当前期刊: "热门"类期刊
显示样式:        排序: 导出
我的关注
我的收藏
您暂时未登录!
登录
  • The Use and Misuse of Transparency in Research: Science and Rulemaking at the Environmental Protection Agency
    JAMA (IF 51.273) Pub Date : 2020-01-23
    Harvey V. Fineberg; David B. Allison

    Transparency in science is a laudable goal. By describing with sufficient clarity, detail, and completeness the methods they use, and by making available the raw data that underlie their analyses, scientists can help ensure the reproducibility of their results and thus increase the trustworthiness of their findings and conclusions. At the same time, transparency is not in an of itself a definitive standard for the usefulness of science in policy making. A proposed rule at the Environmental Protection Agency (EPA), “Strengthening Transparency in Regulatory Science,”1 goes too far in barring from pivotal consideration in regulations any scientific study that does not have all data and analytic models made publicly available, unless special dispensations are granted. In particular, epidemiological and clinical studies that are designed to protect the confidentiality of personal health information may be highly germane to establishing environmental standards yet ethically barred from making all data publicly available. Other studies may rely on proprietary information, and their main findings may have been replicated in independent, proprietary studies, yet under the proposed rule, such studies similarly could not be relied on as a basis for regulation. The proposed rule provoked hundreds of thousands of comments and also was the subject of a recent congressional hearing.2 While sometimes falling short in its use of science,3 the EPA has traditionally strived to base regulations on the best available scientific evidence. For example, in 1997 the EPA adopted new air pollution regulations based mainly on 2 large epidemiological studies. The Harvard Six Cities study had begun in the 1970s to monitor the health of more than 8000 adults and children in 6 cities over 15 years while simultaneously tracking levels of air pollution, mainly related to burning of fossil fuels to generate electricity. Published in December 1993, the study found a strong gradient of mortality associated with increasing levels of airborne small particulates (diameter <2.5 μm).4 A second, independent study by the American Cancer Society followed 500 000 people in 154 cities for 8 years and reached similar conclusions in 1995.5

    更新日期:2020-01-23
  • Improving the Residency Application and Selection Process: An Optional Early Result Acceptance Program
    JAMA (IF 51.273) Pub Date : 2020-01-23
    Maya M. Hammoud; John Andrews; Susan E. Skochelak

    The process of securing a residency position following medical school has become increasingly arduous and complicated. The mean number of applications per applicant for US and Canadian medical school graduates has increased across all specialties in the last decade, with several specialties seeing a doubling in number of applications. For instance, from 2011 to 2019, applications per applicant increased from 15.2 to 34.8 for family medicine, from 30.5 to 61.3 for obstetrics and gynecology, and from 21.6 to 51.9 for psychiatry.1 Similarly, the number of applications received by each program also has increased across all specialties, some by more than 200%. For example, from 2011 to 2019, the mean number of applications received by family medicine programs increased from 76 to 251 and received by psychiatry programs increased from 115 to 446.1 A cycle involving increased numbers of applications and increased reliance on standardized testing has resulted in behavioral changes in both applicants and residency programs. Currently, senior medical students spend large amounts of time and money during the last year of medical school applying to an increasing number of programs and meeting the demands of the residency application process. Yet, in 2019, even though the ratio of first-year positions available per active US senior medical student was 1.7 (32 194 positions offered to 18 925 US applicants), the highest on record, the percentage of all US senior medical students who matched to their first-choice programs was 47.1%, the lowest on record (down from 52.6% in 2011). Furthermore, 5.8% of students did not match, an increase from 5.2% in 2011, and more than 20% of students matched to a program they ranked fourth or lower on their list.2 Meanwhile, to process the high volume of applications received, programs are likely relying more on quantitative metrics, such as United States Medical Licensing Examination (USMLE) Step 1 scores, for screening. Results of the 2018 National Resident Matching Program’s Program Director Survey showed that 94% of residency programs cited the USMLE Step 1 score/COMLEX Level 1 score as an important factor in selecting applicants to interview, an increase from 73% in 2012.3 Moreover, some programs report using minimum USMLE Step 1 scores when screening applications in an effort to reduce the number of applications to be reviewed. For example, 83% (89 of 107) of the 151 orthopedic surgery programs that responded to a survey reported use of a USMLE Step 1 minimum score when screening applications, and 53% of programs reported requiring a score greater than 230.4 Whether this is true for all applicants, or some, is unknown.

    更新日期:2020-01-23
  • Coronavirus Infections—More Than Just the Common Cold
    JAMA (IF 51.273) Pub Date : 2020-01-23
    Catharine I. Paules; Hilary D. Marston; Anthony S. Fauci

    Human coronaviruses (HCoVs) have long been considered inconsequential pathogens, causing the “common cold” in otherwise healthy people. However, in the 21st century, 2 highly pathogenic HCoVs—severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV)—emerged from animal reservoirs to cause global epidemics with alarming morbidity and mortality. In December 2019, yet another pathogenic HCoV, 2019 novel coronavirus (2019-nCoV), was recognized in Wuhan, China, and has caused serious illness and death. The ultimate scope and effect of this outbreak is unclear at present as the situation is rapidly evolving. Coronaviruses are large, enveloped, positive-strand RNA viruses that can be divided into 4 genera: alpha, beta, delta, and gamma, of which alpha and beta CoVs are known to infect humans.1 Four HCoVs (HCoV 229E, NL63, OC43, and HKU1) are endemic globally and account for 10% to 30% of upper respiratory tract infections in adults. Coronaviruses are ecologically diverse with the greatest variety seen in bats, suggesting that they are the reservoirs for many of these viruses.2 Peridomestic mammals may serve as intermediate hosts, facilitating recombination and mutation events with expansion of genetic diversity. The surface spike (S) glycoprotein is critical for binding of host cell receptors and is believed to represent a key determinant of host range restriction.1 Until recently, HCoVs received relatively little attention due to their mild phenotypes in humans. This changed in 2002, when cases of severe atypical pneumonia were described in Guangdong Province, China, causing worldwide concern as disease spread via international travel to more than 2 dozen countries.2 The new disease became known as severe acute respiratory syndrome (SARS), and a beta-HCoV, named SARS-CoV, was identified as the causative agent. Because early cases shared a history of human-animal contact at live game markets, zoonotic transmission of the virus was strongly suspected.3 Palm civets and raccoon dogs were initially thought to be the animal reservoir(s); however, as more viral sequence data became available, consensus emerged that bats were the natural hosts.

    更新日期:2020-01-23
  • Blinding may be unnecessary, but please divest
    BMJ (IF 27.604) Pub Date : 2020-01-23
    Fiona Godlee

    In the hierarchy of evidence, randomised trials are near the top, trumped only by meta-analysis of such trials, with blinding of patients and clinicians firmly established as being key to their validity. But new research published in The BMJ this week casts doubt on the benefits of blinding. Helene Moustgaard and colleagues have meta-analysed 142 Cochrane meta-analyses, incorporating 1153 randomised trials. They conclude that there’s no evidence that a lack of blinding leads to exaggerated estimates of treatment effects (doi:10.1136/bmj.l6802). This apparent lack of benefit should be seen in the …

    更新日期:2020-01-23
  • Investing in humanity: The BMJ’s divestment campaign
    BMJ (IF 27.604) Pub Date : 2020-01-23
    Kamran Abbasi; Fiona Godlee

    Health professionals and medical organisations must act now How do we restore hope for humanity? Many of us feel despair at a disintegrating political consensus to save our planet from fire, flood, disease, and conflict. We feel trapped in our high carbon lives and disempowered by commercial influence of companies whose products damage the planet and people’s wellbeing. Evidence for the effects of the politico-commercial complex is clear and alarming.1 On our current trajectory we will miss carbon emission targets and sustainable development goals, both agreed by international consensus.2 Populist politicians rubbish science confirming the harmful effects of climate change. Big business obfuscates, distorts, and denies evidence for the adverse effects of its products. When future historians, if such a future exists, look back on our stewardship of Planet Earth, what will be their judgment? That we allowed politics and profits to harm our home planet and ourselves? Health professionals and medical organisations should not accept the world as it is. This is not a matter of playing party politics or anticorporate posturing. Taking action is a duty to the people we serve and to future generations. And we can act: by divesting from health harming industries. Divestment offers health professionals and medical organisations, for the duty is both individual and collective, an opportunity to influence politicians and industry towards behaviours that are better for the planet and people’s health (box 1). Box 1 ### What do we mean by divestment for health? Divestment is the opposite of investment. It is the reduction or, as in this case, the complete removal of stocks, bonds, or investment funds that are unethical because of the harm to health.RETURN TO TEXT The case for divestment from the tobacco industry is established. Tobacco products are harmful, and the industry’s history of manipulating science on the effects of tobacco …

