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Journal Cover   The Lancet
  [SJR: 11.563]   [H-I: 514]   [1378 followers]  Follow
    
   Full-text available via subscription Subscription journal
   ISSN (Print) 0140-6736 - ISSN (Online) 1474-547X
   Published by Elsevier Homepage  [2586 journals]
  • Public mental health: evidenced-based priorities
    • Abstract: Publication date: 11–17 April 2015
      Source:The Lancet, Volume 385, Issue 9976
      Author(s): Nisha Mehta , Tim Croudace , Dame Sally C Davies



      PubDate: 2015-04-12T04:57:40Z
       
  • Arxula adeninivorans causing invasive pulmonary mycosis and fungaemia in
           cystic fibrosis
    • Abstract: Publication date: 11–17 April 2015
      Source:The Lancet, Volume 385, Issue 9976
      Author(s): Jobst F Roehmel , Kathrin Tintelnot , Anne Bernhardt , Michael Seibold , Doris Staab , Carsten Schwarz



      PubDate: 2015-04-12T04:57:40Z
       
  • The case for stepped-wedge studies: a trial of falls prevention
    • Abstract: Publication date: Available online 9 April 2015
      Source:The Lancet
      Author(s): Sarah E Lamb



      PubDate: 2015-04-12T04:57:40Z
       
  • Fall rates in hospital rehabilitation units after individualised patient
           and staff education programmes: a pragmatic, stepped-wedge,
           cluster-randomised controlled trial
    • Abstract: Publication date: Available online 9 April 2015
      Source:The Lancet
      Author(s): Anne-Marie Hill , Steven M McPhail , Nicholas Waldron , Christopher Etherton-Beer , Katharine Ingram , Leon Flicker , Max Bulsara , Terry P Haines
      Background Falls are the most frequent adverse events that are reported in hospitals. We examined the effectiveness of individualised falls-prevention education for patients, supported by training and feedback for staff, delivered as a ward-level programme. Methods Eight rehabilitation units in general hospitals in Australia participated in this stepped-wedge, cluster-randomised study, undertaken during a 50 week period. Units were randomly assigned to intervention or control groups by use of computer-generated, random allocation sequences. We included patients admitted to the unit during the study with a Mini-Mental State Examination (MMSE) score of more than 23/30 to receive individualised education that was based on principles of changes in health behaviour from a trained health professional, in addition to usual care. We provided information about patients' goals, feedback about the ward environment, and perceived barriers to engagement in falls-prevention strategies to staff who were trained to support the uptake of strategies by patients. The coprimary outcome measures were patient rate of falls per 1000 patient-days and the proportion of patients who were fallers. All analyses were by intention to treat. This trial is registered with the Australian New Zealand Clinical Trials registry, number ACTRN12612000877886). Findings Between Jan 13, and Dec 27, 2013, 3606 patients were admitted to the eight units (n=1983 control period; n=1623 intervention period). There were fewer falls (n=196, 7·80/1000 patient-days vs n=380, 13·78/1000 patient-days, adjusted rate ratio 0·60 [robust 95% CI 0·42–0·94], p=0·003), injurious falls (n=66, 2·63/1000 patient-days vs 131, 4·75/1000 patient-days, 0·65 [robust 95% CI 0·42–0·88], p=0·006), and fallers (n=136 [8·38%] vs n=248 [12·51%] adjusted odds ratio 0·55 [robust 95% CI 0·38 to 0·81], p=0·003) in the intervention compared with the control group. There was no significant difference in length of stay (intervention median 11 days [IQR 7–19], control 10 days [6–18]). Interpretation Individualised patient education programmes combined with training and feedback to staff added to usual care reduces the rates of falls and injurious falls in older patients in rehabilitation hospital-units. Funding State Health Research Advisory Council, Department of Health, Government of Western Australia.


      PubDate: 2015-04-12T04:57:40Z
       
  • Chronic myeloid leukaemia
    • Abstract: Publication date: 11–17 April 2015
      Source:The Lancet, Volume 385, Issue 9976
      Author(s): Jane F Apperley
      In less than 10 years, the prognosis of chronic myeloid leukaemia has changed from that of a fatal disease to a disorder amenable simply to lifelong oral medication and compatible with a normal lifespan. This change has been made possible by a deep understanding of the molecular pathogenesis and a determination to develop targeted and selective drugs. This Seminar summarises the presentation, pathophysiology, diagnosis and monitoring technology, treatment options, side-effects, and outcomes of chronic myeloid leukaemia, and discusses the possibility of cure—ie, stable undetectable or low level disease in the absence of medication. Chronic myeloid leukaemia continues to instruct us in the mechanisms of leukaemogenesis and provides hope not only for similar developments in management of other malignancies, but also for the remarkable speed with which these can move from bench to bedside.


