tbuckley/cabot-search huggingface dataset:
King’s Fund management for specialist registrars
Authors: Fiona Pathiraja
Journal: BMJ (2010)

There is a plethora of leadership courses on offer to trainees these days. With the exception of an MBA or a masters in leadership, however, it is widely recognised that the King’s Fund offers the gold standard in leadership and management courses for trainees and consultants. Indeed, many other courses are based on its innovative teaching techniques and content, developed over the past 30 years.

The course is intended to equip specialist registrars on the cusp of their first consultant post with the skills to facilitate entry into management and leadership roles.

The course I attended was slightly different because a group of junior doctors, on secondment to a national leadership scheme, had worked with the King’s Fund faculty to create a bespoke leadership and management course tailored to our needs. Our cohort of 15 individuals ranged from foundation year 2 doctors to specialty trainees year 7 and covered a wide variety of specialties.

The course is …
Blood HER2 and Uromodulin as Causal Mediators of CKD
Authors: Jennifer Sjaarda, Hertzel C. Gerstein, Salim Yusuf, Darin Treleaven, Michael Walsh, Johannes F.E. Mann, Sibylle Hess, Guillaume Paré
Journal: Journal of the American Society of Nephrology (2018)

Many biomarkers have been epidemiologically linked with CKD; however, the possibility that such associations are due to reverse causation or confounding limits the utility of these biomarkers. To overcome this limitation, we used a Mendelian randomization (MR) approach to identify causal mediators of CKD. We performed MR by first identifying genetic determinants of 227 serum protein biomarkers assayed in 4147 participants of the Outcome Reduction with Initial Glargine Intervention (ORIGIN) trial who had early or prediabetes, and assessing the effects of these biomarkers on CKD in the CKD genetics consortium (n=117,165; 12,385 cases) using the inverse-variance weighted (fixed-effects) method. We then estimated the relationship between the serum concentration of each biomarker identified and incident CKD in ORIGIN participants. MR identified uromodulin (UMOD) and human EGF receptor 2 (HER2) as novel, causal mediators of CKD (UMOD: odds ratio [OR], 1.30 per SD; 95% confidence interval [95% CI], 1.25 to 1.35; P<5×10-20; HER2: OR, 1.30 per SD; 95% CI, 1.14 to 1.48; P=8.0×10-5). Consistent with these findings, blood HER2 concentration associated with CKD events in ORIGIN participants (OR, 1.07 per SD; 95% CI, 1.01 to 1.13; P=0.01). Additional exploratory MR analyses identified angiotensin-converting enzyme (ACE) as a regulator of HER2 levels (β=0.13 per SD; 95% CI, 0.08 to 0.16; P=2.5×10-7). This finding was corroborated by an inverse relationship between ACE inhibitor use and HER2 levels. Thus, UMOD and HER2 are independent causal mediators of CKD in humans, and serum HER2 levels are regulated in part by ACE. These biomarkers are potential therapeutic targets for CKD prevention.
Statin use and outcomes of patients (pts) with metastatic castration resistant prostate cancer (mCRPC) being treated with abiraterone (Abi).
Authors: Jacob A Gordon, Bernhard J. Eigl, Jennifer A. Locke, Gregory Russell Pond, Cyrus Chehroudi, Daniel Khalaf, Kim N. Chi, Michael E. Cox
Journal: Journal of Clinical Oncology (2018)

