tbuckley/cabot-search huggingface dataset:
Evolution of neuropsychiatric adverse events of enzalutamide and abiraterone acetate treatments reported in EudraVigilance in metastatic castration resistant prostate cancer patients.
Authors: Maria Paola Moreno Perez, Miguel Sanchez Iznaola, Angela Garcia, Jacobo Muñoz del Toro, Rafael Parra
Journal: Journal of Clinical Oncology (2018)

343 Background: Abiraterone acetate plus prednisone (AAP) and enzalutamide (ENZ), oral hormonal treatment of metastatic castration resistant prostate cancer (mCRPC), can have neuropsychiatric impact. Methods: The Proportional Reporting Ratio (PRR) was used to analyze evolution of suspected adverse drug reactions (ADRs) reported in real world, in EudraVigilance from March to August 2017. Results: From the total ADRs of AAP and ENZ reported in Eudra from March to August 2017, 1,162 were related to AAP and 5,101 were related to ENZ. ADRs of ENZ reported in Eudra in August were higher than those reported in March 2017, in all the neuropsychiatry ADRs analyzed. In the case of AAP, 44% of the neuropsychiatric suspected ADRs analyzed did not show new cases reported and 56% of the ADRs shown an increase, although it was not higher than 15 new cases reported. Conclusions: In August 2017, the updated ADRs of AAP and ENZ from Eudra were consistent with those observed in March 2017 (Iznaola et al.). It confirms an increasing trend of reporting neuropsychiatric ADRs of ENZ in mCRPC. Suspected ADRs of AAP reported remained steady.[Table: see text]
2015 American College of Rheumatology Workforce Study
Authors: Marcy B. Bolster, Anne R. Bass, Jonathan S. Hausmann, Chad Deal, Marcia Ditmyer, Kamilah L. Greene, Seetha U. Monrad, Daniel F. Battafarano
Journal: Arthritis & Rheumatology (2018)

Graduate medical education (GME), through fellowship training, plays a critical role in preparing new rheumatologists for our workforce and is an essential component when addressing the gap of excess demand for adult rheumatology care. This study was undertaken to assess the demographic characteristics and employment trends of new entrants entering the rheumatology workforce and the impact this will have on the supply of rheumatologits over the next 15 years.Primary and secondary data sources were used to develop an integrated workforce model. Factors specific to new graduates entering the workforce included available and filled fellowship positions, gender shifts, planned work schedules (part-time or full-time), practice settings (academic or non-academic, private practice), and number of international medical graduates (IMGs) anticipating US practice.In 2015, there were 113 adult rheumatology programs, with 431 of 468 available positions filled. Using the 215 actual positions available annually in fellowship programs as a starting point, after all factors were applied, the projected clinical full-time equivalent number entering the workforce each year was 107; this number was affected significantly by gender and generational trends. In addition, 17% of IMGs self-identified their plan to practice outside the US. Confounding predictions included a large proportion of current rheumatologists planning retirement with substantially reduced patient loads by 2030.The current US adult rheumatology workforce is in jeopardy of accelerated decline at a time when demands on the workforce face tremendous growth. The current GME training structure cannot support the increased demand. Potential strategies to address this gap include innovative mechanisms for GME funding to increase fellowship training positions, incentives for pursuing rheumatology training (e.g., loan repayment programs), and novel means for recruitment of care to underserved areas of the US.
CATHETER ABLATION VESUS RATE CONTROL IN ATRIAL FIBRILLATION AND HEART FAILURE WITH REDUCED EJECTION FRACTION
Authors: Abel Casso Dominguez, Yasmin Herrera, Farid Gholitabar, Shawn Lee, Alejandro Lemor, Emad Aziz, Bing Yue
Journal: Journal of the American College of Cardiology (2018)
The independent contribution of <i>Pseudomonas aeruginosa</i> infection to long-term clinical outcomes in bronchiectasis
Authors: David Araújo, Michal Shteinberg, Stefano Aliberti, Pieter C. Goeminne, Adam T. Hill, Thomas C. Fardon, Dusanka Obradovic, Glenda Stone, Marion Trautmann, Angela Davis, Katerina Dimakou, Eva Polverino, Anthony De Soyza, Melissa J. McDonnell, James D. Chalmers
Journal: European Respiratory Journal (2018)

