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https://www.readbyqxmd.com/read/28453898/electrophysiological-effects-of-anthracyclines-in-adult-survivors-of-pediatric-malignancy
#1
Timothy M Markman, Kathryn Ruble, David Loeb, Allen Chen, Yiyi Zhang, Gary S Beasley, W Reid Thompson, Saman Nazarian
BACKGROUND: Anthracycline use is limited by cardiotoxicity, including arrhythmias and left ventricular (LV) dysfunction. We aim to characterize the association between electrophysiological changes and LV dysfunction. METHODS: A retrospective chart review was conducted, including all 147 pediatric cancer survivors at our institution over 18 years of age and treated with an anthracycline. One hundred thirty-four patients who had at least one electrocardiogram (ECG) and echocardiogram were analyzed...
April 28, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28449209/the-frequency-of-qtc-prolongation-among-pediatric-and-young-adult-patients-receiving-methadone-for-cancer-pain
#2
Kevin Madden, Minjeong Park, Diane Liu, Eduardo Bruera
INTRODUCTION: A prolonged corrected QT (QTc) interval in pediatric patients is defined as ≥470 msec. Methadone can cause a prolonged QTc interval that can lead to ventricular arrhythmias. The risk of methadone-induced prolongation of the QTc interval in children and young adults is unknown. The purpose of the study was to determine the frequency of QTc prolongation among pediatric and young adult patients with cancer pain on methadone treatment. METHODS: We retrospectively reviewed data for all patients on methadone during the study period...
April 27, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28444890/utilizing-pbpk-modeling-to-evaluate-the-potential-of-a-significant-drug-drug-interaction-between-clopidogrel-and-dasabuvir-a-scientific-perspective
#3
V Arya, P Zhao, K S Reynolds, P Mishra, I R Younis
Dasabuvir, a component of VIEKIRA PAK, is a substrate of CYP2C8 enzymes. Prescribing information for VIEKIRA PAK contraindicates gemfibrozil, a strong CYP2C8 inhibitor, because coadministration significantly increases dasabuvir exposures, which may increase the risk of QT prolongation. Clopidogrel may increase dasabuvir exposures primarily due to CYP2C8 inhibition by clopidogrel-acyl-β-D-glucuronide. This commentary outlines the US Food and Drug Administration (FDA) interdisciplinary review team's scientific perspective to address the potential for a significant drug-drug interaction (DDI) between clopidogrel and VIEKIRA PAK...
April 26, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28443483/aneurysm-size-and-the-windkessel-effect-an-analysis-of-contrast-intensity-in-digital-subtraction-angiography
#4
Ahmed E Hussein, Darian R Esfahani, Andreas Linninger, Fady T Charbel, Chih-Yang Hsu, Fady T Charbel, Ali Alaraj
Large cerebral aneurysms are considered more dangerous than their smaller counterparts, with higher risk of subarachnoid hemorrhage. Understanding the hemodynamics of large aneurysms has potential to predict their response to treatment. Digital subtraction angiography images for patients with intracranial aneurysms over a seven-year period were reviewed. Unruptured solitary aneurysms of the internal carotid artery (ICA) proximal to the terminus and posterior communicating artery were included. Contrast intensity over time was analyzed at the center of the M1 segment of the middle cerebral artery distal to the aneurysm and compared to the contralateral side...
January 1, 2017: Interventional Neuroradiology
https://www.readbyqxmd.com/read/28421417/estimation-of-qt-interval-prolongation-through-model-averaging
#5
Peter L Bonate
The current method to analyze concentration-QT interval data, which is based on predictions conditional on a best model, fails to take into account the uncertainty of the model. Previous studies have suggested that failure to take into account model uncertainty using a best model approach can result in confidence intervals that are overly optimistic and may be too narrow. Theoretically, more realistic estimates are obtained using model-averaging where the overall point estimate and confidence interval are a weighted-average from a set of candidate models, the weights of which are equal to each model's Akaike weight...
