tbuckley/cabot-search huggingface dataset:
Azedra (iobenguane I 131) in patients with malignant, recurrent and/or unresectable pheochromocytoma or paraganglioma (PPGL): Updated efficacy and safety results from a multi-center, open-label, pivotal phase 2 study.
Authors: Daniel Pryma, Bennett Chin, Richard Noto, Joseph Dillon, Lilja Solnes, Theresa White, Nancy Stambler, Tess Lin, Vincent A. DiPippo, Jessica Donato Jensen, Syed Mahmood, Vivien Wong, Camilo Jimenez
Journal: Journal of Clinical Oncology (2018)

4005 Background: AZEDRA, a high-specific-activity iodine-131 meta-iodobenzylguanidine (HSA I-131 MIBG), has been developed for the treatment of iobenguane-avid malignant (metastatic) or recurrent or unresectable pheochromocytoma or paraganglioma (PPGL). Methods: MIBG-avid PPGL patients (pts) ineligible for curative surgery or chemotherapy, and on a stable antihypertensive regimen for tumor-related hypertension were enrolled. Pts received a dosimetric dose (111-222 MBq) followed by up to 2 therapeutic doses (each at 296 MBq/kg to a maximum of 18.5 GBq) approximately 3 months (mths) apart. Pts were followed for 12-mths (efficacy period) and an additional 4 years for long-term follow-up. The primary endpoint was defined as proportion of pts with at least 50% reduction, including discontinuation, of all antihypertensive medications lasting ≥6 mths beginning during the efficacy period. Secondary endpoints included objective tumor response (OTR) by RECIST and overall survival (OS). Results: Of 81 pts enrolled, 74 pts received a dosimetric dose of AZEDRA. 68 pts received 1 therapeutic dose (full analysis; FA) and 50 received two (per protocol; PP). At study entry, 52% (35/68) had prior surgery and systemic therapy (I-131 MIBG and/or chemotherapy) for PPGL. 50% (32/64) of evaluable pts had lung and/or liver metastases at baseline. The primary endpoint was met by 25% (95% CI 16%-37%) of FA and 32% (95% CI 21%-46%) of PP pts, achieving pre-specified success criteria. For OTR, 23% and 30% of FA and PP populations achieved partial response (PR). The 12-month OS was 91% in FA pts. Median OS was 36.7 mths (95% CI 29.9, 49.1), and median survival appeared similar in pts with and without lung/liver metastasis at baseline (42.6 and 41.1 mths, respectively). The most common (≥50%) treatment-emergent adverse events were myelosuppression, nausea, and fatigue. No acute drug-related hypertensive events were observed. Conclusions: Updated results from this pivotal phase 2 study suggest that AZEDRA is an efficacious and safe treatment for an ultra-orphan disease with no approved therapies in the United States. Clinical trial information: NCT00874614.
Abstract 16188: A Comparative Analysis of Cost and Cost-effectiveness of Rhythm vs. Rate Control Strategies in the Treatment of Atrial Fibrillation Patients
Authors: Edward Ewen, Paulo Carita, Laurent Eckert, Alice Guirard, Christine Taniou, Claudine T Jurkovitz, Paul Kolm, William S Weintraub
Journal: Circulation (2010)

Background: Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia, with a prevalence of 5–6% in people aged 65 years rising to 10% in those aged 80 years and older. Currently the...
Diagnostic and therapeutic approaches of mixed cryoglobulinemia in PITER (Piattaforma Italiana per lo studio della Terapia delle Epatiti viRali) cohort
Authors: L.A. Kondili, M. Monti, G.B. Gaeta, V. Rizzo, G. Borgia, E. Zappulo, L. Chemello, L. Cavalletto, M. Vinci, S. Palladini, P. Andreone, M. Margotti, M. Puoti, E. Danieli, M. Persico, M. Masarone, S. Madonia, M.R. Brunetto, B. Coco, D. Ieluzzi, N. Passigato, M.G. Rumi, V. Sciola, M. Massari, R. Corsini, G. Mazzella, G. Lazzarini, G. Taliani, E. Biliotti, M. Andreoni, C. Cerva, A. Alberti, M. Gonzo, L. Chessa, M.C. Pasetto, A. Federico, M. Dallio, M.G. Quaranta, L.E. Weimer, S. Vella, A.L. Zignego
Journal: Journal of Hepatology (2017)
Integrated care for people with long-term mental and physical health conditions in low-income and middle-income countries
Authors: Graham Thornicroft, Shalini Ahuja, Sarah Barber, Daniel Chisholm, Pamela Y Collins, Sumaiyah Docrat, Lara Fairall, Heidi Lempp, Unaiza Niaz, Vicky Ngo, Vikram Patel, Inge Petersen, Martin Prince, Maya Semrau, Jürgen Unützer, Huang Yueqin, Shuo Zhang
Journal: The Lancet Psychiatry (2018)
Longer waiting times in Northern Ireland than in rest of UK deemed “unacceptable”
Authors: Ingrid Torjesen
Journal: BMJ (2018)

Over 100 000 patients in Northern Ireland have waited more than a year for hospital treatment, official figures show.

