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https://www.readbyqxmd.com/read/28819760/effect-of-alisertib-an-investigational-aurora-a-kinase-inhibitor-on-the-qtc-interval-in-patients-with-advanced-malignancies
#1
Xiaofei Zhou, John Nemunaitis, Shubham Pant, Todd M Bauer, Manish Patel, John Sarantopoulos, A Craig Lockhart, Daniel Goodman, Dirk Huebner, Diane R Mould, Karthik Venkatakrishnan
Aims A primary objective of this study was to investigate the effect of single and multiple doses of alisertib, an investigational Aurora A kinase inhibitor, on the QTc interval in patients with advanced malignancies. The dose regimen used was the maximum tolerated dose which was also the recommended phase 3 dose (50 mg twice daily [BID] for 7 days in 21-day cycles). Methods Patients received a single dose of alisertib (50 mg) on Day 1, and multiple doses of alisertib (50 mg BID) on Days 4 through to the morning of Day 10 of the first cycle of treatment...
August 18, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28817488/risk-management-of-hospitalized-psychiatric-patients-taking-multiple-qtc-prolonging-drugs
#2
Eline Vandael, Bert Vandenberk, Rik Willems, Johan Reyntens, Joris Vandenberghe, Veerle Foulon
PURPOSE/BACKGROUND: Drug-related QTc prolongation has been linked with Torsade de Pointes and sudden cardiac death. The objective of this study was to investigate the impact of starting an additional QTc-prolonging drug on the QTc interval of psychiatric inpatients. METHODS: An observational study was performed between May 2011 and December 2014 in 6 Belgian psychiatric hospitals. Inpatients who were already taking 1 QTc-prolonging drug or more could be included in the study when an additional QTc-prolonging drug was started...
August 16, 2017: Journal of Clinical Psychopharmacology
https://www.readbyqxmd.com/read/28803378/qt-interval-prolongation-in-hospitalized-patients-on-cardiology-wards-a-prospective-observational-study
#3
Qasim Khan, Mohammad Ismail, Iqbal Haider, Inam Ul Haq, Sidra Noor
PURPOSE: Prolonged QT interval may lead to a lethal form of arrhythmia, torsades de pointes (TdP), which is associated with cardiovascular mortality. Therefore, we aimed to identify prevalence of QT interval prolongation, compare clinical characteristics of patients with normal and prolonged QT interval, and identify predictors of QT interval prolongation. METHODS: A prospective observational study was conducted in cardiology wards of two teaching hospitals in Pakistan...
August 12, 2017: European Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28800628/genome-wide-analysis-of-sotalol-induced-ikr-inhibition-during-ventricular-repolarization-generepol-study-lack-of-common-variants-with-large-effect-sizes
#4
Joe-Elie Salem, Marine Germain, Jean-Sébastien Hulot, Pascal Voiriot, Bruno Lebourgeois, Jean Waldura, David-Alexandre Tregouet, Beny Charbit, Christian Funck-Brentano
Many drugs used for non-cardiovascular and cardiovascular purposes, such as sotalol, have the side effect of prolonging cardiac repolarization, which can trigger life-threatening cardiac arrhythmias by inhibiting the potassium-channel IKr (KCNH2). On the electrocardiogram (ECG), IKr inhibition induces an increase in QTc and Tpeak-Tend (TpTe) interval and a decrease of T wave maximal amplitude (TAmp). These changes vary markedly between subjects, suggesting the existence of predisposing genetic factors. 990 healthy individuals, prospectively challenged with an oral 80mg sotalol dose, were monitored for changes in ventricular repolarization on ECG between baseline and 3 hours post dosing...