      PubDate: 2015-04-12T04:57:40Z
       
  • IgG4-related disease
    • Abstract: Publication date: 11–17 April 2015
      Source:The Lancet, Volume 385, Issue 9976
      Author(s): Terumi Kamisawa , Yoh Zen , Shiv Pillai , John H Stone
      IgG4-related disease is a protean condition that mimics many malignant, infectious, and inflammatory disorders. This multi-organ immune-mediated condition links many disorders previously regarded as isolated, single-organ diseases without any known underlying systemic condition. It was recognised as a unified entity only 10 years ago. Histopathology is the key to diagnosis. The three central pathology features of IgG4-related disease are lymphoplasmacytic infiltration, storiform fibrosis, and obliterative phlebitis. The extent of fibrosis is an important determinant of responsiveness to immunosuppressive therapies. IgG4-related disease generally responds to glucocorticoids in its inflammatory stage, but recurrent or refractory cases are common. Important mechanistic insights have been derived from studies of patients treated by B-cell depletion. Greater awareness of this disease is needed to ensure earlier diagnoses, which can prevent severe organ damage, disabling tissue fibrosis, and even death. Identification of specific antigens and T-cell clones that drive the disease will be the first steps to elucidate the pathogenesis of IgG4-related disease.


      PubDate: 2015-04-12T04:57:40Z
       
  • Omission of dacarbazine or bleomycin, or both, from the ABVD regimen in
           treatment of early-stage favourable Hodgkin's lymphoma (GHSG HD13): an
           open-label, randomised, non-inferiority trial
    • Abstract: Publication date: 11–17 April 2015
      Source:The Lancet, Volume 385, Issue 9976
      Author(s): Karolin Behringer , Helen Goergen , Felicitas Hitz , Josée M Zijlstra , Richard Greil , Jana Markova , Stephanie Sasse , Michael Fuchs , Max S Topp , Martin Soekler , Stephan Mathas , Julia Meissner , Martin Wilhelm , Peter Koch , Hans-Walter Lindemann , Enrico Schalk , Robert Semrau , Jan Kriz , Tom Vieler , Martin Bentz , Elisabeth Lange , Rolf Mahlberg , Andre Hassler , Martin Vogelhuber , Dennis Hahn , Jörg Mezger , Stefan W Krause , Nicole Skoetz , Boris Böll , Bastian von Tresckow , Volker Diehl , Michael Hallek , Peter Borchmann , Harald Stein , Hans Eich , Andreas Engert
      Background The role of bleomycin and dacarbazine in the ABVD regimen (ie, doxorubicin, bleomycin, vinblastine, and dacarbazine) has been questioned, especially for treatment of early-stage favourable Hodgkin's lymphoma, because of the drugs' toxicity. We aimed to investigate whether omission of either bleomycin or dacarbazine, or both, from ABVD reduced the efficacy of this regimen in treatment of Hodgkin's lymphoma. Methods In this open-label, randomised, multicentre trial (HD13) we compared two cycles of ABVD with two cycles of the reduced-intensity regimen variants ABV (doxorubicin, bleomycin, and vinblastine), AVD (doxorubicin, vinblastine, and dacarbazine), and AV (doxorubicin and vinblastine), in patients with newly diagnosed, histologically proven, classic or nodular, lymphocyte predominant Hodgkin's lymphoma. In each treatment group, 30 Gy involved-field radiotherapy (IFRT) was given after both cycles of chemotherapy were completed. From Jan 28, 2003, patients were centrally randomly assigned (1:1:1:1) with a minimisation method to the four groups. Because of high event rates, assignment to the AV and ABV groups stopped early, on Sept 30, 2005, and Feb 10, 2006; assignment to ABVD and AVD continued (1:1) until Sept 30, 2009. Our primary objective was to show non-inferiority of the experimental variants compared with ABVD in terms of freedom from treatment failure (FFTF), by excluding a difference of 6% after 5 years corresponding to a hazard ratio (HR) of 1·72, via a 95% CI. Analyses reported here include qualified patients only, and between-group comparisons include only patients recruited during the same period. The trial was registered, number ISRCTN63474366. Findings Of 1502 qualified patients, 566, 198, 571, and 167 were randomly assigned to receive ABVD, ABV, AVD, or AV, respectively. 5 year FFTF was 93·1%, 81·4%, 89·2%, and 77·1% with ABVD, ABV, AVD, and AV, respectively. Compared with ABVD, inferiority of the dacarbazine-deleted variants was detected with 5 year differences of −11·5% (95% CI −18·3 to −4·7; HR 2·06 [1·21 to 3·52]) for ABV and −15·2% (−23·0 to −7·4; HR 2·57 [1·51 to 4·40]) for AV. Non-inferiority of AVD compared with ABVD could also not be detected (5 year difference −3·9%, −7·7 to −0·1; HR 1·50, 1·00 to 2·26). 178 (33%) of 544 patients given ABVD had WHO grade III or IV toxicity, compared with 53 (28%) of 187 given ABV, 142 (26%) of 539 given AVD, and 40 (26%) of 151 given AV. Leucopenia was the most common event, and highest in the groups given bleomycin. Interpretation Dacarbazine cannot be omitted from ABVD without a substantial loss of efficacy. With respect to our predefined non-inferiority margin, bleomycin cannot be safely omitted either, and the standard of care for patients with early-stage favourable Hodgkin's lymphoma should remain ABVD followed by IFRT. Funding Deutsche Krebshilfe and Swiss State Secretariat for Education and Research.


