tbuckley/cabot-search huggingface dataset:
Assessment of Expected Out-of-Pocket Spending for Rheumatoid Arthritis Biologics Among Patients Enrolled in Medicare Part D, 2010-2019
Authors: Alexandra Erath, Stacie B. Dusetzina
Journal: JAMA Network Open (2020)

<h3>Importance</h3> The closure of the Medicare Part D coverage gap from 2010 to 2019 was intended to help decrease out-of-pocket costs for beneficiaries, especially those taking high-cost drugs. However, yearly increases in list prices and the introduction of newer and more expensive drugs may have limited savings for beneficiaries. <h3>Objective</h3> To assess the association of closure in the Medicare Part D coverage gap with projected annual out-of-pocket costs from 2010 through 2019 for rheumatoid arthritis (RA) biologics. <h3>Design, Setting, and Participants</h3> This cross-sectional analysis used data from the Medicare Formulary and Pricing Files for the first quarter (January 1 to March 31) in each calendar year from 2010 to 2019 for 17 RA biologic drug and strength combinations. <h3>Exposures</h3> Medicare Part D plan design and drug price by year. <h3>Main Outcomes and Measures</h3> Expected annual out-of-pocket costs for 1 year of treatment. <h3>Results</h3> Among the 17 drug and strength combinations assessed, list prices increased each year for every product, with a mean increase of 160% for the 6 drugs available during the entire study period. For the 6 products available during the entire study period, projected mean (SD) annual out-of-pocket costs were 34% (2%) lower in 2011 than in 2010 ($6108 in 2010 to $4026 in 2011) but only 21% (8%) lower in 2019 ($4801) because of yearly increases in list price. All 4 products with higher out-of-pocket costs in 2019 than in the first year available entered the market between 2011 and 2015. For all products studied, the percentage of money spent in the catastrophic phase increased each year and was a mean (SD) of 22% (14%) higher in 2019 than in 2010 or the year first available. <h3>Conclusions and Relevance</h3> Although beneficiaries experienced large reductions in out-of-pocket spending from 2010 to 2011, more than half of those savings were lost by 2019 because of annual increases in list prices, even as the coverage gap continued to close in subsequent years.
Evaluation and Management of Premature Ventricular Complexes
Authors: Gregory M. Marcus
Journal: Circulation (2020)

Premature ventricular complexes (PVCs) are extremely common, found in the majority of individuals undergoing long-term ambulatory monitoring. Increasing age, a taller height, a higher blood pressure, a history of heart disease, performance of less physical activity, and smoking each predict a greater PVC frequency. Although the fundamental causes of PVCs remain largely unknown, potential mechanisms for any given PVC include triggered activity, automaticity, and reentry. PVCs are commonly asymptomatic but can also result in palpitations, dyspnea, presyncope, and fatigue. The history, physical examination, and 12-lead ECG are each critical to the diagnosis and evaluation of a PVC. An echocardiogram is indicated in the presence of symptoms or particularly frequent PVCs, and cardiac magnetic resonance imaging is helpful when the evaluation suggests the presence of associated structural heart disease. Ambulatory monitoring is required to assess PVC frequency. The prognosis of those with PVCs is variable, with ongoing uncertainty regarding the most informative predictors of adverse outcomes. An increased PVC frequency may be a risk factor for heart failure and death, and the resolution of systolic dysfunction after successful catheter ablation of PVCs demonstrates that a causal relationship can be present. Patients with no or mild symptoms, a low PVC burden, and normal ventricular function may be best served with simple reassurance. Either medical treatment or catheter ablation are considered first-line therapies in most patients with PVCs associated with symptoms or a reduced left ventricular ejection fraction, and patient preference plays a role in determining which to try first. If medical treatment is selected, either β-blockers or nondihydropyridine calcium channel blockers are reasonable drugs in patients with normal ventricular systolic function. Other antiarrhythmic drugs should be considered if those initial drugs fail and ablation has been declined, has been unsuccessful, or has been deemed inappropriate. Catheter ablation is the most efficacious approach to eradicate PVCs but may confer increased upfront risks. Original research remains necessary to identify individuals at risk for PVC-induced cardiomyopathy and to identify preventative and therapeutic approaches targeting the root causes of PVCs to maximize effectiveness while minimizing risk.
Clonal Evolution and Heterogeneity of Osimertinib Acquired Resistance Mechanisms in EGFR Mutant Lung Cancer
Authors: Nitin Roper, Anna-Leigh Brown, Jun S. Wei, Svetlana Pack, Christopher Trindade, Chul Kim, Olivia Restifo, Shaojian Gao, Sivasish Sindiri, Farid Mehrabadi, Rajaa El Meskini, Zoe Weaver Ohler, Tapan K. Maity, Abhilash Venugopalan, Constance M. Cultraro, Elizabeth Akoth, Emerson Padiernos, Haobin Chen, Aparna Kesarwala, DeeDee K. Smart, Naris Nilubol, Arun Rajan, Zofia Piotrowska, Liqiang Xi, Mark Raffeld, Anna R. Panchenko, Cenk Sahinalp, Stephen Hewitt, Chuong D. Hoang, Javed Khan, Udayan Guha
Journal: Cell Reports Medicine (2020)

