tbuckley/cabot-search huggingface dataset:
Association of Naloxone Coprescription Laws With Naloxone Prescription Dispensing in the United States
Authors: Minji Sohn, Jeffery C. Talbert, Zhengyan Huang, Michelle R. Lofwall, Patricia R. Freeman
Journal: JAMA Network Open (2019)

To mitigate the opioid overdose crisis, states have implemented a variety of legal interventions aimed at increasing access to the opioid antagonist naloxone. Recently, Virginia and Vermont mandated the coprescription of naloxone for potentially at-risk patients.To assess the association between naloxone coprescription legal mandates and naloxone dispensing in retail pharmacies.This was a population-based, state-level cohort study. The sample included all prescriptions dispensed for naloxone in the retail pharmacy setting contained in IQVIA's national prescription audit, which represents 90% of all retail pharmacies in the United States. The unit of observation was state-month and the study period was January 1, 2011, to December 31, 2017.State legal intervention mandating naloxone coprescription.Number of naloxone prescriptions dispensed. State rates of naloxone prescriptions dispensed per month per 100 000 standard population were calculated.The rate of naloxone dispensing increased after implementation of legal mandates for naloxone coprescription. An estimated 88 naloxone prescriptions per 100 000 were dispensed in Virginia and 111 prescriptions per 100 000 were dispensed in Vermont during the first full month the legal requirement was effective. In comparison, 16 naloxone prescriptions per 100 000 were dispensed in the 10 states (including the District of Columbia) with the highest opioid overdose death rates and 6 prescriptions per 100 000 were dispensed in the 39 remaining states. The number of naloxone prescriptions dispensed was associated with the legal mandate for naloxone coprescription (incidence rate ratio [IRR], 7.75; 95% CI, 1.22-49.35). Implementation of the naloxone coprescription mandate was associated with an estimated 214 additional naloxone prescriptions dispensed per month in the period following the mandates, holding all other variables constant. Among covariates, naloxone access laws (IRR, 1.37; 1.05-1.78), opioid overdose death rates (IRR, 1.06; 95% CI, 1.04-1.08), the percentage of naloxone prescriptions paid by third-party payers (IRR 1.009; 1.008-1.010), and time (IRR, 1.06; 95% CI, 1.05-1.07) were significantly associated with naloxone prescription dispensing.These study findings suggest that legally mandated naloxone prescription for those at risk for opioid overdose may be associated with substantial increases in naloxone dispensing and further reduction in opioid-related harm.
Astrocytic connexin 43 potentiates myelin injury in ischemic white matter disease
Authors: Minghuan Wang, Chuan Qin, Xiang Luo, Jie Wang, Xuxia Wang, Minjie Xie, Jing Hu, Jie Cao, Ting Hu, Steven A. Goldman, Maiken Nedergaard, Wei Wang
Journal: Theranostics (2019)

Rational: Myelin loss is a characteristic feature of both ischemic white matter disease and its associated vascular dementia, and is a hallmark of chronic cerebral hypoperfusion due to carotid artery stenosis.Yet the cellular mechanisms involved in ischemic dysmyelination are not well-understood, and no effective treatment has emerged to prevent or slow hypoperfusion-related demyelination.In a study employing the bilateral common carotid artery stenosis (BCAS) mouse model, we found reduced cerebral blood flow velocity and arteriolar pulsatility, and confirmed that prolonged BCAS provoked myelin disruption.These pathological features were associated with marked cognitive decline, in the absence of evident damage to axons.Methods: To assess the role of astroglial communication in BCAS-associated demyelination, we investigated the effect of deleting or inhibiting connexin 43 (Cx43), a constituent of astroglial gap junctions and hemichannels.Results: Genetic deletion and pharmacological inhibition of gap junctions both protected myelin integrity and rescued cognitive decline in the BCAS-treated mice.Gap junction inhibition also suppressed the transient increase in extracellular glutamate observed in the callosal white matter of wild-type mice exposed to BCAS.Conclusion: These findings suggest that astrocytic Cx43 may be a viable target for attenuating the demyelination and cognitive decline associated with chronic cerebral hypoperfusion.
Abstract 14180: Real-time Visual Feedback During Training Improves Lay People’s CPR Quality: A Randomized Controlled Manikin Study
Authors: Enrico Baldi, Enrico Contri, Alberto Somaschini, Francesco Epis, Cinzia Dossena, Elisa Zambaiti, Marzia Di Maggio, Stefano Cornara
Journal: Circulation (2015)

