tbuckley/cabot-search huggingface dataset:
Drug Interactions With Non–Vitamin K Oral Anticoagulants—Reply
Authors: Shang-Hung Chang, Ming-Shien Wen, Chang-Fu Kuo
Journal: JAMA (2018)

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THE CREATININE TO UROMODULIN RATIO IN SERUM PREDICTS MAJOR CARDIOVASCULAR EVENTS INDEPENDENTLY FROM THE PRESENCE OF TYPE 2 DIABETES
Authors: Andreas Leiherer, Axel Muendlein, Christoph Saely, Janine Ebner, Eva-Maria Brandtner, Peter Fraunberger, Heinz Drexel
Journal: Journal of the American College of Cardiology (2018)
Abstract 12252: Effects of the Cholesteryl Ester Transfer Protein Inhibitor, Evacetrapib, Administered as Monotherapy or in Combination With Statins on Cholesterol Efflux and HDL Particles in Patients With Dyslipidemia
Authors: Daniel J Rader, Giacomo Ruotolo, John P Kane, Ming-Dauh Wang, Kathryn A Krueger, Steven E Nissen, Stephen J Nicholls, Bryan H Brewer
Journal: Circulation (2014)

Objectives: The CETP inhibitor evacetrapib (EVA) has been shown to substantially increase HDL-C and apoA-I levels as monotherapy and combined with statins. The effects of EVA on cholesterol efflux capacity and HDL particle distribution have not been described and were evaluated in this study. Methods: Samples from patients (n=398) with elevated LDL-C or low HDL-C enrolled in the multicenter, randomized, double-blind, parallel, placebo-controlled trial (JAMA 2011;306:2099-2109, NCT01105975) were studied. Percent changes from baseline in cholesterol efflux capacity (global, ABCA1- and non-ABCA1-mediated), preβ HDL (measured by immunofixation and 2D-gel), and other HDL subclasses (measured by 2D-gel and NMR) were evaluated after 12 weeks of placebo (PBO), statins alone, EVA alone, and EVA with statins. Results: Results are shown in the table. Statins alone decreased global and ABCA1-mediated cholesterol efflux and preβ-1 HDL (by 2D-gel). EVA alone and combined with statins increased global (28% and 21%, respectively), ABCA1- (17% and 15%, respectively), and non-ABCA1-mediated (35% and 27%, respectively) cholesterol efflux. EVA alone increased preβ-1 as measured by 2D-gel (20%) and immunofixation (32%); EVA combined with statins increased preβ-1 as measured by 2D-gel (27%). While statins alone had no significant effect on large and very large HDL (α-1 and α-2 HDL by 2D-gel, and large HDL by NMR), EVA alone and combined with statins increased these more buoyant HDL particles. Statins alone and EVA alone had no effect on small HDL, whereas EVA combined with statins significantly decreased small HDL particles as measured by NMR. Conclusion: In subjects with elevated LDL-C or low HDL-C, EVA alone and combined with statins increased global, ABCA1- and non-ABCA1-mediated cholesterol efflux. This improved global cholesterol efflux capacity was accompanied by a significant increase in preβ-1 and large and very large HDL particles.
Guidance is launched to improve job planning for SAS doctors
Authors: Helen Jaques
Journal: BMJ (2012)

New guidance has been launched for staff, associate specialist, and specialty (SAS) doctors that aims to align the job planning and professional development opportunities that doctors in these grades receive with those of their consultant colleagues.

The UK-wide guidance—developed jointly by NHS Employers, the BMA, and the devolved administrations—also aims to help SAS doctors and their managers take a collaborative approach to job planning and to improve multidisciplinary team planning.

A job plan should be a prospective agreement that sets out a doctor’s duties, responsibilities, and objectives for the coming year …
Clinical impact of obesity-related factors in perioperative management of esophageal cancer.
Authors: HIROYA TAKEUCHI, Yuji Kikuchi, Hirofumi Kawakubo, Koichi Suda, Yuko Kitagawa
Journal: Journal of Clinical Oncology (2018)

