Heather A. Jaynes

Development and Validation of a Risk Score to Predict QT Interval Prolongation in Hospitalized Patients

Background—Identifying hospitalized patients at risk for QT interval prolongation could lead to interventions to reduce the risk of torsades de pointes. Our objective was to develop and validate a risk score for QT prolongation in hospitalized patients. Methods and Results—In this study, in a single tertiary care institution, consecutive patients (n=900) admitted to cardiac care units comprised the risk score development group. The score was then applied to 300 additional patients in a validation group. Corrected QT (QTc) interval prolongation (defined as QTc>500 ms or an increase of >60 ms from baseline) occurred in 274 (30.4%) and 90 (30.0%) patients in the development group and validation group, respectively. Independent predictors of QTc prolongation included the following: female (odds ratio, 1.5; 95% confidence interval, 1.1–2.0), diagnosis of myocardial infarction (2.4 [1.6–3.9]), sepsis (2.7 [1.5–4.8]), left ventricular dysfunction (2.7 [1.6–5.0]), administration of a QT-prolonging drug (2.8 [2.0–4.0]), ≥2 QT-prolonging drugs (2.6 [1.9–5.6]), or loop diuretic (1.4 [1.0–2.0]), age >68 years (1.3 [1.0–1.9]), serum K+ <3.5 mEq/L (2.1 [1.5–2.9]), and admitting QTc >450 ms (2.3; confidence interval [1.6–3.2]). Risk scores were developed by assigning points based on log odds ratios. Low-, moderate-, and high-risk ranges of 0 to 6, 7 to 10, and 11 to 21 points, respectively, best predicted QTc prolongation (C statistic=0.823). A high-risk score ≥11 was associated with sensitivity=0.74, specificity=0.77, positive predictive value=0.79, and negative predictive value=0.76. In the validation group, the incidences of QTc prolongation were 15% (low risk); 37% (moderate risk); and 73% (high risk). Conclusions—A risk score using easily obtainable clinical variables predicts patients at highest risk for QTc interval prolongation and may be useful in guiding monitoring and treatment decisions.

Effectiveness of a Clinical Decision Support System for Reducing the Risk of QT Interval Prolongation in Hospitalized Patients

Background—We evaluated the effectiveness of a computer clinical decision support system (CDSS) for reducing the risk of QT interval prolongation in hospitalized patients. Methods and Results—We evaluated 2400 patients admitted to cardiac care units at an urban academic medical center. A CDSS incorporating a validated risk score for QTc prolongation was developed and implemented using information extracted from patients’ electronic medical records. When a drug associated with torsades de pointes was prescribed to a patient at moderate or high risk for QTc interval prolongation, a computer alert appeared on the screen to the pharmacist entering the order, who could then consult the prescriber on alternative therapies and implement more intensive monitoring. QTc interval prolongation was defined as QTc interval >500 ms or increase in QTc of ≥60 ms from baseline; for patients who presented with QTc >500 ms, QTc prolongation was defined solely as increase in QTc ≥60 ms from baseline. End points were assessed before (n=1200) and after (n=1200) implementation of the CDSS. CDSS implementation was independently associated with a reduced risk of QTc prolongation (adjusted odds ratio, 0.65; 95% confidence interval, 0.56–0.89; P<0.0001). Furthermore, CDSS implementation reduced the prescribing of noncardiac medications known to cause torsades de pointes, including fluoroquinolones and intravenous haloperidol (adjusted odds ratio, 0.79; 95% confidence interval, 0.63–0.91; P=0.03). Conclusions—A computer CDSS incorporating a validated risk score for QTc prolongation influences the prescribing of QT-prolonging drugs and reduces the risk of QTc interval prolongation in hospitalized patients with torsades de pointes risk factors.

Evaluation of specialized medication packaging combined with medication therapy management: Adherence, outcomes, and costs among medicaid patients

