Hot off the presses! Oct 03 Lancet

The Oct 03 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:

• A (prime) boost for HIV vaccine research?
  - Lancet 374(9696):1119 (2009)
  
• The World Health Summit: intentions and expectations
  - Lancet 374(9696):1120 (2009)
  
• Dealing with the ethical dimension of dementia care
  - Lancet 374(9696):1120 (2009)
  
• Realising the human right to health
  - Lancet 374(9696):1121-1122 (2009)
  
• Health is global
  - Lancet 374(9696):1122-1123 (2009)
  
• Nutrition in early life: a global priority
  - Lancet 374(9696):1123-1125 (2009)
  
• The changing horizon of acute coronary syndrome
  - Lancet 374(9696):1125-1127 (2009)
  
• Clinically important head injuries after head trauma in children
  - Lancet 374(9696):1127-1129 (2009)
  
• UPLIFTing care for chronic obstructive pulmonary disease
  - Lancet 374(9696):1129-1130 (2009)
  
• The poisoning of Victor Yushchenko
  McKee M - Lancet 374(9696):1131-1132 (2009)
  
• Germany to host World Health Summit
  - Lancet 374(9696):1133-1136 (2009)
  
• An attack on the autonomy of patients
  - Lancet 374(9696):1137-1138 (2009)
  
• Mafioso medic
  - Lancet 374(9696):1138 (2009)
  
• James Vaupel: an innovator in the demography of ageing
  - Lancet 374(9696):1139 (2009)
  
• Diabetes and the public's health
  - Lancet 374(9696):1140-1141 (2009)
  
• Alan Berkman
  - Lancet 374(9696):1142 (2009)
  
• CLOTS: an opportunity missed
  - Lancet 374(9696):1143 (2009)
  
• CLOTS: an opportunity missed – Author's reply
  - Lancet 374(9696):1143-1144 (2009)
  
• Disease eradication is possible and ethical
  - Lancet 374(9696):1144 (2009)
  
• Disease eradication is possible and ethical – Author's reply
  - Lancet 374(9696):1144 (2009)
  
• Adverse events in diabetes drug trial
  - Lancet 374(9696):1144 (2009)
  
• Adverse events in diabetes drug trial – Authors' reply
  - Lancet 374(9696):1144-1145 (2009)
  
• Underestimation of the effect of bleeding in clinical trials
  - Lancet 374(9696):1145 (2009)
  
• Underestimation of the effect of bleeding in clinical trials – Authors' reply
  - Lancet 374(9696):1145-1146 (2009)
  
• Towards a global fund for the health MDGs?
  - Lancet 374(9696):1146 (2009)
  
• Monitoring and evaluation of PEPFAR treatment programmes
  - Lancet 374(9696):1146-1147 (2009)
  
• The feminisation of general practice—crisis or business as usual?
  - Lancet 374(9696):1147 (2009)
  
• Violation of human rights by doctors today
  - Lancet 374(9696):1147-1148 (2009)
  
• They think they are playing chess but really they are playing poker
  - Lancet 374(9696):1148 (2009)
  
• Department of Error
  - Lancet 374(9696):1148 (2009)
  
• Department of Error
  - Lancet 374(9696):1148 (2009)
  
• Department of Error
  - Lancet 374(9696):1148 (2009)
  
