Hot off the presses! Apr 15 LANCET

The Apr 15 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 of lesbian, gay, bisexual, and transgender populations
  - LANCET 377(9773):1211 (2011)
  
• HIV and injecting drug use: a global call for action
  - LANCET 377(9773):1212 (2011)
  
• Rational reform to medical education in India
  - LANCET 377(9773):1212 (2011)
  
• Long-term safety and efficacy of drug-eluting stents
  - LANCET 377(9773):1213-1214 (2011)
  
• How many cholera deaths can be averted in Haiti?
  - LANCET 377(9773):1214-1216 (2011)
  
• A cytomegalovirus vaccine tames the troll of transplantation
  - LANCET 377(9773):1216-1218 (2011)
  
• New medical data and leadership on tobacco control in China
  - LANCET 377(9773):1218-1220 (2011)
  
• Intensified glucose control in type 2 diabetes—whose agenda?
  - LANCET 377(9773):1220-1222 (2011)
  
• Health-systems strengthening: current and future activities
  - LANCET 377(9773):1222-1223 (2011)
  
• Offline: Face to face, side by side
  - LANCET 377(9773):1224 (2011)
  
• Norway investigates Gaza's drug crisis
  - LANCET 377(9773):1225-1226 (2011)
  
• Tackling hepatitis C: a tale of two countries
  - LANCET 377(9773):1227-1228 (2011)
  
• Digging in the dirt
  - LANCET 377(9773):1229 (2011)
  
• From tropical medicine to global health—Ade Lucas's journey
  - LANCET 377(9773):1230 (2011)
  
• Blood
  - LANCET 377(9773):1231 (2011)
  
• Anne Johnson
  - LANCET 377(9773):1231 (2011)
  
• Elizabeth Evans Hughes—surviving starvation therapy for diabetes
  - LANCET 377(9773):1232-1233 (2011)
  
• Philip Anthony Musgrove
  - LANCET 377(9773):1234 (2011)
  
• Transforming health professionals' education
  - LANCET 377(9773):1235 (2011)
  
• Transforming health professionals' education
  - LANCET 377(9773):1235 (2011)
  
• Transforming health professionals' education
  - LANCET 377(9773):1235-1236 (2011)
  
• Transforming health professionals' education
  - LANCET 377(9773):1236 (2011)
  
• Transforming health professionals' education
  - LANCET 377(9773):1236-1237 (2011)
  
• Transforming health professionals' education
  - LANCET 377(9773):1237 (2011)
  
• Transforming health professionals' education
  - LANCET 377(9773):1237 (2011)
  
• Transforming health professionals' education
  - LANCET 377(9773):1238 (2011)
  
• Transforming health professionals' education – Authors' reply
  - LANCET 377(9773):1238-1239 (2011)
  
• Lessons from Japanese physicians' education and UK budget increase
  - LANCET 377(9773):1239 (2011)
  
• Disclosure of conflict of interest should not be a decorative statement
  - LANCET 377(9773):1239 (2011)
  
• Disclosure of conflict of interest should not be a decorative statement – Authors' reply
  - LANCET 377(9773):1239-1240 (2011)
  
• Two important issues when promoting healthier food
  - LANCET 377(9773):1240 (2011)
  
