tbuckley/cabot-search huggingface dataset:
I have just started as a senior house officer as part of my GP training. Once finished, I would like to spend some time working in France. Any ideas on how to go about getting work as a GP in France?
Authors: James Sherifi
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>
Abstract PD4-01: The role of FGF/FGFR axis in resistance to SERDs and CDK4/6 inhibitors in ER+ breast cancer
Authors: P Mao, J Kusiel, O Cohen, N Wagle
Journal: Cancer Research (2018)

Abstract Approximately 70% of breast cancers express the estrogen receptor (ER), and estrogen signaling drives breast cancer cell growth and progression. ER-directed therapies are commonly used to treat ER+ breast cancer and have improved survival for patients, yet resistance to those therapies inevitably occurs. Mutations in the estrogen receptor itself occur in ∼25-30% of patients with ER+ metastatic breast cancer that has developed resistance to aromatase inhibitors. Beyond these ER mutations, other resistance mechanisms are not well described. Moreover, clinical mechanisms of resistance to another class of ER-targeted agents, selective estrogen receptor degraders (SERDs), such as fulvestrant have not been clearly identified. Here we report two FGFR2 mutations identified in patients with resistant ER+ metastatic breast cancer, N550K and M538I. N550K is a well-known activating FGFR2 mutation; M538I stabilizes the active kinase conformation and it has not previously been described in breast cancer. When expressed in ER+ T47D cells, FGFR2 M538I and N550K led to resistance to fulvestrant, and the CDK4/6 inhibitor palbociclib and the combination of the two agents. FGFR2 M538I induced hyperactivity of p-FRS2, p-ERK and p-AKT, which is higher than wildtype FGFR2 and comparable to other known activating mutations N550K and K660N. In addition, overexpression of M538I mutant reduced sensitivity to FGFR inhibitors PD173074 and dovitinib in T47D cells, suggesting M538I is also functionally activating. Due to the hyperactive downstream signaling elicited by the mutation, cells overexpressing FGFR2 M538I achieved optimal growth in the presence of low dose of FGFR inhibitor. Under such conditions, FGFR2 M538I conferred more potent resistance to fulvestrant as compared to wildtype FGFR2. However, drug resistance resulting from M538I mutant can be fully resensitized to fulvestrant and/or palbociclib with high dose of FGFR inhibitors. In summary, we have identified activating FGFR2 mutations (M538I and N550K) in ER+ breast cancer patients, which may contribute to the development of resistance to SERDs and CDK4/6 inhibitors. Additional FGFR2 mutations have been recently identified in other cohorts of patients with resistant ER+ metastatic breast cancer, suggesting that this may be a clinical mechanism of resistance in some patients. Patients with activating FGFR2 mutations may benefit from the treatment with an FGFR inhibitor in combination with SERDs and CDK4/6 inhibitors. Citation Format: Mao P, Kusiel J, Cohen O, Wagle N. The role of FGF/FGFR axis in resistance to SERDs and CDK4/6 inhibitors in ER+ 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 PD4-01.
Notes for a Chord
Authors: Beverly Greenspan
Journal: JAMA (2018)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Medical leadership and management—are postgraduate qualifications the answer?
Authors: Jonathan Mills, Alex Till
Journal: BMJ (2016)

Doctors have responsibilities to the teams, units, and systems they work in, as well as to their patients.1 Most undergraduate and postgraduate training does not develop the skills or competencies needed for leadership roles, and as a result doctors are often asked to take on these positions having little knowledge or experience. There is a chronic shortage of good leaders within the NHS.23

Doctors, as well as health and educational organisations, must accept responsibility to develop leadership as an essential skill. This is often done through leadership programmes or courses, and formal postgraduate qualifications are one option to address the current deficit of leadership training within medical education.

