tbuckley/cabot-search huggingface dataset:
First Smallpox Drug Approved
Authors: Rebecca Voelker
Journal: JAMA (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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
When Parents Refuse: Resolving Entrenched Disagreements Between Parents and Clinicians in Situations of Uncertainty and Complexity
Authors: Janine Penfield Winters
Journal: The American Journal of Bioethics (2018)

When shared decision making breaks down and parents and medical providers have developed entrenched and conflicting views, ethical frameworks are needed to find a way forward. This article reviews the evolution of thought about the best interest standard and then discusses the advantages of the harm principle (HP) and the zone of parental discretion (ZPD). Applying these frameworks to parental refusals in situations of complexity and uncertainty presents challenges that necessitate concrete substeps to analyze the big picture and identify key questions. I outline and defend a new decision-making tool that includes three parts: identifying the nature of the disagreement, checklists for key elements of the HP and ZPD, and a "think list" of specific questions designed to enhance use of the HP and ZPD in clinical decision making. These tools together will assist those embroiled in complex disagreements to disentangle the issues to find a path to resolution.
Peter Fisher: homeopathic physician to the Queen
Authors: John Illman
Journal: BMJ (2018)

Peter Fisher was probably the nearest anyone will ever get to being homeopathic royalty: homeopathic physician to the Queen, president of the Faculty of Homeopathy, and chair of the World Health Organization’s working group on homeopathy. But what made him remarkable was his single minded determination to promote homeopathy despite the unrelenting flood of criticism and scientific evidence against it. His career was a masterclass for politicians on how to stay on message. Vowing that he would “debate anyone, anytime,” he was an accomplished writer and speaker.

Fisher could not have chosen a better time to start specialising in homeopathy. He graduated from Cambridge in 1976 during the evolution of the new “pick n’ mix” medical culture and amid a growing realisation that care professionals could never provide the personal engagement many patients wanted. The thalidomide scandal had shaken public faith in modern medicines, and homeopathy and other forms of complementary medicine were coming in from the cold—with a helping hand from Prince Charles and an unquestioning media that gave more prominence to royal patronage than to …
Full time GPs fall by over 500 in three months
Authors: Abi Rimmer
Journal: BMJ (2018)

The total number of full time equivalent GPs in England fell by 523 in three months this year, from 33 686 in March to 33 163 in June, data from NHS Digital have shown.1

Provisional figures from June and final data from March show that the total number of headcount GPs (full and part time GPs) also fell by almost 500, from 41 848 in March to 41 360 in June. The figures suggest that the government is struggling to …
Human Cardiac Fibroblasts Engage the Sarcoplasmic Reticulum in Induced Pluripotent Stem Cell-Derived Cardiomyocyte Excitation–Contraction Coupling
Authors: Christopher Kane, Cesare M. Terracciano
Journal: Journal of the American College of Cardiology (2018)

Ca2+-induced Ca2+ release (CICR), the process whereby a small influx of Ca2+ across the sarcolemma triggers a significantly larger Ca2+ release from the sarcoplasmic reticulum (SR), is at the heart of efficient cardiac excitation–contraction coupling (ECC). This process is rudimentary in neonatal
Abstract 18610: Preliminary Evaluation of a Wrist Wearable Heart Rate Sensor for the Detection of Undiagnosed Atrial Fibrillation in a Real-World Setting
Authors: Giorgio Quer, Nima Nikzad, Shraddha Lanka, Reinier van Mourik, Onur Dur, Steven R Steinhubl
Journal: Circulation (2017)

Introduction: As part of a large digital medicine study investigating the identification of asymptomatic atrial fibrillation (AF) using a continuous single-lead ECG patch, we evaluated the usabilit...
Abstract 11490: Increased Late Sodium Current Contributes to Excess Prolongation of Canine Ventricular Repolarization Induced by Dofetilide
Authors: Xiaoliang(Shawn) Qiu, Samuel Chauveau, Anyukhovsky P Evgeny, Tania Rahim, Ya-Ping Jiang, Erin R Harleton, Steven J Feinmark, Richard Z Lin, Tove S Rosen, Ira S Cohen, Michael R Rosen
Journal: Circulation (2015)