2017: PloS One
https://www.readbyqxmd.com/read/28799823/lack-of-qt-prolongation-for-2-o-methoxyethyl-modified-antisense-oligonucleotides-based-on-retrospective-exposure-response-analysis-of-ten-phase-1-dose-escalation-placebo-controlled-studies-in-healthy-subjects
#5
Rosie Z Yu, Rudy Gunawan, Richard S Geary, Steven G Hughes, Scott P Henry, Yanfeng Wang
The potential of QT prolongation of ten 2'-O-methoxyethyl-modified (2'-MOE) antisense oligonucleotides (ASOs) was evaluated retrospectively via exposure/response (ER) analysis using data from Phase 1 clinical studies in healthy subjects. All Phase 1 studies were double-blind, placebo-controlled, single and multiple ascending dose studies designed to assess the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics of the ASOs in healthy subjects. The active doses in these studies ranged from 50 to 450 mg administered by subcutaneous (SC) injection in single and multiple ascending dose cohorts...
August 11, 2017: Nucleic Acid Therapeutics
https://www.readbyqxmd.com/read/28797793/bpc-157-counteracts-qtc-prolongation-induced-by-haloperidol-fluphenazine-clozapine-olanzapine-quetiapine-sulpiride-and-metoclopramide-in-rats
#6
Dean Strinic, Zeljka Belosic Halle, Kresimir Luetic, Ana Nedic, Igor Petrovic, Mario Sucic, Gordana Zivanovic Posilovic, Dijana Balenovic, Sanja Strbe, Mario Udovicic, Domagoj Drmic, Mirjana Stupnisek, Martina Lovric Bencic, Sven Seiwerth, Predrag Sikiric
AIM: Commonly, neuroleptics and prokinetics induce a prolonged QTc interval. In this study, stable gastric pentadecapeptide BPC 157 counteracts the prolongation of the QTc interval in Wistar rats that underwent daily administration of dopamine neuroleptics or prokinetics. Previously, in rats and mice, BPC 157 counteracted neuroleptic-induced catalepsy and gastric ulcers. MAIN METHODS: To counteract neuroleptic- or prokinetic-induced prolongation of the QTc interval, rats were given a BPC 157 regimen once daily over seven days (10μg, 10ng/kg ip) immediately after each administrations of haloperidol (0...
August 7, 2017: Life Sciences
https://www.readbyqxmd.com/read/28794082/loss-of-function-kcne2-variants-true-monogenic-culprits-of-long-qt-syndrome-or-proarrhythmic-variants-requiring-secondary-provocation
#7
Jason D Roberts, Andrew D Krahn, Michael J Ackerman, Ram K Rohatgi, Arthur J Moss, Babak Nazer, Rafik Tadros, Brenda Gerull, Shubhayan Sanatani, Yanushi D Wijeyeratne, Alban-Elouen Baruteau, Alison R Muir, Benjamin Pang, Julia Cadrin-Tourigny, Mario Talajic, Lena Rivard, David J Tester, Taylor Liu, Isaac R Whitman, Julianne Wojciak, Susan Conacher, Lorne J Gula, Peter Leong-Sit, Jaimie Manlucu, Martin S Green, Robert Hamilton, Jeff S Healey, Coeli M Lopes, Elijah R Behr, Arthur A Wilde, Michael H Gollob, Melvin M Scheinman
BACKGROUND: Insight into type 6 long-QT syndrome (LQT6), stemming from mutations in the KCNE2-encoded voltage-gated channel β-subunit, is limited. We sought to further characterize its clinical phenotype. METHODS AND RESULTS: Individuals with reported pathogenic KCNE2 mutations identified during arrhythmia evaluation were collected from inherited arrhythmia clinics and the Rochester long-QT syndrome (LQTS) registry. Previously reported LQT6 cases were identified through a search of the MEDLINE database...
August 2017: Circulation. Arrhythmia and Electrophysiology
https://www.readbyqxmd.com/read/28793044/reproducibility-and-reliability-of-qtc-and-qtcd-measurements-and-their-relationships-with-left-ventricular-hypertrophy-in-hemodialysis-patients
#8
Maria Angélica Gonçalves Alonso, Valentine de Almeida Costa de Castro Lima, Maria Angela Magalhães de Queiroz Carreira, Jocemir Ronaldo Lugon
Background: Left ventricular hypertrophy (LVH) is very common in hemodialysis patients and an independent risk factor for mortality in this population. The myocardial remodeling underlying the LVH can affect ventricular repolarization causing abnormalities in QT interval. Objective: to evaluate the reproducibility and reliability of measurements of corrected QT interval (QTc) and its dispersion (QTcd) and correlate these parameters with LVH in hemodialysis patients...
