tbuckley/cabot-search huggingface dataset:
As a newly qualified GP I do not wish to turn immediately to partnership. A full time out of hours job is available. What are the pros and cons of such a career move?
Authors: Judith Harvey
Journal: BMJ (2005)

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I am interested in doing genitourinary medicine. I have two years' work experience in this field in India. What are my chances of getting a senior house officer job in this field? Can I apply for an attachment before taking my PLAB test part 2?
Authors: Alison Bigrigg
Journal: BMJ (2004)

<i>Got a career or related problem that needs answering? Can9t find the right person to point you in the right direction? Log on to the Advice Zone (www.bmjcareers.com/advicezone) for reliable medical careers advice. You can post a question or see if one of our 300 advisers has already answered a similar question. Here is a selection of questions and answers posted on the site.</i>
Data show big rise in deaths of people with neurological disorders
Authors: Jacqui Thornton
Journal: BMJ (2018)

The number of deaths in England relating to neurological disorders rose by 39% over 13 years while deaths in the general population fell by 6%, a new analysis of mortality has indicated.

Deaths of people with epilepsy increased by 70% between 2001 and 2014, with mortality in the most deprived areas nearly three times that in the least deprived.

The Neurological Alliance, a campaigning group that represents 80 organisations, described the epilepsy figures as “shocking” and a “stark illustration of health inequalities.”

The report, by Public Health England, said that improved survival among people with other conditions and better diagnosis of neurological conditions were likely to be the two main factors contributing to the divergence in mortality rates.1

The researchers analysed 366 728 death certificates that recorded one of seven neurological conditions (epilepsy; motor neurone disease and spinal muscular atrophy; multiple sclerosis and inflammatory disorders; neuromuscular diseases; Parkinsonism and other extrapyramidal/tic disorders; traumatic brain and spine injury; and tumours of the nervous system). …
N-Terminal Pro–B-Type Natriuretic Peptide in the Emergency Department
Authors: James L. Januzzi, Annabel A. Chen-Tournoux, Robert H. Christenson, Gheorghe Doros, Judd E. Hollander, Phillip D. Levy, John T. Nagurney, Richard M. Nowak, Peter S. Pang, Darshita Patel, W. Franklin Peacock, E. Joy Rivers, Elizabeth L. Walters, Hanna K. Gaggin
Journal: Journal of the American College of Cardiology (2018)

Contemporary reconsideration of diagnostic N-terminal pro-B-type natriuretic peptide (NT-proBNP) cutoffs for diagnosis of heart failure (HF) is needed.This study sought to evaluate the diagnostic performance of NT-proBNP for acute HF in patients with dyspnea in the emergency department (ED) setting.Dyspneic patients presenting to 19 EDs in North America were enrolled and had blood drawn for subsequent NT-proBNP measurement. Primary endpoints were positive predictive values of age-stratified cutoffs (450, 900, and 1,800 pg/ml) for diagnosis of acute HF and negative predictive value of the rule-out cutoff to exclude acute HF. Secondary endpoints included sensitivity, specificity, and positive (+) and negative (-) likelihood ratios (LRs) for acute HF.Of 1,461 subjects, 277 (19%) were adjudicated as having acute HF. The area under the receiver-operating characteristic curve for diagnosis of acute HF was 0.91 (95% confidence interval [CI]: 0.90 to 0.93; p < 0.001). Sensitivity for age stratified cutoffs of 450, 900, and 1,800 pg/ml was 85.7%, 79.3%, and 75.9%, respectively; specificity was 93.9%, 84.0%, and 75.0%, respectively. Positive predictive values were 53.6%, 58.4%, and 62.0%, respectively. Overall LR+ across age-dependent cutoffs was 5.99 (95% CI: 5.05 to 6.93); individual LR+ for age-dependent cutoffs was 14.08, 4.95, and 3.03, respectively. The sensitivity and negative predictive value for the rule-out cutoff of 300 pg/ml were 93.9% and 98.0%, respectively; LR- was 0.09 (95% CI: 0.05 to 0.13).In acutely dyspneic patients seen in the ED setting, age-stratified NT-proBNP cutpoints may aid in the diagnosis of acute HF. An NT-proBNP <300 pg/ml strongly excludes the presence of acute HF.
What should you do if you think your references are unfair and the superior you worked for has a personal vendetta against you?
Authors: Carl Gray
Journal: BMJ (2006)

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Abstract P4-13-08: Robotical-assisted laparoscopy for latissimus dorsi flap harvesting in breast reconstruction : A 23 consecutive cases report
Authors: G Houvenaeghel, S Rua, O Franké, M Cohen, E Lambaudie
Journal: Cancer Research (2018)