Introduction: Drugs are screened for delayed rectifier potassium current (IKr) blockade to predict QT prolongation and proarrhythmic potential, but recent in vitro cell studies have shown chronic exposure (hours) to some IKr blockers (e.g. dofetilide, D) prolongs repolarization by increasing late sodium current (INa-L) via PI3 kinase inhibition. Hypothesis: Chronic D administration to intact dogs prolongs repolarization by blocking IKr and increasing INa-L. Methods: We continuously infused D into 6 dogs (6-9 μg/kg bolus+6-9 μg/kg/h IV infusion) for 7h, maintaining D plasma levels within the therapeutic range(2.4±0.2 to 5.2±0.6ng/ml). Acute and chronic D effects on action potential duration (APD) were studied in canine left ventricular (LV) subendocardial slabs using microelectrode techniques. Results: D infusion increased QTc and repolarization time (RT) continuously from baseline to 7h (Table). The INa-L blocker lidocaine (2mg/kg bolus) reduced all variables at 6.5h&gt;0.5h (Table) (e.g. QTc: 19±2% vs 8±1%, P&lt;.05). Chronic, but not acute, D increased apico-basal dispersion of RT, and lidocaine significantly attenuated this effect (Table). In LV subendocardium in vitro, D superfusion (0.2 μM) increased APD at 90% repolarization (APD90) from 232±8ms at baseline to 303±7 at 0.5h (P&lt;.05) and 372±6 at 6.5h (P&lt;.05 vs .5h)(n=6). Lidocaine (20 μM) decreased APD90 by 8±1% at 0.5h and 23±1% at 6.5h (P&lt;.05). In comparison, moxifloxacin (100 μM), an IKr blocker with no effect on INa-L increased APD90 from 216±3ms to 282±5 at 1h (P&lt;.05), and 289±5 at 6.5h (P&gt;.05 vs 1h). Lidocaine reduced APD90 equally by 8% at both 1h and 6.5h (P&gt;.05 for 1h vs 6.5h). Conclusions: Chronic D prolongs ventricular repolarization by blocking Ikr and increasing INa-L. Acquired LQT during chronic D dosing may be attributable to the INa-L increase, highlighting the need to include time and INa-L in evaluating the PI3K inhibition-derived proarrhythmic potential of new drugs.
Abstract 19528: Association of Neutrophil Gelatinase-Associated Lipocalin With Mortality and Cardiovascular Events: Results From the Dallas Heart Study
Authors: Hurst M Hall, Jessica Joseph, Colby R Ayers, Anand Rohatgi, Ambarish Pandey, Jarett D Berry, James A de Lemos, Sandeep R Das
Journal: Circulation (2016)

Background: Neutrophil gelatinase-associated lipocalin (NGAL), a small protein located primarily in activated neutrophils, has been implicated in the prediction of adverse cardiovascular (CV) events in patients without pre-existing CV disease. However, prior cohorts have been limited by size, homogeneous race/ethnicity, and older age. Methods: Plasma NGAL levels were measured in participants enrolled in the Dallas Heart Study, a multi-ethnic probability based sample of Dallas County residents ages 30-65. After excluding patients with a history of myocardial infarction, stroke, or heart failure (n=255), a total of 3043 participants were included and followed for clinical events. NGAL was log-transformed and analyzed in Cox proportional hazards models adjusted for age, sex, race, diabetes status, hypertension, body mass index, tobacco use, and renal function. Outcomes included all-cause death, CV death, and nonfatal CV events. Results: Over a median follow-up period of 6.4 years, 173 total deaths occurred (...
Abstract 12158: Impact of Modifiable Risk Factors on Circulating Concentrations of B-type Natriuretic Peptide and Cardiac Troponin T
Authors: Pratyaksh K Srivastava, Aruna D Pradhan, Nancy R Cook, Paul M Ridker, Brendan M Everett
Journal: Circulation (2015)

