Drug misuse and abuse are major health problems. Harmful drugs are regulated according to classification systems that purport to relate to the harms and risks of each drug. However, the methodology and processes underlying classification systems are generally neither specified nor transparent, which reduces confidence in their accuracy and undermines health education messages. We developed and explored the feasibility of the use of a nine-category matrix of harm, with an expert delphic procedure, to assess the harms of a range of illicit drugs in an evidence-based fashion. We also included five legal drugs of misuse (alcohol, khat, solvents, alkyl nitrites, and tobacco) and one that has since been classified (ketamine) for reference. The process proved practicable, and yielded roughly similar scores and rankings of drug harm when used by two separate groups of experts. The ranking of drugs produced by our assessment of harm differed from those used by current regulatory systems. Our methodology offers a systematic framework and process that could be used by national and international regulatory bodies to assess the harm of current and future drugs of abuse.

Sound statistics are a key component of evidence. However, many institutional, political, and practical barriers impede effective use of data to inform policy. In the fourth paper in this Series on health statistics, we look at the relation between health statistics and policymaking at country and global levels. We propose a fourfold framework to help the transition from data to policy. Good practices include: (1) reconciling statistics from different sources; (2) fostering communication and transparency, including reaching out to the media for dissemination; (3) promoting country ownership of data and statistical analyses; and (4) addressing conflicts of interest, including those arising when workers responsible for attainment of health goals are also charged with measurement and monitoring of progress. Further investments are needed not only in primary data collection across a full range of sources but also in building capacity in countries to analyse, interpret, and present statistics effectively in ways that are meaningful and useful for policymaking.

Pelvic organ prolapse is downward descent of female pelvic organs, including the bladder, uterus or post-hysterectomy vaginal cuff, and the small or large bowel, resulting in protrusion of the vagina, uterus, or both. Prolapse development is multifactorial, with vaginal child birth, advancing age, and increasing body-mass index as the most consistent risk factors. Vaginal delivery, hysterectomy, chronic straining, normal ageing, and abnormalities of connective tissue or connective-tissue repair predispose some women to disruption, stretching, or dysfunction of the levator ani complex, connective-tissue attachments of the vagina, or both, resulting in prolapse. Patients generally present with several complaints, including bladder, bowel, and pelvic symptoms; however, with the exception of vaginal bulging, none is specific to prolapse. Women with symptoms suggestive of prolapse should undergo a pelvic examination and medical history check. Radiographic assessment is usually unnecessary. Many women with pelvic organ prolapse are asymptomatic and do not need treatment. When prolapse is symptomatic, options include observation, pessary use, and surgery. Surgical strategies for prolapse can be categorised broadly by reconstructive and obliterative techniques. Reconstructive procedures can be done by either an abdominal or vaginal approach. Although no effective prevention strategy for prolapse has been identified, considerations include weight loss, reduction of heavy lifting, treatment of constipation, modification or reduction of obstetric risk factors, and pelvic-floor physical therapy.

Politicians, policymakers, and public-health professionals make complex decisions on the basis of estimates of disease burden from different sources, many of which are "marketed" by skilled advocates. To help people who rely on such statistics make more informed decisions, we explain how health estimates are developed, and offer basic guidance on how to assess and interpret them. We describe the different levels of estimates used to quantify disease burden and its correlates; understanding how closely linked a type of statistic is to disease and death rates is crucial in designing health policies and programmes. We also suggest questions that people using such statistics should ask and offer tips to help separate advocacy from evidence-based positions. Global health agencies have a key role in communicating robust estimates of disease, as do policymakers at national and subnational levels where key public-health decisions are made. A common framework and standardised methods, building on the work of Child Health Epidemiology Reference Group (CHERG) and others, are urgently needed.

Although functional somatic syndromes (FSS) show substantial overlap, treatment research is mostly confined to single syndromes, with a lack of valid and generally accepted diagnostic criteria across medical specialties. Here, we review management for the full variety of FSS, drawn from systematic reviews and meta-analyses since 2001, and give recommendations for a stepped care approach that differentiates between uncomplicated and complicated FSS. Non-pharmacological treatments involving active participation of patients, such as exercise and psychotherapy, seem to be more effective than those that involve passive physical measures, including injections and operations. Pharmacological agents with CNS action seem to be more consistently effective than drugs aiming at restoration of peripheral physiological dysfunction. A balance between biomedical, organ-oriented, and cognitive interpersonal approaches is most appropriate at this truly psychosomatic interface. In view of the iatrogenic component in the maintenance of FSS, doctor-centred interventions and close observation of the doctor-patient relationship are of particular importance.

