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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).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.This was a retrospective observational study using inpatient data from 28 healthcare facilities in the western United States. This risk score ranges from zero to 23 with weights applied to each risk factor based on a previous validation study. Logistic regression and a generalized linear model were performed to assess the relationship between QTc-RS and mortality and length of stay.Between April and December 2020, a QTc-RS was calculated for 92,383 hospitalized patients. Common risk factors were female (55.0%); age 67 years (32.1%); and receiving a medication with known risk of TdP (24.5%). A total of 2770 (3%) patients died during their hospitalization. Relative to patients with QTc-RS 7, the odds ratio for mortality was 4.80 (95%CI:4.42-5.21) for patients with QTc-RS = 7-10 and 11.51 (95%CI:10.23-12.94) for those with QTc-RS ≥ 11. Length of hospital stay increased by 0.7 day for every unit increase in the risk score (p 0.0001).There is a strong relationship between increased mortality as well as longer duration of hospitalization with an increasing QTc-RS.

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. METHODS We utilized a software tool that can evaluate patient drug lists and identified groups of patients most likely to benefit from implementation of a PGX testing program in a major medical system population. RESULTS Medication lists were obtained for sixteen patient groups with a total of 82 613 patients. The percent of patients in each group with testing 'Recommended', 'Strongly recommended', or 'Required' ranged from 12.7% in the outpatient pediatric psychiatry group to 75.7% in the any adult inpatient age >50 years group. Some of the highest yield drugs identified were citalopram, simvastatin, escitalopram, metoprolol, clopidogrel, tramadol, and ondansetron. CONCLUSION We demonstrate a significant number of patients in each group may have benefit, but targeting certain ones for pre-emptive testing may result in the initial highest yield for a health system.

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.

Introduction: Torsades de pointes (TdP) is a life-threatening arrhythmia associated with prolongation of the heart rate-corrected QT (QTc) interval. QTc prolongation is associated with increased mortality. A QTc Risk Score (QTc-RS) advisory has been developed, but the ability of the QTc-RS to predict mortality is unknown. Objective: To evaluate the relationship between a validated QTc-RS and mortality among hospitalized patients. Methods: An advisory incorporating a previously validated QTc-RS was implemented as a clinical decision support tool at 28 inpatient facilities. When an order was initiated for a known QTc-prolonging medication, a QTc-RS (maximum score = 21) was electronically calculated and, if the score was > 11, prescribers received a warning that included patient-specific risk factors. The advisory also provided single click actions for laboratory tests, electrocardiogram orders, cancelling incoming medication orders or discontinuing existing QTc-prolonging medications. Results: Between April and November 2020, there were 144,148 QTc-RS scores calculated. Among the 7923 warnings with a score >11, the majority (51%) had a score of 12, 29% had a score of 13, 12% had a score of 14, and 8% had a score ≥ 15. The most common risk factors were: age > 67 years (66%); sepsis (65%); ≥ 1 QTc-prolonging medication(s) (60%); female (59%); heart failure (34%); serum potassium < 3.5 mEq/L (28%); and a loop diuretic (21%). Among those with a QTc-RS >11, 11.9% (944/7923) expired during the inpatient encounter. The proportion of deaths increased as the risk score increased (Table 1). Relative to individuals with QTc-RS 12-14, the odds ratio for inpatient mortality in those with scores >17 was 3.0 (95% CI:1.7-5.5). Conclusions: An increasing QTc-RS was associated with an increased likelihood of in-hospital mortality

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.

Health care is trending towards an increasing reliance on data management, technology, analytics, and automation which is also reflected in pharmacy education. This study aimed to identify and characterize doctor of pharmacy (PharmD)/master of science in health informatics (MSHI) dual-degree offerings at pharmacy institutions within the United States (US).A list of PharmD/MSHI programs was obtained from the American Association of Colleges of Pharmacy and the Pharmacy College Application Service. Furthermore, websites of the 143 accredited schools and colleges of pharmacy in the US were inspected to identify additional PharmD/MSHI dual degrees not identified with the previous sources and to verify that the dual degree was being actively offered at each institution. A 26-item questionnaire focusing on program structure, admissions, and output was developed and administered to program representatives via phone interview. Descriptive statistics were calculated.Thirteen schools offering a PharmD/MSHI dual degree were identified, of which 10 participated (response rate = 77%). All programs were created within the last 10 years. Programs were similar in terms of admission requirements such as grade point average thresholds and standardized testing. Variances existed in program structure and output, such as accreditation status and number of enrollees/graduates.Although health informatics has become more prominent in health care, health informatics education is not yet as pervasive in the pharmacy field. The information collected may be useful for schools considering implementing or modifying their own dual degree program or for students who are interested in health informatics-specialized educational opportunities.

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.