39 Background: Obese patients with esophageal cancer have been increasing worldwide. However, the impact of obesity on esophagectomy still remains controversial. In this study, we clarified the relations between obesity and postoperative outcomes after esophagectomy in patients with esophageal cancer. Methods: A total of 215 patients who underwent esophagectomy for esophageal cancer between 2008 and 2014 were retrospectively assessed. We qualified the body mass index (BMI), visceral fat area (VFA) and subcutaneous fat area (SFA) using CYNAPSE VINCENT™. Clincopathological factors, postoperative morbidity, and survival after esophagectomy were assessed with these obesity-related factors. Results: The mean BMI, VFA, and SFA were 22.0 kg/m², 83.0cm², and 87.3cm². BMI, VFA and SFA were significantly correlated each other (P &lt; 0.001). The prevalence of diabetes mellitus and hypertension were significantly more in high SFA than normal SFA (20% vs 10%, 30% vs 14%). When the patients were divided to two groups according to BMI (&lt; 25 or ≥25kg/m²), VFA ( &lt; 100 or ≥100cm²) and SFA ( &lt; 100 or ≥100cm²), operative time was significantly longer in high SFA (P = 0.03) than normal SFA, and tended to be longer in high BMI, but blood loss were similar in each groups. Maximum level of postoperative CRP was significantly higher in high BMI (P &lt; 0.001), in high VFA (P &lt; 0.001), and in high SFA (P &lt; 0.001). Length of systemic inflammatory response syndrome was significantly longer in high BMI than normal BMI (1.9 days vs 1.4 days P = 0.04), and length of ventilator support was significantly longer in high SFA than normal SFA (3.0 days vs 2.2 days P = 0.006). The incidence of anastomotic leakage and surgical site infection were significantly higher in high SFA than normal SFA (27% vs 10%, 37% vs 19%). There were no significant difference in overall survival, however, patients in high VFA tended to be longer survival than those in normal VFA (P = 0.078). Conclusions: Anastomotic leakage and surgical site infection occurred more frequently in high SFA. It might be useful to examine SFA preoperatively in obese patients with esophageal cancer for prevention of postoperative complications. Patients in high VFA tended to be longer survival than those in normal VFA.
A common neural circuit mechanism for internally guided and externally reinforced forms of motor learning
Authors: Erin Hisey, Matthew Gene Kearney, Richard Mooney
Journal: Nature Neuroscience (2018)

The complex skills underlying verbal and musical expression can be learned without external punishment or reward, indicating their learning is internally guided. The neural mechanisms that mediate internally guided learning are poorly understood, but a circuit comprising dopamine-releasing neurons in the midbrain ventral tegmental area (VTA) and their targets in the basal ganglia are important to externally reinforced learning. Juvenile zebra finches copy a tutor song in a process that is internally guided and, in adulthood, can learn to modify the fundamental frequency (pitch) of a target syllable in response to external reinforcement with white noise. Here we combined intersectional genetic ablation of VTA neurons, reversible blockade of dopamine receptors in the basal ganglia, and singing-triggered optogenetic stimulation of VTA terminals to establish that a common VTA-basal ganglia circuit enables internally guided song copying and externally reinforced syllable pitch learning.
STATIN DISCONTINUATION, PERCEIVED LACK OF NEED FOR A STATIN AND CARDIOVASCULAR DISEASE RISK: DATA FROM THE REASONS FOR GEOGRAPHIC AND RACIAL DIFFERENCES IN STROKE STUDY
Authors: Matthew Mefford, Robert Rosenson, Meredith Kilgore, Lisandro Colantonio, Rikki Tanner, Katherine Mues, Monika M. Safford, Paul Muntner
Journal: Journal of the American College of Cardiology (2018)
A biopsy-based genomic classifier to predict biochemical failure after definitive radiation without hormone therapy in a prospective cohort of intermediate risk prostate cancer.
Authors: Melvin Chua, Jure Murgic, Ali Hosni, Adriana Salcedo, Suzanne Kamel-Reid, Alejandro Berlin, Melania Pintile, Michael Fraser, Theodorus Van Der Kwast, Paul Christopher Boutros, Robert G. Bristow
Journal: Journal of Clinical Oncology (2018)