    更新日期:2020-01-23
  • Better health and wellbeing for all
    BMJ (IF 27.604) Pub Date : 2020-01-23
    David J Hunter; Richard Alderslade

    The challenges facing new WHO leadership in Europe The imminent change of leadership at the top of the World Health Organization’s European region gives member states an important opportunity to extend policy making on health and wellbeing for all. Hans Kluge takes over as European regional director from Zsuzsanna Jakab in early February, having been elected last September by a large majority of member states. This makes it an opportune time to take stock and consider what has been achieved and what more needs to be done under new leadership. Health has improved across the WHO European region, but not everywhere and not equally. For example, life expectancy varies between 70 and 83.1 years across countries.1 The region faces many challenges, including a high burden of non-communicable diseases; the increasing prevalence of mental health problems; health effects of climate change; inequitable access to, and affordability of, care and medicines; increasing migration; shortages of healthcare workers; and poor progress in realising the opportunities in digital health. Dealing with these challenges requires …

    更新日期:2020-01-23
  • Syncope in a young woman
    BMJ (IF 27.604) Pub Date : 2020-01-23
    Krishna Kumar Mohanan Nair; Narayanan Namboodiri; Ajitkumar Valaparambil

    A previously well and active 25 year old woman with no underlying structural heart disease presented with recurrent episodes of new onset syncope over a period of six hours. Her pulse was irregularly irregular at a rate of 230 beats/min. She was hypotensive with a blood pressure of 80/60 mm Hg. Twelve lead surface electrocardiogram (ECG) taken on admission is shown in fig 1. She was immediately electrically cardioverted to sinus rhythm with 150 J. She reported no history of recreational drug use or family history of sudden cardiac death. Surface electrocardiogram during …

    更新日期:2020-01-23
  • When medical information comes from Nazi atrocities
    BMJ (IF 27.604) Pub Date : 2020-01-23
    Susan Mackinnon

    The nerve surgeon Susan Mackinnon discovered that an old but precise textbook she relied on was created by a Viennese anatomist who had dissected Hitler’s victims to produce his detailed illustrations. Should we still be using the illustrations, she asks I first met the Atlas of Topographical and Applied Human Anatomy1 in 1982, when I was 32, during my hand fellowship at the Curtis National Hand Center in Baltimore and later at the University of Toronto. The atlas became my dissection partner during the many long hours spent in the anatomy laboratory at Johns Hopkins Hospital. For several years, I knew the Pernkopf atlas (named after its author, Eduard Pernkopf, chair of anatomy and president of the University of Vienna) only as a unique and valued piece of science and art. However, in the late 1980s, I came across essays by Gerald Weissman, an Austrian born US physician-scientist at New York University, and David Williams, a medical illustrator of Purdue University, Indiana, exposing the origin of my dissection partner,23 calling it the “atlas of the Shoah,” derived during the Holocaust. Once I, a gentile, came to know the truth of its origin, my attitude changed. I secured the atlas in my operative room locker, with printed copies of Weissman’s and Williams’s essays slipped into the atlas as a marker to anyone who might use it and a warning to “enter with caution.” However, having already spent many years with the atlas, still the most detailed anatomy book I’ve ever seen, I continued to feel the need to refer to it occasionally for the sake of improving my patients’ surgical outcomes. Several times a month, while operating, I would struggle with the anatomical nuances of nerve pathways. The atlas showed me the way—an exact and safe surgical approach to the …

    更新日期:2020-01-23
  • Value of kindness: “I went to the doctor and he didn’t even look at me”
    BMJ (IF 27.604) Pub Date : 2020-01-23
    Sebastian Kraemer

    The title of Klaber and Bailey’s editorial, Kindness: an underrated currency, conceals a greater wisdom embedded in the text—namely, the promotion in medical practice of “relationships, connections, challenge, and trust” and “gentle honesty in discussions.” …

    更新日期:2020-01-23
  • Kindness: “Hello, my name is” badges have helped
    BMJ (IF 27.604) Pub Date : 2020-01-23
    Samuel E Mercer

    I agree with Klaber and Bailey that we should all try to be more kind to each other.1 How one achieves that in …

    更新日期:2020-01-23
  • Scurvy in children . . . and other stories
    BMJ (IF 27.604) Pub Date : 2020-01-23
    British Medical Journal Publishing Group

    Scurvy once occurred in seafarers and long distance travellers. Currently, the most vulnerable group seems to be children with autism or developmental delay who will eat only highly selective diets. Ten children seen at a rheumatology clinic in North America had been referred because of pain and difficulty in walking and weight bearing (J Pediatr doi:10.1016/j.jpeds.2019.10.059). Before the correct diagnosis was made, conditions such as juvenile arthritis, osteomyelitis, and vasculitis were considered and investigated. All responded quickly to vitamin C supplements. In rich countries, obesity is commonest among poorer people, while overweight …

    更新日期:2020-01-23
  • An unexpected side effect of gardening
    BMJ (IF 27.604) Pub Date : 2020-01-23
    Faraz Ali; AA Mughal

    This is a picture of phytophotodermatitis (fig 1). The patient was a 50 year old man with three days of erythematous blistering across …

    更新日期:2020-01-23
  • Half of patients with acute aortic dissection in England die before reaching a specialist centre
    BMJ (IF 27.604) Pub Date : 2020-01-23
    Elisabeth Mahase

    Around 20% of patients with acute aortic dissection die before reaching any hospital and 50% die before reaching a specialist centre, according to an investigation by the Healthcare Safety Investigation Branch.1 The report on delayed recognition of acute aortic dissection analysed hospital activity and other national datasets, and found that it may occur in around 4.5 per 100 000 of the population per year, equal to around 2500 cases per year in England. It showed that a delay in diagnosis occurs in around 16-40% of cases and is more likely if patients walk in to the hospital or if doctors initially suspect that there is a cardiac cause for chest pain. The report said hospitals in England …

    更新日期:2020-01-23
  • Poverty status is linked to worse quality of care
    BMJ (IF 27.604) Pub Date : 2020-01-23
    Adrian O'Dowd

    People living in England’s most deprived areas of England seem to receive the worst quality of healthcare across various types of service, concludes new research from health experts.1 Examples of inequality included spending longer in hospital accident and emergency departments and having worse experiences when making GP appointments. The research from QualityWatch, a joint programme of the health think tanks the Nuffield Trust and the Health Foundation, involved looking at 23 measures of healthcare quality to see how these were affected by deprivation. The measures included avoidable mortality rate, smoking prevalence, emergency admissions for various types of care, obesity prevalence in children, infant mortality rate, experience of making a GP appointment and …

    更新日期:2020-01-23
  • Europe’s drug regulator wins court backing for data transparency policy
    BMJ (IF 27.604) Pub Date : 2020-01-23
    Clare Dyer

    The European Union’s highest court has decisively upheld the European Medicines Agency’s right to publish clinical trial data from drug companies’ applications to market their products in the EU. In two keenly awaited judgments, the European Court of Justice has comprehensively rejected appeals by two companies against rulings in 2018 by the General Court of the European Union upholding the European Medicines Agency’s open data policy.12 In 2010 the agency adopted a policy of making available all documents underlying a successful drug licence application from January 2014, setting aside its previous presumption of confidentiality. But the move was resisted by pharmaceutical companies, which mounted legal challenges, arguing that their commercial confidentiality was at risk. Now the European Court …

    更新日期:2020-01-23
  • Running for deputy leader of the Labour Party: five minutes with . . . Rosena Allin-Khan
    BMJ (IF 27.604) Pub Date : 2020-01-23
    Elisabeth Mahase

