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Journal Cover The Lancet
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   ISSN (Print) 0140-6736 - ISSN (Online) 1474-547X
   Published by Elsevier Homepage  [3040 journals]
  • Management of patients with early mild asthma and infrequent symptoms
    • Authors: Alberto Papi; Leonardo M Fabbri
      Pages: 129 - 130
      Abstract: Publication date: 14–20 January 2017
      Source:The Lancet, Volume 389, Issue 10065
      Author(s): Alberto Papi, Leonardo M Fabbri


      PubDate: 2017-01-19T08:21:07Z
      DOI: 10.1016/s0140-6736(16)32111-0
       
  • Household energy and health: where next for research and practice'
    • Authors: Majid Ezzati; Jill C Baumgartner
      Pages: 130 - 132
      Abstract: Publication date: 14–20 January 2017
      Source:The Lancet, Volume 389, Issue 10065
      Author(s): Majid Ezzati, Jill C Baumgartner


      PubDate: 2017-01-19T08:21:07Z
      DOI: 10.1016/s0140-6736(16)32506-5
       
  • Non-specialist health workers to treat excessive alcohol consumption and
           depression
    • Authors: Roberta Agabio
      Pages: 133 - 135
      Abstract: Publication date: 14–20 January 2017
      Source:The Lancet, Volume 389, Issue 10065
      Author(s): Roberta Agabio


      PubDate: 2017-01-19T08:21:07Z
      DOI: 10.1016/s0140-6736(16)32566-1
       
  • Mentoring clinical trainees: a need for high touch
    • Authors: Michael Wilkes; Mitchell D Feldman
      Pages: 135 - 137
      Abstract: Publication date: 14–20 January 2017
      Source:The Lancet, Volume 389, Issue 10065
      Author(s): Michael Wilkes, Mitchell D Feldman


      PubDate: 2017-01-19T08:21:07Z
      DOI: 10.1016/s0140-6736(16)32571-5
       
  • Can Myanmar's older people lead the way to universal health coverage'
    • Authors: Nazaneen Nikpour Hernandez; Soe Myint
      Pages: 137 - 139
      Abstract: Publication date: 14–20 January 2017
      Source:The Lancet, Volume 389, Issue 10065
      Author(s): Nazaneen Nikpour Hernandez, Soe Myint


      PubDate: 2017-01-19T08:21:07Z
      DOI: 10.1016/s0140-6736(16)32065-7
       
  • The Lancet Planetary Health: a new journal for a new discipline—a
           call for papers
    • Authors: Raffaella Bosurgi; Richard Horton
      First page: 139
      Abstract: Publication date: 14–20 January 2017
      Source:The Lancet, Volume 389, Issue 10065
      Author(s): Raffaella Bosurgi, Richard Horton


      PubDate: 2017-01-19T08:21:07Z
      DOI: 10.1016/s0140-6736(16)32590-9
       
  • Offline: The possible impossibility of universal health coverage
    • Authors: Richard Horton
      First page: 140
      Abstract: Publication date: 14–20 January 2017
      Source:The Lancet, Volume 389, Issue 10065
      Author(s): Richard Horton


      PubDate: 2017-01-19T08:21:07Z
      DOI: 10.1016/s0140-6736(17)30081-8
       
  • Experts confident of Congressional funding for US Cures Act
    • Authors: Susan Jaffe
      Pages: 141 - 142
      Abstract: Publication date: 14–20 January 2017
      Source:The Lancet, Volume 389, Issue 10065
      Author(s): Susan Jaffe


      PubDate: 2017-01-19T08:21:07Z
      DOI: 10.1016/s0140-6736(17)30078-8
       
  • New research centre focuses on conflict in the Middle East
    • Authors: Talha Burki
      First page: 143
      Abstract: Publication date: 14–20 January 2017
      Source:The Lancet, Volume 389, Issue 10065
      Author(s): Talha Burki


      PubDate: 2017-01-19T08:21:07Z
      DOI: 10.1016/s0140-6736(17)30079-x
       
  • Profile: Swiss School of Public Health, Zurich, Switzerland
    • Authors: John Maurice
      First page: 144
      Abstract: Publication date: 14–20 January 2017
      Source:The Lancet, Volume 389, Issue 10065
      Author(s): John Maurice


      PubDate: 2017-01-19T08:21:07Z
      DOI: 10.1016/s0140-6736(17)30080-6
       
  • Bridging the theory–practice gap in global health research
    • Authors: Osman Sankoh
      First page: 145
      Abstract: Publication date: 14–20 January 2017
      Source:The Lancet, Volume 389, Issue 10065
      Author(s): Osman Sankoh


      PubDate: 2017-01-19T08:21:07Z
      DOI: 10.1016/s0140-6736(17)30008-9
       
  • Fighting for an end to violence against women
    • Authors: Fiona Mitchell
      First page: 146
      Abstract: Publication date: 14–20 January 2017
      Source:The Lancet, Volume 389, Issue 10065
      Author(s): Fiona Mitchell


      PubDate: 2017-01-19T08:21:07Z
      DOI: 10.1016/s0140-6736(17)30009-0
       
  • Mental illness in Han Kang's The Vegetarian
    • Authors: Daniel Marchalik; Ann Jurecic
      First page: 147
      Abstract: Publication date: 14–20 January 2017
      Source:The Lancet, Volume 389, Issue 10065
      Author(s): Daniel Marchalik, Ann Jurecic


      PubDate: 2017-01-19T08:21:07Z
      DOI: 10.1016/s0140-6736(17)30010-7
       
  • Performing magic, performing medicine
    • Authors: Roger L Kneebone
      Pages: 148 - 149
      Abstract: Publication date: 14–20 January 2017
      Source:The Lancet, Volume 389, Issue 10065
      Author(s): Roger L Kneebone


      PubDate: 2017-01-19T08:21:07Z
      DOI: 10.1016/s0140-6736(17)30011-9
       
  • Neil Blair Pride
    • Authors: Geoff Watts
      First page: 150
      Abstract: Publication date: 14–20 January 2017
      Source:The Lancet, Volume 389, Issue 10065
      Author(s): Geoff Watts


      PubDate: 2017-01-19T08:21:07Z
      DOI: 10.1016/s0140-6736(17)30012-0
       
  • Zika rash and increased risk of congenital brain abnormalities
    • Authors: Patrick Gérardin; Van-Mai Cao-Lormeau; Didier Musso; Philippe Desprès; Marianne Besnard
      Pages: 151 - 152
      Abstract: Publication date: 14–20 January 2017
      Source:The Lancet, Volume 389, Issue 10065
      Author(s): Patrick Gérardin, Van-Mai Cao-Lormeau, Didier Musso, Philippe Desprès, Marianne Besnard


      PubDate: 2017-01-19T08:21:07Z
      DOI: 10.1016/s0140-6736(17)30014-4
       
  • Zika virus: are we going too far'
    • Authors: Manon Vouga; Didier Musso; Bruno Schaub; Alice Panchaud; David Baud
      First page: 151
      Abstract: Publication date: 14–20 January 2017
      Source:The Lancet, Volume 389, Issue 10065
      Author(s): Manon Vouga, Didier Musso, Bruno Schaub, Alice Panchaud, David Baud


