Group Purchasing Organizations, Health Care Costs, and Drug Shortages JAMA (IF 47.661) Pub Date : 2018-10-18 William E. Bruhn, Elizabeth A. Fracica, Martin A. Makary
Most medical centers today acquire supplies, medications, and devices through group purchasing organizations (GPOs) rather than directly from a manufacturer. GPOs are intermediaries that catalog medical supplies so medical centers can purchase them from manufacturers. According to the American Hospital Association, 68% of hospitals used a GPO for their main purchasing needs in 2000, and by 2014, an estimated 98% of hospitals used a GPO.1 The nation’s largest GPO, Vizient Inc, claims to own 30% of the national market for all medical supplies, and, collectively, the 4 largest GPOs in the United States account for 90% of the market for medical supplies. In this Viewpoint, we explore the role of GPOs in health care, concerns with their current payment structure, and potential solutions. GPOs provide many benefits for hospitals. Since their inception in 1910, GPOs have simplified the way hospitals purchase supplies, ranging from bathroom items (eg, hand soap) to epinephrine vials. GPOs spare hospitals the work and expense of negotiating and contracting with hundreds of different manufacturers. GPOs instead offer hospitals a catalog of thousands of products and product training and support services to accompany some products. GPOs also have volume purchasing leverage to negotiate lower prices. Moreover, the ability of GPOs to list multiple comparable products in their catalogs can promote competition and reward innovation. However, there have been some concerns about how the current business model of GPOs may be undermining price competition and limiting hospital access to medical supplies. In 1972, Congress enacted the Anti-Kickback Statute as part of the Social Security Act Amendments that banned kickbacks, bribes, or rebates in return for furnishing items or services; the statute was intended to protect patients and federal health programs from the inherent conflict of interest. However, in 1987, group purchasers were granted an exception to the antikickback law, known as the safe harbor exemption. The exemption allowed creative strategies for GPOs to increase their profits. Today, GPOs ask manufacturers to pay them undisclosed vendor fees as a condition to have their products placed in the GPO catalogs. This issue can be problematic when GPOs go further and invite a manufacturer to pay a premium fee to become a sole supplier, allowing the manufacturer that is the highest bidder to essentially purchase market share, rendering hospitals and patients dependent on a single manufacturer’s supply chain. Hospitals in turn are sometimes asked to enter into contracts with GPOs that offer greater discounts for longer, more exclusive contracts.
Scientific Misconduct and Medical Journals JAMA (IF 47.661) Pub Date : 2018-10-19 Howard Bauchner, Phil B. Fontanarosa, Annette Flanagin, Joe Thornton
According to the US Department of Health and Human Services, “Research misconduct means fabrication, falsification, or plagiarism in proposing, performing, or reviewing research, or in reporting research results.”1 Other important irregularities involving the biomedical research process include, but are not limited to, ethical issues (eg, failure to obtain informed consent, failure to obtain appropriate approval from an institutional review board, and mistreatment of research participants), issues involving authorship responsibilities and disputes, duplicate publication, and failure to report conflicts of interest. When authors are found to have been involved with research misconduct or other serious irregularities involving articles that have been published in scientific journals, editors have a responsibility to ensure the accuracy and integrity of the scientific record.2,3 Although not much is known about the prevalence of scientific misconduct, several studies with limited methods have estimated that the prevalence of scientists who have been involved in scientific misconduct ranges from 1% to 2%.4-6 During the last 5 years, JAMA and the JAMA Network journals have published 12 notices of Retraction about 15 articles (including recent Retractions of 6 articles by the same author)7 and 6 notices of Expression of Concern about 9 articles. These notices were published primarily because the original studies were found to involve fabrication or falsification of data that invalidated the research and the published articles; in some cases, postpublication investigations could not provide evidence that the original research was valid. Since 2015, JAMA and the JAMA Network journals also have retracted and replaced 12 articles for instances of inadvertent pervasive error resulting from incorrect data coding or incorrect analyses and without evidence of research misconduct.8 During the same period, 1021 correction notices have been published in these journals. The JAMA Network policies regarding corrections and retraction with replacement have been published previously.8,9 In this Editorial, the focus is on a more complex and challenging issue—scientific misconduct involving fabrication, falsification, and plagiarism in the reporting of research.1 JAMA and the JAMA Network journals receive numerous communications from readers, such as letters to the editor and emails, that are critical of the published content. Most of the critiques involve matters of interpretation, the need for clarification of content, or differences of opinion; some address ethical concerns, some are frivolous complaints, and some include calls for retraction. However, typically 10 to 12 times each year these journals receive allegations of scientific misconduct. All matters related to allegations of scientific misconduct for articles published in JAMA and the JAMA Network journals are evaluated and managed by the senior staff of JAMA including the editor in chief of JAMA, executive editor, executive managing editor, and the editorial counsel. This provides a consistent process for dealing with potential scientific misconduct. If the allegation involves an article published in a network journal, the editor in chief of that journal is involved and kept informed about the progress of the investigation. In addition, when necessary, additional expertise is obtained.
