Real-World Characteristics of Patients with Wild-Type Transthyretin Amyloid Cardiomyopathy: An Analysis of Electronic Healthcare Records in the United States.

BACKGROUND: Tafamidis was approved for the treatment of hereditary and wild-type transthyretin amyloid cardiomyopathy (ATTRwt-CM) in May 2019, based on findings from the Tafamidis in Transthyretin Cardiomyopathy Clinical Trial (ATTR-ACT). METHODS: This retrospective cohort study evaluated the factors associated with tafamidis prescription after diagnosis of ATTRwt-CM in the real world. Between May 2019 and December 2020, 430 patients with 6 months' database activity were indexed from the de-identified US Optum electronic healthcare records at first diagnosis of ATTRwt-CM or prescription of tafamidis, then followed until last activity or death. Of these, 209 patients were prescribed tafamidis during follow-up, 167 (80%) within 1 month, 98% by 6 months, and 100% by 9 months. Median time from index to tafamidis prescription, calculated using the Kaplan-Meier method, was 5.8 months (95% confidence interval [CI] 2.4-not evaluable). RESULTS: Factors associated with tafamidis prescription in a multivariable Cox proportional hazards regression (hazard ratio [95% CI]) included age ≥ 65 years (2.1 [1.07-4.05]), male sex (1.6 [1.07-2.28]), having heart failure/cardiomyopathy (2.4 [1.54-3.82]), and having had technetium-99m pyrophosphate myocardial scintigraphy (1.7 [1.28-2.28]). CONCLUSIONS: The clinical characteristics of patients with ATTRwt-CM who were prescribed tafamidis in the real world were broadly comparable with those who took part in ATTR-ACT. Further studies are needed to evaluate hereditary and ATTRwt-CM patient populations in the real world and assess the long-term outcomes associated with disease management pathways. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov identifier: NCT01994889.

Hemodynamic Effects of Dexmedetomidine in Adults With Reduced Ejection Fraction Heart Failure.

BACKGROUND: Dexmedetomidine (DEX) can cause hypotension complicating its use in critically ill patients with labile hemodynamics secondary to an underlying disease state such as heart failure. The aim of this study was to determine the effect of DEX on mean arterial pressure (MAP) in nonsurgical patients with heart failure and reduced ejection fraction (HFrEF). METHODS: This retrospective single-center cohort study evaluated patients who received DEX in the cardiac care and medical intensive care units at a large academic hospital. The primary end point was the change in MAP within 6 hours following DEX initiation. RESULTS: Sixty-five patients with HFrEF diagnosis were compared 1:1 to a control group without HFrEF. Both groups experienced a decrease in MAP over the study period. Patients with HFrEF had a greater absolute percentage reduction in MAP 1 hour following DEX initiation compared to the control group (-9.6% vs -5.2%; P < .01). When accounting for the combined effect of DEX initiation and HFrEF diagnosis on the primary end point, patients with HFrEF did not have a significant difference in MAP compared to the control group over the study period. CONCLUSIONS: Within 6 hours following DEX initiation, both groups experienced a decrease in MAP. The effect of DEX on MAP over the composite time period was not found to be significantly different in the HFrEF group compared to the non-HFrEF group. However, patients with HFrEF experienced a greater reduction in MAP in the first hour following DEX initiation compared to the non-HFrEF group. Prospective studies are needed to evaluate the effect of DEX on patients with acute decompensated HFrEF compared to patients with compensated HFrEF.

Impact of Chlorhexidine Bathing on Antimicrobial Utilization in Surgical Intensive Care Unit.

