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Journal Cover The Lancet
   [1031 followers]  Follow    
   Full-text available via subscription Subscription journal
     ISSN (Print) 0140-6736 - ISSN (Online) 1474-547X
     Published by Elsevier Homepage  [2563 journals]   [SJR: 7.074]   [H-I: 477]
  • International comparisons of acute myocardial infarction –
           Authors'reply
    • Abstract: Publication date: 26 July–1 August 2014
      Source:The Lancet, Volume 384, Issue 9940
      Author(s): Sheng-Chia Chung , Adam Timmis , John Deanfield , Tomas Jernberg , Harry Hemingway



      PubDate: 2014-07-28T15:08:51Z
       
  • International comparisons of acute myocardial infarction
    • Abstract: Publication date: 26 July–1 August 2014
      Source:The Lancet, Volume 384, Issue 9940
      Author(s): Björn Redfors , Yangzhen Shao , Elmir Omerovic



      PubDate: 2014-07-28T15:08:51Z
       
  • International comparisons of acute myocardial infarction
    • Abstract: Publication date: 26 July–1 August 2014
      Source:The Lancet, Volume 384, Issue 9940
      Author(s): Emmanuel N Lazaridis , Lucia Gavalova , Simon Jones , Tom Quinn , Clive Weston



      PubDate: 2014-07-28T15:08:51Z
       
  • Combination HIV prevention for female sex workers: what is the
           evidence'
    • Abstract: Publication date: Available online 22 July 2014
      Source:The Lancet
      Author(s): Linda-Gail Bekker , Leigh Johnson , Frances Cowan , Cheryl Overs , Donela Besada , Sharon Hillier , Willard Cates Jr
      Sex work occurs in many forms and sex workers of all genders have been affected by HIV epidemics worldwide. The determinants of HIV risk associated with sex work occur at several levels, including individual biological and behavioural, dyadic and network, and community and social environmental levels. Evidence indicates that effective HIV prevention packages for sex workers should include combinations of biomedical, behavioural, and structural interventions tailored to local contexts, and be led and implemented by sex worker communities. A model simulation based on the South African heterosexual epidemic suggests that condom promotion and distribution programmes in South Africa have already reduced HIV incidence in sex workers and their clients by more than 70%. Under optimistic model assumptions, oral pre-exposure prophylaxis together with test and treat programmes could further reduce HIV incidence in South African sex workers and their clients by up to 40% over a 10-year period. Combining these biomedical approaches with a prevention package, including behavioural and structural components as part of a community-driven approach, will help to reduce HIV infection in sex workers in different settings worldwide.


      PubDate: 2014-07-28T15:08:51Z
       
  • Dispelling myths about sex workers and HIV
    • Abstract: Publication date: Available online 22 July 2014
      Source:The Lancet
      Author(s): Steffanie A Strathdee , Anna-Louise Crago , Jenny Butler , Linda-Gail Bekker , Chris Beyrer



      PubDate: 2014-07-28T15:08:51Z
       
  • Global epidemiology of HIV among female sex workers: influence of
           structural determinants
    • Abstract: Publication date: Available online 22 July 2014
      Source:The Lancet
      Author(s): Kate Shannon , Steffanie A Strathdee , Shira M Goldenberg , Putu Duff , Peninah Mwangi , Maia Rusakova , Sushena Reza-Paul , Joseph Lau , Kathleen Deering , Michael R Pickles , Marie-Claude Boily
      Female sex workers (FSWs) bear a disproportionately large burden of HIV infection worldwide. Despite decades of research and programme activity, the epidemiology of HIV and the role that structural determinants have in mitigating or potentiating HIV epidemics and access to care for FSWs is poorly understood. We reviewed available published data for HIV prevalence and incidence, condom use, and structural determinants among this group. Only 87 (43%) of 204 unique studies reviewed explicitly examined structural determinants of HIV. Most studies were from Asia, with few from areas with a heavy burden of HIV such as sub-Saharan Africa, Russia, and eastern Europe. To further explore the potential effect of structural determinants on the course of epidemics, we used a deterministic transmission model to simulate potential HIV infections averted through structural changes in regions with concentrated and generalised epidemics, and high HIV prevalence among FSWs. This modelling suggested that elimination of sexual violence alone could avert 17% of HIV infections in Kenya (95% uncertainty interval [UI] 1–31) and 20% in Canada (95% UI 3–39) through its immediate and sustained effect on non-condom use) among FSWs and their clients in the next decade. In Kenya, scaling up of access to antiretroviral therapy among FSWs and their clients to meet WHO eligibility of a CD4 cell count of less than 500 cells per μL could avert 34% (95% UI 25–42) of infections and even modest coverage of sex worker-led outreach could avert 20% (95% UI 8–36) of infections in the next decade. Decriminalisation of sex work would have the greatest effect on the course of HIV epidemics across all settings, averting 33–46% of HIV infections in the next decade. Multipronged structural and community-led interventions are crucial to increase access to prevention and treatment and to promote human rights for FSWs worldwide.