277 Background: Epidemiologic studies support an association between statin use and improved prostate cancer specific mortality. Several different biologic mechanisms for such an effect have been proposed, including a potential role in reducing androgen precursor bioavailability. It is hypothesized that statins may therefore improve outcomes specifically in patients treated with the CYP17 inhibitor Abi. Di Lorenzo (2017) recently published an analysis of 187 pts showing a relationship between Abi and improved survival (OS). We report the results of a larger confirmatory analysis in a separate cohort. Methods: Disease outcome and statin use were assessed retrospectively in locally advanced or metastatic CRPC patients receiving Abi in British Columbia, Canada. The Kaplan-Meier method was used to estimate survival times, Cox proportional hazards and logistic regression were used to investigate factors potentially prognostic of overall survival and PSA response respectively. A multivariable model was constructed using factors with limited missing data and known biologic rationale. Impact of statins was then assessed adjusting for factors included in the multivariable model. Results: 301 patients receiving Abi were assessed, of whom 84 (28%) were statin users. Median OS of Abi patients was 11.3 months for non-statin users and 16.2 months for statin users (hazard ratio = 0.79, 95% CI = 0.61-1.03, p = 0.079). Effect of statin use remained borderline after adjusting (n = 279, hazard ratio = 0.78, 95% CI = 0.59-1.04, p = 0.087) for age, prior prostatectomy, radiation, Docetaxel, time from diagnosis, neutrophils-lymphocyte ratio and presence of metastases. Forty-eight percent of statin users and 37% of non-statin users had a PSA response (multivariable odds ratio = 1.59, 95% CI = 0.91-2.78, p = 0.11). Conclusions: Although limited by sample size, our data showed a trend that statins may mildly enhance the anti-tumor effects of Abi in CRPC patients. These results support the findings of Di Lorenzo et al. (2017), and suggest that depletion of de novo cholesterol production may further limit androgen synthesis in concert with CYP17A1 inhibition. Further studies are warranted.
Response to Comment on Edelman and Polonsky. Type 2 Diabetes in the Real World: The Elusive Nature of Glycemic Control. Diabetes Care 2017;40:1425–1432
Authors: Steven V. Edelman, William H. Polonsky
Journal: Diabetes Care (2018)

We thank Giugliano et al. (1) for their comments on our article (2) bringing to light two important issues. First, while we highlighted the importance of problematic medication adherence in diabetes care in our article and briefly examined several of the key contributors, we …
Writing features for Career Focus
Authors: Graham Easton
Journal: BMJ (2004)

Features are written in the format and style you might see in a magazine. Here's what we are looking for.

These are articles that take an in-depth look at a topical issue, such as inter-professional learning, the European Working Time Directive, or flexible training. Please always suggest ideas to us first (via email). Make sure you spell out clearly how the issue will affect our …
SPAZO2 (SOGUG): Outcomes of patients treated with pazopanib as first line in mRC according to gender in real world.
Authors: Constanza Maximiano, Javier Luis Puertas Alvarez, Jose Pablo Maroto Rey, Alvaro Pinto, Maria Jose Miranda Pallares, Cristina Suarez, Miguel A. Climent, Iciar Garcia Carbonero, Jose Carlos Villa Guzman, Pablo Borrega, Guillermo De Velasco, Eva Fernandez Parra, Guillermo Crespo, Rocío García Domínguez, Enrique Gallardo Diaz, Andres Meana Garcia, Rosa Garcia Marrero, Jose Luis Gonzalez Larriba, Sara Perez Ramirez, Jose Angel Arranz Arija
Journal: Journal of Clinical Oncology (2018)

