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Journal Cover The Lancet
   Journal TOC RSS feeds Export to Zotero [1073 followers]  Follow    
   Full-text available via subscription Subscription journal
     ISSN (Print) 0140-6736 - ISSN (Online) 1474-547X
     Published by Elsevier Homepage  [2563 journals]   [SJR: 7.074]   [H-I: 477]
  • The safety of addition of nitrous oxide to general anaesthesia in at-risk
           patients having major non-cardiac surgery (ENIGMA-II): a randomised,
           single-blind trial
    • Abstract: Publication date: Available online 17 August 2014
      Source:The Lancet
      Author(s): Paul S Myles , Kate Leslie , Matthew T V Chan , Andrew Forbes , Philip J Peyton , Michael J Paech , W Scott Beattie , Daniel I Sessler , P J Devereaux , Brendan Silbert , Thomas Schricker , Sophie Wallace
      Background Nitrous oxide is commonly used in general anaesthesia but concerns exist that it might increase perioperative cardiovascular risk. We aimed to gather evidence to establish whether nitrous oxide affects perioperative cardiovascular risk. Methods We did an international, randomised, assessor-blinded trial in patients aged at least 45 years with known or suspected coronary artery disease having major non-cardiac surgery. Patients were randomly assigned via automated telephone service, stratified by site, to receive a general anaesthetic with or without nitrous oxide. Attending anaesthetists were aware of patients' group assignments, but patients and assessors were not. The primary outcome measure was a composite of death and cardiovascular complications (non-fatal myocardial infarction, stroke, pulmonary embolism, or cardiac arrest) within 30 days of surgery. Our modified intention-to-treat population included all patients randomly assigned to groups and undergoing induction of general anaesthesia for surgery. This trial is registered at ClinicalTrials.gov, number NCT00430989. Findings Of 10 102 eligible patients, we enrolled 7112 patients between May 30, 2008, and Sept 28, 2013. 3543 were assigned to receive nitrous oxide and 3569 were assigned not to receive nitrous oxide. 3483 patients receiving nitrous oxide and 3509 not receiving nitrous oxide were assessed for the primary outcome. The primary outcome occurred in 283 (8%) patients receiving nitrous oxide and in 296 (8%) patients not receiving nitrous oxide (relative risk 0·96, 95% CI 0·83–1·12; p=0·64). Surgical site infection occurred in 321 (9%) patients assigned to nitrous oxide, and in 311 (9%) patients in the no-nitrous oxide group (p=0·61), and severe nausea and vomiting occurred in 506 patients (15%) assigned to nitrous oxide and 378 patients (11%) not assigned to nitrous oxide (p<0·0001). Interpretation Our findings support the safety profile of nitrous oxide use in major non-cardiac surgery. Nitrous oxide did not increase the risk of death and cardiovascular complications or surgical-site infection, the emetogenic effect of nitrous oxide can be controlled with antiemetic prophylaxis, and a desired effect of reduced volatile agent use was shown. Funding Australian National Health and Medical Research Council; Australian and New Zealand College of Anaesthetists; Heart and Stroke Foundation of Quebec, Heart and Stroke Foundation of Ontario, Canada; General Research Fund of the Research Grant Council, Hong Kong Special Administrative Region, China.


      PubDate: 2014-08-18T15:23:55Z
       
  • August 16–22, 2014
    • Abstract: Publication date: 16–22 August 2014
      Source:The Lancet, Volume 384, Issue 9943




      PubDate: 2014-08-18T15:23:55Z
       
  • Quantifying the social impact of research and medical journals
    • Abstract: Publication date: 16–22 August 2014
      Source:The Lancet, Volume 384, Issue 9943
      Author(s): The Lancet



      PubDate: 2014-08-18T15:23:55Z
       
  • Prescribing antibiotics: a battle of resistance
    • Abstract: Publication date: 16–22 August 2014
      Source:The Lancet, Volume 384, Issue 9943
      Author(s): The Lancet



      PubDate: 2014-08-18T15:23:55Z
       
  • Priorities for people with disabilities in New Zealand
    • Abstract: Publication date: 16–22 August 2014
      Source:The Lancet, Volume 384, Issue 9943
      Author(s): The Lancet