Pseudomonas aeruginosa is responsible for chronic infection in many bronchiectasis patients but it is not known whether it is associated with worse clinical outcomes independent of the underlying severity of disease. This study analysed data from 2596 bronchiectasis patients included from 10 different bronchiectasis clinical centres across Europe and Israel, with a 5-year follow-up period. Prevalence of P. aeruginosa chronic infection and its independent impact on exacerbations, hospitalisations, quality of life and mortality was assessed. The prevalence of P. aeruginosa chronic infection was 15.0% (n=389). P. aeruginosa was associated with a higher mortality in a univariate analysis (hazard ratio (HR) 2.02; 95% (confidence interval) CI 1.53–2.66; p&lt;0.0001) but an independent impact on mortality was not found in a multivariate analysis (HR 0.98; 95% CI 0.70–1.36; p=0.89). P. aeruginosa was independently associated with increased mortality only in patients with frequent exacerbations (two or more per year) (HR 2.03; 95% CI 1.36–3.03; p=0.001). An independent association with worse quality of life of 7.46 points (95% CI 2.93–12.00; p=0.001) was found in a multivariable linear regression. P. aeruginosa was therefore found to be independently associated with exacerbation frequency, hospital admissions and worse quality of life. Mortality was increased in patients with P. aeruginosa particularly in the presence of frequent exacerbations.
Abstract 243: A Novel <i>PRKAG2</i> Mutation (K475E): Infantile-onset Hypertrophic Cardiomyopathy Phenotype and Impact on mTOR Signaling
Authors: Yanchun Xu, Hong Liu, Chanika Phornphutkul, D. Grahame Hardie, SC Dudley, James Padbury, Yi-Tang Tseng
Journal: Circulation Research (2016)

Objective: PRKAG2 encodes the 2 subunit isoform of the 5’ AMP-activated protein kinase (AMPK), a heterotrimeric enzyme with major roles in regulation of energy metabolism in response to cellular stress. Mutations in PRKAG2 have been implicated in a unique hypertrophic cardiomyopathy (HCM) characterized by cardiac glycogen overload and hypertrophy. We identified a novel PRKAG2 mutation in a neonate with prenatal onset of HCM noted on a 27-week prenatal ultrasound. Molecular testing for HCM revealed a de novo PRKAG2 mutation (K475E). We aim to investigate the signaling pathway of mutation in PRKAG2 gene. Methods: HEK-293 and H9C2 cells stably expressing wild type (WT) or K475E FLAG-tagged 2 from a tetracycline-inducible promoter were established. Basal AMPK activities were measured at varying AMP concentrations. Phenformin-stimulated AMPK activity and T172-phosphorylation were also measured. Changes in mTOR signaling pathway were accessed by Western blot. Cells were treated with angiotensin II, rapamycin (RAPA) or both followed by staining or flow cytometry to assess cell area/size. Primary fibroblasts from the K475E patient and non-diseased controls were cultured and compared. Finally, transgenic mice with cardiac-specific overexpression of human wild type (Tg WT ) or K475E (TgK 475E ) were established for further study of the PRKAG2 phenotype by histology and echocardiography. Result: HEK-293 cells: K475E mutation induced a markedly increase in the basal AMPK activity and T172-phosphorylation, reduced sensitivity to AMP in allosteric activation and loss of response to phenformin. H9c2 cells: K475E mutation induced increases in the phosphorylation of p-P70S6K, p-4EBP1 and a hypertrophy phenotype which was reversed by RAPA. Transgenic mice: Tg K475E mice had an early onset hypertrophy and were prone to sudden death. Histology revealed large vacuoles and high glycogen content in Tg K475E myocytes throughout the ventricles. Echocardiography confirmed significantly enlarged heart in Tg K475E mice. Conclusions: We identified a novel infantile-onset PRKAG2 mutation with a severe cardiac phenotype. In vitro study revealed involvement of mTOR signaling pathway and reversal of the hypertrophy phenotype by mTOR inhibitor.
Plymouth practical arthroscopy course
Authors: Manav Bawa, Christoph McAllen
Journal: BMJ (2012)

The Plymouth practical arthroscopy course is a two day hands-on course organised by the orthopaedic department in Derriford Hospital, Plymouth. It aims to teach basic arthroscopy skills to doctors in surgical training.

This new course is designed for core surgical trainees with an interest in orthopaedics and for junior orthopaedic registrars who wish to improve their skills in arthroscopy.

