Hot off the presses! Apr 01 LANCET

The Apr 01 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:

• Health care: an African solution
  - LANCET 377(9771):1047 (2011)
  
• Key indicators of health in the USA
  - LANCET 377(9771):1048 (2011)
  
• Managing acute upper gastrointestinal bleeding
  - LANCET 377(9771):1048 (2011)
  
• Acute MI: triple-markers resurrected or Bayesian dice?
  - LANCET 377(9771):1049-1050 (2011)
  
• Size still matters…but not in the way we once thought
  - LANCET 377(9771):1051-1052 (2011)
  
• Tranexamic acid for trauma
  - LANCET 377(9771):1052-1054 (2011)
  
• Disasters and a register for foreign medical teams
  - LANCET 377(9771):1054-1055 (2011)
  
• Research to achieve health care for all in India
  - LANCET 377(9771):1055-1057 (2011)
  
• The case for a global rare-diseases registry
  - LANCET 377(9771):1057-1059 (2011)
  
• Cardiology: a call for papers
  - LANCET 377(9771):1059 (2011)
  
• A thank you to all our peer reviewers in 2010
  - LANCET 377(9771):1059 (2011)
  
• Offline: Where was Europe?
  - LANCET 377(9771):1060 (2011)
  
• Japan: the aftermath
  - LANCET 377(9771):1061-1062 (2011)
  
• Gairdner Foundation names global health award winner
  - LANCET 377(9771):1063 (2011)
  
• And the 2011 Gairdner International Award winners are…
  - LANCET 377(9771):1064 (2011)
  
• A clone speaks from his soul
  - LANCET 377(9771):1065-1066 (2011)
  
• Lost childhoods
  - LANCET 377(9771):1066 (2011)
  
• Lucica Ditiu: putting people at the forefront of tuberculosis care
  - LANCET 377(9771):1067 (2011)
  
• Paying attention to the bipartite brain
  - LANCET 377(9771):1068-1069 (2011)
  
• John Raymond McClean
  - LANCET 377(9771):1070 (2011)
  
• Effect of consent rituals on mortality in emergency care research
  - LANCET 377(9771):1071-1072 (2011)
  
• Risk assessment for recurrent venous thrombosis
  - LANCET 377(9771):1072 (2011)
  
• Risk assessment for recurrent venous thrombosis
  - LANCET 377(9771):1072-1073 (2011)
  
• Risk assessment for recurrent venous thrombosis
  - LANCET 377(9771):1073 (2011)
  
• Risk assessment for recurrent venous thrombosis – Authors' reply
  - LANCET 377(9771):1073-1074 (2011)
  
• Renal sympathetic denervation for refractory hypertension
  - LANCET 377(9771):1074 (2011)
  
• Renal sympathetic denervation for refractory hypertension – Author's reply
  - LANCET 377(9771):1074-1075 (2011)
  
• Raised liver enzymes in patients taking statins
  - LANCET 377(9771):1075 (2011)
  
• Raised liver enzymes in patients taking statins – Authors' reply
  - LANCET 377(9771):1075-1076 (2011)
  
• Elder abuse in residential care
  - LANCET 377(9771):1076 (2011)
  
• Department of Error
  - LANCET 377(9771):1076 (2011)
  