      PubDate: 2014-07-28T15:08:51Z
       
  • An open letter for the people in Gaza
    • Abstract: Publication date: Available online 23 July 2014
      Source:The Lancet
      Author(s): Paola Manduca , Iain Chalmers , Derek Summerfield , Mads Gilbert , Swee Ang



      PubDate: 2014-07-28T15:08:51Z
       
  • Time for a revolution in reporting of global health data
    • Abstract: Publication date: Available online 22 July 2014
      Source:The Lancet
      Author(s): Rifat Atun



      PubDate: 2014-07-28T15:08:51Z
       
  • An action agenda for HIV and sex workers
    • Abstract: Publication date: Available online 22 July 2014
      Source:The Lancet
      Author(s): Chris Beyrer , Anna-Louise Crago , Linda-Gail Bekker , Jenny Butler , Kate Shannon , Deanna Kerrigan , Michele R Decker , Stefan D Baral , Tonia Poteat , Andrea L Wirtz , Brian W Weir , Françoise Barré-Sinoussi , Michel Kazatchkine , Michel Sidibé , Karl-Lorenz Dehne , Marie-Claude Boily , Steffanie A Strathdee
      The women, men, and transgender people who sell sex globally have disproportionate risks and burdens of HIV in countries of low, middle, and high income, and in concentrated and generalised epidemic contexts. The greatest HIV burdens continue to be in African female sex workers. Worldwide, sex workers still face reduced access to needed HIV prevention, treatment, and care services. Legal environments, policies, police practices, absence of funding for research and HIV programmes, human rights violations, and stigma and discrimination continue to challenge sex workers' abilities to protect themselves, their families, and their sexual partners from HIV. These realities must change to realise the benefits of advances in HIV prevention and treatment and to achieve global control of the HIV pandemic. Effective combination prevention and treatment approaches are feasible, can be tailored for cultural competence, can be cost-saving, and can help to address the unmet needs of sex workers and their communities in ways that uphold their human rights. To address HIV in sex workers will need sustained community engagement and empowerment, continued research, political will, structural and policy reform, and innovative programmes. But such actions can and must be achieved for sex worker communities everywhere.


      PubDate: 2014-07-28T15:08:51Z
       
  • Do patients with acute low-back pain need paracetamol'
    • Abstract: Publication date: Available online 23 July 2014
      Source:The Lancet
      Author(s): Bart W Koes , Wendy T Enthoven



      PubDate: 2014-07-28T15:08:51Z
       
  • How to hinder tuberculosis control: five easy steps
    • Abstract: Publication date: Available online 23 July 2014
      Source:The Lancet
      Author(s): Mishal S Khan , Richard J Coker



      PubDate: 2014-07-28T15:08:51Z
       
  • Efficacy of paracetamol for acute low-back pain: a double-blind,
           randomised controlled trial
    • Abstract: Publication date: Available online 23 July 2014
      Source:The Lancet
      Author(s): Christopher M Williams , Christopher G Maher , Jane Latimer , Andrew J McLachlan , Mark J Hancock , Richard O Day , Chung-Wei Christine Lin
      Background Regular paracetamol is the recommended first-line analgesic for acute low-back pain; however, no high-quality evidence supports this recommendation. We aimed to assess the efficacy of paracetamol taken regularly or as-needed to improve time to recovery from pain, compared with placebo, in patients with low-back pain. Methods We did a multicentre, double-dummy, randomised, placebo controlled trial across 235 primary care centres in Sydney, Australia, from Nov 11, 2009, to March 5, 2013. We randomly allocated patients with acute low-back pain in a 1:1:1 ratio to receive up to 4 weeks of regular doses of paracetamol (three times per day; equivalent to 3990 mg paracetamol per day), as-needed doses of paracetamol (taken when needed for pain relief; maximum 4000 mg paracetamol per day), or placebo. Randomisation was done according to a centralised randomisation schedule prepared by a researcher who was not involved in patient recruitment or data collection. Patients and staff at all sites were masked to treatment allocation. All participants received best-evidence advice and were followed up for 3 months. The primary outcome was time until recovery from low-back pain, with recovery defined as a pain score of 0 or 1 (on a 0–10 pain scale) sustained for 7 consecutive days. All data were analysed by intention to treat. This study is registered with the Australian and New Zealand Clinical Trial Registry, number ACTN 12609000966291. Findings 550 participants were assigned to the regular group (550 analysed), 549 were assigned to the as-needed group (546 analysed), and 553 were assigned to the placebo group (547 analysed). Median time to recovery was 17 days (95% CI 14–19) in the regular group, 17 days (15–20) in the as-needed group, and 16 days (14–20) in the placebo group (regular vs placebo hazard ratio 0·99, 95% CI 0·87–1·14; as-needed vs placebo 1·05, 0·92–1·19; regular vs as-needed 1·05, 0·92–1·20). We recorded no difference between treatment groups for time to recovery (adjusted p=0·79). Adherence to regular tablets (median tablets consumed per participant per day of maximum 6; 4·0 [IQR 1·6–5·7] in the regular group, 3·9 [1·5–5·6] in the as-needed group, and 4·0 [1·5–5·7] in the placebo group), and number of participants reporting adverse events (99 [18·5%] in the regular group, 99 [18·7%] in the as-needed group, and 98 [18·5%] in the placebo group) were similar between groups. Interpretation Our findings suggest that regular or as-needed dosing with paracetamol does not affect recovery time compared with placebo in low-back pain, and question the universal endorsement of paracetamol in this patient group. Funding National Health and Medical Research Council of Australia and GlaxoSmithKline Australia.