BACKGROUND: This secondary analysis compared antimicrobial utilization among surgical intensive care unit patients randomized to every other day chlorhexidine bathing (chlorhexidine) versus daily soap and water bathing (soap-and-water) using data from the CHlorhexidine Gluconate BATHing trial. MATERIALS AND METHODS: Antimicrobial utilization was quantified using defined daily dose (DDD)/100 patient-days and agent-days/100 patient-days for systemic antimicrobials. Antivirals (except oseltamivir), antiparasitics, and prophylaxis agents were excluded. The 2018 anatomic therapeutic chemical/DDD index was used to calculate DDD. Agent-days were calculated as the sum of calendar days where antimicrobials were administered. Patient-days were defined as time patients were at risk for health care-acquired infections plus up to 14 d. Primary analyses were conducted using linear regression adjusted for baseline Acute Physiology and Chronic Health Evaluation II scores. RESULTS: Of 325 CHlorhexidine Gluconate BATHing trial patients, 312 (157 in soap-and-water and 155 in chlorhexidine) were included. The median (interquartile range) of total antimicrobial DDD/100 patient-days was 135.4 (75.2-231.8) for soap-and-water and 129.9 (49.2-215.3) for chlorhexidine. The median (interquartile range) of total antimicrobial agent-days/100 patient-days was 155.6 (83.3-243.2) for soap-and-water and 146.7 (66.7-217.4) for chlorhexidine. After adjusting for Acute Physiology and Chronic Health Evaluation II scores, chlorhexidine bathing was associated with a nonsignificant reduction in total antimicrobial DDD/100 patient-days (-3.9; 95% confidence interval, -33.9 to 26.1; P = 0.80) and total antimicrobial agent-days/100 patient-days (-10.3; 95% confidence interval, -34.7 to 14.1; P = 0.41). CONCLUSIONS: Compared with daily soap and water bathing, every other day chlorhexidine bathing did not significantly reduce total antimicrobial utilization in surgical intensive care unit patients.

Comparison of Levothyroxine Dosing in Patients with and without Heart Failure.

Background: Evidence has shown that low thyroid hormone levels may lead to worse prognosis including a higher mortality rate in patients with heart failure (HF). Thyroid replacement increases cardiac output and exercise performance without causing significant adverse events. The purpose of this study is to compare levothyroxine doses in patients with and without HF.Methods: This single center, retrospective cohort study compared levothyroxine doses in ambulatory hypothyroid patients with a history of HF to those without a history of HF. Patients were stratified into three groups: no HF, HF with reduced ejection fraction (HFrEF, EF<40%), and other types of HF. The primary endpoint of average levothyroxine dose was analyzed using multivariable linear regression with variables determined a priori.Results: Three hundred patients were included in the study with 100 patients in each arm. Average levothyroxine doses (mcg/kg) were 1.5 ± 0.7, 1.6 ± 0.8, and 1.6 ± 0.9 for no HF, other types of HF, HFrEF, respectively (p= .61). Factors found to be significantly related to levothyroxine dosing included gender, drug-drug interactions, and the timing of clinic visit to lab draw. No differences were found in secondary outcomes including TSH levels, free T4, T3, and percentage of patients with elevated thyroid-stimulating hormone (TSH) among HFrEF, other types of HF, and no HF patients. Among HF patients, average ejection fractions were also similar comparing patients with elevated TSH, normal TSH, and low TSH.Conclusion: The dose of levothyroxine was not significantly different in HF patients compared to patients without HF.

A systematic approach to optimize electronic health record medication alerts in a health system.

