tbuckley/cabot-search huggingface dataset:
Dangers of Private Vehicle Transportation vs Emergency Medical Services Transportation—Reply
Authors: Michael W. Wandling, Elliott R. Haut
Journal: JAMA Surgery (2018)

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 Surgery 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 Surgery journal
c15-162: Phase IB trial of radium 223 and niraparib in patients with castrate resistant prostate cancer (NiraRad).
Authors: James Luke Godwin, Jean H. Hoffman-Censits, Robert Benjamin Den, Karen E. Knudsen, Matthew Joseph Schiewer, Benjamin E. Leiby, Traci Southwell, Christine Hubert, Akash Patnaik, Guru Sonpavde, A. Oliver Sartor, Eddy Shih-Hsin Yang, William Kevin Kelly
Journal: Journal of Clinical Oncology (2018)

TPS385 Background: PARP1 is a key regulator of the transition to lethal castrate resistant prostate cancer (CRPC); niraparib is a potent and selective PARP-1 and PARP-2 inhibitor that has shown single agent clinical activity in CRPC. Radium-223 is an alpha particle emitter that causes DNA double strand breaks and is FDA approved for use in CRPC. The addition of a PARP inhibitor (niraparib) may further enhance the clinical benefit of Radium-223 through inhibition of DNA repair and modifications in the bone microenvironment. We hypothesize that targeting the PARP1/androgen receptor (AR) axis in combination with radiopharmaceutical therapy will be safe and may improve clinical outcomes for men with advanced CRPC. Furthermore, combining clinical and pathologic features with correlative studies on tumor tissue, blood, and circulating tumor cells (CTCs) may help us develop biomarkers for future use in the treatment of CRPC. Methods: This is aphase IB dose finding study of patients with metastatic CRPC using a time-to-event continual reassessment (TITE-CRM) design to identify the maximum tolerated dose (MTD) of niraparib (100, 200, or 300 mg QD) in combination with standard doses of Radium-223 in patients with and without prior chemotherapy. Niraparib dosing will continue after 6 cycles of radium-223 until disease progression or intolerable adverse events. Correlative studies include the assessment of tumor biopsy tissues using DNA and RNA next-generation sequencing to assay for the presence of DNA repair aberrations in genes; targeted gene expression profiling of serial RNA (baseline and after cycles 1 and 3) performed on whole blood using the Nanostring PanCancer panel; and evaluation of pre- and post-therapy bone marrow biopsies in a subcohort to characterize the effects of the combined therapy on the bone microenvironment. Additional correlative studies that will be performed on CTC include: assay for nuclear AR expression; immunostaining for the presence of persistent g-H2AX foci, (markers of unrepaired DNA double strand breaks); NFkB activity assayed by immunostaining for p-p65). Enrollment to Dose Level 1 began in October 2017. Clinical trial information: NCT03076203.
DOES HOSPITAL VOLUME AFFECT IN-HOSPITAL MORTALITY IN PATIENTS PRESENTING WITH ST-SEGMENT ELEVATION MYOCARDIAL INFARCTION COMPLICATED BY CARDIOGENIC SHOCK? RESULTS FROM A NATIONWIDE REAL-WORLD REGISTRY
Authors: Gaurav Patel, Sukrut Nanavaty, Toralben Patel, Samir Pancholy
Journal: Journal of the American College of Cardiology (2018)
Membership exam fees frozen for physicians but set to rise in other specialties
Authors: Helen Jaques
Journal: BMJ (2013)

The fees for the examinations for membership of the Royal College of Physicians have been frozen for 2014, whereas fees for other royal college membership exams are set to creep up next year.

The Federation of Royal Colleges of Physicians of the UK has announced that fees for the part 1, part 2, and part 2 clinical examination (PACES) of its membership exam will not increase between 2013 and 2014.