      PubDate: 2014-07-28T15:08:51Z
       
  • Fever, night sweats, and abnormal liver enzymes
    • Abstract: Publication date: 26 July–1 August 2014
      Source:The Lancet, Volume 384, Issue 9940
      Author(s): Ami Schattner , Jacob Gotler



      PubDate: 2014-07-28T15:08:51Z
       
  • MDG 6 and beyond: from halting and reversing AIDS to ending the epidemic
    • Abstract: Publication date: Available online 26 July 2014
      Source:The Lancet
      Author(s): Michel Sidibé , Mark Dybul , Deborah Birx



      PubDate: 2014-07-28T15:08:51Z
       
  • TIPPing practice away from anticoagulation in pregnancy
    • Abstract: Publication date: Available online 24 July 2014
      Source:The Lancet
      Author(s): Paul S Gibson , Kara A Nerenberg



      PubDate: 2014-07-28T15:08:51Z
       
  • Antepartum dalteparin versus no antepartum dalteparin for the prevention
           of pregnancy complications in pregnant women with thrombophilia (TIPPS): a
           multinational open-label randomised trial
    • Abstract: Publication date: Available online 24 July 2014
      Source:The Lancet
      Author(s): Marc A Rodger , William M Hague , John Kingdom , Susan R Kahn , Alan Karovitch , Mathew Sermer , Anne Marie Clement , Suzette Coat , Wee Shian Chan , Joanne Said , Evelyne Rey , Sue Robinson , Rshmi Khurana , Christine Demers , Michael J Kovacs , Susan Solymoss , Kim Hinshaw , James Dwyer , Graeme Smith , Sarah McDonald , Jill Newstead-Angel , Anne McLeod , Meena Khandelwal , Robert M Silver , Gregoire Le Gal , Ian A Greer , Erin Keely , Karen Rosene-Montella , Mark Walker , Philip S Wells
      Background Thrombophilias are common disorders that increase the risk of pregnancy-associated venous thromboembolism and pregnancy loss and can also increase the risk of placenta-mediated pregnancy complications (severe pre-eclampsia, small-for-gestational-age infants, and placental abruption). We postulated that antepartum dalteparin would reduce these complications in pregnant women with thrombophilia. Methods In this open-label randomised trial undertaken in 36 tertiary care centres in five countries, we enrolled consenting pregnant women with thrombophilia at increased risk of venous thromboembolism or with previous placenta-mediated pregnancy complications. Eligible participants were randomly allocated in a 1:1 ratio to either antepartum prophylactic dose dalteparin (5000 international units once daily up to 20 weeks' gestation, and twice daily thereafter until at least 37 weeks' gestation) or to no antepartum dalteparin (control group). Randomisation was done by a web-based randomisation system, and was stratified by country and gestational age at randomisation day with a permuted block design (block sizes 4 and 8). At randomisation, site pharmacists (or delegates) received a randomisation number and treatment allocation (by fax and/or e-mail) from the central web randomisation system and then dispensed study drug to the local coordinator. Patients and study personnel were not masked to treatment assignment, but the outcome adjudicators were masked. The primary composite outcome was independently adjudicated severe or early-onset pre-eclampsia, small-for-gestational-age infant (birthweight <10th percentile), pregnancy loss, or venous thromboembolism. We did intention-to-treat and on-treatment analyses. This trial is registered with ClinicalTrials.gov, number NCT00967382, and with Current Controlled Trials, number ISRCTN87441504. Findings Between Feb 28, 2000, and Sept 14, 2012, 292 women consented to participate and were randomly assigned to the two groups. Three women were excluded after randomisation because of ineligibility (two in the antepartum dalteparin group and one in the control group), leaving 146 women assigned to antepartum dalteparin and 143 assigned to no antepartum dalteparin. Some patients crossed over to the other group during treatment, and therefore for on-treatment and safety analysis there were 143 patients in the dalteparin group and 141 in the no dalteparin group. Dalteparin did not reduce the incidence of the primary composite outcome in both intention-to-treat analysis (dalteparin 25/146 [17·1%; 95% CI 11·4–24·2%] vs no dalteparin 27/143 [18·9%; 95% CI 12·8–26·3%]; risk difference −1·8% [95% CI −10·6% to 7·1%)) and on-treatment analysis (dalteparin 28/143 [19·6%] vs no dalteparin 24/141 [17·0%]; risk difference +2·6% [95% CI −6·4 to 11·6%]). In safety analysis, the occurrence of major bleeding did not differ between the two groups. However, minor bleeding was more common in the dalteparin group (28/143 [19·6%]) than in the no dalteparin group (13/141 [9·2%]; risk difference 10·4%, 95% CI 2·3–18·4; p=0·01). Interpretation Antepartum prophylactic dalteparin does not reduce the occurrence of venous thromboembolism, pregnancy loss, or placenta-mediated pregnancy complications in pregnant women with thrombophilia at high risk of these complications and is associated with an increased risk of minor bleeding.
      PubDate: 2014-07-28T15:08:51Z
       
