tbuckley/cabot-search huggingface dataset:
Medical model of care needs updating, say experts
Authors: Gareth Iacobucci
Journal: BMJ (2018)

The NHS should shift its focus away from the medical model of care and place more emphasis on tackling social determinants of health, a panel of experts has said.

An overemphasis on medical care would not defeat “the five giants” of want, disease, ignorance, squalor, and idleness that the NHS and the welfare state were founded to tackle, said speakers at the 2018 Nuffield Trust Health Policy Summit on 1 March.

The panel—consisting of Jonathon Tomlinson, a GP in inner city London, Nick Timmins, senior associate at …
Call for new impetus to tackle TB across Europe
Authors: Rory Watson
Journal: BMJ (2018)

The number of new tuberculosis (TB) cases in Europe is falling by just over 4% a year. But this trend is not fast enough to meet the international goal of ending the epidemic by 2030, according to a new report by the European Centre for Disease Prevention and Control (ECDC) and the WHO Regional Office for Europe.1

After reaching a peak in 1999, the incidence of TB in the 53 countries of the WHO European region has consistently decreased. The average annual decline between 2007 and 2016 was 4.3%, with 4.4% recorded between …
Identification of ALDH2 Interacting Proteins by Chemical Crosslinking, Co-Immunoprecipitation and Mass Spectrometry
Authors: Jutaro Fukumoto, Helena Hernández-Cuervo, Venkata Ramireddy Narala, Sahebgowda S. Patil, Ramani Soundararajan, Matthew Alleyn, Mason T. Breitzig, Richard F. Lockey, Narasaiah Kolliputi
Journal: Journal of Allergy and Clinical Immunology (2018)
Active Bone Marrow With Focal FDG Accumulation Mimicking Bone Metastasis With a Case of Early Esophageal Cancer
Authors: Chio Okuyama, Naomi Sasaki, Motoki Nishimura, Shigenori Matsushima, Rika Yoshimatsu
Journal: Clinical Nuclear Medicine (2018)

A 68-year-old man underwent F-FDG PET/CT for the staging of esophageal carcinoma discovered by a medical checkup. Increased focal accumulation in some vertebrae, right humerus, and right femoral bone was noted on FDG-PET, whereas CT showed relatively high attenuation, and MRI showed hypointense lesions on T1- and T2-weighted imaging. A bone biopsy revealed mildly hypercellular bone marrow in the thoracic spine with FDG accumulation and markedly hypocellular bone marrow in the pelvic bone without an increased uptake. InCl scintigraphy showed a similar distribution and confirmed the diagnosis of bone marrow reconversion.
Glypican 3 (GPC3) expression in a lethal subgroup of refractory cisplatin-resistant testicular germ cell tumor (TGCT).
Authors: Jad Chahoud, Miao Zhang, Song-Chang Lin, Sue-Hwa Lin, Shi-Ming Tu
Journal: Journal of Clinical Oncology (2018)

