Whether the two drug-eluting stents approved by the US Food and Drug Administration-a sirolimus-eluting stent and a paclitaxel-eluting stent-are associated with increased risks of death, myocardial infarction, or stent thrombosis compared with bare-metal stents is uncertain. Our aim was to compare the safety and effectiveness of these stents.

Since the last decades of the 19th century, technological advances have brought substantial improvements in the efficiency with which energy can be exploited to service human needs. That trend has been accompanied by an equally notable increase in energy consumption, which strongly correlates with socioeconomic development. Nonetheless, feasible gains in the efficiency and technology of energy use in towns and cities and in homes have the potential to contribute to the mitigation of greenhouse-gas emissions, and to improve health, for example, through protection against temperature-related morbidity and mortality, and the alleviation of fuel poverty. A shift towards renewable energy production would also put increasing focus on cleaner energy carriers, especially electricity, but possibly also hydrogen, which would have benefits to urban air quality. In low-income countries, a vital priority remains the dissemination of affordable technology to alleviate the burdens of indoor air pollution and other health effects in individuals obliged to rely on biomass fuels for cooking and heating, as well as the improvement in access to electricity, which would have many benefits to health and wellbeing.

The absence of reliable access to clean energy and the services it provides imposes a large disease burden on low-income populations and impedes prospects for development. Furthermore, current patterns of fossil-fuel use cause substantial ill-health from air pollution and occupational hazards. Impending climate change, mainly driven by energy use, now also threatens health. Policies to promote access to non-polluting and sustainable sources of energy have great potential both to improve public health and to mitigate (prevent) climate disruption. There are several technological options, policy levers, and economic instruments for sectors such as power generation, transport, agriculture, and the built environment. However, barriers to change include vested interests, political inertia, inability to take meaningful action, profound global inequalities, weak technology-transfer mechanisms, and knowledge gaps that must be addressed to transform global markets. The need for policies that prevent dangerous anthropogenic interference with the climate while addressing the energy needs of disadvantaged people is a central challenge of the current era. A comprehensive programme for clean energy should optimise mitigation and, simultaneously, adaption to climate change while maximising co-benefits for health--eg, through improved air, water, and food quality. Intersectoral research and concerted action, both nationally and internationally, will be required.

Food provides energy and nutrients, but its acquisition requires energy expenditure. In post-hunter-gatherer societies, extra-somatic energy has greatly expanded and intensified the catching, gathering, and production of food. Modern relations between energy, food, and health are very complex, raising serious, high-level policy challenges. Together with persistent widespread under-nutrition, over-nutrition (and sedentarism) is causing obesity and associated serious health consequences. Worldwide, agricultural activity, especially livestock production, accounts for about a fifth of total greenhouse-gas emissions, thus contributing to climate change and its adverse health consequences, including the threat to food yields in many regions. Particular policy attention should be paid to the health risks posed by the rapid worldwide growth in meat consumption, both by exacerbating climate change and by directly contributing to certain diseases. To prevent increased greenhouse-gas emissions from this production sector, both the average worldwide consumption level of animal products and the intensity of emissions from livestock production must be reduced. An international contraction and convergence strategy offers a feasible route to such a goal. The current global average meat consumption is 100 g per person per day, with about a ten-fold variation between high-consuming and low-consuming populations. 90 g per day is proposed as a working global target, shared more evenly, with not more than 50 g per day coming from red meat from ruminants (ie, cattle, sheep, goats, and other digastric grazers).

We examine the links between fossil-fuel-based transportation, greenhouse-gas emissions, and health. Transport-related carbon emissions are rising and there is increasing consensus that the growth in motorised land vehicles and aviation is incompatible with averting serious climate change. The energy intensity of land transport correlates with its adverse health effects. Adverse health effects occur through climate change, road-traffic injuries, physical inactivity, urban air pollution, energy-related conflict, and environmental degradation. For the world's poor people, walking is the main mode of transport, but such populations often experience the most from the harms of energy-intensive transport. New energy sources and improvements in vehicle design and in information technology are necessary but not sufficient to reduce transport-related carbon emissions without accompanying behavioural change. By contrast, active transport has the potential to improve health and equity, and reduce emissions. Cities require safe and pleasant environments for active transport with destinations in easy reach and, for longer journeys, public transport that is powered by renewable energy, thus providing high levels of accessibility without car use. Much investment in major road projects does not meet the transport needs of poor people, especially women whose trips are primarily local and off road. Sustainable development is better promoted through improving walking and cycling infrastructures, increasing access to cycles, and investment in transport services for essential needs. Our model of London shows how increased active transport could help achieve substantial reductions in emissions by 2030 while improving population health. There exists the potential for a global contraction and convergence in use of fossil-fuel energy for transport to benefit health and achieve sustainability.