  • Rwanda 20 years on: investing in life
    • Abstract: Publication date: 26 July–1 August 2014
      Source:The Lancet, Volume 384, Issue 9940
      Author(s): Agnes Binagwaho , Paul E Farmer , Sabin Nsanzimana , Corine Karema , Michel Gasana , Jean de Dieu Ngirabega , Fidele Ngabo , Claire M Wagner , Cameron T Nutt , Thierry Nyatanyi , Maurice Gatera , Yvonne Kayiteshonga , Cathy Mugeni , Placidie Mugwaneza , Joseph Shema , Parfait Uwaliraye , Erick Gaju , Marie Aimee Muhimpundu , Theophile Dushime , Florent Senyana , Jean Baptiste Mazarati , Celsa Muzayire Gaju , Lisine Tuyisenge , Vincent Mutabazi , Patrick Kyamanywa , Vincent Rusanganwa , Jean Pierre Nyemazi , Agathe Umutoni , Ida Kankindi , Christian Ntizimira , Hinda Ruton , Nathan Mugume , Denis Nkunda , Espérance Ndenga , Joel M Mubiligi , Jean Baptiste Kakoma , Etienne Karita , Claude Sekabaraga , Emmanuel Rusingiza , Michael L Rich , Joia S Mukherjee , Joseph Rhatigan , Corrado Cancedda , Didi Bertrand-Farmer , Gene Bukhman , Sara N Stulac , Neo M Tapela , Cassia van der Hoof Holstein , Lawrence N Shulman , Antoinette Habinshuti , Matthew H Bonds , Michael S Wilkes , Chunling Lu , Mary C Smith-Fawzi , JaBaris D Swain , Michael P Murphy , Alan Ricks , Vanessa B Kerry , Barbara P Bush , Richard W Siegler , Cori S Stern , Anne Sliney , Tej Nuthulaganti , Injonge Karangwa , Elisabetta Pegurri , Ophelia Dahl , Peter C Drobac
      Two decades ago, the genocide against the Tutsis in Rwanda led to the deaths of 1 million people, and the displacement of millions more. Injury and trauma were followed by the effects of a devastated health system and economy. In the years that followed, a new course set by a new government set into motion equity-oriented national policies focusing on social cohesion and people-centred development. Premature mortality rates have fallen precipitously in recent years, and life expectancy has doubled since the mid-1990s. Here we reflect on the lessons learned in rebuilding Rwanda's health sector during the past two decades, as the country now prepares itself to take on new challenges in health-care delivery.


      PubDate: 2014-07-28T15:08:51Z
       
  • Can available interventions end preventable deaths in mothers, newborn
           babies, and stillbirths, and at what cost'
    • Abstract: Publication date: 26 July–1 August 2014
      Source:The Lancet, Volume 384, Issue 9940
      Author(s): Zulfiqar A Bhutta , Jai K Das , Rajiv Bahl , Joy E Lawn , Rehana A Salam , Vinod K Paul , M Jeeva Sankar , Hannah Blencowe , Arjumand Rizvi , Victoria B Chou , Neff Walker
      Progress in newborn survival has been slow, and even more so for reductions in stillbirths. To meet Every Newborn targets of ten or fewer neonatal deaths and ten or fewer stillbirths per 1000 births in every country by 2035 will necessitate accelerated scale-up of the most effective care targeting major causes of newborn deaths. We have systematically reviewed interventions across the continuum of care and various delivery platforms, and then modelled the effect and cost of scale-up in the 75 high-burden Countdown countries. Closure of the quality gap through the provision of effective care for all women and newborn babies delivering in facilities could prevent an estimated 113 000 maternal deaths, 531 000 stillbirths, and 1·325 million neonatal deaths annually by 2020 at an estimated running cost of US$4·5 billion per year (US$0·9 per person). Increased coverage and quality of preconception, antenatal, intrapartum, and postnatal interventions by 2025 could avert 71% of neonatal deaths (1·9 million [range 1·6–2·1 million]), 33% of stillbirths (0·82 million [0·60–0·93 million]), and 54% of maternal deaths (0·16 million [0·14–0·17 million]) per year. These reductions can be achieved at an annual incremental running cost of US$5·65 billion (US$1·15 per person), which amounts to US$1928 for each life saved, including stillbirths, neonatal, and maternal deaths. Most (82%) of this effect is attributable to facility-based care which, although more expensive than community-based strategies, improves the likelihood of survival. Most of the running costs are also for facility-based care (US$3·66 billion or 64%), even without the cost of new hospitals and country-specific capital inputs being factored in. The maximum effect on neonatal deaths is through interventions delivered during labour and birth, including for obstetric complications (41%), followed by care of small and ill newborn babies (30%). To meet the unmet need for family planning with modern contraceptives would be synergistic, and would contribute to around a halving of births and therefore deaths. Our analysis also indicates that available interventions can reduce the three most common cause of neonatal mortality—preterm, intrapartum, and infection-related deaths—by 58%, 79%, and 84%, respectively.


