Raymond L Woosley

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Scholarly Contributions

Chapters

• Woosley, R. L. (2021). Drug-induced Torsades de Pointes. In Torsades de Pointes(pp Chapter 8).
• Woosley, R. L., & Woosley, R. D. (2021). QT drugs and the CredibleMeds Website: Clinical and Research Applications. In On the QT(pp Chapter 12).
• Woosley, R. L., & Schwartz, P. J. (2019). Drug-induced Long QT Syndrome and Torsades de pointes. In Cardiac Repolarization. New York: Springer.
• Woosley, R., & Schwartz, P. J. (2019). Drug-induced Long QT Syndrome and Torsades de Pointes. In Cardiac repolarization(pp 185-200). New York: Springer.

Journals/Publications

• Arora, A., Zareba, W., Woosley, R. L., Klimentidis, Y. C., Patel, I. Y., Quan, S. F., Wendel, C., Shamoun, F., Guerra, S., Parthasarathy, S., & Patel, S. I. (2023). Genetic QT Score and Sleep Apnea as Predictors of Sudden Cardiac Death in the UK Biobank. medRxiv : the preprint server for health sciences.
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  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.
• Patel, S. I., Zareba, W., Wendel, C., Perez, K., Patel, I., Quan, S. F., Youngstedt, S. D., Parthasarathy, S., & Woosley, R. L. (2023). A QTc risk score in patients with obstructive sleep apnea. Sleep medicine, 103, 159-164.
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  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.
• Tan, M. S., Heise, C. W., Gallo, T., Tisdale, J. E., Woosley, R. L., Antonescu, C. C., Gephart, S. M., & Malone, D. C. (2023). Relationship between a risk score for QT interval prolongation and mortality across rural and urban inpatient facilities. Journal of electrocardiology, 77, 4-9.
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  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).
• Gallo, T., Heise, C. W., Woosley, R. L., Tisdale, J. E., Antonescu, C. C., Gephart, S. M., & Malone, D. C. (2022). Clinician Satisfaction With Advanced Clinical Decision Support to Reduce the Risk of Torsades de Pointes.. Journal of patient safety, 18(6), e1010-e1013. doi:10.1097/pts.0000000000000996
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  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..The advanced TdP CDS was developed and implemented across a health system comprising 29 hospitals. The advisory presents patient-specific information including relevant risk factors, laboratory values, and 1-click options to help manage the condition in high-risk patients. A short electronic survey was created to gather clinician feedback on the advisory..After implementation, an email invitation to complete the anonymous advisory-related survey was sent to 442 clinicians who received the advisory. Among the 38 respondents, feedback was generally positive, with 79% of respondents reporting that the advisory helps them care for their patients and 87% responding that alternative actions for them to consider were clearly specified. However, 46% of respondents indicated the alert appeared too frequently..Advanced TdP risk CDS that provides relevant, patient-specific information and 1-click management options can be generally viewed favorably by clinicians who receive the advisory.
• Gallo, T., Heise, C. W., Woosley, R. L., Tisdale, J. E., Tan, M. S., Antonescu, C. C., Gephart, S. M., & Malone, D. C. (2022). Clinician Responses to a Clinical Decision Support Advisory for High Risk of Torsades de Pointes. Journal of the American Heart Association, 11(11). doi:10.1161/jaha.122.024338
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  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. Other risk‐management options can potentially be incorporated in TdP risk CDS. Our goal was to evaluate actions clinicians take in response to a CDS advisory that uses a modified Tisdale QT risk score and presents management options that are easily selected (eg, single click). Methods and Results We implemented an inpatient TdP risk advisory systemwide across a large health care system comprising 30 hospitals. This CDS was programmed to appear when prescribers attempted ordering medications with a known risk of TdP in a patient with a QT risk score ≥12. The CDS displayed patient‐specific information and offered relevant management options including canceling offending medications and ordering electrolyte replacement protocols or ECGs. We retrospectively studied the actions clinicians took within the advisory and separated by drug class. During an 8‐month period, 7794 TdP risk advisories were issued. Antibiotics were the most frequent trigger of the advisory (n=2578, 33.1%). At least 1 action was taken within the advisory window for 2700 (34.6%) of the advisories. The most frequent action taken was ordering an ECG (n=1584, 20.3%). Incoming medication orders were canceled in 793 (10.2%) of the advisories. The frequency of each action taken varied by drug class ( P
• Zareba, W., Xia, X., Woosley, R. L., Patel, S. I., Patel, I., Parthasarathy, S., Mashaqi, S., Couderc, J., & Combs, D. (2021). 479 The association of QTc and QT Variability with Severity of Sleep Disordered Breathing. Sleep, 44. doi:10.1093/sleep/zsab072.478
• Gress, K. L., Gallo, T., Urits, I., Geng, X., Viswanath, O., Kaye, A. D., & Woosley, R. L. (2020). Investigating the Impact of Gadolinium-Based Contrast Agents on the Corrected QT Interval. Cureus, 12(8), e9668.
