There is strong consensus in the global health community, among donors, recipient countries, and policy makers, about the need for health-system strengthening in low-income and middle-income countries.1,2 Traditional donors and new disease-specific aid initiatives, such as the GAVI Alliance, the US President's Emergency Plan for AIDS Relief (PEPFAR), and the Global Fund to Fight AIDS, Tuberculosis and Malaria, are directly or indirectly funding health-system strengthening. The need for greater capacity to produce a better evidence-base for health-system strengthening has resulted in the first global symposium on health-systems research, to be held in Montreux, Switzerland, in November, 2010.

On April 23, 2008, the European Parliament and Council adopted Directive 2008/46/EC,1 with the sole purpose of amending the deadline for the 27 European Union member states to implement a previous Directive, 2004/40/EC,2 in their domestic legislation. This apparently minor technical amendment was greeted with great relief by the European MRI community. Some 5 years previously, MRI scientists had realised that Directive 2004/40/EC, otherwise known as the Physical Agents (Electromagnetic Fields) Directive, had the potential to seriously harm clinical and research uses of MRI in Europe.

In patients undergoing PCI for acute coronary syndromes, a 7-day double-dose clopidogrel regimen was associated with a reduction in cardiovascular events and stent thrombosis compared with the standard dose. Efficacy and safety did not differ between high-dose and low-dose aspirin. A double-dose clopidogrel regimen can be considered for all patients with acute coronary syndromes treated with an early invasive strategy and intended early PCI.

Acute coronary syndromes typically arise from rupture of a cholesterol-laden plaque with subsequent thrombotic occlusion of the coronary artery. Whether the vessel stays occluded or is recanalised—either by the body's endogenous fibrinolytic system or by external incursion (most commonly, percutaneous coronary intervention [PCI])—determines the extent of myonecrosis and eventual prognosis. An early invasive strategy with PCI can reduce death, myocardial (re)infarction, and recurrent ischaemia in acute coronary syndromes.

Our data suggest that oral sucrose does not significantly affect activity in neonatal brain or spinal cord nociceptive circuits, and therefore might not be an effective analgesic drug. The ability of sucrose to reduce clinical observational scores after noxious events in newborn infants should not be interpreted as pain relief.

In The Lancet today, Rebeccah Slater and colleagues1 present a randomised trial in which they evaluated sucrose as an analgesic in newborn babies. The cortical evoked responses that they recorded from newborn babies treated with sucrose or sterile water were similar. They concluded that sucrose “might not be an effective analgesic drug”, but we think their conclusion is premature.

The benefits of 150 mg dabigatran at reducing stroke, 110 mg dabigatran at reducing bleeding, and both doses at reducing intracranial bleeding versus warfarin were consistent irrespective of centres' quality of INR control. For all vascular events, non-haemorrhagic events, and mortality, advantages of dabigatran were greater at sites with poor INR control than at those with good INR control. Overall, these results show that local standards of care affect the benefits of use of new treatment alternatives.

Our results support the importance of heart-rate reduction with ivabradine for improvement of clinical outcomes in heart failure and confirm the important role of heart rate in the pathophysiology of this disorder.

Our analysis confirms that high heart rate is a risk factor in heart failure. Selective lowering of heart rates with ivabradine improves cardiovascular outcomes. Heart rate is an important target for treatment of heart failure.

Individuals with the ABCB1 3435 TT genotype have reduced platelet inhibition and are at increased risk of recurrent ischaemic events during clopidogrel treatment. In patients with acute coronary syndromes who have undergone percutaneous intervention, when both ABCB1 and CYP2C19 are taken into account, nearly half of the population carries a genotype associated with increased risk of major adverse cardiovascular events while on standard doses of clopidogrel.

Ticagrelor is a more efficacious treatment for acute coronary syndromes than is clopidogrel, irrespective of CYP2C19 and ABCB1 polymorphisms. Use of ticagrelor instead of clopidogrel eliminates the need for presently recommended genetic testing before dual antiplatelet treatment.

Overwhelming evidence lends supports to the use of oral anticoagulants as thromboprophylaxis in patients with atrial fibrillation, traditionally with vitamin K antagonists, such as warfarin (to maintain the international normalised ratio [INR] to 2·0–3·0)1 but more recently with the novel oral anticoagulant dabigatran.2 The development of new oral anticoagulants grew from the inherent difficulties associated with vitamin K antagonists, particularly their complex pharmacokinetic profile: narrow therapeutic range (INR 2·0–3·0) needing regular monitoring; slow onset and offset of action; several interactions with food, alcohol, and drugs; and potential ethnic, genetic, and age-related variations in dose response.

