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https://www.readbyqxmd.com/read/27899938/detailed-analysis-of-the-impact-of-age-on-the-qt-interval
#1
Simon W Rabkin, Xin-Bo Justin Cheng, Darby Js Thompson
OBJECTIVE: To analyze the effect of age on the ECG QT interval, an important predictor of cardiovascular mortality and drug-induced cardiac arrhythmias, and determine whether QT-heart rate correction formulae (QTc) have differential relationships with age and sex. METHODS: Data were examined from the US National Health and Nutrition Examination Survey (NHANES) II and III, civilian population aged 25 to 90 years. QT weighted means and standard deviations were calculated for all ages...
September 2016: Journal of Geriatric Cardiology: JGC
https://www.readbyqxmd.com/read/27896662/investigating-the-additive-interaction-of-qt-prolonging-drugs-in-older-people-using-claims-data
#2
Andreas D Meid, Anna von Medem, Dirk Heider, Jürgen-Bernhard Adler, Christian Günster, Hanna M Seidling, Renate Quinzler, Hans-Helmut König, Walter E Haefeli
INTRODUCTION: Drugs that potentially prolong the QT interval carry the risk of life-threatening Torsades de pointes (TdP) ventricular arrhythmia. OBJECTIVE: The objective of this study was to investigate the potential additive risk for ventricular arrhythmia with concomitant prescriptions of QT-prolonging drugs. METHODS: Claims data for persons aged ≥65 years between 2010 and 2012 in Germany were analyzed and all cases hospitalized for ventricular arrhythmia were selected...
November 29, 2016: Drug Safety: An International Journal of Medical Toxicology and Drug Experience
https://www.readbyqxmd.com/read/27878411/reckless-administration-of-qt-interval-prolonging-agents-in-elderly-patients-with-drug-induced-torsade-de-pointes
#3
Galia Jackobson, Narin Nard Carmel, Dor Lotan, Anjelika Kremer, Dan Justo
A systematic review was conducted for all published case reports on drug-induced torsade de pointes (TdP) in elderly (≥80 years) patients to study if the administration of the offending agent was reckless. Overall, 61 reports on drug-induced TdP in patients aged 80-97 years were included in the analysis. Non-modifiable risk factors for drug-induced TdP (e.g. acute coronary syndrome, female gender and congestive heart failure), modifiable risk factors (e.g. hypokalemia, severe hypomagnesemia and digitalis toxicity) and reckless administration of a QT interval-prolonging agent (e...
November 22, 2016: Zeitschrift Für Gerontologie und Geriatrie
https://www.readbyqxmd.com/read/27875065/evaluation-of-a-new-solid-non-aqueous-self-double-emulsifying-drug-delivery-system-for-topical-application-of-quercetin
#4
Qiang Wang, Caibiao Hu, Hong Zhang, Yali Zhang, Tian Liu, Airui Qian, Qiang Xia
This study aimed at the evaluation of a new solid non-aqueous self-double-emulsifying drug delivery system (SDEDDS) for topical application of quercetin. The new formulation was prepared through two-step emulsification process and could spontaneously form oil-in-oil-in-water (O/O/W) double emulsions after dilution with aqueous medium, with inner oil phase mainly containing the drug. Solid state characterization was performed by DSC and X-ray powder diffraction. Furthermore, the optimized QT-SDEDDS displayed sustained release profile and was found to be stable up to 30 days under 4°C and 25°C...
November 22, 2016: Journal of Microencapsulation
https://www.readbyqxmd.com/read/27868350/an-elderly-jervell-and-lange-nielsen-patient-heterozygous-compound-for-two-new-kcnq1-mutations
#5
Eliecer Coto, Francisco J García-Fernández, David Calvo, Ricardo Salgado-Aranda, Javier Martín-González, Belén Alonso, Sara Iglesias, Juan Gómez
We present the case of a 66-year-old female with early onset deafness and seizures, who was diagnosed with epilepsy at the age of 2 years. She received antiepileptic drugs and was free of syncope episodes for 32 years. After a syncope at the age of 34, the ECG was characteristic of long-QT syndrome and was treated with antiarrhythmic drugs. Sequencing of the KCNQ1 gene identified two novel KCNQ1 variants interpreted to be pathogenic, and the patient was finally diagnosed with Jervell and Lange-Nielsen syndrome...