      PubDate: 2014-08-18T15:23:55Z
       
  • Under-use of the Ross operation—a lost opportunity
    • Abstract: Publication date: 16–22 August 2014
      Source:The Lancet, Volume 384, Issue 9943
      Author(s): Magdi H Yacoub , Ismail El-Hamamsy , Hans-Hinrich Sievers , Blase A Carabello , Robert O Bonow , Paul Stelzer , Francisco D A da Costa , Hans J Schäfers , Peter Skillington , Efstratios I Charitos , Giovanni Battista Luciani , Johanna J M Takkenberg



      PubDate: 2014-08-18T15:23:55Z
       
  • Telemonitoring implants for patients with heart failure
    • Abstract: Publication date: 16–22 August 2014
      Source:The Lancet, Volume 384, Issue 9943
      Author(s): Martin R Cowie



      PubDate: 2014-08-18T15:23:55Z
       
  • Risk and decision making in patients with hypertension
    • Abstract: Publication date: 16–22 August 2014
      Source:The Lancet, Volume 384, Issue 9943
      Author(s): Paolo Verdecchia , Gianpaolo Reboldi



      PubDate: 2014-08-18T15:23:55Z
       
  • Heparin monotherapy for percutaneous coronary intervention'
    • Abstract: Publication date: 16–22 August 2014
      Source:The Lancet, Volume 384, Issue 9943
      Author(s): A Michael Lincoff



      PubDate: 2014-08-18T15:23:55Z
       
  • Dyslipidaemia in perspective
    • Abstract: Publication date: 16–22 August 2014
      Source:The Lancet, Volume 384, Issue 9943
      Author(s): John J P Kastelein



      PubDate: 2014-08-18T15:23:55Z
       
  • Cardiology: a call for papers
    • Abstract: Publication date: 16–22 August 2014
      Source:The Lancet, Volume 384, Issue 9943
      Author(s): Stuart Spencer



      PubDate: 2014-08-18T15:23:55Z
       
  • EC Chief Scientific Adviser position gets strong backing
    • Abstract: Publication date: 16–22 August 2014
      Source:The Lancet, Volume 384, Issue 9943
      Author(s): Talha Khan Burki



      PubDate: 2014-08-18T15:23:55Z
       
  • Of pigs and people—WHO prepares to battle cysticercosis
    • Abstract: Publication date: 16–22 August 2014
      Source:The Lancet, Volume 384, Issue 9943
      Author(s): John Maurice



      PubDate: 2014-08-18T15:23:55Z
       
  • The Lancet Technology: August, 2014
    • Abstract: Publication date: 16–22 August 2014
      Source:The Lancet, Volume 384, Issue 9943
      Author(s): Naomi Lee



      PubDate: 2014-08-18T15:23:55Z
       
  • The age of miracles
    • Abstract: Publication date: 16–22 August 2014
      Source:The Lancet, Volume 384, Issue 9943
      Author(s): Ishani Kar-Purkayastha



      PubDate: 2014-08-18T15:23:55Z
       
  • Donald Nixon Ross
    • Abstract: Publication date: 16–22 August 2014
      Source:The Lancet, Volume 384, Issue 9943
      Author(s): Jeremy Laurance



      PubDate: 2014-08-18T15:23:55Z
       
  • Israel–Gaza conflict
    • Abstract: Publication date: 16–22 August 2014
      Source:The Lancet, Volume 384, Issue 9943
      Author(s): Faheem Ahmed , Na'eem Ahmed , Yahya Hussin , Bayard Roberts , Shameq Sayeed



      PubDate: 2014-08-18T15:23:55Z
       
  • Israel–Gaza conflict
    • Abstract: Publication date: 16–22 August 2014
      Source:The Lancet, Volume 384, Issue 9943
      Author(s): Jeffrey J Goldberger , Richard L Popp , Douglas P Zipes



      PubDate: 2014-08-18T15:23:55Z
       
  • Israel–Gaza conflict
    • Abstract: Publication date: 16–22 August 2014
      Source:The Lancet, Volume 384, Issue 9943
      Author(s): Nancy Murray



      PubDate: 2014-08-18T15:23:55Z
       
  • Israel–Gaza conflict
    • Abstract: Publication date: 16–22 August 2014
      Source:The Lancet, Volume 384, Issue 9943
      Author(s): Adi Leiba , Moshe Pinkert , Yitshak Kreiss



      PubDate: 2014-08-18T15:23:55Z
       
  • Adhesion barriers for abdominal surgery and oncology
    • Abstract: Publication date: 16–22 August 2014
      Source:The Lancet, Volume 384, Issue 9943
      Author(s): Aurélien Dupré , David Pérol , Michel Rivoire