623 Background: Treatment of mRC is not affected by gender, studying possible differences in a real-world study, could increase the knowledge of toxicity and possible prognostic factors. Methods: SPAZO2 (NCT03091465) was a retrospective real-world study to analyze the effectiveness of 1st-line pazopanib and subsequent therapies in mRC. Data from 530 pt treated outside CT were collected in 50 spanish centers, and externally monitored. Ineligibility criteria: ECOG &gt; 1, pure nonclear-cell, Hgb &lt; 9 g/dl, renal failure, severe cardiovascular disease, chronic liver disease, or recent neoplasia Results: 530 pt were included, 67.2% men (M), mean age was 66.2 years (26-92). There were no significant differences (M vs W) in the age &gt; 75 (24.7 vs 24.1%), clear cell carcinoma (77.2 vs 79.9%), nephrectomy (72.5 vs 68.4%), IMDC (favourable: 15.2 vs 12.1%, intermediate: 59.3 vs 64.4%, poor: 25.6 vs 23.6%), metastases (lymph nodes: 46.1 vs 43.1%, lung: 69,7 vs 67,2 %, liver: 16 vs 20.1%, bone: 27 vs 24.1%, skin/soft tissues: 1.1 vs 3,4% and CNS: 4,8% vs 6.3%). Discontinuation due to toxicity or comorbidities was 12.4 vs 9.8%. There were no differences in the second lines received (57.9 vs 56.9%), neither response, PFS and OS (table). Median follow up was 39 mo. The gender has no prognostic value when adjusted for the prognostic groups of IMDC (HR of PFS 0.96, CI 95% 0.78-1.2, HR of OS: 0.92, CI 95% 0.72-1.14). Only diarrhea and elevation of uric acid were higher in the men group. Conclusions: Pazopanib was safe and effective in both groups with similar outcome. Women had less diarrhea and less increased uric acid. There were not differences in OS or PFS. In IMDC subgroup analysis, there is a trend towards a better evolution or PFS in the poor prognosis women subgroup. Clinical trial information: NCT03091465. [Table: see text]
Risk factors associated with outcomes following neoadjuvant chemoradiotherapy prior to esophagectomy in patients with adenocarcinoma of the esophagus.
Authors: Khalil Boussi, Tarita Thomas, Sam G. Pappas, Brendan Martin
Journal: Journal of Clinical Oncology (2018)

186 Background: The study was conducted to evaluate risk factors associated with treatment outcomes following concurrent chemoradiotherapy (CRT) and esophagectomy in patients diagnosed with resectable esophageal cancer. Methods: IRB approval was obtained to evaluate patients with esophageal cancer treated at our center from 2002 to 2017 with neoadjuvant CRT followed by esophagectomy. Patient characteristics pre and post-surgery including age, number of positive lymph nodes, length of time between neoadjuvant therapy and surgery were evaluated. Univariable and multivariable frailty survival analysis were used to evaluate the association between risk factors and treatment outcomes. Results: 74 patients met inclusion criteria of CRT and esophagectomy. Controlling for the number of days between the end of radiotherapy and surgery, the hazard of death for patients who developed metastatic cancer following completion of therapy was 2.08 (95 CI: 1.04 – 4.13) times higher compared to patients who did not develop metastasis (p = .04). Adjusting for metastatic cancer, for every five additional days between the end of radiotherapy and surgery, patients’ hazard of death increased 5% (HR = 1.05, 95 CI: 1.02 – 1.07, p &lt; .001). Controlling for metastatic cancer and the number of positive nodes, for every one-year increase in age, patients’ hazard of recurrence decreased 5% (HR = 0.95, 95 CI: 0.91 – 0.99, p = .04). Adjusting for age and the number of positive nodes, the hazard of recurrence for patients who developed metastatic cancer was 28.57 (95 CI: 6.58-123.97) times higher compared to patients without metastasis (p &lt; .0001). Conclusions: Longer duration between completion of CRT and surgery as well as developing metastatic disease are associated with a significantly higher hazard of death. Additionally, developing metastatic cancer, increase in age, and additional positive lymph nodes are all associated with a significantly higher hazard of recurrence. Optimal timing between neoadjuvant therapy and surgery needs to be evaluated further, as increasing hazard of death following therapy suggests that there may be a role for adjuvant chemotherapy in these patients.
Should This Patient Receive Hormone Therapy for Her Menopausal Symptoms?
Authors: Eileen E. Reynolds, Carol Bates, Martha Richardson, Risa B. Burns
Journal: Annals of Internal Medicine (2018)