The management board for the exams has said that it chose to freeze fees to recognise the difficult financial situation currently faced by junior doctors, such …
Risk Stratification for Melanoma: Models Derived and Validated in a Purpose-Designed Prospective Cohort
Authors: Catherine M Olsen, Nirmala Pandeya, Bridie S Thompson, Jean Claude Dusingize, Penelope M Webb, Adele C Green, Rachel E Neale, David C Whiteman
Journal: JNCI Journal of the National Cancer Institute (2018)

Risk stratification can improve the efficacy and cost-efficiency of screening programs for early detection of cancer. We sought to derive a risk stratification tool for melanoma that was suitable for the general population using only self-reported information. We used melanoma risk factor information collected at baseline from QSKIN, a prospective cohort study of Queensland adults age 40 to 69 years at recruitment (n = 41 954). We examined two separate outcomes: 1) invasive melanomas and 2) all melanomas (invasive + in situ) obtained through data linkage to the cancer registry. We used stepwise Cox proportional hazards modeling to derive the risk models in a randomly selected two-thirds sample of the data set and assessed model performance in the remaining one-third validation sample. After a median follow-up of 3.4 years, 655 (1.6%) participants developed melanoma (257 invasive, 398 in situ). The prediction model for invasive melanoma included seven terms. At baseline, the strongest predictors of invasive melanoma were age, sex, tanning ability, number of moles at age 21 years, and number of skin lesions treated destructively. The model for "all melanomas" (ie, invasive and in situ) included five additional terms. Discrimination in the validation data set was high for both models (C-index = 0.69, 95% confidence interval [CI] = 0.62 to 0.76, and C-index = 0.72, 95% CI = 0.69 to 0.75, respectively), and calibration was acceptable. Such a tool could be used to target surveillance activities to those at highest predicted risk of developing melanoma over a median duration of 3.4 years.
Avoid routinely prescribing medicines for non-specific low back pain
Authors: Adrian C Traeger, Rachelle Buchbinder, Ian A Harris, Ornella M Clavisi, Chris G Maher
Journal: British Journal of Sports Medicine (2018)

Low back pain causes more disability worldwide than any other health condition.1 Although many people self-manage their condition without needing to seek care,2 low back pain is the second most frequent symptom to prompt attendance in general practice after the common cold.3 Most low back pain is ‘non-specific’ meaning there is no identifiable spinal pathology. While the available evidence suggests a limited role for medicines in the management of an acute episode of non-specific low back pain, medicine prescription remains almost routine.4 Many patients with persisting symptoms also continue to take medicines long-term despite the low likelihood of ongoing benefits. We suggest a different approach that emphasises selective prescribing, and discontinuing medicines that are no longer of benefit, for patients with non-specific low back pain.

Recent guidelines indicate a reduced role for medicines in the management of non-specific low back pain. The 2017 Danish Guideline does not recommend any medicine.5 The 2016 UK guideline from the National Institute for Health and Care Excellence only recommends non-steroidal anti-inflammatory drugs (NSAIDs) and ‘weak’ opioids.6 The 2017 US guideline from the American College of Physicians (ACP) makes a similar recommendation and includes the addition of skeletal muscle relaxants for acute non-specific low back pain (ie, pain for <12 weeks), but explicitly states that the initial treatment of non-specific low back pain should be non-pharmacological.7 These guidelines reflect new evidence suggesting that in patients with non-specific low back pain, many pain medicines have little or no benefit over placebo, and potential for harm. For a detailed description of the evidence on benefits and harms of medicines for low back pain, we refer readers to the evidence document accompanying the ACP guideline.7 Below we focus on evidence (see box 1 for our search strategy) for medicines that …
<i>I have had a personality clash with my boss. Do I have to ask her for a reference?</i>
Authors: Sarah Burnett
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>
Protein kinase N1 critically regulates cerebellar development and long-term function
Authors: Stephanie zur Nedden, Rafaela Eith, Christoph Schwarzer, Lucia Zanetti, Hartwig Seitter, Friedrich Fresser, Alexandra Koschak, Angus J.M. Cameron, Peter J. Parker, Gottfried Baier, Gabriele Baier-Bitterlich
Journal: Journal of Clinical Investigation (2018)

