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https://www.readbyqxmd.com/read/28438924/analysis-of-the-effects-on-the-qt-interval-of-a-gatifloxacin-containing-regimen-versus-standard-treatment-of-pulmonary-tuberculosis
#1
Piero L Olliaro, Corinne Merle, Thuli Mthiyane, Boubacar Bah, Ferdinand Kassa, Evans Amukoye, Alimatou N' Diaye, Christian Perronne, Christian Lienhardt, Helen Mcilleron, Katherine Fielding
Background: The effects on ventricular repolarisation - recorded on the ECG as lengthening of the QT interval - of acute tuberculosis and those of standard and alternative anti-tuberculosis regimens are under-documented. A correction factor (QTc) is introduced to make the QT independent of the heart rate, translating into the slope of the regression line between QT and heart rate being close to zero.Methods: ECGs were performed pre- and 1-5 hours post-dosing (month 1, 2, end of treatment) around drugs' peak concentration time in tuberculosis patients treated with either the standard 6-month treatment (rifampicin and isoniazid for 6 months, pyrazinamide and ethambutol for 2 months; "control") or a test regimen with gatifloxacin, rifampicin and isoniazid given for 4 months (pyrazinamide for the first 2 months) as part of the OFLOTUB study, a randomized controlled trial conducted in five African countries...
April 24, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28438721/clinical-profile-and-mutation-spectrum-of-long-qt-syndrome-in-saudi-arabia-the-impact-of-consanguinity
#2
Zuhair N Al-Hassnan, Majid Al-Fayyadh, Bander Al-Ghamdi, Azam Shafquat, Yaseen Mallawi, Faten Al-Hadeq, Sahar Tulbah, Zarghuna Ma Shinwari, Abdulrahman Almesned, Ali Alakhfash, Fadel Al Fadly, Ahmed S Hersi, Abdullah Alhayani, Amal Al-Hashem, Dia Arafah, Nduna Dzimiri, Brian Meyer, Monther Rababh, Waleed Al-Manea
BACKGROUND: Congenital long QT syndrome (LQTS) is an inherited potentially fatal arrhythmogenic disorder. At least 16 genes have been implicated in LQTS; the yield of genetic analysis of 3 genes (KCNQ1, KCNH2, and SCN5A) is about 70% with KCNQ1 mutations accounting for ∼50% of positive cases. LQTS is mostly inherited in an autosomal dominant pattern. Systemic analysis of LQTS has not been previously conducted in a population with a high degree of consanguinity. OBJECTIVES: We aim to describe the clinical and molecular profiles of LQTS in the highly consanguineous Saudi population...
April 21, 2017: Heart Rhythm: the Official Journal of the Heart Rhythm Society
https://www.readbyqxmd.com/read/28437484/ecg-view-ii-a-freely-accessible-electrocardiogram-database
#3
Young-Gun Kim, Dahye Shin, Man Young Park, Sukhoon Lee, Min Seok Jeon, Dukyong Yoon, Rae Woong Park
The Electrocardiogram Vigilance with Electronic data Warehouse II (ECG-ViEW II) is a large, single-center database comprising numeric parameter data of the surface electrocardiograms of all patients who underwent testing from 1 June 1994 to 31 July 2013. The electrocardiographic data include the test date, clinical department, RR interval, PR interval, QRS duration, QT interval, QTc interval, P axis, QRS axis, and T axis. These data are connected with patient age, sex, ethnicity, comorbidities, age-adjusted Charlson comorbidity index, prescribed drugs, and electrolyte levels...
2017: PloS One
https://www.readbyqxmd.com/read/28437058/psychotic-and-bipolar-disorders-antipsychotic-drugs
#4
Sarah D Holder, Alaina L Edmunds, Sherri Morgan
Antipsychotic drugs block dopamine receptors and are used to manage psychosis as well as other mental illnesses that may or may not have psychotic features, such as bipolar disorders and major depressive disorder. First-generation antipsychotic drugs are more likely to cause adverse effects such as extrapyramidal symptoms and tardive dyskinesia. Adverse effects of second-generation antipsychotic drugs typically are related to metabolic abnormalities such as weight gain, abnormal blood glucose levels, and elevated lipid levels...
