Hot off the presses! Feb 04 LANCET

The Feb 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:

• The end of our National Health Service
  - LANCET 377(9763):353 (2011)
  
• Statins—should we adjust the risk:benefit ratio?
  - LANCET 377(9763):354 (2011)
  
• Abortion in the USA
  - LANCET 377(9763):354 (2011)
  
• Health in southeast Asia
  - LANCET 377(9763):355-356 (2011)
  
• Addressing the complexity of cardiovascular disease by design
  - LANCET 377(9763):356-358 (2011)
  
• Sustaining platelet counts in chronic ITP
  - LANCET 377(9763):358-360 (2011)
  
• What is publication? The case of eltrombopag
  - LANCET 377(9763):360-361 (2011)
  
• Tying up loose threads in delivery of a newborn care package
  - LANCET 377(9763):361-363 (2011)
  
• European academic institutions for global health
  - LANCET 377(9763):363-365 (2011)
  
• Respiratory medicine—a call for research papers
  - LANCET 377(9763):365 (2011)
  
• Offline: Shockingly direct
  - LANCET 377(9763):366 (2011)
  
• The UK's fix for fixated threats
  - LANCET 377(9763):367-368 (2011)
  
• Russia's drug-supply system leaves HIV patients wanting
  - LANCET 377(9763):369-370 (2011)
  
• Back to the future—and to the drawing board
  - LANCET 377(9763):371-372 (2011)
  
• Taking a stand in Burma
  - LANCET 377(9763):372 (2011)
  
• Carole Presern—versatile new Director of PMNCH
  - LANCET 377(9763):373 (2011)
  
• Dying in isolation
  - LANCET 377(9763):374-375 (2011)
  
• Tsung-yi Lin
  - LANCET 377(9763):376 (2011)
  
• Elsevier statement on Research4Life
  - LANCET 377(9763):377 (2011)
  
• Structural variations in attention-deficit hyperactivity disorder
  - LANCET 377(9763):377-378 (2011)
  
• Structural variations in attention-deficit hyperactivity disorder – Authors' reply
  - LANCET 377(9763):378 (2011)
  
• Structural variations in attention-deficit hyperactivity disorder
  - LANCET 377(9763):378-379 (2011)
  
• SNPs and coronary heart disease
  - LANCET 377(9763):379 (2011)
  
• SNPs and coronary heart disease
  - LANCET 377(9763):379 (2011)
  
• SNPs and coronary heart disease – Authors' reply
  - LANCET 377(9763):379-380 (2011)
  
• Early versus delayed treatment of relapsed ovarian cancer
  - LANCET 377(9763):380-381 (2011)
  
• Injustice and health: is the health community listening?
  - LANCET 377(9763):381 (2011)
  
• Dengue vaccine prospects: a step forward
  - LANCET 377(9763):381-382 (2011)
  
• Department of Error
  - LANCET 377(9763):382 (2011)
  
