Hot off the presses! Mar 04 LANCET

The Mar 04 issue of the LANCET is now up on Pubget (About LANCET): if you're at a subscribing institution, just click the link in the latest link at the home page. (Note you'll only be able to get all the PDFs in the issue if your institution subscribes to Pubget.)

Latest Articles Include:

• Guidance on food allergy in children
  - LANCET 377(9767):691 (2011)
  
• Rooting out tuberculosis in homeless communities
  - LANCET 377(9767):692 (2011)
  
• Better spending needed for neglected diseases
  - LANCET 377(9767):692 (2011)
  
• BLISS! Lupus learns its lessons
  - LANCET 377(9767):693-694 (2011)
  
• Triggers of MI for the individual and in the community
  - LANCET 377(9767):694-696 (2011)
  
• Lowering blood pressure in acute stroke: the SCAST trial
  - LANCET 377(9767):696-698 (2011)
  
• Cell-culture-derived influenza vaccine production
  - LANCET 377(9767):698-700 (2011)
  
• Mental health in southeast Asia
  - LANCET 377(9767):700-702 (2011)
  
• Towards a truly universal Indian health system
  - LANCET 377(9767):702-703 (2011)
  
• Offline: The case for books (and journals)
  - LANCET 377(9767):704 (2011)
  
• NIH proposes new drug development centre
  - LANCET 377(9767):705-706 (2011)
  
• In Lebanon, mental health is on the mend
  - LANCET 377(9767):707-708 (2011)
  
• Nature's sexy selection
  - LANCET 377(9767):709 (2011)
  
• Hullo clouds, hullo sky
  - LANCET 377(9767):710 (2011)
  
• Babatunde Osotimehin: New Executive Director of UNFPA
  - LANCET 377(9767):711 (2011)
  
• Prescientific death rites, vampires, and the human soul
  - LANCET 377(9767):712-713 (2011)
  
• Ronald Hinchcliffe
  - LANCET 377(9767):714 (2011)
  
• Efficacy and safety of more intensive lowering of LDL cholesterol
  - LANCET 377(9767):715 (2011)
  
• Efficacy and safety of more intensive lowering of LDL cholesterol
  - LANCET 377(9767):715 (2011)
  
• Efficacy and safety of more intensive lowering of LDL cholesterol – Authors' reply
  - LANCET 377(9767):715-716 (2011)
  
• Chest-compression-only versus standard CPR
  - LANCET 377(9767):716 (2011)
  
• Chest-compression-only versus standard CPR
  - LANCET 377(9767):716 (2011)
  
• Chest-compression-only versus standard CPR
  - LANCET 377(9767):717 (2011)
  
• Chest-compression-only versus standard CPR
  - LANCET 377(9767):717-718 (2011)
  
• Chest-compression-only versus standard CPR
  - LANCET 377(9767):718 (2011)
  
• Chest-compression-only versus standard CPR – Authors' reply
  - LANCET 377(9767):718-719 (2011)
  
• Human papillomavirus vaccine trials in India
  - LANCET 377(9767):719 (2011)
  
• Europe and the century of biomedical discovery and implementation
  - LANCET 377(9767):719-720 (2011)
  
• Canadian hypocrisy regarding chrysotile
  - LANCET 377(9767):720 (2011)
  
• Department of Error
  - LANCET 377(9767):720 (2011)
  