The Astana Declaration: the future of primary health care? Lancet (IF 53.254) Pub Date : 2018-10-20 The Lancet
Primary health care for the 21st century, universal health coverage, and the Sustainable Development Goals Lancet (IF 53.254) Pub Date : 2018-10-20 Tedros Adhanom Ghebreyesus, Henrietta Fore, Yelzhan Birtanov, Zsuzsanna Jakab
How primary health care can make universal health coverage a reality, ensure healthy lives, and promote wellbeing for all Lancet (IF 53.254) Pub Date : 2018-10-20 Hans Kluge, Ed Kelley, Shannon Barkley, Pavlos N Theodorakis, Naoko Yamamoto, Alexey Tsoy, Ainur Aiypkhanova, Vidhya Ganesh, David B Hipgrave, Stefan Swartling Peterson, Jose M Valderas, Elias Mossialos
Primary health care and universal health coverage: competing discourses? Lancet (IF 53.254) Pub Date : 2018-10-20 Peter S Hill
Putting nursing and midwifery at the heart of the Alma-Ata vision Lancet (IF 53.254) Pub Date : 2018-10-20 Nigel Crisp, Elizabeth Iro
Patient education and engagement in treat-to-target gout care Lancet (IF 53.254) Pub Date : 2018-10-20 Tuhina Neogi, Nicola Dalbeth
Intensive care: balancing risk and benefit to facilitate informed decisions BMJ (IF 23.259) Pub Date : 2018-10-19 Jamie Gross, Barry Williams, Premila Fade, Stephen J Brett
More efforts are needed to engage with the wider healthcare community and the public about what intensive care can—and can’t—achieve, say Jamie Gross and colleaguesChanging population demographics and improved chronic disease management have led to a growing proportion of patients being admitted to intensive care units (ICUs) with co-existing chronic disease and frailty.12 This has contributed to greater demand for intensive care services, which is steadily increasing at a rate of about 4% a year.3 Limited bed capacity in ICUs results in cancelled urgent operations and in non-clinical transfers to other such units.4 Given that intensive care is an expensive resource with healthcare costs for survivors that commonly extend well beyond admission,5 this trend is unlikely to be sustainable. Crucially, for patients with chronic disease and established frailty, undergoing the burden of a prolonged stay in intensive care for an acute illness may not deliver sustainable benefit,56 with the important caveat that the definition of “benefit” is a very individual thing.Can anything be done to tackle the mismatch between supply and demand for intensive care? Perhaps part of this increasing demand is due to unrealistic expectations of what medicine—in particular intensive care—can achieve, along with an underappreciation of the burdens of both a critical care stay and future survivorship.7 One approach might be to increase public awareness about what admission to intensive care could mean for patients and their families, to facilitate informed decision making.The onset of critical illness can be a highly stressful time for patients and their families. Most people do not express their wishes for the management of a future hypothetical life threatening crisis, so when a patient is incapacitated by acute illness relatives are often faced with the burden of trying to determine what that …
GP trainees recruited in England surpass target BMJ (IF 23.259) Pub Date : 2018-10-19 Abi Rimmer
The number of doctors entering GP training in England this year has surpassed the target set by Health Education England (HEE) by more than 200.HEE said that 3473 trainees were starting their GP training this year (beginning either in August 2018 or February 2019), compared with a recruitment target of 3250. Figures show that 3039 doctors entered GP training in England last year, so this year’s figures represent a 14% increase.1 …
No benefit of chlamydia screening in primary care? Lancet (IF 53.254) Pub Date : 2018-10-20 Paul C Adamson, Jeffrey D Klausner
Update on STPs: Five minutes with . . . Anna Charles BMJ (IF 23.259) Pub Date : 2018-10-19 Gareth Iacobucci
The King’s Fund’s senior policy adviser explains how plans to integrate services are now less focused on reducing bed numbers“Our latest report1 looks at the progress of London’s five sustainability and transformation partnerships (STPs). It was commissioned by the mayor of London, Sadiq Khan, and follows work we’ve done looking at all 44 STPs across England.“The main message from the report is that things have moved on since STP plans were first published in 2016 (http://sandpit.bmj.com/graphics/2016/stpMap/index.html). The perception then was that the plans had quite challenging assumptions around how local systems would achieve financial balance—and what that might mean for changes to …
BMJ Awards: nominations open with seven new categories for 2019 BMJ (IF 23.259) Pub Date : 2018-10-19 Susan Mayor
Nominations opened on 22 October for The BMJ Awards 2019, celebrating outstanding achievement in medicine.Doctors have until Friday 18 January 2019 to put themselves—or colleagues—forward in 15 categories across a range of specialties in the UK’s leading medical awards. They aim to recognise the inspirational work of healthcare teams across the country and promote excellence in healthcare.The award winners will be announced at a glittering ceremony on Wednesday 24 April 2019 after a rigorous judging process in which shortlisted teams …
NEJM retracts article from former researcher once hailed as heart stem cell pioneer BMJ (IF 23.259) Pub Date : 2018-10-19 Owen Dyer
The New England Journal of Medicine has retracted one paper1 and issued an “expression of concern” about two others2 within days of Harvard Medical School and Brigham and Women’s Hospital announcing that they had asked various journals to retract 31 papers from a laboratory once hailed for pioneering stem cell research but now discredited by findings of research misconduct.The articles came from the laboratory of Piero Anversa, who came to prominence when he appeared to produce evidence for his long standing contention that science had underestimated the heart’s capacity for self repair.In its retraction notice, NEJM said that several of Anversa’s coauthors asked the journal to retract the 2011 study Evidence for human lung stem cells.The unnamed authors wrote to tell NEJM that a review by Harvard …
Steroid injection or wrist splint for first-time carpal tunnel syndrome? Lancet (IF 53.254) Pub Date : 2018-10-20 Isam Atroshi