      PubDate: 2017-01-19T08:21:07Z
      DOI: 10.1016/s0140-6736(17)30013-2
       
  • Zika rash and increased risk of congenital brain abnormalities –
           Authors' reply
    • Authors: Cesar G Victora; Marcia C Castro; Giovanny V A França; Lavinia Schuler-Faccini; Fernando C Barros
      First page: 152
      Abstract: Publication date: 14–20 January 2017
      Source:The Lancet, Volume 389, Issue 10065
      Author(s): Cesar G Victora, Marcia C Castro, Giovanny V A França, Lavinia Schuler-Faccini, Fernando C Barros


      PubDate: 2017-01-19T08:21:07Z
      DOI: 10.1016/s0140-6736(17)30015-6
       
  • The possibility of vascular care for prevention of dementia
    • Authors: Tomohiro Morita; Asaka Higuchi; Akihiko Ozaki; Yuki Shimada; Tetsuya Tanimoto
      Pages: 152 - 153
      Abstract: Publication date: 14–20 January 2017
      Source:The Lancet, Volume 389, Issue 10065
      Author(s): Tomohiro Morita, Asaka Higuchi, Akihiko Ozaki, Yuki Shimada, Tetsuya Tanimoto


      PubDate: 2017-01-19T08:21:07Z
      DOI: 10.1016/s0140-6736(17)30016-8
       
  • Hypertension control and cardiovascular disease
    • Authors: Franz H Messerli; Urs Fischer; Stefano F Rimoldi; Sripal Bangalore
      First page: 153
      Abstract: Publication date: 14–20 January 2017
      Source:The Lancet, Volume 389, Issue 10065
      Author(s): Franz H Messerli, Urs Fischer, Stefano F Rimoldi, Sripal Bangalore


      PubDate: 2017-01-19T08:21:07Z
      DOI: 10.1016/s0140-6736(17)30017-x
       
  • Hypertension control and cardiovascular disease – Authors' reply
    • Authors: Jacques Blacher; Bernard I Levy; Jean-Jacques Mourad; Michel E Safar; George Bakris
      Pages: 154 - 155
      Abstract: Publication date: 14–20 January 2017
      Source:The Lancet, Volume 389, Issue 10065
      Author(s): Jacques Blacher, Bernard I Levy, Jean-Jacques Mourad, Michel E Safar, George Bakris


      PubDate: 2017-01-19T08:21:07Z
      DOI: 10.1016/s0140-6736(17)30019-3
       
  • Hypertension control and cardiovascular disease
    • Authors: Jack E James
      First page: 154
      Abstract: Publication date: 14–20 January 2017
      Source:The Lancet, Volume 389, Issue 10065
      Author(s): Jack E James


      PubDate: 2017-01-19T08:21:07Z
      DOI: 10.1016/s0140-6736(17)30018-1
       
  • Effect of staffing on improving newborn health
    • Authors: Zeshan Qureshi
      First page: 155
      Abstract: Publication date: 14–20 January 2017
      Source:The Lancet, Volume 389, Issue 10065
      Author(s): Zeshan Qureshi


      PubDate: 2017-01-19T08:21:07Z
      DOI: 10.1016/s0140-6736(17)30020-x
       
  • Open letter on access to the BIA 10-2474 clinical trial data
    • Authors: Kim Brøsen; Christian Funck-Brentano; Heyo K. Kroemer; Munir Pirmohamed; Matthias Schwab
      First page: 156
      Abstract: Publication date: 14–20 January 2017
      Source:The Lancet, Volume 389, Issue 10065
      Author(s): Kim Brøsen, Christian Funck-Brentano, Heyo K. Kroemer, Munir Pirmohamed, Matthias Schwab


      PubDate: 2017-01-19T08:21:07Z
      DOI: 10.1016/s0140-6736(16)32515-6
       
  • Should recommendations about starting inhaled corticosteroid treatment for
           mild asthma be based on symptom frequency: a post-hoc efficacy analysis of
           the START study
    • Authors: Helen K Reddel; William W Busse; Søren Pedersen; Wan C Tan; Yu-Zhi Chen; Carin Jorup; Dan Lythgoe; Paul M O'Byrne
      Pages: 157 - 166
      Abstract: Publication date: 14–20 January 2017
      Source:The Lancet, Volume 389, Issue 10065
      Author(s): Helen K Reddel, William W Busse, Søren Pedersen, Wan C Tan, Yu-Zhi Chen, Carin Jorup, Dan Lythgoe, Paul M O'Byrne
      Background Low-dose inhaled corticosteroids (ICS) are highly effective for reducing asthma exacerbations and mortality. Conventionally, ICS treatment is recommended for patients with symptoms on more than 2 days per week, but this criterion has scant evidence. We aimed to assess the validity of the previous symptom-based cutoff for starting ICS by establishing whether there was a differential response to budesonide versus placebo for severe asthma exacerbations, lung function, and asthma symptom control across subgroups identified by baseline asthma symptom frequency. Methods We did a post-hoc analysis of the 3 year inhaled Steroid Treatment As Regular Therapy (START) study, done in 32 countries, with clinic visits every 3 months. Patients (aged 4–66 years) with mild asthma diagnosed within the previous 2 years and no previous regular corticosteroids were randomised to receive once daily, inhaled budesonide 400 μg (those aged <11 years 200 μg) or placebo. Coprimary outcomes for this analysis were time to first severe asthma-related event (SARE; hospital admission, emergency treatment, or death) and change from baseline in lung function after bronchodilator. Interaction with baseline symptom frequency was investigated, with patients grouped by more than two symptom days per week and two or fewer symptom days per week (divided into no days to 1 day, and more than 1 day to 2 days). Analysis was done by intention to treat. Findings Of 7138 patients (n=3577 budesonide; n=3561 placebo), baseline symptom frequency was 0–1 days per week for 2184 (31%) participants, more than 1 and less than or equal to 2 symptom days per week for 1914 (27%) participants, and more than 2 symptom days per week for 3040 (43%) participants. For budesonide versus placebo, time to first SARE was longer across symptom frequency subgroups (hazard ratios 0·54 [95% CI 0·34–0·86] for 0–1 symptom days per week, 0·60 [0·39–0·93] for >1 to ≤2 symptom days per week, 0·57 [0·41–0·79] >2 symptom days per week, pinteraction=0·94), and the decline in postbronchodilator lung function was less at 3 years' follow-up (pinteraction=0·32). For budesonide versus placebo, severe exacerbations requiring oral or systemic corticosteroids were reduced (rate ratio 0·48 [0·38–0·61] 0–1 symptom days per week, 0·56 [0·44–0·71] >1 to ≤2 symptom days per week, and 0·66 [0·55–0·80] >2 symptom days per week, pinteraction=0·11), prebronchodilator lung function was higher, and symptom-free days were more frequent (p<0·0001 for all three subgroups), with no interaction by symptom frequency (prebronchodilator pinteraction=0·43; symptom-free days pinteraction=0·53). Similar results were noted when participants were classified by any guidelines criterion as so-called persistent versus so-called intermittent asthma. Interpretation In mild recent-onset asthma, once daily, low-dose budesonide decreases SARE risk, reduces lung function decline, and improves symptom control similarly across all symptom subgroups. The results do not support restriction of inhaled corticosteroids to patients with symptoms on more than 2 days per week and suggest that treatment recommendations for mild asthma should consider both risk reduction and symptoms. Funding AstraZeneca.

