tbuckley/cabot-search huggingface dataset:
“Them and us” attitude hinders trainees’ leadership development
Authors: Matthew Limb
Journal: BMJ (2015)

Traditional professional hierarchies, abusive behaviour, and a “them and us” attitude are persistent barriers to the development of medical trainees as leaders, researchers say.

Lisi Gordon of the School of Medicine at the University of Dundee and colleagues say they gained fresh insight into the way “leadership and followership” were experienced in NHS workplaces by analysing medical trainees’ personal stories. Their examination of interviews with 65 trainees highlighted the factors that can help or impede their development as medical leaders and identified barriers in the wider health system. The research underlined the persistence of traditional medical and interprofessional hierarchies and certain “abusive” types of behaviour.

Gordon told BMJ Careers, “Sometimes the hierarchies or the systems, structures, or protocols don’t necessarily allow trainees to take on leadership as much as they would like. But the …
False-Positive 18F-FDG PET/CT Due to Filgrastim That Induced Extramedullary Liver Hematopoiesis in a Burkitt Lymphoma
Authors: Anna Margherita Maffione, Lucia Rampin, Paolini Rossella, Sara Pecori, Patrick M. Colletti, Domenico Rubello
Journal: Clinical Nuclear Medicine (2018)

We report a case of Burkitt lymphoma with largely extranodal disease localizations at staging. Chemotherapy was given, thus obtaining a complete metabolic response in all previous disease sites as shown at a control PET, however associated to the appearance of new focal uptake areas in the liver; these findings were confirmed at US and MRI. Chemotherapy determined also neutropenia that was treated by filgrastim, followed by a prompt and important medullary response. Liver biopsy revealed extramedullary hematopoiesis, probably filgrastim induced. Filgrastim administration may cause false-positive findings in the liver at FDG PET.
Ventricular Fibrillation Conversion Testing After Implantation of a Subcutaneous Implantable Cardioverter Defibrillator
Authors: Daniel J. Friedman, Craig S. Parzynski, E. Kevin Heist, Andrea M. Russo, Joseph G. Akar, James V. Freeman, Jeptha P. Curtis, Sana M. Al-Khatib
Journal: Circulation (2018)

Compared with transvenous implantable cardioverter defibrillators (ICDs), subcutaneous (S)-ICDs require a higher energy for effective defibrillation. Although ventricular fibrillation conversion testing (CT) is recommended after S-ICD implantation to ensure an adequate margin between the defibrillation threshold and maximum device output (80J), prior work found that adherence to this recommendation is declining.We studied first-time recipients of S-ICDs (between September 28, 2012, and April 1, 2016) in the National Cardiovascular Database Registry ICD Registry to determine predictors of use of CT, predictors of an insufficient safety margin (ISM, defined as ventricular fibrillation conversion energy >65J) during testing, and inhospital outcomes associated with use of CT. Multivariable logistic regression analysis was used to predict use of CT and ISM. Inverse probability weighted logistic regression analysis was used to examine the association between use of CT and inhospital adverse events including death.CT testing was performed in 70.7% (n=5624) of 7960 patients with S-ICDs. Although deferral of CT was associated with several patient characteristics (including increased body mass index, increased body surface area, severely reduced ejection fraction, dialysis dependence, warfarin use, anemia, and hypertrophic cardiomyopathy), the facility effect was comparatively more important (area under the curve for patient level versus generalized linear mixed model: 0.619 versus 0.877). An ISM occurred in 6.9% (n=336) of 4864 patients without a prior ICD and was more common among white patients and those with ventricular pacing on the preimplant ECG, higher preimplant blood pressure, larger body surface area, higher body mass index, and lower ejection fraction. A risk score was able to identify patients at low (<5%), medium (5% to 10%), and high risk (>10%) for ISM. CT testing was not associated with a composite of inhospital complications including death.Use of CT testing after S-ICD implantation was driven by facility preference to a greater extent than patient factors and was not associated with a composite of inhospital complications or death. ISM was relatively uncommon and is associated with several widely available patient characteristics. These data may inform ICD system selection and a targeted approach to CT.
IDH1 mutations drive an oxygen-sparing metabolic phenotype to permit tumour growth
Authors: Kate Hollinshead, Haydn Munford, Katherine Eales, Cristina Escribano Gonzalez, Alpesh Thakker, Federica Cuozzo, Robert Murren, Christian Ludwig, Daniel Tennant
Journal: Neuro-Oncology (2018)