      PubDate: 2015-04-12T04:57:40Z
       
  • Crohn's disease management after intestinal resection: a randomised trial
    • Abstract: Publication date: 11–17 April 2015
      Source:The Lancet, Volume 385, Issue 9976
      Author(s): Peter De Cruz , Michael A Kamm , Amy L Hamilton , Kathryn J Ritchie , Efrosinia O Krejany , Alexandra Gorelik , Danny Liew , Lani Prideaux , Ian C Lawrance , Jane M Andrews , Peter A Bampton , Peter R Gibson , Miles Sparrow , Rupert W Leong , Timothy H Florin , Richard B Gearry , Graham Radford-Smith , Finlay A Macrae , Henry Debinski , Warwick Selby , Ian Kronborg , Michael J Johnston , Rodney Woods , P Ross Elliott , Sally J Bell , Steven J Brown , William R Connell , Paul V Desmond
      Background Most patients with Crohn's disease need an intestinal resection, but a majority will subsequently experience disease recurrence and require further surgery. This study aimed to identify the optimal strategy to prevent postoperative disease recurrence. Methods In this randomised trial, consecutive patients from 17 centres in Australia and New Zealand undergoing intestinal resection of all macroscopic Crohn's disease, with an endoscopically accessible anastomosis, received 3 months of metronidazole therapy. Patients at high risk of recurrence also received a thiopurine, or adalimumab if they were intolerant to thiopurines. Patients were randomly assigned to parallel groups: colonoscopy at 6 months (active care) or no colonoscopy (standard care). We used computer-generated block randomisation to allocate patients in each centre to active or standard care in a 2:1 ratio. For endoscopic recurrence (Rutgeerts score ≥i2) at 6 months, patients stepped-up to thiopurine, fortnightly adalimumab with thiopurine, or weekly adalimumab. The primary endpoint was endoscopic recurrence at 18 months. Patients and treating physicians were aware of the patient's study group and treatment, but central reading of the endoscopic findings was undertaken blind to the study group and treatment. Analysis included all patients who received at least one dose of study drug. This trial is registered with ClinicalTrials.gov, number NCT00989560. Findings Between Oct 13, 2009, and Sept 28, 2011, 174 (83% high risk across both active and standard care groups) patients were enrolled and received at least one dose of study drug. Of 122 patients in the active care group, 47 (39%) stepped-up treatment. At 18 months, endoscopic recurrence occurred in 60 (49%) patients in the active care group and 35 (67%) patients in the standard care group (p=0·03). Complete mucosal normality was maintained in 27 (22%) of 122 patients in the active care group versus four (8%) in the standard care group (p=0·03). In the active care arm, of those with 6 months recurrence who stepped up treatment, 18 (38%) of 47 patients were in remission 12 months later; conversely, of those in remission at 6 months who did not change therapy recurrence occurred in 31 (41%) of 75 patients 12 months later. Smoking (odds ratio [OR] 2·4, 95% CI 1·2–4·8, p=0·02) and the presence of two or more clinical risk factors including smoking (OR 2·8, 95% CI 1·01–7·7, p=0·05) increased the risk of endoscopic recurrence. The incidence and type of adverse and severe adverse events did not differ significantly between patients in the active care and standard care groups (100 [82%] of 122 vs 45 [87%] of 52; p=0·51) and (33 [27%] of 122 vs 18 [35%] of 52; p=0·36), respectively. Interpretation Treatment according to clinical risk of recurrence, with early colonoscopy and treatment step-up for recurrence, is better than conventional drug therapy alone for prevention of postoperative Crohn's disease recurrence. Selective immune suppression, adjusted for early recurrence, rather than routine use, leads to disease control in most patients. Clinical risk factors predict recurrence, but patients at low risk also need monitoring. Early remission does not preclude the need for ongoing monitoring. Funding AbbVie, Gutsy Gro...
      PubDate: 2015-04-12T04:57:40Z
       
  • Department of Error
    • Abstract: Publication date: 11–17 April 2015
      Source:The Lancet, Volume 385, Issue 9976




      PubDate: 2015-04-12T04:57:40Z
       
  • Department of Error
    • Abstract: Publication date: 11–17 April 2015
      Source:The Lancet, Volume 385, Issue 9976




      PubDate: 2015-04-12T04:57:40Z
       
  • Efficacy and safety of LDL-lowering therapy among men and women:
           meta-analysis of individual data from 174 000 participants in 27
           randomised trials
    • Abstract: Publication date: 11–17 April 2015
      Source:The Lancet, Volume 385, Issue 9976