      PubDate: 2014-07-28T15:08:51Z
       
  • International comparisons of acute myocardial infarction
    • Abstract: Publication date: 26 July–1 August 2014
      Source:The Lancet, Volume 384, Issue 9940
      Author(s): Peter A Kavsak



      PubDate: 2014-07-28T15:08:51Z
       
  • International comparisons of acute myocardial infarction
    • Abstract: Publication date: 26 July–1 August 2014
      Source:The Lancet, Volume 384, Issue 9940
      Author(s): Johan Ejerhed , Helena Nordenstedt , Ann-Charlotte Laska



      PubDate: 2014-07-28T15:08:51Z
       
  • Ebola in Sierra Leone: a call for action
    • Abstract: Publication date: 26 July–1 August 2014
      Source:The Lancet, Volume 384, Issue 9940
      Author(s): Rashid Ansumana , Jesse Bonwitt , David A Stenger , Kathryn H Jacobsen



      PubDate: 2014-07-28T15:08:51Z
       
  • Joep Lange
    • Abstract: Publication date: 26 July–1 August 2014
      Source:The Lancet, Volume 384, Issue 9940
      Author(s): John Maurice



      PubDate: 2014-07-28T15:08:51Z
       
  • Engineered autologous cartilage tissue for nasal reconstruction after
           tumour resection: an observational first-in-human trial
    • Abstract: Publication date: 26 July–1 August 2014
      Source:The Lancet, Volume 384, Issue 9940
      Author(s): Ilario Fulco , Sylvie Miot , Martin D Haug , Andrea Barbero , Anke Wixmerten , Sandra Feliciano , Francine Wolf , Gernot Jundt , Anna Marsano , Jian Farhadi , Michael Heberer , Marcel Jakob , Dirk J Schaefer , Ivan Martin
      Background Autologous native cartilage from the nasal septum, ear, or rib is the standard material for surgical reconstruction of the nasal alar lobule after two-layer excision of non-melanoma skin cancer. We assessed whether engineered autologous cartilage grafts allow safe and functional alar lobule restoration. Methods In a first-in-human trial, we recruited five patients at the University Hospital Basel (Basel, Switzerland). To be eligible, patients had to be aged at least 18 years and have a two-layer defect (≥50% size of alar subunit) after excision of non-melanoma skin cancer on the alar lobule. Chondrocytes (isolated from a 6 mm cartilage biopsy sample from the nasal septum harvested under local anaesthesia during collection of tumour biopsy sample) were expanded, seeded, and cultured with autologous serum onto collagen type I and type III membranes in the course of 4 weeks. The resulting engineered cartilage grafts (25 mm × 25 mm × 2 mm) were shaped intra-operatively and implanted after tumour excision under paramedian forehead or nasolabial flaps, as in standard reconstruction with native cartilage. During flap refinement after 6 months, we took biopsy samples of repair tissues and histologically analysed them. The primary outcomes were safety and feasibility of the procedure, assessed 12 months after reconstruction. At least 1 year after implantation, when reconstruction is typically stabilised, we assessed patient satisfaction and functional outcomes (alar cutaneous sensibility, structural stability, and respiratory flow rate). Findings Between Dec 13, 2010, and Feb 6, 2012, we enrolled two women and three men aged 76–88 years. All engineered grafts contained a mixed hyaline and fibrous cartilage matrix. 6 months after implantation, reconstructed tissues displayed fibromuscular fatty structures typical of the alar lobule. After 1 year, all patients were satisfied with the aesthetic and functional outcomes and no adverse events had been recorded. Cutaneous sensibility and structural stability of the reconstructed area were clinically satisfactory, with adequate respiratory function. Interpretation Autologous nasal cartilage tissues can be engineered and clinically used for functional restoration of alar lobules. Engineered cartilage should now be assessed for other challenging facial reconstructions. Funding Foundation of the Department of Surgery, University Hospital Basel; and Krebsliga beider Basel.