Since the description of mutations in isocitrate dehydrogenase 1 (IDH1) in adult glial tumours in 2008, many studies have focused on the role of the oncometabolite 2-hydroxyglutarate in determining the pheontype of affected gliomas. However, another aspect of IDH1 activity - its redox-dependency - may also represent an important determinant of IDH1-mutant glioma phenotype. To examine the effect of IDH1 mutations on redox homeostasis, we traced their use of redox-active metabolic pathways using nutrients enriched in the stable isotope, 13C. We found that cells expressing the IDH1 R132H mutant demonstrated enhanced proline synthesis, but that unexpectedly the proline produced was excreted rather than used for biosynthetic processes. As proline synthesis is a highly redox-dependent pathway, we hypothesised that this represented a metabolic response to altered isocitrate metabolism by the IDH1 mutant enzyme. We furthermore showed that metabolic response was dependent on pyrroline 5-carboxylate reductase 1 (PYCR1), and was important for the oxidation of mitochondrial NADH. Consistent with this, knockdown of PYCR1 resulted in a compensatory increase in cell respiration. We therefore show that cells with IDH1 mutations require proline synthesis in order to retain normal TCA cycle activity while using less oxygen. This may mean that IDH1 mutant tumours are in general less hypoxic, and therefore more responsive to treatment.
I would like to change career from specialist registrar in hospital to general practice. I have 24 months of recognised training posts for general practice and have my VTR2 forms completed. Will I be penalised for giving up a hospital career?
Authors: Brian Keighley
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>
Self-Reported Receipt of Advice and Action Taken To Reduce Dietary Sodium Among Adults With and Without Hypertension — Nine States and Puerto Rico, 2015
Authors: Puthiery Va, Cecily Luncheon, Angela M. Thompson-Paul, Jing Fang, Robert Merritt, Mary E. Cogswell
Journal: MMWR Morbidity and Mortality Weekly Report (2018)

Hypertension is a major cardiovascular disease risk factor (1,2). Advice given by health professionals can result in lower sodium intake and lower blood pressure (3).The 2017 Hypertension Guideline released by the American College of Cardiology and the American Heart Association emphasizes nonpharmacologic approaches, including sodium reduction, as important components of hypertension prevention and treatment (4). Data from 50,576 participants in the sodium module of the 2015 Behavioral Risk Factor Surveillance System (BRFSS) in nine states and Puerto Rico were analyzed to determine the prevalence of reported sodium reduction advice and action among participants with and without self-reported hypertension. Among participants with self-reported hypertension, adjusted prevalence of receiving sodium reduction advice from a health professional was 41.9%, compared with 12.8% among participants without hypertension. Among those with hypertension, adjusted prevalence of reported action to reduce sodium intake was 80.9% among participants who received advice and 55.7% among those who did not receive advice. Among participants without hypertension, adjusted prevalence of taking action to reduce sodium intake was 72.7% among those who received advice and 46.9% among those who did not receive advice. The provision of advice on sodium reduction by health professionals is associated with respondent action to watch or reduce sodium intake. Fewer than half of patients with hypertension received this advice from their health professionals, a circumstance that represents a substantial missed opportunity to promote hypertension prevention and treatment.
T follicular helper–like cells contribute to skin fibrosis
Authors: Devon K. Taylor, Nanette Mittereder, Ellen Kuta, Tracy Delaney, Timothy Burwell, Karma Dacosta, Weiguang Zhao, Lily I. Cheng, Charles Brown, Anmarie Boutrin, Xiang Guo, Wendy I. White, Jie Zhu, Huifang Dong, Michael A. Bowen, Jia Lin, Changshou Gao, Li Yu, Madhu Ramaswamy, Marie-Claude Gaudreau, Rob Woods, Ronald Herbst, Gianluca Carlesso
Journal: Science Translational Medicine (2018)

T follicular helper–like cells and IL-21 are drivers of skin fibrosis in systemic sclerosis.
BMA raises concern over discrimination in RCGP exam
Authors: Helen Jaques
Journal: BMJ (2013)

The BMA has written to the Royal College of General Practitioners to express concern over differences between UK and overseas candidates’ pass rates in the college’s membership examination.