• A 2-h diagnostic protocol to assess patients with chest pain symptoms in the Asia-Pacific region (ASPECT): a prospective observational validation study
  - LANCET 377(9771):1077-1084 (2011)
  Background Patients with chest pain contribute substantially to emergency department attendances, lengthy hospital stay, and inpatient admissions. A reliable, reproducible, and fast process to identify patients presenting with chest pain who have a low short-term risk of a major adverse cardiac event is needed to facilitate early discharge. We aimed to prospectively validate the safety of a predefined 2-h accelerated diagnostic protocol (ADP) to assess patients presenting to the emergency department with chest pain symptoms suggestive of acute coronary syndrome. Methods This observational study was undertaken in 14 emergency departments in nine countries in the Asia-Pacific region, in patients aged 18 years and older with at least 5 min of chest pain. The ADP included use of a structured pre-test probability scoring method (Thrombolysis in Myocardial Infarction [TIMI] score), electrocardiograph, and point-of-care biomarker panel of troponin, creatine kinase MB, and myoglobin. The primary endpoint was major adverse cardiac events within 30 days after initial presentation (including initial hospital attendance). This trial is registered with the Australia-New Zealand Clinical Trials Registry, number ACTRN12609000283279. Findings 3582 consecutive patients were recruited and completed 30-day follow-up. 421 (11·8%) patients had a major adverse cardiac event. The ADP classified 352 (9·8%) patients as low risk and potentially suitable for early discharge. A major adverse cardiac event occurred in three (0·9%) of these patients, giving the ADP a sensitivity of 99·3% (95% CI 97·9–99·8), a negative predictive value of 99·1% (97·3–99·8), and a specificity of 11·0% (10·0–12·2). Interpretation This novel ADP identifies patients at very low risk of a short-term major adverse cardiac event who might be suitable for early discharge. Such an approach could be used to decrease the overall observation periods and admissions for chest pain. The components needed for the implementation of this strategy are widely available. The ADP has the potential to affect health-service delivery worldwide. Funding Alere Medical (all countries), Queensland Emergency Medicine Research Foundation and National Health and Medical Research Council (Australia), Christchurch Cardio-Endocrine Research Group (New Zealand), Medquest Jaya Global (Indonesia), Science International (Hong Kong), Bio Laboratories Pte (Singapore), National Heart Foundation of New Zealand, and Progressive Group (Taiwan).
• Separate and combined associations of body-mass index and abdominal adiposity with cardiovascular disease: collaborative analysis of 58 prospective studies
  - LANCET 377(9771):1085-1095 (2011)
  Background Guidelines differ about the value of assessment of adiposity measures for cardiovascular disease risk prediction when information is available for other risk factors. We studied the separate and combined associations of body-mass index (BMI), waist circumference, and waist-to-hip ratio with risk of first-onset cardiovascular disease. Methods We used individual records from 58 cohorts to calculate hazard ratios (HRs) per 1 SD higher baseline values (4·56 kg/m2 higher BMI, 12·6 cm higher waist circumference, and 0·083 higher waist-to-hip ratio) and measures of risk discrimination and reclassification. Serial adiposity assessments were used to calculate regression dilution ratios. Results Individual records were available for 221 934 people in 17 countries (14 297 incident cardiovascular disease outcomes; 1·87 million person-years at risk). Serial adiposity assessments were made in up to 63 821 people (mean interval 5·7 years [SD 3·9]). In people with BMI of 20 kg/m2 or higher, HRs for cardiovascular disease were 1·23 (95% CI 1·17–1·29) with BMI, 1·27 (1·20–1·33) with waist circumference, and 1·25 (1·19–1·31) with waist-to-hip ratio, after adjustment for age, sex, and smoking status. After further adjustment for baseline systolic blood pressure, history of diabetes, and total and HDL cholesterol, corresponding HRs were 1·07 (1·03–1·11) with BMI, 1·10 (1·05–1·14) with waist circumference, and 1·12 (1·08–1·15) with waist-to-hip ratio. Addition of information on BMI, waist circumference, or waist-to-hip ratio to a cardiovascular disease risk prediction model containing conventional risk factors did not importantly improve risk di! scrimination (C-index changes of −0·0001, −0·0001, and 0·0008, respectively), nor classification of participants to categories of predicted 10-year risk (net reclassification improvement −0·19%, −0·05%, and −0·05%, respectively). Findings were similar when adiposity measures were considered in combination. Reproducibility was greater for BMI (regression dilution ratio 0·95, 95% CI 0·93–0·97) than for waist circumference (0·86, 0·83–0·89) or waist-to-hip ratio (0·63, 0·57–0·70). Interpretation BMI, waist circumference, and waist-to-hip ratio, whether assessed singly or in combination, do not importantly improve cardiovascular disease risk prediction in people in developed countries when additional information is available for systolic blood pressure, history of diabetes, and lipids. Funding British Heart Foundation and UK Medical Research Council.
• The importance of early treatment with tranexamic acid in bleeding trauma patients: an exploratory analysis of the CRASH-2 randomised controlled trial
  - LANCET 377(9771):1096-1101, 1101.e1-1101.e2 (2011)
  Background The aim of the CRASH-2 trial was to assess the effects of early administration of tranexamic acid on death, vascular occlusive events, and blood transfusion in trauma patients with significant haemorrhage. Tranexamic acid significantly reduced all-cause mortality. Because tranexamic acid is thought to exert its effect through inhibition of fibrinolysis, we undertook exploratory analyses of its effect on death due to bleeding. Methods The CRASH-2 trial was undertaken in 274 hospitals in 40 countries. 20 211 adult trauma patients with, or at risk of, significant bleeding were randomly assigned within 8 h of injury to either tranexamic acid (loading dose 1 g over 10 min followed by infusion of 1 g over 8 h) or placebo. Patients were randomly assigned by selection of the lowest numbered treatment pack from a box containing eight numbered packs that were identical apart from the pack number. Both participants and study staff (site investigators and trial coordinating centre staff) were masked to treatment allocation. We examined the effect of tranexamic acid on death due to bleeding according to time to treatment, severity of haemorrhage as assessed by systolic blood pressure, Glasgow coma score (GCS), and type of injury. All analyses were by intention to treat. The trial is registered as ISRCTN86750102, ClinicalTrials.gov NCT00375258, and South African Clinical Trial Register/Department of Health DOH-27-0607! -1919. Findings 10 096 patients were allocated to tranexamic acid and 10 115 to placebo, of whom 10 060 and 10 067, respectively, were analysed. 1063 deaths (35%) were due to bleeding. We recorded strong evidence that the effect of tranexamic acid on death due to bleeding varied according to the time from injury to treatment (test for interaction p<0·0001). Early treatment (≤1 h from injury) significantly reduced the risk of death due to bleeding (198/3747 [5·3%] events in tranexamic acid group vs 286/3704 [7·7%] in placebo group; relative risk [RR] 0·68, 95% CI 0·57–0·82; p<0·0001). Treatment given between 1 and 3 h also reduced the risk of death due to bleeding (147/3037 [4·8%] vs 184/2996 [6·1%]; RR 0·79, 0·64–0·97; p=0·03). Treatment given after 3 h seemed to increase the risk of death due to bleeding (144/3272 [4·4%] vs 103/3362 [3·1%]; RR 1·44, 1·12–1·84; p=0·004). We recorded no evidence that the effect of tranexamic acid on death due to bleeding varied by ! systolic blood pressure, Glasgow coma score, or type of injury. Interpretation Tranexamic acid should be given as early as possible to bleeding trauma patients. For trauma patients admitted late after injury, tranexamic acid is less effective and could be harmful. Funding UK NIHR Health Technology Assessment programme, Pfizer, BUPA Foundation, and J P Moulton Charitable Foundation.
• Placental vasa previa
  - LANCET 377(9771):1102 (2011)
  
