tbuckley/cabot-search huggingface dataset:
Changes Over Time in the Differential Mortality Gap in Individuals With Mental Disorders
Authors: Oleguer Plana-Ripoll, Nanna Weye, Natalie C. Momen, Maria K. Christensen, Kim M. Iburg, Thomas Munk Laursen, John J. McGrath
Journal: JAMA Psychiatry (2020)

Changes Over Time in the Differential Mortality Gap in Individuals With Mental DisordersPeople with mental disorders have increased mortality rates and reduced life expectancies. 1,2The life-years lost (LYLs), which estimates life expectancy for people with a disorder compared with the general population, 1,3,4 have been estimated to be 10 and 7 years, respectively, for men and women with any mental disorder. 1,2For schizophrenia, LYLs related to suicide and unintentional deaths (ie, external causes) had fallen over a 20-year period, but these gains were offset by worsening LYLs related to deaths from general medical conditions (ie, natural causes). 5The aim of this Research Letter is to examine changes in mortality rate ratios (MRRs) and LYLs for both external and natural causes over 20 years for specific mental disorders.
A phase II study of early up-front red blood cell transfusion followed by maintenance epoetin-alpha subcutaneously support during chemotherapy
Authors: J. W. Nortier, A. Ogilvie
Journal: Journal of Clinical Oncology (2009)

e20719 Background: To determine in patients with cancer related anaemia (Hb&lt;11,3 g/d) starting with their chemotherapy the efficacy and safety of up-front red blood cell transfusion and subsequently maintenance epoetin-alpha (Epo) administration. The study target was the range of low-normal Hb levels of 11,3 to 12,9 g/dL aiming at improving tumor oxygenation. Methods: A multicenter, open label, single-arm phase II study. All eligible patients with metastatic solid cancers received around their first or second chemotherapy cycle a transfusion of 1–3 units of erythrocytes depending on their Hb level. This was followed by Epo subcutaneously weekly at an initial dose of 40,000 IU during the chemotherapy period. Epo was only administered when the Hb level was below the lower margin of the target Hb range. All patients started with pre-emptive oral iron suppletion. Primary objectives were: correction of anemia to the Hb level target range and safety. Secondary objectives were: Quality of Life, Length of Treatment Duration and Time to Treatment Failure. Safety included: blood pressure, thrombo-embolic events, adverse events and serious adverse event. Results: 18 Patients enrolled in this study from March 30, 2006 to November 11, 2008. An intention-to-treatment analysis was performed for the primary objectives in 16 patients (8 with breast-, 4 with colorectal-, 1 with ovarian- and 1 with pancreatic cancer) and reported here. Patients were during a median of 12 weeks (range 1 to 32 weeks) on study. Median Hb increased from 10,2 g/dL to 11,2 g/dL after transfusion and stayed at that level during the first 19 weeks of Epo administration; Hb levels were between 10,0 and 11,5 g/dL. In the following period until the final 32nd studyweek, Hb levels increased slightly, ranging from 10,3 to 11,8 g/dL. Two patients remained during the study in the Hb level target range. The safety of Epo was good. Grade 3/4 adverse events and serious adverse events that occurred were found to be all chemotherapy or progressive disease related. Conclusions: Although this up-front treatment increased Hb to stable levels during chemotherapy, the target Hb levels were not reached in most patients. This was presumably related to the lesser than projected yield of the red blood cell transfusion. [Table: see text]
After Heart Attack, Growth Factor Improves Scar Quality and Heart Function in Pig Study
Authors: Tracy Hampton
Journal: JAMA (2020)

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
How to improve care across boundaries
Authors: Charles Coughlan, Nishma Manek, Yasmin Razak, Robert E Klaber
Journal: BMJ (2020)

What you need to know• Integrated care aims to improve coordination and continuity of care for patients across organisational boundaries• There are many different approaches to improving care across boundaries• Improving care calls for effective and accountable leadership, agreement on a shared vision of improvement, and sustained patient involvement
Mortality and Hepatic Decompensation in Patients With Cirrhosis and Atrial Fibrillation Treated With Anticoagulation
Authors: Marina Serper, Ethan M. Weinberg, Jordana B. Cohen, Peter P. Reese, Tamar H. Taddei, David E. Kaplan
Journal: Hepatology (2020)

