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QTc prolongation

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https://www.readbyqxmd.com/read/28634852/incidence-of-prolonged-qtc-and-severe-hypoglycemia-in-type-1-diabetes-the-eurodiab-prospective-complications-study
#1
Cristina Amione, Sara Giunti, Paolo Fornengo, Sabita S Soedamah-Muthu, Nish Chaturvedi, J H Fuller, Federica Barutta, Gabriella Gruden, Graziella Bruno
AIMS: To assess the independent role of severe hypoglycemia on 7-year cumulative incidence of prolonged QTc in a large cohort of patients with type 1 diabetes. METHODS: People with type 1 diabetes recruited by the EURODIAB Prospective Complications Study who had normal QTc were examined at baseline and after 7 years with standardized methods (n = 1415; mean age ± SD 32.1 ± 9.6 years; diabetes duration 14.2 ± 8.8 years). Hypoglycemic episodes were assessed by a questionnaire...
June 20, 2017: Acta Diabetologica
https://www.readbyqxmd.com/read/28634649/assessment-of-cabozantinib-treatment-on-qt-interval-in-a-phase-3-study-in-medullary-thyroid-cancer-evaluation-of-indirect-qt-effects-mediated-through-treatment-induced-changes-in-serum-electrolytes
#2
Dale R Miles, Steven A Lacy, David R Wada, Steve Milwee, Yifah Yaron, Linh T Nguyen
PURPOSE: This study evaluated factors impacting QTc interval in a phase 3 trial of cabozantinib in progressive, metastatic, medullary thyroid cancer (MTC). METHODS: Electrocardiogram (12-lead ECG) measurements were obtained at screening, and at pre-dose, and 2, 4, and 6 h post-dose on Days 1 and 29 in a phase 3 study in patients with MTC treated with cabozantinib (140 mg/day). Central tendency analyses were conducted on baseline-corrected QTc values. Linear and nonlinear mixed-effects models were used to evaluate potential factors affecting the QTc interval, including serum electrolytes, patient demographics, and cabozantinib concentration...
June 20, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28634536/telavancin-a-novel-semisynthetic-lipoglycopeptide-agent-to-counter-the-challenge-of-resistant-gram-positive-pathogens
#3
REVIEW
Biswadeep Das, Chayna Sarkar, Debasmita Das, Amit Gupta, Arnav Kalra, Shubham Sahni
Telavancin (TD-6424), a semisynthetic lipoglycopeptide vancomycin-derivative, is a novel antimicrobial agent developed by Theravance for overcoming resistant Gram-positive bacterial infections, specifically methicillin-resistant Staphylococcus aureus (MRSA). The US Food and Drug Administration (USFDA) had approved telavancin in 2009 for the treatment of complicated skin and skin structure infections (cSSSIs) caused by Gram-positive bacteria, including MRSA (S. aureus, Streptococcus agalactiae, Streptococcus pyogenes, Streptococcus anginosus group, or Enterococcus faecalis)...
March 2017: Therapeutic Advances in Infectious Disease
https://www.readbyqxmd.com/read/28634147/csahi-study-2-validation-of-multi-electrode-array-systems-mea60-2100-for-prediction-of-drug-induced-proarrhythmia-using-human-ips-cell-derived-cardiomyocytes-assessment-of-reference-compounds-and-comparison-with-non-clinical-studies-and-clinical-information
#4
Yumiko Nozaki, Yayoi Honda, Hitoshi Watanabe, Shota Saiki, Kiyotaka Koyabu, Tetsuji Itoh, Chiho Nagasawa, Chiaki Nakamori, Chiaki Nakayama, Hiroshi Iwasaki, Shinobu Suzuki, Kohji Tanaka, Etsushi Takahashi, Kaori Miyamoto, Kaoru Morimura, Atsuhiro Yamanishi, Hiroko Endo, Junko Shinozaki, Hisashi Nogawa, Tadahiro Shinozawa, Fumiyo Saito, Takeshi Kunimatsu
With the aim of reconsidering ICH S7B and E14 guidelines, a new in vitro assay system has been subjected to worldwide validation to establish a better prediction platform for potential drug-induced QT prolongation and the consequent TdP in clinical practice. In Japan, CSAHi HEART team has been working on hiPS-CMs in the MEA (hiPS-CMs/MEA) under a standardized protocol and found no inter-facility or lot-to-lot variability for proarrhythmic risk assessment of 7 reference compounds. In this study, we evaluated the responses of hiPS-CMs/MEA to another 31 reference compounds associated with cardiac toxicities, and gene expression to further clarify the electrophysiological characteristics over the course of culture period...