• Ventricular septal defect
  - LANCET 377(9771):1103-1112 (2011)
  Ventricular septal defects account for up to 40% of all congenital cardiac malformations. The diagnosis encompasses a broad range of anomalies, including isolated defects and those associated with other congenital cardiac malformations. Presentation, symptoms, natural history, and management of ventricular septal defects depend on size and anatomical associations of the anomaly, patient's age, and local diagnostic and interventional expertise. In this Seminar, we describe the anatomical range of ventricular septal defects and discuss present management of these malformations. Genetic determinants, diagnostic techniques, physiological considerations, and management challenges are examined in detail. Unfortunately, in many circumstances, evidence on which to guide optimum management is scarce. We present some longer term considerations of ventricular septal defects in adolescents and adults, with particular emphasis on patients with raised pulmonary vascular resistance a! nd Eisenmenger's syndrome.
• Medical schools in sub-Saharan Africa
  - LANCET 377(9771):1113-1121 (2011)
  Small numbers of graduates from few medical schools, and emigration of graduates to other countries, contribute to low physician presence in sub-Saharan Africa. The Sub-Saharan African Medical School Study examined the challenges, innovations, and emerging trends in medical education in the region. We identified 168 medical schools; of the 146 surveyed, 105 (72%) responded. Findings from the study showed that countries are prioritising medical education scale-up as part of health-system strengthening, and we identified many innovations in premedical preparation, team-based education, and creative use of scarce research support. The study also drew attention to ubiquitous faculty shortages in basic and clinical sciences, weak physical infrastructure, and little use of external accreditation. Patterns recorded include the growth of private medical schools, community-based education, and international partnerships, and the benefit of research for faculty development. Ten ! recommendations provide guidance for efforts to strengthen medical education in sub-Saharan Africa.
• Health district development and the need to dig deeper
  - LANCET 377(9771):1122-1123 (2011)
  
• Donor-derived adult T-cell leukaemia
  - LANCET 377(9771):1124 (2011)