Hot off the presses! Sep 05 Lancet

The Sep 05 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:

• South Africa steps up
  - Lancet 374(9692):757 (2009)
  
• Organ donation in China
  - Lancet 374(9692):758 (2009)
  
• Dispelling myths about drug research
  - Lancet 374(9692):758 (2009)
  
• South Africa's health: departing for a better future?
  - Lancet 374(9692):759-760 (2009)
  
• Clinical research in South Africa: a core asset under pressure
  - Lancet 374(9692):760-762 (2009)
  
• Otamixaban in acute coronary syndromes
  - Lancet 374(9692):762-764 (2009)
  
• Raltegravir: a new choice in HIV and new chances for research
  - Lancet 374(9692):764-766 (2009)
  
• Children's mental health in Afghanistan
  - Lancet 374(9692):766-767 (2009)
  
• Fad diets in Sweden, of all places
  - Lancet 374(9692):767-769 (2009)
  
• Crohn's disease as an immune deficiency?
  - Lancet 374(9692):769-770 (2009)
  
• Rural hospital beats the odds in South Africa
  - Lancet 374(9692):771-772 (2009)
  
• Poultry, politics, and antibiotic resistance
  - Lancet 374(9692):773-774 (2009)
  
• The story of Hamilton Naki and Christiaan Barnard
  - Lancet 374(9692):775 (2009)
  
• Aaron Motsoaledi: South African Minister of Health
  - Lancet 374(9692):776 (2009)
  
• Hoosen Coovadia: an icon of South African health
  - Lancet 374(9692):777 (2009)
  
• The global and the local: changes at Groote Schuur Hospital
  - Lancet 374(9692):778-779 (2009)
  
• Steve Andrews
  - Lancet 374(9692):780 (2009)
  
• The Indian Polycap Study (TIPS)
  - Lancet 374(9692):781 (2009)
  
• The Indian Polycap Study (TIPS)
  - Lancet 374(9692):781 (2009)
  
• The Indian Polycap Study (TIPS)
  - Lancet 374(9692):781-782 (2009)
  
• The Indian Polycap Study (TIPS) – Authors' reply
  - Lancet 374(9692):782 (2009)
  
• WHO position statement on IMCI
  - Lancet 374(9692):782-783 (2009)
  
• Venice Statement on global health initiatives and health systems
  - Lancet 374(9692):783-784 (2009)
  
• Non-communicable diseases and the Paris Declaration
  - Lancet 374(9692):784-785 (2009)
  
• Sustainability of ivermectin distribution programmes
  - Lancet 374(9692):785-786 (2009)
  
• Avoidable waste in the production and reporting of evidence
  - Lancet 374(9692):786 (2009)
  
• Department of Error
  - Lancet 374(9692):786 (2009)
  