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  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. A single-lead electrocardiogram was recorded using the AliveCor Kardia® ECG (Mountain View, CA) device before and after injection. The rate-corrected QT interval was subsequently measured by two independent investigators. The QT interval was corrected for rate using the two most common formulas, originally cited by Bazett and Fridericia. These rate-corrected QT intervals from before and after gadolinium-based MRI contrast agent injection were compared using the Wilcoxon signed-rank test paired analysis. Results A total of 24 consenting adults had electrocardiogram that were free of motion artifact. The mean age of the final patient cohort was 59.4 years. There was an equal split of 12 men and 12 women. The mean pre-injection, rate-corrected QT interval, corrected using Bazett's formula, was 395 msec. The mean post-injection, rate-corrected QT interval, corrected using Bazett's formula, was 396 msec. The corrections using Fridericia's formula were 384 and 381 msec, respectively. There was no statistically significant change in Bazett-corrected QT interval (QTc-B) when pre-injection and post-injection values were directly compared. Discussion The results of the present investigation support the conclusion that gadolinium-based MRI contrast agents do not commonly affect rate-corrected QT interval in routine clinical use. While the frequency of rate-corrected QT interval prolongation might be overstated, the severity of adverse events is definitively not. A role for concomitant rate-corrected QT interval-prolonging drugs or unidentified rare factors such as genetic predisposition cannot be ruled out. The limitations of this study include its relatively small size and the implementation of a single-lead electrocardiogram to measure rate-corrected QT interval. Conclusion The present investigation revealed that significant rate-corrected QT interval prolongation, while previously reported in as many as 55% of patients after gadolinium-based MRI contrast agent injection, is not a common occurrence in the routine clinical setting.
• Heise, C. W., Gallo, T., Curry, S. C., & Woosley, R. L. (2020). Identification of populations likely to benefit from pharmacogenomic testing. Pharmacogenetics and genomics, 30(5), 91-95.
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  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.
• Woosley, R. L. (2020). Arrhythmogenic foods - A growing medical problem. Trends in cardiovascular medicine, 30(5), 310-312.
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  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). Two recent studies that employed the industry-standard "thorough QT" trial design leave no doubt that grapefruit juice and some energy drinks can prolong the QTc interval and to exceed 500 msec. in some patients with cLQTS, a threshold known to signal imminent danger. These reports raise numerous clinically important questions such as which other patients may be at risk of arrhythmias. For example, patients with multiple clinical risk factors for TdP (hypokalemia, bradycardia, female sex, etc.) may be at risk from these and possibly other dietary ingredients ingested by millions of people each day. It is essential that further research evaluate the safety of these and similar food products and that vulnerable patients, especially those with cLQTS, be warned of this serious and emerging threat.
• Woosley, R. L. (2020). Assisted prescribing: Clinical decision support with MedSafety Scan now available. Trends in cardiovascular medicine.
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  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. AZCERT, a non-profit created in 1999 with federal funding has helped hospitals develop these systems and has released an internet-based CDS program to assist in the safe prescribing of medications. This CDS program, MedSafety Scan, can be customized for any clinical venue and is available as an open-source program for all healthcare providers at www.medsafetyscan.org.
