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Journal Cover   The Lancet
  [SJR: 11.563]   [H-I: 514]   [1255 followers]  Follow
    
   Full-text available via subscription Subscription journal
   ISSN (Print) 0140-6736 - ISSN (Online) 1474-547X
   Published by Elsevier Homepage  [2811 journals]
  • Larry Jameson: at the helm of the USA's oldest medical school
    • Abstract: Publication date: 16–22 May 2015
      Source:The Lancet, Volume 385, Issue 9981
      Author(s): Richard Lane



      PubDate: 2015-05-21T06:40:32Z
       
  • The first American medical school: the formative years
    • Abstract: Publication date: 16–22 May 2015
      Source:The Lancet, Volume 385, Issue 9981
      Author(s): Elizabeth Fee



      PubDate: 2015-05-21T06:40:32Z
       
  • Living kidney donation: outcomes, ethics, and uncertainty
    • Abstract: Publication date: 16–22 May 2015
      Source:The Lancet, Volume 385, Issue 9981
      Author(s): Peter P Reese , Neil Boudville , Amit X Garg
      Since the first living-donor kidney transplantation in 1954, more than half a million living kidney donations have occurred and research has advanced knowledge about long-term donor outcomes. Donors in developed countries have a similar life expectancy and quality of life as healthy non-donors. Living kidney donation is associated with an increased risk of end-stage renal disease, although this outcome is uncommon (<0·5% increase in incidence at 15 years). Kidney donation seems to elevate the risks of gestational hypertension and pre-eclampsia. Many donors incur financial expenses due to factors such as lost wages, need for sick days, and travel expenses. Yet, most donors have no regrets about donation. Living kidney donation is practised ethically when informed consent incorporates information about risks, uncertainty about outcomes is acknowledged when it exists, and a donor's risks are proportional to benefits for the donor and recipient. Future research should determine whether outcomes are similar for donors from developing countries and donors with pre-existing conditions such as obesity.


      PubDate: 2015-05-21T06:40:32Z
       
  • Autosomal dominant polycystic kidney disease: the changing face of
           clinical management
    • Abstract: Publication date: 16–22 May 2015
      Source:The Lancet, Volume 385, Issue 9981
      Author(s): Albert C M Ong , Olivier Devuyst , Bertrand Knebelmann , Gerd Walz
      Autosomal dominant polycystic kidney disease is the most common inherited kidney disease and accounts for 7–10% of all patients on renal replacement therapy worldwide. Although first reported 500 years ago, this disorder is still regarded as untreatable and its pathogenesis is poorly understood despite much study. During the past 40 years, however, remarkable advances have transformed our understanding of how the disease develops and have led to rapid changes in diagnosis, prognosis, and treatment, especially during the past decade. This Review will summarise the key findings, highlight recent developments, and look ahead to the changes in clinical practice that will likely arise from the adoption of a new management framework for this major kidney disease.


      PubDate: 2015-05-21T06:40:32Z
       
  • Pathophysiological advances in membranous nephropathy: time for a shift in
           patient's care
    • Abstract: Publication date: 16–22 May 2015
      Source:The Lancet, Volume 385, Issue 9981
      Author(s): Pierre Ronco , Hanna Debiec
      Membranous nephropathy is a major cause of nephrotic syndrome of non-diabetic origin in adults. It is the second or third leading cause of end-stage renal disease in patients with primary glomerulonephritis, and is the leading glomerulopathy that recurs after kidney transplantation (occurring in about 40% of patients). Treatment with costly and potentially toxic drugs remains controversial and challenging, partly because of insufficient insight into the pathogenesis of the disease and absence of sensitive biomarkers of disease activity. The disease is caused by the formation of immune deposits on the outer aspect of the glomerular basement membrane, which contain podocyte or planted antigens and circulating antibodies specific to those antigens, resulting in complement activation. In 2002, podocyte neutral endopeptidase was identified as an antigenic target of circulating antibodies in alloimmune neonatal nephropathy, and in 2009, podocyte phospholipase A2 receptor (PLA2R) was reported as an antigenic target in autoimmune adult membranous nephropathy. These major breakthroughs were translated to clinical practice very quickly. Measurement of anti-PLA2R antibodies in serum and detection of PLA2R antigen in glomerular deposits can now be done routinely. Anti-PLA2R antibodies have high specificity (close to 100%), sensitivity (70–80%), and predictive value. PLA2R detection in immune deposits allows for retrospective diagnosis of PLA2R-related membranous nephropathy in archival kidney biopsies. These tests already have a major effect on diagnosis and monitoring of treatment, including after transplantation.


