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Journal Cover The Lancet
  [SJR: 14.638]   [H-I: 600]   [2183 followers]  Follow
    
   Full-text available via subscription Subscription journal
   ISSN (Print) 0140-6736 - ISSN (Online) 1474-547X
   Published by Elsevier Homepage  [3048 journals]
  • 2017 Prince Mahidol Award winners announced
    • Authors: Andrew Green
      Abstract: Publication date: 18–24 November 2017
      Source:The Lancet, Volume 390, Issue 10109
      Author(s): Andrew Green


      PubDate: 2017-11-18T15:48:58Z
      DOI: 10.1016/s0140-6736(17)32902-1
       
  • Effectiveness trials in asthma: time to SaLSA'
    • Authors: Peter Gibson
      Pages: 2217 - 2218
      Abstract: Publication date: 18–24 November 2017
      Source:The Lancet, Volume 390, Issue 10109
      Author(s): Peter Gibson


      PubDate: 2017-11-18T15:48:58Z
      DOI: 10.1016/s0140-6736(17)32398-x
       
  • Population-based screening for vascular disease
    • Authors: Chadi Ayoub; M Hassan Murad
      Pages: 2218 - 2220
      Abstract: Publication date: 18–24 November 2017
      Source:The Lancet, Volume 390, Issue 10109
      Author(s): Chadi Ayoub, M Hassan Murad


      PubDate: 2017-11-18T15:48:58Z
      DOI: 10.1016/s0140-6736(17)32291-2
       
  • Antiangiogenesis to curb urothelial cancer
    • Authors: Joaquim Bellmunt
      Pages: 2220 - 2221
      Abstract: Publication date: 18–24 November 2017
      Source:The Lancet, Volume 390, Issue 10109
      Author(s): Joaquim Bellmunt


      PubDate: 2017-11-18T15:48:58Z
      DOI: 10.1016/s0140-6736(17)32388-7
       
  • Ireland's Public Health Bill: crucial to reduce alcohol harm
    • Authors: Frank Murray
      Pages: 2222 - 2223
      Abstract: Publication date: 18–24 November 2017
      Source:The Lancet, Volume 390, Issue 10109
      Author(s): Frank Murray


      PubDate: 2017-11-18T15:48:58Z
      DOI: 10.1016/s0140-6736(17)32759-9
       
  • Improving evidence for health in humanitarian crises
    • Authors: Udani Samarasekera; Richard Horton
      Pages: 2223 - 2224
      Abstract: Publication date: 18–24 November 2017
      Source:The Lancet, Volume 390, Issue 10109
      Author(s): Udani Samarasekera, Richard Horton


      PubDate: 2017-11-18T15:48:58Z
      DOI: 10.1016/s0140-6736(17)31353-3
       
  • Where is the science in humanitarian health'
    • Authors: Ronald J Waldman; Michael J Toole
      Pages: 2224 - 2226
      Abstract: Publication date: 18–24 November 2017
      Source:The Lancet, Volume 390, Issue 10109
      Author(s): Ronald J Waldman, Michael J Toole


      PubDate: 2017-11-18T15:48:58Z
      DOI: 10.1016/s0140-6736(17)31275-8
       
  • Humanitarian medicine is more than a technical exercise
    • Authors: Vickie Hawkins; André Heller Pérache
      Pages: 2226 - 2228
      Abstract: Publication date: 18–24 November 2017
      Source:The Lancet, Volume 390, Issue 10109
      Author(s): Vickie Hawkins, André Heller Pérache


      PubDate: 2017-11-18T15:48:58Z
      DOI: 10.1016/s0140-6736(17)31352-1
       
  • Research ethics and evidence for humanitarian health
    • Authors: Dónal O'Mathúna; Chesmal Siriwardhana
      Pages: 2228 - 2229
      Abstract: Publication date: 18–24 November 2017
      Source:The Lancet, Volume 390, Issue 10109
      Author(s): Dónal O'Mathúna, Chesmal Siriwardhana


      PubDate: 2017-11-18T15:48:58Z
      DOI: 10.1016/s0140-6736(17)31276-x
       
  • Offline: WHO—a roadmap to renewal'
    • Authors: Richard Horton
      First page: 2230
      Abstract: Publication date: 18–24 November 2017
      Source:The Lancet, Volume 390, Issue 10109
      Author(s): Richard Horton


      PubDate: 2017-11-18T15:48:58Z
      DOI: 10.1016/s0140-6736(17)32904-5
       
  • Towards introducing ACOs in the NHS
    • Authors: Talha Burki
      First page: 2231
      Abstract: Publication date: 18–24 November 2017
      Source:The Lancet, Volume 390, Issue 10109
      Author(s): Talha Burki


      PubDate: 2017-11-18T15:48:58Z
      DOI: 10.1016/s0140-6736(17)32901-x
       
  • Moses Massaquoi: health leader in humanitarian crises
    • Authors: Richard Lane
      First page: 2232
      Abstract: Publication date: 18–24 November 2017
      Source:The Lancet, Volume 390, Issue 10109
      Author(s): Richard Lane


      PubDate: 2017-11-18T15:48:58Z
      DOI: 10.1016/s0140-6736(17)31569-6
       
  • Picturing health: Rohingya refugees in Bangladesh
    • Authors: Danielle Villasana
      Pages: 2233 - 2242
      Abstract: Publication date: 18–24 November 2017
      Source:The Lancet, Volume 390, Issue 10109
      Author(s): Danielle Villasana


      PubDate: 2017-11-18T15:48:58Z
      DOI: 10.1016/s0140-6736(17)32862-3
       
  • Charlottesville: blatant racism, not grievances, on display
    • Authors: Mary T Bassett; Nancy Krieger; Zinzi Bailey
      First page: 2243
      Abstract: Publication date: 18–24 November 2017
      Source:The Lancet, Volume 390, Issue 10109
      Author(s): Mary T Bassett, Nancy Krieger, Zinzi Bailey


      PubDate: 2017-11-18T15:48:58Z
      DOI: 10.1016/s0140-6736(17)32855-6
       
  • Bisphosphonates in osteoporosis: NICE and easy'
    • Authors: Nicholas C Harvey; Eugene McCloskey; John A Kanis; Juliet Compston; Cyrus Cooper
      Pages: 2243 - 2244
      Abstract: Publication date: 18–24 November 2017
      Source:The Lancet, Volume 390, Issue 10109
      Author(s): Nicholas C Harvey, Eugene McCloskey, John A Kanis, Juliet Compston, Cyrus Cooper


      PubDate: 2017-11-18T15:48:58Z
      DOI: 10.1016/s0140-6736(17)32850-7
       
  • On evidence-based medicine
    • Authors: Marjolein A van der Marck; René J F Melis; Marcel G M Olde Rikkert
      Pages: 2244 - 2245
      Abstract: Publication date: 18–24 November 2017
      Source:The Lancet, Volume 390, Issue 10109
      Author(s): Marjolein A van der Marck, René J F Melis, Marcel G M Olde Rikkert


      PubDate: 2017-11-18T15:48:58Z
      DOI: 10.1016/s0140-6736(17)32851-9
       
  • On evidence-based medicine
    • Authors: Jan Matthys
      First page: 2245
      Abstract: Publication date: 18–24 November 2017
      Source:The Lancet, Volume 390, Issue 10109
      Author(s): Jan Matthys