    The emergency department doctor and Tooting MP tells Elisabeth Mahase about her priorities as a politician “I’m a doctor first. I didn’t become an MP to stop being a doctor. Working shifts in the emergency department also helps me form coherent evidence based arguments. I see the effects of austerity every time I do a shift, and I can talk about that with real legitimacy. An emergency waiting room is like a microcosm of society. When I’m working, I can see the impact of cuts not …

    更新日期:2020-01-23
  • CQC to reinspect dozens of care homes after uncovering “duplicate material” in reports
    BMJ (IF 27.604) Pub Date : 2020-01-23
    Gareth Iacobucci

    The Care Quality Commission (CQC) is to carry out dozens of reinspections of care and nursing homes after an internal audit revealed that inspection reports contained “duplicate material.” The regulator found evidence of duplication in 108 reports. Some 68 care homes will now be reinspected. The remaining 40 reports will …

    更新日期:2020-01-23
  • Babylon Health holds talks with “significant” number of NHS trusts
    BMJ (IF 27.604) Pub Date : 2020-01-23
    Gareth Iacobucci

    The digital provider Babylon Health is in talks with a “significant number” of hospital trusts in England as it seeks to expand its service in the NHS, the company has told The BMJ. Babylon’s managing director for NHS services, Paul Bate, said that the company wanted to spearhead a “fundamental transformation” in the way people accessed healthcare. His comments came as Babylon announced a major 10 year partnership with Royal Wolverhampton NHS Trust, a large acute and community provider that also runs 10 general practices, to deliver joined-up digital care to the city’s population. The service, which is expected to go live later this year, will allow patients …

    更新日期:2020-01-23
  • Seven days in medicine: 15-21 Jan 2020
    BMJ (IF 27.604) Pub Date : 2020-01-23
    British Medical Journal Publishing Group

    Only 41% of clinical trials reported their results to the US clinical trials registry within a year of completion as required by law, a study found. Researchers from Oxford University, UK, who identified 2497 clinical trials that had breached the rules, called for better enforcement from the US Food and Drug Administration. The FDA Amendments Act 2007 requires trial sponsors to report results directly to ClinicalTrials.gov within one year of completion, whether results are positive or negative. Medical leaders in the UK warned that doctors and patients were being placed at risk after an NHS hospital encouraged doctors to discharge patients early because of a lack of beds. In an internal email to senior clinicians the Royal Cornwall Hospitals Trust had said that it was considering discharging patients “earlier than some clinicians would like” because of “significant pressure” on services. Chaand Nagpaul, BMA council chair, said that the BMA was writing to the trust and the General Medical Council to express “serious concerns.” (Full story doi:10.1136/bmj.m164) Cancer-causing HPV 16 and 18 infections are now extremely uncommon in young sexually active women in England after the introduction of human papillomavirus (HPV) vaccination in 2008, said Public Health England. The infections were found in under 2% of women aged 16-18 in 2014-18, down from 15% in 2008. HPV …

    更新日期:2020-01-23
  • Yeshi Dhonden: personal physician to the 14th Dalai Lama
    BMJ (IF 27.604) Pub Date : 2020-01-23
    Rebecca Wallersteiner

    Yeshi Dhonden, the foremost Tibetan doctor in the world, has died from respiratory failure at his residence in Dharamsala, northern India, surrounded by his family. He was born in Namrao village, in Tibet, into a farming family. He entered monastic life when he was 6 years old and took novice vows as a Buddhist monk two years later. When he was 11, he joined the Chakpori Institute of Tibetan Medicine, where he studied for nine years and displayed impressive skills during the study of the four tantra. One of his teachers was his uncle, the famous Tibetan doctor and teacher Khenrab Norbu. At 20, Dhonden was recognised as the best in his class. He passed his exams with distinction and was made an honorary doctor of the 14th Dalai Lama. From 1951 onwards, he practised medicine in Tibet in his native region, where he became renowned for his skill as a physician after he managed an influenza epidemic. He became the foremost expert in Sowa-Rigpa, the Tibetan herbal medicinal system that combines the ancient healing systems of India and China, practised for thousands of years in Tibet. In 1959 he chose to accompany the Dalai Lama into exile in India, when he fled the Chinese invasion of Tibet. In 1961, when the Dalai Lama re-established the Men-Tsee-Khang, the Tibetan Medical and Astro-Science Institute, …

    更新日期:2020-01-23
  • Duchenne muscular dystrophy
    BMJ (IF 27.604) Pub Date : 2020-01-23
    Hannah Fox; Luke Millington; Indu Mahabeer; Henriette van Ruiten

    Consider Duchenne muscular dystrophy in boys with delayed motor milestones, positive Gowers’ sign, abnormal gait, muscle pains, calf hypertrophy, unexplained elevated liver enzymes, learning difficulties, behavioural problems, or speech and language delay Test for creatine kinase levels if you suspect any neuromuscular condition. Refer children with raised creatine kinase promptly to a neuromuscular specialist Early diagnosis means early access to treatment, improved outcomes, and better informed family planning Early genetic diagnosis is important, as it can enable entry into appropriate clinical trials Where patients have breathlessness, palpitations and arrhythmias, morning headaches, and repeated chest infections or weight loss, suspect deterioration and refer for prompt specialist review Duchenne muscular dystrophy (DMD) is a progressive and disabling neuromuscular condition that is often diagnosed late.1 In the UK the mean age of diagnosis has remained fairly static over the past 30 years, currently around 4.3 years of age.2 On average it takes 1.6 years from first parental concern to diagnosis of DMD,2 by which time muscle function has already declined (box 1, case study). Delayed diagnosis of DMD can be devastating for patients and their families. Outcomes for people with DMD can be improved with optimum care at the earliest opportunity, and patients are now living into their fourth decades.34 Early diagnosis also enables parents to make informed decisions about family planning and can provide access to innovative treatments and clinical trials. International guidelines for diagnosis and management of DMD have been established by the DMD Care Considerations Working Group.567 Patient A presented with speech delay at age 2 and poor fine and gross motor skills at 2.5 years. He had been referred to several different teams for these symptoms, including physiotherapy for his poor motor skills and behavioural psychology. He initially walked at …

    更新日期:2020-01-23
  • Meningitis vaccine: cases fall in UK, but herd immunity remains elusive in Australia
    BMJ (IF 27.604) Pub Date : 2020-01-23
    Jacqui Wise

    The UK’s infant vaccination programme against group B meningococcal disease has resulted in a significant reduction in cases of the disease in young children, according to research from Public Health England published in the New England Journal of Medicine.1 However, an Australian study published in the same journal found that while the meningitis B vaccine also works in teenagers it does not provide herd protection against the meningococcal bacteria so will only protect those who are adequately immunised.2 In September 2015 the UK became the first country to offer the 4CMenB vaccine (Bexsero) to babies at 8 and 16 weeks of age, followed by a booster at 12 months. The results show that from September 2015 through to August 2018 there …

    更新日期:2020-01-23
  • Gene therapy delivering a paraoxonase 1 variant offers long-term prophylactic protection against nerve agents in mice
    Sci. Transl. Med. (IF 17.161) Pub Date : 2020-01-22
    Venkaiah Betapudi, Reena Goswami, Liliya Silayeva, Deborah M. Doctor, Nageswararao Chilukuri

    Chemical warfare nerve agents are organophosphorus chemical compounds that induce cholinergic crisis, leaving little or no time for medical intervention to prevent death. The current chemical treatment regimen may prevent death but does not prevent postexposure complications such as brain damage and permanent behavioral abnormalities. In the present study, we have demonstrated an adeno-associated virus 8 (AAV8)–mediated paraoxonase 1 variant IF-11 (PON1-IF11) gene therapy that offers asymptomatic prophylactic protection to mice against multiple lethal doses of G-type chemical warfare nerve agents, namely, tabun, sarin, cyclosarin, and soman, for up to 5 months in mice. A single injection of liver-specific adeno-associated viral particles loaded with PON1-IF11 gene resulted in expression and secretion of recombinant PON1-IF11 in milligram quantities, which has the catalytic power to break down G-type chemical warfare nerve agents into biologically inactive products in vitro and in vivo in rodents. Mice containing milligram concentrations of recombinant PON1-IF11 in their blood displayed no clinical signs of toxicity, as judged by their hematological parameters and serum chemistry profiles. Our study unfolds avenues to develop a one-time application of gene therapy to express a near-natural and circulating therapeutic PON1-IF11 protein that can potentially protect humans against G-type chemical warfare nerve agents for several weeks to months.