PURPOSE: The effectiveness of a systematic, streamlined approach to optimize drug-drug interaction alerts in an electronic health record for a health system was studied. METHODS: An 81-week quasi-experimental study was conducted to evaluate interventions made to medication-related clinical decision-support (CDS) alerts. Medication-related CDS alerts were systematically reduced using a multi disciplinary healthcare committee. The primary endpoint was weekly overall, modification, and acknowledgement rates of medication alerts after drug-drug interaction reclassification. Secondary endpoints included sub analysis of types of medication alerts (drug-drug interaction and duplicate therapy alerts) and alert use by providers (pharmacist and prescribers). Data was analyzed using interrupted time series regression analysis. RESULTS: After implementation of the new alert system, total number of weekly inpatient alerts decreased from 68,900 (66,300-70,900) and 50,300 (48,600-53,600) in the postintervention period (p < 0.001). The perentage of alerts acknowledged weekly increased from 11.8% (IQR, 11.4-12.1%) in the preintervention period to 13.7% (IQR, 13.3-14.0%) in the postintervention period (p < 0.001). The percentage of alerts that were modified also increased from 5.0% (IQR, 4.9-5.3%) in the preintervention period to 7.3% (IQR, 7.0-7.6%) in the postintervention period (p < 0.001). Both increases were primarily seen with pharmacists versus other healthcare professionals (p < 0.001). CONCLUSION: A committee-led systematic approach to optimizing drug-drug interactions facilitated a significant decrease in the overall number of alerts and an increase in both medication alert acknowledgement and modification rates.

Quality indicators to measure the effect of opioid stewardship interventions in hospital and emergency department settings.

PURPOSE: The purpose of this project was to develop a set of valid and feasible quality indicators used to track opioid stewardship efforts in hospital and emergency department settings. METHODS: Candidate quality indicators were extracted from published literature. Feasibility screening excluded quality indicators that cannot be reliably extracted from the electronic health record or that are irrelevant to pain management in the hospital and emergency department settings. Validity screening used an electronic survey of key stakeholders including pharmacists, nurses, physicians, administrators, and researchers. Stakeholders used a 9-point Likert scale to rate the validity of each quality indicator based on predefined criteria. During expert panel discussions, stakeholders revised quality indicator wording, added new quality indicators, and voted to include or exclude each quality indicator. Priority ranking used a second electronic survey and a 9-point Likert scale to prioritize the included quality indicators. RESULTS: Literature search yielded 76 unique quality indicators. Feasibility screening excluded 9 quality indicators. The validity survey was completed by 46 (20%) of 228 stakeholders. Expert panel discussions yielded 19 valid and feasible quality indicators. The top 5 quality indicators by priority were: the proportion of patients with (1) naloxone administrations, (2) as needed opioids with duplicate indications, and (3) long acting or extended release opioids if opioid-naïve, (4) the average dose of morphine milligram equivalents administered per day, and (5) the proportion of opioid discharge prescriptions exceeding 7 days. CONCLUSION: Multi-professional stakeholders across a health system participated in this consensus process and developed a set of 19 valid and feasible quality indicators for opioid stewardship interventions in the hospital and emergency department settings.

Implementation and evaluation of a sterile compounding robot in a satellite oncology pharmacy.

PURPOSE: The purpose of this study was to quantify the impact of robotic technology on efficiency, accuracy, and cost in a satellite oncology pharmacy. METHODS: A 33-week quasi-experimental study was conducted at an academic, quaternary care institution with 1,119 licensed beds from June 2016 to February 2017 to evaluate the turnaround time (TAT) for preparations compounded by automated robotic compounding technology (ARCT) versus historical procedures. Secondary endpoints included mean preparation time and percentage of doses with a TAT of <30 minutes before and after the implementation of ARCT and were evaluated using time-segmented regression analysis. The cost savings in the satellite oncology pharmacy was determined by comparing usage of closed-system transfer devices (CSTDs) and labor costs between study phases. Accuracy of the intervention was expressed through a descriptive analysis of mean ARCT dose preparation deviations and preparation failures. RESULTS: Data for 1,453 preparations were included for analysis. The mean ± S.D. preimplementation TAT was 64.1 ± 27.9 minutes, which decreased to 53.2 ± 32.2 minutes after ARCT implementation (p < 0.01). Financial benefit was demonstrated through supply cost savings. Breakeven was estimated at 8.6 years after capital expenditure, with an annualized projected savings of $129,477. The mean ± S.D. deviation of the doses compounded using ARCT was -0.58% ± 0.01% from the ordered dosage. CONCLUSION: Adoption of ARCT for compounding of admixtures containing 4 oncology agents reduced TAT and preparation time and led to lower expenditures for CSTDs.