559 Background: The oncofetal protein GPC3 has been tested as a therapy target. Early phase clinical trials established the safety and efficacy of anti-GPC3 chimeric antigen receptor modified T cells in patients with refractory or relapsed GPC3+ hepatocellular carcinoma. In TGCT, GPC3 is preferentially expressed at presentation in certain germ cell histological phenotypes (yolk sac tumor [YST], choriocarcinoma), but not in others (embryonal carcinoma, teratoma, seminoma). The aim of this study is to evaluate GPC3 expression in a lethal subgroup of refractory cisplatin-resistant TGCT. Methods: We retrospectively evaluated 615 patients diagnosed with TGCT from January 2000 to December 2010. We identified patients who died from their TGCT. The histologic makeup of primary tumors, next-generation sequencing data and the clinical course of disease were determined for each patient. We prospectively evaluated GPC3 expression by immunohistochemistry (IHC) using a mouse monoclonal antibody (YP7), on tumor tissue from these patients with lethal, heavily pretreated, cisplatin-resistant TGCT. Results: We identified seven patients with fatal and cisplatin-resistant TGCT, with a median age of 30 (28-50) years and a median number of prior therapies of 5 (2-8), including 3 patients who received high-dose chemotherapy with autologous stem-cell transplant. The prospectively collected samples were from different sites of metastasis: lymph nodes (n = 4), peritoneal carcinomatosis (n = 2), and lung (n = 1). The tissue histology comprised YST (n = 2), YST + choriocarcinoma (n = 1), YST + teratoma (n = 1), teratoma (n = 1), and somatic transformation (n = 2). No consistent genetic aberration was detected. The viable germ cell tumor components comprising YST and choriocarcinoma (n = 4) stained strongly positive in a membranous distribution for GPC3. While samples with teratoma and somatic transformation histology (n = 3) did not stain for GPC3. Conclusions: Potentially lethal, heavily pretreated, cisplatin-resistant viable germ cell tumors have enhanced expression of GPC3. Targeted therapy directed against GPC3 could benefit patients harboring such tumors and further investigation is of value.
I am a Malaysian citizen, contemplating going to either the UK or the Republic of Ireland to study medicine. Is a UK degree recognised in the Republic of Ireland, and vice versa? By that I mean, would one have to sit for any special exams before seeking a job in the other country?
Authors: Jim Sherifi
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>
EVALUATION OF HIV-ASSOCIATED DYSPNEA USING CARDIAC MAGNETIC RESONANCE CARDIOPULMONARY EXERCISE TESTING (CMR-CPET)
Authors: Sadeer G. Al-Kindi, Rahul Thomas, Amer Alaiti, Ben Ravaee, Trevor Jenkins, Steven Sawicki, Nicole Seiberlich, Wei-Ching Lo, Evelyn Watson, Christopher Longenecker, Grace McComsey, Brian Hoit, Orlando Simonetti, Sanjay Rajagopalan
Journal: Journal of the American College of Cardiology (2018)
High Proportions of Coexisting Aortic Dilations Call for Total Aortic Scan
Authors: Lasse M. Obel, Axel C. Diederichsen, Flemming H. Steffensen, Lars Frost, Jess Lambrechtsen, Martin Busk, Grazina Urbonaviciene, Kenneth Egstrup, Lars M. Rasmussen, Jes S. Lindholt
Journal: Journal of the American College of Cardiology (2018)
Abstract 037: Cost-effectiveness of Financial Incentives for Improving Diet Through Medicare and Medicaid
Authors: Yujin Lee, Dariush Mozaffarian, Yue Huang, Junxiu Liu, Stephen Sy, Parke E Wilde, Shafika Abrahams-Gessel, Thiago V Jardim, Thomas A Gaziano, Renata Micha
Journal: Circulation (2018)

Background: While economic incentives through health insurance are being considered to promote healthy behaviors, little is known about health or financial impacts of incentivizing diet, a leading risk factor for CVD. We estimated health and economic impacts of programs to incentivize healthful foods through Medicare and Medicaid over a 5, 10, and 20 y horizon. Methods: A validated microsimulation model, CVD PREDICT, was used to estimate reductions in CVD events, gains in quality-adjusted life-years (QALYs), costs, and cost-effectiveness of two policy scenarios within Medicare and Medicaid: (1) 20% subsidy on fruits and vegetables (F&amp;V), and (2) 20% subsidy on broader healthful foods including F&amp;V, whole grains, nuts/seeds, seafood and plant-based oils. Model inputs included national demographic and dietary data from NHANES 2009-2014, policy effects from pricing meta-analyses, diet-disease effects from meta-analyses, and policy costs including program and healthcare costs, inflated to constant 2017 US dollars and discounted at 3% annually. Productivity gains were conservatively excluded. Results: Both incentive programs were cost-effective from a healthcare (government affordability) perspective ( Table ). Over 20 y, a 20% F&amp;V subsidy could prevent 1.24M CVD events; while a broader 20% healthful food subsidy could prevent 1.91M CVD events. Incremental cost-effectiveness ratios for the F&amp;V program ranged from $19,773/QALY for dual eligible to $26,862/QALY for Medicaid beneficiaries; and for the broader healthful food program, from $9,020/QALY for dual eligible to $13,484/QALY for Medicare beneficiaries. Findings were robust to a range of sensitivity analyses; within Medicare, the incentive program was more cost-effective among individuals with lower income. These incentive programs were also cost-effective at 5 and 10 y (not shown). Conclusions: Economic incentives for healthier foods through either Medicare or Medicaid could generate substantial health gains and healthcare cost savings.
Balancing exercise‐induced weight loss with protein caloric requirement remains a challenge in overweight patients with cirrhosis
Authors: Amritpal Dhaliwal, Jenny Towey, Geoffrey Haydon, Ahmed M. Elsharkawy, Matthew J. Armstrong
Journal: Hepatology (2018)