Abstract Background : Latissimus dorsi (LD) flap is a classic and usual procedure for immediate or secondary breast reconstruction with good results and poor complication rate. The principal issue is the long and often painful dorsal scar. The feasibility of laparoscopic LD flap harvesting and more recently robotically-assisted laparoscopy were described in short series. We report in this article the largest series of robotically-assisted laparoscopic LD flap harvesting. We describe its feasibility and the immediate and early post operative outcomes. Material et methods : Between January 27th and December 21th of 2016, we performed 23 robotically-assisted laparoscopic LD flap harvestings in immediate and secondary breast reconstruction. Every patient was systematically sent for an evaluation of aesthetic result, pain and satisfaction on the second, the sixth and the twelth month. Results : 78,3% of surgeries were realized for infiltrative breast cancer.17 (73,9%) LD flaps were harvested in immediate reconstruction after nipple or skin sparing mastectomies (NSM -34,8%-or SSM -43,5%). The global mean operative time was 360,1 minutes, including bilateral and robotically-assisted mastectomies. The mean hospital stay duration was 5 days (2-8 days). We described one failure for secondary LD flap reconstruction (infection). The other cases resulted in successful reconstructions without heavy complications. Discussion :Our series is the largest reported. It confirms the feasibility of a robotically-assisted procedure in breast reconstruction with LD flaps. Our study describes a reliable option for LD flap breast reconstruction without any additional scar. Some procedures were combined in selected patients with a robotic NSM with a single axillar incision. Citation Format: Houvenaeghel G, Rua S, Franké O, Cohen M, Lambaudie E. Robotical-assisted laparoscopy for latissimus dorsi flap harvesting in breast reconstruction : A 23 consecutive cases report [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 P4-13-08.
Biological significance of novel populations of prostate cancer circulating tumor cells (CTC).
Authors: Ian D. Davis, Carmel Jo Pezaro, Hady Wardan, Pavel Sluka
Journal: Journal of Clinical Oncology (2018)

315 Background: Decisions regarding selection and sequencing of treatment in advanced prostate cancer (PC) are often made empirically, without information on the PC molecular profile at the time of treatment. CTC provide real time information regarding contemporaneous biologically relevant cancer subtypes. Current assays often rely on EpCAM or other epithelial markers and may underestimate or exclude other CTC populations of clinical relevance. We devised a novel, simple, rapid and cheap method for isolation of CTC subsets including those without epithelial markers. Methods: Five mL of blood was processed as follows: CD45+ depletion (RosetteSep Human CD45 Depletion Cocktail, Stemcell Technologies); Ficoll centrifugation; antibody staining (mix of EpCAM-PE, PSMA-APC, N-cadherin-AF488, E-cadherin-PerCP/Cy5.5, CD45-APC-H7); Sytox Blue live/dead cell stain; followed by sorting (Becton Dickinson FACSAria Fusion cell sorter). Live cells were sorted into 4 categories denoted E, E+P, P, N (Table). N and P are not identifiable using existing conventional CTC techniques. CTC were assayed for prostate markers ( AR, FOLH1 (PSMA), KLK3 (PSA), TMPRSS2, AMACR) and malignant markers ( PTEN copy number) using digital droplet PCR. Results: Preliminary data are derived from 62 patient samples providing 47 sorted populations. Details are in the Table. Spiking experiments reliably identified as few as 10 CTC / 7.5 mL of blood. P cells were detected in all patients, often outnumbering sum of E and E+P; E and N were never co-expressed. P and N samples frequently expressed prostate markers. Only 1/27 showed no expression of any of these five prostate markers. PTEN deletion assays are in progress. Conclusions: “Unconventional” EpCAM neg CTC appear to be derived from PC and can be detected using broader cell selection criteria. These CTC may provide information on treatment resistance or escape mechanisms. [Table: see text]
<i>Who is eligible for flexible training? I have a LAT. Can I train flexibly?</i>
Authors: Anita Houghton
Journal: BMJ (2004)

Got a career or related problem that needs answering? Can't 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.
Phase II trial of 6 months ADT/abiraterone acetate plus prednisone (AAP) and definitive radiotherapy (AbiRT) for men with intermediate to high risk localized prostate cancer.
Authors: Bridget F. Koontz, Karen E. Hoffman, Patrick Healy, Daniel J. George, Michael Roger Harrison, Tian Zhang, W. Robert Lee, William R. Berry, Thomas J Pugh, Paul Gettys Corn, LuEllen Bratt, Kellie Shobe, Blair Thornburg, Donna M. Allen, Katie Brummer, Beth Tojong, Bridget Hobbs, Susan Halabi, Andrew J. Armstrong
Journal: Journal of Clinical Oncology (2018)

