Genetic QT Score and Sleep Apnea as Predictors of Sudden Cardiac Death in the UK Biobank.

Introduction: The goal of this study was to evaluate the association between a polygenic risk score (PRS) for QT prolongation (QTc-PRS), QTc intervals and mortality in patients enrolled in the UK Biobank with and without sleep apnea.

Methods: The QTc-PRS was calculated using allele copy number and previously reported effect estimates for each single nuclear polymorphism SNP. Competing-risk regression models adjusting for age, sex, BMI, QT prolonging medication, race, and comorbid cardiovascular conditions were used for sudden cardiac death (SCD) analyses.

A QTc risk score in patients with obstructive sleep apnea.

Introduction: Patients with obstructive sleep apnea (OSA) are at risk for QTc prolongation, a known risk factor for increased mortality. The pro-QTc score can help identify individuals at increased risk for mortality associated with increased QTc however, it has not been evaluated in patients with OSA. The goal of this study was to evaluate the pro-QTc score in patients with OSA.

Relationship between a risk score for QT interval prolongation and mortality across rural and urban inpatient facilities.

Objectives: To evaluate the relationship between a modified Tisdale QTc-risk score (QTc-RS) and inpatient mortality and length of stay in a broad inpatient population with an order for a medication with a known risk of torsades de pointes (TdP).

Background: Managing the risk of TdP is challenging due to the number of medications with known risk of TdP and the complexity of precipitating factors. A model to predict risk of mortality may be useful to guide treatment decisions.

Clinician Responses to a Clinical Decision Support Advisory for High Risk of Torsades de Pointes.

Background Torsade de pointes (TdP) is a potentially fatal cardiac arrhythmia that is often drug induced. Clinical decision support (CDS) may help minimize TdP risk by guiding decision making in patients at risk. CDS has been shown to decrease prescribing of high-risk medications in patients at risk of TdP, but alerts are often ignored.

Markers of ventricular repolarization and overall mortality in sleep disordered breathing.

Introduction: Variability and prolongation of ventricular repolarization - measured by changes in QT interval and QT variability are independently associated with ventricular arrhythmias, sudden death, and mortality but such studies did not examine the role of sleep-disordered breathing. We aimed to determine whether sleep-disordered breathing moderated the association between measures of ventricular repolarization and overall mortality.

Methods: Eight hundred participants were randomly selected from each of the following four groups in the Sleep Heart Health Study: mild, moderate, severe or no sleep disordered breathing (n = 200 each).

Limited Genomics Training Among Physicians Remains a Barrier to Genomics-Based Implementation of Precision Medicine.

The field of precision medicine has undergone significant growth over the past 10 years. Despite increasing applications of clinical genetic and genomic testing, studies consistently report limited knowledge of genetics and genomics among healthcare providers. This study explored barriers to the implementation of precision medicine by surveying physicians working in a large academic medical center.

Clinician Satisfaction With Advanced Clinical Decision Support to Reduce the Risk of Torsades de Pointes.

Objectives: Clinical decision support (CDS) can potentially help clinicians identify and manage patients who are at risk for torsades de pointes (TdP). However, computer alerts are often ignored and might contribute to alert fatigue. The goals of this project were to create an advanced TdP CDS advisory that presents patient-specific, relevant information, including 1-click management options, and to determine clinician satisfaction with the CDS.

Synoptic assessment of coastal total alkalinity through community science.

Comprehensive sampling of the carbonate system in estuaries and coastal waters can be difficult and expensive because of the complex and heterogeneous nature of near-shore environments. We show that sample collection by community science programs is a viable strategy for expanding estuarine carbonate system monitoring and prioritizing regions for more targeted assessment. 'Shell Day' was a single-day regional water monitoring event coordinating coastal carbonate chemistry observations by 59 community science programs and seven research institutions in the northeastern United States, in which 410 total alkalinity (TA) samples from 86 stations were collected.

Linking Technology to Address the Social and Medical Determinants of Health for Safe Medicines Use.

Objectives: Both social and medical factors can negatively affect health outcomes, especially in vulnerable populations. To address these 2 types of factors in a postdischarge population, 2 nonprofit organizations collaborated to combine their novel decision support programs and address the question: Could combined programs have greater potential for improved health outcomes?

Methods: HomeMeds, a social health program in which trained social services staff make home visits to vulnerable clients, was combined with MedSafety Scan, a medical health, clinical decision support tool. Data captured in the home visits were entered into the HomeMeds and MedSafety Scan programs to detect those patients at the greatest risk of adverse health outcomes because of medications.

Assisted prescribing: Clinical decision support with MedSafety Scan now available.

Too often, adverse events due to prescription medications are a cause of death and disability. Many of these events could be prevented, but most efforts to do so have had limited success, mainly due to the challenges of having the information that is necessary for safe prescribing available at the time when prescriptions are being written. Hospital-based Clinical Decision Support (CDS) systems are being developed to manage this information, identify at- risk patients, and help mitigate their risk of medication-induced harm.