      PubDate: 2017-11-18T15:48:58Z
      DOI: 10.1016/s0140-6736(17)32852-0
       
  • On evidence-based medicine
    • Authors: Feras Ali Mustafa
      First page: 2245
      Abstract: Publication date: 18–24 November 2017
      Source:The Lancet, Volume 390, Issue 10109
      Author(s): Feras Ali Mustafa


      PubDate: 2017-11-18T15:48:58Z
      DOI: 10.1016/s0140-6736(17)32853-2
       
  • On evidence-based medicine – Authors' reply
    • Authors: Benjamin Djulbegovic; Gordon H Guyatt
      Pages: 2245 - 2246
      Abstract: Publication date: 18–24 November 2017
      Source:The Lancet, Volume 390, Issue 10109
      Author(s): Benjamin Djulbegovic, Gordon H Guyatt


      PubDate: 2017-11-18T15:48:58Z
      DOI: 10.1016/s0140-6736(17)32854-4
       
  • Practical applications of evolutionary biology in public health
    • Authors: C Mary Schooling
      First page: 2246
      Abstract: Publication date: 18–24 November 2017
      Source:The Lancet, Volume 390, Issue 10109
      Author(s): C Mary Schooling


      PubDate: 2017-11-18T15:48:58Z
      DOI: 10.1016/s0140-6736(17)32462-5
       
  • Population screening and intervention for vascular disease in Danish men
           (VIVA): a randomised controlled trial
    • Authors: Jes S Lindholt; Rikke Søgaard
      Pages: 2256 - 2265
      Abstract: Publication date: 18–24 November 2017
      Source:The Lancet, Volume 390, Issue 10109
      Author(s): Jes S Lindholt, Rikke Søgaard
      Background Abdominal aortic aneurysm is the only cardiovascular disease targeted by population screening. In this study, we test the effect of screening and subsequent intervention for abdominal aortic aneurysm, peripheral arterial disease, and hypertension combined. Methods In this randomised controlled trial, we randomly allocated (1:1) all men aged 65–74 years living in the Central Denmark Region to screening for abdominal aortic aneurysm, peripheral arterial disease, and hypertension, or to no screening. We based allocation on computer-generated random numbers from 1 to 100 in blocks of 1067 to 4392, stratified by 19 municipalities. Only the non-screening group and the investigator assessing outcomes were masked. We invited participants who were found to have abdominal aortic aneurysm or peripheral arterial disease back for confirmation and eventual initiation of relevant pharmacological therapy. We further offered participants with abdominal aortic aneurysm annual control or surgical repair. We referred participants with suspected hypertension to their general practitioner. The primary outcome was all-cause mortality, assessed 5 years after randomisation, analysed in all randomly allocated participants except for those who had incorrect person identification numbers. This trial is registered at ClinicalTrials.gov, number NCT00662480. Findings Between Oct 8, 2008, and Jan 11, 2011, we randomly allocated 50 156 participants, with 25 078 (50%) each in the screening and non-screening groups. Four (<1%) participants in the screening group were lost to follow-up. After a median follow-up of 4·4 years (IQR 3·9–4·8), 2566 (10·2%) of 25 074 participants in the screening group and 2715 (10·8%) of 25 078 in the non-screening group had died. This finding resulted in a significant hazard ratio of 0·93 (95% CI 0·88–0·98; p=0·01), an absolute risk reduction of 0·006 (0·001–0·011), and a number needed to invite of 169 (89–1811). Incidences of diabetes (3995 per 100 000 person-years in the screening group vs 4129 per 100 000 person-years in the non-screening group), intracerebral haemorrhage (146 vs 140), renal failure (612 vs 649), cancer (3578 vs 3719), or 30 day mortality after cardiovascular surgery (44·57 vs 39·33) did not differ between groups. Interpretation The observed reduction of mortality risk from abdominal aortic aneurysm, peripheral arterial disease, and hypertension has never been seen before in the population screening literature and can be linked primarily to initiation of pharmacological therapy. Health policy makers should consider implementing combined screening whether no screening or isolated abdominal aortic aneurysm screening is currently offered. Funding The 7th European Framework Programme, Central Denmark Region, Viborg Hospital, and the Danish Council for Independent Research.

      PubDate: 2017-11-18T15:48:58Z
      DOI: 10.1016/s0140-6736(17)32250-x
       
  • Attacks against health care in Syria, 2015–16: results from a
           real-time reporting tool
    • Authors: Mohamed Elamein; Hilary Bower; Camilo Valderrama; Daher Zedan; Hazem Rihawi; Khaled Almilaji; Mohammed Abdelhafeez; Nabil Tabbal; Naser Almhawish; Sophie Maes; Alaa AbouZeid
      Pages: 2278 - 2286
      Abstract: Publication date: 18–24 November 2017
      Source:The Lancet, Volume 390, Issue 10109
      Author(s): Mohamed Elamein, Hilary Bower, Camilo Valderrama, Daher Zedan, Hazem Rihawi, Khaled Almilaji, Mohammed Abdelhafeez, Nabil Tabbal, Naser Almhawish, Sophie Maes, Alaa AbouZeid
      Background Collecting credible data on violence against health services, health workers, and patients in war zones is a massive challenge, but crucial to understanding the extent to which international humanitarian law is being breached. We describe a new system used mainly in areas of Syria with a substantial presence of armed opposition groups since November, 2015, to detect and verify attacks on health-care services and describe their effect. Methods All Turkey health cluster organisations with a physical presence in Syria, either through deployed and locally employed staff, were asked to participate in the Monitoring Violence against Health Care (MVH) alert network. The Turkey hub of the health cluster, a UN-activated humanitarian health coordination body, received alerts from health cluster partners via WhatsApp and an anonymised online data-entry tool. Field staff were asked to seek further information by interviewing victims and other witnesses when possible. The MVH data team triangulated alerts to identify individual events and distributed a preliminary flash update of key information (location, type of service, modality of attack, deaths, and casualties) to partners, WHO, United Nations Office for the Coordination of Humanitarian Affairs, and donors. The team also received and entered alerts from several large non-health cluster organisations (known as external partners, who do their own information-gathering and verification processes before sharing their information). Each incident was then assessed in a stringent process of information-matching. Attacks were deemed to be verified if they were reported by a minimum of one health cluster partner and one external partner, and the majority of the key datapoints matched. Alerts that did not meet this standard were deemed to be unverified. Results were tabulated to describe attack occurrence and impact, disaggregated where possible by age, sex, and location. Findings Between early November, 2015, and Dec 31 2016, 938 people were directly harmed in 402 incidents of violence against health care: 677 (72%) were wounded and 261 (28%) were killed. Most of the dead were adult males (68%), but the highest case fatality (39%) was seen in children aged younger than 5 years. 24% of attack victims were health workers. Around 44% of hospitals and 5% of all primary care clinics in mainly areas with a substantial presence of armed opposition groups experienced attacks. Aerial bombardment was the main form of attack. A third of health-care services were hit more than once. Services providing trauma care were attacked more than other services. Interpretation The data system used in this study addressed double-counting, reduced the effect of potentially biased self-reports, and produced credible data from anonymous information. The MVH tool could be feasibly deployed in many conflict areas. Reliable data are essential to show how far warring parties have strayed from international law protecting health care in conflict and to effectively harness legal mechanisms to discourage future perpetrators. Funding None.