      Background Whether statin therapy is as effective in women as in men is debated, especially for primary prevention. We undertook a meta-analysis of statin trials in the Cholesterol Treatment Trialists' (CTT) Collaboration database to compare the effects of statin therapy between women and men. Methods We performed meta-analyses on data from 22 trials of statin therapy versus control (n=134 537) and five trials of more-intensive versus less-intensive statin therapy (n=39 612). Effects on major vascular events, major coronary events, stroke, coronary revascularisation and mortality were weighted per 1·0 mmol/L reduction in LDL cholesterol and effects in men and women compared with a Cox model that adjusted for non-sex differences. For subgroup analyses, we used 99% CIs to make allowance for the multiplicity of comparisons. Findings 46 675 (27%) of 174 149 randomly assigned participants were women. Allocation to a statin had similar absolute effects on 1 year lipid concentrations in both men and women (LDL cholesterol reduced by about 1·1 mmol/L in statin vs control trials and roughly 0·5 mmol/L for more-intensive vs less-intensive therapy). Women were generally at lower cardiovascular risk than were men in these trials. The proportional reductions per 1·0 mmol/L reduction in LDL cholesterol in major vascular events were similar overall for women (rate ratio [RR] 0·84, 99% CI 0·78–0·91) and men (RR 0·78, 99% CI 0·75–0·81, adjusted p value for heterogeneity by sex=0·33) and also for those women and men at less than 10% predicted 5 year absolute cardiovascular risk (adjusted heterogeneity p=0·11). Likewise, the proportional reductions in major coronary events, coronary revascularisation, and stroke did not differ significantly by sex. No adverse effect on rates of cancer incidence or non-cardiovascular mortality was noted for either sex. These net benefits translated into all-cause mortality reductions with statin therapy for both women (RR 0·91, 99% CI 0·84–0·99) and men (RR 0·90, 99% CI 0·86–0·95; adjusted heterogeneity p=0·43). Interpretation In men and women at an equivalent risk of cardiovascular disease, statin therapy is of similar effectiveness for the prevention of major vascular events. Funding UK Medical Research Council, British Heart Foundation, Australian National Health and Medical Research Council, European Community Biomed Program.


      PubDate: 2015-04-12T04:57:40Z
       
  • Thrombolysis in acute stroke
    • Abstract: Publication date: 11–17 April 2015
      Source:The Lancet, Volume 385, Issue 9976
      Author(s): Valeria Caso , Patrik Michel



      PubDate: 2015-04-12T04:57:40Z
       
  • Thrombolysis in acute stroke – Authors' reply
    • Abstract: Publication date: 11–17 April 2015
      Source:The Lancet, Volume 385, Issue 9976
      Author(s): Jonathan Emberson , Kennedy R Lees , Patrick Lyden , Colin Baigent , Peter Sandercock , Werner Hacke



      PubDate: 2015-04-12T04:57:40Z
       
  • Thrombolysis in acute stroke
    • Abstract: Publication date: 11–17 April 2015
      Source:The Lancet, Volume 385, Issue 9976
      Author(s): Peter Appelros , Andreas Terént



      PubDate: 2015-04-12T04:57:40Z
       
  • Thrombolysis in acute stroke
    • Abstract: Publication date: 11–17 April 2015
      Source:The Lancet, Volume 385, Issue 9976
      Author(s): Mattias Brunström , Bo Carlberg



      PubDate: 2015-04-12T04:57:40Z
       
  • Thrombolysis in acute stroke
    • Abstract: Publication date: 11–17 April 2015
      Source:The Lancet, Volume 385, Issue 9976
      Author(s): David H Newman



      PubDate: 2015-04-12T04:57:40Z
       
  • Ebola and provision of critical care
    • Abstract: Publication date: 11–17 April 2015
      Source:The Lancet, Volume 385, Issue 9976
      Author(s): Srinivas Murthy



      PubDate: 2015-04-12T04:57:40Z
       
  • Prevention of HIV spread during the Ebola outbreak in Guinea
    • Abstract: Publication date: 11–17 April 2015
      Source:The Lancet, Volume 385, Issue 9976
      Author(s): Jacques D A Ndawinz , Mohamed Cissé , Mohamadou S K Diallo , Cheik T Sidibé , Eric D'Ortenzio



      PubDate: 2015-04-12T04:57:40Z
       
  • On the (f)utility of pain
    • Abstract: Publication date: 11–17 April 2015
      Source:The Lancet, Volume 385, Issue 9976
      Author(s): Scott D Stonington



      PubDate: 2015-04-12T04:57:40Z
       
  • Warren Berggren
    • Abstract: Publication date: 11–17 April 2015
      Source:The Lancet, Volume 385, Issue 9976
      Author(s): Alison Snyder



      PubDate: 2015-04-12T04:57:40Z
       
  • 20 years of the ICRC Code of Conduct for Disaster Relief: what do we need
           to improve'
    • Abstract: Publication date: 11–17 April 2015
      Source:The Lancet, Volume 385, Issue 9976
      Author(s): Ana Borovecki , Jónína Einarsdóttir , Dónal O'Mathúna , Paulina Pospieszna , Orly Maya Stern , Natália Oliva Teles



      PubDate: 2015-04-12T04:57:40Z
       
  • Ebola and provision of critical care
    • Abstract: Publication date: 11–17 April 2015
      Source:The Lancet, Volume 385, Issue 9976
      Author(s): Colin Brown , Benno Kreuels , Peter Baker , Tim Baker , Tom Boyles , Marta Lado , Oliver Johnson