Hormone therapy (HT) was widely prescribed in the 1980s and 1990s and has been controversial since the initial results of the Women's Health Initiative (WHI) trial in the early 2000s suggested that it increased risk for breast cancer and coronary heart disease and did not prolong life. However, more recent data and reexamination of the WHI results suggest that HT is safe and effective for many women when used around the time of menopause. Two experts debate the 2017 Hormone Therapy Position Statement of The North American Menopause Society, which recommends HT as first-line treatment of vasomotor symptoms, and apply it to the care of Ms. R, a 52-year-old woman with severe hot flashes, sleep disturbance, and irritability.
TRIM59 Promotes Gliomagenesis by Inhibiting TC45 Dephosphorylation of STAT3
Authors: Youzhou Sang, Yanxin Li, Lina Song, Angel A. Alvarez, Weiwei Zhang, Deguan Lv, Jianming Tang, Feng Liu, Zhijie Chang, Shigetsugu Hatakeyama, Bo Hu, Shi-Yuan Cheng, Haizhong Feng
Journal: Cancer Research (2018)

Aberrant EGFR signaling is a common driver of glioblastoma (GBM) pathogenesis; however, the downstream effectors that sustain this oncogenic pathway remain unclarified. Here we demonstrate that tripartite motif-containing protein 59 (TRIM59) acts as a new downstream effector of EGFR signaling by regulating STAT3 activation in GBM. EGFR signaling led to TRIM59 upregulation through SOX9 and enhanced the interaction between TRIM59 and nuclear STAT3, which prevents STAT3 dephosphorylation by the nuclear form of T-cell protein tyrosine phosphatase (TC45), thereby maintaining transcriptional activation and promoting tumorigenesis. Silencing TRIM59 suppresses cell proliferation, migration, and orthotopic xenograft brain tumor formation of GBM cells and glioma stem cells. Evaluation of GBM patient samples revealed an association between EGFR activation, TRIM59 expression, STAT3 phosphorylation, and poor prognoses. Our study identifies TRIM59 as a new regulator of oncogenic EGFR/STAT3 signaling and as a potential therapeutic target for GBM patients with EGFR activation.Significance: These findings identify a novel component of the EGFR/STAT3 signaling axis in the regulation of glioma tumorigenesis. Cancer Res; 78(7); 1792-804. ©2018 AACR.
PROGNOSTIC VALUE OF POST PROCEDURE STROKE VOLUME INDEX AFTER TRANCATHETER AORTIC VALVE REPLACEMENT IN LOW-GRADIENT SEVERE AORTIC STENOSIS
Authors: Yugo Nara, Akihisa Kataoka, Yusuke Watanabe, Makoto Nakashima, Hirofumi Hioki, Hideyuki Kawashima, Fukuko Nagura, Ken Kozuma, Shinichi Shirai, Tada Norio, Motoharu Araki, Toru Naganuma, Futoshi Yamanaka, Hiroshi Ueno, Minoru Tabata, Kazuki Mizutani, Akihiro Higashimori, Kensuke Takagi, Masanori Yamamoto, Kentaro Hayashida
Journal: Journal of the American College of Cardiology (2018)
Professor Peter Abrahams—GP, author, and academic clinical anatomist
Authors: Peter Gogalniceanu
Journal: BMJ (2008)

Peter Abrahams is a general practitioner in Willesden, London, and professor of clinical anatomy at the University of Warwick. He is a fellow of Girton College, Cambridge, and examiner for the Royal College of Surgeons.

I originally intended to become a geography teacher. I did A levels in geography, history, and French and then went with VSO to the jungles of Borneo to teach geography to schoolchildren. While I was there, they discovered that I had done a first aid course. Consequently, I ran a clinic every night for a year, 50 miles from the nearest village, let alone hospital. I enjoyed it so much that when I came back to England I decided to take up medicine. The irony, of course, is that I still ended up being a geography teacher—only I teach the geography of the human body.