April 2017: FP Essentials
https://www.readbyqxmd.com/read/28434969/translational-science-approach-for-assessment-of-cardiovascular-effects-and-proarrhythmogenic-potential-of-the-beta-3-adrenergic-agonist-mirabegron
#5
Cees Korstanje, Masanori Suzuki, Koichiro Yuno, Shuichi Sato, Masashi Ukai, Marlowe J Schneidkraut, Gan X Yan
INTRODUCTION: Translational assessment of cardiac safety parameters is a challenge in clinical development of beta-3 adrenoceptor agonists. The preclinical tools are presented that were used for assessing human safety for mirabegron. METHODS: Studies were performed on electrical conductance at ion channels responsible for cardiac repolarization (IKr, IKs, Ito, INa, and ICa,L), on QT-interval, subendocardial APD90, Tpeak-end interval, and arrhythmia's in ventricular dog wedge tissue in vitro and on cardiovascular function (BP, HR, and QTc) in conscious dogs...
April 20, 2017: Journal of Pharmacological and Toxicological Methods
https://www.readbyqxmd.com/read/28429460/automated-t-wave-analysis-can-differentiate-acquired-qt-prolongation-from-congenital-long-qt-syndrome
#6
Alan Sugrue, Peter A Noseworthy, Vaclav Kremen, J Martijn Bos, Bo Qiang, Ram K Rohatgi, Yehu Sapir, Zachi I Attia, Peter Brady, Pedro J Caraballo, Samuel J Asirvatham, Paul A Friedman, Michael J Ackerman
BACKGROUND: Prolongation of the QT on the surface electrocardiogram can be due to either genetic or acquired causes. Distinguishing congenital long QT syndrome (LQTS) from acquired QT prolongation has important prognostic and management implications. We aimed to investigate if quantitative T-wave analysis could provide a tool for the physician to differentiate between congenital and acquired QT prolongation. METHODS: Patients were identified through an institution-wide computer-based QT screening system which alerts the physician if the QTc ≥ 500 ms...
April 21, 2017: Annals of Noninvasive Electrocardiology
https://www.readbyqxmd.com/read/28421417/estimation-of-qt-interval-prolongation-through-model-averaging
#7
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/28419747/a-randomized-placebo-and-positive-controlled-single-dose-crossover-thorough-qt-qtc-study-assessing-the-effect-of-daprodustat-on-cardiac-repolarization-in-healthy-subjects
#8
Stephen Caltabiano, Jon Collins, Gul Serbest, Lisa Morgan, Deborah A Smith, Ramiya Ravindranath, Alexander R Cobitz
Daprodustat (GSK1278863) is a prolyl hydroxylase inhibitor in phase 3 clinical studies for the treatment of anemia associated with chronic kidney disease. This study was conducted to evaluate the effect of daprodustat on cardiac repolarization and enrolled 55 healthy adult male (29) and female (26) subjects who received single-dose 75 and 500 mg daprodustat, 400 mg moxifloxacin, and placebo. Mean placebo-corrected change from baseline QT interval for daprodustat showed no statistically significant increase...
April 17, 2017: Clinical Pharmacology in Drug Development
https://www.readbyqxmd.com/read/28419650/cardiovascular-safety-in-refractory-incontinent-patients-with-overactive-bladder-receiving-add-on-mirabegron-therapy-to-solifenacin-beside
#9
Marcus J Drake, Scott MacDiarmid, Christopher R Chapple, Adil Esen, Stavros Athanasiou, Javier Cambronero Santos, David Mitcheson, Sender Herschorn, Emad Siddiqui, Moses Huang, Matthias Stoelzel
AIMS/OBJECTIVES: In the BESIDE study, combination therapy (antimuscarinic [solifenacin] and β3 -adrenoceptor agonist [mirabegron]) improved efficacy over solifenacin monotherapy without exacerbating anticholinergic side effects in overactive bladder (OAB) patients; however, a potential synergistic effect on the cardiovascular (CV) system requires investigation. METHODS: OAB patients remaining incontinent despite daily solifenacin 5 mg during 4-week single-blind run-in, were randomised 1:1:1 to double-blind daily combination (solifenacin 5 mg/mirabegron 25 mg, increasing to 50 mg after week 4), solifenacin 5 or 10 mg for 12 weeks...