      PubDate: 2017-11-18T15:48:58Z
      DOI: 10.1016/s0140-6736(17)31328-4
       
  • Evidence on public health interventions in humanitarian crises
    • Authors: Karl Blanchet; Anita Ramesh; Severine Frison; Emily Warren; Mazeda Hossain; James Smith; Abigail Knight; Nathan Post; Christopher Lewis; Aniek Woodward; Maysoon Dahab; Alexander Ruby; Vera Sistenich; Sara Pantuliano; Bayard Roberts
      Pages: 2287 - 2296
      Abstract: Publication date: 18–24 November 2017
      Source:The Lancet, Volume 390, Issue 10109
      Author(s): Karl Blanchet, Anita Ramesh, Severine Frison, Emily Warren, Mazeda Hossain, James Smith, Abigail Knight, Nathan Post, Christopher Lewis, Aniek Woodward, Maysoon Dahab, Alexander Ruby, Vera Sistenich, Sara Pantuliano, Bayard Roberts
      Recognition of the need for evidence-based interventions to help to improve the effectiveness and efficiency of humanitarian responses has been increasing. However, little is known about the breadth and quality of evidence on health interventions in humanitarian crises. We describe the findings of a systematic review with the aim of examining the quantity and quality of evidence on public health interventions in humanitarian crises to identify key research gaps. We identified 345 studies published between 1980 and 2014 that met our inclusion criteria. The quantity of evidence varied substantially by health topic, from communicable diseases (n=131), nutrition (n=77), to non-communicable diseases (n=8), and water, sanitation, and hygiene (n=6). We observed common study design and weaknesses in the methods, which substantially reduced the ability to determine causation and attribution of the interventions. Considering the major increase in health-related humanitarian activities in the past three decades and calls for a stronger evidence base, this paper highlights the limited quantity and quality of health intervention research in humanitarian contexts and supports calls to scale up this research.

      PubDate: 2017-11-18T15:48:58Z
      DOI: 10.1016/s0140-6736(16)30768-1
       
  • Public health information in crisis-affected populations: a review of
           methods and their use for advocacy and action
    • Authors: Francesco Checchi; Abdihamid Warsame; Victoria Treacy-Wong; Jonathan Polonsky; Mark van Ommeren; Claudine Prudhon
      Pages: 2297 - 2313
      Abstract: Publication date: 18–24 November 2017
      Source:The Lancet, Volume 390, Issue 10109
      Author(s): Francesco Checchi, Abdihamid Warsame, Victoria Treacy-Wong, Jonathan Polonsky, Mark van Ommeren, Claudine Prudhon
      Valid and timely information about various domains of public health underpins the effectiveness of humanitarian public health interventions in crises. However, obstacles including insecurity, insufficient resources and skills for data collection and analysis, and absence of validated methods combine to hamper the quantity and quality of public health information available to humanitarian responders. This paper, the second in a Series of four papers, reviews available methods to collect public health data pertaining to different domains of health and health services in crisis settings, including population size and composition, exposure to armed attacks, sexual and gender-based violence, food security and feeding practices, nutritional status, physical and mental health outcomes, public health service availability, coverage and effectiveness, and mortality. The paper also quantifies the availability of a minimal essential set of information in large armed conflict and natural disaster crises since 2010: we show that information was available and timely only in a small minority of cases. On the basis of this observation, we propose an agenda for methodological research and steps required to improve on the current use of available methods. This proposition includes setting up a dedicated interagency service for public health information and epidemiology in crises.

      PubDate: 2017-11-18T15:48:58Z
      DOI: 10.1016/s0140-6736(17)30702-x
       
  • Recurrent failings of medical humanitarianism: intractable, ignored, or
           just exaggerated'
    • Authors: Sandro Colombo; Enrico Pavignani
      Pages: 2314 - 2324
      Abstract: Publication date: 18–24 November 2017
      Source:The Lancet, Volume 390, Issue 10109
      Author(s): Sandro Colombo, Enrico Pavignani
      Humanitarian health workers operate in dangerous and uncertain contexts, in which mistakes and failures are common, often have severe consequences, and are regularly repeated, despite being documented by many reviews. This Series paper aims to discuss the failures of medical humanitarianism. We describe why some of these recurrent failings, which are often not identified until much later, seem intractable: they are so entrenched in humanitarian action that they cannot be addressed by simple technical fixes. We argue that relief health-care interventions should be contextualised. Perhaps medical humanitarianism deserves a better reputation than the one at times tarnished by unfair criticism, resulting from inapplicable guiding principles and unrealistic expectations. The present situation is not conducive to radical reforms of humanitarian medicine; complex crises multiply and no political, diplomatic, or military solutions are in sight. Relief agencies have to compete for financial resources that do not increase at the same pace as health needs. Avoiding the repetition of failures requires recognising previous mistakes and addressing them through different policies by donors, stronger documentation and analysis of humanitarian programmes and interventions, increased professionalisation, improved, opportunistic relationships with the media, and better ways of working together with local health stakeholders and through indigenous institutions.

      PubDate: 2017-11-18T15:48:58Z
      DOI: 10.1016/s0140-6736(17)31277-1
       
  • Alcohol and cancer
    • Authors: Lancet
      Abstract: Publication date: 18–24 November 2017
      Source:The Lancet, Volume 390, Issue 10109
      Author(s): The Lancet


      PubDate: 2017-11-18T15:48:58Z
       
  • Does mobile health matter'
    • Authors: Lancet
      Abstract: Publication date: 18–24 November 2017
      Source:The Lancet, Volume 390, Issue 10109
      Author(s): The Lancet


      PubDate: 2017-11-18T15:48:58Z
       
  • Food industry must act to safeguard the future of antibiotics
    • Authors: Lancet
      Abstract: Publication date: 18–24 November 2017
      Source:The Lancet, Volume 390, Issue 10109
      Author(s): The Lancet


      PubDate: 2017-11-18T15:48:58Z
       
  • Department of Error
    • Abstract: Publication date: 18–24 November 2017
      Source:The Lancet, Volume 390, Issue 10109


      PubDate: 2017-11-18T15:48:58Z
       
  • Effectiveness of fluticasone furoate plus vilanterol on asthma control in
           clinical practice: an open-label, parallel group, randomised controlled
           trial
    • Authors: Ashley Woodcock; Vestbo Nawar Diar Bakerly John New Martin Gibson
      Abstract: Publication date: 18–24 November 2017
      Source:The Lancet, Volume 390, Issue 10109
      Author(s): Ashley Woodcock, Jørgen Vestbo, Nawar Diar Bakerly, John New, J Martin Gibson, Sheila McCorkindale, Rupert Jones, Susan Collier, James Lay-Flurrie, Lucy Frith, Loretta Jacques, Joanne L Fletcher, Catherine Harvey, Henrik Svedsater, David Leather
      Background Evidence for management of asthma comes from closely monitored efficacy trials done in highly selected patient groups. There is a need for randomised trials that are closer to usual clinical practice. Methods We did an open-label, randomised, controlled, two-arm effectiveness trial at 74 general practice clinics in Salford and South Manchester, UK. Patients aged 18 years or older with a general practitioner's diagnosis of symptomatic asthma and on maintenance inhaler therapy were randomly assigned to initiate treatment with a once-daily inhaled combination of either 100 μg or 200 μg fluticasone furoate with 25 μg vilanterol or optimised usual care and followed up for 12 months. The primary endpoint was the percentage of patients who achieved an asthma control test (ACT) score of 20 or greater or an increase in ACT score from baseline of 3 or greater at 24 weeks (termed responders), in patients with a baseline ACT score less than 20 (the primary effectiveness analysis population). All effectiveness analyses were done according to the intention-to-treat principle. This study is registered with ClinicalTrials.gov, number NCT01706198. Findings Between Nov 12, 2012, and Dec 16, 2016, 4725 patients were enrolled and 4233 randomly assigned to initiate treatment with fluticasone furoate and vilanterol (n=2114) or usual care (n=2119). 1207 patients (605 assigned to usual care, 602 to fluticasone furoate and vilanterol) had a baseline ACT score greater than or equal to 20 and were thus excluded from the primary effectiveness analysis population. At week 24, the odds of being a responder were higher for patients who initiated treatment with fluticasone furoate and vilanterol than for those on usual care (977 [71%] of 1373 in the fluticasone furoate and vilanterol group vs 784 [56%] of 1399 in the usual care group; odds ratio [OR] 2·00 [95% CI 1·70–2·34], p<0·0001). At week 24, the adjusted mean ACT score increased by 4·4 points from baseline in patients initiated with fluticasone furoate and vilanterol, compared with 2·8 points in the usual care group (difference 1·6 [95% CI 1·3–2·0], p<0·0001). This result was consistent for the duration of the study. Pneumonia was uncommon, with no differences between groups; there was no difference in other serious adverse events between the groups. Interpretation In patients with a general practitioner's diagnosis of symptomatic asthma and on maintenance inhaler therapy, initiation of a once-daily treatment regimen of combined fluticasone furoate and vilanterol improved asthma control without increasing the risk of serious adverse events when compared with optimised usual care. Funding GlaxoSmithKline.