The latest waiting time statistics from Northern Ireland’s Department of Health show that more than 18 000 patients have waited more than a year for inpatient treatment and that almost 88 600 have waited more than a year for an outpatient appointment.1

The Royal College of Surgeons said that the proportion of long waits was substantially worse than in the rest of the UK and called …
Increased Risk of Rehospitalization for Acute Diabetes Complications and Suicide Attempts in Patients With Type 1 Diabetes and Comorbid Schizophrenia
Authors: Karine Goueslard, Jean-Michel Petit, Jonathan Cottenet, Jean-Christophe Chauvet-Gelinier, Fabrice Jollant, Catherine Quantin
Journal: Diabetes Care (2018)

The aim of this large retrospective cohort study was to estimate the supplementary morbidity and mortality risks conferred by the co-occurrence of schizophrenia among young people with type 1 diabetes.This nationwide population-based study included individuals aged 15-35 years hospitalized in France for type 1 diabetes from 2009 to 2012 with or without schizophrenia. For assessment of the occurrence of rehospitalization for acute diabetes complications, suicide attempts, and hospital mortality, multivariate logistic regressions and survival analysis adjusted for age, sex, and Charlson comorbidity index scores were performed. The association between hospitalization for suicide attempts and acute diabetes complications was further explored in a survival analysis, with the exposure of acute diabetes complications as a time-dependent covariate.Among 45,655 individuals aged 15-35 years who were hospitalized for type 1 diabetes, 341 (0.75%) had a previous or contemporary hospitalization for schizophrenia. Within 3 years of follow-up, schizophrenia was associated with increased risks of rehospitalization for hypoglycemia (adjusted odds ratio 3.21 [95% CI 1.99-5.20]), hyperglycemia (7.01 [3.53-13.90]), ketoacidosis (2.01 [1.49-2.70]), and coma (3.17 [1.90-5.27]); hospitalization for suicide attempts (12.15 [8.49-17.38]); and hospital mortality (2.83 [1.50-5.36]). Hospitalization for a suicide attempt was associated with an increased risk of hospitalization for acute diabetes complications independently from schizophrenia (hazard ratio 3.46 [95% CI 2.74-4.38]).Patients suffering from the combination of type 1 diabetes and schizophrenia are at increased risk of hospitalization for acute diabetes complications as well as suicide and hospital mortality. These individuals may require specific care programs and close monitoring of mental, somatic, and social health.
Abstract 19355: BET Bromodomain Proteins Are Critical Regulators of Molecular Reprogramming in Genetic Dilated Cardiomyopathy
Authors: Michael A Burke, Hiroko Wakimoto, Joshua M Gorham, Steven R DePalma, David A Conner, Zhe Jiao, Jun Qi, Jonathan G Seidman, James E Bradner, Jonathan D Brown, Saptarsi M Haldar, Christine E Seidman
Journal: Circulation (2017)

Pathologic gene expression is a hallmark of DCM. Mice carrying a human DCM mutation in phospholamban (PLNR9C) develop fibrosis, DCM and premature death. Temporal RNAseq and pathway analysis in PLNR...
Effect of Dextroamphetamine on Poststroke Motor Recovery
Authors: Larry B. Goldstein, Laura Lennihan, Meheroz J. Rabadi, David C. Good, Michael J. Reding, Alexander W. Dromerick, Gregory P. Samsa, John Pura
Journal: JAMA Neurology (2018)