      PubDate: 2015-05-21T06:40:32Z
       
  • Worldwide access to treatment for end-stage kidney disease: a systematic
           review
    • Abstract: Publication date: 16–22 May 2015
      Source:The Lancet, Volume 385, Issue 9981
      Author(s): Thaminda Liyanage , Toshiharu Ninomiya , Vivekanand Jha , Bruce Neal , Halle Marie Patrice , Ikechi Okpechi , Ming-hui Zhao , Jicheng Lv , Amit X Garg , John Knight , Anthony Rodgers , Martin Gallagher , Sradha Kotwal , Alan Cass , Vlado Perkovic
      Background End-stage kidney disease is a leading cause of morbidity and mortality worldwide. Prevalence of the disease and worldwide use of renal replacement therapy (RRT) are expected to rise sharply in the next decade. We aimed to quantify estimates of this burden. Methods We systematically searched Medline for observational studies and renal registries, and contacted national experts to obtain RRT prevalence data. We used Poisson regression to estimate the prevalence of RRT for countries without reported data. We estimated the gap between needed and actual RRT, and projected needs to 2030. Findings In 2010, 2·618 million people received RRT worldwide. We estimated the number of patients needing RRT to be between 4·902 million (95% CI 4·438–5·431 million) in our conservative model and 9·701 million (8·544–11·021 million) in our high-estimate model, suggesting that at least 2·284 million people might have died prematurely because RRT could not be accessed. We noted the largest treatment gaps in low-income countries, particularly Asia (1·907 million people needing but not receiving RRT; conservative model) and Africa (432 000 people; conservative model). Worldwide use of RRT is projected to more than double to 5·439 million (3·899–7·640 million) people by 2030, with the most growth in Asia (0·968 million to a projected 2·162 million [1·571–3·014 million]). Interpretation The large number of people receiving RRT and the substantial number without access to it show the need to both develop low-cost treatments and implement effective population-based prevention strategies. Funding Australian National Health and Medical Research Council.


      PubDate: 2015-05-21T06:40:32Z
       
  • Ebola vaccine trial in west Africa faces criticism
    • Abstract: Publication date: 16–22 May 2015
      Source:The Lancet, Volume 385, Issue 9981
      Author(s): Miriam Shuchman



      PubDate: 2015-05-21T06:40:32Z
       
  • Tanzania's model peritoneal dialysis programme
    • Abstract: Publication date: 16–22 May 2015
      Source:The Lancet, Volume 385, Issue 9981
      Author(s): Talha Burki



      PubDate: 2015-05-21T06:40:32Z
       
  • Andrzej Więcek: east meets west in nephrology
    • Abstract: Publication date: 16–22 May 2015
      Source:The Lancet, Volume 385, Issue 9981
      Author(s): David Holmes



      PubDate: 2015-05-21T06:40:32Z
       
  • Thomas Browne: a dialogue across the centuries HughAldersey-WilliamsThe
           Adventures of Sir Thomas Browne in the 21st
           Century2015Granta9781847089007352£20·00
    • Abstract: Publication date: 16–22 May 2015
      Source:The Lancet, Volume 385, Issue 9981
      Author(s): Thomas Wright



      PubDate: 2015-05-21T06:40:32Z
       
  • Disparities in worldwide treatment of kidney failure
    • Abstract: Publication date: 16–22 May 2015
      Source:The Lancet, Volume 385, Issue 9981
      Author(s): Josef Coresh , Tazeen H Jafar



      PubDate: 2015-05-21T06:40:32Z
       
  • Meeting demand for family planning within a generation: the post-2015
           agenda
    • Abstract: Publication date: 16–22 May 2015
      Source:The Lancet, Volume 385, Issue 9981
      Author(s): Madeleine S Fabic , Yoonjoung Choi , John Bongaarts , Jacqueline E Darroch , John A Ross , John Stover , Amy O Tsui , Jagdish Upadhyay , Ellen Starbird



      PubDate: 2015-05-21T06:40:32Z
       
  • Renal medicine—a call for papers
    • Abstract: Publication date: 16–22 May 2015
      Source:The Lancet, Volume 385, Issue 9981
      Author(s): Philippa Berman , Andrzej Więcek



      PubDate: 2015-05-21T06:40:32Z
       
  • Offline: The Scottish Enlightenment, part 2
    • Abstract: Publication date: 16–22 May 2015
      Source:The Lancet, Volume 385, Issue 9981
      Author(s): Richard Horton



      PubDate: 2015-05-21T06:40:32Z
       
  • For every woman, every child, everywhere: a universal agenda for the
           health of women, children, and adolescents
    • Abstract: Publication date: 16–22 May 2015
      Source:The Lancet, Volume 385, Issue 9981
      Author(s): Sarah Zeid , Flavia Bustreo , Maha Taysir Barakat , Peter Maurer , Kate Gilmore



      PubDate: 2015-05-21T06:40:32Z
       
  • A new ASPECT for complicated urinary tract infections
    • Abstract: Publication date: 16–22 May 2015
      Source:The Lancet, Volume 385, Issue 9981
      Author(s): Jasper Fuk-Woo Chan , Kwok-Yung Yuen



      PubDate: 2015-05-21T06:40:32Z
       
  • Renal denervation superior to drug therapy in hypertension
    • Abstract: Publication date: 16–22 May 2015
      Source:The Lancet, Volume 385, Issue 9981
      Author(s): Dagmara Hering



      PubDate: 2015-05-21T06:40:32Z
       
  • On the alert for outcome improvement in acute kidney injury
    • Abstract: Publication date: 16–22 May 2015
      Source:The Lancet, Volume 385, Issue 9981
      Author(s): Chris Laing



      PubDate: 2015-05-21T06:40:32Z
       
  • CRVS systems: a cornerstone of sustainable development
    • Abstract: Publication date: 16–22 May 2015
      Source:The Lancet, Volume 385, Issue 9981
      Author(s): The Lancet



      PubDate: 2015-05-21T06:40:32Z
       
  • Research in kidney disease: an acute and chronic history
    • Abstract: Publication date: 16–22 May 2015
      Source:The Lancet, Volume 385, Issue 9981
      Author(s): The Lancet



      PubDate: 2015-05-21T06:40:32Z
       
  • The Hispanic paradox
    • Abstract: Publication date: 16–22 May 2015
      Source:The Lancet, Volume 385, Issue 9981
      Author(s): The Lancet