Introduction: It has been demonstrated that feedback devices could have a role in improving CPR quality, but the results regarding lay people are controversial. Hypothesis: Our aim is to verify whether the use of CPR feedback devices improves lay people’s CPR quality after a training course and if the final quality reached is influenced by the amount of time spent training with them. Methods: 450 lay participants to BLS-D courses were randomly divided into three groups with an allocation ratio 1:1:1; group 0 attended a course without any feedback, group 1 a course with 1 minute training with real-time visual feedback and group 10 a course with 10 minutes training with real-time visual feedback. There were no statistically significant differences among the three groups for the anthropometric variables. At the end of each course we recorded 1-min of compression-only CPR. Results: There was a statistically significant overall difference among the three groups. In particular, comparing group 0 vs group 1 and group 0 vs group 10 there was a significant improvement in the percentage of compressions with correct depth (66.6% (95%CI, 60.1-73.1) in gr.0 vs 77.8% (95%CI, 72.8-82.8) in gr.1, p=0.005 and 66.6% (95%CI, 60.1-73.1) in gr.0 vs 75.7% (95%CI, 70.7-80.8) in gr.10, p=0.022), in the percentage of compressions with complete chest recoil (71.7% (95%CI, 66.2-77.2) in gr. 0 vs 86.6% (95%CI, 82.4-90.8) in gr. 1, p&lt;0.001 and 71.7% (95%CI, 66.2-77.2) in gr. 0 vs 88.8% (95%CI, 85.6-92.2) in gr. 10, p&lt;0.001), in the percentage of compressions with correct hand position (93.2% (95%CI, 89.7-96.6) in gr.0 vs 98.2% (95%CI, 96.7-99.8) in gr.10, p&lt;0.001 and 93.2% (95%CI, 89.7-96.6) in gr.0 vs 99.3% (95%CI, 98.6-100) in gr.10, p=0.002) and in Total CPR score (79.4% (95%CI, 75.5-83.2) in gr.0 vs 90.2% (95%CI, 87.8-92.5) in gr.1, p&lt;0.001 and 79.4% (95%CI, 75.5-83.2) in gr.0 vs 92.5% (95%CI, 91-94) in gr.10, p&lt;0.001) in the groups in which the feedback was used. Furthermore, there were no statistically significant differences for all the parameters between group 1 and group 10. Conclusions: Real-time visual feedback improves lay people CPR quality, thus could improve OHCA survival. 1-minute of feedback is sufficient to reach a better CPR quality and we suggest its use in every BLS-D course.
Abstract 12007: Long-Term Aspirin Use is Associated With a Lower Prevalence of Mobility Limitation in Older Men
Authors: Ariela R Orkaby, Laiji Yang, Alyssa B Dufour, Thomas G Travison, Howard D Sesso, J M Gaziano, Jane A Driver, Luc Djousse
Journal: Circulation (2018)