      PubDate: 2014-08-18T15:23:55Z
       
  • Adhesion barriers for abdominal surgery and oncology – Authors'
           reply
    • Abstract: Publication date: 16–22 August 2014
      Source:The Lancet, Volume 384, Issue 9943
      Author(s): Richard P G ten Broek , Harry van Goor



      PubDate: 2014-08-18T15:23:55Z
       
  • Better treatment of XDR tuberculosis needed in South Africa
    • Abstract: Publication date: 16–22 August 2014
      Source:The Lancet, Volume 384, Issue 9943
      Author(s): Helen Cox , Gilles van Cutsem , Vivian Cox



      PubDate: 2014-08-18T15:23:55Z
       
  • Better treatment of XDR tuberculosis needed in South Africa –
           Author's reply
    • Abstract: Publication date: 16–22 August 2014
      Source:The Lancet, Volume 384, Issue 9943
      Author(s): Keertan Dheda



      PubDate: 2014-08-18T15:23:55Z
       
  • Department of Error
    • Abstract: Publication date: 16–22 August 2014
      Source:The Lancet, Volume 384, Issue 9943




      PubDate: 2014-08-18T15:23:55Z
       
  • Department of Error
    • Abstract: Publication date: 16–22 August 2014
      Source:The Lancet, Volume 384, Issue 9943




      PubDate: 2014-08-18T15:23:55Z
       
  • Department of Error
    • Abstract: Publication date: 16–22 August 2014
      Source:The Lancet, Volume 384, Issue 9943




      PubDate: 2014-08-18T15:23:55Z
       
  • Department of Error
    • Abstract: Publication date: 16–22 August 2014
      Source:The Lancet, Volume 384, Issue 9943




      PubDate: 2014-08-18T15:23:55Z
       
  • Implant-based multiparameter telemonitoring of patients with heart failure
           (IN-TIME): a randomised controlled trial
    • Abstract: Publication date: 16–22 August 2014
      Source:The Lancet, Volume 384, Issue 9943
      Author(s): Gerhard Hindricks , Milos Taborsky , Michael Glikson , Ullus Heinrich , Burghard Schumacher , Amos Katz , Johannes Brachmann , Thorsten Lewalter , Andreas Goette , Michael Block , Josef Kautzner , Stefan Sack , Daniela Husser , Christopher Piorkowski , Peter Søgaard
      Background An increasing number of patients with heart failure receive implantable cardioverter-defibrillators (ICDs) or cardiac resynchronisation defibrillators (CRT-Ds) with telemonitoring function. Early detection of worsening heart failure, or upstream factors predisposing to worsening heart failure, by implant-based telemonitoring might enable pre-emptive intervention and improve outcomes, but the evidence is weak. We investigated this possibility in IN-TIME, a clinical trial. Methods We did this randomised, controlled trial at 36 tertiary clinical centres and hospitals in Australia, Europe, and Israel. We enrolled patients with chronic heart failure, NYHA class II–III symptoms, ejection fraction of no more than 35%, optimal drug treatment, no permanent atrial fibrillation, and a recent dual-chamber ICD or CRT-D implantation. After a 1 month run-in phase, patients were randomly assigned (1:1) to either automatic, daily, implant-based, multiparameter telemonitoring in addition to standard care or standard care without telemonitoring. Investigators were not masked to treatment allocation. Patients were masked to allocation unless they were contacted because of telemonitoring findings. Follow-up was 1 year. The primary outcome measure was a composite clinical score combining all-cause death, overnight hospital admission for heart failure, change in NYHA class, and change in patient global self-assessment, for the intention-to-treat population. The trial is registered with ClinicalTrials.gov, number NCT00538356. Findings We enrolled 716 patients, of whom 664 were randomly assigned (333 to telemonitoring, 331 to control). Mean age was 65·5 years and mean ejection fraction was 26%. 285 (43%) of patients had NYHA functional class II and 378 (57%) had NYHA class III. Most patients received CRT-Ds (390; 58·7%). At 1 year, 63 (18·9%) of 333 patients in the telemonitoring group versus 90 (27·2%) of 331 in the control group (p=0·013) had worsened composite score (odds ratio 0·63, 95% CI 0·43–0·90). Ten versus 27 patients died during follow-up. Interpretation Automatic, daily, implant-based, multiparameter telemonitoring can significantly improve clinical outcomes for patients with heart failure. Such telemonitoring is feasible and should be used in clinical practice. Funding Biotronik SE & Co. KG.