      PubDate: 2015-05-21T06:40:32Z
       
  • Automated, electronic alerts for acute kidney injury: a single-blind,
           parallel-group, randomised controlled trial
    • Abstract: Publication date: 16–22 May 2015
      Source:The Lancet, Volume 385, Issue 9981
      Author(s): F Perry Wilson , Michael Shashaty , Jeffrey Testani , Iram Aqeel , Yuliya Borovskiy , Susan S Ellenberg , Harold I Feldman , Hilda Fernandez , Yevgeniy Gitelman , Jennie Lin , Dan Negoianu , Chirag R Parikh , Peter P Reese , Richard Urbani , Barry Fuchs
      Background Acute kidney injury often goes unrecognised in its early stages when effective treatment options might be available. We aimed to determine whether an automated electronic alert for acute kidney injury would reduce the severity of such injury and improve clinical outcomes in patients in hospital. Methods In this investigator-masked, parallel-group, randomised controlled trial, patients were recruited from the hospital of the University of Pennsylvania in Philadelphia, PA, USA. Eligible participants were adults aged 18 years or older who were in hospital with stage 1 or greater acute kidney injury as defined by Kidney Disease Improving Global Outcomes creatinine-based criteria. Exclusion criteria were initial hospital creatinine 4·0 mg/dL (to convert to μmol/L, multiply by 88·4) or greater, fewer than two creatinine values measured, inability to determine the covering provider, admission to hospice or the observation unit, previous randomisation, or end-stage renal disease. Patients were randomly assigned (1:1) via a computer-generated sequence to receive an acute kidney injury alert (a text-based alert sent to the covering provider and unit pharmacist indicating new acute kidney injury) or usual care, stratified by medical versus surgical admission and intensive care unit versus non-intensive care unit location in blocks of 4–8 participants. The primary outcome was a composite of relative maximum change in creatinine, dialysis, and death at 7 days after randomisation. All analyses were by intention to treat. This study is registered with ClinicalTrials.gov, number NCT01862419. Findings Between Sept 17, 2013, and April 14, 2014, 23 664 patients were screened. 1201 eligible participants were assigned to the acute kidney injury alert group and 1192 were assigned to the usual care group. Composite relative maximum change in creatinine, dialysis, and death at 7 days did not differ between the alert group and the usual care group (p=0·88), or within any of the four randomisation strata (all p>0·05). At 7 days after randomisation, median maximum relative change in creatinine concentrations was 0·0% (IQR 0·0–18·4) in the alert group and 0·6% (0·0–17·5) in the usual care group (p=0·81); 87 (7·2%) patients in the alert group and 70 (5·9%) patients in usual care group had received dialysis (odds ratio 1·25 [95% CI 0·90–1·74]; p=0·18); and 71 (5·9%) patients in the alert group and 61 (5·1%) patients in the usual care group had died (1·16 [0·81–1·68]; p=0·40). Interpretation An electronic alert system for acute kidney injury did not improve clinical outcomes among patients in hospital. Funding Penn Center for Healthcare Improvement and Patient Safety.


      PubDate: 2015-05-21T06:40:32Z
       
  • Ureteric colic: evidence empowers responsible treatment
    • Abstract: Publication date: Available online 18 May 2015
      Source:The Lancet
      Author(s): Jean de la Rosette , M Pilar Laguna



      PubDate: 2015-05-21T06:40:32Z
       
  • Medical expulsive therapy in adults with ureteric colic: a multicentre,
           randomised, placebo-controlled trial
    • Abstract: Publication date: Available online 18 May 2015
      Source:The Lancet
      Author(s): Robert Pickard , Kathryn Starr , Graeme MacLennan , Thomas Lam , Ruth Thomas , Jennifer Burr , Gladys McPherson , Alison McDonald , Kenneth Anson , James N'Dow , Neil Burgess , Terry Clark , Mary Kilonzo , Katie Gillies , Kirsty Shearer , Charles Boachie , Sarah Cameron , John Norrie , Samuel McClinton
      Background Meta-analyses of previous randomised controlled trials concluded that the smooth muscle relaxant drugs tamsulosin and nifedipine assisted stone passage for people managed expectantly for ureteric colic, but emphasised the need for high-quality trials with wide inclusion criteria. We aimed to fulfil this need by testing effectiveness of these drugs in a standard clinical care setting. Methods For this multicentre, randomised, placebo-controlled trial, we recruited adults (aged 18–65 years) undergoing expectant management for a single ureteric stone identified by CT at 24 UK hospitals. Participants were randomly assigned by a remote randomisation system to tamsulosin 400 μg, nifedipine 30 mg, or placebo taken daily for up to 4 weeks, using an algorithm with centre, stone size (≤5 mm or >5 mm), and stone location (upper, mid, or lower ureter) as minimisation covariates. Participants, clinicians, and trial personnel were masked to treatment assignment. The primary outcome was the proportion of participants who did not need further intervention for stone clearance within 4 weeks of randomisation, analysed in a modified intention-to-treat population defined as all eligible patients for whom we had primary outcome data. This trial is registered with the European Clinical Trials Database, EudraCT number 2010-019469-26, and as an International Standard Randomised Controlled Trial, number 69423238. Findings Between Jan 11, 2011, and Dec 20, 2013, we randomly assigned 1167 participants, 1136 (97%) of whom were included in the primary analysis (17 were excluded because of ineligibility and 14 participants were lost to follow-up). 303 (80%) of 379 participants in the placebo group did not need further intervention by 4 weeks, compared with 307 (81%) of 378 in the tamsulosin group (adjusted risk difference 1·3% [95% CI −5·7 to 8·3]; p=0·73) and 304 (80%) of 379 in the nifedipine group (0·5% [–5·6 to 6·5]; p=0·88). No difference was noted between active treatment and placebo (p=0·78), or between tamsulosin and nifedipine (p=0·77). Serious adverse events were reported in three participants in the nifedipine group (one had right loin pain, diarrhoea, and vomiting; one had malaise, headache, and chest pain; and one had severe chest pain, difficulty breathing, and left arm pain) and in one participant in the placebo group (headache, dizziness, lightheadedness, and chronic abdominal pain). Interpretation Tamsulosin 400 μg and nifedipine 30 mg are not effective at decreasing the need for further treatment to achieve stone clearance in 4 weeks for patients with expectantly managed ureteric colic. Funding UK National Institute for Health Research Health Technology Assessment Programme.