Clonal evolution of osimertinib-resistance mechanisms in EGFR mutant lung adenocarcinoma is poorly understood. Using multi-region whole-exome and RNA sequencing of prospectively collected pre- and post-osimertinib-resistant tumors, including at rapid autopsies, we identify a likely mechanism driving osimertinib resistance in all patients analyzed. The majority of patients acquire two or more resistance mechanisms either concurrently or in temporal sequence. Focal copy-number amplifications occur subclonally and are spatially and temporally separated from common resistance mutations such as EGFR C797S. MET amplification occurs in 66% (n = 6/9) of first-line osimertinib-treated patients, albeit spatially heterogeneous, often co-occurs with additional acquired focal copy-number amplifications and is associated with early progression. Noteworthy osimertinib-resistance mechanisms discovered include neuroendocrine differentiation without histologic transformation, PD-L1, KRAS amplification, and ESR1-AKAP12, MKRN1-BRAF fusions. The subclonal co-occurrence of acquired genomic alterations upon osimertinib resistance will likely require targeting multiple resistance mechanisms by combination therapies.
Abstract 15584: Left Ventricular Post-Infarct Remodeling: Impact on Outcome in the Modern Era
Authors: Pieter van der Bijl, Rachid Abou, Laurien Goedemans, Bernard J Gersh, David R Holmes, Nina Ajmone Marsan, Victoria Delgado, Jeroen J Bax
Journal: Circulation (2018)

Introduction: Left ventricular (LV) remodeling after an ST-segment elevation myocardial infarction (STEMI) has been associated with heart failure and increased mortality. The long-term prognostic i...
Abstract 12338: Use of Automated Self-administered24-hour (asa24®) Dietary Assessment Tool in Estimation of Magnesium Intake
Authors: Hamza Lodhi, Ursa Bezan Petric, Jere Mitchell, Scott A Smith, Lona Sandon, Naim Maalouf, Wanpen Vongpatanasin
Journal: Circulation (2019)

Introduction: Increasing dietary intake of magnesium (Mg), calcium (Ca), and potassium (K) via increased fruits and vegetable consumption is one of the nonpharmacologic interventions for lowering B...
Sensitivity of Continuous Electroencephalography to Detect Ictal Activity After Cardiac Arrest
Authors: Jonathan Elmer, Patrick J. Coppler, Pawan Solanki, M. Brandon Westover, Aaron F. Struck, Maria E. Baldwin, Michael C. Kurz, Clifton W. Callaway
Journal: JAMA Network Open (2020)