      PubDate: 2017-11-18T15:48:58Z
       
  • Ramucirumab plus docetaxel versus placebo plus docetaxel in patients with
           locally advanced or metastatic urothelial carcinoma after platinum-based
           therapy (RANGE): a randomised, double-blind, phase 3 trial
    • Authors: Daniel Petrylak; Ronald Wit Kim Chi Alexandra Drakaki Cora Sternberg
      Abstract: Publication date: 18–24 November 2017
      Source:The Lancet, Volume 390, Issue 10109
      Author(s): Daniel P Petrylak, Ronald de Wit, Kim N Chi, Alexandra Drakaki, Cora N Sternberg, Hiroyuki Nishiyama, Daniel Castellano, Syed Hussain, Aude Fléchon, Aristotelis Bamias, Evan Y Yu, Michiel S van der Heijden, Nobuaki Matsubara, Boris Alekseev, Andrea Necchi, Lajos Géczi, Yen-Chuan Ou, Hasan Senol Coskun, Wen-Pin Su, Miriam Hegemann, Ivor J Percent, Jae-Lyun Lee, Marcello Tucci, Andrey Semenov, Fredrik Laestadius, Avivit Peer, Giampaolo Tortora, Sufia Safina, Xavier Garcia del Muro, Alejo Rodriguez-Vida, Irfan Cicin, Hakan Harputluoglu, Ryan C Widau, Astra M Liepa, Richard A Walgren, Oday Hamid, Annamaria H Zimmermann, Katherine M Bell-McGuinn, Thomas Powles
      Background Few treatments with a distinct mechanism of action are available for patients with platinum-refractory advanced or metastatic urothelial carcinoma. We assessed the efficacy and safety of treatment with docetaxel plus either ramucirumab—a human IgG1 VEGFR-2 antagonist—or placebo in this patient population. Methods We did a randomised, double-blind, phase 3 trial in patients with advanced or metastatic urothelial carcinoma who progressed during or after platinum-based chemotherapy. Patients were enrolled from 124 sites in 23 countries. Previous treatment with one immune-checkpoint inhibitor was permitted. Patients were randomised (1:1) using an interactive web response system to receive intravenous docetaxel 75 mg/m2 plus either intravenous ramucirumab 10 mg/kg or matching placebo on day 1 of repeating 21-day cycles, until disease progression or other discontinuation criteria were met. The primary endpoint was investigator-assessed progression-free survival, analysed by intention-to-treat in the first 437 randomised patients. This study is registered with ClinicalTrials.gov, number NCT02426125. Findings Between July, 2015, and April, 2017, 530 patients were randomly allocated either ramucirumab plus docetaxel (n=263) or placebo plus docetaxel (n=267). Progression-free survival was prolonged significantly in patients allocated ramucirumab plus docetaxel versus placebo plus docetaxel (median 4·07 months [95% CI 2·96–4·47] vs 2·76 months [2·60–2·96]; hazard ratio [HR] 0·757, 95% CI 0·607–0·943; p=0·0118). A blinded independent central analysis was consistent with these results. An objective response was achieved by 53 (24·5%, 95% CI 18·8–30·3) of 216 patients allocated ramucirumab and 31 (14·0%, 9·4–18·6) of 221 assigned placebo. The most frequently reported treatment-emergent adverse events, regardless of causality, in either treatment group (any grade) were fatigue, alopecia, diarrhoea, decreased appetite, and nausea. These events occurred predominantly at grade 1–2 severity. The frequency of grade 3 or worse adverse events was similar for patients allocated ramucirumab and placebo (156 [60%] of 258 vs 163 [62%] of 265 had an adverse event), with no unexpected toxic effects. 63 (24%) of 258 patients allocated ramucirumab and 54 (20%) of 265 assigned placebo had a serious adverse event that was judged by the investigator to be related to treatment. 38 (15%) of 258 patients allocated ramucirumab and 43 (16%) of 265 assigned placebo died on treatment or within 30 days of discontinuation, of which eight (3%) and five (2%) deaths were deemed related to treatment by the investigator. Sepsis was the most common adverse event leading to death on treatment (four [2%] vs none [0%]). One fatal event of neutropenic sepsis was reported in a patient allocated ramucirumab. Interpretation To the best of our knowledge, ramucirumab plus docetaxel is the first regimen in a phase 3 study to show superior progression-free survival over chemotherapy in patients with platinum-refractory advanced urothelial carcinoma. These data validate inhibition of VEGFR-2 signalling as a potential new therapeutic treatment option for patients with urothelial carcinoma. Funding Eli Lilly and Company.

      PubDate: 2017-11-18T15:48:58Z
       
  • Misoprostol drug to be withdrawn from French market
    • Authors: Barbara Casassus
      Abstract: Publication date: Available online 16 November 2017
      Source:The Lancet
      Author(s): Barbara Casassus


      PubDate: 2017-11-18T15:48:58Z
      DOI: 10.1016/s0140-6736(17)32908-2
       
  • Retraction and republication—Misoprostol drug to be withdrawn from
           French market
    • Authors: The Editors of The Lancet
      Abstract: Publication date: Available online 16 November 2017
      Source:The Lancet
      Author(s): The Editors of The Lancet


