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  • Probiotics to Prevent Clostridium difficile Infection in Patients Receiving Antibiotics
    JAMA (IF 47.661) Pub Date : 2018-07-19
    Joshua Z. Goldenberg, Dominik Mertz, Bradley C. Johnston
    更新日期:2018-07-20
  • Potential Child Health Consequences of the Federal Policy Separating Immigrant Children From Their Parents
    JAMA (IF 47.661) Pub Date : 2018-07-19
    Howard A. Zucker, Danielle Greene

    Actions taken by the US federal government during the past 18 months suggest that the health and welfare of children, particularly children from marginalized groups, may no longer be a priority. The most recent example is the policy of separating children from their parents when the family enters the United States illegally or seeks asylum at the border. In the face of mounting public and political pressure the Trump administration reversed its policy, but more than 2300 children have been removed from their parents at the border in Texas, New Mexico, and Arizona and sent to 17 different states as far away as Illinois, New York, and Washington State.1 A federal judge ruled that family separation must stop, reunification must occur within 30 days, and children younger than 5 years must be reunited with their parents within 14 days, but reunification plans remain vague. As of July 10, some children have been reunited with their families, but more than 2000 remain separated from their parents.2 The immediate consequences of separating children from their parents may be easy to comprehend—anxiety, loss of appetite, poor sleeping, withdrawal, or aggressive behavior. Reports of children who are depressed, suicidal, or otherwise in danger of harming themselves have already surfaced.3 But even if children are reunited with their families, the long-term effects may be more insidious, permanent, and devastating. After the nation’s attention has moved to the next crisis, these children and their families will still be confronting the potentially long-lasting physical and emotional effects of forced separation.

    更新日期:2018-07-20
  • Advancing global health and strengthening the HIV response in the era of the Sustainable Development Goals: the International AIDS Society—Lancet Commission
    Lancet (IF 53.254) Pub Date : 2018-07-19
    Linda-Gail Bekker, George Alleyne, Stefan Baral, Javier Cepeda, Demetre Daskalakis, David Dowdy, Mark Dybul, Serge Eholie, Kene Esom, Geoff Garnett, Anna Grimsrud, James Hakim, Diane Havlir, Michael T Isbell, Leigh Johnson, Adeeba Kamarulzaman, Parastu Kasaie, Michel Kazatchkine, Nduku Kilonzo, Michael Klag, Marina Klein, Sharon R Lewin, Chewe Luo, Keletso Makofane, Natasha K Martin, Kenneth Mayer, Gregorio Millett, Ntobeko Ntusi, Loyce Pace, Carey Pike, Peter Piot, Anton Pozniak, Thomas C Quinn, Jurgen Rockstroh, Jirair Ratevosian, Owen Ryan, Serra Sippel, Bruno Spire, Agnes Soucat, Ann Starrs, Steffanie A Strathdee, Nicholas Thomson, Stefano Vella, Mauro Schechter, Peter Vickerman, Brian Weir, Chris Beyrer
    更新日期:2018-07-20
  • Tackling global health inequities in the HIV response
    Lancet (IF 53.254) Pub Date : 2018-07-19
    Keletso Makofane, Bruno Spire, Phumi Mtetwa
    更新日期:2018-07-20
  • Safe staffing
    BMJ (IF 23.259) Pub Date : 2018-07-19
    Fiona Godlee

    How many doctors does it take to staff a hospital? This might seem a simple question, but even asking it seems brave to some. What if the answer shows how few hospitals have safe medical cover? After the scandal of Mid Staffordshire, Robert Francis called on the National Institute for Health and Clinical Excellence to draw up safe staffing levels, to be policed by the Care Quality Commission. NICE has produced guidelines for the number of nurses needed but not for doctors.The Royal College of Physicians has now taken up this challenge. As Matthew Limb reports (doi:10.1136/bmj.k3136), the college’s review, summarised in our accompanying infographic, gives indicative figures for how many person hours for junior, middle ranking, and senior doctors are needed in the assessment and admissions team, on a medical ward in the week and at weekends, and for day and night on-call cover in different sized hospitals. Where possible, the college has suggested the number of posts needed to cover these hours; crucially, these estimates recognise that doctors take annual, study, and sick leave. This basic fact hasn’t been properly accounted for in the past, says the college’s president elect, Andrew Goddard. And as for the cost of proper staffing, let’s not forget that the NHS spent £3bn (€4.4bn; $4bn) last year on locums. “The NHS already spends a lot of money trying to fill rota gaps and shortages and a lot of money trying to sort out problems when something’s gone wrong with patient care that could be prevented by having adequate staffing levels.”The UK has fewer doctors and nurses per head of population than similar economies in Europe, write Azeem Majeed and colleagues (doi:10.1136/bmj.k3036). Tackling staff shortages will be key to improving outcomes in the NHS, they say. So too will integrating general practice and specialist services within one organisation, providing a single point of contact for urgent care, investing in specialty services, and improving the use of digital technology. And then there is the need to consider the wider determinants of health: housing, education, employment, and the environment. These social inequalities drive poorer outcomes, especially in children and elderly people, they say.Few people have done more to highlight the effects of social inequality on health than Julian Tudor Hart, who died earlier this month (doi:10.1136/bmj.k3052). His lasting contribution was the “inverse care law,” the idea that the people who most need good medical care are the least likely to get it. It also says that this effect is strongest where medical care is most exposed to market forces and weakest where this exposure is reduced. As we ponder the future of the NHS, we would do well to remember this.