June 17, 2017: Regulatory Toxicology and Pharmacology: RTP
https://www.readbyqxmd.com/read/28624887/voriconazole-induced-qt-prolongation-among-hemato-oncologic-patients-clinical-characteristics-and-risk-factors
#5
I Gueta, R Loebstein, N Markovits, Y Kamari, H Halkin, G Livni, H Yarden-Bilavsky
PURPOSE: The purpose of this study is to determine the rate of QTcP and associated risk factors in patients treated with voriconazole. METHODS: We conducted a retrospective chart review of all patients treated with voriconazole in a large tertiary center between 2009 and 2015, using paired comparison of QTc intervals on and off voriconazole treatment, adjusted for comorbidities, electrolyte abnormalities, and concurrent medications. RESULTS: Fifty-four patients were included, of whom 53 were diagnosed with oncologic/hemato-oncologic disease...
June 17, 2017: European Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28621260/meta-analysis-of-the-incidence-and-risks-of-interstitial-lung-disease-and-qtc-prolongation-in-non-small-cell-lung-cancer-patients-treated-with-alk-inhibitors
#6
Liping Lin, Juanjuan Zhao, Ning Kong, Yan He, Jiazhu Hu, Fuxi Huang, Jianjun Han, Xiaolong Cao
BACKGROUND: To conduct a systematic review and meta-analysis to assess the overall incidence and risk of interstitial lung disease (ILD) and QTc prolongation associated with anaplastic lymphoma kinase (ALK)-tyrosine kinase inhibitors (-TKIs) in non-small-cell lung cancer (NSCLC) patients. RESULTS: A total of 1,770 patients from 8 clinical trials were included. The incidences of high-grade ILD and QTc prolongation was 2.5% (95% CI 1.7-3.6%), and 2.8% (95% CI 1.8-4...
May 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28617054/in-response-to-loperamide-metabolite-induced-cardiomyopathy-and-qtc-prolongation
#7
William Eggleston, Jeanna M Marraffa, Nicholas Nacca
No abstract text is available yet for this article.
June 15, 2017: Clinical Toxicology
https://www.readbyqxmd.com/read/28612304/cardiovascular-effects-and-fatality-may-differ-according-to-the-formulation-of-glyphosate-salt-herbicide
#8
Jeong Mi Moon, Byeong Jo Chun, Yong Soo Cho, Sung Do Lee, Young Joon Hong, Min Ho Shin, Eu Jene Jung, Hyun Ho Ryu
This study aimed to compare adverse cardiovascular events and fatalities and to identify the risk factors for fatalities associated with the glyphosate salt herbicide formulation. Additionally, we examined whether glyphosate ammonium salt herbicides increased serum ammonia levels. One hundred forty-seven patients were divided into an ammonium group (glyphosate ammonium salt herbicide) and an isopropylamine (IPA) group (glyphosate IPA salt herbicide) according to the type of glyphosate salt formulation ingested...
June 13, 2017: Cardiovascular Toxicology
https://www.readbyqxmd.com/read/28611540/evaluation-of-qtc-interval-prolongation-in-breast-cancer-patients-after-treatment-with-epirubicin-cyclophosphamide-and-docetaxel-and-the-influence-of-interobserver-variation
#9
Julian Puppe, Deborah van Ooyen, Jeanne Neise, Fabinshy Thangarajah, Christian Eichler, Stefan Krämer, Roman Pfister, Peter Mallmann, Marina Wirtz, Guido Michels
BACKGROUND: Chemotherapy with anthracyclines is associated with life-threatening electrocardiographic alterations including corrected QT (QTc) interval prolongation. PATIENTS AND METHODS: In this study we assessed the effect of epirubicin, cyclophosphamide, and docetaxel (EC-Doc) on the QTc interval in 10 patients with early breast cancer. Cardiac toxicity was assessed with symptoms, transthoracic echocardiography, electrocardiography (ECG), and serum cardiac markers at baseline and after 4 cycles of EC and 4 cycles of docetaxel...
March 2017: Breast Care
https://www.readbyqxmd.com/read/28600177/compound-heterozygous-kcnq1-mutations-a300t-p535t-in-a-child-with-sudden-unexplained-death-insights-into-possible-molecular-mechanisms-based-on-protein-modeling
#10
Erika Antúnez-Argüelles, Arturo Rojo-Domínguez, Ana Leticia Arregui-Mena, Leonor Jacobo-Albavera, Manlio Fabio Márquez, Pedro Iturralde-Torres, María Teresa Villarreal-Molina
Sudden death in a child is a devastating event with important medical implications for surviving relatives. Because it may be the first manifestation of unknown inherited cardiac disease, molecular autopsy can be helpful to determine the cause of death and identify at risk family members. The aim of the study was to perform a molecular autopsy in a seven year-old girl with sudden unexplained death, to find evidence supporting the possible pathogenicity of mutations identified in inherited cardiac disease genes, and to clinically and genetically assess first-degree relatives...
