tbuckley/cabot-search huggingface dataset:
Development of multi-institutional nation-wide tumor board system for testicular cancer in Japan.
Authors: Takashi Kawahara, Koji Kawai, Takahiro Kojima, Takeshi Kishida, Nobuo Shinohara, Yukihiro Kondo, Norio Nonomura, Yoshiyuki Kakehi, Hiroyuki Nishiyama
Journal: Journal of Clinical Oncology (2018)

562 Background: The standard treatments have been established for metastatic germ cell tumors and the cure rates are quite improving. Cumulative experience by centralization is required for expertise in all aspects of care but it is quite difficult due to its rarity and the present medical situations in Japan. To resolve this problem, we established the nation-wide internet tumor board system for testicular cancer from 2012. Methods: To start with, 28 members from 14 institutions were registered in the internet mailing list (ML) for this tumor board, then the members who wanted to join this system were added to this ML. The tumor board was operated in semi-closed system and with no consultant fee. The member can present the case by e-mail at any time when he encounters the difficult case. Then the other members replied and commented their opinions or experiences against his questions by e-mail. All members could read his case-presentation and comments of consultants in e-mail. In this study, we summarized the initial 5-year experience and the discussed contents and the usage status were analyzed to assess the quality of this internet nation-wide reference system. Results: The number of members and discussed cases increased gradually. At the present, this ML consists with 179 members from 79 institutions all over Japan. We discussed 100 testicular cancer cases during 5 years. Discussed cases were categorized into 10 categories. 44% of the cases discussed in the ML were poor prognostic cases or extragonadal cases. In 63 cases, the consultants were replied within 24 hours when the case was presented in ML, and some comments were replied within at 5 days in all cases. The median number of comments was 6, and active discussions with 10 or more comments were performed in 26 cases (26%). Conclusions: The nation-wide internet tumor board system for testicular tumor was growing in Japan and useful to decide treatment strategy for difficult cases. It might be helpful for members in low volume centers to gain cumulative experience.
Risk of fall in patients with COPD
Authors: Ali Hakamy, Charlotte E Bolton, Jack E Gibson, Tricia M McKeever
Journal: Thorax (2018)

A matched cohort study was conducted to determine the incidence of falls in patients following a diagnosis of COPD using a UK primary care database. 44 400 patients with COPD and 175 545 non-COPD subjects were identified. The incidence rate of fall per 1000 person-years in patients with COPD was higher (44.9; 95% CI 44.1 to 45.8) compared with non-COPD subjects (24.1; 95% CI 23.8 to 24.5) (P<0.0001). Patients with COPD were 55% more likely to have an incident record of fall than non-COPD subjects (adjusted HR, 1.55; 95% CI 1.50 to 1.59). The greater falls risk in patients with COPD needs consideration and modifiable factors addressed.
Flt-3L Expansion of Recipient CD8α+ Dendritic Cells Deletes Alloreactive Donor T Cells and Represents an Alternative to Posttransplant Cyclophosphamide for the Prevention of GVHD
Authors: Kate A. Markey, Rachel D. Kuns, Daniel J. Browne, Kate H. Gartlan, Renee J. Robb, J. Paulo Martins, Andrea S. Henden, Simone A. Minnie, Melody Cheong, Motoko Koyama, Mark J. Smyth, Raymond J. Steptoe, Gabrielle T. Belz, Thomas Brocker, Mariapia A. Degli-Esposti, Steven W. Lane, Geoffrey R. Hill
Journal: Clinical Cancer Research (2018)