<h3>Importance</h3> Epileptiform electroencephalographic (EEG) patterns are common after resuscitation from cardiac arrest, are associated with patient outcome, and may require treatment. It is unknown whether continuous EEG monitoring is needed to detect these patterns or if brief intermittent monitoring is sufficient. If continuous monitoring is required, the necessary duration of observation is unknown. <h3>Objective</h3> To quantify the time-dependent sensitivity of continuous EEG for epileptiform event detection, and to compare continuous EEG to several alternative EEG-monitoring strategies for post–cardiac arrest outcome prediction. <h3>Design, Setting, and Participants</h3> This observational cohort study was conducted in 2 academic medical centers between September 2010 and January 2018. Participants included 759 adults who were comatose after being resuscitated from cardiac arrest and who underwent 24 hours or more of EEG monitoring. <h3>Main Outcomes and Measures</h3> Epileptiform EEG patterns associated with neurological outcome at hospital discharge, such as seizures likely to cause secondary injury. <h3>Results</h3> Overall, 759 patients were included in the analysis; 281 (37.0%) were female, and the mean (SD) age was 58 (17) years. Epileptiform EEG activity was observed in 414 participants (54.5%), of whom only 26 (3.4%) developed potentially treatable seizures. Brief intermittent EEG had an estimated 66% (95% CI, 62%-69%) to 68% (95% CI, 66%-70%) sensitivity for detection of prognostic epileptiform events. Depending on initial continuity of the EEG background, 0 to 51 hours of monitoring were needed to achieve 95% sensitivity for the detection of prognostic epileptiform events. Brief intermittent EEG had a sensitivity of 7% (95% CI, 4%-12%) to 8% (95% CI, 4%-12%) for the detection of potentially treatable seizures, and 0 to 53 hours of continuous monitoring were needed to achieve 95% sensitivity for the detection of potentially treatable seizures. Brief intermittent EEG results yielded similar information compared with continuous EEG results when added to multivariable models predicting neurological outcome. <h3>Conclusions and Relevance</h3> Compared with continuous EEG monitoring, brief intermittent monitoring was insensitive for detection of epileptiform events. Monitoring EEG results significantly improved multimodality prediction of neurological outcome, but continuous monitoring appeared to add little additional information compared with brief intermittent monitoring.
Drug-Eluting Stent Update 2007
Authors: Joost Daemen, Patrick W. Serruys
Journal: Circulation (2007)

has been called the Achilles heel of coronary stenting and is caused by a combination of factors, including neointimal proliferation, elastic recoil, reorganization of thrombus, remodeling, and inflammation. 1Long-term follow-up (Ͼ6 years) in patients with bare metal stents (BMS) shows that tissue proliferation reaches its peak at around 6 to 12 months and then regresses. 2This pattern fits with the observed increase in revascularization rates up to 1 year, after which a plateau occurs.After drug-eluting stent (DES) implantation, Carter et al 3 showed a late catch-up of restenosis in sirolimus-eluting stents (SES) in porcine models.Although a 50% reduction of restenosis was observed at 30 days, restenosis rates for SES and BMS were equivalent at 6 months. 3A similar catch-up phenomenon was observed after implantation of paclitaxel-eluting stents (PES) and tacrolimus-eluting stents in porcine models. 4,5Conversely, in humans, there does not seem to be reason for concern about late catch-up for up to 4 years on both clinical and angiographic end points. 6 -10However, several long-term DES studies showed that, in contrast to BMS, the neointima continued to grow up to 2 years as assessed by intravascular ultrasound. 11The discrepancy between porcine and clinical data is influenced by the temporal differences in arterial response in humans compared with animal models but also may be due to differences in species response to sirolimus and paclitaxel and physiological stimuli for neointimal formation.
Cardiomyocyte Expression of ZO-1 Is Essential for Normal Atrioventricular Conduction but Does Not Alter Ventricular Function
Authors: Jianlin Zhang, Kevin P. Vincent, Angela K. Peter, Matthew Klos, Hongqiang Cheng, Selina M. Huang, Jordan K. Towne, Debbie Ferng, Yusu Gu, Nancy D. Dalton, Yunghang Chan, Ruixia Li, Kirk L. Peterson, Ju Chen, Andrew D. McCulloch, Kirk U. Knowlton, Robert S. Ross
Journal: Circulation Research (2020)