Background and Aims Outcomes with anticoagulation (AC) are understudied in advanced liver disease. We investigated effects of AC with warfarin and direct oral anticoagulants (DOACs) on all‐cause mortality and hepatic decompensation as well as ischemic stroke, major adverse cardiovascular events, splanchnic vein thrombosis, and bleeding in a cohort with cirrhosis and atrial fibrillation (AF). Approach and Results This was a retrospective, longitudinal study using national data of U.S. veterans with cirrhosis at 128 medical centers, including patients with cirrhosis with incident AF, from January 1, 2012 to December 31, 2017 followed through December 31, 2018. To assess the effects of AC on outcomes, we applied propensity score (PS) matching and marginal structural models (MSMs) to account for confounding by indication and time‐dependent confounding. The final cohort included 2,694 veterans with cirrhosis with AF (n = 1,694 and n = 704 in the warfarin and DOAC cohorts after PS matching, respectively) with a median of 4.6 years of follow‐up. All‐cause mortality was lower with warfarin versus no AC (PS matched: hazard ratio [HR], 0.65; 95% confidence interval [CI], 0.55‐0.76; MSM models: HR, 0.54; 95% CI, 0.40‐0.73) and DOACs versus no AC (PS matched: HR, 0.68; 95% CI, 0.50‐0.93; MSM models: HR, 0.50; 95% CI, 0.31‐0.81). In MSM models, warfarin (HR, 0.29; 95% CI, 0.09‐0.90) and DOACs (HR, 0.23; 95% CI, 0.07‐0.79) were associated with reduced ischemic stroke. In secondary analyses, bleeding was lower with DOACs compared to warfarin (HR, 0.49; 95% CI, 0.26‐0.94). Conclusions Warfarin and DOACs were associated with reduced all‐cause mortality. Warfarin was associated with more bleeding compared to no AC. DOACs had a lower incidence of bleeding compared to warfarin in exploratory analyses. Future studies should prospectively investigate these observed associations.
Clinical impact of combined epigenetic and molecular analysis of pediatric low-grade gliomas
Authors: Kohei Fukuoka, Yasin Mamatjan, Ruth Tatevossian, Michal Zapotocky, Scott Ryall, Ana Guerreiro Stucklin, Julie Bennett, Liana Figueiredo Nobre, Anthony Arnoldo, Betty Luu, Ji Wen, Kaicen Zhu, Alberto Leon, Dax Torti, Trevor J Pugh, Lili-Naz Hazrati, Normand Laperriere, James Drake, James T Rutka, Peter Dirks, Abhaya V Kulkarni, Michael D Taylor, Ute Bartels, Annie Huang, Gelareh Zadeh, Kenneth Aldape, Vijay Ramaswamy, Eric Bouffet, Matija Snuderl, David Ellison, Cynthia Hawkins, Uri Tabori
Journal: Neuro-Oncology (2020)

Abstract Background Both genetic and methylation analysis have been shown to provide insight into the diagnosis and prognosis of many brain tumors. However, the implication of methylation profiling and its interaction with genetic alterations in pediatric low-grade gliomas (PLGGs) are unclear. Methods We performed a comprehensive analysis of PLGG with long-term clinical follow-up. In total 152 PLGGs were analyzed from a range of pathological subtypes, including 40 gangliogliomas. Complete molecular analysis was compared with genome-wide methylation data and outcome in all patients. For further analysis of specific PLGG groups, including BRAF p.V600E mutant gliomas, we compiled an additional cohort of clinically and genetically defined tumors from 3 large centers. Results Unsupervised hierarchical clustering revealed 5 novel subgroups of PLGG. These were dominated by nonneoplastic factors such as tumor location and lymphocytic infiltration. Midline PLGG clustered together while deep hemispheric lesions differed from lesions in the periphery. Mutations were distributed throughout these location-driven clusters of PLGG. A novel methylation cluster suggesting high lymphocyte infiltration was confirmed pathologically and exhibited worse progression-free survival compared with PLGG harboring similar molecular alterations (P = 0.008; multivariate analysis: P = 0.035). Although the current methylation classifier revealed low confidence in 44% of cases and failed to add information in most PLGG, it was helpful in reclassifying rare cases. The addition of histopathological and molecular information to specific methylation subgroups such as pleomorphic xanthoastrocytoma–like tumors could stratify these tumors into low and high risk (P = 0.0014). Conclusion The PLGG methylome is affected by multiple nonneoplastic factors. Combined molecular and pathological analysis is key to provide additional information when methylation classification is used for PLGG in the clinical setting.
Blockade of the Neonatal Fc Receptor (FcRn) Represents an Effective Mechanism for the Removal of Pathogenic Autoantibodies in Primary Immune Thrombocytopenia
Authors: Alison Eddleston, Kevin Greenslade, Omar Qureshi, Shauna West, Paul Atherfold, Ali Amirkhosravi, Hina Desai, Mildred Rivera-Amaya, Bryan Smith, Anthony Shock
Journal: Blood (2017)
Inhibition of uric acid or IL‐1β ameliorates respiratory syncytial virus immunopathology and development of asthma
Authors: Charles F. Schuler, Carrie‐Anne Malinczak, Shannon K. K. Best, Susan B. Morris, Andrew J. Rasky, Catherine Ptaschinski, Nicholas W. Lukacs, Wendy Fonseca
Journal: Allergy (2020)

