Background-In a recent cohort study, prolongation of the corrected QT interval (QTc) was associated with an independent increased risk of sudden cardiac death (SCD). We evaluated determinants of prolonged QTc and the relationship of prolonged QTc to SCD risk among patients with coronary artery disease in the general population. Methods and Results-A case-control design was used. Cases were SCD patients with coronary artery disease among a metropolitan area of 1 000 000 residents (2002 to 2006); controls were area residents with coronary artery disease but no history of SCD. All cases were required to have an ECG suitable for QTc analysis before and unrelated to the occurrence of SCD. A total of 373 cases and 309 controls met criteria for analysis. Mean QTc was significantly longer in cases than in controls (450Ϯ45 versus 433Ϯ37 ms; PϽ0.0001). In a multivariate model, gender, diabetes mellitus, and QTc-prolonging drugs were significant determinants of QTc prolongation in controls. In a logistic regression model predicting SCD, diabetes mellitus (odds ratio, 1.97; 95% confidence interval, 1.32 to 2.96) and use of QTc-prolonging drugs (odds ratio, 2.90; 95% confidence interval, 1.92 to 4.37) were significant predictors of SCD among subjects with normal or borderline QTc. However, abnormally prolonged QTc in the absence of diabetes and QT-prolonging medications was the strongest predictor of SCD (odds ratio, 5.53; 95% confidence interval, 3.20 to 9.57). Conclusions-Diabetes mellitus and QTc-affecting drugs determined QTc prolongation and were predictors of SCD in coronary artery disease. However, idiopathic abnormal QTc prolongation was associated with 5-fold increased odds of SCD. A continued search for novel determinants of QTc prolongation such as genomic factors is likely to enhance risk stratification for SCD in coronary artery disease. (Circulation. 2009;119:663-670.)

Telemedicine is the delivery of health care services using information or communication technology. In the current pandemic scenario, telemedicine can supplement health-care delivery in the absence of in-person visit. The Government of India has recently launched the e-sanjeevani OPD, a National teleconsultation service, which has been adopted by many state governments as mandatory for health-care providers. With Indian Medical Association issuing an advisory against the use of telemedicine except in few situations, a lot of confusion exists in the mind of a pediatrician. Despite the uncertain situation, we have to remember that other diseases shall not stall in the face of a pandemic. Since telemedicine is an evolving subject, training of medical professionals, clear guidelines and good quality internet service systems will go a long way in increasing the acceptability of telemedicine in the Indian population. We herein discuss issues related to using telemedicine during the SARS-CoV-2 pandemic.

Background Following myocardial infarction, individual patients can have wide variations in extent of LV systolic dysfunction and increased LV mass. Both affect risk of sudden cardiac death but only LV ejection fraction is used for risk prediction. Objective We evaluated the independent as well as additive contributions of increased LV mass and decreased LV ejection fraction to sudden cardiac death in the general population. Methods In the ongoing Oregon Sudden Unexpected Death Study, we studied consecutive SCD cases (n=191) and coronary artery disease controls (n=203) from the Portland, Oregon metropolitan area (population approx. 1,000,000; 2002–2008). Comparisons of echocardiographic LV mass obtained prior and unrelated to SCD were conducted and a logistic regression model evaluated the relationship between SCD, severe LVSD, LV mass and other relevant clinical variables. Results In a multivariate model, both severe LVSD and LVH were associated with increased SCD risk (OR 1.9, 95% CI 1.1 – 3.2 for severe LVSD; OR 1.8, 95% CI 1.1 – 2.9 for LVH). In patients with coexisting severe LVSD and LVH, risk of SCD was additive (OR 3.5, 95% CI 1.7 – 7.2). In the same model, increased age, atrial fibrillation/flutter, elevated creatinine and diabetes independently increased risk, and use of angiotensin receptor blockers attenuated risk. Conclusions Reduced LV ejection fraction and increased LV mass had independent and additive effects on risk of sudden death. Despite the significant overlap between the two conditions, these findings point toward the existence of independent mechanistic pathways for ventricular arrhythmias that occur due to LV systolic dysfunction and LV hypertrophy.

Coronavirus pandemic has caused a vast number of deaths worldwide. Thus creating an urgent need to develop effective counteragents against novel coronavirus disease (COVID-19). Many antiviral drugs have been repurposed for treatment but implicated minimal recovery, which further advanced the need for clearer insights and innovation to derive effective therapeutics. Strategically, Noscapine, an approved antitussive drug with positive effects on lung linings may show favorable outcomes synergistically with antiviral drugs in trials. Hence, we have theoretically examined the combinatorial drug therapy by culminating the existing experimental results with in silico analyses. We employed the antitussive noscapine in conjugation with antiviral drugs (Chloroquine, Umifenovir, Hydroxychloroquine, Favlplravir and Galidesivir). We found that Noscapine-Hydroxychloroquine (Nos-Hcq) conjugate has strong binding affinity for the main protease (Mpro) of SARS-CoV-2, which performs key biological function in virus infection and progression. Nos-Hcq was analyzed through molecular dynamics simulation. The MD simulation for 100 ns affirmed the stable binding of conjugation unprecedentedly through RMSD and radius of gyration plots along with critical reaction coordinate binding free energy profile. Also, dynamical residue cross-correlation map with principal component analysis depicted the stable binding of Nos-Hcq conjugate to Mpro domains with optimal secondary structure statistics of complex dynamics. Also, we reveal the drugs with stable binding to major domains of Mpro can significantly improve the work profile of reaction coordinates, drug accession and inhibitory regulation of Mpro. The designed combinatorial therapy paves way for further prioritized in vitro and in vivo investigations for drug with robust binding against Mpro of SARS-CoV-2.