Background:This study evaluates the effect of a program combing specialized medication packaging and telephonic medication therapy management on medication adherence, health care utilization, and costs among Medicaid patients. Research Design:A retrospective cohort design compared Medicaid participants who voluntarily enrolled in the program (n=1007) compared with those who did not (n=13,614). Main outcome measures were medication adherence at 12 months, hospital admissions and emergency department visits at 6 and 12 months, and total paid claim costs at 6 and 12 months. Multivariate regression models were used to adjust for the effect of age, sex, race, comorbidities, and 12-month preenrollment health care utilization. Results:Measures of medication adherence were significantly improved in the program cohort compared with the usual care cohort. At 6 months, adjusted all-cause hospitalization was marginally less in the program cohort compared with the usual care cohort [odds ratio=0.73, 95% confidence interval (CI), 0.54–1.0, P=0.05]. No statistically significant differences were observed between the 2 cohorts for any of the other adjusted utilization endpoints at 6 or 12 months. Adjusted total cost at 6 and 12 months were higher in the program cohort (6-month cost ratio=1.76, 95% CI,1.65–1.89; 12-month cost ratio=1.84, 95% CI,1.72–1.97), primarily because of an increase in prescription costs. Emergency department visits and hospitalization costs did not differ between groups. Conclusions:The program improved measures of medication adherence, but the effect on health care utilization and nonpharmacy costs at 6 and 12 months was not different from the usual care group. Reasons for these findings may reflect differences in the delivery of the specialized packaging and the medication therapy management program, health care behaviors in this Medicaid cohort, unadjusted confounding, or time required for the benefit of the intervention to manifest.

Evaluation of Pharmacist Care for Hypertension in the Veterans Affairs Patient-centered Medical Home: A Retrospective Case-control Study

OBJECTIVE The study objective was to evaluate a pharmacist hypertension care management program within the patient-centered medical home. METHODS This was a retrospective case-control study. Cases included all patients with hypertension who were referred to the care management program, and controls included patients with hypertension who were not referred to the program during the same 1-year period. Each case was matched to a maximum of 3 controls on the basis of primary care physician, age ±5 years, gender, diagnoses of diabetes and kidney disease, baseline systolic blood pressure ±10 mm Hg, and number of unique antihypertensive medications. Pharmacists provided a hypertension care management program under an approved scope of practice that allowed pharmacists to meet individually with patients, adjust medications, and provide patient education. Primary outcomes were systolic blood pressure and diastolic blood pressure at 6 and 12 months. Multivariate regression models compared each blood pressure end point between cases and controls adjusting for age, comorbidities, baseline blood pressure, and baseline number of blood pressure medications. RESULTS A total of 573 patients were referred to the hypertension program; 86% (465/543) had at least 1 matched control and were included as cases in the analyses; 3:1 matching was achieved in 90% (418/465) of cases. At baseline, cases and controls did not differ with respect to age, gender, race, or comorbidity; baseline blood pressure was higher (139.9/80.0 mm Hg vs 136.7/78.2 mm Hg, P ≤ .0002) in the cases compared with controls. Multivariate regression modeling identified significantly lower systolic blood pressure for the cases compared with controls at both 6 and 12 months (6-month risk ratio [RR], 9.7; 95% confidence interval [CI], 2.7-35.3; 12-month RR, 20.3; 95% CI, 4.1-99.2; P < .01 for both comparisons). Diastolic blood pressure was significantly lower at 12 months (RR, 2.9; 95% CI, 1.2-7.1; P < .01) but not at 6 months (RR, 1.0; 95% CI, 0.31-3.4; P = .9) for the cases compared with controls. CONCLUSIONS Patients who were referred to the pharmacist hypertension care management program had a significant improvement in most blood pressure outcomes. This program may be an effective method of improving blood pressure control among patients in a medical home model of primary care.

Efavirenz Inhibits the Human Ether-A-Go-Go Related Current (hERG) and Induces QT Interval Prolongation in CYP2B6*6*6 Allele Carriers

Efavirenz (EFV) has been associated with torsade de pointes despite marginal QT interval lengthening. Since EFV is metabolized by the cytochrome P450 (CYP) 2B6 enzyme, we hypothesized that EFV would lengthen the rate‐corrected QT (QTcF) interval in carriers of the CYP2B6*6 decreased functional allele.

Hypertension Treatment Intensification Among Stroke Survivors With Uncontrolled Blood Pressure

Background and Purpose— We examined blood pressure 1 year after stroke discharge and its association with treatment intensification. Methods— We examined the systolic blood pressure (SBP) stratified by discharge SBP (⩽140, 141–160, or >160 mm Hg) among a national cohort of Veterans discharged after acute ischemic stroke. Hypertension treatment opportunities were defined as outpatient SBP >160 mm Hg or repeated SBPs >140 mm Hg. Treatment intensification was defined as the proportion of treatment opportunities with antihypertensive changes (range, 0%–100%, where 100% indicates that each elevated SBP always resulted in medication change). Results— Among 3153 patients with ischemic stroke, 38% had ≥1 elevated outpatient SBP eligible for treatment intensification in the 1 year after stroke. Thirty percent of patients had a discharge SBP ⩽140 mm Hg, and an average 1.93 treatment opportunities and treatment intensification occurred in 58% of eligible visits. Forty-seven percent of patients discharged with SBP 141 to160 mm Hg had an average of 2.1 opportunities for intensification and treatment intensification occurred in 60% of visits. Sixty-three percent of the patients discharged with an SBP >160 mm Hg had an average of 2.4 intensification opportunities, and treatment intensification occurred in 65% of visits. Conclusions— Patients with discharge SBP >160 mm Hg had numerous opportunities to improve hypertension control. Secondary stroke prevention efforts should focus on initiation and review of antihypertensives before acute stroke discharge; management of antihypertensives and titration; and patient medication adherence counseling.

