabant.

The four dengue viruses are transmitted in tropical countries that circle the globe. All can cause syndromes that are self-limited or severe. The common severe syndrome--dengue haemorrhagic fever/dengue shock syndrome (DHF/DSS)--is characterised by sudden vascular permeability generated by cytokines released when T cells attack dengue-infected cells. Dengue 1 virus became prevalent in Hawaii where it was transmitted by Aedes albopictus, producing a classic virgin soil epidemic, with clinical disease seen largely in adults. In Cuba and Singapore, sequential dengue infections at long intervals produced unusually severe disease in adults. Evidence suggests that enhancing and cross-reactive neutralising antibodies regulate dengue epidemics and disease severity. Classic DHF/DSS arises during initial dengue infections in infants with low circulating amounts of maternal dengue antibodies, an observation that precludes an exclusive causal role for secondary T-cell responses. Here, I review and discuss data on clinical diagnosis and pathophysiology of vascular permeability and coagulopathy, parenteral treatment of DHF/DSS, and new laboratory tests.

Combined oral contraceptives are classified by the International Agency for Research on Cancer as a cause of cervical cancer. As the incidence of cervical cancer increases with age, the public-health implications of this association depend largely on the persistence of effects long after use of oral contraceptives has ceased. Information from 24 studies worldwide is pooled here to investigate the association between cervical carcinoma and pattern of oral contraceptive use.

Despite declines in prevalence during the past two decades, sudden infant death syndrome (SIDS) continues to be the leading cause of death for infants aged between 1 month and 1 year in developed countries. Behavioural risk factors identified in epidemiological studies include prone and side positions for infant sleep, smoke exposure, soft bedding and sleep surfaces, and overheating. Evidence also suggests that pacifier use at sleep time and room sharing without bed sharing are associated with decreased risk of SIDS. Although the cause of SIDS is unknown, immature cardiorespiratory autonomic control and failure of arousal responsiveness from sleep are important factors. Gene polymorphisms relating to serotonin transport and autonomic nervous system development might make affected infants more vulnerable to SIDS. Campaigns for risk reduction have helped to reduce SIDS incidence by 50-90%. However, to reduce the incidence even further, greater strides must be made in reducing prenatal smoke exposure and implementing other recommended infant care practices. Continued research is needed to identify the pathophysiological basis of SIDS.

In the 1960s, total hip replacement revolutionised management of elderly patients crippled with arthritis, with very good long-term results. Today, young patients present for hip-replacement surgery hoping to restore their quality of life, which typically includes physically demanding activities. Advances in bioengineering technology have driven development of hip prostheses. Both cemented and uncemented hips can provide durable fixation. Better materials and design have allowed use of large-bore bearings, which provide an increased range of motion with enhanced stability and very low wear. Minimally invasive surgery limits soft-tissue damage and facilitates accelerated discharge and rehabilitation. Short-term objectives must not compromise long-term performance. Computer-assisted surgery will contribute to reproducible and accurate placement of implants. Universal economic constraints in healthcare services dictate that further developments in total hip replacement will be governed by their cost-effectiveness.

Velocardiofacial syndrome, DiGeorge syndrome, and some other clinical syndromes have in common a high frequency of hemizygous deletions of chromosome 22q11.2. This deletion syndrome is very common, affecting nearly one in 3000 children. Here, we focus on recent advances in cardiac assessment, speech, immunology, and pathophysiology of velocardiofacial syndrome. The complex medical care of patients needs a multidisciplinary approach, and every patient has his own unique clinical features that need a tailored approach. Patients with chromosome 22q11.2 deletion syndrome might have high level of functioning, but most often need interventions to improve the function of many organ systems.

The time is right to shift the focus of the global maternal health community to the challenges of effective implementation of services within districts. 20 years after the launch of the Safe Motherhood Initiative, the community has reached a broad consensus about priority interventions, incorporated these interventions into national policy documents, and organised globally in coalition with the newborn and child health communities. With changes in policy processes to emphasise country ownership, funding harmonisation, and results-based financing, the capacity of countries to implement services urgently needs to be strengthened. In this article, four global maternal health initiatives draw on their complementary experiences to identify a set of the central lessons on which to build a new, collaborative effort to implement equitable, sustainable maternal health services at scale. This implementation effort should focus on specific steps for strengthening the capacity of the district health system to convert inputs into functioning services that are accessible to and used by all segments of the population.

Why do some global health initiatives receive priority from international and national political leaders whereas others receive little attention? To analyse this question we propose a framework consisting of four categories: the strength of the actors involved in the initiative, the power of the ideas they use to portray the issue, the nature of the political contexts in which they operate, and characteristics of the issue itself. We apply this framework to the case of a global initiative to reduce maternal mortality, which was launched in 1987. We undertook archival research and interviewed people connected with the initiative, using a process-tracing method that is commonly employed in qualitative research. We report that despite two decades of effort the initiative remains in an early phase of development, hampered by difficulties in all these categories. However, the initiative's 20th year, 2007, presents opportunities to build political momentum. To generate political priority, advocates will need to address several challenges, including the creation of effective institutions to guide the initiative and the development of a public positioning of the issue to convince political leaders to act. We use the framework and case study to suggest areas for future research on the determinants of political priority for global health initiatives, which is a subject that has attracted much speculation but little scholarship.