• Bivalirudin in patients undergoing primary angioplasty for acute myocardial infarction (HORIZONS-AMI): 1-year results of a randomised controlled trial
  - Lancet 374(9696):1149-1159 (2009)
  Background In the HORIZONS-AMI trial, patients with acute ST-segment elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI) who were treated with the thrombin inhibitor bivalirudin had substantially lower 30-day rates of major haemorrhagic complications and net adverse clinical events than did patients assigned to heparin plus a glycoprotein IIb/IIIa inhibitor (GPI). Here, we assess whether these initial benefits were maintained at 1 year of follow-up. Methods Patients aged 18 years or older were eligible for enrolment in this multicentre, open-label, randomised controlled trial if they had STEMI, presented within 12 h after the onset of symptoms, and were undergoing primary PCI. 3602 eligible patients were randomly assigned by interactive voice response system in a 1:1 ratio to receive bivalirudin (0·75 mg/kg intravenous bolus followed by 1·75 mg/kg per h infusion; n=1800) or heparin plus a GPI (control; 60 IU/kg intravenous bolus followed by boluses with target activated clotting time 200–250 s; n=1802). The two primary trial endpoints were major bleeding and net adverse clinical events (NACE; consisting of major bleeding or composite major adverse cardiovascular events [MACE; death, reinfarction, target vessel revascularisation for ischaemia, or stroke]). This prespecified analysis reports data for the 1-year follow-up. Analysis was by intention to treat. Patients with missing data were censored at the time of withdrawal fr! om the study or at last follow-up. This trial is registered with ClinicalTrials.gov, number NCT00433966. Findings 1-year data were available for 1696 patients in the bivalirudin group and 1702 patients in the control group. Reasons for participant dropout were loss to follow-up and withdrawal of consent. The rate of NACE was lower in the bivalirudin group than in the control group (15·6% vs 18·3%, hazard ratio [HR] 0·83, 95% CI 0·71–0·97, p=0·022), as a result of a lower rate of major bleeding in the bivalirudin group (5·8% vs 9·2%, HR 0·61, 0·48–0·78, p<0·0001). The rate of MACE was similar between groups (11·9% vs 11·9%, HR 1·00, 0·82–1·21, p=0·98). The 1-year rates of cardiac mortality (2·1% vs 3·8%, HR 0·57, 0·38–0·84, p=0·005) and all-cause mortality (3·5% vs 4·8%, HR 0·71, 0·51–0·98, p=0·037) were lower in the bivalirudin group than in the control group. Interpretation In patients with STEMI undergoing primary PCI, anticoagulation with bivalirudin reduced the rates of net adverse clinical events and major bleeding at 1 year compared with treatment with heparin plus a GPI. This finding has important clinical implications for the selection of optimum treatment strategies for patients with STEMI. Funding Cardiovascular Research Foundation, with unrestricted grant support from Boston Scientific Corporation and The Medicines Company.
• Identification of children at very low risk of clinically-important brain injuries after head trauma: a prospective cohort study
  - Lancet 374(9696):1160-1170 (2009)
  Background CT imaging of head-injured children has risks of radiation-induced malignancy. Our aim was to identify children at very low risk of clinically-important traumatic brain injuries (ciTBI) for whom CT might be unnecessary. Methods We enrolled patients younger than 18 years presenting within 24 h of head trauma with Glasgow Coma Scale scores of 14–15 in 25 North American emergency departments. We derived and validated age-specific prediction rules for ciTBI (death from traumatic brain injury, neurosurgery, intubation >24 h, or hospital admission ≥2 nights). Findings We enrolled and analysed 42 412 children (derivation and validation populations: 8502 and 2216 younger than 2 years, and 25 283 and 6411 aged 2 years and older). We obtained CT scans on 14 969 (35·3%); ciTBIs occurred in 376 (0·9%), and 60 (0·1%) underwent neurosurgery. In the validation population, the prediction rule for children younger than 2 years (normal mental status, no scalp haematoma except frontal, no loss of consciousness or loss of consciousness for less than 5 s, non-severe injury mechanism, no palpable skull fracture, and acting normally according to the parents) had a negative predictive value for ciTBI of 1176/1176 (100·0%, 95% CI 99·7–100 0) and sensitivity of 25/25 (100%, 86·3–100·0). 167 (24·1%) of 694 CT-imaged patients younger than 2 years were in this low-risk group. The prediction rule for children aged 2 years and older (normal mental status, no loss of consciousness, no vomiting, non-severe injury mechanism, no signs of basilar skull fra! cture, and no severe headache) had a negative predictive value of 3798/3800 (99·95%, 99·81–99·99) and sensitivity of 61/63 (96·8%, 89·0–99·6). 446 (20.1%) of 2223 CT-imaged patients aged 2 years and older were in this low-risk group. Neither rule missed neurosurgery in validation populations. Interpretation These validated prediction rules identified children at very low risk of ciTBIs for whom CT can routinely be obviated. Funding The Emergency Medical Services for Children Programme of the Maternal and Child Health Bureau, and the Maternal and Child Health Bureau Research Programme, Health Resources and Services Administration, US Department of Health and Human Services.
• Effect of tiotropium on outcomes in patients with moderate chronic obstructive pulmonary disease (UPLIFT): a prespecified subgroup analysis of a randomised controlled trial
  - Lancet 374(9696):1171-1178 (2009)