Abstract Background Respiratory syncytial virus (RSV) affects most infants early in life and is associated with increased asthma risk. The specific mechanism remains unknown. Objective To investigate the role of uric acid (UA) and IL‐1β in RSV immunopathology and asthma predisposition. Methods Tracheal aspirates from human infants with and without RSV were collected and analyzed for pro‐IL‐1β mRNA and protein to establish a correlation in human disease. Neonatal mouse models of RSV were employed, wherein mice infected at 6‐7 days of life were analyzed at 8 days postinfection, 5 weeks postinfection, or after a chronic cockroach allergen asthma model. A xanthine oxidase inhibitor or IL‐1 receptor antagonist was administered during RSV infection. Results Human tracheal aspirates from RSV‐infected infants showed elevated pro‐IL‐1β mRNA and protein. Inhibition of UA or IL‐1β during neonatal murine RSV infection decreased mucus production, reduced cellular infiltrates to the lung (especially ILC2s), and decreased type 2 immune responses. Inhibition of either UA or IL‐1β during RSV infection led to chronic reductions in pulmonary immune cell composition and reduced type 2 immune responses and reduced similar responses after challenge with cockroach antigen. Conclusions Inhibiting UA and IL‐1β during RSV infection ameliorates RSV immunopathology, reduces the consequences of allergen‐induced asthma, and presents new therapeutic targets to reduce early‐life viral‐induced asthma development.
High rate of profound clonal and renal responses with daratumumab treatment in heavily pre‐treated patients with <scp>light chain (AL)</scp> amyloidosis and high bone marrow plasma cell infiltrate
Authors: Paolo Milani, Francesca Fazio, Marco Basset, Tamara Berno, Alessandra Larocca, Andrea Foli, Marcello Riva, Francesca Benigna, Stefania Oliva, Mario Nuvolone, Lara Rodigari, Maria Teresa Petrucci, Giampaolo Merlini, Giovanni Palladini
Journal: American Journal of Hematology (2020)

Daratumumab demonstrated activity in the treatment of AL amyloidosis in two recently concluded phase II clinical trials in relapsed and refractory patients. Its role in upfront therapy is under evaluation in a phase III study. In this report we evaluated the safety and efficacy of 28-day cycles of daratumumab (single agent or combined with bortezomib or lenalidomide) in 72 previously treated patients with multiple myeloma and AL amyloidosis. Fifty (69%) were refractory to the last line of therapy. After eight infusions of daratumumab, 59 patients (82%) achieved a hematologic response, with 12 (16%) complete responses (CRs) and 30 (42%) very good partial responses (VGPRs). After 16 infusions, the quality of response improved with 22 patients (30%) achieving CR and 21 (29%) attaining VGPR. Cardiac response was observed in 11 of 37 evaluable patients (29%) and renal response in 23 of 38 patients (60%). Daratumumab is highly effective in heavily pretreated patients with relapsed/refractory AL amyloidosis and high bone marrow plasma cell burden. Renal responses, which are usually rare in this setting, were frequently observed.
Endothelial function in cardiovascular medicine: a consensus paper of the European Society of Cardiology Working Groups on Atherosclerosis and Vascular Biology, Aorta and Peripheral Vascular Diseases, Coronary Pathophysiology and Microcirculation, and Thrombosis
Authors: Yvonne Alexander, Elena Osto, Arno Schmidt-Trucksäss, Michael Shechter, Danijela Trifunovic, Dirk J Duncker, Victor Aboyans, Magnus Bäck, Lina Badimon, Francesco Cosentino, Marco De Carlo, Maria Dorobantu, David G Harrison, Tomasz J Guzik, Imo Hoefer, Paul D Morris, Giuseppe D Norata, Rosa Suades, Stefano Taddei, Gemma Vilahur, Johannes Waltenberger, Christian Weber, Fiona Wilkinson, Marie-Luce Bochaton-Piallat, Paul C Evans
Journal: Cardiovascular Research (2020)