      PubDate: 2014-07-28T15:08:51Z
       
  • Tissue-engineered autologous vaginal organs in patients: a pilot cohort
           study
    • Abstract: Publication date: 26 July–1 August 2014
      Source:The Lancet, Volume 384, Issue 9940
      Author(s): Atlántida M Raya-Rivera , Diego Esquiliano , Reyna Fierro-Pastrana , Esther López-Bayghen , Pedro Valencia , Ricardo Ordorica-Flores , Shay Soker , James J Yoo , Anthony Atala
      Background Several disorders might require vaginal reconstruction, such as congenital abnormalities, injury, or cancer. Reconstructive techniques for which non-vaginal tissue is used can be associated with complications. We assessed the use of engineered vaginal organs in four patients with vaginal aplasia caused by Mayer-Rokitansky-Küster-Hauser syndrome (MRKHS). Methods We invited to participate four consecutive patients who presented over a 3-year period with congenital vaginal aplasia due to MRKHS. Patients were aged 13–18 years. We obtained a vulvar biopsy of autologous tissue from every patient. We cultured, expanded, and seeded epithelial and muscle cells onto biodegradable scaffolds. The organs were constructed and allowed to mature in an incubator in a facility approved for human-tissue manufacturing. We used a perineal approach to surgically implant these organs. We recorded history, physical examination, vaginoscopy, serial tissue biopsies, MRIs, and self-administered Female Sexual Function Index questionnaire results for all patients, with a follow-up of up to 8 years. Findings We noted no long-term postoperative surgical complications. Yearly serial biopsies showed a tri-layered structure, consisting of an epithelial cell-lined lumen surrounded by matrix and muscle, with expected components of vaginal tissue present. Immunohistochemical analysis confirmed the presence of phenotypically normal smooth muscle and epithelia. The MRIs, which showed the extent of the vaginal aplasia before surgery, showed the engineered organs and the absence of abnormalities after surgery, which was confirmed with yearly vaginoscopy. A validated self-administered Female Sexual Function Index questionnaire showed variables in the normal range in all areas tested, such as desire, arousal, lubrication, orgasm, satisfaction, and painless intercourse. Interpretation Vaginal organs, engineered from the patient's own cells and implanted, showed normal structural and functional variables with a follow-up of up to 8 years. These technologies could be useful in patients requiring vaginal reconstruction. Funding Wake Forest University and Hospital Infantil de México Federico Gómez.


      PubDate: 2014-07-28T15:08:51Z
       
  • Sorafenib in radioactive iodine-refractory, locally advanced or metastatic
           differentiated thyroid cancer: a randomised, double-blind, phase 3 trial
    • Abstract: Publication date: 26 July–1 August 2014
      Source:The Lancet, Volume 384, Issue 9940
      Author(s): Marcia S Brose , Christopher M Nutting , Barbara Jarzab , Rossella Elisei , Salvatore Siena , Lars Bastholt , Christelle de la Fouchardiere , Furio Pacini , Ralf Paschke , Young Kee Shong , Steven I Sherman , Johannes W A Smit , John Chung , Christian Kappeler , Carol Peña , István Molnár , Martin J Schlumberger
      Background Patients with radioactive iodine (131I)-refractory locally advanced or metastatic differentiated thyroid cancer have a poor prognosis because of the absence of effective treatment options. In this study, we assessed the efficacy and safety of orally administered sorafenib in the treatment of patients with this type of cancer. Methods In this multicentre, randomised, double-blind, placebo-controlled, phase 3 trial (DECISION), we investigated sorafenib (400 mg orally twice daily) in patients with radioactive iodine-refractory locally advanced or metastatic differentiated thyroid cancer that had progressed within the past 14 months. Adult patients (≥18 years of age) with this type of cancer were enrolled from 77 centres in 18 countries. To be eligible for inclusion, participants had to have at least one measurable lesion by CT or MRI according to Response Evaluation Criteria In Solid Tumors (RECIST); Eastern Cooperative Oncology Group performance status 0–2; adequate bone marrow, liver, and renal function; and serum thyroid-stimulating hormone concentration lower than 0·5 mIU/L. An interactive voice response system was used to randomly allocate participants in a 1:1 ratio to either sorafenib or matching placebo. Patients, investigators, and the study sponsor were masked to treatment assignment. The primary endpoint was progression-free survival, assessed every 8 weeks by central independent review. Analysis was by intention to treat. Patients in the placebo group could cross over to open-label sorafenib upon disease progression. Archival tumour tissue was examined for BRAF and RAS mutations, and serum thyroglobulin was measured at baseline and at each visit. This study is registered with ClinicalTrials.gov, number NCT00984282, and with the EU Clinical Trials Register, number EudraCT 2009–012007–25. Findings Patients were randomly allocated on a 1:1 basis to sorafenib or placebo. The intention-to-treat population comprised 417 patients (207 in the sorafenib group and 210 in the placebo group) and the safety population was 416 patients (207 in the sorafenib group and 209 in the placebo group). Median progression-free survival was significantly longer in the sorafenib group (10·8 months) than in the placebo group (5·8 months; hazard ratio [HR] 0·59, 95% CI 0·45–0·76; p<0·0001). Progression-free survival improved in all prespecified clinical and genetic biomarker subgroups, irrespective of mutation status. Adverse events occurred in 204 of 207 (98·6%) patients receiving sorafenib during the double-blind period and in 183 of 209 (87·6%) patients receiving placebo. Most adverse events were grade 1 or 2. The most frequent treatment-emergent adverse events in the sorafenib group were hand–foot skin reaction (76·3%), diarrhoea (68·6%), alopecia (67·1%), and rash or desquamation (50·2%). Interpretation Sorafenib significantly improved progression-free survival compared with placebo in patients with progressive radioactive iodine-refractory differentiated thyroid cancer. Adverse events were consistent with the known safety profile of sorafenib. These results suggest that sorafenib is a new treatment option for patients with progressive radioactive iodine-refractory differentiated thyroid cancer. Funding Bayer HealthCare Pharmaceuticals and Onyx Pharmaceuticals (an Amgen subsidiary).


