tbuckley/cabot-search huggingface dataset:
David Delvin: GMC rebel and bestselling author
Authors: John Illman
Journal: BMJ (2018)

Every doctor writing for the media today owes a great debt to David Delvin—one of the few doctors who has been both the subject of a complaint to the General Medical Council and a council member. As a young doctor in the 1960s, he developed a passion for writing, but the deeply conservative GMC was only too ready to rule that any doctor exposing themselves to the limelight of publicity was self advertising. Doctors were justifiably afraid about either talking to journalists or writing for newspapers or magazines.

But Delvin reflected the values for which the “swinging sixties” are now remembered. The revolt of the age was symbolised by the Rolling Stones, the Beatles, student uprisings, the civil rights movement, the Campaign for Nuclear Disarmament, the anti-Vietnam war movement, women’s liberation, and the advent of the contraceptive pill, a driver of the sexual revolution. Nothing was sacred any more.

Delvin was adamant that doctors should not be compelled to write under pseudonyms, but was …
GPs demand abolition of practice boundary pilots
Authors: Helen Jaques
Journal: BMJ (2012)

Government pilot schemes to allow patients to register at a practice away from where they live should be abolished, GPs at the annual conference of local medical committees have said.

The pilots, currently taking place in London, Manchester, and Salford, are designed to allow patients to register with a general practice outside their normal area of residence or to visit a practice away from home on a consultation only basis ( BMJ Careers , 12 Apr, http://careers.bmj.com/careers/advice/view-article.html?id=20007086).

However, the plan threatens the …
Criminal offence of wilful neglect may undermine, rather than improve, patient safety
Authors: Pallavi Bradshaw
Journal: BMJ (2015)

Doctors facing the challenges of everyday clinical practice could be forgiven for not noticing the passing of an act of parliament. But a few lines of legislation could have a life changing effect on doctors and inflict a fundamental blow to openness and transparency in the NHS. <b>Pallavi Bradshaw </b>investigates
THE EFFICACY AND TOLERABILITY OF ANACETRAPIB IN THE TREATMENT OF DYSLIPIDEMIA: A POOLED ANALYSIS OF RANDOMIZED CONTROLLED STUDIES
Authors: Ahmed Elgebaly, Amr Menshawy, Abdelrahman Aboshouk, Mohamed Shehata, Mohamed Abdelmaboud, Ahmed Elkaryoni
Journal: Journal of the American College of Cardiology (2018)
Impact of enzalutamide (ENZA) vs. bicalutamide (BIC) on health-related quality of life (HRQoL) of patients (pts) with castration-resistant prostate cancer (CRPC): STRIVE study.
Authors: Raoul Concepcion, Andrew J. Armstrong, Lawrence Ivan Karsh, Stefan Holmstrom, Cristina Ivanescu, Curtis Dunshee, Neeraj Agarwal, Michael O'Kelly, Shevani Naidoo, Carl A. Olsson, De Phung, Bohdana Ratitch, Fong Wang, Pavol Kral, David F. Penson
Journal: Journal of Clinical Oncology (2018)

234 Background: In STRIVE pts with CRPC (M0 n = 139; M1 n = 257), median time to 10-point decrease from baseline in FACT-P total for ENZA vs. BIC was 8.4 vs. 8.3 months (hazard ratio [HR] 0.91; 95% confidence interval [CI] 0.70, 1.19; p = 0.49). That assumed missing data was missing at random (MAR) and censored pts with no deterioration in FACT-P at last assessment. As HRQoL may worsen after progression/adverse events, for all STRIVE pts we replaced the MAR assumption with assumptions more likely to reflect clinically plausible HRQoL decline. Methods: Analyses of HRQoL decline (minimum clinically important difference or higher decrease in FACT-P vs. baseline) used a missing not at random (MNAR) assumption using a pattern mixture model (PMM) via sequential modeling with multiple imputation when imputation varies by reason of treatment discontinuation. Analysis of time to first clinically meaningful deterioration vs. baseline used a piecewise exponential survival multiple imputation model with reason-specific ∆ adjustment patterns similar to PMM analysis. Results: PMM analysis showed differences at week 61 in mean HRQoL change from baseline favoring ENZA vs. BIC for 7 of 10 scores: physical (PWB), functional, emotional (EWB), and social (SWB) well-being; FACT-P trial outcome index; FACT-G total; FACT-P total (all clinically meaningful except PWB). In the piecewise exponential survival imputation model, ENZA had a significantly lower risk of first deterioration in FACT-P total (0.76 [0.60, 0.95]), FACT-G total (0.66 [0.52, 0.83]), Prostate Cancer Subscale (PCS) pain-related (0.78 [0.62, 0.97]), SWB (0.49 [0.38, 0.64]), and EWB (0.58 [0.45, 0.75]) vs. BIC. For remaining domain scores, ENZA reduces risk of first deterioration (HR &lt; 1) but the 95% CI includes 1 (which means not significant); sensitivity analysis showed similar results. Conclusions: In STRIVE pts, declines in all FACT-P scores were smaller for ENZA vs. BIC up to week 61. Comparison of change from baseline at week 61 favored ENZA for 7 of 10 scores (6 clinically meaningful). ENZA had a significantly lower risk of first deterioration in FACT-P or FACT-G total, PCS pain-related, EWB, and SWB. Clinical trial information: NCT01664923.
Multiple common comorbidities produce left ventricular diastolic dysfunction associated with coronary microvascular dysfunction, oxidative stress, and myocardial stiffening
Authors: Oana Sorop, Ilkka Heinonen, Matthijs van Kranenburg, Jens van de Wouw, Vincent J de Beer, Isabel T N Nguyen, Yanti Octavia, Richard W B van Duin, Kelly Stam, Robert-Jan van Geuns, Piotr A Wielopolski, Gabriel P Krestin, Anton H van den Meiracker, Robin Verjans, Marc van Bilsen, A H Jan Danser, Walter J Paulus, Caroline Cheng, Wolfgang A Linke, Jaap A Joles, Marianne C Verhaar, Jolanda van der Velden, Daphne Merkus, Dirk J Duncker
Journal: Cardiovascular Research (2018)

