tbuckley/cabot-search huggingface dataset:
CaPSURE update: Examining primary treatment and survival among men with prostate cancer and bony metastatic disease.
Authors: Hala Borno, Janet E. Cowan, Shoujun Zhao, Peter Carroll, Charles J. Ryan
Journal: Journal of Clinical Oncology (2018)

275 Background: New data is emerging to guide primary treatment of patients with metastatic (M+) disease. Among the CHAARTED and LATITUDE cohorts, 27.2% and 5% of patients with M+ disease had prior local therapy, respectively. This study utilizes the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) registry to examine survival among patients with M+ disease. Methods: CaPSURE is a registry of men diagnosed with prostate cancer. We examined sociodemographics, disease biology, primary therapy, and survival among patients who were diagnosed with cM+ disease or developed metastasis. We performed a multivariate Cox model to evaluate the association between timing of metastasis and prostate cancer specific mortality (PCSM), adjusted for age, primary treatment, and follow-up therapy. Results: Of the 14,753 patients diagnosed with prostate cancer from 1990-2016, 717(4.9%) had M+ disease. 328(2.2%) had cM+ disease and 389(2.6%) progressed to bony metastasis. For all patients with M+ disease, 490(68.3%) were &gt; = 65 yo, 627(87.4%) had Medicare, and 239(33.3%) had an annual income &lt; $30,000 (P &lt; 0.01). PSA at diagnosis was &gt; 20 ng/mL for 355(49.5%) and biopsy Gleason was 4+3 or 8 to 10 for 403(56.2%) (P &lt; 0.01). Among patients with cM+ disease, 49(14.9%) received primary local therapy and 279(85.1%) received primary hormonal therapy. Among patients who progressed to M+ disease, 258(66.3%) received primary local therapy and 131(33.7%) received primary hormonal therapy. The risk of PCSM was worse for patients with M+ disease who received hormonal therapy for primary treatment compared to patients who received combined local and hormonal therapy (HR 1.47 (95% CI 1.15 to 1.88), P &lt; .01). Timing of metastatic disease was not associated with PCSM. Primary treatment with hormonal therapy compared to local therapy was associated with higher risk of PCSM (HR 1.40 (95% CI 1.00-1.97), P = 0.05) for patients diagnosed with Gleason &gt; = 4+3 disease. Conclusions: In our analysis, patients with primary local therapy were examined as a subset of all patients with M+ disease. We observed that patients with cM+ disease have a worse prognosis then patients who develop M+ disease with antecedent primary local therapy.
B.A.R.D. in the practice: A Guide for Family Doctors to Consult Efficiently, Effectively and Happily
Authors: Bill Irish
Journal: BMJ (2006)

Ed Warren

Radcliffe, 2005, £21.95, 136 pages

ISBN: 1 85775 665 7

Rating: ★★★★★/5



It is quite simply the key to an easy life. If you consult well you can get away with anything; if you can't—it doesn't matter how many types of porphyria you can remember—you're doomed.

I really got into this sort of stuff when I first started out as an examiner for the MRCGP (Membership of the Royal College of General Practitioners). The bit I secretly dreaded was sitting down to mark a huge …
NON-INVASIVE SCREENING TEST FOR SARCOPENIA IS A USEFUL PREDICTOR OF FUTURE CARDIOVASCULAR EVENTS IN PATIENTS WITH CHRONIC KIDNEY DISEASE
Authors: Shinsuke Hanatani, Masahiro Yamamoto, Toshifumi Ishida, Satoru Yamamura, Yuichi Kimura, Satoshi Araki, Yasuhiro Izumiya, Kenichi Tsujita
Journal: Journal of the American College of Cardiology (2018)
Anti–Programmed Death 1 (PD-1) Antibodies and the Pancreas: A Diabetic Storm Ahead?
Authors: Lucien Marchand, Arnaud Thivolet, Pierre Saintigny, Nicole Fabien, Julien Vouillarmet, Charles Thivolet
Journal: Diabetes Care (2018)