April 16, 2017: International Journal of Clinical Practice
https://www.readbyqxmd.com/read/28419455/human-electrical-muscular-incapacitation-and-effects-on-qtc-interval
#10
John A Gibbons, Andrew J Mojica, Mark E Peele
Human Electrical Muscular Incapacitation (HEMI) is used to subdue combative individuals. Changes in cardiac electrical activity have been proposed as the cause of death in a small fraction of these individuals. The current study sought to determine whether changes in QTc interval occur after HEMI exposure. Twenty-four participants had EKG readings before a 5-second HEMI exposure and within 30 min after exposure. All subject EKGs were read by a data-blinded cardiac electrophysiologist who calculated a QT corrected (QTc) interval...
April 17, 2017: Journal of Forensic Sciences
https://www.readbyqxmd.com/read/28417026/cardiovascular-complications-of-acute-amphetamine-abuse-cross-sectional-study
#11
Elham Bazmi, Farinaz Mousavi, Leila Giahchin, Tahmineh Mokhtari, Behnam Behnoush
OBJECTIVES: This study aimed to evaluate cardiovascular complications among patients who abuse amphetamines. METHODS: This cross-sectional study took place between April 2014 and April 2015 among 3,870 patients referred to the Toxicology Emergency Department of Baharlou Hospital, Tehran University of Medical Sciences, Tehran, Iran. Those with clinical signs of drug abuse and positive urine screening tests were included in the study, while cases of chronic abuse were excluded...
February 2017: Sultan Qaboos University Medical Journal
https://www.readbyqxmd.com/read/28409011/utility-of-t-wave-amplitude-as-a-non-invasive-risk-marker-of-sudden-cardiac-death-in-hypertrophic-cardiomyopathy
#12
Alan Sugrue, Ammar M Killu, Christopher V DeSimone, Anwar A Chahal, Josh C Vogt, Vaclav Kremen, JoJo Hai, David O Hodge, Nancy G Acker, Jeffrey B Geske, Michael J Ackerman, Steve R Ommen, Grace Lin, Peter A Noseworthy, Peter A Brady
OBJECTIVE: Sudden cardiac arrest (SCA) is the most devastating outcome in hypertrophic cardiomyopathy (HCM). We evaluated repolarisation features on the surface electrocardiogram (ECG) to identify the potential risk factors for SCA. METHODS: Data was collected from 52 patients with HCM who underwent implantable cardioverter defibrillator (ICD) implantation. Leads V2 and V5 from the ECG closest to the time of ICD implant were utilised for measuring the Tpeak-Tend interval (Tpe), QTc, Tpe/QTc, T-wave duration and T-wave amplitude...
2017: Open Heart
https://www.readbyqxmd.com/read/28408648/azithromycin-causes-a-novel-proarrhythmic-syndrome
#13
Zhenjiang Yang, Joseph K Prinsen, Kevin R Bersell, Wangzhen Shen, Liudmila Yermalitskaya, Tatiana Sidorova, Paula B Luis, Lynn Hall, Wei Zhang, Liping Du, Ginger Milne, Patrick Tucker, Alfred L George, Courtney M Campbell, Robert A Pickett, Christian M Shaffer, Nagesh Chopra, Tao Yang, Bjorn C Knollmann, Dan M Roden, Katherine T Murray
BACKGROUND: The widely used macrolide antibiotic azithromycin increases risk of cardiovascular and sudden cardiac death, although the underlying mechanisms are unclear. Case reports, including the one we document here, demonstrate that azithromycin can cause rapid, polymorphic ventricular tachycardia in the absence of QT prolongation, indicating a novel proarrhythmic syndrome. We investigated the electrophysiological effects of azithromycin in vivo and in vitro using mice, cardiomyocytes, and human ion channels heterologously expressed in human embryonic kidney (HEK 293) and Chinese hamster ovary (CHO) cells...
