Hot off the presses! Jul 25 Lancet

The Jul 25 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:

• England's Big Care Debate
  - Lancet 374(9686):265 (2009)
  
• Political activism needed for patent pools for HIV drugs
  - Lancet 374(9686):266 (2009)
  
• Maintaining momentum for malaria elimination
  - Lancet 374(9686):266 (2009)
  
• Best pharmacological practice in prehospital intubation
  - Lancet 374(9686):267-268 (2009)
  
• HPV vaccine for all
  - Lancet 374(9686):268-270 (2009)
  
• Unemployment and suicide
  - Lancet 374(9686):270-271 (2009)
  
• If NICE was in the USA
  - Lancet 374(9686):272-273 (2009)
  
• Clinical experts or methodologists to write clinical guidelines?
  - Lancet 374(9686):273-275 (2009)
  
• Expanding HIV care in Africa: making men matter
  - Lancet 374(9686):275-276 (2009)
  
• Countries race to contain resistance to key antimalarial
  - Lancet 374(9686):277-280 (2009)
  
• Rethinking the role of the World Bank in the battle against hunger
  - Lancet 374(9686):281-282 (2009)
  
• Outside of the box
  - Lancet 374(9686):282 (2009)
  
• Suneeta Mittal: safeguarding women's health in India
  - Lancet 374(9686):283 (2009)
  
• Sarah Bernhardt's missing leg
  - Lancet 374(9686):284-285 (2009)
  
• Edwin Shneidman
  - Lancet 374(9686):286 (2009)
  
• Epoetins and mortality in patients with cancer
  - Lancet 374(9686):287 (2009)
  
• Epoetins and mortality in patients with cancer
  - Lancet 374(9686):287 (2009)
  
• Epoetins and mortality in patients with cancer – Authors' reply
  - Lancet 374(9686):287-288 (2009)
  
• Home management of malaria
  - Lancet 374(9686):288-289 (2009)
  
• Home management of malaria – Authors' reply
  - Lancet 374(9686):289 (2009)
  
• Home management of malaria
  - Lancet 374(9686):289-290 (2009)
  
• Responsibility for lack of psychopharmacological innovation
  - Lancet 374(9686):290 (2009)
  
• Responsibility for lack of psychopharmacological innovation – Author's reply
  - Lancet 374(9686):290-291 (2009)
  
• Retaining health manpower in developing countries
  - Lancet 374(9686):291 (2009)
  
• Retaining health manpower in developing countries
  - Lancet 374(9686):291-292 (2009)
  
• Flat-line funding for PEPFAR: a recipe for chaos
  - Lancet 374(9686):292 (2009)
  
• Multidrug-resistant tuberculosis and quality-assured medicines
  - Lancet 374(9686):292 (2009)
  
• Department of Error
  - Lancet 374(9686):292 (2009)
  