The continuum of care has become a rallying call to reduce the yearly toll of half a million maternal deaths, 4 million neonatal deaths, and 6 million child deaths. The continuum for maternal, newborn, and child health usually refers to continuity of individual care. Continuity of care is necessary throughout the lifecycle (adolescence, pregnancy, childbirth, the postnatal period, and childhood) and also between places of caregiving (including households and communities, outpatient and outreach services, and clinical-care settings). We define a population-level or public-health framework based on integrated service delivery throughout the lifecycle, and propose eight packages to promote health for mothers, babies, and children. These packages can be used to deliver more than 190 separate interventions, which would be difficult to scale up one by one. The packages encompass three which are delivered through clinical care (reproductive health, obstetric care, and care of sick newborn babies and children); four through outpatient and outreach services (reproductive health, antenatal care, postnatal care and child health services); and one through integrated family and community care throughout the lifecycle. Mothers and babies are at high risk in the first days after birth, and the lack of a defined postnatal care package is an important gap, which also contributes to discontinuity between maternal and child health programmes. Similarly, because the family and community package tends not to be regarded as part of the health system, few countries have made systematic efforts to scale it up or integrate it with other levels of care. Building the continuum of care for maternal, newborn, and child health with these packages will need effectiveness trials in various settings; policy support for integration; investment to strengthen health systems; and results-based operational management, especially at district level.

There is a large amount of research into maternal health as a health issue, but maternal health as a development issue has been less explored. This Review analyses the evidence from the past 20 years on the links between maternal health and development to examine maternal health within a development framework. We note that although existing evidence suggests that these links are strong, further research is needed to definitively substantiate how and to what extent maternal health and development affect each other. Further, we find that progress and investment in maternal health have lagged far behind estimates of what is needed to achieve the Millennium Development Goals.

The overall clinical benefit of thiazolidinediones (TZDs) as a treatment for hyperglycaemia can be difficult to assess because of the risk of congestive heart failure due to TZD-related fluid retention. Since prediabetic and diabetic patients are at high cardiovascular risk, the outcome and natural history of such risks need to be better understood. We aimed to examine the risk of congestive heart failure and of cardiac death in patients given TZDs.

The provision of electricity has been a great benefit to society, particularly in health terms, but it also carries health costs. Comparison of different forms of commercial power generation by use of the fuel cycle methods developed in European studies shows the health burdens to be greatest for power stations that most pollute outdoor air (those based on lignite, coal, and oil). The health burdens are appreciably smaller for generation from natural gas, and lower still for nuclear power. This same ranking also applies in terms of greenhouse-gas emissions and thus, potentially, to long-term health, social, and economic effects arising from climate change. Nuclear power remains controversial, however, because of public concern about storage of nuclear waste, the potential for catastrophic accident or terrorist attack, and the diversion of fissionable material for weapons production. Health risks are smaller for nuclear fusion, but commercial exploitation will not be achieved in time to help the crucial near-term reduction in greenhouse-gas emissions. The negative effects on health of electricity generation from renewable sources have not been assessed as fully as those from conventional sources, but for solar, wind, and wave power, such effects seem to be small; those of biofuels depend on the type of fuel and the mode of combustion. Carbon dioxide (CO2) capture and storage is increasingly being considered for reduction of CO2 emissions from fossil fuel plants, but the health effects associated with this technology are largely unquantified and probably mixed: efficiency losses mean greater consumption of the primary fuel and accompanying increases in some waste products. This paper reviews the state of knowledge regarding the health effects of different methods of generating electricity.

The exploitation of fossil fuels is integral to modern living and has been a key element of the rapid technological, social, and cultural changes of the past 250 years. Although such changes have brought undeniable benefits, this exploitation has contributed to a burden of illness through pollution of local and regional environments, and is the dominant cause of climate change. This pattern of development is therefore unsustainable at a global level. At the same time, about 2.4 billion of the world's population, disadvantaged by lack of access to clean energy, are exposed to high levels of indoor air pollutants from the inefficient burning of biomass fuels. Even in high-income countries, many people live in fuel poverty, and throughout the world, increasingly sedentary lifestyles (to which fossil-fuel-dependent transport systems contribute) are leading to chronic disease and injuries. Energy security is also an issue of growing concern to many governments in both the developed and developing world, and a potential source of international tension and conflict. In this Series, we examine the opportunities to improve health, reduce climate effects, and promote development through realistic adjustments in the way energy and food are produced and consumed.