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.

Management of psoriasis begins with identification of the extent of cutaneous disease. However, a holistic, contractual approach to treatment is encouraged, with particular reference to psychosocial disability and quality-of-life issues. The presence of psoriasis on palms, soles, body folds, genitals, face, or nails, and concomitant joint disease, are also important when considering treatment options. An evidence-based approach is essential in delineating differences between the many available treatments. However, archaic approaches, especially combinational ones, are routinely used by some clinicians, with inadequate prospective or comparative evidence. Treatments currently available are: topical agents used predominantly for mild disease and for recalcitrant lesions in more severe disease; phototherapy for moderate disease; and systemic agents including photochemotherapy, oral agents, and newer injectable biological agents, which have revolutionised the management of severe psoriasis. Other innovative treatments are undergoing clinical studies, with the aim of maintaining safe, long-term control of the condition.

Psoriasis, a papulosquamous skin disease, was originally thought of as a disorder primarily of epidermal keratinocytes, but is now recognised as one of the commonest immune-mediated disorders. Tumour necrosis factor alpha, dendritic cells, and T-cells all contribute substantially to its pathogenesis. In early-onset psoriasis (beginning before age 40 years), carriage of HLA-Cw6 and environmental triggers, such as beta-haemolytic streptococcal infections, are major determinants of disease expression. Moreover, at least nine chromosomal psoriasis susceptibility loci have been identified. Several clinical phenotypes of psoriasis are recognised, with chronic plaque (psoriasis vulgaris) accounting for 90% of cases. Comorbidities of psoriasis are attracting interest, and include impairment of quality of life and associated depressive illness, cardiovascular disease, and a seronegative arthritis known as psoriatic arthritis. A more complete understanding of underlying pathomechanisms is leading to new treatments, which will be discussed in the second part of this Series.

Polar expeditions include treks and stays at summer camps or year-round research stations. People on such expeditions generally undergo psychological changes resulting from exposure to long periods of isolation and confinement, and the extreme physical environment. Symptoms include disturbed sleep, impaired cognitive ability, negative affect, and interpersonal tension and conflict. Seasonal occurrence of these symptoms suggests the existence of three overlapping syndromes: the winter-over syndrome, the polar T3 syndrome, and subsyndromal seasonal affective disorder. About 5% of people on expeditions meet DSM-IV or ICD criteria for psychiatric disorders. However, they also experience positive or so-called salutogenic outcomes resulting from successfully coping with stress and enhanced self-sufficiency, improved health, and personal growth. Prevention of pathogenic psychological outcomes is best accomplished by psychological and psychiatric screening procedures to select out unsuitable candidates, and by providing access to psychological support, including telephone counselling. Promotion of salutogenic experiences is best accomplished by screening for suitable personality traits, and training participants in individual coping strategies, group interaction, and team leadership.

Drug therapy is essential when caring for elderly patients, but clearly it is a double-edged sword. Elderly patients are at high risk of having drug interactions, but the prevalence of these interactions is not well documented. Several types of interactions exist: drug-drug, drug-disease, drug-food, drug-alcohol, drug-herbal products, and drug-nutritional status. Factors such as age-related changes in pharmacokinetics and pharmacodynamics, frailty, interindividual variability, reduced homoeostatic mechanisms, and psychosocial issues need to be considered when drug interactions are assessed. Software can help clinicians to detect drug interactions, but many programmes have not been updated with the evolving knowledge of these interactions, and do not take into consideration important factors needed to optimise drug treatment in elderly patients. Any generated recommendations have to be tempered by a holistic, geriatric, multiprofessional approach that is team-based. This second paper in a series of two on prescribing in elderly people proposes an approach to categorise drug interactions, along with strategies to assist in their detection, management, and prevention.

Prescription of medicines is a fundamental component of the care of elderly people, and optimisation of drug prescribing for this group of patients has become an important public-health issue worldwide. Several characteristics of ageing and geriatric medicine affect medication prescribing for elderly people and render the selection of appropriate pharmacotherapy a challenging and complex process. In the first paper in this series we aim to define and categorise appropriate prescribing in elderly people, critically review the instruments that are available to measure it and discuss their predictive validity, critically review recent randomised controlled intervention studies that assessed the effect of optimisation strategies on the appropriateness of prescribing in elderly people, and suggest directions for future research and practice.

Achondroplasia is the most common form of short limb dwarfism in human beings, affecting more than 250,000 individuals worldwide. More than 95% of patients have the same point mutation in the gene for fibroblast growth factor receptor 3 (FGFR3) and more than 80% of these are new mutations. The mutation, which causes gain of FGFR3 function, affects many tissues, most strikingly the cartilaginous growth plate in the growing skeleton, leading to a variety of manifestations and complications. The biology of FGFR3 and the molecular and cellular consequences of the achondroplasia mutation are being elucidated, providing a more complete understanding of the disorder and a basis for future treatments targeted directly at relevant pathogenetic pathways. Furthermore, the natural history of the condition, which has been well delineated in childhood and adolescence, is being defined more fully in adults with achondroplasia; most of the serious complications can be modified favourably or prevented by anticipation and early treatment. Possible future treatments include chemical inhibition of receptor signalling, antibody blockade of receptor activation, and alteration of pathways that modulate the downstream propagation of FGFR3 signals.