August 7, 2017: Arquivos Brasileiros de Cardiologia
https://www.readbyqxmd.com/read/28791782/predicting-short-term-risk-of-arrhythmia-among-patients-with-syncope-the-canadian-syncope-arrhythmia-risk-score
#9
Venkatesh Thiruganasambandamoorthy, Ian G Stiell, Marco L A Sivilotti, Brian H Rowe, Muhammad Mukarram, Kirtana Arcot, Kenneth Kwong, Andrew D McRae, George A Wells, Monica Taljaard
BACKGROUND: Syncope can be caused by serious occult arrhythmias not evident during initial emergency department (ED) evaluation. We sought to develop a risk-tool for predicting 30-day arrhythmia or death after ED disposition. METHODS: We conducted a multicenter prospective cohort study at six tertiary-care EDs and included adults (≥16 years) with syncope. We collected standardized variables from clinical evaluation, and investigations including ECG and troponin at index presentation...
August 9, 2017: Academic Emergency Medicine: Official Journal of the Society for Academic Emergency Medicine
https://www.readbyqxmd.com/read/28791627/influence-of-intravenous-administration-of-the-antipsychotic-drug-benperidol-on-the-qt-interval
#10
Alexander Schmidt, Peter Fischer, Beate Wally, Joachim Scharfetter
A group effect is generally assumed regarding the prolongation of the QT interval through butyrophenone antipsychotics like haloperidol. Consequently intravenous administration of benperidol is seen critically notwithstanding sparse evidence; thus benperidol and haloperidol were compared regarding their cardiac risk of prolonging the QT interval when administered intravenously for acute sedation of psychotic patients. The QT interval was measured by a 12-lead ECG. For the correction of QT values Bazett's formula was used...
August 8, 2017: Neuropsychiatrie: Klinik, Diagnostik, Therapie und Rehabilitation
https://www.readbyqxmd.com/read/28783871/cardiac-safety-of-ozanimod-a-novel-sphingosine-1-phosphate-receptor-modulator-results-of-a-thorough-qt-qtc-study
#11
Jonathan Q Tran, Jeffrey P Hartung, Allan D Olson, Boaz Mendzelevski, Gregg A Timony, Marcus F Boehm, Robert J Peach, Sheila Gujrathi, Paul A Frohna
Ozanimod is a novel, selective, oral sphingosine-1-phosphate (1 and 5) receptor modulator in development for multiple sclerosis and inflammatory bowel disease. This randomized, double-blind, placebo-controlled, positive-controlled, parallel-group thorough QT study characterized the effects of ozanimod on cardiac repolarization in healthy subjects. Eligible subjects were randomized to 1 of 2 groups: ozanimod (escalated from 0.25 to 2 mg over 14 days) or placebo (for 14 days). A single dose of moxifloxacin 400 mg or placebo was administered on days 2 and 17...
August 7, 2017: Clinical Pharmacology in Drug Development
https://www.readbyqxmd.com/read/28782696/heritability-in-a-scn5a-mutation-founder-population-with-increased-female-susceptibility-to-non-nocturnal-ventricular-tachyarrhythmia-and-sudden-cardiac-death
#12
Rachel M A Ter Bekke, Aaron Isaacs, Andrei Barysenka, Marije B Hoos, Jan D H Jongbloed, Jan C A Hoorntje, Alfons S M Patelski, Apollonia T J M Helderman-van den Enden, Arthur van den Wijngaard, Monika Stoll, Paul G A Volders
BACKGROUND: Heritable cardiac sodium-channel dysfunction is associated with various arrhythmia syndromes, some predisposing to ventricular fibrillation. Phenotypic diversity among carriers of identical-by-descent mutations is often remarkable, suggesting influences of genetic modifiers. OBJECTIVE: We identified a unique SCN5A-mutation founder population with mixed clinical phenotypes and sudden cardiac death, and investigated the heritability of electromechanical traits besides the SCN5A-mutation effect...