    更新日期:2018-07-20
  • Plasma-first resuscitation to treat haemorrhagic shock during emergency ground transportation in an urban area: a randomised trial
    Lancet (IF 53.254) Pub Date : 2018-07-19
    Hunter B Moore, Ernest E Moore, Michael P Chapman, Kevin McVaney, Gary Bryskiewicz, Robert Blechar, Theresa Chin, Clay Cothren Burlew, Fredric Pieracci, F Bernadette West, Courtney D Fleming, Arsen Ghasabyan, James Chandler, Christopher C Silliman, Anirban Banerjee, Angela Sauaia
    更新日期:2018-07-20
  • A pain in the back
    BMJ (IF 23.259) Pub Date : 2018-07-19
    Nadia Hitchen, Harriet Weststrate, Arshad Sheriff

    A 72 year old man with a history of atrial fibrillation was admitted with a basal ganglia interventricular haemorrhage. Warfarin was stopped on admission. Five days after presentation, he developed gradual, cramping, left sided abdominal pain radiating to the flank with urinary frequency but no haematuria. His inflammatory markers were elevated, serum urea and creatinine were normal, and urine microscopy was negative for blood, white cells, and bacteria. A computed tomography scan was arranged (fig 1). What does it show?Axial computed tomography abdominal sliceWedge shaped low attenuation areas in the left kidney with surrounding normal renal parenchyma suggest renal infarct.Renal infarction is most commonly caused by thromboembolism or in situ thrombosis,1 which makes atrial fibrillation a substantial …

    更新日期:2018-07-20
  • How online GP services are tackling safety concerns
    BMJ (IF 23.259) Pub Date : 2018-07-19
    Nick Renaud-Komiya

    Nick Renaud-Komiya examines how digital primary care providers are responding to the Care Quality Commission’s first inspections of their servicesIn March, the Care Quality Commission (CQC) published the findings from its first programme of inspections into companies that provide digital primary care services, such as online consultations. Critics of these commercial services seized on the finding that 43% of the 35 providers inspected since November 2016 were deemed not to be meeting safety standards by February 2018.However, safety was also the area where the healthcare regulator saw the greatest improvement over the inspection period, according to its report (86% were not fully compliant at their first inspection)1—and the changes the providers are making to meet the requirements offer insight into the development of this growing sector.Ruth Rankine, the CQC’s deputy chief inspector of general practice, says, “Patients being supported online deserve the same standards of quality and safety as they would see in more traditional healthcare settings, and we are happy to be working with the sector ... to tackle challenges around this and promote innovation.”The companies, which typically charge for each use or have a monthly fee, offer services ranging from video based medical consultations to home delivery of prescription medicines and sexual health treatments.Thirty seven online healthcare companies are registered with the CQC. Although audited figures on the use of their services are scarce, the evidence suggests that there is a demand. The CQC has reported that Push Doctor, for example, which offers video GP consultations through a smartphone app, was providing roughly 10 000 consultations a month with a team of 72 GPs in March 2017.2Chair …

    更新日期:2018-07-20
  • New strategies for inpatients with HIV and tuberculosis
    Lancet (IF 53.254) Pub Date : 2018-07-19
    Ruvandhi R Nathavitharana, Madhukar Pai
    更新日期:2018-07-20
  • Constant structural reorganisation has never improved or transformed healthcare
    BMJ (IF 23.259) Pub Date : 2018-07-19
    Andrew N Bamji

    Goodman does not go back far enough.12 Kenneth Robinson, when minister of health in the 1960s, began to tinker with the organisation, and rejigging of regional hospital boards and area and district health authorities began …

    更新日期:2018-07-20
  • No gains with plasma-first resuscitation in urban settings?
    Lancet (IF 53.254) Pub Date : 2018-07-19
    David N Naumann, Heidi Doughty, Bryan A Cotton
    更新日期:2018-07-20
  • Reorganisation costs much of the increased funding for the NHS
    BMJ (IF 23.259) Pub Date : 2018-07-19
    Keith Dudleston

    Constant structural reorganisation may not improve or transform healthcare,1 but an objective observer might wonder if these shake-ups have been in the financial interests of the organisations, partnerships, individuals, and companies associated with them.2 The NHS budget doubled in 20 years: from £60bn …

    更新日期:2018-07-20
  • Beyond the silos: integrating HIV and global health
    Lancet (IF 53.254) Pub Date : 2018-07-19
    Pamela Das, Richard Horton
    更新日期:2018-07-20
  • Reorganisation costs lives
    BMJ (IF 23.259) Pub Date : 2018-07-19
    Chris C Gunstone

    On the subject of NHS reorganisation, it is worth remembering the Francis report …

    更新日期:2018-07-20
  • Constant structural reorganisation is likely to continue
    BMJ (IF 23.259) Pub Date : 2018-07-19
    Neville W Goodman

    Oliver is right that constant structural reorganisation won’t improve or transform healthcare, but he does not go back far enough.1 Modern reorganisation of the NHS started with Kenneth Clarke’s 1989 white paper, when Clarke was seeking “less waste and greater efficiency.”2 Whether the overabundance of “redisorganisation”3 since then has given us less waste and greater efficiency is, I suspect, a political and not …

