"Quick flutter skip": midlife women's descriptions of palpitations.

OBJECTIVE: The objective of this study is to describe peri- and postmenopausal women's experiences of palpitations (quality, frequency, severity, distress, duration and temporal pattern, aura, associated symptoms, and aggravating/alleviating factors) and related healthcare experiences. METHODS: Qualitative descriptive methods were used. Semistructured interviews were conducted with women who reported palpitations and were enrolled in a larger case-control pilot study comparing electrocardiographic results between women with and without palpitations. Authors analyzed women's narratives using standard content analytic procedures. RESULTS: Fourteen participants (mean age, 54.5 y [SD = 4.8 y]; range, 46-62 y; 79% postmenopausal) completed interviews. The interviews revealed that women (a) often had difficulty describing their palpitations until prompted by the interviewer; (b) experienced noteworthy variations in the quality and other dimensions of their palpitations; (c) had a wide variety of healthcare experiences related to their palpitations, including not reporting their symptoms to providers, having providers dismiss their symptoms, and having providers be aware of their symptoms and provide diagnostic tests; and (d) at times, created worst case scenarios (downward shifts) under which they would seek treatment for their palpitations, thus enabling them to minimize their symptoms and avoid healthcare. CONCLUSION: This study advances understanding of how women describe their palpitations and related healthcare experiences. Findings could have implications for building research and clinical tools to guide assessment, communication, and/or education for patients and/or providers about palpitations and for developing and testing behavioral interventions to address this poorly understood symptom in peri- and postmenopausal women.

Disparities in Medicare beneficiaries' receiving medication synchronization.

BACKGROUND: Medication synchronization (med-sync) aligns patients' monthly or quarterly chronic medications to a predetermined single pickup date at a community pharmacy. The study objective was to examine med-sync enrollment disparities based on Medicare beneficiaries' predisposing, enabling, and need characteristics. METHODS: This was a retrospective cohort study using a Medicare dataset of beneficiaries receiving medications from pharmacies that self-identified as providing med-sync. Medicare beneficiaries who were continuously enrolled in fee-for-service medical and pharmacy benefits during the study period (2014-2016) were included. Study cohorts (med-sync and non-med-sync patients) were defined, and bivariate and multivariable logistic regression analyses were performed. Andersen's Health Services Utilization Model guided our inclusion of predisposing, enabling, and need characteristics to examine for association with med-sync enrollment. RESULTS: A total of 170,180 beneficiaries were included, of which 13,193 comprised the med-sync cohort and 156,987 comprised the non-med-sync cohort. Bivariate logistic regression analysis revealed statistically significant differences (P < 0.05) in cohorts based on age, geographic region, type of residence, number of unique chronic medications, comorbidities, outpatient visits, and inpatient hospitalizations. Beneficiaries had higher odds of being enrolled in med-sync with increasing age (adjusted odds ratio [AOR] 1.003 [95% CI 1.001-1.005]) and if they resided in the Northeast (AOR 1.094 [95% CI 1.018-1.175]), South (AOR 1.109 [95% CI 1.035-1.188]), and West (AOR 1.113 [95% CI 1.020-1.215]) than those in the Midwest. Beneficiaries residing in nonmetro areas had lower odds of enrollment (AOR 0.914 [95% CI 0.863-0.969]) than those in metro areas. Beneficiaries with previous fewer inpatient hospitalizations (AOR 0.945 [95% CI 0.914-0.977]) were more likely to be enrolled, and those with more outpatient visits (AOR 1.003 [95% CI 1.001-1.004]) were more likely to be enrolled. Those taking a higher number of oral chronic medications (AOR 1.005 [95% CI 1.002-1.008]) had greater odds of enrollment in med-sync. CONCLUSIONS: Med-sync program expansion opportunities exist to address potential enrollment disparities based on age, geographic region, metropolitan area, and prior health utilization. Further studies are needed to develop and examine strategies among pharmacies to improve med-sync enrollment outreach to these subgroups of patients.

Preparing for the spread of patient-reported outcome (PRO) data collection from primary care to community pharmacy: a mixed-methods study.