    更新日期:2020-01-23
  • Deep phenotyping during pregnancy for predictive and preventive medicine
    Sci. Transl. Med. (IF 17.161) Pub Date : 2020-01-22
    Alison G. Paquette, Leroy Hood, Nathan D. Price, Yoel Sadovsky

    Deep phenotyping during pregnancy offers an opportunity to define the antecedents of lifelong health and wellness, and to improve pregnancy outcomes.

    更新日期:2020-01-23
  • The IDH-TAU-EGFR triad defines the neovascular landscape of diffuse gliomas
    Sci. Transl. Med. (IF 17.161) Pub Date : 2020-01-22
    Ricardo Gargini, Berta Segura-Collar, Beatriz Herránz, Vega García-Escudero, Andrés Romero-Bravo, Felipe J. Núñez, Daniel García-Pérez, Jacqueline Gutiérrez-Guamán, Angel Ayuso-Sacido, Joan Seoane, Angel Pérez-Núñez, Juan M. Sepúlveda-Sánchez, Aurelio Hernández-Laín, María G. Castro, Ramón García-Escudero, Jesús Ávila, Pilar Sánchez-Gómez

    Gliomas that express the mutated isoforms of isocitrate dehydrogenase 1/2 (IDH1/2) have better prognosis than wild-type (wt) IDH1/2 gliomas. However, how these mutant (mut) proteins affect the tumor microenvironment is still a pending question. Here, we describe that the transcription of microtubule-associated protein TAU (MAPT), a gene that has been classically associated with neurodegenerative diseases, is epigenetically controlled by the balance between wt and mut IDH1/2 in mouse and human gliomas. In IDH1/2 mut tumors, we found high expression of TAU that decreased with tumor progression. Furthermore, MAPT was almost absent from tumors with epidermal growth factor receptor (EGFR) mutations, whereas its trancription negatively correlated with overall survival in gliomas carrying wt or amplified (amp) EGFR. We demonstrated that the overexpression of TAU, through the stabilization of microtubules, impaired the mesenchymal/pericyte-like transformation of glioma cells by blocking EGFR, nuclear factor kappa-light-chain-enhancer of activated B (NF-κB) and the transcriptional coactivator with PDZ-binding motif (TAZ). Our data also showed that mut EGFR induced a constitutive activation of this pathway, which was no longer sensitive to TAU. By inhibiting the transdifferentiation capacity of EGFRamp/wt tumor cells, TAU protein inhibited angiogenesis and favored vascular normalization, decreasing glioma aggressiveness and increasing their sensitivity to chemotherapy.

    更新日期:2020-01-23
  • Pan-viral protection against arboviruses by activating skin macrophages at the inoculation site
    Sci. Transl. Med. (IF 17.161) Pub Date : 2020-01-22
    Steven R. Bryden, Marieke Pingen, Daniella A. Lefteri, Janne Miltenburg, Leen Delang, Sofie Jacobs, Rana Abdelnabi, Johan Neyts, Emilie Pondeville, Jack Major, Marietta Müller, Henna Khalid, Andrew Tuplin, Margus Varjak, Andres Merits, Julia Edgar, Gerard J. Graham, Kave Shams, Clive S. McKimmie

    Arthropod-borne viruses (arboviruses) are important human pathogens for which there are no specific antiviral medicines. The abundance of genetically distinct arbovirus species, coupled with the unpredictable nature of their outbreaks, has made the development of virus-specific treatments challenging. Instead, we have defined and targeted a key aspect of the host innate immune response to virus at the arthropod bite that is common to all arbovirus infections, potentially circumventing the need for virus-specific therapies. Using mouse models and human skin explants, we identify innate immune responses by dermal macrophages in the skin as a key determinant of disease severity. Post-exposure treatment of the inoculation site by a topical TLR7 agonist suppressed both the local and subsequent systemic course of infection with a variety of arboviruses from the Alphavirus, Flavivirus, and Orthobunyavirus genera. Clinical outcome was improved in mice after infection with a model alphavirus. In the absence of treatment, antiviral interferon expression to virus in the skin was restricted to dermal dendritic cells. In contrast, stimulating the more populous skin-resident macrophages with a TLR7 agonist elicited protective responses in key cellular targets of virus that otherwise proficiently replicated virus. By defining and targeting a key aspect of the innate immune response to virus at the mosquito bite site, we have identified a putative new strategy for limiting disease after infection with a variety of genetically distinct arboviruses.

    更新日期:2020-01-23
  • Hitting a double to treat cancer
    Sci. Transl. Med. (IF 17.161) Pub Date : 2020-01-22
    Asmaa El-Kenawi

    Simultaneous targeting of polyamine and methionine pathways may be a promising strategy to treat prostate cancer.

    更新日期:2020-01-23
  • Neurodevelopment and risk for ADHD and depression
    Sci. Transl. Med. (IF 17.161) Pub Date : 2020-01-22
    Dylan G. Gee

    Childhood brain connectivity predicts psychiatric difficulties four years later.

    更新日期:2020-01-23
  • Angling for a bug-inspired method of coating therapeutics onto microneedles
    Sci. Transl. Med. (IF 17.161) Pub Date : 2020-01-22
    Eoin O’Cearbhaill

    Mimicking the microstructures on the surface of European true bugs may help optimize loading of therapeutics onto transdermal microneedle patches.

    更新日期:2020-01-23
  • PI4KIIIβ is a therapeutic target in chromosome 1q–amplified lung adenocarcinoma
    Sci. Transl. Med. (IF 17.161) Pub Date : 2020-01-22
    Xiaochao Tan, Priyam Banerjee, Edward A. Pham, Florentine U. N. Rutaganira, Kaustabh Basu, Neus Bota-Rabassedas, Hou-Fu Guo, Caitlin L. Grzeskowiak, Xin Liu, Jiang Yu, Lei Shi, David H. Peng, B. Leticia Rodriguez, Jiaqi Zhang, Veronica Zheng, Dzifa Y. Duose, Luisa M. Solis, Barbara Mino, Maria Gabriela Raso, Carmen Behrens, Ignacio I. Wistuba, Kenneth L. Scott, Mark Smith, Khanh Nguyen, Grace Lam, Ingrid Choong, Abhijit Mazumdar, Jamal L. Hill, Don L. Gibbons, Powel H. Brown, William K. Russell, Kevan Shokat, Chad J. Creighton, Jeffrey S. Glenn, Jonathan M. Kurie

    Heightened secretion of protumorigenic effector proteins is a feature of malignant cells. Yet, the molecular underpinnings and therapeutic implications of this feature remain unclear. Here, we identify a chromosome 1q region that is frequently amplified in diverse cancer types and encodes multiple regulators of secretory vesicle biogenesis and trafficking, including the Golgi-dedicated enzyme phosphatidylinositol (PI)-4-kinase IIIβ (PI4KIIIβ). Molecular, biochemical, and cell biological studies show that PI4KIIIβ-derived PI-4-phosphate (PI4P) synthesis enhances secretion and accelerates lung adenocarcinoma progression by activating Golgi phosphoprotein 3 (GOLPH3)–dependent vesicular release from the Golgi. PI4KIIIβ-dependent secreted factors maintain 1q-amplified cancer cell survival and influence prometastatic processes in the tumor microenvironment. Disruption of this functional circuitry in 1q-amplified cancer cells with selective PI4KIIIβ antagonists induces apoptosis and suppresses tumor growth and metastasis. These results support a model in which chromosome 1q amplifications create a dependency on PI4KIIIβ-dependent secretion for cancer cell survival and tumor progression.

