Incidence and prevalence of hypopituitarism are estimated to be 4.2 per 100,000 per year and 45.5 per 100,000, respectively. Although the clinical symptoms of this disorder are usually unspecific, it can cause life-threatening events and lead to increased mortality. Current research has refined the diagnosis of hypopituitarism. Identification of growth hormone and corticotropin deficiency generally requires a stimulation test, whereas other deficiencies can be detected by basal hormones in combination with clinical judgment. Newly developed formulations of replacement hormones are convenient and physiological. Work has shown that many patients with brain damage--such as traumatic brain injury or aneurysmal subarachnoid haemorrhage--are at high risk of (sometimes unrecognised) hypopituitarism. Thus, a much increased true prevalence of this disorder needs to be assumed. As a result, hypopituitarism is not a rare disease and should be recognised by the general practitioner.

A major proportion of the disease burden and deaths for young people in developed nations is attributable to misuse of alcohol and illicit drugs. Patterns of substance use established in adolescence are quite stable and predict chronic patterns of use, mortality, and morbidity later in life. We integrated findings of systematic reviews to summarise evidence for interventions aimed at prevention and reduction of harms related to adolescent substance use. Evidence of efficacy was available for developmental prevention interventions that aim to prevent onset of harmful patterns in settings such as vulnerable families, schools, and communities, and universal strategies to reduce attractiveness of substance use. Regulatory interventions aim to increase perceived costs and reduce availability and accessibility of substances. Increasing price, restricting settings of use, and raising legal purchase age are effective in reducing use of alcohol and tobacco and related harms. Screening and brief intervention are efficacious, but efficacy of a range of treatment approaches has not been reliably established. Harm-reduction interventions are effective in young people involved in risky and injecting substance use.

Ankylosing spondylitis is a common inflammatory rheumatic disease that affects the axial skeleton, causing characteristic inflammatory back pain, which can lead to structural and functional impairments and a decrease in quality of life. New imaging techniques and therapies have substantially changed the management of this disease in the past decade. Whether inhibition of radiographic progression and structural damage can be reached with available drugs is as yet unclear. Furthermore, treatment with non-steroidal anti-inflammatory agents and physiotherapy remains an important approach to long-term management of patients with ankylosing spondylitis. The new treatment options with tumour necrosis factor blockers seems a breakthrough for patients refractory to conventional treatment.

Worldwide eradication of wild polioviruses is likely to yield substantial health and financial benefits, provided we finish the job. Challenges in the four endemic areas combined with continuing demands for financial resources for eradication have led some to question the goal of eradication and to suggest switching to a policy of control.

Mental disorders account for a large proportion of the disease burden in young people in all societies. Most mental disorders begin during youth (12-24 years of age), although they are often first detected later in life. Poor mental health is strongly related to other health and development concerns in young people, notably lower educational achievements, substance abuse, violence, and poor reproductive and sexual health. The effectiveness of some interventions for some mental disorders in this age-group have been established, although more research is urgently needed to improve the range of affordable and feasible interventions, since most mental-health needs in young people are unmet, even in high-income countries. Key challenges to addressing mental-health needs include the shortage of mental-health professionals, the fairly low capacity and motivation of non-specialist health workers to provide quality mental-health services to young people, and the stigma associated with mental disorder. We propose a population-based, youth focused model, explicitly integrating mental health with other youth health and welfare expertise. Addressing young people's mental-health needs is crucial if they are to fulfil their potential and contribute fully to the development of their communities.

Autosomal dominant polycystic kidney disease is the most prevalent, potentially lethal, monogenic disorder. It is associated with large interfamilial and intrafamilial variability, which can be explained to a large extent by its genetic heterogeneity and modifier genes. An increased understanding of the disorder's underlying genetic, molecular, and cellular mechanisms and a better appreciation of its progression and systemic manifestations have laid out the foundation for the development of clinical trials and potentially effective treatments.