Purpose: Allogeneic bone marrow transplantation (BMT) provides curative therapy for leukemia via immunologic graft-versus-leukemia (GVL) effects. In practice, this must be balanced against life threatening pathology induced by graft-versus-host disease (GVHD). Recipient dendritic cells (DC) are thought to be important in the induction of GVL and GVHD.Experimental Design: We have utilized preclinical models of allogeneic BMT to dissect the role and modulation of recipient DCs in controlling donor T-cell-mediated GVHD and GVL.Results: We demonstrate that recipient CD8α+ DCs promote activation-induced clonal deletion of allospecific donor T cells after BMT. We compared pretransplant fms-like tyrosine kinase-3 ligand (Flt-3L) treatment to the current clinical strategy of posttransplant cyclophosphamide (PT-Cy) therapy. Our results demonstrate superior protection from GVHD with the immunomodulatory Flt-3L approach, and similar attenuation of GVL responses with both strategies. Strikingly, Flt-3L treatment permitted maintenance of the donor polyclonal T-cell pool, where PT-Cy did not.Conclusions: These data highlight pre-transplant Flt-3L therapy as a potent new therapeutic strategy to delete alloreactive T cells and prevent GVHD, which appears particularly well suited to haploidentical BMT where the control of infection and the prevention of GVHD are paramount. Clin Cancer Res; 24(7); 1604-16. ©2018 AACR.
Genetic landscape of ultra-stable chronic lymphocytic leukemia patients
Authors: S. Raponi, I. Del Giudice, M. Marinelli, J. Wang, L. Cafforio, C. Ilari, A. Piciocchi, M. Messina, S. Bonina, S. Tavolaro, M. Bordyuh, P. Mariglia, N. Peragine, F.R. Mauro, S. Chiaretti, S. Molica, M. Gentile, A. Visentin, L. Trentin, G.M. Rigolin, A. Cuneo, F. Diop, D. Rossi, G. Gaidano, A. Guarini, R. Rabadan, R. Foà
Journal: Annals of Oncology (2018)
Treatment with PD-1 inhibitors in NSCLC beyond disease progression: Impact on symptoms and cost.
Authors: Mor Tal Moskovitz, Priscilla M Matthews, Alexandra M Pavel, Wei Xu, Penelope Ann Bradbury, Geoffrey Liu, Frances A. Shepherd, Natasha B. Leighl
Journal: Journal of Clinical Oncology (2018)

174 Background: Immunotherapy with PD-1 axis inhibitors has become standard of care in the treatment of patients with advanced non-small cell lung cancer (NSCLC), with improved survival and less toxicity than chemotherapy. Response patterns to PD-1 axis inhibitors can be unconventional, including pseudoprogression. Identifying disease progression using RECIST has been challenging. We explored treatment past progression (TPP) with PD-1 inhibitors and its impact on patient symptoms and costs. Methods: Retrospective analysis of consecutive patients with advanced NSCLC that received single agent PD-1 inhibitors at the Princess Margaret Cancer Centre (PMH) between 2013 and 2017. Patient symptom burden was assessed by Edmonton Symptom Assessment Scale (ESAS) at outpatient clinic visits. Drug acquisition costs were calculated using hospital-based costs for the agents used and both actual and fixed dosing recommendations. Results: The study cohort included 89 patients with advanced NSCLC. Median age was 62, half were female and 75% had adenocarcinoma. Most, 70%, developed disease progression during treatment, 19% stopped due to toxicity. Twenty-one patients received TPP (23% of entire cohort, 34% of those with progression). Demographic characteristics except age and baseline symptom scores were similar between groups. Younger patients (p = 0.046), those with lower symptom burden upon RECIST progression (mean ESAS 14.7 vs. 27.2 non-TPP, p = 0.013) and greater symptom improvement from baseline (mean ESAS change -11.7 vs. -2.3 non-TPP, p = 0.11) were more likely to receive TPP. During TPP, only 1 patient achieved tumor response. TPP represented 29% of total treatment costs. This did not vary significantly between weight- based and fixed dosing. However, the costs of treatment of the entire cohort was 23% higher using fixed dosing compared to weight-based. Conclusions: : Treatment with immunotherapy beyond RECIST progression is common in advanced lung cancer, although patient benefit is rare. This can lead to substantial expenditure without clear value for most patients. Better methods for detecting early failure of immunotherapy in advanced NSCLC are needed, to allow patients to switch to more active treatment.
Concepts of epidemiology
Authors: Lorna M Gibson
Journal: BMJ (2012)

This course is aimed at doctors, nurses, health researchers, and health policy makers who would like to get to grips with the basics of epidemiology to inform their clinical or research work. The content follows the chapter headings of Concepts of Epidemiology by Raj Bhopal, professor of public health at Edinburgh University, who runs the course.1 It is most suited to people with an interest in public health, although participants from a variety of backgrounds attend the course. It has been designed to distil the essential elements of the masters degree in epidemiology into an intensive five day course for people who can’t dedicate a full year to study.

During my academic foundation year 2, in December 2011.