June 6, 2017: Gene
https://www.readbyqxmd.com/read/28595573/a-novel-kcnq1-nonsense-variant-in-the-isoform-specific-first-exon-causes-both-jervell-and-lange-nielsen-syndrome-1-and-long-qt-syndrome-1-a-case-report
#11
Motoi Nishimura, Marehiko Ueda, Ryota Ebata, Emi Utsuno, Takuma Ishii, Kazuyuki Matsushita, Osamu Ohara, Naoki Shimojo, Yoshio Kobayashi, Fumio Nomura
BACKGROUND: According to previous KCNQ1 (potassium channel, voltage gated, KQT-like subfamily, member 1) gene screening studies, missense variants, but not nonsense or frame-shift variants, cause the majority of long QT syndrome (LQTS; Romano-Ward syndrome [RWS]) 1 cases. Several missense variants are reported to cause RWS by a dominant-negative mechanism, and some KCNQ1 variants can cause both Jervell and Lange-Nielsen Syndrome (JLNS; in an autosomal recessive manner) and LQTS1 (in an autosomal dominant manner), while other KCNQ1 variants cause only JLNS...
June 8, 2017: BMC Medical Genetics
https://www.readbyqxmd.com/read/28583014/evaluation-of-the-effects-of-quetiapine-on-qtc-prolongation-in-critically-ill-patients
#12
Kevin M Dube, Jeremy DeGrado, Benjamin Hohlfelder, Paul M Szumita
Quetiapine, an atypical antipsychotic used in the intensive care unit (ICU) to manage delirium, has a possible adverse effect of corrected QT (QTc) interval prolongation. The objective of this analysis was to describe the impact of quetiapine on QTc interval prolongation in critically ill patients. This was a single-center, prospective cohort analysis of ICU patients who received quetiapine between October 2015 and February 2016. The major end point was the incidence of QTc prolongation greater than 60 milliseconds above baseline during therapy...
January 1, 2017: Journal of Pharmacy Practice
https://www.readbyqxmd.com/read/28576628/incidence-of-torsade-de-pointes-in-a-tertiary-hospital-population
#13
Eline Vandael, Bert Vandenberk, Joris Vandenberghe, Hilde Pincé, Rik Willems, Veerle Foulon
BACKGROUND: Multiple risk factors play a role in the development of QTc-prolongation and Torsade de Pointes (TdP). Cases of TdP are underreported and data on the incidence of TdP is scarce. The aim of this study was to investigate the incidence of TdP in a Belgian university hospital and describe the characteristics of TdP-cases using a risk score. METHODS: All cases from 2011 till 2013 coded with the ICD-9 code 427.1 in the University Hospitals of Leuven were selected...
May 19, 2017: International Journal of Cardiology
https://www.readbyqxmd.com/read/28550929/arrhythmia-and-clinical-cardiac-findings-in-children-with-anderson-fabry-disease
#14
Hunter C Wilson, Robert J Hopkin, Peace C Madueme, Richard J Czosek, Laurie A Bailey, Michael D Taylor, John L Jefferies
Anderson-Fabry Disease (AFD) is a lysosomal storage disorder that results in progressive cardiovascular hypertrophy, scarring, and arrhythmia burden; yet, the early cardiac phenotype of AFD is still poorly defined. To further characterize early cardiac features in AFD, we evaluated electrocardiographic and clinical findings contained in a local cohort of pediatric AFD patients and arrhythmia data in children enrolled in the Fabry Registry. Twenty-six local patients aged <18 years were identified (average age 9...
July 15, 2017: American Journal of Cardiology
https://www.readbyqxmd.com/read/28550094/safety-of-outpatient-initiation-of-disopyramide-for-obstructive-hypertrophic-cardiomyopathy-patients
#15
Arnon Adler, Dana Fourey, Adaya Weissler-Snir, Waseem Hindieh, Raymond H Chan, Michael H Gollob, Harry Rakowski
BACKGROUND: Disopyramide is effective in ameliorating symptoms in patients with hypertrophic cardiomyopathy; however, its potential for proarrhythmic effect has raised concerns about its use in the ambulatory setting. The risk of initiating disopyramide in this manner has never been evaluated. METHODS AND RESULTS: All charts of patients seen in the outpatient hypertrophic cardiomyopathy clinic between 2010 and 2014 were screened for initiation of disopyramide and data were extracted...