• Otamixaban for the treatment of patients with non-ST-elevation acute coronary syndromes (SEPIA-ACS1 TIMI 42): a randomised, double-blind, active-controlled, phase 2 trial
  - Lancet 374(9692):787-795 (2009)
  Background Otamixaban is an intravenous direct factor Xa inhibitor. We aimed to assess its efficacy and safety in non-ST-elevation acute coronary syndromes and to identify the optimum dose range for further assessment in a phase 3 study. Methods In this double-blind, phase 2 trial undertaken in 196 sites in 36 countries, 3241 patients with non-ST-elevation acute coronary syndromes were randomly assigned via a central, telephone-based interactive voice response system to one of five doses of otamixaban (0·08 mg/kg bolus followed by infusions of 0·035 [n=125], 0·070 [676], 0·105 [662], 0·140 [658], or 0·175 [671] mg/kg/h) or to a control of unfractionated heparin (60 IU/kg intravenous bolus followed by an infusion of 12 IU/kg/h) plus eptifibatide (180 μg/kg intravenous bolus followed by an infusion of 1·0–2·0 μg/kg/min [n=449]). Both investigators and patients were unaware of treatment allocation. Enrolment into the lowest dose group was stopped early at the recommendation of the Data Monitoring Committee. The primary efficacy endpoint was a composite of death, myocardial infarction, urgent revascularisation, or bailout glycoprotein IIb/IIIa inhibitor use up to 7 days. The primary safety endpoint was TIMI ! major or minor bleeding not related to coronary-artery bypass grafting. Efficacy analyses were by intention to treat; safety analyses were in treated patients. This study is registered with ClinicalTrials.gov, number NCT00317395. Findings Rates of the primary efficacy endpoint in the five otamixaban doses were 7·2% (nine of 125) with 0·035 mg/kg/h, 4·6% (31/676) with 0·070 mg/kg/h, 3·8% (25/662) with 0·105 mg/kg/h, 3·6% (24/658) with 0·140 mg/kg/h, and 4·3% (29/671) with 0·175 mg/kg/h (p=0·34 for trend). In the control group, the rate was 6·2% (28/449), yielding relative risks for the five otamixaban doses of 1·16 (95% CI 0·56–2·38), 0·74 (0·45–1·21), 0·61 (0·36–1·02), 0·58 (0·34–1·00), and 0·69 (0·42–1·15), respectively. Rates of the primary safety endpoint in the five otamixaban doses were 1·6% (two of 122), 1·6% (11/669), 3·1% (20/651), 3·4% (22/651), and 5·4% (36/664), respectively (p=0·0001 for trend); the rate in the control group was 2·7% (12/448). Interpretation In patients with non-ST-elevation acute coronary syndromes, otamixaban infusions of 0·100–0·140 mg/kg/h might reduce ischaemic events and have a safety profile similar to unfractionated heparin plus eptifibatide. Further testing in a phase 3 trial is warranted. Funding Sanofi-Aventis.
• Safety and efficacy of raltegravir-based versus efavirenz-based combination therapy in treatment-naive patients with HIV-1 infection: a multicentre, double-blind randomised controlled trial
  - Lancet 374(9692):796-806 (2009)
  Background Use of raltegravir with optimum background therapy is effective and well tolerated in treatment-experienced patients with multidrug-resistant HIV-1 infection. We compared the safety and efficacy of raltegravir with efavirenz as part of combination antiretroviral therapy for treatment-naive patients. Methods Patients from 67 study centres on five continents were enrolled between Sept 14, 2006, and June 5, 2008. Eligible patients were infected with HIV-1, had viral RNA (vRNA) concentration of more than 5000 copies per mL, and no baseline resistance to efavirenz, tenofovir, or emtricitabine. Patients were randomly allocated by interactive voice response system in a 1:1 ratio (double-blind) to receive 400 mg oral raltegravir twice daily or 600 mg oral efavirenz once daily, in combination with tenofovir and emtricitabine. The primary efficacy endpoint was achievement of a vRNA concentration of less than 50 copies per mL at week 48. The primary analysis was per protocol. The margin of non-inferiority was 12%. This study is registered with ClinicalTrials.gov, number NCT00369941. Findings 566 patients were enrolled and randomly allocated to treatment, of whom 281 received raltegravir, 282 received efavirenz, and three were never treated. At baseline, 297 (53%) patients had more than 100 000 vRNA copies per mL and 267 (47%) had CD4 counts of 200 cells per μL or less. The main analysis (with non-completion counted as failure) showed that 86·1% (n=241 patients) of the raltegravir group and 81·9% (n=230) of the efavirenz group achieved the primary endpoint (difference 4·2%, 95% CI −1·9 to 10·3). The time to achieve such viral suppression was shorter for patients on raltegravir than on efavirenz (log-rank test p<0·0001). Significantly fewer drug-related clinical adverse events occurred in patients on raltegravir (n=124 [44·1%]) than those on efavirenz (n=217 [77·0%]; difference −32·8%, 95% CI −40·2 to −25·0, p<0·0001). Serious drug-related clinical adverse events occurred in less than 2% of patients in each drug group. Interpretation Raltegravir-based combination treatment had rapid and potent antiretroviral activity, which was non-inferior to that of efavirenz at week 48. Raltegravir is a well tolerated alternative to efavirenz as part of a combination regimen against HIV-1 in treatment-naive patients. Funding Merck.
• Violence, suffering, and mental health in Afghanistan: a school-based survey
  - Lancet 374(9692):807-816 (2009)
