In this paper, we take a broad perspective on maternal health and place it in its wider context. We draw attention to the economic and social vulnerability of pregnant women, and stress the importance of concomitant broader strategies, including poverty reduction and women's empowerment. We also consider outcomes beyond mortality, in particular, near-misses and long-term sequelae, and the implications of the close association between the mother, the fetus, and the child. We make links to a range of global survival initiatives, particularly neonatal health, HIV, and malaria, and to reproductive health. Finally, after examining the political and financial context, we call for action. The need for strategic vision, financial resources, human resources, and information are discussed.

Despite having achieved an average life expectancy of 75 years, much the same as that of more developed countries, Mexico entered the 21st century with a health system marred by its failure to offer financial protection in health to more than half of its citizens; this was both a result and a cause of the social inequalities that have marked the development process in Mexico. Several structural limitations have hampered performance and limited the progress of the health system. Conscious that the lack of financial protection was the major bottleneck, Mexico has embarked on a structural reform to improve health system performance by establishing the System of Social Protection in Health (SSPH), which has introduced new financial rules and incentives. The main innovation of the reform has been the Seguro Popular (Popular Health Insurance), the insurance-based component of the SSPH, aimed at funding health care for all those families, most of them poor, who had been previously excluded from social health insurance. The reform has allowed for a substantial increase in public investment in health while realigning incentives towards better technical and interpersonal quality. This paper describes the main features and initial results of the Mexican reform effort, and derives lessons for other countries considering health-system transformations under similarly challenging circumstances.

The optimum treatment choice between initial highly-active antiretroviral therapy (HAART) with a protease inhibitor (PI) versus a non-nucleoside reverse transcriptase inhibitor (NNRTI) is uncertain. An indirect analysis reported that PI-based HAART was better than NNRTI-based HAART. However, direct evidence for competing interventions is deemed more reliable than indirect evidence for making treatment decisions. We did a meta-analysis of head-to-head trials and compared the results with those of indirect analyses.

Coverage of cost-effective maternal health services remains poor due to insufficient supply and inadequate demand for these services among the poorest groups. Households pay too great a share of the costs of maternal health services, or do not seek care because they cannot afford the costs. Available evidence creates a strong case for removal of user fees and provision of universal coverage for pregnant women, particularly for delivery care. To be successful, governments must also replenish the income lost through the abolition of user fees. Where insurance schemes exist, maternal health care needs to be included in the benefits package, and careful design is needed to ensure uptake by the poorest people. Voucher schemes should be tested in low-income settings, and their costs and relative cost-effectiveness assessed. Further research is needed on methods to target financial assistance for transport and time costs. Current investment in maternal health is insufficient to meet the fifth Millennium Development Goal (MDG), and much greater resources are needed to scale up coverage of maternal health services and create demand. Existing global estimates are too crude to be of use for domestic planning, since resource requirements will vary; budgets need first to be developed at country-level. Donors need to increase financial contributions for maternal health in low-income countries to help fill the resource gap. Resource tracking at country and donor levels will help hold countries and donors to account for their commitments to achieving the maternal health MDG.

Use of drugs that inhibit the renin-angiotensin system is an effective way to intervene in the pathogenesis of cardiovascular and renal disorders. The idea of blocking the renin system at its origin by inhibition of renin has existed for more than 30 years. Renin inhibition suppresses the generation of the active peptide angiotensin II. The first generation of orally active renin inhibitors were never used clinically because of low bioavailability and weak blood-pressure-lowering activity. At present, aliskiren is the first non-peptide orally active renin inhibitor to progress to phase-III clinical trials. It might become the first renin inhibitor with indications for the treatment of hypertension and cardiovascular and renal disorders. Novel compounds with improved oral bioavailability, specificity, and efficacy are now in preclinical development. This Review summarises the development of oral renin inhibitors and their pharmacokinetic and pharmacodynamic properties, with a focus on aliskiren.

Individual trials to test effectiveness of antibiotics in children with acute otitis media have been too small for valid subgroup analyses. We aimed to identify subgroups of children who would and would not benefit more than others from treatment with antibiotics.

Because most women prefer professionally provided maternity care when they have access to it, and since the needed clinical interventions are well known, we discuss in their paper what is needed to move forward from apparent global stagnation in provision and use of maternal health care where maternal mortality is high. The main obstacles to the expansion of care are the dire scarcity of skilled providers and health-system infrastructure, substandard quality of care, and women's reluctance to use maternity care where there are high costs and poorly attuned services. To increase the supply of professional skilled birthing care, strategic decisions must be made in three areas: training, deployment, and retention of health workers. Based on results from simulations, teams of midwives and midwife assistants working in facilities could increase coverage of maternity care by up to 40% by 2015. Teams of providers are the efficient option, creating the possibility of scaling up as much as 10 times more quickly than would be the case with deployment of solo health workers in home deliveries with dedicated or multipurpose workers.