Dual antiplatelet therapy (aspirin plus clopidogrel) is the standard of care for patients with acute coronary syndrome who are managed medically or by percutaneous coronary intervention (PCI).1,2 Clopidogrel has substantial benefit in patients undergoing PCI and stent implantation.1,2 However, major adverse cardiovascular events, including stent thrombosis, can occur despite antiplatelet therapy, and a recent meta-analysis showed that persistent platelet reactivity on clopidogrel treatment confers a five-fold increased risk of major adverse cardiovascular events.

Wisely and slowly, they stumble that run fastWilliam Shakespeare (Romeo and Juliet, Act II, Scene iii)In The Lancet today, investigators provide support for Shakespeare's admonishment, in two articles from the Systolic Heart failure treatment with the If inhibitor ivabradine Trial (SHIFT).1,2 The investigators randomised 6558 patients with symptomatic (New York Heart Association II–IV) chronic heart failure and systolic dysfunction (left-ventricular ejection fraction [LVEF] ≤35%) to placebo or ivabradine.

On June 14, the world's two richest men, Mexico's Carlos Slim Helú and the USA's Bill Gates, jointly announced that they would each contribute US$50 million to the Latam health project to increase vaccinations and improve child nutrition and natal health in central America.1 Slim already contributes reputedly $2·5 billion annually to his Instituto Carlos Slim de la Salud, which runs a large variety of health programmes in Latin America.2 The latest announcement will naturally attract widespread acclaim as an outstanding example of philanthropy.

Lymphatic filariasis and onchocerciasis are parasitic helminth diseases that constitute a serious public health issue in tropical regions. The filarial nematodes that cause these diseases are transmitted by blood-feeding insects and produce chronic and long-term infection through suppression of host immunity. Disease pathogenesis is linked to host inflammation invoked by the death of the parasite, causing hydrocoele, lymphoedema, and elephantiasis in lymphatic filariasis, and skin disease and blindness in onchocerciasis.

Eltrombopag is effective for management of chronic immune thrombocytopenia, and could be particularly beneficial for patients who have not responded to splenectomy or previous treatment. These benefits should be balanced with the potential risks associated with eltrombopag treatment.

In 2004, reports showed that two biotechnology products—romiplostim and eltrombopag—mimicked the biological effects of thrombopoietin, the physiological regulator of platelet production. These novel thrombopoietic agonists promoted megakaryocyte growth and maturation by binding to the thrombopoietin receptor, c-Mpl.1,2 The primary disease target of thrombopoietin mimetics is chronic immune thrombocytopenia (also known as immune thrombocytopenic purpura [ITP]) in which autoantibodies accelerate platelet destruction and block platelet production, leading to low and sometimes dangerous decreases in platelet count.

HEV 239 is well tolerated and effective in the prevention of hepatitis E in the general population in China, including both men and women age 16–65 years.

Hepatitis E virus (HEV) remains one of the least understood and perplexing viruses pathogenic to human beings. From 5% to 20% of people in developed countries show a steady increase in the titre of anti-HEV IgG with increasing age,1 but infection with the prevalent genotype in Europe and the USA, genotype 3, rarely results in symptoms. Although this genotype has been recovered from feral and domestic pigs—and sometimes from people who have eaten raw pork or offal—convincing epidemiological evidence that this zoonotic reservoir is the source of most human exposures or infections remains elusive.

Kidneys from controlled cardiac-death donors provide good graft survival and function up to 5 years in first-time recipients, and are equivalent to kidneys from brain-death donors. Allocation policy for kidneys from cardiac-death donors should reduce cold ischaemic time, avoid large age mismatches between donors and recipients, and restrict use of kidneys poorly matched for HLA in young recipients.

Dominic Summers and colleagues, in The Lancet today,1 have carefully analysed the factors that affect outcome after transplantation of kidneys from deceased donors in the UK. Outcomes were for kidneys donated after cardiac death (cessation of cardiac activity) and after brain-stem death. Today's analysis includes more than 9000 recipients of kidney transplants from 2000 to 2007, during which time 10% of patients received a kidney from a cardiac-death donor and the remaining patients received kidneys from brain-death donors.

The approval of febuxostat, a non-purine-analogue inhibitor of xanthine oxidase, by the European Medicines Agency and the US Food and Drug Administration heralds a new era in the treatment of gout. The use of modified uricases to rapidly reduce serum urate concentrations in patients with otherwise untreatable gout is progressing. Additionally, advances in our understanding of the transport of uric acid in the renal proximal tubule and the inflammatory response to monosodium urate crystals are translating into potential new treatments.