More than 50% of patients with heart failure have preserved ejection fraction characterized by diastolic dysfunction. The prevalance of diastolic dysfunction is higher in females and associates with multiple comorbidities such as hypertension (HT), obesity, hypercholesterolemia (HC), and diabetes mellitus (DM). Although its pathophysiology remains incompletely understood, it has been proposed that these comorbidities induce systemic inflammation, coronary microvascular dysfunction, and oxidative stress, leading to myocardial fibrosis, myocyte stiffening and, ultimately, diastolic dysfunction. Here, we tested this hypothesis in a swine model chronically exposed to three common comorbidities.DM (induced by streptozotocin), HC (produced by high fat diet), and HT (resulting from renal artery embolization), were produced in 10 female swine, which were followed for 6 months. Eight female healthy swine on normal pig-chow served as controls. The DM + HC + HT group showed hyperglycemia, HC, hypertriglyceridemia, renal dysfunction and HT, which were associated with systemic inflammation. Myocardial superoxide production was markedly increased, due to increased NOX activity and eNOS uncoupling, and associated with reduced NO production, and impaired coronary small artery endothelium-dependent vasodilation. These abnormalities were accompanied by increased myocardial collagen content, reduced capillary/fiber ratio, and elevated passive cardiomyocyte stiffness, resulting in an increased left ventricular end-diastolic stiffness (measured by pressure-volume catheter) and a trend towards a reduced E/A ratio (measured by cardiac MRI), while ejection fraction was maintained.The combination of three common comorbidities leads to systemic inflammation, myocardial oxidative stress, and coronary microvascular dysfunction, which associate with myocardial stiffening and LV diastolic dysfunction with preserved ejection fraction.
OUTCOMES OF PATIENTS BRIDGED WITH CONTINUOUS FLOW-LEFT VENTRICULAR ASSIST DEVICE TO REPEAT HEART TRANSPLANT COMPARED TO FIRST HEART TRANSPLANT: A PROPENSITY SCORING MATCHED ANALYSIS OF THE UNOS DATABASE
Authors: Setri Fugar, Ahmed Kolkailah, Ahmed Al-Ogaili, Ali Ayoub, Muhammad Khan, Alfed Solomon, Chimezie Mbachi, Jayakumar Sreenivasan, Ijeoma Ezeife, Alexis Okoh
Journal: Journal of the American College of Cardiology (2018)
Half of public health consultants in local authorities want to leave their jobs, survey finds
Authors: Abi Rimmer
Journal: BMJ (2014)

Half of public health consultants and specialists working for local authorities are looking for work elsewhere in the public health system, a survey by the Centre for Workforce Intelligence has found.1

The centre carried out its survey of public health consultants and specialists after it was commissioned by Public Health England, Health Education England, and the Department of Health to gather data to inform workforce decisions. The survey received 574 responses from …
Combination therapy of low-dose gemcitabine and paclitaxel in every 4 weeks for patients with platinum-resistant urothelial cancer whose performance status is 2 or 3.
Authors: Tomohiro Matsuo, Yasuyoshi Miyata, Yuji Sagara, Kojiro Ohba, Hideki Sakai
Journal: Journal of Clinical Oncology (2018)