Increasing evidence suggests that synapse dysfunctions are a major determinant of several neurodevelopmental and neurodegenerative diseases. Here we identify protein kinase N1 (PKN1) as a novel key player in fine-tuning the balance between axonal outgrowth and presynaptic differentiation in the parallel fiber-forming (PF-forming) cerebellar granule cells (Cgcs). Postnatal Pkn1-/- animals showed a defective PF-Purkinje cell (PF-PC) synapse formation. In vitro, Pkn1-/- Cgcs exhibited deregulated axonal outgrowth, elevated AKT phosphorylation, and higher levels of neuronal differentiation-2 (NeuroD2), a transcription factor preventing presynaptic maturation. Concomitantly, Pkn1-/- Cgcs had a reduced density of presynaptic sites. By inhibiting AKT with MK-2206 and siRNA-mediated knockdown, we found that AKT hyperactivation is responsible for the elongated axons, higher NeuroD2 levels, and reduced density of presynaptic specifications in Pkn1-/- Cgcs. In line with our in vitro data, Pkn1-/- mice showed AKT hyperactivation, elevated NeuroD2 levels, and reduced expression of PF-PC synaptic markers during stages of PF maturation in vivo. The long-term effect of Pkn1 knockout was further seen in cerebellar atrophy and mild ataxia. In summary, our results demonstrate that PKN1 functions as a developmentally active gatekeeper of AKT activity, thereby fine-tuning axonal outgrowth and presynaptic differentiation of Cgcs and subsequently the correct PF-PC synapse formation.
Inhibiting core fucosylation attenuates glucose-induced peritoneal fibrosis in rats
Authors: Longkai Li, Nan Shen, Nan Wang, Weidong Wang, Qingzhu Tang, Xiangning Du, Juan Jesus Carrero, Keping Wang, Yiyao Deng, Zhitong Li, Hongli Lin, Taihua Wu
Journal: Kidney International (2018)
REDUCTION IN MYOCYTE AUTOPHAGY CONTRIBUTES TO LEFT VENTRICULAR REMODELING AFTER MYOCARDIAL INFARCTION IN RABBITS: NORMALIZATION BY ANTIOXIDANTS
Authors: Rui-Fang Chi, Jia-Pu Wang, Ke Wang, Xiao-Li Zhang, Yue-An Zhang, Fu-Zhong Qin, Xue-Bin Han
Journal: Journal of the American College of Cardiology (2018)
Abstract P5-07-11: BHLHE40-AS1 is an enhancer associated noncoding RNA critical to breast cancer progression
Authors: RKS DeVaux, H Schimjawicz, C Coarfa, F Behbod, JI Herschkowitz
Journal: Cancer Research (2018)

Abstract Increased emphasis on breast cancer screening has led to a dramatic increase in diagnosis of ductal carcinoma in situ (DCIS). DCIS lesions are nonobligate precursors of invasive ductal carcinoma (IDC) and thus, the current standard-of-care is aggressive therapy to prevent invasive and metastatic disease. However, only ˜40% of DCIS cases are predicted to progress leading to a current state of overtreatment and overdiagnosis. Thus, there is a critical need to identify functional determinants of progression of DCIS to IDC to allow discrimination between indolent and aggressive breast cancers and refine patient treatment strategies. We propose that long noncoding RNAs (lncRNAs) functionally drive breast cancer progression and their expression can discriminate between innocuous and potentially invasive DCIS. Using biopsies from women with tandem DCIS and IDC lesions, we identified the lncRNA BHLHE40-AS1 as enriched in patient IDC. Furthermore, BHLHE40-AS1 is enriched in multiple breast cancer progression models, in HER2+ cell lines, and can be induced by expression of HER2. BHLHE40-AS1 is transcribed from a known super-enhancer that we find becomes rewired in breast cancer progression. In addition, the lncRNA is found antisense to BHLHE40, a transcription factor critical to many core processes (apoptosis, EMT, circadian rhythm). Depletion of the lncRNA attenuates expression of BHLHE40. Future studies are focused on mechanistically elaborating its function, its impact on the associated enhancer and chromatin looping, and determining the utility of BHLHE40-AS1 as a clinically relevant biomarker and therapeutic target in invasive breast cancer. Citation Format: DeVaux RKS, Schimjawicz H, Coarfa C, Behbod F, Herschkowitz JI. BHLHE40-AS1 is an enhancer associated noncoding RNA critical to breast cancer progression [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 P5-07-11.
Frequency of liver test increases on abiraterone acetate in men with castrate-resistant prostate cancer (CRPC): Natural history, management, and outcome.
Authors: Emeline Colomba, Grégoire Marret, Giulia Baciarello, Christophe Massard, Yohann Loriot, Laurence Albiges, Edith Carton, Jerome Alexandre, Olivier Huillard, Stephane Culine, Karim Fizazi
Journal: Journal of Clinical Oncology (2018)