      PubDate: 2015-04-12T04:57:40Z
       
  • Sargent the aesthete
    • Abstract: Publication date: 11–17 April 2015
      Source:The Lancet, Volume 385, Issue 9976
      Author(s): Tamara Lucas



      PubDate: 2015-04-12T04:57:40Z
       
  • Plenty of bite WillSelfShark2015Penguin9780141046389480£8·99.
    • Abstract: Publication date: 11–17 April 2015
      Source:The Lancet, Volume 385, Issue 9976
      Author(s): Stephen Ginn



      PubDate: 2015-04-12T04:57:40Z
       
  • Ralph Kohn: philanthropic pharmacologist with all the right notes
    • Abstract: Publication date: 11–17 April 2015
      Source:The Lancet, Volume 385, Issue 9976
      Author(s): Geoff Watts



      PubDate: 2015-04-12T04:57:40Z
       
  • Achieving respectful care for women and babies
    • Abstract: Publication date: 11–17 April 2015
      Source:The Lancet, Volume 385, Issue 9976
      Author(s): The Lancet



      PubDate: 2015-04-12T04:57:40Z
       
  • Thrombolysis for stroke: clinical judgment at its apogee
    • Abstract: Publication date: 11–17 April 2015
      Source:The Lancet, Volume 385, Issue 9976
      Author(s): The Lancet



      PubDate: 2015-04-12T04:57:40Z
       
  • The quality narrative in health care
    • Abstract: Publication date: 11–17 April 2015
      Source:The Lancet, Volume 385, Issue 9976
      Author(s): Oliver P Keown , Ara Darzi



      PubDate: 2015-04-12T04:57:40Z
       
  • Offline: What is medicine's 5 sigma'
    • Abstract: Publication date: 11–17 April 2015
      Source:The Lancet, Volume 385, Issue 9976
      Author(s): Richard Horton



      PubDate: 2015-04-12T04:57:40Z
       
  • UK medical research gets political
    • Abstract: Publication date: 11–17 April 2015
      Source:The Lancet, Volume 385, Issue 9976
      Author(s): Becky McCall



      PubDate: 2015-04-12T04:57:40Z
       
  • Israeli clinic provides lifeline for refugees
    • Abstract: Publication date: 11–17 April 2015
      Source:The Lancet, Volume 385, Issue 9976
      Author(s): Talha Burki



      PubDate: 2015-04-12T04:57:40Z
       
  • Is malaria control better with both treated nets and spraying'
    • Abstract: Publication date: 11–17 April 2015
      Source:The Lancet, Volume 385, Issue 9976
      Author(s): Jo Lines , Immo Kleinschmidt



      PubDate: 2015-04-12T04:57:40Z
       
  • Making sense of health estimates
    • Abstract: Publication date: 11–17 April 2015
      Source:The Lancet, Volume 385, Issue 9976
      Author(s): Irene Agyepong , Tumani Corrah , Yan Guo , Bruce Hollingsworth , Michael Klag , Kim Longfield , Maria de Fatima Marinho de Souza , Peter Piot , JVR Prasada Rao , John-Arne Røttingen , Peter Smith , Marc Sprenger , Trevor Sutton , Sarah Curran , Edmond SW Ng



      PubDate: 2015-04-12T04:57:40Z
       
  • Sex, statins, and statistics
    • Abstract: Publication date: 11–17 April 2015
      Source:The Lancet, Volume 385, Issue 9976
      Author(s): Lori Mosca



      PubDate: 2015-04-12T04:57:40Z
       
  • Surgery for Crohn's disease: look harder, act faster
    • Abstract: Publication date: 11–17 April 2015
      Source:The Lancet, Volume 385, Issue 9976
      Author(s): Ashwin N Ananthakrishnan



      PubDate: 2015-04-12T04:57:40Z
       
  • Hodgkin's lymphoma: better outcomes with fewer drugs'
    • Abstract: Publication date: 11–17 April 2015
      Source:The Lancet, Volume 385, Issue 9976
      Author(s): Olivier Casasnovas , Bertrand Coiffier



      PubDate: 2015-04-12T04:57:40Z
       
  • Ebola: the battle plan must include specific treatments
    • Abstract: Publication date: 11–17 April 2015
      Source:The Lancet, Volume 385, Issue 9976
      Author(s): Jake Dunning , William Fischer II



      PubDate: 2015-04-12T04:57:40Z
       
  • China's medical research integrity questioned
    • Abstract: Publication date: 11–17 April 2015
      Source:The Lancet, Volume 385, Issue 9976
      Author(s): The Lancet



