tbuckley/cabot-search huggingface dataset:
I wish to pursue a career in chemical pathology. I do not want to do any more clinical medicine if I can help it. Can I apply straight away for this specialty or do I need membership and higher degrees?
Authors: Adrian Park
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>
GMC introduces new rules to speed up fitness to practise hearings
Authors: Helen Jaques
Journal: BMJ (2013)

The General Medical Council has introduced 15 new rules to speed up hearings of doctors’ fitness to practise at its Medical Practitioners Tribunal Service (MPTS).

Thirteen of the rules take effect immediately. One of these is that doctors will not be told in cases where complaints against them have been closed at triage, except those cases concerning vexatious complaints and …
Effect of region and hospital attribute on outcome of gastric patients treated with apatinib: Data from post-marketing phase IV study.
Authors: Haijun Zhong, Shukui Qin, Jin Li, Wenying Deng, Lu Wen, Junsheng Wang, Guifang Zhang, Tongfu Jia, Jianwei Yang, Yi Ba, Yuxian Bai, Mei Wang, Lin Wang, Likun Liu, Yifu He, Min Tao, Congying Xie, Feng Ye, Xiang-yuan Wu, Xiaoyan Lin
Journal: Journal of Clinical Oncology (2018)

40 Background: The single-arm, open-label, multi-center, Phase IV trial of apatinib was conducting in patients (pts) with advanced or metastatic adenocarcinoma of stomach or gastroesophageal junction with a target sample size of 2000+. We aimed to analyze the effect of region and hospital attributes on clinical outcomes. Methods: From April 2015 to July 2017, 1037 subjects were enrolled, among which 820 were evaluable in the survival analysis. Results: The incidences of adverse events (AEs) and severe AEs (SAEs) are listed in Table. Overall, both incidences were higher in Southern center compared to Northern Center (p=0.002 and &lt;0.001). More SAEs occurred in developed cities (p=0.028) and in hospitals not specialized in oncology (p=0.028). For efficacy, the median overall survival (mOS) of subjects in Northern Center and Southern centers were 8.71 and 5.72 mos (p&lt;0.001), and the median progression free survival (mPFS) was 5.36 and 3.25 mos (p=0.002), respectively. The mOS of subjects in developed and developing cities were 6.18 and 5.72 mos (p=0.105), and the mPFS was 3.02 and 4.73 mos (p=0.013), respectively. The mOS of subjects in hospital specialized and those not in oncology were 7.59 and 5.78 mos (p=0.014), and the mPFS was 4.73 and 3.84 mos (p=0.068), respectively. Conclusions: Region and attribute hospital can affect the safety and clinical outcome of apatinib in treating gastric cancer in the real world. Patients Northern, developing city or hospitals specialized in oncology experience less SAEs but have better clinical benefit. Clinical trial information: NCT02426034. [Table: see text]
Benefits and Harms of Cranial Electrical Stimulation for Chronic Painful Conditions, Depression, Anxiety, and Insomnia
Authors: Paul G. Shekelle, Ian A. Cook, Isomi M. Miake-Lye, Marika Suttorp Booth, Jessica M. Beroes, Selene Mak
Journal: Annals of Internal Medicine (2018)

This systematic review of 26 randomized trials examines evidence about the benefits and harms of cranial electrical stimulation for adults with chronic painful conditions, depression, anxiety, and ...
Abstract P3-10-02: Presence of atypia in ductal lavage and risk of subsequent breast cancer in a prospective study
Authors: A De Censi, M Cazzaniga, S Gandini, C Casadio, L Chiapparini, A Guerrieri-Gonzaga, D Macis, P Veronesi, B Bonanni
Journal: Cancer Research (2018)