      PubDate: 2014-08-18T15:23:55Z
       
  • Blood pressure-lowering treatment based on cardiovascular risk: a
           meta-analysis of individual patient data
    • Abstract: Publication date: 16–22 August 2014
      Source:The Lancet, Volume 384, Issue 9943

      Background We aimed to investigate whether the benefits of blood pressure-lowering drugs are proportional to baseline cardiovascular risk, to establish whether absolute risk could be used to inform treatment decisions for blood pressure-lowering therapy, as is recommended for lipid-lowering therapy. Methods This meta-analysis included individual participant data from trials that randomly assigned patients to either blood pressure-lowering drugs or placebo, or to more intensive or less intensive blood pressure-lowering regimens. The primary outcome was total major cardiovascular events, consisting of stroke, heart attack, heart failure, or cardiovascular death. Participants were separated into four categories of baseline 5-year major cardiovascular risk using a risk prediction equation developed from the placebo groups of the included trials (<11%, 11–15%, 15–21%, >21%). Findings 11 trials and 26 randomised groups met the inclusion criteria, and included 67 475 individuals, of whom 51 917 had available data for the calculation of the risk equations. 4167 (8%) had a cardiovascular event during a median of 4·0 years (IQR 3·4–4·4) of follow-up. The mean estimated baseline levels of 5-year cardiovascular risk for each of the four risk groups were 6·0% (SD 2·0), 12·1% (1·5), 17·7% (1·7), and 26·8% (5·4). In each consecutive higher risk group, blood pressure-lowering treatment reduced the risk of cardiovascular events relatively by 18% (95% CI 7–27), 15% (4–25), 13% (2–22), and 15% (5–24), respectively (p=0·30 for trend). However, in absolute terms, treating 1000 patients in each group with blood pressure-lowering treatment for 5 years would prevent 14 (95% CI 8–21), 20 (8–31), 24 (8–40), and 38 (16–61) cardiovascular events, respectively (p=0·04 for trend). Interpretation Lowering blood pressure provides similar relative protection at all levels of baseline cardiovascular risk, but progressively greater absolute risk reductions as baseline risk increases. These results support the use of predicted baseline cardiovascular disease risk equations to inform blood pressure-lowering treatment decisions. Funding None.


      PubDate: 2014-08-18T15:23:55Z
       
  • Bivalirudin versus heparin in patients planned for percutaneous coronary
           intervention: a meta-analysis of randomised controlled trials
    • Abstract: Publication date: 16–22 August 2014
      Source:The Lancet, Volume 384, Issue 9943
      Author(s): Matthew A Cavender , Marc S Sabatine
      Background Bivalirudin is an alternative to heparin in patients undergoing percutaneous coronary intervention (PCI). We aimed to define the effects of a bivalirudin-based anticoagulation regimen compared with a heparin-based anticoagulation regimen on ischaemic and bleeding outcomes. Methods We searched Medline, the Cochrane Library, and relevant meeting abstracts (search done on April 9, 2014) for randomised trials that assessed bivalirudin versus heparin in patients planned for PCI. The primary efficacy endpoint was the incidence of major adverse cardiac events (MACE) up to 30 days. Secondary efficacy endpoints were death, myocardial infarction, ischaemia-driven revascularisation, and stent thrombosis. The primary safety endpoint was major bleeding up to 30 days. We calculated pooled risk ratios and 95% CIs using random-effects models. Findings We included data from 16 trials involving 33 958 patients, of whom 2422 experienced MACE and 1406 had a major bleed. There was an increase in the risk of MACE with bivalirudin-based regimens compared with heparin-based regimens (risk ratio 1·09, 95% CI 1·01–1·17; p=0·0204), which was largely driven by increases in myocardial infarction (1·12, 1·03–1·23) and seemingly also by ischaemia-driven revascularisation (1·16, 0·997–1·34) with bivalirudin compared with heparin, with no effect on mortality (0·99, 0·82–1·18). Bivalirudin increased the risk of stent thrombosis (risk ratio 1·38, 95% CI 1·09–1·74; p=0·0074), which was primarily due to an increase in acute cases in ST-segment elevation myocardial infarction (4·27, 2·28–8·00; p<0·0001). Overall, bivalirudin-based regimens lowered the risk of major bleeding (risk ratio 0·62, 95% CI 0·49–0·78; p<0·0001), but the magnitude of this effect varied greatly (p<0·0001) depending on whether glycoprotein IIb/IIIa inhibitors were used predominantly in the heparin arm only (0·53, 0·47–0·61; p<0·0001), provisionally in both arms (0·78, 0·51–1·19; p=0·25), or planned in both arms (1·07, 0·87–1·31; p=0·53). Interpretation Compared with a heparin-based regimen, a bivalirudin-based regimen increases the risk of myocardial infarction and stent thrombosis, but decreases the risk of bleeding, with the magnitude of the reduction depending on concomitant glycoprotein IIb/IIIa inhibitor use. Physicians should weigh the trade-off between ischaemic and bleeding events when choosing between different anticoagulant regimens. Funding None.