• Woosley, R. L., Parthasarathy, S., Lafleur, B., Couderc, J., Zareba, W., Xia, X., Woosley, R., Torabzadeh, E., Patel, S. I., Parthasarathy, S., Lafleur, B., & Couderc, J. (2020). 0571 Repolarization Variability Predicts Cardiovascular Death in Obstructive Sleep Apnea. Sleep, 43(Supplement_1), A219-A219. doi:10.1093/sleep/zsaa056.568
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  Abstract Introduction Patients with untreated obstructive sleep apnea (OSA) have a 2-3—fold increased risk of cardiovascular mortality (CVD) compared with individuals without OSA. QTc prolongation and increased QT variability among OSA patients may contribute to this association. Methods Patients with OSA from the Sleep Heart Health study were identified based on polysomnography criteria and their continuous electrocardiograms (ECG) analyzed for QTc duration and QT variability. Both Fridericia’s and Bazett’s heart rate corrections were used to calculate QTc. QT variability was measured as standard deviation of QT intervals (SDQT) and normalized QT interval variance (QTVN) at 1- and 5-minute intervals and short-term interval beat-to-beat QT variability (STVQT) was measured at 5-minute intervals. Lasso with elastic-net regularization was used as the variable/covariate selection method. Cox proportional hazards regression models were used to determine predictors of CVD. Results Data from 365 patients with OSA were screened. Ninety-seven patients were excluded from analysis due to low quality ECG data (n=50) or extremely high (> ln (10)) variability in QT/QTc and/or QT variability (n=12). Fifty two percent of the sample was male with mean age 65 years (±10). Fifty-six of these patients died of CVD. The mean (SD) QTc in the group that died was 411 (30) ms and 416 (34) ms compared to 406 (24) ms and 411 (25) ms using Fridericia (Cox LR p-value 0.055) and Bazett (p=0.090), respectively. Gender, age, race, diabetes, SDQT and STVQT were significant predictors for CVD. We fit models with the covariates and SDQT (at both 1 and 5 min) and STVQT as three models and demonstrate that both SDQT and STVQT are significantly associated with CVD death (p-values of 0.0048, 0.0089, and 0.0113, respectively) and all models had high area under the curve (0.8095, 0.8085, and 0.8125, respectively). Conclusion In patients with OSA, QT variability was associated with CVD. Support American Academy of Sleep Medicine Foundation
• Gallo, T., Curry, S. C., Padilla-Jones, A., Heise, C. W., Ramos, K. S., Woosley, R. L., & Raschke, R. A. (2019). A computerized scoring system to improve assessment of heparin-induced thrombocytopenia risk. Journal of thrombosis and haemostasis : JTH, 17(2), 383-388.
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  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. The new score could potentially improve HIT diagnosis via incorporation into decision support. SUMMARY: Background (HIT) is an immune-mediated adverse drug event associated with life-threatening thrombotic complications. The 4Ts score is widely used to estimate the risk for HIT and guide diagnostic testing, but it is not easily amenable to computerized clinical decision support (CDS) implementation. Objectives Our main objective was to develop an HIT computerized risk (HIT-CR) scoring system that provides platelet count surveillance for timing and degree of thrombocytopenia to identify those for whom diagnostic testing should be considered. Our secondary objective was to evaluate clinical management and subsequent outcomes in those identified as being at risk for HIT. Methods We retrospectively analyzed data from a stratified sample of 150 inpatients treated with heparin to compare the performance of the HIT-CR scoring system with that of a clinically calculated 4Ts score. We took a 4Ts score of ≥ 4 as the gold standard to determine whether HIT diagnostic testing should be performed. Results The best cutoff point of the HIT-CR score was a score of 3, which yielded 85% raw agreement with the 4Ts score and a kappa of 0.69 (95% confidence interval 0.57-0.81). Ninety per cent of patients with 4Ts score of ≥ 4 failed to undergo conventionally recommended diagnostic testing; 38% of these experienced persistent, unexplained thrombocytopenia, and 4% suffered life-threatening thrombotic complications suggestive of undiagnosed HIT. Conclusion The HIT-CR scoring system is practical for computerized CDS, agrees well with the 4Ts score, and should be prospectively evaluated for its ability to identify patients who should be tested for HIT.
• Romero, K., Woosley, D., Gallo, T., Tate, J., Heise, C., & Woosley, R. (2019). Drug labels, QT prolongation and ECG recommendations. Cardiology Today.
• Schwartz, P. J., Woosley, R. L., & Crotti, L. (2019). When prescribing drugs, do medical doctors and healthcare professionals realize that their patient has the long QT syndrome?. European heart journal, 40(37), 3118-3120.
• Vicente, J., Simlund, J., Johannesen, L., Sundh, F., Florian, J., Ugander, M., Wagner, G. S., Woosley, R. L., & Strauss, D. G. (2019). Investigation of potential mechanisms of sex differences in quinidine-induced torsade de pointes risk. Journal of electrocardiology, 48(4), 533-8.
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  The electrocardiographic index Tpeak-Tend has been proposed as a marker of dispersion of repolarization and may be a stronger predictor of torsade de pointes risk than QTc prolongation.