The BMA is worried about differential pass rates in the exam’s clinical skills assessment (CSA) component. The chairman of the trainees subcommittee of the BMA’s General Practitioners Committee, Krishna Kasaraneni, said that he had been approached by association members who believed that the CSA discriminated against medical graduates who qualified outside the United Kingdom. 

The subcommittee has suggested that CSA exams be video recorded so that the college could revisit and analyse the examination …
J B Wilson
Authors: Fiona Wilson
Journal: BMJ (2018)

Jack Wilson was born in 1921 in Edinburgh. He went to school at George Watson’s, leaving aged 16, then on to Edinburgh University, where he qualified in 1943. After a six month house appointment at Leith Hospital he was called up for the Royal Navy as a probationary surgeon. He first joined HMS Saladin , a small destroyer that escorted convoys from Milford Haven to Portsmouth. In May 1944 it was involved in Operation Tiger, when an amphibious exercise off Slapton Sands was attacked by German E Boats and hundreds of American troops perished. Jack’s service in the Royal Navy continued in the Bay of Bengal. After the end of the war, he took several jobs as a …
Synthetic design of growth factor sequestering extracellular matrix mimetic hydrogel for promoting in vivo bone formation
Authors: Hong Ji Yan, Tommaso Casalini, Gry Hulsart-Billström, Shujiang Wang, Oommen P. Oommen, Matteo Salvalaglio, Sune Larsson, Jöns Hilborn, Oommen P. Varghese
Journal: Biomaterials (2018)
Broad based training recruitment is closed to help fill more GP training posts
Authors: Abi Rimmer
Journal: BMJ (2015)

Recruitment to broad based training has been closed to help fill more general practice training posts, Health Education England (HEE) has announced. Trainees will not be able to apply to any broad based training posts in England that start in August 2016.

Broad based training was developed in 2012 by the Academy of Medical Royal Colleges to provide specialty trainees with experience in delivering patient focused healthcare across the whole of the health and social care …
Quality-of-life (QoL) in RANGE: A phase 3 study of ramucirumab (RAM) plus docetaxel (DOC) versus placebo (P) plus DOC in platinum-refractory locally advanced or metastatic urothelial carcinoma (UC).
Authors: Andrea Necchi, Hiroyuki Nishiyama, Nobuaki Matsubara, Jae-Lyun Lee, Daniel Peter Petrylak, Ronald De Wit, Alexandra Drakaki, Astra M. Liepa, Annamaria Zimmermann, Katherine M. Bell-McGuinn, Thomas Powles
Journal: Journal of Clinical Oncology (2018)

419 Background: RAM + DOC in RANGE (NCT02426125) improved progression free survival (hazard ratio [HR] = 0.757) with a higher objective response rate (24.5% vs 14%) and an acceptable safety profile (Petrylak, et al Lancet 2017). QoL was a secondary objective. Methods: Patients (pts) whose UC progressed following platinum-based therapy were randomized to receive RAM (10 mg/kg) + DOC (75 mg/m 2 ) or P + DOC on Day 1 of a 21-day cycle. Treatment continued until disease progression or unacceptable toxicity with a maximum of 10 cycles for DOC. Pts completed the EORTC QLQ-C30 (v3) prior to each cycle &amp; at the 30-day follow up visit. QoL scales were analyzed for: 1) rates of improved/stable scores (compared with Fisher’s exact test) &amp; 2) time to sustained deterioration (TtD), defined as randomization to first worsening with no subsequent non-worsened assessment (compared with unstratified log-rank test). A ≥10 point change (on 100-point scale) was deemed clinically meaningful. Results: 530 pts were randomized. 254/263 (97%) RAM-DOC &amp; 260/267 (97%) P-DOC pts provided baseline (BL) QoL data &amp; ≥85% for post-BL, on-therapy assessments. Median number of cycles was 4 for RAM-DOC &amp; 3 for P-DOC. Mean BL scores were similar between arms &amp; indicated greatest impairment for global QoL, fatigue, pain, &amp; insomnia. For all scales, rates of improved/stable scores were not different, except for pain at Cycles 4 &amp; 7 where rates were higher for RAM-DOC (p &lt; 0.05). Relative to other QoL scales, pain generally had highest rates of improved scores in both arms (14-25% for RAM-DOC &amp; 8-24% for P-DOC for Cycles 1-4). In a post hoc analysis, Cycles 1-4 rates of improved pain scores were 31-32% for RAM-DOC &amp; 14-26% for P-DOC in tumor responders, but 17-29% for RAM-DOC &amp; 16-28% for P-DOC in pts with stable disease. For TtD, 14/15 QoL scales had HRs &lt; 1, indicating similar or numerically longer TtD in QoL for RAM-DOC (HRs 0.67- 1.06; all 95% confidence intervals included 1). Conclusions: The addition of RAM to DOC for platinum-refractory UC pts did not adversely impact QoL relative to P-DOC. Trends in improved TtD and improved rates of pain associated with tumor response favored RAM-DOC. Clinical trial information: NCT02426125.
I am interested in gastrointestinal surgery and am also becoming more interested in general practice. How I can combine general practice with general surgery?
Authors: Alan R Watson
Journal: BMJ (2005)