Abstract Background: Atypical hyperplasia is considered a nearly obligate precursor of breast cancer and is associated with a higher risk of developing breast cancer (BC). Attempts to improve early detection of breast cancer and to provide individualized breast cancer risk assessment would greatly benefit from sampling cellular material from the target tissue. Ductal lavage (DL) is a minimally invasive technique which provides adequate material to detect atypical cells in mammary ducts. However, long term data of the association between atypia from ductal lavage and BC risk are lacking. We studied the prevalence of atypia in DL in different risk categories and its ability to predict BC development in women at risk. Methods: From March 2000 to July 2012 we performed DL in a consecutive series of 348 women with median age of 45 years (range 19-74) at increased BC risk based on the following characteristics: 5 yrs Gail model &amp;gt; 1.66% or &amp;gt; 10% probability of BRCA mutation (n = 155), history of contralateral BC (CBC, n = 161), presence of a BRCA pathogenic variant (n = 32). We analyzed the presence of atypical cells in the baseline specimen of ductal lavage and in repeated lavage and observed their evolution during follow-up. Results: The procedure was safe and well tolerated in most women, with pain and disconfort preventing the procedure in 5.4% of subjects. Overall, 126 (36%) women had atypia at baseline, with a prevalence of 32%, 39%, and 41% in the Gail, CBC and BRCA groups, respectively (p = 0.38). The overall prevalence of atypia considering all visits was 44% (range 36-51). After a median follow up of 6 years, cumulative BC events were 8% in women without atypia versus 14% in those with atypia (log-rank p = 0.08). In the highest risk groups (CBC and BRCA pathogenic variants), the number of BC events was 16 (21%) in women with atypia versus 11 (10%) in women without atypia (p = 0.02 after adjustment for age). Conclusions: Our findings suggest that cytologic atypia in the fluid obtained by DL predicts subsequent BC in women at increased risk, providing individual risk assessment. The reversal of atypia in DL should be evaluated as a surrogate biomarker of BC therapeutic prevention. Supported by: Associazione Italiana per la Ricerca sul Cancro (AIRC), Lega Italina per la Lotta contro i Tumori (LILT), AVON Foundation for Women. Citation Format: De Censi A, Cazzaniga M, Gandini S, Casadio C, Chiapparini L, Guerrieri-Gonzaga A, Macis D, Veronesi P, Bonanni B. Presence of atypia in ductal lavage and risk of subsequent breast cancer in a prospective study [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 P3-10-02.
Detection of germline deleterious mutations in prostate cancer patients with use of a validated 30-gene sequencing assay.
Authors: Panagiotis J. Vlachostergios, Ana M. Molina, Himisha Beltran, David M. Nanus, Scott T. Tagawa
Journal: Journal of Clinical Oncology (2018)

223 Background: Germline DNA repair gene alterations in men with metastatic prostate cancer (PC) unselected for family history of malignancy occur in a greater frequency compared to localized PC and the general population. We hypothesized that assessing heritable alterations in a broader panel of high-susceptibility genes, may be relevant for detecting familial associations with other cancers in PC patients. Methods: We examined a cohort of 52 PC patients (median age 60, range 45-80) with histologically confirmed PC (17 localized, 35 metastatic). Germline DNA was isolated from blood lymphocytes or buccal swabs, and targeted next-generation sequencing was conducted with use of a previously validated panel of 30 genes associated with an elevated risk for common cancers (Color Genomics). As a reference for gene aberration frequencies we used the Exome Aggregation Consortium (ExAC) database. Results: The majority of patients (48/52, 92%) had a positive family history of cancer in any relative. Nine deleterious pathogenic mutations were identified in germline DNA samples from 8/52 (15%) patients, affecting the following genes: APC (n = 2, 3.8%), BRCA2 (n = 2, 3.8%), CHEK2 (n = 3, 5.7%), ATM (n = 1, 1.9%), RAD51D (n = 1, 1.9%). APC mutations were significantly more frequent in our cohort compared to the ExAC database (0.3%, p &lt; 0.001). The frequency of DNA repair gene alterations (7/52, 13.5%) was also significantly higher compared to the ExAC database (0.3%, p &lt; 0.001). The median overall survival (OS) between patients with and without germline gene alterations was similar (81.5 versus 74 months, respectively). The presence of heritable gene alterations from the 30-gene panel was significantly more frequent in patients with a positive family history of any cancer (p &lt; 0.001) or prostate, breast, ovarian cancer (p = 0.001) in a first degree relative. Conclusions: The use of a targeted panel of high-susceptibility cancer-associated genes in PC not only confirms the enrichment of germline mutations in men with PC. It can also reveal associations of PC with other cancers which may portend implications for treatment and prognosis.
The web they weave
Authors: Wendy Brown
Journal: BMJ (2008)