BACKGROUND: Medication non-adherence is a significant public health problem. Patient-reported outcomes (PROs) offer a rich data source to facilitate resolution of medication non-adherence. PatientToc™ is an electronic PRO data collection software originally implemented at primary care practices in California, United States (US). Currently, the use of standardized PRO data collection systems in US community pharmacies is limited. Thus, we are conducting a two-phase evaluation of the spread and scale of PatientToc™ to US Midwestern community pharmacies. This report focuses on the first phase of the evaluation. The objective of this phase was to prepare for implementation of PatientToc™ in community pharmacies by conducting a pre-implementation developmental formative evaluation to (1) identify potential barriers, facilitators, and actionable recommendations to PatientToc™ implementation and (2) create a draft implementation toolkit. METHODS: Data collection consisted of demographics, observations, audio-recorded contextual inquiries, and semi-structured interviews with staff (e.g., primary care providers, pharmacists, pharmacy technicians) and patients during 1-day site visits to a purposive sample of (1) primary care practices currently using PatientToc™ and (2) community pharmacies in Indiana, Wisconsin, and Minnesota interested in the future use of PatientToc™. Post-visit site observation debriefs were also audio-recorded. Verbatim transcripts of all recordings were coded using deductive/inductive approaches and intra-/inter-site summaries were produced identifying potential barriers, facilitators, and actionable recommendations mapped to the Consolidated Framework for Implementation Research constructs. A stakeholder advisory panel engaged in an Evidence-Based Quality Improvement (EBQI) implementation process. This included "member checking" and prioritizing findings, and feedback on the adapted PatientToc™ application, implementation strategies, and accompanying toolkit for community pharmacy implementation. RESULTS: Two primary care practices, nine pharmacies, and 89 individuals participated. Eight major themes (four barriers and four facilitators) and 14 recommendations were identified. Throughout the four EBQI sessions, the panel (1) confirmed findings; (2) designated high priority recommendations: (a) explain PatientToc™ and its benefits clearly and simply to patients, (b) ensure patients can complete questionnaires within 10 min, and (c) provide hands-on training/resources for pharmacy teams; and (3) provided feedback on the adapted PatientToc™ application and finalized toolkit items for initial community pharmacy implementation. CONCLUSIONS: Adoption of electronically captured PROs in community pharmacies is warranted. The implementation strategies systematically developed in this study can serve as a model for implementation of technology-driven health information patient care services, in the understudied context of community pharmacies.

Evaluation of a modified and abbreviated scale for assessing chronic illness care for medication therapy management practice.

BACKGROUND: The central goals of MTM align with those of the Chronic Care Model (CCM). However, reliable and valid assessments are needed to estimate the extent to which components of MTM care delivery are consistent with the CCM. The Assessment of Chronic Illness Care (ACIC) is a 34-item scale for administration in primary care offices to estimate the extent to which chronic care delivery aligns with the six elements of the CCM. The ACIC appears to be responsive for care delivery interventions aimed at improving various chronic illnesses. However, the potential value of the ACIC as a measure for evaluating MTM delivery is unknown. OBJECTIVE: A modified and abbreviated version of the ACIC could be a useful evaluation tool for pharmacist-provided medication therapy management (MTM). The objective of this study was to assess the construct and criterion-related validity, and internal consistency, of the abbreviated (12-item) "MTM ACIC." METHODS: The abbreviated MTM ACIC was administered to pharmacists employed at 27,560 community pharmacies. Construct validity and internal consistency were estimated through principal components analysis, item-to-total correlations, and Cronbach's alpha estimate of internal consistency. To assess criterion-related validity, a univariate negative binomial model estimated the association between ACIC scores and pharmacy-level MTM completion rates. RESULTS: A one-component model accounted for 64% of the variance, and Cronbach's alpha was 0.95. Scores on the abbreviated MTM ACIC were associated with MTM completion rates (rate ratio: 1.02; 95% CI: 1.01 to 1.03). CONCLUSION: The abbreviated MTM ACIC exhibited acceptable construct and criterion-related validity and internal consistency and could serve as a valuable tool for evaluating chronic illness care within the MTM setting.

Accuracy of a single-lead mobile smartphone electrocardiogram for QT interval measurement in patients undergoing maintenance methadone therapy.