Varicella-zoster virus, a herpesvirus, causes varicella (chickenpox) and, after endogenous reactivation, herpes zoster (shingles). Varicella, which is recognised by a characteristic vesicular rash, arises mainly in young children, although older individuals can be affected. In immunocompetent patients, symptoms are usually mild to moderate, but an uncomplicated severe case can have more than 1000 lesions and severe constitutional symptoms. Serious complications--including central nervous system involvement, pneumonia, secondary bacterial infections, and death--are sometimes seen. Varicella can be prevented by vaccination. Vaccine is about 80-85% effective against all disease and highly (more than 95%) effective in prevention of severe disease. In the USA, a routine childhood immunisation programme has reduced disease incidence, complications, hospital admissions, and deaths in children and in the general population, indicating strong herd immunity. Similar immunisation programmes have been adopted by some other countries, including Uruguay, Germany, Taiwan, Canada, and Australia, and are expected to be implemented more widely in future.

The concept of knowing what works in terms of reducing maternal mortality is complicated by a huge diversity of country contexts and of determinants of maternal health. Here we aim to show that, despite this complexity, only a few strategic choices need to be made to reduce maternal mortality. We begin by presenting the logic that informs our strategic choices. This logic suggests that implementation of an effective intrapartum-care strategy is an overwhelming priority. We also discuss the alternative configurations of such a strategy and, using the best available evidence, prioritise one strategy based on delivery in primary-level institutions (health centres), backed up by access to referral-level facilities. We then go on to discuss strategies that complement intrapartum care. We conclude by discussing the inexplicable hesitation in decision-making after nearly 20 years of safe motherhood programming: if the fifth Millennium Development Goal is to be achieved, then what needs to be prioritised is obvious. Further delays in getting on with what works begs questions about the commitment of decision-makers to this goal.

Necrotising enterocolitis is one of the most common gastrointestinal emergencies in newborn infants. Here we review the epidemiology, clinical presentation, and pathophysiology of the disease, as well as strategies for diagnosis, management, and prevention. Necrotising enterocolitis is one of the most devastating and unpredictable diseases affecting premature infants. Despite decades of research, its pathogenesis remains unclear; diagnosis can be difficult; and treatment is challenging. We will need to improve our understanding of intestinal defences in premature infants, dietary and bacterial factors, and genetic effects that could predispose infants to necrotising enterocolitis before we can develop new strategies for prevention and treatment.

Vesicovaginal fistula is a devastating injury in which an abnormal opening forms between a woman's bladder and vagina, resulting in urinary incontinence. This condition is rare in developed countries, but in developing countries it is a common complication of childbirth resulting from prolonged obstructed labour. Estimates suggest that at least 3 million women in poor countries have unrepaired vesicovaginal fistulas, and that 30 000-130 000 new cases develop each year in Africa alone. The general public and the world medical community remain largely unaware of this problem. In this article I review the pathophysiology of vesicovaginal fistula in obstructed labour and describe the effect of this condition on the lives of women in developing countries. Policy recommendations to combat this problem include enhancing public awareness, raising the priority of women's reproductive health for developing countries and aid agencies, expanding access to emergency obstetric services, and creation of fistula repair centres.

The risk of a woman dying as a result of pregnancy or childbirth during her lifetime is about one in six in the poorest parts of the world compared with about one in 30 000 in Northern Europe. Such a discrepancy poses a huge challenge to meeting the fifth Millennium Development Goal to reduce maternal mortality by 75% between 1990 and 2015. Some developed and transitional countries have managed to reduce their maternal mortality during the past 25 years. Few of these, however, began with the very high rates that are now estimated for the poorest countries-in which further progress is jeopardised by weak health systems, continuing high fertility, and poor availability of data. Maternal deaths are clustered around labour, delivery, and the immediate postpartum period, with obstetric haemorrhage being the main medical cause of death. Local variation can be important, with unsafe abortion carrying huge risk in some populations, and HIV/AIDS becoming a leading cause of death where HIV-related mortaliy rates are high. Inequalities in the risk of maternal death exist everywhere. Targeting of interventions to the most vulnerable--rural populations and poor people--is essential if substantial progress is to be achieved by 2015.