While deaneries are giving applicants marks out of four for demonstrating development in skills relevant to the specialty, the <i>BMJ</i> thought it was time to turn the tables. Since the government scrapped the medical training application service, the centralised system used last year, just how well have the deaneries developed the skills to provide a clear and informative website for specialty training applicants? Wendy Brown assesses their performance and gives them a star rating (maximum=5)
Lockbox for Registered Trials of Unapproved Devices
Authors: Tony Tse, Annice Bergeris, Deborah A Zarin
Journal: New England Journal of Medicine (2018)

Lockbox for Trials of Unapproved Devices The “lockbox” allows a sponsor of a device trial in ClinicalTrials.gov to deposit the registration data but to shield it from public view. This letter reviews its use since January 2017.
P068 Increase of aerobic glycolysis mediated by activated t helper cells drives synovial fibroblasts towards an inflammatory phenotype
Authors: P Kvacskay, M Souto-Carneiro, R de Albuquerque Carvalho, J-H Schnotz, S Krienke, KD Klika, T Tretter, H-M Lorenz, L-O Tykocinski
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Introduction</h3> There is growing evidence for a dysregulated glucose metabolism of synovial fibroblasts (SF) in rheumatoid arthritis (RA) being a prerequisite for their aggressive phenotype. As yet, little is known about the influence of immune cells on the metabolism of SF although local infiltration of leucocytes constitutes a hallmark in the pathogenesis of RA. <h3>Objectives</h3> In this study, we investigated the effect of T helper (T<sub>h</sub>) cells on the glucose metabolism and cytokine production of non-inflammatory and inflammatory SF <i>in vitro.</i> <h3>Methods</h3> RASF as well as SF from patients with osteoarthritis (OA) were cultured in the presence of a stable glucose isotope (U-<sup>13</sup>C) and stimulated with culture supernatants (SN) of activated T<sub>h</sub> cells. Lactate production was measured by proton nuclear magnetic resonance spectroscopy (H-NMR). Secretion of interleukin (IL)−6, IL-8 and matrix metalloprotease (MMP)−3 was quantified by ELISA. The expression of hexokinase (HK)-II, pyruvate kinase (PK)-M2 and pyruvate dehydrogenase (PDH) was analysed by PCR, western blot and immunofluorescence. Janus kinases (JAKs) were blocked by Baricitinib or Tofacitinib, glycolysis was inhibited by 3-Bromopyruvate (3 BP) or Fx11. <h3>Results</h3> In the absence of stimulation, RASF showed a significantly higher lactate production and IL-6 and MMP-3 secretion compared to OASF. Stimulation by T<sub>h</sub> cell SN strikingly changed the metabolic profile of both RASF and OASF by inducing a shift towards aerobic glycolysis with strongly increased lactate production. In parallel, a significant increase in IL-6 and MMP-3 secretion was induced. Interestingly, Bariticinib and Tofacitinib as well as glycolytic inhibitors significantly reduced both the production of lactate and the secretion of inflammatory cytokines. Finally, perpetual stimulation of non-inflammatory OASF by T<sub>h</sub> cell SN triggered an inflammatory phenotype characterised by significantly higher amounts of lactate, IL-6 and MMP-3 compared to non- or single stimulated SF. <h3>Conclusions</h3> Chronic stimulation of non-inflammatory SF by activated T<sub>h</sub> cells provoked an aggressive phenotype with strongly increased glycolytic activity and upregulated secretion of inflammatory cytokines. This was blocked by both JAK- and glycolytic inhibitors. These observations suggest that the T<sub>h</sub> cell-mediated metabolic switch towards aerobic glycolysis in SF is an important step in the pathogenesis of RA. Targeting this mechanism could provide a new strategy in the therapy of RA. <h3>Disclosure of interest</h3> None declared
Serum levels of advanced glycation end-products (AGEs) and the decoy soluble receptor for AGEs (sRAGE) can identify non-alcoholic fatty liver disease in age-, sex- and BMI-matched normo-glycemic adults
Authors: Susana A. Palma-Duran, Meropi D. Kontogianni, Antonis Vlassopoulos, Shudong Zhao, Aikaterini Margariti, Michael Georgoulis, George Papatheodoridis, Emilie Combet
Journal: Metabolism (2018)
Thunderstorm asthma: controlling (deadly) grass pollen allergy
Authors: Janet M Davies, Francis Thien, Mark Hew
Journal: BMJ (2018)