      PubDate: 2017-01-19T08:21:07Z
      DOI: 10.1016/s0140-6736(16)31399-x
       
  • A cleaner burning biomass-fuelled cookstove intervention to prevent
           pneumonia in children under 5 years old in rural Malawi (the Cooking and
           Pneumonia Study): a cluster randomised controlled trial
    • Authors: Kevin Mortimer; Chifundo B Ndamala; Andrew W Naunje; Jullita Malava; Cynthia Katundu; William Weston; Deborah Havens; Daniel Pope; Nigel G Bruce; Moffat Nyirenda; Duolao Wang; Amelia Crampin; Jonathan Grigg; John Balmes; Stephen B Gordon
      Pages: 167 - 175
      Abstract: Publication date: 14–20 January 2017
      Source:The Lancet, Volume 389, Issue 10065
      Author(s): Kevin Mortimer, Chifundo B Ndamala, Andrew W Naunje, Jullita Malava, Cynthia Katundu, William Weston, Deborah Havens, Daniel Pope, Nigel G Bruce, Moffat Nyirenda, Duolao Wang, Amelia Crampin, Jonathan Grigg, John Balmes, Stephen B Gordon
      Background WHO estimates exposure to air pollution from cooking with solid fuels is associated with over 4 million premature deaths worldwide every year including half a million children under the age of 5 years from pneumonia. We hypothesised that replacing open fires with cleaner burning biomass-fuelled cookstoves would reduce pneumonia incidence in young children. Methods We did a community-level open cluster randomised controlled trial to compare the effects of a cleaner burning biomass-fuelled cookstove intervention to continuation of open fire cooking on pneumonia in children living in two rural districts, Chikhwawa and Karonga, of Malawi. Clusters were randomly allocated to intervention and control groups using a computer-generated randomisation schedule with stratification by site, distance from health centre, and size of cluster. Within clusters, households with a child under the age of 4·5 years were eligible. Intervention households received two biomass-fuelled cookstoves and a solar panel. The primary outcome was WHO Integrated Management of Childhood Illness (IMCI)-defined pneumonia episodes in children under 5 years of age. Efficacy and safety analyses were by intention to treat. The trial is registered with ISRCTN, number ISRCTN59448623. Findings We enrolled 10 750 children from 8626 households across 150 clusters between Dec 9, 2013, and Feb 28, 2016. 10 543 children from 8470 households contributed 15 991 child-years of follow-up data to the intention-to-treat analysis. The IMCI pneumonia incidence rate in the intervention group was 15·76 (95% CI 14·89–16·63) per 100 child-years and in the control group 15·58 (95% CI 14·72–16·45) per 100 child-years, with an intervention versus control incidence rate ratio (IRR) of 1·01 (95% CI 0·91–1·13; p=0·80). Cooking-related serious adverse events (burns) were seen in 19 children; nine in the intervention and ten (one death) in the control group (IRR 0·91 [95% CI 0·37–2·23]; p=0·83). Interpretation We found no evidence that an intervention comprising cleaner burning biomass-fuelled cookstoves reduced the risk of pneumonia in young children in rural Malawi. Effective strategies to reduce the adverse health effects of household air pollution are needed. Funding Medical Research Council, UK Department for International Development, and Wellcome Trust.

      PubDate: 2017-01-19T08:21:07Z
      DOI: 10.1016/s0140-6736(16)32507-7
       
  • The Healthy Activity Program (HAP), a lay counsellor-delivered brief
           psychological treatment for severe depression, in primary care in India: a
           randomised controlled trial
    • Authors: Vikram Patel; Benedict Weobong; Helen A Weiss; Arpita Anand; Bhargav Bhat; Basavraj Katti; Sona Dimidjian; Ricardo Araya; Steve D Hollon; Michael King; Lakshmi Vijayakumar; A-La Park; David McDaid; Terry Wilson; Richard Velleman; Betty R Kirkwood; Christopher G Fairburn
      Pages: 176 - 185
      Abstract: Publication date: 14–20 January 2017
      Source:The Lancet, Volume 389, Issue 10065
      Author(s): Vikram Patel, Benedict Weobong, Helen A Weiss, Arpita Anand, Bhargav Bhat, Basavraj Katti, Sona Dimidjian, Ricardo Araya, Steve D Hollon, Michael King, Lakshmi Vijayakumar, A-La Park, David McDaid, Terry Wilson, Richard Velleman, Betty R Kirkwood, Christopher G Fairburn
      Background Although structured psychological treatments are recommended as first-line interventions for depression, only a small fraction of people globally receive these treatments because of poor access in routine primary care. We assessed the effectiveness and cost-effectiveness of a brief psychological treatment (Healthy Activity Program [HAP]) for delivery by lay counsellors to patients with moderately severe to severe depression in primary health-care settings. Methods In this randomised controlled trial, we recruited participants aged 18–65 years scoring more than 14 on the Patient Health Questionnaire 9 (PHQ-9) indicating moderately severe to severe depression from ten primary health centres in Goa, India. Pregnant women or patients who needed urgent medical attention or were unable to communicate clearly were not eligible. Participants were randomly allocated (1:1) to enhanced usual care (EUC) alone or EUC combined with HAP in randomly sized blocks (block size four to six [two to four for men]), stratified by primary health centre and sex, and allocation was concealed with use of sequential numbered opaque envelopes. Physicians providing EUC were masked. Primary outcomes were depression symptom severity on the Beck Depression Inventory version II and remission from depression (PHQ-9 score of <10) at 3 months in the intention-to-treat population, assessed by masked field researchers. Secondary outcomes were disability, days unable to work, behavioural activation, suicidal thoughts or attempts, intimate partner violence, and resource use and costs of illness. We assessed serious adverse events in the per-protocol population. This trial is registered with the ISRCTN registry, number ISRCTN95149997. Findings Between Oct 28, 2013, and July 29, 2015, we enrolled and randomly allocated 495 participants (247 [50%] to the EUC plus HAP group [two of whom were subsequently excluded because of protocol violations] and 248 [50%] to the EUC alone group), of whom 466 (95%) completed the 3 month primary outcome assessment (230 [49%] in the EUC plus HAP group and 236 [51%] in the EUC alone group). Participants in the EUC plus HAP group had significantly lower symptom severity (Beck Depression Inventory version II in EUC plus HAP group 19·99 [SD 15·70] vs 27·52 [13·26] in EUC alone group; adjusted mean difference −7·57 [95% CI −10·27 to −4·86]; p<0·0001) and higher remission (147 [64%] of 230 had a PHQ-9 score of <10 in the HAP plus EUC group vs 91 [39%] of 236 in the EUC alone group; adjusted prevalence ratio 1·61 [1·34–1·93]) than did those in the EUC alone group. EUC plus HAP showed better results than did EUC alone for the secondary outcomes of disability (adjusted mean difference −2·73 [–4·39 to −1·06]; p=0·001), days out of work (−2·29 [–3·84 to −0·73]; p=0·004), intimate partner physical violence in women (0·53 [0·29–0·96]; p=0·04), behavioural activation (2·17 [1·34–3·00]; p<0·0001), and suicidal thoughts or attempts (0·61 [0·45–0·83]; p=0·001). The incremental cost per quality-adjusted life-year gained was $9333 (95% CI 3862–28 169; 2015 international dollars), with an 87% chance of being cost-effective in the study setting. Serious adverse events were infrequent and similar between groups (nine [4%] in the EUC plus HAP group vs ten [4%] in the EUC alone group; p=1·00). Interpretation HAP delivered by lay counsellors plus EUC was better than EUC alone was for patients with moderately severe to severe depression in routine primary care in Goa, India. HAP was readily accepted by this previously untreated population and was cost-effective in this setting. HAP could be a key strategy to reduce the treatment gap for depressive disorders, the leading mental health disorder worldwide. Funding Wellcome Trust.
      ...
      PubDate: 2017-01-19T08:21:07Z
      DOI: 10.1016/s0140-6736(16)31589-6
       
