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.

Tuberculosis is still a leading cause of death in low-income and middle-income countries, especially those of sub-Saharan Africa where tuberculosis is an epidemic because of the increased susceptibility conferred by HIV infection. The effectiveness of the Bacille Calmette Guérin (BCG) vaccine is partial, and that of treatment of latent tuberculosis is unclear in high-incidence settings. The routine diagnostic methods that are used in many parts of the world are still very similar to those used 100 years ago. Multidrug treatment, within the context of structured, directly observed therapy, is a cost-effective control strategy. Nevertheless, the duration of treatment needed reduces its effectiveness, as does the emergence of multidrug-resistant and extensively drug-resistant disease; the latter has recently become widespread. The rapid expansion of basic, clinical, and operational research, in addition to increasing knowledge of tuberculosis, is providing new diagnostic, treatment, and preventive measures. The challenge is to apply these advances to the populations most at risk. The development of a comprehensive worldwide plan to stop tuberculosis might facilitate this process by coordinating the work of health agencies. However, massive effort, political will, and resources are needed for this plan to succeed.

Neglected diseases remain one of the largest causes of disease and mortality. In addition to the difficulties in provision of appropriate drugs for specific diseases, many other factors contribute to the prevalence of such diseases and the difficulties in reducing their burden. We address the role that poor governance and politically motivated oppression have on the epidemiology of neglected diseases. We give case examples including filariasis in eastern Burma and vector-borne diseases (Chagas' disease, leishmaniasis, and yellow fever) in Colombia, we show the links between systematic human rights violations and the effects of infectious disease on health. We also discuss the role of researchers in advocating for and researching within oppressed populations.

Atrial fibrillation is the most common sustained cardiac rhythm disorder, and confers a substantial mortality and morbidity from stroke, thromboembolism, heart failure, and impaired quality of life. With the increasingly elderly population in the developed world, as well as improvements in the management of myocardial infarction and heart failure, the prevalence of atrial fibrillation is increasing, resulting in a major public-health problem. This Review aims to provide an overview on the modern management of atrial fibrillation, with particular emphasis on pharmacological and non-pharmacological approaches. Irrespective of a rate-control or rhythm-control strategy, stroke prevention with appropriate thromboprophylaxis still remains central to the management of this common arrhythmia. Electrophysiological approaches could hold some promise for a curative approach in atrial fibrillation.

Essential hypertension can be defined as a rise in blood pressure of unknown cause that increases risk for cerebral, cardiac, and renal events. In industrialised countries, the risk of becoming hypertensive (blood pressure >140/90 mm Hg) during a lifetime exceeds 90%. Essential hypertension usually clusters with other cardiovascular risk factors such as ageing, being overweight, insulin resistance, diabetes, and hyperlipidaemia. Subtle target-organ damage such as left-ventricular hypertrophy, microalbuminuria, and cognitive dysfunction takes place early in the course of hypertensive cardiovascular disease, although catastrophic events such as stroke, heart attack, renal failure, and dementia usually happen after long periods of uncontrolled hypertension only. All antihypertensive drugs lower blood pressure (by definition) and this decline is the best determinant of cardiovascular risk reduction. However, differences between drugs exist with respect to reduction of target-organ disease and prevention of major cardiovascular events. Most hypertensive patients need two or more drugs for blood-pressure control and concomitant statin treatment for risk factor reduction. Despite the availability of effective and safe antihypertensive drugs, hypertension and its concomitant risk factors remain uncontrolled in most patients.

Paediatric palliative care is an emerging subspecialty that focuses on achieving the best possible quality of life for children with life-threatening conditions and their families. To achieve this goal, the individuals working in this field need to: clearly define the population served; better understand the needs of children with life-threatening conditions and their families; develop an approach that will be appropriate across different communities; provide care that responds adequately to suffering; advance strategies that support caregivers and health-care providers; and promote needed change by cultivating educational programmes. Despite these challenges, advances in paediatric palliative care have been achieved in a short period of time; we expect far greater progress as the field becomes more formalised and research networks are established.

Organophosphorus pesticide self-poisoning is an important clinical problem in rural regions of the developing world, and kills an estimated 200,000 people every year. Unintentional poisoning kills far fewer people but is a problem in places where highly toxic organophosphorus pesticides are available. Medical management is difficult, with case fatality generally more than 15%. We describe the limited evidence that can guide therapy and the factors that should be considered when designing further clinical studies. 50 years after first use, we still do not know how the core treatments--atropine, oximes, and diazepam--should best be given. Important constraints in the collection of useful data have included the late recognition of great variability in activity and action of the individual pesticides, and the care needed cholinesterase assays for results to be comparable between studies. However, consensus suggests that early resuscitation with atropine, oxygen, respiratory support, and fluids is needed to improve oxygen delivery to tissues. The role of oximes is not completely clear; they might benefit only patients poisoned by specific pesticides or patients with moderate poisoning. Small studies suggest benefit from new treatments such as magnesium sulphate, but much larger trials are needed. Gastric lavage could have a role but should only be undertaken once the patient is stable. Randomised controlled trials are underway in rural Asia to assess the effectiveness of these therapies. However, some organophosphorus pesticides might prove very difficult to treat with current therapies, such that bans on particular pesticides could be the only method to substantially reduce the case fatality after poisoning. Improved medical management of organophosphorus poisoning should result in a reduction in worldwide deaths from suicide.

Sun exposure is the main cause of photocarcinogenesis, photoageing, and photosensitivity; thus, photoprotection is an important issue. In a skin cancer prevention strategy, behavioural measures--eg, wearing sun protective clothes and a hat and reducing sun exposure to a minimum--should be preferred to sunscreens. Often this solution is deemed to be unacceptable in our global, outdoor society, and sunscreens could become the predominant mode of sun protection for various societal reasons (eg, healthiness of a tan, relaxation in the sun). The application of a liberal quantity of sunscreen has been shown to be by far the most important factor for effectiveness of the sunscreen, followed by the uniformity of application and the specific absorption spectrum of the agent used. The sunscreen market--crowded by numerous products--shows various differences worldwide. Nevertheless, sunscreens should not be abused in an attempt to increase time in the sun to a maximum. Controversies about safety of sunscreens and clinical recommendations are discussed.