Postgraduate qualifications can be done …
Tumor grade, Ki 67%, and relantionship with the 21-gene recurrence score assay in early breast cancer tumors.
Authors: Ioana Bonta, Dacian Bonta, Rita A. Blanchard
Journal: Journal of Clinical Oncology (2014)

e11540 Background: 21-gene recurrence score assay (Oncotype Dx) is diagnostic tool that estimates the likelihood of breast cancer recurrence as well as the chemotherapy benefit for patients with early stage, hormone-receptor positive breast cancer. The goal of our research is to compare Oncotype Dx with 2 pathologic prognostic markers routinely reported by the pathology labs: KI67% and tumor grade. Methods: We performed a retrospective analysis of a dataset of 105 patients with ER-positive, M0, breast cancer, treated at Boston University Medical Center between November 2006 and May 2013. The recorded data included ER/PR status, Ki67%, TNM stage, tumor grade and Oncotype Dx recurrence score. The database also included information about recurrence status and development of other malignancies (second oncologic event). Statistical methods employed were linear correlation and t-test. Results: The average Oncotype Dx score was 17.3 for grade 1 tumors; 19.0 for grade 2 tumors; and 26.4 for grade 3 tumors. The correlation coefficient between Oncotype Dx and Ki67% was 0.41. When stratified by tumor grade, the correlation between Oncotype Dx and Ki67% persisted for grade 2 and 3 tumors, but was not observed for grade 1 tumors. Patients with a second oncologic event had an average Oncotype Dx score of 23.5, significantly higher than patients without a second oncologic event (average Oncotype Dx score 19.1), p=0.04. Conclusions: 1) In our dataset, Oncotype Dx recurrence score is correlated with tumor grade. Oncotype Dx and Ki67% are correlated for grade 2 and 3 tumors. 2) Increased Oncotype Dx score is correlated with the occurrence of a second oncologic event.
EVITA—a double-blind, vehicle-controlled, randomized phase II trial of vitamin K1 cream as prophylaxis for cetuximab-induced skin toxicity
Authors: R.-D. Hofheinz, S. Lorenzen, J. Trojan, J. Ocvirk, T.J. Ettrich, S.-E. Al-Batran, H. Schulz, N. Homann, H.-P. Feustel, M. Schatz, M. Kripp, N. Schulte, M. Tetyusheva, S. Heeger, S. Vlassak, K. Merx
Journal: Annals of Oncology (2018)

Acne-like skin rash is a frequently occurring adverse event associated with drugs against the epidermal growth factor receptor. This randomized vehicle-controlled study investigated the addition of vitamin K1 cream to doxycycline in patients with metastatic colorectal cancer treated with cetuximab.Patients receiving first-line cetuximab + FOLFIRI were randomly assigned to prophylactic treatment with doxycylin and vitamin K1 cream or doxycycline and the vehicle. The primary end point of the study was the incidence of grade ≥ 2 skin rash (NCI CTCAE version 4.02) during 8 weeks of skin treatment. Secondary end points comprised skin rash according to a more thorough tripartite skin toxicity score (WoMo), quality of life, efficacy, and compliance. The study had 80% power to show a 20% reduction of the incidence of grade ≥ 2 skin rash.A total of 126 patients were analyzed. The incidence of skin rash grade ≥ 2 was comparable between the arms. Likewise, no difference was seen in the WoMo score with respect to the percentage of skin affected. However, starting in week 5 and increasing over time patients treated with vitamin K1 cream had less severe rash and fewer fissures. Quality of life as well as efficacy and compliance with study medication and anticancer treatment was comparable in both arms.The primary end point of decreasing grade ≥ 2 skin rash was not met. However, using vitamin K1 cream as part of prophylactic treatment decreased the severity of acne-like skin rash according to WoMo, an alternative and more thorough skin toxicity scoring tool.
Extended radical prostatectomy following neoadjuvant chemohormononal therapy (low dose estrmustine + LHRH agonist/antagonist) contributes to good cancer control for patients with high risk localized prostate cancer.
Authors: Hideki Enokida, Hirofumi Yoshino, Masayuki Nakagawa
Journal: Journal of Clinical Oncology (2018)