Ebola: WHO expresses “very serious concern” about Congo outbreak BMJ (IF 23.259) Pub Date : 2018-10-19 Sophie Arie
An outbreak of Ebola virus disease in the Democratic Republic of the Congo is likely to spread to neighbouring countries but is not yet a global public health emergency, a committee of experts decided on 17 October.The committee, convened by the World Health Organization, is “very seriously concerned” about an outbreak that has killed 139 people since it was declared on 1 August, and the situation is “likely to deteriorate significantly” if the international response does not intensify, said the committee chair, Robert Steffen.Fighting among …
MPs call for 10 year social care plan to match the imminent NHS long term plan BMJ (IF 23.259) Pub Date : 2018-10-19 Adrian O'Dowd
The government should produce a 10 year, fully costed plan for social care to run alongside the imminent NHS long term plan due out before the end of the year, say MPs on an influential committee.Despite around 20 years of efforts to ensure closer integration of health and social care, the two areas were still too disparate and lacking in coordination of services, said MPs on the Public Accounts Committee.In a report1 on the interface between health and adult social care, the committee said that the government still lacked an effective overall strategy to achieve effective integration of the two sectors.It was broadly accepted that integration and joint working was the right way forward for the health and social care systems in order to …
Time for a new obesity narrative Lancet (IF 53.254) Pub Date : 2018-10-10 Johanna Ralston, Hannah Brinsden, Kent Buse, Vanessa Candeias, Ian Caterson, Trevor Hassell, Shiriki Kumanyika, Patricia Nece, Sania Nishtar, Ian Patton, Joseph Proietto, Ximena Ramos Salas, Srinath Reddy, Donna Ryan, Arya M Sharma, Boyd Swinburn, John Wilding, Euan Woodward
Brexit: hospitals told to identify contracts that could be affected by “no deal” BMJ (IF 23.259) Pub Date : 2018-10-19 Gareth Iacobucci
The UK government has told NHS hospitals in England to draw up a list of all contracts that could be affected in the event of the UK failing to negotiate a deal to exit from the European Union.In a letter to all NHS trust chief executives and heads of procurement on 12 October, the health and social care secretary for England, Matt Hancock, instructed all hospitals to provide the department with a list of contracts where the supply chain was …
MPs slam “outrageous” 25% uptake of flu vaccine among social care staff BMJ (IF 23.259) Pub Date : 2018-10-19 Jacqui Thornton
MPs have criticised the low uptake of flu vaccination among staff in social care settings, putting it at best around 25%, far lower than the rate among frontline NHS staff.1The House of Commons Science and Technology Committee carried out an inquiry into uptake after the high burden of flu seen in 2017-18, high numbers of hospital admissions, and evidence of variable uptake of the flu vaccine.In March 2018 the committee held a one-off oral evidence session on the flu vaccination programme and heard from Public Health England, …
Doctors need to improve their conversations with dying patients, says RCP BMJ (IF 23.259) Pub Date : 2018-10-19 Adrian O’Dowd
Doctors need to speak to patients with terminal illnesses in a timelier way and handle conversations with greater compassion and confidence, says a report from the Royal College of Physicians.1The report, which examined why clinicians find it difficult to talk to patients about death, found that some doctors thought that death could be perceived as a failure and that modern medicine was expected to cure all ailments. However, evidence from patients and carers indicated that many people wanted to talk about death and that planning helped them feel more empowered about their care and decision making.Almost half of all deaths in the UK are estimated to occur in hospital, and many patients admitted to hospital are in their last year of life. The college said it believed it was essential for doctors and other professionals to have the knowledge and skills to undertake sensitive conversations at an appropriate time when patients were ready.The report was based on conversations with doctors at all levels, patients and carers, and medical organisations.A range of clinicians from medical students to consultants said that they were uncomfortable about initiating conversations about the future with patients. Students and junior doctors had little practice with real patients and said that training did not prioritise the “soft” skills they needed.Other barriers to talking about death included confusion over whether hospital doctors or GPs should be having the conversation, workforce pressures, lack of privacy, lack of prioritised time for conversations, and the need to be sensitive to different cultural and religious beliefs.One key issue identified by the report was that healthcare professionals needed to begin conversations about planning for care at the end of life care nearer to when patients are given a terminal diagnosis. Early conversations give patients more choice and control over the remainder of their lives.The evidence showed that patients who had these conversations and had care plans put in place had a better experience than those for whom the conversations came in the final days or hours of life.The authors offer solutions and resources to help build clinicians’ compassion and confidence in this area of care and detail four case studies of hospitals that lead the way in supporting conversations about care at the end of life. The report highlighted the University Hospitals Bristol supportive and palliative care team for its Poor Prognosis Letter Project, a scheme that has enabled local GPs to identify patients approaching death more easily and earlier, so they can start discussing end of life care.The Royal College of Physicians’ president, Andrew Goddard, said, “This report is a big step forward in helping patients, relatives, and doctors to talk honestly about death and dying.“We must minimise the barriers in our systems and culture that prevent this happening. This is not just about palliative care in the final days but about having a series of conversations much earlier after a terminal diagnosis.”