<h3>Importance</h3> Data from animal models show that the administration of dextroamphetamine combined with task-relevant training facilitates recovery after focal brain injury. Results of clinical trials in patients with stroke have been inconsistent. <h3>Objectives</h3> To collect data important for future studies evaluating the effect of dextroamphetamine combined with physiotherapy for improving poststroke motor recovery and to test the efficacy of the approach. <h3>Design, Setting, Participants</h3> This pilot, double-blind, block-randomized clinical trial included patients with cortical or subcortical ischemic stroke and moderate or severe motor deficits from 5 rehabilitation hospitals or units. Participants were screened and enrolled from March 2001 through March 2003. The primary outcome was assessed 3 months after stroke. Study analysis was completed December 31, 2015. A total of 1665 potential participants were screened and 64 were randomized. Participants had to begin treatment 10 to 30 days after ischemic stroke. Data analysis was based on intention to treat. <h3>Interventions</h3> Participants were allocated to a regimen of 10 mg of dextroamphetamine (n = 32) or placebo (n = 32) combined with a 1-hour physical therapy session beginning 1 hour after drug or placebo administration every 4 days for 6 sessions in addition to standard rehabilitation. <h3>Main Outcomes and Measures</h3> The primary outcome was the difference between groups in change in Fugl-Meyer motor scores from baseline to 3 months after stroke (intention to treat with dextroamphetamine). Secondary exploratory measures included the National Institutes of Health Stroke Scale, Canadian Neurological Scale, Action Research Arm Test, modified Rankin Scale score, Functional Independence Measure, Ambulation Speed and Distance, Mini-Mental State Examination, Beck Depression Inventory, and Stroke Impact Scale. <h3>Results</h3> Among the 64 patients randomized to dextroamphetamine vs placebo (55% men; median age, 66 years; age range, 27-91 years), no overall treatment-associated difference in the mean (SEM) change in Fugl-Meyer motor scores from baseline to 3 months after stroke was noted (−18.65 [2.27] points with dextroamphetamine vs −20.83 [2.94] points with placebo;<i>P</i> = .58). No overall treatment-associated differences in any of the study's secondary measures and no differences in subgroups based on stroke location or baseline severity were found. No adverse events were attributed to study treatments. <h3>Conclusions and Relevance</h3> Treatment with dextroamphetamine combined with physical therapy did not improve recovery of motor function compared with placebo combined with physical therapy as assessed 3 months after hemispheric ischemic stroke. The studied treatment regimen was safe. <h3>Trial Registration</h3> ClinicalTrials.gov identifier:NCT01905371
Central Nervous System Myelomatosis Delineated by High-Resolution Brain Images From Fully Digital 18F-FDG PET
Authors: Achraf Bahloul, Mathieu Perrin, Samir Amlal, Pierre-Yves Marie, Antoine Verger
Journal: Clinical Nuclear Medicine (2018)

Abstract Central nervous system myelomatosis is uncommon and is associated with a particularly poor prognosis. PET images, from a 53-year-old man referred to a fully digital 18 F-FDG PET for relapsed multiple myeloma, revealed high 18 F-FDG uptakes located in the cortex and sulci of the right central area and within the meningeal envelopes of the cerebellum, the trigeminal nerves, and on the spinal canal. These particular uptakes gave evidence of a central nervous system myelomatosis subsequently confirmed by plasma cells documented in cerebrospinal fluid. Such interesting images could be obtained owing to the potential of high-resolution images provided by fully digital 18 F-FDG PET.
Altered mitochondrial function in insulin-deficient and insulin-resistant states
Authors: Gregory N. Ruegsegger, Ana L. Creo, Tiffany M. Cortes, Surendra Dasari, K. Sreekumaran Nair
Journal: Journal of Clinical Investigation (2018)

Diabetes profoundly alters fuel metabolism; both insulin deficiency and insulin resistance are characterized by inefficient mitochondrial coupling and excessive production of reactive oxygen species (ROS) despite their association with normal to high oxygen consumption. Altered mitochondrial function in diabetes can be traced to insulin's pivotal role in maintaining mitochondrial proteome abundance and quality by enhancing mitochondrial biogenesis and preventing proteome damage and degradation, respectively. Although insulin enhances gene transcription, it also induces decreases in amino acids. Thus, if amino acid depletion is not corrected, increased transcription will not result in enhanced translation of transcripts to proteins. Mitochondrial biology varies among tissues, and although most studies in humans are performed in skeletal muscle, abnormalities have been reported in multiple organs in preclinical models of diabetes. Nutrient excess, especially fat excess, alters mitochondrial physiology by driving excess ROS emission that impairs insulin action. Excessive ROS irreversibly damages DNA and proteome with adverse effects on cellular functions. In insulin-resistant people, aerobic exercise stimulates both mitochondrial biogenesis and efficiency concurrent with enhancement of insulin action. This Review discusses the association between both insulin-deficient and insulin-resistant diabetes and alterations in mitochondrial proteome homeostasis and function that adversely affect cellular functions, likely contributing to many diabetic complications.
Diagnostic heuristics in dermatology, part 2: metacognition and other fixes
Authors: E.J. Lowenstein, R. Sidlow
Journal: British Journal of Dermatology (2018)