Free to read via publisher Andrew and colleagues examine the ambulance responses in the catastrophic epidemic thunderstorm asthma event in Melbourne in 2016.1 Beyond preparing emergency services, we need public health responses, including forecasting and control of known asthma, to prevent the acute consequences of thunderstorm asthma.
Na+‐taurocholate cotransporting polypeptide inhibition has hepatoprotective effects in cholestasis in mice
Authors: Davor Slijepcevic, Reinout L.P. Roscam Abbing, Claudia D. Fuchs, Lizette C.M. Haazen, Ulrich Beuers, Michael Trauner, Ronald P.J. Oude Elferink, Stan F.J. van de Graaf
Journal: Hepatology (2018)

Accumulation of bile salts (BSs) during cholestasis leads to hepatic and biliary injury, driving inflammatory and fibrotic processes. The Na + ‐Taurocholate Cotransporting Polypeptide (NTCP) is the major hepatic uptake transporter of BSs, and can be specifically inhibited by myrcludex B. We hypothesized that inhibition of NTCP dampens cholestatic liver injury. Acute cholestasis was induced in mice by a 3.5‐diethoxycarbonyl‐1.4‐dihydrocollidine (DDC) diet or by bile duct ligation (BDL). Chronic cholestasis was investigated in Atp8b1 ‐G308V and Abcb4/ Mdr2 deficient mice. Mice were injected daily with myrcludex B or vehicle. Myrcludex B reduced plasma alkaline phosphatase (ALP) levels in DDC‐fed, Atp8b1 ‐G308V and BDL mice by 39%, 27% and 48% respectively. Expression of genes involved in fibrosis, proliferation and inflammation was reduced by myrcludex B treatment in DDC‐fed and Atp8b1 ‐G308V mice. NTCP‐inhibition increased plasma BS levels from 604±277 to 1746±719 μm in DDC‐fed mice, 432±280 to 762±288 μm in Atp8b1 ‐G308V mice and from 522±130 to 3625±378 μm in BDL mice. NTCP‐inhibition strongly aggravated weight loss in BDL mice, but not in other cholestatic models studied. NTCP‐inhibition reduced biliary BS output in DDC‐fed and Atp8b1 ‐G308V mice by ∼50% while phospholipid (PL) output was maintained, resulting in a higher PL/BS ratio. Conversely, liver injury in Abcb4 deficient mice, lacking biliary phospholipid output, was aggravated after myrcludex B treatment. Conclusion : NTCP‐inhibition by myrcludex B has hepatoprotective effects, by reducing BS load in hepatocytes and increasing the biliary PL/BS ratio. High micromolar plasma BS levels after NTCP‐inhibition were well tolerated. NTCP‐inhibition may be beneficial in selected forms of cholestasis. (H epatology 2018).
Treatment outcome of everolimus against neuroendocrine prostate cancer (NEPC).
Authors: Tatsuya Shimomura, Takashi Kurauchi, Keigo Sakanaka, Shin Egawa
Journal: Journal of Clinical Oncology (2018)