Yelzhan Birtanov: leading Kazakhstan to universal health coverage Lancet (IF 53.254) Pub Date : 2018-10-20 Richard Lane
Cannabis: Canada sees queues and shortages as it legalises recreational use BMJ (IF 23.259) Pub Date : 2018-10-18 Owen Dyer
On 17 October Canada became the second country to legalise the possession, consumption, and licensed sale of cannabis, after Uruguay.Legalisation is a typically Canadian patchwork quilt, as each of 10 provinces and three territories has made its own arrangements for the sale and regulation of cannabis. In Ontario you may smoke it in public wherever tobacco is permitted, but in Manitoba this will incur a C$672 (£394; €449; US$515) fine. In some provinces the minimum age is 18, in others 19, and in Quebec the new government threatens to raise it to 21.In Alberta 17 private retailers have opened. In Quebec long lines formed outside 12 stores operated by a new public monopoly. In Ontario only online sales are permitted through the official Ontario Cannabis Store, but dozens of private stores will open in April. In Saskatchewan shortages of product left many stores unable to open. …
Chinese government fines vaccine company £1bn for string of violations BMJ (IF 23.259) Pub Date : 2018-10-18 Owen Dyer
Chinese authorities have imposed an unprecedented fine of ¥9.1bn (£1bn, €1.14bn) on one of the country’s biggest vaccine makers and removed its permit to produce drugs in an effort to reassure the public, after a defective rabies vaccine set Chinese social media ablaze this summer.1The hashtag #Changsheng vaccine case# was viewed over 470 million times in two weeks in July after news emerged that 15 people had been detained following a surprise inspection of the facilities of Changchun Changsheng Life Sciences. Among them was the company’s chairwoman and owner, Gao Junfang.The government’s action was accompanied by widespread censorship of online and media criticism, the arrest of activists, and apparent intimidation of parents who said their children had suffered vaccine injury.Announcing the fine, China’s National Medical Products Administration (NMPA) said that the company had mixed different vaccine batches then given them fake batch …
Less than half of women are diagnosed with ovarian cancer within a month of seeing a doctor, finds survey BMJ (IF 23.259) Pub Date : 2018-10-18 Susan Mayor
Less than half of women with symptoms that are common in ovarian cancer are diagnosed within one month of first seeing a doctor, a large global survey of women with the disease1 has found. Results also revealed low levels of awareness of the cancer among women and delays in seeking medical help.“This study, for the first time, provides powerful evidence of the challenges faced by women diagnosed with ovarian cancer across the world, and sets an agenda for global change,” said Anwen Jones, chief executive officer of Target Ovarian Cancer in the UK and co-chair of the study, which was funded by …
SHERPA: a new model for clinical decision making in patients with multimorbidity Lancet (IF 53.254) Pub Date : 2018-10-20 Edmund Jack, Neal Maskrey, Richard Byng
Data on how to improve the care of patients with multimorbidity are lacking. Evidence-based medicine and the teaching of consultation skills—two of the cornerstones of modern clinical practice—are not sufficient for making decisions with and for patients with multimorbidity. Therefore, we have developed a new model that supports the translation of population-based, evidence-based medicine and complex consultation models into simpler, natural conversations about care appropriate for and agreed with individual patients.
