tbuckley/cabot-search huggingface dataset:
NHS must invest in engaging doctors in leadership, King’s Fund says
Authors: Matthew Limb
Journal: BMJ (2014)

The NHS must invest more money in medical engagement in leadership, because it improves the quality of care and of organisational performance and cannot “be left to chance,” the King’s Fund has said.

NHS boards must be committed to making medical engagement a central part of hospital leadership, the organisation said in a report published on 10 July.1 Vijaya Nath, coauthor of the report and assistant director of leadership development at the King’s Fund, said that many organisations still had poor medical engagement, with few doctors taking up leadership positions. Financially stable trusts had the necessary funds to prioritise investment in medical engagement, but those that were struggling would need help, she said. “More money is needed to fund this, and if it can’t come from the organisation it must come from outside. Where that investment is put in we see what it gets by way of results,” she told BMJ Careers.

High levels of medical …
Bone Morphogenetic Protein 9 Reduces Cardiac Fibrosis and Improves Cardiac Function in Heart Failure
Authors: Kevin J. Morine, Xiaoying Qiao, Sam York, Peter S. Natov, Vikram Paruchuri, Yali Zhang, Mark J. Aronovitz, Richard H. Karas, Navin K. Kapur
Journal: Circulation (2018)

Background: Heart failure is a growing cause of morbidity and mortality worldwide. Transforming growth factor beta (TGF-β1) promotes cardiac fibrosis, but also activates counterregulatory pathways that serve to regulate TGF-β1 activity in heart failure. Bone morphogenetic protein 9 (BMP9) is a member of the TGFβ family of cytokines and signals via the downstream effector protein Smad1. Endoglin is a TGFβ coreceptor that promotes TGF-β1 signaling via Smad3 and binds BMP9 with high affinity. We hypothesized that BMP9 limits cardiac fibrosis by activating Smad1 and attenuating Smad3, and, furthermore, that neutralizing endoglin activity promotes BMP9 activity. Methods: We examined BMP9 expression and signaling in human cardiac fibroblasts and human subjects with heart failure. We used the transverse aortic constriction–induced model of heart failure to evaluate the functional effect of BMP9 signaling on cardiac remodeling. Results: BMP9 expression is increased in the circulation and left ventricle (LV) of human subjects with heart failure and is expressed by cardiac fibroblasts. Next, we observed that BMP9 attenuates type I collagen synthesis in human cardiac fibroblasts using recombinant human BMP9 and a small interfering RNA approach. In BMP9 –/– mice subjected to transverse aortic constriction, loss of BMP9 activity promotes cardiac fibrosis, impairs LV function, and increases LV levels of phosphorylated Smad3 (pSmad3), not pSmad1. In contrast, treatment of wild-type mice subjected to transverse aortic constriction with recombinant BMP9 limits progression of cardiac fibrosis, improves LV function, enhances myocardial capillary density, and increases LV levels of pSmad1, not pSmad3 in comparison with vehicle-treated controls. Because endoglin binds BMP9 with high affinity, we explored the effect of reduced endoglin activity on BMP9 activity. Neutralizing endoglin activity in human cardiac fibroblasts or in wild-type mice subjected to transverse aortic constriction–induced heart failure limits collagen production, increases BMP9 protein levels, and increases levels of pSmad1, not pSmad3. Conclusions: Our results identify a novel functional role for BMP9 as an endogenous inhibitor of cardiac fibrosis attributable to LV pressure overload and further show that treatment with either recombinant BMP9 or disruption of endoglin activity promotes BMP9 activity and limits cardiac fibrosis in heart failure, thereby providing potentially novel therapeutic approaches for patients with heart failure.
NICE recommends kidney cancer drug “likely to be less effective” than current treatments after price deal
Authors: Susan Mayor
Journal: BMJ (2018)

The National Institute for Health and Care Excellence (NICE) has recommended tivozanib as an option for treating adults with previously untreated advanced renal cell carcinoma, after the manufacturer agreed a discount to make the cost lower than existing treatments even though the appraisal committee found it “likely to be less effective.”