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>
UroEmerge: practical skills in emergency urology
Authors: Kate Clayton
Journal: BMJ (2011)

This one day intensive course, open to all foundation and specialist trainee doctors and held at the Royal London Hospital, focuses on the practical skills needed to cope with common urological emergencies. The course was developed several years ago in response to changing trends in surgical training. Its aim is to help candidates develop a simple and practical approach to managing urological emergencies, within the context of the multidisciplinary team.

Like many other junior doctors I had relatively little opportunity to gain experience in this important specialty as a medical student or house officer. While working in accident and emergency I realised how common urological emergencies are and resolved to improve my knowledge and skills before …
SGLT2 INHIBITORS REDUCE MAJOR ADVERSE CARDIOVASCULAR EVENTS IN TYPE 2 DIABETIC PATIENTS: A META-ANALYSIS OF RANDOMIZED CONTROLLED TRIALS
Authors: Shamna Haris, Sukhchain Singh, Sana Chaudhary, Mahwash Siddiqui, Onyambu Steve Biko, Sarabjeet Singh, Haris Hamsakutty, Sandeep Khosla, Rohit Arora
Journal: Journal of the American College of Cardiology (2018)
Editor’s Choice: Looking ahead
Authors: Tom Moberly
Journal: BMJ (2016)

Medical leadership and medical research are too often too poor. Poor leadership has been repeatedly cited as a factor contributing to failures in patient care in the health service. And the problems with poor quality medical research highlighted in Doug Altman’s classic 1994 BMJ paper (doi:10.1136/bmj.308.6924.283) still persist—some may even be more prevalent than …
Comment on Ooi and Wong. Twin Pregnancy With Gestational Diabetes Mellitus: A Double Whammy? Diabetes Care 2018;41:e15–e16
Authors: Rachel T. McGrath, Gregory R. Fulcher, Sarah J. Glastras
Journal: Diabetes Care (2018)

We read with interest the findings of Ooi and Wong (1) in their recent article on gestational diabetes mellitus (GDM) in twin pregnancy. Whereas a major goal of GDM management in singleton pregnancies is to reduce fetal overgrowth, twin pregnancies are inherently associated with restricted fetal growth and uncommonly reach full-term gestation. Therefore, it is important to evaluate birth weight outcomes for GDM in twin pregnancy. The authors reported that women with GDM in twin pregnancy have a similar rate of small-for-gestational-age (SGA) (birth weight <10th centile for gestational age and sex) neonates compared with either singleton pregnancy or uncomplicated twin pregnancy, and, as expected, large-for-gestational-age (LGA) neonatal …
Long Terminal Repeat CRISPR-CAR-Coupled “Universal” T Cells Mediate Potent Anti-leukemic Effects
Authors: Christos Georgiadis, Roland Preece, Lauren Nickolay, Aniekan Etuk, Anastasia Petrova, Dariusz Ladon, Alexandra Danyi, Neil Humphryes-Kirilov, Ayokunmi Ajetunmobi, Daesik Kim, Jin-Soo Kim, Waseem Qasim
Journal: Molecular Therapy (2018)
Case 5-2018: A 63-Year-Old Man with Confusion after Stem-Cell Transplantation
Authors: Areej R. El-Jawahri, Pamela W. Schaefer, Joseph B. El Khoury, Maria Martinez-Lage
Journal: New England Journal of Medicine (2018)