  • Counselling for Alcohol Problems (CAP), a lay counsellor-delivered brief
           psychological treatment for harmful drinking in men, in primary care in
           India: a randomised controlled trial
    • Authors: Abhijit Nadkarni; Benedict Weobong; Helen A Weiss; Jim McCambridge; Bhargav Bhat; Basavaraj Katti; Pratima Murthy; Michael King; David McDaid; A-La Park; G Terence Wilson; Betty Kirkwood; Christopher G Fairburn; Richard Velleman; Vikram Patel
      Pages: 186 - 195
      Abstract: Publication date: 14–20 January 2017
      Source:The Lancet, Volume 389, Issue 10065
      Author(s): Abhijit Nadkarni, Benedict Weobong, Helen A Weiss, Jim McCambridge, Bhargav Bhat, Basavaraj Katti, Pratima Murthy, Michael King, David McDaid, A-La Park, G Terence Wilson, Betty Kirkwood, Christopher G Fairburn, Richard Velleman, Vikram Patel
      Background Although structured psychological treatments are recommended as first-line interventions for harmful drinking, only a small fraction of people globally receive these treatments because of poor access in routine primary care. We assessed the effectiveness and cost-effectiveness of Counselling for Alcohol Problems (CAP), a brief psychological treatment delivered by lay counsellors to patients with harmful drinking attending routine primary health-care settings. Methods In this randomised controlled trial, we recruited male harmful drinkers defined by an Alcohol Use Disorders Identification Test (AUDIT) score of 12–19 who were aged 18–65 years from ten primary health centres in Goa, India. We excluded patients who needed emergency medical treatment or inpatient admission, who were unable to communicate clearly, and who were intoxicated at the time of screening. Participants were randomly allocated (1:1) by trained health assistants based at the primary health centres to enhanced usual care (EUC) alone or EUC combined with CAP, in randomly sized blocks of four to six, stratified by primary health centre, and allocation was concealed with use of sequential numbered opaque envelopes. Physicians providing EUC and those assessing outcomes were masked. Primary outcomes were remission (AUDIT score of <8) and mean daily alcohol consumed in the past 14 days, at 3 months. Secondary outcomes were the effect of drinking, disability score, days unable to work, suicide attempts, intimate partner violence, and resource use and costs of illness. Analyses were on an intention-to-treat basis. We used logistic regression analysis for remission and zero-inflated negative binomial regression analysis for alcohol consumption. We assessed serious adverse events in the per-protocol population. This trial is registered with the ISCRTN registry, number ISRCTN76465238. Findings Between Oct 28, 2013, and July 29, 2015, we enrolled and randomly allocated 377 participants (188 [50%] to the EUC plus CAP group and 190 [50%] to the EUC alone group [one of whom was subsequently excluded because of a protocol violation]), of whom 336 (89%) completed the 3 month primary outcome assessment (164 [87%] in the EUC plus CAP group and 172 [91%] in the EUC alone group). The proportion with remission (59 [36%] of 164 in the EUC plus CAP group vs 44 [26%] of 172 in the EUC alone group; adjusted prevalence ratio 1·50 [95% CI 1·09–2·07]; p=0·01) and the proportion abstinent in the past 14 days (68 [42%] vs 31 [18%]; adjusted odds ratio 3·00 [1·76–5·13]; p<0·0001) were significantly higher in the EUC plus CAP group than in the EUC alone group, but we noted no effect on mean daily alcohol consumed in the past 14 days among those who reported drinking in this period (37·0 g [SD 44·2] vs 31·0 g [27·8]; count ratio 1·08 [0·79–1·49]; p=0·62). We noted an effect on the percentage of days abstinent in the past 14 days (adjusted mean difference [AMD] 16·0% [8·1–24·1]; p<0·0001), but no effect on the percentage of days of heavy drinking (AMD −0·4% [–5·7 to 4·9]; p=0·88), the effect of drinking (Short Inventory of Problems score AMD–0·03 [–1·93 to 1·86]; p=0.97), disability score (WHO Disability Assessment Schedule score AMD 0·62 [–0·62 to 1·87]; p=0·32), days unable to work (no days unable to work adjusted odds ratio 1·02 [0·61–1·69]; p=0.95), suicide attempts (adjusted prevalence ratio 1·8 [–2·4 to 6·0]; p=0·25), and intimate partner violence (adjusted prevalence ratio 3·0 [–10·4 to 4·4]; p=0·57). The incremental cost per additional remission was $217 (95% CI 50–1073), with an 85% chance of being cost-effective in the study setting. We noted no significant difference in the number of serious adverse events between the two groups (six [4%] in the EUC plus CAP group vs 13 [8%] in the EUC alone group; p=0·11). Interpretation CAP delivered by lay counsellors plus EUC was better than EUC alone was for harmful drinkers in routine primary health-care settings, and might be cost-effective. CAP could be a key strategy to reduce the treatment gap for alcohol use di...
      PubDate: 2017-01-19T08:21:07Z
      DOI: 10.1016/s0140-6736(16)31590-2
       
  • Plain film signs of sickle β-thalassaemia
    • Authors: Layla A Nasr; Ali A Haydar
      First page: 196
      Abstract: Publication date: 14–20 January 2017
      Source:The Lancet, Volume 389, Issue 10065
      Author(s): Layla A Nasr, Ali A Haydar


      PubDate: 2017-01-19T08:21:07Z
      DOI: 10.1016/s0140-6736(16)30182-9
       
  • Acute myocardial infarction
    • Authors: Grant W Reed; Jeffrey E Rossi; Christopher P Cannon
      Pages: 197 - 210
      Abstract: Publication date: 14–20 January 2017
      Source:The Lancet, Volume 389, Issue 10065
      Author(s): Grant W Reed, Jeffrey E Rossi, Christopher P Cannon
      Acute myocardial infarction has traditionally been divided into ST elevation or non-ST elevation myocardial infarction; however, therapies are similar between the two, and the overall management of acute myocardial infarction can be reviewed for simplicity. Acute myocardial infarction remains a leading cause of morbidity and mortality worldwide, despite substantial improvements in prognosis over the past decade. The progress is a result of several major trends, including improvements in risk stratification, more widespread use of an invasive strategy, implementation of care delivery systems prioritising immediate revascularisation through percutaneous coronary intervention (or fibrinolysis), advances in antiplatelet agents and anticoagulants, and greater use of secondary prevention strategies such as statins. This seminar discusses the important topics of the pathophysiology, epidemiological trends, and modern management of acute myocardial infarction, focusing on the recent advances in reperfusion strategies and pharmacological treatment approaches.