The first day was a “diagnostic day” and the second was a “therapeutic day.” On both days delegates rotated around a number of stations—two knee and two …
BMA is “deeply concerned” by 35% rise in spending on private providers in three years
Authors: Jacqui Thornton
Journal: BMJ (2018)

Spending on independent sector providers (ISPs) for NHS services by the Department of Health has risen by £2.5bn (€2.8bn; $3.5bn) over three years to £9bn, an analysis by the BMA has found.1

The BMA says that it remains “deeply concerned” about the growing role of private providers in NHS care because of a worrying lack of transparency and accountability about their activities, despite progress in some areas. It said that it will continue to lobby for greater openness and ultimately for legislative change to move beyond what it calls the current “discredited competition framework” in England.

The BMA’s report1 covers 2013-14 to 2016-17 and shows that the …
ECHOCARDIOGRAPHIC GUIDANCE FOR TRANS-CATHETER DEVICE CLOSURE OF PATENT DUCTUS ARTERIOSUS IN EXTREMELY LOW BIRTH WEIGHT INFANTS
Authors: Govinda Paudel, Ranjit Philip, David Zurakowski, Kaitlin Balduf, Sarah Fahnhorst, Benjamin Waller, Shyam Sathanandam
Journal: Journal of the American College of Cardiology (2018)
Long-Term Outcomes of Hypertrophic Cardiomyopathy Diagnosed During Childhood
Authors: Peta M.A. Alexander, Alan W. Nugent, Piers E.F. Daubeney, Katherine J. Lee, Lynn A. Sleeper, Tibor Schuster, Christian Turner, Andrew M. Davis, Chris Semsarian, Steven D. Colan, Terry Robertson, James Ramsay, Robert Justo, Gary F. Sholler, Ingrid King, Robert G. Weintraub
Journal: Circulation (2018)

Background: Late survival and symptomatic status of children with hypertrophic cardiomyopathy have not been well defined. We examined long-term outcomes for pediatric hypertrophic cardiomyopathy. Methods: The National Australian Childhood Cardiomyopathy Study is a longitudinal population-based cohort study of children (0–10 years of age) diagnosed with cardiomyopathy between 1987 and 1996. The primary study end point was time to death or cardiac transplantation. Results: There were 80 patients with hypertrophic cardiomyopathy, with a median age at diagnosis of 0.48 (interquartile range, 0.1, 2.5) years. Freedom from death/transplantation was 86% (95% confidence interval [CI], 77.0–92.0) 1 year after presentation, 80% (95% CI, 69.0–87.0) at 10 years, and 78% (95% CI, 67.0–86.0) at 20 years. From multivariable analyses, risk factors for death/transplantation included symmetrical left ventricular hypertrophy at the time of diagnosis (hazard ratio, 4.20; 95% CI, 1.60–11.05; P =0.004), Noonan syndrome (hazard ratio, 2.88; 95% CI, 1.02–8.08; P =0.045), higher posterior wall thickness z score (hazard ratio, 1.45; 95% CI, 1.22–1.73; P &lt;0.001), and lower fractional shortening z score (hazard ratio, 0.84; 95% CI, 0.74–0.95; P =0.005) during follow-up. Nineteen (23%) subjects underwent left ventricular myectomy. At a median of 15.7 years of follow-up, 27 (42%) of 63 survivors were treated with β-blocker, and 13 (21%) had an implantable cardioverter-defibrillator. Conclusions: The highest risk of death or transplantation for children with hypertrophic cardiomyopathy is within 1 year after diagnosis, with low attrition rates thereafter. Many subjects receive medical, surgical, or device therapy.
Daily versus weekly prostate cancer image-guided radiotherapy: A phase 3, multicenter, randomized trial.
Authors: Renaud de Crevoisier, Mohamed-Amine Bayar, Pascal Pommier, Xavier Muracciole, Francoise Pene, Philippe Dudouet, Igor Latorzeff, Veronique Beckendorf, Jean-Marc Bachaud, Agnes Laplanche, Stephane Supiot, Bruno Chauvet, TD N'Guyen, Alberto Bossi, Gilles Crehange, Jean-Leon Lagrange
Journal: Journal of Clinical Oncology (2018)

