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.

Several trials have studied the role of unconventional fractionated radiotherapy in head and neck squamous cell carcinoma, but the effect of such treatment on survival is not clear. The aim of this meta-analysis was to assess whether this type of radiotherapy could improve survival.

The common disease asthma is probably not a single disease, but rather a complex of multiple, separate syndromes that overlap. Although clinicians have recognised these different phenotypes for many years, they have remained poorly characterised, with little known about the underlying pathobiology contributing to them. Development of targeted therapies for asthma, and phenotype-specific clinical trials have raised interest in these phenotypes. Improved understanding of these phenotypes in complex diseases such as asthma will also improve our ability to link specific genotypes to their associated disease, which should help development of biomarkers. However, there is no standardised method to define asthma phenotypes. This Review analyses some of the methods that have been used to define asthma phenotypes and proposes an integrated method of classification to improve our understanding of these phenotypes.

Patients with mild persistent asthma rarely see their doctor with symptoms of the disease. Partly as a result of this situation, mild asthma is generally undertreated. Findings of several large randomised clinical trials have shown benefits for this population of regular treatment with low doses of inhaled corticosteroids. Additional drugs are rarely needed, and although leukotriene modifiers are effective, they are less so than inhaled corticosteroids. People with moderate persistent asthma are not well controlled on low doses of inhaled corticosteroids. A combination of this drug and long-acting inhaled beta2 agonists provides improved control compared with doubling of the maintenance dose of inhaled corticosteroids. The combination of budesonide and formoterol has been assessed as both maintenance and reliever treatment. This approach further reduces the risk for severe exacerbations. With these strategies, most individuals can achieve good control of their asthma. For patients who do not achieve asthma control despite taking drugs, measurement of the inflammatory response in the airway in induced sputum could provide further information to guide treatment.

There has been a recent increase in the prevalence of asthma worldwide; however, the 5-10% of patients with severe disease account for a substantial proportion of the health costs. Although most asthma cases can be satisfactorily managed with a combination of anti-inflammatory drugs and bronchodilators, patients who remain symptomatic despite maximum combination treatment represent a heterogeneous group consisting of those who are under-treated or non-adherent with their prescribed medication. After excluding under-treatment and poor compliance, corticosteroid refractory asthma can be identified as a subphenotype characterised by a heightened neutrophilic airway inflammatory response in the presence or absence of eosinophils, with evidence of increased tissue injury and remodelling. Although a wide range of environmental factors such as allergens, smoking, air pollution, infection, hormones, and specific drugs can contribute to this phenotype, other features associated with changes in the airway inflammatory response should be taken into account. Aberrant communication between an injured airway epithelium and underlying mesenchyme contributes to disease chronicity and refractoriness to corticosteroids. The importance of identifying underlying causative factors and the recent introduction of novel therapeutic approaches, including the targeting of immunoglobulin E and tumour necrosis factor alpha with biological agents, emphasise the need for careful phenotyping of patients with severe disease to target improved management of the individual patient's needs.

Millions of individuals with coronary artery or valvular heart disease have been given a new chance at life by heart surgery, but the potential for neurological injury is an Achilles heel. Technological advancements and innovations in surgical and anaesthetic technique have allowed us to offer surgical treatment to patients at the extremes of age and infirmity-the group at greatest risk for neurological injury. Neurocognitive dysfunction is a complication of cardiac surgery that can restrict the improved quality of life that patients usually experience after heart surgery. With a broader understanding of the frequency and effects of neurological injury from cardiac surgery and its implications for patients in both the short term and the long term, we should be able to give personalised treatments and thus preserve both their quantity and quality of life. We describe these issues and the controversies that merit continued investigation.

Peripartum cardiomyopathy (PPCM) is a disorder in which initial left ventricular systolic dysfunction and symptoms of heart failure occur between the late stages of pregnancy and the early postpartum period. It is common in some countries and rare in others. The causes and pathogenesis are poorly understood. Molecular markers of an inflammatory process are found in most patients. Clinical presentation includes usual signs and symptoms of heart failure, and unusual presentations relating to thromboembolism. Clinicians should consider PPCM in any peripartum patient with unexplained disease. Conventional heart failure treatment includes use of diuretics, beta blockers, and angiotensin-converting enzyme inhibitors. Effective treatment reduces mortality rates and increases the number of women who fully recover left ventricular systolic function. Outcomes for subsequent pregnancy after PPCM are better in women who have first fully recovered heart function. Areas for future research include immune system dysfunction, the role of viruses, non-conventional treatments such as immunosuppression, immunoadsorption, apheresis, antiviral treatment, suppression of proinflammatory cytokines, and strategies for control and prevention.

Cardiovascular disease is the leading cause of death, with 80% of cases occurring in developing countries. We therefore aimed to establish whether use of evidence-based multidrug regimens for patients at high risk for cardiovascular disease would be cost-effective in low-income and middle-income countries.

Studies of the association between obesity, and total mortality and cardiovascular events in patients with coronary artery disease (CAD) have shown contradictory results. We undertook a systematic review to determine the extent and nature of this association.

Many human conceptions are genetically abnormal and end in miscarriage, which is the commonest complication of pregnancy. Recurrent miscarriage, the loss of three or more consecutive pregnancies, affects 1% of couples trying to conceive. It is associated with psychological morbidity, and has often proven to be frustrating for both patient and clinician. A third of women attending specialist clinics are clinically depressed, and one in five have levels of anxiety that are similar to those in psychiatric outpatient populations. Many conventional beliefs about the cause and treatment of women with recurrent miscarriage have not withstood scrutiny, but progress has been made. Research has emphasised the importance of recurrent miscarriage in the range of reproductive failure linking subfertility and late pregnancy complications and has allowed us to reject practice based on anecdotal evidence in favour of evidence-based management.

Angiotensin-converting-enzyme (ACE) inhibitors reduce cardiovascular mortality and morbidity in patients with heart failure or left ventricular systolic dysfunction (LVSD). Three large trials have assessed the effect of ACE inhibitors in stable patients without these conditions but with atherosclerosis. We undertook a systematic review of the Heart Outcomes Prevention Evaluation (HOPE), the European trial on Reduction Of cardiac events with Perindopril among patients with stable coronary Artery disease (EUROPA), and the Prevention of Events with ACE inhibition (PEACE) studies to determine the consistency with which ACE inhibitors reduce total mortality and fatal and non-fatal cardiovascular events.