Margaret McGarrity BMJ (IF 23.259) Pub Date : 2018-10-18 John McGarrity
Margaret McGarrity (née McClymont) admitted she chose to study medicine not to be outdone by her older brothers, Leo and Calum, who were already qualified. Her first house job was doing medicine at Monklands Hospital in Airdrie. It was here that she met John (q Aberdeen 1986).She then moved to do surgery and urology at the Freeman Hospital in Newcastle. After this Margaret did locums in medicine and rheumatology, but soon after marrying John …
Renal replacement therapy: summary of NICE guidance BMJ (IF 23.259) Pub Date : 2018-10-19 James Gilbert, Kate Lovibond, Andrew Mooney, Jan Dudley
Start exploring the options of dialysis, transplantation, or conservative management with patients at least a year before they are likely to need itRecommend patients start dialysis at an estimated glomerular filtration rate (eGFR) of 5-7 mL/min/1.73 m2 or sooner if symptoms of their chronic kidney disease are affecting their daily lifeHaemodiafiltration is a form of haemodialysis with additional convection and is more effective than standard haemodialysis with a similar patient experienceTransplantation has better outcomes than any form of dialysis, with pre-emptive transplantation being more effective than transplantation after dialysisPatients should not be excluded from receiving a kidney transplant based on body mass index aloneApproximately 8000 people a year start renal replacement therapy in the UK.1 Box 1 describes the options available for people approaching the need for renal replacement therapy. Around 60 000 people are currently living with a kidney transplant or are receiving dialysis. Transplant is the most common form of renal replacement therapy (approximately 54% of prevalent renal replacement therapy patients), followed by haemodialysis (40%), and then peritoneal dialysis (6%).1 The number of new transplants was around 3000 in 2016; this has gradually increased more recently. Some people will receive a kidney from a living donor, but those who have to join the waiting list for a kidney donation can expect to wait for 2.5-3 years.2 Among those receiving dialysis, most people opt for haemodialysis or haemodiafiltration done at hospital or in a satellite centre rather than at home.Renal replacement therapy comprises either transplantation or dialysis. Some people decide not to receive renal replacement therapy but choose conservative management, which comprises full supportive management (including advance care planning and control of symptoms and complications).Can be from living or deceased donorsCan be done pre-emptively (before the point at which dialysis …
Cystic fibrosis: triple drug regimens that target defective ion channel improve lung function, studies show BMJ (IF 23.259) Pub Date : 2018-10-19 Susan Mayor
Triple drug combinations that improve the activity of the cystic fibrosis transmembrane conductance regulator (CFTR), the anion channel that is defective or deficient in the condition, significantly improve lung function in patients with cystic fibrosis who have the most common CFTR gene mutations, two early stage randomised trials have reported.12“These reports represent a major breakthrough in cystic fibrosis therapeutics, with the potential for improving health and possibly survival in all patients who carry the most common CFTR mutation,” said Fernando Holguin of the University of Colorado in Aurora, USA, in an accompanying editorial.3Both trials evaluated the efficacy and safety of one of two new generation, small molecule CFTR correctors, VX-659 and VX-445. These compounds …
Partnerships with the alcohol industry: opportunities and risks Lancet (IF 53.254) Pub Date : 2018-09-20 John N Newton, Paul Cosford
Notions from Kavanaugh hearings contradict medical facts Lancet (IF 53.254) Pub Date : 2018-10-05 Homer Venters
Survivors of sexual abuse around the world are reeling from the horrifying and compelling details emerging from the Senate Judiciary Committee confirmation hearings of Judge Brett Kavanaugh. What has shocked me most, as a health professional, is the harmful and untrue narrative that has surfaced during the hearings: the idea that the incomplete memory of an assault, or a delay in reporting abuse, reflects on the truth of the abuse itself. Physicians for Human Rights has trained thousands of health-care professionals across the globe to evaluate survivors of abuse, from the USA to Kenya and the Democratic Republic of the Congo, to the former Yugoslavia, and to Iraq. Through our work, we know that this rationale is fundamentally flawed and blatantly untrue.
Department of Error Lancet (IF 53.254) Pub Date : 2018-10-20
Powles T, Durán I, van der Heijden M, et al. Atezolizumab versus chemotherapy in patients with platinum-treated locally advanced or metastatic urothelial carcinoma (IMvigor211): a multicentre, open-label, phase 3 randomised controlled trial. Lancet 2018; 391: 748–57—In the Results section of this Article, in the sentence that reads “For patients receiving chemotherapy, vinflunine outperformed study expectations; unstratified HRs were 0·95 (95% CI 0·62–1·45) and 0·69 (0·44–1·10) in subgroups based on chemotherapy stratification with vinflunine (n=106) and taxanes (n=128), respectively”, the totals for vinflunine and taxanes are the wrong way around. The sentence should read “For patients receiving chemotherapy, vinflunine outperformed study expectations; unstratified HRs were 0·95 (95% CI 0·62–1·45) and 0·69 (0·44–1·10) in subgroups based on chemotherapy stratification with vinflunine (n=128) and taxanes (n=106), respectively.” These corrections have been made to the online version as of Oct 18, 2018.
Department of Error Lancet (IF 53.254) Pub Date : 2018-10-20
Gupta A, Mackay J, Whitehouse A, et al. Long-term mortality after blood pressure-lowering and lipid-lowering treatment in patients with hypertension in the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) Legacy study: 16-year follow-up results of a randomised factorial trial. Lancet 2018; 392: 1127–37—In this Article, the fourth sentence of the findings section of the summary has been corrected to read “there was no overall difference in cardiovascular mortality between treatments”. This correction has been made to the online version as of Oct 18, 2018.