STUDY OBJECTIVE: Methadone is associated with QT interval prolongation and torsades de pointes. Expert panel recommendations advocate a pre-methadone electrocardiogram (ECG) and another ECG at 30 days of therapy in patients with risk factors. Some guidelines recommend a pre-methadone ECG and routine ECG monitoring in all methadone patients, but this is controversial due to the resources required. Availability of a convenient, less resource-intensive method of ECG monitoring for patients taking methadone is desirable. The objective of this study was to assess the accuracy of a handheld smartphone ECG (iECG) for QT measurement in patients on maintenance methadone therapy in an urban opioid treatment program. DESIGN: Prospective study. SETTING: Urban opioid treatment program. PATIENTS: n = 115 patients in normal sinus rhythm who were on steady-state maintenance methadone therapy INTERVENTION: Patients (n = 115) underwent a simultaneous 12-lead ECG and a single-lead iECG. MEASUREMENTS AND MAIN RESULTS: The first three QT and RR intervals from lead II of the 12-lead ECG and simulated lead I from the iECG were compared using the Bland-Altman analysis of measurement agreement. Mean [± standard deviation) age was 34 ± 11 years; 71% were female, 75% were white. Compared to the 12-lead ECG, the iECG was associated with a QTc bias of - 0.14 ms (SD = 12 ms, 95% CI = -2.4 to 2.1 ms). The absolute mean difference in QTc between the two methods was 9.5 ± 7.1 ms. For identification of patients with methadone-associated QTc prolongation, the iECG performed moderately well [c-statistic 0.97 (95% CI 0.91-0.99); sensitivity and specificity 75% (95% CI 43-95%) and 99% (95% CI 94-99%), respectively]. The positive and negative likelihood ratios of the iECG for identifying patients with methadone-associated QTc prolongation were 77.25 (95% CI 10.69 to 558.18) and 0.25 (95% CI 0.09 to 0.67), respectively, while the positive and negative predictive values were 90% (95% CI 56-99%) and 97% (95% CI 92-99%), respectively. The accuracy of the iECG for identifying patients with QTc prolongation was 97% (95% CI 91-99%). CONCLUSION: A handheld smartphone ECG is accurate for QT interval measurement in patients taking maintenance methadone therapy, and its performance is moderately good for identifying patients with methadone-associated QTc prolongation.

An evaluation of the spread and scale of PatientToc™ from primary care to community pharmacy practice for the collection of patient-reported outcomes: A study protocol.

BACKGROUND: Medication non-adherence is a problem of critical importance, affecting approximately 50% of all persons taking at least one regularly scheduled prescription medication and costing the United States more than $100 billion annually. Traditional data sources for identifying and resolving medication non-adherence in community pharmacies include prescription fill histories. However, medication possession does not necessarily mean patients are taking their medications as prescribed. Patient-reported outcomes (PROs), measuring adherence challenges pertaining to both remembering and intention to take medication, offer a rich data source for pharmacists and prescribers to use to resolve medication non-adherence. PatientToc™ is a PROs collection software developed to facilitate collection of PROs data from low-literacy and non-English speaking patients in Los Angeles. OBJECTIVES: This study will evaluate the spread and scale of PatientToc™ from primary care to community pharmacies for the collection and use of PROs data pertaining to medication adherence. METHODS: The following implementation and evaluation steps will be conducted: 1) a pre-implementation developmental formative evaluation to determine community pharmacy workflow and current practices for identifying and resolving medication non-adherence, potential barriers and facilitators to PatientToc™ implementation, and to create a draft implementation toolkit, 2) two plan-do-study-act cycles to refine an implementation toolkit for spreading and scaling implementation of PatientToc™ in community pharmacies, and 3) a comprehensive, theory-driven evaluation of the quality of care, implementation, and patient health outcomes of spreading and scaling PatientToc™ to community pharmacies. EXPECTED IMPACT: This research will inform long-term collection and use of PROs data pertaining to medication adherence in community pharmacies.

Transdermal Testosterone Attenuates Drug-Induced Lengthening of Both Early and Late Ventricular Repolarization in Older Men.