    更新日期:2018-07-20
  • HIV: from exceptionalism to endgame
    Lancet (IF 53.254) Pub Date : 2018-07-19
    Peter Sands
    更新日期:2018-07-20
  • Psychiatrist wins injunction to stop disciplinary proceedings against her
    BMJ (IF 23.259) Pub Date : 2018-07-19
    Clare Dyer

    A consultant psychiatrist has won a High Court interim injunction stopping her employers going ahead this month with disciplinary proceedings that could result in her summary dismissal.1Caroline Ardron has launched a High Court action claiming that the gross misconduct proceedings are a breach of her employment contract with Sussex Partnership NHS Foundation Trust.Pushpinder Saini QC, sitting as a deputy High Court judge, halted the disciplinary proceedings pending an expedited trial of her breach of contract claim against Sussex Partnership NHS Foundation Trust. She claims that the findings of facts …

    更新日期:2018-07-20
  • Seven days in medicine: 11-17 July
    BMJ (IF 23.259) Pub Date : 2018-07-19
    British Medical Journal Publishing Group

    The UK National Institute for Health and Clinical Excellence recommended dinutuximab beta (Qarziba) for treatment of high risk neuroblastoma, after an agreement with the company EUSA Pharma to offer the NHS a discount on the average list price of £152 200 (€172 300; $201 400). The rare cancer mainly affects children and adolescents. Dinutuximab beta will be given to those who have at least partly responded to first stage chemotherapy followed by myeloablative therapy and stem cell transplantation. The potential survival gain is substantial, although uncertainty remains about the drug’s long term benefits, said NICE (https://www.nice.org.uk/guidance/gid-ta10069/documents/final-appraisal-determination-document).Benralizumab (marketed as Fasenra by AstraZeneca) should be an option for people with severe eosinophilic asthma whose symptoms are not adequately controlled with standard treatments, NICE said in draft guidance. The drug is cost effective for people who have had at least three exacerbations in the past year and who have a blood eosinophil count of ≥400 cells/μL and when the biological treatment mepolizumab is not appropriate. AstraZeneca agreed a discount on the list price of £1955 for a 30 mg prefilled syringe.All patients with a brain tumour who could benefit from 5-aminolevulinic acid (5-ALA) before surgery should have it, NICE said. The dye, known as the pink drink, shows tumour cells glowing pink under …

    更新日期:2018-07-20
  • Adrenaline after cardiac arrest doubles risk of serious brain damage, finds trial
    BMJ (IF 23.259) Pub Date : 2018-07-19
    Nigel Hawkes

    A randomised trial of use of adrenaline in patients who have a cardiac arrest outside hospital leaves paramedics with a dilemma.More patients were alive 30 days after their hearts had been restarted with adrenaline, but their chances of serious brain damage were almost doubled, show the findings, reported in the New England Journal of Medicine.1 The finding is likely to lead to a change in guidelines for treating cardiac arrest, though the trial’s lead author, Gavin Perkins of Warwick University, was reluctant to commit himself.Speaking at a briefing at the Science Media Centre in London, Perkins said it would need a broader consideration of the findings by bodies such as the …

    更新日期:2018-07-20
  • Rapid urine-based screening for tuberculosis in HIV-positive patients admitted to hospital in Africa (STAMP): a pragmatic, multicentre, parallel-group, double-blind, randomised controlled trial
    Lancet (IF 53.254) Pub Date : 2018-07-19
    Ankur Gupta-Wright, Elizabeth L Corbett, Joep J van Oosterhout, Douglas Wilson, Daniel Grint, Melanie Alufandika-Moyo, Jurgens A Peters, Lingstone Chiume, Clare Flach, Stephen D Lawn, Katherine Fielding
    更新日期:2018-07-20
  • Evidence and tips on the use of medication compliance aids
    BMJ (IF 23.259) Pub Date : 2018-07-19
    Daniel S Furmedge, Jennifer M Stevenson, Rebekah Schiff, J Graham Davies

    Medication compliance aids (MCAs) such as Dossett boxes are used to support people taking medication who may find it difficult because of cognitive impairment or the complexity of their regimen.There is little evidence to say whether these devices improve compliance, safety, satisfaction, or convenience taking medication.Many commonly prescribed medicines may not be suitable for long term storage in a multi-compartment MCA because they can break down or expire when outside the standard sealed packaging. Drugs that are taken only when needed or those subject to frequent changes in dosage schedule are also unsuitable for multi-compartment MCAs.Multi-compartment MCAs are often prepared in advance—make sure any changes in the medication regimen are clearly communicated to the pharmacist preparing the MCA.Offer an annual medication review to all patients who are dispensed their medications in a multi-compartment MCA to minimise the chance that people continue inappropriate medicationOlder people, and those with frailty and multiple comorbidities can have complex medication regimens, which can be challenging for patients, carers, and healthcare practitioners to manage. Some patients choose not to take all their medications (intentional non-adherence)—this accounts for approximately 50% of non-adherence in patients over the age of 65.123 Others, for example those with cognitive impairment, may forget or find it difficult to manage taking their medication (unintentional non-adherence).To address unintentional non-adherence, patients can use electronic reminders and devices, support from carers, and medication compliance aids (MCAs) to help them follow their medication regimens.4 Use of multi-compartment MCAs seems to be increasing, although there are no reliable data on UK prevalence.5 Multi-compartment MCAs can be called multi-dose drug dispensing systems, or “Dossett Boxes” after one of the original marketed versions.567 Examples or other brands include NOMAD and Venalink. Importantly, these devices only store …