68 Background: Recently, NCCN adopted the Zumsteg-Spratt subclassification to define NCCN favorable and unfavorable intermediate-risk prostate cancer (IR-PCa). NCCN unfavorable disease is recommended to receive combination androgen deprivation therapy (ADT) and radiotherapy. To determine if genomics could help identify a subset who may safely avoid ADT, we evaluated the Decipher genomic classifier (GC) in IR-PCa treated with dose-escalated image-guided radiotherapy (DE-IGRT) alone. Methods: Our cohort comprised of 121 patients with NCCN favorable (N = 49, 40%) and unfavorable (N = 74, 60%) IR-PCa, who received 78 Gy without ADT. Diagnostic needle biopsies with the highest Gleason score (GS) and %tumor involvement were macrodissected for RNA extraction. GC scores were determined from the Decipher prostate cancer classifier assay (GenomeDx Biosciences, San Diego, CA). Primary clinical endpoint was biochemical relapse ([BCR], PSA nadir + 2ng/ml) post-DE-IGRT. We compared association with BCR against known clinicopathologic prognostic indices and the NCCN risk strata. Results: With a median follow up of 7.5y, 24 (19%) patients experienced BCR. Individual clinical indices did not predict BCR-free survival rate (BFS). NCCN risk strata was however associated with a small but significant difference in BFS (5-y 93%, favorable vs 88%, unfavourable, P = 0.046). GC scores stratified 85 (70%), 19 (16%), and 17 (14%) men into low, intermediate, and high risk of recurrence; 5-y BFS were 95%, 89%, and 59%, respectively (P &lt; 0.001). On multivariable analysis, a hazard ratio of 4.71 (95% CI 1.81-12.28, P = 0.0015) for BCR was observed for the GC high risk group compared to low/intermediate; NCCN risk strata and intraductal variant did not achieve significance. Conclusions: In IR-PCa men treated with DE-IGRT monotherapy, Decipher GC was an independent predictor of BCR. While most men in this our cohort were stratified as NCCN unfavorable IR-PCa, the majority were GC low risk with excellent outcomes from DE-IGRT alone. In contrast, a minority with GC high risk had suboptimal outcomes, and may benefit from ADT intensification.
Is this the end?⇓
Authors: Nicola Sharp
Journal: BMJ (2004)

“We've done it,” said Martha. She sat on a deckchair in Dr Goodwood's potting shed.

“Let's not be too hasty,” Dr Goodwood filled a hanging basket with compost.

“We've saved Murkton Moor Hospital,” said Martha.

“Not yet.” Dr Goodwood tipped a geranium out of its plastic pot.

“We're famous,” said Martha. “We're everywhere: the Murkton Moor Gazette , the Sun , the Times , the Independent , BBC1, ITV.”

“Don't let fame go to your head,” said Dr Goodwood.

“My priority is the hospital,” said Martha, “but don't you think the Times had a good photo of me?”

“Being famous doesn't mean we've achieved what we set out to achieve.” Dr Goodwood stuck the geranium in the middle of the hanging basket.

“We had fifteen thousand people on our march. We beat Kidderminster. They only had twelve thousand.”

“It isn't a competition.”

“But we must have saved the hospital.”

“No we've not. We've raised public awareness. We have the council and most of the hospital management on our side.”

“What do you mean?”

“What I say.”

“But they won't close the hospital now.”

“They might. The whole country could have marched. It wouldn't necessarily have saved the hospital.” …
Moorfields accident and emergency course
Authors: Ben Kirkpatrick
Journal: BMJ (2013)

Working in the emergency department as a foundation year doctor can be a challenging experience because patients present with a broad range of problems that span many specialties. Of the numerous cases seen in a department, dealing with eye diseases can be one of the most daunting. I attended this course to learn more about ophthalmology and to improve my clinical skills and help me manage and refer patients more confidently.

The course is specific to ophthalmology in an emergency setting and focuses on common and rare eye conditions relevant to the emergency department. It is aimed at health professionals exposed to ocular problems, ranging from doctors to nurse practitioners, and it is tailored to suit all abilities. Attendees were varied and included a mix of foundation year doctors, ophthalmology trainees, optometrists, general practitioners, and neurologists. Although knowledge of the topic is not essential, …
DIABETES AND OUTCOME OF PERCUTANEOUS CORONARY INTERVENTION IN PATIENTS WITH CHRONIC TOTAL OCCLUSION LESIONS: A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Wasawat Vutthikraivit, Pavida Pachariyanon, Saranapoom Klomjit, Pattara Rattanawong, Pakpoom Tantrachoti, Awapa Prombandankul, Weera Sukhumthammarat, Prapaipan Putthapiban, Mohammad Ansari
Journal: Journal of the American College of Cardiology (2018)
Junior doctors agree key issues for potential contract negotiations
Authors: Helen Jaques
Journal: BMJ (2013)

Trainees at the BMA’s annual junior doctors conference have agreed on the key topics to target should the union proceed with negotiations over the junior doctor contract.

Delegates passed motions calling for protected teaching time to be written into any new contract for junior doctors, working patterns and monitoring to be a priority, and pay to at least be maintained. 