  Background Studies in Afghanistan have shown substantial mental health problems in adults. We did a survey of young people (11–16 years old) in the country to assess mental health, traumatic experiences, and social functioning. Methods In 2006, we interviewed 1011 children, 1011 caregivers, and 358 teachers, who were randomly sampled in 25 government-operated schools within three purposively chosen areas (Kabul, Bamyan, and Mazar-e-Sharif municipalities). We assessed probable psychiatric disorder and social functioning in students with the Strength and Difficulties Questionnaire multi-informant (child, parent, teacher) ratings. We also used the Depression Self-Rating Scale and an Impact of Events Scale. We assessed caregiver mental health with both international and culturally-specific screening instruments (Self-Reported Questionnaire and Afghan Symptom Checklist). We implemented a checklist of traumatic events to examine the exposure to, and nature of, traumatic experiences. We analysed risk factors for mental health and reports of traumatic experiences. Findings Trauma exposure and caregiver mental health were predictive across all child outcomes. Probable psychiatric ratings were associated with female gender (odds ratio [OR] 2·47, 95% CI 1·65–3·68), five or more traumatic events (2·58, 1·36–4·90), caregiver mental health (1·11, 1·08–1·14), and residence areas (0·29, 0·17–0·51 for Bamyan and 0·37, 0·23–0·57 for Mazar-e-Sharif vs Kabul). The same variables predicted symptoms of depression. Two thirds of children reported traumatic experiences. Symptoms of post-traumatic stress were associated with five or more traumatic events (3·07, 1·78–5·30), caregiver mental health (1·06, 1·02–1·09), and child age (1·19, 1·04–1·36). Children's most distressing traumatic experiences included accidents, medical treatment, domestic and community violence, and war-related events. Interpretation Young Afghans experience violence that is persistent and not confined to acts of war. Our study emphasises the value of school-based initiatives to address child mental health, and the importance of understanding trauma in the context of everyday forms of suffering, violence, and adversity. Funding Wellcome Trust.
• The health and health system of South Africa: historical roots of current public health challenges
  - Lancet 374(9692):817-834 (2009)
  The roots of a dysfunctional health system and the collision of the epidemics of communicable and non-communicable diseases in South Africa can be found in policies from periods of the country's history, from colonial subjugation, apartheid dispossession, to the post-apartheid period. Racial and gender discrimination, the migrant labour system, the destruction of family life, vast income inequalities, and extreme violence have all formed part of South Africa's troubled past, and all have inexorably affected health and health services. In 1994, when apartheid ended, the health system faced massive challenges, many of which still persist. Macroeconomic policies, fostering growth rather than redistribution, contributed to the persistence of economic disparities between races despite a large expansion in social grants. The public health system has been transformed into an integrated, comprehensive national service, but failures in leadership and stewardship and weak manage! ment have led to inadequate implementation of what are often good policies. Pivotal facets of primary health care are not in place and there is a substantial human resources crisis facing the health sector. The HIV epidemic has contributed to and accelerated these challenges. All of these factors need to be addressed by the new government if health is to be improved and the Millennium Development Goals achieved in South Africa.
• Saving the lives of South Africa's mothers, babies, and children: can the health system deliver?
  - Lancet 374(9692):835-846 (2009)
  South Africa is one of only 12 countries in which mortality rates for children have increased since the baseline for the Millennium Development Goals (MDGs) in 1990. Continuing poverty and the HIV/AIDS epidemic are important factors. Additionally, suboptimum implementation of high-impact interventions limits programme effectiveness; between a quarter and half of maternal, neonatal, and child deaths in national audits have an avoidable health-system factor contributing to the death. Using the LiST model, we estimate that 11 500 infants' lives could be saved by effective implementation of basic neonatal care at 95% coverage. Similar coverage of dual-therapy prevention of mother-to-child transmission with appropriate feeding choices could save 37 200 children's lives in South Africa per year in 2015 compared with 2008. These interventions would also avert many maternal deaths and stillbirths. The total cost of such a target package is US$1·5 billion per year, 24% of the ! public-sector health expenditure; the incremental cost is $220 million per year. Such progress would put South Africa squarely on track to meet MDG 4 and probably also MDG 5. The costs are affordable and the key gap is leadership and effective implementation at every level of the health system, including national and local accountability for service provision.
• Rethinking the responsiveness requirement for international research
  - Lancet 374(9692):847-849 (2009)
  
• Searching for the needle in the Haystacks
  - Lancet 374(9692):850 (2009)