November 21, 2016: American Journal of Medical Genetics. Part A
https://www.readbyqxmd.com/read/27866063/anticancer-therapy-induced-vascular-toxicity-vegf-inhibition-and-beyond
#6
REVIEW
Daniela Di Lisi, Rosalinda Madonna, Concetta Zito, Enrico Bronte, Giuseppe Badalamenti, Paolo Parrella, Ines Monte, Carlo Gabriele Tocchetti, Antonio Russo, Giuseppina Novo
Cardiotoxicity induced by chemotherapeutic agents and radiotherapy is a growing problem. In recent years, an increasing number of new drugs with targeted action have been designed. These molecules, such as monoclonal antibodies and tyrosine kinase inhibitors, can cause different type of toxicities compared to traditional chemotherapy. However, they can also cause cardiac complications such as heart failure, arterial hypertension, QT interval prolongation and arrhythmias. Currently, a field of intense research is the vascular toxicity induced by new biologic drugs, particularly those which inhibit vascular endothelial growth factor (VEGF) and its receptor (VEGF-R) and other tyrosine kinases...
November 9, 2016: International Journal of Cardiology
https://www.readbyqxmd.com/read/27864903/long-term-monitoring-of-cardiorespiratory-patterns-in-drug-resistant-epilepsy
#7
Daniel M Goldenholz, Amanda Kuhn, Alison Austermuehle, Martin Bachler, Christopher Mayer, Siegfried Wassertheurer, Sara K Inati, William H Theodore
OBJECTIVE: Sudden unexplained death in epilepsy (SUDEP) during inpatient electroencephalography (EEG) monitoring has been a rare but potentially preventable event, with associated cardiopulmonary markers. To date, no systematic evaluation of alarm settings for a continuous pulse oximeter (SpO2 ) has been performed. In addition, evaluation of the interrelationship between the ictal and interictal states for cardiopulmonary measures has not been reported. METHODS: Patients with epilepsy were monitored using video-EEG, SpO2 , and electrocardiography (ECG)...
November 16, 2016: Epilepsia
https://www.readbyqxmd.com/read/27863364/interactions-of-digitalis-and-class-iii-antiarrhythmic-drugs-amiodarone-versus-dronedarone
#8
Gerrit Frommeyer, Dirk Puckhaber, Christian Ellermann, Dirk G Dechering, Simon Kochhäuser, Patrick Leitz, Florian Reinke, Lars Eckardt
BACKGROUND: A post hoc analysis of the PALLAS trial suggested possible interactions of dronedarone and digitalis glycosides. The aim of the present study was to compare the effects dronedarone or amiodarone in combination with digitalis glycosides. METHODS AND RESULTS: Eleven female rabbits underwent chronic oral treatment with amiodarone (50mg/kg/d for 6weeks). Ten rabbits were treated with dronedarone (50mg/kg/d for 6weeks). Ten rabbits were used as controls. Hearts were isolated and Langendorff-perfused...
November 7, 2016: International Journal of Cardiology
https://www.readbyqxmd.com/read/27862994/colchicine-increases-ventricular-vulnerability-in-an-experimental-whole-heart-model
#9
Gerrit Frommeyer, Julius Krawczyk, Dirk G Dechering, Simon Kochhäuser, Patrick Leitz, Michael Fehr, Lars Eckardt
The traditional gout medication colchicine has been reported to effectively prevent atrial fibrillation recurrence after atrial fibrillation ablation or cardiac surgery in a few clinical trials. Severe adverse events have not yet been reported. The aim of the present study was to assess possible direct electrophysiological effects in an experimental whole-heart model. Ten rabbit hearts were isolated and Langendorff-perfused. Thereafter, colchicine was administered in 2 concentrations (1μM and 3μM). Eight endo- and epicardial monophasic action potentials and a 12-lead ECG showed a stable QT interval and action potential duration during colchicine infusion...
November 11, 2016: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/27861363/efficacy-safety-and-tolerability-of-a-24-month-treatment-regimen-including-delamanid-in-a-child-with-extensively-drug-resistant-tuberculosis-a-case-report-and-review-of-the-literature
#10
Susanna Esposito, Samantha Bosis, Marina Tadolini, Sonia Bianchini, Giovanni Battista Migliori, Nicola Principi
RATIONAL: Multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis (TB) are emerging problems in several countries. These infections require long and expensive treatment regimens. Recently, 2 new drugs, bedaquiline and delamanid, have been approved in several countries for use in adults with severe, difficult-to-treat MDR-TB, and it has been suggested that they could also be administered to children with MDR-TB and limited treatment options. However, no study has been completed on their efficacy...