Bipolar II disorder (recurrent depressive and hypomanic episodes) and related disorders (united in the bipolar spectrum) are understudied, despite a prevalence of about 5% in the community and about 50% in depressed outpatients. The apparent increase in prevalence of the bipolar spectrum is related to several changes in diagnostic criteria, including improved probing for history of hypomania (focused more on overactivity than on mood change), lower minimum duration of hypomania, and inclusion of unipolar depressions with bipolar signs (eg, family history of bipolar disorder, mixed depression). Prevalence of mixed depression, a combination of depression and manic or hypomanic symptoms, is high in patients with bipolar disorders. Controlled studies are needed to investigate treatment of mixed depression; antidepressants can worsen manic and hypomanic symptoms, and mood stabilising agents might be necessary.

25 years after the first HIV/AIDS cases emerged in 1981, the disease continues to spread worldwide, with about 15 000 new infections every day. Although highly active antiretroviral therapy (HAART) has greatly reduced the rate of HIV infection, and the spread of the epidemic, this effect has largely been seen in developed countries. More than 90% of HIV-infected people live in developing countries, most of whom do not have access to this treatment. The development of efficient, widely available, and low-cost microbicides (gels and creams can be applied topically before sex) to prevent sexually transmitted HIV infections should be given high priority. We review different categories of microbicide drugs and lead compounds, their mechanism of action, current status of development, and progress in phase III trials.

Increases in international funding for health have been accompanied by accelerating demand for more and better statistics, which are needed to track performance and ensure accountability. Worldwide interest in the monitoring of development, as exemplified in the Millennium Development Goals (MDGs), generates pressure for high-quality and timely data for reporting on country progress. This rapid escalation of demand has exposed major gaps in the supply of health statistics for developing countries but also provides major opportunities to increase the supply and use of sound health statistics. First, the emphasis on monitoring and evaluation is leading to proliferation of indicators and excessive reporting requirements, and needs to be refocused on systematic investments in data generation and analysis. Second, the risk of inadequate or poorly targeted investments can be kept to a minimum by understanding the causes of poor availability of health statistics, including lack of accurate measurement instruments, application of suboptimum methods of data collection, and inadequate use of methods and analyses to produce comparable estimates. Third, the preoccupation with MDGs does not take into account the rapid health transition, which implies that health statistics should systematically include a much wider array of health issues from acute infectious diseases to chronic non-communicable diseases and injuries, disaggregated by socioeconomic position. Fourth, the growing number of national household surveys, which are the main source of most population health statistics, need to be streamlined into cohesive and comprehensive country health survey programmes. Now is the time to accelerate the production and use of accurate, complete, and timely health statistics for decision-making by investing in country health information systems that should be based on an efficient and effective mix of standardised methods of data collection and analysis that meet country and international needs.

Juvenile idiopathic arthritis is a broad term that describes a clinically heterogeneous group of arthritides of unknown cause, which begin before 16 years of age. This term encompasses several disease categories, each of which has distinct methods of presentation, clinical signs, and symptoms, and, in some cases, genetic background. The cause of disease is still poorly understood but seems to be related to both genetic and environmental factors, which result in the heterogeneity of the illness. Although none of the available drugs has a curative potential, prognosis has greatly improved as a result of substantial progresses in disease management. The most important new development has been the introduction of drugs such as anticytokine agents, which constitute a valuable treatment option for patients who are resistant to conventional antirheumatic agents. Further insights into the disease pathogenesis and treatment will be provided by the continuous advances in understanding of the mechanisms connected to the immune response and inflammatory process, and by the development of new drugs that are able to inhibit selectively single molecules or pathways.