    更新日期:2018-07-20
  • Subacromial decompression versus diagnostic arthroscopy for shoulder impingement: randomised, placebo surgery controlled clinical trial
    BMJ (IF 23.259) Pub Date : 2018-07-19
    Mika Paavola, Antti Malmivaara, Simo Taimela, Kari Kanto, Jari Inkinen, Juha Kalske, Ilkka Sinisaari, Vesa Savolainen, Jonas Ranstam, Teppo L N Järvinen

    Objective To assess the efficacy of arthroscopic subacromial decompression (ASD) by comparing it with diagnostic arthroscopy, a placebo surgical intervention, and with a non-operative alternative, exercise therapy, in a more pragmatic setting.Design Multicentre, three group, randomised, double blind, sham controlled trial.Setting Orthopaedic departments at three public hospitals in Finland.Participants 210 patients with symptoms consistent with shoulder impingement syndrome, enrolled from 1 February 2005 with two year follow-up completed by 25 June 2015.Interventions ASD, diagnostic arthroscopy (placebo control), and exercise therapy.Main outcome measures Shoulder pain at rest and on arm activity (visual analogue scale (VAS) from 0 to 100, with 0 denoting no pain), at 24 months. The threshold for minimal clinically important difference was set at 15.Results In the primary intention to treat analysis (ASD versus diagnostic arthroscopy), no clinically relevant between group differences were seen in the two primary outcomes at 24 months (mean change for ASD 36.0 at rest and 55.4 on activity; for diagnostic arthroscopy 31.4 at rest and 47.5 on activity). The observed mean difference between groups (ASD minus diagnostic arthroscopy) in pain VAS were −4.6 (95% confidence interval −11.3 to 2.1) points (P=0.18) at rest and −9.0 (−18.1 to 0.2) points (P=0.054) on arm activity. No between group differences were seen between the ASD and diagnostic arthroscopy groups in the secondary outcomes or adverse events. In the secondary comparison (ASD versus exercise therapy), statistically significant differences were found in favour of ASD in the two primary outcomes at 24 months in both VAS at rest (−7.5, −14.0 to −1.0, points; P=0.023) and VAS on arm activity (−12.0, −20.9 to −3.2, points; P=0.008), but the mean differences between groups did not exceed the pre-specified minimal clinically important difference. Of note, this ASD versus exercise therapy comparison is not only confounded by lack of blinding but also likely to be biased in favour of ASD owing to the selective removal of patients with likely poor outcome from the ASD group, without comparable exclusions from the exercise therapy group.Conclusions In this controlled trial involving patients with a shoulder impingement syndrome, arthroscopic subacromial decompression provided no benefit over diagnostic arthroscopy at 24 months.Trial registration Clinicaltrials.gov NCT00428870.

    更新日期:2018-07-20
  • Opioid prescriptions outnumber patients in some parts of the US
    BMJ (IF 23.259) Pub Date : 2018-07-19
    Bob Roehr

    Prescribing rates for opioids are up to sevenfold higher in rural areas compared with urban ones in the United States, according to a new analysis of prescribing patterns by congressional district.Heading the list was Alabama’s 4th district, where doctors wrote 166.69 opioid prescriptions per 100 persons. The largely rural area sprawls across the northern region of the state and is 88% white, compared with 73% white for the state as a whole.At the bottom of the list were two congressional districts in Brooklyn, New York, where the prescribing rate …

    更新日期:2018-07-20
  • Time to deliver: report of the WHO Independent High-Level Commission on NCDs
    Lancet (IF 53.254) Pub Date : 2018-06-01
    Sania Nishtar, Sauli Niinistö, Maithripala Sirisena, Tabaré Vázquez, Veronika Skvortsova, Adolfo Rubinstein, Festus Gontebanye Mogae, Pirkko Mattila, Seyyed Hassan Ghazizadeh Hashemi, Sicily Kariuki, José Narro Robles, Isaac F Adewole, Adboulaye Diouf Sarr, Kim Yong Gan, Saia Ma'u Piukala, Abdul Rahman Bin Mohammed Al Owais, Eric Hargan, George Alleyne, Ala Alwan, Arnaud Bernaert, Michael Bloomberg, Katie Dain, Tom Frieden, Vikram Harshad Patel, Annette Kennedy, Ilona Kickbusch

    The 2030 Agenda for Sustainable Development, with its pledge to leave no one behind, is our boldest agenda for humanity. It will require equally bold actions from Heads of State and Government. They must deliver on their time-bound promise to reduce, by one-third, premature mortality from NCDs through prevention and treatment and promote mental health and wellbeing.