Introduction: Mobility limitation is a component of frailty that shares a bidirectional relationship with cardiovascular disease (CVD). Whether established CVD prevention therapies such as aspirin ...
AB1380-HPR THE EFFECTS OF CERVICAL RANGE OF MOTION ON POSTURAL STABILITY IN PATIENTS WITH CHRONIC NECK PAIN
Authors: Onur Aydogdu, Glsah Kili, Tolga Tasbas, Zbeyir Sari
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Neck pain is a common musculoskeletal problem within chronic pain and it effectuates up to 71% of adult population during their life time (1). Chronic neck pain is related to a series of disabilities: a range of reported pain, postural stability problems, and cognitive dysfunction (2). However, there is no report that investigate the relationship between range of motion and postural stability in patients with chronic neck pain. <h3>Objectives</h3> The purpose of this study was to investigate the effects of limitations in cervical range of motion on postural stability in patients with chronic neck pain. We hypothesized that the patients who have extension limitation might have postural stability deficit with flexion direction. <h3>Methods</h3> Thirty subjects of mean age 28.50 10.95 years who admitted with chronic neck pain to a Private Physiotherapy Clinic were participated in this study. While goniometer was used for cervical range of motion, pedalo sensamove system was used for postural stability. In addition, pain and disability were measured with visual analogue scale, neck disability index, respectively. <h3>Results</h3> It was found that limitation of cervical range of motion was not correlated to postural stability deficits (p&gt;0.05). The neck pain and disability status was not associated with level of postural stability (p&gt;0.05). <h3>Conclusion</h3> The findings of this study showed that postural stability may not be affected by the limitation of cervical range of motion, and also neck pain intensity, neck disability status in patients with chronic neck pain. Further research with larger sample sizes is warranted. <h3>References</h3> [1] Demirbken I, zgl B, Kuru olak T, Aydogdu O, Sari Z, Yurdalan SU. Kinesiophobia in relation to physical activity in chronic neck pain. J Back Musculoskelet Rehabil. 2016;29(1):41-7. [2] Nazari G, Bobos P, Billis E, MacDermid JC. Cervical flexor muscle training reduces pain, anxiety, and depression levels in patients with chronic neck pain by a clinically important amount: A prospective cohort study. Physiother Res Int. 2018 Jul;23(3):e1712. <h3>Disclosure of Interests</h3> None declared
PB2391 MYOCARDIAL CONTRACTILE FRACTION BY MAGNETIC RESONANCE AND RISK OF CARDIAC COMPLICATIONS IN THALASSEMIA MAJOR
Authors: A. Meloni, L. Pistoia, R. Rosso, P. P. Bitti, M. Caini, A. Carollo, S. Armari, C. Gerardi, M. G. Roberti, M. F. Fiorenza, R. Sarli, S. Renne, V. Positano, A. Pepe
Journal: HemaSphere (2019)

Background: The analysis of cine cardiovascular magnetic resonance (CMR) images allows the quantification of the myocardial contraction fraction (MCF), a volumetric analog of myocardial deforming, that is calculated by dividing left ventricular (LV) stroke volume by LV myocardial volume. Aims: We verified the association of this new marker with myocardial iron overload and cardiac events (heart failure, arrhythmias and pulmonary hypertension) in thalassemia major (TM) patients. Methods: We considered 1492 TM patients (771 females, 31.06 ± 8.95 yrs) enrolled in the MIOT network. Myocardial iron overload (MIO) was quantified by the multislice multiecho T2∗ technique and biventricular morphological and functional parameters by cine sequences. Results: MCF values were significantly lower in males (0.94 ± 0.22 vs 1.01 ± 0.22; P &lt; 0.0001) and decreased with increasing age (R = −0.129 P &lt; 0.0001). Patients with MIO (global heart T2∗ &lt; 20 ms; N = 400) showed significant lower MCF values than patients without MIO (0.91 ± 0.20 vs 1.00 ± 0.22; P &lt; 0.0001). The patient population was randomly divided in two groups of equal size (N = 746). In the first group 99 patients had at least one cardiac complication and at receiver‐operating characteristic (ROC) curve analysis a MCF ≤ 0.87 was the best predictor of cardiac complications (area under the curve 0.659, 95% CI 0.64 to 0.69; sensitivity 60%, specificity 67%). In order to validate the result, the obtained value was tested in the remaining 746 patients (group 2). One hundred and thirty‐five patients had a cardiac complication and patients with a MCF ≤ 0.87 were more likely to have cardiac complications (odds ratio – OR = 2.73, 95%CI = 1.86‐4.01; P &lt; 0.0001), also adjusting for cardiac iron (see Figure). Summary/Conclusion: Contractile function is reduced in patients with MIO. A MCF ≤0.87 can help to identify patients with a significant higher risk of adverse cardiovascular events, independently by the presence of MIO. image
Robust Method for Detecting Convergent Shifts in Evolutionary Rates
Authors: Raghavendran Partha, Amanda Kowalczyk, Nathan L Clark, Maria Chikina
Journal: Molecular Biology and Evolution (2019)