      PubDate: 2014-08-18T15:23:55Z
       
  • LDL cholesterol: controversies and future therapeutic directions
    • Abstract: Publication date: 16–22 August 2014
      Source:The Lancet, Volume 384, Issue 9943
      Author(s): Paul M Ridker
      Lifelong exposure to raised concentrations of LDL cholesterol increases cardiovascular event rates, and the use of statin therapy as an adjunct to diet, exercise, and smoking cessation has proven highly effective in reducing the population burden associated with hyperlipidaemia. Yet, despite consistent biological, genetic, and epidemiological data, and evidence from randomised trials, there is controversy among national guidelines and clinical practice with regard to LDL cholesterol, its measurement, the usefulness of population-based screening, the net benefit-to-risk ratio for different LDL-lowering drugs, the benefit of treatment targets, and whether aggressive lowering of LDL is safe. Several novel therapies have been introduced for the treatment of people with genetic defects that result in loss of function within the LDL receptor, a major determinant of inherited hyperlipidaemias. Moreover, the usefulness of monoclonal antibodies that extend the LDL-receptor lifecycle (and thus result in substantial lowering of LDL cholesterol below the levels achieved with statins alone) is being assessed in phase 3 trials that will enrol more than 60 000 at-risk patients worldwide. These trials represent an exceptionally rapid translation of genetic observations into clinical practice and will address core questions of how low LDL cholesterol can be safely reduced, whether the mechanism of LDL-cholesterol lowering matters, and whether ever more aggressive lipid-lowering provides a safe, long-term mechanism to prevent atherothrombotic complications.


      PubDate: 2014-08-18T15:23:55Z
       
  • HDL and cardiovascular disease
    • Abstract: Publication date: 16–22 August 2014
      Source:The Lancet, Volume 384, Issue 9943
      Author(s): Daniel J Rader , G Kees Hovingh
      The cholesterol contained within HDL is inversely associated with risk of coronary heart disease and is a key component of predicting cardiovascular risk. However, despite its properties consistent with atheroprotection, the causal relation between HDL and atherosclerosis is uncertain. Human genetics and failed clinical trials have created scepticism about the HDL hypothesis. Nevertheless, drugs that raise HDL-C concentrations, cholesteryl ester transfer protein inhibitors, are in late-stage clinical development, and other approaches that promote HDL function, including reverse cholesterol transport, are in early-stage clinical development. The final chapters regarding the effect of HDL-targeted therapeutic interventions on coronary heart disease events remain to be written.


      PubDate: 2014-08-18T15:23:55Z
       
  • Triglycerides and cardiovascular disease
    • Abstract: Publication date: 16–22 August 2014
      Source:The Lancet, Volume 384, Issue 9943
      Author(s): Børge G Nordestgaard , Anette Varbo
      After the introduction of statins, clinical emphasis first focussed on LDL cholesterol-lowering, then on the potential for raising HDL cholesterol, with less focus on lowering triglycerides. However, the understanding from genetic studies and negative results from randomised trials that low HDL cholesterol might not cause cardiovascular disease as originally thought has now generated renewed interest in raised concentrations of triglycerides. This renewed interest has also been driven by epidemiological and genetic evidence supporting raised triglycerides, remnant cholesterol, or triglyceride-rich lipoproteins as an additional cause of cardiovascular disease and all-cause mortality. Triglycerides can be measured in the non-fasting or fasting states, with concentrations of 2–10 mmol/L conferring increased risk of cardiovascular disease, and concentrations greater than 10 mmol/L conferring increased risk of acute pancreatitis and possibly cardiovascular disease. Although randomised trials showing cardiovascular benefit of triglyceride reduction are scarce, new triglyceride-lowering drugs are being developed, and large-scale trials have been initiated that will hopefully provide conclusive evidence as to whether lowering triglycerides reduces the risk of cardiovascular disease.