Abstract Endothelial cells (ECs) are sentinels of cardiovascular health. Their function is reduced by the presence of cardiovascular risk factors, and is regained once pathological stimuli are removed. In this European Society for Cardiology Position Paper, we describe endothelial dysfunction as a spectrum of phenotypic states and advocate further studies to determine the role of EC subtypes in cardiovascular disease. We conclude that there is no single ideal method for measurement of endothelial function. Techniques to measure coronary epicardial and micro-vascular function are well established but they are invasive, time-consuming, and expensive. Flow-mediated dilatation (FMD) of the brachial arteries provides a non-invasive alternative but is technically challenging and requires extensive training and standardization. We, therefore, propose that a consensus methodology for FMD is universally adopted to minimize technical variation between studies, and that reference FMD values are established for different populations of healthy individuals and patient groups. Newer techniques to measure endothelial function that are relatively easy to perform, such as finger plethysmography and the retinal flicker test, have the potential for increased clinical use provided a consensus is achieved on the measurement protocol used. We recommend further clinical studies to establish reference values for these techniques and to assess their ability to improve cardiovascular risk stratification. We advocate future studies to determine whether integration of endothelial function measurements with patient-specific epigenetic data and other biomarkers can enhance the stratification of patients for differential diagnosis, disease progression, and responses to therapy.
Multidisciplinary research priorities for the COVID-19 pandemic: a call for action for mental health science
Authors: Emily A Holmes, Rory C O'Connor, V Hugh Perry, Irene Tracey, Simon Wessely, Louise Arseneault, Clive Ballard, Helen Christensen, Roxane Cohen Silver, Ian Everall, Tamsin Ford, Ann John, Thomas Kabir, Kate King, Ira Madan, Susan Michie, Andrew K Przybylski, Roz Shafran, Angela Sweeney, Carol M Worthman, Lucy Yardley, Katherine Cowan, Claire Cope, Matthew Hotopf, Ed Bullmore
Journal: The Lancet Psychiatry (2020)
8O_PR MUCIN-1 Protein and Mrna Expression in Breast Cancer Patients Treated with Neoadjuvant Chemotherapy
Authors: B.V. Sinn, G. von Minckwitz, C. Denkert, H. Eidtmann, S. Darb-Esfahani, A. Belau, R. Kronenwett, H. Holzhausen, K. Mehta, S. Loibl
Journal: Annals of Oncology (2012)
Prognostic and predictive value of the Immunoscore in stage III colon cancer patients treated with oxaliplatin in the prospective IDEA France PRODIGE-GERCOR cohort study
Authors: F. Pagès, T. André, J. Taieb, D. Vernerey, J. Henriques, C. Borg, F. Marliot, R. Ben Jannet, C. Louvet, L. Mineur, J. Bennouna, J. Desrame, R. Faroux, A. Kirilovsky, A. Duval, P. Laurent-Puig, M. Svrcek, F. Hermitte, A. Catteau, J. Galon, J.-F. Emile
Journal: Annals of Oncology (2020)
Comparison of Drugs Used for Adjuvant and Metastatic Therapy of Colon, Breast, and Non–Small Cell Lung Cancers
Authors: Scott Parsons, Edward B. Maldonado, Vinay Prasad
Journal: JAMA Network Open (2020)