“The estimated costs savings are high enough to compensate for the estimated lower effectiveness,” said the final …
SPARTAN, a phase 3 double-blind, randomized study of apalutamide (APA) versus placebo (PBO) in patients (pts) with nonmetastatic castration-resistant prostate cancer (nmCRPC).
Authors: Eric Jay Small, Fred Saad, Simon Chowdhury, Boris A. Hadaschik, Julie Nicole Graff, David Olmos, Paul N. Mainwaring, Hiroji Uemura, Angela Lopez-Gitlitz, Geralyn Carol Trudel, Byron M. Espina, Youyi Shu, Youn C. Park, Wayne R. Rackoff, Margaret K. Yu, Matthew Raymond Smith
Journal: Journal of Clinical Oncology (2018)

161 Background: Pts with nmCRPC are at risk for developing metastatic disease and cancer-specific mortality. There are no approved treatments for nmCRPC. APA is an orally administered next-generation androgen receptor inhibitor with antitumor activity in CRPC. SPARTAN evaluated the effects of APA on metastasis-free survival (MFS) in men with nmCRPC. Methods: Pts with nmCRPC and prostate-specific antigen doubling time (PSADT) of ≤ 10 mos were randomized 2:1 to APA (240 mg QD) or PBO. The primary end point was MFS, defined as the time from randomization to first radiographic distant metastasis (per blinded central review) or death. Secondary end points included time to metastasis (TTM), progression-free survival (PFS), time to symptomatic progression (SymProg), and overall survival (OS). Pts were eligible to receive study-provided abiraterone acetate plus prednisone after developing distant metastases. Second progression-free survival (PFS2, the time from randomization to disease progression or death after first treatment for metastatic CRPC) was also evaluated. Results: 1207 pts were randomized. Baseline PSADT was &lt; 5 mos in both groups. APA decreased the risk of distant metastasis or death by 72% (HR = 0.28; 95% CI, 0.23-0.35; p &lt; 0.0001), with a median MFS of 40.5 vs 16.2 mos in the PBO group. Secondary end points (TTM, PFS, and SymProg) were all significantly improved. At an interim analysis for OS, there was a trend favoring APA. At a median follow-up of 20.3 mos, 61% of APA and 30% of PBO pts were still on treatment. Rates of discontinuation due to adverse events were low in both groups (10.7% APA, 6.3% PBO). Mean baseline health-related quality of life scores were maintained with treatment, with no difference between groups over time. Of those whose disease progressed, 80% of PBO and 56% of APA pts received therapy for metastatic CRPC. PFS2 was significantly longer for APA vs PBO. Conclusions: APA significantly improved median MFS by 2 years in men with nmCRPC. APA also significantly increased TTM, PFS, SymProg, and PFS2. APA was associated with improved OS. These results support the addition of APA to androgen deprivation therapy in men with nmCRPC. Clinical trial information: NCT01946204.
Postgraduate Certificate in Academic Practice
Authors: David Ogilvie
Journal: BMJ (2005)

Anyone who teaches in higher education—not just university lecturers, but anyone with teaching responsibilities, such as specialist registrars or research fellows.

During my final two years as a specialist registrar in public health medicine (2003-4), while I was based in an academic unit.

I found myself teaching with little to go on except my own experiences as …
Comparison of patient (POEM), observer (EASI, SASSAD, TIS) and corneometry measures of emollient effectiveness in children with eczema: findings from the COMET feasibility trial
Authors: M.J. Ridd, D.M. Gaunt, R.H. Guy, N.M. Redmond, K. Garfield, S. Hollinghurst, N. Ball, L. Shaw, S. Purdy, C. Metcalfe
Journal: British Journal of Dermatology (2018)

Eczema affects around 20% of children, but multiple different outcome measures have hampered research into the effectiveness of different treatments.To compare the change in scores and correlations within and between five measures of eczema severity: Patient-Orientated Eczema Measure (POEM), Eczema Area and Severity Index (EASI), Six Area, Six Sign Atopic Dermatitis (SASSAD), Three Item Severity (TIS) and skin hydration (corneometry).Data from a feasibility trial that randomized young children with eczema to one of four emollients were used. Participants were followed for 3 months (84 days). Descriptive statistics (by emollient over time) and Spearman's correlation coefficients comparing scores at each time point and absolute change (between adjacent time points) for each outcome measure were calculated.In total, 197 children, mean ± SD age 21·7 ± 12·8 months, were randomized. POEM and TIS appeared to capture a range of eczema severity at baseline, but only POEM had close approximation to normal distribution. Mean POEM, EASI, SASSAD and TIS scores improved month by month, with POEM showing the greatest sensitivity (effect size 0·42). Correlations within POEM, EASI, SASSAD and TIS were moderate to good, decreasing over time. Correlations between measures were strongest for EASI, SASSAD and TIS. By contrast, corneometry scores were more variable, correlated less well over time and were poorly correlated with the other measures.Except for corneometry, all measures appear to change in relation to emollient use over time and correlate well with themselves. POEM demonstrated the greatest range of scores at baseline and change in eczema severity over the first 28 days.
The new president of the Medical Women's Federation
Authors: Karen Hebert
Journal: BMJ (2005)