A 63-year-old man presented with confusion and weakness 5 months after he had undergone allogeneic stem-cell transplantation for chronic lymphocytic leukemia. MRI did not show evidence of acute brain abnormalities. Diagnostic tests were performed.
Enzalutamide and metformin combination therapy to overcome autophagy resistance in castration resistant prostate cancer (CRPC): Current results from a phase I study.
Authors: Mamta Parikh, Jasmine C Hyunh, Primo Lara, Chong-xian Pan, Daniel Robles, Christopher P. Evans
Journal: Journal of Clinical Oncology (2018)

281 Background: Preclinical models have shown that autophagy is a resistance mechanism of enzalutamide (enza), a small molecule suppressing the androgen pathway approved for treatment of CRPC. Metformin, an autophagy inhibitor, enhances preclinical therapeutic responses when combined with Enza, thus prompting a Phase I clinical trial evaluating the combination. We present results to date. Methods: Eligible patients (pts) had established CRPC, ECOG 0-2, adequate hematologic and organ function, and ≤ 2 prior treatments for CRPC. Major exclusion criteria included prior enza or metformin treatment, presence of brain metastases, history of DM2 or seizures. An initial cohort of 3 pts were treated with enza 160 mg PO qdaily and metformin 500 mg PO bid (DL1), with metformin dose escalated to 1000 mg PO bid (DL2) in subsequent 3 pts if dose-limiting toxicity (DLT) was observed in ≤1 pt in DL1. Primary objective was to establish the maximum tolerated dose (MTD), with secondary objectives of evaluating PSA response of ≥ 50%, PSA progression, and safety. Results: A total of 12 pts have been enrolled to date; mean age was 77 (range 60-95). No DLTs were observed at DL1; 1 DLT due to Grade 3 abdominal pain was observed at DL2, with an additional 6 pts subsequently enrolled in expansion. The only adverse effects ≥ Grade 3 were: syncope (1/12), hallucinations (1/12), and abdominal pain (2/12). One pt withdrew consent, 2 required dose reduction of metformin, and 1 died of progressive disease. Of 10 evaluable pts, PSA response was seen in 8 pts. Conclusions: The combination of enza 160 mg qdaily and metformin 1000 mg PO bid is safe and well-tolerated. Efficacy results to date support continued study of the combination in pts with CRPC. Clinical trial information: NCT02339168.
Communication is ranked as number one risk for general practices
Authors: Helen Jaques
Journal: BMJ (2012)

Communication with patients and practice staff, in particular electronically, has been identified as a key risk by more than 150 general practices in the United Kingdom.

Data collected by the Medical Protection Society in 2011 also found that many general practices rated confidentiality, health and safety, prescribing, and record keeping as leading risks.

Traditionally, confidentiality has …
IFN-γ to improve immunotherapy for melanoma.
Authors: Marco Donia, Morten Hansen, Sarah Louise Sendrup, Eva Ellebaek, Trine Zeeberg Iversen, Mads Hald Andersen, Per thor Straten, Inge Marie Svane
Journal: Journal of Clinical Oncology (2012)

2565 Background: Adoptive cell therapy (ACT) with tumor infiltrating lymphocytes (TILs) holds the promise to change the long-term prognosis of patients with metastatic melanoma. In this study we have explored strategies to improve the efficacy of cell products for infusion through tumor immune-sensitization. Methods: We examined whether objective responses in our pilot ACT trial (NCT937625) were associated with the number of tumor-reactive T cells infused. Subsequently, we assessed the ability of immune-sensitizing agents to modulate the constitutive response of 12 clinical grade TIL products to matched autologous short-term cultured melanoma cell lines. Results: Our data showed that a high absolute number of infused tumor-reactive T cells is critical to achieve an objective response. In addition, a defective population of tumor-specific CD8+ and CD4+ T cells unable to exert antitumor effector functions ex vivo was detected in most TIL products. However, an antitumor specific response could be restored by pretreatment of the autologous tumor cells with low dose IFN-γ. Of note, IFN-γ treatment was invariably associated with increased cancer immunogenicity as demonstrated by up-regulation of MHC molecules. Conclusions: Combination strategies represent the next frontier of cancer immunotherapy. Although previous trials in melanoma showed that IFN-γ does not mediate clinical benefit when used as monotherapy, our findings show that its ability to increase tumor cell immunogenicity may enhance the efficacy of current immune-based therapies such as ACT through improved activation of pre-existing but unresponsive tumor specific lymphocytes. Therefore, additional studies on the possibility of a sequential combination of low dose IFN-γ and ACT are highly warranted.