Substantial inequalities exist in cancer survival rates across countries. In addition to prevention of new cancers by reduction of risk factors, strategies are needed to close the gap between developed and developing countries in cancer survival and the effects of the disease on human suffering. We challenge the public health community's assumption that cancers will remain untreated in poor countries, and note the analogy to similarly unfounded arguments from more than a decade ago against provision of HIV treatment.

Primary ovarian insufficiency is a subclass of ovarian dysfunction in which the cause is within the ovary. In most cases, an unknown mechanism leads to premature exhaustion of the resting pool of primordial follicles. Primary ovarian insufficiency might also result from genetic defects, chemotherapy, radiotherapy, or surgery. The main symptom is absence of regular menstrual cycles, and the diagnosis is confirmed by detection of raised follicle-stimulating hormone and declined oestradiol concentrations in the serum, suggesting a primary ovarian defect.

In a subgroup of patients with acute osteoporotic vertebral compression fractures and persistent pain, percutaneous vertebroplasty is effective and safe. Pain relief after vertebroplasty is immediate, is sustained for at least a year, and is significantly greater than that achieved with conservative treatment, at an acceptable cost.

Every year, 1·4 million patients present with vertebral compression fractures worldwide.1 These fractures cause pain, disability, and diminished quality of life,2,3 and are associated with an increased risk of future vertebral fractures.4 Most of these fractures are due to osteoporosis and occur spontaneously or with minimum trauma, and the vertebrae heal in a deformed state with non-surgical management that includes analgesia, bed rest, physiotherapy, and back bracing. Pain can resolve slowly and persist.

Maternal weight gain during pregnancy increases birthweight independently of genetic factors. In view of the apparent association between birthweight and adult weight, obesity prevention efforts targeted at women during pregnancy might be beneficial for offspring.

The greater the gestational weight gain, the heavier the baby at birth. In The Lancet today, David Ludwig and Janet Currie1 report the use of birth-certificate data from more than half a million women in Michigan and New Jersey, USA, to examine the link between gestational weight gain and birthweight. They found a remarkably consistent relation between the two, such that every additional kg gained by the mother increases birthweight by about 7·35 g. Infants of mothers who gained 20–22 kg, and more than 24 kg, weighed roughly 100 g and 150 g more, respectively, than did infants of women who gained 8–10 kg.

Rare diseases are a clinically heterogeneous group of about 6500 disorders,1 and in fewer than 200 000 individuals in the USA.2 They are commonly diagnosed during childhood, often inherited, and can have deleterious long-term effects. Although any one condition is rare, their cumulative public health burden is substantial, with 6–8% of people having a rare disease at some point during life.3

Adverse events are worryingly common in both developed and developing countries. In the UK, around 850 000 errors occur annually in hospitals, contributing towards 40 000 deaths.1 In England and Wales, 27% of inhospital reports of patients' safety incidents were related to problems arising from medical devices or equipment.2 Because most adverse events mix latent and direct contributing factors, what is the role of new technology in addressing patients' safety for global health? Developing safe, effective, and accessible health-care technologies is a major focus of WHO Patient Safety.

To address the shortfall of doctors in rural India, the Medical Council of India is starting an innovative Bachelor of Medicine and of Surgery (MBBS) rural degree.1 Although details of this course are still emerging, reports suggest that it will be shorter in duration (4 years) than the standard MBBS in India (5·5 years, which includes a 1-year mandatory internship), and the qualifying doctors will be allowed to practise only in rural areas for the first 10 years, after which time they might be eligible to work in urban areas.

WHO estimates that up to 25% of the global burden of disease is due to preventable environmental exposures. Children are especially vulnerable because they receive a higher dose than adults, with more extreme consequences. The unborn child's health can also be affected, because the environment can influence gene expression and organogenesis. The burden of disease is unevenly distributed, with greatest exposure to children in developing and low-income countries. While children in such countries still have to cope with traditional threats, including lack of access to safe water, poor sanitation and hygiene, and infectious diseases, they suffer from emerging environmental exposures that threaten their health, such as the effects of rapid globalisation, an upsurge in urbanisation, transboundary chemical transport, and unsustainable consumption.

Stampedes are not an infrequent tragedy during religious festivities. The stampede at Ram Janki Temple on March 4, 2010, in the northern Indian state of Uttar Pradesh, killed 63 people and injured scores more,1 which makes it the fourth major trampling during religious events in India in the last 3 years. Many other events that result in fewer serious casualties go unreported. Surprisingly, these unique events have received little attention from the scientific community and disaster planners, resulting in limited understanding of the mechanics of injury patterns and the psychological and behavioural aspects that contribute to increased mortality.