Bhupinder Sandhu is the new president of the Medical Women9s Federation. Combining a career as a high flying professor of paediatric gastroenterology with family life, she epitomises everything that the federation stands for. Karen Hebert spent 15 minutes with her and found out all about smallpox, DIY, and her involvement in the Medical Women9s Federation.
Sequencing radium 223 (RA223) for metastatic castration-resistant prostate cancer (mCRPC) patients (pts) in the daily practice: Preliminary results from a retrospective study in Italian centers.
Authors: Orazio Caffo, Viviana Frantellizzi, Luca Galli, Fabio Monari, Gaetano Facchini, Sergio Baldari, Marcello Tucci, Filippo Alongi, Roberto Bortolus, Stefania Agostini, Elisa Biasco, Stefano Fanti, Sabrina Rossetti, Salvatore Pignata, Clizia Zichi, Matteo Salgarello, Eugenio Borsatti, Enrico Cortesi, Andrea Sbrana, Giuseppe De Vincentis
Journal: Journal of Clinical Oncology (2018)

322 Background: The potential advantage of the sequential use of the active drugs (ADs) able to prolong overall survival (OS) in mCRPC (abiraterone, cabazitaxel, docetaxel, enzalutamide, RA223) could be limited by the development of common mechanisms of resistance. According to its unique targeted alpha-radiation mechanism of action, it could be postulated that RA223 does not induce and is not affected by cross-resistance with other agents and consequently its incorporation in therapeutic sequences may improve clinical outcomes. The present study is aimed to describe the clinical outcomes of pts who received RA223 and at least two other ADs for mCRPC. Methods: We collected data of pts who received sequentially 3 or more ADs of which one was RA223. For each pt we recorded the clinical outcome of all treatments received for mCRPC. We also compared the cumulative survival from the start of the first line to that of a contemporary series of 405 mCRPC pts without visceral mets sequentially treated with 3 or 4 ADs not comprising RA223. Results: A consecutive series of 119 mCRPC pts was collected: the median age was 72 yrs. Six pts received all 5 available ADs, 53 pts 4 ADs, and the remaining pts 3 ADs. Most of the pts received RA223 as the 3 rd or 4 th line of treatment (62 and 42, respectively), and the remaining were treated in less or more advanced lines (10 and 5 pts respectively). Overall the full 6-cycle treatment was completed in 61 pts (51.3%) and in 61.3% and 38.1% of pts when Ra223 was administered as 3 rd and 4 th treatment line respectively (p = 0.02). Partial response and stable disease as best objective response to RA223 was achieved in 11.3% and 24.5% of pts respectively, while a PSA reduction of ≥ 50% was observed in 7.2% of pts. Median OS from the start of the first line was 48 mos. In pts treated with 3 or 4 ADs that included Ra223, the median OS was significantly longer compared to that of pts whose treatment sequence did not include RA223 (48.4 vs 39.2 mos, p = 0.03). Conclusions: Despite the limitations of its retrospective nature, this preliminary data suggests that treatment sequencing of ADs that includes RA223 offers a survival advantage in mCRPC.
Trained Innate Immunity as a Novel Mechanism Linking Infection and the Development of Atherosclerosis
Authors: Jenneke Leentjens, Siroon Bekkering, Leo A.B. Joosten, Mihai G. Netea, David P. Burgner, Niels P. Riksen
Journal: Circulation Research (2018)