      PubDate: 2014-07-28T15:08:51Z
       
  • Etrolizumab as induction therapy for ulcerative colitis: a randomised,
           controlled, phase 2 trial
    • Abstract: Publication date: 26 July–1 August 2014
      Source:The Lancet, Volume 384, Issue 9940
      Author(s): Séverine Vermeire , Sharon O'Byrne , Mary Keir , Marna Williams , Timothy T Lu , John C Mansfield , Christopher A Lamb , Brian G Feagan , Julian Panes , Azucena Salas , Daniel C Baumgart , Stefan Schreiber , Iris Dotan , William J Sandborn , Gaik W Tew , Diana Luca , Meina T Tang , Lauri Diehl , Jeffrey Eastham-Anderson , Gert De Hertogh , Clementine Perrier , Jackson G Egen , John A Kirby , Gert van Assche , Paul Rutgeerts
      Background Etrolizumab is a humanised monoclonal antibody that selectively binds the β7 subunit of the heterodimeric integrins α4β7 and αEβ7. We aimed to assess etrolizumab in patients with moderately-to-severely active ulcerative colitis. Methods In this double-blind, placebo-controlled, randomised, phase 2 study, patients with moderately-to-severely active ulcerative colitis who had not responded to conventional therapy were recruited from 40 referral centres in 11 countries. Eligible patients (aged 18–75 years; Mayo Clinic Score [MCS] of 5 of higher [or ≥6 in USA]; and disease extending 25 cm or more from anal verge) were randomised (1:1:1) to one of two dose levels of subcutaneous etrolizumab (100 mg at weeks 0, 4, and 8, with placebo at week 2; or 420 mg loading dose [LD] at week 0 followed by 300 mg at weeks 2, 4, and 8), or matching placebo. The primary endpoint was clinical remission at week 10, defined as MCS of 2 or less (with no individual subscore of >1), analysed in the modified intention-to-treat population (mITT; all randomly assigned patients who had received at least one dose of study drug, had at least one post-baseline disease-activity assessment, and had a centrally read screening endoscopic subscore of ≥2). This study is registered with ClinicalTrials.gov, number NCT01336465. Findings Between Sept 2, 2011, and July 11, 2012, 124 patients were randomly assigned, of whom five had a endoscopic subscore of 0 or 1 and were excluded from the mITT population, leaving 39 patients in the etrolizumab 100 mg group, 39 in the etrolizumab 300 mg plus LD group, and 41 in the placebo group for the primary analyses. No patients in the placebo group had clinical remission at week 10, compared with eight (21% [95% CI 7–36]) patients in the etrolizumab 100 mg group (p=0·0040) and four (10% [0·2–24]) patients in the 300 mg plus LD group (p=0·048). Adverse events occurred in 25 (61%) of 41 patients in the etrolizumab 100 mg group (five [12%] of which were regarded as serious), 19 (48%) of 40 patients in the etrolizumab 300 mg plus LD group (two [5%] serious), and 31 (72%) of 43 patients in the placebo group (five [12%] serious). Interpretation Etrolizumab was more likely to lead to clinical remission at week 10 than was placebo. Therefore, blockade of both α4β7 and αEβ7 might provide a unique therapeutic approach for the treatment of ulcerative colitis, and phase 3 studies have been planned. Funding Genentech.


      PubDate: 2014-07-28T15:08:51Z
       
  • Time for universal provision of take-home naloxone
    • Abstract: Publication date: 26 July–1 August 2014
      Source:The Lancet, Volume 384, Issue 9940
      Author(s): Tim Crocker-Buque , Chris Lovitt



      PubDate: 2014-07-28T15:08:51Z
       
  • Department of Error
    • Abstract: Publication date: 26 July–1 August 2014
      Source:The Lancet, Volume 384, Issue 9940




      PubDate: 2014-07-28T15:08:51Z
       
  • Medical education leaders' perceptions of postgraduate medical education
           reform
    • Abstract: Publication date: 26 July–1 August 2014
      Source:The Lancet, Volume 384, Issue 9940
      Author(s): Pavel V Ovseiko , Crispin Jenkinson , Alastair M Buchan



      PubDate: 2014-07-28T15:08:51Z
       
  • Keeping pace with population growth
    • Abstract: Publication date: 26 July–1 August 2014
      Source:The Lancet, Volume 384, Issue 9940
      Author(s): Vladimíra Kantorová , Ann Biddlecom , Holly Newby



      PubDate: 2014-07-28T15:08:51Z
       
  • What is the alternative' ErikaJanikMarketplace of the Marvelous: The
           Strange Origins of Modern Medicine2014Beacon
           Press9780807022085352US$28·95.
    • Abstract: Publication date: 26 July–1 August 2014
      Source:The Lancet, Volume 384, Issue 9940
      Author(s): Helen Bynum



      PubDate: 2014-07-28T15:08:51Z
       
  • Rana Dajani: stem-cell research and ethics in the Middle East
    • Abstract: Publication date: 26 July–1 August 2014
      Source:The Lancet, Volume 384, Issue 9940
      Author(s): Farhat Yaqub



