An analysis of QTc prolongation with atypical antipsychotic medications and selective serotonin reuptake inhibitors using a large ECG record database

<p><b>Background:</b> This study evaluated the effects of atypical antipsychotic drugs and selective serotonin reuptake inhibitors (SSRIs) on the corrected QT (QTc) interval using a large database obtained from clinical settings. Additionally, the effects of factors including age on QTc intervals were estimated.</p> <p><b>Methods:</b> Using an open-access QT database (ECG-ViEW), QTc-lengthening effects of 14 selected atypical antipsychotics and SSRIs were compared to those of a positive control drug, cilostazol, and a negative control drug, diazepam. We also evaluated effects of age, sexgender, and select electrolyte levels on observed QTc intervals.</p> <p><b>Results:</b> The frequency of QTc prolongation with the pooled data of the 14 study drugs was lower than that with cilostazol (age-adjusted odds ratio (OR) = 0.43, 95% confidence interval (CI) = 0.27-0.69), but no significant difference was found relative to when compared with that with diazepam (age-adjusted OR = 0.89, 95% CI = 0.55-1.47). Furthermore, administration of the 14 study drugs significantly increased the QTc interval by 2.89 ms after each 10-year age increment (p-value < 0.0001).</p> <p><b>Conclusions:</b> This study suggests that atypical antipsychotic drugs and SSRIs are less likely to be associated with QTc prolongation in clinical settings. In addition, age showed a significant association with the QTc interval. Further studies with well-characterized cohorts are warranted.</p

The Effects of Moxifloxacin on QTc Interval in Healthy Korean Male Subjects

BACKGROUND AND OBJECTIVE: Moxifloxacin 400 mg is a widely used positive control in thorough QT (TQT) studies, but its QT-prolonging effects in Korean subjects have not been studied. The present study was conducted to collect pilot data in Korean subjects after moxifloxacin administration to evaluate the adequacy of moxifloxacin as a positive control. METHODS: Thirty-eight, healthy, Korean, male subjects were recruited for pharmacokinetic (PK) blood sampling and electrocardiography (ECG) recordings at three different study sites. On day 1, a baseline 12-lead ECG was recorded, and on day 2, ECG recordings were conducted after placebo, or moxifloxacin 400- or 800-mg administration. Baseline-corrected, placebo-adjusted, corrected QT (ΔΔQTc) values were calculated. Blood samples were collected after moxifloxacin administration and PK parameters were assessed. RESULTS: A total of 33 subjects completed the study. The largest time-matched ΔΔQTc occurred approximately 4 h after dosing, with ΔΔQTcI (QT interval corrected by individual QT-RR regression model) values of 11.66 ms (moxifloxacin 400 mg) and 20.96 ms (800 mg). The mean and 90 % confidence intervals of ΔΔQTcI did not include zero at any of the measurement time points. There was a positive correlation between plasma moxifloxacin concentration and ΔΔQTcI (r = 0.422). Dose-proportional PK profiles were observed. CONCLUSION: Moxifloxacin 400 mg is an adequate positive control in Korean TQT studies. Our results indicate that moxifloxacin 400 mg can be used to evaluate the cardiac safety of a drug in Korean subjects

An analysis of QTc prolongation with atypical antipsychotic medications and selective serotonin reuptake inhibitors using a large ECG record database