    更新日期:2018-07-20
  • Hibernoma mimicking liposarcoma
    Lancet (IF 53.254) Pub Date : 2018-07-21
    Lucie Pothen, Philippe D'Abadie, Alexandra Kozyreff, Anne Mourin, Laurent Coubeau
    更新日期:2018-07-20
  • Evaluation of a mosaic HIV-1 vaccine in a multicentre, randomised, double-blind, placebo-controlled, phase 1/2a clinical trial (APPROACH) and in rhesus monkeys (NHP 13-19)
    Lancet (IF 53.254) Pub Date : 2018-07-06
    Dan H Barouch, Frank L Tomaka, Frank Wegmann, Daniel J Stieh, Galit Alter, Merlin L Robb, Nelson L Michael, Lauren Peter, Joseph P Nkolola, Erica N Borducchi, Abishek Chandrashekar, David Jetton, Kathryn E Stephenson, Wenjun Li, Bette Korber, Georgia D Tomaras, David C Montefiori, Glenda Gray, Nicole Frahm, M Juliana McElrath, Lindsey Baden, Jennifer Johnson, Julia Hutter, Edith Swann, Etienne Karita, Hannah Kibuuka, Juliet Mpendo, Nigel Garrett, Kathy Mngadi, Kundai Chinyenze, Frances Priddy, Erica Lazarus, Fatima Laher, Sorachai Nitayapan, Punnee Pitisuttithum, Stephan Bart, Thomas Campbell, Robert Feldman, Gregg Lucksinger, Caroline Borremans, Katleen Callewaert, Raphaele Roten, Jerald Sadoff, Lorenz Scheppler, Mo Weijtens, Karin Feddes-de Boer, Daniëlle van Manen, Jessica Vreugdenhil, Roland Zahn, Ludo Lavreys, Steven Nijs, Jeroen Tolboom, Jenny Hendriks, Zelda Euler, Maria G Pau, Hanneke Schuitemaker
    更新日期:2018-07-20
  • Baricitinib for systemic lupus erythematosus: a double-blind, randomised, placebo-controlled, phase 2 trial
    Lancet (IF 53.254) Pub Date : 2018-07-21
    Daniel J Wallace, Richard A Furie, Yoshiya Tanaka, Kenneth C Kalunian, Marta Mosca, Michelle A Petri, Thomas Dörner, Mario H Cardiel, Ian N Bruce, Elisa Gomez, Tara Carmack, Amy M DeLozier, Jonathan M Janes, Matthew D Linnik, Stephanie de Bono, Maria E Silk, Robert W Hoffman
    更新日期:2018-07-20
  • Outbreak of Ebola virus disease in the Democratic Republic of the Congo, April–May, 2018: an epidemiological study
    Lancet (IF 53.254) Pub Date : 2018-06-29
    Ahmadou Barry, Steve Ahuka-Mundeke, Yahaya Ali Ahmed, Yokouide Allarangar, Julienne Anoko, Brett Nicholas Archer, Aaron Aruna Abedi, Jayshree Bagaria, Marie Roseline Darnycka Belizaire, Sangeeta Bhatia, Théophile Bokenge, Emanuele Bruni, Anne Cori, Ernest Dabire, Amadou Mouctar Diallo, Boubacar Diallo, Christl Ann Donnelly, Ilaria Dorigatti, Tshewang Choden Dorji, Aura Rocio Escobar Corado Waeber, Ibrahima Socé Fall, Neil M Ferguson, Richard Gareth FitzJohn, Gervais Leon Folefack Tengomo, Pierre Bernard Henri Formenty, Alpha Forna, Anne Fortin, Tini Garske, Katy AM Gaythorpe, Celine Gurry, Esther Hamblion, Mamoudou Harouna Djingarey, Christopher Haskew, Stéphane Alexandre Louis Hugonnet, Natsuko Imai, Benido Impouma, Guylain Kabongo, Oly Ilunga Kalenga, Emerencienne Kibangou, Theresa Min-Hyung Lee, Charles Okot Lukoya, Ousmane Ly, Sheila Makiala-Mandanda, Augustin Mamba, Placide Mbala-Kingebeni, Franck Fortune Roland Mboussou, Tamayi Mlanda, Vital Mondonge Makuma, Oliver Morgan, Anastasie Mujinga Mulumba, Patrick Mukadi Kakoni, Daniel Mukadi-Bamuleka, Jean-Jaques Muyembe, Ndjoloko Tambwe Bathé, Patricia Ndumbi Ngamala, Roland Ngom, Guillaume Ngoy, Pierre Nouvellet, Justus Nsio, Kevin Babila Ousman, Emilie Peron, Jonathan Aaron Polonsky, Michael J. Ryan, Alhassane Touré, Rodney Towner, Gaston Tshapenda, Reinhilde Van De Weerdt, Maria Van Kerkhove, Annika Wendland, N'Da Konan Michel Yao, Zabulon Yoti, Etienne Yuma, Guy Kalambayi Kabamba, Jean de Dieu Lukwesa Mwati, Gisele Mbuy, Leopold Lubula, Anny Mutombo, Oscar Mavila, Yyonne Lay, Emma Kitenge
    更新日期:2018-07-20
  • The how: a message for the UN high-level meeting on NCDs
    Lancet (IF 53.254) Pub Date : 2018-06-28
    Kent Buse, Robert Marten, Sarah Hawkes, George Alleyne, Phillip Baker, Fran Baum, Robert Beaglehole, Chantal Blouin, Ruth Bonita, Luisa Brumana, John Butler, Simon Capewell, Sally Casswell, José Luis Castro, Mickey Chopra, Helen Clark, Katie Dain, Sandro Demaio, Andrea Feigl, Patricia Frenz, Peter Friberg, Sharon Friel, Amanda Glassman, Unni Gopinathan, Lawrence Gostin, Sofia Gruskin, Corinna Hawkes, David Hipgrave, Paula Johns, Alexandra Jones, Sowmya Kadandale, Roger Magnusson, Patricio V. Marquez, Martin McKee, Benjamin Mason Meier, Carlos A. Monteiro, Modi Mwatsama, Rachel Nugent, David Patterson, Stefan Peterson, Yogan Pillay, Johanna Ralston, Srinath Reddy, Juan A. Rivera, Sandhya Singh, Sudhvir Singh, Tim Sladden, Richard Smith, Kristina Sperkova, Thaksaphon Thamarangsi, Francis Thompson, Douglas Webb