Potential conflict of interest: Nothing to report. To the Editor: We read with interest the single‐arm 16‐week intervention study by Berzigotti et al., in which diet and moderate‐intensity exercise reduced body weight and hepatic venous pressure gradients in overweight patients with portal hypertension.1 The once‐weekly exercise sessions were tailored to a modest Borg Rating of Perceived Exertion Scale of 10‐12 (able to hold a conversation), and on average patients walked for 1.1 hours per day. However, the fact that almost two thirds of the cohort declared a completely sedentary lifestyle at baseline highlights a significant increase in energy expenditure from their baseline. With this in mind, the authors' target protein intake of only 0.8 g/kg daily appears suboptimal for preventing protein catabolism and maintaining muscle mass and functionality, especially when the desirable intake of protein in a stable patient with cirrhosis is consistently reported as 1.2‐1.5 g/kg daily.2 Muscle stores a large proportion of amino acids and proteins, which are mobilized in catabolic conditions, such as cirrhosis. Patients with stable cirrhosis exhibit an increased requirement for protein and are prone to rapid protein wasting in periods of metabolic stress, fasting, or reduced caloric intake. Unsurprisingly, protein caloric malnutrition occurs in 50%‐90% of patients with cirrhosis, and the resultant muscle wasting ("sarcopenia") is related to a higher rate of morbidity and mortality in patients with cirrhosis.3 Even though Berzigotti and colleagues reassuringly highlighted that there was no significant impact of the lifestyle intervention on lean mass at 16 weeks, there were no measures of skeletal muscle mass or recorded clinical outcomes at 6‐month follow‐up in order to exclude any longer‐term adverse effects. Furthermore, serial bioimpedance measurements have limitations in this setting as their accuracy is dependent on the absence of diuretics, fluid shifts, and retention, which can be difficult to exclude without imaging. Indeed, the authors report that one participant was able to stop spironolactone as result of the resolution of peripheral edema. At a minimum, measures of mid‐arm muscle circumference (mass change) and handgrip strength (functional change) would enable a more comprehensive assessment to rule out any deleterious effects of strict lifestyle interventions on muscle mass and functionality.4 Due to the rise in the coexistence of obesity and cirrhosis, we commend the authors on their innovative study to assess the safety of intense lifestyle interventions in this setting. However, striking a safe balance between lifestyle‐induced weight loss and nutritional (protein caloric) requirements remains a challenge in overweight patients with cirrhosis.
Hepatic stellate cell–derived platelet‐derived growth factor receptor‐alpha‐enriched extracellular vesicles promote liver fibrosis in mice through SHP2
Authors: Enis Kostallari, Petra Hirsova, Alena Prasnicka, Vikas K. Verma, Usman Yaqoob, Nicha Wongjarupong, Lewis R. Roberts, Vijay H. Shah
Journal: Hepatology (2018)

Liver fibrosis is characterized by the activation and migration of hepatic stellate cells (HSCs), followed by matrix deposition. Recently, several studies have shown the importance of extracellular vesicles (EVs) derived from liver cells, such as hepatocytes and endothelial cells, in liver pathobiology. While most of the studies describe how liver cells modulate HSC behavior, an important gap exists in the understanding of HSC‐derived signals and more specifically HSC‐derived EVs in liver fibrosis. Here, we investigated the molecules released through HSC‐derived EVs, the mechanism of their release, and the role of these EVs in fibrosis. Mass spectrometric analysis showed that platelet‐derived growth factor (PDGF) receptor‐alpha (PDGFRα) was enriched in EVs derived from PDGF‐BB‐treated HSCs. Moreover, patients with liver fibrosis had increased PDGFRα levels in serum EVs compared to healthy individuals. Mechanistically, in vitro tyrosine720‐to‐phenylalanine mutation on the PDGFRα sequence abolished enrichment of PDGFRα in EVs and redirected the receptor toward degradation. Congruently, the inhibition of Src homology 2 domain tyrosine phosphatase 2, the regulatory binding partner of phosphorylated tyrosine720, also inhibited PDGFRα enrichment in EVs. EVs derived from PDGFRα‐overexpressing cells promoted in vitro HSC migration and in vivo liver fibrosis. Finally, administration of Src homology 2 domain tyrosine phosphatase 2inhibitor, SHP099, to carbon tetrachloride–administered mice inhibited PDGFRα enrichment in serum EVs and reduced liver fibrosis. Conclusion: PDGFRα is enriched in EVs derived from PDGF‐BB‐treated HSCs in an Src homology 2 domain tyrosine phosphatase 2–dependent manner and these PDGFRα‐enriched EVs participate in development of liver fibrosis. (Hepatology 2018;68:333‐348).
Government calls for relaxation of Working Time Directive in NHS
Authors: Helen Jaques
Journal: BMJ (2013)