365 Background: Neuroendocrine prostate cancer (NEPC) is a lethal disease subset with median overall survival of less than 1 year from time of detection. The treatment strategy against NEPC is not yet established. Some clinical trials are ongoing now. Recently, clinical trial (RADIIANT4) showed that treatment with everolimus was associated with significant improvement in survival in patients with progressive lung or gastrointestinal neuroendocrine tumors. And FDA approved new indication for everolimus for progressive, nonfunctional GI and lung neuroendocrine tumors last year. In this study we tried to introduce everolimus against pathologically proven NEPC and investigated the clinical outcomes of this agent. Methods: Total of seven cases were included in this study. All cases were proven the existence of neuroendocrine prostate cancer pathologically. Everolimus (10mg/d) were introduced into all cases. We investigated the neuroendocrine tumor markers (neuron-specific enolase: NSE, and pro-gastrin-releasing peptide: pro GRP), radiologic examination and survival. Results: The median follow up period was 6 months. At least one of the tumor markers increased above normal limit in all cases. NSE increased in four cases, pro GRP increased in five cases and both markers increased in two cases. Tumor markers decreased in five of seven (71.4%) cases (NSE: 2 of 4 cases, pro GRP: 4 of 5 cases) after introduction of everolimus. Median decreasing rate were 67.1% in NSE and 65.5% in pro GRP. Two of seven (28.6%) cases progressed in radiologic examination and died from prostate cancer. One case was very advanced disease and everolimus was introduced after failure of systemic chemotherapy (CDDP + etoposide). Another case was advanced disease with bone marrow carcinomatosis. In terms of adverse event, 4 cases had stomatitis and one case had hyperglycemia. Conclusions: In this study, evelolimus showed efficacy against NEPC. It decreased tumor markers and stabilized the tumor status. Although this study was retrospective and number of cases was limited, there is a possibility that evelolimus would be a one of the treatment options against NEPC.
CHANGES IN HOSPITAL PERFORMANCE AND TRANSITION-CARE MEASURES 1-YEAR AFTER INITIATION OF THE PATIENT NAVIGATOR PROGRAM
Authors: Nancy M. Albert, Tyler Gluckman, Robert McNamara, Gregg C. Fonarow, Adnan Malik, Ralph Brindis, Di Lu, Matthew Roe, Judy Tingley, Smita Negi, Lee R. Goldberg, Susan Rogers, Julie Mobayed, Shilpa Patel, Beth Pruski, Kathleen Hewitt, Zaher Fanari, Joseph Lucas
Journal: Journal of the American College of Cardiology (2018)
I am about to start year two of my anaesthetic rotation next month but have decided I want to be a GP. The earliest I would be eligible to take up a GP VTS post is in six months because I have just missed the last round of applications. I do not really want to do a full six months of anaesthetics until then, however. Please advise.
Authors: Kay Mohanna
Journal: BMJ (2006)

Have a career or related problem that needs answering? Can9t find the right person to point you in the right direction? Log on to the Advice Zone for reliable medical careers advice. You can post a question or see if one of our 300 advisers has already answered a similar question. Here is a selection of questions and answers posted on the site. <b>www.bmjcareers.com/advicezone</b>
Highest billing US doctor sentenced to 17 years for Medicare fraud
Authors: Owen Dyer
Journal: BMJ (2018)

A Florida ophthalmologist who for years billed Medicare more than any other doctor must repay $42.5m (£30.2m; €34.4m) to the government and has been sentenced to 17 years in a federal prison.

Salomon Melgen, 62, who has often been named as America’s richest practising physician, was convicted last May on 67 counts of fraud.1 His fraudulent billing amounted at least $73.4m, said Judge Kenneth Marra, of which $42.5m was paid out by Medicare. From 2008 to 2013 Melgen was …
HIV treatment eligibility expansion and timely antiretroviral treatment initiation following enrollment in HIV care: A metaregression analysis of programmatic data from 22 countries
Authors: Olga Tymejczyk, Ellen Brazier, Constantin Yiannoutsos, Kara Wools-Kaloustian, Keri Althoff, Brenda Crabtree-Ramírez, Kinh Van Nguyen, Elizabeth Zaniewski, Francois Dabis, Jean d'Amour Sinayobye, Nanina Anderegg, Nathan Ford, Radhika Wikramanayake, Denis Nash
Journal: PLoS Medicine (2018)