462 Background: Platinum-based regimens are standard therapy for advanced urothelial cancer (UC). However, second-line chemotherapy is still not established. Therefore, best supportive care is often selected in patients with poor performance status (PS). In our hospital, combination therapy of low-dose gemcitabine and paclitaxel every 4 weeks is administered as second-line therapy for platinum-resistant patients with PS 2 or 3. We investigated the quality of life (QoL) and safety of our regimen in these patients. Methods: Forty-two advanced UC patients were treated with gemcitabine (700 mg/m 2 on day 1) and paclitaxel (70 mg/m 2 on day 1) every 4 weeks (experimental group). The QoL was evaluated using the short-form survey (SF)-36, and the data were collected on the day before the first cycle was started and 8 weeks after starting the therapy. In addition, survival analysis was performed between these patients and 30 patients who received no second-line therapy (control group). Results: In experimental group, one patient showed grade 3 anemia after the treatment. However, this patient also had severe hematuria before staring of the therapy. No patient had severe adverse events (grade 3 and higher) because of this therapy. The QoL score decreased after the therapy; however, the difference was not significant. With regard to efficacy, partial response was found in two patients, and the mean/SD survival period of the experimental group was 9.2/7.2 months. This period was significantly (P &lt; 0.01) longer than that in the control group (5.8/2.4 months). In addition, 13 (31.0%) and 6 patients (14.3%) survived over 12 and 18 months, respectively. Conclusions: Combined therapy of low-dose gemcitabine and paclitaxel every 4 weeks was well tolerated, and the patient’s QoL was maintained after treatment. Some patients showed relatively long survival periods. We suggest that this treatment regimen is worthy of consideration as second-line therapy for patients with advanced UC with PS 2 or 3.
Peripherally derived T regulatory and γδ T cells have opposing roles in the pathogenesis of intractable pediatric epilepsy
Authors: Dan Xu, Andrew P. Robinson, Toshiyuki Ishii, D’Anne S. Duncan, Tord D. Alden, Gwendolyn E. Goings, Igal Ifergan, Joseph R. Podojil, Pablo Penaloza-MacMaster, Jennifer A. Kearney, Geoffrey T. Swanson, Stephen D. Miller, Sookyong Koh
Journal: The Journal of Experimental Medicine (2018)

The pathophysiology of drug-resistant pediatric epilepsy is unknown. Flow cytometric analysis of inflammatory leukocytes in resected brain tissues from 29 pediatric patients with genetic (focal cortical dysplasia) or acquired (encephalomalacia) epilepsy demonstrated significant brain infiltration of blood-borne inflammatory myeloid cells and memory CD4+ and CD8+ T cells. Significantly, proinflammatory (IL-17– and GM-CSF–producing) γδ T cells were concentrated in epileptogenic lesions, and their numbers positively correlated with disease severity. Conversely, numbers of regulatory T (T reg) cells inversely correlated with disease severity. Correspondingly, using the kainic acid model of status epilepticus, we show ameliorated seizure activity in both γδ T cell– and IL-17RA–deficient mice and in recipients of T reg cells, whereas T reg cell depletion heightened seizure severity. Moreover, both IL-17 and GM-CSF induced neuronal hyperexcitability in brain slice cultures. These studies support a major pathological role for peripherally derived innate and adaptive proinflammatory immune responses in the pathogenesis of intractable epilepsy and suggest testing of immunomodulatory therapies.
I am desperate to work in Italy as a doctor. I lived there for a year and speak Italian. I am training in psychiatry but would be equally happy doing general practice. I know it is notoriously difficult to pursue a medical career in Italy. Any suggestions?
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 (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.
Comprehensive antibiotic-linked mutation assessment by resistance mutation sequencing (RM-seq)
Authors: Romain Guérillot, Lucy Li, Sarah Baines, Brian Howden, Mark B. Schultz, Torsten Seemann, Ian Monk, Sacha J. Pidot, Wei Gao, Stefano Giulieri, Anders Gonçalves da Silva, Anthony D’Agata, Takehiro Tomita, Anton Y. Peleg, Timothy P. Stinear, Benjamin P. Howden
Journal: Genome Medicine (2018)