I think the fact that I spent my youth in a Third World country gave me insights into how difficult are the lives of people around the world. As an academic I’ve always been sympathetic to people from underdeveloped countries—whether teaching, examining, or lecturing. I also worked with the World Health Organization to help set up a medical school in the desert area of Beersheba …
How can I go about changing specialties from paediatrics to radiology?
Authors: Sarah Burnett
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>
CONGENITAL HEART DISEASE SURVIVAL IN LOW AND MIDDLE INCOME COUNTRIES: LINKING INVESTMENT AND OUTCOMES
Authors: Sarah Rahman, K.M. Cherian, Jan Christensen, Kaitlin Doherty, David de Ferranti, Kimberlee Gauvreau, Patricia Hickey, Krishna Kumar, Jennifer Kupiec, William Novick, Nestor Sandoval, Bistra Zheleva, Kathy Jenkins
Journal: Journal of the American College of Cardiology (2018)
QUALITY OF ANTICOAGULATION MANAGEMENT IN WARFARIN TREATED PATIENTS WITH NON-VALVULAR ATRIAL FIBRILLATION: A DESCRIPTIVE REAL-WORLD STUDY IN A PRIVATE SETTING IN BRAZIL
Authors: Pedro De Barros e Silva, Henry Sznejder, Rafael Vasconcellos, Georgette Charles, Hugo-Tannus Mendonca-Filho, Jack Mardekian, Rodrigo Nascimento, Stephen Dukacz, Manuela Di Fusco
Journal: Journal of the American College of Cardiology (2018)
Moving on from clinical practice
Authors: Rebecca Ghani
Journal: BMJ (2012)

Non-vocational degrees are broad enough for graduates to ponder on which way their careers might develop as they meander through undergraduate life. English, maths, and the humanities, to name a few, allow graduates breathing space to consider their options. Some would see this as a benefit: there is no burden of expectation; things remain flexible. And some would view this as a disadvantage with no clear career path or likelihood of employment in a definite sector.

Medicine, on the other hand, leads graduates down a structured path into their chosen career, on the basis of a choice that was usually made—in most of Europe, Asia, and Australia—at around age 17. Medical graduates are signposted through the next steps of training to full qualification. Although there are choices to be made within medicine, the broad direction is set.

Should medical graduates feel obliged to follow this set path? If medical school and the reality of practising as a doctor don’t match up to expectations, should medical students go off piste? What are the alternatives, and how feasible and realistic is it to look outside the clinical sphere?

In the US, medical school is at postgraduate level, after completion of a general undergraduate degree—typically four years at each stage, taking the average age for starting medical school to 24.1 Is this a more sensible age to make a decision about a lifelong career?

A cohort study by the BMA followed the career paths of 545 UK medical graduates from the class of 1995. One of the main findings was that “while three quarters of cohort doctors are currently satisfied with practising medicine, a fifth report a lukewarm desire to practise medicine and the remainder have little or no desire to practise medicine.”⇓2



Reason for leaving medicine as a career: …
REFERRAL OF PATIENTS FOR FRACTIONAL FLOW RESERVE USING CORONARY CONTRAST-FLOW QUANTITATIVE FLOW RATIO
Authors: Jeff Smit, Gerhard Koning, Alexander van Rosendael, Mohammed El Mahdiui, Bart Mertens, Johan Jukema, Victoria Delgado, Johan Reiber, Jeroen J. Bax, Arthur Scholte
Journal: Journal of the American College of Cardiology (2018)
2D Superparamagnetic Tantalum Carbide Composite MXenes for Efficient Breast-Cancer Theranostics
Authors: Zhuang Liu, Han Lin, Menglong Zhao, Chen Dai, Shengjian Zhang, Weijun Peng, Yu Chen
Journal: Theranostics (2018)

: The emergence of two-dimensional MXenes has spurred their versatile applications in broad fields, but the exploring of novel MXene-based family members and their potential applications in theranostic nanomedicine (concurrent diagnostic imaging and therapy) have been rarely explored. In this work, we report the construction of a novel superparamagnetic MXene-based theranostic nanoplatform for efficient breast-cancer theranostics, which was based on intriguing tantalum carbide (Ta
Second NHS pension choice exercise to begin in autumn
Authors: Abi Rimmer
Journal: BMJ (2014)

Members of the NHS pension scheme will be given a second chance to decide whether they want to move from the 1995 to the 2008 scheme.