April 18, 2017: Journal of Pharmacokinetics and Pharmacodynamics
https://www.readbyqxmd.com/read/28416468/cardiac-transplantation-in-children-and-adolescents-with-long-qt-syndrome
#6
Angela M Kelle, J Martijn Bos, Susan P Etheridge, Bryan C Cannon, Randall M Bryant, Jonathan N Johnson, Michael J Ackerman
BACKGROUND: Long QT syndrome (LQTS) is a potentially lethal, yet highly treatable, cardiac channelopathy. Cardiac transplantation has been reported anecdotally for patients with severe LQTS refractory to standard therapies. OBJECTIVE: We evaluated the incidence and risk factors for cardiac transplantation among children evaluated and treated in an LQTS specialty center. METHODS: This was a retrospective review of 349 children with LQTS (mean age at diagnosis, 8...
April 14, 2017: Heart Rhythm: the Official Journal of the Heart Rhythm Society
https://www.readbyqxmd.com/read/28413954/computational-models-for-understanding-of-structure-function-and-pharmacology-of-the-cardiac-potassium-channel-kv11-1-herg
#7
Sören Wacker, Sergei Yu Noskov, Laura L Perissinotti
The rapid delayed rectifier current IKr is one of the major K+ currents involved into repolarization of the human cardiac action potential. Various inherited or drug-induced forms of the long QT syndrome (LQTS) in humans are linked to functional and structural modifications in the IKr conducting channels. IKr is carried by the potassium channel Kv11.1 encoded by the gene KCNH2 (commonly referred to as human ether-a-go-go-related gene or hERG) [1][2]. The first necessary step for predicting emergent drug effects on the heart is determining and modeling the binding thermodynamics and kinetics of primary and major off-target drug interactions with subcellular targets...
April 14, 2017: Current Topics in Medicinal Chemistry
https://www.readbyqxmd.com/read/28412158/lidocaine-attenuation-testing-an-in-vivo-investigation-of-putative-lqt3-associated-variants-in-the-scn5a-encoded-sodium-channel
#8
M D Heather N Anderson, J Martijn Bos, Jamie D Kapplinger, Jana M Meskill, Dan Ye, Michael J Ackerman
BACKGROUND: Long QT type 3 (LQT3) accounts for 5-10% of LQTS and results from gain-of-function mutations in the SCN5A-encoded sodium channel. Nearly 2% of healthy individuals host rare SCN5A variants of uncertain significance (VUS). Distinction of true LQT3-causative mutations from background genetic noise is essential. OBJECTIVE: This study was designed to assess the utility of the lidocaine attenuation test (LAT) in evaluating patients with possible LQT3. METHODS: We reviewed LAT results and medical records for 25 patients with a possible LQT3-associated SCN5A variant...
April 12, 2017: Heart Rhythm: the Official Journal of the Heart Rhythm Society
https://www.readbyqxmd.com/read/28408211/cardiac-voltage-gated-ion-channels-in-safety-pharmacology-review-of-the-landscape-leading-to-the-cipa-initiative
#9
REVIEW
Hai Huang, Michael K Pugsley, Bernard Fermini, Michael J Curtis, John Koerner, Michael Accardi, Simon Authier
Voltage gated ion channels are central in defining the fundamental properties of the ventricular cardiac action potential (AP), and are also involved in the development of drug-induced arrhythmias. Many drugs can inhibit cardiac ion currents, including the Na(+) current (INa), L-type Ca(2+) current (Ica-L), and K(+) currents (Ito, IK1, IKs, and IKr), and thereby affect AP properties in a manner that can trigger or sustain cardiac arrhythmias. Since publication of ICH E14 and S7B over a decade ago, there has been a focus on drug effects on QT prolongation clinically, and on the rapidly activating delayed rectifier current (IKr), nonclinically, for evaluation of proarrhythmic risk...
April 11, 2017: Journal of Pharmacological and Toxicological Methods
https://www.readbyqxmd.com/read/28407402/cirrhotic-cardiomyopathy-implications-for-liver-transplantation
#10
REVIEW
Hongqun Liu, Saumya Jayakumar, Mouhieddin Traboulsi, Samuel S Lee
The majority of the patients on a waiting list for liver transplantation have end-stage liver disease. Due to the marked peripheral vasodilatation of end stage cirrhosis that masks a latent myocardial dysfunction, cardiac abnormalities in the resting state are usually subclinical and escape the attention of physicians. However, when challenged, the systolic and diastolic contractile responses are attenuated. In addition to these contractile abnormalities, morphological changes such as enlargement or hypertrophy of cardiac chambers and electrophysiological repolarization changes including a prolonged QT interval can be observed...