Efficacy and cost-effectiveness of nurse-led care involving education and engagement of patients and a treat-to-target urate-lowering strategy versus usual care for gout: a randomised controlled trial Lancet (IF 53.254) Pub Date : 2018-10-20 Michael Doherty, Wendy Jenkins, Helen Richardson, Aliya Sarmanova, Abhishek Abhishek, Deborah Ashton, Christine Barclay, Sally Doherty, Lelia Duley, Rachael Hatton, Frances Rees, Matthew Stevenson, Weiya Zhang
Population effectiveness of opportunistic chlamydia testing in primary care in Australia: a cluster-randomised controlled trial Lancet (IF 53.254) Pub Date : 2018-10-20 Jane S Hocking, Meredith Temple-Smith, Rebecca Guy, Basil Donovan, Sabine Braat, Matthew Law, Jane Gunn, David Regan, Alaina Vaisey, Liliana Bulfone, John Kaldor, Christopher K Fairley, Nicola Low
The clinical and cost-effectiveness of corticosteroid injection versus night splints for carpal tunnel syndrome (INSTINCTS trial): an open-label, parallel group, randomised controlled trial Lancet (IF 53.254) Pub Date : 2018-10-20 Linda S Chesterton, Milica Blagojevic-Bucknall, Claire Burton, Krysia S Dziedzic, Graham Davenport, Sue M Jowett, Helen L Myers, Raymond Oppong, Trishna Rathod-Mistry, Danielle A van der Windt, Elaine M Hay, Edward Roddy
External left atrium compression by spinal osteophytes Lancet (IF 53.254) Pub Date : 2018-10-20 Hourmazd Haghbayan, Eric A Coomes, Asim N Cheema
Alma-Ata at 40 years: reflections from the Lancet Commission on Investing in Health Lancet (IF 53.254) Pub Date : 2018-10-20 David A Watkins, Gavin Yamey, Marco Schäferhoff, Olusoji Adeyi, George Alleyne, Ala Alwan, Seth Berkley, Richard Feachem, Julio Frenk, Gargee Ghosh, Sue J Goldie, Yan Guo, Sanjeev Gupta, Felicia Knaul, Margaret Kruk, Rachel Nugent, Osondu Ogbuoji, Jinyuan Qi, Srinath Reddy, Helen Saxenian, Agnés Soucat, Dean T Jamison, Lawrence H Summers
Revisiting Alma-Ata: what is the role of primary health care in achieving the Sustainable Development Goals? Lancet (IF 53.254) Pub Date : 2018-10-20 Thomas Hone, James Macinko, Christopher Millett
Effectiveness and sustainability of a diagonal investment approach to strengthen the primary health-care system in Ethiopia Lancet (IF 53.254) Pub Date : 2018-10-20 Yibeltal Assefa, Dessalegn Tesfaye, Wim Van Damme, Peter S Hill
Building the case for embedding global health security into universal health coverage: a proposal for a unified health system that includes public health Lancet (IF 53.254) Pub Date : 2018-10-20 Ngozi A Erondu, Jerry Martin, Robert Marten, Gorik Ooms, Robert Yates, David L Heymann
In the wake of the recent west African Ebola epidemic, there is global consensus on the need for strong health systems; however, agreement is less apparent on effective mechanisms for establishing and maintaining these systems, particularly in resource-constrained settings and in the presence of multiple and sustained stresses (eg, conflict, famine, climate change, and globalisation). The construction of the International Health Regulations (2005) guidelines and the WHO health systems framework, has resulted in the separation of public health functions and health-care services, which are interdependent in actuality and must be integrated to ensure a continuous, unbroken national health system. By analysing efforts to strengthen health systems towards attaining universal health coverage and investments to improve global health security, we examine areas of overlap and offer recommendations for construction of a unified national health system that includes public health. One way towards achieving universal health coverage is to broaden the definition of a health system.
Mixed-effects association of single cells identifies an expanded effector CD4+ T cell subset in rheumatoid arthritis Sci. Transl. Med. (IF 16.71) Pub Date : 2018-10-17 Chamith Y. Fonseka, Deepak A. Rao, Nikola C. Teslovich, Ilya Korsunsky, Susan K. Hannes, Kamil Slowikowski, Michael F. Gurish, Laura T. Donlin, James A. Lederer, Michael E. Weinblatt, Elena M. Massarotti, Jonathan S. Coblyn, Simon M. Helfgott, Derrick J. Todd, Vivian P. Bykerk, Elizabeth W. Karlson, Joerg Ermann, Yvonne C. Lee, Michael B. Brenner, Soumya Raychaudhuri
High-dimensional single-cell analyses have improved the ability to resolve complex mixtures of cells from human disease samples; however, identifying disease-associated cell types or cell states in patient samples remains challenging because of technical and interindividual variation. Here, we present mixed-effects modeling of associations of single cells (MASC), a reverse single-cell association strategy for testing whether case-control status influences the membership of single cells in any of multiple cellular subsets while accounting for technical confounders and biological variation. Applying MASC to mass cytometry analyses of CD4+ T cells from the blood of rheumatoid arthritis (RA) patients and controls revealed a significantly expanded population of CD4+ T cells, identified as CD27− HLA-DR+ effector memory cells, in RA patients (odds ratio, 1.7; P = 1.1 × 10−3). The frequency of CD27− HLA-DR+ cells was similarly elevated in blood samples from a second RA patient cohort, and CD27− HLA-DR+ cell frequency decreased in RA patients who responded to immunosuppressive therapy. Mass cytometry and flow cytometry analyses indicated that CD27− HLA-DR+ cells were associated with RA (meta-analysis P = 2.3 × 10−4). Compared to peripheral blood, synovial fluid and synovial tissue samples from RA patients contained about fivefold higher frequencies of CD27− HLA-DR+ cells, which comprised ~10% of synovial CD4+ T cells. CD27− HLA-DR+ cells expressed a distinctive effector memory transcriptomic program with T helper 1 (TH1)– and cytotoxicity-associated features and produced abundant interferon-γ (IFN-γ) and granzyme A protein upon stimulation. We propose that MASC is a broadly applicable method to identify disease-associated cell populations in high-dimensional single-cell data.