Pharmaceutical Role Expansion and Developments in Pharmacist-Physician Communication

Expanded clinical pharmacist professional roles in the team-based patient-centered medical home (PCMH) primary care environment require cooperative and collaborative relationships among pharmacists and primary care physicians (PCPs), but many PCPs have not previously worked in such a direct fashion with pharmacists. Additional roles, including formulary control, add further elements of complexity to the clinical pharmacist–PCP relationship that are not well described. Our objective was to characterize the nature of clinical pharmacist–PCP interprofessional collaboration across seven federally funded hospitals and associated primary care clinics, following pharmacist placement in primary care clinics and incorporation of expanded pharmacist roles. In-depth and semistructured interviews were conducted with 25 practicing clinical pharmacists and 17 PCPs. Qualitative thematic analysis revealed three major themes: (1) the complexities of electronic communication (particularly electronic nonformulary requests) as contributing to interprofessional tensions or misunderstandings for both groups, (2) the navigation of new roles and traditional hierarchy, with pharmacists using indirect communication to prevent PCP defensiveness to recommendations, and (3) a preference for onsite colocation for enhanced communication and professional relationships. Clinical pharmacists’ indirect communication practices may hold important implications for patient safety in the context of medication use, and it is important to foster effective communication skills and an environment where all team members across hierarchies can feel comfortable speaking up to reduce error when problems are suspected. Also, the lack of institutional communication about managing drug formulary issues and related electronic nonformulary request processes was apparent in this study and merits further attention for both researchers and practitioners.

Predictors of Medication-Related Problems Among Medicaid Patients Participating in a Pharmacist-Provided Telephonic Medication Therapy Management Program

To identify predictors of medication‐related problems (MRPs) among Medicaid patients participating in a telephonic medication therapy management (MTM) program.

Influence of Oral Progesterone Administration on Drug-Induced QT Interval Lengthening: A Randomized, Double-Blind, Placebo-Controlled Crossover Study

OBJECTIVES We tested the hypothesis that oral progesterone administration attenuates drug-induced QT interval lengthening. BACKGROUND Evidence from preclinical and human investigations suggests that higher serum progesterone concentrations may be protective against drug-induced QT interval lengthening. METHODS In this prospective, double-blind, crossover study, 19 healthy female volunteers (21-40 years) were randomized to receive progesterone 400 mg or matching placebo orally once daily for 7 days timed to the menses phase of the menstrual cycle (between-phase washout period = 49 days). On day 7, ibutilide 0.003 mg/kg was infused over 10 minutes, after which QT intervals were recorded and blood samples collected for 12 hours. Prior to the treatment phases, subjects underwent ECG monitoring for 12 hours to calculate individualized heart rate-corrected QT intervals (QTcI). RESULTS Fifteen subjects completed all study phases. Maximum serum ibutilide concentrations in the progesterone and placebo phases were similar (1247±770 vs 1172±709 pg/mL, p=0.43). Serum progesterone concentrations were higher during the progesterone phase (16.2±11.0 vs 1.2±1.0 ng/mL, p<0.0001), while serum estradiol concentrations in the two phases were similar (89.3±62.8 vs 71.8±31.7 pg/mL, p=0.36). Pre-ibutilide lead II QTcI was significantly lower in the progesterone phase (412±15 vs 419±14 ms, p=0.04). Maximum ibutilide-associated QTcI (443±17 vs 458±19 ms, p=0.003), maximum percent increase in QTcI from pretreatment value (7.5±2.4 vs 9.3±3.4%, p=0.02) and area under the effect (QTcI) curve during the first hour post-ibutilide (497±13 vs 510±16 ms-hr, p=0.002) were lower during the progesterone phase. Progesterone-associated adverse effects included fatigue/malaise and vertigo. CONCLUSIONS Oral progesterone administration attenuates drug-induced QTcI lengthening.

Influence of Zoledronic Acid on Atrial Electrophysiological Parameters and Electrocardiographic Measurements

Our objective was to determine effects of zoledronic acid (ZA) on atrial electrophysiological parameters and electrocardiographic measurements.