• Unrestricted randomised use of two new generation drug-eluting coronary stents: 2-year patient-related versus stent-related outcomes from the RESOLUTE All Comers trial
  - LANCET 377(9773):1241-1247 (2011)
  Background In the RESOLUTE All Comers trial, the Resolute zotarolimus-eluting stent was non-inferior to the Xience V everolimus-eluting stent for the primary stent-related endpoint of target lesion failure (cardiac death, target vessel myocardial infarction, and ischaemia-driven target lesion revascularisation) at 1 year. However, data for long-term safety and efficacy from randomised studies of new generation drug-eluting coronary stents in patients treated in routine clinical practice are scarce. We report the prespecified 2-year clinical outcomes from the RESOLUTE All Comers trial. Methods In 2008, patients with at least one coronary lesion 2·25–4·0 mm in diameter, with greater than 50% stenosis, were randomly assigned to a Resolute zotarolimus-eluting stent or a Xience V everolimus-eluting stent at 17 centres in Europe and Israel. Randomisation was by an interactive voice response system stratified by centre. Study investigators were not masked to treatment allocation; but those who did data management and analysis, and patients were masked. There were no restrictions as to the number of vessels or lesions treated, or the number of stents implanted. We assessed prespecified safety and efficacy outcomes at 2 years with specific focus on patient-related composite (all death, all myocardial infarction, all revascularisation) and stent-related composite outcomes. Analyses were by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00617084. Findings 1140 patients were assigned to the zotarolimus-eluting stent and 1152 to the everolimus-eluting stent; 1121 and 1128 patients, respectively, completed 2-year follow-up. The patient-related outcome (231 [20·6%] zotarolimus vs 231 [20·5%] everolimus; difference 0·1%, 95% CI −3·2 to 3·5; p=0·958) and stent-related outcome (126 [11·2%] vs 121 [10·7%]; difference 0·5%, −2·1 to 3·1; p=0·736) did not differ between groups, although rates of the stent-related outcome were substantially lower than were those for the patient-related outcome. Three patients in each group (0·3%) had very late (after 1 year) stent thrombosis. Interpretation Similar safety and efficacy outcomes were sustained between two new generation drug-eluting stents at 2-year follow-up. The greater number of patient-related than stent-related events in patients with complex clinical and lesion characteristics emphasises that during long-term follow-up, the optimisation of secondary prevention is at least as important as the selection of which new generation drug-eluting stent to implant in a specific lesion. Funding Medtronic (USA).
• Transmission dynamics and control of cholera in Haiti: an epidemic model
  - LANCET 377(9773):1248-1255 (2011)
  Background Official projections of the cholera epidemic in Haiti have not incorporated existing disease trends or patterns of transmission, and proposed interventions have been debated without comparative estimates of their effect. We used a mathematical model of the epidemic to provide projections of future morbidity and mortality, and to produce comparative estimates of the effects of proposed interventions. Methods We designed mathematical models of cholera transmission based on existing models and fitted them to incidence data reported in Haiti for each province from Oct 31, 2010, to Jan 24, 2011. We then simulated future epidemic trajectories from March 1 to Nov 30, 2011, to estimate the effect of clean water, vaccination, and enhanced antibiotic distribution programmes. Findings We project 779 000 cases of cholera in Haiti (95% CI 599 000–914 000) and 11 100 deaths (7300–17 400) between March 1 and Nov 30, 2011. We expect that a 1% per week reduction in consumption of contaminated water would avert 105 000 cases (88 000–116 000) and 1500 deaths (1100–2300). We predict that the vaccination of 10% of the population, from March 1, will avert 63 000 cases (48 000–78 000) and 900 deaths (600–1500). The proposed extension of the use of antibiotics to all patients with severe dehydration and half of patients with moderate dehydration is expected to avert 9000 cases (8000–10 000) and 1300 deaths (900–2000). Interpretation A decline in cholera prevalence in early 2011 is part of the natural course of the epidemic, and should not be interpreted as indicative of successful intervention. Substantially more cases of cholera are expected than official estimates used for resource allocation. Combined, clean water provision, vaccination, and expanded access to antibiotics might avert thousands of deaths. Funding National Institutes of Health.
• Cytomegalovirus glycoprotein-B vaccine with MF59 adjuvant in transplant recipients: a phase 2 randomised placebo-controlled trial
  - LANCET 377(9773):1256-1263 (2011)