Introduction: Alcohol use, physical activity, diet, and cigarette smoking are modifiable cardiovascular risk factors that have a substantial impact on the risk of myocardial infarction, stroke, and cardiovascular death. Hypothesis: We hypothesized that these behaviors may alter concentrations of cardiac troponin, a marker of myocyte injury, and B-type natriuretic peptide, a marker of myocyte stress. Both markers have shown strong association with adverse cardiovascular outcomes. Methods: In 564 women with no evidence of cardiovascular disease, we measured circulating concentrations of cardiac troponin T, measured using a high-sensitivity assay (hsTnT), and the N-terminal fragment of B-type natriuretic peptide (NT-proBNP). We used logistic regression to determine if these behaviors were associated with detectable hsTnT (&gt;= 3ng/L) or with NT-proBNP in the highest quartile (≥117.4 ng/L). Results: The median (Q1-Q3) NT-proBNP of the cohort was 64.2 (37.8-117.4), and 30.3% (171/564) of the cohort had detectable circulating hsTnT. In adjusted models, women who drank 1-6 drinks per week had a lower odds of having a detectable hsTnT (OR 0.54, 95% CI: 0.33-0.89, P-trend=0.001) or an elevated NT-proBNP (OR 0.48, 95% CI 0.19-1.19, P-trend =0.03; Figure). We validated the results for B-type natriuretic peptide in a large independent cohort. No significant associations were seen for diet, exercise, or smoking. Conclusion: Regular alcohol consumption is associated with lower concentrations of hsTnT and NT-proBNP, two cardiovascular biomarkers associated with increased cardiovascular risk. These results raise the hypothesis that the beneficial effects of alcohol consumption may be mediated by direct effects on the myocardium.
Post-mortem microbiology in sudden death: sampling protocols proposed in different clinical settings
Authors: A. Fernández-Rodríguez, J.L. Burton, L. Andreoletti, J. Alberola, P. Fornes, I. Merino, M.J. Martínez, P. Castillo, B. Sampaio-Maia, I.M. Caldas, V. Saegeman, M.C. Cohen
Journal: Clinical Microbiology and Infection (2018)
FDG-PET response and outcome from anti-PD-1 therapy in metastatic melanoma
Authors: A.C. Tan, L. Emmett, S. Lo, V. Liu, R. Kapoor, M.S. Carlino, A.D. Guminski, G.V. Long, A.M. Menzies
Journal: Annals of Oncology (2018)

Immune checkpoint inhibitor therapy has resulted in impressive and durable clinical activity for many cancers including melanoma; however, there remain few reliable predictors for long-term response. This study investigated whether [18F]2-fluoro-2-deoxy-D-glucose (FDG-PET) imaging may better predict long-term outcomes compared with standard computed tomography (CT) response criteria.Retrospective analysis of metastatic melanoma patients treated with anti-PD-1-based immunotherapy with baseline and 1-year FDG-PET and CT imaging at Melanoma Institute Australia. One-year response was determined using RECIST for CT and EORTC criteria for PET, coded as complete response (CR or CMR), partial response (PR or PMR), stable disease (SD or SMD) or progressive disease (PD or PMD). Progression-free survival (PFS) was determined from the 1-year landmark.Patients (n = 104) were evaluated with median follow-up 30.1 months and 98% remain alive. Most received anti-PD-1 as monotherapy (67%) or combined with ipilimumab (31%). At 1 year, 28% had CR, 66% had PR and 6% had SD on CT, while 75% had CMR, 16% PMR and 9% SMD/PMD on PET. CMR was observed in 68% of patients with PR on CT. RECIST PFS post 1-year landmark was similar in patients with CR versus PR/SD, but improved in patients with CMR versus non-CMR {median not reached [NR] versus 12.8 month; hazard ratio [HR] 0.06 [95% confidence interval (CI) 0.02-0.23]; P < 0.01}. In patients with PR on CT, PFS was improved in patients with PR + CMR versus PR + non-CMR (median NR versus 12.8 months; HR 0.07 [95% CI 0.02-0.27]; P < 0.01). In the 78 CMR patients, 78% had discontinued treatment and 96% had ongoing response.Whilst only a small proportion of patients have a CR at 1 year, most patients with a PR have CMR on PET. Almost all patients with CMR at 1 year have ongoing response to therapy thereafter. PET may have utility in predicting long-term benefit and help guide discontinuation of therapy.
Publisher Correction: Single-cell profiling of breast cancer T cells reveals a tissue-resident memory subset associated with improved prognosis
Authors: Peter Savas, Balaji Virassamy, Chengzhong Ye, Agus Salim, Christopher P. Mintoff, Franco Caramia, Roberto Salgado, David J. Byrne, Zhi L. Teo, Sathana Dushyanthen, Ann Byrne, Lironne Wein, Stephen J. Luen, Catherine Poliness, Sophie S. Nightingale, Anita S. Skandarajah, David E. Gyorki, Chantel M. Thornton, Paul A. Beavis, Stephen B. Fox, Phillip K. Darcy, Terence P. Speed, Laura K. Mackay, Paul J. Neeson, Sherene Loi
Journal: Nature Medicine (2018)
Physiological and clinical characteristics of patients with COPD admitted to an inpatient pulmonary rehabilitation program: A real-life study
Authors: Roberto Maestri, Claudio Bruschi, Claudio Fracchia, Gian Domenico Pinna, Francesco Fanfulla, Nicolino Ambrosino
Journal: Pulmonology (2018)