11 Background: Combined external beam radiotherapy (RT) and androgen deprivation therapy (ADT) improves survival over RT alone for high risk prostate cancer (PC). Long-term ADT use, currently recommended for high risk PC, also increases toxicity. Recent data suggests synergistic efficacy with the addition of abiraterone acetate plus prednisone (AAP) to RT/ADT. Potent androgen blockade may provide biochemical control with short-term ADT course in men with aggressive but localized PC. Methods: This was a two center prospective phase 2 single arm clinical trial within the Department of Defense PCCTC (NCT01717053). Eligibility included 2+ intermediate or 1 high NCCN risk factors and no metastatic disease. Men received 6 months of ADT concurrently with 1000mg AA/5mg P daily and 78 Gy RT to prostate/SV. Primary endpoint was PSA &lt; 0.1 ng/ml at 1 year. Secondary objectives included BPFS, PSA nadir, testosterone recovery, toxicity, and patient-reported QOL. Results: We enrolled 37 men (82% white, 18% black) with intermediate to high risk localized PC; 33 completed course of treatment (4 patients halted early for personal preference (N = 2), planned prostatectomy, or renal artery stenosis). Median age was 66 years; 46% Gleason 8-10, 40% Gleason 4+3 = 7, 62% T1c. Median follow-up is 23 months. Regimen was well tolerated with 12 (32%) G3 toxicities (10 hypertension, 2 hyperglycemia, 1 hypokalemia); no G4-5 or unexpected toxicities were observed. At 12 months from enrollment, PSA remained at undetectable levels in 52% of men. Testosterone recovery to normal lab value occurred in 12 (62%) at 12 months. In those patients, 20 (95%) and 21 (100%) remained with PSA under 0.5 and 1.0 ng/ml, respectively. No patient has failed by Phoenix definition to date. 1 year EPIC QOL had median summary scores above 90 for incontinence, urinary, bowel, hormonal, and satisfaction. Sexual summary score fell from median of 46 at baseline to 26 at 1 year. Conclusions: In men with high risk intermediate or limited high risk PC, utilizing short-term ADT/AAP with definitive RT shows 1) high rate of testosterone recovery and good quality of life and 2) excellent PSA control at 1 and 2 years. Clinical trial information: NCT01717053.
The junior doctor dispute was about more than just the contract
Authors: S Alderson, P Dacombe, M Dias, T Duncan, T Foley, S Gauher, G Hill-Cawthorne, W K Wong, S Mehta, S Mukhtar, K Patel, S Panchal, I Rodrigues, H Ryland, F Taylor, S J Wang, K Whitfield, M Wittenberg, W Wynn-Jones
Journal: BMJ (2016)

The junior doctors’ contract dispute has shown the need for major and sustained changes in education, training, and policy, say Steven Alderson and colleagues
TRITON2: An international, multicenter, open-label, phase II study of the PARP inhibitor rucaparib in patients with metastatic castration-resistant prostate cancer (mCRPC) associated with homologous recombination deficiency (HRD).
Authors: Wassim Abida, Alan Haruo Bryce, Arjun Vasant Balar, Gurkamal S. Chatta, Nancy Ann Dawson, Elizabeth A. Guancial, Arif Hussain, Gautam Gopalji Jha, David Uri Lipsitz, Akash Patnaik, Daniel Peter Petrylak, Charles J. Ryan, Thomas S. Stanton, Nicholas J. Vogelzang, Jingsong Zhang, Andrew Simmons, Jowell Go, Tony Golsorkhi, Simon Chowdhury, Howard I. Scher
Journal: Journal of Clinical Oncology (2018)