August 3, 2017: Heart Rhythm: the Official Journal of the Heart Rhythm Society
https://www.readbyqxmd.com/read/28782310/ecg-changes-in-young-healthy-smokers-a-simple-and-cost-effective-method-to-assess-cardiovascular-risk-according-to-pack-years-of-smoking
#13
Nirmal Kumar Sharma, Kapil Kumar Jaiswal, S R Meena, Rahul Chandel, Saurabh Chittora, Prem Singh Goga, H B Harish, Rajesh Sagar
OBJECTIVE: To document the prevalence of ECG abnormalities in young healthy smokers and compare ECG changes in smokers, young healthy non-smokers and amongst smokers with different pack years. METHODS: This was a prospective case-control study consisting of 200 young healthy male and female individuals, 150 smokers and 50 non-smokers between ages 25-40 years, further categorized and compared according to age, sex and pack years of smoking. The ECG recordings were analyzed for different ECG parameters like heart rate, P-wave duration, P-wave amplitude, PR interval, QRS duration, RR-interval, ST-segment duration, QT interval and QTc interval...
June 2017: Journal of the Association of Physicians of India
https://www.readbyqxmd.com/read/28776165/prolongation-of-the-qtc-interval-in-hiv-infected-individuals-compared-to-the-general-population
#14
Nico Reinsch, Marina Arendt, Marie Henrike Geisel, Christina Schulze, Volker Holzendorf, Anna Warnke, Till Neumann, Norbert H Brockmeyer, Dirk Schadendorf, Lewin Eisele, Raimund Erbel, Susanne Moebus, Karl-Heinz Jöckel, Stefan Esser
OBJECTIVES: Prolonged QT interval is associated with arrhythmias and sudden death. An increased prevalence of QT interval prolongation in human immunodeficiency virus-infected (HIV) subjects was previously described. The impact of different medications and HIV infection itself on the QT interval is rarely investigated in large HIV+ cohorts. METHODS: We compared QT interval measurement in 496 HIV(+) patients of the HIV-HEART study (HIVH) and 992 sex- and age-matched controls of the population-based German Heinz Nixdorf Recall study (HNR)...
August 3, 2017: Infection
https://www.readbyqxmd.com/read/28772335/qtc-interval-in-adolescents-and-young-athletes-influence-of-correction-formulas
#15
Salvatore Francesco Gervasi, Massimiliano Bianco, Vincenzo Palmieri, Francesco Cuccaro, Paolo Zeppilli
A QTc interval at the upper limits in young athletes can be challenging. Regardless of factors able to influence it (age, electrolytes, etc.), several authors underlined that rate correction formulas can often underestimate/overestimate it. Our objective was to identify the most reliable formula and relative upper normal limit of QTc for this population. The rest ECG of 701 healthy elite male athletes was analyzed. QTc was calculated with 4 formulas (Bazett, Fridericia, Framingham, Hodges). Correlation/regression analysis of QTc vs...
August 3, 2017: International Journal of Sports Medicine
https://www.readbyqxmd.com/read/28765838/sex-specific-molecular-responses-of-quick-to-court-protein-in-indian-malarial-vector-anopheles-culicifacies-conflict-of-mating-versus-blood-feeding-behaviour
#16
Tanwee Das De, Punita Sharma, Charu Rawal, Seena Kumari, Sanjay Tavetiya, Jyoti Yadav, Yasha Hasija, Rajnikant Dixit
Understanding the molecular basis of mosquito behavioural complexity plays a central role in designing novel molecular tools to fight against their vector-borne diseases. Although the olfactory system plays an important role in guiding and managing many behavioural responses including feeding and mating, but the sex-specific regulation of olfactory responses remain poorly investigated. From our ongoing transcriptomic data annotation of olfactory tissue of blood fed adult female An. culicifacies mosquitoes; we have identified a 383 bp long unique transcript encoding a Drosophila homolog of the quick-to-court protein...