Abstract Identifying genomic elements underlying phenotypic adaptations is an important problem in evolutionary biology. Comparative analyses learning from convergent evolution of traits are gaining momentum in accurately detecting such elements. We previously developed a method for predicting phenotypic associations of genetic elements by contrasting patterns of sequence evolution in species showing a phenotype with those that do not. Using this method, we successfully demonstrated convergent evolutionary rate shifts in genetic elements associated with two phenotypic adaptations, namely the independent subterranean and marine transitions of terrestrial mammalian lineages. Our original method calculates gene-specific rates of evolution on branches of phylogenetic trees using linear regression. These rates represent the extent of sequence divergence on a branch after removing the expected divergence on the branch due to background factors. The rates calculated using this regression analysis exhibit an important statistical limitation, namely heteroscedasticity. We observe that the rates on branches that are longer on average show higher variance, and describe how this problem adversely affects the confidence with which we can make inferences about rate shifts. Using a combination of data transformation and weighted regression, we have developed an updated method that corrects this heteroscedasticity in the rates. We additionally illustrate the improved performance offered by the updated method at robust detection of convergent rate shifts in phylogenetic trees of protein-coding genes across mammals, as well as using simulated tree data sets. Overall, we present an important extension to our evolutionary-rates-based method that performs more robustly and consistently at detecting convergent shifts in evolutionary rates.
Lymphocytic subsets play distinct roles in heart diseases
Authors: Jing Wang, Yi Duan, Joost PG Sluijter, Junjie Xiao
Journal: Theranostics (2019)