      PubDate: 2014-08-18T15:23:55Z
       
  • Acute retinal necrosis presenting as bilateral acute angle closure
    • Abstract: Publication date: 16–22 August 2014
      Source:The Lancet, Volume 384, Issue 9943
      Author(s): Sushmita Kaushik , Neiwete Lomi , Mini P Singh , Surinder Singh Pandav , Amod Gupta



      PubDate: 2014-08-18T15:23:55Z
       
  • Israel–Gaza conflict
    • Abstract: Publication date: Available online 14 August 2014
      Source:The Lancet
      Author(s): Leonid Eidelman , Arnon Afek



      PubDate: 2014-08-18T15:23:55Z
       
  • Gas in the retropharyngeal space: descending necrotising mediastinitis
    • Abstract: Publication date: Available online 14 August 2014
      Source:The Lancet
      Author(s): Kenta Watanabe , Yuki Kimura , Tetsuya Obara



      PubDate: 2014-08-18T15:23:55Z
       
  • Safety and tolerability of chikungunya virus-like particle vaccine in
           healthy adults: a phase 1 dose-escalation trial
    • Abstract: Publication date: Available online 14 August 2014
      Source:The Lancet
      Author(s): Lee-Jah Chang , Kimberly A Dowd , Floreliz H Mendoza , Jamie G Saunders , Sandra Sitar , Sarah H Plummer , Galina Yamshchikov , Uzma N Sarwar , Zonghui Hu , Mary E Enama , Robert T Bailer , Richard A Koup , Richard M Schwartz , Wataru Akahata , Gary J Nabel , John R Mascola , Theodore C Pierson , Barney S Graham , Julie E Ledgerwood
      Background Chikungunya virus—a mosquito-borne alphavirus—is endemic in Africa and south and southeast Asia and has recently emerged in the Caribbean. No drugs or vaccines are available for treatment or prevention. We aimed to assess the safety, tolerability, and immunogenicity of a new candidate vaccine. Methods VRC 311 was a phase 1, dose-escalation, open-label clinical trial of a virus-like particle (VLP) chikungunya virus vaccine, VRC-CHKVLP059-00-VP, in healthy adults aged 18–50 years who were enrolled at the National Institutes of Health Clinical Center (Bethesda, MD, USA). Participants were assigned to sequential dose level groups to receive vaccinations at 10 μg, 20 μg, or 40 μg on weeks 0, 4, and 20, with follow-up for 44 weeks after enrolment. The primary endpoints were safety and tolerability of the vaccine. Secondary endpoints were chikungunya virus-specific immune responses assessed by ELISA and neutralising antibody assays. This trial is registered with ClinicalTrials.gov, NCT01489358. Findings 25 participants were enrolled from Dec 12, 2011, to March 22, 2012, into the three dosage groups: 10 μg (n=5), 20 μg (n=10), and 40 μg (n=10). The protocol was completed by all five participants at the 10 μg dose, all ten participants at the 20 μg dose, and eight of ten participants at the 40 μg dose; non-completions were for personal circumstances unrelated to adverse events. 73 vaccinations were administered. All injections were well tolerated, with no serious adverse events reported. Neutralising antibodies were detected in all dose groups after the second vaccination (geometric mean titres of the half maximum inhibitory concentration: 2688 in the 10 μg group, 1775 in the 20 μg group, and 7246 in the 40 μg group), and a significant boost occurred after the third vaccination in all dose groups (10 μg group p=0·0197, 20 μg group p<0·0001, and 40 μg group p<0·0001). 4 weeks after the third vaccination, the geometric mean titres of the half maximum inhibitory concentration were 8745 for the 10 μg group, 4525 for the 20 μg group, and 5390 for the 40 μg group. Interpretation The chikungunya VLP vaccine was immunogenic, safe, and well tolerated. This study represents an important step in vaccine development to combat this rapidly emerging pathogen. Further studies should be done in a larger number of participants and in more diverse populations. Funding Intramural Research Program of the Vaccine Research Center, National Institute of Allergy and Infectious Diseases, and National Institutes of Health.