• Identification of ADAMTS7 as a novel locus for coronary atherosclerosis and association of ABO with myocardial infarction in the presence of coronary atherosclerosis: two genome-wide association studies
  - LANCET 377(9763):383-392 (2011)
  Background We tested whether genetic factors distinctly contribute to either development of coronary atherosclerosis or, specifically, to myocardial infarction in existing coronary atherosclerosis. Methods We did two genome-wide association studies (GWAS) with coronary angiographic phenotyping in participants of European ancestry. To identify loci that predispose to angiographic coronary artery disease (CAD), we compared individuals who had this disorder (n=12 393) with those who did not (controls, n=7383). To identify loci that predispose to myocardial infarction, we compared patients who had angiographic CAD and myocardial infarction (n=5783) with those who had angiographic CAD but no myocardial infarction (n=3644). Findings In the comparison of patients with angiographic CAD versus controls, we identified a novel locus, ADAMTS7 (p=4·98×10−13). In the comparison of patients with angiographic CAD who had myocardial infarction versus those with angiographic CAD but no myocardial infarction, we identified a novel association at the ABO locus (p=7·62×10−9). The ABO association was attributable to the glycotransferase-deficient enzyme that encodes the ABO blood group O phenotype previously proposed to protect against myocardial infarction. Interpretation Our findings indicate that specific genetic predispositions promote the development of coronary atherosclerosis whereas others lead to myocardial infarction in the presence of coronary atherosclerosis. The relation to specific CAD phenotypes might modify how novel loci are applied in personalised risk assessment and used in the development of novel therapies for CAD. Funding The PennCath and MedStar studies were supported by the Cardiovascular Institute of the University of Pennsylvania, by the MedStar Health Research Institute at Washington Hospital Center and by a research grant from GlaxoSmithKline. The funding and support for the other cohorts contributing to the paper are described in the webappendix.
• Eltrombopag for management of chronic immune thrombocytopenia (RAISE): a 6-month, randomised, phase 3 study
  - LANCET 377(9763):393-402 (2011)
  Background Eltrombopag is an oral thrombopoietin receptor agonist for the treatment of thrombocytopenia. We aimed to compare the response to once daily eltrombopag versus placebo in patients with chronic immune thrombocytopenia during a 6-month period. Methods We undertook a phase 3, double-blind, placebo-controlled study in adults with previously treated immune thrombocytopenia of more than 6 months' duration who had baseline platelet counts lower than 30 000 per μL. Patients were randomly allocated (in a 2:1 ratio) treatment with local standard of care plus 50 mg eltrombopag or matching placebo once daily for 6 months. Randomisation was done centrally with a computer-generated randomisation schedule and was stratified by baseline platelet count (≤15 000 per μL), use of treatment for immune thrombocytopenia, and splenectomy status. Patients, investigators, and those assessing data were masked to allocation. Dose modifications were made on the basis of platelet response. Patients were assessed for response to treatment (defined as a platelet count of 50 000–400 000 per μL) weekly during the first 6 weeks and at least once every 4 weeks thereafter; the primary endpoint was the odds of response to eltrombopag versus placebo. ! Analysis was by intention to treat. This study is registered at ClinicalTrials.gov, number NCT00370331. Findings Between Nov 22, 2006, and July 31, 2007, 197 patients were randomly allocated to treatment groups and were included in the intention-to-treat analysis (135 eltrombopag, 62 placebo). 106 (79%) patients in the eltrombopag group responded to treatment at least once during the study, compared with 17 (28%) patients in the placebo group. The odds of responding were greater in patients in the eltrombopag group compared with those in the placebo group throughout the 6-month treatment period (odds ratio 8·2, 99% CI 3·59–18·73; p<0·0001). 37 (59%) patients receiving eltrombopag reduced concomitant treatment versus ten (32%) patients receiving placebo (p=0·016). 24 (18%) patients receiving eltrombopag needed rescue treatment compared with 25 (40%) patients receiving placebo (p=0·001). Three (2%) patients receiving eltrombopag had thromboembolic events compared with none in patients on placebo. Nine (7%) eltrombopag-treated patients and two (3%) in the placebo group had mild in! creases in alanine aminotransferase concentration, and five (4%) eltrombopag-treated patients (vs none allocated to placebo) had increases in total bilirubin. Four (7%) patients taking placebo had serious bleeding events, compared with one (<1%) patient treated with eltrombopag. Interpretation 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. Funding GlaxoSmithKline.
• Improvement of perinatal and newborn care in rural Pakistan through community-based strategies: a cluster-randomised effectiveness trial
  - LANCET 377(9763):403-412 (2011)