      PubDate: 2014-07-28T15:08:51Z
       
  • Polio provocation: solving a mystery with the help of history
    • Abstract: Publication date: 26 July–1 August 2014
      Source:The Lancet, Volume 384, Issue 9940
      Author(s): Stephen E Mawdsley



      PubDate: 2014-07-28T15:08:51Z
       
  • UK general practice in crisis: time for a rethink'
    • Abstract: Publication date: 26 July–1 August 2014
      Source:The Lancet, Volume 384, Issue 9940
      Author(s): Emma Wilkinson



      PubDate: 2014-07-28T15:08:51Z
       
  • We are the dead RichardBarnettThe Sick Rose: Or; Disease and the Art of
           Medical Illustration2014Thames and Hudson9780500517345256£19·95.
           
    • Abstract: Publication date: 26 July–1 August 2014
      Source:The Lancet, Volume 384, Issue 9940
      Author(s): Niall Boyce



      PubDate: 2014-07-28T15:08:51Z
       
  • Offline: The moribund body of medical history
    • Abstract: Publication date: 26 July–1 August 2014
      Source:The Lancet, Volume 384, Issue 9940
      Author(s): Richard Horton



      PubDate: 2014-07-28T15:08:51Z
       
  • MH17 tragedy: HIV community mourns loss of colleagues
    • Abstract: Publication date: 26 July–1 August 2014
      Source:The Lancet, Volume 384, Issue 9940
      Author(s): Udani Samarasekera



      PubDate: 2014-07-28T15:08:51Z
       
  • Anthrax and smallpox errors highlight gaps in US biosafety
    • Abstract: Publication date: 26 July–1 August 2014
      Source:The Lancet, Volume 384, Issue 9940
      Author(s): Brian Owens



      PubDate: 2014-07-28T15:08:51Z
       
  • The Wakley Essay Prize 2014: the best of both worlds
    • Abstract: Publication date: 26 July–1 August 2014
      Source:The Lancet, Volume 384, Issue 9940
      Author(s): Joanna Palmer , Niall Boyce



      PubDate: 2014-07-28T15:08:51Z
       
  • Highlights 2014: picturing health
    • Abstract: Publication date: 26 July–1 August 2014
      Source:The Lancet, Volume 384, Issue 9940
      Author(s): Joanna Palmer , Zoë Mullan



      PubDate: 2014-07-28T15:08:51Z
       
  • New era for treatment in differentiated thyroid cancer
    • Abstract: Publication date: 26 July–1 August 2014
      Source:The Lancet, Volume 384, Issue 9940
      Author(s): Sigurdis Haraldsdottir , Manisha H Shah



      PubDate: 2014-07-28T15:08:51Z
       
  • Tissue engineering's green shoots of disruptive innovation
    • Abstract: Publication date: 26 July–1 August 2014
      Source:The Lancet, Volume 384, Issue 9940
      Author(s): Martin A Birchall , Alexander M Seifalian



      PubDate: 2014-07-28T15:08:51Z
       
  • More multiarm randomised trials of superiority are needed
    • Abstract: Publication date: 26 July–1 August 2014
      Source:The Lancet, Volume 384, Issue 9940
      Author(s): Mahesh K B Parmar , James Carpenter , Matthew R Sydes



      PubDate: 2014-07-28T15:08:51Z
       
  • Etrolizumab in moderate-to-severe ulcerative colitis
    • Abstract: Publication date: 26 July–1 August 2014
      Source:The Lancet, Volume 384, Issue 9940
      Author(s): Alessandro Armuzzi , Carla Felice



      PubDate: 2014-07-28T15:08:51Z
       
  • STOP TB—moving out and moving on
    • Abstract: Publication date: 26 July–1 August 2014
      Source:The Lancet, Volume 384, Issue 9940
      Author(s): The Lancet



      PubDate: 2014-07-28T15:08:51Z
       
  • The real meaning of US hospital rankings
    • Abstract: Publication date: 26 July–1 August 2014
      Source:The Lancet, Volume 384, Issue 9940
      Author(s): The Lancet



      PubDate: 2014-07-28T15:08:51Z
       
  • Making primary care people-centred: a 21st century blueprint
    • Abstract: Publication date: 26 July–1 August 2014
      Source:The Lancet, Volume 384, Issue 9940
      Author(s): The Lancet



      PubDate: 2014-07-28T15:08:51Z
       
  • Hepatitis C beware—the end is nigh
    • Abstract: Publication date: Available online 27 July 2014
      Source:The Lancet
      Author(s): Ed Gane



      PubDate: 2014-07-28T15:08:51Z
       
  • July 26–August 1, 2014
    • Abstract: Publication date: 26 July–1 August 2014
      Source:The Lancet, Volume 384, Issue 9940




      PubDate: 2014-07-28T15:08:51Z
       
  • Department of Error
    • Abstract: Publication date: Available online 22 June 2014
      Source:The Lancet




      PubDate: 2014-06-27T14:44:30Z
       
 
 
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