Background The effect of antiretroviral treatment (ART) eligibility expansions on patient outcomes, including rates of timely ART initiation among those enrolling in care, has not been assessed on a large scale. In addition, it is not known whether ART eligibility expansions may lead to "crowding out" of sicker patients. Methods and findings We examined changes in timely ART initiation (within 6 months) at the original site of HIV care enrollment after ART eligibility expansions among 284,740 adult ART-naïve patients at 171 International Epidemiology Databases to Evaluate AIDS (IeDEA) network sites in 22 countries where national policies expanding ART eligibility were introduced between 2007 and 2015. Half of the sites included in this analysis were from Southern Africa, one-third were from East Africa, and the remainder were from the Asia-Pacific, Central Africa, North America, and South and Central America regions. The median age of patients enrolling in care at contributing sites was 33.5 years, and the median percentage of female patients at these clinics was 62.5%. We assessed the 6-month cumulative incidence of timely ART initiation (CI-ART) before and after major expansions of ART eligibility (i.e., expansion to treat persons with CD4 ≤ 350 cells/μL [145 sites in 22 countries] and CD4 ≤ 500 cells/μL [152 sites in 15 countries]). Random effects metaregression models were used to estimate absolute changes in CI-ART at each site before and after guideline expansion. The crude pooled estimate of change in CI-ART was 4.3 percentage points (95% confidence interval [CI] 2.6 to 6.1) after ART eligibility expansion to CD4 ≤ 350, from a baseline median CI-ART of 53%; and 15.9 percentage points (pp) (95% CI 14.3 to 17.4) after ART eligibility expansion to CD4 ≤ 500, from a baseline median CI-ART of 57%. The largest increases in CI-ART were observed among those newly eligible for treatment (18.2 pp after expansion to CD4 ≤ 350 and 47.4 pp after expansion to CD4 ≤ 500), with no change or small increases among those eligible under prior guidelines (CD4 ≤ 350: −0.6 pp, 95% CI −2.0 to 0.7 pp; CD4 ≤ 500: 4.9 pp, 95% CI 3.3 to 6.5 pp). For ART eligibility expansion to CD4 ≤ 500, changes in CI-ART were largest among younger patients (16–24 years: 21.5 pp, 95% CI 18.9 to 24.2 pp). Key limitations include the lack of a counterfactual and difficulty accounting for secular outcome trends, due to universal exposure to guideline changes in each country. Conclusions These findings underscore the potential of ART eligibility expansion to improve the timeliness of ART initiation globally, particularly for young adults.
CALCULATED PLASMA VOLUME STATUS PREDICTS OUTCOMES AFTER TRANSCATHETER AORTIC VALVE REPLACEMENT
Authors: Annette Maznyczka, Omar Aldalati, Mohamad F. Barakat, Mehdi Eskandari, Vasileios Tzalamouras, Rafal Dworakowski, Ranjit Deshpande, Jonathan Byrne, Mark Monaghan, Ajay Shah, Olaf Wendler, Philip MacCarthy, Darlington Okonko
Journal: Journal of the American College of Cardiology (2018)
SYSTEMIC VENTRICULAR STRAIN IS ABNORMAL IN OBESE ADULTS WITH CONGENITAL HEART DISEASE
Authors: Rajesh U. Shenoy, Himanshu Adlakha, Preeti Malik, Rakesh Donthula, Hari Rajagopal, Allen Kan, Ruchika Karnik, Shubhika Srivastava
Journal: Journal of the American College of Cardiology (2018)
The role of angiotensin receptor–neprilysin inhibitors in cardiovascular disease—existing evidence, knowledge gaps, and future directions
Authors: Andrew P. Ambrosy, Robert J. Mentz, Mona Fiuzat, John G.F. Cleland, Stephen J. Greene, Christopher M. O'Connor, John R. Teerlink, Faiez Zannad, Scott D. Solomon
Journal: European Journal of Heart Failure (2018)