tbuckley/cabot-search huggingface dataset:
I am approaching my third year of specialist training in endocrinology and diabetes. I feel I've made the wrong choice and want to change to gastroenterology. How feasible is this? Would the year of high intensity medicine at specialist registrar level be counted for another number?
Authors: Rebecca Fitzgerald
Journal: BMJ (2006)

Have a career or related problem that needs answering? Can9t find the right person to point you in the right direction? Log on to the Advice Zone for reliable medical careers advice. You can post a question or see if one of our 300 advisers has already answered a similar question. Here is a selection of questions and answers posted on the site. <b>www.bmjcareers.com/advicezone</b>
INCIDENCE, PREDICTORS, CHARACTERISTICS, MANAGEMENT AND OUTCOMES OF CORONARY PERFORATIONS
Authors: Arslan Shaukat, Yader Sandoval, Larissa Stanberry, Ross Garberich, Amy McMeans, M. Nicholas Burke, Ivan Chavez, Mario Gossl, Timothy Henry, Daniel Lips, Michael Mooney, Anil Poulose, Paul Sorajja, Jay Traverse, Yale Wang, Steven Bradley, Emmanouil Brilakis
Journal: Journal of the American College of Cardiology (2018)
PD-1 Blockade and CD27 Stimulation Activate Distinct Transcriptional Programs That Synergize for CD8+ T-Cell–Driven Antitumor Immunity
Authors: Sarah L. Buchan, Mohannad Fallatah, Stephen M. Thirdborough, Vadim Y. Taraban, Anne Rogel, Lawrence J. Thomas, Christine A. Penfold, Li-Zhen He, Michael A. Curran, Tibor Keler, Aymen Al-Shamkhani
Journal: Clinical Cancer Research (2018)

PD-1 checkpoint blockade has revolutionized the field of cancer immunotherapy, yet the frequency of responding patients is limited by inadequate T-cell priming secondary to a paucity of activatory dendritic cells (DC). DC signals can be bypassed by CD27 agonists, and we therefore investigated if the effectiveness of anti-PD-1/L1 could be improved by combining with agonist anti-CD27 monoclonal antibodies (mAb).
Sleep medicine course
Authors: Jasvinder Singh
Journal: BMJ (2012)

Sleep, why do we need it? What purpose does it serve in humans? Why does it vary between people? How do we diagnose and treat sleep disorders? These questions intrigue me. Unfortunately, there is a dearth of courses in the United Kingdom covering this interesting field of medicine—but one exception is the sleep medicine course in Edinburgh. 

One of a kind in the UK and possibly Europe, this course has something for everyone who has an interest in or deals with sleep and its disorders and sleep technology. It is aimed at anyone with a medical background who has an interest in sleep medicine or is involved in the diagnosis and management of adult sleep disorders. The course is primarily aimed at sleep physicians, respiratory and general physicians, psychiatrists, psychologists, physiologists, physiotherapists, nurses, anaesthetists, neurologists and other allied health professionals, general practitioners, ear, nose, and throat surgeons, and dentists. 

I am a higher specialty trainee in psychiatry and have had …
Abstract P1-03-12: The ratio of omega-3 to omega-6 PUFAs impact cancer cell phenotype in the tumor microenvironment
Authors: L Winikka, D Quach, B Harlow, A Brenner, N Munoz, S Tiziani, L deGraffenried
Journal: Cancer Research (2018)

