Hot off the presses! Nov 19 LANCET

The Nov 19 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:

• "Claptrap" from the UK's Department of Health
  - LANCET 376(9753):1617 (2010)
  
• UK versus US health care: Atlantic rift
  - LANCET 376(9753):1618 (2010)
  
• Lack of treatment of South Africa's infants with HIV
  - LANCET 376(9753):1618 (2010)
  
• Chronic diseases: global action must match global evidence
  - LANCET 376(9753):1619-1621 (2010)
  
• For severe malaria, artesunate is the answer
  - LANCET 376(9753):1621-1622 (2010)
  
• Is intensive LDL-cholesterol lowering beneficial and safe?
  - LANCET 376(9753):1622-1624 (2010)
  
• Poliomyelitis eradication: another step forward
  - LANCET 376(9753):1624-1625 (2010)
  
• Research priorities for malaria elimination
  - LANCET 376(9753):1626-1627 (2010)
  
• Croatia moves away from fostering research integrity
  - LANCET 376(9753):1627-1628 (2010)
  
• Cardiology—call for papers
  - LANCET 376(9753):1629 (2010)
  
• Diabetes—call for papers
  - LANCET 376(9753):1629 (2010)
  
• Stroke—call for papers
  - LANCET 376(9753):1629 (2010)
  
• Offline: No added sugar
  - LANCET 376(9753):1630 (2010)
  
• Defrauding of the Global Fund gives Sweden cold feet
  - LANCET 376(9753):1631 (2010)
  
• US foreign aid restructuring: is it "a very big deal"?
  - LANCET 376(9753):1632 (2010)
  
• India is failing the mentally ill as abuses continue
  - LANCET 376(9753):1633-1634 (2010)
  
• Landscapes of the mind
  - LANCET 376(9753):1635 (2010)
  
• Coping after combat—a soldier's story
  - LANCET 376(9753):1636 (2010)
  
• Ke Yang—reforming medical education in China
  - LANCET 376(9753):1637 (2010)
  
• Technophilia and the pharmaceutical fix
  - LANCET 376(9753):1638-1639 (2010)
  
• Georges Mathé
  - LANCET 376(9753):1640 (2010)
  
• Arsenic exposure from drinking water and mortality in Bangladesh
  - LANCET 376(9753):1641 (2010)
  
• Arsenic exposure from drinking water and mortality in Bangladesh
  - LANCET 376(9753):1641-1642 (2010)
  
• Arsenic exposure from drinking water and mortality in Bangladesh – Authors' reply
  - LANCET 376(9753):1642 (2010)
  
• Vitamin C and E to prevent pre-eclampsia in diabetic women
  - LANCET 376(9753):1642-1643 (2010)
  
• Vitamin C and E to prevent pre-eclampsia in diabetic women – Authors' reply
  - LANCET 376(9753):1643 (2010)
  
• Neonatal vitamin A supplementation and infant survival
  - LANCET 376(9753):1643-1644 (2010)
  
• HPV vaccine suspension in India
  - LANCET 376(9753):1644-1645 (2010)
  
• Hepatosplenic schistosomiasis
  - LANCET 376(9753):1645 (2010)
  
• Another lesson unlearned: access to family planning in Niger
  - LANCET 376(9753):1645-1646 (2010)
  
• The influence of women in medicine
  - LANCET 376(9753):1646 (2010)
  
• Department of Error
  - LANCET 376(9753):1646 (2010)
  
• Department of Error
  - LANCET 376(9753):1646 (2010)
  
• Department of Error
  - LANCET 376(9753):1646 (2010)
  