I …
Randomized, open label, multicenter, phase II trial comparing transarterial chemoembolization (TACE) plus sorafenib with TACE alone in patients with hepatocellular carcinoma (HCC): TACTICS trial.
Authors: Masatoshi Kudo, Kazuomi Ueshima, Masafumi Ikeda, Takuji Torimura, Nobukazu Tanabe, Hiroshi Aikata, Namiki Izumi, Takahiro Yamasaki, Shunsuke Nojiri, Keisuke Hino, Hidetaka Tsumura, Teiji Kuzuya, Norio Isoda, Kohichiroh Yasui, Kenichi Yoshimura, Takuji Okusaka, Junji Furuse, Norihiro Kokudo, Kiwamu Okita, Yasuaki Arai
Journal: Journal of Clinical Oncology (2018)

206 Background: There is no proven evidence that combination therapy of TACE with sorafenib (TS group) prolong progression-free survival (PFS) and/or overall survival (OS) compared to TACE alone (T group) in patients with unresectable HCC. Methods: In this randomized, open label, multicenter, comparative trial (NCT01217034), patients with unresectable HCC, Child-Pugh score ≤7, ECOG performance status 0-1, no vascular invasion (VI), no extrahepatic spread (EHS), size≤10 cm and number≤10 and adequate organ function were randomized 1:1 (stratification by institution, Milan criteria in or out, and number of previous TACE 0 or 1-2) to T or TS. In TS group, sorafenib 400 mg once daily was pretreated for 2-3 weeks prior to TACE followed by 800mg once daily during on-demand conventional TACE sessions until the time to untreatable progression (TTUP), which was defined as the time to the date of a state when TACE continuation is not possible due to untreatable tumor progression, deterioration to Child-Pugh C or appearance of VI/EHS. Co-primary endpoints are PFS and OS. Multiplicity is adjusted using a gatekeeping hierarchical testing. PFS event in this trial was defined as death or time to TTUP. Key secondary endpoints were time to progression and safety. PFS is expected to 40% extension from 18 months (control arm) to 25 months, target HR was 0.71, with a power of 0.80. Results: The trial was conducted in 33 institutions and a total of 156 patients were randomized to T (n = 76) or TS (n = 80). Median PFS in the T group and TS group was 13.5 and 25.2 months (HR = 0.59, 95%CI 0.41-0.87; p = 0.006), respectively. The number of OS events has not reached. Median TTP was 13.5 and 24.1 months in the T and TS groups (HR = 0.56, 95%CI 0.38-0.83; p = 0.004). Median TTUP was 20.6 and 26.7 months in the T and TS groups (HR = 0.57, 95%CI 0.35-0.92; p = 0.02), respectively. There was no unexpected toxicity. Conclusions: Sorafenib in combination with TACE significantly improved PFS over TACE alone in patients with unresectable HCC. Adverse events were consistent with the known safety profile with previous TACE combination trials. Clinical trial information: NCT01217034.
How can I apply for a job without GMC registration, and how can I get GMC registration without a job?
Authors: Jo Constable
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.
IMPACT OF NEOINTIMAL TISSUE CHARACTERISTICS ON DEVELOPMENT PROCESS OF VERY LATE IN-STENT RESTENOSIS AFTER DRUG-ELUTING STENT: A FOUR SERIAL CORONARY ANGIOGRAMS STUDY
Authors: Kenichi Fujii, Satoru Otsuji, Shin Takiuchi, Wataru Yamamoto, Kasumi Ishibuchi, Hiroto Tamaru, Katsuyuki Hasegawa, Rui Ishii, Sho Nakabayashi, Motoaki Ibuki, Shinya Nagayama, Yorihiko Higashino
Journal: Journal of the American College of Cardiology (2018)
CONTEMPORARY OUTCOMES OF PULMONARY ARTERY CATHETER USE IN THE MANAGEMENT OF CARDIOGENIC SHOCK DUE TO ACUTE MYOCARDIAL INFARCTION
Authors: Le Dung Ha, Gbolahan Ogunbayo, Naoki Misumida, Suartcha Prueksaritanond, Karam Ayoub, Ahmed Abdul-Latif, Ayman Elbadawi, Odunayo Olorunfemi, Adrian Messerli, Maya Guglin
Journal: Journal of the American College of Cardiology (2018)
Markers of non-coeliac wheat sensitivity in patients with myalgic encephalomyelitis/chronic fatigue syndrome
Authors: Melanie Uhde, Alyssa C Indart, Xuechen B Yu, Sophie S Jang, Roberto De Giorgio, Peter H R Green, Umberto Volta, Suzanne D Vernon, Armin Alaedini
Journal: Gut (2018)

We recently reported in Gut that non-coeliac wheat sensitivity (NCWS) is associated with a state of systemic immune activation in conjunction with a compromised intestinal epithelium.1 Patients with NCWS experience GI symptoms, most commonly including abdominal pain and bloating, as well as extraintestinal symptoms, among which fatigue, headache and cognitive difficulties feature prominently.1 2 A principal component analysis of the generated data from our study, including markers of antibody reactivity to wheat gluten, intestinal cell damage and systemic innate and adaptive immune responses to microbial components, found clustering of the patients and controls into discernible groups and demonstrated the potential utility of the identified biomarkers for identifying patients with NCWS.1