Investigating the Impact of Gadolinium-Based Contrast Agents on the Corrected QT Interval.

Introduction The manufacturing labels for all currently marketed gadolinium-based MRI contrast agents describe adverse cardiac events reported during post-market use. The goal of this study was to determine prolongation of the rate-corrected QT interval occurs in the immediate setting after gadolinium-based MRI contrast agent injection. Methods This study enrolled adults scheduled to have a gadolinium-based MRI contrast agent injection as part of a diagnostic MRI.

Global Ocean Spectrophotometric pH Assessment: Consistent Inconsistencies.

Ocean acidification (OA)-or the decrease in seawater pH resulting from ocean uptake of CO released by human activities-stresses ocean ecosystems and is recognized as a Climate and Sustainable Development Goal Indicator that needs to be evaluated and monitored. Monitoring OA-related pH changes requires a high level of precision and accuracy. The two most common ways to quantify seawater pH are to measure it spectrophotometrically or to calculate it from total alkalinity (TA) and dissolved inorganic carbon (DIC).

Identification of populations likely to benefit from pharmacogenomic testing.

Objectives: Pharmacogenomic testing (PGX) implementation is rapidly expanding, including pre-emptive testing funded by health systems. PGX continues to develop an evidence base that it saves money and improves clinical outcomes. Identifying the potential impact of pre-emptive testing in specific populations may aid in the development of a business case.

Arrhythmogenic foods - A growing medical problem.

Arrhythmogenic ingredients in our diet such as mushrooms, licorice, toxic honey, liquid protein drinks, etc. have long been recognized as rare but important considerations in the differential diagnosis of arrhythmias. Anecdotal reports of torsades de pointes (TdP), arrhythmias and/or sudden death and small studies in normal subjects have suggested that simple ingredients such as grapefruit juice or ingredients in energy drinks marketed as dietary supplements could have direct arrhythmogenic actions, especially in patients with congenital long QT syndrome (cLQTS).

Summary of Torsades de Pointes (TdP) Reports Associated with Intravenous Drug Formulations Containing the Preservative Chlorobutanol.

Introduction: Drug-induced torsades de pointes (TdP) is a potentially lethal ventricular arrhythmia that is associated with drugs that prolong the QT interval on the electrocardiogram (ECG) due to their interference with the cardiac potassium current, I. Intravenous (IV) formulations of methadone have been associated with TdP and contain the preservative chlorobutanol, which, like methadone, blocks I. The combinations of chlorobutanol with methadone or terfenadine, another I blocker, produce synergistic I block.

A computerized scoring system to improve assessment of heparin-induced thrombocytopenia risk.

Essentials Current risk scores for heparin-induced thrombocytopenia (HIT) are not computer-friendly. We compared a new computerized risk score with the 4Ts score in a large healthcare system. The computerized risk score agrees with the 4Ts score 85% of the time.

CredibleMeds.org: What does it offer?

Since the 1990s, when numerous non-cardiac drugs were first recognized to have the potential to prolong the QT interval and cause torsades de pointes (TdP), clinicians, drug regulators, drug developers, and clinical investigators have become aware of the complexities of assessing evidence and determining TdP causality for the many drugs being marketed or under development. To facilitate better understanding, the Arizona Center for Education and Research on Therapeutics, known as AZCERT, has developed the CredibleMeds.org website which includes QTdrugs, a listing of over 220 drugs placed in four risk categories based on their association with QT prolongation and TdP.

Adverse Drug Event Causality Analysis (ADECA): A Process for Evaluating Evidence and Assigning Drugs to Risk Categories for Sudden Death.

Growing evidence indicates that many drugs have the ability to cause a potentially lethal cardiac arrhythmia, torsades de pointes (TdP). This necessitates the development of a compilation of drugs that have this potential toxicity. Such a list is helpful in identifying the etiology of TdP in patients taking multiple drugs and assists decision making by those caring for patients at high risk of TdP.

Common Genetic Variant Risk Score Is Associated With Drug-Induced QT Prolongation and Torsade de Pointes Risk: A Pilot Study.

Background: Drug-induced QT interval prolongation, a risk factor for life-threatening ventricular arrhythmias, is a potential side effect of many marketed and withdrawn medications. The contribution of common genetic variants previously associated with baseline QT interval to drug-induced QT prolongation and arrhythmias is not known.

Methods: We tested the hypothesis that a weighted combination of common genetic variants contributing to QT interval at baseline, identified through genome-wide association studies, can predict individual response to multiple QT-prolonging drugs.

Coupling Data Mining and Laboratory Experiments to Discover Drug Interactions Causing QT Prolongation.

Background: QT interval-prolonging drug-drug interactions (QT-DDIs) may increase the risk of life-threatening arrhythmia. Despite guidelines for testing from regulatory agencies, these interactions are usually discovered after drugs are marketed and may go undiscovered for years.

Objectives: Using a combination of adverse event reports, electronic health records (EHR), and laboratory experiments, the goal of this study was to develop a data-driven pipeline for discovering QT-DDIs.