Rationale: There is strong epidemiological evidence for an association between acute and chronic infections and the occurrence of atherosclerotic cardiovascular disease. The underlying pathophysiological mechanisms remain unclear. Monocyte-derived macrophages are the most abundant immune cells in atherosclerotic plaques. It has recently been established that monocytes/macrophages can develop a long-lasting proinflammatory phenotype after brief stimulation with micro-organisms or microbial products, which has been termed trained immunity. Objective: The aim of this study is to assess whether trained immunity mediates the link between infections and atherosclerotic cardiovascular disease. Methods and Results: Brief exposure of monocytes to various micro-organisms results in the development of macrophages with a persistent proinflammatory phenotype: this represents a de facto nonspecific innate immune memory, which has been termed trained immunity. This is mediated by epigenetic reprogramming at the level of histone methylation and a profound rewiring of intracellular metabolism. Although this mechanism offers powerful protection against reinfection, trained macrophages display an atherogenic phenotype in terms of cytokine production and foam cell formation. Trained monocytes are present up to 3 months after experimental infection in humans. Moreover, a trained immunity phenotype is present in patients with established atherosclerosis. Conclusions: We propose that trained immunity provides the missing mechanistic link that explains the association between infections and atherosclerosis. Therefore, pharmacological modulation of trained immunity has the potential to prevent infection-related atherosclerotic cardiovascular disease in the future.
A Review on Accelerometry-Based Gait Analysis and Emerging Clinical Applications
Authors: Delaram Jarchi, James Pope, Tracey K. M. Lee, Larisa Tamjidi, Amirhosein Mirzaei, Saeid Sanei
Journal: IEEE Reviews in Biomedical Engineering (2018)

Gait analysis continues to be an important technique for many clinical applications to diagnose and monitor certain diseases. Many mental and physical abnormalities cause measurable differences in a person's gait. Gait analysis has applications in sport, computer games, physical rehabilitation, clinical assessment, surveillance, human recognition, modeling, and many other fields. There are established methods using various sensors for gait analysis, of which accelerometers are one of the most often employed. Accelerometer sensors are generally more user friendly and less invasive. In this paper, we review research regarding accelerometer sensors used for gait analysis with particular focus on clinical applications. We provide a brief introduction to accelerometer theory followed by other popular sensing technologies. Commonly used gait phases and parameters are enumerated. The details of selecting the papers for review are provided. We also review several gait analysis software. Then we provide an extensive report of accelerometry-based gait analysis systems and applications, with additional emphasis on trunk accelerometry. We conclude this review with future research directions.
Are student electives equivalent to clinical attachments? Which is better on a CV, and which helps more in finding UK SHO posts?
Authors: Faisal Hanif
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>
London mayor candidate says that he “stands with” junior doctors
Authors: Tom Moberly
Journal: BMJ (2016)

Sadiq Khan, Labour’s candidate for London mayor, has said that he “stands with” junior doctors and that he would push the government to resolve the ongoing dispute over the junior doctor contract.

He told BMJ Careers that the government’s actions during the current dispute had been “appalling” and led to “unnecessary upheaval” for the health service and patients.

“I stand with the junior doctors and lay the blame squarely at the door of …
BMA says it will resist any new contract that is bad for junior doctors
Authors: Abi Rimmer
Journal: BMJ (2015)

The BMA has said that it will resist the imposition of a new contract for junior doctors if it is “bad for patients, bad for junior doctors, and bad for the NHS.”

The statement came after the Department of Health for England announced that it would impose a new contract for junior doctors in England in August 2016, for both new starters and new appointees. Last month the BMA Junior Doctors Committee said that it would not re-enter negotiations with NHS Employers over a new contract.1 …
Hemoglobin A<sub>1c</sub> Targets for Glycemic Control With Pharmacologic Therapy for Nonpregnant Adults With Type 2 Diabetes Mellitus: A Guidance Statement Update From the American College of Physicians
Authors: Amir Qaseem, Timothy J. Wilt, Devan Kansagara, Carrie Horwitch, Michael J. Barry, Mary Ann Forciea
Journal: Annals of Internal Medicine (2018)