      PubDate: 2015-05-21T06:40:32Z
       
  • Prognostic value of grip strength: findings from the Prospective Urban
           Rural Epidemiology (PURE) study
    • Abstract: Publication date: Available online 13 May 2015
      Source:The Lancet
      Author(s): Darryl P Leong , Koon K Teo , Sumathy Rangarajan , Patricio Lopez-Jaramillo , Alvaro Avezum Jr , Andres Orlandini , Pamela Seron , Suad H Ahmed , Annika Rosengren , Roya Kelishadi , Omar Rahman , Sumathi Swaminathan , Romaina Iqbal , Rajeev Gupta , Scott A Lear , Aytekin Oguz , Khalid Yusoff , Katarzyna Zatonska , Jephat Chifamba , Ehimario Igumbor , Viswanathan Mohan , Ranjit Mohan Anjana , Hongqiu Gu , Wei Li , Salim Yusuf
      Background Reduced muscular strength, as measured by grip strength, has been associated with an increased risk of all-cause and cardiovascular mortality. Grip strength is appealing as a simple, quick, and inexpensive means of stratifying an individual's risk of cardiovascular death. However, the prognostic value of grip strength with respect to the number and range of populations and confounders is unknown. The aim of this study was to assess the independent prognostic importance of grip strength measurement in socioculturally and economically diverse countries. Methods The Prospective Urban-Rural Epidemiology (PURE) study is a large, longitudinal population study done in 17 countries of varying incomes and sociocultural settings. We enrolled an unbiased sample of households, which were eligible if at least one household member was aged 35–70 years and if household members intended to stay at that address for another 4 years. Participants were assessed for grip strength, measured using a Jamar dynamometer. During a median follow-up of 4·0 years (IQR 2·9–5·1), we assessed all-cause mortality, cardiovascular mortality, non-cardiovascular mortality, myocardial infarction, stroke, diabetes, cancer, pneumonia, hospital admission for pneumonia or chronic obstructive pulmonary disease (COPD), hospital admission for any respiratory disease (including COPD, asthma, tuberculosis, and pneumonia), injury due to fall, and fracture. Study outcomes were adjudicated using source documents by a local investigator, and a subset were adjudicated centrally. Findings Between January, 2003, and December, 2009, a total of 142 861 participants were enrolled in the PURE study, of whom 139 691 with known vital status were included in the analysis. During a median follow-up of 4·0 years (IQR 2·9–5·1), 3379 (2%) of 139 691 participants died. After adjustment, the association between grip strength and each outcome, with the exceptions of cancer and hospital admission due to respiratory illness, was similar across country-income strata. Grip strength was inversely associated with all-cause mortality (hazard ratio per 5 kg reduction in grip strength 1·16, 95% CI 1·13–1·20; p<0·0001), cardiovascular mortality (1·17, 1·11–1·24; p<0·0001), non-cardiovascular mortality (1·17, 1·12–1·21; p<0·0001), myocardial infarction (1·07, 1·02–1·11; p=0·002), and stroke (1·09, 1·05–1·15; p<0·0001). Grip strength was a stronger predictor of all-cause and cardiovascular mortality than systolic blood pressure. We found no significant association between grip strength and incident diabetes, risk of hospital admission for pneumonia or COPD, injury from fall, or fracture. In high-income countries, the risk of cancer and grip strength were positively associated (0·916, 0·880–0·953; p<0·0001), but this association was not found in middle-income and low-income countries. Interpretation This study suggests that measurement of grip strength is a simple, inexpensive risk-stratifying method for all-cause death, cardiovascular death, and cardiovascular disease. Further research is needed to identify determinants of muscular strength and to test whether improvement in strength reduces mortality and cardiovascular disease. Funding Full funding sources listed at end of paper (see Acknowledgments).


      PubDate: 2015-05-21T06:40:32Z
       
  • Platelet interaction with erythrocytes and propensity to aggregation in
           essential thrombocythaemia
    • Abstract: Publication date: Available online 14 May 2015
      Source:The Lancet
      Author(s): Mia-Jeanne van Rooy , Etheresia Pretorius



      PubDate: 2015-05-21T06:40:32Z
       
  • Grip strength and mortality: a biomarker of ageing'
    • Abstract: Publication date: Available online 13 May 2015
      Source:The Lancet
      Author(s): Avan Aihie Sayer , Thomas B L Kirkwood