Extreme fatigue, in particular one that does not improve with rest, is a hallmark of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).3 Immune system abnormalities have been found to be associated with symptoms in a substantial number of patients with ME/CFS.4 5 Furthermore, many patients complain of GI symptoms of unknown aetiology. …
Limitations of GMC survey on overseas doctors
Authors: Sunanda Ghosh
Journal: BMJ (2004)

EDITOR—I was interested to read about the survey conducted by the GMC (General Medical Council) on career prospects for overseas doctors in the United Kingdom.1 The GMC surveyed a sample of recently passed PLAB (Professional and Linguistic Assessment Board) candidates and concluded that more than 75% of these doctors got a job within eight months of their arrival. This is completely at variance with the experience of overseas doctors on the ground.

It would have been helpful if the GMC …
Striatal neurons directly converted from Huntington’s disease patient fibroblasts recapitulate age-associated disease phenotypes
Authors: Matheus B. Victor, Michelle Richner, Hannah E. Olsen, Seong Won Lee, Alejandro M. Monteys, Chunyu Ma, Christine J. Huh, Bo Zhang, Beverly L. Davidson, X. William Yang, Andrew S. Yoo
Journal: Nature Neuroscience (2018)
1-Year Outcomes of Patients Undergoing Primary Angioplasty for Myocardial Infarction Treated With Prasugrel Versus Ticagrelor
Authors: Zuzana Motovska, Ota Hlinomaz, Petr Kala, Milan Hromadka, Jiri Knot, Ivo Varvarovsky, Jaroslav Dusek, Jiri Jarkovsky, Roman Miklik, Richard Rokyta, Frantisek Tousek, Petra Kramarikova, Michal Svoboda, Bohumil Majtan, Stanislav Simek, Marian Branny, Jan Mrozek, Pavel Cervinka, Jiri Ostransky, Petr Widimsky
Journal: Journal of the American College of Cardiology (2017)

Early outcomes of patients in the PRAGUE-18 (Comparison of Prasugrel and Ticagrelor in the Treatment of Acute Myocardial Infarction) study did not find any significant differences between 2 potent P2Y12 inhibitors.The 1-year follow-up of the PRAGUE-18 study focused on: 1) a comparison of efficacy and safety between prasugrel and ticagrelor; and 2) the risk of major ischemic events related to an economically motivated post-discharge switch to clopidogrel.A total of 1,230 patients with acute myocardial infarction (MI) treated with primary percutaneous coronary intervention were randomized to prasugrel or ticagrelor with an intended treatment duration of 12 months. The combined endpoint was cardiovascular death, MI, or stroke at 1 year. Because patients had to cover the costs of study medication after hospital discharge, some patients decided to switch to clopidogrel.The endpoint occurred in 6.6% of prasugrel patients and in 5.7% of ticagrelor patients (hazard ratio: 1.167; 95% confidence interval: 0.742 to 1.835; p = 0.503). No significant differences were found in: cardiovascular death (3.3% vs. 3.0%; p = 0.769), MI (3.0% vs. 2.5%; p = 0.611), stroke (1.1% vs. 0.7%; p = 0.423), all-cause death (4.7% vs. 4.2%; p = 0.654), definite stent thrombosis (1.1% vs. 1.5%; p = 0.535), all bleeding (10.9% vs. 11.1%; p = 0.999), and TIMI (Thrombolysis In Myocardial Infarction) major bleeding (0.9% vs. 0.7%; p = 0.754). The percentage of patients who switched to clopidogrel for economic reasons was 34.1% (n = 216) for prasugrel and 44.4% (n = 265) for ticagrelor (p = 0.003). Patients who were economically motivated to switch to clopidogrel had (compared with patients who continued the study medications) a lower risk of major cardiovascular events; however, they also had lower ischemic risk.Prasugrel and ticagrelor are similarly effective during the first year after MI. Economically motivated early post-discharge switches to clopidogrel were not associated with an increased risk of ischemic events. (Comparison of Prasugrel and Ticagrelor in the Treatment of Acute Myocardial Infarction [PRAGUE-18]; NCT02808767).
Abstract 16294: A Theory Based Pedometer App Intervention to Promote Physical Activity Among African American Women: The ChangeMySteps Project
Authors: Chileshe Nkonde-Price, Judy Shea, Roy Rosin, Raina Merchant
Journal: Circulation (2015)