      PubDate: 2015-04-12T04:57:40Z
       
  • Efficacy of indoor residual spraying with dichlorodiphenyltrichloroethane
           against malaria in Gambian communities with high usage of long-lasting
           insecticidal mosquito nets: a cluster-randomised controlled trial
    • Abstract: Publication date: 11–17 April 2015
      Source:The Lancet, Volume 385, Issue 9976
      Author(s): Margaret Pinder , Musa Jawara , Lamin B S Jarju , Kolawole Salami , David Jeffries , Majidah Adiamoh , Kalifa Bojang , Simon Correa , Balla Kandeh , Harparkash Kaur , David J Conway , Umberto D'Alessandro , Steve W Lindsay
      Background Although many malaria control programmes in sub-Saharan Africa use indoor residual spraying with long-lasting insecticidal nets (LLINs), the two studies assessing the benefit of the combination of these two interventions gave conflicting results. We aimed to assess whether the addition of indoor residual spraying to LLINs provided a significantly different level of protection against clinical malaria in children or against house entry by vector mosquitoes. Methods In this two-arm cluster, randomised, controlled efficacy trial we randomly allocated clusters of Gambian villages using a computerised algorithm to LLINs alone (n=35) or indoor residual spraying with dichlorodiphenyltrichloroethane plus LLINs (n=35). In each cluster, 65–213 children, aged 6 months to 14 years, were surveyed at the start of the 2010 transmission season and followed in 2010 and 2011 by passive case detection for clinical malaria. Exposure to parasite transmission was assessed by collection of vector mosquitoes with both light and exit traps indoors. Primary endpoints were the incidence of clinical malaria assessed by passive case detection and number of Anopheles gambiae sensu lato mosquitoes collected per light trap per night. Intervention teams had no role in data collection and the data collection teams were not informed of the spray status of villages. The trial is registered at the ISRCTN registry, number ISRCTN01738840. Findings LLIN coverage in 2011 was 3510 (93%) of 3777 children in the indoor residual spraying plus LLIN group and 3622 (95·5%) of 3791 in the LLIN group. In 2010, 7845 children were enrolled, 7829 completed passive case detection, and 7697 (98%) had complete clinical and covariate data. In 2011, 7009 children remained in the study, 648 more were enrolled, 7657 completed passive case detection, and 7545 (98·5%) had complete data. Indoor residual spraying coverage per cluster was more than 80% for both years in the indoor residual spraying plus LLIN group. Incidence of clinical malaria was 0·047 per child-month at risk in the LLIN group and 0·044 per child-month at risk in the indoor residual spraying plus LLIN group in 2010, and 0·032 per child-month at risk in the LLIN group and 0·034 per child-month at risk in the indoor residual spraying plus LLIN group in 2011. The incident rate ratio was 1·08 (95% CI 0·80–1·46) controlling for confounders and cluster by mixed-effect negative binomial regression on all malaria attacks for both years. No significant difference was recorded in the density of vector mosquitoes caught in light traps in houses over the two transmission seasons; the mean number of A gambiae sensu lato mosquitoes per trap per night was 6·7 (4·0–10·1) in the LLIN group and 4·5 (2·4–7·4) in the indoor residual spraying plus LLIN group (p=0·281 in the random-effects linear regression model). Interpretation We identified no significant difference in clinical malaria or vector density between study groups. In this area with high LLIN coverage, moderate seasonal transmission, and susceptible vectors, indoor residual spraying did not provide additional benefit. Funding UK Medical Research Council.


      PubDate: 2015-04-12T04:57:40Z
       
  • Severe Ebola virus disease with vascular leakage and multiorgan failure:
           treatment of a patient in intensive care
    • Abstract: Publication date: 11–17 April 2015
      Source:The Lancet, Volume 385, Issue 9976
      Author(s): Timo Wolf , Gerrit Kann , Stephan Becker , Christoph Stephan , Hans-Reinhardt Brodt , Philipp de Leuw , Thomas Grünewald , Thomas Vogl , Volkhard A J Kempf , Oliver T Keppler , Kai Zacharowski
      Background In the current epidemic of Ebola virus disease in western Africa, many aid workers have become infected. Some of these aid workers have been transferred to specialised hospitals in Europe and the USA for intensified treatment, providing the potential for unique insight into the clinical course of Ebola virus disease under optimised supportive measures in isolation units. Methods A 38-year-old male doctor who had contracted an Ebola virus infection in Sierra Leone was airlifted to University Hospital Frankfurt, Germany, on day 5 after disease onset. Within 72 h of admission to the hospital's high-level isolation unit, the patient developed signs of severe multiorgan failure, including lungs, kidneys, and gastrointestinal tract. In addition to clinical parameters, the diagnostic work-up included radiography, ultrasound, pulse contour cardiac output technology, and microbiological and clinical chemistry analyses. Respiratory failure with pulmonary oedema and biophysical evidence of vascular leak syndrome needed mechanical ventilation. The patient received a 3 day treatment course with FX06 (MChE-F4Pharma, Vienna, Austria), a fibrin-derived peptide under clinical development for vascular leak syndrome. After FX06 administration and concurrent detection of Ebola-virus-specific antibodies and a fall in viral load, vascular leak syndrome and respiratory parameters substantially improved. We gave broad-spectrum empiric antimicrobial therapy and the patient needed intermittent renal replacement therapy. The patient fully recovered. Findings This case report shows the feasibility of delivery of successful intensive care therapy to patients with Ebola virus disease under biosafety level 4 conditions. Interpretation The effective treatment of vascular leakage and multiorgan failure by combination of ventilatory support, antibiotic treatment, and renal replacement therapy can sustain a patient with severe Ebola virus disease until virological remission. FX06 could potentially be a valuable agent in contribution to supportive therapy. Funding University Hospital of Frankfurt.