May 26, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/28542844/the-inward-rectifier-current-inhibitor-pa-6-terminates-atrial-fibrillation-and-does-not-cause-ventricular-arrhythmias-in-dedicated-goat-and-dog-models
#16
Yuan Ji, Rosanne Varkevisser, Dragan Opacic, Alexandre Bossu, Marion Kuiper, Jet D M Beekman, Sihyung Yang, Azinwi Phina Khan, Dobromir Dobrev, Niels Voigt, Michael Zhuo Wang, Sander Verheule, Marc A Vos, Marcel A G Van der Heyden
BACKGROUND AND PURPOSE: Inward rectifier current (IK1 ) density increases in atrial fibrillation (AF), shortening effective refractory period and thus promotes atrial reentry. Pentamidine-Analogue 6 (PA-6) is a selective and potent IK1 inhibitor. We tested PA-6 for anti-AF efficacy and potential proarrhythmia, in established large animal models. EXPERIMENTAL APPROACH: PA-6 was applied i.v. in anaesthetized goats with rapid pacing induced AF and anaesthetized chronic AV block dogs...
May 24, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28538401/atrial-fibrillation-was-changed-into-sinus-bradycardia-in-a-ros1-positive-advanced-lung-adenocarcinoma-patient-who-achieved-durable-response-to-crizotinib-a-case-report-and-literature-review
#17
Lan Liu, Jing Wu, Wei Zhao, Mei-Juan Huang
RATIONAL: The c-ros oncogene 1 receptor tyrosine kinase (ROS1)-rearrangements represent a new and rare genetic subtype of non-small-cell lung cancer. In recent years, the use of crizotinib in ROS1-rearranged lung cancer exhibits significant clinical efficacy. Crizotinib is generally well tolerated and the most frequent adverse events include visual disorders, gastrointestinal disturbances, cardiac, and endocrine abnormalities. From a cardiac perspective, crizotinib is associated with 2 main cardiac effects, QT interval prolongation and bradycardia...
May 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28535735/clenbuterol-attenuates-herg-channel-by-promoting-the-mature-channel-degradation
#18
Ling Luo, Peijing Hu, Changqing Miao, Aiqun Ma, Tingzhong Wang
Clenbuterol, a β2-selective adrenergic receptor agonist, is illicitly used in weight loss and performance enhancement and animal production. Increasing evidence demonstrates that clenbuterol induces various kinds of arrhythmias and QTc interval prolongation. However, little is known about the underlying mechanism. Most drugs are associated with QTc prolongation through interfering with human ether-a-go-go-related gene (hERG) K(+) channels. The present study aims to investigate the effects and underlying mechanisms of clenbuterol on the hERG channel...
January 1, 2017: International Journal of Toxicology
https://www.readbyqxmd.com/read/28513513/electrocardiographic-changes-and-troponin-t-levels-in-children-with-severe-malaria-anemia-and-heart-failure
#19
W E Sadoh, J O Uduebor
BACKGROUND: Severe malaria anemia is a major cause of childhood heart failure in malaria endemic countries. The resulting hypoxic-ischemic injuries may cause myocardial damage detectable by electrocardiogram (ECG) and elevated troponin T (cTnT) levels. OBJECTIVE: Evaluate the ECG changes and cTnT levels in children with severe malaria anemia compared with those who had uncomplicated malaria without anemia. METHODS: Consecutive children with severe malaria anemia were recruited as subjects while controls were age- and gender-matched children with uncomplicated malaria without anemia...
May 2017: Nigerian Journal of Clinical Practice
https://www.readbyqxmd.com/read/28511997/thorough-qt-tqt-studies-concordance-with-torsadogenesis-and-an-evolving-cardiac-safety-testing-paradigm
#20
Barbara Wiśniowska, Zofia Tylutki, Sebastian Polak
Since 2005, when the International Conference on Harmonisation (ICH) E14 guideline was adopted, no drug has been withdrawn because of QTc prolongation or torsade de pointes arrhythmia. There are, however, costs associated with this success. In addition to the time and money invested, thorough QT (TQT) studies have limited the efficiency of the drug development pipeline. In this paper, we discuss the relevance of TQT trials as a tool for proarrhythmic risk prediction as a part of the debate regarding their usefulness...
May 13, 2017: Drug Discovery Today
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