• Woosley, R. D., Romero, K., Heise, C. W., Gallo, T., Tate, J., & Woosley, R. L. (2019). Summary of Torsades de Pointes (TdP) Reports Associated with Intravenous Drug Formulations Containing the Preservative Chlorobutanol. Drug safety, 42(7), 907-913.
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  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.
• Schwartz, J. B., Woosley, R. L., & Peck, C. C. (2018). Farewell to Our Good Friend, Outstanding Mentor, and Colleague Darrell R. Abernethy (1949-2017). Clinical pharmacology and therapeutics.
• Woosley, R. L., Black, K., Heise, C. W., & Romero, K. (2018). CredibleMeds.org: What does it offer?. Trends in cardiovascular medicine, 28(2), 94-99.
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  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. Since the site was launched in 1999, it has become the single and most reliable source of information of its kind for patients, healthcare providers, and research scientists. Over 96,000 registered users rely on the QTdrugs database as their primary resource to inform their medication use, their prescribing or their clinical research into the impact of QT-prolonging drugs and drug-induced arrhythmias. The QTdrugs lists are increasingly used as the basis for clinical decision support systems in healthcare and for metrics of prescribing quality by healthcare insurers. A free smartphone app and an application program interface enable rapid and mobile access to the lists. Also, the CredibleMeds website offers numerous educational resources for patients, educators and healthcare providers that foster the safe use of medications.
• Strauss, D. G., Vicente, J., Johannesen, L., Blinova, K., Mason, J. W., Weeke, P., Behr, E. R., Roden, D. M., Woosley, R., Kosova, G., Rosenberg, M. A., & Newton-Cheh, C. (2017). A Common Genetic Variant Risk Score is Associated with Drug-Induced QT Prolongation and Torsade de Pointes Risk: A Pilot Study. Circulation, 135, 1300-1310.
• Strauss, D. G., Vicente, J., Johannesen, L., Blinova, K., Mason, J. W., Weeke, P., Behr, E. R., Roden, D. M., Woosley, R., Kosova, G., Rosenberg, M. A., & Newton-Cheh, C. (2017). Common Genetic Variant Risk Score Is Associated With Drug-Induced QT Prolongation and Torsade de Pointes Risk: A Pilot Study. Circulation, 135(14), 1300-1310.
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  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.
• Woosley, R. L., & Schwartz, P. J. (2017). Counterfeit drugs: A plot worthy of John le Carrè. International journal of cardiology, 243, 279-280.
• Woosley, R. L., Romero, K., Heise, C. W., Gallo, T., Tate, J., Woosley, R. D., & Ward, S. (2017). Adverse Drug Event Causality Analysis (ADECA): A Process for Evaluating Evidence and Assigning Drugs to Risk Categories for Sudden Death. Drug safety, 40(6), 465-474.
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  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. The Arizona Center for Education and Research on Therapeutics (AZCERT) has developed a process to standardize the identification of drugs and place them in risk categories for their clinical ability to cause TdP and QT prolongation. AZCERT's Adverse Drug Event Causality Analysis (ADECA) utilizes 16 types of data drawn from four sources to compile an open-source knowledge base, QTdrugs, which is maintained on the CredibleMeds.org website. Because the evidence for most drugs is incomplete, the ADECA process is used to place drugs into one of three categories that represent different levels of certainty: known TdP risk, possible TdP risk, and conditional TdP risk. Each category has strict evidentiary requirements for clinical evidence of TdP and/or QT prolongation. These are described in this paper. Because evidence can evolve over time, the ADECA process includes the continuous gathering and analysis of newly emerging evidence to revise the lists. The QTdrugs lists have proven to be a valued, readily available, commercial influence-free resource for healthcare providers, patients, researchers, and authors of consensus guidelines for the safe use of medicines.
• Lorberbaum, T., Sampson, K. J., Chang, J. B., Iyer, V., Woosley, R. L., Kass, R. S., & Tatonetti, N. P. (2016). Coupling Data Mining and Laboratory Experiments to Discover Drug Interactions Causing QT Prolongation. Journal of the American College of Cardiology, 68(16), 1756-1764.
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  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.
• Lorberbaum, T., Sampson, K. J., Woosley, R. L., Kass, R. S., & Tatonetti, N. P. (2016). An Integrative Data Science Pipeline to Identify Novel Drug Interactions that Prolong the QT Interval. Drug safety, 39(5), 433-41.