The American College of Physicians developed this guidance statement to guide clinicians in selecting targets for pharmacologic treatment of type 2 diabetes.The National Guideline Clearinghouse and the Guidelines International Network library were searched (May 2017) for national guidelines, published in English, that addressed hemoglobin A1c (HbA1c) targets for treating type 2 diabetes in nonpregnant outpatient adults. The authors identified guidelines from the National Institute for Health and Care Excellence and the Institute for Clinical Systems Improvement. In addition, 4 commonly used guidelines were reviewed, from the American Association of Clinical Endocrinologists and American College of Endocrinology, the American Diabetes Association, the Scottish Intercollegiate Guidelines Network, and the U.S. Department of Veterans Affairs and Department of Defense. The AGREE II (Appraisal of Guidelines for Research and Evaluation II) instrument was used to evaluate the guidelines.Clinicians should personalize goals for glycemic control in patients with type 2 diabetes on the basis of a discussion of benefits and harms of pharmacotherapy, patients' preferences, patients' general health and life expectancy, treatment burden, and costs of care.Clinicians should aim to achieve an HbA1c level between 7% and 8% in most patients with type 2 diabetes.Clinicians should consider deintensifying pharmacologic therapy in patients with type 2 diabetes who achieve HbA1c levels less than 6.5%.Clinicians should treat patients with type 2 diabetes to minimize symptoms related to hyperglycemia and avoid targeting an HbA1c level in patients with a life expectancy less than 10 years due to advanced age (80 years or older), residence in a nursing home, or chronic conditions (such as dementia, cancer, end-stage kidney disease, or severe chronic obstructive pulmonary disease or congestive heart failure) because the harms outweigh the benefits in this population.
CARDIAC AND GERIATRIC DETERMINANTS OF FUNCTIONAL STATUS AND SURVIVAL IN OLDER ADULTS UNDERGOING TRANSCATHETER AORTIC VALVE REPLACEMENT
Authors: Mina Girgis, Nicolo Piazza, Giuseppe Martucci, Dae Hyun Kim, Jeffrey Popma, Sandra Lauck, John Webb, Anita Asgar, Louis Perrault, Thierry Lefevre, Marino Labinaz, Andre Lamy, Mark Peterson, Rakesh C. Arora, Nicolas Noiseux, Philippe Généreux, Marco Spaziano, José Morais, Jonathan Afilalo
Journal: Journal of the American College of Cardiology (2018)
Core medical training needs “urgent” reform to drive up quality, says RCP
Authors: Abi Rimmer
Journal: BMJ (2014)

Urgent changes are needed to improve the quality of core medical training (CMT), a report by the Royal College of Physicians (RCP) and the Joint Royal Colleges of Physicians Training Board (JRCPTB) has suggested.

The report found that CMT trainees were spending too much time providing services and not enough time receiving training. It also raised concerns that trainees were often not able to attend outpatient clinics and training sessions, and that many did not receive enough feedback from senior colleagues.

The RCP carried out a survey in June last year of junior doctors undertaking CMT, and received responses from 779 trainees. In a report on the survey, the RCP warned the findings suggested that, if CMT were not improved, recruitment to the programme would “continue to decrease” and it would become increasingly difficult to recruit to medical specialties.1 “Urgent changes must be made to improve the quality of training for CMT trainees who are the future consultants of our medical workforce,” the report said.

In total, 91% of respondents to the survey said that they had spent 80% to 100% …
OVOL2 in metastasis prevention in NPC
Authors: Kyung-A Song, Anthony C. Faber
Journal: Theranostics (2018)

Metastasis remains a critical -and largely elusive -target in the race to prevent cancer-related deaths.Such is true in nasopharyngeal carcinoma (NPC), where the presentation or development of metastatic disease is usually fatal.In this edition of Theranostics, Qi et al. demonstrate a critical role of the zinc-finger transcription factor, OVOL2, in suppressing metastasis and maintaining an epithelial phenotype.These data add to the depth of understanding of the metastatic program in NPC, and may eventually lead to a druggable target in late-stage NPC.
Deep Learning for Prediction of Obstructive Disease From Fast Myocardial Perfusion SPECT
Authors: Julian Betancur, Frederic Commandeur, Mahsaw Motlagh, Tali Sharir, Andrew J. Einstein, Sabahat Bokhari, Mathews B. Fish, Terrence D. Ruddy, Philipp Kaufmann, Albert J. Sinusas, Edward J. Miller, Timothy M. Bateman, Sharmila Dorbala, Marcelo Di Carli, Guido Germano, Yuka Otaki, Balaji K. Tamarappoo, Damini Dey, Daniel S. Berman, Piotr J. Slomka
Journal: JACC. Cardiovascular imaging (2018)
How to pass the MRCOG
Authors: Peter Cross
Journal: BMJ (2004)

<i>As part of our series to help you succeed in the current postgraduate Royal College exams,</i> Sabina Dosani <i>and</i> Peter Cross <i>give the lowdown on the membership exam of the Royal College of Obstetricians and Gynaecologists and interview examiners and candidates for their tips on passing it.</i>