We have previously reported that transdermal testosterone attenuates drug-induced QT interval lengthening in older men. However, it is unknown whether this is due to modulation of early ventricular repolarization, late repolarization, or both. In a secondary analysis of a prospective, randomized, double-blind, placebo-controlled three-way crossover study, we determined if transdermal testosterone and oral progesterone attenuate drug-induced lengthening of early and late ventricular repolarization, represented by the electrocardiographic measurements J-Tpeak c and Tpeak -Tend , respectively, as well as Tpeak -Tend /QT, a measure of transmural dispersion of repolarization. Male volunteers ≥ 65 years of age (n = 14) were randomized to receive transdermal testosterone 100 mg, oral progesterone 400 mg, or matching transdermal/oral placebo daily for 7 days. On the morning following the seventh day, subjects received intravenous ibutilide 0.003 mg/kg, after which electrocardiograms were performed serially. One subject was excluded due to difficulty in T-wave interpretation. Pre-ibutilide J-Tpeak c was lower during the testosterone phase than during progesterone and placebo (216 ± 23 vs. 227 ± 28 vs. 227 ± 21 ms, P = 0.002). Maximum post-ibutilide J-Tpeak c was also lower during the testosterone phase (233 ± 22 vs. 246 ± 29 vs. 248 ± 23 ms, P < 0.0001). Pre-ibutilide Tpeak -Tend was not significantly different during the three phases, but maximum post-ibutilide Tpeak -Tend was lower during the testosterone phase (80 ± 12 vs. 89 ± 18 vs. 86 ± 15 ms, P = 0.002). Maximum Tpeak -Tend /QT was also lower during the testosterone phase (0.199 ± 0.023 vs. 0.216 ± 0.035 vs. 0.209 ± 0.031, P = 0.005). Progesterone exerted minimal effect on drug-induced lengthening of J-Tpeak c, and no effect on Tpeak -Tend or Tpeak -Tend /QT. Transdermal testosterone attenuates drug-induced lengthening of both early and late ventricular repolarization in older men.

A user-centered evaluation of medication therapy management alerts for community pharmacists: Recommendations to improve usability and usefulness.

BACKGROUND: Community pharmacists provide comprehensive medication reviews (CMRs) through pharmacy contracts with medication therapy management (MTM) vendors. These CMRs are documented in the vendors' web-based MTM software platforms, which often integrate alerts to assist pharmacists in the detection of medication therapy problems. Understanding pharmacists' experiences with MTM alerts is critical to optimizing alert design for patient care. OBJECTIVES: The objectives of this study were to 1) assess the usability and usefulness of MTM alerts for MTM vendor-contracted community pharmacists and 2) generate recommendations for improving MTM alerts for use by community pharmacists. METHODS: This was a convergent, parallel mixed-methods evaluation of data collected from 3 sources, with individual pharmacists contributing data to one or more sources: 1) community pharmacists' submissions of observational data about MTM alerts encountered during routine MTM provision, 2) videos of naturalistic usability testing of MTM alerts, and 3) semi-structured interviews to elicit pharmacists' perspectives on MTM alert usefulness and usability. MTM alert data submitted by pharmacists were summarized with descriptive statistics. Usability testing videos were analyzed to determine pharmacists' time spent on MTM alerts and to identify negative usability incidents. Interview transcripts were analyzed using a hybrid approach of deductive and inductive codes to identify emergent themes. Triangulation of data (i.e., determination of convergence/divergence in findings across all data sources) occurred through investigator discussion and identified overarching findings pertaining to key MTM alert challenges. These resulted in actionable recommendations to improve MTM alerts for use by community pharmacists. RESULTS: Collectively, two and four overarching key challenges pertaining to MTM alert usability and usefulness, respectively, were identified, resulting in 15 actionable recommendations for improving the design of MTM alerts from a user-centered perspective. CONCLUSIONS: Recommendations are expected to inform enhanced MTM alert designs that can improve pharmacist efficiency, patient and prescriber satisfaction with MTM, and patient outcomes.

Methadone-associated QT interval prolongation in patients undergoing maintenance therapy in an urban opioid treatment program.