332 Background: Abiraterone acetate (abiraterone) in combination with prednisone is a standard of care for patients with metastatic CRPC. Abiraterone is seldom associated with liver toxicity and systematic monitoring of ALT and AST is required. Clinical management and outcome of these patients have not been described. Methods: We retrospectively identified 22 men with mCRPC with liver tests disorder occurring during abiraterone therapy from December 2009 to September 2017 from three oncology centers in France. Results: Thirty nine liver disorder events occurred in 22 patients during abiraterone therapy. The median age was 62 (50-80) years. Only one patient had liver metastasis. No patient had a history of chronic alcoholism. Accountability of the liver tests increase to abiraterone was doubtful in two patients who were receiving antibiotics when the event occurred. The incidence of AST increase (19 events) and that of ALT (20 events) were similar. Liver toxicity was of grade 1, 2, and 3 (CTCAEv4) in 5 (22.7%), 5 (22.7%), and 9 (40.9%) patients for ALT, and in 9 (40.9%), 6 (27.3%), and 5 (22.7%) for AST, respectively. The median time from abiraterone initiation to the detection of liver toxicity was 15.8 (4-95) weeks. The median time from highest ALT/AST increase to normalization was 7.7 (2-15) weeks. Normalization of liver test was observed in 19 (86.4%) patients, and 3 patients died of cancer progression before their liver tests had normalized. In 12 patients (54.4%), liver tests spontaneously returned to baseline values, while abiraterone was continued at full dose. Abiraterone was discontinued in 6 patients (27.7%) due to liver test increase. It was reintroduced after a break in four patients and then discontinued in two for a subsequent liver disorder event. No patient reported symptoms clearly related to liver test increase. Conclusions: Liver tests increase is a quite rare event that typically occurs within the first 4 months on abiraterone, though it can also happen up to 20 months later. It is typically asymptomatic and most patients experience normalization of tests, either spontaneously or after dose reduction/discontinuation.
Abstract 14025: Mild QTc Prolongation was Associated With Cardiovascular Events in Japanese Male Patients With Cardiovascular Risk Japan Morning Surge Home Blood Pressure (J-HOP) Study
Authors: Seigo Arima, Tomoyuki Kabutoya, Satoshi Hoshide, Kazuomi Kario
Journal: Circulation (2016)

Introduction: The relationships between QTc intervals and the risk of cardiovascular (CV) events could differ among ethnicities or between subjects with/without left ventricular hypertrophy (LVH). Hypothesis: We hypothesized that mild QTc prolongation was associated with CV events in Japanese patients with CV risk factors. Methods: Subjects were 3,592 patients enrolled in the Japan Morning Surge Home Blood Pressure Study who had one or more CV risk factors. Corrected QT intervals (QTc) were calculated using the Bazett formula. Prolonged QTc interval was defined as ≥440 ms in men and ≥460 ms in women on electrocardiogram (ECG). We divided patients into 3 subgroups according to the percentile of QTc (shortest 10%, middle 80%, and longest 10%). The primary endpoints were fatal/nonfatal CV events (myocardial infarction, stroke, hospitalization for heart failure, aortic dissection). The Sokolow-Lyon criteria (RV5(6)+SV1) ≥35 mm were used to diagnose LVH. Results: During the mean follow-up period of 48±39 months, there were 138 CV events. In male patients, those with prolonged QTc (N=57) were more likely to suffer CV events than those without prolonged QTc (N=1523) (log rank 6.22, p=0.013). A Cox proportional hazards model including age, hypertension, dyslipidemia and diabetes revealed that prolonged QTc was a significant independent predictor of CV events in male patients (hazard ratio 2.21, 95%CI 1.01-4.82, p=0.047). In female patients, CV events were similar in prolonged QTc (N=33) and non- prolonged QTc patients (N=1766, p=0.73). In male patients, the longest 10% of QTc patients (QTc≥406ms, N=157) were more likely to suffer CV events than those in the middle 80% of QTc patients (QTc 332-405ms, N=1265) and shortest 10% of QTc patients (QTc&lt;332ms, N=157) (log rank 16.57, p&lt;0.001). In the absence of LVH (N=1308), male patients in longest 10% of QTc suffered more CV events than those in the other groups (log rank 6.61, p=0.037), and in the presence of LVH (N=272), males in the longest 10% of QTc also suffered more CV events than those in the other groups (log rank 13.73, p=0.001).In female patients, CV events were similar in three subgroups. Conclusions: Mild QTc prolongation was associated with CV events in Japanese male patients with a CV risk with or without ECG-LVH.
Insight in schizophrenia spectrum disorders: relationship with behavior, mood and perceived quality of life, underlying causes and emerging treatments
Authors: Paul H. Lysaker, Michelle L. Pattison, Bethany L. Leonhardt, Scott Phelps, Jenifer L. Vohs
Journal: World Psychiatry (2018)