Mutation acquisition is a major mechanism of bacterial antibiotic resistance that remains insufficiently characterised. Here we present RM-seq, a new amplicon-based deep sequencing workflow based on a molecular barcoding technique adapted from Low Error Amplicon sequencing (LEA-seq). RM-seq allows detection and functional assessment of mutational resistance at high throughput from mixed bacterial populations. The sensitive detection of very low-frequency resistant sub-populations permits characterisation of antibiotic-linked mutational repertoires in vitro and detection of rare resistant populations during infections. Accurate quantification of resistance mutations enables phenotypic screening of mutations conferring pleiotropic phenotypes such as in vivo persistence, collateral sensitivity or cross-resistance. RM-seq will facilitate comprehensive detection, characterisation and surveillance of resistant bacterial populations ( https://github.com/rguerillot/RM-seq ).
Lymphopenia and outcomes of patients with unresectable hepatocellular carcinoma treated with radiotherapy.
Authors: Sweet Ping Ng, Amy Liu, Randa Tao, Emma Brey Holliday, Zachary Brownlee, Ahmed Omar Kaseb, Kanwal Pratap Singh Raghav, Jean-Nicolas Vauthey, Bruce D. Minsky, Joseph M. Herman, Prajnan Das, Cullen M. Taniguchi, Sunil Krishnan, Christopher H. Crane, Theodore S. Hong, Radhe Mohan, Eugene Jon Koay
Journal: Journal of Clinical Oncology (2018)

278 Background: The immune system plays a crucial role in cancer surveillance. Lymphopenia during cancer treatment portends poor prognosis. Here, we aim to quantify lymphocyte count changes during radiotherapy (RT) for patients with hepatocellular carcinoma (HCC) treated with proton or photon RT. Methods: Patients with HCC treated with definitive RT from 2006 to 2016 with ≥3 months follow-up were studied. Patient characteristics, tumor features, treatment specifics were recorded. Serial absolute lymphocyte counts (ALC) were collected and graded according to CTCAE v4.0. Overall survival (OS) and distant metastasis free survival (DMFS) were analysed using the Kaplan-Meier method. To investigate difference in ALC between treatment modalities, we performed a paired cohort analysis (15 proton and 15 photon cases, matched to treatment volume). Results: 110 patients were studied. Median age was 67 years. 70% of the cohort had Child-Pugh A5 liver disease and 54% had venous tumor thrombosis (VTT). 75 (68%) had photon RT and 35 (32%) had proton RT. Median OS was 13 months. Overall, there was a 60% drop in ALC during RT. Splenic volume correlated with Grade 3 (G3) lymphopenia (p &lt; 0.0001). Pre-treatment ALC and splenic volume did not correlate with OS or DMFS. Patients who had G3 lymphopenia during RT had poorer DMFS (14 vs 34 months, p = 0.006) and OS (16 vs 34 months, p = 0.015) than their counterparts. Those who received proton RT had a higher ALC nadir (0.56 vs 0.40 k/ul, p = 0.041), lower rate of ALC drop (0.07 vs 0.05 k/ul/day) and better OS (30 vs 22 months) than those who had photon RT. Paired cohort dosimetric analyses revealed that there was a significantly higher low dose volume in the photon group (V1Gy and V10Gy, p &lt; 0.0001 for both; V5Gy, p = 0.002). Higher volume of low dose bath correlated with lower ALC (r = -0.34, p = 0.06 for V1Gy; r = -0.44, p = 0.01 for V5Gy; r = -0.51, p = 0.004 for V10Gy). Splenic irradiation dose correlated with ALC nadir, and proton cases had significantly less splenic dose (p &lt; 0.0001). Conclusions: G3 lymphopenia during RT portends poorer outcomes for patients with HCC. Protons may mitigate RT-induced lymphopenia. An ongoing phase III trial will compare proton and photon RT for HCC to determine the effect on OS.
Venous Thromboembolism Prevention in Emergency General Surgery
Authors: Patrick B. Murphy, Kelly N. Vogt, Brandyn D. Lau, Jonathan Aboagye, Neil G. Parry, Michael B. Streiff, Elliott R. Haut
Journal: JAMA Surgery (2018)