185 Background: Patients with high-risk prostate cancer (PCa) according to D’Amico risk categories are prone to a pathological diagnosis of positive margins or lymph node invasion and biochemical recurrence, despite having undergone radical prostatectomy (RP). Therefore, it is controversial whether RP should be done for high risk PC patients. Methods: 87 high-risk PCa patients prospectively underwent ‘extended’ RP following neoadjuvant chemohormonal therapy (NAC); primarily 6 months of estramustine phosphate 280 mg bid, along with a LH-RH agonist/antagonist. Our surgical technique was developed to reduce the rates of positive surgical margins. The goal is to approach the muscle layer of the rectum by dissecting the mesorectal fascia and continuing the dissection through the mesorectum until the muscle layer of the rectum is exposed. The procedure was safely performed as a result of good recognition of the structure between the perineal body and the rectal surface. We also performed extended lymphadenectomy if the patients meet two or more of D’Amico risk categories Results: More than 1 year had elapsed after surgery in 69 of the 87 patients with the median follow-up period of 36.2 months. Among those 69 patients, 18 (26.1%) experienced PSA failure. Kaplan-Meier analyses revealed that significant poorer PSA progression-free survival were observed in patients with higher positive biopsy core ratio, lymph node metastasis, and higher pathological stage (pT3a/b). Multivariate Cox-regression analysis revealed that higher pathological stage (pT3a/b) was the only independent valuable for predicting PSA progression failure. These 18 cases received salvage androgen deprivation therapy followed-by external beam radiotherapy and showed no progression after the salvage therapies (median follow-up period, 34.6 months after PSA progression). Conclusions: NAC concordant with extended RP is feasible and contributes to negative surgical margins that might provide good cancer control for patients with high-risk PCa.
Cinemeducation: a comprehensive guide to using film in medical education
Authors: Deana Midmer
Journal: BMJ (2005)

Eds Matthew Alexander, Patricia Lenahan, Anna Pavlov

Radcliffe Publishing, 2004, £27.95, 272 pages

ISBN 1 85775 692 4

Rating: ⋆⋆⋆⋆/5



While reviewing this book today I found two mentions of the use of cinema in the newspaper.1 One relates to whether a degree in cinema studies is the new MBA. The second is the use by British psychotherapists of feature films to encourage people to discuss their problems, a practice supported by the Royal College of Psychiatrists. This book on cinemeducation could not be …
Emergency medicine is in a spiral of deskilling, trainees warn
Authors: Abi Rimmer
Journal: BMJ (2014)

Emergency medicine trainees have warned that they risk becoming deskilled because they are carrying out fewer procedures than their predecessors. 

The Emergency Medicine Trainees’ Association and the BMA held a meeting on 25 July to identify ways of improving trainees’ working lives. Among the issues discussed at the event were concerns that emergency medicine doctors were becoming deskilled because they were relied on to triage rather than treat patients. 

Sarah Payne, a year 5 specialty trainee (ST5) in emergency medicine, said, “A big problem we have is that you get these skills as a fairly junior trainee, but you then go to departments where you cannot practise them as higher trainees. When you become a consultant you have lost confidence in yourself. You then can’t supervise your juniors to perform them, and it just becomes a self fulfilling cycle.”

She added, “Unless we have consultants …
Grumpy old doctors: Appointments
Authors: Brian Keighley
Journal: BMJ (2005)

Some of us in general practice are old enough to remember a golden age when appointments were events that were arranged for the convenience of the doctor, rather than the patient. Appointments used to be offered for extraordinary events such as medical examinations or as an occasional arrangement so that one could spend more time with a patient with a complicated, usually emotional, problem.

Political correctness and our patient centred NHS now demand that convenience is something for patients , not for the mere technicians whom the service is still pleased to call its doctors. At least, that is the theory, according to the “Gospel of New Labour.” The reality is something quite different.

The introduction of appointments systems in the 1970s had a good evidence base. Professor John Howie, that rare oxymoron—a practical academic, carried out research which showed that doctors were less stressed when they could plan their work through appointments, and that longer appointments produced more satisfied patients and fewer prescriptions. So far so good.