Patient selection criteria and experimental interventions of randomized controlled trials may not reflect how things work in practice. The aim of this study was to describe the characteristics of chronic obstructive pulmonary disease (COPD) patients undergoing an inpatient pulmonary rehabilitation program (PRP) and the correlates of success. Retrospective database review of 975 consecutive patients transferred from acute care hospitals after an acute exacerbation (group A: 14.6%) or admitted from home (group B: 75.4%), from 2010 to 2017. Patients were also divided according to the associated registered main diagnosis: COPD (group 1: 30.6%); COPD and respiratory failure (group 2: 51.7%); COPD and obstructive sleep apnea (group 3: 17.6%). Baseline correlates of post-PRP changes in six minute walking test (6MWT) were also evaluated. Global Initiative for Chronic Obstructive Lung Disease stages 3 and 4 were the most commonly represented in group 2 (p=0.0001). Comorbidity Index of all patients was 3.9±1.8. The overall in-hospital mortality rate was 1.3% (5.6% vs 0.6%, in groups A and B, respectively; p=0.0001). Hypertension, cardiac diseases and obesity were observed in 65.2, 52.2 and 29.6% of patients, respectively. Post-PRP 6MWT increased in all groups. Age, male gender, airway obstruction and baseline 6MWT were correlated with a post-PRP 30 meter increase in 6MWT. Confirming data of literature, this real-life study shows the characteristics of COPD patients undergoing an inpatient PRP with significant improvement in exercise capacity, independent of whether in stable state or after a recent exacerbation or of the associated main diagnosis.
Abstract 13474: Balloon Pulmonary Angioplasty Improves Clinical Status and Hemodynamics in Patients With Non-operable Chronic Thromboembolic Pulmonary Hypertension in Comparison to Pulmonary Endarterectomy in Operable Patients
Authors: Kazuya Miyagawa, Noriaki Emoto, Yu Taniguchi, Hiroto Kinutani, Kazuhiko Nakayama, Toshiro Shinke, Ken-ichi Hirata, Kenji Okada, Yutaka Okita
Journal: Circulation (2013)

Backgrounds: Chronic thromboembolic pulmonary hypertension (CTEPH) is caused by stenosis and obstruction of pulmonary artery with non-resolving organized thromboemboli, and the prognosis is poor wi...
Abstract 4050: Circumferential Mid-Ventricular Intramyocardial Injections of Alginate Hydrogel Improve Left Ventricular Function and Prevent Progressive Remodeling in Dogs With Chronic Heart Failure
Authors: Hani N Sabbah, Mengjun Wang, Alice Jiang, Itamar Ilsar, Michael S Sabbah, S Helgerson, R Peterson, N Tarazona, R Lee
Journal: Circulation (2009)

Background: Progressive LV enlargement and increased chamber sphericity are characteristics of heart failure (HF) and are associated with increased mortality and morbidity. We tested the hypothesis...
Lack of DNA Damage Response at Low Radiation Doses in Adult Stem Cells Contributes to Organ Dysfunction
Authors: Peter W. Nagle, Nynke A. Hosper, Lara Barazzuol, Anne L. Jellema, Mirjam Baanstra, Marc-Jan van Goethem, Sytze Brandenburg, Ulrich Giesen, Johannes A. Langendijk, Peter van Luijk, Rob P. Coppes
Journal: Clinical Cancer Research (2018)

Abstract Purpose: Radiotherapy for head and neck cancer may result in serious side effects, such as hyposalivation, impairing the patient's quality of life. Modern radiotherapy techniques attempt to reduce the dose to salivary glands, which, however, results in low-dose irradiation of the tissue stem cells. Here we assess the low-dose sensitivity of tissue stem cells and the consequences for tissue function. Experimental Design: Postirradiation rat salivary gland secretory function was determined after pilocarpine induction. Murine and patient-derived salivary gland and thyroid gland organoids were irradiated and clonogenic survival was assessed. The DNA damage response (DDR) was analyzed in organoids and modulated using different radiation modalities, chemical inhibition, and genetic modification. Results: Relative low-dose irradiation to the high-density stem cell region of rat salivary gland disproportionally impaired function. Hyper-radiosensitivity at doses &amp;lt;1 Gy, followed by relative radioresistance at doses ≥1 Gy, was observed in salivary gland and thyroid gland organoid cultures. DDR modulation resulted in diminished, or even abrogated, relative radioresistance. Furthermore, inhibition of the DDR protein ATM impaired DNA repair after 1 Gy, but not 0.25 Gy. Irradiation of patient-derived salivary gland organoid cells showed similar responses, whereas a single 1 Gy dose to salivary gland–derived stem cells resulted in greater survival than clinically relevant fractionated doses of 4 × 0.25 Gy. Conclusions: We show that murine and human glandular tissue stem cells exhibit a dose threshold in DDR activation, resulting in low-dose hyper-radiosensitivity, with clinical implications in radiotherapy treatment planning. Furthermore, our results from patient-derived organoids highlight the potential of organoids to study normal tissue responses to radiation.
Abstract 15042: Partial Nephrectomy Regulates Cardiac Tissue MicroRNA-29b-3p and Causes Cardiac Fibrosis Through a Na/K-ATPase-Src-NF-kappa B Mediated Pathway in Mice
Authors: Christopher A Drummond, Xiaoming Fan, Huilin Shi, Jeffrey X Xie, Steven T Haller, Chrsitopher J Cooper, Jiang Tian
Journal: Circulation (2016)