TPS388 Background: Up to 25% of patients with advanced prostate cancer, including mCRPC, have a deleterious germline or somatic mutation in BRCA1, BRCA2, ATM or another homologous recombination (HR) DNA repair gene that can serve as a molecular marker to select those who may respond to poly(ADP-ribose) polymerase inhibitors (PARPis). PARPis are lethal to cells with HRD, and PARPi treatment has shown preliminary evidence of an antitumor effect in patients with mCRPC who harbor a mutation in an HR DNA repair gene (Mateo et al. N Engl J Med. 2015;373:1697-708). These data provide a compelling rationale for evaluating rucaparib, a potent PARP1, PARP2 and PARP3 inhibitor, in patients with mCRPC associated with HRD. Methods: TRITON2 (NCT02952534) is a phase 2 study evaluating rucaparib 600 mg BID in patients with mCRPC. Patients with a deleterious germline or somatic BRCA1, BRCA2 or ATM mutation (per prior local test or central test during screening) will be enrolled into 1 of 2 cohorts based on the presence or absence of measurable visceral and/or nodal disease. An exploratory cohort will enroll patients with an alteration in any of 12 other prespecified HR genes (eg, RAD51C, RAD51D and PALB2), with or without measurable visceral and/or nodal disease. Patients must have progressed on androgen receptor signaling–directed therapy and 1 prior taxane-based chemotherapy for mCRPC. Patients who received prior treatment with a PARPi, mitoxantrone, cyclophosphamide or platinum-based chemotherapy are excluded. The primary endpoint is objective response rate measured using modified RECIST v1.1/PCWG3 for patients with soft-tissue disease and prostate-specific antigen response for patients with nonmeasurable disease. Secondary endpoints include duration of response, radiographic progression-free survival, overall survival, clinical benefit rate and safety. Pretreatment blood samples collected from all patients will enable development of a plasma-based companion diagnostic to select patients who may benefit from rucaparib treatment. Patients (≈160) will be enrolled at &gt; 100 sites worldwide. Clinical trial information: NCT02952534.
The neurosurgeon who separates Siamese twins
Authors: Sadat Edroos
Journal: BMJ (2004)

P rofessor Keith Goh qualified from the National University of Singapore Medical School in 1985. After completing his basic surgical training, he moved to Prince of Wales Hospital in Hong Kong in 1992 to specialise in neurosurgery. He later took up a clinical training fellowship at the Beth Israel Institute of Neurology and Neurosurgery in New York, where he specialised in paediatric neurosurgery. Keith Goh and his wife returned home to Singapore in 1999, and two years later he headed the first of three operations to separate conjoined twins. The second of these was unprecedented in that it involved an adult pair. Laleh and Ladan Bijani were 29 at the time, and their story captured the imagination not just of Singaporeans but of the whole world.1 Unfortunately, they died during the operation. Professor Goh is currently working in Hong Kong.

I began my surgical career late, compared with most people. I had a lot of fun in medical school. I got by in my exams but didn't really excel. I began searching for which path to take as a doctor, and that's when I tried family …
Pupillary Responses to Full-Field Chromatic Stimuli Are Reduced in Patients with Early-Stage Primary Open-Angle Glaucoma
Authors: Raymond P. Najjar, Sourabh Sharma, Eray Atalay, Annadata V. Rukmini, Christopher Sun, Jing Zhan Lock, Mani Baskaran, Shamira A. Perera, Rahat Husain, Ecosse Lamoureux, Joshua J. Gooley, Tin Aung, Dan Milea
Journal: Ophthalmology (2018)

To evaluate the ability of chromatic pupillometry to reveal abnormal pupillary responses to light in patients with early-stage primary open-angle glaucoma (POAG) and to test whether the degree of pupillometric impairment correlates with structural hallmarks of optic nerve damage in the disease.Cross-sectional study.Forty-six patients with early-stage POAG (63.4±8.3 years, 63% male, 87% ethnic-Chinese) and 90 age-matched healthy controls (61.4±8.6 years, 34% male, 89% ethnic-Chinese). Patients with POAG had a visual field mean deviation (VFMD) of -6 decibels or better on automated perimetry.Each participant underwent a monocular 2-minute exposure to blue light (462 nm) followed by another 2-minute exposure to red light (638 nm) using a modified Ganzfeld dome equipped with a light-emitting diode lighting system. The light stimuli intensity was increased logarithmically to evaluate the combined extrinsic and intrinsic response of intrinsically photosensitive retinal ganglion cells (ipRGCs). Light-induced changes in horizontal pupil diameter were assessed monocularly using infrared pupillography.Baseline-adjusted, light-induced pupillary constriction amplitudes were calculated, and individual irradiance-response curves were constructed for each stimulus. Pupillary constriction amplitudes were compared between groups and across light intensities using a linear mixed model analysis. The linear relationship between pupillometric parameters and different structural and functional features of glaucoma was assessed using Pearson's correlation analysis.Light-induced pupillary constriction was reduced in patients with early-stage POAG compared with controls at moderate to high irradiances (≥11 Log photons/cm2/s) of blue (P = 0.003) and red (P < 0.001) light. Maximal pupillary constriction amplitude was correlated with retinal nerve fiber layer thickness (RNFL) thickness (blue: r = 0.51, P < 0.001; red: r = 0.45, P = 0.002) in patients with POAG but not in controls. Conversely, pupillometric parameters were not correlated with visual field scores in patients with early-stage POAG.Patients with early-stage POAG exhibit reduced pupillary responses to moderate and high irradiances of blue and red lights. This wavelength-independent functional alteration correlates with structural thinning of the RNFL and could be the consequence of dysfunction or loss of melanopsin expressing ipRGCs in the early stages of the disease.
Status of Hypertension in China
Authors: Zengwu Wang, Zuo Chen, Linfeng Zhang, Xin Wang, Guang Hao, Zugui Zhang, Lan Shao, Ye Tian, Ying Dong, Congyi Zheng, Jiali Wang, Manlu Zhu, William S. Weintraub, Runlin Gao
Journal: Circulation (2018)