Maternal and neonatal tetanus are important causes of maternal and neonatal mortality, claiming about 180 000 lives worldwide every year, almost exclusively in developing countries. Although easily prevented by maternal immunisation with tetanus toxoid vaccine, and aseptic obstetric and postnatal umbilical-cord care practices, maternal and neonatal tetanus persist as public-health problems in 48 countries, mainly in Asia and Africa. Survival of tetanus patients has improved substantially for those treated in hospitals with modern intensive-care facilities; however, such facilities are often unavailable where the tetanus burden is highest. The Maternal and Neonatal Tetanus Elimination Initiative assists countries in which maternal and neonatal tetanus has not been eliminated to provide immunisation with tetanus toxoid to women of childbearing age. The ultimate goal of this initiative is the worldwide elimination of maternal and neonatal tetanus. Since tetanus spores cannot be removed from the environment, sustaining elimination will require improvements to presently inadequate immunisation and health-service infrastructures, and universal access to those services. The renewed worldwide commitment to the reduction of maternal and child mortality, if translated into effective action, could help to provide the systemic changes needed for long-term elimination of maternal and neonatal tetanus.

Cervical cancer is the second most common cancer in women worldwide, and knowledge regarding its cause and pathogenesis is expanding rapidly. Persistent infection with one of about 15 genotypes of carcinogenic human papillomavirus (HPV) causes almost all cases. There are four major steps in cervical cancer development: infection of metaplastic epithelium at the cervical transformation zone, viral persistence, progression of persistently infected epithelium to cervical precancer, and invasion through the basement membrane of the epithelium. Infection is extremely common in young women in their first decade of sexual activity. Persistent infections and precancer are established, typically within 5-10 years, from less than 10% of new infections. Invasive cancer arises over many years, even decades, in a minority of women with precancer, with a peak or plateau in risk at about 35-55 years of age. Each genotype of HPV acts as an independent infection, with differing carcinogenic risks linked to evolutionary species. Our understanding has led to improved prevention and clinical management strategies, including improved screening tests and vaccines. The new HPV-oriented model of cervical carcinogenesis should gradually replace older morphological models based only on cytology and histology. If applied wisely, HPV-related technology can minimise the incidence of cervical cancer, and the morbidity and mortality it causes, even in low-resource settings.

Psychological stress elicits measurable changes in sympathetic-parasympathetic balance and the tone of the hypothalamic-pituitary-adrenal axis, which might negatively affect the cardiovascular system both acutely-by precipitating myocardial infarction, left-ventricular dysfunction, or dysrhythmia; and chronically-by accelerating the atherosclerotic process. We provide an overview of the association between stress and cardiovascular morbidity, discuss the mechanisms for this association, and address possible therapeutic implications.

About 14% of the global burden of disease has been attributed to neuropsychiatric disorders, mostly due to the chronically disabling nature of depression and other common mental disorders, alcohol-use and substance-use disorders, and psychoses. Such estimates have drawn attention to the importance of mental disorders for public health. However, because they stress the separate contributions of mental and physical disorders to disability and mortality, they might have entrenched the alienation of mental health from mainstream efforts to improve health and reduce poverty. The burden of mental disorders is likely to have been underestimated because of inadequate appreciation of the connectedness between mental illness and other health conditions. Because these interactions are protean, there can be no health without mental health. Mental disorders increase risk for communicable and non-communicable diseases, and contribute to unintentional and intentional injury. Conversely, many health conditions increase the risk for mental disorder, and comorbidity complicates help-seeking, diagnosis, and treatment, and influences prognosis. Health services are not provided equitably to people with mental disorders, and the quality of care for both mental and physical health conditions for these people could be improved. We need to develop and evaluate psychosocial interventions that can be integrated into management of communicable and non-communicable diseases. Health-care systems should be strengthened to improve delivery of mental health care, by focusing on existing programmes and activities, such as those which address the prevention and treatment of HIV, tuberculosis, and malaria; gender-based violence; antenatal care; integrated management of childhood illnesses and child nutrition; and innovative management of chronic disease. An explicit mental health budget might need to be allocated for such activities. Mental health affects progress towards the achievement of several Millennium Development Goals, such as promotion of gender equality and empowerment of women, reduction of child mortality, improvement of maternal health, and reversal of the spread of HIV/AIDS. Mental health awareness needs to be integrated into all aspects of health and social policy, health-system planning, and delivery of primary and secondary general health care.