    更新日期:2020-01-23
  • Long-gap peripheral nerve repair through sustained release of a neurotrophic factor in nonhuman primates
    Sci. Transl. Med. (IF 17.161) Pub Date : 2020-01-22
    Neil B. Fadia, Jacqueline M. Bliley, Gabriella A. DiBernardo, Donald J. Crammond, Benjamin K. Schilling, Wesley N. Sivak, Alexander M. Spiess, Kia M. Washington, Matthias Waldner, Han-Tsung Liao, Isaac B. James, Danielle M. Minteer, Casey Tompkins-Rhoades, Adam R. Cottrill, Deok-Yeol Kim, Riccardo Schweizer, Debra A. Bourne, George E. Panagis, M. Asher Schusterman, Francesco M. Egro, Insiyah K. Campwala, Tyler Simpson, Douglas J. Weber, Trent Gause, Jack E. Brooker, Tvisha Josyula, Astrid A. Guevara, Alexander J. Repko, Christopher M. Mahoney, Kacey G. Marra

    Severe injuries to peripheral nerves are challenging to repair. Standard-of-care treatment for nerve gaps >2 to 3 centimeters is autografting; however, autografting can result in neuroma formation, loss of sensory function at the donor site, and increased operative time. To address the need for a synthetic nerve conduit to treat large nerve gaps, we investigated a biodegradable poly(caprolactone) (PCL) conduit with embedded double-walled polymeric microspheres encapsulating glial cell line–derived neurotrophic factor (GDNF) capable of providing a sustained release of GDNF for >50 days in a 5-centimeter nerve defect in a rhesus macaque model. The GDNF-eluting conduit (PCL/GDNF) was compared to a median nerve autograft and a PCL conduit containing empty microspheres (PCL/Empty). Functional testing demonstrated similar functional recovery between the PCL/GDNF-treated group (75.64 ± 10.28%) and the autograft-treated group (77.49 ± 19.28%); both groups were statistically improved compared to PCL/Empty-treated group (44.95 ± 26.94%). Nerve conduction velocity 1 year after surgery was increased in the PCL/GDNF-treated macaques (31.41 ± 15.34 meters/second) compared to autograft (25.45 ± 3.96 meters/second) and PCL/Empty (12.60 ± 3.89 meters/second) treatment. Histological analyses included assessment of Schwann cell presence, myelination of axons, nerve fiber density, and g-ratio. PCL/GDNF group exhibited a statistically greater average area occupied by individual Schwann cells at the distal nerve (11.60 ± 33.01 μm2) compared to autograft (4.62 ± 3.99 μm2) and PCL/Empty (4.52 ± 5.16 μm2) treatment groups. This study demonstrates the efficacious bridging of a long peripheral nerve gap in a nonhuman primate model using an acellular, biodegradable nerve conduit.

    更新日期:2020-01-23
  • 更新日期:2020-01-23
  • Corporate sponsorship of patient groups
    BMJ (IF 27.604) Pub Date : 2020-01-22
    Bethany Bruno; Susannah Rose

    It’s time for mandatory disclosure Non-profit patient groups provide support services to patients and families, increase public awareness through educational outreach, participate in the development of clinical guidelines, lobby on policies affecting access and care, and invest in novel research on therapeutics. Although many focus on a particular disease, others focus on the needs and interests of healthcare consumers more generally. Various sources provide financial assistance, including pharmaceutical and medical device companies. Given the considerable power of patient groups to influence healthcare policy and individual medical decision making, and given research documenting the effects of even small payments on physician practices,1 monetary relationships between patient groups and industry have prompted recent concern. In the linked paper (doi:10.1136/bmj.l6925), Fabbri and colleagues provide the first systematic review on this topic to examine the extent of ties between patient groups and industry, the policies of patient groups surrounding corporate sponsorship, and the effect of industry support on the public position statements made by patient groups.2 This builds on …

    更新日期:2020-01-23
  • The struggle for GPs to get the right care for patients with gender dysphoria
    BMJ (IF 27.604) Pub Date : 2020-01-22
    Sally Howard

    Family doctors lack training and feel under pressure to prescribe, finds Sally Howard Gender dysphoria can be difficult terrain for primary care doctors. Gender identity and gender dysphoria are not part of the GP curriculum.1 Patients face an average 18 month wait for specialist referral.2 And the NHS’s frontline doctors may bear the brunt of some patients’ distrust of a system that can’t cope with the current demand for services. Specialist gender identity clinics (GICs) have seen referrals at least double over the five years to 2018, said James Palmer, medical director for specialised services at NHS England.3 As of 2019, about 7839 adults were waiting for a first appointment.2 Some 4000 young people are waiting for a specialist appointment.4 Chris Preece, a GP in North Yorkshire, told The BMJ that the two year wait for patients to be seen by his local gender identity clinic puts pressure …

    更新日期:2020-01-23
  • Perinatal management for premature babies should be multidisciplinary and personalised
    BMJ (IF 27.604) Pub Date : 2020-01-22
    E J Verweij; I K M Reiss

    We read the new framework from the British Association of Perinatal Medicine1 and The BMJ’s related news story2 with interest. This is a big step forward in perinatal management for extremely premature neonates. We agree with the risk assessment proposed but would like it to be more individualised. As …

    更新日期:2020-01-23
  • Coronavirus: UK screens direct flights from Wuhan after US case
    BMJ (IF 27.604) Pub Date : 2020-01-22
    Elisabeth Mahase

    The government has announced that health teams in the UK will meet each direct flight aircraft from Wuhan, China, to check for symptoms of novel coronavirus (2019-nCoV) and to provide information in English, Mandarin, and Cantonese to all passengers about symptoms and what to do if they become ill. A joint statement released on 22 January by the Department of Health and Social Care and Public Health England said that the risk level had been raised from “very low” to “low” because of “current evidence on the likelihood of cases being imported into this country.” But it said that no confirmed cases of the infection had currently been found in the UK and that a prototype specific laboratory test for diagnosing 2019-nCoV had now been developed. The update …

    更新日期:2020-01-23
  • US cancer centre leaders secretly worked for China, internal report finds
    BMJ (IF 27.604) Pub Date : 2020-01-22
    Owen Dyer

    Six researchers who resigned last month from Florida’s Moffitt Cancer Center admitted to opening secret bank accounts in China to hide millions that they received from China’s Thousand Talents programme, say the preliminary findings of an internal investigation. Among the six were Alan List, Moffitt’s president and chief executive officer, and the centre’s director, Thomas Sellers. They are the latest and most senior researchers to lose their jobs in a nationwide hunt for academics suspected of working for China, in what US authorities claim is an organised attempt to steal intellectual property. At least 200 people are being investigated at 71 US hospitals, universities, and research institutions. Most of these investigations began when letters arrived from the US …

    更新日期:2020-01-23
  • Assisted dying: Belgian doctors stand trial in landmark case
    BMJ (IF 27.604) Pub Date : 2020-01-22
    Rory Watson

    Three Belgian doctors—two GPs and a psychiatrist—are being accused of unlawfully killing a 38 year old patient by poisoning almost 10 years ago, in the country’s first criminal case involving assisted dying. The high profile trial is focusing on the conditions in the 2002 legislation that must be fulfilled before a request for assisted dying can be acted on. It is also revealing possible gaps in the law and the many emotions that patients, their families, and medical professionals may feel when involved in such a procedure. After several suicide attempts and with severe psychiatric problems and a broken relationship, …

    更新日期:2020-01-23
  • Gillian Bluck
    BMJ (IF 27.604) Pub Date : 2020-01-22
    Jules Gray

    Gillian Bluck (“Gill”) was the daughter of a Methodist preacher and a Methodist lay preacher. She grew up in Oldbury and Uttoxeter, and later attended Culford School near Bury St Edmunds. After graduating from Manchester, she …

    更新日期:2020-01-23
  • Brian Bartley
    BMJ (IF 27.604) Pub Date : 2020-01-22
    Adrian Bartley

    After enjoying national service as an army captain in Hong Kong and undertaking an obstetrics placement at the British Hospital for Mothers and Babies in Woolwich, Brian Bartley worked as a …

    更新日期:2020-01-23
  • John Phillips Mckay
    BMJ (IF 27.604) Pub Date : 2020-01-22
    Simon Mckay; Hannah Mckay

    John Phillips Mckay was the loving husband of Marjorie of blessed memory, a much loved dad, uncle, grandad, friend, mentor, and inspiration. To many thousands of patients and their families he was either Dr John or Dr Mckay, depending on their preference. John was born in Llandrindod Wells, Wales, owing to war time evacuation of his mother (a teacher). They returned to Liverpool after the war ended. He went on to attend Liverpool medical school graduating in 1966. He started his career at Birkenhead General Hospital, moved on to the forensic psychiatric unit at Rainhill Hospital, and ultimately settled in general practice, initially in Wallasey …