Heart diseases are one of the leading causes of death for humans in the world. Increasing evidence has shown that myocardial injury induced innate and adaptive immune responses upon early cellular damage but also during chronic phases post-injury. The immune cells can not only aggravate the injury but also play an essential role in the induction of wound healing responses, which means they play a complex role throughout the acute inflammatory response and reparative response after cardiac injury. This review will summarize the current experimental and clinical evidence of lymphocytes, one of the major types of immune cells, participate in heart diseases and try to explain the possible role of these immune cells following cardiac injury.
AB0649 B CELL DEPLETION THERAPY IN VERY EARLY SYSTEMIC SCLEROSIS. A POTENTIAL WINDOW OF OPPORTUNITY?
Authors: Dimitrios Daoussis, Pantelis Kraniotis, Ioannis Antonopoulos, Konstantinos Melissaropoulos, Stamatis-Nick Liossis
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Our group, among others, has shown that B cell depletion therapy may improve skin thickening and interstitial lung disease (ILD) related to systemic sclerosis (SSc). All studies assessing the clinical efficacy of B cell depletion therapy in SSc have recruited patients with established disease fulfilling the old classification criteria. In our previous studies we have found that patients with shorter disease duration had a better clinical response to RTX. <h3>Objectives</h3> It is unknown whether treatment in very early SSc can affect long term outcomes. We aimed at assessing the effect of rituximab (RTX) in patients with very early SSc. <h3>Methods</h3> We report 2 cases where RTX was administered within 24 months from the appearance of Raynaud's. <h3>Results</h3> A 56 year-year-old female with an 18-month history of Raynaud's developed interstitial lung disease (ILD) with extensive ground glass lesions, a normal FVC (82%) but decreased DLco (44%). A diagnosis of SSc was made based on the presence of positive anti-centromere antibodies, puffy fingers, telangiectasias, positive capillaroscopy, ILD and Raynaud's. Six months following RTX treatment, her PFT's had increased (FVC 94% and DLco 55%) and chest HRCT showed an obvious improvement. One year later the patient no longer reported dyspnea. She remained on RTX for 5 years with no respiratory symptoms, stable PFTs and no evidence of disease progression. The second case is a 27-year old female with a 1-year history of Raynaud's, puffy fingers, positive anti-Scl70 and capillaroscopy. Within a few months her skin thickened rapidly reaching an MRSS of 12 and developed tendon friction rubs. Six months following RTX treatment skin thickening had almost resolved; she only had mild sclerodactyly. Tendon friction rubs disappeared. The patient received 8 consecutive RTX courses throughout a period of 4 years. During this period the patient remained in a steady clinical condition with no signs of disease progression. <h3>Conclusion</h3> It is generally accepted that autoimmunity/immune dysregulation and vasculopathy are the primary events in SSc that eventually trigger the fibrotic process. Based on this pathogenetic model, one can hypothesize that a therapeutic intervention very early in the disease course, prior to the appearance of fibrotic manifestations could potentially prevent permanent organ damage. Our data suggest that there may be a window of opportunity in SSc. This is why we propose that large scale, controlled studies assessing the efficacy of RTX (or other immune based therapies such as mycophenolate) in patients with very early disease are highly needed. <h3>Disclosure of interests</h3> None declared
Abstract 17824: Infective Endocarditis in Patients With Cancer: Incidence, Provoking Factors, and the Potential Need for Preprocedural Antibiotic Prophylaxis
Authors: Kyu Kim, Darae Kim, Sang-Eun Lee, In Jeong Cho, Chi Young Shim, Geu-Ru Hong, Jong-Won Ha
Journal: Circulation (2017)

Introduction: The incidence of infective endocarditis (IE) in patients with cancer is increasing. However, little is known regarding the characteristics, provoking factors, and outcomes of IE in pa...
PS1119 PNH CLONE SIZE BY FLOW CYTOMETRY AND ITS CORRELATION TO PIG GENE MUTATION
Authors: D. Jeong, H.S. Park, S. Choi, H. Seo, S.‐M. Kim, K. Im, K. Lim, J. Yun, J.‐A. Kim, K. Kim, J.H. Kim, D.S. Lee
Journal: HemaSphere (2019)

Background: Routine diagnosis of paroxysmal nocturnal hemoglobinuria (PNH) is based on flow cytometric measurement of PNH clone in RBC and granulocyte. However there is no well‐established consensus on the clinically significant size of PNH clone. Aims: So we investigated whether quantitative results of PNH clone size measured by flow cytometry (FCM) correlate with mutant burden of PIG gene. Methods: A total of 89 specimens from 63 patients whose PNH clone size was ≥0.1% by FCM was enrolled. We performed ultra‐deep sequencing for PIGA , PIGM and PIGX genes on these 89 consecutive specimens. Also, we followed up 6 patients who were treated with Eculizumab and analyzed their laboratory changes including hemoglobin, lactate dehydrogenase level, PNH flow cytometry and PIG gene mutant burden. Treatment response was evaluated every 6 months. Results: Sixteen out of 63 patients had &gt;10% granulocyte PNH clone and they all had PIG gene mutation. Fifteen (93.8%) had PIGA mutation and one (6.3%) PIGM mutation. Patients with &gt;15% RBC PNH clone (n = 12) all had PNH‐related symptoms (p &lt;0.001). Granulocyte clone size showed better correlation with VAF than RBC clone size (Granulocyte r = 0.61, p = 0.01, RBC r = 0.39, p = 0.14). On the other hand, RBC clone size was better reflective of PNH‐related symptoms with a cut‐off of 15% (p &lt;0.001). We found no significant laboratory parameter for prediction of Eculizumab treatment response. Summary/Conclusion: Patients with &gt;10% granulocyte PNH clone by FCM were always accompanied by PIG gene mutation. Those with &gt;15% RBC PNH clone by FCM all had PNH‐related symptoms. Weak correlation between granulocyte clone size and VAF of PIG gene mutation implies that granulocyte clone reflects the real PNH clonal burden. image
The Extracellular Matrix in Ischemic and Nonischemic Heart Failure
Authors: Nikolaos G. Frangogiannis
Journal: Circulation Research (2019)