Abstract Background: Studies have shown that obesity is associated with a worse breast cancer prognosis. Besides the effect of different stages of diagnosis and co-morbidities, recent data from our published in vitro and retrospective studies suggests that this phenomenon may occur because the obese state promotes a more aggressive cancer phenotype through the cyclooxygenase (COX-2) pathway and its production of prostaglandin E2 (PGE2). The metabolization of omega-3 fatty acids decreases the production of PGE2, and have been shown to have potential benefit to cancer patients by decreasing inflammation-related signaling. Our previous clinical trial showed mixed results in the effect of omega-3 PUFA supplements on PGE2 production in post-menopausal obese women. This led us to the hypothesis that the ratio of omega-3 to omega-6 PUFAs have differential effects on cell types within the tumor microenvironment, impacting cancer cell phenotype. Approach: In vitro experiments, including wound-healing assays to determine motility, and clonogenic assays to determine overall survival, were performed to determine if exposure to higher ratios of omega-6 to omega-3 fatty acids lead to a more aggressive cancer phenotype. MCF-7 breast cancer cells were treated with the following fatty acid ratios of omega-6 (arachidonic acid (AA)) to omega-3 (eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)): 46:1, 20:1, 10:1, and 1.3:1. The wound-healing assays showed greater motility with higher ratios of omega-6 to omega-3 fatty acids conditions and the clonogenic assays showed greater survival with the higher ratios. Conclusion: These data indicate that lowering ratios of omega-6 to omega-3 fatty acids may lessen the aggressiveness of breast cancer cells and be beneficial to some patients. Studies are on-going to investigate the impact of PUFA ratios on cancer cell phenotype directly, including proliferation and invasion, as well as the indirect effects from modulation of the other cells within the tumor microenvironment, including the macrophages and adipocytes. Citation Format: Winikka L, Quach D, Harlow B, Brenner A, Munoz N, Tiziani S, deGraffenried L. The ratio of omega-3 to omega-6 PUFAs impact cancer cell phenotype in the tumor microenvironment [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P1-03-12.
Providing antiretroviral therapy outside the hospital in a low-resource setting: a pilot study
Authors: Y Kambai Avong, G Ayodele Kayode, B Jatau, E Bosede Avong, V Adekanmbi, A Abimiku, C Olalekan Mensah, P Dakum
Journal: The Lancet Global Health (2018)

BackgroundFor nearly three decades, hospitals have been the only source of antiretroviral therapy (ART) for many people living with HIV. Yet, developing countries with the largest burden of HIV commonly lack the hospitals and health-care workers to care for these patients. In 2013, WHO recommended the use of structures outside hospitals for management of HIV. We piloted a community pharmacy ART model in communities with high HIV prevalence in Nigeria. The purpose was to develop a treatment model that could be expanded into an overarching comprehensive response to HIV management, especially in resource-limited settings with weak health systems.MethodsRegistered community pharmacies linked to participating hospitals were recruited between February 2016 and May 2017. Patients with stable viral loads (≤20 copies/mL) who were willing to have their care devolved to a community pharmacy were referred by trained contact persons at the hospitals. Registered pharmacists at the community pharmacies counselled referred patients and refilled their prescriptions. Biodemographic and clinical data were collected from Feb 25, 2016, to May 31, 2017. The outcome measures were percentage of patients retained in care and adherence to therapy. Mean difference in the viral load at the baseline (≤20 copies/mL) and after 6 months was assessed using a paired sample t-test.Findings26 community pharmacies and 14 hospitals were included in the pilot. 375 patients (median baseline viral load 19 copies/mL [IQR 19–32]; median CD4 count 460 cells/mL [277–648]) had their care devolved to the community pharmacies. After 12 months, almost all the patients (374 [99·7%] of 375) were retained in care and adherence to medication (measured by prescription refill) was 100%. After 6 months of follow-up, 19 patients received results of their second viral load test, showing no significant difference in the mean viral load between baseline and after 6 months (p<0·46).InterpretationWe show that patients can conveniently access ART in community pharmacies linked to hospitals, with no adverse effects on adherence or viral load. The model will be rolled-out to other regions in Nigeria, and could potentially be applied elsewhere.FundingPEPFAR.
Health secretary orders review into use of medical manslaughter
Authors: Gareth Iacobucci
Journal: BMJ (2018)

England’s health secretary, Jeremy Hunt, has announced a review of the application of gross negligence manslaughter in the NHS in the wake of the Hadiza Bawa-Garba case.

The High Court ruling to strike off the trainee paediatrician from the UK medical register has prompted widespread concern among doctors, who claim that Bawa-Garba was scapegoated, given the multiple system failures that led to the death of 6 year old Jack Adcock.1 Bawa-Garba was convicted for manslaughter in 2015,2 and the High Court verdict came after the General Medical Council (GMC) appealed against a medical practitioners tribunal decision to suspend her for 12 months rather than erase her.3

Norman Williams, former president of the Royal College of Surgeons, will lead the review, with support from senior …
H2 Receptor Antagonist Use and Mortality in Pulmonary Hypertension: Insight from the VA-CART Program
Authors: Peter J. Leary, Edward Hess, Anna E. Barón, Kelley R. Branch, Gaurav Choudhary, Catherine L. Hough, Bradley A. Maron, David D. Ralph, John J. Ryan, Ryan J. Tedford, Noel S. Weiss, Roham T. Zamanian, Tim Lahm
Journal: American Journal of Respiratory and Critical Care Medicine (2018)

