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.

Legal instruments and litigation as a way to enforce the rights to life and to health is a relatively new strategy that is increasingly common. We show how legal measures have been used to attain health and human rights with case examples from India and South Africa that resulted in large public-health benefits.

Iron deficiency is one of the leading risk factors for disability and death worldwide, affecting an estimated 2 billion people. Nutritional iron deficiency arises when physiological requirements cannot be met by iron absorption from diet. Dietary iron bioavailability is low in populations consuming monotonous plant-based diets. The high prevalence of iron deficiency in the developing world has substantial health and economic costs, including poor pregnancy outcome, impaired school performance, and decreased productivity. Recent studies have reported how the body regulates iron absorption and metabolism in response to changing iron status by upregulation or downregulation of key intestinal and hepatic proteins. Targeted iron supplementation, iron fortification of foods, or both, can control iron deficiency in populations. Although technical challenges limit the amount of bioavailable iron compounds that can be used in food fortification, studies show that iron fortification can be an effective strategy against nutritional iron deficiency. Specific laboratory measures of iron status should be used to assess the need for fortification and to monitor these interventions. Selective plant breeding and genetic engineering are promising new approaches to improve dietary iron nutritional quality.

Individuals and populations suffer violations of their rights that affect health and wellbeing. Health professionals have a part to play in reduction and prevention of these violations and ensuring that health-related policies and practices promote rights. This needs efforts in terms of advocacy, application of legal standards, and public-health programming. We discuss the changing views of human rights in the context of the HIV/AIDS epidemic and propose further development of the right to health by increased practice, evidence, and action.

Clotting factor transfusions are vital for people with diseases such as haemophilia. In the 1970s and 1980s, transfusions with pooled plasma led to a devastatingly high number of recipients becoming infected with blood-borne pathogens such as HIV and hepatitis C. This epidemic triggered the development of virus-free factor concentrates through a combination of improved donor selection and screening, effective virucidal technologies, and recombinant protein expression biotechnology. There is now a wide range of recombinant factor concentrates, and an impressive safety record with respect to pathogen transmission. However, remaining therapeutic challenges include the potential threat of transmission of prions and other pathogens, the formation of inhibitory alloantibodies, and the international disparity that exists in product availability due to differences in licensure status as well as prohibitively high costs. In the future, it is likely that bioengineered recombinant proteins that have been modified to enhance pharmacokinetic properties or reduce immunogenicity, or both, will be used increasingly in clinical practice.

Ever since platelet transfusions were shown to reduce mortality from haemorrhage in patients with acute leukaemia in the 1950s, the use of this therapy has steadily grown to become an essential part of the treatment of cancer, haematological malignancies, marrow failure, and haematopoietic stem cell transplantation. Today, more than 1.5 million platelet products are transfused in the USA each year, 2.9 million products in Europe. However, platelet transfusion can transmit infections and trigger serious immune reactions and they can be rendered ineffective by alloimmunisation. There are several types of platelet components and all can be modified to reduce the chances of many of the complications of platelet transfusion. Transfusion practices, including indications for transfusion, dose of platelets transfused, and methods of treating alloimmunised recipients vary between countries, and even within countries. We review commonly used platelet components, product modifications, transfusion practices, and adverse consequences of platelet transfusions.

Every year, about 75 million units of blood are collected worldwide. Red blood cell (RBC) transfusion is one of the few treatments that adequately restore tissue oxygenation when oxygen demand exceeds supply. Although the respiratory function of blood has been studied intensively, the trigger for RBC transfusion remains controversial, and doctors rely primarily on clinical experience. Laboratory assays that indicate failing tissue oxygenation would be ideal to guide the need for transfusion, but none has proved easy, reproducible, and sensitive to regional tissue hypoxia. The clinical importance of the RBCs storage lesion (ie, the time-dependent metabolic, biochemical, and molecular changes that stored blood cells undergo) is poorly understood. RBCs can be filtered, washed, frozen, or irradiated for specific indications. Donor screening and testing have dramatically reduced infectious risks in the developed world, but infection remains a major hazard in developing countries, where 13 million units of blood are not tested for HIV or hepatitis viruses. Pathogen inactivation techniques are in clinical trials for RBCs, but none is available for use. Despite serious immunological and non-immunological complications, RBC transfusion holds a therapeutic index that exceeds that of many common medications.

In-vitro fertilisation has been done for nearly 30 years; in developed countries at least 1% of births are from assisted reproductive therapies (ART). These children now represent a substantial proportion of the population but little is known about their health. Some of the morbidity associated with ART does not result from the techniques but from the underlying health risks of being subfertile. Much of the amplified risk associated with ART is related to high birth order. However, risk of intrauterine and subsequent perinatal complications is enhanced after ART, and urogenital malformations can be present in boys, even in singleton infants. No increase in discord or other difficulties within families has been recorded. Long-term follow-up of children born after ART to reproductive age and beyond is necessary.

Chronic myeloid leukaemia (CML) was the first neoplastic disease for which knowledge of the genotype led to a rationally designed therapy. As a result of its well known pathophysiology, straightforward diagnosis, well established prognostic factors, and treatment for the cause of disease, CML has been studied to an extent that far exceeds that expected from its frequency, and serves as a model disease for other cancers. Imatinib, an inhibitor of BCR-ABL tyrosine kinase, has revolutionised treatment of this disease, and is now recommended as standard treatment for chronic-phase CML. Interferon alfa is an acceptable alternative treatment in the early chronic phase for patients who do not tolerate imatinib. If imatinib treatment fails, allogeneic stem-cell transplantation, a dose increase of imatinib, or new drugs are recommended. Up to 87% of patients achieve complete cytogenetic remission, therefore we provide guidance for monitoring disease status. Many trials of new drugs and combination therapies that include imatinib are underway.

Evidence supporting similar recurrence rates between video-assisted and open surgery for the treatment of recurrent pneumothorax is questionable, because the number of randomised trials is sparse and they are underpowered to detect any meaningful difference. Our aim was to do a systematic review of randomised and non-randomised studies to compare recurrence rates between the two forms of surgical access.

Whether cannabis can cause psychotic or affective symptoms that persist beyond transient intoxication is unclear. We systematically reviewed the evidence pertaining to cannabis use and occurrence of psychotic or affective mental health outcomes.