      PubDate: 2017-01-19T08:21:07Z
      DOI: 10.1016/s0140-6736(16)30677-8
       
  • Viral bronchiolitis
    • Authors: Todd A Florin; Amy C Plint; Joseph J Zorc
      Pages: 211 - 224
      Abstract: Publication date: 14–20 January 2017
      Source:The Lancet, Volume 389, Issue 10065
      Author(s): Todd A Florin, Amy C Plint, Joseph J Zorc
      Viral bronchiolitis is a common clinical syndrome affecting infants and young children. Concern about its associated morbidity and cost has led to a large body of research that has been summarised in systematic reviews and integrated into clinical practice guidelines in several countries. The evidence and guideline recommendations consistently support a clinical diagnosis with the limited role for diagnostic testing for children presenting with the typical clinical syndrome of viral upper respiratory infection progressing to the lower respiratory tract. Management is largely supportive, focusing on maintaining oxygenation and hydration of the patient. Evidence suggests no benefit from bronchodilator or corticosteroid use in infants with a first episode of bronchiolitis. Evidence for other treatments such as hypertonic saline is evolving but not clearly defined yet. For infants with severe disease, the insufficient available data suggest a role for high-flow nasal cannula and continuous positive airway pressure use in a monitored setting to prevent respiratory failure.

      PubDate: 2017-01-19T08:21:07Z
      DOI: 10.1016/s0140-6736(16)30951-5
       
  • Stressed brain, stressed heart'
    • Authors: Ilze Bot; Johan Kuiper
      Abstract: Publication date: Available online 12 January 2017
      Source:The Lancet
      Author(s): Ilze Bot, Johan Kuiper


      PubDate: 2017-01-19T08:21:07Z
      DOI: 10.1016/s0140-6736(17)30044-2
       
  • Relation between resting amygdalar activity and cardiovascular events: a
           longitudinal and cohort study
    • Authors: Ahmed Tawakol; Amorina Ishai; Richard AP Takx; Amparo L Figueroa; Abdelrahman Ali; Yannick Kaiser; Quynh A Truong; Chloe JE Solomon; Claudia Calcagno; Venkatesh Mani; Cheuk Y Tang; Willem JM Mulder; James W Murrough; Udo Hoffmann; Matthias Nahrendorf; Lisa M Shin; Zahi A Fayad; Roger K Pitman
      Abstract: Publication date: Available online 12 January 2017
      Source:The Lancet
      Author(s): Ahmed Tawakol, Amorina Ishai, Richard AP Takx, Amparo L Figueroa, Abdelrahman Ali, Yannick Kaiser, Quynh A Truong, Chloe JE Solomon, Claudia Calcagno, Venkatesh Mani, Cheuk Y Tang, Willem JM Mulder, James W Murrough, Udo Hoffmann, Matthias Nahrendorf, Lisa M Shin, Zahi A Fayad, Roger K Pitman
      Background Emotional stress is associated with increased risk of cardiovascular disease. We imaged the amygdala, a brain region involved in stress, to determine whether its resting metabolic activity predicts risk of subsequent cardiovascular events. Methods Individuals aged 30 years or older without known cardiovascular disease or active cancer disorders, who underwent 18F-fluorodexoyglucose PET/CT at Massachusetts General Hospital (Boston, MA, USA) between Jan 1, 2005, and Dec 31, 2008, were studied longitudinally. Amygdalar activity, bone-marrow activity, and arterial inflammation were assessed with validated methods. In a separate cross-sectional study we analysed the relation between perceived stress, amygdalar activity, arterial inflammation, and C-reactive protein. Image analyses and cardiovascular disease event adjudication were done by mutually blinded researchers. Relations between amygdalar activity and cardiovascular disease events were assessed with Cox models, log-rank tests, and mediation (path) analyses. Findings 293 patients (median age 55 years [IQR 45·0–65·5]) were included in the longitudinal study, 22 of whom had a cardiovascular disease event during median follow-up of 3·7 years (IQR 2·7–4·8). Amygdalar activity was associated with increased bone-marrow activity (r=0·47; p<0·0001), arterial inflammation (r=0·49; p<0·0001), and risk of cardiovascular disease events (standardised hazard ratio 1·59, 95% CI 1·27–1·98; p<0·0001), a finding that remained significant after multivariate adjustments. The association between amygdalar activity and cardiovascular disease events seemed to be mediated by increased bone-marrow activity and arterial inflammation in series. In the separate cross-sectional study of patients who underwent psychometric analysis (n=13), amygdalar activity was significantly associated with arterial inflammation (r=0·70; p=0·0083). Perceived stress was associated with amygdalar activity (r=0·56; p=0·0485), arterial inflammation (r=0·59; p=0·0345), and C-reactive protein (r=0·83; p=0·0210). Interpretation In this first study to link regional brain activity to subsequent cardiovascular disease, amygdalar activity independently and robustly predicted cardiovascular disease events. Amygdalar activity is involved partly via a path that includes increased bone-marrow activity and arterial inflammation. These findings provide novel insights into the mechanism through which emotional stressors can lead to cardiovascular disease in human beings. Funding None.

      PubDate: 2017-01-19T08:21:07Z
      DOI: 10.1016/s0140-6736(16)31714-7
       
  • Infantile haemangioma
    • Authors: Christine Léauté-Labrèze; John I Harper; Peter H Hoeger
      Abstract: Publication date: Available online 13 January 2017
      Source:The Lancet
      Author(s): Christine Léauté-Labrèze, John I Harper, Peter H Hoeger
      With a prevalence of 4·5%, infantile haemangiomas are the most common benign tumours of infancy, arising in the first few weeks of life and exhibiting a characteristic sequence of growth and spontaneous involution. Most infantile haemangiomas do not require therapy. However, to identify at-risk haemangiomas, close follow-up is crucial in the first weeks of life; 80% of all haemangiomas reach their final size by 3 months of age. The main indications for treatment are life-threatening infantile haemangioma (causing heart failure or respiratory distress), tumours posing functional risks (eg, visual obstruction, amblyopia, or feeding difficulties), ulceration, and severe anatomic distortion, especially on the face. Oral propranolol is now the first-line treatment, which should be administered as early as possible to avoid potential complications. Haemangioma shrinkage is rapidly observed with oral propranolol, but a minimum of 6 months of therapy is recommended.