November 2016: Medicine (Baltimore)
https://www.readbyqxmd.com/read/27861123/tecrl-a-new-life-threatening-inherited-arrhythmia-gene-associated-with-overlapping-clinical-features-of-both-lqts-and-cpvt
#11
Harsha D Devalla, Roselle Gélinas, Elhadi H Aburawi, Abdelaziz Beqqali, Philippe Goyette, Christian Freund, Marie-A Chaix, Rafik Tadros, Hui Jiang, Antony Le Béchec, Jantine J Monshouwer-Kloots, Tom Zwetsloot, Georgios Kosmidis, Frédéric Latour, Azadeh Alikashani, Maaike Hoekstra, Jurg Schlaepfer, Christine L Mummery, Brian Stevenson, Zoltan Kutalik, Antoine Af de Vries, Léna Rivard, Arthur Am Wilde, Mario Talajic, Arie O Verkerk, Lihadh Al-Gazali, John D Rioux, Zahurul A Bhuiyan, Robert Passier
Genetic causes of many familial arrhythmia syndromes remain elusive. In this study, whole-exome sequencing (WES) was carried out on patients from three different families that presented with life-threatening arrhythmias and high risk of sudden cardiac death (SCD). Two French Canadian probands carried identical homozygous rare variant in TECRL gene (p.Arg196Gln), which encodes the trans-2,3-enoyl-CoA reductase-like protein. Both patients had cardiac arrest, stress-induced atrial and ventricular tachycardia, and QT prolongation on adrenergic stimulation...
December 1, 2016: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/27856406/efficacy-and-safety-of-high-dose-ivermectin-for-reducing-malaria-transmission-ivermal-protocol-for-a-double-blind-randomized-placebo-controlled-dose-finding-trial-in-western-kenya
#12
Menno R Smit, Eric Ochomo, Ghaith Aljayyoussi, Titus Kwambai, Bernard Abong'o, Nabie Bayoh, John Gimnig, Aaron Samuels, Meghna Desai, Penelope A Phillips-Howard, Simon Kariuki, Duolao Wang, Steve Ward, Feiko O Ter Kuile
BACKGROUND: Innovative approaches are needed to complement existing tools for malaria elimination. Ivermectin is a broad spectrum antiparasitic endectocide clinically used for onchocerciasis and lymphatic filariasis control at single doses of 150 to 200 mcg/kg. It also shortens the lifespan of mosquitoes that feed on individuals recently treated with ivermectin. However, the effect after a 150 to 200 mcg/kg oral dose is short-lived (6 to 11 days). Modeling suggests higher doses, which prolong the mosquitocidal effects, are needed to make a significant contribution to malaria elimination...
November 17, 2016: JMIR Research Protocols
https://www.readbyqxmd.com/read/27829538/pharmacokinetic-drug-interaction-study-between-overactive-bladder-drugs-mirabegron-and-tolterodine-in-japanese-healthy-postmenopausal-females
#13
Yuki Nomura, Hiromi Iitsuka, Junko Toyoshima, Kentaro Kuroishi, Toshifumi Hatta, Atsunori Kaibara, Masataka Katashima, Selina Moy, Taiji Sawamoto
Mirabegron, the first selective β3-adrenoceptor agonist for the treatment of overactive bladder (OAB), inhibits cytochrome P450 isozyme CYP2D6. This study was performed in Japanese healthy postmenopausal female volunteers to assess any pharmacokinetic drug interaction between mirabegron and tolterodine, another OAB drug and a sensitive substrate of CYP2D6. Tolterodine 4 mg was orally administered from Days 1-7 and co-administered with mirabegron 50 mg from Days 8-14. Mirabegron 50 mg increased maximum concentration (Cmax) and area under the concentration-time curve from zero to 24 h after dosing (AUC24h) of tolterodine by 2...
August 18, 2016: Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/27826330/management-of-patients-with-long-qt-syndrome
#14
REVIEW
Yongkeun Cho
Long QT syndrome (LQTS) is a rare cardiac channelopathy associated with syncope and sudden death due to torsades de pointes and ventricular fibrillation. Syncope and sudden death are frequently associated with physical and emotional stress. Management of patients with LQTS consists of life-style modification, β-blockers, left cardiac sympathetic denervation (LCSD), and implantable cardioverter-defibrillator (ICD) implantation. Prohibition of competitive exercise and avoidance of QT-prolonging drugs are important issues in life-style modification...