Nivolumab, a human IgG4 programmed death 1 (PD-1) immune checkpoint–inhibitor antibody, disrupts PD-1–mediated signaling and restores antitumor immunity (1). Many recent studies have emphasized the importance of anti–PD-1 antibodies to improve survival outcomes among patients with advanced melanoma or lung cancer. Several endocrinological side effects have been reported and a few patients developed insulin-requiring diabetes (2). Some …
A well-designed/conducted study on alpha-1 antitrypsin epidemiology not quoted
Authors: Ignacio Blanco
Journal: European Respiratory Journal (2018)

We read with interest the outstanding European Respiratory Society (ERS) statement on α1-antitrypsin deficiency (AATD) led by R.A. Stockley and M. Miravitlles with the collaboration of 13 European experts on the subject [1]. Recall of a historical study on the epidemiology of the alpha-1 antitrypsin gene <http://ow.ly/yXAH30hZXiQ>
Professor Sir Andrew Haines⇓
Authors: Graham Easton
Journal: BMJ (2005)

P rofessor Andy Haines, director of the London School of Hygiene and Tropical Medicine (LSHTM), received a knighthood in this year's New Year's honours. He has played a leading part in the development of the NHS research and development programme and made a major contribution to thinking about how to address the health needs of disadvantaged populations. His research interests include primary care and the study of environmental influences on health.

I received a letter from 10 Downing Street when I returned from a trip abroad some weeks before Christmas. I was asked to keep it confidential until the New Year's honours list was published. I regard the knighthood largely as recognition of the outstanding work of colleagues at the LSHTM in advancing public health nationally and internationally.

After my house jobs in London, I spent five months in Jamaica. I undertook further hospital training in the United Kingdom and subsequently worked in Nepal for a year with the Britain Nepal Medical Trust, focusing …
A histone deacetylase 3–dependent pathway delimits peripheral myelin growth and functional regeneration
Authors: Xuelian He, Liguo Zhang, Luis F Queme, Xuezhao Liu, Andrew Lu, Ronald R Waclaw, Xinran Dong, Wenhao Zhou, Grahame Kidd, Sung-Ok Yoon, Andres Buonanno, Joshua B Rubin, Mei Xin, Klaus-Armin Nave, Bruce D Trapp, Michael P Jankowski, Q Richard Lu
Journal: Nature Medicine (2018)
MRCGP examination: applied knowledge test and clinical skills assessment
Authors: Naomi Katz
Journal: BMJ (2008)

Completion of the new exam for membership of the Royal College of General Practitioners (MRCGP) is now compulsory for all general practitioner registrars to attain their certificate of completion of training. The exam has three components. The first is an applied knowledge test, which is a multiple choice question exam that is done online at Pearson Vue (driving test) centres around the country. The second is a clinical skills assessment exam, which takes place at a purpose built centre in Croydon. This involves a simulated surgery of 10-minute appointments where you are examined on 13 cases, with 12 being real and one pilot. The final component is a workplace based assessment, which entails completing an e-portfolio which is filled in online …
Fabrication and characterization of spearmint oil loaded nanoemulsions as cytotoxic agents against oral cancer cell
Authors: Sukannika Tubtimsri, Chutima Limmatvapirat, Siripan Limsirichaikul, Prasert Akkaramongkolporn, Yutaka Inoue, Sontaya Limmatvapirat
Journal: Asian Journal of Pharmaceutical Sciences (2018)