Definition of abbreviations: CABG = coronary artery bypass graft; H2RA = H2 receptor antagonist; MI = myocardial infarction; PCI = percutaneous coronary intervention; PS = propensity score.Data are mean 6 SD, unless otherwise specified.*Pulmonary vascular resistance [(mean pulmonary artery pressure 2 wedge pressure)/cardiac output] was determined for each participant and then averaged.
Socioeconomic disparities in first stroke incidence, quality of care, and survival: a nationwide registry-based cohort study of 44 million adults in England
Authors: Benjamin D Bray, Lizz Paley, Alex Hoffman, Martin James, Patrick Gompertz, Charles D A Wolfe, Harry Hemingway, Anthony G Rudd
Journal: The Lancet Public Health (2018)

We aimed to estimate socioeconomic disparities in the incidence of hospitalisation for first-ever stroke, quality of care, and post-stroke survival for the adult population of England.In this cohort study, we obtained data collected by a nationwide register on patients aged 18 years or older hospitalised for first-ever acute ischaemic stroke or primary intracerebral haemorrhage in England from July 1, 2013, to March 31, 2016. We classified socioeconomic status at the level of Lower Super Output Areas using the Index of Multiple Deprivation, a neighbourhood measure of deprivation. Multivariable models were fitted to estimate the incidence of hospitalisation for first stroke (negative binomial), quality of care using 12 quality metrics (multilevel logistic), and all-cause 1 year case fatality (Cox proportional hazards).Of the 43·8 million adults in England, 145 324 were admitted to hospital with their first-ever stroke: 126 640 (87%) with ischaemic stroke, 17 233 (12%) with intracerebral haemorrhage, and 1451 (1%) with undetermined stroke type. We observed a socioeconomic gradient in the incidence of hospitalisation for ischaemic stroke (adjusted incidence rate ratio 2·0, 95% CI 1·7-2·3 for the most vs least deprived deciles) and intracerebral haemorrhage (1·6, 1·3-1·9). Patients from the lowest socioeconomic groups had first stroke a median of 7 years earlier than those from the highest (p<0·0001), and had a higher prevalence of pre-stroke disability and diabetes. Patients from lower socioeconomic groups were less likely to receive five of 12 care processes but were more likely to receive early supported discharge (adjusted odds ratio 1·14, 95% CI 1·07-1·22). Low socioeconomic status was associated with a 26% higher adjusted risk of 1-year mortality (adjusted hazard ratio 1·26, 95% CI 1·20-1·33, for highest vs lowest deprivation decile), but this gradient was largely attenuated after adjustment for the presence of pre-stroke diabetes, hypertension, and atrial fibrillation (1·11, 1·05-1·17).Wide socioeconomic disparities exist in the burden of ischaemic stroke and intracerebral haemorrhage in England, most notably in stroke hospitalisation risk and case fatality and, to a lesser extent, in the quality of health care. Reducing these disparities requires interventions to improve the quality of acute stroke care and address disparities in cardiovascular risk factors present before stroke.NHS England and the Welsh Government.
Heart failure with mid‐range ejection fraction in CHARM: characteristics, outcomes and effect of candesartan across the entire ejection fraction spectrum
Authors: Lars H. Lund, Brian Claggett, Jiankang Liu, Carolyn S. Lam, Pardeep S. Jhund, Giuseppe M. Rosano, Karl Swedberg, Salim Yusuf, Christopher B. Granger, Marc A. Pfeffer, John J.V. McMurray, Scott D. Solomon
Journal: European Journal of Heart Failure (2018)
30 DAY RESULTS OF THE SCOUT I STUDY IN PATIENTS WITH SEVERE TRICUSPID REGURGITATION (TR)
Authors: Christopher Meduri, Charles Davidson, Scott Lim, Tamim Nazif, Mark Ricciardi, Vivek Rajagopal, Gorav Ailawadi, Mani Vannan, James Thomas, Dale Fowler, Stuart Rich, Susheel K. Kodali, Rebecca T. Hahn
Journal: Journal of the American College of Cardiology (2018)
A bilayer swellable drug-eluting ureteric stent: Localized drug delivery to treat urothelial diseases
Authors: Wei Shan Lim, Kenneth Chen, Tsung Wen Chong, Gordon Minru Xiong, William R. Birch, Jisheng Pan, Bae Hoon Lee, Pei Shan Er, Abhijit Vijay Salvekar, Subbu S. Venkatraman, Yingying Huang
Journal: Biomaterials (2018)
Abstract P020: Atrial Fibrillation and White Matter Microstructural Integrity: The Atherosclerosis Risk in Communities Neurocognitive Study
Authors: Iris Yuefan Shao, Melinda Power, Thomas Mosley, Rebecca Gottesman, Lin Chen, Faye Norby, Elsayed Soliman, Alvaro Alonso
Journal: Circulation (2018)