STUDY OBJECTIVE: Methadone is associated with QT interval prolongation and torsades de pointes. The objective of this study was to (a) determine the incidence of QT interval prolongation among patients on maintenance methadone therapy in an urban opioid treatment program (OTP), (b) compare characteristics of patients who developed methadone-associated QT prolongation with those who did not develop QT prolongation, and (c) investigate the relationship between QT interval prolongation and stereospecific serum methadone and metabolite [2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP)] concentrations. DESIGN: Prospective study. SETTING: Urban opioid treatment program (OTP). PATIENTS: n = 93 patients on maintenance methadone therapy in an urban OTP. INTERVENTION: Patients underwent a 12-lead electrocardiogram (ECG) prior to initiating methadone and again during steady-state maintenance methadone therapy. In a subset (n = 43), blood was obtained to determine serum (S)- and (R)-methadone and (S)- and (R)-EDDP concentrations, which were compared in patients who developed Bazett's-corrected QT (QTc) prolongation [≥470 ms (men) or ≥480 ms (women) and/or ≥60 ms lengthening from pretreatment value] with those who did not have QTc prolongation. MEASUREMENTS AND MAIN RESULTS: Mean [± standard deviation (SD)] age was 36 ± 12 years; 73% were female, and 74% were white. QTc prolongation occurred in 14 (15.1%) patients. Patients who developed QTc prolongation were older (41 ± 13 vs. 35 ± 9 years, p = 0.03) and had a longer pre-methadone QTc compared with those who did not have QTc prolongation (429 ± 11 vs. 420 ± 20 ms, respectively, p = 0.02). Serum (S)-methadone concentrations were higher in patients with QTc prolongation compared to patients without prolongation (199 ± 81 vs. 128 ± 68 ng/ml, respectively, p = 0.01), whereas the difference in serum (R)-methadone concentrations between the groups did not reach significance (189 ± 68 vs. 125 ± 60 ng/ml, respectively, p = 0.08). Serum (R)-methadone concentrations correlated with QTc intervals [R2  = 0.15 (95% confidence interval (CI) 0.11-0.62, p = 0.0009)]. The correlation between serum (S)-methadone concentrations and QTc did not reach significance [R2  = 0.08 (95% CI -0.01 to 0.54, p = 0.06)]. Serum (S)-and (R)-EDDP concentrations were not significantly different between the groups and did not significantly correlate with QTc intervals. CONCLUSIONS: Approximately 15% of patients taking maintenance methadone therapy developed QT interval prolongation. Both serum (S)- and (R)-methadone concentrations, but not (S)- or (R)-EDDP, contribute to methadone-associated QT prolongation.

Enhanced Response to Drug-Induced QT Interval Lengthening in Patients with Heart Failure with Preserved Ejection Fraction.

BACKGROUND: Patients with heart failure (HF) with reduced ejection fraction demonstrate enhanced response to drug-induced QT interval lengthening and are at increased risk for torsades de pointes. The influence of HF with preserved ejection fraction (HFpEF) on response to drug-induced QT lengthening is unknown. METHODS AND RESULTS: We administered intravenous ibutilide 0.003 mg/kg to 10 patients with HFpEF and 10 age- and sex-matched control subjects without HF. Serial 12-lead electrocardiograms were obtained for determination of QT intervals. Demographics, maximum serum ibutilide concentrations, area under the serum ibutilide concentration vs time curves, and baseline Fridericia-corrected QT (QTF) (417 ± 14 vs 413 ± 15 ms, P = .54) were similar in the HFpEF and control groups. Area under the effect (QTFvs time) curve (AUEC) from 0 to 1.17 hours during and following the ibutilide infusion was greater in the HFpEF group (519 ± 19 vs 497 ± 18 ms·h, P= .04), as was AUEC from 0 to 8.17 hours (3576 ± 125 vs 3428 ± 161 ms·h, P = .03) indicating greater QTF interval exposure. Maximum QTF (454 ± 15 vs 443 ± 22 ms, P = .18) and maximum percent increase in QTF from baseline (8.2 ± 2.1 vs 6.7 ± 1.9%, P = .10) in the 2 groups were not significantly different. CONCLUSIONS: HFpEF is associated with enhanced response to drug-induced QT interval lengthening.