Spearmint oil (SMO), a commonly used essential oil for oral care products, possesses various interesting functions, especially for anticancer property. However, the application of SMO for cancer treatment is limited due to water insoluble. In the present study, nanoemulsions, which have been widely accepted as dosage forms for poorly water-soluble drugs, were selected as candidate carriers for SMO to inhibit oral cancer cell. The nanoemulsions were fabricated using phase inversion temperature method. The factors affecting formation and properties of nanoemulsions including type and amount of surfactants, oil loading and ratio of SMO to virgin coconut oil (VCO) were investigated. Among the surfactants used, the nanoemulsions containing polyoxyethylene castor oil derivatives (Kolliphor®EL; PCO35, Cremophor®RH40; PCO40, Eumulgin®CO60; PCO60) and polyoxyethylene sorbitan fatty acid esters (PSF80) showed 100% creaming after temperature cycling test indicating excellent physical stability while those containing PCO40 demonstrated more transparency and better physical stability. With an increasing amount of PCO40, the droplet size tended to decrease and was in the nano-size range (<1000 nm) after increasing to more than 5% (w/w). SMO-VCO loading also influenced on the droplet size. At 5% (w/w) PCO40, the maximum SMO-VCO loading of 25% (w/w) to attain nanoemulsions was observed. Moreover, the composition of oils had an impact on size of emulsions. The transparent nanoemulsions were only prepared in the range of SMO-VCO from 40:60 to 80:20, suggesting the optimum ratio of SMO to surfactant and the composition of oils were the critical factors for formation of nanoemulsions. NMR study disclosed that the interaction between PCO40 with both VCO and SMO should be a possible stabilization mechanism. Furthermore, the SMO-VCO nanoemulsions exhibited significant cytotoxic effect against oral carcinoma (KON) cell line using MTT assay. The finding, therefore, revealed the good feasibility of SMO-VCO nanoemulsions as novel carriers for treating of oral cancer.
Safety and efficacy of pirfenidone in patients carrying telomerase complex mutation
Authors: Aurélien Justet, Gabriel Thabut, Effrosyni Manali, Maria Molina Molina, Caroline Kannengiesser, Jacques Cadranel, Vincent Cottin, Anne Gondouin, Hilario Nunes, Eline Magois, Cécile Tromeur, Grégoire Prevot, Spyros Papiris, Sylvain Marchand-Adam, Anne Sophie Gamez, Martine Reynaud-Gaubert, Lidwine Wemeau, Bruno Crestani, Raphael Borie
Journal: European Respiratory Journal (2018)

The most frequent mutations in familial pulmonary fibrosis (FPF) involve genes of the telomerase complex such as TERT , TERC , RTEL1 , PARN or DKC1 [1]. Mutations within TERT and TERC are found in 15–20% of FPF and are associated with blood, liver and skin disorders. Idiopathic pulmonary fibrosis (IPF) is the most frequent multidisciplinary diagnosis in TERT and TERC mutation carriers [1, 2]. Treatment of IPF in patients who carry a TERT or TERC mutation has not been previously defined. Recently, danazol, a synthetic androgen, was shown to increase telomere length, and seemed to stabilise forced vital capacity (FVC) and diffusing capacity of the lung for carbon monoxide ( D LCO) in telomerase complex mutation carriers [3]. Pirfenidone has been shown to reduce FVC decline and to improve progression-free survival in IPF [4, 5]; however, pirfenidone has not been specifically evaluated in telomerase complex mutation carriers. The aim of this multicentre retrospective study was to evaluate the safety and efficacy of pirfenidone in patient carriers of TERT / TERC mutations. In this retrospective study, a beneficial effect of pirfenidone on lung function decline could not be demonstrated in patients carrying TERT/TERC mutation <http://ow.ly/VYpJ30i5wSr>
MANAGEMENT OF PATIENTS WITH NON-VALVULAR ATRIAL FIBRILLATION FOLLOWING A FIRST CLINICALLY RELEVANT BLEED: A REAL-WORLD STUDY BASED ON UK CLINICAL PRACTICE RESEARCH DATALINK - HOSPITAL EPISODE STATISTICS DATA
Authors: Sreeram Ramagopalan, Mihail Samnaliev, Laura McDonald, Nathan Hill, Gillian Stynes, Cinira Lefevre, Cormac Sammon
Journal: Journal of the American College of Cardiology (2018)
THE COMPASS CRITERIA APPLIED TO A REAL LIFE POPULATION FROM THE FAST-MI 2005 AND 2010 REGISTRIES
Authors: Francois Schiele, Etienne Puymirat, Marion Chatot, Karl Isaaz, Bruno Farah, Brahim Harbaoui, Philoktimon Plastaras, Gregory Ducrocq, Jean Ferrières, Tabassome Simon, Nicolas Meneveau, Nicolas Danchin
Journal: Journal of the American College of Cardiology (2018)
BILATERAL SEVERE VALVULAR REGURGITATION AFTER MEDIASTINAL RADIOTHERAPY IN A HODGKIN'S LYMPHOMA SURVIVOR: RADIATION DOES NOT READ TEXT BOOKS
Authors: Abdelrahman Ahmed, Mohamed Shokr, Ahmed Rashed, Tushar Mishra, Ahmed S. Yassin, Anupama Kottam
Journal: Journal of the American College of Cardiology (2018)
Working as a doctor in the third sector
Authors: Elvina Chu, Rajendra Shah, Zerak Al-Salihy
Journal: BMJ (2013)