Recently, Benjamin Chapman and colleagues,1 in a new trend in health inequalities research, showed that US adults of low and high socioeconomic status differ substantially in their personality profiles. These researchers focused on the so-called Big Five personality traits2 and noted that people of low socioeconomic status had raised levels of neuroticism and agreeableness and diminished levels of extraversion, openness, and conscientiousness. Because some of these factors are also predictors of mortality, differences in personality accounted for around 20% of inequalities in mortality related to socioeconomic status in this cohort.

People are over-consuming salt, causing up to 30% of all cases of hypertension.1 In the Pan-American region, hypertension prevalence ranges from 20% to 35%, with the higher proportions more often seen in Latin America.2,3 Salt intake, where measured, can be as high as 11·5 g a day per person, with by far the largest source in most cases being commercially processed foods.4,5 The Pan American Health Organization (PAHO) has responded with an initiative, “Cardiovascular Disease Prevention through Dietary Salt Reduction”.

Over the past decade, there has been lively discussion about the optimum oxygen concentration for resuscitation of newborn babies.1,2 Until recently, the routine had been to use 100% oxygen for resuscitation at birth, but was this harmful? Elemental oxygen was discovered in about 1775 and, by 1780, it was being used to resuscitate newborns. It took, however, 200 years before this unproven practice was questioned3 and systematic experimental and clinical studies were done to assess the short-term and long-term effects of oxygen.

Primary research, systematic reviews, meta-analyses, and clinical guidelines rely on what accumulates from millions of doctor–patient interactions over time. This information is distilled into those different formats to provide an evidence-based approach to medical practice. But what of the individual interactions that occur? Each one is different. Each patient is unique. Each scenario varies. The dynamic of the consultation will never be replicated. Case reports provide an opportunity for some of these individual—and important—stories to be told.

The Havasu ‘Baaja tribe, or as they are more generally referred to, the Havasupai, has about 650 members. This tiny band of Native Americans has won a momentous lawsuit that might demand rethinking about the way biological materials are obtained for use in scientific research.

Support for prospective registration of protocols for systematic reviews has been gathering momentum.1–3 The PRISMA statement, a guideline for reporting systematic reviews and meta-analyses of studies that evaluate health-care interventions, advocates registration.1,2 Well-conducted systematic reviews are accepted as the best-quality evidence to inform policy and practice, and the dramatic upward trend in the number of systematic reviews published annually (figure) is set to continue.3 However, there is currently no single facility for identifying this type of research in advance of the appearance of the results of the review.

Evaluation of large-scale programmes and initiatives aimed at improvement of health in countries of low and middle income needs a new approach. Traditional designs, which compare areas with and without a given programme, are no longer relevant at a time when many programmes are being scaled up in virtually every district in the world. We propose an evolution in evaluation design, a national platform approach that: uses the district as the unit of design and analysis; is based on continuous monitoring of different levels of indicators; gathers additional data before, during, and after the period to be assessed by multiple methods; uses several analytical techniques to deal with various data gaps and biases; and includes interim and summative evaluation analyses.

AGREE II;1 an update of the Appraisal of Guidelines for Research & Evaluation instrument,2 has recently been published online. This update is worth celebrating because AGREE has made, and will continue to make, an important contribution to improving the quality of clinical care.

Improvements in public-health strategies and monitoring are needed to reduce disparities for more than 2 billion people without adequate access to surgical care.

Surgery can provide definitive treatment for trauma, musculoskeletal disorders, obstructed labour, cataract blindness, and a large range of cancers and cardiovascular diseases. 11% of the world's disability-adjusted life years are attributable to conditions that can be treated with surgery.1 The wealthiest third of the global population receives 75% of the world's total number of surgical procedures, estimated at 234 million every year, while the poorest third receives only 4% of these operations.

In her Art of Medicine essay in The Lancet today, Alice Wexler1 recounts the stigma faced by those with Huntington's disease, a cruelly progressive and incurable neurodegenerative condition that usually (not invariably) presents in mid-life. The disease is inherited as an autosomal dominant trait so that children of a parent with Huntington's disease are all at risk, with each having a 50% chance of developing the disease if they live a normal lifespan. The stigma of Huntington's disease, therefore, attaches to those who are at risk as well as to those with symptoms.

Azria D, Bourgier C. Partial breast irradiation: new standard for selected patients. Lancet 2010; published online June 5. DOI: 10.1016/S0140-6736(10)60898-7—In this Comment, the third sentence of paragraph 3 should have read: “For instance, a dose of 15 Gy prescribed at 2 mm with a typical applicator of 3·5 cm diameter will deliver 10·6 Gy at a depth of 5 mm.” This correction has been made to the online version as of June 8, and will be made to the printed Comment.