Evaluating the effects of a multidisciplinary transition care management program on hospital readmissions.

PURPOSE: To measure the effect of a pharmacist-initiated transitions of care (TOC) program on rates of 30-day all-cause readmissions and primary care follow-up. METHODS: A retrospective cohort study was conducted to evaluate a pharmacist-initiated TOC program for patients discharged from hospitals of a large health system from September 2015 through July 2016. Discharged patients of 13 primary care physicians (the intervention cohort) received TOC program services, and discharged patients seen by 12 other primary care physicians (the control cohort) received usual care. Patients in both cohorts were followed for 90 days. The primary outcome was 30-day all-cause readmissions, and secondary outcomes were 14-day primary care visits, TOC pharmacist identification and resolution of medication therapy problems (MTPs), and transition care management (TCM) billing. Multivariable modeling was performed to test the associations of patient receipt of TOC services with 30-day readmissions and 14-day primary care visits, with controlling for patient demographics and baseline healthcare utilization. RESULTS: A total of 492 patients received the TOC intervention, and 379 were followed in the usual care cohort. Among intervention patients, 960 MTPs were identified, and 85.7% of identified MTPs were resolved. Moreover, 9% of intervention cohort patients were readmitted within 30 days, compared to 15% of control cohort patients, and this effect was significant in the multivariable model (odds ratio, 1.82; 95% confidence interval, 1.15-2.89; P = 0.0108). Rates of primary care visits did not differ significantly between the groups; 65% of intervention group visits were billed using TCM codes. CONCLUSION: A pharmacist-initiated TOC program was effective in reducing 30-day all-cause readmissions.

Factors associated with comprehensive medication review completion rates: A national survey of community pharmacists.

BACKGROUND: Completion rates for medication therapy management (MTM) services have been lower than desired and the Centers for Medicare and Medicaid Services has added MTM comprehensive medication review (CMR) completion rates as a Part D plan star measure. Over half of plans utilize community pharmacists via contracts with MTM vendors. OBJECTIVES: The primary objective of this survey study was to identify factors associated with the CMR completion rates of community pharmacies contracted with a national MTM vendor. METHODSL: Representatives from 27,560 pharmacy locations contracted with a national MTM vendor were surveyed. The dependent variable of interest was the pharmacies' CMR completion rate. Independent variables included the pharmacy's progressiveness stratum and number of CMRs assigned by the MTM vendor during the time period, as well as self-reported data to characterize MTM facilitators, barriers, delivery strategies, staffing, selected items from a modified Assessment of Chronic Illness Care, and pharmacist/pharmacy demographics. Univariate negative binomial models were fit for each independent variable, and variables significant at p < 0.05 were entered into a multivariable model. RESULTS: Representatives from 3836 (13.9%) pharmacy locations responded; of these, 90.9% (n = 3486) responses were useable. The median CMR completion rate was 0.42. Variables remaining significant at p < 0.05 in the multivariable model included: progressiveness strata; pharmacy type; scores on the facilitators scale; responses to two potential barriers items; scores on the patient/caregiver delivery strategies sub-scale; providing MTM at multiple locations; reporting that the MTM vendor sending the survey link is the primary MTM vendor for which the respondent provides MTM; and the number of hours per week that the pharmacy is open. CONCLUSIONS: Factors at the respondent (e.g., responses to facilitators scale) and pharmacy (e.g., pharmacy type) levels were associated with CMR completion rates. These findings could be used by MTM stakeholders to improve CMR completion rates.

Progesterone pretreatment reduces the incidence of drug-induced torsades de pointes in atrioventricular node-ablated isolated perfused rabbit hearts.