    This September's UN General Assembly high-level meeting (HLM) on non-communicable diseases (NCDs) provides a strategic opportunity to propel the response—from “where do we want to be” to “how do we get there”.

    更新日期:2018-07-20
  • Reducing NCDs globally: the under-recognised role of environmental risk factors
    Lancet (IF 53.254) Pub Date : 2018-06-28
    Rajiv Chowdhury, Rian Lawrence, Kim van Daalen, Sarah Hawkes, Joerg Feldmann

    This month, the WHO Independent High-Level Commission on Non-Communicable Diseases (NCDs) published a set of recommendations to accelerate progress towards achieving the Sustainable Development Goals Target 3.4 for reducing NCDs by 2030.1 Unfortunately, this globally important report had a major omission: recognising the detrimental role of environmental risk factors, beyond the conventional behavioural factors (tobacco and alcohol use, physical inactivity, and unhealthy diet), in enhancing global NCD burden and health inequality.

    更新日期:2018-07-20
  • 更新日期:2018-07-20
  • Regional population structures at a glance
    Lancet (IF 53.254) Pub Date : 2018-07-21
    Ilya Kashnitsky, Jonas Schöley
    更新日期:2018-07-20
  • Jonathan E Fine
    Lancet (IF 53.254) Pub Date : 2018-07-21
    Adam Marcus, Ivan Oransky
    更新日期:2018-07-20
  • Taking to tobacco
    Lancet (IF 53.254) Pub Date : 2018-07-21
    Phil Withington
    更新日期:2018-07-20
  • Death
    Lancet (IF 53.254) Pub Date : 2018-07-21
    Sam Guglani
    更新日期:2018-07-20
  • Charles Dickens' scientific network
    Lancet (IF 53.254) Pub Date : 2018-07-21
    Wendy Moore
    更新日期:2018-07-20
  • The beginning of the end of fingersticks?
    Lancet (IF 53.254) Pub Date : 2018-07-21
    Michael Y Song, Steven R Steinhubl, Eric J Topol
    更新日期:2018-07-20
  • Setbacks in the fight to eradicate polio
    Lancet (IF 53.254) Pub Date : 2018-07-21
    Sharmila Devi
    更新日期:2018-07-20
  • PEPFAR at 15 years
    Lancet (IF 53.254) Pub Date : 2018-07-21
    Paul Webster
    更新日期:2018-07-20
  • Changes to dolutegravir policy in several African countries
    Lancet (IF 53.254) Pub Date : 2018-07-21
    Esther Nakkazi
    更新日期:2018-07-20
  • Offline: What is science for?
    Lancet (IF 53.254) Pub Date : 2018-07-21
    Richard Horton
    更新日期:2018-07-20
  • Global child and adolescent health: a call for papers
    Lancet (IF 53.254) Pub Date : 2018-07-17
    Jane Godsland, Udani Samarasekera, Esther Lau, Richard Horton
    更新日期:2018-07-20
  • Homeless reduction act in England: impact on health services
    Lancet (IF 53.254) Pub Date : 2018-07-21
    Vibhu Paudyal, Karen Saunders
    更新日期:2018-07-20
  • Three global health-care quality reports in 2018
    Lancet (IF 53.254) Pub Date : 2018-07-21
    Donald M Berwick, Edward Kelley, Margaret E Kruk, Sania Nishtar, Muhammad Ali Pate
    更新日期:2018-07-20
  • A new step towards an HIV/AIDS vaccine
    Lancet (IF 53.254) Pub Date : 2018-07-06
    George N Pavlakis, Barbara K Felber
    更新日期:2018-07-20
  • Baricitinib for systemic lupus erythematosus
    Lancet (IF 53.254) Pub Date : 2018-07-21
    Johanna Mucke, Matthias Schneider
    更新日期:2018-07-20
  • Ebola virus disease: 11 323 deaths later, how far have we come?
    Lancet (IF 53.254) Pub Date : 2018-06-29
    Joseph A Lewnard
    更新日期:2018-07-20
  • Cannabinoids: just like any other medication?
    Lancet (IF 53.254) Pub Date : 2018-07-21
    The Lancet
    更新日期:2018-07-20
  • Gender and health are also about boys and men
    Lancet (IF 53.254) Pub Date : 2018-07-21
    The Lancet
    更新日期:2018-07-20
  • UK life science research: time to burst the biomedical bubble
    Lancet (IF 53.254) Pub Date : 2018-07-21
    The Lancet
    更新日期:2018-07-20
  • PP2A inhibition is a druggable MEK inhibitor resistance mechanism in KRAS-mutant lung cancer cells
    Sci. Transl. Med. (IF 16.71) Pub Date : 2018-07-18
    Otto Kauko, Caitlin M. O’Connor, Evgeny Kulesskiy, Jaya Sangodkar, Anna Aakula, Sudeh Izadmehr, Laxman Yetukuri, Bhagwan Yadav, Artur Padzik, Teemu Daniel Laajala, Pekka Haapaniemi, Majid Momeny, Taru Varila, Michael Ohlmeyer, Tero Aittokallio, Krister Wennerberg, Goutham Narla, Jukka Westermarck