Between 2009 and 2012 a choice exercise was run to allow NHS employees to decide whether they wished to move from the 1995 to the 2008 scheme. From September this year to February 2015 around 500 000 eligible members of the 1995 scheme without full protection under the 2015 pension scheme …
BMA and government reach agreement on doctors’ bonus scheme
Authors: Abi Rimmer
Journal: BMJ (2018)

The BMA and the government have reached an agreement out of court to retain local incentive payments for doctors in England.

The BMA had taken legal action against the government over clinical excellence award (CEA) payments, as part of ongoing negotiations on changes to the consultant contract in England.

The association took action after the government said that CEAs were non-contractual and didn’t need to be retained in the terms of a new contract. The BMA argued that the awards were part of a doctor’s contract and …
Abstract P4-12-08: Palbociclib in hormone receptor positive advanced breast cancer: A cost-utility analysis
Authors: J Raphael, J Helou, DM Naimark
Journal: Cancer Research (2018)

Abstract Introduction The addition of palbociclib to letrozole improves progression free survival (PFS) and response rates compared to letrozole alone in the 1st line treatment of hormone receptor positive advanced breast cancer. However palbociclib increases toxicity (i.e. neutropenia) and costs more than $6,250 per month in Canada. This study assesses the cost-utility of palbociclib from the Canadian healthcare payer perspective. Methods To evaluate the cost-utility of palbociclib, a probabilistic discrete event simulation model was developed. The model was parameterized with data from the phase 2 and 3 PALOMA 1 and 2 trials and other sources. The incremental cost per quality-adjusted life-month (QALM) gained for palbociclib was calculated. A time horizon of 15 years was used in the base case with costs and effectiveness discounted 5% annually. The time to progression and death were derived from a Weibull and exponential distribution. Expected costs were based on Ontario fees and other sources. Probabilistic sensitivity analyses were conducted to account for parameter uncertainty. Results Compared to letrozole alone, the addition of palbociclib provided an additional 14.7 QALM at an incremental cost of $161,508. The resulting incremental cost-effectiveness ratio was $10,999 per QALM gained. Assuming a willingness to pay (WTP) of $4,167 per QALM, the addition of palbociclib was not cost-effective and the probability of palbociclib to be cost-effective was 0%. Cost-effectiveness acceptability curves derived from a probabilistic sensitivity analysis showed that at a WTP of $11,667 per QALM gained, the probability of palbociclib to be cost-effective was 50%. Conclusion Compared with letrozole alone, the addition of palbociclib is unlikely to be cost-effective for the treatment of advanced breast cancer from a Canadian healthcare perspective with its current price. While advanced breast cancer patients derive a meaningful clinical benefit from palbociclib, considerations should be given to increase the WTP threshold and reduce the drug pricing, to render this strategy more affordable. Citation Format: Raphael J, Helou J, Naimark DM. Palbociclib in hormone receptor positive advanced breast cancer: A cost-utility analysis [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 P4-12-08.
Health Education England launches group to encourage more GP students
Authors: Abi Rimmer
Journal: BMJ (2015)

Health Education England (HEE) has announced that it will launch a group to promote careers in general practice to medical students. Speaking at a BMA general practice event on Wednesday HEE’s director of programmes, Patrick Mitchell, said that a “task and finish” group would be launched by HEE and the Medical Schools Council.

Simon Gregory, director of education and quality at HEE Midlands and East and lead for …