INTRODUCTION: Higher progesterone concentrations are protective against drug-induced prolongation of ventricular repolarization. We tested the hypothesis that pretreatment with progesterone reduces the incidence of drug-induced torsades de pointes (TdP). METHODS AND RESULTS: Female New Zealand white rabbits (2.5-3.2 kg) underwent ovariectomy and were randomized to undergo implantation with subcutaneous 21-day sustained release pellets containing progesterone 50 mg (n = 22) or placebo (n = 23). After 20 days, hearts were excised, mounted, and perfused with modified Krebs-Henseleit solution. The atrioventricular (AV) node was destroyed manually. Following a 15-minute equilibration period, hearts were perfused with dofetilide 100 nM for 30 minutes, during which the electrocardiogram was recorded continuously. Incidences of spontaneous TdP, other ventricular arrhythmias and mean QTc intervals were compared. Median serum progesterone concentrations were higher in progesterone vs placebo-treated rabbits (3.8 [range, 2.8-5.1] vs 0.7 [0.4-1.7] ng/mL, P < 0.0001). Median serum estradiol concentrations were similar (58 [22-72] vs 53 [34-62] pg/mL), P = 0.79). The incidence of TdP was lower in hearts from progesterone-treated rabbits (27% vs 61%, P = 0.049). The incidences of bigeminy (36% vs 74%, P = 0.03) and trigeminy (18% vs 57%, P = 0.01) were also lower in hearts from progesterone-treated rabbits. There was no significant difference between groups in incidence of couplets (59% vs 74%, P = 0.54) or monomorphic ventricular tachycardia (14% vs 30%, P = 0.28). Maximum QT c interval and short-term beat-to-beat QT interval variability during dofetilide perfusion were significantly shorter in hearts from progesterone-treated rabbits. CONCLUSIONS: Pretreatment with progesterone reduces the incidence of drug-induced TdP, bigeminy, and trigeminy in isolated perfused AV node-ablated rabbit hearts.

Amiodarone for prevention of atrial fibrillation following esophagectomy.

OBJECTIVES: Atrial fibrillation (AF) is a common complication after esophagectomy and is associated with symptoms, hemodynamic instability, prolonged hospital stay, and an increased incidence of mortality. Our objective was to determine the efficacy and safety of intravenous amiodarone for prophylaxis of postesophagectomy AF. METHODS: In this retrospective cohort study, 309 patients who underwent esophagectomy formed the initial cohort. Following propensity score-matching, 110 patients who received prophylactic amiodarone 43.75 mg/hour via continuous intravenous infusion over 96 hours (total dose, 4200 mg) were matched to a control group of patients who did not undergo amiodarone prophylaxis (n = 110). The propensity score was obtained using a multivariate logistic regression model with amiodarone as the variable and the following covariates: age, sex, surgical approach, history of neoadjuvant chemotherapy and/or radiation, chronic obstructive pulmonary disease, heart failure, cardiovascular disease, alcohol use (>7 drinks/week), preadmission ß-blockers discontinued during hospitalization, preoperative use of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, preoperative use of corticosteroids, postoperative use of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, postoperative use of corticosteroids, postoperative use of statins, and preoperative Charlson comorbidity index. RESULTS: The incidence of AF requiring treatment due to rapid ventricular rate and symptoms was lower in the amiodarone group (17 out of 110 [15.5%] vs 32 out of 110 [29.1%]; odds ratio, 0.45; 95% confidence interval, 0.23-0.86; P = .015). There were no significant differences between the groups in median postoperative length of hospital stay, incidence of pulmonary complications, or mortality. The incidences of hypotension requiring treatment (42.7% vs 21.8%; P = .001), bradycardia (8.2% vs 0.0%; P = .002), and corrected QT interval prolongation (10.9% vs 0.0%; P ≤ .0001) were significantly higher in the amiodarone group. CONCLUSIONS: Prophylactic intravenous amiodarone is associated with a reduction in the incidence of AF following esophagectomy, but is not associated with shorter postoperative length of hospital stay. Intravenous amiodarone for prophylaxis of postesophagectomy AF is associated with hypotension, bradycardia, and corrected QT interval prolongation.

Variation in Medication Therapy Management Delivery: Implications for Health Care Policy.