      PubDate: 2017-11-18T15:48:58Z
      DOI: 10.1016/s0140-6736(17)32907-0
       
  • Investment in child and adolescent health and development: key messages
           from Disease Control Priorities, 3rd Edition
    • Authors: Donald A P Bundy; Nilanthi de Silva; Susan Horton; George C Patton; Linda Schultz; Dean T Jamison; Amina Abubakara; Amrita Ahuja; Harold Alderman; Nicolas Allen; Laura Appleby; Elisabetta Aurino; Peter Azzopardi; Sarah Baird; Louise Banham; Jere Behrman; Habib Benzian; Sonia Bhalotra; Zulfiqar Bhutta; Maureen Black; Paul Bloem; Chris Bonell; Mark Bradley; Sally Brinkman; Simon Brooker; Carmen Burbano; Nicolas Burnett; Tania Cernuschi; Sian Clarke; Carolyn Coffey; Peter Colenso; Kevin Croke; Amy Daniels; Elia De la Cruz; Damien de Walque; Anil Deolaikar; Lesley Drake; Lia Fernald; Meena Fernandes; Deepika Fernando; Günther Fink; Rae Galloway; Aulo Gelli; Andreas Georgiadis; Caroline Gitonga; Boitshepo Giyosa; Paul Glewwe; Joseph Gona Nzovu; Amber Gove; Natasha Graham; Brian Greenwood; Elena Grigorenko; Cai Heath; Joan Hamory Hicks; Melissa Hidrobo; Kenneth Hill; Tara Hill; T. Deirdre Hollingsworth; Elissa Kennedy; Imran Khan; Josephine Kiamba; Jane Kim; Michael Kremer; D. Scott LaMontagne; Zohra Lassi; Ramanan Laxminarayan; Jacqueline Mahon; Lu Mai; Sebastián Martínez; Sergio Meresman; Katherine A. Merseth; Edward Miguel; Arlene Mitchell; Sophie Mitra; Anoosh Moin; Ali Mokdad; Daniel Mont; Arindam Nandi; Joaniter Nankabirwa; Daniel Plaut; Elina Pradhan; Rachel Pullan; Nicola Reavley; Joan Santelli; Bachir Sarr; Susan M Sawyer
      Abstract: Publication date: Available online 16 November 2017
      Source:The Lancet
      Author(s): Donald A P Bundy, Nilanthi de Silva, Susan Horton, George C Patton, Linda Schultz, Dean T Jamison
      The realisation of human potential for development requires age-specific investment throughout the 8000 days of childhood and adolescence. Focus on the first 1000 days is an essential but insufficient investment. Intervention is also required in three later phases: the middle childhood growth and consolidation phase (5–9 years), when infection and malnutrition constrain growth, and mortality is higher than previously recognised; the adolescent growth spurt (10–14 years), when substantial changes place commensurate demands on good diet and health; and the adolescent phase of growth and consolidation (15–19 years), when new responses are needed to support brain maturation, intense social engagement, and emotional control. Two cost-efficient packages, one delivered through schools and one focusing on later adolescence, would provide phase-specific support across the life cycle, securing the gains of investment in the first 1000 days, enabling substantial catch-up from early growth failure, and leveraging improved learning from concomitant education investments.

      PubDate: 2017-11-18T15:48:58Z
      DOI: 10.1016/s0140-6736(17)32417-0
       
  • India—a tale of one country, but stories of many states
    • Authors: Lancet
      Abstract: Publication date: Available online 14 November 2017
      Source:The Lancet
      Author(s): The Lancet


      PubDate: 2017-11-18T15:48:58Z
       
  • Nations within a nation: variations in epidemiological transition across
           the states of India, 1990–2016 in the Global Burden of Disease Study
    • Authors: India State-level; Disease Burden Initiative CollaboratorsLalitDandonaRakhiDandonaG AnilKumarD KShuklaVinod KPaulKalpanaBalakrishnanDorairajPrabhakaranNikhilTandonSundeepSalviA PDashANandakumarVikramPatelSanjay
      Abstract: Publication date: Available online 14 November 2017
      Source:The Lancet
      Author(s): India State-level Disease Burden Initiative CollaboratorsLalitDandonaRakhiDandonaG AnilKumarD KShuklaVinod KPaulKalpanaBalakrishnanDorairajPrabhakaranNikhilTandonSundeepSalviA PDashANandakumarVikramPatelSanjay KAgarwalPrakash CGuptaR SDhaliwalPrashantMathurAvulaLaxmaiahPreet KDhillonSubhojitDeyManu RMathurAshkanAfshinChristinaFitzmauriceEmmanuelaGakidouPeterGethingSimon IHayNicholas JKassebaumHmweKyuStephen SLimMohsenNaghaviGregory ARothJeffrey DStanawayHarveyWhitefordVineet KChadhaSunil DKhapardeRaghuramRaoKirankumarRadePuneetDewanMelissaFurtadoElizaDuttaChris MVargheseRaviMehrotraPJambulingamTanvirKaurMeenakshiSharmaShaliniSinghRashmiAroraReetaRasailyRanjit MAnjanaViswanathanMohanAnuragAgrawalArvindChopraAshish JMathewDeekshaBhardwajPallaviMuraleedharanParulMutrejaKellyBienhoffScottGlennRizwan SAbdulkaderAshutosh NAggarwalRakeshAggarwalSandraAlbertAtulAmbekarMonikaAroraDamodarBachaniAshishBavdekarGufranBeigAnilBhansaliAnuragBhargavaEeshBhatiaBilaliCamaraD JChristopherSiddharth KDasParesh VDaveSagnikDeyAloke GGhoshalNGopalakrishnanRandeepGuleriaRajeevGuptaSubodh SGuptaTarunGuptaM DGupteGGururajSivadasanpillaiHarikrishnanVeenaIyerSudhir KJainPanniyamamkalJeemonVasnaJoshuaRajniKantAnitaKarAmal CKatakiKiranKatochAjayKheraSanjayKinraParvaiz AKoulAnandKrishnanAvdheshKumarRaman KKumarRashmiKumarAnuraKurpadLaishramLadusinghRakeshLodhaP AMaheshRajeshMalhotraMatthewsMathaiDileepMavalankarMuraliMohan BVSatinathMukhopadhyayManojMurhekarG V SMurthySanjeevNairSreenivas ANairLipikaNandaRomi SNongmaithemAnu MOommenJeyaraj DPandianSapanPandyaSreejithParameswaranSanghamitraPatiKameshwarPrasadNarayanPrasadManoramaPurwarAsmaRahimSreebhushanRajuSiddarthRamjiTharaRangaswamyGoura KRathAmbujRoyYogeshSabdeK SSachdevaHarsiddhaSadhuRajeshSagarMari JSankarRajendraSharmaAnitaShetShreyaShirudeRajanShuklaSharvari RShuklaGagandeepSinghNarinder PSinghVirendraSinghAnjuSinhaDhirendra NSinhaR KSrivastavaASrividyaVanitaSuriRajaramanSwaminathanP NSylajaBabasahebTandaleJ SThakurKavumpurathu RThankappanNihalThomasSrikanthTripathyMathewVargheseSantoshVarugheseSVenkateshKVenugopalLakshmiVijayakumarDenisXavierChittaranjan SYajnikGeevarZachariahSanjayZodpeyJ V R PrasadaRaoTheoVosK SrinathReddyChristopher J LMurraySoumyaSwaminathan
      Background 18% of the world's population lives in India, and many states of India have populations similar to those of large countries. Action to effectively improve population health in India requires availability of reliable and comprehensive state-level estimates of disease burden and risk factors over time. Such comprehensive estimates have not been available so far for all major diseases and risk factors. Thus, we aimed to estimate the disease burden and risk factors in every state of India as part of the Global Burden of Disease (GBD) Study 2016. Methods Using all available data sources, the India State-level Disease Burden Initiative estimated burden (metrics were deaths, disability-adjusted life-years [DALYs], prevalence, incidence, and life expectancy) from 333 disease conditions and injuries and 84 risk factors for each state of India from 1990 to 2016 as part of GBD 2016. We divided the states of India into four epidemiological transition level (ETL) groups on the basis of the ratio of DALYs from communicable, maternal, neonatal, and nutritional diseases (CMNNDs) to those from non-communicable diseases (NCDs) and injuries combined in 2016. We assessed variations in the burden of diseases and risk factors between ETL state groups and between states to inform a more specific health-system response in the states and for India as a whole. Findings DALYs due to NCDs and injuries exceeded those due to CMNNDs in 2003 for India, but this transition had a range of 24 years for the four ETL state groups. The age-standardised DALY rate dropped by 36·2% in India from 1990 to 2016. The numbers of DALYs and DALY rates dropped substantially for most CMNNDs between 1990 and 2016 across all ETL groups, but rates of reduction for CMNNDs were slowest in the low ETL state group. By contrast, numbers of DALYs increased substantially for NCDs in all ETL state groups, and increased significantly for injuries in all ETL state groups except the highest. The all-age prevalence of most leading NCDs increased substantially in India from 1990 to 2016, and a modest decrease was recorded in the age-standardised NCD DALY rates. The major risk factors for NCDs, including high systolic blood pressure, high fasting plasma glucose, high total cholesterol, and high body-mass index, increased from 1990 to 2016, with generally higher levels in higher ETL states; ambient air pollution also increased and was highest in the low ETL group. The incidence rate of the leading causes of injuries also increased from 1990 to 2016. The five leading individual causes of DALYs in India in 2016 were ischaemic heart disease, chronic obstructive pulmonary disease, diarrhoeal diseases, lower respiratory infections, and cerebrovascular disease; and the five leading risk factors for DALYs in 2016 were...
      PubDate: 2017-11-18T15:48:58Z
       