  Background Newborn deaths account for 57% of deaths in children younger than 5 years in Pakistan. Although a large programme of trained lady health workers (LHWs) exists, the effectiveness of this training on newborn outcomes has not been studied. We aimed to evaluate the effectiveness of a community-based intervention package, principally delivered through LHWs working with traditional birth attendants and community health committees, for reduction of perinatal and neonatal mortality in a rural district of Pakistan. Methods We undertook a cluster randomised trial between February, 2006, and March, 2008, in Hala and Matiari subdistricts, Pakistan. Catchment areas of primary care facilities and all affiliated LHWs were used to define clusters, which were allocated to intervention and control groups by restricted, stratified randomisation. The intervention package delivered by LHWs through group sessions consisted of promotion of antenatal care and maternal health education, use of clean delivery kits, facility births, immediate newborn care, identification of danger signs, and promotion of careseeking; control clusters received routine care. Independent data collectors undertook quarterly household surveillance to capture data for births, deaths, and household practices related to maternal and newborn care. Data collectors were masked to cluster allocation; those analysing data were not. The primary outcome was perinatal and all-cause neonatal mortality. Analysis was by intention to treat. This t! rial is registered, ISRCTN16247511. Findings 16 clusters were assigned to intervention (23 353 households, 12 391 total births) and control groups (23 768 households, 11 443 total births). LHWs in the intervention clusters were able to undertake 4428 (63%) of 7084 planned group sessions, but were only able to visit 2943 neonates (24%) of a total 12 028 livebirths in their catchment villages. Stillbirths were reduced in intervention clusters (39·1 stillbirths per 1000 total births) compared with control (48·7 per 1000; risk ratio [RR] 0·79, 95% CI 0·68–0·92; p=0·006). The neonatal mortality rate was 43·0 deaths per 1000 livebirths in intervention clusters compared with 49·1 per 1000 in control groups (RR 0·85, 0·76–0·96; p=0·02). Interpretation Our results support the scale-up of preventive and promotive maternal and newborn interventions through community health workers and emphasise the need for attention to issues of programme management and coverage for such initiatives to achieve maximum potential. Funding WHO; Saving Newborn Lives Program of Save the Children USA, funded by the Bill & Melinda Gates Foundation.
• Chronic diseases and injuries in India
  - LANCET 377(9763):413-428 (2011)
  Chronic diseases (eg, cardiovascular diseases, mental health disorders, diabetes, and cancer) and injuries are the leading causes of death and disability in India, and we project pronounced increases in their contribution to the burden of disease during the next 25 years. Most chronic diseases are equally prevalent in poor and rural populations and often occur together. Although a wide range of cost-effective primary and secondary prevention strategies are available, their coverage is generally low, especially in poor and rural populations. Much of the care for chronic diseases and injuries is provided in the private sector and can be very expensive. Sufficient evidence exists to warrant immediate action to scale up interventions for chronic diseases and injuries through private and public sectors; improved public health and primary health-care systems are essential for the implementation of cost-effective interventions. We strongly advocate the need to strengthen soci! al and policy frameworks to enable the implementation of interventions such as taxation on bidis (small hand-rolled cigarettes), smokeless tobacco, and locally brewed alcohols. We also advocate the integration of national programmes for various chronic diseases and injuries with one another and with national health agendas. India has already passed the early stages of a chronic disease and injury epidemic; in view of the implications for future disease burden and the demographic transition that is in progress in India, the rate at which effective prevention and control is implemented should be substantially increased. The emerging agenda of chronic diseases and injuries should be a political priority and central to national consciousness, if universal health care is to be achieved.
• Health and health-care systems in southeast Asia: diversity and transitions
  - LANCET 377(9763):429-437 (2011)
  Southeast Asia is a region of enormous social, economic, and political diversity, both across and within countries, shaped by its history, geography, and position as a major crossroad of trade and the movement of goods and services. These factors have not only contributed to the disparate health status of the region's diverse populations, but also to the diverse nature of its health systems, which are at varying stages of evolution. Rapid but inequitable socioeconomic development, coupled with differing rates of demographic and epidemiological transitions, have accentuated health disparities and posed great public health challenges for national health systems, particularly the control of emerging infectious diseases and the rise of non-communicable diseases within ageing populations. While novel forms of health care are evolving in the region, such as corporatised public health-care systems (government owned, but operating according to corporate principles and with pri! vate-sector participation) and financing mechanisms to achieve universal coverage, there are key lessons for health reforms and decentralisation. New challenges have emerged with rising trade in health services, migration of the health workforce, and medical tourism. Juxtaposed between the emerging giant economies of China and India, countries of the region are attempting to forge a common regional identity, despite their diversity, to seek mutually acceptable and effective solutions to key regional health challenges. In this first paper in the Lancet Series on health in southeast Asia, we present an overview of key demographic and epidemiological changes in the region, explore challenges facing health systems, and draw attention to the potential for regional collaboration in health.
• Blind, breathless, and paralysed from benign malaria
  - LANCET 377(9763):438 (2011)