The ECM (extracellular matrix) network plays a crucial role in cardiac homeostasis, not only by providing structural support, but also by facilitating force transmission, and by transducing key signals to cardiomyocytes, vascular cells, and interstitial cells. Changes in the profile and biochemistry of the ECM may be critically implicated in the pathogenesis of both heart failure with reduced ejection fraction and heart failure with preserved ejection fraction. The patterns of molecular and biochemical ECM alterations in failing hearts are dependent on the type of underlying injury. Pressure overload triggers early activation of a matrix-synthetic program in cardiac fibroblasts, inducing myofibroblast conversion, and stimulating synthesis of both structural and matricellular ECM proteins. Expansion of the cardiac ECM may increase myocardial stiffness promoting diastolic dysfunction. Cardiomyocytes, vascular cells and immune cells, activated through mechanosensitive pathways or neurohumoral mediators may play a critical role in fibroblast activation through secretion of cytokines and growth factors. Sustained pressure overload leads to dilative remodeling and systolic dysfunction that may be mediated by changes in the interstitial protease/antiprotease balance. On the other hand, ischemic injury causes dynamic changes in the cardiac ECM that contribute to regulation of inflammation and repair and may mediate adverse cardiac remodeling. In other pathophysiologic conditions, such as volume overload, diabetes mellitus, and obesity, the cell biological effectors mediating ECM remodeling are poorly understood and the molecular links between the primary insult and the changes in the matrix environment are unknown. This review article discusses the role of ECM macromolecules in heart failure, focusing on both structural ECM proteins (such as fibrillar and nonfibrillar collagens), and specialized injury-associated matrix macromolecules (such as fibronectin and matricellular proteins). Understanding the role of the ECM in heart failure may identify therapeutic targets to reduce geometric remodeling, to attenuate cardiomyocyte dysfunction, and even to promote myocardial regeneration.
Development and Validation of a Combined Hypoxia and Immune Prognostic Classifier for Head and Neck Cancer
Authors: Jill M. Brooks, Albert N. Menezes, Maha Ibrahim, Lucinda Archer, Neeraj Lal, Christopher J. Bagnall, Sandra V. von Zeidler, Helen R. Valentine, Rachel J. Spruce, Nikolaos Batis, Jennifer L. Bryant, Margaret Hartley, Baksho Kaul, Gordon B. Ryan, Riyue Bao, Arun Khattri, Steven P. Lee, Kalu U.E. Ogbureke, Gary Middleton, Daniel A. Tennant, Andrew D. Beggs, Jonathan Deeks, Catharine M. L. West, Jean-Baptiste Cazier, Benjamin E. Willcox, Tanguy Y. Seiwert, Hisham Mehanna
Journal: Clinical Cancer Research (2019)

Intratumoral hypoxia and immunity have been correlated with patient outcome in various tumor settings. However, these factors are not currently considered for treatment selection in head and neck cancer (HNC) due to lack of validated biomarkers. Here we sought to develop a hypoxia-immune classifier with potential application in patient prognostication and prediction of response to targeted therapy.