• Artesunate versus quinine in the treatment of severe falciparum malaria in African children (AQUAMAT): an open-label, randomised trial
  - LANCET 376(9753):1647-1657 (2010)
  Background Severe malaria is a major cause of childhood death and often the main reason for paediatric hospital admission in sub-Saharan Africa. Quinine is still the established treatment of choice, although evidence from Asia suggests that artesunate is associated with a lower mortality. We compared parenteral treatment with either artesunate or quinine in African children with severe malaria. Methods This open-label, randomised trial was undertaken in 11 centres in nine African countries. Children (<15 years) with severe falciparum malaria were randomly assigned to parenteral artesunate or parenteral quinine. Randomisation was in blocks of 20, with study numbers corresponding to treatment allocations kept inside opaque sealed paper envelopes. The trial was open label at each site, and none of the investigators or trialists, apart from for the trial statistician, had access to the summaries of treatment allocations. The primary outcome measure was in-hospital mortality, analysed by intention to treat. This trial is registered, number ISRCTN50258054. Findings 5425 children were enrolled; 2712 were assigned to artesunate and 2713 to quinine. All patients were analysed for the primary outcome. 230 (8·5%) patients assigned to artesunate treatment died compared with 297 (10·9%) assigned to quinine treatment (odds ratio [OR] stratified for study site 0·75, 95% CI 0·63–0·90; relative reduction 22·5%, 95% CI 8·1–36·9; p=0·0022). Incidence of neurological sequelae did not differ significantly between groups, but the development of coma (65/1832 [3·5%] with artesunate vs 91/1768 [5·1%] with quinine; OR 0·69 95% CI 0·49–0·95; p=0·0231), convulsions (224/2712 [8·3%] vs 273/2713 [10·1%]; OR 0·80, 0·66–0·97; p=0·0199), and deterioration of the coma score (166/2712 [6·1%] vs 208/2713 [7·7%]; OR 0·78, 0·64–0·97; p=0·0245) were all significantly less frequent in artesunate recipients than in quinine recipients. Post-treatment hypoglycaemia was also less frequent in patients assigned to artesunate than in thos! e assigned to quinine (48/2712 [1·8%] vs 75/2713 [2·8%]; OR 0·63, 0·43–0·91; p=0·0134). Artesunate was well tolerated, with no serious drug-related adverse effects. Interpretation Artesunate substantially reduces mortality in African children with severe malaria. These data, together with a meta-analysis of all trials comparing artesunate and quinine, strongly suggest that parenteral artesunate should replace quinine as the treatment of choice for severe falciparum malaria worldwide. Funding The Wellcome Trust.
• Intensive lowering of LDL cholesterol with 80 mg versus 20 mg simvastatin daily in 12 064 survivors of myocardial infarction: a double-blind randomised trial
  - LANCET 376(9753):1658-1669 (2010)
  Background Lowering of LDL cholesterol reduces major vascular events, but whether more intensive therapy safely produces extra benefits is uncertain. We aimed to establish efficacy and safety of more intensive statin treatment in patients at high cardiovascular risk. Methods We undertook a double-blind randomised trial in 12 064 men and women aged 18–80 years with a history of myocardial infarction. Participants were either currently on or had clear indication for statin therapy, and had a total cholesterol concentration of at least 3·5 mmol/L if already on a statin or 4·5 mmol/L if not. Randomisation to either 80 mg or 20 mg simvastatin daily was done centrally using a minimisation algorithm. Participants were assessed at 2, 4, 8, and 12 months after randomisation and then every 6 months until final follow-up. The primary endpoint was major vascular events, defined as coronary death, myocardial infarction, stroke, or arterial revascularisation. Analysis was by intention to treat. This study is registered, number ISRCTN74348595. Findings 6031 participants were allocated 80 mg simvastatin daily, and 6033 allocated 20 mg simvastatin daily. During a mean follow-up of 6·7 (SD 1·5) years, allocation to 80 mg simvastatin produced an average 0·35 (SE 0·01) mmol/L greater reduction in LDL cholesterol compared with allocation to 20 mg. Major vascular events occurred in 1477 (24·5%) participants allocated 80 mg simvastatin versus 1553 (25·7%) of those allocated 20 mg, corresponding to a 6% proportional reduction (risk ratio 0·94, 95% CI 0·88–1·01; p=0·10). There were no apparent differences in numbers of haemorrhagic strokes (24 [0·4%] vs 25 [0·4%]) or deaths attributed to vascular (565 [9·4%] vs 572 [9·5%]) or non-vascular (399 [6·6%] vs 398 [6·6%]) causes. Compared with two (0·03%) cases of myopathy in patients taking 20 mg simvastatin daily, there were 53 (0·9%) cases in the 80 mg group. Interpretation The 6% (SE 3·5%) reduction in major vascular events with a further 0·35 mmol/L reduction in LDL cholesterol in our trial is consistent with previous trials. Myopathy was increased with 80 mg simvastatin daily, but intensive lowering of LDL cholesterol can be achieved safely with other regimens. Funding Merck; The Clinical Trial Service Unit also receives funding from the UK Medical Research Council and the British Heart Foundation.
• Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170 000 participants in 26 randomised trials
  - LANCET 376(9753):1670-1681 (2010)
  Background Lowering of LDL cholesterol with standard statin regimens reduces the risk of occlusive vascular events in a wide range of individuals. We aimed to assess the safety and efficacy of more intensive lowering of LDL cholesterol with statin therapy. Methods We undertook meta-analyses of individual participant data from randomised trials involving at least 1000 participants and at least 2 years' treatment duration of more versus less intensive statin regimens (five trials; 39 612 individuals; median follow-up 5·1 years) and of statin versus control (21 trials; 129 526 individuals; median follow-up 4·8 years). For each type of trial, we calculated not only the average risk reduction, but also the average risk reduction per 1·0 mmol/L LDL cholesterol reduction at 1 year after randomisation. Findings In the trials of more versus less intensive statin therapy, the weighted mean further reduction in LDL cholesterol at 1 year was 0·51 mmol/L. Compared with less intensive regimens, more intensive regimens produced a highly significant 15% (95% CI 11–18; p<0·0001) further reduction in major vascular events, consisting of separately significant reductions in coronary death or non-fatal myocardial infarction of 13% (95% CI 7–19; p<0·0001), in coronary revascularisation of 19% (95% CI 15–24; p<0·0001), and in ischaemic stroke of 16% (95% CI 5–26; p=0·005). Per 1·0 mmol/L reduction in LDL cholesterol, these further reductions in risk were similar to the proportional reductions in the trials of statin versus control. When both types of trial were combined, similar proportional reductions in major vascular events per 1·0 mmol/L LDL cholesterol reduction were found in all types of patient studied (rate ratio [RR] 0·78, 95% CI 0·76–0·80; p<0·0001), including thos! e with LDL cholesterol lower than 2 mmol/L on the less intensive or control regimen. Across all 26 trials, all-cause mortality was reduced by 10% per 1·0 mmol/L LDL reduction (RR 0·90, 95% CI 0·87–0·93; p<0·0001), largely reflecting significant reductions in deaths due to coronary heart disease (RR 0·80, 99% CI 0·74–0·87; p<0·0001) and other cardiac causes (RR 0·89, 99% CI 0·81–0·98; p=0·002), with no significant effect on deaths due to stroke (RR 0·96, 95% CI 0·84–1·09; p=0·5) or other vascular causes (RR 0·98, 99% CI 0·81–1·18; p=0·8). No significant effects were observed on deaths due to cancer or other non-vascular causes (RR 0·97, 95% CI 0·92–1·03; p=0·3) or on cancer incidence (RR 1·00, 95% CI 0·96–1·04; p=0·9), even at low LDL cholesterol concentrations. Interpretation Further reductions in LDL cholesterol safely produce definite further reductions in the incidence of heart attack, of revascularisation, and of ischaemic stroke, with each 1·0 mmol/L reduction reducing the annual rate of these major vascular events by just over a fifth. There was no evidence of any threshold within the cholesterol range studied, suggesting that reduction of LDL cholesterol by 2–3 mmol/L would reduce risk by about 40–50%. Funding UK Medical Research Council, British Heart Foundation, European Community Biomed Programme, Australian National Health and Medical Research Council, and National Heart Foundation.
• Immunogenicity of bivalent types 1 and 3 oral poliovirus vaccine: a randomised, double-blind, controlled trial
  - LANCET 376(9753):1682-1688 (2010)
  Background Poliovirus types 1 and 3 co-circulate in poliomyelitis-endemic countries. We aimed to assess the immunogenicity of a novel bivalent types 1 and 3 oral poliovirus vaccine (bOPV). Methods We did a randomised, double-blind, controlled trial to assess the superiority of monovalent type 2 OPV (mOPV2), mOPV3, or bOPV over trivalent OPV (tOPV), and the non-inferiority of bivalent vaccine compared with mOPV1 and mOPV3. The study was done at three centres in India between Aug 6, 2008, and Dec 26, 2008. Random allocation was done by permuted blocks of ten. The primary outcome was seroconversion after one monovalent or bivalent vaccine dose compared with a dose of trivalent vaccine at birth. The secondary endpoints were seroconversion