April 2017: Circulation. Arrhythmia and Electrophysiology
https://www.readbyqxmd.com/read/28408211/cardiac-voltage-gated-ion-channels-in-safety-pharmacology-review-of-the-landscape-leading-to-the-cipa-initiative
#14
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
#15
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/28403766/controversies-in-diagnosis-and-management-of-community-acquired-pneumonia
#16
REVIEW
Sarah Sparham, Patrick Gp Charles
Community-acquired pneumonia (CAP) is a common condition; however, it appears to be overdiagnosed. Diagnosing CAP too frequently may be adding to the problems of overuse of antibiotics, such as bacterial resistance in the community and greater costs and complications in individuals. Data support that most patients with non-severe CAP can be treated for 3-5 days; however, most patients with CAP are receiving much longer courses of therapy. Macrolides such as azithromycin have the potential to prolong the QT interval, although large population studies show that this does not appear to result in excess cardiac mortality...
April 17, 2017: Medical Journal of Australia
https://www.readbyqxmd.com/read/28403196/validation-of-automatic-measurement-of-qt-interval-variability
#17
Peter R Rijnbeek, Marten E van den Berg, Gerard van Herpen, Henk J Ritsema van Eck, Jan A Kors
BACKGROUND: Increased variability of beat-to-beat QT-interval durations on the electrocardiogram (ECG) has been associated with increased risk for fatal and non-fatal cardiac events. However, techniques for the measurement of QT variability (QTV) have not been validated since a gold standard is not available. In this study, we propose a validation method and illustrate its use for the validation of two automatic QTV measurement techniques. METHODS: Our method generates artificial standard 12-lead ECGs based on the averaged P-QRS-T complexes from a variety of existing ECG signals, with simulated intrinsic (QT interval) and extrinsic (noise, baseline wander, signal length) variations...
2017: PloS One
https://www.readbyqxmd.com/read/28394491/randomized-blinded-placebo-and-positive-controlled-crossover-study-to-determine-the-effect-of-deferiprone-on-the-qtc-interval-in-healthy-subjects
#18
Caroline Fradette, Anna Rozova, Anne Stilman, Yu Chung Tsang, Mark J Allison, Fernando Tricta
This study evaluated whether deferiprone, an oral iron chelator, acts to prolong the QT interval. Fifty healthy volunteers received single doses of each of the following: therapeutic dose of deferiprone (33 mg/kg), supratherapeutic dose (50 mg/kg), placebo, or moxifloxacin, a positive control known to significantly prolong QT interval. Following each dose, subjects underwent cardiac monitoring, pharmacokinetics assessments, and safety assessments. Based on the QT interval obtained using the Fridericia correction for heart rate (QTcF), the upper bound of the 1-sided 95% confidence interval of the mean difference between deferiprone and placebo was <10 milliseconds (the threshold of concern defined by authorities) at all time points for both doses: maximum difference of 3...
April 10, 2017: Clinical Pharmacology in Drug Development
https://www.readbyqxmd.com/read/28394409/evaluation-of-qtc-in-rett-syndrome-correlation-with-age-severity-and-genotype
#19
Jane Crosson, Siddharth Srivastava, Genila M Bibat, Siddharth Gupta, Aditi Kantipuly, Constance Smith-Hicks, Scott M Myers, Abanti Sanyal, Gayane Yenokyan, Joel Brenner, Sakkubai R Naidu
Rett syndrome (RTT) is caused by MECP2 mutations, resulting in various neurological symptoms. Prolonged corrected QT interval (QTc) is also reported and is a speculated cause of sudden death in RTT. The purpose of this study was to correlate QTc in RTT patients with age, clinical severity, and genotype. 100 RTT patients (98 females, 2 males) with MECP2 mutations underwent baseline neurological evaluation (KKI-RTT Severity Scale) and QTc measurement (standard 12 lead electrocardiogram) as part of our prospective natural history study...
April 10, 2017: American Journal of Medical Genetics. Part A
https://www.readbyqxmd.com/read/28390652/a-fast-noise-tolerant-ecg-feature-recognition-algorithm-based-on-probabilistic-analysis-of-gradient-discontinuity
#20
Peter A Watterson
PURPOSE: Improvement in real-time electrocardiogram (ECG) interpretation is still needed, especially for QT estimation. This paper proposes a fast algorithm for ECG feature recognition, based on locating turning points in the waveform gradient. METHODS: The algorithm places the fiducial point at the maximal value of a probabilistic decision function, assessing line intervals of best fit before and after the point and the point location relative to R-wave peaks already found...
March 14, 2017: Journal of Electrocardiology
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