  • The health system in India: the underserved majority
    • Authors: Patralekha Chatterjee
      Abstract: Publication date: Available online 14 November 2017
      Source:The Lancet
      Author(s): Patralekha Chatterjee


      PubDate: 2017-11-18T15:48:58Z
      DOI: 10.1016/s0140-6736(17)32860-x
       
  • Lalit Dandona: surveying the burden of disease in India
    • Authors: Geoff Watts
      Abstract: Publication date: Available online 14 November 2017
      Source:The Lancet
      Author(s): Geoff Watts


      PubDate: 2017-11-18T15:48:58Z
      DOI: 10.1016/s0140-6736(17)32861-1
       
  • Extended-release naltrexone: good but not a panacea
    • Authors: David C Lott
      Abstract: Publication date: Available online 14 November 2017
      Source:The Lancet
      Author(s): David C Lott


      PubDate: 2017-11-18T15:48:58Z
      DOI: 10.1016/s0140-6736(17)32872-6
       
  • Comparative effectiveness of extended-release naltrexone versus
           buprenorphine-naloxone for opioid relapse prevention (X:BOT): a
           multicentre, open-label, randomised controlled trial
    • Authors: Joshua D Lee; Edward V Nunes; Patricia Novo; Ken Bachrach; Genie L Bailey; Snehal Bhatt; Sarah Farkas; Marc Fishman; Phoebe Gauthier; Candace C Hodgkins; Jacquie King; Robert Lindblad; David Liu; Abigail G Matthews; Jeanine May; K Michelle Peavy; Stephen Ross; Dagmar Salazar; Paul Schkolnik; Dikla Shmueli-Blumberg; Don Stablein; Geetha Subramaniam; John Rotrosen
      Abstract: Publication date: Available online 14 November 2017
      Source:The Lancet
      Author(s): Joshua D Lee, Edward V Nunes, Patricia Novo, Ken Bachrach, Genie L Bailey, Snehal Bhatt, Sarah Farkas, Marc Fishman, Phoebe Gauthier, Candace C Hodgkins, Jacquie King, Robert Lindblad, David Liu, Abigail G Matthews, Jeanine May, K Michelle Peavy, Stephen Ross, Dagmar Salazar, Paul Schkolnik, Dikla Shmueli-Blumberg, Don Stablein, Geetha Subramaniam, John Rotrosen
      Background Extended-release naltrexone (XR-NTX), an opioid antagonist, and sublingual buprenorphine-naloxone (BUP-NX), a partial opioid agonist, are pharmacologically and conceptually distinct interventions to prevent opioid relapse. We aimed to estimate the difference in opioid relapse-free survival between XR-NTX and BUP-NX. Methods We initiated this 24 week, open-label, randomised controlled, comparative effectiveness trial at eight US community-based inpatient services and followed up participants as outpatients. Participants were 18 years or older, had Diagnostic and Statistical Manual of Mental Disorders-5 opioid use disorder, and had used non-prescribed opioids in the past 30 days. We stratified participants by treatment site and opioid use severity and used a web-based permuted block design with random equally weighted block sizes of four and six for randomisation (1:1) to receive XR-NTX or BUP-NX. XR-NTX was monthly intramuscular injections (Vivitrol; Alkermes) and BUP-NX was daily self-administered buprenorphine-naloxone sublingual film (Suboxone; Indivior). The primary outcome was opioid relapse-free survival during 24 weeks of outpatient treatment. Relapse was 4 consecutive weeks of any non-study opioid use by urine toxicology or self-report, or 7 consecutive days of self-reported use. This trial is registered with ClinicalTrials.gov, NCT02032433. Findings Between Jan 30, 2014, and May 25, 2016, we randomly assigned 570 participants to receive XR-NTX (n=283) or BUP-NX (n=287). The last follow-up visit was Jan 31, 2017. As expected, XR-NTX had a substantial induction hurdle: fewer participants successfully initiated XR-NTX (204 [72%] of 283) than BUP-NX (270 [94%] of 287; p<0·0001). Among all participants who were randomly assigned (intention-to-treat population, n=570) 24 week relapse events were greater for XR-NTX (185 [65%] of 283) than for BUP-NX (163 [57%] of 287; hazard ratio [HR] 1·36, 95% CI 1·10–1·68), most or all of this difference accounted for by early relapse in nearly all (70 [89%] of 79) XR-NTX induction failures. Among participants successfully inducted (per-protocol population, n=474), 24 week relapse events were similar across study groups (p=0·44). Opioid-negative urine samples (p<0·0001) and opioid-abstinent days (p<0·0001) favoured BUP-NX compared with XR-NTX among the intention-to-treat population, but were similar across study groups among the per-protocol population. Self-reported opioid craving was initially less with XR-NTX than with BUP-NX (p=0·0012), then converged by week 24 (p=0·20). With the exception of mild-to-moderate XR-NTX injection site reactions, treatment-emergent adverse events including overdose did not differ between treatment groups. Five fatal overdoses occurred (two in the XR-NTX group and three in the BUP-NX group). Interpretation In this population it is more difficult to initiate patients to XR-NTX than BUP-NX, and this negatively affected overall relapse. However, once initiated, both medications were equally safe and effective. Future work should focus on facilitating induction to XR-NTX and on improving treatment retention for both medications. Funding NIDA Clinical Trials Network.