      PubDate: 2015-04-12T04:57:40Z
       
  • Left ventricular non-compaction cardiomyopathy
    • Abstract: Publication date: Available online 9 April 2015
      Source:The Lancet
      Author(s): Jeffrey A Towbin , Angela Lorts , John Lynn Jefferies
      Left ventricular non-compaction, the most recently classified form of cardiomyopathy, is characterised by abnormal trabeculations in the left ventricle, most frequently at the apex. It can be associated with left ventricular dilation or hypertrophy, systolic or diastolic dysfunction, or both, or various forms of congenital heart disease. Affected individuals are at risk of left or right ventricular failure, or both. Heart failure symptoms can be induced by exercise or be persistent at rest, but many patients are asymptomatic. Patients on chronic treatment for compensated heart failure sometimes present acutely with decompensated heart failure. Other life-threatening risks of left ventricular non-compaction are ventricular arrhythmias or complete atrioventricular block, presenting clinically as syncope, and sudden death. Genetic inheritance arises in at least 30–50% of patients, and several genes that cause left ventricular non-compaction have been identified. These genes seem generally to encode sarcomeric (contractile apparatus) or cytoskeletal proteins, although, in the case of left ventricular non-compaction with congenital heart disease, disturbance of the NOTCH signalling pathway seems part of a final common pathway for this form of the disease. Disrupted mitochondrial function and metabolic abnormalities have a causal role too. Treatments focus on improvement of cardiac efficiency and reduction of mechanical stress in patients with systolic dysfunction. Further, treatment of arrhythmia and implantation of an automatic implantable cardioverter-defibrillator for prevention of sudden death are mainstays of therapy when deemed necessary and appropriate. Patients with left ventricular non-compaction and congenital heart disease often need surgical or catheter-based interventions. Despite progress in diagnosis and treatment in the past 10 years, understanding of the disorder and outcomes need to be improved.


      PubDate: 2015-04-12T04:57:40Z
       
  • Induction of labour versus expectant management for large-for-date
           fetuses: a randomised controlled trial
    • Abstract: Publication date: Available online 8 April 2015
      Source:The Lancet
      Author(s): Michel Boulvain , Marie-Victoire Senat , Franck Perrotin , Norbert Winer , Gael Beucher , Damien Subtil , Florence Bretelle , Elie Azria , Dominique Hejaiej , Françoise Vendittelli , Marianne Capelle , Bruno Langer , Richard Matis , Laure Connan , Philippe Gillard , Christine Kirkpatrick , Gilles Ceysens , Gilles Faron , Olivier Irion , Patrick Rozenberg
      Background Macrosomic fetuses are at increased risk of shoulder dystocia. We aimed to compare induction of labour with expectant management for large-for-date fetuses for prevention of shoulder dystocia and other neonatal and maternal morbidity associated with macrosomia. Methods We did this pragmatic, randomised controlled trial between Oct 1, 2002, and Jan 1, 2009, in 19 tertiary-care centres in France, Switzerland, and Belgium. Women with singleton fetuses whose estimated weight exceeded the 95th percentile, were randomly assigned (1:1), via computer-generated permuted-block randomisation (block size of four to eight) to receive induction of labour within 3 days between 37+0 weeks and 38+6 weeks of gestation, or expectant management. Randomisation was stratified by centre. Participants and caregivers were not masked to group assignment. Our primary outcome was a composite of clinically significant shoulder dystocia, fracture of the clavicle, brachial plexus injury, intracranial haemorrhage, or death. We did analyses by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00190320. Findings We randomly assigned 409 women to the induction group and 413 women to the expectant management group, of whom 407 women and 411 women, respectively, were included in the final analysis. Mean birthweight was 3831 g (SD 324) in the induction group and 4118 g (392) in the expectant group. Induction of labour significantly reduced the risk of shoulder dystocia or associated morbidity (n=8) compared with expectant management (n=25; relative risk [RR] 0·32, 95% CI 0·15–0·71; p=0·004). We recorded no brachial plexus injuries, intracranial haemorrhages, or perinatal deaths. The likelihood of spontaneous vaginal delivery was higher in women in the induction group than in those in the expectant management group (RR 1·14, 95% CI 1·01–1·29). Caesarean delivery and neonatal morbidity did not differ significantly between the groups. Interpretation Induction of labour for suspected large-for-date fetuses is associated with a reduced risk of shoulder dystocia and associated morbidity compared with expectant management. Induction of labour does not increase the risk of caesarean delivery and improves the likelihood of spontaneous vaginal delivery. These benefits should be balanced with the effects of early-term induction of labour. Funding Assistance Publique–Hôpitaux de Paris and the University of Geneva.