Impact of intraoperative factor concentrates on blood product transfusions during orthotopic liver transplantation.

BACKGROUND: Major bleeding in orthotopic liver transplantation is associated with significant morbidity and mortality. Limited literature exists regarding comparative effectiveness of prothrombin complex concentrate and fibrinogen concentrate during orthotopic liver transplantation on blood product utilization. STUDY DESIGN AND METHODS: This retrospective, single-institution study evaluated the impact of prothrombin complex concentrate and fibrinogen concentrate on blood product utilization during orthotopic liver transplantation from December 2013 to April 2016. This study included patients age 18 years or older and excluded patients who received simultaneous heart or lung transplantation or did not meet documentation criteria. A propensity score matching technique was used to match patients who were exposed to prothrombin complex concentrate with unexposed patients, at a 2 to 1 ratio, to control for selection bias. RESULTS: During this study, 212 patients received orthotopic liver transplantation with 39 prothrombin complex concentrate exposures. The matched study population included 39 patients who were exposed to prothrombin complex concentrate and 78 unexposed patients. Overall, 84.6% of patients who were exposed to prothrombin complex concentrate also received concomitant fibrinogen concentrate, whereas only 2% of patients in the control group received fibrinogen concentrate. After propensity score matching, no other factors that were included in the model differed significantly or had a standardized mean difference of 0.11 or greater. There was no statistical difference in the utilization of red blood cells or fresh frozen plasma for the exposed group versus the unexposed group after matching (mean ± standard deviation: red blood cell units, 12.4 ± 8.0 units vs. 9.7 ± 5.6 units [p = 0.058]; fresh-frozen plasma units, 10.0 ± 6.3 vs. 12.7 ± 9.7 units [p = 0.119], respectively). CONCLUSION: The intraoperative use of prothrombin complex concentrate and fibrinogen concentrate during orthotopic liver transplantation did not reduce intraoperative blood product requirements at a single institution.

Discharge medication complexity and 30-day heart failure readmissions.

BACKGROUND: Limited research exists regarding Medication Regimen Complexity Index (MRCI) and its utility in identifying patients at risk for hospital readmission. OBJECTIVE: This study evaluates the association between discharge MRCI and 30-day rehospitalization in patients with heart failure (HF) after discharge. METHODS: The study involved a retrospective, cohort study at a large tertiary teaching facility from the University HealthSystem Consortium. The consortium database was used to identify HF patients hospitalized from January 2011 to December 2013. A 30-day readmission was defined as being readmitted to the same hospital within 30 days of discharge with a principal discharge diagnosis of HF. Index hospitalizations was defined as the first hospitalization, and readmission was the subsequent hospitalization for HF. A pilot analysis was conducted to compare manual MRCI collection tool and a computerized scoring MRCI system. Multivariable logistic regression was used to examine the association of computerized MRCI (≥15) and 30-day rehospitalization after controlling for other variables. RESULTS: A total of 1,452 patients were included in the study with 81 patients (5.9%) readmitted within 30 days of discharge. The manual and computerized MRCIs were correlated with an R of 0.74 and R2 of 0.55. The multivariate logistic regression analysis found computerized MRCI ≥15 (OR: 1.62; 95% CI: 1.01-2.59) was associated with 30-day rehospitalization after controlling for other factors. Patients prescribed angiotensin-converting-enzyme inhibitors or angiotensin receptor blockers, were less likely (OR: 0.54; CI: 0.33-0.89) to be readmitted 30 days after discharge, and patients with coronary artery disease were more likely (OR: 1.76; CI: 1.03-3.00) to be readmitted 30 days after discharge. CONCLUSIONS: The computerized MRCI score was moderately correlated with manual MRCI score. A significant association was found between computerized MRCI and 30-day HF readmission. Such predictive tools may allow pharmacists to prioritize patient care and optimize patient outcomes through medication therapy management.