    更新日期:2020-01-23
  • Jonathan Maw
    BMJ (IF 27.604) Pub Date : 2020-01-22
    David Maw

    Dane Stephen Jonathan Maw, known as Jonathan, was born in Bath on 8 September 1937. His life was one of duty and service, dedicated to healing, but it was also one of relish and pleasure. He savoured the finer things of life in the arts and culture, in good food and wine, and in the company of friends and family. Jonathan grew up in Bath, where his parents were teachers. He attended Kingswood School and studied Latin, Greek, and ancient history at A level; but rather than pursuing Greats at university, he took up a scholarship in 1956 to study medicine and train as a physician at St Mary’s Hospital, University of London. There he won the Waller prize for physiology in 1958 and qualified in 1962. He was admitted to the fellowship of the Royal College …

    更新日期:2020-01-23
  • Jeannette Alexandra Smith
    BMJ (IF 27.604) Pub Date : 2020-01-22
    Pamela J F Smith

    Jeannette Alexandra Ferguson was born on Guernsey, the daughter of Alexander and Emily Ferguson and the youngest of four girls. She stayed on the island during the German occupation, and the resilience and resourcefulness of her fellow islanders helped to shape her character. After studying for her A levels on the mainland she was accepted by the medical school at the University of Liverpool. She joined the Methodist Society, where she became secretary and then president. …

    更新日期:2020-01-23
  • Risk of herpes zoster after exposure to varicella to explore the exogenous boosting hypothesis: self controlled case series study using UK electronic healthcare data
    BMJ (IF 27.604) Pub Date : 2020-01-22
    Harriet Forbes; Ian Douglas; Adam Finn; Judith Breuer; Krishnan Bhaskaran; Liam Smeeth; Simon Packer; Sinéad M Langan; Kathryn E Mansfield; Robin Marlow; Heather Whitaker; Charlotte Warren-Gash

    Objective To assess the magnitude and duration of any hypothesised protective effect of household exposure to a child with varicella on the relative incidence of herpes zoster in adults. Design Self controlled case series. Setting UK general practices contributing to Clinical Practice Research Datalink. Participants 9604 adults (≥18 years) with a diagnosis of herpes zoster (in primary care or hospital records) between 1997 and 2018, who during their observation period lived with a child (<18 years) with a diagnosis of varicella. Main outcome measures Relative incidence of herpes zoster in the 20 years after exposure to a child with varicella in the household compared with baseline time (all other time, excluding the 60 days before exposure). Results 6584 of the 9604 adults with herpes zoster (68.6%) were women. Median age of exposure to a child with varicella was 38.3 years (interquartile range 32.3-48.8 years) and median observation period was 14.7 (11.1-17.7) years. 4116 adults developed zoster in the baseline period, 433 in the 60 days before exposure and 5055 in the risk period. After adjustment for age, calendar time, and season, strong evidence suggested that in the two years after household exposure to a child with varicella, adults were 33% less likely to develop zoster (incidence ratio 0.67, 95% confidence interval 0.62 to 0.73) compared with baseline time. In the 10-20 years after exposure, adults were 27% less likely to develop herpes zoster (0.73, 0.62 to 0.87) compared with baseline time. A stronger boosting effect was observed among men than among women after exposure to varicella. Conclusions The relative incidence of zoster was lower in the periods after exposure to a household contact with varicella, with modest but long lasting protective effects observed. This study suggests that exogenous boosting provides some protection from the risk of herpes zoster, but not complete immunity, as assumed by previous cost effectiveness estimates of varicella immunisation.

    更新日期:2020-01-23
  • Industry funding of patient and health consumer organisations: systematic review with meta-analysis
    BMJ (IF 27.604) Pub Date : 2020-01-22
    Alice Fabbri; Lisa Parker; Cinzia Colombo; Paola Mosconi; Giussy Barbara; Maria Pina Frattaruolo; Edith Lau; Cynthia M Kroeger; Carole Lunny; Douglas M Salzwedel; Barbara Mintzes

    Objective To investigate pharmaceutical or medical device industry funding of patient groups. Design Systematic review with meta-analysis. Data sources Ovid Medline, Embase, Web of Science, Scopus, and Google Scholar from inception to January 2018; reference lists of eligible studies and experts in the field. Eligibility criteria for selecting studies Observational studies including cross sectional, cohort, case-control, interrupted time series, and before-after studies of patient groups reporting at least one of the following outcomes: prevalence of industry funding; proportion of industry funded patient groups that disclosed information about this funding; and association between industry funding and organisational positions on health and policy issues. Studies were included irrespective of language or publication type. Review methods Reviewers carried out duplicate independent data extraction and assessment of study quality. An amended version of the checklist for prevalence studies developed by the Joanna Briggs Institute was used to assess study quality. A DerSimonian-Laird estimate of single proportions with Freeman-Tukey arcsine transformation was used for meta-analyses of prevalence. GRADE (Grading of Recommendations Assessment, Development, and Evaluation) was used to assess the quality of the evidence for each outcome. Results 26 cross sectional studies met the inclusion criteria. Of these, 15 studies estimated the prevalence of industry funding, which ranged from 20% (12/61) to 83% (86/104). Among patient organisations that received industry funding, 27% (175/642; 95% confidence interval 24% to 31%) disclosed this information on their websites. In submissions to consultations, two studies showed very different disclosure rates (0% and 91%), which appeared to reflect differences in the relevant government agency’s disclosure requirements. Prevalence estimates of organisational policies that govern corporate sponsorship ranged from 2% (2/125) to 64% (175/274). Four studies analysed the relationship between industry funding and organisational positions on a range of highly controversial issues. Industry funded groups generally supported sponsors’ interests. Conclusion In general, industry funding of patient groups seems to be common, with prevalence estimates ranging from 20% to 83%. Few patient groups have policies that govern corporate sponsorship. Transparency about corporate funding is also inadequate. Among the few studies that examined associations between industry funding and organisational positions, industry funded groups tended to have positions favourable to the sponsor. Patient groups have an important role in advocacy, education, and research, therefore strategies are needed to prevent biases that could favour the interests of sponsors above those of the public. Systematic review registration PROSPERO CRD42017079265.

    更新日期:2020-01-23
  • How to be involved in peer teaching
    BMJ (IF 27.604) Pub Date : 2020-01-22
    Rebecca Choong; Fiona Macauslan

    In peer teaching, learners are taught by those similar in age or at a similar educational stage. Many peer teaching programmes in medical school involve junior students being taught by senior students.1 Some evidence suggests that the closer learners are in training stage to their teacher, the better the learning outcomes.2 This might be because peers have better ideas of the relative importance of different topics.3 Students also say that peer teaching enables them to direct their own education.4 Peer teaching doesn’t just help learners—teachers can benefit too.45 It provides an opportunity for revision and furthering knowledge. Developing ways to explain challenging concepts to peers promotes effective communication skills, which are essential for working in teams and with patients. This article provides some tips on how to set up a peer teaching initiative on the basis of the authors’ experiences. This type of teaching can be coordinated formally within a whole year group, or ad hoc by a group of students on placement. It is particularly useful preparation for OSCEs (objective structured clinical examinations) and is most effective in groups of three to five. Students take turns in playing the roles of examiner and candidate. You …

    更新日期:2020-01-23
  • David Oliver: The risks of discharging patients early against doctors’ judgment
    BMJ (IF 27.604) Pub Date : 2020-01-22
    David Oliver

    On 13 January the BBC reported the contents of an internal email to doctors from the medical director and chief nursing officer at the Royal Cornwall Hospital.1 In response to “significant pressure,” and to free up bed capacity, the email urged doctors to discharge patients “earlier than some clinicians would like.” Last month the Guardian had carried a similar story from Norfolk and Norwich University Hospital, reporting internal memos urging senior doctors to find the “least unsafe option” in identifying patients to discharge.2 No doubt, senior operational and clinician managers at those trusts face an almost impossible balancing act. I’m sure that you’d find similar emails in dozens of acute hospitals around the NHS, given that they start each day in negative bed equity, with patients queuing in the emergency department, sometimes on trolleys in corridors. What struck me about both cases was that the …

    更新日期:2020-01-23
  • Advancing Safety and Equity Together
    N. Engl. J. Med. (IF 70.670) Pub Date : 2020-01-23
    Karthik Sivashanker; Tejal K. Gandhi

    Audio Interview Interview with Dr. Karthik Sivashanker on leveraging models from patient-safety efforts to increase equity. (12:56)Download There are widespread inequities in health outcomes in the United States based on race, sex, language, and other factors. But there is no such thing as high-quality, safe care that is inequitable. Health systems can leverage patient-safety programs to advance equity.