April 13, 2017: Liver Transplantation
https://www.readbyqxmd.com/read/28382321/electrophysiological-mechanisms-of-long-and-short-qt-syndromes
#11
REVIEW
Gary Tse, Yin Wah Fiona Chan, Wendy Keung, Bryan P Yan
The QT interval on the human electrocardiogram is normally in the order of 450 ms, and reflects the summated durations of action potential (AP) depolarization and repolarization of ventricular myocytes. Both prolongation and shortening in the QT interval have been associated with ventricular tachy-arrhythmias, which predispose affected individuals to sudden cardiac death. In this article, the molecular determinants of the AP duration and the causes of long and short QT syndromes (LQTS and SQTS) are explored...
March 2017: IJC Heart & Vasculature
https://www.readbyqxmd.com/read/28382197/attention-deficit-hyperactivity-disorder-medication-use-factors-involved-in-prescribing-safety-aspects-and-outcomes
#12
REVIEW
Jose Martinez-Raga, Amparo Ferreros, Carlos Knecht, Raquel de Alvaro, Eloisa Carabal
While treatment of patients with attention-deficit hyperactivity disorder (ADHD) is based on a multimodal approach that combines medication with specific psychological interventions, pharmacotherapy alone is generally considered an essential and cost-effective element. This paper aims to comprehensively and critically review factors involved in prescribing and medication use in individuals diagnosed with ADHD, focusing on the difficulties facing patients with ADHD seeking treatment, as well as the safety and tolerability aspects of ADHD pharmacotherapies, with particular attention on the cardiovascular adverse events and the potential risk of misuse or diversion of ADHD medications...
March 2017: Therapeutic Advances in Drug Safety
https://www.readbyqxmd.com/read/28371864/a-multicentre-study-of-patients-with-timothy-syndrome
#13
Mark A Walsh, Christian Turner, Katherine W Timothy, Neil Seller, Dominic L Hares, Andrew F James, Jules C Hancox, Orhan Uzun, Dean Boyce, Alan G Stuart, Paul Brennan, Caroline Sarton, Karen McGuire, Ruth A Newbury-Ecob, Karen Mcleod
Aims: Timothy syndrome (TS) is an extremely rare multisystem disorder characterized by marked QT prolongation, syndactyly, seizures, behavioural abnormalities, immunodeficiency, and hypoglycaemia. The aim of this study was to categorize the phenotypes and examine the outcomes of patients with TS. Methods and results: All patients diagnosed with TS in the United Kingdom over a 24-year period were reviewed. Fifteen centres in the British Congenital Arrhythmia Group network were contacted to partake in the study...
March 24, 2017: Europace: European Pacing, Arrhythmias, and Cardiac Electrophysiology
https://www.readbyqxmd.com/read/28356904/clinical-utility-of-patiromer-sodium-zirconium-cyclosilicate-and-sodium-polystyrene-sulfonate-for-the-treatment-of-hyperkalemia-an-evidence-based-review
#14
REVIEW
Mario V Beccari, Calvin J Meaney
INTRODUCTION: Hyperkalemia is a serious medical condition that often manifests in patients with chronic kidney disease and heart failure. Renin-angiotensin-aldosterone system inhibitors are known to improve outcomes in these disease states but can also cause drug-induced hyperkalemia. New therapeutic options exist for managing hyperkalemia in these patients which warrant evidence-based evaluation. AIM: The objective of this article was to review the efficacy and safety evidence for patiromer, sodium zirconium cyclosilicate (ZS9), and sodium polystyrene sulfonate (SPS) for the treatment of hyperkalemia...