Rationale: ZO-1 (Zonula occludens-1), a plasma membrane-associated scaffolding protein regulates signal transduction, transcription, and cellular communication. Global deletion of ZO-1 in the mouse is lethal by embryonic day 11.5. The function of ZO-1 in cardiac myocytes (CM) is largely unknown. Objective: To determine the function of CM ZO-1 in the intact heart, given its binding to other CM proteins that have been shown instrumental in normal cardiac conduction and function. Methods and Results: We generated ZO-1 CM-specific knockout (KO) mice using α-Myosin Heavy Chain-nuclear Cre (ZO-1cKO) and investigated physiological and electrophysiological function by echocardiography, surface ECG and conscious telemetry, intracardiac electrograms and pacing, and optical mapping studies. ZO-1cKO mice were viable, had normal Mendelian ratios, and had a normal lifespan. Ventricular morphometry and function were not significantly different between the ZO-1cKO versus control (CTL) mice, basally in young or aged mice, or even when hearts were subjected to hemodynamic loading. Atrial mass was increased in ZO-1cKO. Electrophysiological and optical mapping studies indicated high-grade atrioventricular (A-V) block in ZO-1cKO comparing to CTL hearts. While ZO-1-associated proteins such as vinculin, connexin 43, N-cadherin, and α-catenin showed no significant change with the loss of ZO-1, Connexin-45 and Coxsackie-adenovirus (CAR) proteins were reduced in atria of ZO-1cKO. Further, with loss of ZO-1, ZO-2 protein was increased significantly in ventricular CM in a presumed compensatory manner but was still not detected in the AV nodal myocytes. Importantly, the expression of the sodium channel protein NaV1.5 was altered in AV nodal cells of the ZO-1cKO versus CTL. Conclusions: ZO-1 protein has a unique physiological role in cardiac nodal tissue. This is in alignment with its known interaction with CAR and Cx45, and a new function in regulating the expression of NaV1.5 in AV node. Uniquely, ZO-1 is dispensable for function of the working myocardium.
Patients with lupus are not protected from COVID-19
Authors: Amr H Sawalha
Journal: Annals of the Rheumatic Diseases (2020)

The comment provided by Joob and Wiwanitkit contains serious factual errors that need to be urgently corrected to prevent harm to patients.1 Their claim that ‘there is no case of SLE with covid-19’ is false. It is puzzling how they can make such a claim without providing supporting evidence. An initial analysis of patients included in the COVID-19 Global Rheumatology Alliance registry shows that 19 (17%) of 110 patients with rheumatic diseases who have been diagnosed with COVID-19 as of 1 April 2020 were patients with lupus.2 The frequency of patients with lupus who have …
TRIM24 facilitates antiviral immunity through mediating K63-linked TRAF3 ubiquitination
Authors: Qingchen Zhu, Tao Yu, Shucheng Gan, Yan Wang, Yifei Pei, Qifan Zhao, Siyu Pei, Shumeng Hao, Jia Yuan, Jing Xu, Fajian Hou, Xuefeng Wu, Chao Peng, Ping Wu, Jun Qin, Yichuan Xiao
Journal: The Journal of Experimental Medicine (2020)

Ubiquitination is an essential mechanism in the control of antiviral immunity upon virus infection. Here, we identify a series of ubiquitination-modulating enzymes that are modulated by vesicular stomatitis virus (VSV). Notably, TRIM24 is down-regulated through direct transcriptional suppression induced by VSV-activated IRF3. Reducing or ablating TRIM24 compromises type I IFN (IFN-I) induction upon RNA virus infection and thus renders mice more sensitive to VSV infection. Mechanistically, VSV infection induces abundant TRIM24 translocation to mitochondria, where TRIM24 binds with TRAF3 and directly mediates K63-linked TRAF3 ubiquitination at K429/K436. This modification of TRAF3 enables its association with MAVS and TBK1, which consequently activates downstream antiviral signaling. Together, these findings establish TRIM24 as a critical positive regulator in controlling the activation of antiviral signaling and describe a previously unknown mechanism of TRIM24 function.
Tumor Heterogeneity
Authors: Steven Maron, Adam Bass
Journal: JAMA Network Open (2020)

Joseph Chao, MD; Victoria Bedell, BS; Jeeyun Lee, MD; Min Sierra Li, PhD; Peiguo Chu, MD, PhD; Yate-Ching Yuan, PhD; Dan Zhao, MD, PhD; Samuel J. Klempner, MD; Ren-Jang Lin, PhD
Single-cell transcriptomics combined with interstitial fluid proteomics defines cell type–specific immune regulation in atopic dermatitis
Authors: Thomas B. Rojahn, Vera Vorstandlechner, Thomas Krausgruber, Wolfgang M. Bauer, Natalia Alkon, Christine Bangert, Felix M. Thaler, Farzaneh Sadeghyar, Nikolaus Fortelny, Victoria Gernedl, Katharina Rindler, Adelheid Elbe-Bürger, Christoph Bock, Michael Mildner, Patrick M. Brunner
Journal: Journal of Allergy and Clinical Immunology (2020)
Isolated Intravascular Prostate Carcinoma Recurrence Confirmed With 18F-Fluciclovine PET/CT and MRI
Authors: Ali Agely, Akash Sharma, Ephraim E. Parent, Anem Nawaz, Manoj K. Jain
Journal: Clinical Nuclear Medicine (2020)