      PubDate: 2017-01-19T08:21:07Z
      DOI: 10.1016/s0140-6736(16)00645-0
       
  • Department of Error
    • Abstract: Publication date: Available online 13 January 2017
      Source:The Lancet


      PubDate: 2017-01-19T08:21:07Z
       
  • Department of error
    • Abstract: Publication date: 14–20 January 2017
      Source:The Lancet, Volume 389, Issue 10065


      PubDate: 2017-01-19T08:21:07Z
       
  • ACA repeal and the AMA
    • Authors: Lancet
      Abstract: Publication date: 14–20 January 2017
      Source:The Lancet, Volume 389, Issue 10065
      Author(s): The Lancet


      PubDate: 2017-01-19T08:21:07Z
       
  • Clinical guidance for bronchiolitis
    • Authors: Lancet
      Abstract: Publication date: 14–20 January 2017
      Source:The Lancet, Volume 389, Issue 10065
      Author(s): The Lancet


      PubDate: 2017-01-19T08:21:07Z
       
  • Health in India, 2017
    • Authors: Lancet
      Abstract: Publication date: 14–20 January 2017
      Source:The Lancet, Volume 389, Issue 10065
      Author(s): The Lancet


      PubDate: 2017-01-19T08:21:07Z
       
  • Enhanced terminal room disinfection and acquisition and infection caused
           by multidrug-resistant organisms and Clostridium difficile (the Benefits
           of Enhanced Terminal Room Disinfection study): a cluster-randomised,
           multicentre, crossover study
    • Authors: Deverick J Anderson; Luke F Chen; David J Weber; Rebekah W Moehring; Sarah S Lewis; Patricia F Triplett; Michael Blocker; Paul Becherer; J Conrad Schwab; Lauren P Knelson; Yuliya Lokhnygina; William A Rutala; Hajime Kanamori; Maria F Gergen; Daniel J Sexton
      Abstract: Publication date: Available online 17 January 2017
      Source:The Lancet
      Author(s): Deverick J Anderson, Luke F Chen, David J Weber, Rebekah W Moehring, Sarah S Lewis, Patricia F Triplett, Michael Blocker, Paul Becherer, J Conrad Schwab, Lauren P Knelson, Yuliya Lokhnygina, William A Rutala, Hajime Kanamori, Maria F Gergen, Daniel J Sexton
      Background Patients admitted to hospital can acquire multidrug-resistant organisms and Clostridium difficile from inadequately disinfected environmental surfaces. We determined the effect of three enhanced strategies for terminal room disinfection (disinfection of a room between occupying patients) on acquisition and infection due to meticillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci, C difficile, and multidrug-resistant Acinetobacter. Methods We did a pragmatic, cluster-randomised, crossover trial at nine hospitals in the southeastern USA. Rooms from which a patient with infection or colonisation with a target organism was discharged were terminally disinfected with one of four strategies: reference (quaternary ammonium disinfectant except for C difficile, for which bleach was used); UV (quaternary ammonium disinfectant and disinfecting ultraviolet [UV-C] light except for C difficile, for which bleach and UV-C were used); bleach; and bleach and UV-C. The next patient admitted to the targeted room was considered exposed. Every strategy was used at each hospital in four consecutive 7-month periods. We randomly assigned the sequence of strategies for each hospital (1:1:1:1). The primary outcomes were the incidence of infection or colonisation with all target organisms among exposed patients and the incidence of C difficile infection among exposed patients in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT01579370. Findings 31 226 patients were exposed; 21 395 (69%) met all inclusion criteria, including 4916 in the reference group, 5178 in the UV group, 5438 in the bleach group, and 5863 in the bleach and UV group. 115 patients had the primary outcome during 22 426 exposure days in the reference group (51·3 per 10 000 exposure days). The incidence of target organisms among exposed patients was significantly lower after adding UV to standard cleaning strategies (n=76; 33·9 cases per 10 000 exposure days; relative risk [RR] 0·70, 95% CI 0·50–0·98; p=0·036). The primary outcome was not statistically lower with bleach (n=101; 41·6 cases per 10 000 exposure days; RR 0·85, 95% CI 0·69–1·04; p=0·116), or bleach and UV (n=131; 45·6 cases per 10 000 exposure days; RR 0·91, 95% CI 0·76–1·09; p=0·303) among exposed patients. Similarly, the incidence of C difficile infection among exposed patients was not changed after adding UV to cleaning with bleach (n=38 vs 36; 30·4 cases vs 31·6 cases per 10 000 exposure days; RR 1·0, 95% CI 0·57–1·75; p=0·997). Interpretation A contaminated health-care environment is an important source for acquisition of pathogens; enhanced terminal room disinfection decreases this risk. Funding US Centers for Disease Control and Prevention.

      PubDate: 2017-01-19T08:21:07Z
      DOI: 10.1016/s0140-6736(16)31588-4
       
  • Laryngeal mask airways in anaesthetised infants: a paradigm shift'
    • Authors: John Fiadjoe; Ronald Litman
      Abstract: Publication date: Available online 18 January 2017
      Source:The Lancet
      Author(s): John Fiadjoe, Ronald Litman


      PubDate: 2017-01-19T08:21:07Z
      DOI: 10.1016/s0140-6736(17)30120-4
       
  • Terminal room disinfection: how much BETR can it get'
    • Authors: Matthew P Crotty; Patricia J Jackson
      Abstract: Publication date: Available online 17 January 2017
      Source:The Lancet
      Author(s): Matthew P Crotty, Patricia J Jackson


      PubDate: 2017-01-19T08:21:07Z
      DOI: 10.1016/s0140-6736(16)32412-6
       
  • What will Donald Trump's presidency mean for health' A scorecard
    • Authors: Martin McKee; Scott L Greer; David Stuckler
      Abstract: Publication date: Available online 19 January 2017
      Source:The Lancet
      Author(s): Martin McKee, Scott L Greer, David Stuckler
      US Presidents make their mark on health, for better or worse. Donald Trump campaigned on a populist platform to “make America great again”. While the actual policies his administration will pursue—and the priority he will place on each of them—remain in many ways uncertain, both his statements and his nominations for key government posts suggest that his presidency could have profound implications for health. His proposal to repeal and replace the Affordable Care Act with a “better reform”, his stance on reproductive rights, and his approaches to other areas, such as science policy and climate change, coupled with his stated intention to put “America first” are creating anxiety and uncertainty about America's domestic health policies and its global leadership role in areas such as security and development. We propose criteria on which the global health community can judge the success or failure of a Trump presidency, based on a selection of the 17 Sustainable Development Goals that apply to health.