Poor insight in schizophrenia is prevalent across cultures and phases of illness. In this review, we examine the recent research on the relationship of insight with behavior, mood and perceived quality of life, on its complex roots, and on the effects of existing and emerging treatments. This research indicates that poor insight predicts poorer treatment adherence and therapeutic alliance, higher symptom severity and more impaired community function, while good insight predicts a higher frequency of depression and demoralization, especially when coupled with stigma and social disadvantage. This research also suggests that poor insight may arise in response to biological, experiential, neuropsychological, social‐cognitive, metacognitive and socio‐political factors. Studies of the effects of existing and developing treatments indicate that they may influence insight. In the context of earlier research and historical models, these findings support an integrative model of poor insight. This model suggests that insight requires the integration of information about changes in internal states, external circumstances, others’ perspectives and life trajectory as well as the multifaceted consequences and causes of each of those changes. One implication is that treatments should, beyond providing education, seek to assist persons with schizophrenia to integrate the broad range of complex and potentially deeply painful experiences which are associated with mental illness into their own personally meaningful, coherent and adaptive picture.
Overseas doctors and more trainees may be needed to help “struggling” acute medicine departments, colleges say
Authors: Tom Moberly
Journal: BMJ (2014)

Overseas doctors and a wider range of trainees may need to be drafted into acute medicine departments to relieve pressure on medical registrars, three royal colleges have said.

The Royal College of Physicians of London, the Royal College of Physicians of Edinburgh, and the Royal College of Physicians and Surgeons of Glasgow have issued a joint statement setting out measures to …
Liver transplantation for locally advanced intrahepatic cholangiocarcinoma treated with neoadjuvant therapy: a prospective case-series
Authors: Keri E Lunsford, Milind Javle, Kirk Heyne, Rachna T Shroff, Reham Abdel-Wahab, Nakul Gupta, Constance M Mobley, Ashish Saharia, David W Victor, Duc T Nguyen, Edward A Graviss, Ahmed O Kaseb, Robert S McFadden, Thomas A Aloia, Claudius Conrad, Xian C Li, Howard P Monsour, A Osama Gaber, Jean-Nicolas Vauthey, R Mark Ghobrial
Journal: The Lancet. Gastroenterology & hepatology (2018)
MSc in surgical technology
Authors: Ragavan Navaratnam
Journal: BMJ (2012)

This postgraduate degree offered by Imperial College London is aimed not only at surgeons hoping to further their knowledge in the subject but also at healthcare professionals interested in the fields of surgery and technology—for example, operating department practitioners and theatre staff.

I did this course at the start of my core training year 1, opting to do the course part time over two years.

I decided to study for an MSc relevant to my chosen field of specialisation to enhance my CV before applying for higher surgical training. The MSc in surgical technology gave me an opportunity to learn and explore new and different aspects of modern surgical practice and to gain a better understanding of the potential future direction of the specialty. Having …