A dysbiotic microbiome triggers TH17 cells to mediate oral mucosal immunopathology in mice and humans Sci. Transl. Med. (IF 16.71) Pub Date : 2018-10-17 Nicolas Dutzan, Tetsuhiro Kajikawa, Loreto Abusleme, Teresa Greenwell-Wild, Carlos E. Zuazo, Tomoko Ikeuchi, Laurie Brenchley, Toshiharu Abe, Charlotte Hurabielle, Daniel Martin, Robert J. Morell, Alexandra F. Freeman, Vanja Lazarevic, Giorgio Trinchieri, Patricia I. Diaz, Steven M. Holland, Yasmine Belkaid, George Hajishengallis, Niki M. Moutsopoulos
Periodontitis is one of the most common human inflammatory diseases, yet the mechanisms that drive immunopathology and could be therapeutically targeted are not well defined. Here, we demonstrate an expansion of resident memory T helper 17 (TH17) cells in human periodontitis. Phenocopying humans, TH17 cells expanded in murine experimental periodontitis through local proliferation. Unlike homeostatic oral TH17 cells, which accumulate in a commensal-independent and interleukin-6 (IL-6)–dependent manner, periodontitis-associated expansion of TH17 cells was dependent on the local dysbiotic microbiome and required both IL-6 and IL-23. TH17 cells and associated neutrophil accumulation were necessary for inflammatory tissue destruction in experimental periodontitis. Genetic or pharmacological inhibition of TH17 cell differentiation conferred protection from immunopathology. Studies in a unique patient population with a genetic defect in TH17 cell differentiation established human relevance for our murine experimental studies. In the oral cavity, human TH17 cell defects were associated with diminished periodontal inflammation and bone loss, despite increased prevalence of recurrent oral fungal infections. Our study highlights distinct functions of TH17 cells in oral immunity and inflammation and paves the way to a new targeted therapeutic approach for the treatment of periodontitis.
Harnessing the immune response to improve functional healing Sci. Transl. Med. (IF 16.71) Pub Date : 2018-10-17 Julianne L. Holloway
Interleukin-4–conjugated gold nanoparticles promote M2 macrophage polarization and functional muscle recovery in an ischemic mouse model.
Health and societal implications of medical and technological advances Sci. Transl. Med. (IF 16.71) Pub Date : 2018-10-17 Victor J. Dzau, Celynne A. Balatbat
Scientific and technological breakthroughs are transforming the future of medicine and health, but they inevitably carry risks and have societal implications that need to be addressed proactively.
Avidity-based binding to HER2 results in selective killing of HER2-overexpressing cells by anti-HER2/CD3 Sci. Transl. Med. (IF 16.71) Pub Date : 2018-10-17 Dionysos Slaga, Diego Ellerman, T. Noelle Lombana, Rajesh Vij, Ji Li, Maria Hristopoulos, Robyn Clark, Jennifer Johnston, Amy Shelton, Elaine Mai, Kapil Gadkar, Amy A. Lo, James T. Koerber, Klara Totpal, Rodney Prell, Genee Lee, Christoph Spiess, Teemu T. Junttila
A primary barrier to the success of T cell–recruiting bispecific antibodies in the treatment of solid tumors is the lack of tumor-specific targets, resulting in on-target off-tumor adverse effects from T cell autoreactivity to target-expressing organs. To overcome this, we developed an anti-HER2/CD3 T cell–dependent bispecific (TDB) antibody that selectively targets HER2-overexpressing tumor cells with high potency, while sparing cells that express low amounts of HER2 found in normal human tissues. Selectivity is based on the avidity of two low-affinity anti-HER2 Fab arms to high target density on HER2-overexpressing cells. The increased selectivity to HER2-overexpressing cells is expected to mitigate the risk of adverse effects and increase the therapeutic index. Results included in this manuscript not only support the clinical development of anti-HER2/CD3 1Fab–immunoglobulin G TDB but also introduce a potentially widely applicable strategy for other T cell–directed therapies. The potential of this discovery has broad applications to further enable consideration of solid tumor targets that were previously limited by on-target, but off-tumor, autoimmunity.