Regulation of doctors’ hours should be repatriated to the United Kingdom, the prime minister, David Cameron, has said, as ministers reveal plans to limit the NHS’s application of European working regulations.

Doctors’ organisations are split on whether harmonisation of doctors’ hours across Europe benefits or hinders trainees. Surgeons believe that the European Working Time Directive should be relaxed, but the BMA argues that the directive protects trainees.

In a speech last week on the UK’s place in the European Union, Cameron argued that member states should have more power to legislate independently.1 One of the principles he set out in his speech was that power must be able “to flow back to member states, not just …
The Strategy of PIKing a Target: What Is AKTually Most Effective?
Authors: Carlotta Costa, Ana Bosch
Journal: Clinical Cancer Research (2018)

Breast and gynecologic cancers harboring PIK3CA mutations showed no significant responses to AZD5363, a pan-AKT catalytic inhibitor, in contrast with previous in vitro data showing activity of the drug in this subset of cancers. These results raise the question of how to select the most accurate predictive biomarkers of response. Clin Cancer Res; 24(9); 2029-31. ©2018 AACRSee related article by Banerji et al., p. 2050.
Vascular Anastomotic Workshop
Authors: David Bosanquet
Journal: BMJ (2010)

The Vascular Anastomotic Workshop is a two day theoretical and practical course looking at common and frequently performed vascular operations. It is ideal for junior surgeons, from foundation year 1 through to registrar, who are interested in vascular surgery as a career or are working as part of a vascular firm.

Held annually at the Royal Glamorgan Hospital, Llantrisant, South Wales, the course costs £100. This covers lectures from a variety of speakers, life-like practical models on which to practise surgical skills, lunches, an evening meal on the first night, accommodation, and a course handbook. The course is sponsored by various drug companies, which keeps the cost low.

I did this course during year 2 of my core surgical training, while I was working on a vascular firm.

In short, for the opportunity to improve my operating skills and to learn more about the fundamentals of vascular surgery. …
Incidence and seasonality of respiratory syncytial virus hospitalisations in young children in Denmark, 2010 to 2015
Authors: Martin T. Jepsen, Ramona Trebbien, Hanne Dorthe Emborg, Tyra G. Krause, Kristian Schønning, Marianne Voldstedlund, Jens Nielsen, Thea K. Fischer
Journal: Eurosurveillance (2018)

For future decisions on respiratory syncytial virus (RSV)-vaccination strategies and implementation into national immunisation-programmes, we used national registry data (hospitalisation, microbiology and vital statistics) to determine the age-specific incidence and direct medical costs of annual RSV-associated admissions in children &lt; 5 years-old for the period of 2010–2015. We identified ca 2,500 RSV-associated hospitalisations annually amounting to total direct medical-costs of ca EUR 4.1 million per year. The incidence of RSV-associated hospitalisations peaked in infants 1–2 months of age followed by infants 2–3 months of age, and infants &lt; 1 month of age, respectively. Infant boys were at higher risk of severe RSV infection as compared to infant girls: male-to-female ratio peaked with 1.4 at four months of age and gradually levelled out with increasing age to 1.0 at 4 years of age. Five RSV-associated deaths were identified. Our findings demonstrate that in a western country as Denmark, RSV constitutes a considerable burden on childhood health. Furthermore, the best approach to reduce the high incidence of RSV-associated hospitalisations in young infants &lt; 3 months of age may be maternal vaccination due to general challenges in achieving sufficient and protective immune responses in young infants.
An OX40/OX40L interaction directs successful immunity to hepatitis B virus
Authors: Jean Publicover, Anuj Gaggar, Jillian M. Jespersen, Ugur Halac, Audra J. Johnson, Amanda Goodsell, Lia Avanesyan, Stephen L. Nishimura, Meghan Holdorf, Keith G. Mansfield, Joyce Bousquet Judge, Arya Koshti, Michael Croft, Adil E. Wakil, Philip Rosenthal, Eric Pai, Stewart Cooper, Jody L. Baron
Journal: Science Translational Medicine (2018)