      PubDate: 2017-11-18T15:48:58Z
      DOI: 10.1016/s0140-6736(17)32812-x
       
  • Medications for opioid use disorder: bridging the gap in care
    • Authors: Nora D Volkow
      Abstract: Publication date: Available online 14 November 2017
      Source:The Lancet
      Author(s): Nora D Volkow


      PubDate: 2017-11-18T15:48:58Z
      DOI: 10.1016/s0140-6736(17)32893-3
       
  • Department of Error
    • Abstract: Publication date: Available online 14 November 2017
      Source:The Lancet


      PubDate: 2017-11-18T15:48:58Z
       
  • Health and wellbeing of Indigenous adolescents in Australia: a systematic
           synthesis of population data
    • Authors: Peter S Azzopardi; Susan M Sawyer; John B Carlin; Louisa Degenhardt; Ngiare Brown; Alex D Brown; George C Patton
      Abstract: Publication date: Available online 13 November 2017
      Source:The Lancet
      Author(s): Peter S Azzopardi, Susan M Sawyer, John B Carlin, Louisa Degenhardt, Ngiare Brown, Alex D Brown, George C Patton
      Background Indigenous populations have high rates of disease and premature mortality. Most Indigenous communities are young, and adolescence (age 10–24 years) provides great opportunities for population health gain. However, the absence of a comprehensive account of Indigenous adolescents' health has been a barrier to effective policy. We aimed to report a national health profile for Indigenous adolescents in Australia. Methods We undertook a systematic synthesis of population data to report the health and wellbeing of Indigenous adolescents in Australia. A reporting framework for Indigenous adolescent health in Australia was defined to measure health outcomes, health risks, and sociocultural determinants. Available data (primary data from national surveys and administrative datasets, and available published data) were mapped against the defined reporting framework, and the quality graded, with the highest quality data selected to report a health profile for Indigenous adolescents. Comparison with non-Indigenous adolescents was made where possible, and estimates (disaggregated by age, sex, and remoteness) were reported as relative risks. A national advisory group (six Indigenous young people, three Indigenous adult community members, three researchers, three policy makers, and two service providers, all aged ≥16 years) provided input about the reporting framework, interpretation of findings, and policy recommendations. Findings Data were available for 184 (79%) of 234 elements of the reporting framework. All-cause mortality for Indigenous adolescents (70 per 100 000) was more than twice that of non-Indigenous adolescents, with about 60% of deaths due to intentional self-harm and road traffic injury. 80% of all deaths among Indigenous adolescents were considered as potentially avoidable in the current health system. Communicable diseases (particularly sexually transmitted infections) were leading contributors to morbidity. Almost a third of Indigenous adolescents aged 18–24 years reported high levels of psychological distress (twice the non-Indigenous rate). There was an excess burden of mental disorders and substance use, alongside emerging type 2 diabetes and ischaemic heart disease. Additionally, there were excess intentional and unintentional injuries. Many aspects of this health profile differed markedly from that of non-Indigenous adolescents: rates of acute rheumatic fever, pneumococcal infection, gonorrhoea, and type 2 diabetes resulting in admission to hospital were ten times higher; rates of assault and childbirth in those aged 15–19 years were five times higher; whereas rates of eating disorders, melanoma and other skin cancers, and anaphylaxis were significantly lower. Risks for future ill-health were common; 43% of 15–24 year olds were current tobacco smokers and about 45% had high body mass (overweight or obese). Disadvantage across sociocultural health determinants also emerged, particularly around education. Interpretation Despite Australia's adolescents having one of the best health profiles globally, Indigenous adolescents have largely been left behind. Adequate responses will require intersectoral actions, including a health system responsive to the needs of Indigenous adolescents. Without a specific focus on adolescents, Australia will not redress Indigenous health inequalities. Funding Australia's National Health and Medical Research Council, Sidney Myer Foundation, and the Murdoch Children's Research Institute.

      PubDate: 2017-11-18T15:48:58Z
      DOI: 10.1016/s0140-6736(17)32141-4
       
  • Treatment concentration of high-sensitivity C-reactive protein
    • Authors: Erin D Michos; Roger S Blumenthal
      Abstract: Publication date: Available online 13 November 2017
      Source:The Lancet
      Author(s): Erin D Michos, Roger S Blumenthal


      PubDate: 2017-11-18T15:48:58Z
      DOI: 10.1016/s0140-6736(17)32865-9
       
  • Relationship of C-reactive protein reduction to cardiovascular event
           reduction following treatment with canakinumab: a secondary analysis from
           the CANTOS randomised controlled trial
    • Authors: Paul M Ridker; Jean G MacFadyen; Brendan M Everett; Peter Libby; Tom Thuren; Robert J Glynn; Paul M Ridker; Jean G MacFadyen; Brendan M Everett; Peter Libby; Tom Thuren; Robert J Glynn; John Kastelein; Wolfgang Koenig; Jacques Genest; Alberto Lorenzatti; John Varigos; Peter Siostrzonek; Peter Sinnaeve; Francisco Fonseca; Jose Nicolau; Nina Gotcheva; Huo Yong; Miguel Urina-Triana; Davor Milicic; Renata Cifkova; Riina Vettus; Stephan D Anker; Athanasios J Manolis; Fernando Wyss; Tamas Forster; Axel Sigurdsson; Prem Pais; Alessandro Fucili; Hisao Ogawa; Hiroaki Shimokawa; Irina Veze; Birute Petrauskiene; Leon Salvador; Jan Hein Cornel; Tor Ole Klemsdal; Felix Medina; Andrzej Budaj; Luminita Vida-Simiti; Zhanna Kobalava; Petar Otasevic; Daniel Pella; Mitja Lainscak; Ki-Bae Seung; Patrick Commerford; Mikael Dellborg; Marc Donath; Juey-Jen Hwang; Hakan Kultursay; Marcus Flather; Christie Ballantyne; Seth Bilazarian; William Chang; Cara East; Les Forgosh; Barry Harris; Monica Ligueros
      Abstract: Publication date: Available online 13 November 2017
      Source:The Lancet
      Author(s): Paul M Ridker, Jean G MacFadyen, Brendan M Everett, Peter Libby, Tom Thuren, Robert J Glynn
      Background Canakinumab, a monoclonal antibody targeting interleukin-1β, reduces inflammation and cardiovascular event rates with no effect on lipid concentrations. However, it is uncertain which patient groups benefit the most from treatment and whether reductions in the inflammatory biomarker high-sensitivity C-reactive protein (hsCRP) correlate with clinical benefits for individual patients. Methods The Canakinumab Anti-Inflammatory Thrombosis Outcomes Study (CANTOS) used computer-generated codes to randomly allocate 10 061 men and women with a history of myocardial infarction to placebo or one of three doses of canakinumab (50 mg, 150 mg, or 300 mg) given subcutaneously once every 3 months. In a prespecified secondary analysis designed to address the relationship of hsCRP reduction to event reduction in CANTOS, we evaluated the effects of canakinumab on rates of major adverse cardiovascular events, cardiovascular mortality, and all-cause mortality according to on-treatment concentrations of hsCRP. We used multivariable modelling to adjust for baseline factors associated with achieved hsCRP and multiple sensitivity analyses to address the magnitude of residual confounding. The median follow-up was 3·7 years. The trial is registered with ClinicalTrials.gov, number NCT01327846. Findings Baseline clinical characteristics did not define patient groups with greater or lesser cardiovascular benefits when treated with canakinumab. However, trial participants allocated to canakinumab who achieved hsCRP concentrations less than 2 mg/L had a 25% reduction in major adverse cardiovascular events (multivariable adjusted hazard ratio [HRadj]=0·75, 95% CI 0·66–0·85, p<0·0001), whereas no significant benefit was observed among those with on-treatment hsCRP concentrations of 2 mg/L or above (HRadj=0·90, 0·79–1·02, p=0·11). For those treated with canakinumab who achieved on-treatment hsCRP concentrations less than 2 mg/L, cardiovascular mortality (HRadj=0·69, 95% CI 0·56–0·85, p=0·0004) and all-cause mortality (HRadj=0·69, 0·58–0·81, p<0·0001) were both reduced by 31%, whereas no significant reduction in these endpoints was observed among those treated with canakinumab who achieved hsCRP concentrations of 2 mg/L or above. Similar differential effects were found in analyses of the trial prespecified secondary cardiovascular endpoint (which additionally included hospitalisation for unstable angina requiring unplanned revascularisation) and in sensitivity analyses alternatively based on median reductions in hsCRP, on 50% or greater reductions in hsCRP, on the median percent reduction in hsCRP, in dose-specific analyses, and in analyses using a causal inference approach to estimate the effect of treatment among individuals who would achieve a targeted hsCRP concentration. Interpretation The magnitude of hsCRP reduction following a single dose of canakinumab might provide a simple clinical method to identify individuals most likely to accrue the largest benefit from continued treatment. These data further suggest that lower is better for inflammation reduction with canakinumab. Funding Novartis Pharmaceuticals.

