Results of recent clinical trials suggest that probiotic supplementation reduces the risk of necrotising enterocolitis in preterm neonates. We aimed to systematically review randomised controlled trials evaluating efficacy and safety of any probiotic supplementation (started within first 10 days, duration > or =7 days) in preventing stage 2 or greater necrotising enterocolitis in preterm neonates (gestation <33 weeks) with very low birthweight (<1500 g).

Randomised trials have shown that aspirin reduces the short-term risk of recurrent colorectal adenomas in patients with a history of adenomas or cancer, but large trials have shown no effect in primary prevention of colorectal cancer during 10 years' follow-up. However, the delay from the early development of adenoma to presentation with cancer is at least 10 years. We aimed to assess the longer-term effect of aspirin on the incidence of cancers.

For developmental as well as epidemiological reasons, young people need youth-friendly models of primary care. Over the past two decades, much has been written about barriers faced by young people in accessing health care. Worldwide, initiatives are emerging that attempt to remove these barriers and help reach young people with the health services they need. In this paper, we present key models of youth-friendly health provision and review the evidence for the effect of such models on young people's health. Unfortunately, little evidence is available, since many of these initiatives have not been appropriately assessed. Appropriate controlled assessments of the effect of youth-friendly health-service models on young people's health outcomes should be the focus of future research agendas. Enough is known to recommend that a priority for the future is to ensure that each country, state, and locality has a policy and support to encourage provision of innovative and well assessed youth-friendly services.

Acute respiratory distress syndrome and acute lung injury are well defined and readily recognised clinical disorders caused by many clinical insults to the lung or because of predispositions to lung injury. That this process is common in intensive care is well established. The mainstay of treatment for this disorder is provision of excellent supportive care since these patients are critically ill and frequently have coexisting conditions including sepsis and multiple organ failure. Refinements in ventilator and fluid management supported by data from prospective randomised trials have increased the methods available to effectively manage this disorder.

In its severest form, developmental dysplasia of the hip is one of the most common congenital malformations. The pathophysiology and natural history of the range of morphological and clinical disorders that constitute developmental dysplasia of the hip are poorly understood. Neonatal screening programmes, based on clinical screening examinations, have been established for more than 40 years but their effectiveness remains controversial. Whereas systematic sonographic imaging of newborn and young infants has afforded insights into normal and abnormal hip development in early life, we do not clearly understand the longer-term outcomes of developmental hip dysplasia, its contribution to premature degenerative hip disorders in adult life, and the benefits and harms of newborn screening. High quality studies of the adult outcomes of developmental hip dysplasia and the childhood origins of early degenerative hip disease are needed, as are randomised trials to assess the effectiveness and safety of neonatal screening and early treatment.

In this review, we aim to focus attention on the interaction between adolescents with chronic conditions and the health systems that support them. At least 12% of adolescents live with a chronic condition. Some conditions are characterised by increasing incidence (eg, diabetes) or improving survival rates (eg, cystic fibrosis), while others are concerning because of differentially poorer outcomes in adolescents in comparison to both children and adults (eg cancer). Growing evidence suggests that young people with chronic conditions are doubly disadvantaged--engaging in risky behaviours to at least similar if not higher rates as healthy peers, while having the potential for greater adverse health outcomes from these behaviours. In addition to efforts at improving survival, in order to improve their life chances, we need to better understand how the social and emotional outcomes of young people with a chronic disease can be improved, and better support young people's emerging capacity for self-management.

The autopsy is now often regarded as of marginal use in modern clinical practice. In this Review we contend that the autopsy remains an important procedure with substantial, if largely underused, potential to advance medical knowledge and improve clinical practice. Many doctors lack familiarity with autopsy practices, and are insufficiently aware of the benefits for not only bereaved families but also present and future patients. In this Review, which has an international perspective, we consider the ascent and decline of the autopsy, the legal frameworks that govern its use, the value and potential pitfalls of alternatives to the conventional method, and the autopsy's role in undergraduate medical education. We also draw attention to the continuing ability of autopsies to improve the completeness and reliability of death certification, which is important for public-health strategies and for some bereaved families.

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.