November 2016: Korean Circulation Journal
https://www.readbyqxmd.com/read/27816319/contribution-of-a-kcnh2-variant-in-genotyped-long-qt-syndrome-romano-ward-syndrome-under-double-mutations-and-acquired-long-qt-syndrome-under-heterozygote
#15
Yusuke Fujii, Yuichi Matsumoto, Kenshi Hayashi, Wei-Guang Ding, Yukinori Tomita, Daisuke Fukumoto, Yuko Wada, Mari Ichikawa, Keiko Sonoda, Junichi Ozawa, Takeru Makiyama, Seiko Ohno, Masakazu Yamagishi, Hiroshi Matsuura, Minoru Horie, Hideki Itoh
BACKGROUND: Long QT syndrome (LQTS) presents two clinical phenotypes, congenital and acquired forms. This study aims to evaluate the genetic contribution of a KCNH2 variant for the two LQTS phenotypes. METHODS: From 1996 to 2014, genetic screening for LQTS probands was performed for five major genes: KCNQ1, KCNH2, SCN5A, KCNE1, and KCNE2 and 389 probands were found to be mutation carriers. We analyzed the clinical phenotypes of p.His492Tyr carriers in KCNH2. RESULTS: Heterozygous p...
November 2, 2016: Journal of Cardiology
https://www.readbyqxmd.com/read/27814325/fatal-cardiac-arrest-in-2-children-possible-role-of-ondansetron
#16
Scott M Brenner, Jenny Boucher
INTRODUCTION: Ondansetron is commonly used to treat vomiting in gastroenteritis, but has a United States Food and Drug Administration black box warning for risk of Q wave to T wave time interval (QT) prolongation. We report 2 pediatric cases of fatal refractory cardiac arrest after administration of ondansetron. CASES: A 10-year-old previously healthy boy presented to the emergency room with gastroenteritis symptoms. After intravenous fluids, morphine, antibiotics, and 2 doses of ondansetron, the patient became unresponsive with agonal respirations and a wide complex tachycardia consistent with ventricular tachycardia...
November 2016: Pediatric Emergency Care
https://www.readbyqxmd.com/read/27813448/early-assessment-of-pro-arrhythmic-risk-of-drugs-using-the-in-vitro-data-and-single-cell-based-in-silico-models-proof-of-concept
#17
Mitra Abbasi, Ben G Small, Nikunjkumar Patel, Masoud Jamei, Sebastian Polak
BACKGROUND AND PURPOSE: To determine the predictive performance of in silico models using drug-specific preclinical cardiac electrophysiology data to investigate drug-induced arrhythmia risk (e.g. Torsade de Pointes (TdP)) in virtual human subjects. EXPERIMENTAL APPROACH: To assess drug proarrhythmic risk, we used a set of in vitro electrophysiological measurements describing ion channel inhibition triggered by the investigated drugs. The Cardiac Safety Simulator (CSS V2...
November 4, 2016: Toxicology Mechanisms and Methods
https://www.readbyqxmd.com/read/27813438/targeting-histone-deacetylases-in-t-cell-lymphoma
#18
Alison J Moskowitz, Steven M Horwitz
Histone deacetylase inhibitors (HDACi) are epigenetic modifiers with single-agent activity in patients with cutaneous and peripheral T-cell lymphoma (CTCL, PTCL). The mechanisms for this preferential activity remain unclear, and although some would term this as 'class effect,' there are differences in efficacy and safety, likely a result of the varying chemical structures/classes, histone and non-histone targets, potencies, and clinical dosing for each. Three HDACi have single-agent approval in relapsed/refractory TCL in the United States: romidepsin in CTCL and PTCL, vorinostat in CTCL, and belinostat in PTCL...
November 4, 2016: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/27798210/solithromycin-a-novel-macrolide-does-not-prolong-cardiac-repolarization-a-randomized-three-way-crossover-study-in-healthy-subjects
#19
Borje Darpo, Philip T Sager, Prabhavathi Fernandes, Brian D Jamieson, Kara Keedy, Meijian Zhou, David Oldach
BACKGROUND: Macrolide antibiotics may cause QT prolongation. OBJECTIVES: To study the QT effect of a novel macrolide, solithromycin. METHODS: This was a thorough QT study with a three-way crossover design performed in healthy male and female subjects to evaluate the ECG effects of a novel macrolide, solithromycin. Forty-eight subjects were randomized to receive 800 mg of intravenous (iv) solithromycin, 400 mg of oral moxifloxacin and placebo in three separate treatment periods...
October 26, 2016: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/27785856/minimal-t-wave-representation-and-its-use-in-the-assessment-of-drug-arrhythmogenicity
#20
Saeed Shakibfar, Claus Graff, Jørgen K Kanters, Jimmi Nielsen, Samuel Schmidt, Johannes J Struijk
BACKGROUND: Recently, numerous models and techniques have been developed for analyzing and extracting features from the T wave which could be used as biomarkers for drug-induced abnormalities. The majority of these techniques and algorithms use features that determine readily apparent characteristics of the T wave, such as duration, area, amplitude, and slopes. METHODS: In the present work the T wave was down-sampled to a minimal rate, such that a good reconstruction was still possible...
October 27, 2016: Annals of Noninvasive Electrocardiology
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