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  Drug-induced prolongation of the QT interval on the electrocardiogram (long QT syndrome, LQTS) can lead to a potentially fatal ventricular arrhythmia known as torsades de pointes (TdP). Over 40 drugs with both cardiac and non-cardiac indications are associated with increased risk of TdP, but drug-drug interactions contributing to LQTS (QT-DDIs) remain poorly characterized. Traditional methods for mining observational healthcare data are poorly equipped to detect QT-DDI signals due to low reporting numbers and lack of direct evidence for LQTS.
• Schwartz, P. J., & Woosley, R. L. (2016). Predicting the Unpredictable: Drug-Induced QT Prolongation and Torsades de Pointes. Journal of the American College of Cardiology, 67(13), 1639-1650.
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  Drug-induced long QT syndrome (diLQTS) and congenital LQTS (cLQTS) share many features, and both syndromes can result in life-threatening torsades de pointes (TdP). Our understanding of their mechanistic and genetic similarities has led to their improved clinical management. However, our inability to prevent diLQTS has resulted in removal of many medicines from the market and from development. Genetic and clinical risk factors for diLQTS and TdP are well known and raise the possibility of TdP prevention. Clinical decision support systems (CDSS) can scan the patient's electronic health records for clinical risk factors predictive of diLQTS and warn when a drug that can cause TdP is prescribed. CDSS have reduced prescriptions of QT-prolonging drugs, but these relatively small changes lack the power to reduce TdP. The growing genetic evidence linking diLQTS to cLQTS suggests that prevention of TdP in the future may require inclusion of both genetic and clinical predictors into CDSS.
• Woosley, R. L., Whyte, J., Mohamadi, A., & Romero, K. (2016). Medical decision support systems and therapeutics: The role of autopilots. Clinical pharmacology and therapeutics, 99(2), 161-4.
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  For decades, medical practice has increasingly relied on prescription medicines to treat, cure, or prevent illness but their net benefit is reduced by prescribing errors that result in adverse drug reactions (ADRs) and tens of thousands of deaths each year. Optimal prescribing requires effective management of massive amounts of data. Clinical decision support systems (CDSS) can help manage information and support optimal therapeutic decisions before errors are made by operating as the prescribers' "autopilot."
• Postema, P. G., & Woosley, R. L. (2014). Use of Drugs in Long QT Syndrome Type 3 and Brugada Syndrome. Cardiac Electrophysiology Clinics, 6(4), 811-817. doi:10.1016/j.ccep.2014.08.004
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  SUMMARYIn long QT syndrome type 3 and Brugada syn-drome, both cardiovascular and noncardiovascu-lar drugs may have detrimental effects on theintermediate phenotype of QT prolongation anddevelopment of the type-1 Brugada ECG, andmay subsequently result in potentially fatal ar-rhythmias. Cautious and considered use of drugsin these syndromes is thus warranted. In this re-view, we have intended to provide a knowledgebase, considerations, and recommendations ad-dressing this issue.REFERENCES 1. Van der Werf C, van Langen IM, Wilde AA. Suddendeath in the young: what do we know about it andhow to prevent? Circ Arrhythm Electrophysiol 2010;3:96–104.2. Schwartz PJ, Stramba-Badiale M, Crotti L, et al.Prevalence of the congenital long-QT syndrome.Circulation 2009;120:1761–7.3. Postema PG. About Brugada syndrome and itsprevalence. Europace 2012;14:925–8.4. Cerrone M, Cummings S, Alansari T, et al. A clinicalapproach to inherited arrhythmias. Circ CardiovascGenet 2012;5:581–90.5. Crotti L, Marcou CA, Tester DJ, et al. Spectrum andprevalence of mutations involving BrS1- through
• Curtis, L. H., Stoddard, J., Radeva, J. I., Hutchison, S., Dans, P. E., Wright, A., Woosley, R. L., & Schulman, K. A. (2006). Geographic variation in the prescription of schedule II opioid analgesics among outpatients in the United States.. Health services research, 41(3 Pt 1), 837-55. doi:10.1111/j.1475-6773.2006.00511.x
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  To measure geographic variation in opioid use in a large, commercially insured, outpatient population in the United States..Outpatient prescription drug claims database of a national pharmaceutical benefit manager for 7,873,337 subjects with at least one prescription drug claim in 2000..We measured the period prevalence of claims for opioid analgesics and controlled-release oxycodone at the state level. We measured geographic variation using the weighted coefficient of variation and systematic component of variation. In county-level multivariable regression, we explored associations between potential explanatory variables and claims for opioid analgesics and controlled-release oxycodone..A total of 567,778 (64.2 per 1,000 total claims) were for oral opioid analgesics. Claim rates by state ranged from 100 claims per 1,000 total claims. States with long-standing prescription monitoring programs had among the lowest rates. In the county-level data, presence of a statewide prescription monitoring program and proportions of the population aged 15-24 and 65 years and older were independently and negatively associated with claim rates for all opioid analgesics. Surgeons per 1,000, proportion of the population reporting illicit drug use, and proportion who were female were independently and positively associated with claim rates for all opioid analgesics. Only the proportion of the population aged 25-34 and number of surgeons per 1,000 were independently and positively associated with claim rates for oxycodone..Claim rates for opioid analgesics vary significantly by state. Presence of a statewide prescription monitoring program is associated with lower claim rates at the county level. Future research should use individual-level data to assess whether these findings reflect a reduction in abuse and diversion or suboptimal treatment of pain.