Background: Evidence suggests atrial fibrillation (AF) is associated with increased risk of cognitive decline and dementia, even in the absence of stroke. Pathways such as AF-induced brain hypoperfusion and small vessel disease resulting in white matter abnormalities may also compromise cerebrovasculature and brain tissue, which would lead to cognitive impairment and dementia. However, mechanisms responsible for the association between AF and cognitive impairment independent of stroke and cerebral infarcts remain relatively unexplored. The study aims to assess the cross-sectional association between prevalent AF and white matter microstructural integrity (WMMI) as a marker for cerebrovascular disease. Methods: We performed a cross-sectional analysis of 1937 participants attending the ARIC-Neurocognitive Study (ARIC-NCS) in 2011-2013 that were either black or white and with brain magnetic resonance imaging (MRI). Prevalent AF was defined by a history of AF based on study ECG and hospitalization record. WMMI was defined using regional average fractional anisotropy and mean diffusivity from Diffusion Tensor Imaging measurements in the MRI. We excluded participants with a prior history of stroke or cerebral infarct. A multivariable regression model was used to assess the association between AF and WMMI measures. Results: Among 1943 participants (mean age = 76 years, 28% black, 60% female), 7% (N= 133) had prevalent AF. After multivariable adjustment, prevalence of AF was not associated with WMMI measurements (Table). Conclusion: In a community-based study, prevalent AF was not independently associated with WMMI in the absence of stroke or cerebral infarct. However, the reduced sample size of the AF population as well as the cross-sectional study design are important limitations. Further longitudinal studies are needed to investigate prospectively the association of AF with early markers of white matter disease.
Abstract P1-02-03: The Y537S ESR1 mutation carries unique metabolomics profiling in breast cancer
Authors: G Gu, B Piyarathna, C Coarfa, L Ellis, S Ando', S Fuqua
Journal: Cancer Research (2018)