      PubDate: 2014-08-18T15:23:55Z
       
  • Chikungunya virus control: is a vaccine on the horizon'
    • Abstract: Publication date: Available online 14 August 2014
      Source:The Lancet
      Author(s): Ann M Powers



      PubDate: 2014-08-18T15:23:55Z
       
  • Congress stalls on BRAIN Initiative funding
    • Abstract: Publication date: Available online 13 August 2014
      Source:The Lancet
      Author(s): Susan Jaffe



      PubDate: 2014-08-14T15:18:38Z
       
  • Body-mass index and risk of 22 specific cancers: a population-based cohort
           study of 5·24 million UK adults
    • Abstract: Publication date: Available online 13 August 2014
      Source:The Lancet
      Author(s): Krishnan Bhaskaran , Ian Douglas , Harriet Forbes , Isabel dos-Santos-Silva , David A Leon , Liam Smeeth
      Background High body-mass index (BMI) predisposes to several site-specific cancers, but a large-scale systematic and detailed characterisation of patterns of risk across all common cancers adjusted for potential confounders has not previously been undertaken. We aimed to investigate the links between BMI and the most common site-specific cancers. Methods With primary care data from individuals in the Clinical Practice Research Datalink with BMI data, we fitted Cox models to investigate associations between BMI and 22 of the most common cancers, adjusting for potential confounders. We fitted linear then non-linear (spline) models; investigated effect modification by sex, menopausal status, smoking, and age; and calculated population effects. Findings 5·24 million individuals were included; 166 955 developed cancers of interest. BMI was associated with 17 of 22 cancers, but effects varied substantially by site. Each 5 kg/m2 increase in BMI was roughly linearly associated with cancers of the uterus (hazard ratio [HR] 1·62, 99% CI 1·56–1·69; p<0·0001), gallbladder (1·31, 1·12–1·52; p<0·0001), kidney (1·25, 1·17–1·33; p<0·0001), cervix (1·10, 1·03–1·17; p=0·00035), thyroid (1·09, 1·00–1·19; p=0·0088), and leukaemia (1·09, 1·05–1·13; p≤0·0001). BMI was positively associated with liver (1·19, 1·12–1·27), colon (1·10, 1·07–1·13), ovarian (1·09, 1.04–1.14), and postmenopausal breast cancers (1·05, 1·03–1·07) overall (all p<0·0001), but these effects varied by underlying BMI or individual-level characteristics. We estimated inverse associations with prostate and premenopausal breast cancer risk, both overall (prostate 0·98, 0·95–1·00; premenopausal breast cancer 0·89, 0·86–0·92) and in never-smokers (prostate 0·96, 0·93–0·99; premenopausal breast cancer 0·89, 0·85–0·94). By contrast, for lung and oral cavity cancer, we observed no association in never smokers (lung 0·99, 0·93–1·05; oral cavity 1·07, 0·91–1·26): inverse associations overall were driven by current smokers and ex-smokers, probably because of residual confounding by smoking amount. Assuming causality, 41% of uterine and 10% or more of gallbladder, kidney, liver, and colon cancers could be attributable to excess weight. We estimated that a 1 kg/m2 population-wide increase in BMI would result in 3790 additional annual UK patients developing one of the ten cancers positively associated with BMI. Interpretation BMI is associated with cancer risk, with substantial population-level effects. The heterogeneity in the effects suggests that different mechanisms are associated with different cancer sites and different patient subgroups. Funding National Institute for Health Research, Wellcome Trust, and Medical Research Council.


      PubDate: 2014-08-14T15:18:38Z
       
  • Africa's child demographics and the world's future
    • Abstract: Publication date: Available online 13 August 2014
      Source:The Lancet
      Author(s): Jeffrey O’Malley , Tessa Wardlaw , Danzhen You , Lucia Hug , David Anthony



      PubDate: 2014-08-14T15:18:38Z
       
  • Obesity: a certain and avoidable cause of cancer
    • Abstract: Publication date: Available online 13 August 2014
      Source:The Lancet
      Author(s): Peter T Campbell



      PubDate: 2014-08-14T15:18:38Z
       
  • Letter in support of Richard Horton
    • Abstract: Publication date: Available online 11 August 2014
      Source:The Lancet
      Author(s): Lincoln Chen , Jennifer Leaning



      PubDate: 2014-08-14T15:18:38Z
       
  • Israel–Gaza conflict
    • Abstract: Publication date: Available online 11 August 2014
      Source:The Lancet
      Author(s): Yoram Blachar



      PubDate: 2014-08-14T15:18:38Z
       
  • Risk factors and early origins of chronic obstructive pulmonary disease
    • Abstract: Publication date: Available online 11 August 2014
      Source:The Lancet
      Author(s): Dirkje S Postma , Andrew Bush , Maarten van den Berge
      Chronic obstructive pulmonary disease is mainly a smoking-related disorder and affects millions of people worldwide, with a large effect on individual patients and society as a whole. Although the disease becomes clinically apparent around the age of 40–50 years, its origins can begin very early in life. Different risk factors in very early life—ie, in utero and during early childhood—drive the development of clinically apparent chronic obstructive pulmonary disease in later life. In discussions of which risk factors drive chronic obstructive pulmonary disease, it is important to realise that the disease is very heterogeneous and at present is largely diagnosed by lung function only. In this Review, we will discuss the evidence for risk factors for the various phenotypes of chronic obstructive pulmonary disease during different stages of life.