Introduction: Cardiac fibrosis is a common pathological process in different cardio-renal diseases. We have previously reported that activation of Na/K-ATPase signaling by its ligands, cardiotonic steroids (CTS), contributes to cardiac fibrosis in animal models with CKD. Our recent study revealed that Na/K-ATPase mediated regulation of Src kinase signaling regulates collagen synthesis in cardiac fibroblasts through decreasing expression of microRNA-29b-3p (miR-29b). Methods: To test whether the same mechanism mediates PNx-induced cardiac fibrosis in vivo, we performed the commonly used model of CKD, 5/6th partial nephrectomy (PNx) surgery on mice with a C57/BL6 background. Twelve weeks after PNx or sham surgery, these mice were injected with pNaKtide, a Src inhibiting peptide, at a dose of 25mg/kg intraperitoneally one time every other week before sacrifice was performed at the end of 16th week following surgery. Mice injected with similar volumes of saline were used as control. Results: The experimental ...
Abstract 19428: Exercise-Augmented Pulsatile Shear Stress Mediates Pparγ-scd1 Pathway to Promote Athero-Protective Metabolomic Profiles
Authors: Rongsong Li, Nelson Jen, Kyung I Baek, Curt Sigmund, James Tidball, Tzung Hsiai
Journal: Circulation (2017)

Hemodynamic shear stress imparts both biomechanical and metabolic effects to maintain vascular homeostasis. Pulsatile shear stress (PSS) developed in the straight portion of the vasculature is cons...
NT-proBNP–guided and conventional therapies did not differ for readmission or mortality in acute decompensated HF
Authors: Arunima Misra, Anita Deswal
Journal: Annals of Internal Medicine (2018)

Source Citation Stienen S, Salah K, Moons AH, et al. NT-proBNP (N-terminal pro-B-type natriuretic peptide)-guided therapy in acute decompensated heart failure: PRIMA II randomized controlled trial (Can NT-ProBNP-Guided Therapy During Hospital Admission for Acute Decompensated Heart Failure Reduce Mortality and Readmissions?). Circulation. 2018;137:1671-83. 29242350
Applications of Immunopharmacogenomics: Predicting, Preventing, and Understanding Immune-Mediated Adverse Drug Reactions
Authors: Jason H. Karnes, Matthew A. Miller, Katie D. White, Katherine C. Konvinse, Rebecca K. Pavlos, Alec J. Redwood, Jonathan G. Peter, Rannakoe Lehloenya, Simon A. Mallal, Elizabeth J. Phillips
Journal: The Annual Review of Pharmacology and Toxicology (2018)

Adverse drug reactions (ADRs) are a significant health care burden. Immune-mediated adverse drug reactions (IM-ADRs) are responsible for one-fifth of ADRs but contribute a disproportionately high amount of that burden due to their severity. Variation in human leukocyte antigen ( HLA) genes has emerged as a potential preprescription screening strategy for the prevention of previously unpredictable IM-ADRs. Immunopharmacogenomics combines the disciplines of immunogenomics and pharmacogenomics and focuses on the effects of immune-specific variation on drug disposition and IM-ADRs. In this review, we present the latest evidence for HLA associations with IM-ADRs, ongoing research into biological mechanisms of IM-ADRs, and the translation of clinical actionable biomarkers for IM-ADRs, with a focus on T cell-mediated ADRs.
Palatal Swelling in a Patient With Refractory Leukemia
Authors: Katherine France, Eric T. Stoopler, Takako I. Tanaka
Journal: JAMA Dermatology (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 Dermatology 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 Dermatology journal