• Rehfeld, R. A., Woosley, R. L., Woosley, R. L., Skrepnek, G. H., Rehfeld, R. A., Murphy, J. E., Malone, D. C., Grizzle, A. J., Armstrong, E. P., & Abarca, J. A. (2006). Workload and availability of technology in metropolitan community pharmacies.. Journal of the American Pharmacists Association : JAPhA, 46(2), 154-60. doi:10.1331/154434506776180667
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  To assess workload characteristics and the presence of prescription processing technologies within metropolitan community pharmacies in the United States..Cross-sectional postal survey..18 metropolitan statistical areas (MSAs) in the United States..3000 managers located in community pharmacies processing at least 500 third-party claims per month for four major pharmacy benefits managers..34-item survey instrument designed to collect data about the pharmacy including demographics, workload issues, handling of drug-drug interactions (DDIs), and pharmacists' attitudes toward computerized DDI alerts..Workload (hours of operation, prescription volume, staffing hours, prescription processing intensity) and prescription processing technologies (telecommunication systems, automated counting/filling or verification devices, number of computer terminals, and computer software vendors)..Overall, 736 usable surveys were returned (response rate, 25.3%). On average, respondents reported a volume of approximately 1340 prescriptions per week processed at a rate of almost 17 prescriptions per hour. Independent pharmacies processed approximately 3 prescriptions per hour more than chain pharmacies even though a statistically equal or slightly lower proportion of those pharmacies had automated technologies. The presence of technology was generally high for all pharmacies, particularly countertop tablet/capsule-counting devices and telefacsimile machines. The most common software vendors differed considerably between chain and independent pharmacies..The number of prescriptions processed per hour and number of technologies available increased with the total weekly volume of prescriptions processed in this national survey. A majority of pharmacies had at least one type of automated prescription processing technology and an automated telecommunication system for accepting new or refill prescriptions. Independent pharmacies processed more prescriptions per hour than did chains but did so with fewer categories of technologies.
• Woosley, R. L., Woosley, R. L., Timmermann, B. N., Teufel-shone, N., Taylor, A. M., Strich, H., Pereira, E., Martinez, A., Malone, D. C., Johnson, L., & Drummond, R. (2006). Use of herbal remedies by diabetic Hispanic women in the southwestern United States.. Phytotherapy research : PTR, 20(4), 250-5. doi:10.1002/ptr.1820
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  The primary purpose of this study was to examine the use and documentation of herbal remedies used by Hispanic women with Type II diabetes enrolled in two Community Health Centers in the Southwest USA. A secondary purpose was to review the literature on identified herbs to assess their likely effects on diabetes..Open-ended structured interviews were conducted on a convenience sample (n = 23) of participants. Medical and medication charts were reviewed for the interviewed participants, and for a random sample of enrolled Hispanic diabetic patients (n = 81) who were not interviewed..Two Community Health Centers in the Southwest USA..Enrolled patient, Hispanic females with Type II diabetes..Subjects were interviewed about their use of herbal therapies and supplements. Information collected from medical and pharmaceutical charts included documented use of herbal remedies; standard therapies prescribed and diabetes control (hemoglobin A1C values). For those herbal remedies reported, literature reviews were conducted to determine if there was supporting evidence of harm or efficacy for the stated condition..Reports of herbal use, and types of remedies used..Among the interviewed participants, 21 of 23 (91%) reported using one or more herbal remedies. Among a random sample of patient medical charts, seven (6.7%) contained documentation of diabetes-specific herbs, and 16 (15.4%) had documented general herb use. A total of 77 different herbal remedies were identified, most of which were contained as part of commercial preparations, and appeared to supplement, rather than replace standard medical therapy for diabetes..Use of herbal therapies is not uncommon among diabetic patients. Many of the herbs reported have potential efficacy in treating diabetes or may result in adverse effects or interactions. In practical use, however, the herbs reported in this study are unlikely to have a significant effect on clinical outcomes in diabetes, either positively or negatively.