The heparin-induced thrombocytopenia computerised risk (HIT-CR) score is designed to aid in the diagnosis of HIT. We sought to evaluate its potential clinical utility. In this retrospective cohort study, we collected HIT-CR scores on all inpatients receiving heparin over a 4-month period and performed chart reviews on the subset who independently underwent clinical diagnostic testing for HIT to identify patients with HIT. In all, 34 342 patients received heparin, 1744 had high-risk HIT-CR scores of ≥3 and 220 had the maximal risk score of 4. Only 6% of high-risk and 10% of maximal-risk patients underwent testing for HIT. Conversely, among all 317 patients who underwent independent testing for HIT, 67% had low-risk HIT-CR scores (

Purpose To determine whether tidal volume/predicted body weight (TV/PBW) or driving pressure (DP) are associated with mortality in a heterogeneous population of hypoxic mechanically ventilated patients. Methods A retrospective cohort study involving 18 intensive care units included consecutive patients ≥18 years old, receiving mechanical ventilation for ≥3 days, with a PaO2/FiO2 ratio ≤300 mmHg, whether or not they met full criteria for ARDS. The main outcome was hospital mortality. Multiple logistic regression (MLR) incorporated TV/PBW, DP, and potential confounders including age, APACHE IVa® predicted hospital mortality, respiratory system compliance (CRS), and PaO2/FiO2. Predetermined strata of TV/PBW were compared using MLR. Results Our cohort comprised 5,167 patients with mean age 61.9 years, APACHE IVa® score 79.3, PaO2/FiO2 166 mmHg and CRS 40.5 ml/cm H2O. Regression analysis revealed that patients receiving DP one standard deviation above the mean or higher (≥19 cmH20) had an adjusted odds ratio for mortality (ORmort) = 1.10 (95% CI: 1.06–1.13, p = 0.009). Regression analysis showed a U-shaped relationship between strata of TV/PBW and adjusted mortality. Using TV/PBW 4–6 ml/kg as the referent group, patients receiving >10 ml/kg had similar adjusted ORmort, but those receiving 6–7, 7–8 and 8–10 ml/kg had lower adjusted ORmort (95%CI) of 0.81 (0.65–1.00), 0.78 (0.63–0.97) and 0.80 0.67–1.01) respectively. The adjusted ORmort in patients receiving 4–6 ml/kg was 1.26 (95%CI: 1.04–1.52) compared to patients receiving 6–10 ml/kg. Conclusions Driving pressures ≥19 cmH2O were associated with increased adjusted mortality. TV/PBW 4-6ml/kg were used in less than 15% of patients and associated with increased adjusted mortality compared to TV/PBW 6–10 ml/kg used in 82% of patients. Prospective clinical trials are needed to prove whether limiting DP or the use of TV/PBW 6–10 ml/kg versus 4–6 ml/kg benefits mortality.

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.

Objective. To gather feedback from focus groups regarding health informatics competencies that should be taught in a Doctor of Pharmacy (PharmD) curricula and to revise the competencies based on this feedback. Methods. The pharmacy informatics task force of the American Association of Colleges of Pharmacy (AACP) used 11 sources to create a list of pharmacy informatics competencies. Subsequently, faculty feedback about the competency list was obtained via two synchronous online focus groups in August 2015. The list was then revised based on the feedback. Results. Eight people (a department chair, six faculty members and a graduate student) participated in the focus groups (six were from private and two were from public institutions). Participants felt the list had too many competencies to be covered in a timely manner and some indicated that basic computer and Internet competencies should be considered pre-requisites. Participants also recommended that competencies be split by proposed curricular placement (eg, prerequisite, required, elective, didactic, experiential) for each objective. The competency list was revised in response to focus group feedback. Conclusion. The proposed curriculum aligns with the new Accreditation Council for Pharmacy Education (ACPE) standards requiring that professional pharmacy curricula cover multiple aspects of health informatics. The proposed competencies list can serve as a reference to assist in the development of the curriculum and ensure compliance with the new standards.

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, IKR. Intravenous (IV) formulations of methadone have been associated with TdP and contain the preservative chlorobutanol, which, like methadone, blocks IKR. The combinations of chlorobutanol with methadone or terfenadine, another IKR blocker, produce synergistic IKR block. The aim of this study was to examine and summarize the evidence available to address the question: what other IV drug formulations contain chlorobutanol and are they associated with TdP? IV drug products containing the preservative chlorobutanol were identified by searching the websites DailyMed ( https://dailymed.nlm.nih.gov/dailymed/index.cfm ) and Drugs@FDA ( https://www.accessdata.fda.gov/scripts/cder/daf/ ). For each drug identified, PubMed and the FDA’s Adverse Event Reporting System (FAERS) were searched for reports of TdP and/or QT prolongation and FAERS data were analyzed for disproportionality of reports. The search found nine drugs (methadone, epinephrine, papaverine, oxytocin, vasopressin, testosterone, estradiol, isoniazid, and desmopressin) that contain chlorobutanol 2.5 (n = 1) or 5.0 mg/mL. All nine drugs had reports of QT prolongation or TdP reported in FAERS and all but estradiol, testosterone, desmopressin, and isoniazid had reports of QT prolongation or TdP in PubMed. Two of the nine drugs (epinephrine and methadone) had positive signals (by disproportionality analysis) for TdP in FAERS (EB05 2.88 and 23.81, respectively) and four (methadone, epinephrine, papaverine, and vasopressin) were reported in published articles as the suspect drugs in cases of TdP. The pharmacologic profile of chlorobutanol (synergistic IKR block) and its association with reports of TdP and QT prolongation suggest the need for a full evaluation of its cardiac safety when used as a preservative in IV drug and vitamin formulations.