      PubDate: 2015-05-21T06:40:32Z
       
  • Financing universal health coverage—effects of alternative tax
           structures on public health systems: cross-national modelling in 89
           low-income and middle-income countries
    • Abstract: Publication date: Available online 14 May 2015
      Source:The Lancet
      Author(s): Aaron Reeves , Yannis Gourtsoyannis , Sanjay Basu , David McCoy , Martin McKee , David Stuckler
      Background How to finance progress towards universal health coverage in low-income and middle-income countries is a subject of intense debate. We investigated how alternative tax systems affect the breadth, depth, and height of health system coverage. Methods We used cross-national longitudinal fixed effects models to assess the relationships between total and different types of tax revenue, health system coverage, and associated child and maternal health outcomes in 89 low-income and middle-income countries from 1995–2011. Findings Tax revenue was a major statistical determinant of progress towards universal health coverage. Each US$100 per capita per year of additional tax revenues corresponded to a yearly increase in government health spending of $9·86 (95% CI 3·92–15·8), adjusted for GDP per capita. This association was strong for taxes on capital gains, profits, and income ($16·7, 9·16 to 24·3), but not for consumption taxes on goods and services (−$4·37, −12·9 to 4·11). In countries with low tax revenues (<$1000 per capita per year), an additional $100 tax revenue per year substantially increased the proportion of births with a skilled attendant present by 6·74 percentage points (95% CI 0·87–12·6) and the extent of financial coverage by 11·4 percentage points (5·51–17·2). Consumption taxes, a more regressive form of taxation that might reduce the ability of the poor to afford essential goods, were associated with increased rates of post-neonatal mortality, infant mortality, and under-5 mortality rates. We did not detect these adverse associations with taxes on capital gains, profits, and income, which tend to be more progressive. Interpretation Increasing domestic tax revenues is integral to achieving universal health coverage, particularly in countries with low tax bases. Pro-poor taxes on profits and capital gains seem to support expanding health coverage without the adverse associations with health outcomes observed for higher consumption taxes. Progressive tax policies within a pro-poor framework might accelerate progress toward achieving major international health goals. Funding Commission of the European Communities (FP7–DEMETRIQ), the European Union's HRES grants, and the Wellcome Trust.


      PubDate: 2015-05-21T06:40:32Z
       
  • Universal health coverage: progressive taxes are key
    • Abstract: Publication date: Available online 14 May 2015
      Source:The Lancet
      Author(s): Robert Yates



      PubDate: 2015-05-21T06:40:32Z
       
  • Granulomatous sarcoid aortitis: a serious complication of a well-known
           multisystem disease
    • Abstract: Publication date: 16–22 May 2015
      Source:The Lancet, Volume 385, Issue 9981
      Author(s): Louis W Wang , Abdullah Omari , Louise Emmett , Paul C Jansz , Ravi Huilgol , Stephen Rainer , Rajesh N Subbiah



      PubDate: 2015-05-21T06:40:32Z
       
  • Neoadjuvant chemotherapy for ovarian cancer: do we have enough
           evidence'
    • Abstract: Publication date: Available online 19 May 2015
      Source:The Lancet
      Author(s): Sokbom Kang



      PubDate: 2015-05-21T06:40:32Z
       
  • Long-term effects of lithium on renal, thyroid, and parathyroid function:
           a retrospective analysis of laboratory data
    • Abstract: Publication date: Available online 20 May 2015
      Source:The Lancet
      Author(s): Brian Shine , Rebecca F McKnight , Laurence Leaver , John R Geddes
      Background Lithium is a widely used and highly effective treatment for mood disorders, but causes poorly characterised adverse effects in kidney and endocrine systems. We aimed to analyse laboratory information system data to determine the incidence of renal, thyroid, and parathyroid dysfunction associated with lithium use. Methods In a retrospective analysis of laboratory data from Oxford University Hospitals National Health Service Trust (Oxfordshire, UK), we investigated the incidence of renal, thyroid, and parathyroid dysfunction in patients (aged ≥18 years) who had at least two creatinine, thyrotropin, calcium, glycated haemoglobin, or lithium measurements between Oct 1, 1982, and March 31, 2014, compared with controls who had not had lithium measurements taken. We used survival analysis and Cox regression to estimate the hazard ratio (HR) for each event with lithium use, age, sex, and diabetes as covariates. Findings Adjusting for age, sex, and diabetes, presence of lithium in serum was associated with an increased risk of stage three chronic kidney disease (HR 1·93, 95% CI 1·76–2·12; p<0·0001), hypothyroidism (2·31, 2·05–2·60; p<0·0001), and raised total serum calcium concentration (1·43, 1·21–1·69; p<0·0001), but not with hyperthyroidism (1·22, 0·96–1·55; p=0·1010) or raised adjusted calcium concentration (1·08, 0·88–1·34; p=0·4602). Women were at greater risk of development of renal and thyroid disorders than were men, with younger women at higher risk than older women. The adverse effects occurred early in treatment (HR <1 for length of treatment with lithium). Higher than median lithium concentrations were associated with increased risk of all adverse outcomes. Interpretation Lithium treatment is associated with a decline in renal function, hypothyroidism, and hypercalcaemia. Women younger than 60 years and people with lithium concentrations higher than median are at greatest risk. Because lithium remains a treatment of choice for bipolar disorder, patients need baseline measures of renal, thyroid, and parathyroid function and regular long-term monitoring. Funding None.