4 Background: The optimal frequency of prostate cancer image-guided radiation therapy (IGRT) has not yet been clearly identified. This study sought to compare the safety and efficacy of daily versus weekly IGRT. Methods: This Phase III randomized trial recruited 470 patients with N0 localized prostate cancer, from 21 centers between June 2007 and November 2012. Total IGRT doses ranged from 70 to 80 Gy. Patients were randomly assigned (1:1) to two prostate IGRT control frequency groups: daily or weekly (Days 1, 2, and 3, then weekly). The primary outcome was 5-year recurrence-free survival (RFS). Secondary outcomes included overall survival (OS) and toxicity (CTCAE V.3.0). Post-hoc analyses included biochemical progression-free interval (BPFI), clinical progression-free interval (CPFI) and second cancer-free interval (SCFI). Results: Median follow-up was 4.1 years (Q 1 – Q 3 = 3.1 – 5.1).There was no statistically-significant difference in RFS between the groups (hazard ratio [HR] = 0.81 [95% CI: 0.52 – 1.25]; p = 0.330). OS was worse in the daily control group versus the weekly control group (HR = 2.12 [95% CI: 1.03 – 4.37]; p = 0.042). Late rectal toxicity (Grade ≥1) incidence was significantly lower in the daily control group (HR = 0.71 [95% CI: 0.53 – 0.96]; p = 0.027). BPFI was better in the daily control group versus the weekly control group (HR = 0.45 [95% CI: 0.25 – 0.80]; p = 0.007). CPFI was better in the daily control group (HR = 0.50 [95% CI: 0.24 – 1.02]; p = 0.057). SCFI was worse in the daily control group versus the weekly control group (HR = 2.21 [95% CI: 1.10 – 4.44]; p = 0.026). Conclusions: Compared to weekly control, daily IGRT control in prostate cancer significantly decreases the risks of recurrence and late rectal toxicity but is associated with an increased risk of second cancer. Clinical trial information: NCT00433706.
Activity of afatinib administered in a window pre-operative study in squamous cell carcinoma of the head and neck (SCCHN) : EORTC-90111.
Authors: Jean-Pascal H. Machiels, Jessica Menis, Michela Lia, Catherine Fortpied, Renaud Lhommel, Marc Lemort, Marco Guzzo, Roberto Bianchi, Flavio Crippa, Pasquale Quattrone, Paolo Bossi, Sandra Schmitz, Thierry Duprez, Yassine Lalami, Marie Quiriny, Nicolas de Saint Aubain, Paul M. Clement, Ruxandra Coropciuc, Esther Hauben, Lisa F. Licitra
Journal: Journal of Clinical Oncology (2016)

6049 Background: Targeted agents (TA) are often investigated in unselected end-stage cancer patients (pts), making difficult to fully evaluate their activity and impairing translational research. One way to resolve this issue is to perform
CONFIRM—Comparing Colonoscopy and Fecal Occult Testing
Authors: Aasma Shaukat, Douglas J. Robertson, Jason Dominitz
Journal: JAMA Internal Medicine (2017)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
Patterns of progression in bone and soft tissue following treatment with Ra-223 in metastatic castrate resistant prostate cancer (mCRPC).
Authors: Megan Ann McNamara, Michala Ritz, Bennett Chin, Jorge Oldan, Aseem Anand, Taofik Oyekunle, Monika Anand, Andrew J. Armstrong, Daniel J. George
Journal: Journal of Clinical Oncology (2018)