      PubDate: 2017-01-19T08:21:07Z
      DOI: 10.1016/s0140-6736(17)30122-8
       
  • The effect of endotracheal tubes versus laryngeal mask airways on
           perioperative respiratory adverse events in infants: a randomised
           controlled trial
    • Authors: Thomas F E Drake-Brockman; Anoop Ramgolam; Guicheng Zhang; Graham L Hall; Britta S von Ungern-Sternberg
      Abstract: Publication date: Available online 18 January 2017
      Source:The Lancet
      Author(s): Thomas F E Drake-Brockman, Anoop Ramgolam, Guicheng Zhang, Graham L Hall, Britta S von Ungern-Sternberg
      Background Perioperative respiratory adverse events (PRAE) are the most common critical incidents in paediatric anaesthesia and occur more often in infants. Use of laryngeal mask airways (LMAs) is associated with reduced PRAE compared with endotracheal tubes in older children (>1 year). We aimed to evaluate the effect of these devices on the incidence of PRAE in infants. Methods We did a randomised controlled trial at the Princess Margaret Hospital for Children in Perth (WA, Australia) by recruiting infants (aged 0–12 months) undergoing general (with or without regional or local) anaesthesia with anticipated fentanyl dose 1 μg/kg or lower for minor elective surgery. We excluded patients contraindicated for LMA or endotracheal tube; who had known cardiac disease or airway or thoracic malformations; who were receiving midazolam premedication; who were undergoing airway, thoracic, or abdomen surgery at the time of participation; and if the parents did not speak English. Written parental or guardian consent was obtained before enrolment. Participants were randomly assigned (1:1), by computer-generated variable block randomisation, to receive an LMA (PRO-Breathe, Well Lead Medical Co Ltd, Panyu, China) or an endotracheal tube (Microcuff, Halyard Health Inc, Atlanta, GA, USA). Sealed randomisation envelopes were used to conceal device assignment. An interim analysis was planned once half the number of infants needed (145) had been recruited. The primary outcome was incidence of PRAE, assessed in the intention-to-treat population. The institutional ethics committee at the Princess Margaret Hospital for Children granted ethical approval (1786/EP). The trial is registered with the Australian New Zealand Clinical Trials Registry (ACTRN12610000250033). Findings The trial began on July 8, 2010, and was ended early on May 7, 2015, after the interim analysis results met the study stopping rules. During this time, 239 infants were assessed and 181 eligible infants were randomly assigned to receive an LMA (n=85) or an endotracheal tube (n=95). Four infants were not included in the analysis (two due to cancelled procedures, one did not meet inclusion criteria, and one with missing dataset). In the intention-to-treat analysis, PRAE occurred in 50 (53%) infants in the endotracheal tube group and in 15 (18%) infants in the LMA group (risk ratio [RR] 2·94, 95% CI 1·79–4·83, p<0·0001). Laryngospasm and bronchospasm (major PRAE) were recorded in 18 (19%) infants in the endotracheal tube group and in three (4%) infants in the LMA group (RR 5·30, 95% CI 1·62–17·35, p=0·002). No deaths were reported. Interpretation In infants undergoing minor elective procedures, LMAs were associated with clinically significantly fewer PRAE and lower occurrence of major PRAE (laryngospasm and bronchospasm) than endotracheal tubes. This difference should be a consideration in airway device selection. Funding Princess Margaret Hospital Foundation, National Health and Australian Medical Research Council, Stan Perron Charitable Trust, and Callahan Estate.

      PubDate: 2017-01-19T08:21:07Z
      DOI: 10.1016/s0140-6736(16)31719-6
       
  • CEPI—a new global R&amp;D organisation for epidemic preparedness
           and response
    • Authors: Brende Jeremy; Farrar Diane Gashumba Carlos Moedas Trevor Mundel Yasuhisa
      Abstract: Publication date: Available online 19 January 2017
      Source:The Lancet
      Author(s): Børge Brende, Jeremy Farrar, Diane Gashumba, Carlos Moedas, Trevor Mundel, Yasuhisa Shiozaki, Harsh Vardhan, Johanna Wanka, John-Arne Røttingen


      PubDate: 2017-01-19T08:21:07Z
       
  • Evidence for underuse of effective medical services around the world
    • Authors: Paul Glasziou; Sharon Straus; Shannon Brownlee; Lyndal Trevena; Leonila Dans; Gordon Guyatt; Adam G Elshaug; Robert Janett; Vikas Saini
      Abstract: Publication date: Available online 9 January 2017
      Source:The Lancet
      Author(s): Paul Glasziou, Sharon Straus, Shannon Brownlee, Lyndal Trevena, Leonila Dans, Gordon Guyatt, Adam G Elshaug, Robert Janett, Vikas Saini
      Underuse—the failure to use effective and affordable medical interventions—is common and responsible for substantial suffering, disability, and loss of life worldwide. Underuse occurs at every point along the treatment continuum, from populations lacking access to health care to inadequate supply of medical resources and labour, slow or partial uptake of innovations, and patients not accessing or declining them. The extent of underuse for different interventions varies by country, and is documented in countries of high, middle, and low-income, and across different types of health-care systems, payment models, and health services. Most research into underuse has focused on measuring solutions to the problem, with considerably less attention paid to its global prevalence or its consequences for patients and populations. Although focused effort and resources can overcome specific underuse problems, comparatively little is spent on work to better understand and overcome the barriers to improved uptake of effective interventions, and methods to make them affordable.

      PubDate: 2017-01-12T11:44:47Z
      DOI: 10.1016/s0140-6736(16)30946-1
       
  • Intracerebral haemorrhage: no good treatment but treatment helps
    • Authors: Alejandro A Rabinstein
      Abstract: Publication date: Available online 10 January 2017
      Source:The Lancet
      Author(s): Alejandro A Rabinstein


      PubDate: 2017-01-12T11:44:47Z
      DOI: 10.1016/s0140-6736(17)30002-8
       
  • Thrombolytic removal of intraventricular haemorrhage in treatment of
           severe stroke: results of the randomised, multicentre, multiregion,
           placebo-controlled CLEAR III trial
    • Authors: Daniel F Hanley; Karen Lane; Nichol McBee; Wendy Ziai; Stanley Tuhrim; Kennedy R Lees; Jesse Dawson; Dheeraj Gandhi; Natalie Ullman; W Andrew Mould; Steven W Mayo; A David Mendelow; Barbara Gregson; Kenneth Butcher; Paul Vespa; David W Wright; Carlos S Kase; J Ricardo Carhuapoma; Penelope M Keyl; Marie Diener-West; John Muschelli; Joshua F Betz; Carol B Thompson; Elizabeth A Sugar; Gayane Yenokyan; Scott Janis; Sayona John; Sagi Harnof; George A Lopez; E Francois Aldrich; Mark R Harrigan; Safdar Ansari; Jack Jallo; Jean-Louis Caron; David LeDoux; Opeolu Adeoye; Mario Zuccarello; Harold P Adams; Michael Rosenblum; Richard E Thompson; Issam A Awad
      Abstract: Publication date: Available online 10 January 2017
      Source:The Lancet
      Author(s): Daniel F Hanley, Karen Lane, Nichol McBee, Wendy Ziai, Stanley Tuhrim, Kennedy R Lees, Jesse Dawson, Dheeraj Gandhi, Natalie Ullman, W Andrew Mould, Steven W Mayo, A David Mendelow, Barbara Gregson, Kenneth Butcher, Paul Vespa, David W Wright, Carlos S Kase, J Ricardo Carhuapoma, Penelope M Keyl, Marie Diener-West, John Muschelli, Joshua F Betz, Carol B Thompson, Elizabeth A Sugar, Gayane Yenokyan, Scott Janis, Sayona John, Sagi Harnof, George A Lopez, E Francois Aldrich, Mark R Harrigan, Safdar Ansari, Jack Jallo, Jean-Louis Caron, David LeDoux, Opeolu Adeoye, Mario Zuccarello, Harold P Adams, Michael Rosenblum, Richard E Thompson, Issam A Awad
      Background Intraventricular haemorrhage is a subtype of intracerebral haemorrhage, with 50% mortality and serious disability for survivors. We aimed to test whether attempting to remove intraventricular haemorrhage with alteplase versus saline irrigation improved functional outcome. Methods In this randomised, double-blinded, placebo-controlled, multiregional trial (CLEAR III), participants with a routinely placed extraventricular drain, in the intensive care unit with stable, non-traumatic intracerebral haemorrhage volume less than 30 mL, intraventricular haemorrhage obstructing the 3rd or 4th ventricles, and no underlying pathology were adaptively randomly assigned (1:1), via a web-based system to receive up to 12 doses, 8 h apart of 1 mg of alteplase or 0·9% saline via the extraventricular drain. The treating physician, clinical research staff, and participants were masked to treatment assignment. CT scans were obtained every 24 h throughout dosing. The primary efficacy outcome was good functional outcome, defined as a modified Rankin Scale score (mRS) of 3 or less at 180 days per central adjudication by blinded evaluators. This study is registered with ClinicalTrials.gov, NCT00784134. Findings Between Sept 18, 2009, and Jan 13, 2015, 500 patients were randomised: 249 to the alteplase group and 251 to the saline group. 180-day follow-up data were available for analysis from 246 of 249 participants in the alteplase group and 245 of 251 participants in the placebo group. The primary efficacy outcome was similar in each group (good outcome in alteplase group 48% vs saline 45%; risk ratio [RR] 1·06 [95% CI 0·88–1·28; p=0·554]). A difference of 3·5% (RR 1·08 [95% CI 0·90–1·29], p=0·420) was found after adjustment for intraventricular haemorrhage size and thalamic intracerebral haemorrhage. At 180 days, the treatment group had lower case fatality (46 [18%] vs saline 73 [29%], hazard ratio 0·60 [95% CI 0·41–0·86], p=0·006), but a greater proportion with mRS 5 (42 [17%] vs 21 [9%]; RR 1·99 [95% CI 1·22–3·26], p=0·007). Ventriculitis (17 [7%] alteplase vs 31 [12%] saline; RR 0·55 [95% CI 0·31–0·97], p=0·048) and serious adverse events (114 [46%] alteplase vs 151 [60%] saline; RR 0·76 [95% CI 0·64–0·90], p=0·002) were less frequent with alteplase treatment. Symptomatic bleeding (six [2%] in the alteplase group vs five [2%] in the saline group; RR 1·21 [95% CI 0·37–3·91], p=0·771) was similar. Interpretation In patients with intraventricular haemorrhage and a routine extraventricular drain, irrigation with alteplase did not substantially improve functional outcomes at the mRS 3 cutoff compared with irrigation with saline. Protocol-based use of alteplase with extraventricular drain seems safe. Future investigation is needed to determine whether a greater frequency of complete intraventricular haemorrhage removal via alteplase produces gains in functional status. Funding National Institute of Neurological Disorders and Stroke.