July 2017: Heliyon
https://www.readbyqxmd.com/read/28764153/correlation-of-adiposity-indices-with-electrocardiographic-ventricular-variables-and-vascular-stiffness-in-young-adults
#17
Varrshine Ravikumar, Hemamalini Ramasamy VajraVelu, Saravanan Ayyavoo, Balaji Ramraj
INTRODUCTION: Excess adiposity constitute an important public health problem because of the associated increased risk of hypertension, coronary heart disease, type 2 diabetes and other disorders. Not only the contribution of general measures of adiposity but also central measures of adiposity have been observed. AIM: To compare and correlate the central and general adiposity indices with ventricular electrocardiographic variables and vascular stiffness indices in normal, overweight and obese young adults...
June 2017: Journal of Clinical and Diagnostic Research: JCDR
https://www.readbyqxmd.com/read/28763575/cardiac-safety-of-rupatadine-in-a-single-ascending-dose-and-multiple-ascending-dose-study-in-healthy-japanese-subjects-using-intensive-electrocardiogram-assessments-comparison-with-the-previous-white-caucasian-thorough-qt-study
#18
J Täubel, G Ferber, S Fernandes, E Santamaría, I Izquierdo
A thorough QT/QTc study in healthy white Caucasian subjects demonstrated that rupatadine has no proarrhythmic potential and raised no cardiac safety concerns. The present phase 1 study aimed to confirm the cardiac safety of rupatadine in healthy Japanese subjects. In this randomized, double-blind, placebo-controlled study, 27 healthy Japanese subjects were administered single and multiple escalating rupatadine doses of 10, 20, and 40 mg or placebo. Triplicate electrocardiogram (ECG) recordings were performed on days -1, 1, and 5 at several points, and time-matched pharmacokinetic samples were also collected...
August 1, 2017: Clinical Pharmacology in Drug Development
https://www.readbyqxmd.com/read/28762916/-predictors-of-electrical-myocardial-instability-in-men-with-arterial-hypertension-and-obstructive-sleep-apnea-hypopnea-syndrome
#19
O V Lyshova, N V Borodin, I I Kostenko
OBJECTIVE: To access the detectability of corrected QT interval (QTc) prolongation ( more or equal 450 ms) and increased QT dispersion (QTd more or equal 60 ms) in men with obstructive sleep apnea-hypopnea syndrome (OSAS) and newly diagnosed arterial hypertension (AH). MATERIAL AND METHODS: We included in this study 138 men (mean age 40.5+/-6.9 years, body mass index 34.5+/-4.7 kg/m2, all with more or equal 3 risk factors of AH development, 34% with subclinical target organs damage)...
May 2017: Kardiologiia
https://www.readbyqxmd.com/read/28759086/assessment-of-myocardial-repolarisation-parameters-in-patients-with-familial-mediterranean-fever
#20
Kayihan Karaman, Metin Karayakali, Ertuğrul Erken, Ahmet Demirtaş, Mustafa Öztürk, Fatih Altunkaş, Arif Arisoy, Oğuzhan Ekrem Turan, Köksal Ceyhan, Ataç Çelik
BACKGROUND: Familial Mediterranean fever (FMF) is a chronic, recurrent auto-inflammatory disease characterised by self-terminating attacks of fever and sterile polyserositis. The main cause of death in auto-inflammatory diseases is cardiovascular events. Additionally, auto-inflammatory diseases have potential effects on the myocardial repolarisation parameters, including the T-wave peak-to-end (Tp-Te) interval, cTp-Te interval (corrected Tp-Te) and the cTp-Te/QT ratio. The aim of this study was to analyse the efficacy of myocardial repolarisation alterations in anticipation of cardiovascular risks in patients with FMF...
May 2017: Cardiovascular Journal of Africa
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