  Background The beneficial effects of pharmacotherapy for chronic obstructive pulmonary disease (COPD) are well established. However, there are few data for treatment in the early stages of the disease. We examined the effect of tiotropium on outcomes in a large subgroup of patients with moderate COPD. Methods The Understanding Potential Long-Term Impacts on Function with Tiotropium (UPLIFT) study was a randomised, double-blind, placebo-controlled trial undertaken in 487 centres in 37 countries. 5993 patients aged 40 years or more with COPD were randomly assigned to receive 4 years of treatment with either once daily tiotropium (18 μg; n=2987) or matching placebo (n=3006), delivered by an inhalation device. Randomisation was by computer-generated blocks of four, with stratification according to study site. In a prespecified subgroup analysis, we investigated the effects of tiotropium in patients with Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage II disease. Primary endpoints were the yearly rates of decline in prebronchodilator forced expiratory volume in 1 s (FEV1) and in postbronchodilator FEV1, beginning on day 30 until completion of double-blind treatment. The analysis included all patients who had at least three measurements of pulmonary function. This ! study is registered with ClinicalTrials.gov, number NCT00144339. Findings 2739 participants (mean age 64 years [SD 9]) had GOLD stage II disease at randomisation (tiotropium, n=1384; control, n=1355), with a mean postbronchodilator FEV1 of 1·63 L (SD 0·37; 59% of predicted value). 1218 patients in the tiotropium group and 1157 in the control group had three or more measurements of postbronchodilator pulmonary function after day 30 and were included in the analysis. The rate of decline of mean postbronchodilator FEV1 was lower in the tiotropium group than in the control group (43 mL per year [SE 2] vs 49 mL per year [SE 2], p=0·024). For prebronchodilator pulmonary function, 1221 patients in the tiotropium group and 1158 in the control group had three or more measurements and were included in the analysis. The rate of decline of mean prebronchodilator FEV1 did not differ between groups (35 mL per year [SE 2] vs 37 mL per year [SE 2]; p=0·38). Health status, measured with the St George's Respiratory Questionnaire, was better at all timepoints in! the tiotropium group than in the control group (p≤0·006 for all timepoints). Time to first exacerbation and time to exacerbation resulting in hospital admission were also longer in the tiotropium group than in the control group (hazard ratio 0·82, 95% CI 0·75–0·90, and 0·74, 0·62–0·88, respectively). Interpretation Tiotropium seemed to reduce the rate of decline of postbronchodilator FEV1 in patients with GOLD stage II COPD. This finding and the other improvements in outcomes suggest that treatment of COPD should begin at an early stage of the disease. Funding Boehringer Ingelheim and Pfizer Pharmaceuticals.
• 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) poisoning in Victor Yushchenko: identification and measurement of TCDD metabolites
  Sorg O Zennegg M Schmid P Fedosyuk R Valikhnovskyi R Gaide O Kniazevych V Saurat JH - Lancet 374(9696):1179-1185 (2009)
  Background 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) has a long half-life of 5–10 years in human beings as a result of its high lipophilicity, and little or no metabolism. We monitored TCDD, its form, distribution, and elimination in Victor Yushchenko after he presented with severe poisoning. Methods In late December, 2004, a patient presented with TCDD poisoning; the levels in his blood serum (108000 pg/g lipid weight) were more than 50 000-fold greater than those in the general population. We identified TCDD and its metabolites, and monitored their levels for 3 years using gas chromatography and high-resolution mass spectrometry in samples of blood serum, adipose tissue, faeces, skin, urine, and sweat, after they were extracted and cleaned with different organic solvents. Findings The amount of unmodified TCDD in the samples that were analysed accounted for about 60% of TCDD eliminated from the body during the same period. Two TCDD metabolites—2,3,7-trichloro-8-hydroxydibenzo-p-dioxin and 1,3,7,8-tetrachloro-2-hydroxydibenzo-p-dioxin—were identified in the faeces, blood serum, and urine. The faeces contained the highest concentration of TCDD metabolites, and were the main route of elimination. Altogether, the different routes of elimination of TCDD and its metabolites accounted for 98% of the loss of the toxin from the body. The half-life of TCDD in our patient was 15·4 months. Interpretation This case of poisoning with TCDD suggests that the design of methods for routine assessment of TCDD metabolites in human beings should be a main aim of TCDD research in the metabolomic era. Funding University of Geneva Dermatology Fund, and Swiss Centre for Applied Human Toxicology.
• Health reform in central and eastern Europe and the former Soviet Union
  - Lancet 374(9696):1186-1195 (2009)
  In the two decades since the fall of the Berlin Wall, former communist countries in Europe have pursued wide-ranging changes to their health systems. We describe three key aspects of these changes—an almost universal switch to health insurance systems, a growing reliance on out-of-pocket payments (both formal and informal), and efforts to strengthen primary health care, often with a model of family medicine delivered by general practitioners. Many decisions about health policy, such as the introduction of health insurance systems or general practice, took into account political issues more than they did evidence. Evidence for whether health reforms have achieved their intended results is sparse. Of crucial importance is that lessons are learnt from experiences of countries to enable development of health systems that meet present and future health needs of populations.
• Ageing populations: the challenges ahead
  - Lancet 374(9696):1196-1208 (2009)
  If the pace of increase in life expectancy in developed countries over the past two centuries continues through the 21st century, most babies born since 2000 in France, Germany, Italy, the UK, the USA, Canada, Japan, and other countries with long life expectancies will celebrate their 100th birthdays. Although trends differ between countries, populations of nearly all such countries are ageing as a result of low fertility, low immigration, and long lives. A key question is: are increases in life expectancy accompanied by a concurrent postponement of functional limitations and disability? The answer is still open, but research suggests that ageing processes are modifiable and that people are living longer without severe disability. This finding, together with technological and medical development and redistribution of work, will be important for our chances to meet the challenges of ageing populations.
• How to maintain surveillance for novel influenza A H1N1 when there are too many cases to count
  - Lancet 374(9696):1209-1211 (2009)
  
• Cyanide poisoning in Taiwan
  - Lancet 374(9696):1212 (2009)