What those who rushed to embrace appointment systems failed to anticipate was a …
IMPACT OF ADENOSINE A2A RECEPTOR POLYMORPHISM RS5751876 ON PLATELET REACTIVITY IN TICAGRELOR TREATED PATIENTS
Authors: Monica Verdoia, Matteo Nardin, Lucia Barbieri, Roberta Rolla, Gennaro Galasso, Paolo Marino, Giorgio Bellomo, Giuseppe De Luca
Journal: Journal of the American College of Cardiology (2018)
Associations between Methylated Metabolites of Arsenic and Selenium in Urine of Pregnant Bangladeshi Women and Interactions between the Main Genes Involved
Authors: Helena Skröder, Karin Engström, Doris Kuehnelt, Maria Kippler, Kevin Francesconi, Barbro Nermell, Fahmida Tofail, Karin Broberg, Marie Vahter
Journal: Environmental Health Perspectives (2018)

Background: It has been proposed that interactions between selenium and arsenic in the body may affect their kinetics and toxicity. However, it is unknown how the elements influence each other in humans. Objectives: We aimed to investigate potential interactions in the methylation of selenium and arsenic. Methods: Urinary selenium (U-Se) and arsenic (U-As) were measured using inductively coupled plasma mass spectrometry (ICPMS) in samples collected from pregnant women (n=226) in rural Bangladesh at gestational weeks (GW) 8, 14, 19, and 30. Urinary concentrations of trimethyl selenonium ion (TMSe) were measured by HPLC–vapor generation–ICPMS, as were inorganic arsenic (iAs), methylarsonic acid (MMA), and dimethylarsinic acid (DMA). Methylation efficiency was assessed based on relative amounts (%) of arsenic and selenium metabolites in urine. Genotyping for the main arsenite and selenium methyltransferases, AS3MT and INMT, was performed using TaqMan probes or Sequenom. Results: Multivariable-adjusted linear regression analyses indicated that %TMSe (at GW8) was positively associated with %MMA (β=1.3, 95% CI: 0.56, 2.0) and U-As, and inversely associated with %DMA and U-Se in producers of TMSe (INMT rs6970396 AG+AA, n=74), who had a wide range of urinary TMSe (12–42%). Also, %TMSe decreased in parallel to %MMA during pregnancy, especially in the first trimester (−0.58 %TMSe per gestational week). We found a gene–gene interaction for %MMA (p-interaction=0.076 for haplotype 1). In analysis stratified by INMT genotype, the association between %MMA and both AS3MT haplotypes 1 and 3 was stronger in women with the INMT GG (TMSe nonproducers, 5th–95th percentile: 0.2–2%TMSe) vs. AG+AA genotype. Conclusions: Our findings for Bangladeshi women suggest a positive association between urinary %MMA and %TMSe. Genes involved in the methylation of selenium and arsenic may interact on associations with urinary %MMA. https://doi.org/10.1289/EHP1912
Survival outcomes and costs of trimodal therapy compared with radical cystectomy among patients diagnosed with localized muscle-invasive bladder cancer.
Authors: Stephen Bentley Williams, Yong Shan, Usama Jazzar, Hemalkumar B Mehta, Jacques G. Baillargeon, Jinhai (Stephen) Huo, Eduardo Orihuela, Douglas S. Tyler, Todd A. Swanson, Ashish M. Kamat
Journal: Journal of Clinical Oncology (2018)

421 Background: Radical cystectomy is the guideline-recommended treatment for muscle-invasive bladder cancer. Recently there has been a resurgence in trimodal therapy with limited data on comparative outcomes, and especially attributable costs. Methods: A total of 3,200 patients aged 66 years or older diagnosed with clinical stage T2-4a bladder cancer from January 1, 2002- December 31, 2011 from the Surveillance, Epidemiology, and End Results (SEER)-Medicare data were analyzed. Cox regression analysis and propensity score matching methods were used to determine predictors for overall and cancer-specific survival. Results: A total of 3,200 patients met inclusion criteria. After propensity score matching, 687 patients underwent trimodal therapy and 687 patients underwent radical cystectomy. Patients who underwent trimodal therapy had significantly decreased overall (Hazard Ratio (HR) 1.49, 95% Confidence Interval (CI), 1.31-1.69, p &lt; 0.001) and cancer-specific (HR 1.55, 95% CI 1.32-1.83, p &lt; 0.001) survival, respectively. While there was no difference in costs at 30 days, median total costs were significantly higher with trimodal therapy than radical cystectomy at 90-d ($63,355 vs. $73,420, p &lt; 0.001) and 180-d ($98,005 vs. $164,720, p &lt; 0.001), respectively. Extrapolating these figures to the total US population results in excess spending of $179 million for trimodal therapy compared to less costly radical cystectomy for patients diagnosed in 2011. Conclusions: Trimodal therapy was associated with significantly decreased overall and cancer-specific survival resulting in excess national spending of $179 million in 2011 compared with radical cystectomy. These findings have important health policy implications regarding appropriate use of high-value based care among patients who are candidates for either treatment.
Transform your life: Become the person you want to be
Authors: Marcia Willis
Journal: BMJ (2006)