• Curtis, L. H., Østbye, T., Sendersky, V., Hutchison, S., Dans, P. E., Wright, A., Woosley, R. L., & Schulman, K. A. (2004). Inappropriate prescribing for elderly Americans in a large outpatient population.. Archives of internal medicine, 164(15), 1621-5. doi:10.1001/archinte.164.15.1621
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  We sought to determine the extent of potentially inappropriate outpatient prescribing for elderly patients, as defined by the Beers revised list of drugs to be avoided in elderly populations..We conducted a retrospective cohort study using the outpatient prescription claims database of a large, national pharmaceutical benefit manager. The cohort included 765,423 subjects 65 years or older, who were covered by a pharmaceutical benefit manager and filed 1 or more prescription drug claims during 1999. Main outcome measures were the proportion of subjects who filled a prescription for 1 or more drugs of concern and the proportion of subjects who filled prescriptions for 2 or more of the drugs..A total of 162,370 subjects (21%) filled a prescription for 1 or more drugs of concern. Amitriptyline and doxepin accounted for 23% of all claims for Beers list drugs, and 51% of those claims were for drugs with the potential for severe adverse effects. More than 15% of subjects filled prescriptions for 2 drugs of concern, and 4% filled prescriptions for 3 or more of the drugs within the same year. The most commonly prescribed classes were psychotropic drugs and neuromuscular agents..The common use of potentially inappropriate drugs should serve as a reminder to monitor their use closely. Pharmaceutical claims databases can be important tools for accomplishing this task, though clinical and laboratory data are needed to improve the sensitivity and specificity of patient-specific alerts.
• Cohen-mansfield, J., Lipson, S., Werner, P., Billig, N., Taylor, L., & Woosley, R. L. (1999). Withdrawal of haloperidol, thioridazine, and lorazepam in the nursing home: a controlled, double-blind study.. Archives of internal medicine, 159(15), 1733-40. doi:10.1001/archinte.159.15.1733
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  Ongoing regimens of haloperidol, thioridazine, and lorazepam are commonly administered to manage behavior problems in nursing home residents. Nevertheless, there is controversy over whether periodic drug withdrawal should be attempted when those medications are prescribed. This study addressed that issue by examining the effects of discontinuing treatment with haloperidol, thioridazine, and lorazepam among residents of a large suburban nursing home..In a double-blind, crossover study, half of 58 nursing home residents (43 women and 15 men with a mean age of 86 years) continued to take the psychotropic medication they had been prescribed, whereas the other half were tapered to placebo. After 6 weeks of taking placebo or original drug, patients were tapered to the reverse schedule and remained on it for 6 weeks. Assessments included informant ratings by the nursing staff who completed the Brief Psychiatric Rating Scale and the Cohen-Mansfield Agitation Inventory..Analyses comparing residents taking placebo to those taking medication after completion of the first phase showed no impact of drug therapy discontinuation on their behavior. Similarly, using the crossover design to compare residents' behaviors while taking placebo vs. taking drugs, withdrawal of medication had no impact on Cohen-Mansfield Agitation Inventory or Brief Psychiatric Rating Scale scores..Results of this work suggest that longterm use of haloperidol, thioridazine, and lorazepam in nursing homes to manage agitation should be closely monitored for their efficacy. Furthermore, routine attempts at drug withdrawal should be considered for most residents taking psychotropic medication.