At the end of last year, NHS Employers called for the junior doctor contact in the United Kingdom to be renegotiated.1 Its “scoping report” into the current arrangements suggested that the existing contract was inflexible, had created opposing financial incentives for employers and doctors …
Fever after anti-programmed cell death-1 treatment to predict the response in advanced hepatocellular carcinoma.
Authors: San-Chi Chen
Journal: Journal of Clinical Oncology (2018)

90 Background: Anti-programmed cell death (PD)-1, an immune checkpoint inhibitor, has been recently approved for the treatment of patients with HCC following prior sorafenib. However, a reliable predictor of treatment response has not been established. Patients who experienced immune-related adverse events (irAEs) of any grade yielded a significantly higher response rate than did those did not experience irAEs. Methods: Three cases of advanced HCC with or without previous sorafenib treatment, underwent anti-PD-1 treatment (pembrolizumab, 2 mg/kg, at 3-week interval) with or without combination of sorafenib (400mg daily). Results: Case 1 Fever (38.3°C) developed 2 days after anti-PD-1 treatment. The fever persisted for 2 months and gradually subsided (Figure 2B). Follow-up computed tomography (CT) revealed persistent tumor shrinkage and complete response at the latest time of examination (Figure 1B); the treatment is ongoing. Case 2 Spiking fever developed after each time of anti-PD-1 treatment. Follow-up CT revealed a remarkable decrease in the tumor size (3 cm), resulting in a partial response (Figure 1D); the treatment is ongoing. Case 3 Twelve days after the treatment, the patient complained of fever and general weakness. Laboratory data revealed tumor lysis syndrome and disseminated intravascular coagulopathy (DIC). HBV, hepatitis B virus; HCV, hepatitis C virus; BCLC, Barcelona Clinic Liver Cancer; AFP, alpha-fetoprotein; TACE, transarterial chemoembolization; CR, complete response; PR, partial response. Conclusions: Fever may be an early predictor of response to anti-PD-1 treatment. The degree of fever seemed to be correlated with tumor burden. High fever may suggest cytokine storm and possible tumor lysis syndrome. Early detection is necessary for the immediate prescription of steroids and management of tumor lysis.[Table: see text]
Hemodynamic and Echocardiographic Comparison of the Lotus and CoreValve Transcatheter Aortic Valves in Patients With High and Extreme Surgical Risk
Authors: Federico M. Asch, Mani A. Vannan, Siddharth Singh, Bijoy Khandheria, Stephen H. Little, Dominic J. Allocco, Ian T. Meredith, Ted E. Feldman, Michael J. Reardon, Neil J. Weissman
Journal: Circulation (2018)

Comparative echocardiographic data on transcatheter aortic valve replacement systems from randomized trials are limited. The REPRISE III trial (Repositionable Percutaneous Replacement of Stenotic Aortic Valve through Implantation of Lotus Valve System - Randomized Clinical Evaluation) is a multicenter, randomized comparison of a mechanically expanded (Lotus) versus self-expanding (CoreValve) transcatheter aortic valve replacement device. This analysis rigorously assesses Doppler-derived valve hemodynamics and the impact on outcomes at 1 year in patients with extreme/high surgical risk treated with Lotus and CoreValve from REPRISE III.REPRISE III includes patients with extreme- and high-risk aortic stenosis. Patients were enrolled at 55 centers. All transthoracic echocardiograms with Doppler were obtained following a standard protocol up to 12 months postimplant and analyzed by a core laboratory. Valve size, mean gradient, aortic valve area, and Doppler velocity index and their impact on clinical outcomes are reported. Additional parameters including paravalvular leak were evaluated using a multiparametric approach.A total of 912 patients were randomly assigned (2:1 ratio; 607 Lotus:305 CoreValve). Median age was 84 years, 51% of the patients were women, and the Society of Thoracic Surgeons score was 6.8±4.1. CoreValve demonstrated lower gradients and larger aortic valve area and Doppler velocity index than Lotus at discharge; the difference decreased in subsequent follow-up up to a year (all P<0.01). Lotus had lower rates of paravalvular leak that persisted over time (P<0.05). Similar outcomes were seen when comparing each valve type by size group (small, medium, large). The hemodynamic differences between valves did not translate into worse clinical outcomes. All-cause mortality was not different between the 2 groups in any of the 3 valve sizes. When comparing patients with normal valve gradients (<20 mm Hg, n=780) with those with abnormal gradients (>20 mm Hg, n=48) in the entire patient population, all-cause mortality was not different. This was also not significant when evaluating each valve type separately. Similarly, there were no differences for aortic valve area >1.1 cm2 or <1.1 cm2 and for Doppler velocity index >0.35 or <0.35 (all P=not significant).Lotus had significantly greater freedom from moderate or severe paravalvular leak and smaller valve area and higher gradients than CoreValve. The hemodynamic differences were not associated with any clinical differences in the composite end point of mortality, disabling stroke, and moderate paravalvular leak or with quality of life at 1 year of follow-up.URL: https://www.clinicaltrials.gov. Unique identifier: NCT02202434.
HEV-positive blood donations represent a relevant infection risk for immunosuppressed recipients
Authors: Dirk Westhölter, Jens Hiller, Ulrike Denzer, Susanne Polywka, Francis Ayuk, Meike Rybczynski, Thomas Horvatits, Svantje Gundlach, Johanna Blöcker, Julian Schulze zur Wiesch, Nicole Fischer, Marylyn M. Addo, Sven Peine, Burkhard Göke, Ansgar W. Lohse, Marc Lütgehetmann, Sven Pischke
Journal: Journal of Hepatology (2018)
Heart Failure with Preserved Ejection Fraction
Authors: James D. Gladden, Antoine H. Chaanine, Margaret M. Redfield
Journal: Annual Review of Medicine (2018)