    Kinase inhibitor resistance constitutes a major unresolved clinical challenge in cancer. Furthermore, the role of serine/threonine phosphatase deregulation as a potential cause for resistance to kinase inhibitors has not been thoroughly addressed. We characterize protein phosphatase 2A (PP2A) activity as a global determinant of KRAS-mutant lung cancer cell resistance across a library of >200 kinase inhibitors. The results show that PP2A activity modulation alters cancer cell sensitivities to a large number of kinase inhibitors. Specifically, PP2A inhibition ablated mitogen-activated protein kinase kinase (MEK) inhibitor response through the collateral activation of AKT/mammalian target of rapamycin (mTOR) signaling. Combination of mTOR and MEK inhibitors induced cytotoxicity in PP2A-inhibited cells, but even this drug combination could not abrogate MYC up-regulation in PP2A-inhibited cells. Treatment with an orally bioavailable small-molecule activator of PP2A DT-061, in combination with the MEK inhibitor AZD6244, resulted in suppression of both p-AKT and MYC, as well as tumor regression in two KRAS-driven lung cancer mouse models. DT-061 therapy also abrogated MYC-driven tumorigenesis. These data demonstrate that PP2A deregulation drives MEK inhibitor resistance in KRAS-mutant cells. These results emphasize the need for better understanding of phosphatases as key modulators of cancer therapy responses.

    更新日期:2018-07-19
  • MHC proteins confer differential sensitivity to CTLA-4 and PD-1 blockade in untreated metastatic melanoma
    Sci. Transl. Med. (IF 16.71) Pub Date : 2018-07-18
    Scott J. Rodig, Daniel Gusenleitner, Donald G. Jackson, Evisa Gjini, Anita Giobbie-Hurder, Chelsea Jin, Han Chang, Scott B. Lovitch, Christine Horak, Jeffrey S. Weber, Jason L. Weirather, Jedd D. Wolchok, Michael A. Postow, Anna C. Pavlick, Jason Chesney, F. Stephen Hodi

    Combination anti–cytotoxic T lymphocyte antigen 4 (CTLA-4) and anti–programmed cell death protein 1 (PD-1) therapy promotes antitumor immunity and provides superior benefit to patients with advanced-stage melanoma compared with either therapy alone. T cell immunity requires recognition of antigens in the context of major histocompatibility complex (MHC) class I and class II proteins by CD8+ and CD4+ T cells, respectively. We examined MHC class I and class II protein expression on tumor cells from previously untreated melanoma patients and correlated the results with transcriptional and genomic analyses and with clinical response to anti–CTLA-4, anti–PD-1, or combination therapy. Most (>50% of cells) or complete loss of melanoma MHC class I membrane expression was observed in 78 of 181 cases (43%), was associated with transcriptional repression of HLA-A, HLA-B, HLA-C, and B2M, and predicted primary resistance to anti–CTLA-4, but not anti–PD-1, therapy. Melanoma MHC class II membrane expression on >1% cells was observed in 55 of 181 cases (30%), was associated with interferon-γ (IFN-γ) and IFN-γ–mediated gene signatures, and predicted response to anti–PD-1, but not anti–CTLA-4, therapy. We conclude that primary response to anti–CTLA-4 requires robust melanoma MHC class I expression. In contrast, primary response to anti–PD-1 is associated with preexisting IFN-γ–mediated immune activation that includes tumor-specific MHC class II expression and components of innate immunity when MHC class I is compromised. The benefits of combined checkpoint blockade may be attributable, in part, to distinct requirements for melanoma-specific antigen presentation to initiate antitumor immunity.

    更新日期:2018-07-19
  • Play it again, Mom: How babies recognize melodies
    Sci. Transl. Med. (IF 16.71) Pub Date : 2018-07-18
    Rebecca M. Jones

    Playing familiar songs during sleep increased hippocampal activation in toddlers.

    更新日期:2018-07-19
  • Re-engineering the heart with the correct components
    Sci. Transl. Med. (IF 16.71) Pub Date : 2018-07-18
    Kory Lavine

    Modulation of retinoic acid signaling generates atrial versus ventricular cardiomyocytes from human induced pluripotent stem cells.

    更新日期:2018-07-19
  • A cytokine duet regulates inflammatory bowel disease
    Sci. Transl. Med. (IF 16.71) Pub Date : 2018-07-18
    Hu Zeng

    Inhibition of IL-17F, but not IL-17A, promotes microbiota-mediated regulatory T cell generation in the colon and ameliorates intestinal inflammation in mice.