Diagnostic errors are the most common, costly and dangerous of medical mistakes. In part 1 of this series, we described how general and dermatology‐specific cognitive and perceptual biases underlie most of our correct diagnoses, as well as being a source of diagnostic medical errors. In this second part of the series, we describe some tactics to combat diagnostic error. Metacognition, or thinking about how we think, is the central approach advocated to avoid errors of 'uncritical' diagnostic thinking. Current individual and medical cultural attitudes need to be modified in order to incorporate improvements in diagnosis. Algorithms, artificial intelligence and system changes are being developed to address error and improve diagnostic accuracy.
Comparing Spending on Medical Care in the United States and Other Countries
Authors: Louis J. Goodman, Joseph Valenti
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 Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Oncologic patients attitudes and participation in clinical trials.
Authors: Nethanel Asher, Ido Wolf, Sharon Pelles, Ravit Geva
Journal: Journal of Clinical Oncology (2017)

e18029 Background: Clinical trials are an essential part of the oncological care. However, literature indicates low accrual of only 2-4% of the oncologic population. One of the leading known barriers is the patient's hesitant attitude toward participation. This study aimed to evaluate the patients' population treated in the Tel Aviv Sourasky Medical Center (TASMC) oncology division and their understanding of clinical research in order to improve local recruitment strategies. Methods: An observatory, questionnaire based research was conducted. Patients receiving active oncology treatment in the TASMC oncologic day care unit were asked to complete an anonymous questionnaire, which was comprised of two main parts: the first evaluate demographic information and past experience in clinical research. The second investigated basic knowledge true/false test regarding clinical trials. The questionnaire was validated by both external and internal validity tests (α-Cronbach validity test) and was approved by the local ethics committee. Results: Two hundred patients completed the questionnaires. Median age was 60. 64% would consider participating in a clinical study. 23% (N = 46) had past experience in research, and compared to those with no experience they were found to have higher academic education (67.4% vs 36.9%, p &lt; 0.0001), be more secular (76.1% vs 58.3, p = 0.037) and to have a better understanding of medical research (84.4%, vs 36.5%, p &lt; 0.0001). They were also more inclined to participate in a future research (73% vs 44.9%, p = 0.01). Of those who would decline to participate and had failed the knowledge test (score less than 60%), the most frequent concern was related to the placebo arm (p = 0.055), ability to reject consent, and to trust issues with the treating oncologist. Conclusions: Despite a noteworthy readiness to enroll in clinical trials among the TASMC oncologic population, there were found significant knowledge and basic understanding gaps regarding clinical trials. Further efforts are needed to better understand specific accrual barriers and to develop an adapted information system.
Multifocal Primary Prostate Cancer Exhibits High Degree of Genomic Heterogeneity
Authors: Marthe Løvf, Sen Zhao, Ulrika Axcrona, Bjarne Johannessen, Anne Cathrine Bakken, Kristina Totland Carm, Andreas M. Hoff, Ola Myklebost, Leonardo A. Meza-Zepeda, A. Kathrine Lie, Karol Axcrona, Ragnhild A. Lothe, Rolf I. Skotheim
Journal: European Urology (2018)
A Five-MicroRNA Signature Predicts Survival and Disease Control of Patients with Head and Neck Cancer Negative for HPV Infection
Authors: Julia Hess, Kristian Unger, Cornelius Maihoefer, Lars Schüttrumpf, Ludmila Wintergerst, Theresa Heider, Peter Weber, Sebastian Marschner, Herbert Braselmann, Daniel Samaga, Sebastian Kuger, Ulrike Pflugradt, Philipp Baumeister, Axel Walch, Christine Woischke, Thomas Kirchner, Martin Werner, Kristin Werner, Michael Baumann, Volker Budach, Stephanie E. Combs, Jürgen Debus, Anca-Ligia Grosu, Mechthild Krause, Annett Linge, Claus Rödel, Martin Stuschke, Daniel Zips, Horst Zitzelsberger, Ute Ganswindt, Michael Henke, Claus Belka
Journal: Clinical Cancer Research (2018)