      PubDate: 2015-05-21T06:40:32Z
       
  • Climate and health: mortality attributable to heat and cold
    • Abstract: Publication date: Available online 20 May 2015
      Source:The Lancet
      Author(s): Keith Dear , Zhan Wang



      PubDate: 2015-05-21T06:40:32Z
       
  • Primary chemotherapy versus primary surgery for newly diagnosed advanced
           ovarian cancer (CHORUS): an open-label, randomised, controlled,
           non-inferiority trial
    • Abstract: Publication date: Available online 19 May 2015
      Source:The Lancet
      Author(s): Sean Kehoe , Jane Hook , Matthew Nankivell , Gordon C Jayson , Henry Kitchener , Tito Lopes , David Luesley , Timothy Perren , Selina Bannoo , Monica Mascarenhas , Stephen Dobbs , Sharadah Essapen , Jeremy Twigg , Jonathan Herod , Glenn McCluggage , Mahesh Parmar , Ann-Marie Swart
      Background The international standard of care for women with suspected advanced ovarian cancer is surgical debulking followed by platinum-based chemotherapy. We aimed to establish whether use of platinum-based primary chemotherapy followed by delayed surgery was an effective and safe alternative treatment regimen. Methods In this phase 3, non-inferiority, randomised, controlled trial (CHORUS) undertaken in 87 hospitals in the UK and New Zealand, we enrolled women with suspected stage III or IV ovarian cancer. We randomly assigned women (1:1) either to undergo primary surgery followed by six cycles of chemotherapy, or to three cycles of primary chemotherapy, then surgery, followed by three more cycles of completion chemotherapy. Each 3-week cycle consisted of carboplatin AUC5 or AUC6 plus paclitaxel 175 mg/m2, or an alternative carboplatin combination regimen, or carboplatin monotherapy. We did the random assignment by use of a minimisation method with a random element, and stratified participants according to the randomising centre, largest radiological tumour size, clinical stage, and prespecified chemotherapy regimen. Patients and investigators were not masked to group assignment. The primary outcome measure was overall survival. Primary analyses were done in the intention-to-treat population. To establish non-inferiority, the upper bound of a one-sided 90% CI for the hazard ratio (HR) had to be less than 1·18. This trial is registered, number ISRCTN74802813, and is closed to new participants. Findings Between March 1, 2004, and Aug 30, 2010, we randomly assigned 552 women to treatment. Of the 550 women who were eligible, 276 were assigned to primary surgery and 274 to primary chemotherapy. All were included in the intention-to-treat analysis; 251 assigned to primary surgery and 253 to primary chemotherapy were included in the per-protocol analysis. As of May 31, 2014, 451 deaths had occurred: 231 in the primary-surgery group versus 220 in the primary-chemotherapy group. Median overall survival was 22·6 months in the primary-surgery group versus 24·1 months in primary chemotherapy. The HR for death was 0·87 in favour of primary chemotherapy, with the upper bound of the one-sided 90% CI 0·98 (95% CI 0·72–1·05). Grade 3 or 4 postoperative adverse events and deaths within 28 days after surgery were more common in the primary-surgery group than in the primary-chemotherapy group (60 [24%] of 252 women vs 30 [14%] of 209, p=0·0007, and 14 women [6%] vs 1 woman [<1%], p=0·001). The most common grade 3 or 4 postoperative adverse event was haemorrhage in both groups (8 women [3%] in the primary-surgery group vs 14 [6%] in the primary-chemotherapy group). 110 (49%) of 225 women receiving primary surgery and 102 (40%) of 253 receiving primary chemotherapy had a grade 3 or 4 chemotherapy related toxic effect (p=0·0654), mostly uncomplicated neutropenia (20% and 16%, respectively). One fatal toxic effect, neutropenic sepsis, occurred in the primary-chemotherapy group. Interpretation In women with stage III or IV ovarian cancer, survival with primary chemotherapy is non-inferior to primary surgery. In this study population, giving primary chemotherapy before surgery is an acceptable standard of care for women with advanced ovarian cancer. Funding Cancer Research UK and the Royal College of Obstetricians and Gynaecologists.


      PubDate: 2015-05-21T06:40:32Z
       
  • Lithium therapy in bipolar disorder: a balancing act'
    • Abstract: Publication date: Available online 20 May 2015
      Source:The Lancet
      Author(s): Gin S Malhi



      PubDate: 2015-05-21T06:40:32Z
       
  • Mortality risk attributable to high and low ambient temperature: a
           multicountry observational study
    • Abstract: Publication date: Available online 20 May 2015
      Source:The Lancet
      Author(s): Antonio Gasparrini , Yuming Guo , Masahiro Hashizume , Eric Lavigne , Antonella Zanobetti , Joel Schwartz , Aurelio Tobias , Shilu Tong , Joacim Rocklöv , Bertil Forsberg , Michela Leone , Manuela De Sario , Michelle L Bell , Yue-Liang Leon Guo , Chang-fu Wu , Haidong Kan , Seung-Muk Yi , Micheline de Sousa Zanotti Stagliorio Coelh , Paulo Hilario Nascimento Saldiva , Yasushi Honda , Ho Kim , Ben Armstrong
      Background Although studies have provided estimates of premature deaths attributable to either heat or cold in selected countries, none has so far offered a systematic assessment across the whole temperature range in populations exposed to different climates. We aimed to quantify the total mortality burden attributable to non-optimum ambient temperature, and the relative contributions from heat and cold and from moderate and extreme temperatures. Methods We collected data for 384 locations in Australia, Brazil, Canada, China, Italy, Japan, South Korea, Spain, Sweden, Taiwan, Thailand, UK, and USA. We fitted a standard time-series Poisson model for each location, controlling for trends and day of the week. We estimated temperature–mortality associations with a distributed lag non-linear model with 21 days of lag, and then pooled them in a multivariate metaregression that included country indicators and temperature average and range. We calculated attributable deaths for heat and cold, defined as temperatures above and below the optimum temperature, which corresponded to the point of minimum mortality, and for moderate and extreme temperatures, defined using cutoffs at the 2·5th and 97·5th temperature percentiles. Findings We analysed 74 225 200 deaths in various periods between 1985 and 2012. In total, 7·71% (95% empirical CI 7·43–7·91) of mortality was attributable to non-optimum temperature in the selected countries within the study period, with substantial differences between countries, ranging from 3·37% (3·06 to 3·63) in Thailand to 11·00% (9·29 to 12·47) in China. The temperature percentile of minimum mortality varied from roughly the 60th percentile in tropical areas to about the 80–90th percentile in temperate regions. More temperature-attributable deaths were caused by cold (7·29%, 7·02–7·49) than by heat (0·42%, 0·39–0·44). Extreme cold and hot temperatures were responsible for 0·86% (0·84–0·87) of total mortality. Interpretation Most of the temperature-related mortality burden was attributable to the contribution of cold. The effect of days of extreme temperature was substantially less than that attributable to milder but non-optimum weather. This evidence has important implications for the planning of public-health interventions to minimise the health consequences of adverse temperatures, and for predictions of future effect in climate-change scenarios. Funding UK Medical Research Council.