    更新日期:2018-07-19
  • A bullet against gallbladder cancer
    Sci. Transl. Med. (IF 16.71) Pub Date : 2018-07-18
    Ming Yang

    ERBB2/3 mutations in gallbladder cancer are associated with immunosuppression and aggressive tumor development and can be targeted by ERBB2/3 inhibitors.

    更新日期:2018-07-19
  • Selective neuronal silencing using synthetic botulinum molecules alleviates chronic pain in mice
    Sci. Transl. Med. (IF 16.71) Pub Date : 2018-07-18
    Maria Maiarù, Charlotte Leese, Michelangelo Certo, Irene Echeverria-Altuna, Antonina S. Mangione, Jason Arsenault, Bazbek Davletov, Stephen P. Hunt

    Chronic pain is a widespread debilitating condition affecting millions of people worldwide. Although several pharmacological treatments for relieving chronic pain have been developed, they require frequent chronic administration and are often associated with severe adverse events, including overdose and addiction. Persistent increased sensitization of neuronal subpopulations of the peripheral and central nervous system has been recognized as a central mechanism mediating chronic pain, suggesting that inhibition of specific neuronal subpopulations might produce antinociceptive effects. We leveraged the neurotoxic properties of the botulinum toxin to specifically silence key pain-processing neurons in the spinal cords of mice. We show that a single intrathecal injection of botulinum toxin conjugates produced long-lasting pain relief in mouse models of inflammatory and neuropathic pain without toxic side effects. Our results suggest that this strategy might be a safe and effective approach for relieving chronic pain while avoiding the adverse events associated with repeated chronic drug administration.

    更新日期:2018-07-19
  • Antibody blockade of IL-15 signaling has the potential to durably reverse vitiligo
    Sci. Transl. Med. (IF 16.71) Pub Date : 2018-07-18
    Jillian M. Richmond, James P. Strassner, Lucio Zapata, Madhuri Garg, Rebecca L. Riding, Maggi A. Refat, Xueli Fan, Vincent Azzolino, Andrea Tovar-Garza, Naoya Tsurushita, Amit G. Pandya, J. Yun Tso, John E. Harris

    Vitiligo is an autoimmune disease of the skin mediated by CD8+ T cells that kill melanocytes and create white spots. Skin lesions in vitiligo frequently return after discontinuing conventional treatments, supporting the hypothesis that autoimmune memory is formed at these locations. We found that lesional T cells in mice and humans with vitiligo display a resident memory (TRM) phenotype, similar to those that provide rapid, localized protection against reinfection from skin and mucosal-tropic viruses. Interleukin-15 (IL-15)–deficient mice reportedly have impaired TRM formation, and IL-15 promotes TRM function ex vivo. We found that both human and mouse TRM express the CD122 subunit of the IL-15 receptor and that keratinocytes up-regulate CD215, the subunit required to display the cytokine on their surface to promote activation of T cells. Targeting IL-15 signaling with an anti-CD122 antibody reverses disease in mice with established vitiligo. Short-term treatment with anti-CD122 inhibits TRM production of interferon-γ (IFNγ), and long-term treatment depletes TRM from skin lesions. Short-term treatment with anti-CD122 can provide durable repigmentation when administered either systemically or locally in the skin. On the basis of these data, we propose that targeting CD122 may be a highly effective and even durable treatment strategy for vitiligo and other tissue-specific autoimmune diseases involving TRM.

    更新日期:2018-07-19
  • The FDA and the Next Wave of Drug Abuse — Proactive Pharmacovigilance
    N. Engl. J. Med. (IF 79.258) Pub Date : 2018-07-19
    Douglas C. Throckmorton; Scott Gottlieb; Janet Woodcock

    In response to the opioid crisis, the Food and Drug Administration (FDA) has taken action on multiple fronts. We have approved better measures for treating opioid use disorder and preventing deaths from overdose, have launched efforts to inform more appropriate prescribing as a way to limit clinical exposure to opioids, have taken actions to reduce the excess opioids available for abuse, and are working to facilitate development of new therapeutics that can effectively and safely help patients suffering from pain. Going forward, the FDA needs to remain vigilant to recognize shifting trends in the addiction landscape. Taking a systematic approach to monitoring such trends should allow us to intervene promptly and appropriately and protect the public from associated risks.

    更新日期:2018-07-19
  • Turning the Tables — The New European General Data Protection Regulation
    N. Engl. J. Med. (IF 79.258) Pub Date : 2018-07-19
    Charlotte J. Haug

    “Action required: Make sure you receive important information!” was the alarming message my Internet service provider recently sent me. It turned out they wanted me to review my privacy settings — or, really, to agree that they could continue using data about me just as they had before. People throughout Europe have been inundated with such messages over recent weeks. Almost every Web page or app you open presents you with a pop-up window and an “I agree” button that must be hurdled before you can buy your train ticket, access your music, or browse content. Why this sudden concern about privacy settings? The reason is the General Data Protection Regulation (GDPR), a new European privacy law that will be fully enforced this summer.1 Given that the regulation was proposed in 2012 and adopted in May 2016, it should come as no surprise that it has become fully enforceable throughout the European Union (EU) now, after a 2-year grace period.

    更新日期:2018-07-19
Some contents have been Reproduced with permission of the American Chemical Society.
Some contents have been Reproduced by permission of The Royal Society of Chemistry.
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