Transform your life: become the person you want to be is published by Infinite Ideas. Readers of BMJ Careers can purchase the book at the special price of £9.99 with free P&P (normal book RRP £12.99). For credit card orders please call 01865 514 888 or send a cheque to Infinite Ideas, 36 St. Giles, Oxford OX1 3LD. Please quote the promotional code of “Brilliant 111”. For more information about Infinite Ideas visit their website at www.infideas.com



Penny Ferguson.

Infinite Ideas, 2004, £12.99, 240 pages

ISBN 1 90490 223 5

Rating: ★★★★/5



“Oh no,” I hear you say. But don't be put off by the title. And before you ask, I have …
Real-world experience with docetaxel for castration-sensitive prostate cancer from a population-based analysis.
Authors: Jean-Michel Lavoie, Kevin Zou, Daniel Khalaf, Bernhard J. Eigl, Christian K. Kollmannsberger, Joanna Vergidis, Krista Noonan, Muhammad Zulfiqar, Daygen L. Finch, Kim N. Chi
Journal: Journal of Clinical Oncology (2018)

297 Background: Phase III clinical trials have demonstrated efficacy with an overall survival (OS) benefit for the addition of docetaxel (DOC) to androgen deprivation therapy (ADT) for the treatment of metastatic castration-sensitive prostate cancer (mCSPC). The clinical effectiveness of DOC with ADT in the general patient population remains undefined. Methods: A population-based retrospective review was conducted of patients (pts) with mCSPC who received DOC at the BC Cancer Agency from 04/2015 to 02/2017. Patient and disease characteristics were extracted. Safety and clinical-effectiveness were evaluated. Results: 183 records were identified; 156 pts received DOC in the mCSPC setting. Baseline characteristics included a median age of 67 years (range 44-86) and visceral metastases (mets) present in 18%; 80% had high volume disease with 74% having &gt; 3, and 54% &gt; 10 bone mets; 76% had de-novo metastatic disease. All 6 planned DOC cycles were delivered in 126 cases (81%); it was stopped early for: toxicity in 15 (10%), unrelated death in 1 (0.6%), pt preference in 5 (3%) or disease progression in 9 (6%) cases. Dose reductions and delays were required in 61 (39%) and 25 (16%) cases, respectively. Grade 3-5 adverse events were noted in 62 (40%) cases, with 28 (18%) cases of febrile neutropenia (FN); there were no treatment-related deaths. Pts with FN had more bone mets (p = 0.046), but there was no difference in time from start of ADT to initiation of docetaxel, age, baseline performance status, PSA, or visceral involvement. PSA ≤ 0.2 ng/L was achieved in 41 (28%) cases after 6 months of ADT and maintained in 13 (8%) cases after 12 months. 41% of pts had developed CRPC within 1-yr, with a median time to CRPC of 14.3 months. Treatment for CRPC was given in 54 cases, with most pts receiving either abiraterone or enzalutamide (87%) with a PSA decline ≥50% occurring in 47%. Conclusions: Effectiveness of DOC with ADT in a general population of pts with mCSPC was associated with poorer outcomes and high rates of toxicity compared to the phase III studies. Response rates to first-line treatment for mCRPC with abiraterone or enzalutamide appear similar to those previously reported.
Medical student debts could be paid as incentive to work in Wales, Plaid Cymru says
Authors: Abi Rimmer
Journal: BMJ (2014)

Medical students who go on to work as doctors in Wales could have their debts paid off, under plans announced by Plaid Cymru. The plans also propose quotas for Welsh speakers in Welsh medical schools.

In a white paper the party said that Wales could adopt a system whereby doctors who agreed to undertake postgraduate training received a financial incentive to stay in Wales.1 “This could take the form of having a fixed amount of student loan repaid for each year of service once a qualifying period of training has been agreed,” the white paper said.

The proposal is based on the New Zealand bond scheme, which rewards doctors who agree to …