BACKGROUND: Medication therapy management (MTM) program evaluations have revealed mixed outcomes, with some studies finding favorable outcomes and others finding no differences between patients who received MTM versus those who did not. One possible reason for outcomes variability is differences in delivery of MTM programs. The Chronic Care Model (CCM) provides a framework for how health care organizations can improve care for the chronically ill through 6 elements: organization of health care, delivery system design, clinical information systems, decision support, self-management, and linkages to community resources. OBJECTIVE: To apply the CCM to understand variation in MTM delivery and formulate policy recommendations. METHODS: This study used a mixed-methods descriptive analysis of MTM delivery. Investigators conducted visits to a purposeful sample of MTM practices to observe MTM and interview participants. The pharmacists and staff of these practices completed a modified Assessment of Chronic Illness Care (ACIC). Pairs of investigators analyzed interview transcripts to identify themes. Demographics and ACIC scores were summarized using descriptive statistics. After analysis, investigators discussed overarching themes and policy implications organized by CCM elements. RESULTS: Seven practices participated, and 87 participants were interviewed. Based on ACIC scores, MTM patient volume, and payer mix, practices were categorized as Early Maturity Level or Later Maturity Level. From the model, organization of health care themes included whether MTM was the practice's core competence, belief/confidence in the MTM process, lack of formal rewards, and the influence of organizational goals and external environment. Delivery system design themes pertained to the extent that MTM processes were formalized. Clinical information systems themes were the extent to which systems were influenced by payers, efficiency strategies, and the accuracy and availability of information. In considering clinical decision support themes, alert design limitations and variation in user approaches to alerts based on experience were noted. We observed strong support for patient self-management; when present, barriers were attributed to the patient, MTM provider, or payer. Referral to community resources was minimal. Numerous policy implications were identified. CONCLUSIONS: Our research identified numerous ways by which MTM delivery varies, particularly by MTM practice maturity level. These findings provide evidence for several policy changes that could be considered to optimize MTM delivery, encourage alignment with the CCM, and promote practice maturation. DISCLOSURES: This research and a portion of Snyder's salary were supported by grant number K08HS022119 from the Agency for Healthcare Research and Quality. The content is solely the responsibility of the authors and does not necessarily represent the official views of the Agency for Healthcare Research and Quality. Snyder reports consulting fees from Westat for an evaluation of the CMS Enhanced MTM program. The other authors have nothing to disclose. Portions of this research have been presented as abstracts at the following conferences: (a) 2017 Academy Health Annual Research Meeting; June 25-27, 2017; New Orleans, LA; (b) 2015 American Society of Health-System Pharmacists Clinical Midyear Meeting; December 4-8, 2015; New Orleans, LA; and

Characterization of actions taken during the delivery of medication therapy management: A time-and-motion approach.

OBJECTIVES: To characterize actions performed by pharmacists and support staff during provision of medication therapy management (MTM) and to compare actions performed according to practice characteristics. METHODS: A purposeful sample of 7 MTM practices (2 call centers and 5 community practices) was identified and visited by investigators. Pharmacists and support staff were observed during their routine provision of MTM. Investigators characterized "major" (e.g., preparation for a comprehensive medication review) and "minor" (i.e., specific steps in overarching major action) actions with the use of a time-and-motion approach. RESULTS: A total of 32 major and 469 minor actions were observed. Practices were characterized as Later Maturity Level or Early Maturity Level on the basis of their self-reported MTM appointment volume, self-assessment of the extent of integration of chronic care model principles, and payer mix. Later Maturity Level practices were more likely to deliver follow-up medication therapy reviews and comprehensive medication reviews (CMRs) as opposed to targeted medication reviews (TMRs) and to receive physician referrals for MTM. Later Maturity Level practices were also more likely to use paid interns than pharmacy rotation students. CMR activities observed at Later Maturity Level practices lasted a median of 30.8 minutes versus 20.3 minutes for CMR activities at Early Maturity Level practices. Similarly, TMR activities observed at Later Maturity Level practices were longer: a median of 31.0 minutes versus 12.3 minutes. At Later Maturity Level practices, pharmacists spent a greater proportion of time providing patient education, while support staff spent a greater proportion of time on tasks such as capturing demographics and introducing or explaining MTM. CONCLUSION: MTM activities were longer at Later Maturity Level practices, and these practices were more likely to use paid pharmacy interns and to receive physician referrals for MTM. This work provides a foundation for future research.

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

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 ∆∆QTcF were observed at 6 hours (14 milliseconds; 95% CI [1; 27]), 12 hours (18 milliseconds; 95% CI [-4; 40]), and 18 hours (6 milliseconds; 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.

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.

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.