Background: Improving physical activity (PA) levels among all Americans is a national priority. National surveys indicate that African American (AA) women have low levels of PA. Smartphone applications (apps) that promote PA offer an innovation solution. Little is known about their feasibility and acceptability among AA women. Methods: A 2-phase mixed methods study design was used. First, in-depth interviews about barriers and facilitators of PA were conducted in AA women recruited from the hair salon setting. Second, themes from interviews were incorporated into the design of a theory-based smartphone pedometer app (Moves App) intervention. The intervention, The ChangeMySteps Project, was piloted in the target population (n=24) in a 1 month, single arm pre and post study design. We measured participant demographics, feasibility (retention rate) and acceptability (ability to incorporate into everyday life, impact on participant hair maintenance and participant satisfaction). In addition, as a secondary outcome we measured daily step count. Results: Themes from interviews (n=32; median age= 34) revealed that lack of time (competing responsibilities) and hair maintenance (negative effect of moisture on hair) were the most commonly cite barriers. Social support (exercise partners and online social network support) were the most commonly cited facilitators. The Smartphone Pedometer App intervention successfully engaged 6 teams (n=24; median age = 36). Retention rates were high (83%).The majority of participants (83%) reported that they were “able” or “very able” to incorporate the intervention into everyday life. The majority (90%) denied any negative effect on hair maintenance. Participant satisfaction rates were high including (100%) likelihood to recommend. Additionally, participants demonstrated an increase in mean daily step count from 5661 (SD 3652) steps /day at baseline to 8071 (SD 3804) steps/day step per day at 1 month (p = 0.03). Conclusion: The ChangeMySteps Project successfully engaged community dwelling AA women to participate in a theory based smartphone pedometer app intervention tailored to the needs of AA women. Findings suggest the intervention was feasible and well accepted among AA women.
Diffusion-weighted imaging and mri-based fractal analysis as quantitative metrics for preoperative prediction of atypia in meningiomas
Authors: Christopher G Filippi, Alexis Demopoulos, Hesham Radwan, Jian Li, Michael Schulder, Marcin Czyz
Journal: Neuro-Oncology (2018)

The purpose of this study was to use fractal MR analysis and diffusion-weighted imaging (DWI) to determine if either can reliably differentiate WHO I benign from atypical WHO II meningiomas. 27 patients with atypical meningioma (WHO II) and 27 patients with benign meningioma (WHO I) were recruited from an institutional database (54 patients: 34 female, 20 male, mean age 62 +/- 15 yrs). All patients had standard contrast-enhanced preoperative brain MR exams including DWI. Mean diffusivity was quantified for tumor core using GE and Philips Workstations. Fractal analysis with box-count method was performed on post-contrast images to determine average (FDa) and maximum (FDm) fractal dimension of the enhancing portions of the tumor, and Image J1.49 software was used for MR fractal analysis. Mean diffusivity did not differ significantly from these two groups. Isointensity of signal was significantly associated with WHO I meningiomas (odds ratio 0.17; 95% CI .44-.62, p < .008). Ki-67 was significantly higher in atypical meningiomas than the benign group (p < .0001). Both the FDa and FDm were significantly higher in the atypical groups (p < .0001) and correlated with the Ki-67 index. Multivariate regression model using MR Fractal analysis and DWI isointensity reached significance, P = .001 and AUC 0.87 (95% CI 0.74–0.94). Maximum fractal dimension, FDm, > 1.31 was a significant predictor of atypical WHO II meningioma (OR 12.30, p < .02). Mean diffusivity and signal characteristics on DWI were not reliable predictors of WHO II atypical meningioma. Tumor fractal dimension analysis on preoperative MR appears to reliably correlate with atypical WHO II meningioma. Mean diffusivity does not reliably distinguish WHO I from WHO II meningioma but isointensity of signal seems to significantly correlate with WHO I meningioma.
Training to resume at Bedford Hospital’s paediatrics department
Authors: Matthew Limb
Journal: BMJ (2014)

The training of junior doctors is to resume at Bedford Hospital’s paediatrics department after the lifting of a suspension imposed last year over safety concerns.

Health Education East of England said it was confident that training standards would be met at Bedford Hospital after an inspection had taken place and staffing numbers, “processes,” and “assurance” had all improved.

Hospital chief executive Stephen Conroy said trainees would start to return from August 2014 with “better support” than in the past and a further assessment would take place after six months …