      PubDate: 2017-01-12T11:44:47Z
      DOI: 10.1016/s0140-6736(16)32410-2
       
  • Clinical development of hepatitis C virus host-targeting agents
    • Authors: Mirjam B Zeisel; Thomas F Baumert
      Abstract: Publication date: Available online 11 January 2017
      Source:The Lancet
      Author(s): Mirjam B Zeisel, Thomas F Baumert


      PubDate: 2017-01-12T11:44:47Z
      DOI: 10.1016/s0140-6736(17)30043-0
       
  • Safety, tolerability, and antiviral effect of RG-101 in patients with
           chronic hepatitis C: a phase 1B, double-blind, randomised controlled trial
           
    • Authors: Meike H van der Ree; J Marleen de Vree; Femke Stelma; Sophie Willemse; Marc van der Valk; Svend Rietdijk; Richard Molenkamp; Janke Schinkel; Ad C van Nuenen; Ulrich Beuers; Salah Hadi; Marten Harbers; Eva van der Veer; Kai Liu; John Grundy; Amy K Patick; Adam Pavlicek; Jacqueline Blem; Michael Huang; Paul Grint; Steven Neben; Neil W Gibson; Neeltje A Kootstra; Hendrik W Reesink
      Abstract: Publication date: Available online 11 January 2017
      Source:The Lancet
      Author(s): Meike H van der Ree, J Marleen de Vree, Femke Stelma, Sophie Willemse, Marc van der Valk, Svend Rietdijk, Richard Molenkamp, Janke Schinkel, Ad C van Nuenen, Ulrich Beuers, Salah Hadi, Marten Harbers, Eva van der Veer, Kai Liu, John Grundy, Amy K Patick, Adam Pavlicek, Jacqueline Blem, Michael Huang, Paul Grint, Steven Neben, Neil W Gibson, Neeltje A Kootstra, Hendrik W Reesink
      Background miR-122 is an important host factor for hepatitis C virus (HCV) replication. The aim of this study was to assess the safety and tolerability, pharmacokinetics, and antiviral effect of a single dose of RG-101, a hepatocyte targeted N-acetylgalactosamine conjugated oligonucleotide that antagonises miR-122, in patients with chronic HCV infection with various genotypes. Methods In this randomised, double-blind, placebo-controlled, multicentre, phase 1B study, patients were randomly assigned to RG-101 or placebo (7:1). We enrolled men and postmenopausal or hysterectomised women (aged 18–65 years) with chronic HCV genotype 1, 3, or 4 infection diagnosed at least 24 weeks before screening who were either treatment naive to or relapsed after interferon-α based therapy. Patients with co-infection (hepatitis B virus or HIV infection), evidence of decompensated liver disease, or a history of hepatocellular carcinoma were excluded. Randomisation was done by an independent, unblinded, statistician using the SAS procedure Proc Plan. The first cohort received one subcutaneous injection of 2 mg/kg RG-101 or placebo; the second cohort received one subcutaneous injection of 4 mg/kg or placebo. Patients were followed up for 8 weeks (all patients) and up to 76 weeks (patients with no viral rebound and excluding those who were randomised to the placebo group) after randomisation. The primary objective was safety and tolerability of RG-101. This trial was registered with EudraCT, number 2013-002978-49. Findings Between June 4, 2014, and Oct 27, 2014, we enrolled 32 patients with chronic HCV genotype 1 (n=16), 3 (n=10), or 4 (n=6) infections. In the first cohort, 14 patients were randomly assigned to receive 2 mg/kg RG-101 and two patients were randomly assigned to receive placebo, and in the second cohort, 14 patients were randomly assigned to receive 4 mg/kg RG-101 and two patients were randomly assigned to receive placebo. Overall, 26 of the 28 patients dosed with RG-101 reported at least one treatment-related adverse event. At week 4, the median viral load reduction from baseline was 4·42 (IQR 3·23–5·00) and 5·07 (4·19–5·35) log10 IU/mL in patients dosed with 2 mg/kg RG-101 or 4 mg/kg RG-101. Three patients had undetectable HCV RNA levels 76 weeks after a single dose of RG-101. Viral rebound at or before week 12 was associated with the appearance of resistance associated substitutions in miR-122 binding regions in the 5′ UTR of the HCV genome. Interpretation This study showed that one administration of 2 mg/kg or 4 mg/kg RG-101, a hepatocyte targeted N-acetylgalactosamine conjugated anti-miR-122 oligonucleotide, was well tolerated and resulted in substantial viral load reduction in all treated patients within 4 weeks, and sustained virological response in three patients for 76 weeks. Funding Regulus Therapeutics, Inc.

      PubDate: 2017-01-12T11:44:47Z
      DOI: 10.1016/s0140-6736(16)31715-9
       
 
 
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