In utero priming of highly functional effector T cell responses to human malaria Sci. Transl. Med. (IF 16.71) Pub Date : 2018-10-17 Pamela M. Odorizzi, Prasanna Jagannathan, Tara I. McIntyre, Rachel Budker, Mary Prahl, Ann Auma, Trevor D. Burt, Felistas Nankya, Mayimuna Nalubega, Esther Sikyomu, Kenneth Musinguzi, Kate Naluwu, Abel Kakuru, Grant Dorsey, Moses R. Kamya, Margaret E. Feeney
Malaria remains a significant cause of morbidity and mortality worldwide, particularly in infants and children. Some studies have reported that exposure to malaria antigens in utero results in the development of tolerance, which could contribute to poor immunity to malaria in early life. However, the effector T cell response to pathogen-derived antigens encountered in utero, including malaria, has not been well characterized. Here, we assessed the frequency, phenotype, and function of cord blood T cells from Ugandan infants born to mothers with and without placental malaria. We found that infants born to mothers with active placental malaria had elevated frequencies of proliferating effector memory fetal CD4+ T cells and higher frequencies of CD4+ and CD8+ T cells that produced inflammatory cytokines. Fetal CD4+ and CD8+ T cells from placental malaria–exposed infants exhibited greater in vitro proliferation to malaria antigens. Malaria-specific CD4+ T cell proliferation correlated with prospective protection from malaria during childhood. These data demonstrate that placental malaria is associated with the generation of proinflammatory malaria-responsive fetal T cells. These findings add to our current understanding of fetal immunity and indicate that a functional and protective pathogen-specific T cell response can be generated in utero.
To Prevent Cardiovascular Disease, Pay Attention to Pregnancy Complications JAMA (IF 47.661) Pub Date : 2018-10-17 Jennifer Abbasi
The Supreme Court’s Crisis Pregnancy Center Case — Implications for Health Law N. Engl. J. Med. (IF 79.258) Pub Date : 2018-10-18 Wendy E. Parmet; Micah L. Berman; Jason A. Smith
States frequently compel health professionals and commercial entities to disclose information relevant to patient or consumer decision making. For many years, such laws were presumed to be constitutional, despite the First Amendment’s protection of free speech. But after the Supreme Court’s decision in National Institute of Family and Life Advocates v. Becerra (NIFLA) in late June 2018,1 the status of such laws is an open question.
Abortion “Reversal” — Legislating without Evidence N. Engl. J. Med. (IF 79.258) Pub Date : 2018-10-18 Daniel Grossman; Kari White
Women up to 10 weeks pregnant who are having a medication abortion generally take one dose of mifepristone, which blocks the progesterone receptor, followed within 48 hours by a dose of misoprostol, a prostaglandin that causes cervical dilation and uterine contractions, leading to expulsion of the pregnancy tissue. Four states (Arkansas, Idaho, South Dakota, and Utah) require abortion providers to tell their patients about treatment that may reverse the effect of mifepristone if they change their mind after starting a medication abortion. So-called abortion reversal involves administering repeated doses of progesterone. Since 2017, other states have proposed similar bills and the California Board of Registered Nursing approved a course on medication-abortion reversal for continuing-education credit. This trend is troubling because of the lack of medical evidence demonstrating the safety and efficacy of the treatment; laws promoting it essentially encourage women to participate in an unmonitored research experiment.
Extensively Drug-Resistant Typhoid — Are Conjugate Vaccines Arriving Just in Time? N. Engl. J. Med. (IF 79.258) Pub Date : 2018-10-18 Jason R. Andrews; Farah N. Qamar; Richelle C. Charles; Edward T. Ryan
In Hyderabad, Pakistan, an outbreak of extensively drug-resistant (XDR) Salmonella enterica ssp. enterica serovar Typhi, resistant to chloramphenicol, ampicillin, trimethoprim–sulfamethoxazole, fluoroquinolones, and third-generation cephalosporins, was recognized in November 2016 and has now spread to Karachi, home to more than 14 million people. More than 1000 cases have been confirmed by blood culture; since most typhoid cases are treated empirically, however, the true number of cases is probably many times greater. The outbreak is being caused by the H58 clade, a multidrug-resistant haplotype of S. Typhi that is common in Asia and areas of Africa. The H58 S. Typhi involved in the outbreak contains a chromosomally integrated antimicrobial-resistance cassette imparting resistance to chloramphenicol, ampicillin, and trimethoprim–sulfamethoxazole, and the XDR variant also contains an IncY plasmid that carries not only the fluoroquinolone-resistance gene qnrS but also the CTX-M-15 gene bla that mediates resistance to ceftriaxone.1 S. Typhi already causes invasive disease in 12 million to 22 million people each year, many of whom live in South and Southeast Asia, and the emergence of an XDR variant in this densely populated area is extremely worrisome.2
Some contents have been Reproduced by permission of The Royal Society of Chemistry.
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