As more organisations seek to provide health services, many UK doctors are considering opportunities in the third sector. <b>Elvina Chu</b>, <b>Rajendra Shah</b>, and <b>Zerak Al-Salihy</b> describe their experiences of moving between NHS and third sector roles
Evaluation of ability of low-molecular-weight protein tyrosine phosphatase expression to predict primary hormone therapy efficacy among men with metastatic hormone-naïve prostate cancer.
Authors: Yutaro Hayashi, Yasuhide Miyoshi, Masato Yasui, Mari Ohtaka, Takashi Kawahara, Yumiko Yokomizo, Narihiko Hayashi, Masahiro Yao, Hiroji Uemura
Journal: Journal of Clinical Oncology (2018)

316 Background: Protein tyrosine phosphorylation is an important event associated with the processes of cellular metabolism and is regulated by protein tyrosine kinases and protein tyrosine phosphatases (PTPs). Recent studies showed that low-molecular-weight protein tyrosine phosphatase (LMW-PTP) could be a biomarker for predicting overall survival among men with metastatic hormone-naïve prostate cancer (mHNPC). In this study, we evaluated the value of LMW-PTP expression for predicting primary hormone therapy efficacy among men with mHNPC. Methods: A total of 45 men with mHNPC diagnosed from 2003 to 2009 were enrolled in this retrospective study. All patients had received androgen ablation therapy as first-line treatment. Prostate cancer tissues obtained by needle biopsies before treatment were immunohistochemically stained for LMW-PTP. Correlations between the baseline clinical factors of age, PSA, Gleason scores, T stage, N stage, extent of disease on bone scan (EOD), LMW-PTP expression and primary hormone therapy efficacy (time to castration-resistant prostate cancer [CRPC]) were investigated by multivariate analysis using the Cox proportional hazard model. Continuous variables were classified as dichotomous. Results: Median age and PSA were 70.0 years and 87.8 ng/mL, respectively. Distribution number of Gleason score 8-10/6-7, T4/≤3, N1/0, and EOD 3-4/0-2 were 30 (66.7%)/15 (33.3%), 13 (28.9%)/32 (71.1%), 25 (55.6%)/20 (44.4%), and 7 (15.5%)/38 (84.5%). Median time to CRPC was 40.2 months. Patients with high LMW-PTP expression had significantly shorter time to CRPC than those with low expression (p = 0.005). Multivariate analysis showed that age (≥70 vs &lt; 70, HR 2.5, 95%CI 0.96-6.32, p = 0.060) and LMW-PTP expression (high vs low; HR 3.3, 95%CI 1.2-8.6, p = 0.02) were significant prognostic biomarkers for predicting time to CRPC. Conclusions: LMW-PTP expression could be a potential biomarker for predicting primary hormone therapy efficacy among men with mHNPC.
BMA must work with medical schools to promote careers in general practice, GPs say
Authors: Abi Rimmer
Journal: BMJ (2014)

The BMA must work with medical schools to encourage students into careers in general practice, GPs have said.