      PubDate: 2014-08-14T15:18:38Z
       
  • Israel–Gaza conflict
    • Abstract: Publication date: Available online 11 August 2014
      Source:The Lancet
      Author(s): Hind Khalifeh



      PubDate: 2014-08-14T15:18:38Z
       
  • Antenatal corticosteroids 40 years on: we can do better
    • Abstract: Publication date: Available online 12 August 2014
      Source:The Lancet
      Author(s): Stuart R Dalziel , Caroline A Crowther , Jane E Harding



      PubDate: 2014-08-14T15:18:38Z
       
  • Use of antenatal corticosteroids and tocolytic drugs in preterm births in
           29 countries: an analysis of the WHO Multicountry Survey on Maternal and
           Newborn Health
    • Abstract: Publication date: Available online 12 August 2014
      Source:The Lancet
      Author(s): Joshua P Vogel , João Paulo Souza , A Metin Gülmezoglu , Rintaro Mori , Pisake Lumbiganon , Zahida Qureshi , Guillermo Carroli , Malinee Laopaiboon , Bukola Fawole , Togoobaatar Ganchimeg , Jun Zhang , Maria Regina Torloni , Meghan Bohren , Marleen Temmerman
      Background Despite the global burden of morbidity and mortality associated with preterm birth, little evidence is available for use of antenatal corticosteroids and tocolytic drugs in preterm births in low-income and middle-income countries. We analysed data from the WHO Multicountry Survey on Maternal and Newborn Health (WHOMCS) to assess coverage for these interventions in preterm deliveries. Methods WHOMCS is a facility-based, cross-sectional survey database of birth outcomes in 359 facilities in 29 countries, with data collected prospectively from May 1, 2010, to Dec 31, 2011. For this analysis, we included deliveries after 22 weeks' gestation and we excluded births that occurred outside a facility or quicker than 3 h after arrival. We calculated use of antenatal corticosteroids in women who gave birth between 26 and 34 weeks' gestation, when antenatal corticosteroids are known to be most beneficial. We also calculated use in women at 22–25 weeks' and 34–36 weeks' gestation. We assessed tocolytic drug use, with and without antenatal corticosteroids, in spontaneous, uncomplicated preterm deliveries at 26–34 weeks' gestation. Findings Of 303 842 recorded deliveries after 22 weeks' gestation, 17 705 (6%) were preterm. 3900 (52%) of 7547 women who gave birth at 26–34 weeks' gestation, 94 (19%) of 497 women who gave birth at 22–25 weeks' gestation, and 2276 (24%) of 9661 women who gave birth at 35–36 weeks' gestation received antenatal corticosteroids. Rates of antenatal corticosteroid use varied between countries (median 54%, range 16–91%; IQR 30–68%). Of 4677 women who were potentially eligible for tocolysis drugs, 1276 (27%) were treated with bed rest or hydration and 2248 (48%) received no treatment. β-agonists alone (n=346, 7%) were the most frequently used tocolytic drug. Only 848 (18%) of potentially eligible women received both a tocolytic drug and antenatal corticosteroids. Interpretation Use of interventions was generally poor, despite evidence for their benefit for newborn babies. A substantial proportion of antenatal corticosteroid use occurred at gestational ages at which benefit is controversial, and use of less effective or potentially harmful tocolytic drugs was common. Implementation research and contextualised health policies are needed to improve drug availability and increase compliance with best obstetric practice. Funding UNDP–UNFPA–UNICEF–WHO–World Bank Special Programme of Research, Development and Research Training in Human Reproduction (HRP); WHO; USAID; Ministry of Health, Labour and Welfare of Japan; Gynuity Health Projects.


      PubDate: 2014-08-14T15:18:38Z
       
  • Israel–Gaza conflict
    • Abstract: Publication date: Available online 7 August 2014
      Source:The Lancet
      Author(s): Cindy Sousa , Amy Hagopian , Nancy Stoller



      PubDate: 2014-08-09T15:13:35Z
       
 
 
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