Hot off the presses! Dec 09 The Lancet

The Dec 09 issue of the The Lancet is now up on Pubget (About The 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:

• December 3â€"9, 2011
  - The Lancet 378(9807):i (2011)
  
• Championing good health for people with disabilities
  - The Lancet 378(9807):1895 (2011)
  
• The Global Fund and a new modus operandi
  - The Lancet 378(9807):1896 (2011)
  
• Political commitment for HIV/AIDS control in China
  - The Lancet 378(9807):1896 (2011)
  
• Assessment of the burden of influenza in children
  - The Lancet 378(9807):1897-1898 (2011)
  
• Tilting the AXIS towards therapeutic limits in renal cancer
  - The Lancet 378(9807):1898-1900 (2011)
  
• Polymer drug-eluting stents: is the future biodegradable?
  - The Lancet 378(9807):1900-1902 (2011)
  
• The Commission on Macroeconomics and Health: was it the right recipe?
  - The Lancet 378(9807):1902-1903 (2011)
  
• Africa's health and the Commission on Macroeconomics and Health
  - The Lancet 378(9807):1904-1905 (2011)
  
• Offline: Reasons to be disappointed
  - The Lancet 378(9807):1906 (2011)
  
• The Commission on Macroeconomics and Health: 10 years on
  - The Lancet 378(9807):1907-1908 (2011)
  
• Health policy: from the clinical to the economic gaze
  - The Lancet 378(9807):1909 (2011)
  
• Revolution in health care
  - The Lancet 378(9807):1910 (2011)
  
• Stephen Lawrie: PsySTAR trek, the next generation
  - The Lancet 378(9807):1911 (2011)
  
• Wilson Greatbatch
  - The Lancet 378(9807):1912 (2011)
  
• Role of acute infection in HIV transmission
  - The Lancet 378(9807):1913 (2011)
  
• Role of acute infection in HIV transmission
  - The Lancet 378(9807):1913-1914 (2011)
  
• Role of acute infection in HIV transmission â€" Authors' reply
  - The Lancet 378(9807):1914-1915 (2011)
  
• Bivalirudin for patients with ST-elevation myocardial infarction
  - The Lancet 378(9807):1915 (2011)
  
• Bivalirudin for patients with ST-elevation myocardial infarction â€" Authors' reply
  - The Lancet 378(9807):1915-1916 (2011)
  
• HPV vaccine in Rwanda: different disease, same double standard
  - The Lancet 378(9807):1916 (2011)
  
• Social accountability in health professionals' training
  - The Lancet 378(9807):e12-e13 (2011)
  
• Keeping women's and children's health at the forefront
  - The Lancet 378(9807):e13-e15 (2011)
  
• Primary health care and early childhood development
  - The Lancet 378(9807):e16 (2011)
  
• Parenting resources matter
  - The Lancet 378(9807):e16-e17 (2011)
  
• Advocacy training and social accountability of health professionals
  - The Lancet 378(9807):e17 (2011)
  
• Quality of care in Japan: an additional strategy
  - The Lancet 378(9807):e17 (2011)
  
• Spinal tuberculosis
  - The Lancet 378(9807):e18 (2011)
  