2017: Core Evidence
https://www.readbyqxmd.com/read/28345744/eleven-years-of-children-methadone-poisoning-in-a-referral-center-a-review-of-453-cases
#15
Hossein Hassanian-Moghaddam, Masumeh Hakiminejhad, Fariba Farnaghi, Amirhossein Mirafzal, Nasim Zamani, Ali Kabir
OBJECTIVES: Methadone can be fatal due to respiratory failure even in little doses. This study aimed to evaluate the possible risk factors of death and/or intubation in methadone-poisoned children of 12 years or younger. DESIGN: Retrospective routine database study. SETTING: The only tertiary hospital for children poisoning in Tehran. PATIENTS: Four hundred fifty-three methadone-poisoned patients aged 12 or younger were studied between 2001 and 2012...
January 2017: Journal of Opioid Management
https://www.readbyqxmd.com/read/28343764/channelopathies-genetic-testing-and-risk-stratification
#16
Arthur A M Wilde, Ahmad Amin
The cardiac channelopathies are a group of diseases with (disease-) specific electrocardiographic (ECG) characteristics and a disease-specific risk of sudden cardiac death (SCD). This group includes the Long QT Syndromes (LQTS), Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT), Brugada Syndrome (BrS), Short QT Syndromes (SQTS), and Early Repolarization Syndrome (ERS). In the past 2 decades the genetic basis for these disease entities has largely been unraveled and that, together with the identification of the genetic basis of the cardiomyopathies, has paved the way for the complete new field of Cardiogenetics...
March 18, 2017: International Journal of Cardiology
https://www.readbyqxmd.com/read/28340164/denervation-of-the-extrinsic-cardiac-sympathetic-nervous-system-as-a-treatment-modality-for-arrhythmia
#17
Chance M Witt, Luciana Bolona, Michelle O Kinney, Christopher Moir, Michael J Ackerman, Suraj Kapa, Samuel J Asirvatham, Christopher J McLeod
Denervation of the extrinsic cardiac sympathetic nervous system is a method of altering the autonomic tone experienced by the heart and vasculature. It has been studied and employed as a therapy for cardiac disease for decades. Currently, there is a high level of interest in using cardiac denervation for treatment of arrhythmias. This review describes the anatomy and physiology of the cardiac autonomic nervous system followed by a discussion of the mechanistic studies which provide a basis for the therapeutic use of sympathetic denervation...
March 10, 2017: Europace: European Pacing, Arrhythmias, and Cardiac Electrophysiology
https://www.readbyqxmd.com/read/28334543/-functional-impact-of-herg-from-physiological-role-to-target-of-anticancer-therapy
#18
Júlia Šatková, Markéta Bébarová
The human ether-à-go-go related gene (hERG; officially designated as KCNH2) encodes the structure of protein forming α-subunit of voltage-gated ion channel which conducts the rapid component of delayed rectifier K+ current (IKr). This current plays an important role namely in the cardiac repolarization. Mutations in hERG result in inherited arrhythmogenic syndromes characterized by a lenghtening or shortening of QT interval on the electrocardiogram and by an increased occurrence of life-threatening arrhythmias...
2017: Vnitr̆ní Lékar̆ství
https://www.readbyqxmd.com/read/28323171/acquired-long-qt-syndrome-in-hospitalized-patients
#19
Haixu Yu, Li Zhang, Jinqiu Liu, Ying Liu, Peter R Kowey, Yanli Zhang, Yue Chen, Yushan Wei, Lianjun Gao, Huihua Li, Jie Du, Yunlong Xia
BACKGROUND: Acquired long QT syndrome (ALQTS) has long been overlooked in clinical practice. Recent studies reported that severe ALQTS (QTc ≥500 ms) in hospitalized patients is associated with increased all-cause mortality. OBJECTIVE: We aimed to determine the role of ALQTS in the clinical outcomes of hospitalized patients. METHODS: Electronic medical records were reviewed to identify severe ALQTS in hospitalized patients in a single study center from 9-1-2013 to 2-28-2014...
March 16, 2017: Heart Rhythm: the Official Journal of the Heart Rhythm Society
https://www.readbyqxmd.com/read/28318666/temporary-removal-cardiac-sympathetic-denervation-100-years-later-jonnesco-would-have-never-believed-it
#20
Peter J Schwartz, Gaetano M De Ferrari, Luigi Pugliese
The publisher regrets that this article has been temporarily removed. A replacement will appear as soon as possible in which the reason for the removal of the article will be specified, or the article will be reinstated. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy.
March 8, 2017: International Journal of Cardiology
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