• Etomidate versus ketamine for rapid sequence intubation in acutely ill patients: a multicentre randomised controlled trial
  - Lancet 374(9686):293-300 (2009)
  Background Critically ill patients often require emergency intubation. The use of etomidate as the sedative agent in this context has been challenged because it might cause a reversible adrenal insufficiency, potentially associated with increased in-hospital morbidity. We compared early and 28-day morbidity after a single dose of etomidate or ketamine used for emergency endotracheal intubation of critically ill patients. Methods In this randomised, controlled, single-blind trial, 655 patients who needed sedation for emergency intubation were prospectively enrolled from 12 emergency medical services or emergency departments and 65 intensive care units in France. Patients were randomly assigned by a computerised random-number generator list to receive 0·3 mg/kg of etomidate (n=328) or 2 mg/kg of ketamine (n=327) for intubation. Only the emergency physician enrolling patients was aware of group assignment. The primary endpoint was the maximum score of the sequential organ failure assessment during the first 3 days in the intensive care unit. We excluded from the analysis patients who died before reaching the hospital or those discharged from the intensive care unit before 3 days (modified intention to treat). This trial is registered with ClinicalTrials.gov, number NCT00440102. Findings 234 patients were analysed in the etomidate group and 235 in the ketamine group. The mean maximum SOFA score between the two groups did not differ significantly (10·3 [SD 3·7] for etomidate vs 9·6 [3·9] for ketamine; mean difference 0·7 [95% CI 0·0–1·4], p=0·056). Intubation conditions did not differ significantly between the two groups (median intubation difficulty score 1 [IQR 0–3] in both groups; p=0·70). The percentage of patients with adrenal insufficiency was significantly higher in the etomidate group than in the ketamine group (OR 6·7, 3·5–12·7). We recorded no serious adverse events with either study drug. Interpretation Our results show that ketamine is a safe and valuable alternative to etomidate for endotracheal intubation in critically ill patients, and should be considered in those with sepsis. Funding French Ministry of Health.
• Efficacy of human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine against cervical infection and precancer caused by oncogenic HPV types (PATRICIA): final analysis of a double-blind, randomised study in young women
  - Lancet 374(9686):301-314 (2009)
  Background The human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine was immunogenic, generally well tolerated, and effective against HPV-16 or HPV-18 infections, and associated precancerous lesions in an event-triggered interim analysis of the phase III randomised, double-blind, controlled PApilloma TRIal against Cancer In young Adults (PATRICIA). We now assess the vaccine efficacy in the final event-driven analysis. Methods Women (15–25 years) were vaccinated at months 0, 1, and 6. Analyses were done in the according-to-protocol cohort for efficacy (ATP-E; vaccine, n=8093; control, n=8069), total vaccinated cohort (TVC, included all women receiving at least one vaccine dose, regardless of their baseline HPV status; represents the general population, including those who are sexually active; vaccine, n=9319; control, n=9325), and TVC-naive (no evidence of oncogenic HPV infection at baseline; represents women before sexual debut; vaccine, n=5822; control, n=5819). The primary endpoint was to assess vaccine efficacy against cervical intraepithelial neoplasia 2+ (CIN2+) that was associated with HPV-16 or HPV-18 in women who were seronegative at baseline, and DNA negative at baseline and month 6 for the corresponding type (ATP-E). This trial is registered with ClinicalTrials.gov, number NCT00122681. Findings Mean follow-up was 34·9 months (SD 6·4) after the third dose. Vaccine efficacy against CIN2+ associated with HPV-16/18 was 92·9% (96·1% CI 79·9–98·3) in the primary analysis and 98·1% (88·4–100) in an analysis in which probable causality to HPV type was assigned in lesions infected with multiple oncogenic types (ATP-E cohort). Vaccine efficacy against CIN2+ irrespective of HPV DNA in lesions was 30·4% (16·4–42·1) in the TVC and 70·2% (54·7–80·9) in the TVC-naive. Corresponding values against CIN3+ were 33·4% (9·1–51·5) in the TVC and 87·0% (54·9–97·7) in the TVC-naive. Vaccine efficacy against CIN2+ associated with 12 non-vaccine oncogenic types was 54·0% (34·0–68·4; ATP-E). Individual cross-protection against CIN2+ associated with HPV-31, HPV-33, and HPV-45 was seen in the TVC. Interpretation The HPV-16/18 AS04-adjuvanted vaccine showed high efficacy against CIN2+ associated with HPV-16/18 and non-vaccine oncogenic HPV types and substantial overall effect in cohorts that are relevant to universal mass vaccination and catch-up programmes. Funding GlaxoSmithKline Biologicals.
• The public health effect of economic crises and alternative policy responses in Europe: an empirical analysis
  - Lancet 374(9686):315-323 (2009)
  Background There is widespread concern that the present economic crisis, particularly its effect on unemployment, will adversely affect population health. We investigated how economic changes have affected mortality rates over the past three decades and identified how governments might reduce adverse effects. Methods We used multivariate regression, correcting for population ageing, past mortality and employment trends, and country-specific differences in health-care infrastructure, to examine associations between changes in employment and mortality, and how associations were modified by different types of government expenditure for 26 European Union (EU) countries between 1970 and 2007. Findings We noted that every 1% increase in unemployment was associated with a 0·79% rise in suicides at ages younger than 65 years (95% CI 0·16–1·42; 60–550 potential excess deaths [mean 310] EU-wide), although the effect size was non-significant at all ages (0·49%, −0·04 to 1·02), and with a 0·79% rise in homicides (95% CI 0·06–1·52; 3–80 potential excess deaths [mean 40] EU-wide). By contrast, road-traffic deaths decreased by 1·39% (0·64–2·14; 290–980 potential fewer deaths [mean 630] EU-wide). A more than 3% increase in unemployment had a greater effect on suicides at ages younger than 65 years (4·45%, 95% CI 0·65–8·24; 250–3220 potential excess deaths [mean 1740] EU-wide) and deaths from alcohol abuse (28·0%, 12·30–43·70; 1550–5490 potential excess deaths [mean 3500] EU-wide). We noted no consistent evidence across the EU that all-cause mortality rates increased when unemployment rose, although populations varied substantially in how sensi! tive mortality was to economic crises, depending partly on differences in social protection. Every US$10 per person increased investment in active labour market programmes reduced the effect of unemployment on suicides by 0·038% (95% CI −0·004 to −0·071). Interpretation Rises in unemployment are associated with significant short-term increases in premature deaths from intentional violence, while reducing traffic fatalities. Active labour market programmes that keep and reintegrate workers in jobs could mitigate some adverse health effects of economic downturns. Funding Centre for Crime and Justice Studies, King's College, London, UK; and Wates Foundation (UK).
• Multiple myeloma
  - Lancet 374(9686):324-339 (2009)
  Multiple myeloma is characterised by clonal proliferation of malignant plasma cells, and mounting evidence indicates that the bone marrow microenvironment of tumour cells has a pivotal role in myeloma pathogenesis. This knowledge has already expanded treatment options for patients with multiple myeloma. Prototypic drugs thalidomide, bortezomib, and lenalidomide have each been approved for the treatment of this disease by targeting both multiple myeloma cells and the bone marrow microenvironment. Although benefit was first shown in relapsed and refractory disease, improved overall response, duration of response, and progression-free and overall survival can be achieved when these drugs are part of first-line regimens. This treatment framework promises to improve outcome not only for patients with multiple myeloma, but also with other haematological malignancies and solid tumours.
• Genomic copy number variation, human health, and disease
  - Lancet 374(9686):340-350 (2009)
  Despite the long recognised effects of chromosomal structural abnormalities and completion of the Human Genome Project, much of the structural variation in the genome has gone unrecognised until recently. Deletions and duplications of DNA strands of between a few hundred bp and several million bp—collectively referred to as copy number variants—are now known to be widespread. Since 2007, rigorous and adequately powered genome-wide association studies based on single nucleotide polymorphisms have yielded replicated associations to several common diseases. Some copy number variants explain rare, previously uncharacterised disorders, and they are now expected to explain some of the genetic contribution to common diseases. We review efforts to map copy number variants and discuss present and future prospects for assessment of their relation to human health and disease.
• The decade of NICE
  - Lancet 374(9686):351-352 (2009)
  
• Medical ethics at Guantanamo Bay detention centre and in the US military: a time for reform
  - Lancet 374(9686):353-355 (2009)
  
• The emergence of lymphogranuloma venereum in Europe
  - Lancet 374(9686):356 (2009)