    更新日期:2020-01-23
  • Payment for Services Rendered — Updating Medicare’s Valuation of Procedures
    N. Engl. J. Med. (IF 70.670) Pub Date : 2020-01-23
    Andrew W. Mulcahy; Katie Merrell; Ateev Mehrotra

    For most surgical procedures, Medicare and many other insurers give physicians a single bundled payment that covers both the procedure itself and related postoperative care. But reports suggest that the bulk of expected postoperative visits aren’t taking place.

    更新日期:2020-01-23
  • Healing as a Servant Instead of a Prophet
    N. Engl. J. Med. (IF 70.670) Pub Date : 2020-01-23
    Michael Lee

    J. needed me to be honest with him — to tell him that I suspected his symptoms were manifestations of depression rather than a primarily gastrointestinal issue, and that help was available — but I hesitated, knowing how often such conversations went poorly.

    更新日期:2020-01-23
  • Vaccination of Infants with Meningococcal Group B Vaccine (4CMenB) in England
    N. Engl. J. Med. (IF 70.670) Pub Date : 2020-01-23
    Shamez N. Ladhani; Nick Andrews; Sydel R. Parikh; Helen Campbell; Joanne White; Michael Edelstein; Xilian Bai; Jay Lucidarme; Ray Borrow; Mary E. Ramsay

    Background In September 2015, the United Kingdom introduced the multicomponent meningococcal group B vaccine (4CMenB, Bexsero) into its publicly funded national immunization program at a reduced two-dose priming schedule for infants, with a 12-month booster. Methods Using data from enhanced national surveillance of invasive meningococcal disease in England, we evaluated the effect of vaccination on the incidence of meningococcal group B disease during the first 3 years of the program. The effect of vaccination was assessed by comparing the observed incidence of disease with the expected incidence based on the incidence during the 4-year prevaccination period in equivalent cohorts and with the use of disease trends in cohorts of children younger than 5 years of age who were not eligible to receive the vaccine. Vaccine effectiveness was estimated with the use of the indirect screening method. Results 4CMenB uptake in England remained consistently high; data from the first 3 months of 2018 showed that 92.5% of children had completed the primary immunizations by their first birthday and 87.9% had received all three doses by 2 years. From September 2015 through August 2018, the incidence of meningococcal group B disease in England (average annual birth cohort, approximately 650,000 infants) was significantly lower in vaccine-eligible cohorts than the expected incidence (63 observed cases as compared with 253 expected cases; incidence rate ratio, 0.25; 95% confidence interval [CI], 0.19 to 0.36), with a 75% reduction in age groups that were fully eligible for vaccination. The adjusted vaccine effectiveness against meningococcal group B disease was 52.7% (95% CI, −33.5 to 83.2) with a two-dose priming schedule for infants and 59.1% (95% CI, −31.1 to 87.2) with a two-dose priming schedule plus a booster at 1 year). Over the 3-year period, there were 169 cases of meningococcal group B disease in the vaccine-eligible cohorts, and an estimated 277 cases (95% CI, 236 to 323) were prevented. Conclusions The 4CMenB program was associated with continued positive effect against meningococcal group B disease in children in England, and protection after three doses of the vaccine was sustained for at least 2 years. (Funded by Public Health England.) QUICK TAKE VIDEO SUMMARY Effect of Group B Meningococcal Vaccination  02:04

    更新日期:2020-01-23
  • Meningococcal B Vaccine and Meningococcal Carriage in Adolescents in Australia
    N. Engl. J. Med. (IF 70.670) Pub Date : 2020-01-23
    Helen S. Marshall; Mark McMillan; Ann P. Koehler; Andrew Lawrence; Thomas R. Sullivan; Jenny M. MacLennan; Martin C.J. Maiden; Shamez N. Ladhani; Mary E. Ramsay; Caroline Trotter; Ray Borrow; Adam Finn; Charlene M. Kahler; Jane Whelan; Kumaran Vadivelu; Peter Richmond

    Background The meningococcal group B vaccine 4CMenB is a new, recombinant protein-based vaccine that is licensed to protect against invasive group B meningococcal disease. However, its role in preventing transmission and, therefore, inducing population (herd) protection is uncertain. Methods We used cluster randomization to assign, according to school, students in years 10 to 12 (age, 15 to 18 years) in South Australia to receive 4CMenB vaccination either at baseline (intervention) or at 12 months (control). The primary outcome was oropharyngeal carriage of disease-causing Neisseria meningitidis (group A, B, C, W, X, or Y) in students in years 10 and 11, as identified by polymerase-chain-reaction assays for PorA (encoding porin protein A) and N. meningitidis genogroups. Secondary outcomes included carriage prevalence and acquisition of all N. meningitidis and individual disease-causing genogroups. Risk factors for carriage were assessed at baseline. Results A total of 237 schools participated. During April through June 2017, a total of 24,269 students in years 10 and 11 and 10,220 students in year 12 were enrolled. At 12 months, there was no difference in the prevalence of carriage of disease-causing N. meningitidis between the vaccination group (2.55%; 326 of 12,746) and the control group (2.52%; 291 of 11,523) (adjusted odds ratio, 1.02; 95% confidence interval [CI], 0.80 to 1.31; P=0.85). There were no significant differences in the secondary carriage outcomes. At baseline, the risk factors for carriage of disease-causing N. meningitidis included later year of schooling (adjusted odds ratio for year 12 vs. year 10, 2.75; 95% CI, 2.03 to 3.73), current upper respiratory tract infection (adjusted odds ratio, 1.35; 95% CI, 1.12 to 1.63), cigarette smoking (adjusted odds ratio, 1.91; 95% CI, 1.29 to 2.83), water-pipe smoking (adjusted odds ratio, 1.82; 95% CI, 1.30 to 2.54), attending pubs or clubs (adjusted odds ratio, 1.54; 95% CI, 1.28 to 1.86), and intimate kissing (adjusted odds ratio, 1.65; 95% CI, 1.33 to 2.05). No vaccine safety concerns were identified. Conclusions Among Australian adolescents, the 4CMenB vaccine had no discernible effect on the carriage of disease-causing meningococci, including group B. (Funded by GlaxoSmithKline; ClinicalTrials.gov number, NCT03089086.)

    更新日期:2020-01-23
  • Elagolix for Heavy Menstrual Bleeding in Women with Uterine Fibroids
    N. Engl. J. Med. (IF 70.670) Pub Date : 2020-01-23
    William D. Schlaff; Ronald T. Ackerman; Ayman Al-Hendy; David F. Archer; Kurt T. Barnhart; Linda D. Bradley; Bruce R. Carr; Eve C. Feinberg; Sandra M. Hurtado; JinHee Kim; Ran Liu; R. Garn Mabey; Charlotte D. Owens; Alfred Poindexter; Elizabeth E. Puscheck; Henry Rodriguez-Ginorio; James A. Simon; Ahmed M. Soliman; Elizabeth A. Stewart; Nelson B. Watts; Ozgul Muneyyirci-Delale