Delegates at the BMA’s Local Medical Committee’s (LMCs) conference voted for a motion which called on the general practitioners committee (GPC) to work “with a matter of urgency” on issues concerning GP education and training. The motion asked the GPC to work to “encourage a career in general practice from year one in …
OUTCOME PREDICTION BY NOVEL ECHOCARDIOGRAPHIC MEASURE OF RIGHT VENTRICULAR MYOCARDIAL STIFFNESS IN PATIENTS WITH PULMONARY HYPERTENSION
Authors: Orawan Anupraiwan, Ioana Petrescu, Anusith Tunhasiriwet, Filip Ionescu, Sorin Pislaru, Patricia Pellikka, Garvan Kane, Cristina Pislaru
Journal: Journal of the American College of Cardiology (2018)
The Association Between <scp>HLA</scp> Genetic Susceptibility Markers and Sonographic Enthesitis in Psoriatic Arthritis
Authors: Ari Polachek, Richard Cook, Vinod Chandran, Fatima Abji, Dafna Gladman, Lihi Eder
Journal: Arthritis & Rheumatology (2018)

Objective Enthesitis is an important pathophysiologic component of psoriatic arthritis (PsA). HLA genes are implicated in the pathogenesis of PsA. Little is known about the relationship between HLA genetic susceptibility markers and enthesitis in PsA patients. Our aim was to examine the association between HLA genetic susceptibility markers and sonographic enthesitis in PsA. Methods A cross‐sectional analysis was conducted in patients with PsA. Sonographic enthesitis was assessed according to the Madrid Sonography Enthesitis Index scoring system. HLA genotyping was performed using sequence‐specific oligonucleotide probes. The association between 6 HLA susceptibility markers of PsA and the severity of sonographic enthesitis was assessed using multivariate regression models adjusted for age, sex, body mass index, and disease duration. Results Two hundred twenty‐five patients were included, 57.8% of whom were men. The mean ± SD age was 56.1 ± 12.7 years, and the mean ± SD PsA duration was 16.9 ± 12.3 years. In the multivariate regression model, HLA –B*27 was associated with a higher enthesitis score (β = 4.24 [95% confidence interval {95% CI } 0.02, 8.46]), and the interaction between HLA –B*27 and PsA duration was statistically significant, showing an increasing effect of HLA –B*27 with longer PsA duration (β = 4.62 [95% CI 1.38, 7.86]). Conclusion HLA –B*27 is associated with more severe sonographic enthesitis in PsA, particularly in patients with longer disease duration. This finding highlights the possible role of genetic variants in predisposing to PsA subphenotypes.
Northern Ireland has “no desire” to impose junior doctor contract
Authors: Abi Rimmer
Journal: BMJ (2015)

The Northern Ireland government has said that it has “no desire whatsoever to impose a new contract on junior doctors.” In a statement the Northern Irish health minister, Simon Hamilton, said, “An imposed contract would be the worst possible outcome. I have sympathy for HM Government’s desire to create a seven day NHS, but it is essential that we work with …
Population description and clinical response assessment for spinal metastases: part 2 of the SPIne response assessment in Neuro-Oncology (SPINO) group report
Authors: Ilya Laufer, Simon S Lo, Eric L Chang, Jason Sheehan, Matthias Guckenberger, Moon-Jun Sohn, Samuel Ryu, Matthew Foote, Alexander Muacevic, Scott G Soltys, Samuel Chao, Sten Myrehaug, Peter C Gerszten, Eric Lis, Pejman Maralani, Mark Bilsky, Charles Fisher, Laurence Rhines, Jorrit-Jan Verlaan, David Schiff, Michael G Fehlings, Lijun Ma, Susan Chang, Wendy R Parulekar, Michael A Vogelbaum, Arjun Sahgal
Journal: Neuro-Oncology (2018)