      PubDate: 2017-11-18T15:48:58Z
      DOI: 10.1016/s0140-6736(17)32814-3
       
  • Planetary health: protecting human health on a rapidly changing planet
    • Authors: Samuel S Myers
      Abstract: Publication date: Available online 13 November 2017
      Source:The Lancet
      Author(s): Samuel S Myers
      The impact of human activities on our planet's natural systems has been intensifying rapidly in the past several decades, leading to disruption and transformation of most natural systems. These disruptions in the atmosphere, oceans, and across the terrestrial land surface are not only driving species to extinction, they pose serious threats to human health and wellbeing. Characterising and addressing these threats requires a paradigm shift. In a lecture delivered to the Academy of Medical Sciences on Nov 13, 2017, I describe the scale of human impacts on natural systems and the extensive associated health effects across nearly every dimension of human health. I highlight several overarching themes that emerge from planetary health and suggest advances in the way we train, reward, promote, and fund the generation of health scientists who will be tasked with breaking out of their disciplinary silos to address this urgent constellation of health threats. I propose that protecting the health of future generations requires taking better care of Earth's natural systems.

      PubDate: 2017-11-18T15:48:58Z
      DOI: 10.1016/s0140-6736(17)32846-5
       
  • Morbidity and mortality in homeless individuals, prisoners, sex workers,
           and individuals with substance use disorders in high-income countries: a
           systematic review and meta-analysis
    • Authors: Robert W Aldridge; Alistair Story; Stephen W Hwang; Merete Nordentoft; Serena A Luchenski; Greg Hartwell; Emily J Tweed; Dan Lewer; Srinivasa Vittal Katikireddi; Andrew C Hayward
      Abstract: Publication date: Available online 12 November 2017
      Source:The Lancet
      Author(s): Robert W Aldridge, Alistair Story, Stephen W Hwang, Merete Nordentoft, Serena A Luchenski, Greg Hartwell, Emily J Tweed, Dan Lewer, Srinivasa Vittal Katikireddi, Andrew C Hayward
      Background Inclusion health focuses on people in extremely poor health due to poverty, marginalisation, and multimorbidity. We aimed to review morbidity and mortality data on four overlapping populations who experience considerable social exclusion: homeless populations, individuals with substance use disorders, sex workers, and imprisoned individuals. Methods For this systematic review and meta-analysis, we searched MEDLINE, Embase, and the Cochrane Library for studies published between Jan 1, 2005, and Oct 1, 2015. We included only systematic reviews, meta-analyses, interventional studies, and observational studies that had morbidity and mortality outcomes, were published in English, from high-income countries, and were done in populations with a history of homelessness, imprisonment, sex work, or substance use disorder (excluding cannabis and alcohol use). Studies with only perinatal outcomes and studies of individuals with a specific health condition or those recruited from intensive care or high dependency hospital units were excluded. We screened studies using systematic review software and extracted data from published reports. Primary outcomes were measures of morbidity (prevalence or incidence) and mortality (standardised mortality ratios [SMRs] and mortality rates). Summary estimates were calculated using a random effects model. Findings Our search identified 7946 articles, of which 337 studies were included for analysis. All-cause standardised mortality ratios were significantly increased in 91 (99%) of 92 extracted datapoints and were 11·86 (95% CI 10·42–13·30; I 2=94·1%) in female individuals and 7·88 (7·03–8·74; I 2=99·1%) in men. Summary SMR estimates for the International Classification of Diseases disease categories with two or more included datapoints were highest for deaths due to injury, poisoning, and other external causes, in both men (7·89; 95% CI 6·40–9·37; I 2=98·1%) and women (18·72; 13·73–23·71; I 2=91·5%). Disease prevalence was consistently raised across the following categories: infections (eg, highest reported was 90% for hepatitis C, 67 [65%] of 103 individuals for hepatitis B, and 133 [51%] of 263 individuals for latent tuberculosis infection), mental health (eg, highest reported was 9 [4%] of 227 individuals for schizophrenia), cardiovascular conditions (eg, highest reported was 32 [13%] of 247 individuals for coronary heart disease), and respiratory conditions (eg, highest reported was 9 [26%] of 35 individuals for asthma). Interpretation Our study shows that homeless populations, individuals with substance use disorders, sex workers, and imprisoned individuals experience extreme health inequities across a wide range of health conditions, with the relative effect of exclusion being greater in female individuals than male individuals. The high heterogeneity between studies should be explored further using improved data collection in population subgroups. The extreme health inequity identified demands intensive cross-sectoral policy and service action to prevent exclusion and improve health outcomes in individuals who are already marginalised. Funding Wellcome Trust, National Institute for Health Research, NHS England, NHS Research Scotland Scottish Senior Clinical Fellowship, Medical Research Council, Chief Scientist Office, and the Central and North West London NHS Trust.

      PubDate: 2017-11-18T15:48:58Z
      DOI: 10.1016/s0140-6736(17)31869-x
       
  • Inclusion health: addressing the causes of the causes
    • Authors: Michael Marmot
      Abstract: Publication date: Available online 12 November 2017
      Source:The Lancet
      Author(s): Michael Marmot


      PubDate: 2017-11-18T15:48:58Z
      DOI: 10.1016/s0140-6736(17)32848-9
       
  • What works in inclusion health: overview of effective interventions for
           marginalised and excluded populations
    • Authors: Serena Luchenski; Nick Maguire; Robert W Aldridge; Andrew Hayward; Alistair Story; Patrick Perri; James Withers; Sharon Clint; Suzanne Fitzpatrick; Nigel Hewett
      Abstract: Publication date: Available online 12 November 2017
      Source:The Lancet
      Author(s): Serena Luchenski, Nick Maguire, Robert W Aldridge, Andrew Hayward, Alistair Story, Patrick Perri, James Withers, Sharon Clint, Suzanne Fitzpatrick, Nigel Hewett
      Inclusion health is a service, research, and policy agenda that aims to prevent and redress health and social inequities among the most vulnerable and excluded populations. We did an evidence synthesis of health and social interventions for inclusion health target populations, including people with experiences of homelessness, drug use, imprisonment, and sex work. These populations often have multiple overlapping risk factors and extreme levels of morbidity and mortality. We identified numerous interventions to improve physical and mental health, and substance use; however, evidence is scarce for structural interventions, including housing, employment, and legal support that can prevent exclusion and promote recovery. Dedicated resources and better collaboration with the affected populations are needed to realise the benefits of existing interventions. Research must inform the benefits of early intervention and implementation of policies to address the upstream causes of exclusion, such as adverse childhood experiences and poverty.

      PubDate: 2017-11-18T15:48:58Z
      DOI: 10.1016/s0140-6736(17)31959-1
       
  • Eliminating viral hepatitis: time to match visions with action
    • Authors: Lancet
      Abstract: Publication date: 11–17 November 2017
      Source:The Lancet, Volume 390, Issue 10108
      Author(s): The Lancet


      PubDate: 2017-11-11T06:03:24Z
       
 
 
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