Resources for mental health include policy and infrastructure within countries, mental health services, community resources, human resources, and funding. We discuss here the general availability of these resources, especially in low-income and middle-income countries. Government spending on mental health in most of the relevant countries is far lower than is needed, based on the proportionate burden of mental disorders and the availability of cost-effective and affordable interventions. The poorest countries spend the lowest percentages of their overall health budgets on mental health. Most care is now institutionally based, and the transition to community care would require additional funds that have not been made available in most countries. Human resources available for mental health care in most low-income and middle-income countries are very limited, and shortages are likely to persist. Not only are resources for mental health scarce, they are also inequitably distributed-between countries, between regions, and within communities. Populations with high rates of socioeconomic deprivation have the highest need for mental health care, but the lowest access to it. Stigma about mental disorders also constrains use of available resources. People with mental illnesses are also vulnerable to abuse of their human rights. Inefficiencies in the use of available resources for mental health care include allocative and technical inefficiencies in financing mechanisms and interventions, and an overconcentration of resources in large institutions. Scarcity of available resources, inequities in their distribution, and inefficiencies in their use pose the three main obstacles to better mental health, especially in low-income and middle-income countries.

Despite the publication of high-profile reports and promising activities in several countries, progress in mental health service development has been slow in most low-income and middle-income countries. We reviewed barriers to mental health service development through a qualitative survey of international mental health experts and leaders. Barriers include the prevailing public-health priority agenda and its effect on funding; the complexity of and resistance to decentralisation of mental health services; challenges to implementation of mental health care in primary-care settings; the low numbers and few types of workers who are trained and supervised in mental health care; and the frequent scarcity of public-health perspectives in mental health leadership. Many of the barriers to progress in improvement of mental health services can be overcome by generation of political will for the organisation of accessible and humane mental health care. Advocates for people with mental disorders will need to clarify and collaborate on their messages. Resistance to decentralisation of resources must be overcome, especially in many mental health professionals and hospital workers. Mental health investments in primary care are important but are unlikely to be sustained unless they are preceded or accompanied by the development of community mental health services, to allow for training, supervision, and continuous support for primary care workers. Mobilisation and recognition of non-formal resources in the community must be stepped up. Community members without formal professional training and people who have mental disorders and their family members, need to partake in advocacy and service delivery. Population-wide progress in access to humane mental health care will depend on substantially more attention to politics, leadership, planning, advocacy, and participation.

We call for the global health community, governments, donors, multilateral agencies, and other mental health stakeholders, such as professional bodies and consumer groups, to scale up the coverage of services for mental disorders in all countries, but especially in low-income and middle-income countries. We argue that a basic, evidence-based package of services for core mental disorders should be scaled up, and that protection of the human rights of people with mental disorders and their families should be strengthened. Three questions are critical to the scaling-up process. What resources are needed? How can progress towards these goals be monitored? What should be the priorities for mental health research? To address these questions, we first estimated that the amount needed to provide services on the necessary scale would be US$2 per person per year in low-income countries and $3-4 in lower middle-income countries, which is modest compared with the requirements for scaling-up of services for other major contributors to the global burden of disease. Second, we identified a series of core and secondary indicators to track the progress that countries make toward achievement of mental health goals; many of these indicators are already routinely monitored in many countries. Third, we did a priority-setting exercise to identify gaps in the evidence base in global mental health for four categories of mental disorders. We show that funding should be given to research that develops and assesses interventions that can be delivered by people who are not mental health professionals, and that assesses how health systems can scale up such interventions across all routine-care settings. We discuss strategies to overcome the five main barriers to scaling-up of services for mental disorders; one major strategy will be sustained advocacy by diverse stakeholders, especially to target multilateral agencies, donors, and governments. This Series has provided the evidence for advocacy. Now we need political will and solidarity, above all from the global health community, to translate this evidence into action. The time to act is now.

We review the evidence on effectiveness of interventions for the treatment and prevention of selected mental disorders in low-income and middle-income countries. Depression can be treated effectively in such countries with low-cost antidepressants or with psychological interventions (such as cognitive-behaviour therapy and interpersonal therapies). Stepped-care and collaborative models provide a framework for integration of drug and psychological treatments and help to improve rates of adherence to treatment. First-generation antipsychotic drugs are effective and cost effective for the treatment of schizophrenia; their benefits can be enhanced by psychosocial treatments, such as community-based models of care. Brief interventions delivered by primary-care professionals are effective for management of hazardous alcohol use, and pharmacological and psychosocial interventions have some benefits for people with alcohol dependence. Policies designed to reduce consumption, such as increased taxes and other control strategies, can reduce the population burden of alcohol abuse. Evidence about the efficacy of interventions for developmental disabilities is inadequate, but community-based rehabilitation models provide a low-cost, integrative framework for care of children and adults with chronic mental disabilities. Evidence for mental health interventions for people who are exposed to conflict and other disasters is still weak-especially for interventions in the midst of emergencies. Some trials of interventions for prevention of depression and developmental delays in low-income and middle-income countries show beneficial effects. Interventions for depression, delivered in primary care, are as cost effective as antiretroviral drugs for HIV/AIDS. The process and effectiveness of scaling up mental health interventions has not been adequately assessed. Such research is needed to inform the continuing process of service reform and innovation. However, we recommend that policymakers should act on the available evidence to scale up effective and cost-effective treatments and preventive interventions for mental disorders.