Approximately 40% of metastatic cancer patients will develop spinal metastases. The current report provides recommendations for standardization of metrics used for spinal oncology patient population description and outcome assessment beyond local control endpoints on behalf of the SPIne response assessment in Neuro-Oncology (SPINO) group.The SPINO group survey was conducted in order to determine the preferences for utilization of clinician-based and patient-reported outcome measures for description of patients with spinal metastases. Subsequently, ClinicalTrials.gov registry was searched for spinal oncology clinical trials, and measures for patient description and outcome reporting were identified for each trial. These two searches were used to identify currently used descriptors and instruments. A literature search was performed focusing on the measures identified in the survey and clinical trial search in order to assess their validity in the metastatic spinal tumor patient population. References for this manuscript were identified through PubMed and Medline searches.Published literature, expert survey, and ongoing clinical trials were used to synthesize recommendations for instruments for reporting of spinal stability, epidural tumor extension, neurological and functional status, and symptom severity.Accurate description of patient population and therapy effects requires a combination of clinician-based and patient-reported outcome measures. The current report provides international consensus recommendations for the systematic reporting of patient- and clinician-reported measures required to develop trials applicable to surgery for spinal metastases and postoperative spine stereotactic body radiotherapy (SBRT).
HOXA9 Cooperates with Activated JAK/STAT Signaling to Drive Leukemia Development
Authors: Charles E. de Bock, Sofie Demeyer, Sandrine Degryse, Delphine Verbeke, Bram Sweron, Olga Gielen, Roel Vandepoel, Carmen Vicente, Marlies Vanden Bempt, Antonis Dagklis, Ellen Geerdens, Simon Bornschein, Rik Gijsbers, Jean Soulier, Jules P. Meijerink, Merja Heinäniemi, Susanna Teppo, Maria Bouvy-Liivrand, Olli Lohi, Enrico Radaelli, Jan Cools
Journal: Cancer Discovery (2018)

Abstract Leukemia is caused by the accumulation of multiple genomic lesions in hematopoietic precursor cells. However, how these events cooperate during oncogenic transformation remains poorly understood. We studied the cooperation between activated JAK3/STAT5 signaling and HOXA9 overexpression, two events identified as significantly co-occurring in T-cell acute lymphoblastic leukemia. Expression of mutant JAK3 and HOXA9 led to a rapid development of leukemia originating from multipotent or lymphoid-committed progenitors, with a significant decrease in disease latency compared with JAK3 or HOXA9 alone. Integrated RNA sequencing, chromatin immunoprecipitation sequencing, and Assay for Transposase-Accessible Chromatin using sequencing (ATAC-seq) revealed that STAT5 and HOXA9 have co-occupancy across the genome, resulting in enhanced STAT5 transcriptional activity and ectopic activation of FOS/JUN (AP1). Our data suggest that oncogenic transcription factors such as HOXA9 provide a fertile ground for specific signaling pathways to thrive, explaining why JAK/STAT pathway mutations accumulate in HOXA9-expressing cells. Significance: The mechanism of oncogene cooperation in cancer development remains poorly characterized. In this study, we model the cooperation between activated JAK/STAT signaling and ectopic HOXA9 expression during T-cell leukemia development. We identify a direct cooperation between STAT5 and HOXA9 at the transcriptional level and identify PIM1 kinase as a possible drug target in mutant JAK/STAT/HOXA9-positive leukemia cases. Cancer Discov; 8(5); 616–31. ©2018 AACR. This article is highlighted in the In This Issue feature, p. 517
Assessment of patient selection bias in prospective studies for heart failure
Authors: J. J. G. Gert-Jan De Vries, I. Sokoreli, G. Geleijnse, S. C. Pauws, J. M. Riistama, A. Tesanovic, A. Crundall-Goode, K. M. Goode, J. G. Cleland, A. L. Clark
Journal: European Journal of Heart Failure (2016)
Foundation programme is oversubscribed by nearly 300 applicants
Authors: Helen Jaques
Journal: BMJ (2013)

The foundation programme for 2013 is oversubscribed by 298 applicants, up from 81 in 2012 and 184 in 2011.

A total of 7242 (96%) applicants were successfully allocated to foundation schools, with nearly 89% getting into one of their top five schools. Applicants who did not get a place on the foundation programme starting in August 2013 have been placed on a reserve list for allocation on set dates as vacancies arise. In 2011 and 2012, withdrawals were sufficient …