Worldwide, societal shifts and behavioural patterns exacerbated by unique developmental vulnerabilities create a confluence of factors that place today's adolescents at heightened risks for poor health outcomes. Country-level data show that continued investment in effective prevention and treatment strategies is essential to protect adolescents' sexual and reproductive health. Whereas strategies must be tailored to the developmental needs of this age group and their social contexts, effective approaches are multifaceted. All adolescents need access to quality youth-friendly services provided by clinicians trained to work with this population. Sex education programmes should offer accurate, comprehensive information while building skills for negotiating sexual behaviours. Girls and boys also need equal access to youth development programmes that connect them with supportive adults and with educational and economic opportunities. Although progress has been made since the 1994 International Conference on Population and Development, adolescents continue to be disproportionately burdened by threats to their sexual and reproductive health.

The renin-angiotensin system is a major regulatory system of cardiovascular and renal function. Basic research has revealed exciting new aspects, which could lead to novel or modified therapeutic approaches. Renin-angiotensin system blockade exerts potent antiatherosclerotic effects, which are mediated by their antihypertensive, anti-inflammatory, antiproliferative, and oxidative stress lowering properties. Inhibitors of the system-ie, angiotensin converting enzyme inhibitors and angiotensin receptor blockers, are now first-line treatments for hypertensive target organ damage and progressive renal disease. Their effects are greater than expected by their ability to lower blood pressure alone. Angiotensin receptor blockers reduce the frequency of atrial fibrillation and stroke. Renin-angiotensin system blockade delays or avoids the onset of type 2 diabetes and prevents cardiovascular and renal events in diabetic patients. Thus, blockade of this system will remain a cornerstone of our strategies to reduce cardiovascular risk.

Bubonic plague is an often fulminant systemic zoonosis, caused by Yersinia pestis. Conventional microbiology, bacterial population genetics, and genome sequence data, all suggest that Y pestis is a recently evolved clone of the enteric pathogen Yersinia pseudotuberculosis. The genetic basis of this organism's rapid adaptation to its insect vector (the flea) with transmission between mammalian hosts by novel subcutaneous and pneumonic routes of infection is becoming clearer. This transition provides a paradigm for the way in which new pathogens could emerge. Plague in humans is controlled by suppression of rodent reservoir hosts and their fleas and by early detection and treatment of cases of disease. Detection systems for plague in non-endemic regions might now be needed because of a bioterrorism threat. Rapid diagnostic tests are available and a subunit vaccine is in clinical trials.

Puberty is accompanied by physical, psychological, and emotional changes adapted to ensure reproductive and parenting success. Human puberty stands out in the animal world for its association with brain maturation and physical growth. Its effects on health and wellbeing are profound and paradoxical. On the one hand, physical maturation propels an individual into adolescence with peaks in strength, speed, and fitness. Clinicians have viewed puberty as a point of maturing out of childhood-onset conditions. However, puberty's relevance for health has shifted with a modern rise in psychosocial disorders of young people. It marks a transition in risks for depression and other mental disorders, psychosomatic syndromes, substance misuse, and antisocial behaviours. Recent secular trends in these psychosocial disorders coincide with a growing mismatch between biological and social maturation, and the emergence of more dominant youth cultures.

The number of travellers undertaking long-distance flights has continued to increase. Such flights are associated with travel fatigue and jet lag, the symptoms of which are considered here, along with their similarities, differences, and causes. Difficulties with jet lag because of sleep loss and decreased performance are emphasised. Since jet lag is caused mainly by inappropriate timing of the body clock in the new time zone, the pertinent properties of the body clock are outlined, with a description of how the body clock can be adjusted. The methods, both pharmacological and behavioural, that have been used to alleviate the negative results of time-zone transitions, are reviewed. The results form the rationale for advice to travellers flying in different directions and crossing several time zones. Finally, there is an account of the main problems that remain unresolved.

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.