      PubDate: 2015-05-21T06:40:32Z
       
  • Optimum and stepped care standardised antihypertensive treatment with or
           without renal denervation for resistant hypertension (DENERHTN): a
           multicentre, open-label, randomised controlled trial
    • Abstract: Publication date: 16–22 May 2015
      Source:The Lancet, Volume 385, Issue 9981
      Author(s): Michel Azizi , Marc Sapoval , Philippe Gosse , Matthieu Monge , Guillaume Bobrie , Pascal Delsart , Marco Midulla , Claire Mounier-Véhier , Pierre-Yves Courand , Pierre Lantelme , Thierry Denolle , Caroline Dourmap-Collas , Hervé Trillaud , Helena Pereira , Pierre-François Plouin , Gilles Chatellier
      Background Conflicting blood pressure-lowering effects of catheter-based renal artery denervation have been reported in patients with resistant hypertension. We compared the ambulatory blood pressure-lowering efficacy and safety of radiofrequency-based renal denervation added to a standardised stepped-care antihypertensive treatment (SSAHT) with the same SSAHT alone in patients with resistant hypertension. Methods The Renal Denervation for Hypertension (DENERHTN) trial was a prospective, open-label randomised controlled trial with blinded endpoint evaluation in patients with resistant hypertension, done in 15 French tertiary care centres specialised in hypertension management. Eligible patients aged 18–75 years received indapamide 1·5 mg, ramipril 10 mg (or irbesartan 300 mg), and amlodipine 10 mg daily for 4 weeks to confirm treatment resistance by ambulatory blood pressure monitoring before randomisation. Patients were then randomly assigned (1:1) to receive either renal denervation plus an SSAHT regimen (renal denervation group) or the same SSAHT alone (control group). The randomisation sequence was generated by computer, and stratified by centres. For SSAHT, after randomisation, spironolactone 25 mg per day, bisoprolol 10 mg per day, prazosin 5 mg per day, and rilmenidine 1 mg per day were sequentially added from months two to five in both groups if home blood pressure was more than or equal to 135/85 mm Hg. The primary endpoint was the mean change in daytime systolic blood pressure from baseline to 6 months as assessed by ambulatory blood pressure monitoring. The primary endpoint was analysed blindly. The safety outcomes were the incidence of acute adverse events of the renal denervation procedure and the change in estimated glomerular filtration rate from baseline to 6 months. This trial is registered with ClinicalTrials.gov, number NCT01570777. Findings Between May 22, 2012, and Oct 14, 2013, 1416 patients were screened for eligibility, 106 of those were randomly assigned to treatment (53 patients in each group, intention-to-treat population) and 101 analysed because of patients with missing endpoints (48 in the renal denervation group, 53 in the control group, modified intention-to-treat population). The mean change in daytime ambulatory systolic blood pressure at 6 months was −15·8 mm Hg (95% CI −19·7 to −11·9) in the renal denervation group and −9·9 mm Hg (−13·6 to −6·2) in the group receiving SSAHT alone, a baseline-adjusted difference of −5·9 mm Hg (−11·3 to −0·5; p=0·0329). The number of antihypertensive drugs and drug-adherence at 6 months were similar between the two groups. Three minor renal denervation-related adverse events were noted (lumbar pain in two patients and mild groin haematoma in one patient). A mild and similar decrease in estimated glomerular filtration rate from baseline to 6 months was observed in both groups. Interpretation In patients with well defined resistant hypertension, renal denervation plus an SSAHT decreases ambulatory blood pressure more than the same SSAHT alone at 6 months. This additional blood pressure lowering effect may contribute to a reduction in cardiovascular morbidity if maintained in the long term after renal denervation. Funding French Ministry of Health.


      PubDate: 2015-05-21T06:40:32Z
       
  • Sickle cell trait, exertional rhabdomyolysis, and compartment syndrome
    • Abstract: Publication date: 16–22 May 2015
      Source:The Lancet, Volume 385, Issue 9981
      Author(s): Philippe Connes