<h3>Importance</h3> Drugs are used in the adjuvant, metastatic, or both settings in cancer, but the rate, direction, and speed with which drugs are tested and indicated in each setting are unknown. <h3>Objective</h3> To identify the number of unique agents that are currently category 1 or 2A per National Comprehensive Cancer Network (NCCN) guidelines in metastatic and adjuvant settings of non–small cell lung cancer (NSCLC), breast cancer, and colon cancer, as well as the mean delay between use in these 2 settings and the quality of supporting evidence. <h3>Design, Setting, and Participants</h3> This cross-sectional study used NCCN treatment guidelines current as of May 15, 2019, and the clinical trials cited either by these guidelines or within corresponding drug labels. Trials published between 1970 and 2019 were evaluated. The analysis included published clinical trials of systemic therapy options deemed by the NCCN as category 1 or 2A. Participants included patients with early or metastatic NSCLC, breast cancer, or colon cancer who were included in clinical trials evaluating current NCCN-recommended systemic therapy options. Data analysis was performed from March 2019 to May 2019. <h3>Exposures</h3> Systemic therapy regimens used as either adjuvant treatment or as therapy for metastatic disease in the 3 cancer types. <h3>Main Outcomes and Measures</h3> Number of agents recommended for use in adjuvant and metastatic settings of NSCLC, colon cancer, and breast cancer, the mean delay between use in these 2 settings, and the percentage of agents supported by trials with substantial improvement in either progression-free survival (disease-free survival for adjuvant agents) or overall survival. <h3>Results</h3> This study identified 69 agents recommended for use in metastatic disease compared with 25 agents recommended for adjuvant use. For agents used in both settings, the mean (SD) delay between use in metastatic disease and as adjuvant therapy was 10.0 (7.5) years. On the basis of trials with positive outcomes, 39 of 69 agents (56.5%) were approved or recommended in the metastatic setting, compared with 23 of 25 agents (92.0%) approved for use as adjuvant therapy. <h3>Conclusions and Relevance</h3> There is a substantial difference in the number of agents available for use, as well as the timing of supporting evidence, in the metastatic and adjuvant settings for NSCLC, breast cancer, and colon cancer. Given the potential benefit of adjuvant therapy in these cancer types, further investigation into additional adjuvant systemic therapy options is warranted.
Enterovirus A71 Oncolysis of Malignant Gliomas
Authors: Xiaowei Zhang, Hanzhong Wang, Yuhan Sun, Mi Qi, Wei Li, Zhiping Zhang, Xian-En Zhang, Zongqiang Cui
Journal: Molecular Therapy (2020)

Malignant gliomas, the most lethal type of primary brain tumor, continue to be a major therapeutic challenge. Here, we found that enterovirus A71 (EV-A71) can be developed as a novel oncolytic agent against malignant gliomas. EV-A71 preferentially infected and killed malignant glioma cells relative to normal glial cells. The virus receptor human scavenger receptor class B, member 2 (SCARB2), and phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1)-mediated cell death were involved in EV-A71-induced oncolysis. In mice with implanted subcutaneous gliomas, intraneoplastic inoculation of EV-A71 caused significant tumor growth inhibition. Furthermore, in mice bearing intracranial orthotopic gliomas, intraneoplastic inoculation of EV-A71 substantially prolonged survival. By insertion of brain-specific microRNA-124 (miR124) response elements into the viral genome, we improved the tumor specificity of EV-A71 oncolytic therapy by reducing its neurotoxicity while maintaining its replication potential and oncolytic capacity in gliomas. Our study reveals that EV-A71 is a potent oncolytic agent against malignant gliomas and may have a role in treating this tumor in the clinical setting.
A Non–D2-Receptor-Binding Drug for the Treatment of Schizophrenia
Authors: Kenneth S. Koblan, Justine Kent, Seth C. Hopkins, John H. Krystal, Hailong Cheng, Robert Goldman, Antony Loebel
Journal: New England Journal of Medicine (2020)

An oral compound, SEP-363856, that does not act on dopamine D2 receptors but has agonist activity at trace amine–associated receptor 1 (TAAR1) and 5-hydroxytryptamine type 1A (5-HT1A) receptors, may represent a new class of psychotropic agent for the treatment of psychosis in schizophrenia.