• Global burden of respiratory infections due to seasonal influenza in young children: a systematic review and meta-analysis
  - The Lancet 378(9807):1917-1930 (2011)
  Background The global burden of disease attributable to seasonal influenza virus in children is unknown. We aimed to estimate the global incidence of and mortality from lower respiratory infections associated with influenza in children younger than 5 years. Methods We estimated the incidence of influenza episodes, influenza-associated acute lower respiratory infections (ALRI), and influenza-associated severe ALRI in children younger than 5 years, stratified by age, with data from a systematic review of studies published between Jan 1, 1995, and Oct 31, 2010, and 16 unpublished population-based studies. We applied these incidence estimates to global population estimates for 2008 to calculate estimates for that year. We estimated possible bounds for influenza-associated ALRI mortality by combining incidence estimates with case fatality ratios from hospital-based reports and identifying studies with population-based data for influenza seasonality and monthly ALRI mortality. Findings We identified 43 suitable studies, with data for around 8 million children. We estimated that, in 2008, 90 million (95% CI 49–162 million) new cases of influenza (data from nine studies), 20 million (13–32 million) cases of influenza-associated ALRI (13% of all cases of paediatric ALRI; data from six studies), and 1 million (1–2 million) cases of influenza-associated severe ALRI (7% of cases of all severe paediatric ALRI; data from 39 studies) occurred worldwide in children younger than 5 years. We estimated there were 28 000–111 500 deaths in children younger than 5 years attributable to influenza-associated ALRI in 2008, with 99% of these deaths occurring in developing countries. Incidence and mortality varied substantially from year to year in any one setting. Interpretation Influenza is a common pathogen identified in children with ALRI and results in a substantial burden on health services worldwide. Sufficient data to precisely estimate the role of influenza in childhood mortality from ALRI are not available. Funding WHO; Bill & Melinda Gates Foundation.
• Comparative effectiveness of axitinib versus sorafenib in advanced renal cell carcinoma (AXIS): a randomised phase 3 trial
  - The Lancet 378(9807):1931-1939 (2011)
  Background The treatment of advanced renal cell carcinoma has been revolutionised by targeted therapy with drugs that block angiogenesis. So far, no phase 3 randomised trials comparing the effectiveness of one targeted agent against another have been reported. We did a randomised phase 3 study comparing axitinib, a potent and selective second-generation inhibitor of vascular endothelial growth factor (VEGF) receptors, with sorafenib, an approved VEGF receptor inhibitor, as second-line therapy in patients with metastatic renal cell cancer. Methods We included patients coming from 175 sites (hospitals and outpatient clinics) in 22 countries aged 18 years or older with confirmed renal clear-cell carcinoma who progressed despite first-line therapy containing sunitinib, bevacizumab plus interferon-alfa, temsirolimus, or cytokines. Patients were stratified according to Eastern Cooperative Oncology Group performance status and type of previous treatment and then randomly assigned (1:1) to either axitinib (5 mg twice daily) or sorafenib (400 mg twice daily). Axitinib dose increases to 7 mg and then to 10 mg, twice daily, were allowed for those patients without hypertension or adverse reactions above grade 2. Participants were not masked to study treatment. The primary endpoint was progression-free survival (PFS) and was assessed by a masked, independent radiology review and analysed by intention to treat. This trial was registered on ClinicalTrials.gov, number NCT00678392. Findings A total of 723 patients were enrolled and randomly assigned to receive axitinib (n=361) or sorafenib (n=362). The median PFS was 6·7 months with axitinib compared to 4·7 months with sorafenib (hazard ratio 0·665; 95% CI 0·544–0·812; one-sided p<0·0001). Treatment was discontinued because of toxic effects in 14 (4%) of 359 patients treated with axitinib and 29 (8%) of 355 patients treated with sorafenib. The most common adverse events were diarrhoea, hypertension, and fatigue in the axitinib arm, and diarrhoea, palmar-plantar erythrodysaesthesia, and alopecia in the sorafenib arm. Interpretation Axitinib resulted in significantly longer PFS compared with sorafenib. Axitinib is a treatment option for second-line therapy of advanced renal cell carcinoma. Funding Pfizer Inc.
• Long-term clinical outcomes of biodegradable polymer biolimus-eluting stents versus durable polymer sirolimus-eluting stents in patients with coronary artery disease (LEADERS): 4 year follow-up of a randomised non-inferiority trial
  - The Lancet 378(9807):1940-1948 (2011)