• Efficacy and safety of belimumab in patients with active systemic lupus erythematosus: a randomised, placebo-controlled, phase 3 trial
  - LANCET 377(9767):721-731 (2011)
  Background Systemic lupus erythematosus is a heterogeneous autoimmune disease that is associated with B-cell hyperactivity, autoantibodies, and increased concentrations of B-lymphocyte stimulator (BLyS). The efficacy and safety of the fully human monoclonal antibody belimumab (BLyS-specific inhibitor) was assessed in patients with active systemic lupus erythematosus. Methods Patients (aged ≥18 years) who were seropositive with scores of at least 6 on the Safety of Estrogens in Lupus Erythematosus National Assessment–Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) were enrolled in a multicentre phase 3 study, which was done in Latin America, Asia-Pacific, and eastern Europe. Patients were randomly assigned by use of a central interactive voice response system in a 1:1:1 ratio to belimumab 1 mg/kg or 10 mg/kg, or placebo by intravenous infusion in 1 h on days 0, 14, and 28, and then every 28 days until 48 weeks, with standard of care. Patients, investigators, study coordinators, and sponsors were masked to treatment assignment. Primary efficacy endpoint was improvement in the Systemic Lupus Erythematosus Responder Index (SRI) at week 52 (reduction ≥4 points in SELENA-SLEDAI score; no new British Isles Lupus Assessment Group [BILAG] A organ domain score and no more than 1 new B organ domain score; and no worsening [<0·3 i! ncrease] in Physician's Global Assessment [PGA] score) versus baseline. Method of analysis was by modified intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00424476. Findings 867 patients were randomly assigned to belimumab 1 mg/kg (n=289) or 10 mg/kg (n=290), or placebo (n=288). 865 were treated and analysed in the belimumab (1 mg/kg, n=288; 10 mg/kg, n=290) and placebo groups (n=287). Significantly higher SRI rates were noted with belimumab 1 mg/kg (148 [51%], odds ratio 1·55 [95% CI 1·10–2·19]; p=0·0129) and 10 mg/kg (167 [58%], 1·83 [1·30–2·59]; p=0·0006) than with placebo (125 [44%]) at week 52. More patients had their SELENA-SLEDAI score reduced by at least 4 points during 52 weeks with belimumab 1 mg/kg (153 [53%], 1·51 [1·07–2·14]; p=0·0189) and 10 mg/kg (169 [58%], 1·71 [1·21–2·41]; p=0·0024) than with placebo (132 [46%]). More patients given belimumab 1 mg/kg (226 [78%], 1·38 [0·93–2·04]; p=0·1064) and 10 mg/kg (236 [81%], 1·62 [1·09–2·42]; p=0·0181) had no new BILAG A or no more than 1 new B flare than did those in the placebo group (210 [73%]). No worsening in PGA score was noted in more patients wi! th belimumab 1 mg/kg (227 [79%], 1·68 [1·15–2·47]; p=0·0078) and 10 mg/kg (231 [80%], 1·74 [1·18–2·55]; p=0·0048) than with placebo (199 [69%]). Rates of adverse events were similar in the groups given belimumab 1 mg/kg and 10 mg/kg, and placebo: serious infection was reported in 22 (8%), 13 (4%), and 17 (6%) patients, respectively, and severe or serious hypersensitivity reactions on an infusion day were reported in two (<1%), two (<1%), and no patients, respectively. No malignant diseases were reported. Interpretation Belimumab has the potential to be the first targeted biological treatment that is approved specifically for systemic lupus erythematosus, providing a new option for the management of this important prototypic autoimmune disease. Funding Human Genome Sciences and GlaxoSmithKline.
• Public health importance of triggers of myocardial infarction: a comparative risk assessment
  - LANCET 377(9767):732-740 (2011)
  Background Acute myocardial infarction is triggered by various factors, such as physical exertion, stressful events, heavy meals, or increases in air pollution. However, the importance and relevance of each trigger are uncertain. We compared triggers of myocardial infarction at an individual and population level. Methods We searched PubMed and the Web of Science citation databases to identify studies of triggers of non-fatal myocardial infarction to calculate population attributable fractions (PAF). When feasible, we did a meta-regression analysis for studies of the same trigger. Findings Of the epidemiologic studies reviewed, 36 provided sufficient details to be considered. In the studied populations, the exposure prevalence for triggers in the relevant control time window ranged from 0·04% for cocaine use to 100% for air pollution. The reported odds ratios (OR) ranged from 1·05 to 23·7. Ranking triggers from the highest to the lowest OR resulted in the following order: use of cocaine, heavy meal, smoking of marijuana, negative emotions, physical exertion, positive emotions, anger, sexual activity, traffic exposure, respiratory infections, coffee consumption, air pollution (based on a difference of 30 μg/m3 in particulate matter with a diameter <10 μm [PM10]). Taking into account the OR and the prevalences of exposure, the highest PAF was estimated for traffic exposure (7·4%), followed by physical exertion (6·2%), alcohol (5·0%), coffee (5·0%), a difference of 30 μg/m3 in PM10 (4·8%), negative emotions (3·9%), anger (3·1%), heavy meal (2·7%), p! ositive emotions (2·4%), sexual activity (2·2%), cocaine use (0·9%), marijuana smoking (0·8%) and respiratory infections (0·6%). Interpretation In view of both the magnitude of the risk and the prevalence in the population, air pollution is an important trigger of myocardial infarction, it is of similar magnitude (PAF 5–7%) as other well accepted triggers such as physical exertion, alcohol, and coffee. Our work shows that ever-present small risks might have considerable public health relevance. Funding The research on air pollution and health at Hasselt University is supported by a grant from the Flemish Scientific Fund (FWO, Krediet aan navorsers/G.0873.11), tUL-impulse financing, and bijzonder onderzoeksfonds (BOF) and at the Katholieke Universiteit Leuven by the sustainable development programme of BELSPO (Belgian Science Policy).
• The angiotensin-receptor blocker candesartan for treatment of acute stroke (SCAST): a randomised, placebo-controlled, double-blind trial
  - LANCET 377(9767):741-750 (2011)