Background: Although the prevalence of hypertension (HTN) continues to increase in developing countries, including China, recent data are lacking. A nationwide survey was conducted from October 2012 to December 2015 to assess the prevalence of HTN in China. Methods: A stratified multistage random sampling method was used to obtain a nationally representative sample of 451 755 residents ≥18 years of age from 31 provinces in mainland China from October 2012 to December 2015. Blood pressure (BP) was measured after resting for 5 minutes by trained staff using a validated oscillometric BP monitor. HTN was defined as systolic BP (SBP) ≥140 mm Hg/or diastolic BP (DBP) ≥90 mm Hg or use of antihypertensive medication within 2 weeks. Pre-HTN was defined as SBP 120 to 139 mm Hg and DBP 80 to 89 mm Hg without antihypertensive medication. HTN control was defined as SBP &lt;140 mm Hg and DBP&lt;90 mm Hg. In addition, the prevalence of HTN (SBP ≥130 or DBP ≥80 mm Hg) and control rate (SBP &lt;130 and DBP &lt;80 mm Hg) of HTN were also estimated according to the 2017 American College of Cardiology/American Heart Association High Blood Pressure Guideline. Results: Overall, 23.2% (≈244.5 million) of the Chinese adult population ≥18 years of age had HTN, and another 41.3% (≈435.3 million) had pre-HTN according to the Chinese guideline. There were no significant differences of HTN prevalence between urban and rural residents (23.4% versus 23.1%, P =0.819). Among individuals with HTN, 46.9% were aware of their condition, 40.7% were taking prescribed antihypertensive medications, and 15.3% had controlled HTN. Calcium channel blockers were the most commonly used antihypertensive medication (46.5%) as monotherapy, and 31.7% of treated hypertensive patients used ≥2 medications. The prevalence of HTN based on the 2017 American College of Cardiology/American Heart Association guideline was twice as high as that based on 2010 Chinese guideline (46.4%), whereas the control rate fell to 3.0%. Conclusions: In China, there is a high prevalence of HTN and pre-HTN, and awareness, treatment, and control of HTN were low. Management of medical therapy for HTN needs to improve.
FRI0067 Treatment with anakinra reduces the rate of joint destruction and shows accelerated benefit in the second 6 months of treatment for patients with rheumatoid arthritis
Authors: HK Genant, B Bresnihan, E Ng, S Robbins, RD Newmark, D McCabe
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> <h3>Objectives</h3> Evaluate the effect of anakinra treatment on joint destruction in 1) patients completing a previous 6 months of anakinra treatment, and 2) patients completing 24 weeks of placebo. <h3>Methods</h3> 472 Patients with RA entered a 24 week, randomised clinical trial and received placebo or anakinra 30, 75 or 150 mg daily. On completing this phase, patients receiving placebo were re-randomised to one of the treatment groups and patients receiving anakinra continued treatment for a further 24 week extension study. Radiographs, obtained at 0, 24 and 48 weeks, were evaluated for joint damage using a modified Sharp method (Genant AJR '00). <h3>Results</h3> For those patients who rolled over to treatment with anakinra after 6 months of placebo, all three anakinra dose groups showed significant reduction in the rate of joint destruction. Patients who received the same dose of anakinra for the entire 12 months showed an accelerated benefit by slowing radiographic progression in the second 6 months (75 and 150 mg). <h3>Conclusion</h3> In a 24 week study of RA, anakinra significantly reduced the rate of progressive joint damage. When treatment was maintained for a further 24 weeks, the rate of progressive joint damage was significantly slower compared to the first 24 week period.