• Abernethy, D. R., & Woosley, R. L. (1998). 1999 ASCPT clinical pharmacology curriculum review course. Clinical Pharmacology & Therapeutics, 64(6), 694-694. doi:10.1016/s0009-9236(98)90061-3
• Abernethy, D. R., & Woosley, R. L. (1996). 1997 ASCPT Clinical Pharmacology Curriculum Review Course. Clinical Pharmacology & Therapeutics, 60(6), 699-699. doi:10.1016/s0009-9236(96)90221-0
• Abernethy, D. R., & Woosley, R. L. (1995). 1996 ASCPT clinical pharmacology curriculum review course. Clinical Pharmacology & Therapeutics, 58(6), 700-700. doi:10.1016/0009-9236(95)90028-4
• Starnes, V. A., Primm, R. K., Woosley, R. L., Oates, J. A., & Hammon, J. W. (1982). Administration of prostacyclin prevents ventricular fibrillation following coronary occlusion in conscious dogs.. Journal of cardiovascular pharmacology, 4(5), 765-9. doi:10.1097/00005344-198209000-00011
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  The effects of prostacyclin (PGI2) on ventricular arrhythmias following 20 min of coronary occlusion and release were studied in 34 conscious dogs. We administered PGI2 at 100 ng/kg/min and did not observe significant changes in heart rate, blood pressure, or systemic vascular resistance. During the control period, heart rate was 97 +/- 30 (mean +/- SEM) vs. 99 +/- 28 in the PGI2-treated group. Mean arterial pressure was 115 +/- 26 mm Hg and 109 +/- 10 mm Hg in the control and PGI2 groups, respectively. Systemic vascular resistance declined minimally from 2,985 +/- 221 dyn . s . cm-5 to 2,484 +/- 135 dyn . s . cm-5 during the PGI2 infusion (p = NS). Following coronary occlusion, the frequency of ventricular fibrillation was reduced from 53% (9/17) in the control group to 6% (1/17) in the PGI2 group (p less than 0.01). Overall 80-min postinfarction survival was 64% in the group receiving PGI2 infusion compared to 24% in the control group (p less than 0.05). The effects of PGI2 in preventing ventricular fibrillation following acute coronary occlusion can be ascribed to a direct action of this prostaglandin on the myocardium, rather than to an indirect effect due to a reduction in systemic vascular resistance.

Presentations

• Patel, S. I., Zareba, W., Parthasarathy, S., Perez, K., Wendel, C. S., Woosley, R., Xia, X., Patel, I., Quan, S. F., Grandner, M., Youngstedt, S., & Woosley, R. (2022). The Application of a QTc Risk Score in Patients with Obstructive Sleep Apnea. SLEEP.
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  oral and poster presentation

Poster Presentations

• Perez, K., Zareba, W., LaFleur, B. J., Xia, X., Woosley, R., Patel, I., Quan, S. F., Grandner, M., Youngstedt, S., Miller, J., Parthasarathy, S., & Patel, S. I. (2022). Changes in markers of ventricular repolarization and positive airway pressure therapy: A pilot study. SLEEP.
• Patel, S. I., Patel, S. I., Zareba, W., Woosley, R., Combs, D. A., LaFleur, B. J., Couderc, J., LaFleur, B. J., Xia, X., Patel, I., Woosley, R., Mashaqi, S., Combs, D. A., Parthasarathy, S., Zareba, W., Patel, I., Couderc, J., Mashaqi, S., Xia, X., & Parthasarathy, S. (2021, June 10-13). The Relationship between Sleep Disordered Breathing, Markers of Ventricular Repolarization and Cardiovascular Mortality. SLEEP. Virtual: American Academy of Sleep Medicine.
• Xia, X., Mashaqi, S., Mashaqi, S., Patel, S. I., Zareba, W., Woosley, R., Woosley, R., Woosley, R., Couderc, J., Combs, D. A., Combs, D. A., LaFleur, B. J., Couderc, J., Zareba, W., LaFleur, B. J., LaFleur, B. J., Xia, X., Patel, I., Parthasarathy, S., , Patel, I., et al. (2021, June 10-13). The Relationship between Sleep Disordered Breathing, Markers of Ventricular Repolarization and Cardiovascular Mortality. SLEEP. Virtual: American Academy of Sleep Medicine.

Reviews

• Woosley, R. (2017. Antibiotics, QT prolongation, TdP and Sudden Death: Fact or Fiction.
• Woosley, R. (2017. Domperidone Is Commonly Prescribed With QT-Interacting Drugs: Review of a Community-Based Practice and a Postmarketing Adverse Drug Event Reporting Database. PracticeUpdate website.
• Woosley, R. (2017. Higher QT Interval After Energy Drink Consumption Vs. Caffeine.
• Woosley, R. (2017. Smartphone app offers online access to QT-prolonging drugs database(p. 14).
• Woosley, R. (2017. Sudden Cardiac Death: Pharmacotherapy and Proarrhythmic Drugs: A Nationwide Cohort Study in Denmark.
• Woosley, R. (2017. Website publishes risk categories for QT-Prolonging Drugs(p. 25).
• Woosley, R., Black, K., Heise, C. W., & Romero, K. (2017. CredibleMeds.org: What does it offer?.