  Background Cytomegalovirus end-organ disease can be prevented by giving ganciclovir when viraemia is detected in allograft recipients. Values of viral load correlate with development of end-organ disease and are moderated by pre-existing natural immunity. Our aim was to determine whether vaccine-induced immunity could do likewise. Methods We undertook a phase-2 randomised placebo controlled trial in adults awaiting kidney or liver transplantation at the Royal Free Hospital, London, UK. Exclusion criteria were pregnancy, receipt of blood products (except albumin) in the previous 3 months, and simultaneous multiorgan transplantation. 70 patients seronegative and 70 seropositive for cytomegalovirus were randomly assigned from a scratch-off randomisation code in a 1:1 ratio to receive either cytomegalovirus glycoprotein-B vaccine with MF59 adjuvant or placebo, each given at baseline, 1 month and 6 months later. If a patient was transplanted, no further vaccinations were given and serial blood samples were tested for cytomegalovirus DNA by real-time quantitative PCR (rtqPCR). Any patient with one blood sample containing more than 3000 cytomegalovirus genomes per mL received ganciclovir until two consecutive undetectable cytomegalovirus DNA measurements. Safety and immunogenicity were coprimary endpoints and were a! ssessed by intention to treat in patients who received at least one dose of vaccine or placebo. This trial is registered with ClinicalTrials.gov, NCT00299260. Findings 67 patients received vaccine and 73 placebo, all of whom were evaluable. Glycoprotein-B antibody titres were significantly increased in both seronegative (geometric mean titre 12 537 (95% CI 6593–23 840) versus 86 (63–118) in recipients of placebo recipients; p<0·0001) and seropositive (118 395; 64 503–217 272) versus 24 682 (17 909–34 017); p<0·0001) recipients of vaccine. In those who developed viraemia after transplantation, glycoprotein-B antibody titres correlated inversely with duration of viraemia (p=0·0022). In the seronegative patients with seropositive donors, the duration of viraemia (p=0·0480) and number of days of ganciclovir treatment (p=0·0287) were reduced in vaccine recipients. Interpretation Although cytomegalovirus disease occurs in the context of suppressed cell-mediated immunity post-transplantation, humoral immunity has a role in reduction of cytomegalovirus viraemia. Vaccines containing cytomegalovirus glycoprotein B merit further assessment in transplant recipients. Funding National Institute of Allergy and Infectious Diseases, Grant R01AI051355 and Wellcome Trust, Grant 078332. Sponsor: University College London (UCL).
• Viral pneumonia
  - LANCET 377(9773):1264-1275 (2011)
  About 200 million cases of viral community-acquired pneumonia occur every year—100 million in children and 100 million in adults. Molecular diagnostic tests have greatly increased our understanding of the role of viruses in pneumonia, and findings indicate that the incidence of viral pneumonia has been underestimated. In children, respiratory syncytial virus, rhinovirus, human metapneumovirus, human bocavirus, and parainfluenza viruses are the agents identified most frequently in both developed and developing countries. Dual viral infections are common, and a third of children have evidence of viral-bacterial co-infection. In adults, viruses are the putative causative agents in a third of cases of community-acquired pneumonia, in particular influenza viruses, rhinoviruses, and coronaviruses. Bacteria continue to have a predominant role in adults with pneumonia. Presence of viral epidemics in the community, patient's age, speed of onset of illness, symptoms, biomarker! s, radiographic changes, and response to treatment can help differentiate viral from bacterial pneumonia. However, no clinical algorithm exists that will distinguish clearly the cause of pneumonia. No clear consensus has been reached about whether patients with obvious viral community-acquired pneumonia need to be treated with antibiotics. Apart from neuraminidase inhibitors for pneumonia caused by influenza viruses, there is no clear role for use of specific antivirals to treat viral community-acquired pneumonia. Influenza vaccines are the only available specific preventive measures. Further studies are needed to better understand the cause and pathogenesis of community-acquired pneumonia. Furthermore, regional differences in cause of pneumonia should be investigated, in particular to obtain more data from developing countries.
• Osteoporosis: now and the future
  - LANCET 377(9773):1276-1287 (2011)
  Osteoporosis is a common disease characterised by a systemic impairment of bone mass and microarchitecture that results in fragility fractures. With an ageing population, the medical and socioeconomic effect of osteoporosis, particularly postmenopausal osteoporosis, will increase further. A detailed knowledge of bone biology with molecular insights into the communication between bone-forming osteoblasts and bone-resorbing osteoclasts and the orchestrating signalling network has led to the identification of novel therapeutic targets. Novel treatment strategies have been developed that aim to inhibit excessive bone resorption and increase bone formation. The most promising novel treatments include: denosumab, a monoclonal antibody for receptor activator of NF-κB ligand, a key osteoclast cytokine; odanacatib, a specific inhibitor of the osteoclast protease cathepsin K; and antibodies against the proteins sclerostin and dickkopf-1, two endogenous inhibitors of bone format! ion. This overview discusses these novel therapies and explains their underlying physiology.
• An X-traordinary stroke
  - LANCET 377(9773):1288 (2011)