222 Background: Bone scans were not obtained in the phase 3 ALSYMPCA trial, and retrospective series have reported varying rates of development of new lesions and resolution of existing lesions, following treatment with Radium-223 (Ra-223). Methods: We performed a retrospective chart review of all men with mCRPC who received at least one dose of Ra-223 at Duke Cancer Institute from June 1, 2013 to June 1, 2015, in order to specifically describe radiographic changes on bone scan and CT during and following treatment. Radionuclide bone scans were reviewed by two radiologists prior to, during, and following Ra-223 treatment. The automated bone scan index (aBSI) was generated at each time point using EXINI bone BSI v. 2. Results: We identified 61 men with mCRPC (72% white, 28% black, median age 70) who received ≥ 1 dose of Ra-223 (median 5 doses, range 1-6). Prior treatments included: abiraterone (71%), enzalutamide (71%), sipuleucel-T (59%), docetaxel (56%), and cabazitaxel (18%). At baseline, 46% of men had nodal metastases, 3% had liver metastases, and 3% had lung metastases. Post-treatment bone scans demonstrated 0, 1-4, 5-9, 10-20, and &gt; 20 new bone lesions in 15%, 10%, 8%, 8%, and 18%, respectively; 10% had resolution of 1-4 bone lesions. Median aBSI was 2.56 at baseline and 3.07 post-treatment. Progression in soft tissue included lymph node (31%), liver (23%), lung (5%), and epidural (8%). Of men with available imaging during treatment, 10 of 14 (71%) had new lesions on bone scan, 15 of 27 (56%) progressed on CT, and 3 of 14 (21%) progressed on both bone scan and CT; these proportions were 44%, 16%, and 24% following treatment, respectively. Men with prior chemotherapy (n = 33) had higher rates of progression on CT during (73%) and after treatment (40%), compared to men with no prior chemotherapy (36% and 25%, respectively). Conclusions: In a heavily treated population of men with mCRPC, radiographic progression in bone and/or soft tissue is common during and shortly after completion of Ra-223 treatment. Patients with prior chemotherapy have higher rates of non-bone progression, compared to patients with no prior chemotherapy. Bone scan and CT imaging are recommended during and after Ra-223.
ELDERLY PATIENTS PRESENTING WITH STEMI APPEAR TO PRESENT LATER DESPITE TARGETED PROTOCOLS FOR EXPEDITING CARE
Authors: Subir Bhatia, Nandan Sadanand Anavekar, Mohammed Al-Hijji, Jason Sims, Gregory Barsness, Mandeep Singh, Joseph Murphy, Joerg Herrmann, Jacob Jentzer, Malcolm Bell, Scott Wright
Journal: Journal of the American College of Cardiology (2018)
Development and Validation of a Novel RNA Sequencing–Based Prognostic Score for Acute Myeloid Leukemia
Authors: Mei Wang, Johan Lindberg, Daniel Klevebring, Christer Nilsson, Sören Lehmann, Henrik Grönberg, Mattias Rantalainen
Journal: JNCI Journal of the National Cancer Institute (2018)

BackgroundRecent progress in sequencing technologies allows us to explore comprehensive genomic and transcriptomic information to improve the current European LeukemiaNet (ELN) system of acute myeloid leukemia (AML).
Hypoxia-specific therapeutic agents delivery nanotheranostics: A sequential strategy for ultrasound mediated on-demand tritherapies and imaging of cancer
Authors: Qianhua Feng, Yuzhen Li, Xuemei Yang, Wanxia Zhang, Yongwei Hao, Hongling Zhang, Lin Hou, Zhenzhong Zhang
Journal: Journal of Controlled Release (2018)
Immune Checkpoint Inhibition in Hodgkin Lymphoma
Authors: Ryan H. Moy, Anas Younes
Journal: HemaSphere (2018)

Abstract Intricate systems of checkpoints such as the programmed cell death protein 1 (PD‐1)/programmed death ligand 1 (PD‐L1) axis regulate adaptive immune responses to protect against tissue damage. However, diverse cancers can exploit these pathways to evade or suppress antitumor immunity, leading to tumor progression. Correspondingly, immune checkpoint inhibitors that block PD‐1/PD‐L1 signaling have shown marked therapeutic efficacy in certain cancers, such as Hodgkin lymphoma. Reed‐Sternberg cells, the hallmark cells of Hodgkin lymphoma, commonly overexpress PD‐1 ligands, and recent clinical trials have demonstrated impressive response rates with the PD‐1 inhibitors nivolumab and pembrolizumab in relapsed or refractory Hodgkin lymphoma, leading to their FDA approval in this setting. Current efforts are underway to improve clinical responses by incorporating PD‐1 inhibitors into earlier treatment regimens and identifying therapeutic agents that synergize with PD‐1 inhibitors. This review summarizes our understanding of the PD‐1/PD‐L1 axis in Hodgkin lymphoma, recent clinical studies of anti‐PD‐1 monotherapy and promising combination immunotherapy in the pipeline.
Management of the acutely ill neuromedical or neurosurgical patient
Authors: Sathiji Nageshwaran
Journal: BMJ (2012)

The third course on management of the acutely ill neuromedical or neurosurgical patient was held on a single day at the Institute for Child Health in London. The aim of this course, and of other courses held by the not for profit group Evidence Based Peri-operative Medicine (www.ebpom.org), is to allow discussion, explanation, and dissemination of up to date evidence based hospital medicine. Most of the speakers were consultants at London’s academic medical centres. 

This course is targeted primarily at hospital based healthcare professionals involved in the care of patients with acute neurological illness. The information presented would be of particular interest to trainees and consultants in neurology, neurosurgery, neuroanaesthesia, and critical care. The course’s clarity, however, and its emphasis on early recognition and resuscitation of this patient group …
A 35 year old laboratory biomedil scientist with an MSc in applied haematology would like to train as a doctor. Is there a fast track to getting the degree? Will she be accepted?
Authors: Paul O'Neill
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.