More than 85% of the world's population lives in 153 low-income and middle-income countries (LAMICs). Although country-level information on mental health systems has recently become available, it still has substantial gaps and inconsistencies. Most of these countries allocate very scarce financial resources and have grossly inadequate manpower and infrastructure for mental health. Many LAMICs also lack mental health policy and legislation to direct their mental health programmes and services, which is of particular concern in Africa and South East Asia. Different components of mental health systems seem to vary greatly, even in the same-income categories, with some countries having developed their mental health system despite their low-income levels. These examples need careful scrutiny to derive useful lessons. Furthermore, mental health resources in countries seem to be related as much to measures of general health as to economic and developmental indicators, arguing for improved prioritisation for mental health even in low-resource settings. Increased emphasis on mental health, improved resources, and enhanced monitoring of the situation in countries is called for to advance global mental health.

Exacerbations of chronic obstructive pulmonary disease (COPD) are episodes of worsening of symptoms, leading to substantial morbidity and mortality. COPD exacerbations are associated with increased airway and systemic inflammation and physiological changes, especially the development of hyperinflation. They are triggered mainly by respiratory viruses and bacteria, which infect the lower airway and increase airway inflammation. Some patients are particularly susceptible to exacerbations, and show worse health status and faster disease progression than those who have infrequent exacerbations. Several pharmacological interventions are effective for the reduction of exacerbation frequency and severity in COPD such as inhaled steroids, long-acting bronchodilators, and their combinations. Non-pharmacological therapies such as pulmonary rehabilitation, self-management, and home ventilatory support are becoming increasingly important, but still need to be studied in controlled trials. The future of exacerbation prevention is in assessment of optimum combinations of pharmacological and non-pharmacological therapies that will result in improvement of health status, and reduction of hospital admission and mortality associated with COPD.

Although the development of effective treatments for patients with chronic obstructive pulmonary disease (COPD) has not been seen as a high priority, the past decade has seen a substantial increase in the number of clinical studies examining different treatments for this disease. Large studies are needed to adequately assess the effectiveness of treatment because of the chronic nature of the disease and the intermittent occurrence of some key outcomes such as exacerbations. Data from randomised controlled trials show that treatment improves exercise performance by increasing lung volume rather than changing expiratory flow. Although assessment of lung function remains the cornerstone of drug assessment, improvements in health status, the number of exacerbations and admissions to hospital are now recognised as important treatment outcomes. Randomised controlled trial data provide the best evidence for treatment efficacy, but results of these studies can be affected by differences in inclusion criteria and patient dropout during the study. Bronchodilator reversibility testing does not reliably define subgroups that will respond to a particular treatment. Carefully done and adequately powered clinical trials continue to inform, not only our views about treatment, but also our understanding of COPD and how it is best assessed and managed. Ensuring that these expensive studies are done objectively to the highest standard is an important goal for the next decade.

Chronic obstructive pulmonary disease (COPD) continues to be an important cause of morbidity, mortality, and health-care costs worldwide. It is a global health issue, with cigarette smoking being an important risk factor universally; other factors, such as exposure to indoor and outdoor air pollution, occupational hazards, and infections, are also important. As the global population ages, the burden of COPD will increase in years to come. Prevalence estimates of the disorder show considerable variability across populations, suggesting that risk factors can affect populations differently. Other advances in our understanding of COPD are increased recognition of the importance of comorbid disease, identification of different COPD phenotypes, and understanding how factors other than lung function affect outcome in our patients. The challenge we will all face in the next few years will be implementation of cost-effective prevention and management strategies to stem the tide of this disease and its cost.

Polycystic ovary syndrome is a heterogeneous endocrine disorder that affects about one in 15 women worldwide. The major endocrine disruption is excessive androgen secretion or activity, and a large proportion of women also have abnormal insulin activity. Many body systems are affected in polycystic ovary syndrome, resulting in several health complications, including menstrual dysfunction, infertility, hirsutism, acne, obesity, and metabolic syndrome. Women with this disorder have an established increased risk of developing type 2 diabetes and a still debated increased risk of cardiovascular disease. The diagnostic traits of polycystic ovary syndrome are hyperandrogenism, chronic anovulation, and polycystic ovaries, after exclusion of other conditions that cause these same features. A conclusive definition of the disorder and the importance of the three diagnostic criteria relative to each other remain controversial. The cause of polycystic ovary syndrome is unknown, but studies suggest a strong genetic component that is affected by gestational environment, lifestyle factors, or both.

Whether calcium supplementation can reduce osteoporotic fractures is uncertain. We did a meta-analysis to include all the randomised trials in which calcium, or calcium in combination with vitamin D, was used to prevent fracture and osteoporotic bone loss.