      PubDate: 2015-05-21T06:40:32Z
       
  • Ceftolozane-tazobactam compared with levofloxacin in the treatment of
           complicated urinary-tract infections, including pyelonephritis: a
           randomised, double-blind, phase 3 trial (ASPECT-cUTI)
    • Abstract: Publication date: 16–22 May 2015
      Source:The Lancet, Volume 385, Issue 9981
      Author(s): Florian M Wagenlehner , Obiamiwe Umeh , Judith Steenbergen , Guojun Yuan , Rabih O Darouiche
      Background Treatment of complicated urinary-tract infections is challenging due to rising antimicrobial resistance. We assessed the efficacy and safety of ceftolozane-tazobactam, a novel antibacterial with Gram-negative activity, in the treatment of patients with complicated lower-urinary-tract infections or pyelonephritis. Methods ASPECT-cUTI was a randomised, double-blind, double-dummy, non-inferiority trial done in 209 centres in 25 countries. Between July, 2011, and September, 2013, hospital inpatients aged 18 years or older who had pyuria and a diagnosis of a complicated lower-urinary-tract infection or pyelonephritis were randomly assigned in a 1:1 ratio to receive intravenous 1·5 g ceftolozane-tazobactam every 8 h or intravenous high-dose (750 mg) levofloxacin once daily for 7 days. The randomisation schedule was computer generated in blocks of four and stratified by study site. The next allocation was obtained by the study site pharmacist via an interactive voice-response system. The primary endpoint was a composite of microbiological eradication and clinical cure 5–9 days after treatment in the microbiological modified intention-to-treat (MITT) population, with a non-inferiority margin of 10%. This study is registered with ClinicalTrials.gov, numbers NCT01345929 and NCT01345955. Findings Of 1083 patients enrolled, 800 (73·9%), of whom 656 (82·0%) had pyelonephritis, were included in the microbiological MITT population. Ceftolozane-tazobactam was non-inferior to levofloxacin for composite cure (306 [76·9%] of 398 vs 275 [68·4%] of 402, 95% CI 2·3–14·6) and, as the lower bound of the two-sided 95% CI around the treatment difference was positive and greater than zero, superiority was indicated. Adverse event profiles were similar in the two treatment groups and were mainly non-serious. Interpretation Treatment with ceftolozane-tazobactam led to better responses than high-dose levofloxacin in patients with complicated lower-urinary-tract infections or pyelonephritis. Funding Cubist Pharmaceuticals.


      PubDate: 2015-05-21T06:40:32Z
       
  • Success and challenges in fertility preservation after ovarian tissue
           grafting
    • Abstract: Publication date: 16–22 May 2015
      Source:The Lancet, Volume 385, Issue 9981
      Author(s): Genia Rozen , Franca Agresta , Debra Gook , Didi Braat , Catharyn J Stern



      PubDate: 2015-05-21T06:40:32Z
       
  • Success and challenges in fertility preservation after ovarian tissue
           grafting
    • Abstract: Publication date: 16–22 May 2015
      Source:The Lancet, Volume 385, Issue 9981
      Author(s): Claus Yding Andersen



      PubDate: 2015-05-21T06:40:32Z
       
  • Antenatal corticosteroids for preterm births in resource-limited settings
           – Authors' reply
    • Abstract: Publication date: 16–22 May 2015
      Source:The Lancet, Volume 385, Issue 9981
      Author(s): Fernando Althabe , José M Belizán , Elizabeth McClure , Robert L Goldenberg , Pierre M Buekens



      PubDate: 2015-05-21T06:40:32Z
       
  • Mendelian randomisation study for statin treatment
    • Abstract: Publication date: 16–22 May 2015
      Source:The Lancet, Volume 385, Issue 9981
      Author(s): Hiroyuki Morita , Issei Komuro



      PubDate: 2015-05-21T06:40:32Z
       
  • Mendelian randomisation study for statin treatment – Authors' reply
    • Abstract: Publication date: 16–22 May 2015
      Source:The Lancet, Volume 385, Issue 9981
      Author(s): Daniel I Swerdlow , David Preiss , Aroon D Hingorani , Naveed Sattar



      PubDate: 2015-05-21T06:40:32Z
       
  • Antenatal corticosteroids for preterm births in resource-limited settings
    • Abstract: Publication date: 16–22 May 2015
      Source:The Lancet, Volume 385, Issue 9981
      Author(s): Gerard H A Visser , Gian Carlo DiRenzo



      PubDate: 2015-05-21T06:40:32Z
       
  • Antenatal corticosteroids for preterm births in resource-limited settings
    • Abstract: Publication date: 16–22 May 2015
      Source:The Lancet, Volume 385, Issue 9981
      Author(s): Jeffrey Perlman , Sithembiso Velaphi , Hege L Ersdal , Monica Gadhia



      PubDate: 2015-05-21T06:40:32Z
       
  • Antenatal corticosteroids for preterm births in resource-limited settings
    • Abstract: Publication date: 16–22 May 2015
      Source:The Lancet, Volume 385, Issue 9981
      Author(s): Kathy Burgoine , Julian Abeso , Melissa Gladstone , Peter Waiswa , Andrew D Weeks



      PubDate: 2015-05-21T06:40:32Z
       
  • Becoming a good doctor: legal liability and ethics committees Barron
           HLernerThe Good Doctor: A Father, a Son, and the Evolution of Medical
           Ethics2014Beacon Press9780807033401223US$25·95 SandeepJauharDoctored:
           The Disillusionment of an American Physician2014Farrar, Straus and
           Giroux9780374141394268US$26·00
    • Abstract: Publication date: 16–22 May 2015
      Source:The Lancet, Volume 385, Issue 9981
      Author(s): George J Annas



      PubDate: 2015-05-21T06:40:32Z
       
  • Richard Michael Suzman
    • Abstract: Publication date: 16–22 May 2015
      Source:The Lancet, Volume 385, Issue 9981
      Author(s): Geoff Watts



      PubDate: 2015-05-21T06:40:32Z
       
  • Are Colombia's reforms enough for a health-care system in crisis'
    • Abstract: Publication date: 16–22 May 2015
      Source:The Lancet, Volume 385, Issue 9981
      Author(s): Esteban Londoño , Patricia Molano



      PubDate: 2015-05-21T06:40:32Z
       
 
 
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