<p><b>Background:</b> This study evaluated the effects of atypical antipsychotic drugs and selective serotonin reuptake inhibitors (SSRIs) on the corrected QT (QTc) interval using a large database obtained from clinical settings. Additionally, the effects of factors including age on QTc intervals were estimated.</p> <p><b>Methods:</b> Using an open-access QT database (ECG-ViEW), QTc-lengthening effects of 14 selected atypical antipsychotics and SSRIs were compared to those of a positive control drug, cilostazol, and a negative control drug, diazepam. We also evaluated effects of age, sexgender, and select electrolyte levels on observed QTc intervals.</p> <p><b>Results:</b> The frequency of QTc prolongation with the pooled data of the 14 study drugs was lower than that with cilostazol (age-adjusted odds ratio (OR) = 0.43, 95% confidence interval (CI) = 0.27-0.69), but no significant difference was found relative to when compared with that with diazepam (age-adjusted OR = 0.89, 95% CI = 0.55-1.47). Furthermore, administration of the 14 study drugs significantly increased the QTc interval by 2.89 ms after each 10-year age increment (p-value < 0.0001).</p> <p><b>Conclusions:</b> This study suggests that atypical antipsychotic drugs and SSRIs are less likely to be associated with QTc prolongation in clinical settings. In addition, age showed a significant association with the QTc interval. Further studies with well-characterized cohorts are warranted.</p

Hyperglycemia and Hypoglycemia Are Associated with In-Hospital Mortality among Patients with Coronavirus Disease 2019 Supported with Extracorporeal Membrane Oxygenation

Metabolic abnormalities, such as preexisting diabetes or hyperglycemia or hypoglycemia during hospitalization aggravated the severity of COVID-19. We evaluated whether diabetes history, hyperglycemia before and during extracorporeal membrane oxygenation (ECMO) support, and hypoglycemia were risk factors for mortality in patients with COVID-19. This study included data on 195 patients with COVID-19, who were aged &gt;= 19 years and were treated with ECMO. The proportion of patients with diabetes history among nonsurvivors was higher than that among survivors. Univariate Cox regression analysis showed that in-hospital mortality after ECMO support was associated with diabetes history, renal replacement therapy (RRT), and body mass index (BMI) &lt; 18.5 kg/m(2). Glucose at admission &gt;200 mg/dL and glucose levels before ventilator &gt;200 mg/dL were not associated with in-hospital mortality. However, glucose levels before ECMO &gt;200 mg/dL and minimal glucose levels during hospitalization 200 mg/dL before ECMO and minimal glucose &lt;70 mg/dL during hospitalization remained risk factors for in-hospital mortality after adjustment for age, BMI, and RRT. In conclusion, glucose &gt;200 mg/dL before ECMO and minimal glucose level &lt;70 mg/dL during hospitalization were risk factors for in-hospital mortality among COVID-19 patients who underwent ECMO.N

Hyperglycemia and Hypoglycemia Are Associated with In-Hospital Mortality among Patients with Coronavirus Disease 2019 Supported with Extracorporeal Membrane Oxygenation

Metabolic abnormalities, such as preexisting diabetes or hyperglycemia or hypoglycemia during hospitalization aggravated the severity of COVID-19. We evaluated whether diabetes history, hyperglycemia before and during extracorporeal membrane oxygenation (ECMO) support, and hypoglycemia were risk factors for mortality in patients with COVID-19. This study included data on 195 patients with COVID-19, who were aged &ge;19 years and were treated with ECMO. The proportion of patients with diabetes history among nonsurvivors was higher than that among survivors. Univariate Cox regression analysis showed that in-hospital mortality after ECMO support was associated with diabetes history, renal replacement therapy (RRT), and body mass index (BMI) &lt; 18.5 kg/m2. Glucose at admission &gt;200 mg/dL and glucose levels before ventilator &gt;200 mg/dL were not associated with in-hospital mortality. However, glucose levels before ECMO &gt;200 mg/dL and minimal glucose levels during hospitalization &lt;70 mg/dL were associated with in-hospital mortality. Multivariable Cox regression analysis showed that glucose &gt;200 mg/dL before ECMO and minimal glucose &lt;70 mg/dL during hospitalization remained risk factors for in-hospital mortality after adjustment for age, BMI, and RRT. In conclusion, glucose &gt;200 mg/dL before ECMO and minimal glucose level &lt;70 mg/dL during hospitalization were risk factors for in-hospital mortality among COVID-19 patients who underwent ECMO