Abstract Purpose: The objectives of this study were to describe the prevalence of QTc-prolonging medication exposures among hospitalized patients and examine the association between QTc-prolonging medication exposure and new onset QTc-prolongation. Methods: A retrospective cohort study was conducted among a convenience sample of patients hospitalized at Upstate University Hospital during a 6 month time period. Data including patient demographics, medication exposures, and ECG results were collected. Patients with a diagnosis of bundle branch block were excluded. Medications were categorized according to three risk groups for Torsades de Pointes: risk, conditional risk, and possible risk. An abnormal QTc interval was defined as >430 for men and >450 for women. Data were analyzed using SPSS statistical software. Results: One hundred fifty patients were included. Mean age was 62 years (SD, 11.9), 80 patients (53.3%) were female, and the majority of patients were Caucasian (46.3%) or African American (38.3%). Ninety seven (64.7%) patients were prescribed medication associated with some risk for QTc prolongation, including 47 patients (31.3%) who were concurrently prescribed 2 or more QTcprolonging medications. An EKG was performed in 112 (74.7%) patients and 76 (50.7%) had an abnormal QTc interval. Most abnormal QTc intervals were found upon admission with 9 patients experiencing new onset QTc prolongation during hospitalization. No significant association was found between QTc medication exposure and new onset QTc prolongation. Conclusion: Hospitalized patients are at high risk for single and multiple QTc medication exposures. Although a substantial number of patients had an abnormal QTc interval, most were discovered upon admission and few experienced new onset QTc prolongation. A significant association between medication exposure and new onset QTc prolongation was not detected in this study.

During the process of drug discovery and development, living animal models have been widely used ranging from lead compound optimization, structure and activity relationship analyses, pharmacokinetic studies, therapeutic evaluation, to toxicity assessment [1,2]. While being applied in all the processes with large scale and high throughput advantages, cell culture models do not display the full anatomical and physiologic permeability and enzymatic barrier characteristics of physiological systems [3]. As a result, majority of the leading candidates fail in further clinical trials primarily due to the lack of studies on drug metabolic activation, distribution across physiological barrier, and off-target toxicity [4]. Only feasible animal models can essentially bridge those translational gaps to the clinic, thereby providing a viable in vivo system to validate new drugs for therapeutic applications [2]. Zebrafish (Danio rerio) has been considered as a promising model organism for biomedical research and its application is rapidly growing in the past few decades [5,6].