Abstract Purpose: Human papillomavirus (HPV)–negative head and neck squamous cell carcinoma (HNSCC) is associated with unfavorable prognosis, while independent prognostic markers remain to be defined. Experimental Design: We retrospectively performed miRNA expression profiling. Patients were operated for locally advanced HPV-negative HNSCC and had received radiochemotherapy in eight different hospitals (DKTK-ROG; n = 85). Selection fulfilled comparable demographic, treatment, and follow-up characteristics. Findings were validated in an independent single-center patient sample (LMU-KKG; n = 77). A prognostic miRNA signature was developed for freedom from recurrence and tested for other endpoints. Recursive-partitioning analysis was performed on the miRNA signature, tumor and nodal stage, and extracapsular nodal spread. Technical validation used qRT-PCR. An miRNA–mRNA target network was generated and analyzed. Results: For DKTK-ROG and LMU-KKG patients, the median follow-up was 5.1 and 5.3 years, and the 5-year freedom from recurrence rate was 63.5% and 75.3%, respectively. A five-miRNA signature (hsa-let-7g-3p, hsa-miR-6508-5p, hsa-miR-210-5p, hsa-miR-4306, and hsa-miR-7161-3p) predicted freedom from recurrence in DKTK-ROG [hazard ratio (HR) 4.42; 95% confidence interval (CI), 1.98−9.88, P &amp;lt; 0.001], which was confirmed in LMU-KKG (HR 4.24; 95% CI, 1.40−12.81, P = 0.005). The signature also predicted overall survival (HR 3.03; 95% CI, 1.50−6.12, P = 0.001), recurrence-free survival (HR 3.16; 95% CI, 1.65−6.04, P &amp;lt; 0.001), and disease-specific survival (HR 5.12; 95% CI, 1.88−13.92, P &amp;lt; 0.001), all confirmed in LMU-KKG data. Adjustment for relevant covariates maintained the miRNA signature predicting all endpoints. Recursive-partitioning analysis of both samples combined classified patients into low (n = 17), low-intermediate (n = 80), high-intermediate (n = 48), or high risk (n = 17) for recurrence (P &amp;lt; 0.001). Conclusions: The five-miRNA signature is a strong and independent prognostic factor for disease recurrence and survival of patients with HPV-negative HNSCC. See related commentary by Clump et al., p. 1441
Abstract 11727: Anti-Inflammatory Treatment With Colchicine in Acute Myocardial Infarction: A Randomized Study
Authors: Georgios Giannopoulos, Spyridon Deftereos, Christos Angelidis, Nikolaos Alexopoulos, John Lekakis, Christodoulos Stefanadis
Journal: Circulation (2015)

Background: Inflammatory processes have been identified as key mediators of the deleterious effects of ischemia/reperfusion in ST-elevation myocardial infarction (STEMI). Colchicine is a substance with potent anti-inflammatory properties, suitable for safe use in patients with cardiovascular disease. The purpose of this study was to test the hypothesis that a short course of colchicine treatment could lead to reduced infarct size. Methods: Patients presenting with STEMI 12 hours or less from pain onset (treated with primary percutaneous coronary intervention) were randomized to colchicine or placebo for 9 days. The primary outcome parameter was the area under the curve of creatine kinase-MB (CK-MB) concentration. A subset of patients underwent cardiac magnetic resonance imaging (MRI) with late gadolinium enhancement (LGE) 6-9 days after the index STEMI. Results: 151 patients were included (60 in the MRI substudy). The area under the CK-MB curve was 3144 [IQR 1754-6940] ng.h.ml -1 in the colchicine group as compared to 6184 [IQR 4456-6980] ng.h.ml -1 in controls (p&lt;0.001). Indexed MRI-LGE-defined infarct size was 18.3 [IQR 7.6-29.9] ml/1.73 m 2 in the colchicine group versus 23.2 [18.5-33.4] ml/1.73 m 2 in controls (p=0.019). The relative infarct size (as a proportion to left ventricular myocardial volume) was 13.0 [IQR 8.0-25.3]% and 19.8 [IQR 13.7-29.8]%, respectively (p=0.034). Maximal neutrophil count was 7543 [IQR 6549-10118] /μL in the colchicine group versus 8922 [IQR 7880-10307] /μL in controls (p=0.008). It was significantly associated with relative and absolute MRI-LGE infarct size, as well as with the area under the CK-MB curve (p=0.001). Conclusion: These results suggest a potential benefit of colchicine in STEMI, but further clinical trials are necessary to draw secure conclusions, especially considering the fact that the present study was not powered to assess clinical endpoints.