QT interval prolongation is a cardiac condition that increases the risk of serious problems such as the life-threatening cardiac arrhythmia torsades de pointes (TdP).[1][1] Because QT prolongation increases the risk of death, it is important to identify patients who have rate-corrected QT (QTc)

Essentials We previously published a diagnostic algorithm for heparin-induced thrombocytopenia (HIT). In this study, we validated the algorithm in an independent large healthcare system. The accuracy was 98%, sensitivity 82% and specificity 99%. The algorithm has potential to improve accuracy and efficiency in the diagnosis of HIT. SummaryBackground Heparin-induced thrombocytopenia (HIT) is a life-threatening drug reaction caused by antiplatelet factor 4/heparin (anti-PF4/H) antibodies. Commercial tests to detect these antibodies have suboptimal operating characteristics. We previously developed a diagnostic algorithm for HIT that incorporated ‘four Ts’ (4Ts) scoring and a stratified interpretation of an anti-PF4/H enzyme-linked immunosorbent assay (ELISA) and yielded a discriminant accuracy of 0.97 (95% confidence interval [CI], 0.93–1.00). Objectives The purpose of this study was to validate the algorithm in an independent patient population and quantitate effects that algorithm adherence could have on clinical care. Methods A retrospective cohort comprised patients who had undergone anti-PF4/H ELISA and serotonin release assay (SRA) testing in our healthcare system from 2010 to 2014. We determined the algorithm recommendation for each patient, compared recommendations with the clinical care received, and enumerated consequences of discrepancies. Operating characteristics were calculated for algorithm recommendations using SRA as the reference standard. Results Analysis was performed on 181 patients, 10 of whom were ruled in for HIT. The algorithm accurately stratified 98% of patients (95% CI, 95–99%), ruling out HIT in 158, ruling in HIT in 10 and recommending an SRA in 13 patients. Algorithm adherence would have obviated 165 SRAs and prevented 30 courses of unnecessary antithrombotic therapy for HIT. Diagnostic sensitivity was 0.82 (95% CI, 0.48–0.98), specificity 0.99 (95% CI, 0.97–1.00), PPV 0.90 (95% CI, 0.56–0.99) and NPV 0.99 (95% CI, 0.96–1.00). Conclusions An algorithm incorporating 4Ts scoring and a stratified interpretation of the anti-PF4/H ELISA has good operating characteristics and the potential to improve management of suspected HIT patients.

We performed a meta-analysis to evaluate the femoral neck and lumbar spine bone mineral density (BMD) in adults with type 1 diabetes (T1D) compared with controls. Adults with T1D have modestly lower BMD at femoral neck and lumbar spine than adults without diabetes. Fracture risk is four to sixfold higher in adults with T1D. Since BMD is one of the major contributors for fracture risk, we performed a meta-analysis to evaluate differences in femoral neck and lumbar spine BMD between adults with T1D and controls. MEDLINE, Ovid, and the Cochrane library and abstracts from various scientific meetings were searched. Studies reporting the femoral neck and/or lumbar spine BMD in adults (age > 20 years) with T1D in comparison with people without diabetes were selected. General linear mixed models were used to assess differences in BMD at femoral neck and lumbar spine between subjects with T1D and controls adjusting for age, sex, and dual x-ray absorptiometry (DXA) instruments. Sixteen studies met the inclusion criteria. The femoral neck BMD was modestly lower in adults with T1D compared to controls (−0.055 g/cm2; 95% CI: −0.065, −0.045). There were no differences in lumbar spine BMD between adults with T1D and controls (0.0062 g/cm2; 95% CI −0.04, 0.016). However, in a sensitivity analysis, lumbar spine BMD was modestly lower in adults with T1D compared to controls (−0.035 g/cm2; −0.049, −0.02). Studies using Lunar DXA instruments have reported higher lumbar spine and femoral neck BMD compared to studies using Hologic DXA instruments. Femoral neck and lumbar spine BMD were modestly lower in adults with T1D compared to controls. However, this modest reduction in femoral neck and lumbar spine BMD cannot explain much higher observed fracture risk in adults with T1D.