    Background Uterine fibroids are hormone-responsive neoplasms that are associated with heavy menstrual bleeding. Elagolix, an oral gonadotropin-releasing hormone antagonist resulting in rapid, reversible suppression of ovarian sex hormones, may reduce fibroid-associated bleeding. Methods We conducted two identical, double-blind, randomized, placebo-controlled, 6-month phase 3 trials (Elaris Uterine Fibroids 1 and 2 [UF-1 and UF-2]) to evaluate the efficacy and safety of elagolix at a dose of 300 mg twice daily with hormonal “add-back” therapy (to replace reduced levels of endogenous hormones; in this case, estradiol, 1 mg, and norethindrone acetate, 0.5 mg, once daily) in women with fibroid-associated bleeding. An elagolix-alone group was included to assess the impact of add-back therapy on the hypoestrogenic effects of elagolix. The primary end point was menstrual blood loss of less than 80 ml during the final month of treatment and at least a 50% reduction in menstrual blood loss from baseline to the final month; missing data were imputed with the use of multiple imputation. Results A total of 412 women in UF-1 and 378 women in UF-2 underwent randomization, received elagolix or placebo, and were included in the analyses. Criteria for the primary end point were met in 68.5% of 206 women in UF-1 and in 76.5% of 189 women in UF-2 who received elagolix plus add-back therapy, as compared with 8.7% of 102 women and 10% of 94 women, respectively, who received placebo (P<0.001 for both trials). Among the women who received elagolix alone, the primary end point was met in 84.1% of 104 women in UF-1 and in 77% of 95 women in UF-2. Hot flushes (in both trials) and metrorrhagia (in UF-1) occurred significantly more commonly with elagolix plus add-back therapy than with placebo. Hypoestrogenic effects of elagolix, especially decreases in bone mineral density, were attenuated with add-back therapy. Conclusions Elagolix with add-back therapy was effective in reducing heavy menstrual bleeding in women with uterine fibroids. (Funded by AbbVie; Elaris UF-1 and Elaris UF-2 ClinicalTrials.gov numbers, NCT02654054 and NCT02691494.)

    更新日期:2020-01-23
  • Teprotumumab for the Treatment of Active Thyroid Eye Disease
    N. Engl. J. Med. (IF 70.670) Pub Date : 2020-01-23
    Raymond S. Douglas; George J. Kahaly; Amy Patel; Saba Sile; Elizabeth H.Z. Thompson; Renee Perdok; James C. Fleming; Brian T. Fowler; Claudio Marcocci; Michele Marinò; Alessandro Antonelli; Roger Dailey; Gerald J. Harris; Anja Eckstein; Jade Schiffman; Rosa Tang; Christine Nelson; Mario Salvi; Sara Wester; Jeffrey W. Sherman; Thomas Vescio; Robert J. Holt; Terry J. Smith

    Background Thyroid eye disease is a debilitating, disfiguring, and potentially blinding periocular condition for which no Food and Drug Administration–approved medical therapy is available. Strong evidence has implicated the insulin-like growth factor I receptor (IGF-IR) in the pathogenesis of this disease. Methods In a randomized, double-masked, placebo-controlled, phase 3 multicenter trial, we assigned patients with active thyroid eye disease in a 1:1 ratio to receive intravenous infusions of the IGF-IR inhibitor teprotumumab (10 mg per kilogram of body weight for the first infusion and 20 mg per kilogram for subsequent infusions) or placebo once every 3 weeks for 21 weeks; the last trial visit for this analysis was at week 24. The primary outcome was a proptosis response (a reduction in proptosis of ≥2 mm) at week 24. Prespecified secondary outcomes at week 24 were an overall response (a reduction of ≥2 points in the Clinical Activity Score plus a reduction in proptosis of ≥2 mm), a Clinical Activity Score of 0 or 1 (indicating no or minimal inflammation), the mean change in proptosis across trial visits (from baseline through week 24), a diplopia response (a reduction in diplopia of ≥1 grade), and the mean change in overall score on the Graves’ ophthalmopathy-specific quality-of-life (GO-QOL) questionnaire across trial visits (from baseline through week 24; a mean change of ≥6 points is considered clinically meaningful). Results A total of 41 patients were assigned to the teprotumumab group and 42 to the placebo group. At week 24, the percentage of patients with a proptosis response was higher with teprotumumab than with placebo (83% [34 patients] vs. 10% [4 patients], P<0.001), with a number needed to treat of 1.36. All secondary outcomes were significantly better with teprotumumab than with placebo, including overall response (78% of patients [32] vs. 7% [3]), Clinical Activity Score of 0 or 1 (59% [24] vs. 21% [9]), the mean change in proptosis (−2.82 mm vs. −0.54 mm), diplopia response (68% [19 of 28] vs. 29% [8 of 28]), and the mean change in GO-QOL overall score (13.79 points vs. 4.43 points) (P≤0.001 for all). Reductions in extraocular muscle, orbital fat volume, or both were observed in 6 patients in the teprotumumab group who underwent orbital imaging. Most adverse events were mild or moderate in severity; two serious events occurred in the teprotumumab group, of which one (an infusion reaction) led to treatment discontinuation. Conclusions Among patients with active thyroid eye disease, teprotumumab resulted in better outcomes with respect to proptosis, Clinical Activity Score, diplopia, and quality of life than placebo; serious adverse events were uncommon. (Funded by Horizon Therapeutics; OPTIC ClinicalTrials.gov number, NCT03298867, and EudraCT number, 2017-002763-18.) VISUAL ABSTRACT Teprotumumab for Thyroid Eye Disease

    更新日期:2020-01-23
  • Treating Hypertension in Chronic Obstructive Pulmonary Disease
    N. Engl. J. Med. (IF 70.670) Pub Date : 2020-01-23
    Shannon W. Finks; Mark J. Rumbak; Timothy H. Self

    This review considers recent evidence concerning hypertension management in patients with chronic obstructive pulmonary disease, including the effects of antihypertensive-drug classes on exacerbations, hospitalizations, and adverse pulmonary outcomes.

    更新日期:2020-01-23
  • Intrahepatic Biliary Ductal Dilatation
    N. Engl. J. Med. (IF 70.670) Pub Date : 2020-01-23
    Umberto G. Rossi; Maurizio Cariati

    更新日期:2020-01-23
  • Fluorouracil-Induced Hyperpigmentation
    N. Engl. J. Med. (IF 70.670) Pub Date : 2020-01-23
    Jordan K. Schaefer; Nithya Ramnath

    更新日期:2020-01-23
  • Case 3-2020: A 44-Year-Old Man with Weight Loss, Diarrhea, and Abdominal Pain
    N. Engl. J. Med. (IF 70.670) Pub Date : 2020-01-23
    Robert C. Lowe; Jacqueline N. Chu; Theodore T. Pierce; Ana A. Weil; John A. Branda

    A 44-year-old man from the Caribbean was evaluated at the hospital because of diarrhea, weight loss, and abdominal pain. Fever and headache had led to lumbar puncture at another hospital; the cerebrospinal fluid had contained 1306 white cells per microliter, of which 83% were neutrophils. Additional diagnostic tests were performed.

    更新日期:2020-01-23
  • Good News and Bad News — 4CMenB Vaccine for Group B Neisseria meningitidis
    N. Engl. J. Med. (IF 70.670) Pub Date : 2020-01-23
    Lee H. Harrison; David S. Stephens

    This article has no abstract; the first 100 words appear below. Neisseria meningitidis remains a major cause of meningitis, sepsis, and other serious infections globally. Almost all meningococcal infections are caused by one of six capsular groups (A, B, C, W, X, and Y) that are distinguished by different biochemical compositions of the polysaccharide capsules. Over the past two decades, the use of meningococcal capsular polysaccharide–protein conjugate vaccines has led to major successes in the prevention of invasive meningococcal disease. For example, the introduction of monovalent meningococcal capsular group A conjugate vaccine in the “African meningitis belt” (from Senegal to Ethiopia) and meningococcal group C conjugate vaccine in the United Kingdom . . .

    更新日期:2020-01-23
  • Choosing a Mass Immunization Program against Meningococcal B
    N. Engl. J. Med. (IF 70.670) Pub Date : 2020-01-23
    Ken Wu; E. Kim Mulholland; Kathryn M. Edwards

    This interactive feature about an outbreak of meningitis caused by Neisseria meningitidis group B in a public university offers a case vignette accompanied by essays that either support or discourage a mass immunization program.

    更新日期:2020-01-23
Contents have been reproduced by permission of the publishers.
导出
全部期刊列表>>
2020新春特辑
限时免费阅读临床医学内容
ACS材料视界
科学报告最新纳米科学与技术研究
清华大学化学系段昊泓
自然科研论文编辑服务
加州大学洛杉矶分校
上海纽约大学William Glover
南开大学化学院周其林
课题组网站
X-MOL
北京大学分子工程苏南研究院
华东师范大学分子机器及功能材料
中山大学化学工程与技术学院
试剂库存
天合科研
down
wechat
bug