Our aim was to identify which clinical features have value in confirming or excluding the possibility of serious infection in children presenting to ambulatory care settings in developed countries.

Directly observed therapy has been recommended to improve adherence for patients with HIV infection who are on highly active antiretroviral therapy, but the benefit and cost-effectiveness of this approach has not been established conclusively. We did a systematic review and meta-analysis of randomised trials of directly observed versus self-administered antiretroviral treatment.

Neck pain is a common and costly condition for which pharmacological management has limited evidence of efficacy and side-effects. Low-level laser therapy (LLLT) is a relatively uncommon, non-invasive treatment for neck pain, in which non-thermal laser irradiation is applied to sites of pain. We did a systematic review and meta-analysis of randomised controlled trials to assess the efficacy of LLLT in neck pain.

Streptococcus pneumoniae is a leading cause of bacterial pneumonia, meningitis, and sepsis in children worldwide. However, many countries lack national estimates of disease burden. Effective interventions are available, including pneumococcal conjugate vaccine and case management. To support local and global policy decisions on pneumococcal disease prevention and treatment, we estimated country-specific incidence of serious cases and deaths in children younger than 5 years.

Women with gestational diabetes are at increased risk of developing type 2 diabetes, but the risk and time of onset have not been fully quantified. We therefore did a comprehensive systematic review and meta-analysis to assess the strength of association between these conditions and the effect of factors that might modify the risk.

Over the past 20 years, percutaneous transluminal balloon coronary angioplasty (PTCA), bare-metal stents (BMS), and drug-eluting stents (DES) succeeded each other as catheter-based treatments for coronary artery disease. We undertook a systematic overview of randomised trials comparing these interventions with each other and with medical therapy in patients with non-acute coronary artery disease.

Patients undergoing dialysis have a substantially increased risk of cardiovascular mortality and morbidity. Although several trials have shown the cardiovascular benefits of lowering blood pressure in the general population, there is uncertainty about the efficacy and tolerability of reducing blood pressure in patients on dialysis. We did a systematic review and meta-analysis to assess the effect of blood pressure lowering in patients on dialysis.

Some clinicians do lumbar imaging routinely or in the absence of historical or clinical features suggestive of serious low-back problems. We investigated the effects of routine, immediate lumbar imaging versus usual clinical care without immediate imaging on clinical outcomes in patients with low-back pain and no indication of serious underlying conditions.

Early endometrial cancer with low-risk pathological features can be successfully treated by surgery alone. External beam radiotherapy added to surgery has been investigated in several small trials, which have mainly included women at intermediate risk of recurrence. In these trials, postoperative radiotherapy has been shown to reduce the risk of isolated local recurrence but there is no evidence that it improves recurrence-free or overall survival. We report the findings from the ASTEC and EN.5 trials, which investigated adjuvant external beam radiotherapy in women with early-stage disease and pathological features suggestive of intermediate or high risk of recurrence and death from endometrial cancer.

Planning for programme sustainability is a key contributor to health and development, especially in low-income and middle-income countries. A consensus evidence-based operational framework would facilitate policy and research advances in understanding, measuring, and improving programme sustainability. We did a systematic review of both conceptual frameworks and empirical studies about health-programme sustainability. On the basis of the review, we propose that sustainable health programmes are regarded as complex systems that encompass programmes, health problems targeted by programmes, and programmes' drivers or key stakeholders, all of which interact dynamically within any given context. We show the usefulness of this approach with case studies drawn from the authors' experience.

Injecting drug use is an increasingly important cause of HIV transmission in most countries worldwide. Our aim was to determine the prevalence of injecting drug use among individuals aged 15-64 years, and of HIV among people who inject drugs.

In old age, reduction in physical function leads to loss of independence, the need for hospital and long-term nursing-home care, and premature death. We did a systematic review to assess the effectiveness of community-based complex interventions in preservation of physical function and independence in elderly people.

Excess bodyweight, expressed as increased body-mass index (BMI), is associated with the risk of some common adult cancers. We did a systematic review and meta-analysis to assess the strength of associations between BMI and different sites of cancer and to investigate differences in these associations between sex and ethnic groups.

The overall clinical benefit of thiazolidinediones (TZDs) as a treatment for hyperglycaemia can be difficult to assess because of the risk of congestive heart failure due to TZD-related fluid retention. Since prediabetic and diabetic patients are at high cardiovascular risk, the outcome and natural history of such risks need to be better understood. We aimed to examine the risk of congestive heart failure and of cardiac death in patients given TZDs.

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.

Violence and rape are believed to fuel the HIV epidemic in countries affected by conflict. We compared HIV prevalence in populations directly affected by conflict with that in those not directly affected and in refugees versus the nearest surrounding host communities in sub-Saharan African countries.

The HIV epidemic has led to large increases in the frequency of smear-negative pulmonary tuberculosis, which has poor treatment outcomes and excessive early mortality compared with smear-positive disease. We used a combination of systematic review, document analysis, and global expert opinion to review the extent of this problem. We also looked at policies of national tuberculosis control programmes for the diagnosis of smear-negative pulmonary tuberculosis to assess their coverage, identify the diagnostic difficulties, and find ways to improve the diagnosis of this type of tuberculosis, with a focus on resource-constrained settings with high HIV infection rates. We propose that the internationally recommended algorithm for the diagnosis of smear-negative pulmonary tuberculosis should be revised to include HIV status, severity of AIDS and tuberculosis, and early use of chest radiography in the decision tree. Increased use of promising methods of diagnosis such as sputum liquefaction and concentration and increased availability of fluorescence microscopy should be explored and encouraged. Culturing of sputum in resource-constrained settings with high HIV infection rates should also be encouraged, existing facilities should be made full use of and upgraded, and effective quality-assurance systems should be used. Innovative ways to address human resources issues involved in addressing the diagnostic difficulties are also needed. The development of rapid, simple, and accurate tuberculosis diagnostic tools with applicability at point of care and remote location is essential. To achieve these goals, greater political commitment, scientific interest, and investment are needed.

Although surgery offers the best chance of cure for patients with non-small cell lung cancer (NSCLC), the overall 5-year survival rate is modest, and improvements are urgently needed. In the 1990s, much interest was generated from two small trials that reported striking results with neo-adjuvant chemotherapy, and therefore our intergroup randomised trial was designed to investigate whether, in patients with operable non-small cell lung cancer of any stage, outcomes could be improved by giving platinum-based chemotherapy before surgery.

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).