Effective immunity and therapeutic targets are identified with a model of hepatitis B virus clearance and persistence.
Oxford emergency/on-call radiology course
Authors: Fiona Pathiraja
Journal: BMJ (2012)

The idea of being the only radiologist on call overnight fills new radiology trainees with terror. What if I miss a bleed? When do I call my consultant? Do I routinely do ultrasound scans for torsion? The Oxford emergency/on-call radiology course aims to answer these questions and to provide radiology trainees with the confidence to face their first on-call shift. It is specifically designed to provide an overview of and to recap the key things not to miss when on call in emergency radiology.

If you want to be prepared for your first on-call shift as a radiology registrar or want to refresh your general emergency radiology, this is the course for you. Course delegates were mainly new radiology registrars but also included emergency medicine and surgical trainees. Nearly all UK radiology training programmes were …
Prevalence and Prognostic Impact of Diabetes in Takotsubo Syndrome: Insights From the International, Multicenter GEIST Registry
Authors: Thomas Stiermaier, Francesco Santoro, Ibrahim El-Battrawy, Christian Möller, Tobias Graf, Giuseppina Novo, Andrea Santangelo, Enrica Mariano, Francesco Romeo, Pasquale Caldarola, Mario Fanelli, Holger Thiele, Natale Daniele Brunetti, Ibrahim Akin, Ingo Eitel
Journal: Diabetes Care (2018)

OBJECTIVE In view of low prevalence rates, diabetes is discussed as a protective factor for the occurrence of Takotsubo syndrome (TTS). Furthermore, it was associated with improved outcome in a small single-center analysis. Therefore, this study assessed the prevalence and prognostic relevance of concomitant diabetes in TTS. RESEARCH DESIGN AND METHODS A total of 826 patients with TTS were enrolled in an international, multicenter, registry-based study (eight centers in Italy and Germany). All-cause mortality was compared between patients with diabetes and patients without diabetes, and the independent predictive value of diabetes was evaluated in multivariate regression analysis. RESULTS The prevalence of diabetes was 21.1% (n = 174). TTS patients with diabetes were older (P &amp;lt; 0.001), were more frequently male (P = 0.003), had a higher prevalence of hypertension (P &amp;lt; 0.001), physical triggers (P = 0.041), and typical apical ballooning (P = 0.010), had a lower left ventricular ejection fraction (P = 0.008), had a higher rate of pulmonary edema (P = 0.032), and had a longer hospital stay (P = 0.009). However, 28-day all-cause mortality did not differ between patients with diabetes and patients without diabetes (6.4% vs. 5.7%; hazard ratio [HR] 1.11 [95% CI 0.55–2.25]; P = 0.772). Longer-term follow-up after a median of 2.5 years revealed a significantly higher mortality among TTS patients with diabetes (31.4% vs. 16.5%; P &amp;lt; 0.001), and multivariate regression analysis identified diabetes as an independent predictor of adverse outcome (HR 1.66 [95% CI 1.16–2.39]; P = 0.006). CONCLUSIONS Diabetes is not uncommon in patients with TTS, is associated with increased longer-term mortality rates, and is an independent predictor of adverse outcome irrespective of additional risk factors.
ECHOCARDIOGRAPHIC PREDICTORS OF MORTALITY IN WOMEN WITH HEART FAILURE WITH REDUCED EJECTION FRACTION
Authors: Ingrid Lundorff, Morten Sengeløv, Peter Jørgensen, Sune Pedersen, Daniel Modin, Niels Eske Bruun, Thomas Hansen, Jan Jensen, Tor Biering-Sorensen
Journal: Journal of the American College of Cardiology (2018)
<i>What are my chances of getting a job in the UK if I pass the PLAB test?</i>
Authors: Douglas Buchanan
Journal: BMJ (2004)

<i>Got 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 (www.bmjcareers.com/advicezone) 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</i>
I had a caution for shoplifting several years ago. It is now affecting my applications for a new job as I need to submit a criminal record certificate, which compromises my chances of getting a job. Please advise what to do.
Authors: Carl Gray
Journal: BMJ (2004)

Have a career or related problem that needs answering? Can't find the right person to point you in the right direction? Log on to the Advice Zone ( www.bmjcareers.com/advicezone ) 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.