Abstract Late recurrence of prostate cancer after remission with prior radical prostatectomy is uncommon. This is a unique case of biochemical recurrence after being in remission for 12 years. The patient presented with swelling of the right lower extremity with pelvic MRI demonstrating an arterially enhancing filling defect in the right common iliac. An 18 F-fluciclovine PET/CT showed corresponding increased intravascular radiotracer activity. Targeted biopsy of the intravascular lesion showed poorly differentiated carcinoma, suggestive of prostate origin. Although MRI evaluation is the mainstay for pelvic evaluation, characterization with 18 F-fluciclovine PET/CT imaging adds high whole-body specificity and diagnostic accuracy.
Increasing Pulmonary Rehabilitation Uptake after Hospitalization for Chronic Obstructive Pulmonary Disease Exacerbation. Let’s Rise to the Challenge
Authors: Carolyn L. Rochester, Sally J. Singh
Journal: American Journal of Respiratory and Critical Care Medicine (2020)

How do we provide ICS-containing treatment to those who will benefit the most with the fewest side effects, in particular pneumonia?Blood eosinophils is undoubtedly a step in the right direction (13, 14), but better understanding and application of this and future biomarkers could help us better identify those with the biggest benefit.In the meantime, we can appreciate that for patients with COPD with frequent exacerbations we can already provide treatments that make them live both better and longer.
Lowering Dietary Sodium Intake—Implementing and Studying the Effectiveness of Public Health Interventions
Authors: Tracy Y. Wang
Journal: JAMA Internal Medicine (2020)

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In Vivo CD4<sup>+</sup>T Cell Differentiation and Function: Revisiting the Th1/Th2 Paradigm
Authors: Mikel Ruterbusch, Kurt B. Pruner, Laila Shehata, Marion Pepper
Journal: Annual Review of Immunology (2020)

The discovery of CD4 + T cell subset–defining master transcription factors and framing of the Th1/Th2 paradigm ignited the CD4 + T cell field. Advances in in vivo experimental systems, however, have revealed that more complex lineage-defining transcriptional networks direct CD4 + T cell differentiation in the lymphoid organs and tissues. This review focuses on the layers of fate decisions that inform CD4 + T cell differentiation in vivo. Cytokine production by antigen-presenting cells and other innate cells influences the CD4 + T cell effector program [e.g., T helper type 1 (Th1), Th2, Th17]. Signals downstream of the T cell receptor influence whether individual clones bearing hallmarks of this effector program become T follicular helper cells, supporting development of B cells expressing specific antibody isotypes, or T effector cells, which activate microbicidal innate cells in tissues. These bifurcated, parallel axes allow CD4 + T cells to augment their particular effector program and prevent disease.
Prevalence of SARS-CoV-2 Infection in Residents of a Large Homeless Shelter in Boston
Authors: Travis P. Baggett, Harrison Keyes, Nora Sporn, Jessie M. Gaeta
Journal: JAMA (2020)

This study characterizes the prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection detected on polymerase chain reaction (PCR) screening of a large homeless shelter population in Boston prompted by an outbreak of COVID-19 cases among shelter residents.
Contribution of EPIET to public health workforce in the EU, 1995-2008
Authors: A Bosman, B Schimmer, D Coulombier
Journal: Eurosurveillance (2009)

We analyse activities and outputs of fellows of the European Programme for Intervention Epidemiology Training (EPIET) between 1995 and 2008 and describe the employment history of graduates after the training to demonstrate the contribution of this programme and of national EPIET-associated programmes to the public health workforce in the European Union and Norway. Up to 2008, some 161 fellows entered the training: 121 in EPIET and 40 in EPIET-associated programmes. Of these 149 were awarded a diploma. Fellows engaged in projects in all areas of surveillance, in outbreaks and field investigations and produced 340 publications in peer-reviewed journals. Seventy fellows were sent to 98 individual assignments on 65 international missions. The vast majority of graduates (90%) take up a position and remain employed in applied public health, either on regional, national or international level. Several (27) are working outside the EU, all in public health, including 13 working in Switzerland for international organisations. Only three of the 12 EU Member States that joined the EU since 2004, employ EPIET graduates. A major challenge for training the public health workforce is the retention of professionals in countries with limited job opportunities or wages significantly below the EU average.