Medical therapies to ease urinary-stone passage have been reported, but are not generally used. If effective, such therapies would increase the options for treatment of urinary stones. To assess efficacy, we sought to identify and summarise all randomised controlled trials in which calcium-channel blockers or alpha blockers were used to treat urinary stone disease.

Schistosomiasis or bilharzia is a tropical disease caused by worms of the genus Schistosoma. The transmission cycle requires contamination of surface water by excreta, specific freshwater snails as intermediate hosts, and human water contact. The main disease-causing species are S haematobium, S mansoni, and S japonicum. According to WHO, 200 million people are infected worldwide, leading to the loss of 1.53 million disability-adjusted life years, although these figures need revision. Schistosomiasis is characterised by focal epidemiology and overdispersed population distribution, with higher infection rates in children than in adults. Complex immune mechanisms lead to the slow acquisition of immune resistance, though innate factors also play a part. Acute schistosomiasis, a feverish syndrome, is mostly seen in travellers after primary infection. Chronic schistosomal disease affects mainly individuals with long-standing infections in poor rural areas. Immunopathological reactions against schistosome eggs trapped in the tissues lead to inflammatory and obstructive disease in the urinary system (S haematobium) or intestinal disease, hepatosplenic inflammation, and liver fibrosis (S mansoni, S japonicum). The diagnostic standard is microscopic demonstration of eggs in the excreta. Praziquantel is the drug treatment of choice. Vaccines are not yet available. Great advances have been made in the control of the disease through population-based chemotherapy but these required political commitment and strong health systems.

Panic disorder is a common mental disorder that affects up to 5% of the population at some point in life. It is often disabling, especially when complicated by agoraphobia, and is associated with substantial functional morbidity and reduced quality of life. The disorder is also costly for individuals and society, as shown by increased use of health care, absenteeism, and reduced workplace productivity. Some physical illnesses (eg, asthma) commonly occur with panic disorder, and certain lifestyle factors (eg, smoking) increase the risk for the disorder, but causal pathways are still unclear. Genetic and early experiential susceptibility factors also exist, but their exact nature and pathophysiological mechanisms remain unknown. Despite an imprecise, although increased, understanding of cause, strong evidence supports the use of several effective treatments (eg, pharmacological, cognitive-behavioural). The adaptation and dissemination of these treatments to the frontlines of medical-care delivery should be urgent goals for the public-health community.

During the past 6 years, Mexico has undergone a large-scale transformation of its health system. This paper provides an overview of the main features of the Mexican reform experience. Because of its high degree of social inequality, Mexico is a microcosm of the range of problems that affect countries at all levels of development. Its health system had not kept up with the pressures of the double burden of disease, whereby malnutrition, common infections, and reproductive health problems coexist with non-communicable disease and injury. With half of its population uninsured, Mexico was facing an unacceptable paradox: whereas health is a key factor in the fight against poverty, a large number of families became impoverished by expenditures in health care and drugs. The reform was designed to correct this paradox by introducing a new scheme called Popular Health Insurance (Seguro Popular). This innovative initiative is gradually protecting the 50 million Mexicans, most of them poor, who had until now been excluded from formal social insurance. This paper reports encouraging results in the achievement of the ultimate objective of the reform: universal access to high-quality services with social protection for all.

As with many other therapeutic areas in modern-day medicine, scientific advances in drug development (using such techniques as recombinant DNA technology, site-directed mutagenesis, pegylation of molecules, peptide library screening, and gene transfer) have resulted in the development of potential new agents and strategies for stimulating erythropoiesis. These advances are of possible benefit in treating anaemia due to various causes, including chronic renal failure. Several new treatments will soon become clinically available, while others are at present at an early stage of development but are nevertheless of scientific interest. We review these new therapeutic strategies, and discuss at what stage some of the newer products are in relation to their clinical development programme.

Staphylococcus aureus is a gram-positive bacterium that colonises the skin and is present in the anterior nares in about 25-30% of healthy people. Dependent on its intrinsic virulence or the ability of the host to contain its opportunistic behaviour, S aureus can cause a range of diseases in man. The bacterium readily acquires resistance against all classes of antibiotics by one of two distinct mechanisms: mutation of an existing bacterial gene or horizontal transfer of a resistance gene from another bacterium. Several mobile genetic elements carrying exogenous antibiotic resistance genes might mediate resistance acquisition. Of all the resistance traits S aureus has acquired since the introduction of antimicrobial chemotherapy in the 1930s, meticillin resistance is clinically the most important, since a single genetic element confers resistance to the most commonly prescribed class of antimicrobials--the beta-lactam antibiotics, which include penicillins, cephalosporins, and carbapenems.