  Background Raised blood pressure is common in acute stroke, and is associated with an increased risk of poor outcomes. We aimed to examine whether careful blood-pressure lowering treatment with the angiotensin-receptor blocker candesartan is beneficial in patients with acute stroke and raised blood pressure. Methods Participants in this randomised, placebo-controlled, double-blind trial were recruited from 146 centres in nine north European countries. Patients older than 18 years with acute stroke (ischaemic or haemorrhagic) and systolic blood pressure of 140 mm Hg or higher were included within 30 h of symptom onset. Patients were randomly allocated to candesartan or placebo (1:1) for 7 days, with doses increasing from 4 mg on day 1 to 16 mg on days 3 to 7. Randomisation was stratified by centre, with blocks of six packs of candesartan or placebo. Patients and investigators were masked to treatment allocation. There were two co-primary effect variables: the composite endpoint of vascular death, myocardial infarction, or stroke during the first 6 months; and functional outcome at 6 months, as measured by the modified Rankin Scale. Analyses were by intention to treat. The study is registered, number NCT00120003 (ClinicalTrials.gov), and ISRCTN13643354. Findings 2029 patients were randomly allocated to treatment groups (1017 candesartan, 1012 placebo), and data for status at 6 months were available for 2004 patients (99%; 1000 candesartan, 1004 placebo). During the 7-day treatment period, blood pressures were significantly lower in patients allocated candesartan than in those on placebo (mean 147/82 mm Hg [SD 23/14] in the candesartan group on day 7 vs 152/84 mm Hg [22/14] in the placebo group; p<0·0001). During 6 months' follow-up, the risk of the composite vascular endpoint did not differ between treatment groups (candesartan, 120 events, vs placebo, 111 events; adjusted hazard ratio 1·09, 95% CI 0·84–1·41; p=0·52). Analysis of functional outcome suggested a higher risk of poor outcome in the candesartan group (adjusted common odds ratio 1·17, 95% CI 1·00–1·38; p=0·048 [not significant at p≤0·025 level]). The observed effects were similar for all prespecified secondary endpoints (including death from any cause, vas! cular death, ischaemic stroke, haemorrhagic stroke, myocardial infarction, stroke progression, symptomatic hypotension, and renal failure) and outcomes (Scandinavian Stroke Scale score at 7 days and Barthel index at 6 months), and there was no evidence of a differential effect in any of the prespecified subgroups. During follow-up, nine (1%) patients on candesartan and five (<1%) on placebo had symptomatic hypotension, and renal failure was reported for 18 (2%) patients taking candesartan and 13 (1%) allocated placebo. Interpretation There was no indication that careful blood-pressure lowering treatment with the angiotensin-receptor blocker candesartan is beneficial in patients with acute stroke and raised blood pressure. If anything, the evidence suggested a harmful effect. Funding South-Eastern Norway Regional Health Authority; Oslo University Hospital Ullevål; AstraZeneca; Takeda.
• Efficacy, safety, and immunogenicity of a Vero-cell-culture-derived trivalent influenza vaccine: a multicentre, double-blind, randomised, placebo-controlled trial
  - LANCET 377(9767):751-759 (2011)
  Background The use of cell-culture technologies for the manufacture of influenza vaccines might contribute to improved strain selection and robust vaccine supplies. We investigated the safety, immunogenicity, and protective efficacy of a Vero-cell-culture-derived influenza vaccine, and assessed the correlation between vaccine efficacy and haemagglutination inhibition antibody titre. Methods In a double-blind, placebo-controlled, phase 3 trial undertaken in 36 centres in the USA, healthy adults (aged 18–49 years) were randomly assigned in a 1:1 ratio to one injection of either placebo or Vero-cell-culture-derived influenza vaccine during the 2008–09 season. Randomisation was done in blocks by use of the random number generator algorithm, and participants were allocated by use of a centralised telephone system. The primary objective was the efficacy of the vaccine in preventing cell-culture-confirmed influenza infection with viruses that were antigenically matched to one of the vaccine strains. Analysis was by intention to treat. The study is registered with ClinicalTrials.gov, number NCT00566345. Findings 7250 participants were randomly assigned to vaccine (n=3626) and placebo (n=3624). 7236 were analysed for the primary outcome (n=3619 and n=3617, respectively). Overall protective efficacy for antigenically matched influenza infection was 78·5% (95% CI 60·8–88·2). The vaccine was well tolerated with no treatment-related serious adverse events. Adverse events were mainly mild and transient. An HI titre of at least 1:15 provided a reliable correlate of cell-culture-derived influenza vaccine-induced protection; no additional benefit was noted with titres greater than 1:30. Interpretation The data indicate that existing correlates of protection afforded with egg-derived seasonal influenza vaccines also apply to this vaccine. Funding Federal (US Government) funds from the Office for Preparedness and Response, Biomedical Advanced Research and Development Authority, under contract to DynPort Vaccine Company.
• Towards achievement of universal health care in India by 2020: a call to action
  - LANCET 377(9767):760-768 (2011)
  To sustain the positive economic trajectory that India has had during the past decade, and to honour the fundamental right of all citizens to adequate health care, the health of all Indian people has to be given the highest priority in public policy. We propose the creation of the Integrated National Health System in India through provision of universal health insurance, establishment of autonomous organisations to enable accountable and evidence-based good-quality health-care practices and development of appropriately trained human resources, the restructuring of health governance to make it coordinated and decentralised, and legislation of health entitlement for all Indian people. The key characteristics of our proposal are to strengthen the public health system as the primary provider of promotive, preventive, and curative health services in India, to improve quality and reduce the out-of-pocket expenditure on health care through a well regulated integration of the ! private sector within the national health-care system. Dialogue and consensus building among the stakeholders in the government, civil society, and private sector are the next steps to formalise the actions needed and to monitor their achievement. In our call to action, we propose that India must achieve health care for all by 2020.
• A loose screw or two
  - LANCET 377(9767):782 (2011)
  