Abstract Background: Estrogen receptor (ESR1) mutations occur at a high frequency in metastatic breast tumors in patients treated with hormonal therapy in the metastatic setting. We do not know if these mutations changed metabolomics and whether these metabolomics change could affect metastasis. Experimental design and methods: We generated ESR1 Y537S homozygous mutations using CRISPR Casp-9 technology. Globe metabolites screening was performed using 6550 Agilent QTOF instrument. Athymic mice were used in tumor xenograft studies. Affymetrix microarrays were performed to compare gene expression changes in Y537S mutant compared with parental cells. Enriched metabolite pathways and gene expression integrated analysis was analyzed by using online analysis tool http://www.metaboanalyst.ca. Results: We generated CRISPR ESR1 Y537S mutation homozygous knock-in clones in MCF-7 cells. In vivo experiments revealed that mutant cells are dominant drivers of metastasis. Transcriptome profiling revealed elevated expression of Hallmark pathways, including EMT and estrogen-regulated gene expression. We performed globe metabolites screening using MCF-7 Y537S and MCF-7 parental and identified 134 metabolites. Serum starvation media was used and estrogen was used as control for both cell lines. As we expected estrogen treatment induced metabolites changes in parental cells. However, metabolites in mutant cells were not changed significantly under estrogen treatment. Interestingly, metabolites in the mutant cells at baseline were remarkably upregulated (78 out of 134 identified total metabolites) indicating mutant cells in serum starvation condition had significantly different metabolomics compared with parental cells. Top upregulated pathways include protein biosynthesis, betaine metabolism and ammonia recycling. Integration of microarray gene expression and metabolites reviewed several metabolomics pathways significantly changed in mutant compared with parental cells including for example aminoacyl-tRNA biosynthesis, arginine and proline metabolism and alanine, aspartate and glutamate metabolism. Conclusion: The Y537S ER mutation is a driver of distant metastasis in ER-positive breast cancer cells. Y537S ER mutant had globe changes of metabolites expression which was confirmed by integrated analysis combining microarray gene expression. The roles of these metabolites need to be studied to correlate with metastasis. Enzymes responsible for converting these metabolites changes could be served as potential therapeutic targets. Citation Format: Gu G, Piyarathna B, Coarfa C, Ellis L, Ando' S, Fuqua S. The Y537S ESR1 mutation carries unique metabolomics profiling in breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P1-02-03.
EVALUATION OF THE PERFORMANCE OF THE WORLD HEART FEDERATION CRITERIA FOR ECHOCARDIOGRAPHIC DIAGNOSIS OF RHEUMATIC HEART DISEASE: DATA FROM THE PROVAR STUDY
Authors: Bruno Ramos Nascimento, Maria do Carmo Nunes, Craig Sable, Emilly M. Lima, Enrico Antonio Colosimo, Rodrigo C.P. Reis, Clara L. Fraga, Allison R. Tompsett, Antonio Ribeiro
Journal: Journal of the American College of Cardiology (2018)
99MTC-DURAMYCIN IMAGING DETECTS DOXORUBICIN CARDIAC INJURY BEFORE ONSET OF VENTRICULAR DYSFUNCTION
Authors: Takehiro Nakahara, Artiom D. Petrov, Takashi Tanimoto, Nezam Haider, Navneet Narula, Farhan Chaudhry, Jeffrey A. Mattis, Brian D. Gray, Koon Yan Pak, Gagan Sahai, Anry Terersten, Aarti Bhardwaj, Partho Sengupta, Marc R. Dweck, Harry Strauss, Jagat Narula
Journal: Journal of the American College of Cardiology (2017)
Organ Dysfunction After Surgery in Patients Treated With Individualized or Standard Blood Pressure Management—Reply
Authors: Emmanuel Futier, Bruno Pereira, Samir Jaber
Journal: JAMA (2018)

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AORTIC VALVE STENOSIS IN PATIENTS WITH EXTREMELY ELEVATED LIPOPROTEIN(A) LEVELS
Authors: Madan Poudel, Stanley Kirana, Klaus-Peter Mellwig, Dieter Horstkotte, Nikola Bogunovic, Lothar Faber, Cornelius Knabbe, Dennis Hinse, Odile Sauzet, Dana Stoyanova, Frank Van Buuren
Journal: Journal of the American College of Cardiology (2018)
Clinical leaders are more positive than frontline staff about hospitals’ culture of patient safety
Authors: Matthew Limb
Journal: BMJ (2015)

More clinical leaders than frontline clinicians have a positive view of teamwork and the climate of patient safety in hospitals, a European study shows.

The study confirms previous research findings that quality management systems are a “promising factor” in enhancing the safety of patients.

The study covered 210 acute hospitals in seven European countries: the Czech Republic, France, Germany, Poland, Portugal, Spain, and Turkey. The …
NHS saves £270 000 in three cases after court rules law firm advised patients wrongly
Authors: Clare Dyer
Journal: BMJ (2018)

The NHS could be on course to save millions of pounds in legal fees after winning three test cases in which it challenged solicitors’ decisions to advise clinical negligence claimants to switch their funding from legal aid to “no win, no fee” deals.

The Court of Appeal has ruled that Irwin Mitchell, the law firm which advised the switch, cannot collect a success fee on top of its normal costs, nor get back a premium paid to insure against the risk of losing—a total saving of £270 000 (€308 000; $378 000) in the three cases. Dozens of similar cases, in which clients were advised to switch from legal aid before new rules came into force in April 2013, are in the pipeline.

No win, no fee deals, formally known …
MPs call for renegotiation of working time rules
Authors: Helen Jaques
Journal: BMJ (2012)

MPs have called for the government to renegotiate the terms of the European Working Time Directive and to seek practical ways that hospitals and doctors can get around the regulations.

In a debate held by the Backbench Business Committee, MPs heard how the “well meaning” working time regulations are not achieving their aim of improving doctors’ work-life balance and are having a negative effect on junior doctors’ training, patients’ safety, and NHS finances.

Given that members of the European Parliament cite the Working Time Directive as “the least popular piece of legislation ever introduced” by the European Union and that 16 of the 27 EU member states have sought to opt out, the United Kingdom should lead a majority of member states in demanding reform of the legislation, said Andrea Leadsom, Conservative …