  Background The effectiveness of durable polymer drug-eluting stents comes at the expense of delayed arterial healing and subsequent late adverse events such as stent thrombosis (ST). We report the 4 year follow-up of an assessment of biodegradable polymer-based drug-eluting stents, which aim to improve safety by avoiding the persistent inflammatory stimulus of durable polymers. Methods We did a multicentre, assessor-masked, non-inferiority trial. Between Nov 27, 2006, and May 18, 2007, patients aged 18 years or older with coronary artery disease were randomly allocated with a computer-generated sequence to receive either biodegradable polymer biolimus-eluting stents (BES) or durable polymer sirolimus-eluting stents (SES; 1:1 ratio). The primary endpoint was a composite of cardiac death, myocardial infarction, or clinically-indicated target vessel revascularisation (TVR); patients were followed-up for 4 years. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00389220. Findings 1707 patients with 2472 lesions were randomly allocated to receive either biodegradable polymer BES (857 patients, 1257 lesions) or durable polymer SES (850 patients, 1215 lesions). At 4 years, biodegradable polymer BES were non-inferior to durable polymer SES for the primary endpoint: 160 (18·7%) patients versus 192 (22·6%) patients (rate ratios [RR] 0·81, 95% CI 0·66–1·00, p for non-inferiority <0·0001, p for superiority=0·050). The RR of definite ST was 0·62 (0·35–1·08, p=0·09), which was largely attributable to a lower risk of very late definite ST between years 1 and 4 in the BES group than in the SES group (RR 0·20, 95% CI 0·06–0·67, p=0·004). Conversely, the RR of definite ST during the first year was 0·99 (0·51–1·95; p=0·98) and the test for interaction between RR of definite ST and time was positive (pinteraction=0·017). We recorded an interaction with time for events associated with ST but not for other events. For primary endpoint event! s associated with ST, the RR was 0·86 (0·41–1·80) during the first year and 0·17 (0·04–0·78) during subsequent years (pinteraction=0·049). Interpretation Biodegradable polymer BES are non-inferior to durable polymer SES and, by reducing the risk of cardiac events associated with very late ST, might improve long-term clinical outcomes for up to 4 years compared with durable polymer SES. Funding Biosensors Europe SA, Switzerland.
• Idiopathic pulmonary fibrosis
  - The Lancet 378(9807):1949-1961 (2011)
  Idiopathic pulmonary fibrosis is a devastating, age-related lung disease of unknown cause that has few treatment options. This disease was once thought to be a chronic inflammatory process, but current evidence indicates that the fibrotic response is driven by abnormally activated alveolar epithelial cells (AECs). These cells produce mediators that induce the formation of fibroblast and myofibroblast foci through the proliferation of resident mesenchymal cells, attraction of circulating fibrocytes, and stimulation of the epithelial to mesenchymal transition. The fibroblast and myofibroblast foci secrete excessive amounts of extracellular matrix, mainly collagens, resulting in scarring and destruction of the lung architecture. The mechanisms that link idiopathic pulmonary fibrosis with ageing and aberrant epithelial activation are unknown; evidence suggests that the abnormal recapitulation of developmental pathways and epigenetic changes have a role. In this Seminar, we! review recent data on the clinical course, therapeutic options, and underlying mechanisms thought to be involved in the pathogenesis of idiopathic pulmonary fibrosis.
• Serotype replacement in disease after pneumococcal vaccination
  - The Lancet 378(9807):1962-1973 (2011)
  Vaccination with heptavalent pneumococcal conjugate vaccine (PCV7) has significantly reduced the burden of pneumococcal disease and has had an important public health benefit. Because this vaccine targets only seven of the more than 92 pneumococcal serotypes, concerns have been raised that non-vaccine serotypes (NVTs) could increase in prevalence and reduce the benefits of vaccination. Indeed, among asymptomatic carriers, the prevalence of NVTs has increased substantially, and consequently, there has been little or no net change in the bacterial carriage prevalence. In many populations, pneumococcal disease caused by NVT has increased, but in most cases this increase has been less than the increase in NVT carriage. We review the evidence for serotype replacement in carriage and disease, and address the surveillance biases that might affect these findings. We then discuss possible reasons for the discrepancy between near-complete replacement in carriage and partial repl! acement for disease, including differences in invasiveness between vaccine serotypes. We contend that the magnitude of serotype replacement in disease can be attributed, in part, to a combination of lower invasiveness of the replacing serotypes, biases in the pre-vaccine carriage data (unmasking), and biases in the disease surveillance systems that could underestimate the true amount of replacement. We conclude by discussing the future potential for serotype replacement in disease and the need for continuing surveillance.
• What a difference an egg makes
  - The Lancet 378(9807):1974 (2011)