Venous thromboembolism (VTE) is the most preventable cause of morbidity and mortality in US hospitals, and approximately 2.5% of emergency general surgery (EGS) patients will be diagnosed with a VTE event. Emergency general surgery patients are at increased risk of morbidity and mortality because of the nature of acute surgical conditions and the challenges related to prophylaxis.MEDLINE, Embase, and the Cochrane Database of Collected Reviews were searched from January 1, 1990, through December 31, 2015. Nearly all operatively and nonoperatively treated EGS patients have a moderate to high risk of developing a VTE, and individual risk should be assessed at admission. Pharmacologic prophylaxis in the form of unfractionated or low-molecular-weight heparin should be considered unless an absolute contraindication, such as bleeding, exists. Patients should receive the first dose at admission to the hospital, and administration should continue until discharge without missed doses. Certain patient populations, such as those with malignant tumors, may benefit from prolonged VTE prophylaxis after discharge. Mechanical prophylaxis should be considered in all patients, particularly if pharmacologic prophylaxis is contraindicated. Studies that specifically target improved adherence with VTE prophylaxis in EGS patients suggest that efficacy and quality improvement initiatives should be undertaken from a system and institutional perspective.Operatively and nonoperatively treated EGS patients are at a comparatively high risk of VTE. Despite gaps in existing literature with respect to this increasing patient population, successful best practices can be applied. Best practices include assessment of VTE risk, optimal prophylaxis, and physician, nurse, and patient education regarding the use of mechanical and pharmacologic VTE prophylaxis and institutional policies.
Milk-specific IgE and IgG4 responses are lower in Amish than Hutterite children
Authors: Lisa J. Workman, Maya Retterer, Jeffrey M. Wilson, Mark Holbreich, Erika von Mutius, Michelle M. Stein, Carole Ober, Thomas A.E. Platts-Mills
Journal: Journal of Allergy and Clinical Immunology (2018)
EXTERNAL VALIDITY OF CORONARY ARTERY DISEASE CONSORTIUM MODELS FOR PREDICTING OBSTRUCTIVE CORONARY ARTERY DISEASE &amp; CARDIOVASCULAR EVENTS IN ACUTE CHEST PAIN PATIENTS CONSIDERED FOR CORONARY COMPUTED TOMOGRAPHIC ANGIOGRAPHY
Authors: Getu G. Teressa, Philip Lavenburg, Olufunmilayo Agunloye, Gregg Cantor, Mengru Zhang, Jie Yang, Pamela Noack, Michael Poon
Journal: Journal of the American College of Cardiology (2018)
Lessons From the Testosterone Trials
Authors: Peter J Snyder, Shalender Bhasin, Glenn R Cunningham, Alvin M Matsumoto, Alisa J Stephens-Shields, Jane A Cauley, Thomas M Gill, Elizabeth Barrett-Connor, Ronald S Swerdloff, Christina Wang, Kristine E Ensrud, Cora E Lewis, John T Farrar, David Cella, Raymond C Rosen, Marco Pahor, Jill P Crandall, Mark E Molitch, Susan M Resnick, Matthew Budoff, Emile R Mohler, Nanette K Wenger, Harvey Jay Cohen, Stanley Schrier, Tony M Keaveny, David Kopperdahl, David Lee, Denise Cifelli, Susan S Ellenberg
Journal: Endocrine Reviews (2018)

The Testosterone Trials (TTrials) were a coordinated set of seven placebo-controlled, double-blind trials in 788 men with a mean age of 72 years to determine the efficacy of increasing the testosterone levels of older men with low testosterone. Testosterone treatment increased the median testosterone level from unequivocally low at baseline to midnormal for young men after 3 months and maintained that level until month 12. In the Sexual Function Trial, testosterone increased sexual activity, sexual desire, and erectile function. In the Physical Function Trial, testosterone did not increase the distance walked in 6 minutes in men whose walk speed was slow; however, in all TTrial participants, testosterone did increase the distance walked. In the Vitality Trial, testosterone did not increase energy but slightly improved mood and depressive symptoms. In the Cognitive Function Trial, testosterone did not improve cognitive function. In the Anemia Trial, testosterone increased hemoglobin in both men who had anemia of a known cause and in men with unexplained anemia. In the Bone Trial, testosterone increased volumetric bone mineral density and the estimated strength of the spine and hip. In the Cardiovascular Trial, testosterone increased the coronary artery noncalcified plaque volume as assessed using computed tomographic angiography. Although testosterone was not associated with more cardiovascular or prostate adverse events than placebo, a trial of a much larger number of men for a much longer period would be necessary to determine whether testosterone increases cardiovascular or prostate risk.
Medical academics need support as “UK’s intellectual future,” says BMA
Authors: Matthew Limb
Journal: BMJ (2015)

Medical academics face potentially difficult times and need support, as they are vital to the “UK’s intellectual and financial future,” the BMA president has said.

Ilora Finlay said, “The whole welfare of the NHS and health provision depends on academic enterprise. No one should underestimate the importance of medical academics.”

Finlay, a past president of the Royal Society of Medicine and currently president of the Chartered Society of Physiotherapy, spoke at the BMA’s conference of medical academic representatives (COMAR) in London on 15 May. She said that UK research was outstanding and that the country punched “way above its weight” in terms of innovation and papers published in peer reviewed journals. “What we’re not that good at, though some universities are now getting good at it, is …