• Human resources for health in southeast Asia: shortages, distributional challenges, and international trade in health services
  - LANCET 377(9767):769-781 (2011)
  In this paper, we address the issues of shortage and maldistribution of health personnel in southeast Asia in the context of the international trade in health services. Although there is no shortage of health workers in the region overall, when analysed separately, five low-income countries have some deficit. All countries in southeast Asia face problems of maldistribution of health workers, and rural areas are often understaffed. Despite a high capacity for medical and nursing training in both public and private facilities, there is weak coordination between production of health workers and capacity for employment. Regional experiences and policy responses to address these challenges can be used to inform future policy in the region and elsewhere. A distinctive feature of southeast Asia is its engagement in international trade in health services. Singapore and Malaysia import health workers to meet domestic demand and to provide services to international patients. Tha! iland attracts many foreign patients for health services. This situation has resulted in the so-called brain drain of highly specialised staff from public medical schools to the private hospitals. The Philippines and Indonesia are the main exporters of doctors and nurses in the region. Agreements about mutual recognition of professional qualifications for three groups of health workers under the Association of Southeast Asian Nations Framework Agreement on Services could result in increased movement within the region in the future. To ensure that vital human resources for health are available to meet the needs of the populations that they serve, migration management and retention strategies need to be integrated into ongoing efforts to strengthen health systems in southeast Asia. There is also a need for improved dialogue between the health and trade sectors on how to balance economic opportunities associated with trade in health services with domestic health needs and equi! ty issues.