Heart failure (HF) is a clinical syndrome of diverse etiologies and can be associated with preserved, reduced, or mid-range ejection fraction (EF). In the community, heart failure with preserved ejection fraction (HFpEF) is emerging as the most common form of HF. There remains considerable uncertainty regarding its pathogenesis, diagnosis, and optimal therapeutic approach. Hypotheses have been advanced to explain the underlying pathophysiology responsible for HFpEF, but to date, no specific therapy based on these hypotheses has been proven to improve outcomes in HFpEF. We provide a clinically focused review of the epidemiology, clinical presentation, diagnostic approach, pathophysiology, and treatment of HFpEF.
AGITATION IN ACUTE STANFORD TYPE B AORTIC DISSECTION PATIENTS: AN OVERLOOKED INDICATOR OF MORTALITY AND ADVERSE PROGNOSIS
Authors: Yingcong Liang, Jianfang Luo, Ruixin Fan, Yuan Liu, Wenhui Huang, Huanyu Ding, Songyuan Luo, Fan Yang, Yi Zhu
Journal: Journal of the American College of Cardiology (2018)
Medical Overuse of Prostate-Specific Antigen Testing and Overprescription of Antibiotics—Reply
Authors: Daniel J. Morgan, Sanket S. Dhruva, Deborah Korenstein
Journal: JAMA Internal Medicine (2018)

In Reply Dr Prazeres makes salient points regarding overuse that we would like to emphasize. Despite working within different health care systems, with shared research and medical cultures, many aspects of overuse likely apply across countries.
LEFT VENTRICULAR GLOBAL CIRCUMFERENTIAL AND LONGITUDINAL STRAIN WITH FEATURE TRACKING CARDIOVASCULAR MAGNETIC RESONANCE ASSESSMENT AFTER ST-SEGMENT ELEVATION MYOCARDIAL INFARCTION: PROGNOSTIC IMPLICATIONS
Authors: Tomaz Podlesnikar, Gonzalo Pizarro, Rodrigo Fernandez-Jimenez, Jose Manuel Montero Cabezas, Javier Sanchez-Gonzalez, Nina Ajmone Marsan, Chiara Bucciarelli-Ducci, Zlatko Fras, Valentin Fuster, Jeroen J. Bax, Borja Ibanez, Victoria Delgado
Journal: Journal of the American College of Cardiology (2018)
Active immunotherapy with a VEGF targeted vaccine HeberSaVax: The road so far and the future ahead
Authors: M. Bequet-Romero, Y.M. Díaz, J.S. Ramírez, K.-H. Selman-Housein, F. Hernández-Bernal, A. de la Torre Santos, J. Piñero, C. Bermúdez, J.V. Gavilondo Cowley, M. Ayala Avila
Journal: Annals of Oncology (2018)
ROLE OF STENT GRAFTS IN PATIENTS WITH MARFAN SYNDROME PRESENTING WITH ACUTE TYPE B AORTIC DISSECTION: A COMPARISON STUDY
Authors: Muhammad M. Zubair, Santi Trimarchi, Himanshu Patel, Marek Ehrlich, Derek Brinster, Maral Ouzounian, Clayton Kaiser, Valerio Tolva, Marc Schermerhorn, Joseph Coselli, Eduardo Bossone, Kim Eagle, Daniel Montgomery, Eric Isselbacher, Christoph Nienaber, Jean Bismuth
Journal: Journal of the American College of Cardiology (2018)