Four factors have driven China's response to the HIV/AIDS pandemic: (1) existing government structures and networks of relationships; (2) increasing scientific information; (3) external influences that underscored the potential consequences of an HIV/AIDS pandemic and thus accelerated strategic planning; and (4) increasing political commitment at the highest levels. China's response culminated in legislation to control HIV/AIDS-the AIDS Prevention and Control Regulations. Three major initiatives are being scaled up concurrently. First, the government has prioritised interventions to control the epidemic in injection drug users, sex workers, men who have sex with men, and plasma donors. Second, routine HIV testing is being implemented in populations at high risk of infection. Third, the government is providing treatment for infected individuals. These bold programmes have emerged from a process of gradual and prolonged dialogue and collaboration between officials at every level of government, researchers, service providers, policymakers, and politicians, and have led to decisive action.

Endocrine disease frequently interrupts sexual function, and sexual dysfunction may signal serious endocrine disease. Diabetic autonomic neuropathy and endothelial dysfunction impair erectile function, and phosphodiesterase inhibition produces only moderate benefit. The effect of diabetes on women's sexual function is complex: the most consistent finding is a correlation between sexual dysfunction and depression. Reductions in testosterone level in men are associated with low sexual desire and reduced nocturnal erections and ejaculate volume, all of which improve with testosterone supplementation. The age-dependent decline in testosterone production in men is not associated with precise sexual symptoms, and supplementation has not been shown to produce sexual benefit. In women, sexual dysfunction has not been associated with serum testosterone, but this may be confounded by limitations of assays at low concentrations and by the greater importance of intracellular production of testosterone in women than in men. Testosterone supplementation after menopause does improve some aspects of sexual function in women, but long-term outcome data are needed. More research on the sexual effects of abnormal adrenal and thyroid function, hyperprolactinaemia, and metabolic syndrome should also be prioritised. We have good data on local management of the genital consequences of oestrogen lack, but need to better understand the potential role of systemic oestrogen supplementation from menopause onwards in sexually symptomatic women.

Systemic lupus erythematosus is an autoimmune connective-tissue disorder with a wide range of clinical features, which predominantly affects women, especially from certain ethnic groups. Diagnosis is based on clinical assessment supported by investigations, including the finding of autoantibodies. Treatments range from antimalarial agents to corticosteroids and immunosuppressive agents. This Seminar draws attention to advances in the epidemiology, genetics, cardiovascular risks, lupus nephritis, CNS disease, the antiphospholipid syndrome, assessment of disease activity and damage, and pregnancy related and quality of life issues. New therapeutic approaches, such as biological agents and mycophenolate mofetil, will also be discussed.

The advent of non-invasive functional brain imaging has clarified which regions of the brain are recruited during sexual arousal. Injuries to those regions, and to the spinal cord and peripheral nerves that link genitalia to limbic and cognitive centres, can profoundly influence sexual wellbeing. In epilepsy, expressions of hypersexuality and hyposexuality interact with the location of epileptogenic foci in the temporolimbic circuitry, and are tempered by the sexual effects of drug treatments. We outline the sexual consequences of epilepsy, stroke, multiple sclerosis, Parkinson's disease, and other common neurological disorders. Management of sexual dysfunction from both disease and treatment is discussed. Nerve-sparing techniques could mitigate the substantial sexual dysfunction in both men and women through surgical disruption of the autonomic nerves during radical pelvic surgery.

Narcolepsy with cataplexy is a disabling sleep disorder affecting 0.02% of adults worldwide. It is characterised by severe, irresistible daytime sleepiness and sudden loss of muscle tone (cataplexy), and can be associated with sleep-onset or sleep-offset paralysis and hallucinations, frequent movement and awakening during sleep, and weight gain. Sleep monitoring during night and day shows rapid sleep onset and abnormal, shortened rapid-eye-movement sleep latencies. The onset of narcolepsy with cataplexy is usually during teenage and young adulthood and persists throughout the lifetime. Pathophysiological studies have shown that the disease is caused by the early loss of neurons in the hypothalamus that produce hypocretin, a wakefulness-associated neurotransmitter present in cerebrospinal fluid. The cause of neural loss could be autoimmune since most patients have the HLA DQB1*0602 allele that predisposes individuals to the disorder. Treatment is with stimulant drugs to suppress daytime sleepiness, antidepressants for cataplexy, and gamma hydroxybutyrate for both symptoms. Because narcolepsy is an under-recognised disease, it is important that general practitioners and other primary health-care workers identify abnormal daytime sleepiness early.