      PubDate: 2015-04-12T04:57:40Z
       
  • Should pregnancies be induced for impending macrosomia'
    • Abstract: Publication date: Available online 8 April 2015
      Source:The Lancet
      Author(s): Aaron B Caughey



      PubDate: 2015-04-12T04:57:40Z
       
  • When less is more: maintenance therapy in colorectal cancer
    • Abstract: Publication date: Available online 7 April 2015
      Source:The Lancet
      Author(s): Joleen M Hubbard , Axel Grothey



      PubDate: 2015-04-08T04:55:40Z
       
  • Maintenance treatment with capecitabine and bevacizumab in metastatic
           colorectal cancer (CAIRO3): a phase 3 randomised controlled trial of the
           Dutch Colorectal Cancer Group
    • Abstract: Publication date: Available online 7 April 2015
      Source:The Lancet
      Author(s): Lieke H J Simkens , Harm van Tinteren , Anne May , Albert J ten Tije , Geert-Jan M Creemers , Olaf J L Loosveld , Felix E de Jongh , Frans L G Erdkamp , Zoran Erjavec , Adelheid M E van der Torren , Jolien Tol , Hans J J Braun , Peter Nieboer , Jacobus J M van der Hoeven , Janny G Haasjes , Rob L H Jansen , Jaap Wals , Annemieke Cats , Veerle A Derleyn , Aafke H Honkoop , Linda Mol , Cornelis J A Punt , Miriam Koopman
      Background The optimum duration of first-line treatment with chemotherapy in combination with bevacizumab in patients with metastatic colorectal cancer is unknown. The CAIRO3 study was designed to determine the efficacy of maintenance treatment with capecitabine plus bevacizumab versus observation. Methods In this open-label, phase 3, randomised controlled trial, we recruited patients in 64 hospitals in the Netherlands. We included patients older than 18 years with previously untreated metastatic colorectal cancer, with stable disease or better after induction treatment with six 3-weekly cycles of capecitabine, oxaliplatin, and bevacizumab (CAPOX-B), WHO performance status of 0 or 1, and adequate bone marrow, liver, and renal function. Patients were randomly assigned (1:1) to either maintenance treatment with capecitabine and bevacizumab (maintenance group) or observation (observation group). Randomisation was done centrally by minimisation, with stratification according to previous adjuvant chemotherapy, response to induction treatment, WHO performance status, serum lactate dehydrogenase concentration, and treatment centre. Both patients and investigators were aware of treatment assignment. We assessed disease status every 9 weeks. On first progression (defined as PFS1), patients in both groups were to receive the induction regimen of CAPOX-B until second progression (PFS2), which was the study's primary endpoint. All endpoints were calculated from the time of randomisation. Analyses were done by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00442637. Findings Between May 30, 2007, and Oct 15, 2012, we randomly assigned 558 patients to either the maintenance group (n=279) or the observation group (n=279). Median follow-up was 48 months (IQR 36–57). The primary endpoint of median PFS2 was significantly improved in patients on maintenance treatment, and was 8·5 months in the observation group and 11·7 months in the maintenance group (HR 0·67, 95% CI 0·56–0·81, p<0·0001). This difference remained significant when any treatment after PFS1 was considered. Maintenance treatment was well tolerated, although the incidence of hand-foot syndrome was increased (64 [23%] patients with hand-foot skin reaction during maintenance). The global quality of life did not deteriorate during maintenance treatment and was clinically not different between treatment groups. Interpretation Maintenance treatment with capecitabine plus bevacizumab after six cycles of CAPOX-B in patients with metastatic colorectal cancer is effective and does not compromise quality of life. Funding Dutch Colorectal Cancer Group (DCCG). The DCCG received financial support for the study from the Commissie Klinische Studies (CKS) of the Dutch Cancer Foundation (KWF), Roche, and Sanofi-Aventis.


      PubDate: 2015-04-08T04:55:40Z
       
  • China-Africa Health Collaboration
    • Abstract: Publication date: 4–10 April 2015
      Source:The Lancet, Volume 385, Issue 9975
      Author(s): The Lancet



      PubDate: 2015-04-04T04:53:05Z
       
  • Ending the death penalty
    • Abstract: Publication date: 4–10 April 2015
      Source:The Lancet, Volume 385, Issue 9975
      Author(s): The Lancet



      PubDate: 2015-04-04T04:53:05Z
       
  • Imagining a better place: trust, care, and progress in medicine
    • Abstract: Publication date: 4–10 April 2015
      Source:The Lancet, Volume 385, Issue 9975
      Author(s): David A Leon



      PubDate: 2015-04-04T04:53:05Z
       
  • Glaucoma treatment: by the highest level of evidence
    • Abstract: Publication date: 4–10 April 2015
      Source:The Lancet, Volume 385, Issue 9975
      Author(s): Anders Heijl



      PubDate: 2015-04-04T04:53:05Z
       
  • Guidance for clinicians involved in end-of-life care of children
    • Abstract: Publication date: 4–10 April 2015
      Source:The Lancet, Volume 385, Issue 9975
      Author(s): The Lancet



      PubDate: 2015-04-04T04:53:05Z
       
 
 
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