Background Identifying hospitalized patients at risk for QT interval prolongation could lead to interventions to reduce the risk of torsades de pointes (TdP). 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 (DG). The score was then applied to 300 additional patients in a validation group (VG). Corrected QT (QTc) interval prolongation (defined as QTc > 500 ms and/or an increase of > 60 ms from baseline) occurred in 274 (30.4%) and 90 (30.0%) patients in the DG and VG, respectively. Independent predictors of QTc prolongation included: female (odds ratio [OR], 1.5; 95% confidence interval [CI], 1.1–2.0), diagnosis of myocardial infarction [2.5 (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 (1.0–1.8)], serum K+ < 3.5 mEq/L [2.1 (1.5–2.9)], and admitting QTc > 450 ms [2.3; CI (1.6–3.2)]. Risk scores were developed by assigning points based on Log ORs. Low, moderate and high risk ranges of 0–6, 7–10 and 11–21 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 VG, the incidences of QTc prolongation were 15% (low risk); 37% (moderate risk); 73% (high risk). Conclusions A risk score using easily obtainable clinical variables predicts patients at highest risk for QTc prolongation and may be useful in guiding monitoring and treatment decisions.

Background: Patients with heart failure (HF) have been found to have cognitive deficits, but it remains unclear whether these deficits are associated with HF or with aging or comorbid conditions common in HF. Objectives: To 1) determine the types, frequency, and severity of cognitive deficits among patients with chronic HF compared to age- and education-matched healthy participants and participants with major medical conditions other than HF; and 2) evaluate the relationships between HF severity, age, and comorbidities and cognitive deficits. Methods: A sample of 414 participants completed the study (249 HF patients, 63 healthy and 102 medical participants). The HF patients completed measures of HF severity, comorbidity (multiple comorbidity, hypertension, depressive symptoms), and neuropsychological functioning. Blood pressure and oxygen saturation were assessed at interview; clinical variables were abstracted from records. Participants in the comparison groups completed the same measures as the HF patients except those specific to HF. Results: Compared to the healthy and medical participants, HF patients had poorer memory, psychomotor speed, and executive function. Significantly more HF patients (24%) had deficits in three or more domains. Higher (worse) HF severity was associated with more cognitive deficits; HF severity interacted with age to explain deficits in executive function. Surprisingly, men with HF had poorer memory, psychomotor speed, and visuospatial recall ability than women. Multiple comorbidity, hypertension, depressive symptoms, and medications were not associated with cognitive deficits in this sample. Discussion: Heart failure results in losses in memory, psychomotor speed, and executive function in almost one fourth of patients. Patients with more severe HF are at risk for cognitive deficits. Older patients with more severe HF may have more problems in executive function and men with HF may be at increased risk for cognitive deficits. Studies are urgently needed to identify the mechanisms for the cognitive deficits in HF and test innovative interventions to prevent cognitive loss and decline.

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.

Objective To evaluate the effectiveness of a telephonic medication therapy management (MTM) service on reducing hospitalizations among home health patients. Setting Forty randomly selected, geographically diverse home health care centers in the United States. Design Two-stage, randomized, controlled trial with 60-day follow-up. All Medicare-insured home health care patients were eligible to participate. Twenty-eight consecutive patients within each care center were recruited and randomized to usual care or MTM intervention. The MTM intervention consisted of the following: (1) initial phone call by a pharmacy technician to verify active medications; (2) pharmacist-provided medication regimen review by telephone; and (3) follow-up pharmacist phone calls at day seven and as needed for 30 days. The primary outcome was 60-day all-cause hospitalization. Data Collection Data were collected from in-home nursing assessments using the OASIS-C. Multivariate logistic regression modeled the effect of the MTM intervention on the probability of hospitalization while adjusting for patients’ baseline risk of hospitalization, number of medications taken daily, and other OASIS-C data elements. Principal Findings A total of 895 patients (intervention n = 415, control n = 480) were block-randomized to the intervention or usual care. There was no significant difference in the 60-day probability of hospitalization between the MTM intervention and control groups (Adjusted OR: 1.26, 95 percent CI: 0.89–1.77, p = .19). For patients within the lowest baseline risk quartile (n = 232), the intervention group was three times more likely to remain out of the hospital at 60 days (Adjusted OR: 3.79, 95 percent CI: 1.35–10.57, p = .01) compared to the usual care group. Conclusions This MTM intervention may not be effective for all home health patients; however, for those patients with the lowest-risk profile, the MTM intervention prevented patients from being hospitalized at 60 days.

Background-Patients with chronic heart failure (HF) have cognitive deficits in memory, psychomotor speed, and executive function and poor health-related quality of life (HRQL), but the association between cognitive deficits and HRQL is unknown.

Purpose Lung cancer and its treatment impose many demands on family caregivers, which may increase their risk for distress. However, little research has documented aspects of the caregiving experience that are especially challenging for distressed caregivers of lung cancer patients. This study aimed to explore caregivers' key challenges in coping with their family member's lung cancer. Methods Single, semi-structured qualitative interviews were conducted with 21 distressed family caregivers of lung cancer patients. Results Caregivers described three key challenges in coping with their family member's lung cancer. The most common challenge, identified by 38 % of caregivers, was a profound sense of uncertainty regarding the future as they attempted to understand the patient's prognosis and potential for functional decline. Another key challenge, identified by 33 % of caregivers, involved time-consuming efforts to manage the patient's emotional reactions to the illness. Other caregivers (14 %) characterized practical tasks, such as coordinating the patient's medical care, as their greatest challenge. Conclusions Results suggest that clinical efforts are needed to assist distressed caregivers in providing practical and emotional support to the patient and attending to their own emotional needs.

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.

Background 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. Objective The primary objective of this study was to evaluate EFV-associated QT interval changes with regard to CYP2B6 genotype and to explore mechanisms of QT interval lengthening. Methods EFV was administered to healthy volunteers (n=57) as a single 600 mg dose followed by multiple doses to steady-state. Subjects were genotyped for known CYP2B6 alleles and ECGs and EFV plasma concentrations were obtained serially. Whole-cell, voltage-clamp experiments were performed on cells stably expressing hERG and exposed to EFV in the presence and absence of CYP2B6 expression. Results EFV demonstrated a gene-dose effect and exceeded the FDA criteria for QTcF interval prolongation in CYP2B6*6/*6 carriers. The largest mean time-matched differences ΔΔQTcF were observed at 6 hrs (14 ms; 95% CI [1; 27]), 12 hrs (18 ms; 95% CI [−4; 40] and 18 hrs (6 ms; 95% CI [−1; 14]) in the CYP2B6*6/*6 genotype. EFV concentrations exceeding 0.4 µg/mL significantly inhibited outward hERG tail currents (P<0.05). Conclusions This study demonstrates that homozygous carriers of CYP2B6*6 allele may be at increased risk for EFV-induced QTcF interval prolongation via inhibition of hERG.