after two vaccine doses compared with after two trivalent vaccine doses and cumulative two-dose seroconversion. Parents or guardians and study investigators were masked to treatment allocation. Because of multiple comparisons, we defined p≤0·01 as statistically significant. This trial is registered with Current Controlled Trials, ISRCTN 64725429. Results 900 newborn babies were randomly assigned to one of five vaccine groups (about 180 patients per group); of these 70 (8%) discontinued, leaving 830 (92%) for analysis. After the first dose, seroconversion to poliovirus type 1 was 20% for both mOPV1 (33 of 168) and bOPV (32 of 159) compared with 15% for tOPV (25 of 168; p>0·01), to poliovirus type 2 was 21% (35 of 170) for mOPV2 compared with 25% (42 of 168) for tOPV (p>0·01), and to poliovirus type 3 was 12% (20 of 165) for mOPV3 and 7% (11 of 159) for bOPV compared with 4% (7 of 168) for tOPV (mOPV3 vs tOPV p=0·01; bOPV vs tOPV; p>0·01). Cumulative two-dose seroconversion to poliovirus type 1 was 90% (151 of 168) for mOPV1 and 86% (136 of 159) for bOPV compared with 63% (106 of 168) for tOPV (p<0·0001), to poliovirus type 2 was 90% (153 of 170) for mOPV2 compared with 91% (153 of 168) for tOPV (p>0·01), and to poliovirus type 3 was 84% (138 of 165) for mOPV3 and 74% (117 of 159) for bOPV compared with 52% (87 of 168) f! or tOPV (p<0·0001). The vaccines were well tolerated. 19 serious adverse events occurred, including one death; however, these events were not attributed to the trial interventions. Interpretation The findings show the superiority of bOPV compared with tOPV, and the non-inferiority of bOPV compared with mOPV1 and mOPV3. Funding GAVI Alliance, World Health Organization, and Panacea Biotec.
• Raising the priority of preventing chronic diseases: a political process
  - LANCET 376(9753):1689-1698 (2010)
  Chronic diseases, especially cardiovascular diseases, diabetes, cancer, and chronic obstructive respiratory diseases, are neglected globally despite growing awareness of the serious burden that they cause. Global and national policies have failed to stop, and in many cases have contributed to, the chronic disease pandemic. Low-cost and highly effective solutions for the prevention of chronic diseases are readily available; the failure to respond is now a political, rather than a technical issue. We seek to understand this failure and to position chronic disease centrally on the global health and development agendas. To identify strategies for generation of increased political priority for chronic diseases and to further the involvement of development agencies, we use an adapted political process model. This model has previously been used to assess the success and failure of social movements. On the basis of this analysis, we recommend three strategies: reframe the deba! te to emphasise the societal determinants of disease and the inter-relation between chronic disease, poverty, and development; mobilise resources through a cooperative and inclusive approach to development and by equitably distributing resources on the basis of avoidable mortality; and build on emerging strategic and political opportunities, such as the World Health Assembly 2008–13 Action Plan and the high-level meeting of the UN General Assembly in 2011 on chronic disease. Until the full set of threats—which include chronic disease—that trap poor households in cycles of debt and illness are addressed, progress towards equitable human development will remain inadequate.
• Health, agricultural, and economic effects of adoption of healthy diet recommendations
  - LANCET 376(9753):1699-1709 (2010)
  Transition to diets that are high in saturated fat and sugar has caused a global public health concern, as the pattern of food consumption is a major modifiable risk factor for chronic non-communicable diseases. Although agri-food systems are intimately associated with this transition, agriculture and health sectors are largely disconnected in their priorities, policy, and analysis, with neither side considering the complex inter-relation between agri-trade, patterns of food consumption, health, and development. We show the importance of connection of these perspectives through estimation of the effect of adopting a healthy diet on population health, agricultural production, trade, the economy, and livelihoods, with a computable general equilibrium approach. On the basis of case-studies from the UK and Brazil, we suggest that benefits of a healthy diet policy will vary substantially between different populations, not only because of population dietary intake but also b! ecause of agricultural production, trade, and other economic factors.
• What have we here? A man or a fish?
  - LANCET 376(9753):1710 (2010)