BackgroundInitiation of the antiarrhythmic medication dofetilide requires an FDA-mandated 3 days of telemetry monitoring due to heightened risk of toxicity within this time period. Although a recommended dose management algorithm for dofetilide exists, there is a range of real-world approaches to dosing the medication.Methods and resultsIn this multicenter investigation, clinical data from the Antiarrhythmic Drug Genetic (AADGEN) study was examined for 354 patients undergoing dofetilide initiation. Univariate logistic regression identified a starting dofetilide dose of 500 mcg (OR 5.0, 95%CI 2.5–10.0, p<0.001) and sinus rhythm at the start of dofetilide loading (OR 2.8, 95%CI 1.8–4.2, p<0.001) as strong positive predictors of successful loading. Any dose-adjustment during loading (OR 0.19, 95%CI 0.12–0.31, p<0.001) and a history coronary artery disease (OR 0.33, 95%CI 0.19–0.59, p<0.001) were strong negative predictors of successful dofetilide loading. Based on the observation that any dose adjustment was a significant negative predictor of successful initiation, we applied multiple supervised approaches to attempt to predict the dose adjustment decision, but none of these approaches identified dose adjustments better than a probabilistic guess. Principal component analysis and cluster analysis identified 8 clusters as a reasonable data reduction method. These 8 clusters were then used to define patient states in a tabular reinforcement learning model trained on 80% of dosing decisions. Testing of this model on the remaining 20% of dosing decisions revealed good accuracy of the reinforcement learning model, with only 16/410 (3.9%) instances of disagreement.ConclusionsDose adjustments are a strong determinant of whether patients are able to successfully initiate dofetilide. A reinforcement learning algorithm informed by unsupervised learning was able to predict dosing decisions with 96.1% accuracy. Future studies will apply this algorithm prospectively as a data-driven decision aid.

Context: Screening for malaria and coronavirus disease (COVID-19) in all patients with acute febrile illness is necessary in malaria-endemic areas to reduce malaria-related mortality and to prevent the transmission of COVID-19 by isolation. Aims: A pilot study was undertaken to determine the incidence of SARS-CoV-2 infection among febrile patients attending a malaria clinic. Subjects and Methods: All patients were tested for malaria parasite by examining thick and thin blood smears as well as by rapid malaria antigen tests. COVID-19 was detected by rapid antigen test and reverse transcriptase–polymerase chain reaction in patients agreeing to undergo the test. Results: Out of 262 patients examined, 66 (25.19%) were positive for Plasmodium vivax , 45 (17.17%) for Plasmodium falciparum (Pf) with a slide positivity rate of 42.40%, and Pf% of 40.50%. Only 29 patients consented for COVID-19 testing along with malaria; of them, 3 (10.34%) were positive for COVID-19 alone and 2 (6.89%) were positive for both COVID-19 and P. vivax with an incidence of 17.24%. A maximum number of patients (196) did not examine for COVID-19 as they did not agree to do the test. Conclusion: Diagnosis of COVID-19 among three patients (10.34%) is significant both in terms of identification of cases and to isolate them for preventing transmission in the community. Detection of COVID-19 along with malaria is equally important for their proper management.

Sotalol, a Vaughan-Williams Class III antiarrhythmic medication, is used to manage atrial arrhythmias. Due to its QT-prolonging effect and subsequent increased risk of torsade de pointes, many centers admit patients during the initial dosing period. Despite its widespread use, little information is available regarding dosing protocols during this period. In this multicenter investigation, dosing protocols in patients initiating sotalol therapy were examined to identify predictors of successful sotalol initiation. Over a 4-year period, patients admitted to 5 hospitals in the United States for inpatient telemetry monitoring during initiation for nonresearch purposes were enrolled. A 3-day course of 5 of 6 doses of sotalol was considered successful completion of the loading protocol. Of the 213 enrolled patients, over 90% were successfully discharged on sotalol. Significant bradycardia, ineffectiveness, and excessive QT prolongation were reasons for failed completion. Absence of a dose adjustment was a strong predictor of successful initiation (odds ratio: 6.6, 95% confidence interval: 1.3-32.7, P = .02). Hypertension, use of a calcium channel blocker, use of a separate β-blocker, and presence of a pacemaker were predictors of dose adjustments. Marginal structural models (ie, inverse probability weighting based on probability of a dose adjustment) verified that these factors also predicted successful initiation via preventing any dose adjustment and suggests that considering these factors may result in a higher likelihood of successful initiation in future investigations. In conclusion, we found that the majority of patients admitted for sotalol initiation are successfully discharged on the medication. The study findings suggest that factors predicting need for dose adjustment can be used to identify patients who could undergo outpatient initiation. Prospective studies are needed to verify this approach.

No abstract

Central Illustration