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MeSH Disease

Human Phenotype

Transmission

Seroprevalence

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    Mitigating Arrhythmia HP Arrhythmia MESHD Risk in Hydroxychloroquine and Azithromycin Treated COVID-19 Patients using Arrhythmia HP Arrhythmia MESHD Risk Management Plan

    Authors: Kazimieras Maneikis M.D.; Ugne Ringeleviciute M.D.; Justinas Bacevicius M.D.; Egle Dieninyte-Misiune M.D.; Emilija Burokaite M.D.; Gintare Kazbaraite M.D.; Marta Monika Janusaite M.D.; Austeja Dapkeviciute M.D.; Andrius Zucenka M.D.; Valdas Peceliunas M.D. Ph.D.; Lina Kryzauskaite M.D.; Vytautas Kasiulevicius M.D. Ph.D.; Donata Ringaitiene M.D. Ph.D.; Birute Zablockiene M.D. Ph.D.; Tadas Zvirblis; Germanas Marinskis M.D. Ph.D.; Ligita Jancoriene M.D. Ph.D.; Laimonas Griskevicius M.D. Ph.D.

    doi:10.21203/rs.3.rs-50501/v1 Date: 2020-07-29 Source: ResearchSquare

    Background: Hydroxychloroquine and Azithromycin use is associated with QT interval prolongation MESHD and arrhythmias HP arrhythmias MESHD. Despite ongoing multiple clinical trials for treatment of COVID19 infection MESHD, no definite cardiac safety protocols were proposed. The aim of our study was to assess cardiac safety in COVID-19 patients treated with the combination of Hydroxychloroquine and Azithromycin using close monitoring and arrhythmia HP arrhythmia MESHD risk management plan.Methods and results: We retrospectively examined arrhythmia HP arrhythmia MESHD safety of treatment with Hydroxychloroquine and Azithromycin in the setting of pre-defined cardiac arrhythmia MESHD arrhythmia HP risk management plan. 81 patients were included from March 23rd to May 10th 2020. The median age TRANS was 59 years, 58.0% were female TRANS. The majority of the study population (82.7%) had comorbidities, 98.8% had radiological signs of pneumonia HP pneumonia MESHD. 7 patients (8.6%) had QTc prolongation MESHD of ≥500 ms. The treatment was discontinued in 4 patients (4.9%). 14 patients (17.3%) experienced QTc≥480 ms and 16 patients (19.8%) had an increase of QTc≥60 ms. None of the patients developed ventricular tachycardia HP ventricular tachycardia MESHD. The risk factors significantly associated with QTc≥500 ms were hypokalemia HP hypokalemia MESHD (p = 0.032) and use of diuretics during the treatment (p = 0.020). Three patients had a lethal outcome; none of them associated with ventricular arrhythmias HP ventricular arrhythmias MESHD.Conclusion: We recorded a low incidence of QTc prolongation MESHD ≥500 ms and no ventricular tachycardia HP ventricular tachycardia MESHD events in COVID-19 patients treated with Hydroxychloroquine and Azithromycin using cardiac arrhythmia MESHD arrhythmia HP risk management plan.

    Investigational treatments for COVID-19 may increase ventricular arrhythmia HP ventricular arrhythmia MESHD risk through drug interactions

    Authors: Meera Varshneya; Itziar Irurzun-Arana; Chiara Campana; Rafael Dariolli; Amy Gutierrez; Taylor K Pullinger; Eric A Sobie

    doi:10.1101/2020.05.21.20109397 Date: 2020-05-26 Source: medRxiv

    Many drugs that have been proposed for treatment of COVID-19 are reported to cause cardiac adverse events, including ventricular arrhythmias HP ventricular arrhythmias MESHD. In order to properly weigh risks against potential benefits, particularly when decisions must be made quickly, mathematical modeling of both drug disposition and drug action can be useful for predicting patient response and making informed decisions. Here we explored the potential effects on cardiac electrophysiology of 4 drugs proposed to treat COVID-19: lopinavir, ritonavir, chloroquine, and azithromycin, as well as combination therapy involving these drugs. Our study combined simulations of pharmacokinetics (PK) with quantitative systems pharmacology (QSP) modeling of ventricular myocytes to predict potential cardiac adverse events caused by these treatments. Simulation results predicted that drug combinations can lead to greater cellular action potential prolongation, analogous to QT prolongation MESHD, compared with drugs given in isolation. The combination effect can result from both pharmacokinetic and pharmacodynamic drug interactions. Importantly, simulations of different patient groups predicted that females TRANS with pre-existing heart disease MESHD are especially susceptible to drug-induced arrhythmias HP arrhythmias MESHD, compared males TRANS with disease or healthy individuals of either sex. Overall, the results illustrate how PK and QSP modeling may be combined to more precisely predict cardiac risks of COVID-19 therapies.

    Experience with Hydroxychloroquine and Azithromycin in the COVID-19 Pandemic: Implications for QT Interval Monitoring

    Authors: Archana Ramireddy; Harpriya S. Chugh; Kyndaron Reinier; Joseph Ebinger; Eunice Park; Michael Thompson; Eugenio Cingolani; Susan Cheng; Eduardo Marban; Christine Albert; Sumeet S. Chugh

    doi:10.1101/2020.04.22.20075671 Date: 2020-04-25 Source: medRxiv

    Background: Despite a paucity of clinical evidence, hydroxychloroquine and azithromycin are being administered widely to patients with verified or suspected COVID-19. Both drugs may increase risk of lethal arrhythmias HP arrhythmias MESHD associated with QT interval prolongation MESHD. Methods: We performed a case series of COVID-19 positive/suspected patients admitted between 2/1/2020 and 4/4/2020 who were treated with azithromycin, hydroxychloroquine or a combination. We evaluated baseline and post-medication QT interval (QTc, Bazett) using 12-lead ECGs. Critical QTc prolongation MESHD was defined as: a) maximum QTc [≥]500 ms (if QRS <120 ms) or QTc [≥]550 (if QRS [≥]120 ms) and b) increased QTc of [≥]60 ms. Tisdale score and Elixhauser comorbidity index were calculated. Results: Of 490 COVID-19 positive/suspected patients, 314 (64%) received either/both drugs, and 98 (73 COVID-19 positive, 25 suspected) met study criteria ( age TRANS 62{+/-}17 yrs, 61% male TRANS). Azithromycin was prescribed in 28%, hydroxychloroquine in 10%, and both in 62%. Baseline mean QTc was 448{+/-}29 ms and increased to 459{+/-}36ms (p=0.005) with medications. Significant prolongation MESHD was observed only in men (18{+/-}43 ms vs -0.2{+/-}28 ms in women, p=0.02). 12% of patients reached critical QTc prolongation MESHD. In a multivariable logistic regression, age TRANS, sex, Tisdale score, Elixhauser score, and baseline QTc were not associated with critical QTc prolongation MESHD (p>0.14). Changes in QTc were highest with the combination compared to either drug, with many-fold greater prolongation with the combination vs. azithromycin alone (17{+/-}39 vs. 0.5{+/-}40 ms, p=0.07). No patients manifested torsades de pointes HP torsades de pointes MESHD. Conclusions: Overall, 12% of patients manifested critical QTc interval prolongation MESHD, and traditional risk indices failed to flag these patients. With the drug combination, QTc prolongation MESHD was several-fold higher compared to azithromycin alone. The balance between uncertain benefit and potential risk when treating COVID-19 patients with these drugs should be carefully assessed prior to use.

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MeSH Disease
Human Phenotype
Transmission
Seroprevalence


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